source,input,output,input_words,output_words,compression_ratio
scientific_lay_summarisation-elife-norm,"addition of myristic acid to an N-terminal glycine (Boutin, 1997; Gordon et al. , 1991). Functionally, myristoylation often primes proteins for subsequent palmitoylation and a stable protein-membrane association (Martin et al. , 2011; Wright et al. , 2010), however, it has also been shown to facilitate protein-protein interactions (PPIs) (Chow et al. , 1987; Mousnier et al. , 2018), affect protein activity (Zhu et al. , 2019) as well as structure and stability (Zheng et al. , 1993). It is catalysed by N-myristoyl transferase (NMT), which is conserved across many organisms, including Toxoplasma, and has been reported to be a prominent drug target in fungal (Devadas et al. , 1995; Nagarajan et al. , 1997), Trypanosome (Frearson et al. , 2010; Wright et al. , 2016) and Leishmania infections (Hutton et al. , 2014; Wright et al. , 2015). In Plasmodium falciparum (the major causative agent of malaria), inhibition of NMT leads to severe pleiotropic consequences affecting parasite development (Schlott et al. , 2019; Wright et al. , 2014), highlighting the importance of myristoylation for parasite survival and progression. An N-terminal glycine (MG motif) is a requirement, but not a predictor of myristoylation. Approximately 6% of all gene products in Toxoplasma contain an N-terminal glycine and an in silico prediction of myristoylation suggests that ~ 1. 8% of all T. gondii gene products are modified (Alonso et al. , 2019). The functional significance of myristoylation has been described for only a few T. gondii proteins, and mainly in conjunction with adjacent palmitoylation that promotes stable membrane attachment. These proteins include key signal mediators in parasite egress and invasion, for example CDPK3 (Garrison et al. , 2012; McCoy et al. , 2012), PKG (Brown et al. , 2017), PKAr (Jia et al. , 2017b; Uboldi et al. , 2018); proteins involved in invasion, for example IMP1 (Jia et al. , 2017a); parasite gliding, for example GAP45 and GAP70 (Frénal et al. , 2010); division, for example F-box protein 1 and ISP1,2, 3 (Baptista et al. , 2019; Beck et al. , 2010); and correct rhoptry positioning required for invasion, for example ARO (Cabrera et al. , 2012; Mueller et al. , 2013). Collectively, these studies show key roles for myristoylation throughout the parasite’s lytic cycle, but the function of myristoylation in","A microscopic parasite known as Toxoplasma gondii infects around 30% of the human population. Most infections remain asymptomatic, but in people with a compromised immune system, developing fetuses and people infected with particular virulent strains of the parasite, infection can be fatal. T. gondii is closely related to other parasites that also infect humans, including the one that causes malaria. These parasites have complex lifecycles that involve successive rounds of invading the cells of their hosts, growing and then exiting these cells. Signaling proteins found at specific locations within parasite cells regulate the ability of the parasites to interact with and invade host cells. Sometimes these signaling proteins are attached to membranes using lipid anchors, for example through a molecule called myristic acid. An enzyme called NMT can",380,128,0.3368
dialogsum,"#Person1#: I'm about to run out of business cards. I need some new ones. #Person2#: We can print as many as you like. Just tell me how many. #Person1#: Two thousand should get me through the year. #Person2#: Here's a form to get you started. #Person1#: My old card is perfect, so all I want you to do is copy it exactly. #Person2#: I think you'll be very pleased with how well we duplicate your old card. #Person1#: . . . Here you go #Person2#: Thanks. Come back here next Wednesday to pick up your order, please. #Person1#: I'm sorry, but can you give me a three-day turnaround? #Person2#: If you don't mind paying a little extra, it's absolutely no problem. #Person3#: #Person1#: I'm about to run out of business cards. I need some new ones. #Person2#: We can print as many as you like. Just tell me how many. #Person1#: Two thousand should get me through the year. #Person2#: Here's a form to get you started. #Person1#: My old card is perfect, so all I want you to do is copy it exactly. #Person2#: I think you'll be very pleased with how well we duplicate your old card. #Person1#: . . . Here you go #Person2#: Thanks. Come back here next Wednesday to pick up your order, please. #Person1#: I'm sorry, but can you give me a three-day turnaround? #Person2#: If you don't mind paying a little extra, it's absolutely no problem.",#Person2# wants to print 2000 business cards as the old ones. The turnaround could be quicker if extra money is paid.,243,21,0.0864
dialogsum,"#Person1#: It's nearly eight. If you want to catch the nine o'clock train, you'd better go now. #Person2#: Don't worry. I'll drive to the station. #Person1#: In that case, let me go with you. And you drop me off at the city center. I'll go to the open market.",#Person2# will drive to the station. #Person1#'ll go with #Person2# so that #Person2# can drop #Person1# off at the city center.,49,21,0.4286
pubmed-summarization,"behaviors to reduce the amount of bacteria in the oral cavity is regular tooth brushing with a fluoride - containing dentifrice . conditions that compromise good oral hygiene behaviors and oral health are also positively associated with caries risk . these include certain illnesses , physical and mental disabilities , and the presence of existing restorations or oral appliances . fermentable carbohydrate consumption fuels acid formation and demineralization and is associated with caries , particularly in the absence of fluoride . long - term regular doses of medications containing glucose , fructose , or sucrose may also contribute to caries risk . medical conditions such as sjgren 's syndrome , pharmacological agents with xerostomic side effects , and therapeutic radiation to the head and neck lower salivary flow rate to pathological levels and dramatically elevate a patient 's risk of caries . some studies indicate that low buffering capacity , low salivary immunoglobulin a , and low salivary calcium and phosphate may also be linked to increased caries . the inability to maintain good oral hygiene and xerostomia are risk factors of special significance among the elderly , and gingival recession uniquely increases the risk of root caries in elderly populations by exposing previously protected root surfaces to cariogenesis . low indices of socioeconomic status have been associated with elevation in caries and are also associated with reduced access to care , reduced oral health aspirations , low self - efficacy , and health behaviors that may enhance caries risk . older age is positively associated with the prevalence of root caries . over half evidence also suggests that adults who have lived in fluoridated areas throughout most of their lives , including the time of tooth formation , have a lower prevalence of root caries . there appear to be a wide variety of risk indicators and risk factors implicated in root caries . these factors include not only oral factors , but also medical , behavioral , and social factors . it is likely that numerous microbial , genetic , immunological , behavioral , and environmental contributors to risk are at play in determining the occurrence and severity of clinical disease . prevention and treatment can be achieved by identifying and arresting or reversing the disease at an","root caries is one of the most significant dental problems among older adults today . many studies have demonstrated that older adults are at greater risk for developing root caries . here we examine what risk factors older adults are prone to and explain how they contribute to higher rates of oral disease , in particular root caries . the elderly are at risk for root caries due to dentures , lack of dexterity , a shift from complex to simple sugars , and poor oral hygiene . decreased salivary flow and its manifestations with other social / behavioral and medical factors may provide a more comprehensive explanation to a higher frequency of root caries in older adults .",380,119,0.3132
dialogsum,"#Person1#: Sherry, how are you doing with your thesis? #Person2#: Oh my thesis. That's something I definitely don't want to talk about right now. I finished my first draft some time ago. But my supervisor said I should do more research if I want to achieve the quality that he expects of me.","Sherry has finished the first draft, but it doesn't meet the supervisor's expectations.",53,13,0.2453
pubmed-summarization,"for each a - scan . in each case , this boundary pixel was assigned as belonging to the layer below the boundary ; hence pixels along the red line in are counted not as part of the rnfl , but as part of the retinal ganglion cell layer . three structures are delineated : the ilm ( green ) , posterior border of the rnfl ( red ) , and the posterior border of the rpe ( yellow ) . since overall tissue reflectance varies between scans and between individuals , due to factors including differences in the exact focal plane and the quality of preretinal optics , normalization is required to better represent alterations of the tissues ' inherent optical properties rather than the influence of these imaging artefacts . five methods for normalizing the reflectance intensity values were considered : ( 1 ) the mean intensity of pixels within the rnfl divided by the mean intensity of pixels within the posterior vitreous ( i.e. , above the ilm ) , ( 2 ) the mean intensity of pixels within the rnfl divided by the mean intensity of pixels coinciding with the delineated posterior border of the rpe ( the yellow line on . 1 ) , ( 3 ) the mean intensity of pixels within the rnfl divided by the mean intensity of a 5-pixel wide band immediately above the delineated posterior border of the rpe ( designed to be entirely within the high reflectance region of rpe visible on . 1 ) , ( 4 ) the mean intensity of pixels within the rnfl divided by the mean intensity of an 11-pixel wide band centered on the delineated posterior border of the rpe ( designed to be similar to the method used by dwelle et al . ) , and ( 5 ) the mean intensity of pixels within the rnfl divided by the mean intensity of sub - rnfl tissue , extending from one pixel below the posterior border of the rnfl to the posterior border of the rpe ( i.e. , between the red and yellow lines in . 1 ; chosen under the assumption that using a larger portion of the cross - sectional b - scan image should provide increased stability and","purposewe determined whether longitudinal changes in retinal nerve fiber layer ( rnfl ) reflectance provide useful prognostic information about longitudinal changes in function in glaucoma.methodsthe reflectance intensity of each pixel within spectral - domain optical coherence tomography ( sd - oct ) circle scans was extracted by custom software . a repeatability cohort comprising 53 eyes of 27 participants ( average visual field mean deviation [ md ] 1.65 db ) was tested five times within a few weeks . to minimize test retest variability in their data , a reflectance intensity ratio was defined as the mean reflectance intensity of pixels within the rnfl divided by the mean between the rnfl and rpe . this was measured in a separate longitudinal cohort comprising 310 eyes of 205",380,128,0.3368
pubmed-summarization,"pancreatic heterotopia is defined as the presence , outside its usual location , of pancreatic tissue which lacks anatomical and vascular continuity with the pancreas proper ( 1 ) . the heterotopic pancreas ( hp ) is a relatively uncommon congenital anomaly , with an incidence between 0.55% and 13.7% in autopsy series and mean frequency between 1 and 2% . hp has been found in all age groups , predominantly in the sixth decade of life ( 2 ) . the usual locations of hp are in the stomach in 25 - 38% cases , the duodenum in 17 - 36% and the jejunum in 15 - 22% of cases . it is usually silent but it may become clinically evident when complicated by inflammation , bleeding , obstruction or malignant transformation ( 3 ) . symptomatic patients require surgical exploration in order to obtain a definitive diagnosis and to exclude malignancy . a 12 years old male child presented with severe abdominal pain and intermittent vomiting , not relieved with medications . usg showed telescopy of gut loop along with its mesentry into other infraumblical region at the level of anterior superior iliac spine suggestive of ileoileal intesusception . an ileal polyp was found to be the cause of intussusceptions which was removed along with small segment of adjacent bowel and sent for histopathological examination . surgical specimen of resected ileal polyp with adjacent bowel loop ( 1a ) cut surface of which was pale yellow ( 1b ) . histological examination revealed presence of pancreatic tissue in muscularis propria of ileum ( 1c ) ( h&e , x40 ) with overlying mucosa showing congestion and metaplasia ( 1d ) ( h&e , x40 ) on gross examination , the polyp was brown , oval sessile mass with a broad base measuring 63.52 cm ( . the histological examination revealed the presence of pancreatic tissue in the muscularis propria of ileum ( . 1c ) made up of pancreatic acini and dialated ducts interspersed by smooth muscle bundles ( . photomicrograph showing pancreatic acini and ducts ( h&e , x100 ) the patient had an uneventful recovery and remains asymptomatic postoperatively . as stated by hunt and bonesteel ( 5 ) the first case of heterotopic pancreas was","heterotopic , aberrant or ectopic pancreas is defined as the presence of pancreatic tissue in topographic anomaly , with no anatomical , neural or vascular connection to the normal pancreas . it is a rare condition found mainly in stomach , duodenum and jejunum . ileal heterotopic pancreas is an uncommon condition and has been rarely reported in children so far . hereby we report a case of heterotopic pancreas presenting as ileal poyp leading to ileoileal intussusception in a 12 year child .",380,84,0.2211
scientific_lay_summarisation-elife-norm,"normally quiescent pFL. We bilaterally transfected the preBötC with the Gi/o-coupled allatostatin receptors (AlstR), which when activated by allatostatin (Alst) silences transfected preBötC neurons (Tan et al. , 2008). In the same rats, we bilaterally transfected the pFL with the Gq-coupled HM3D DREADD receptor (HM3DR) that when activated by clozapine-N-oxide (CNO) depolarizes (Armbruster et al. , 2007) transfected pFL neurons. We slowed respiration in a controlled manner by titrating the dose of Alst applied to the AlstR-transfected preBötC, allowing us to examine the dynamics of this presumptive coupled oscillator system as we shifted the balance of activity from the preBötC to the pFL. Depressing preBötC activity resulted in quantal slowing of breathing, similar to slowing of breathing following opiate depression of preBötC activity in vitro and in juvenile rats (Mellen et al. , 2003; Janczewski and Feldman, 2006). As preBötC activity waned, burstlets appeared on inspiratory muscle electromyograms (EMGs) and in airflow, consistent with our postulate that burstlets, not bursts, in the preBötC are rhythmogenic (Kam et al. , 2013). In complementary experiments, we applied CNO to the HM3DR transfected pFL to activate this normally quiescent oscillator. We confirmed that pFL activation initiates active expiration (Pagliardini et al. , 2011; Huckstepp et al. , 2015). By combining these protocols, i. e. , silencing the preBötC while simultaneously driving the pFL, we removed some confounding factors from these initial experiments. Importantly, we found that active expiration could not be induced when preBötC inspiratory driven motor activity was suppressed and chemosensory drive was absent, indicating that in adult rats active expiration is driven by the pFL but requires an additional source of network excitation such as ongoing preBötC activity or chemosensory drive. The organization of this coupled oscillator system may have implications for other neural networks that contain multiple central pattern generators. We made two pairs of viral injections in each adult rat, i. e. , bilateral injections into the preBötC (1A, B) and into the pFL (1C, D). In histological sections the preBötC is defined as the neurokinin-1 receptor (NK1R) dense area ventral to the semi-compact nucleus ambiguous (1A, B) and the pFL is defined as the area ventral to the lateral edge of the facial nucleus, juxtaposed to the spinal trigeminal tract (1C, D) (Huckstepp et al. , 2015). In","Mammals breathe air into and out of their lungs to absorb oxygen into the body and to remove carbon dioxide. The rhythm of breathing is most likely controlled by two groups of neurons in a part of the brain called the brain stem. One group called the preBötzinger Complex drives breathing in (inspiration), and normally, breathing out (expiration) occurs when the muscles responsible for inspiration relax. The other group of neurons – known as the lateral parafacial region – controls extra muscles that allow us to increase our breathing when we need to, such as during exercise. Huckstepp et al. set out to determine how these two groups of neurons interact with one another in anesthetized rats to produce a reliable and efficient pattern of breathing. The experiments",380,128,0.3368
dialogsum,"#Person1#: Excuse me. Do you have a minute? I'd like to tell you about the Bucky Card. #Person2#: Well. . . alright. I guess I have a minute. #Person1#: Do you know about the Bucky Card? #Person2#: I've heard about it, but I don't really know about it. #Person1#: The Bucky Card is a great way for you to save money while you have a good time here at school. It gives you discounts on all kinds of things. Movies, pizza, clothing, school supplies. #Person2#: What about beer? #Person1#: The Card doesn't actually give you discounts on beer. But it will give you discounts on certain club cover charges. So if you want to see your favorite band at Amy's or Cosmo's Club, you get a discount on the entrance fee. #Person2#: That's pretty cool. How much of a discount? #Person1#: Usually it's two dollars off the cover price. #Person2#: And all these other things, pizza and movies for instance--how much of a discount do I get on that stuff? #Person1#: This pamphlet shows you what restaurants and movie theaters have discounts. And twice every semester we will send you a new issue of the pamphlet. The Bucky Card has just started. Every couple months we have new businesses joining our program. It's a great way for students to save money! #Person2#: Alright, alright. Let me look at that pamphlet. Hmm. Alessio's Pizza Parlor. That's cool. I go there all the time. And Cosmo's Club. And 4 - D records. Alright. How much does it cost? #Person1#: It costs only 19 dollars a year for a card. #Person2#: Whoa! That's expensive! It should be cheaper. #Person1#: But think of how much money you'll save! You can use it for a year. #Person2#: Yeah, maybe. Alright. Give me an application form.",#Person1# introduces the Bucky Card to #Person2#. #Person2# reads the pamphlet and learns about the benefits. #Person2# thinks the card is expensive at first but finally decides to apply for the card.,300,32,0.1067
dialogsum,"#Person1#: Did you have a part-time job when you were still in school? #Person2#: No, I was way too busy studying all the time. How about you? #Person1#: Yeah, I worked about twenty hours a week in a pizza restaurant. #Person2#: What was that like? #Person1#: It was always very busy there. #Person2#: What did you do? #Person1#: I stood behind the register and took pizza orders. #Person2#: Did you get any perks on the job? #Person1#: Yeah, I got to eat as much pizza as I could for free.",#Person1# has a part-time job while #Person2# is too busy to work part-time.,90,13,0.1444
pubmed-summarization,"- cell defect , as well as to examine possible correlation with patient demographic characteristics , clinical and complete blood count ( cbc ) parameters , and undergoing treatment . in this study , 113 patients with rheumatic diseases ( 94 females , 19 males ; median age : 64 years ) , who presented or were referred to our department s outpatient clinic from february 2009 to february 2013 , were evaluated . the study population included 38 patients with rheumatoid arthritis ( ra ) , 25 patients with systemic lupus erythematosus ( sle ) , 17 patients with sjgren s syndrome ( ss ) , 7 patients with systemic sclerosis ( sc ) , 12 patients with vasculitis ( vsc ) , 2 patients with dermatomyositis ( drm ) , 1 patient with ankylosing spondylitis ( asp ) , and 11 patients with mixed connective tissue disease ( mctd ) . at the time of the evaluation , 86 patients underwent immunosuppressive ( is ) and/or immunomodulary treatment ( i m ) , and 27 received no treatment ( n ) . anemia ( hemoglobin<12.0 g / dl ) was present in 43 ( 38.1% ) patients , neutropenia ( neutrophils < 2.010/lt ) in 14 ( 12.7% ) , lymphopenia ( lymphocytes<1.010/lt ) in 21 ( 18.9% ) , and thrombocytopenia ( platelets<15010/lt ) in 13 ( 11.6% ) patients . cytopenias were further categorized in grades according to their severity ( grade 0 : absence of cytopenia , grade 1 : mild cytopenia , grade 2 : moderate cytopenia , grade 3 : severe cytopenia , grade 4 : life - threatening cytopenia , grade 5 : death related to cytopenia ) ( table 2 ) . the national cancer institute ( nci ) , common terminology criteria for adverse events version 3.0 ( ctcaev3.0 ) ( publish date : august 9 , 2006 ) was used for this purpose . one hundred and twenty - one ( 121 ) healthy blood donors of similar age and gender and 10 patients with pnh were also studied and served as control groups . the cd55- and cd59-deficient red - cell populations were detected using a commercial kit ( diamed - id micro typing system - pnh test","backgroundcomplement has the potential to provoke severe impairment to host tissues , as shown in autoimmune diseases where complement activation has been associated with diminished cd55 and/or cd59 expression on peripheral blood cell membranes . the aim of this study was to evaluate the presence of cd55- and/or cd59-deficient erythrocytic populations in patients with different rheumatic diseases and to investigate possible correlations with clinical or laboratory parameters.material/methodscd55 and cd59 expression was evaluated in erythrocytes of 113 patients with rheumatic diseases , 121 normal individuals , and 10 patients with paroxysmal nocturnal hemoglobinuria ( pnh ) using the sephacryl gel microtyping system . ham and sucrose tests were also performed.resultsinterestingly , the majority of patients ( 104/113 , 92% ) demonstrated cd55- and/or cd59-deficient erythrocytes : 47 ( 41.6%",380,128,0.3368
pubmed-summarization,"be due to large tumor causing the pressure effect , tumor necrosis and intralesional hemorrhage . malignant potential of adrenal myelolipoma has not been reported . in our study , the child presented with pain abdomen and , on investigation diagnosis was confirmed . the lesion is itself hormonally inactive but may be associated with metabolically active adrenal lesion like cushing syndrome , conn 's syndrome , congenital adrenal hyperplasia etc . myelolipoma can be regarded as an exception to the mandatory metabolic work - up of a newly discovered adrenal mass . large myelolipoma usually associated with hematological disorders like hereditary spherocytosis , thalassemia intermedia , thalassemia major , sickle cell anemia and usually bilateral if we get a case of large or bilateral adrenal myelolipoma we have to investigate for chronic hematological disorders . before removal the of tumor , it may be necessary for bone marrow transplantation to avoid aggravation of hemolytic anemia . most accepted theory regarding etiologies are that it arises in response to infection , stress or necrosis causing metaplasia of reticuloendothelial cells of the capillaries of adrenal gland . focal fat density , peripheral calcification and hemorrhage within the tumor can be better identified with cect scan . myelolipoma contains adipocytes with hematopoietic elements , consisting of myeloid and erthyroid precursors , as well as , megakaryocytes . these hematopoietic elements are scattered in the adrenal tissue and separated by sheets and large clusters of mature adipocytes admixed with hemorrhagic foci . though open surgery is the classical method , laparoscopic adrenalectomy has now become the standard of care for the treatment of functioning and non - functioning adrenal tumors , introduced by gagner in 1992 . small asymptomatic myelolipomas can be treated conservatively but the symptomatic one should be treated with surgical excision and/or adrenalectomy .","myelolipoma is a rare benign tumor of adrenal gland and rarer in children . myelolipoma contains adipose tissue and myeloid precursor producing white blood cells ( wbc ) , red blood cells ( rbc ) and megakaryocytes . asymptomatic tumor does not require treatment whereas symptomatic tumor needs operation . we are reporting a rare adrenal myelolipoma in a child with review of literature .",304,65,0.2138
dialogsum,"#Person1#: Excuse me, but I'm a bit lost here. Where does this street lead to? #Person2#: The Queen Street, I guess. #Person1#: So is it the right way to the City Hall? #Person2#: I'm afraid you're going in the opposite direction.",#Person2# says #Person1# is in the opposite direction to the City Hall.,41,12,0.2927
dialogsum,#Person1#: Will you be voting this year? #Person2#: Of course! Will you? #Person1#: This is going to be my first time voting. #Person2#: Are you serious? #Person1#: I'm not sure what I'm doing. #Person2#: Voting is easy. #Person1#: I don't know anything about the bills or laws they're trying to pass. #Person2#: The ballot gives you all that information. #Person1#: Nobody told me that before. #Person2#: You have nothing to worry about. #Person1#: I'm so glad you told me that. #Person2#: Good luck on your first election.,#Person1# is not sure how to vote. #Person2# tells #Person1# to get the information from the ballot.,87,17,0.1954
dialogsum,"#Person1#: Have you ever been in an earthquake? #Person2#: Yes, I experienced one when I was in Tokyo once. The tremors only lasted a few seconds though and then it was over. #Person1#: Do you know where it measured on the Richter scale? #Person2#: I don't remember, but it wasn't very serious. Have you ever been in an earthquake? #Person1#: No, but I was in quite a few tornados when I was younger. #Person2#: Where are you from? #Person1#: I'm from the plains of the Midwest. It's a prime location for tornadoes. #Person2#: Did your house ever get damaged from the winds? #Person1#: Most of the time we were lucky, but once a tree from our front yard was ripped out by its roots and ended up in our living room. #Person2#: Wow, that must have really been scary. #Person1#: Actually, some of my fon best memories of my childhood were of spending time with my family in the basement waiting for the tornados to pass. #Person2#: Have you ever experiences a flood? #Person1#: No, but my father's car was destroyed in a flood once. It actually happened the day after he bought the car! #Person2#: That sure didn't last long!",#Person2# experienced an earthquake in Tokyo. #Person1# hasn't been in an earthquake but was in quite a few tornados when #Person1# was younger and #Person1#'s father's car was destroyed in a flood.,201,32,0.1592
dialogsum,"#Person1#: Do you want to go for a picinc with me tomorrow? #Person2#: I'd like to. How about asking Jenny to go with us? #Person1#: Oh, no. She is busy with her dancing class. You know, there is a very big performance in just a week. #Person2#: Yes, you're right. It is really not good for her to learn dancing. Her leg hasn't completely recovered from that accident. #Person1#: But she doesn't think so. She is crazy about dancing. Will you take your camera with you tomorrow? #Person2#: I want to, but I lent it to Tom yesterday. Do you have one? #Person1#: No, but I know Mary has got one. Let's go and ask her if she'd like to join us. #Person2#: OK.","#Person1# invites #Person2# to a picnic. #Person2# wants to invite Jenny but #Person1# says she's busy with her dancing class. #Person2#'s camera isn't available, so they'll ask Mary who's got one to join them.",124,34,0.2742
dialogsum,"#Person1#: Jane, your new play is going on next week, are you anxious? #Person2#: Well, I'm very pleased to have Malcolm Rush as a director. He doesn't care whether you're tired or not, he'll just continue pushing until every scene is simply perfect. You don't just learn the part. You live it, which takes away any fears you might have of not being able to persuade an audience, you're real. That's very important. #Person1#: Malcolm does have a reputation of being quite the ruler, no one dares speak their opinions here. #Person2#: Well, once you've proved yourself, it's all about being open to changes.",#Person1# asks #Person2# about the new play. #Person2# tells #Person1# about Malcolm Rush who is quite strict.,104,17,0.1635
pubmed-summarization,") : the sham - operated ( so group ) and the severe acute pancreatitis ( sap group ) and then randomly subdivided into 1-h , 2-h , 3-h , and 4-h subgroups , with 10 rats in each subgroup . the rats in the 1-h , 2-h , 3-h , and 4-h subgroups of the sap group , a total of 40 rats , were subdivided into a sap - induced ards group ( ards group ) and a sap without ards group ( non - ards group ) according to the diagnosis of ards for lung tissue , including the presence of dad , qualitatively assessed ( yes or no ) after the operation . the other 20 rats were regarded as the baseline and euthanized without any operation in initial experiments . intra - peritoneal injection of 1% sodium pentobarbital ( 50 mg / kg ; sigma , st . louis , mo , usa ) was used for abdominal cavity anesthesia to all rats of the 1-h , 2-h , 3-h , 4-h subgroups . animal care was in accordance with the national institutes of health guide for the care and use of laboratory animals , and was approved by the animal use and protection committee of soochow university . the abdominal surgery of the so group ( n=40 ) consisted of opening the abdomen , flipping the pancreas , returning them to their original position , then closing the abdominal cavity with 2 layers of sutures . louis , mo , usa ) was administered into the common biliopancreatic duct of the sap group ( n=40 ) by retrograde injection . we identified the duodenal papilla inside the duodenum duct wall , and then used a no . a segmental epidural catheter was inserted into the duodenum cavity through the hole , and inserted retrogradely into the biliary - pancreatic duct through the papilla . this was followed by retrograde transfusion of 4.5% sodium taurocholate solution ( 4.5% ; 0.1 ml/100 g ) by a microinjection pump at 0.1 ml / min . all rats of the 2 groups were injected with normal saline ( 20 ml / kg ) through the vena caudalis to compensate for loss of fluid during surgery . the rats","backgroundthe complexity of multiple - item criteria in acute respiratory distress syndrome ( ards ) often causes inconvenience for physicians in the management of patients with severe acute pancreatitis ( sap ) . we evaluated whether serum sp - a levels in the presence of diffuse alveolar damage ( dad ) can be qualitatively assessed for diagnosis of sap - induced ards.material/methodseighty rats were randomly divided into 2 groups ( n=40 each ) the sham - operated ( so ) group and the sap group and then randomly subdivided into 4 subgroups in a time - course manner . furthermore , rats in the sap group were subdivided into the sap induced - ards group ( ards group ) and the sap without ards group ( non -",380,128,0.3368
pubmed-summarization,", nausea and vomiting , particularly after a fatty meal . abdominal x - ray and ct scanning ( the somatom sensation 16 ; siemens ag , munich , germany ) revealed sporadic air - fluid levels and intestinal wall thickness ( . 2 ) . anti - infective treatment ( cefoperazone and sulbactam , both 1.5 g intravenous infection , q.12.h ; pfizer , inc . , new york , ny , usa ) was administered , but was ineffective . multiple rashes on the lower extremities appeared on the fourth day , and laboratory examinations showed a rheumatoid factor of 20.4 iu / ml ( increased ) , antinuclear antibody 1:320 ( increased ) ; esr 26.00 mm / h ( increased ) ; anti - ribonucleoprotein antibody + + + ( strong ) , anti - smith antibody + + + ( strong ) , anti sjogren 's syndrome a antibody + + + ( strong ) and anti - sjogren 's syndrome b antibody + ( weak ) . antibodies against double stranded - dna was not detected ; complement ( c3 ) , 0.39 g / l ( decreased ) ; crp , 7.0 mg / l ( normal ) ; wbc , 2.510/l ( decreased ) and hgb , 89 g / l ( decreased ) . furthermore , the patient had experienced hair loss and multiple red rashes in response to strong sunlight the previous year . sle and lupus - related ipso were then diagnosed according to american college of rheumatology criteria ( 1997 ) ( 8) , and the systemic lupus erythematosus disease activity index ( sledai ) score was 10 ( 8) . the patient was treated with 2 mg / kg / day methylprednisolone ( pfizer , inc . ) and her general condition improved after 2 days . however , the patient had sudden onset of fever ( 40.4c ) and dyspnea , oxygen saturation ( sao2 ) was 87% , and arterial blood gas analysis revealed a ph of 7.409 , pco2 , 33.6 mmhg and po2 , 83.9 mmhg . further laboratory examination showed : glutamic pyruvic transaminase , 436 u / l ( increased ) ; glutamic oxaloacetic transaminase , 740 u / l (","intestinal pseudo - obstruction ( ipso ) and acute lupus pneumonitis ( alp ) are uncommon severe complications of systemic lupus erythematosus ( sle ) . the present study reports the case of a 26-year - old female who presented with abdominal pain , nausea and vomiting as initial symptoms . computed tomography ( ct ) scanning revealed the jejunal wall was thickened and streaky , mimicking the presentation of intestinal obstruction . following emergency surgery , the patient 's general condition was aggravated , with evident limb erythematous rashes . a series of laboratory examinations revealed sle , and combined with patient 's medical history ipso was diagnosed , with a disease activity index score of 10 . during the therapeutic period , high fever , dyspnea",380,128,0.3368
dialogsum,"#Person1#: Wei! This is a first time you didn't bargain! #Person2#: Bargain? I'd feel way too guilty. #Person1#: But you could have saved money. #Person2#: From a sweet ma?! It's not worth it. Plus, I'd happily pay more for these things I bought! #Person1#: F. Y. I . , there is a flea market nearby, but maybe you're done... #Person2#: Ha! I'm just warming up! Please take me there now!",Wei bought something without bargaining and asks #Person1# to take her to a flea market.,70,15,0.2143
scientific_lay_summarisation-elife-norm,"Hypoxia is a common challenge faced by bacteria during associations with hosts due in part to the formation of densely packed communities (biofilms). cbb3-type cytochrome c oxidases, which catalyze the terminal step in respiration and have a high affinity for oxygen, have been linked to bacterial pathogenesis. The pseudomonads are unusual in that they often contain multiple full and partial (i. e. ‘orphan’) operons for cbb3-type oxidases and oxidase subunits. Here, we describe a unique role for the orphan catalytic subunit CcoN4 in colony biofilm development and respiration in the opportunistic pathogen Pseudomonas aeruginosa PA14. We also show that CcoN4 contributes to the reduction of phenazines, antibiotics that support redox balancing for cells in biofilms, and to virulence in a Caenorhabditis elegans model of infection. These results highlight the relevance of the colony biofilm model to pathogenicity and underscore the potential of cbb3-type oxidases as therapeutic targets. Among the oxidants available for biological reduction, molecular oxygen (O2) provides the highest free energy yield. Since the accumulation of O2 in the atmosphere between ~2. 4 and 0. 54 billion years ago (Kirschvink and Kopp, 2008; Dietrich et al. , 2006b), organisms that can use it for growth and survival, and tolerate its harmful byproducts, have evolved to exploit this energy and increased in complexity (Knoll and Sperling, 2014; Falkowski, 2006). At small scales and in crowded environments, rapid consumption of O2 leads to competition for this resource and has promoted diversification of bacterial and archaeal mechanisms for O2 reduction that has not occurred in eukaryotes (Brochier-Armanet et al. , 2009). The various enzymes that allow bacteria to respire O2 exhibit a range of affinities and proton-pumping efficiencies and likely contribute to competitive success in hypoxic niches (Morris and Schmidt, 2013). Such environments include the tissues of animal and plant hosts that are colonized by bacteria of high agricultural (Preisig et al. , 1996) and clinical (Way et al. , 1999; Weingarten et al. , 2008) significance. The opportunistic pathogen Pseudomonas aeruginosa, a colonizer of both plant and animal hosts (Rahme et al. , 1995), has a branched respiratory chain with the potential to reduce O2 to water using five canonical terminal oxidase complexes: two quinol oxidases (bo3 (Cyo) and a bd-type cyanide-insensitive oxidase (CIO) ) and three cytochrome c oxidases (aa3","Bacteria often form communities called biofilms to make them stronger and more ‘invincible’. However, when these communities become too crowded, oxygen levels can drop, which makes it harder for them to survive. Some types of bacteria, such as Pseudomonas aeruginosa, have found different ways to cope with lower levels of oxygen. For example, they produce enzymes that use oxygen more efficiently or are better at scavenging low concentrations of oxygen. When organisms – including bacteria – produce energy, they break down nutrients into small molecules to extract electrons. These electrons are then transported along their membrane until they reach their final destination – an oxygen molecule. Studies of P. aeruginosa grown in the laboratory have shown that it uses several types of enzymes called terminal oxidases to complete",380,128,0.3368
dialogsum,"#Person1#: Hello, Kevin. I hate to do this, but I have to cancel our appointment. #Person2#: Oh, no! Why? I was looking forward to seeing you at my new place. #Person1#: Yeah, I really wanted to come, too. But something unexpected in Shanghai have come up. I have to fly out for a few days, but I'll be back soon. #Person2#: No problem. Call me when you get back. #Person1#: I should have some free time next week. Say, next Wednesday evening? #Person2#: That's good for me, but do you think you'll be back by then? I'd really like to see you. #Person1#: Yeah, I'm expecting to come back on Tuesday. #Person2#: Great! That's settled then. #Person1#: OK.",#Person1# tells Kevin #Person1# has to cancel their appointment due to something unexpected. Then they make an appointment on Wednesday evening.,118,21,0.178
pubmed-summarization,"of glua2-lacking channels could still be blocked by polyamines during single unitary epscs , and repetitive high - frequency stimulation is required to relieve the block ( rozov and burnashev , 1999 ) . hence , to get an accurate readout of the phtx effect on ampar - mediated currents the influence of endogenous polyamines should first be minimized . to resolve the issue of ca - permeable ampa channels in ca1 pyramidal cells of wild - type ( wt ) , we took recourse to gene - targeted mice lacking either glua2 ( shimshek et al . , 2006 ) or glua1 ( zamanillo et al . , 1999 ) or expressing glua1 in a q / r site - edited version ( sanchis - segura et al . , 2006 ) . this allowed us to analyze the artificial situations of ca1 cell synapses having ampa receptors of maximal ( glua2 mutant mice ) or minimal ( glua1 and glua1(r ) mutants ) sensitivity to polyamines . the presence of ca - permeable ampa channels in wt should then be revealed by increased sensitivity to phtx-433 relative to ampa channels in glua1 and glua1(r ) mouse mutants . no such increase in phtx-433 sensitivity should be observed if wt ca1 pyramidal cell synapses indeed lack ca - permeable ampa channels , as posited by a prevalent view ( adesnik and nicoll , 2007 ) . our data clearly demonstrate that in wt ca1 synapses , 810% of the ampa channels are ca - permeable . transverse hippocampal 250 m slices were prepared from the brains of 4256 day - old wt , glua1 ( zamanillo et al . , 1999 ) , glua1(r ) ( sanchis - segura et al . , 2006 ) and glua2 mice ( shimshek et al . , 2006 ) , killed by decapitation . the slicing chamber contained an oxygenated ice - cold solution [ modified from ( dugue et al . , 2005 ) ] composed of ( in mm ) : k - gluconate , 140 ; n-(2-hydroxyethyl ) piperazine - n-ethanesulfonic acid ( hepes ) , 10 ; na - gluconate , 15 ; ethylene glycol - bis ( 2-aminoethyl)-n , n , n,n-tetraacetic acid ( egta ) ,","the glua2 subunit in heteromeric alpha - amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( ampa ) receptor channels restricts ca2 + permeability and block by polyamines , rendering linear the current - voltage relationship of these glutamate - gated cation channels . although glua2-lacking synaptic ampa receptors occur in gaba - ergic inhibitory neurons , hippocampal ca1 pyramidal cell synapses are widely held to feature only glua2 containing ampa receptors . a controversy has arisen from reports of glua2-lacking ampa receptors at hippocampal ca3-to - ca1 cell synapses and a study contesting these findings . here we sought independent evidence for the presence of glua2-lacking ampa receptors in ca1 pyramidal cell synapses by probing the sensitivity of their gated cation channels in wild - type ( wt ) mice and gene -",380,128,0.3368
dialogsum,"#Person1#: Good morning, I'm Daniel. I'm applying for the positon of manager. #Person2#: Yes. Sit down, please. How did you learn about our company? #Person1#: I got to know your company through such famous brands as LUX, LIPTON and WALLS. After making a customer survey, I was glad to find out how your products are appreciated by millions of Chinese. #Person2#: Why would you like to work with us? #Person1#: It's the job I'm interested in. And your company is the best-known. Although I don't have much experience as a manager, the job description you sent to me was very interesting. It's a job I'Ve been dreaming of and I feel suited to fill it. #Person2#: Oh, really? Would you transfer to another company if it is not what you expected? #Person1#: I don't think so. As the saying goes, ' A great oak needs deep roots. ' I'm really interested in this job. #Person2#: That's fine. Thanks for coming to see us. I hope to be able to let you know about the job within the week.",Daniel wants to apply for the position of manager. #Person2# asks him some questions. He tells #Person2# he chooses the company because he's interested in the job and the company is the best-known.,178,33,0.1854
dialogsum,"#Person1#: You know I just finished some very interesting research for the newspaper about things people do in their spare time. #Person2#: Really? What did you learn? #Person1#: Well, I talked to 20 people and 19 of them watch TV. #Person2#: That's interesting. I never watch it, do you? #Person1#: Not much. Anyway, about half of them, 9 people, play some kind of sport. #Person2#: I'm not surprised. People are getting more exercise these days. #Person1#: Yes, a few of them go to movies. #Person2#: Mm, I do, too. #Person1#: But here is the most interesting result: only one of them reads. #Person2#: That's terrible.",#Person1# finished some research about things people do in their spare time. #Person1# tells #Person2# interesting findings.,105,17,0.1619
scientific_lay_summarisation-elife-norm,"LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon’s disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression improves tissue function in models of aging. We show here that human LAMP1 and LAMP2 bind cholesterol in a manner that buries the cholesterol 3β-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lysosomes. Quantitation of cellular LAMP2 and NPC1 protein levels suggest that LAMP proteins represent a significant cholesterol binding site at the lysosome limiting membrane, and may signal cholesterol availability. Functional rescue experiments show that the ability of human LAMP2 to facilitate cholesterol export from lysosomes relies on its ability to bind cholesterol directly. Eukaryotic lysosomes are acidic, membrane-bound organelles that contain proteases, lipases and nucleases and degrade cellular components to regenerate catabolic precursors for cellular use (Xu and Ren, 2015; Schwake et al. , 2013; Saftig and Klumperman, 2009). Lysosomes are crucial for the degradation of substrates from the cytoplasm, as well as membrane bound compartments derived from the secretory, endocytic, autophagic and phagocytic pathways. The limiting membrane of lysosomes is lined with so-called lysosomal membrane glycoproteins (LAMPs) that are comprised of a short cytoplasmic domain, a single transmembrane span, and a highly, N- and O-glycosylated lumenal domain (Wilke et al. , 2012; Kundra and Kornfeld, 1999; Granger et al. , 1990). Because of their abundance and glycan content, LAMPs have been proposed to serve as a protective barrier to block hydrolase access to the limiting phospholipid bilayer. LAMP1 and LAMP2 are 37% identical and may overlap in function, but knockout of LAMP1 in mouse has a much milder phenotype than depletion of LAMP2 (Tanaka et al. , 2000): LAMP2-deficient mice have very short lifespans, and show massive accumulation of autophagic structures in most tissues. Indeed, LAMPs are required for fusion of lysosomes with phagosomes (Huynh et al. , 2007) and LAMP2 has also been proposed to serve as a receptor for chaperone-mediated autophagy (Cuervo and Dice, 1996,2000; Bandyopadhyay et al. , 2008). Previous work has implicated LAMP2 in cholesterol export from lysosomes, as LAMP-deficient cells show cholesterol accumulation that can be rescued by LAMP2 expression (Eskelinen et al. ,","Living cells contain many membrane-bound compartments surrounded by a gel-like substance called the cytoplasm. Lysosomes are compartments found in most animal cells, which contain enzymes that can break down virtually all kinds of biological molecules. Cell biologists around the world use two proteins called LAMP1 and LAMP2 to mark lysosomes to study them. The loss of LAMP2 causes a condition called Danon disease that is characterized by thickening of the heart muscle. However, relatively little is known about what these proteins actually do. Previous studies had hinted that these proteins might bind to the fatty molecule, cholesterol. Li and Pfeffer set out to test this directly and showed that LAMP1 and LAMP2 proteins do indeed bind to cholesterol. The two LAMP proteins also interact with another two proteins,",380,128,0.3368
dialogsum,"#Person1#: Oh. Hi there. A beauty, isn't she? #Person2#: Well ... #Person1#: Do you want to take her a test ride? #Person2#: Well ... Um. How old is it? #Person1#: Well, it's only three years old? #Person2#: And what's the mileage? #Person1#: Uh, let me check. Oh yes. 75,000 miles. #Person2#: 75,000 miles? That's quite a bit for a car that's only three years old. #Person1#: Well, once you're in the driver's seat, you'll fall in love with her. Get in. #Person2#: Ugh ... Uh, I can't seem to get the door open. [Ah, it's okay.] It could be broken. #Person1#: Ah, just give her a little tap. Ugh. Now she's opened. #Person2#: Great. A door I have to beat up to open. #Person1#: Hey. Get in and start her up. [Woman tries to start the car ...] [Um] Well, it's probably the battery. I know she has enough gas in her, and I had our mechanic check her out just yesterday. Try it again. #Person2#: Uh. It sounds a little rough to me. [Well ...] How much is this minivan anyway? #Person1#: Oh. It's a real bargain today and tomorrow only at $15,775, plus you get the extended warranty covering defects, wear, and tear beyond the normal maintenance on the vehicle for an extra $500 for the next 30,000 miles. [Oh ...] with a few minor exclusions. #Person2#: Like ...? #Person1#: Well, I mean, it covers everything except for the battery, and light bulbs, and brake drums, exhaust system, trim and moldings, upholstery and carpet, paint, tires ... Well, a short list, you know. #Person2#: Uh. Well, almost $16,000 is a little out of my price range, plus the seats covers are torn a little. #Person1#: Well, hey, I might be able to talk the manager into lowering the price another two hundred dollars, but that's about all. #Person2#: No thanks. I think I'll just keep looking.","#Person1# invites #Person2# to have a test ride on the car and shows the mileage of the car, how to open the door and how to start the car. #Person2# asks #Person1# about the price and the maintenance service included and then #Person2# thinks the price is out of the price range.",318,52,0.1635
dialogsum,"#Person1#: Mary, what's your plan for this Saturday? #Person2#: I want to stay at home and watch TV. What's your plan? #Person1#: I'll go to Bird Park. As a matter of fact, I think you should go there, too. #Person2#: Why? #Person1#: Haven't you read in the newspaper about the arts festival that will take place there this weekend? #Person2#: No, I didn't read the newspaper today. My little brother took it away when I was about to read it. What can we do at the festival? #Person1#: We can do lots of things. We can listen to music, look at paintings by local and international painters, enjoy a meal in the park or watch a play. #Person2#: I'm not interested in music, but I do want to look at some paintings. So when is the art exhibition? #Person1#: There are 2 actually. The local painters will show their works from 10:00 AM to 4:00 PM on Saturday, and the international painters will show their works on Sunday. #Person2#: From 10:00 AM to 4:00 PM, too? #Person1#: Yes, so will you go with me? #Person2#: Sure. How can I miss such art exhibitions? And I want to take some pictures of them. #Person1#: You can use my camera then.",#Person1# is going to an arts festival this Saturday and invites Mary to go. Mary isn't interested in music but she wants to look at some paintings. #Person1# tells her about the art exhibition and they will go together.,209,39,0.1866
dialogsum,"#Person1#: Give me your hand. (takes Rose's hand) Close your eyes. Go on. (Rose closes her eyes) Step up. Now hold on to the rail. Keep your eyes closed; don't peek. #Person2#: I'm not. #Person1#: Step up onto the rail. Hold on. Keep your eyes closed. Trust me? #Person2#: I trust you. #Person1#: All right, open your eyes. (Rose opens her eyes. She stretches her arms, and Jack stands behind her, arms around her. ) #Person2#: I'm fling, Jack. (singing) Come, Josephine, in my flying machine. Up she goes, and up she goes. . .",Jack takes Rose's hands. Jack asks Rose to close her eyes and step up onto the rail. They play Titanic.,95,20,0.2105
pubmed-summarization,"health is not only related to the absence of the disease , therefore we need to conceptualize and operationalize what health is . increasingly , we have come to understand that information about functional status is needed in order to appreciate the full picture regarding the health of an individual or a population . an individual 's health fundamentally includes their capacity to carry out the full range of actions , activities and tasks required to fully engage in all areas of human life . the health state of a person can be described in terms of capacity to carry out a set of tasks or actions . in addition , the health state also includes changes in body functions and/or structures arising from a health condition . the impact of the health state on a person 's life can be understood by measuring performance of tasks and actions in the person 's real - life or actual environment . the full picture of the health experience can further be appreciated by taking into cognizance the value that people place on levels of functioning in given domains in association with a health condition . plainly , the concept of functional status is integral to health and its achievement . two individuals with identical diagnoses may have utterly different levels of functioning that determine their actual health status . without fsi , our picture of the health of an individual , or a population , is flawed and incomplete . fsi has , of course , long been collected in various ways and used clinically , especially in rehabilitative medicine ; physical , occupational and speech and language therapy ; and in nursing home and home care settings . fsi is essential for needs assessment as well as the development and monitoring of rehabilitative interventions to restore or maintain functions . it is also essential in this area of health care because the aim of therapy is to assist patients in maximizing their capacities to perform activities needed for their lives . although no one doubts that restoring functioning is restoring health ( the ultimate purpose of all forms of health care ) some clinicians , focusing exclusively on acute - care needs , do not see the need to collect","a common framework for describing functional status information ( fsi ) in health records is needed in order to make this information comparable and of value . the world health organization 's ( who 's ) international classification of functioning , disability and health ( icf ) , which has been approved by all its member states , provides this common language and framework . the biopsychosocial model of functioning and disability embodied in the icf goes beyond disease and conceptualizes functioning from the individual 's body , person , and lived experience vantage points , thereby allowing for planning interventions targeted at the individual 's body , the individual as a whole or toward the environment . this framework then permits the evaluation of both the effectiveness",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The RhoGTPases are characterized as membrane-associated molecular switches that cycle between active, GTP-bound and inactive, GDP-bound states. However, 90–95% of RhoGTPases are maintained in a soluble form by RhoGDI, which is generally viewed as a passive shuttle for inactive RhoGTPases. Our current understanding of RhoGTPase: RhoGDI dynamics has been limited by two experimental challenges: direct visualization of the RhoGTPases in vivo and reconstitution of the cycle in vitro. We developed methods to directly image vertebrate RhoGTPases in vivo or on lipid bilayers in vitro. Using these methods, we identified pools of active and inactive RhoGTPase associated with the membrane, found that RhoGDI can extract both inactive and active RhoGTPases, and found that extraction of active RhoGTPase contributes to their spatial regulation around cell wounds. These results indicate that RhoGDI directly contributes to the spatiotemporal patterning of RhoGTPases by removing active RhoGTPases from the plasma membrane. The Rho family GTPases, including Rho, Rac and Cdc42, are essential signaling proteins that mediate morphological changes in cells by directing local cytoskeletal rearrangements (Bishop and Hall, 2000; Kimura et al. , 1996). These rearrangements are generally initiated at and confined to specific subcellular regions. For example, a narrow, concentrated zone of Rho activity directs the formation of a ring of actin filaments and myosin-2 at the equatorial cortex that drives cytokinesis (Bement et al. , 2005; Yonemura et al. , 2004; Yüce et al. , 2005). Similarly, Rho, Rac and Cdc42 are activated near the leading edge of crawling cells in patterns that correspond to local cycles of protrusion, adhesion and retraction (Machacek et al. , 2009; Martin et al. , 2016). Because tight spatiotemporal regulation of the GTPases is a fundamental feature of these cellular processes, considerable effort has been invested in studying GTPase regulation. The RhoGTPases are classically characterized as cycling between membrane-associated, active states and soluble, inactive states as a result of interactions with three classes of regulatory proteins: guanine nucleotide exchange factors (GEFs), which activate GTPases by promoting exchange of GDP for GTP (Rossman et al. , 2005); GTPase activating proteins (GAPs), which inactivate GTPases by promoting GTP hydrolysis (Moon and Zheng, 2003); and guanine nucleotide dissociation inhibitors (GDIs), which solubilize GTPases to generate a large reservoir of heterodimeric GTPase: GDI complexes in the cytoplasm (Garcia-Mata et al. , 2011).","Organisms rely on many signaling molecules to control how their cells grow, divide and heal. For example, when the cell membrane is damaged, two signaling proteins, Rho and Cdc42, are recruited to wounds and activated to promote repair. Active Rho and active Cdc42 form two concentric rings at the membrane to direct the closure of the wound. Rho and Cdc42 belong to the RhoGTPase family, a group of proteins that act as molecular switches and alternate between active and inactive forms. At the level of the cell, RhoGTPases are only active in the tiny patches of the membrane where they bind. However, individual proteins hop on and off membranes in a matter of seconds, only staying bound for short periods. This mechanism is controlled by a regulatory protein",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. , 2014). Thus, medaka NR and RPE are independently growing tissues with identical topology. As a population, CMZ cells appositionally add new cells in concentric rings as shown by label incorporation with thymidine analogues (Johns, 1977; Centanin et al. , 2011). Individual stem cells labelled by genetic markers form clonal progeny in so-called Arched Continuous Stripes (ArCoS; 1B) (Centanin et al. , 2011; Centanin et al. , 2014). Medaka NR stem cells produce the full complement of neuronal cells in apico-basal clonal columns (— 2A’–B) (Centanin et al. , 2011; Centanin et al. , 2014; Lust and Wittbrodt, 2018). These differentiated retinal cells grow little in size (Johns, 1977), retain their relative position over time (Johns, 1977; Centanin et al. , 2011), and have negligible death rates (Johns and Easter, 1977; Stenkamp, 2007). Thus, the only parameter available to NR and RPE to coordinate their growth rates is the proliferation of the tissue-specific CMZ stem cells. Stem cells have long been defined by an unlimited self-renewal capacity (Watt and Hogan, 2000; Clevers and Watt, 2018). Two general strategies underlie long-term maintenance of stem cells: 1) a deterministic model where every single division produces a stem- and a progenitor daughter cell (‘invariant asymmetry’); and 2) a stochastic model where cells divide symmetrically, and the daughter cells have a probability to stay as stem cells or commit to a progenitor fate (‘neutral drift’) (Watt and Hogan, 2000; Clevers and Watt, 2018). One tenet of this model is neutral competition: Stem cells randomly displace one another, resulting in the ‘loss’ of lineages where all progeny commit to a progenitor fate until the entire niche is occupied by a single clone (Colom and Jones, 2016; Clevers and Watt, 2018). Strikingly, the medaka retina diverges from the neutral drift model. The CMZ maintains a polyclonal stem cell population for both the NR and the RPE, and in particular NR stem cells undergo asymmetric self-renewing divisions throughout the life of the animal (Centanin et al. , 2011; Centanin et al. , 2014). It remains unclear whether stem cell proliferation in the CMZ follows a purely deterministic model, or whether it follows a strategy in-between invariant asymmetry and neutral drift. In this work we combine in vivo and in silico clonal analysis in the NR and","By the time babies reach adulthood, they have grown many times larger than they were at birth. This development is driven by an increase in the number and size of cells in the body. In particular, special types of cells, called stem cells, act as a reservoir for tissues: they divide to create new cells that will mature into various specialized structures. The retina is the light-sensitive part of the eye. It consists of the neural retina, a tissue that contains light-detecting cells, which is supported by the retinal pigment epithelium or RPE. In fish, the RPE and neural retina are replenished by distinct groups of stem cells that do not mix, despite the tissues being close together. Unlike humans, fish grow throughout adulthood, and their eyes must",380,128,0.3368
dialogsum,"#Person1#: Hi, I haven't seen you in a while. #Person2#: Yes, it has been a long time! #Person1#: How long has it been since we last saw each other? #Person2#: I think that we last saw each other two years ago. #Person1#: What have you been doing for the past two years? #Person2#: I have been going to graduate school at USC. #Person1#: What are you majoring in? #Person2#: I am studying international communications. #Person1#: You should easily be able to find a job with that major. #Person2#: I am counting on being able to get a good job.",#Person1# and #Person2# haven't seen each other for two years. #Person2# tells #Person1# what #Person2#'s been doing recently.,99,18,0.1818
pubmed-summarization,". mild proteinuria , usually < 2 g/24 h , is a common finding on routine examination in adpkd patients ; however , the association of nephrotic syndrome with adpkd is considered rare and needs to be investigated further to exclude coexisting glomerular disease . among the anecdotal case reports of adpkd associated with nephrotic syndrome , we report the case of a 26-year - old male with adpkd and concomitant nephrotic syndrome , in which the renal biopsy showed a mesangioproliferative glomerulonephritis in april 2009 , a 24-year - old man was referred to our hospital with a history of adpkd . the patient 's father had a diagnosis of adpkd and the mother was affected by a membranous nephropathy . at first observation , laboratory studies showed a daily urinary protein excretion of 3.19 g , serum creatinine 106.08 mol / l ( 1.2 mg / dl ) , and egfr ( estimated glomerular filtration rate ) 84.7 ml / min/1.73 m. we thus started therapy with an angiotensin - converting enzyme inhibitor ( acei ) , ramipril 5 mg / day . after 6 months , his proteinuria decreased to 1.13 g / day , so we added an angiotensin receptor blocker ( arb ) , losartan potassium 50 mg / day . his proteinuria remained about 1.82 g / day until the end of 2010 . in july 2011 , urine analysis showed a daily protein excretion of 7.4 g and 15 red blood cells per high power field ; the patient had neither peripheral leg oedema nor other symptoms ; urine culture was sterile ; tests for hbsag and hcvab and anti - nuclear antibodies were negative ; igg , iga , igm , c3 , c4 were normal ; there were no monoclonal bands on immunoelectrophoresis of the serum and no monoclonal light chains were detected in the urine . an abdomen ultrasound ( us ) analysis showed the right kidney measuring 11.4 cm in length with multiple cysts ranging in diameter from 1.6 to 3.2 cm , and the left kidney measuring 13.4 cm in length with multiple cysts . due to the persistent presence of nephrotic - range proteinuria , a us - guided biopsy was performed , the diagnosis of which","backgroundautosomal dominant polycystic kidney disease ( adpkd ) is an inherited disorder characterized by the development and growth of cysts in the kidneys and other organs . in adpkd patients , nephrotic range proteinuria is unusual and needs to be investigated further to exclude coexisting glomerular disease . among the anecdotal case reports of adpkd associated with nephrotic syndrome , focal segmental glomerulosclerosis occurs most frequently.methodswe report the case of a 26-year - old male with adpkd and concomitant nephrotic syndrome , in which an ultrasound ( us)-guided renal biopsy showed a mesangioproliferative glomerulonephritis . we treated the patient with prednisone 1 mg / kg / day , because of the failure of treatment with angiotensin - converting enzyme inhibitor / angiotensin receptor blocker association.resultsafter 6 months of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. , 2015; Lee and MacKinnon, 2004; Mihailescu et al. , 2014; Milescu et al. , 2009; Milescu et al. , 2007; Phillips et al. , 2005b). Thus far, however, no structures of toxin-channel complexes have been solved for this class of toxins, and therefore our understanding of toxin-channel interactions within membrane environments is limited. Double-knot toxin (DkTx) is a tarantula toxin isolated from the venom of a Chinese bird spider (Bae et al. , 2012; Bohlen et al. , 2010) that activates the transient receptor potential vanilloid 1 (TRPV1) channel. TRPV1 is a cation channel expressed in nociceptive sensory neurons that plays important roles in the transduction of noxious stimuli as well as thermosensation (Julius, 2013), but the molecular mechanism of heat-dependent activation has remained elusive. From a structural perspective, DkTx is intriguing because it has an unusual bivalent architecture, being comprised of two inhibitor-cysteine-knot (ICK) motifs that have been designated as the K1 and K2 lobes. DkTx is also quite hydrophobic, requiring the use of detergents to efficiently fold in vitro (Bae et al. , 2012), which raises the possibility that the toxin might interact with TRPV1 in a membrane environment, similar to toxins targeting voltage-sensing domains of voltage-activated ion channels. In a recent breakthrough, near-atomic resolution structures of the TRPV1 channel were solved using single-particle cryo-electron microscopy (cryo-EM), including a closed state (apo), a capsaicin-bound state, and an open state with both DkTx and the vanilloid resiniferatoxin (RTx) bound (Cao et al. , 2013; Liao et al. , 2013). The structure of the complex between TRPV1 and DkTx/RTx unambiguously reveals that the DkTx lobes bind to sites at the periphery of the external pore of the channel. However, the resolution of electron density maps was insufficient to reveal the structure of DkTx in atomic detail. Therefore, the binding arrangement of the two DkTx knots is unknown, as is the nature of the interactions between toxin and channel, or whether the interaction occurs in aqueous or membrane environments. How DkTx recognition ultimately results in channel opening, and how this process might relate to the mechanism of temperature-sensing, are also open questions. In the present study, we use nuclear magnetic resonance (NMR) spectroscopy to solve the solution structure of DkTx, and the molecular-modeling suite ROSETTA together with existing cryo-EM","Humans and other mammals sense heat using a protein called the transient receptor potential vanilloid (TRPV1) channel. This protein is found in the membranes of a particular type of nerve cell, and it forms a pore that allows certain ions to pass through the membrane. Along with sensing heat, TRPV1 can also be activated by a toxin called double-knot toxin – which is found in spider venom – and by capsaicin, the active ingredient in chilli peppers. One way to investigate how a protein works is to study its three-dimensional (3D) structure. Here, Bae, Anselmi et al. use a technique called nuclear magnetic resonance (NMR) spectroscopy to produce a detailed model of the 3D structure of double-knot toxin. This model is then combined with 3D maps of TRPV1",380,128,0.3368
dialogsum,"#Person1#: For our lunch meeting with the investors, do we have to make a reservation at the restaurant or do we just show up? #Person2#: Usually for lunch, we don't have to reserve a table, they should allow walk-ins. But to be on the safe side, I'll order a table for half-past twelve. Will that suit your schedule? #Person1#: I've arranged to meet them at the restaurant at twelve. Can you make the reservation a little earlier? If we start earlier, it will give us more time for a longer lunch. #Person2#: Are you planning on treating the investors to a full-course meal? #Person1#: Yes, we'll start with appetizers, follow with a soup and salad course, then main dishes of prime RMB or cordon bleu chicken, and finish up with a delicious rich dessert of some sort. #Person2#: That'll be pretty heavy for a mid-day meal, don't you think? #Person1#: As along as we stay away from anything alcoholic, we should be okay. #Person2#: With your prime RMB and chicken choices, you'd better hope nobody's vegetarian. #Person1#: We can make some special arrangement if we need to. After all, it's the company who is footing the bill.",#Person2# will reserve a table for a lunch meeting. #Person1# asks #Person2# to make it earlier and is planning a full-course meal without alcoholic. #Person2# reminds #Person1# to pay attention to vegetarians.,197,32,0.1624
dialogsum,"#Person1#: So, Fred, what are your plans for after graduation? #Person2#: Well, I've already got a job waiting for me back in my hometown. #Person1#: That's cool. Have you already found an apartment to live in? #Person2#: I'm planning on living with my parents. Won't you? #Person1#: I couldn't even if I wanted to. My parents told me that if I went home, then I'd have to find my own place. #Person2#: You mean they're kicking you out? #Person1#: Not really, they just don't want me living at home. My older sister did that, and she lived at home for seven years. Once she started living at home, it got harder and harder for her to move out. #Person2#: Well, it's not like my parents want me to live at home the rest of my life. They said that it's ok if I move back home to begin with, but they want me to find a place of my own after a year or so. #Person1#: My parents just didn't handle my older sister very well, and because of that, they want me to be more independent. They think that it's important that I should learn how to live on my own. #Person2#: I know I need to learn that myself, but I just don't have the money for it at the moment. Living at home allows me to save up some money before I started finding a place.",Fred has got a job in his hometown and is planning on living with his parents. #Person1#'s parents don't want #Person1# living at home. They want #Person1# to be more independent. Fred thinks he needs to learn to live on his own too but he doesn't have the money.,239,49,0.205
scientific_lay_summarisation-elife-norm,"Infection and tissue damage induces assembly of supramolecular organizing centres (SMOCs) ), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate inflammatory signaling. SMOC assembly is thought to drive digital all-or-none responses, yet TLR activation by diverse microbes induces anything from mild to severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in living macrophages, we find that MyDDosomes assemble within minutes of TLR4 stimulation. TLR4/MD2 activation leads only to formation of TLR4/MD2 heterotetramers, but not oligomers, suggesting a stoichiometric mismatch between activated receptors and MyDDosomes. The strength of TLR4 signalling depends not only on the number and size of MyDDosomes formed but also how quickly these structures assemble. Activated TLR4, therefore, acts transiently nucleating assembly of MyDDosomes, a process that is uncoupled from receptor activation. These data explain how the oncogenic mutation of MyD88 (L265P) assembles MyDDosomes in the absence of receptor activation to cause constitutive activation of pro-survival NF-κB signalling. During infections and tissue injury, large oligomeric complexes of proteins are assembled. The complexes represent supramolecular organizing centers (SMOCs), which serve as the principal subcellular source of signals that promote inflammation (Kagan et al. , 2014). In the Toll-like receptor (TLR) pathways, the most commonly discussed organizing center is the MyDDosome, which induces NF-κB and AP-1 activation to drive inflammatory transcriptional responses to infection (Motshwene et al. , 2009; Lin et al. , 2010; Gay et al. , 2014). Cell death pathways are also regulated by SMOCs, such as the pyroptosis-inducing inflammasomes and the apoptosis- inducing DISC (Lu et al. , 2014; Wang et al. , 2010; Scott et al. , 2009). A common feature of these organizing centers is their ability to be assembled inducibly during infection or other stressful experiences. Structural analysis has also highlighted similarities in the architecture of SMOCs, in that they assemble into helical oligomers (Lu et al. , 2014). Currently, it is believed that the purpose of assembling these complexes is to create an activation threshold in the innate immune system, such that all-or-none responses can be induced during infection. Microbes, however, contain various inflammatory mediators of varying potency. It is unclear how the innate immune system can convert this diversity of microbial stimuli into a digital response, yet single cell analysis of NF-κB activation induced by TLRs suggests that such a response","Cells in the immune system have proteins at their surface that detect molecules produced by invading microbes. One of these proteins is Toll-like receptor 4, TLR4 for short. Once TLR4 is activated, the immune cells form MyDDosomes – intricate complexes made of many different proteins. These structures form a signal that mobilizes the cell to fight the infection. In particular, the complexes set up a chain of events that leads to a gene-regulating protein getting access to the cell’s DNA. There, the protein switches on genes which produce other proteins important for inflammation, one of the body’s most important tools to fight an infection. The activation of TLR4 is thought to be an all-or-nothing mechanism: the receptors are either ‘on’ or ‘off’. However, different microbial molecules recognized by",380,128,0.3368
dialogsum,"#Person1#: What seems to be the trouble, Mr. Brown? #Person2#: I'm in pretty bad shape, Dr. Ford. #Person1#: Oh, in what way? #Person2#: No appetite, always on edge, and I can't sleep well. #Person1#: Did you lose any weight? #Person2#: Yes, I have lost quite a few pounds since last month. #Person1#: When was the last time you had a check-up? #Person2#: About two month ago. #Person1#: Let me take your blood pressure. You look anemic. #Person2#: What? Is that very bad? #Person1#: Well, Mr. Brown, I'm happy to say it's nothing serious. You're just a little run-down from overwork. #Person2#: What am I supposed to do? #Person1#: I think all you need is just a vacation. Try to get outdoors more and be sure to get more rest. #Person2#: Thank you, doctor. I'll do as you say.",Mr. Brown is in bad shape. Dr. Ford checks his body and thinks he is run-down and suggests he get enough rest.,138,22,0.1594
pubmed-summarization,"the possibility of identifying asd or prominent autistic traits . equally , in asd patients it is important to consider the occurrence of eating disorders associated with cognitive and psychosocial peculiarities . the therapeutic basis must respect these development peculiarities and make them part of the therapeutic program . the results imply that young people with an would benefit from a treatment approach tailored to the needs of individuals on the autism spectrum.15 kerbeshian and burd16 have shown an inspiring approach on the case history of a 12-year - old girl with high - functional autism and partial an . they have demonstrated that the treatment approaches used with individuals with neuropsychiatric developmental disorders might be effective in higher functioning individuals with eating disorders . therapeutic implications emphasize the need to improve cognitive and social functions,17 deficits in the field of mentalization,18 and the importance of focusing on working with the family.19 a girl aged 10 years and 9 months was admitted to a children s psychiatric clinic with an eating disorder and an underlying diagnosis of asperger syndrome . the patient s parents had degrees from technical universities and were healthy . the patient s sister , a grammar school student , was 2 years older and had asperger syndrome . she began to form individual words at 8 months and sentences from 24 months , but did not speak much until the age of 4 years . she began to speak fluently at the age of 4 years . at the age of 4.5 years she managed to fit into a small group of children in kindergarten . in the third year of school , she joined a partly new group in a language class and got a new class teacher . she began to dislike going to school ; she had mood swings , sometimes there were suicidal proclamations ; and she withdrew from her peers . at the end of the school year , she did not manage a school trip lasting several days , she ended up disorientated , and she ran away from the teachers several times . she said that she had been confused because of the change in the daily routine that she was used to at school . the diagnosis of","eating disorders frequently occur in conjunction with autism spectrum disorders , posing diagnostic and therapeutic difficulties . the comorbidity of anorexia nervosa and asperger syndrome is a significant clinical complication and has been associated with a poorer prognosis . the authors are presenting the cases of an eleven - year - old girl and a five - and - a - half - year - old girl with comorbid eating disorders and asperger syndrome .",380,75,0.1974
dialogsum,"#Person1#: What are you doing, Mum? #Person2#: I'm getting something ready for tomorrow. Tomorrow is Tre e-planting Day. #Person1#: Tree-planting Day? What do people do on this day, Mum? #Person2#: Many, many people will go and plant trees. #Person1#: Why do they do tha t? #Person2#: To make the earth more beautiful. And to make our life better. #Person1#: But I often see people on TV cut down many big trees. Why do they do that, Mum? #Person2#: Hm, to make paper, houses, and to make our life better. #Person1#: To make our life better, too? I just don't understand. Mum, why do many people go and plant trees on the same day? #Person2#: Oh, my dear son. It's hard to explain to you. When you grow up, you will understand. Just remember trees are very important to us.",#Person1# asks #Person2# about the Tree-planting Day. #Person1# is confused because #Person2# says planting trees and cutting down trees both make our life better.,139,24,0.1727
dialogsum,"#Person1#: Well, you seem to enjoy speaking English. #Person2#: You can't help learning when you're using it all day. You'll see. A few weeks'study in the school will have a similar effect on you. #Person1#: I hope so. You see, at the moment I find it difficult to get used to the teacher's speed and accent. I'm awfully worried, I can't reply as quickly as she seems to expect. #Person2#: Oh, she likes keeping us on our toes by getting us use English throughout the class. She doesn't mind your making mistakes, though. #Person1#: You know, speaking in class is a very good chance to put your English to practical use.",#Person2# is worried about using English throughout the class. #Person1# thinks using English in class is a good way to practice English.,111,22,0.1982
scientific_lay_summarisation-elife-norm,"alternatives. Thus, when the decision maker terminates deliberation, the choice is accompanied by a degree of certainty (i. e. , confidence), based on the same stream of evidence that supported that decision (Fetsch et al. , 2014). This last point remains controversial, however, for there are many instances when the confidence in a decision and the decision itself are dissociable. For example, human decision makers tend to overestimate their certainty about choices based on truly ambiguous evidence (Fischoff et al. , 1982; Baranski and Petrusic, 1994; Erev et al. , 1994; Drugowitsch et al. , 2014; Kiani et al. , 2014a), and they can perform above chance level yet report they are guessing (Kunimoto et al. , 2001). These and other observations have led psychologists to suggest that confidence and choice may be guided by different sources of evidence (Pleskac and Busemeyer, 2010; Zylberberg et al. , 2012; Moran et al. , 2015), or that the evaluation of the same evidence differs fundamentally in the way that it affects choice and confidence (Fleming and Dolan, 2012; Maniscalco and Lau, 2012; De Martino et al. , 2013; Ratcliff and Starns, 2013). The latter distinction is captured by the notion of a 1st-order confidence that is based rationally on the evidence in support of the decision and a 2nd-order confidence that can depart from this evidence. As this distinction rests on a proper understanding of the mechanism that supports choice and confidence, it is possible that some of the observations taken as support for higher order explanations of confidence are simply accounted for by deficiencies of the theory of 1st order choices. Naturally, if a decision maker acquires additional information after committing to a choice, she might wish to revise a decision, or the confidence in that decision, or both. Such changes of mind occur occasionally, even when there appears to be no additional information available after the initial decision has been rendered. The sequential sampling framework (e. g. , bounded evidence accumulation) offers a natural account of this phenomenon, because the mechanism incorporates processing delays, which leave open the possibility that the brain might have access to additional evidence that did not influence the initial decision and which might instead influence a revision. Evidence for such a process was adduced to","To understand how the brain makes decisions is to understand how we think – how we deal with information, interpret it and agree with a particular interpretation of the information. Neuroscience has begun to uncover the mechanisms that underlie these processes by linking the activity of nerve cells in the brain to different aspects of making decisions. These include how long it takes to reach a decision, why we make errors and how confident we feel about a decision. Sometimes when we make a decision and have committed to an answer, we then change our minds. Now, van den Berg et al. have asked whether the brain mechanisms that support a change of mind also support a change in confidence. To investigate this problem, human volunteers were asked",380,128,0.3368
dialogsum,"#Person1#: Hey, Robert, what are you doing this weekend? #Person2#: I didn't have any big plans. #Person1#: We are putting together a birthday party for Mary. #Person2#: That sounds like fun. Where will it be? #Person1#: We thought it would be fun to have a pool party at Jay's house. #Person2#: Oh good! Can I bring anything? #Person1#: We will be providing hot dogs, hamburgers, and cake, but people can bring side dishes. #Person2#: I am assuming that the dress is casual. #Person1#: Dress casually and bring your bathing suit! #Person2#: Wonderful. Just e-mail me the time and date and I'll be there.",#Person1# invites Robert to join a birthday party for Mary at Jay's house this weekend.,103,15,0.1456
scientific_lay_summarisation-elife-norm,"We present a reanalysis of the stochastic model of organelle production and show that the equilibrium distributions for the organelle numbers predicted by this model can be readily calculated in three different scenarios. These three distributions can be identified as standard distributions, and the corresponding exact formulae for their mean and variance can therefore be used in further analysis. This removes the need to rely on stochastic simulations or approximate formulae (derived using the fluctuation dissipation theorem). These calculations allow for further analysis of the predictions of the model. On the basis of this we question the extent to which the model can be used to conclude that peroxisome biogenesis is dominated by de novo production when Saccharomyces cerevisiae cells are grown on glucose medium. Recently a model was presented in which the variation of numbers of a particular type of organelle (Golgi apparatus, vacuoles or peroxisomes) observed in cells was proposed as a diagnostic indicator of the relative importance of different processes by which organelles can be formed and destroyed (Mukherji and O’Shea, 2014; see Mukherji and O’Shea, 2015 for a correction). Here we re-examine the mathematical analysis of this model and show that further insight can be gained from considering exact calculations of the equilibrium distributions. For conciseness we will refer to the model, and the analysis in the associated paper (Mukherji and O’Shea, 2014), by the abbreviation SMOP (stochastic model of organelle production). In the SMOP model, four processes are envisaged for the production and destruction of organelles: de novo synthesis, fission, fusion and decay. These four processes are characterised by one rate constant each, defined in the SMOP paper as kde novo, kfission, kfusion, and γ. Following the definitions in the SMOP paper, the probabilities of each of the four processes occurring in the next small time period δt are given in Table 1. We also include in this table the total rate of each process that would be observed instantaneously in a large population of N cells. 10. 7554/eLife. 10167. 003Table 1. Definition of terms in the SMOP modelDOI: http: //dx. . org/10. 7554/eLife. 10167. 003ProcessProbability of process occurring in next δt in a particular cell containing n organelles1Process changes n byRate of process in sample of N cells2De novokde novoδt1kde novofnNFissionkfissionnδt1kfissionnfnNDecayγnδt-1γnfnNFusionkfusionn (n-1) δt-1kfusionn (n-1)","Any cell that has a nucleus also contains a number of subcellular structures called organelles. The number of organelles inside a cell increases when new organelles are made from scratch (a process known as de novo synthesis), or when an existing organelle divides to produce two organelles in a process called fission. And the number of organelles decreases when an existing organelle decays, or when two organelles fuse together to become one organelle. The actual number of organelles of a particular type inside a cell results from a balance between these creative and destructive processes. Last year researchers at Harvard University developed a model that treats the processes of organelle creation and destruction as if they were chemical reactions, and then used their model to make predictions about",380,128,0.3368
scientific_lay_summarisation-elife-norm,"resulting crystalline lamellae, alternating with amorphous lamellae containing the branch points, stack with a periodicity of ~9–10. 5 nm (Jenkins et al. , 1993). This unique semi-crystalline nature of amylopectin renders starch insoluble. Amylopectin biosynthesis involves multiple enzyme activities, often composed of several isoforms with distinct specificities: four classes of starch synthases (SSs) elongate glucan chains using ADPglucose as glucosyl donor, creating α-1,4 glucose linkages; two classes of branching enzymes (BEs) introduce branches in the form of α-1,6 linked chains; and at least one isoamylase-type debranching enzyme hydrolyzes some branches again, probably tailoring the glucan for crystallization (Pfister and Zeeman, 2016; Tetlow and Emes, 2011; Zeeman et al. , 2010; Jeon et al. , 2010). In contrast, amylose is synthesized by a single class of granule-bound starch synthases (Denyer et al. , 2001). According to the classification of carbohydrate-active enzymes (CAZy; Lombard et al. , 2014), all SSs belong to the glycosyltransferase family 5 (GT5), while BEs and isoamylases belong to distinct subfamilies of the glycoside hydrolase family 13 (GH13). Starches from different plants vary in terms of amylose content, amylopectin structure and glucan modifications (e. g. level of phosphorylation) (Santelia and Zeeman, 2011). However, to date, this variation cannot fully meet industrial needs, necessitating costly physicochemical modifications post-extraction to yield the desired properties (Tharanathan, 2005). Although the starch-biosynthetic enzymes are highly conserved, we still do not have sufficient knowledge required for the rational modification of starch structure and properties in crops. This deficiency has several roots; first, the difficulty in generating plant mutants hinders a systematic analysis in most species. Second, the results obtained from comparable mutants in different plant systems are not always identical (e. g. due to variation in genetic, environmental and/or developmental backgrounds). Third, enzyme kinetics obtained from soluble substrates in vitro may not be representative of how an enzyme acts on a crystallizing surface in vivo (O' Neill and Field, 2015). These problems are further compounded by the fact that the glucans that make up starch are polydisperse, necessitating multiple biochemical and biophysical techniques for their structural characterization. Collectively, these limitations impair our ability to define enzyme functions unambiguously and to derive an overall model of starch biosynthesis. As a result, progress in engineering new starches with enhanced functionalities in planta has been empirical and","Most plants and algae produce a carbohydrate called starch, which provides the plant with a dense store of energy. Starch is also the main carbohydrate in our diet and its unusual physical properties mean that it has many industrial uses. It is made of two different sugar-based molecules known as glucans and forms large, partially crystalline granules inside plant cells. Several enzymes are known to be involved in making starch, yet it is not clear exactly how the process works. Animals and fungi cannot make starch but they do make another type of carbohydrate called glycogen, which is also a glucan. Yeast is a single-celled fungus that is often used in research because it is easy to genetically engineer and quick to grow. To study the plant enzymes",380,128,0.3368
pubmed-summarization,"over the past few months , the health sciences community has engaged in a fierce debate regarding pathways to achieve the goals of open science.1,2,3 there is a significant divide between the potential for the rapid , reproducible health research that is critical to advancing health science , on the one hand , and the current infrastructure and incentives in place that are designed to keep information private and unavailable to others who may benefit from using health data , on the other . all the communities we work with as part of the electronic data methods ( edm ) forum health services research , clinical research informatics , medicine , behavioral health , and numerous others are grappling with these issues to better assess the feasibility , cost , and ultimate benefits of a substantial culture change toward greater openness . indeed , as the president s cancer moonshot demonstrates,4 there is a new imperative to accelerate collaboration in implementation science , learning health systems , and precision medicine.5 writ large , open science includes a suite of approaches to facilitate greater access to both data and the information produced by a process of scientific inquiry ( . 1).6,7 open access ( oa ) publishing is the most well - known of these concepts . as currently defined , oa publishing is designed to enable the free access , use , modification , and sharing of published research for any purpose.8 increasingly in physics and astronomy,9 and more recently in biological health , open data and open source code10,11 accompany oa manuscripts to accelerate the scientific process by contributing research materials and findings in a computable format . the goal of these open scientific efforts is to facilitate more rapid sharing and , therefore , learning across the field , and to promote reproducibility of programs committed to research , discovery , and continuous improvement . certainly , there are legitimate concerns about the need to ensure adequate security and privacy of individual , protected health information ( phi ) in an era of open science . however , there are also substantial prevailing interests arguing against open sharing that do not necessarily represent the public s interest . these include the potential value of intellectual property to investigators","open science includes a variety of approaches to facilitate greater access to data and the information produced by processes of scientific inquiry . recently , the health sciences community has been grappling with the issue of potential pathways and models to achieve the goals of open science namely , to create and rapidly share reproducible health research . egems continued dedication to and milestones regarding the publication of innovative , useful , and timely research to help contribute to the push towards open science is discussed , as well as the edm forum s new data sharing platform , cielo . although strides have been made , there is still more work to be done to help health sciences community truly embrace open science .",380,125,0.3289
dialogsum,"#Person1#: Wait. What are you doing with that soft tomato? #Person2#: I'm throwing it away. #Person1#: I'll take it, and I'll take that hard bread, too. #Person2#: Stop, you can't get that out of the trash. #Person1#: I'm trying to do my part to reduce food waste. And these vegetables are still OK to eat. #Person2#: Fine, but they've been thrown away. #Person1#: What are you going to do with that meat that doesn't look fresh? #Person2#: I'm going to throw that away, too. #Person1#: I'll take it. I'm sure I can make something eatable with it. #Person2#: You can't be serious. I can't bear eating that kind of spoiled meat. #Person1#: It doesn't go bad, it's just beyond the freshness. #Person2#: Well, please, you can have all of the food. #Person1#: And to show my thanks, I'll invite you to lunch tomorrow.","#Person1# takes #Person2#'s soft tomatoes, hard bread and unfresh meat. #Person1#'s surprised but #Person2# tries to reduce food waste. Then #Person2# invites #Person1# to lunch to show thanks.",143,28,0.1958
pubmed-summarization,"in the banks of the karun river , which is the main river in this area . no data is available so far on the prevalence of hev among general population of ahvaz city ; therefore this study was conducted to determine the prevalence of hev among adults in south - west of iran . this cross - sectional study was approved by the ethical committee of ahvaz jundishapur university of medical science with research project number 91112 . to estimate the prevalence of anti - hev igg and igm antibodies in the general population of ahvaz city , 510 blood samples from the adult population of ahvaz city were collected randomly using the multistage cluster sampling method from february to july 2014 . ahvaz is a large city in the south - west of iran that consists of 8 districts and has 94 public health centers . in the first stage , 4 public health centers were selected randomly from each district . in the next stage , the family registry code was used to randomly select 16 households within each public health center . from each family , one subject the trained interviewers visited the subjects in their homes and completed a questionnaire containing information of age , gender , and race / ethnicity for each individual . the subjects who refused to participate in the study were replaced with the next random participants . the serum samples were tested in duplicate for anti - hev igg and igm antibodies by using dia.pro hev ab elisa kit and hev igm elisa kit ( dia.pro , italy ) according to the manufacturer 's instructions . statistical analyses were performed using spss 17 package program ( spss inc . , chicago , il , usa ) and p values of less than 0.05 were considered statistically significant . data were analyzed and compared by descriptive statistics and chi - square test or fisher 's exact test . out of 510 study subjects , 206 ( 40.4% ) were male and 304 ( 59.6% ) were female . the average age of participants was varying from 18 to 81 years while the mean age sd was 45.89 14.63 years . the subjects were classified into six age groups : 1830 ,","background . knowledge regarding prevalence of hev in general population can be an indicator of the public health and hygiene . therefore , this study was conducted to evaluate the prevalence of hev among adults in south - west of iran . methods . blood samples were taken from 510 participants , 206 ( 40.4% ) males and 304 ( 59.6% ) females from february to july 2014 . detection of anti - hev igg and igm antibodies was carried out by elisa test . results . the overall anti - hev igg and igm prevalence rates were 46.1% and 1.4% , respectively . anti - hev igg and igm seropositivity were not statistically associated with gender and race / ethnicity . meanwhile , there were significant differences",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Epigenome modulation potentially provides a mechanism for organisms to adapt, within and between generations. However, neither the extent to which this occurs, nor the mechanisms involved are known. Here we investigate DNA methylation variation in Swedish Arabidopsis thaliana accessions grown at two different temperatures. Environmental effects were limited to transposons, where CHH methylation was found to increase with temperature. Genome-wide association studies (GWAS) revealed that the extensive CHH methylation variation was strongly associated with genetic variants in both cis and trans, including a major trans-association close to the DNA methyltransferase CMT2. Unlike CHH methylation, CpG gene body methylation (GBM) was not affected by growth temperature, but was instead correlated with the latitude of origin. Accessions from colder regions had higher levels of GBM for a significant fraction of the genome, and this was associated with increased transcription for the genes affected. GWAS revealed that this effect was largely due to trans-acting loci, many of which showed evidence of local adaptation. To better understand how genotype and environment interact to affect DNA methylation and transcription, we grew 150 Arabidopsis thaliana accessions from Sweden (Long et al. , 2013) in two different environments, 10°C and 16°C, chosen because they lead to very different flowering behavior (Atwell et al. , 2010). Relying on existing genome sequence information (Long et al. , 2013), methylome- and transcriptome-sequencing data were generated (see ‘Materials and methods’). In plants, DNA methylation occurs on cytosines in the CG, CHG, and CHH contexts (where H is any nucleotide except for C), each of which is catalyzed by independent pathways (Finnegan et al. , 1998; Stroud et al. , 2014). Consistent with previous results (Vaughn et al. , 2007; Eichten et al. , 2013; Schmitz et al. , 2013; Li et al. , 2014; Seymour et al. , 2014; Hagmann et al. , 2015) we found considerable variation between accessions regardless of context, even at the level of genome-wide averages (1A). Temperature, on the other hand, did not appear to affect genome-wide CG or CHG methylation, but had a significant effect on CHH methylation, levels of which were 14% higher at 16°C than at 10°C, on average (1A). To investigate the genetic basis of DNA methylation, we performed genome-wide association studies (GWAS) using different facets of average methylation as the phenotype.","Organisms need to adapt quickly to changes in their environment. Mutations in the DNA sequence of genes can lead to new adaptations, but this can take many generations. Instead, altering how genes are switched on by changing how the DNA is packaged in cells can allow organisms to adapt within and between generations. One way that genes are controlled in organisms is by a process known as DNA methylation, where ‘methyl’ tags are added to DNA and act as markers for other proteins involved in activating genes. DNA is made of four different molecules called ‘nucleotides’ that are arranged in different orders to produce a vast variety of DNA sequences. One type of DNA methylation can happen at sites where a nucleotide called cytosine is followed by two",380,128,0.3368
pubmed-summarization,"idiopathic intracranial hypertension ( iih ) , previously termed pseudotumor cerebri and benign intracranial hypertension , is a syndrome of increased intracranial pressure ( icp ) of unknown etiology , without clinical , laboratory or radiological evidence of intracranial pathology . while the exact pathogenesis remains unclear , the chronic increased icp in this condition may lead to morphological intracranial changes . though traditionally performed to exclude lesions that produce intracranial hypertension , imaging in recent years has been shown to detect changes involving the orbit , sella and sinovenous system , providing important clues to the diagnosis . we describe the case of a lady with chronic headache , where magnetic resonance imaging ( mri ) showed features suggestive of iih , and in addition , highlight the dramatic reversal of these findings following csf drainage , allowing diagnosis to be made with certainty . a 45-year - old housewife presented to the neurology outpatient department with chronic headache for 10 years and recent aggravation for 1 month . though she ignored these symptoms for long , they now hampered her daily household activities . ophthalmological examination showed 6/6 vision in both the eyes , a normal fundus and no visual field defect on perimetry . saggital oblique images through the optic nerve revealed distended perioptic subarachnoid space as well as buckling of the orbital portion of the optic nerve [ 1a ] . a partial empty sella with postero - inferiorly compressed pituitary having a concave superior border and posteriorly displaced infundibulum was also noted [ 2a ] . tof venography showed paucity of the cortical veins and non - visualization of the right transverse sinus ( ts ) [ 3a ] . lumbar puncture ( lp ) done following the mr study showed raised opening pressure of csf of 28 cm of water . twenty milliliters of csf fluid was removed and sent for biochemical and microbiological examination , which was normal . following csf withdrawal , significant improvement in symptoms was noted . repeat mri done 3 days later showed straightening of the intraorbital optic nerve and reduction in perioptic subarachnoid space [ 1b ] . in addition , restoration of the infundibular position with a normal appearing pituitary having a flat superior margin was seen","idiopathic intracranial hypertension ( iih ) is a headache syndrome with raised csf pressure in the absence of an intracranial mass lesion . though earlier confined to excluding intracranial lesions , magnetic resonance imaging ( mri ) in recent years has been shown to identify intracranial changes from prolonged raised csf pressure , suggestive of iih . we present the mri and tof ( time - of - flight ) venography findings involving the orbit , sella tursica and cerebral venous structures in a 45-year - old lady with iih and illustrate their reversibility ( flip - flop ) following csf drainage . our case highlights the role of imaging in evaluation and follow - up of patients with iih , without the need for repeated lumbar punctures",380,128,0.3368
dialogsum,"#Person1#: Hi, Nicole. Did you have a good weekend? #Person2#: Yes, I did. But I feel tired today. #Person1#: Really? Why? #Person2#: Well, on Saturday I cleaned the house and played tennis. Then on Sunday I hiked in the country. #Person1#: And I bet you studied, too. #Person2#: Yeah. I studied on Sunday evening. What about you? #Person1#: Well, I didn't clean the house and I didn't study. I stayed in bed and watched TV. #Person2#: That sounds like fun, but did you exercise? #Person1#: Sort of. I played golf on my computer!",Nicole and #Person1# talk about how they spent their last weekends.,93,11,0.1183
dialogsum,"#Person1#: the dinner was really good. It knocked my socks off. #Person2#: that's very kind of you to say so. Let's try some after-dinner wines. #Person1#: great. Sweet wines are my favorite. They always make a great finish to a decilious meal. #Person2#: do you prefer brandy or ports. #Person1#: port, please. #Person2#: excellent choice. I love its smooth flavor. #Person1#: the port is exquisite. It must have spent years aging in barrels. Am I right? #Person2#: yes. You always have a good nose for wines. #Person1#: next time we are about to dinner we should try some Canadian ice wine. #Person2#: oh, what's that? #Person1#: it's made from natually forzen grapes. #Person2#: why not? It sounds great. #Person1#: oh, here's to your health. #Person2#: thanks. Cheers. #Person1#: cheers.",#Person1# and #Person2# finish a good dinner and have some wines. They choose to drink ports. #Person1# suggests trying Canadian ice wine next time. They cheers.,129,26,0.2016
dialogsum,"#Person1#: I was meaning to ask you if you saw the basketball game on Friday. #Person2#: I wanted to go, but I couldn't. #Person1#: It was a great game. #Person2#: It's too bad that I couldn't make it. Who won? #Person1#: Our team played hard and won. #Person2#: I really wish I went to the game. #Person1#: It was the best game ever. #Person2#: So tell me the final score. #Person1#: The other team lost by three points, 101-98. #Person2#: It must've been a close game. #Person1#: It really was. You should've gone. #Person2#: Hopefully, I'll make it to the next one.",#Person2# didn't see the basketball game. #Person1# tells #Person2# their team won and the final score was 101-98. #Person2#'ll make it to the next one.,102,25,0.2451
dialogsum,"#Person1#: Hi. Can I help you with something? #Person2#: Yes, please. We're looking for the men's department. #Person1#: It's right over there, by the escalator. #Person3#: Here we are . . . and here are the sport shirts. #Person2#: Look at this one. The color is perfect for you! #Person3#: I like it, too. How much is it? #Person2#: It's on sale for $19. 98. #Person3#: That's a good price. But I think they only have it in large. #Person2#: Excuse me! Could you help me? #Person1#: Sure. What can I do for you? #Person2#: Does this shirt come in medium? #Person1#: Yes, it does. Here's a medium. #Person3#: Great. We'll take it. #Person1#: Will that be cash or charge?",#Person1# helps #Person2# and #Person3# find the men's department and find a sport shirt in the medium for #Person3#. They will take the shirt.,120,24,0.2
dialogsum,"#Person1#: I'm searching for an old music box. #Person2#: You came to the right place. Any particular decade? #Person1#: If you had a box made in the ' 20s, that would be nice. #Person2#: We just got one in yesterday, so now we have six. #Person1#: Would any of them have dancing figures? #Person2#: Yes, we still have two boxes left that have dancing figures. #Person1#: Oh, they're both so beautiful. Let me have this one, I think. #Person2#: That one truly is a beautiful piece of work, isn't it? #Person1#: One last question #Person2#: Oh, no. Everything we sell here is ' as is. ' #Person1#: I guess I was asking for too much. #Person2#: If it breaks down, maybe you can find a repairman on the Internet.",#Person2# helps #Person1# search for an old music box with dancing figures. #Person1# takes one.,129,15,0.1163
dialogsum,"#Person1#: Jane, yesterday, I got a call from the local police station to pick up Biggie. She's had her person passport stolen. #Person2#: Poor Biggie. #Person1#: She told me that she found her bag was open at the bus station. She was sure the bag was fastened when she left a souvenir shop. So she searched her bag and found her purse and passport were gone. She rushed back to the shop, but they said nothing was there. She also looked around outside shop, but again couldn't find them. #Person2#: Did she have a lot of money in her purse? #Person1#: Not so much, but you know, her credit card and ID and so on. #Person2#: Has she reported it to the German Embassy? #Person1#: Yes, she has. So all she can do now is just waiting for her passport to be reissued. Oh poor Biggie.","#Person1# and Jane talk about Biggie, whose passport was stolen. She cannot find it anywhere so she has to wait for it to be reissued.",146,25,0.1712
pubmed-summarization,"cervical or endometrial cancer and controls . furthermore , we compared the bone turn - over markers and bmd base on their cancer stages . in this cross - sectional study , patients aged 45 - 57 years who first visited 3 university hospitals ( kosin university , wonkwang university , and inje university ) and were diagnosed with cervical or endometrial cancer without bone metastasis between january 2008 and december 2013 were included in the study . cervical cancer was diagnosed by papanicolaou smear and colposcopically directed biopsy , and endometrial cancer was initially diagnosed by dilatation and curettage of the uterus . technetium-99m - labeled diphosphonate bone scans or 18f - fluorodeoxyglucose positron emission tomography / computed tomography were performed on all cancer patients for confirmation of bone metastasis . all participants received dual - energy x - ray absorptiometry ( dxa ) at the time of diagnosis before any cancer treatment . study subjects who had not reached menopause or who received menopausal hormone therapy were excluded . postmenopausal women aged 48 - 59 years who visited the university hospitals as part of a group check - up for work and lacked specific health problems served as normal controls . all control women underwent a careful physical examination and a thorough review of medical history , and the subjects who had history of current treatment with drugs known to alter bone or calcium metabolism were excluded . finally , 218 patients with cervical cancer , 85 patients with endometrial cancer , and 259 healthy controls were enrolled in this study . bmd data of the lumbar spine and femur and laboratory data of bone turnover markers were collected for all participants . bmd was measured in grams per square centimeter at the first lumbar spine vertebrae ( l1),l2 , l3 , l4 and the femur , using dxa ( lunar radiation corp , madison , wi , usa ) . we used the t - score of total lumber spine , total hip , or femoral neck as single measurement for the diagnosis of osteoporosis . bmd values were categorized into three groups according to the criteria of the world health organization 16 and official positions 2013 of international society for clinical densitometry 17 as normal ,","objective : to evaluate the bone mineral density ( bmd ) in the lumbar spine and femur in postmenopausal women with cervical cancer and endometrial cancer without bone metastasis in comparison with that in healthy control postmenopausal women , and to assess the loss of bmd according to the cancer stage.materials and methods : we analyzed the bmd of the lumbar spine and femur using dual - energy x - ray absorptiometry ( dxa ) in 218 patients with cervical cancer , 85 patients with endometrial cancer , and 259 healthy controls . the serum levels of calcium ( ca ) , phosphorus ( p ) , osteocalcin ( osc ) , and total alkaline phosphatase ( alp ) , and urine deoxypyridinoline(dpl ) were measured in all",380,128,0.3368
dialogsum,"#Person1#: Hello. #Person2#: Hello, Sam. It's me, Jane. My uncle hasn't been well these days. I'm going to see him the day after tomorrow. #Person1#: Oh, really? Where does he live? #Person2#: He lives in Dalian. And I'm going there by train because I don't like the bus. #Person1#: How long will the train journey take? #Person2#: Well, the train leaves at 6:00 in the morning and arrives there at about 10:00. #Person1#: Who will meet you at the station? #Person2#: My aunt is going to meet me. She can drive. #Person1#: What is the weather like there? #Person2#: It is cold and wet. #Person1#: I hope you have a good journey. #Person2#: Thanks a lot, Sam. See you soon. #Person1#: Bye.",Jane tells Sam her uncle hasn't been well. She will take the train to visit him and her aunt will pick her up.,122,23,0.1885
scientific_lay_summarisation-elife-norm,"Brain development relies on an interplay between genetic specification and self-organization. Striking examples of this relationship can be found in the somatosensory brainstem, thalamus, and cortex of rats and mice, where the arrangement of the facial whiskers is preserved in the arrangement of cell aggregates to form precise somatotopic maps. We show in simulation how realistic whisker maps can self-organize, by assuming that information is exchanged between adjacent cells only, under the guidance of gene expression gradients. The resulting model provides a simple account of how patterns of gene expression can constrain spontaneous pattern formation to faithfully reproduce functional maps in subsequent brain structures. Karbowski and Ermentrout, 2004 developed a reaction-diffusion style model of how extrinsic signalling gradients can constrain the emergence of distinct fields from intrinsic cortical dynamics. Their model defines how the fraction of occupied synapses ci⁢ (x, t) and the density of axon branches ai⁢ (x, t) interact at time t, along a 1D anterior-posterior axis x, for N thalamocortical projections indexed by i. The model was derived from the assumption that the rates at which ai and ci grow are reciprocally coupled. Extending the original 1D model to simulate arealization on a 2D cortical sheet, we use ai⁢ (𝐱, t) and ci⁢ (𝐱, t), and model synaptogenesis as (1) ∂⁡ci∂⁡t=-α⁢ci+β⁢ (1-∑j=1Ncj) ⁢[ai]k. Accordingly, where the total fraction of synaptic connections sums to one, connections decay at rate α. Otherwise, ci⁢ (𝐱, t) increases non-linearly (k>1) with the density of axon branching. Axon branching is modelled as (2) ∂ai∂t= ∇ ⋅ (D∇ai−ai∑j=1Mγi, j∇ρj (x) +χi) −∂ci∂t. The first term on the right describes the divergence (indicated by ∇⋅) of the quantity in parentheses, which is referred to as the ‘flux’ of axonal branching. The flux represents diffusion across the cortical sheet, at rate D, and the influence of M molecular signalling fields, ρ⁢ (𝐱). The influence of a given field (indexed by j) on a given thalamic projection (indexed by i), is determined by γi, j, which may be positive or negative in order that axons may branch in the direction of either higher or lower concentrations. Note that computing the divergence in simulation requires cells on the cortical sheet to communicate with immediately adjacent cells only (see Methods). Here χi=0 is a placeholder. The second term","How does the brain wire itself up? One possibility is that a precise genetic blueprint tells every brain cell explicitly how it should be connected to other cells. Another option is that complex patterns emerge from relatively simple interactions between growing cells, which are more loosely controlled by genetic instruction. The barrel cortex in the brains of rats and mice features one of the most distinctive wiring patterns. There, cylindrical clusters of cells – or barrels – are arranged in a pattern that closely matches the arrangement of the whiskers on the face. Neurons in a barrel become active when the corresponding whisker is stimulated. This precise mapping between individual whiskers and their brain counterparts makes the whisker-barrel system ideal for studying brain wiring. Guidance fields are a",380,128,0.3368
pubmed-summarization,"10 torr . the formed qd , with dimensions 14 1 nm in height , 50 2 nm in diameter and density 2 10 cm ( . in particular , the first 15 nm of gaas were grown at ts = 510 c and as2 bep changing from 5 10 to 9 10 torr while the remaining 35 nm under typical mbe conditions : ts = 580 c and bep(as4 ) = 2 10 torr . as expected , coalesced mounds elongated along the gaas [ 1 - 10 ] direction are observed . in this sense , in order to study the resulting cap layer surface morphology and its possible correlation with the buried nanostructures , two different gaas cap layers with thicknesses of 25 and 100 nm were grown . in the case of growing a 25-nm thick cap layer , the growth conditions followed were similar to that used in the case of growing the 50-nm thick cap layer ; thus , the initial 15 nm were grown at ts = 510 c and as2 bep changing from 5 10 to 9 10 torr while the remaining 10 nm of gaas , under typical mbe conditions . as shown below ( . 2a ) , under this process , the cap layer shows a morphology consisting of a flat surface with isolated mounds . in the case of the 100-nm thick cap layer growth , the first 20 nm are initially grown as before , ts = 510 c and as2 bep changing from 5 10 to 9 10 torr , and the remaining 80 nm are deposited at ts = 450 c and bep(as4 ) = 2 10 torr using the almbe growth technique , with the aim of preserving as much as possible the mounding morphology achieved after the growth of the thinner cap layer ( d = 0 25 nm ) . after the growth of either 25- or 100-nm thick gaas cap layers , different amounts of inas were finally deposited to reveal the existence and hierarchy of sites for enhanced nucleation of new nanostructures . in particular 1.4 , 1.5 and 1.6 ml of inas were deposited at 0.01 ml / s , ts = 510 c and bep(as4 ) = 5","in this work , we study the top surface localization of inas quantum dots once capped by a gaas layer grown by molecular beam epitaxy . at the used growth conditions , the underneath nanostructures are revealed at the top surface as mounding features that match their density with independence of the cap layer thickness explored ( from 25 to 100 nm ) . the correspondence between these mounds and the buried nanostructures is confirmed by posterior selective strain - driven formation of new nanostructures on top of them , when the distance between the buried and the superficial nanostructures is short enough ( d = 25 nm ) .",380,110,0.2895
pubmed-summarization,"igg and iga antibodies directed against the intercellular region is lower than that in spontaneously occurring pemphigus ( 13 ) . it has been shown that these antibodies might not be detected in some cases of drug - induced pemphigus like our case ( 13,14 ) . to date , only 2 cases of bucillamine - induced pemphigus were reported in english literature . one was drug - induced pemphigus foliaceus with features of pemphigus vulgaris and the other was subcorneal pustular dermatosis - type iga pemphigus induced by thiol drugs ( 12,14 ) . the discontinuation of d - penicillamine may be inadequate in treatment because it frequently fails to stop disease progression.initial dose of corticosteroid is typically about 0.75 - 1 mg / kg / day . it has been suggested that high - dose or pulse therapy with steroids usually clears blisters promptly . prednisolone at a lower dose of 20 - 30 mg / day can maintain these patients without blistering but other adjuvant immunosuppressive drugs is need to achieve steroid - sparing effect or prevention of relapse ( 15,16 ) . bucillamine may cause pemphigus even at a low rate therefore we have to keep in mind that skin lesions with blisters should be carefully investigated in patients with bucillamine treatment .","bucillamine is a disease modifying anti - rheumatic drug , structurally similar to d - penicillamine . although d - penicillamine - induced pemphigus has been not infrequently demonstrated , pemphigus associated with bucillamine was rarely reported . we describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis ( ra ) and polymyositis ( pm ) overlap syndrome . pm and ra overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months . skin lesions including erythematous flaccid blisters on her chest , axillae , and back were occurred and were compatible with pemphigus vulgaris by typical pathology . withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions .",217,119,0.5484
dialogsum,"#Person1#: Um, sorry to bother you, um. . . my name is Rachel. I'm new here. Can I ask you a favor? #Person2#: Hi Rachel, welcome on board. I'm afraid I can't help you right now. I'm getting ready for a very important meeting. #Person1#: Excuse me, but can I bother you for a sec? #Person3#: You know what, I'd love to help you, but I'm about to meet an important client. Do you wanna try Sean instead? He sits right over there. #Person1#: Sorry to interrupt you Sean, could you do me a quick favor? #Person4#: Actually, I'm working on a document that is due in a couple minutes. I really can't talk to you right now. Sorry about that. #Person1#: Geeze! I just want to know where the bathroom is! What's wrong with you people!","Rachel asks #Person2#, #Person3#, and #Person4# for the way to the bathroom, but all of them are too busy to answer.",137,21,0.1533
dialogsum,"#Person1#: Your exam is over, isn't it? Why aren't you cheerful? #Person2#: Oh, I don't know. It isn't that the questions were too hard, but I always feel uneasy when the exam doesn't seem to have much to do with the book.",#Person2# feels uneasy because the exam doesn't seem to have much to do with the book.,42,16,0.381
scientific_lay_summarisation-elife-norm,"β-selection is the most pivotal event determining αβ T cell fate. Here, surface-expression of a pre-T cell receptor (pre-TCR) induces thymocyte metabolic activation, proliferation, survival and differentiation. Besides the pre-TCR, β-selection also requires co-stimulatory signals from Notch receptors - key cell fate determinants in eukaryotes. Here, we show that this Notch-dependence is established through antagonistic signaling by the pre-TCR/Notch effector, phosphoinositide 3-kinase (PI3K), and by inositol-trisphosphate 3-kinase B (Itpkb). Canonically, PI3K is counteracted by the lipid-phosphatases Pten and Inpp5d/SHIP-1. In contrast, Itpkb dampens pre-TCR induced PI3K/Akt signaling by producing IP4, a soluble antagonist of the Akt-activating PI3K-product PIP3. Itpkb-/- thymocytes are pre-TCR hyperresponsive, hyperactivate Akt, downstream mTOR and metabolism, undergo an accelerated β-selection and can develop to CD4+CD8+ cells without Notch. This is reversed by inhibition of Akt, mTOR or glucose metabolism. Thus, non-canonical PI3K-antagonism by Itpkb restricts pre-TCR induced metabolic activation to enforce coincidence-detection of pre-TCR expression and Notch-engagement. To generate a diverse T cell repertoire reactive against many pathogens, the T cell receptor (TCR) α and β chain genes somatically rearrange in developing thymocytes. TCR functionality is then assessed at various checkpoints. Thymocytes develop from bone marrow (BM) progenitors through successive CD4-CD8-' double-negative' CD44+CD25-c-Kit+ DN1, CD44+CD25+c-Kit+ DN2, HSAhighc-Kit-CD44-CD25+ DN3 and HSAhighCD44-CD25- DN4 stages (Petrie and Zuniga-Pflucker, 2007; Xiong et al. , 2011). Productive rearrangement of one TCRβ-allele causes surface-expression of a pre-TCR comprised of TCRβ, pre-TCRα and signal-transducing CD3 subunits on DN3 cells (Aifantis et al. , 2006). At the first checkpoint, β-selection, ligand-independent pre-TCR signaling triggers DN3 cell metabolic activation, proliferation and survival. It also triggers allelic exclusion of the second TCRβ allele, initiation of TCRα gene-rearrangements and differentiation via CD8+HSAhighTCRβlow immature single positive (ISP) precursors into CD4+CD8+' double-positive' (DP) cells (Petrie and Zuniga-Pflucker, 2007; Xiong et al. , 2011). β-selection ensures that only DN3 cells expressing a functional TCRβ chain develop further. It is the major cell-fate determining event for αβ T cells. Defective β-selection causes a DN3 block and severe immunodeficiency (Juntilla and Koretzky, 2008; Aifantis et al. , 2006). pre-TCR signaling alone is insufficient for DN-to-DP cell differentiation without co-stimulation by thymic microenvironmental signals. In particular, ligand engagement of Notch on DN3/DN4 cells promotes nutrient receptor expression, glucose uptake, metabolism, growth, survival, proliferation and differentiation. But excessive Notch signaling causes thymocyte transformation and T","T cells defend our body against cancer and infectious agents such as viruses. However, they can also cause rheumatoid arthritis and other autoimmune diseases by attacking healthy tissue. T cells recognize target cells via receptor proteins on their surface. To maximize the variety of infections and cancers our immune system can recognize, we generate millions of T cells with different T cell receptors every day. To ensure T cells work correctly, T cell receptors are tested at various checkpoints. The first checkpoint involves a process called beta (β) selection, during which T cells produce their first T cell receptor – the so-called pre-T cell receptor. This receptor causes T cells to divide and mature, and sets their future identity or “fate”. To complete β-selection, T cells must also",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Patterns of spatial positioning of individuals within microbial communities are often critical to community function. However, understanding patterning in natural communities is hampered by the multitude of cell–cell and cell–environment interactions as well as environmental variability. Here, through simulations and experiments on communities in defined environments, we examined how ecological interactions between two distinct partners impacted community patterning. We found that in strong cooperation with spatially localized large fitness benefits to both partners, a unique pattern is generated: partners spatially intermixed by appearing successively on top of each other, insensitive to initial conditions and interaction dynamics. Intermixing was experimentally observed in two obligatory cooperative systems: an engineered yeast community cooperating through metabolite-exchanges and a methane-producing community cooperating through redox-coupling. Even in simulated communities consisting of several species, most of the strongly-cooperating pairs appeared intermixed. Thus, when ecological interactions are the major patterning force, strong cooperation leads to partner intermixing. Biological interactions drive pattern formation at different levels of organization (Murray, 2003), ranging from developmental patterning within multicellular organisms and biofilms (Shapiro, 1998; Lewis, 2008; Vlamakis et al. , 2008; Chuong and Richardson, 2009), to ecological patterning within multi-species communities (Levin, 1992; Rietkerk and van de Koppel, 2008; Momeni et al. , 2011). Patterning, reflecting the relative spatial positioning of individuals with respect to each other, can be critical for the proper functioning of a community. Consider microbial communities: in a synthetic community, three bacterial species, each contributing an essential benefit while simultaneously competing for these benefits, can only grow when they are separated by an intermediate distance (Kim et al. , 2008); different types of patterning are correlated with different levels of biofilm growth (Christensen et al. , 2002; Brenner and Arnold, 2011); branching colony morphology allows more effective spreading across a nutrient-poor surface (Levine and Ben-Jacob, 2004); and in waste treatment granules, the layered pattern of bacteria and archaea is thought to facilitate the sequential degradation of substrates (Satoh et al. , 2007). Despite the wide-ranging importance of microbial communities in, for example, human health and the biogeochemical cycling of elements, it is still unclear how cell–cell and cell–environment interactions govern the patterning of communities (Elias and Banin, 2012). Understanding the mechanistic basis of pattern formation from observations of natural communities is stymied by the multitude of cell–cell and","Microorganisms such as bacteria, archaea and tiny eukaryotes are found throughout the biosphere. Some of these microorganisms are pathogens that cause diseases in animals, while others provide nutrients, including essential amino acids and vitamins; there are also microorganisms that have critical roles in recycling elements such as carbon, nitrogen and oxygen in the biosphere. In the natural world, microorganisms interact with their environment and with each other, often competing for space, light and nutrients, but sometimes they act cooperatively, which benefits all parties involved. Microbial communities exhibit spatial patterns that reflect the relative positioning of different microbes in a community. These patterns can be critical for the proper functioning of a microbial community. For example, in the microbial granules that digest organic compounds in waste water, the stratified",380,128,0.3368
scientific_lay_summarisation-elife-norm,"nucleus is a major open question. Both types of TE chromatin feature extensive cytosine methylation in the CG context catalyzed by MET1 (plant homolog of Dnmt1) (Cokus et al. , 2008; Lister et al. , 2008; Zemach et al. , 2013), and are also methylated at non-CG (CHG and CHH, where H is A, T, or C) cytosines (Stroud et al. , 2014; Zemach et al. , 2013). GC-rich TE sequences have high levels of histone modifications associated with heterochromatin, including methylation of lysine nine of histone H3 (H3K9me), and are therefore known as heterochromatic TEs (Sequeira-Mendes et al. , 2014; Zemach et al. , 2013). Non-CG methylation (mCH) at heterochromatic TEs is catalyzed primarily by chromomethylases (CMTs; CMT3 for CHG methylation and CMT2 for CHH), which are recruited to H3K9 dimethylated (H3K9me2) nucleosomes by histone-tail-interacting domains (Du et al. , 2012; Stoddard et al. , 2019; Stroud et al. , 2014; Zemach et al. , 2013). SUVH family H3K9 methyltransferases are in turn recruited to methylated DNA via SRA domains, forming a self-reinforcing loop (Du et al. , 2014; Johnson et al. , 2007; Rajakumara et al. , 2011). Arabidopsis thaliana plants lacking functional chromomethylases (cmt2cmt3 mutants) almost completely lack mCH at heterochromatic TEs, and their H3K9 methylation is greatly reduced (Stroud et al. , 2014). AT-rich TE sequences are low in H3K9me and other heterochromatic histone modifications, and are therefore known as euchromatic TEs (Sequeira-Mendes et al. , 2014; Zemach et al. , 2013). In contrast to the SUVH/CMT feedback loop that predominates in heterochromatin, RNA-directed DNA methylation (RdDM) catalyzes cytosine methylation within euchromatic TEs (Zemach et al. , 2013; Zhong et al. , 2012). RdDM loci are transcribed by a methylation-tolerant RNA polymerase II derivative (Pol IV) that couples cotranscriptionally with RNA-dependent RNA polymerase 2 (RDR2) to make double stranded RNA, which is processed into 23/24-nt fragments by Dicer-like 3 (DCL3) (Singh and Pikaard, 2019). These 24-nt small RNAs (sRNA) are subsequently denatured and loaded into Argonaute (AGO) protein complexes. AGO–sRNA complexes associate with another Pol II family enzyme, Pol V, to recruit Domains Rearranged Methylases (DRMs; primarily DRM2 in Arabidopsis) (Erdmann and Picard, 2020; Matzke and Mosher, 2014; Raju et al. , 2019; Wendte and Pikaard, 2017). Like the SUVH/CMT pathway, RdDM comprises positive feedback loops.","Cells adapt to different roles by turning different groups of genes on and off. One way cells control which genes are on or off is by creating regions of active and inactive DNA, which are created and maintained by different groups of proteins. Genes in active DNA regions can be turned on, while genes in inactive regions are switched off or silenced. Silenced DNA regions also turn off ‘transposable elements’: pieces of DNA that can copy themselves and move to other regions of the genome if they become active. Transposons can be dangerous if they are activated, because they can disrupt genes or regulatory sequences when they move. There are different types of active and inactive DNA, but it is not always clear why these differences exist, or",380,128,0.3368
dialogsum,"#Person1#: Come in, please. #Person2#: Good afternoon, Mrs. Smith. #Person1#: Good afternoon. Have a seat, please. You are Mr. Sun? #Person2#: Thank you. Yes, I am Dunlin. #Person1#: I have read your resume. I know you have worked for 3 years. Why did you choose to major in mechanical engineering? #Person2#: Many factors led me to major in mechanical engineering. The most important factor is I like tinkering with machines. #Person1#: What are you primarily interested in about mechanical engineering? #Person2#: I like designing products, and one of my designs received an award. Moreover, I am familiar with CAD. But I can do any mechanic well if I am employed. #Person1#: Why did you decide to apply for this position? #Person2#: Your company has a very good reputation, and I am very interested in the field your company is in. #Person1#: What do you think determines an employee's progress in a company such as ours? #Person2#: Interpersonal and technical skills. #Person1#: We have several applicants for this position. Why do you think you are the person we should choose? #Person2#: I have the abilities, qualities and experience that you requested in your job advert, for example I have three years experience in designing products and I got leadership experience while serving the college student union as president. #Person1#: That sounds very good. How do you see your career development? #Person2#: After a few years of gaining experience in the company and furthering my professional qualifications I'd like to put my experience and skills to use in management. I want to become a supervisor in your R & D department. #Person1#: Have you anything to ask about the job? #Person2#: Yes. Do you offer any opportunities for further study? #Person1#: Yes. If you undertake additional courses, provided these are approved, and you complete them successfully, you can claim back part, quite a large part, 75 % of the costs you incurred. Not just the fees, - traveling and other expenses too. #Person2#: That's fine. #Person1#: Anything else? #Person2#: No. #Person1#: Well, thank you very much, Mr. Sun. I'll let you know the result of the interview as soon as possible. Goodbye. #Person2#: Thank you, Mrs. Smith. I do hope the answer will be favorable. Goodbye.","Mrs. Smith's interviewing Mr. Sun. Mr. Sun tells her his interests in mechanical engineering, his reasons for applying for the position, and his strengths and experience. He hopes to become a supervisor in a few years. Mrs. Smith tells him the company offers opportunities for further study and he can claim back part if he completes the courses successfully.",374,59,0.1578
scientific_lay_summarisation-elife-norm,"characterized (Irie et al. , 2010; Ito et al. , 2004; Koishi et al. , 2004; Lee et al. , 2012; Nagura et al. , 2010; Payandeh et al. , 2011; Ren et al. , 2001; Shimomura et al. , 2016; Shimomura et al. , 2011). The simple structure of BacNavs has helped to elucidate the molecular mechanisms of Navs (Irie et al. , 2018; Irie et al. , 2012; Tsai et al. , 2013; Yue et al. , 2002). In addition, BacNavs have been used as a genetic tool for manipulating neuronal excitability in vivo (Bando et al. , 2016; Kamiya et al. , 2019; Lin et al. , 2010). The acquisition of Ca2+ selectivity by BacNavs can be engineered by the introduction of several negatively charged amino acids into the selectivity filter (Tang et al. , 2014; Yue et al. , 2002). A mutant channel NavAb (a BacNav from Arcobacter butzleri) produced in this way, showed high Ca2+ selectivity, and the structural basis of Ca2+ selectivity has been discussed on the basis of its crystal structures (Tang et al. , 2016; Tang et al. , 2014). However, the selectivity filter sequences of CavAb, which were made by mutation of NavAb and contain a large number of aspartates, are quite different from those of the original mammalian Cavs. The evolutional analysis also indicated that BacNavs acquired sodium selectivity independent from that of 24TM Navs (Liebeskind et al. , 2013). From these points of view, ancestor-like prokaryotic Cavs could be expected to help us to understand the structural and functional relationship between BacNavs and 24TM channels. Here, we newly characterized two BacNav homologs, CavMr from Meiothermus ruber and NavPp from Plesiocystis pacifica. These two channels are evolutionarily distant from the previously reported canonical BacNavs. We confirmed that CavMr has clear Ca2+ selectivity, and that NavPp has Na+ selectivity with Ca2+-dependent inhibition. The discovery of these channels suggests the possible importance of voltage-regulated Ca2+ signaling in prokaryotes and may be a new genetic tool for controlling Ca2+ signaling. Furthermore, mutational analyses indicate that the glycine residue of the CavMr selectivity filter is important for Ca2+ selectivity. This glycine residue is also well conserved in the selectivity filter of subdomains I and III of mammalian Cavs. On the basis of these observations,","Electrical signals in the brain and muscles allow animals – including humans – to think, make memories and move around. Cells generate these signals by enabling charged particles known as ions to pass through the physical barrier that surrounds all cells, the cell membrane, at certain times and in certain locations. The ions pass through pores made by various channel proteins, which generally have so-called “selectivity filters” that only allow particular types of ions to fit through. For example, the selectivity filters of a family of channels in mammals known as the Cavs only allow calcium ions to pass through. Another family of ion channels in mammals are similar in structure to the Cavs but their selectivity filters only allow sodium ions to pass through instead of calcium",380,128,0.3368
pubmed-summarization,"patients with chronic hepatitis ( both chronic hepatitis b and chc ) . subsequently , in 1999 , a study of 209 chc patients found liver iron accumulation detected by liver biopsy in 42.1% of patients , the majority of which was mild liver iron accumulation ( 35.4% of the 209 chc patients ) . those with liver iron accumulation had significantly higher levels of serum iron ( si ) , ferritin , and ts ; liver iron accumulation was also found to have a significant relationship with the severity of histological activity based on metavir classification and cirrhosis . in a study of 100 consecutive patients with hcv infection who underwent liver biopsy , 19 patients were found to be hepatic iron stain positive , which is associated with stage iii or iv fibrosis . fifty - five patients had at least one abnormal value of si , ferritin , or ts . in multivariate analysis , the only independent predictive factor of severe hepatic fibrosis was serum ferritin . however , elevated serum ferritin can also be caused by hepatic inflammation . in 1994 , a study of 123 chronic hepatitis patients ( including 63 chc patients ) found increased si , iron saturation , and ferritin in chc patients , while no evidence of hepatic iron accumulation could be found in any of these patients . in this study , serum ferritin was elevated in the absence of liver iron overload , which indicates that elevated serum ferritin may also be caused by inflammation itself . thus , elevated ferritin reflects hepatic iron accumulation , as well as hepatic inflammation , and also predicts severe hepatic fibrosis . in other words , hepatic iron accumulation can lead to elevated ferritin , while elevated ferritin is not only induced by hepatic iron accumulation but also caused by hepatic inflammation . thus , serum ferritin levels only serve as a reference to evaluate liver iron status in chc patients , and liver biopsy is the gold standard for diagnosis of iron overload . so far , plenty of studies have been devoted to exploring the mechanism as to how hcv leads to iron overload . it is generally accepted that hcv alters iron metabolism by reducing the level of","objective : the aim of this study was to summarize the interactions between hepatitis c virus ( hcv ) infection and iron overload , and to understand the mechanisms of iron overload in chronic hepatitis c ( chc ) and the role iron plays in hcv life cycle.data sources : this review was based on data in articles published in the pubmed databases up to january 28 , 2017 , with the keywords hepatitis c virus , iron overload , iron metabolism , hepcidin , translation , and replication.study selection : articles related to iron metabolism , iron overload in patients with chc , or the effects of iron on hcv life cycle were selected for the review.results:iron overload is common in patients with chc . the mechanisms",380,128,0.3368
scientific_lay_summarisation-elife-norm,"onset of gastrulation, emerging mesoderm migrates either anteriorly as so-called embryonic mesodermal wings, or proximally as extra-embryonic mesoderm (Arnold and Robertson, 2009; Sutherland, 2016). Cell lineages studies showed that there is little correlation between the position of mesoderm progenitors in the epiblast and the final localization of mesoderm descendants (Lawson et al. , 1991). Rather, the distribution of mesoderm subpopulations depends on the temporal order and anterior-posterior location of cell recruitment through the primitive streak (Kinder et al. , 1999). Posterior primitive streak cells are the major source of extra-embryonic mesoderm, while cells from middle and anterior primitive streak are mostly destined to the embryo proper. However, there is overlap of fates between cells delaminating at different sites and timings (Kinder et al. , 1999; Kinder et al. , 2001). Extra-embryonic mesoderm contributes to the amnion, allantois, chorion, and visceral yolk sac. It has important functions in maternal-fetal protection and communication, as well as in primitive erythropoiesis (Watson and Cross, 2005). Embryonic mesoderm separates into lateral plate, intermediate, paraxial and axial mesoderm, and ultimately gives rise to cranial and cardiac mesenchyme, blood vessels and hematopoietic progenitors, urogenital system, muscles and bones, among others. Endoderm precursors co-migrate with mesoderm progenitors in the wings and undergo a mesenchymal-epithelial transition to intercalate into the visceral endoderm (Viotti et al. , 2014). Mesoderm migration mechanisms have mostly been studied in fly, fish, frog and chicken embryos. During fly gastrulation, mesodermal cells migrate as a collective (Bae et al. , 2012). In the fish Fundulus heteroclitus, deep cells of the dorsal germ ring move as loose clusters with meandering trajectories (Trinkaus et al. , 1992). At mid-gastrulation, zebrafish lateral mesoderm cells are not elongated and migrate as individuals along indirect paths, while by late gastrulation, cells are more polarized and their trajectories are straighter, resulting in higher speed (Jessen et al. , 2002). In zebrafish prechordal plate, all cells have similar migration properties but they require contact between each other for directional migration (Dumortier et al. , 2012). In chick, cells migrate in a very directional manner at high density. Cells are continually in close proximity, even though they frequently make and break contacts with their neighbors (Chuai et al. , 2012). Relatively little is known about mesoderm migration in mice because most mutant phenotypes","As an embryo develops, its cells divide and specialize to form different tissues and organs. Early in development the cells arrange into so-called germ layers, which each produce particular types of tissue. One of these layers, called the mesoderm, develops into the muscles, bones and circulatory system of the embryo. It also contributes to the support structures that feed and protect the embryo, such as the placenta, umbilical cord and yolk sac. If these ‘extra-embryonic’ structures do not develop correctly, the embryo may not grow properly. Much of what we know about how the cells of the mesoderm move around to form different tissues comes from studies of species that lay eggs; for example, chicks, frogs and fish. The initial steps of embryo development in these animals are",380,128,0.3368
dialogsum,"#Person1#: Hi, Tony. Haven't seen you for a long time. How have you been? #Person2#: OK, I've been looking for a job for days, and I haven't found one yet. It's so hard finding work these days. Have you had any luck? #Person1#: Yes, I've got a job, a waiter's job in a restaurant. #Person2#: Are you well paid? #Person1#: Well, $10 per hour, but I can keep the tips. That comes to roughly $80 every evening #Person2#: Not bad. #Person1#: Actually, there's still another opening. If you are interested, you'll surely get it. #Person2#: That's great! I'll go there right now and speak with the boss. #Person1#: There's no rush. You can see him tomorrow. I've told him about you. He promised to give you the job. #Person2#: That was nice of you, Susan. Thanks a lot. #Person1#: Think nothing of it, Tony. I'm sure you'd do the same for me. #Person2#: Could you tell me a bit more about the work there? I mean, those dos and don'ts. I am a green hand, you know. #Person1#: First of all, you must be punctual. You should be there before 6 p. m. so that you will have half an hour for preparation changing clothes and things like that. Then,remember you should smile. Smile to your customers all the time. Never pull a long face even If you feel awful that day. Anything else? Oh, yes. Never argue with your boss. Learn to say 'Yes, sir. ' #Person2#: Be a yes-man, you mean? #Person1#: You may put it that way if you like. Don't worry. You'll have no problem. #Person2#: I hope not.","Tony hasn't got a job, while Susan has got one as a waiter in a restaurant. Susan has told her boss about Tony and the boss promised to give Tony the job. Tony is grateful. Then Susan talks about the rules of the job.",273,44,0.1612
dialogsum,"#Person1#: What can I do for you? #Person2#: Yes. There is something wrong with my watch. It stopped several hours ago. #Person1#: Let me have a look. Oh, the watch's battery is worn down. #Person2#: How much is a battery? #Person1#: $ 50. #Person2#: How long will it last? #Person1#: About 2 years. #Person2#: Here is the money.",#Person2# has #Person1# changed the battery of #Person2#'s watch.,58,9,0.1552
pubmed-summarization,"- exposed population , as this could be a useful biomarker to predict and prevent health hazards of pesticides . it is recommended that the workers che level should be assessed before they start working at a pesticide applied region . in view of this , the present study was aimed to evaluate the ache and bche activities among agriculture workers occupationally exposed to pesticide . the study was conducted in the neighboring villages of chikkaballapur town , rural bangalore , south india , from december 2010 to march 2011 . this study included 28 rural people who were agriculture workers , engaged in floriculture , and cultivation of cabbage , potato , and grape . a control group consisting of 13 unexposed workers , who never had any exposure to op pesticides , was taken as the reference group . a detailed history , including the personal and occupational details , was recorded through a questionnaire . a written informed consent was taken from all study subjects after explaining the importance of the study in their local language . five milliliters of venous blood was collected in dried heparinized tubes and transported in ice box to the laboratory . blood samples of voluntarily participated agriculture workers ( n = 28 ) who have been involved mainly in pesticide spraying activities in vegetable and grape gardens were collected . a control group consisting of 13 male subjects who belonged to a similar age group and socioeconomic status and were not exposed to any kind of pesticides was selected for the study from the same localities . blood was centrifuged at 4000 rpm for 10 min at 4c to separate the plasma . che activity was determined by the method of ellman et al . as modified by chambers and chambers . three milliliters of 0.25 mm of 5,5-dithiobis ( 2-nitrobenzoic acid ) ( dtnb ) prepared in 0.05 m phosphate buffer was pipetted out into a cuvette , in which 20 l of thoroughly mixed plasma sample and 100 l of 1 mm substrate ( acetylthiocholine iodide for ache assay ) were added . the sample was placed on a uv - vis spectrophotometer set at a wavelength of 410 nm . the change in absorbance with a light path","background : cholinesterase determination indicates whether the person has been under pesticide exposure is not . it is recommended that the workers cholinesterase level should be assessed for workers at a pesticide applied region . hence , cholinesterase activities in blood samples of agricultural workers exposed to vegetables and grape cultivation with age matched , unexposed workers , who never had any exposure to pesticides , were estimated.methods:the detailed occupational history and lifestyle characters were obtained by questionnaire . cholinesterase activity was determined by the method of ellman as modified by chambers and chambers.results:ache was ranging from 1.65 to 3.54moles / min / ml in exposed subjects where as it was ranged from 2.22 to 3.51moles / min / ml in control subjects . bche activity was ranging",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The postnatal neurodevelopmental disorder Rett syndrome, caused by mutations in MECP2, produces a diverse array of symptoms, including loss of language, motor, and social skills and the development of hand stereotypies, anxiety, tremor, ataxia, respiratory dysrhythmias, and seizures. Surprisingly, despite the diversity of these features, we have found that deleting Mecp2 only from GABAergic inhibitory neurons in mice replicates most of this phenotype. Here we show that genetically restoring Mecp2 expression only in GABAergic neurons of male Mecp2 null mice enhanced inhibitory signaling, extended lifespan, and rescued ataxia, apraxia, and social abnormalities but did not rescue tremor or anxiety. Female Mecp2+/- mice showed a less dramatic but still substantial rescue. These findings highlight the critical regulatory role of GABAergic neurons in certain behaviors and suggest that modulating the excitatory/inhibitory balance through GABAergic neurons could prove a viable therapeutic option in Rett syndrome. Maintaining a proper ratio of excitation and inhibition throughout the brain is critical to normal neurological function. Alterations in this excitatory/inhibitory balance are postulated to underlie a number of neuropsychiatric disorders, such as autism (Vattikuti and Chow, 2010; Gogolla et al. , 2009; Rubenstein and Merzenich, 2003), schizophrenia (Belforte et al. , 2010), and Rett syndrome (Dani et al. , 2005). Much of the work on this balance has focused on excitatory neurons, which make up the majority of the brain’s neuronal population, yet it has become increasingly clear that inhibitory neurons, which predominantly release the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), play important roles in the proper function of entire circuits (Xue et al. , 2014) and in the behaviors regulated by these circuits (Yizhar et al. , 2011). Dysfunctional GABAergic signaling has been implicated in multiple neurological and neuropsychiatric disorders (Siniatchkin and Koepp, 2009; Pizzarelli and Cherubini, 2011), including Rett syndrome (Chao et al. , 2010). In fact, deletion of Mecp2 solely in GABAergic neurons is sufficient to reproduce the majority of the Rett-like features of the constitutive Mecp2-null mouse, including ataxia, stereotyped behaviors, seizures, breathing abnormalities, and premature death (Chao et al. , 2010). Rett syndrome (RTT) is caused by mutations in the X-linked gene encoding methyl CpG-binding protein 2 (MeCP2) (Amir et al. , 1999), a protein that is highly expressed throughout the brain and involved in chromatin modulation (Baker et al. , 2013). RTT","Rett syndrome is a childhood brain disorder that mainly affects girls and causes symptoms including anxiety, tremors, uncoordinated movements and breathing difficulties. Rett syndrome is caused by mutations in a gene called MECP2, which is found on the X chromosome. Males with MECP2 mutations are rare but have more severe symptoms and die young. Many researchers who study Rett syndrome use mice as a model of the disorder. In particular, male mice with the mouse equivalent of the human MECP2 gene switched off in every cell in the body (also known as Mecp2-null mice) show many of the features of Rett syndrome and die at a young age. The MECP2 gene is important for healthy brain activity. The brain contains two major types of neurons: excitatory neurons, which",380,128,0.3368
dialogsum,"#Person1#: How are you, Mr. Zhang? #Person2#: Very well, thank you. And you? #Person1#: Fine, too, thanks. We met one year ago. We both took part in a party held by our company last year. #Person2#: That's right. How nice to see you again. #Person1#: Me too. How is your family? #Person2#: they are doing well. #Person1#: Say'hello'to them for me. #Person2#: Of course. They will be happy you asked about them.",Mr. Zhang and #Person1# greet each other for the first time since their meeting last year.,72,16,0.2222
dialogsum,"#Person1#: I want to go try on these clothes. #Person2#: What did you find? #Person1#: I found some jeans, and a new blouse. #Person2#: Go and try it on. #Person1#: What do you think? #Person2#: I love that shirt on you. #Person1#: What about the jeans? #Person2#: They don't really fit you right. #Person1#: I don't think so either. #Person2#: That blouse is absolutely wonderful on you. #Person1#: I'll just buy the shirt. #Person2#: That would be a good idea.",#Person1# tries on some jeans and a blouse. #Person1# decides to buy the shirt. #Person2# agrees.,80,16,0.2
dialogsum,"#Person1#: Hello. Is this room service? #Person2#: Yes. May I help you? #Person1#: This is room 1425. We asked for the room service an hour ago. #Person2#: We're very sorry to cause you a lot of inconvenience. #Person1#: What's the matter? #Person2#: We're rather busy right now. It will take another 15 minutes. #Person1#: Is it really going to take that long? Will you rush the order? #Person2#: I'm afraid it would take 15 minutes at most. #Person1#: Ah, well, we have no choice.",#Person1# asked for the room service an hour ago. #Person2# asks #Person1# to wait another 15 minutes.,84,17,0.2024
dialogsum,"#Person1#: Welcome to Adventure Tours. How may I help you? #Person2#: I want to book a tour with adventure sports. #Person1#: Excellent! Our company has more than ten years of experience in the adventure tourism and sports field. Let me show you some options. This is our most popular choice, our river guides will take you on a whitewater rafting trip followed by a ride in a hot air balloon! #Person2#: I don't really think I'm ready to throw myself down a river full of jagged rocks in a rubber boat or go up in the air in a wicker basket held up by an oversize balloon. What else do you have? #Person1#: Well, in that case, we can take you hang gliding with one of our experienced instructors. It's the closest you can get to flying. #Person2#: What? You mean strap myself to a flimsy kite? No, thank you! Next! #Person1#: Mmm. OK. Well, why don't you tell me a little bit more about what you would like? We have everything from mountain biking, to rock climbing to street luge. #Person2#: I'm thinking something exciting but. safer. #Person1#: I have the perfect option, this package will take you on a hiking trip through the Himalayas for three days and afterwards there's a dog sledding journey! #Person2#: That's more like it!","#Person2# wants to book a tour of adventure sports. #Person1# recommends a whitewater rafting trip and hanging gliding, but #Person2# wants an exciting but safer trip. Then #Person1# recommends a package and #Person2# likes it.",221,35,0.1584
scientific_lay_summarisation-elife-norm,"Almers, 1987; Lollike et al. , 1995). The pore can then expand irreversibly (termed full fusion), which leads to mixing of granule and plasma membrane and release of the bulkier hormone content (Obermüller et al. , 2005; Barg et al. , 2002; Anantharam et al. , 2010). Alternatively, the pore can close indefinitely to allow the granule to be retrieved, apparently intact, into the cell interior (termed kiss-and-run or cavicapture) (Obermüller et al. , 2005; MacDonald et al. , 2006; Taraska et al. , 2003; Tsuboi and Rutter, 2003; Shin et al. , 2018). Estimates in β-cells suggest that 20–50% of all exocytosis in β-cells are transient kiss-and-run events that do not lead to insulin release (Obermüller et al. , 2005; MacDonald et al. , 2006). However, kiss-and-run exocytosis contributes to local signaling within the islet because smaller granule constituents, such as nucleotides, glutamate or GABA, are released even when the fusion pore does not expand. Within the islet, ATP synchronizes β-cells (Hellman et al. , 2004), and has both inhibitory (Salehi et al. , 2005; Poulsen et al. , 1999) and stimulatory (Richards-Williams et al. , 2008) effects on insulin secretion. ATP suppresses glucagon release from α-cells (Tudurí et al. , 2008), and activates macrophages (Weitz et al. , 2018). Interstitial GABA leads to tonic GABA-A receptor activation and α-cell proliferation (Jin et al. , 2013; Ben-Othman et al. , 2017), and glutamate stimulates glucagon secretion (Cabrera et al. , 2008). Regulation of fusion pore behavior is not understood mechanistically, but several cellular signaling events affect both lifetime and flicker behavior. Pore behavior has been shown to be regulated by cytosolic Ca2+, cAMP, PI (4,5) P2, and activation of protein kinase C (PKC) (MacDonald et al. , 2006; Hanna et al. , 2009; Alés et al. , 1999; Calejo et al. , 2013; Scepek et al. , 1998) and recent superresolution imaging indicates that elevated Ca2+ and dynamin promote pore closure (Shin et al. , 2018; Chiang et al. , 2014). Both myosin and the small GTPase dynamin are involved in fusion pore restriction (Jackson et al. , 2015; Tsuboi et al. , 2004; Graham et al. , 2002; Artalejo et al. , 1995; Aoki et al. , 2010), and assembly of filamentous actin promotes fusion pore expansion (Wen","Insulin is the hormone that signals to the body to take up sugar from the blood. Specialized cells in the pancreas – known as β-cells – release insulin after a meal. Before that, insulin molecules are stored in tiny granules inside the β-cells; these granules must fuse with the cells’ surface membranes to release their contents. The first step in this process creates a narrow pore that allows small molecules, but not the larger insulin molecules, to seep out. The pore then widens to release the insulin. Since the small molecules are known to act locally in the pancreas, it is possible that this “molecular sieve” is biologically important. Yet it is not clear how the pore widens. One of the problems for people with type 2 diabetes",380,128,0.3368
pubmed-summarization,"or patient is very important in the practice of ayurveda . several biochemical , genetic , and molecular studies have been performed to relate various features of an individual to prakriti . initial study by patwardhan et al . demonstrated a correlation between hla - drb1 types with the specific prakriti . subsequently , prasher et al . reported biochemical profiles , hematological parameters , and gene expression patterns among vata , pitta , and kapha subjects relating them to inflammatory or cardiovascular diseases . similarly expression of egln1 gene and the association of rs479200 ( c / t ) and rs480902 ( t / c ) in high - altitude adaptation in relation to prakriti was reported . since it is experience and skill based , inter - observer variations will be inherent . a quantitative tool , such as software , could eliminate much of the subjectivity such that it could be reiteratively tested , modified , and adopted to provide similar prakriti determination . therefore , considering the immense potential , an interdisciplinary approach to interrogate ayurvedic principles in the context of contemporary medicine is essential . traditionally , the prakriti assessment is carried out by the ayurvedic physician on the basis of his knowledge and experience and is therefore subject to inter - observer variations . the quantitative approach to the qualitative assessment of prakriti for the practice of personalized medicine both by ayurvedic physician and contemporary science is essential and attempts are made based on the use of psychometric scaling ; however , these lack the physiological and anatomical features in scaling different prakriti types . in order to define traditional prakriti features and clinical phenotypes on the basis of current knowledge and to develop a uniformly acceptable tool , which will provide a quantitative element to the qualitative determination of prakriti , we have evaluated 3416 normal healthy volunteers using prakriti traits as per traditional texts as well as computer - aided prakriti description tool . we have described our attempt to correlate distribution of prakriti among population and also show a dominant prakriti association with body mass index ( bmi ) . the study was carried out over a period of 2 years at three different centers , bangalore ( centre1 ) ,","background : constitutional type of an individual or prakriti is the basic clinical denominator in ayurveda , which defines physical , physiological , and psychological traits of an individual and is the template for individualized diet , lifestyle counseling , and treatment . the large number of phenotype description by prakriti determination is based on the knowledge and experience of the assessor , and hence subject to inherent variations and interpretations.objective:in this study we have attempted to relate dominant prakriti attribute to body mass index ( bmi ) of individuals by assessing an acceptable tool to provide the quantitative measure to the currently qualitative ayurvedic prakriti determination.materials and methods : the study is cross sectional , multicentered , and prakriti assessment of a total of 3416 subjects was",380,128,0.3368
dialogsum,"#Person1#: Dear Aaron, and how are you? #Person2#: Quite well, thank you. #Person1#: I'm celebrating my ninth birthday, the day after tomorrow. #Person2#: Well, where is the function arranged? #Person1#: It is arranged in a hotel. #Person2#: Where is it? #Person1#: It is just next to my house. #Person2#: Will your uncle Vince attend the function? #Person1#: No, but he has sent me a camera as my birthday present.",#Person1# tells #Person2# #Person1# will celebrate #Person1#'s birthday in a hotel. #Person1#'s uncle won't come but already sent a present.,69,20,0.2899
scientific_lay_summarisation-elife-norm,"The backbone of the cartwheel is characterized by a central hub from which nine spokes emanate (Anderson and Brenner, 1971) and is primarily made of the centriolar protein SAS-6 (Kitagawa et al. , 2011; van Breugel et al. , 2011). SAS-6 exists as dimers, which can self-oligomerize in vitro via an N-terminal head domain, forming a ring resembling the central hub, and C-terminal tails pointing outwards as spokes (Kitagawa et al. , 2011; van Breugel et al. , 2011; van Breugel et al. , 2014), albeit not always ninefold symmetric in vitro (Cottee et al. , 2011). Nevertheless, these elegant discoveries raise an exciting proposal that the self-assembly property associated with the N terminus of SAS-6 drives cartwheel and centriole formation. In contrast to the SAS-6 self-assembly model, a template-based assembly model, dependent on the interaction of the C-terminal tail of SAS-6 with the lumen of mother centrioles, has recently been proposed to initiate canonical duplication (Fong et al. , 2014). During S phase, SAS-6 molecules are first recruited to the proximal lumen of the mother centriole prior to centriole duplication, adopting a cartwheel-like organization through interactions with the luminal wall, rather than via their self-oligomerization activity. This leads to a proposal that mother centrioles may function as the template to shape SAS-6 assembly, thereby preserving the geometric shape of the centriole that otherwise cannot be ensured by SAS-6 self-assembly alone. Notably, the template-based model appears incompatible with de novo centriole synthesis in which no pre-existing centrioles are required. However, as the nature of de novo synthesis, for example, whether it is indeed based on SAS-6 self-assembly, has not been determined, it is premature to accept or reject any of these ideas. To characterize de novo formation of centrioles or centrosomes, we used CRISPR/Cas9 gene targeting to sequentially inactivate p53 and SAS-6 genes in retinal pigment epithelial cells (RPE1), generating stable, acentriolar cell lines (SAS-6-/-; p53-/-) in which de novo centrosome formation can be subsequently reconstituted (Izquierdo et al. , 2014) (see ‘Materials and methods’). Pure acentriolar cell lines were established through clonal propagation from single cells, a process taking 4–5 weeks, before these cells were used for experiments. In two independent SAS-6-/-; p53-/- cell lines we generated (clone #1 and #2), frameshift mutations present in the beginning of the","Cells pass on their characteristics or “traits” to new generations in the form of DNA molecules. DNA provides the instructions to make proteins, which may then assemble into larger structures without using any external templates in a process called self-assembly. However, when a cell divides, DNA is not the only element that is passed on to the daughter cells; many large protein structures that have assembled in mother cells are also divided between the daughter cells. The daughter cells may then produce extra copies of these protein structures, but it is not known whether the pre-existing structures are involved in this process. Centrioles are complex structures made of proteins and play a crucial role in cell division. One of the main components of centrioles is a protein called",380,128,0.3368
pubmed-summarization,"for over 90% of lesions and was fractionally accompanied with non - invasive transitional cell carcinoma . the differential diagnosis is usually malignant lymphoma , invasive transitional cell carcinoma , squamous cell carcinoma and small cell carcinoma . ( 5 ) note that it is imperative to distinguish between lelca and malignant lymphoma , as primary bladder lymphoma is extremely rare . therefore , immunochemical staining , such as lca and keratin , may be used for differentiation . ( 8) maintained that immunochemical staining techniques were helpful to distinguish bladder lymphoma from undifferentiated carcinoma . pooly differentiated transitional cell carcinoma ( tcc ) with a lymphoid linfiltrate should be distinguishable from lelca in that the latter is characterizied by syncytia of tumor cell , vesicular nuclei and prominent nuclei ( 7 ) . the microscopic findings of lelca are characterized by the indistinct cytoplasmic border and the syncytial growth pattern with the prominent lymphocytic infiltrate . it is important to check cytokeratin in tumor cells on immunochemical staining , in order to ascertain that cells are originated from epithelial cells ( 1 ) . the principal symptoms of lelca were mostly gross hematuria , solitary mass , and tumors measured 1 to 5 cm ( 10 , 12 ) . the epstein - barr virus is regarded as one of factors of the lelca that occurred in the thymus gland ( 9 ) . however , it has not been elucidated that lelca of the urinary system is related with ebv ( 10 ) , gulley et al . ( 11 ) reported that ebv , detected from nasophayneal carcinoma , was not detected in 9 out of 11 cases of lelca . also in 9 cases of lelca reported by holmang et al . for lelca treatment , surgical therapy and chemotherapy can be applied . in the case of small tumors that measure 5 cm and less , turbt is applied , but in the case of big or invasive tumors , radical cystectomy may be applied . as nasopharyngeal lymphoepithelioma is well reacted to chemotherapy , methotrexate , vinblastine , doxorubicin and cisplatin may be applied to chemotherapy ( 7 ) . 13 ) reported that primary chemotherapy was performed on 3 patients with muscle invasive","a 78-yr - old woman presented with gross hematuria for 2 weeks . on cystoscopy , a frond - like mass was observed at the bladder trigone . transurethral resection of bladder tumor was performed for the mass . histopathological findings showed that 90% of lesions were lymphoepithelioma - like carcinoma ( lelca ) and a few lesions were non - invasive transitional cell carcinoma . on microscopy , syncytial growth pattern and indistinct cytoplasmic borders were observed with the severe infiltration of lymphoid cells . the case was followed - up for 8 months without recurrence . this is the first report of a lelca case in korea .",380,110,0.2895
dialogsum,#Person1#: You didn't come to work yesterday. What happened? #Person2#: I had to look after my son at home. #Person1#: What's wrong with him? #Person2#: He has a fever. #Person1#: Is he getting better now? #Person2#: I think so. Thank you.,#Person2# didn't come to work yesterday because #Person2#'s son had a fever.,41,12,0.2927
dialogsum,"#Person1#: May, we are fools to hang out at noon. It's dying hot today. My skin is too weak to be exposed under the summer sun. #Person2#: Do you have any sunscreen lotion? #Person1#: You know, honey, I used it all on the way over. #Person2#: I think I'm getting a heart stroke. #Person1#: The heat is driving crazy and I hate my new hat. #Person2#: Why? It's brand new, and it's perfect on you. #Person1#: But I bought it to get rid of the heat. Now it does nothing but burning my head. #Person2#: Beauty costs, honey. #Person1#: Laugh all you want, whatever. We need to get out of the heat. #Person2#: Walking under the sun is certainly not the way. #Person1#: Give me a break. It's not funny. #Person2#: Right. Sorry. Anyway, the radio said that it'll rain later today. #Person1#: Hope so! Good thing is that autumn is just around the corner.","#Person1# and May are hanging out, but it's dying hot today. #Person1# suggests getting out of the heat, and #Person2# says it'll rain later today.",155,25,0.1613
scientific_lay_summarisation-elife-norm,"that, in yeast treated with the elongation inhibitor cycloheximide, each ribosome protects a footprint of 28 nucleotides (nt), confirming earlier reports (Steitz, 1969; Wolin and Walter, 1988). While performing ribosome-profiling experiments in Saccharomyces cerevisiae, we serendipitously noticed a population of smaller ribosome-protected fragments. To better capture these fragments and to investigate their origins, we revised the ribosome-profiling protocol originally established by Ingolia et al. Our experiments revealed that, in the absence of cycloheximide, the small ribosome-protected fragments were abundant, consistent with an early observation of short ribosome footprints in the absence of cycloheximide (Wolin and Walter, 1988). We show here that the small fragments originate from ribosomes in a conformation distinct from that previously observed in the presence of cycloheximide. The ability to discern distinct ribosomal structural states by ribosome profiling has given us insight into how codon, tRNA, and amino acid identity and translational speed relate to ribosome structure. This additional dimension of ribosome-profiling data will provide a valuable new layer of molecular and mechanistic information, at codon resolution, for future studies of translation. We began our investigation of ribosome footprint size by isolating ribosome-protected mRNA fragments from yeast using a modified ribosome-profiling procedure. The standard ribosome-profiling protocol includes a size selection for RNA fragments of around 28 nt. To eliminate the bias against smaller fragments, we broadened the initial size range and selected RNA fragments between 18 and 32 nt after RNase I digestion. By selecting fragments in this broader size range, and, importantly, by carrying out the entire procedure in the absence of cycloheximide or other inhibitors, we observed two clearly distinct, abundant populations of ribosome-protected mRNA fragments (‘footprints’), 28–30 nt and 20–22 nt long. We visualized fragment lengths and positions with a three-dimensional ‘metagene’ representation: sequence reads representing the ribosome-protected fragments from all expressed genes were aligned relative to the start codon of the corresponding gene and tallied by fragment length and position to show the average pattern of translation along all annotated coding regions (2A–C, — 1). 10. 7554/eLife. 01257. 004Figure 2. Ribosome-protected fragment positions and size distributions from yeast not treated with elongation inhibitors. (A) The position of each fragment was calculated relative to the start codon of its gene. The 5′ end positions (x axis) and lengths of all fragments (y axis) were","To make a protein from a gene, the gene is first transcribed to produce a molecule of messenger RNA (mRNA), which then passes through a molecular machine called a ribosome. The ribosome reads the genetic code in the mRNA in groups of three letters at a time, and each triplet of letters (or codon) represents an amino acid. The ribosome then joins the relevant amino acids together to build a protein. The ribosome processes about six amino acids per second, on average, but the mRNA is not fed through at a constant rate. Instead, the ribosome changes its shape to ratchet along the mRNA from one codon to the next: it then reads the new codon and adds another amino acid to the protein. However, many of the",380,128,0.3368
pubmed-summarization,", 5 ] . mean bvca pre - operatively was 1.22 log - mar units ( 1.10 - 1.22 log mar units ) . post - operatively , mean bcva was 1.10 log mar units ( 1.0 - 1.52 log mar units ) . improvement of visual acuity was registered in all patients ( 100% ) [ figs . 2 , 4 , 6 ] . there were no intraoperative or post - operative complications . demographic and clinical profile of patients pre - operative optical coherence tomography of patient one post - operative optical coherence tomography of patient one pre - operative optical coherence tomography of patient three post - operative optical coherence tomography of patient three pre - operative fundus photo of patient one post - operative fundus photo of patient one the improvement in technique and development of finer instrumentation in vitreo - retinal surgery has significantly improved the surgical outcome of macular holes in terms of anatomical and functional success . the vitrectomy for treatment of macular hole study group showed a clear benefit in closure rates and final visual acuity with surgery versus observation for stage iii and iv macular hole . the single most reliable factor affecting the surgical outcome following surgery is the size of the hole . a number of studies have established that the mld of the hole is closely related to the rate of anatomic success . also , it has been shown that the most favorable outcomes for visual recovery were associated with better initial visual acuity . among all the different techniques for macular hole surgery , the one with the most positive effect on final outcome is vitrectomy with ilm peeling , in order to release tangential forces acting on the macular hole ( mh ) . in addition to promoting hole closure , peeling of the ilm also reduces the probability of its reopening . dye assisted technique is safe and useful in visualizing the ilm , leading to the performance of successful peeling of ilm with minimal damage to the retina . brilliant blue selectively stains the ilm and can be safely used for staining the ilm . the peeled - off ilm contains mller cell fragments which can induce gliosis and helping in closure","we are presenting the initial results of inverted internal limiting membrane ( ilm ) flap technique for large macular hole . five eyes of five patients with large diameter macular hole ( > 700 m ) were selected . all patients underwent inverted ilm flap technique for macular hole . anatomical closure and functional success were achieved in all patients . there was no loss of best - corrected visual acuity in any of the patients . inverted ilm flap technique in macular hole surgery seems to have a better hole closure rates , especially in large diameter macular holes . larger case series is required to assess the efficacy and safety of this technique .",380,116,0.3053
pubmed-summarization,"most nis have a significant effect since they lengthen hospital stays , increase mortality , and increase complications . at present , studies of nis in pediatric patients with neoplastic diseases are under reported in thailand . to determine ( 1 ) the incidence of nis among pediatric patients with neoplastic diseases , ( 2 ) sites of nis , ( 3 ) causal organisms , and ( 4 ) outcomes of nis . the study was conducted in the 32-bed pediatric hematology / oncology ward of the chiang mai university hospital , chiang mai , thailand . patients in this ward are up to 15 years old and all have neoplastic diseases . we excluded those patients who ( 1 ) had fever of unknown origin , since we could not find any other clinical or radiological signs of infection as well as isolate any causative organisms and therefore could not classify them as having an ni with certainty , ( 2 ) received any antibiotic prophylaxis , and ( 3 ) had viral - related illness diagnosed by clinicians . the clinical symptoms of each patient were monitored daily from admission until hospital discharge by pediatricians and nurses . the findings were recorded during admission on a data extraction form that included demographic data , discharge diagnoses , intrinsic risk factors , extrinsic risk factors , causal organisms , and treatment outcomes . the definitions for nis were based on the criteria outlined by the us centers for disease control and prevention in 2004 . neoplastic diseases in pediatric patients were classified as follows : hematologic neoplasia ( acute lymphoblastic leukemia ( all ) , acute myeloid leukemia ( aml ) , non - hodgkin 's lymphoma , hodgkin 's disease ) , solid tumors ( bone tumors , rhadomyosarcoma , central nervous system tumors , neuroblastoma , and wilm 's tumor ) , and others ( schwanoma , hepatoblastoma , and lymphangioma ) . the data were analyzed by calculating ni rates per 1000 days of hospitalization and per 100 admittances . the relationship between ni rates and various extrinsic factors was analyzed using a chi - square test when there was a need to compare proportional data , using a level of 95% confidence interval .","background . pediatric patients with neoplastic diseases are more likely to develop nosocomial infections ( nis ) . nis may prolong their hospital stay , and increase morbidity and mortality . objectives . the objectives of this study were to determine : ( 1 ) the incidence of nis , ( 2 ) sites of nis , ( 3 ) causal organisms , and ( 4 ) outcomes of nis among pediatric patients with neoplastic diseases . methods . this study was a prospective cohort study of pediatric patients with neoplastic diseases who were admitted to the chiang mai university hospital , thailand . results . a total of 707 pediatric patients with neoplastic diseases were admitted . forty - six episodes of nis in 30 patients were",380,128,0.3368
dialogsum,"#Person1#: May I take your order? #Person2#: We'd like this course for two, please. #Person1#: I'm afraid this course is for four persons. #Person2#: Well, can't you make it for two only? #Person1#: I'm afraid not, sir. #Person2#: I see. Well, what do you recommend then? #Person1#: I would recommend a soup with two or three small dishes. #Person2#: Right, we'll have these three. #Person1#: Would you like rice with your meal? #Person2#: No, thanks. #Person1#: Thank you, sir. Just a moment, please.",#Person2# orders a soup with small dishes on the recommendation of #Person1#.,83,12,0.1446
pubmed-summarization,"patients with ibd should be periodically examined regarding their dermatologic conditions . in a previous report from iran , the prevalence of dermatological manifestations was reported to be 5.9% in patients with ibd with a higher rate in crohn s disease ( 7.29% ) compared with patients with ulcerative colitis ( 4.07% ) . they were more common in women ( 52% ) than in men ( 48% ) . one of the rare dermatological manifestations in patients with ibd is pyoderma gangrenosum . which is more common in patients with ulcerative colitis . since pyoderma gangrenosum is a rare occurrence , its explicit prevalence is unknown , but generally it has been estimated to occur in 3 - 10 million patients annually . in iran , the prevalence of pyoderma gangrenosum in patients with ulcerative colitis has been reported to be 1.4% . the diagnosis of pyoderma gangrenosum is based on physical examination , and examining the lesions regarding its type , number , size , and location as well as associated symptoms of ulcerative colitis . most pustular lesions in patients with ibd should be considered as pyoderma gangrenosum variants and be treated accordingly . even though histopathologic examination is not deemed diagnostic for pyoderma gangrenosum , skin biopsy should be performed to rule out other conditions simulating pyoderma gangrenosum . pyoderma vegetans is a sign of ibd , but rarely occurs in iranian patients . in case of facing pyoderma vegetans in a patient without significant medical history , the mean age for the onset of dermatological manifestations in iranian patients with ibd is 31 years . the patient is a known case of ulcerative colitis limited to her left colon for 15 years under irregular treatments . she was receiving unknown herbal medications for a long time and discontinued her standard treatments in the past three years . she had intermittently developed skin lesions diagnosed as pyoderma gangrenosum in her shoulder , thigh , and genital areas during the past 4 years ( ) . ( a ) pyoderma gangrenosum on the right thigh , ( b ) pyoderma gangrenosum on the shoulder , ( c ) pyoderma gangrenosum on the genital area six months before admission to our center , she developed a small mucosal","some dermatologic manifestations are common in ulcerative colitis ( uc ) . herein , we present a 36-year - old woman with ulcerative colitis and uncommon nasal mucosa pyoderma vegetans . the patient presented to our hospital with symptoms of active colitis and a concomitant 345 cm dermato - mucosal lesion in her left nasal lumen . after surgery of the mucosal lesion , the treatment for her active colitis was initiated with intravenous infliximab and oral asacol . after a 1-year follow - up , no sign of recurrence favoring mucosal lesion was noted and symptoms of ulcerative colitis were managed properly .",380,104,0.2737
pubmed-summarization,"adding a reducing / antioxidant system . practically , 50 l of ferric chloride reagent are transferred into the cuvette containing the thiocyanate derivative reagent . the resulting colored solution , after gently mixing by inversion , undergoes 550 nm photometric reading . then , 10 l of sample milk are added in the same cuvette and the obtained solution is gently mixed and incubated into the thermostatic block for 5 min at 37c . bap test , by exploiting the same chemical principle of the well - known ferric reducing ability of plasma ( frap ) test i . e. the reduction of ferric to ferrous ions provides a reliable measure of biological antioxidant potential of blood plasma and food . an unpaired t test was used for comparison of numerical data between the two groups . statistics were compiled using spss10.0j ( spss inc , chicago , il ) and graph pad prism 4 ( graph pad software , inc . , san diego , ca ) . simple linear regression analysis was used to determine the correlation between different postnatal ages in days and tac . the breast milk was centrifuged at low speed ( 500 g for 25 min ) to settle out the suspended cellular components . next , the cellular components were removed and the decelled milk was centrifuged at high speed ( 5000 g for 30 min ) to separate it into defatted milk and fat content . the same method was used to prepare defatted milk using two types of formula milk having a composition similar to the breast milk of japanese women , and the measurements taken ( table 1 ) . tac levels were determined using the biological anti - oxidant potential ( bap ) test , which is based on the ability of a colored solution , containing a source of ferric ( fe ) ions adequately bound to a special chromogenic substrate , to decolour when fe ions are reduced to ferrous ions ( fe ) , as it occurs by adding a reducing / antioxidant system . practically , 50 l of ferric chloride reagent are transferred into the cuvette containing the thiocyanate derivative reagent . the resulting colored solution , after gently mixing by inversion ,","this study aimed to consider the significance of breast milk in preventing oxidative stress by comparing total antioxidant capacity ( tac ) in breast milk and formula milk for premature infants , demonstrating the relationship between tac in breast milk and postnatal age in days . we used the biological anti - oxidant potential test , a new method to measure tac in breast milk . breast milk for premature infants were stored at 20c and thawed within 48 h of collection . we measured tac in two types of formula milk in the same way . tac was clearly higher in breast milk than formula milk . although a negative correlation was observed between tac in breast milk and age when collected , tac was always higher",380,128,0.3368
scientific_lay_summarisation-elife-norm,"defects, especially in the brain, result in severe and often lethal developmental disorders (Cylwik et al. , 2013). Although the primary organelles of the secretory pathway were first described in neurons (Golgi, 1989; Nissl, 1903), little is known about the N-glycosylation of neuronal membrane proteins. Numerous mRNAs encoding surface and secreted proteins are localized to dendrites (Cajigas et al. , 2012). Yet, how dendritic secretory cargo is processed after local synthesis is still debated. In mammals, neuronal dendrites contain ER, ER-exit sites and ER-Golgi intermediate compartments (ERGIC) and occasionally Golgi outposts, but, for the most part lack canonical Golgi membranes (Torre and Steward, 1996; Gardiol et al. , 1999; Krijnse-Locker et al. , 1995; Horton and Ehlers, 2003; Hanus and Ehlers, 2008; Cui-Wang et al. , 2012; Hanus et al. , 2014). It is thus conceivable that, depending on their synthesis in the soma or dendrites, nascent cargo visits distinct sets of secretory subcompartments, and hence acquire specific types of N-glycans. For example, it is believed that nascent neurotransmitter receptors may follow multiple and specific secretory itineraries (Jeyifous et al. , 2009), but whether this impacts their glycosylation is unknown. Intriguingly, Concanavalin A (ConA), a mannose-binding lectin, has been widely used to block the desensitization of plasma-membrane localized AMPA and kainate glutamate receptors (Reiner and Isacoff, 2014; Hoffman et al. , 1998; Evans and Usherwood, 1985). From a cell-biological perspective, this is puzzling as core-glycosylated (mannose-rich) N-glycans are typically not found at the cell-surface (Moremen et al. , 2012; Aebi et al. , 2010; Grieve and Rabouille, 2011). Indeed, a specific sensitivity to the glycosidase EndoH (which cleaves mannose-rich glycans) is commonly used to identify intracellular immature membrane proteins in total cellular lysates (Shi et al. , 2010; Greger et al. , 2002; Tomita et al. , 2003; Sans et al. , 2001; Tucholski et al. , 2013a). Here we demonstrate that hundreds of neuronal surface membrane proteins are indeed core-glycosylated, resulting in the neuronal membrane displaying atypically high and activity-dependent levels of ConA-reactive species. We found that while N-glycosylation is generally required for the proper expression of membrane proteins at the neuronal surface,' immature' core-glycosylated proteins are sufficient to sustain dendritic development and synaptic transmission, indicating that these proteins are fully functional. Focusing on candidate neurotransmitter receptors and auxiliary","Information is carried around the nervous system by cells called neurons. The ability of neurons to communicate with each other relies on many proteins that are found on the surfaces of the cells. Like in all animal cells, surface proteins are made inside the cell in a compartment called the endoplasmic reticulum. During this process, one or several complex sugar molecules are usually added to newly made proteins. These sugar molecules are then modified as the proteins leave the endoplasmic reticulum and pass through another compartment called the Golgi apparatus on the way to the cell membrane. The precise number and structure of the sugar molecules attached to the protein define its glycosylation profile. Neurons receive information from other neurons at branch-like structures called dendrites, which trigger electrical",380,128,0.3368
dialogsum,"#Person1#: Did you clean your room today? #Person2#: No, not yet. #Person1#: Well, when were you planning on doing that? #Person2#: I'm going to clean it up later. #Person1#: Didn't I ask you to clean it up earlier? #Person2#: I'm going to clean it. #Person1#: I want you to vacuum in your room, and don't forget to dust everything. #Person2#: I know. I'll do it. #Person1#: Make sure you clean it up before you do anything else. #Person2#: I'm not going anywhere until later, so I'll clean it then.",#Person1# urges #Person2# to clean #Person2#'s room as #Person2# didn't clean it up as told.,89,15,0.1685
dialogsum,"#Person1#: Steve, you look pale. What happened? #Person2#: I didn't sleep a wink last night. #Person1#: Did you have something on your mind? You look so concerned. Maybe I can help you. #Person2#: Well, I am under a lot of pressure. My boss is very pushy. He assigned me three projects. Now the deadlines are near, and I still have not finished all of my projects. #Person1#: Is there anything I can do to help you? #Person2#: Well, I guess no one can help me but myself. For the moment, I just need someone to talk to, so that I can relieve my stress.",Steve tells #Person1# he's stressed because he hasn't finished all the projects his boss assigned to him.,104,17,0.1635
scientific_lay_summarisation-elife-norm,"To investigate the mechanisms by which β-subunits influence Nav channel function, we solved the crystal structure of the β2 extracellular domain at 1. 35Å. We combined these data with known bacterial Nav channel structural insights and novel functional studies to determine the interactions of specific residues in β2 with Nav1. 2. We identified a flexible loop formed by 72Cys and 75Cys, a unique feature among the four β-subunit isoforms. Moreover, we found that 55Cys helps to determine the influence of β2 on Nav1. 2 toxin susceptibility. Further mutagenesis combined with the use of spider toxins reveals that 55Cys forms a disulfide bond with 910Cys in the Nav1. 2 domain II pore loop, thereby suggesting a 1: 1 stoichiometry. Our results also provide clues as to which disulfide bonds are formed between adjacent Nav1. 2 912/918Cys residues. The concepts emerging from this work will help to form a model reflecting the β-subunit location in a Nav channel complex. Voltage-gated sodium (Nav) channels are part of membrane-embedded signaling complexes that initiate the rising phase of action potentials, a crucial event in generating and propagating electrical signals throughout the human body (Hille, 2001; Catterall, 2012). As key components of these protein assemblies, β-subunits (1) modify Nav channel-gating properties; (2) regulate channel trafficking and localization to distinct surface compartments; and (3) influence channel oligomerization (Calhoun and Isom, 2014; Namadurai et al. , 2015). Moreover, β-subunits can alter the toxin pharmacology of Nav channels (Gilchrist et al. , 2014), a concept that has been exploited to detect their presence in heterologous expression systems or native tissues (Wilson et al. , 2011; Zhang et al. , 2013; Wilson et al. , 2015; Gilchrist et al. , 2013). Structurally, β-subunits are single-transmembrane segment glycoproteins with a short cytoplasmic C-terminal tail and a large V-type immunoglobulin (Ig) extracellular domain that may participate in homophilic and heterophilic interactions, cell adhesion, and cell migration (Calhoun and Isom, 2014; Namadurai et al. , 2015; Brackenbury et al. , 2008). Although all β-subunits belong to the Ig family, recent atomic resolution information for the β3 and β4 extracellular domain revealed substantial differences in their 3D structure (Gilchrist et al. , 2013; Namadurai et al. , 2014). Given their distinct features and functional roles, it has now become clear that each β-subunit structure","Our bodies run on electricity. The brain, heart and some other organs depend on small electrical signals that are generated by ions moving through specialized protein complexes that sit in the membrane surrounding a cell. One of these channels is a ‘sodium channel’, through which positively charged sodium ions move. Tiny changes in the structure of the sodium channel can cause severe conditions such as epilepsy and heart arrhythmias, so it is crucial that we know how it works Sodium channels consist of different protein building blocks (called α and β) and it was not known exactly how these come together to form the full channel complex. However, previous studies hinted at which parts of the β building block make contact with the α protein. Now, Das, Gilchrist",380,128,0.3368
dialogsum,"#Person1#: I'd like to buy one of these refrigerators. Do I have to pay in cash? #Person2#: No, we have an easy-payment plan. One-third down, and the balance in six months. #Person1#: Fine. Will you work out the details, please? #Person2#: Certainly. Would you sit here please? I'll call our credit manager. #Person1#: Thank you. #Person2#: It's just a formality, but for hire purchase we usually require references. #Person1#: What kind of references do you need? #Person2#: Perhaps your employer could supply us with one. #Person1#: I'm sure he could, but I prefer not to bother him. Would my bank do? #Person2#: Certainly. A simple letter from your bank would be quite satisfactory.",#Person1# wants to buy a refrigerator. #Person2# tells #Person1# #Person1# can pay by an easy-payment plan and explains it in detail.,113,21,0.1858
pubmed-summarization,"a 53-year - old african man was diagnosed with unknown primary undifferentiated carcinoma with mediastinal lymph nodes and thrombosis of superior vena cava in 1993 . the patient was initially treated by 8 cycles of chop ( cyclophosphamide , adriamycin , vincristine , and prednisone ) . he relapsed in 1996 with spinal bone metastases treated by laminectomy , radiotherapy and pfl - vp16 ( cddp , 5fu , leucovorin , etoposide ) . in 1999 he relapsed again with mediastinal lymph nodes treated by 3 cycles of navelbine and cisplatin followed by 3 cycles of carboplatin and navelbine with > 70% treatment response . biopsy at that time revealed large - cell carcinoma of bronchial or thymic origin . in 2002 newly discovered bone , pulmonary and mediastinal metastases were treated successively with taxotere / gemcitabine ( 6 cycles ) , navelbine / xeloda ( 6 cycles ) , iressa ( 6 months ) and tarceva ( 8 months ) . in 2005 , pemetrexed was maintained for only 4 cycles , then was suspended due to hematoxicity despite clinical efficiency . no maintenance treatment was used until april 2007 , when new bone metastases were discovered . the patient was hence treated with pemetrexed , as it once showed its efficacy in 2005 . after the sixth cycle , laboratory examination revealed serum creatinine 400 mol / l , metabolic acidosis ( plasma bicarbonate 21 mmol / l ) , sodium 145 mmol / l , potassium 4,5 mmol / l , urea 21 mmol / l . a 24-h urine collection on the 2nd hospital day revealed a 0.55 g proteinuria without hematuria or leukocyturia . a kidney biopsy was performed showing acute tubular necrosis ( atn ) associated with chronic interstitial fibrosis ( . his current renal function remained stable after 6 months follow - up of the acute renal failure ( arf ) episode with a stable serum creatinine level of 380 mol / l . our patient experienced severe acute kidney injury related to atn and interstitial fibrosis following sequential treatment with pemetrexed for a metastatic undifferentiated carcinoma . only few cases of arf due to pemetrexed have been reported . in a patient treated for metastatic non - small cell lung cancer ,","we report a patient with unknown primary undifferentiated carcinoma who developed acute renal failure associated with interstitial fibrosis following pemetrexed therapy . despite drug withdrawal , renal function remained altered and the patient experienced chronic renal insufficiency . pemetrexed disodium ( alimta ) is a multitargeted antifolate agent approved by the food and drug administration ( fda ) for patients diagnosed with mesothelioma and non - small cell lung cancer . this drug is almost exclusively cleared by renal excretion . the most common side effects are hematologic dose - limiting toxicities and nonhematologic toxicities including fatigue , diarrhea , nausea , mucositis and rash . although few cases of renal failure have been published , no study has reported on the renal pathological findings in this setting",380,128,0.3368
dialogsum,"#Person1#: French is so hard, do you know what's the most difficult part for me? #Person2#: The grammar? #Person1#: Yes, but only one particular area. I can't remember if a word is male or female. #Person2#: You have to just remember those. #Person1#: But there are so many and I can't find a pattern. For instance, the moon is female and the sun is male. I know those are common in different languages, but a chair is female and hair is male. I think that hair would be considered female. I just don't get it. #Person2#: It can be very confusing, don't let it get you down, Andy. You're doing well this term. One bad quiz score will hardly affect your grade. Your reading is excellent and so is your writing, you'll get used to this part of the language soon enough.",Andy thinks it difficult to learn French because it's hard to remember if a word is male or female. #Person2# encourages Andy.,142,22,0.1549
dialogsum,"#Person1#: How is the college search going? #Person2#: It's a huge headache. I have no idea what I want to do. #Person1#: But don't you want to study music? Shouldn't it be easy? #Person2#: It should be, but there are too many options. My grades are good enough that I have a lot of choices, but after that. . . #Person1#: I know. You have to decide if you want to attend a school in a city or in the country, a big school or a small school, a public or private school. . . #Person2#: Yup, you understand. And my parents are trying to pressure me into going to a Catholic college. They both attended one and think that it combines a good education with good discipline. And the tuition is usually pretty low. #Person1#: I see. Well, don't forget to talk to the college counselor at the school. He usually gives good advice and can help point you in the right direction. He gave me some information, and next week I'm going to take a look at some of the colleges he recommended. #Person2#: Thanks for the information. And good luck in your college search.",#Person2# has a headache on #Person2#'s college search because there are too many options. #Person2#'s parents also give #Person2# pressure. #Person1# recommends #Person2# to get advice from the college counselor. #Person2# is grateful.,197,33,0.1675
dialogsum,"#Person1#: Excuse me, does this bus go to the new bookstore? #Person2#: No, you'll have to get off at the bank, and take a No. 50. #Person1#: Thank you. How much is the fare to that stop? #Person2#: One dollar. #Person1#: How many stops are there? #Person2#: Two stops after this one. #Person1#: Could you please tell me when we get there? #Person2#: Sure. #Person1#: By the way, do I need a transfer again after No. 50? #Person2#: No, a No. 50 will take you right there. #Person1#: Thank you.",#Person2# tells #Person1# to get off this bus and take a No.50 to the bookstore.,90,15,0.1667
pubmed-summarization,"the total number of pathology reports was used with one indicating patients having egd done and 0 otherwise ( v1 ) . both user - define phrases ( high - risk phrases , or v2 ) and automatically extracted phrases ( n - gram phrases generated from our machine learning program , or v3 ) were chosen to evaluate the effectiveness of utilizing pathology reports . for the laboratory category , both the laboratory results ( v4 ) and total number of labs done were used ( v5 ) . for the icd-9 category , the total number of cd icd-9 codes assigned ( v6 ) was used for classification . variables for celiac disease classification to evaluate the effectiveness of using different combinations of variables and feature selection methods , we further developed two additional set of variables based on the aforementioned six sets of variables above ( v1v6 ) . combining all first six categories of variables created the variable set 7 ( v7 ) . automatically selecting features out of v6 using a feature selection algorithm resulted in the variable set 8 ( v8 ) [ table 1 ] . for expert - knowledge - driven feature selection , we identified a list of nine key phrases described by clinicians as commonly used in pathology reports as indicators of high - risk cd . these nine key phrases , which were all converted to lower cases , included brunner 's gland hyperplasia , flattening villi , intraepithelial lymphocytes , marsh gland stage , marsh lesion , marsh s3 lesion , shortened villi , villous blunting , and villous atrophy . each key phrase was first converted to a binary variable with the value of one indicating the phrase existed in the pathology report and 0 otherwise . automatically extracted n - gram features were phrases generated using weka , an open source java - based machine - learning program , developed by the university of waikato , new zealand . the maximum number of words included in n - gram feature was chosen to be three resulting in a large set of text features consist of uni- , bi- and tri - grams . we only collected phrases up to trigrams because the length of the longest","background : celiac disease ( cd ) is a common autoimmune disorder . efficient identification of patients may improve chronic management of the disease . prior studies have shown searching international classification of diseases-9 ( icd-9 ) codes alone is inaccurate for identifying patients with cd . in this study , we developed automated classification algorithms leveraging pathology reports and other clinical data in electronic health records ( ehrs ) to refine the subset population preselected using icd-9 code ( 579.0).materials and methods : ehrs were searched for established icd-9 code ( 579.0 ) suggesting cd , based on which an initial identification of cases was obtained . in addition , laboratory results for tissue transglutaminse were extracted . using natural language processing we analyzed pathology reports from",380,128,0.3368
dialogsum,"#Person1#: This is the good life! We have it good don't you think? #Person2#: Yeah of course! Although, don't you ever wonder what ' could have been '? #Person1#: What do you mean? #Person2#: Well, sometimes I think of how things could have turned out if I had done things a little differently. #Person1#: For example? #Person2#: Like for example, if I hadn't studied architecture, I would have become an artist like I wanted to. #Person1#: I see. Yeah now that I think of it, I wouldn't have gotten married if I hadn't moved to this town and met Sally. #Person2#: You see! Everything happens for a reason! We wouldn't even have met if I hadn't been in that car accident ten years ago! #Person1#: Well, I have no regrets! #Person2#: I'll drink to that!",#Person1# and #Person2# talk about what life could have been if they had done things differently.,135,16,0.1185
dialogsum,#Person1#: Hi! Weren't you two at the English Evening yesterday? #Person2#: Yes. How did you like it? #Person1#: I thought it was great! I'm Jeff. What are your names? #Person2#: I'm Allison and this is Melissa. #Person1#: Nice to meet both of you.,Jeff meets Allison and Melissa after the English Evening.,43,9,0.2093
dialogsum,"#Person1#: Jack, would you like to come to my house with your wife for dinner at six tomorrow evening? #Person2#: We would like to. Who else will be there? #Person1#: Well, I also invite the White's. #Person2#: That sounds great. I enjoy making friends, chatting with others. I always stay at home and feel bored. By the way, is it a formal dinner or informal one? #Person1#: Informal, of course, just feel at home. #Person2#: Great! Oh, I can't wait.",#Person1# invites Jack and his wife to have dinner in #Person1#'s house tomorrow evening.,80,14,0.175
dialogsum,"#Person1#: This is today's schedule. At eight thirty, conference with the department managers. At 9 o'clock, live for the workshop where you'll award prizes to the stafffor preventatives. #Person2#: That's great. What are the prizes? #Person1#: 3000 RMB as bonus for each person. #Person2#: To encourage the staff increases. #Person1#: Ok. Next thing is laying the corner-stone for the new plant at 10 AM. At 12 AM, back here for lunch. #Person2#: What about the afternoon? #Person1#: At 2 PM, give a presentation here with the press. At four o'clock sharp, have dinner with Mr. Smith, manager of NCC.",#Person1# tells #Person2# about today's schedule of #Person2# in detail.,99,10,0.101
dialogsum,"#Person1#: What's the life expectancy in your country? #Person2#: I'm not sure, but probably about 75 years. How about in your country? #Person1#: About 70, I think. This newspaper article talks about the problems of an aging population. It's a problem that will soon affect most of the world. #Person2#: I heard that the government might need to increase the retirement age, because otherwise there will not be enough workers to support the young and the elderly. #Person1#: Perhaps we need to have more babies! Tina gave birth to a baby boy yesterday. #Person2#: Did she? That's great. However, if we have too many children, that will have a bad effect on the enviroment. #Person1#: How's your son these days? #Person2#: Oh, he's fine. Kids seem to grow up very quickly nowadays. #Person1#: He'll be a teenager before you know it! Teenagers are often rebellious! When do you think it is a good age to have children? #Person2#: I had mine when I was 24. that's a little young. I'd suggest you wait until you are in your late twenties. , or even in your early thirties if you have a good career. #Person1#: Yes, I think you're right. I'm thinking about having a child, but not just yet. #Person2#: Is there a big generation gap between parents and their children in you country? #Person1#: Yes, there is. Teenagers do not want to live traditional lives. They want to go out, have fun, and explore the world. They want to develop their own view of life. Parents usually try to discourage them, but they don't often succeed. #Person2#: Parents usually give their children more freedom in my country. Sometimes they give them too much freedom. #Person1#: It's almost impossible to get the right balance. If you are too strict, kids might ignore you. If you are too lenient, they might go wild.","#Person1# thinks the aging problem is very serious in the world and #Person2# mentions the government might need to increase the retirement age. #Person1# suggests having more babies, which is not a good solution but changes their topic to children and the relationship between children and parents in their countries.",312,50,0.1603
dialogsum,"#Person1#: what a nice uniform! #Person2#: thanks; do you like it? #Person1#: not really. I was being sarcastic. Does it come with the job? #Person2#: yes, everyone on the sales floor has to wear one. They're supposed to make us look more professional. #Person1#: they're not actually that bad. They could be worse. What do you think about it? #Person2#: I don't mind it, actually. I don't have to worry about what I'm going to wear every day. #Person1#: so are you enjoying your new job? #Person2#: it's much better than my old one. My new boss is great. #Person1#: how do you like working in sales? #Person2#: I like the fact that I get to work with people. It makes the day go by much faster. #Person1#: that's good. Have you met Jane yet? She's the intern in the international travel department. #Person2#: yeah, I've met her. She's a genius saleswoman! #Person1#: I know! She could sell fridges to Eskimos! #Person2#: how do you know her? #Person1#: she's my cousin. #Person2#: why didn't you tell me about that before? #Person1#: I don't know. I didn't think it was that interesting. #Person2#: well, now that I know that, maybe we should all go out for dinner sometime. #Person1#: that's a good idea. Let's discuss after work.","#Person1# doesn't mind wearing salespersons' uniform and enjoys this new job. #Person1# finds Jane, a genius saleswoman, is #Person2#'s cousin and suggests going out together sometime.",216,26,0.1204
scientific_lay_summarisation-elife-norm,"with 7 chromosomes. (F) Frequency of each spindle class among the progeny of XXX wild-type mothers. Insets show polar bodies, marked by asterisks, which were used to identify metaphase II spindles. Bar = 5 μm. : http: //dx. . org/10. 7554/eLife. 06056. 003 Deviations from random segregation are suggested by observations of X chromosomes in Caenorhabditis elegans. In C. elegans, the single unpaired X chromosome from an XXX mother is inherited with unexpectedly low frequency with twice as many haploX ova produced as diploX ova (Hodgkin et al. , 1979). HIM-8 is a zinc finger protein that binds to specific DNA sequences that are enriched on the X chromosome. him-8 mutants have a pairing defect that is completely specific for the X chromosome, resulting in two X univalents and five autosomal bivalents in 95% of diakinesis oocytes (Phillips et al. , 2005). If the two X univalents segregated randomly, him-8 mutants would be expected to produce equal frequencies of nulloX ova and diploX ova. However, Hodgkin et al. (1979) demonstrated a fivefold preponderance of nulloX ova over diploX ova in him-8. Using sex-reversed him-8 XX males, these authors showed the opposite effect in spermatogenesis. Rather than producing the 50% haploX, 25% diploX, 25% nulloX sperm expected from random segregation, him-8 XX males produced 86% haploX, 3% diploX, 11% nulloX sperm, indicating symmetric distribution of univalents during male meiosis. Thus, achiasmate maternal X chromosomes are inherited with unexpectedly low frequency in worms. Five mechanisms might reduce the frequency of trisomic offspring from trisomic or him-8 mothers. First, trisomic embryos might die during embryonic development resulting in undercounting of XXX offspring. This is unlikely in C. elegans because both XXX and him-8 mutant mothers produce a very low frequency of dead embryos (Hodgkin et al. , 1979; Supplementary file 1). A second possibility is that mitotic non-disjunction in the XXX mother results in a mosaic gonad that contains both diploX and triploX oocytes. Selective apoptosis of XXX germ line cells (Bhalla and Dernburg, 2005) would then enrich for XX germ line cells. This does not contribute to the segregation bias in C. elegans, as the most mature diakinesis oocytes in him-8 and wild-type XXX worms have 7 rather than 6 DAPI-staining bodies (Phillips et al. , 2005; this study). A third possibility","Inside cells, DNA is found packaged into structures called chromosomes. Most human and animal cells contain two sets of chromosomes, one inherited from each parent. Chromosomes from one set pair up with the equivalent chromosome from the other set. However, egg and sperm cells only contain one copy of each chromosome, so that when the egg is fertilized, the resulting cell again has two sets of chromosomes. If there are either more or fewer than two copies of a chromosome in the fertilized cell, this can cause birth defects and conditions such as Down syndrome. An egg cell develops from a cell called an oocyte via a process called meiosis. The oocyte first duplicates its DNA so that it contains four copies of each chromosome. The oocyte then",380,128,0.3368
dialogsum,"#Person1#: Emily, what are your plans for this weekend? Andrew and I have decided to go skating this Saturday. Do you want to join us? #Person2#: Sounds interesting. I'd like to, but Sally and I have already made plans. We're going to watch a movie this Sunday. I plan to look up information about the movie on the Internet on Saturday. #Person1#: Cool. What is the name of the movie? #Person2#: Beauty and the Beast. Emma Watson plays the lead role Bell. She is one of my favorite actresses. #Person1#: I once saw the 1991 movie Beauty and the Beast. It is great. #Person2#: Yeah. Actually, the story is adapted from a French fairy tale by Beaumont. I've read that there are some French expressions in the movie. #Person1#: Wow. You have learned much about the movie. Sounds great. You got me wanting to see it. #Person2#: So do you want to join us and enjoy the wonderful story on Sunday? #Person1#: Yes, I do. I will ask Andrew if he would like to. #Person2#: Alright. Then please tell me ahead of time, so that I can book the tickets online in advance. #Person1#: Sure, I will let you know by Saturday evening. #Person2#: OK.","#Person1# invites Emily to go skating with #Person1# and Andrew but Sally and Emily have already decided to watch a movie. They talk about the movie and #Person1# feels like watching the movie, too.",205,34,0.1659
pubmed-summarization,"cervical cancer is a major health challenge with approximately 530,000 news cases and 270,000 deaths annually worldwide despite remarkable advances in screening and prevention through the development of human papillomavirus ( hpv ) vaccine . while the majority of cervical cancer cases can be potentially cured with surgery , chemoradiation or a combination of these strategies , treatment options for recurrent or metastatic disease are limited to pelvic exenteration or palliative chemotherapy . a recent phase iii trial evaluating the combination of cisplatin , paclitaxel and bevacizumab ( monoclonal antibody against vascular endothelial growth factor receptor ) in the first - line treatment of metastatic disease elicited a 50% response rate and median overall survival ( os ) of approximately 17 months ( tewari et al . , 2014 ) . despite these relatively positive data that led to the approval of the first targeted therapy for this disease ( bevacizumab ) , the median progression - free survival of 8 months demonstrates the aggressive behavior of this disease . hence , there is an urgent need to advance the understanding of the molecular abnormalities driving cervical cancer pathogenesis that could lead to novel targeted therapies . comprehensive genomic profiling of metastatic tumors is an increasingly relevant tool to identify somatic alterations leading to additional therapeutic options and a better understanding of tumor molecular pathogenesis . herein , we describe the first three cases of cervical carcinoma harboring fgfr3tacc3 fusions revealed by a next - generation sequencing assay able to detect all classes of genomic alterations including gene fusions . the fusion of the fibroblast growth factor receptor gene 3 ( fgfr3 ) with the transforming acidic coiled - coil containing gene ( tacc3 ) has been described in glioblastoma multiforme , bladder urothelial carcinoma , and non - small cell lung cancer ( wu et al . , 2013 ) . while fgfr mutations have been described in cervical carcinomas , the fgfr3tacc3 fusion has not been reported previously ( cappellen et al . , 1999 ) . this fusion resulting in fgfr pathway activation provided the rationale for treating one of the patients with a fgfr tyrosine kinase inhibitor ( tki ) in a clinical study setting and other molecular alterations involving the pi3k / akt / mtor","cervical cancer epitomizes the success of cancer prevention through the human papillomavirus ( hpv ) vaccine , but significant challenges remain in the treatment of advanced disease . we report the first three cases of cervical carcinoma harboring an fgfr3tacc3 fusion , which serves as a novel therapeutic target . the fusion , identified by comprehensive genomic profiling , activates the fgfr pathway that has been implicated in hpv - driven carcinogenesis . one of the patients whose tumor contained the fgfr3tacc3 fusion was treated with an investigational fgfr tyrosine kinase inhibitor . concomitant molecular alterations involving the pi3k / akt / mtor and raf / mek pathways were also identified and suggest other treatment strategies that deserve investigation . this case series highlights the role of comprehensive",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Some remarkable animal species require an opposite-sex partner for their sexual development but discard the partner’s genome before gamete formation, generating hemi-clonal progeny in a process called hybridogenesis. Here, we discovered a similar phenomenon, termed pseudosexual reproduction, in a basidiomycete human fungal pathogen, Cryptococcus neoformans, where exclusive uniparental inheritance of nuclear genetic material was observed during bisexual reproduction. Analysis of strains expressing fluorescent reporter proteins revealed instances where only one of the parental nuclei was present in the terminal sporulating basidium. Whole-genome sequencing revealed that the nuclear genome of the progeny was identical with one or the other parental genome. Pseudosexual reproduction was also detected in natural isolate crosses where it resulted in mainly MATα progeny, a bias observed in Cryptococcus ecological distribution as well. The mitochondria in these progeny were inherited from the MATa parent, resulting in nuclear-mitochondrial genome exchange. The meiotic recombinase Dmc1 was found to be critical for pseudosexual reproduction. These findings reveal a novel, and potentially ecologically significant, mode of eukaryotic microbial reproduction that shares features with hybridogenesis in animals. Most multicellular organisms in nature undergo (bi) sexual reproduction involving two partners of the opposite sex to produce progeny. In most cases, following the fusion of the two haploid gametes, the diploid zygote receives one copy of the genetic material from each parent. To produce these haploid gametes, a diploid germ cell of the organism undergoes meiosis, which involves recombination between the two parental genomes, generating recombinant product. Recombination confers benefits by bringing together beneficial mutations and segregating away deleterious ones (Dimijian, 2005; Meirmans, 2009). In contrast, some organisms undergo variant forms of sexual reproduction, including parthenogenesis, gynogenesis, androgenesis, and hybridogenesis, and in doing so, produce clonal or hemi-clonal progeny (Avise, 2015; Neaves and Baumann, 2011). In parthenogenesis, a female produces clonal progeny from its eggs without any contribution from a male partner (Avise, 2015; Horandl, 2009). Gynogenesis and androgenesis occur when the fusion of an egg with a sperm induces cell division to produce clonal female or male zygotes, respectively (Lehtonen et al. , 2013). During hybridogenesis, an egg from one species fuses with the sperm from another species to generate a hybrid diploid zygote (Lavanchy and Schwander, 2019). However, one of the parental genomes is excluded during development, in a process termed genome exclusion","Sexual reproduction enables organisms to recombine their genes to generate progeny that have higher levels of evolutionary fitness. This process requires reproductive cells – like the sperm and egg – to fuse together and mix their two genomes, resulting in offspring that are genetically distinct from their parents. In a disease-causing fungus called Cryptococcus neoformans, sexual reproduction occurs when two compatible mating types (MATa and MATα) merge together to form long branched filaments called hyphae. Cells in the hyphae contain two nuclei – one from each parent – which fuse in specialized cells at the end of the branches called basidia. The fused nucleus is then divided into four daughter nuclei, which generate spores that can develop into new organisms. In nature, the mating types of C. neoformans",380,128,0.3368
pubmed-summarization,"development of new - generation dess to reduce the rate of this rare but critical event . apart from the progress in stent platforms ( thinner struts and stent designs ) , recent research in this field has subsequently been focused on the development of new more biocompatible durable polymers or completely biodegradable polymers . third - generation dess using biodegradable polymers , like the biolimus - eluting stent ( bes ) ( nobori ; terumo corporation , tokyo , japan ) , have been developed to overcome the long - term adverse vascular reactions related to the durable polymer . in this article we then discuss the results of recent publications investigating the safety and effectiveness of the use of the third - generation bes ( nobori ) for the treatment of coronary artery lesions . the two major complications of pci , isr and st , have always been the trigger for new stent development.16 indeed , despite the fact that these events are multifactorial , stent structure has been suggested to be one of the leading causes of isr and/or st.1721 isr physiopathology has not yet been fully understood . barotrauma induced by pci is responsible for endothelial denudation and sub - intimal hemorrhages , leading to a local inflammatory response . this inflammatory process induced by vascular damage is thought to be one of the main contributors to the development of restenosis , by promoting vascular smooth muscular cell proliferation and extracellular matrix formation , resulting in neointimal hyperplasia . beside these mechanical factors , other factors have been identified as predictors for isr , including patient - related ( eg , diabetes mellitus , smoking , and renal failure ) and lesion - related ( eg , minimal lumen diameter after pci , severe calcifications , chronic total occlusions , tortuous vessel , and long lesion length ) factors.22 as mentioned above , isr remained the achilles heel of pci until the large use of dess , which were specifically developed to overcome this complication . before the introduction of bare - metal stents ( bmss ) , up to 50% of the patients treated by pci experienced restenosis . even in the bms era , isr remained one of the major limitations of this","first - generation drug - eluting stents have raised concerns regarding the risk of late and very late stent thrombosis compared with bare metal stents and require prolonged dual antiplatelet therapy . despite extensive investigations , the physiopathology of these late events remains incompletely understood . aside from patient- and lesion - related risk factors , stent polymer has been cited as one of the potential causes . in fact , the persistence of durable polymer after complete drug release has been shown to be responsible for local hypersensitivity and inflammatory reactions . third - generation drug - eluting stents with more biocompatible or biodegradable polymers have subsequently been developed to address this problem . in this article , we evaluate and discuss the concept and clinical results",380,128,0.3368
dialogsum,#Person1#: I've been chosen to plan the next family reunion. #Person2#: Fun for you! Do you get to do anything you want? #Person1#: Yep. And I should start planning now. #Person2#: Does everyone usually show up for your family reunions? #Person1#: Just about. There are at least a few hundred in our immediate family alone. #Person2#: How Ay days will the reunion be? #Person1#: Usually it's at least five days and four nights. #Person2#: This is going to be a major production for you!,#Person1# has been chosen to plan the next family reunion. #Person2# asks #Person1# some questions about that.,84,17,0.2024
pubmed-summarization,"calcium level of 8.7 mg / dl , a phosphorous level of 3.6 mg / dl , and a magnesium level of 1.8 mg / dl . neither radiologic study nor neostigmine administration could be performed because of the risk to the fetus . colonoscopy was performed to provide decompression because the patient 's pain and distension worsened after 5 days of conservative care . the colonoscope was passed just beyond the splenic flexure , at which point the lumen was found to be obstructed by a large fecal bezoar ( . 2 ) . attempts to break the fecal bezoar with an endoscopic snare ( olympus disposable electrosurgical snare sd-210u-10 ; olympus medical systems corp . , tokyo , japan ) met with limited success . after suctioning the retained gas and contents of the proximal colon , a drainage catheter ( enbd-7-liguory , 7 fr , 250 cm ; cook medical inc . , winston - salem , nc , usa ) was placed through the working channel of the endoscope . the catheter was irrigated periodically with normal saline to prevent obstruction and ensure that the intestinal contents and gas were drained effectively . the patient 's symptoms improved for a few days after decompression but recurred soon thereafter . additional two attempts at endoscopic decompression were made and a new drainage catheter was inserted in each of the attempts until surgery could be performed . subtotal colectomy with endileostomy was performed electively at a fetal gestational age of 21 weeks . ileorectal anastomosis could not be performed due to the enlarged uterus and was postponed until after delivery . the proximal portion from the cecum to the descending colon was dilated up to 16 cm in diameter and a focally narrowed transitional zone was observed around the sigmoid colon ( . full colonic sections were obtained for histopathological analysis , which revealed no apparent histopathological alteration in the muscularis propria or neural plexuses ( . however , immunohistochemistry for c - kit ( cd 117 ) revealed fewer interstitial cells of cajal ( iccs ) in dilated portions of the colon compared to the undilated part ( . stool passage was normalized after surgery and pregnancy was maintained and resulted in a full - term delivery","chronic intestinal pseudo - obstruction is a rare clinical syndrome which is characterized by intestinal obstruction without occluding lesions in the intestinal lumen and pregnancy is one of the important aggravating factors . here , we report a case of a woman with intractable intestinal pseudo - obstruction that was precipitated by pregnancy . she could not make any stool passage for more than 4 weeks until a fetal gestational age of 17 weeks was reached . however , the patient could be maintained by repetitive colonoscopic decompressions and finally total colectomy could be performed successfully at a fetal gestational age of 21 weeks .",380,105,0.2763
pubmed-summarization,"a patient suffering acute ischemic stroke due to paradoxical embolization of dense fibrous material through a pfo following transvenous lead extraction ( tle ) . endocardial pacemaker leads cause fibrin deposits on their surface which may form sheaths in over 85% of patients 1 or adhere with the vessel walls , tricuspid valves , and endocardium . thrombi can be detected on the leads in around 30% of patients by toe and intracardiac ultrasound 2 , 3 , and findings of asymptomatic pulmonary emboli in up to 15% of patients as well as increased pulmonary pressure point toward a high rate of subclinical embolism in patients with cardiovascular implantable electronic devices ( cieds ) 1 , 3 , 4 . one particular concern is the risk of systemic thromboembolism in patients with intracardiac shunts and cieds ; in all shunts other than pfos , the risk of systemic thromboembolism is doubled 5 and such conditions are at present considered a contraindication for endocardial lead placement 6 . in the case of pfos , the risk is less well documented , but retrospective data points toward a hazard ratio of > 3 for stroke 7 , although study bias may have exaggerated this . tle is a valuable technique for management of device infection and lead failure , and its safety has improved thanks to technological advances and increasing experience . preliminary data from the electra registry 8 , the only prospective european registry of tle , show a relatively low rate of major complications ( 2.53.9% depending on the procedural volume of centers ) . one complication of particular concern when extracting leads is the risk of systemic embolism . indeed , residual fibrous deposits persisting after tle have been described 9 , sometimes large enough as to be described as our case illustrates that these residual deposits may not always be visible with toe , probably because they may be confined to the vessels ( e.g. , innominate or subclavian vein ) but may embolize later . although the rate of stroke seems to be low ( 0.1% ) during tle , our case highlights the potentially dramatic consequences of systemic embolization , even in the absence of visible vegetations on the leads . moreover , current guidelines offer","key clinical messagesystemic embolization is a dreaded complication of transvenous lead extraction ( tle ) , even without visible vegetations . preoperative patent foramen ovale evaluation is important , justifying neurological surveillance or consideration of surgical extraction in selected cases . in case of stroke after tle , mechanical thrombectomy is a successful therapy , and should be readily available .",380,61,0.1605
scientific_lay_summarisation-elife-norm,"Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression. Cancer treatments rely heavily on DNA damaging agents, including radiation and chemotherapeutics, to eliminate cancer cells and decrease tumor burden (Begg et al. , 2011; Lord and Ashworth, 2012; Cheung-Ong et al. , 2013). These cancer therapies activate complex signaling networks, termed the DNA damage response (DDR), that detect and signal the presence of DNA damage to promote cell cycle arrest and DNA repair (Jackson and Bartek, 2009; Ciccia and Elledge, 2010). The apical protein kinase ataxia-telangiectasia mutated (ATM) initiates a large signaling cascade in response to DNA double-strand breaks (DSBs) by phosphorylating many key proteins, including the tumor suppressor p53, to orchestrate the DDR (Shiloh and Ziv, 2013; Stracker et al. , 2013). The DDR regulates cell fate decision pathways including apoptosis, senescence and differentiation. Many of these pathways depend on ATM and/or p53 to enforce tumor suppressive anti-cancer barriers to limit proliferation in response to, and in the presence of, DNA damage (Norbury and Zhivotovsky, 2004; Bartkova et al. , 2005; Gorgoulis et al. , 2005; Bartkova et al. , 2006; Di Micco et al. , 2006; Vousden and Lane, 2007; Sherman et al. , 2011; Roos and Kaina, 2013). However, cancer cells exhibit genome instability (Hanahan and Weinberg, 2011) and often contain endogenous oxidative and replicative damage that can promote genetic alterations to drive malignant transformation (Klaunig et al. , 2010; Hills and Diffley, 2014). Cancer cells evolve a defective","Damaged DNA threatens the normal activity of living cells, so cells use a number of mechanisms to ensure that this damage is repaired. When DNA is damaged, an enzyme called ATM activates several other proteins that ultimately lead to the DNA being repaired. Problems with detecting and repairing damaged DNA have been linked to cancer. Thus, these pathways, including the activity of ATM, were previously thought to only be involved in cancer suppression. Now, Chen et al. report a new cancer-promoting role for ATM. The experiments reveal that reducing the amount of ATM in cancer cells actually made them less able to migrate and less invasive. Likewise, human breast cancer cells in which the levels of ATM had been depleted formed fewer lung tumors than normal breast cancer",380,128,0.3368
scientific_lay_summarisation-elife-norm,"phosphatidylinositol four kinase IIIα (PI4KA) (Berger et al. , 2009; Borawski et al. , 2009; Reiss et al. , 2011; Tai et al. , 2009; Trotard et al. , 2009) and microRNA-122 (miR-122) (Jopling et al. , 2005; Lanford et al. , 2010; Machlin et al. , 2011). miR-122 is highly conserved between humans and other species, including mice, making its expression alone unlikely to explain the weak replication of HCV in murine cells. In an effort to systemically dissect the impact of such replication co-factors during infection, we focused in this study on CypA and how it may contribute to the restricted host range of HCV. CypA is a cytosolic 18 kDa peptidyl-prolyl cis-trans isomerase (PPIase) and a part of the biologically ubiquitous cyclophilin enzyme family (Fischer et al. , 1989), the members of which were first characterized in mammals by their common ability to bind the immunosuppressive drug cyclosporin A (CsA) and their shared cyclophilin-like domain (CLD) which catalyzes the cis-trans isomerization of proline residues (reviewed in Marks, 1996). CypA overexpression has been implicated in a wide variety of human diseases, ranging from cancer to atherosclerosis (reviewed in Nigro et al. , 2013), and it has a demonstrated role in the life cycles of multiple viruses besides HCV (de Wilde et al. , 2018; Frausto et al. , 2013; Li et al. , 2016; Phillips et al. , 2015; Tian et al. , 2010; von Hahn and Ciesek, 2015; Watashi and Shimotohno, 2007; Zhou et al. , 2012). Early work showed that CsA had an inhibitory effect on HCV in chronically infected chimpanzees, but it was not until subsequent in vitro CypA knockdown experiments and dose-response assays with CsA derivatives that CypA was specifically recognized as critical to HCV replication (Chatterji et al. , 2009; Ciesek et al. , 2009; Coelmont et al. , 2009; Kaul et al. , 2009; Liu et al. , 2009b; Yang et al. , 2008b). These studies showed that CypA’s relevance to HCV replication was intimately linked to its PPIase activity, as the introduction of point mutations in the PPIase active site led to impaired viral replication (Chatterji et al. , 2009; Kaul et al. , 2009; Liu et al. , 2009b). Individuals exhibiting an HCV non-permissive phenotype were shown to express a","Hepatitis C is a life-long disease that begins when a virus infects the cells of the liver. Although the infection is curable, it is expensive to treat, and there is not yet a vaccine to prevent the disease. This is largely because the virus that causes hepatitis C, also known as HCV, naturally only infects humans and chimpanzees, which has made it difficult to generate an effective animal model for developing a vaccine. Mice are frequently used as a model for studying disease and can be genetically altered to allow HCV to enter their liver cells. However, once HCV enters mouse cells, it struggles to replicate. As a result, an infection does not develop, and the immune system’s response to the virus cannot be fully explored. Replication of",380,128,0.3368
dialogsum,"#Person1#: I would like to purchase some meat. #Person2#: What kind of meat would you like to get today? #Person1#: First off, I'm going to need a pound of ground beef. #Person2#: A pound of ground beef is $2. 48. #Person1#: That's perfect. #Person2#: What else will you be needing? #Person1#: I'm also going to need three pounds of chicken breasts. #Person2#: The chicken breasts cost $4. 05 per pound. #Person1#: What's the total price for the chicken? #Person2#: It's going to be $12. 15. #Person1#: Okay, I think that will be all for me today.",#Person1# buys some ground beef and some chicken breasts with #Person2#'s assistance.,96,12,0.125
scientific_lay_summarisation-elife-norm,", 1997; Role and Berg, 1996), it is thought that ACh volume transmission in the IPN requires high frequency stimulation of habenular neurons (Ren et al. , 2011). The release of ACh from habenular terminals is consistent with genetic studies demonstrating altered responses to nicotine addiction as a consequence of mutations in nicotinic receptors that are enriched in the MHb-IPN (Antolin-Fontes et al. , 2015; Fowler et al. , 2011; Jackson et al. , 2010; Salas et al. , 2009). Although a clear role for ACh in volume transmission and for nAChRs in nicotine dependence has been established, several observations suggest that ACh may have additional functions in cholinergic neurons. For example, it has been demonstrated in several systems that neurotransmitters can be coreleased (El Mestikawy et al. , 2011; Gras et al. , 2008; Guzman et al. , 2011; Hnasko et al. , 2010; Hnasko and Edwards, 2012; Ren et al. , 2011; Shabel et al. , 2014), and that cooperation between vesicular neurotransmitter transporters located in the same synaptic vesicle (SV) can reciprocally increase the packaging of their respective neurotransmitters into SVs, a process termed vesicular synergy (El Mestikawy et al. , 2011; Gras et al. , 2008; Hnasko et al. , 2010). Furthermore, infusion of glutamate receptor antagonists into the IPN results in decreased nicotine intake (Fowler et al. , 2011) and withdrawal (Zhao-Shea et al. , 2013) suggesting that glutamate-mediated fast synaptic transmission is also important in nicotine addiction. Given evidence that both glutamate and ACh play important roles at habenular-IPN synapses, and that vesicular synergy contributes to the physiology and function of other critical CNS circuits, we were interested in examining the interactions between these transmitter systems in habenular neurons and in determining their contributions to nicotine dependence. To investigate the interactions between glutamate and ACh in the MHb-IPN circuit, we locally eliminated ACh at this synapse by genetic deletion of the ACh-synthesizing enzyme choline acetyltransferase (Chat) in MHb neurons in conditional knockout (cKO) mice. Immunogold electron microscopy revealed that ACh and glutamate vesicular transporters colocalize in a significant fraction of SVs in the central IPN (IPC). Patch clamp recordings showed that glutamatergic miniature excitatory postsynaptic currents (mEPSCs) were smaller in IPC neurons of ChAT-cKO, but unchanged in neurons of the lateral IPN (IPL) which","Neuroscientists are making progress in understanding the brain regions and neural circuits that are involved in reward and addiction. One such region, called the habenula, is found near the center of the brain and sends nerves to another brain region called the interpeduncular nucleus (or IPN for short); this creates a neural circuit that is important for the brain’s responses to nicotine. The habenular-IPN circuit is rich in receptors for a neurotransmitter called acetylcholine. These receptors are also activated by nicotine, the addictive component of tobacco. Neurotransmitters are chemicals that transmit a signal from one nerve to another. These chemicals are packaged into small structures called vesicles, which are found at nerve endings. When a nerve impulse reaches the end of a nerve, it triggers the release of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"been clearly shown in mouse models of SBMA (Katsuno et al. , 2002; Chevalier-Larsen et al. , 2004). Furthermore, the nuclear translocation of AR is also crucial for pathogenesis (Takeyama et al. , 2002; Montie et al. , 2009; Nedelsky et al. , 2010). It has also been suggested that an AR interdomain interaction known as the amino (N) -terminal–carboxy (C) -terminal (N/C) interaction is important for SBMA (Orr et al. , 2010), as are the DNA-binding ability of AR (Nedelsky et al. , 2010) and its post-translational modification including acetylation (Montie et al. , 2011), methylation (Scaramuzzino et al. , 2015), and other modifications (Katsuno et al. , 2012). In addition, several cofactors and regulators of AR can influence SBMA disease pathogenesis (McCampbell et al. , 2000; Taylor et al. , 2003; Palazzolo et al. , 2007; Suzuki et al. , 2009; Nedelsky et al. , 2010; Montie et al. , 2011). Despite extensive studies, however, a precise molecular explanation for SBMA pathology has remained elusive. Given the importance of androgens to SBMA pathogenesis, many approaches to SBMA therapeutics have focused upon depleting androgen levels in patients (Banno et al. , 2009; Katsuno et al. , 2010b; Fernández-Rhodes et al. , 2011; Yamamoto et al. , 2013). Unfortunately, these strategies have not yielded significant results in clinical trials; hence, new approaches are necessary. It has been shown that within prostate cancer cells, wild-type AR physically interacts with Nemo-like kinase (NLK) and that NLK is able to regulate the activity and transcription of AR in this context (Emami et al. , 2009). Interestingly, studies show that NLK interacts either directly or indirectly with a number of neurodegenerative disease-related proteins (Lim et al. , 2006; Ju et al. , 2013), suggesting that it may play an important role in the pathogenesis of neurodegenerative proteinopathies. Indeed, we have found that loss of one copy of Nlk (resulting in a 50% reduction in protein expression) is beneficial in mouse models of the polyQ disease SCA1 (Ju et al. , 2013). NLK is an evolutionarily conserved mitogen-activated protein kinase -like serine/threonine kinase primarily studied in lower model organisms, where it has been linked to a number of signaling pathways (Ishitani et al. , 1999; Ohkawara et al. , 2004; Ishitani et al. , 2010;","Spinal and bulbar muscular atrophy (SBMA) is an inherited disease that eventually leads to degeneration in motor neurons and weakness in muscles. It is caused by a specific genetic mutation in the gene that encodes the androgen receptor protein, which leads to the production of a mutant protein that is larger than normal. Similar mutations in other genes can lead to the development of other so-called ‘polyglutamine’ diseases such as Huntington' s disease and spinocerebellar ataxia. However, the precise details of how these mutations lead to disease symptoms are not known, and there are currently no effective ways of treating these conditions. Previous research has shown that an enzyme called Nemo-like kinase (or NLK for short) regulates the normal androgen receptor in cancer cells. NLK has kinase activity,",380,128,0.3368
pubmed-summarization,"africa , the population size of the city of tshwane in 2011 was roughly equal to 3 million . the city is home to over 5,000 businesses out of which 1,603 businesses operate within the central business district of tshwane , known as pretoria . according to the annual report issued by the city of tshwane metropolitan municipality for the budget year 2010 - 2011 , about 1,734,295 tons of solid waste the solid waste produced by businesses in the city includes trash or garbage such as wood , product packaging , empty bottles , used tyres and car parts , and cans , garden refuse , furniture , clothing , leftover food , newspapers , wires , grease , appliances , paint , pieces of metal , broken containers , sheet metal , used medicine , and the like . these businesses produce massive volumes of solid and liquid waste on a daily basis . taxi ranks , bus stations , open flea markets , food outlets , and small businesses located in pretoria are synonymous with litter , uncontrolled solid and liquid waste , as well as lack of capacity in the efficient management of waste . the annual report released by the city of tshwane metropolitan municipality for the year 2011 shows that massive waste is accumulated during strike action by municipal workers responsible for the removal of waste from households and businesses . the collection , disposal , and processing of waste produced by businesses and households are regulated by legislative policies set out and enforced by the municipality of tshwane and the south african national department of environmental affairs and tourism . the use of an integrated municipal solid waste management system has been shown to be essential for improving overall efficiency in municipal waste management in almost all developed nations of the world . in order for an integrated waste management system to perform efficiently , all relevant stakeholders of the waste chain must play a mutually collaborative role in the collection , disposal , processing and management of waste . a review of the relevant literature shows that such a measure is essential for reducing the overall cost of waste management , and for the protection of the environment . overall efficiency in","objective . the objective was to investigate factors that affect the efficient management of solid waste produced by commercial businesses operating in the city of pretoria , south africa . methods . data was gathered from 1,034 businesses . efficiency in solid waste management was assessed by using a structural time - based model designed for evaluating efficiency as a function of the length of time required to manage waste . data analysis was performed using statistical procedures such as frequency tables , pearson 's chi - square tests of association , and binary logistic regression analysis . odds ratios estimated from logistic regression analysis were used for identifying key factors that affect efficiency in the proper disposal of waste . results . the study showed that 857",380,128,0.3368
dialogsum,"#Person1#: Ahahah! What is that thing on your couch! It just moved! #Person2#: Did you think it wasn't real? That's my pet lizard. #Person1#: You have a pet lizard? Somehow I never would have imagined that. #Person2#: His name is Grunt. Come closer and I'll properly introduce you. #Person1#: Does it bite or scratch? #Person2#: No, he's perfectly harmless. And he's not afraid of strangers either. Here, hold him. #Person1#: Wow. He's heavy! And his skin feels really cool. #Person2#: Stick around and you'll get to know him better. He has a very unusual personality.",#Person2# introduces #Person2#'s pet lizard Grunt to #Person1#. #Person2# tells #Person1# that he's harmless and has an unusual personality.,95,19,0.2
scientific_lay_summarisation-elife-norm,"CaV1. 3 channels regulate excitability in many neurons. As is the case for all voltage-gated channels, it is widely assumed that individual CaV1. 3 channels behave independently with respect to voltage-activation, open probability, and facilitation. Here, we report the results of super-resolution imaging, optogenetic, and electrophysiological measurements that refute this long-held view. We found that the short channel isoform (CaV1. 3S), but not the long (CaV1. 3L), associates in functional clusters of two or more channels that open cooperatively, facilitating Ca2+ influx. CaV1. 3S channels are coupled via a C-terminus-to-C-terminus interaction that requires binding of the incoming Ca2+ to calmodulin (CaM) and subsequent binding of CaM to the pre-IQ domain of the channels. Physically-coupled channels facilitate Ca2+ currents as a consequence of their higher open probabilities, leading to increased firing rates in rat hippocampal neurons. We propose that cooperative gating of CaV1. 3S channels represents a mechanism for the regulation of Ca2+ signaling and electrical activity. CaV1. 3 channels are widely expressed in neurons throughout the brain and spinal cord (Tan et al. , 2011), where they serve a number of critical functions including the modulation of resting potentials, the amplification of synaptic currents and the generation and shaping of repetitive firing (Guzman et al. , 2009; Olson et al. , 2005; Striessnig et al. , 2006). These channels are dihydropyridine-sensitive L-type Ca2+ channels composed of a pore-forming CaV1. 3α1 subunit and accessory β and α2-δ subunits. The carboxy-terminus (C-terminus) of the α1D subunit is structurally complex, containing an EF hand domain as well as pre-IQ and IQ domains to which the Ca2+-binding protein calmodulin (CaM) binds (Ben-Johny and Yue, 2014). Alternative splicing results in the expression of' long' and' short' CaV1. 3 channel isoforms that differ in the length of the C-terminus (Singh et al. , 2008). The splice variant 42A (CaV1. 3S) has a short C-terminus of 183 amino acids long compared to the 695 amino acids of the long isoform (CaV1. 3L). The CaV1. 3S channels lack the so-called C-terminal modulatory domain (CTM), comprised of proximal (PCRD) and distal (DCRD) regulatory domains that block CaM binding to the IQ domain (Figures 1A and B, left). As a consequence, CaV1. 3S channels activate at lower voltages, have a higher open probability, and inactivate faster than CaV1. 3L channels","The electrical charge inside a cell is different from that outside of the cell. Neurons rely on this difference to send signals via electrical impulses. This process involves ions moving across the neuron’s membrane through proteins called ion channels. Cav1. 3 channels are ion channels that open when the membrane’s electrical charge changes to allow positively charged calcium ions into the cell. This generates an electrical current that enables neurons in the brain to produce repetitive impulses. Calcium ions entering through a Cav1. 3 channel can encourage the channel to allow in even more calcium ions. A closely related channel called Cav1. 2, which is essential to the activity of heart muscle, behaves in a similar way. Researchers have recently found that Cav1. 2 channels are arranged in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Toll-like receptors (Jefferies et al. , 2003), Fc receptors (Kawakami et al. , 1994), and G-protein coupled receptors (Tsukada et al. , 1994; Bence et al. , 1997). Btk is critical for the generation of calcium flux in response to receptor activation, because it activates phospholipase C-γ2 (PLC-γ2), which produces the second messengers diaceylglycerol (DAG) and inositol (1,4, 5) -trisphosphate (IP3). Btk dysfunction is the cause of X-linked agammaglobulinemia, a severe disease of primary immunodeficiency (Tsukada et al. , 1993). The Tec family kinases have a lipid-interaction module attached to the N terminus of a Src-like module (i. e. , concatenation of an SH3 domain, an SH2 domain and a tyrosine kinase domain) (1A). Like the non-receptor tyrosine kinase c-Abl, the Tec kinases lack a C-terminal tyrosine phosphorylation site that in Src kinases engages the SH2 domain in an autoinhibitory interaction (Sicheri et al. , 1997; Xu et al. , 1997; Nagar et al. , 2003). The lipid-interaction module of the Tec kinases is an extended plekstrin homology (PH) domain fused to a Tec homology (TH) domain (Hyvönen and Saraste, 1997). The PH-TH binds PIP3 in membranes, or the soluble head group of PIP3, inositol tetrakisphosphate (IP4), in solution. A flexible linker connects the PH-TH module to the Src-like module; its length varies from 26 residues in Itk, the Tec family kinase in T-cells, to 45 residues in Btk. 10. 7554/eLife. 06074. 003Figure 1. Crystal structure of the Src-like module of Btk. (A) Domain architectures of Btk, c-Abl, and c-Src. (B) Model for the Src-like module of Btk, based on the crystal structure of the domain-swapped dimer. (C) Comparison of the Src-like modules of Btk and c-Abl (PDB: 1OPK) (Nagar et al. , 2003), superimposed on the C lobes of the kinase domains. There is a relative rotation of about 15° for the SH2 domains and 20° for the SH3 domains for the two structures. (D) Details of the SH3/SH2-kinase linker interface and the kinase catalytic cleft in Btk. Left panel: a cluster of hydrophobic residues on the SH3 domain packs against the polyproline type-II helix formed by the SH2-kinase linker. This type of interaction is seen in most SH3-peptide ligand complexes. Right panel: the activation loop of Btk folds into the mouth of the catalytic cleft, blocking part of","The human immune system is our defense against a variety of intruders, including bacteria, viruses, and other microbes, and provides our body with long-lasting protection against these invaders. B-cells—one type of immune cell—produce proteins called antibodies that can recognize microbes from previous invasions. This allows other immune cells to find the intruders and destroy them more efficiently. People suffering from a genetic disease called X-linked agammaglobulinemia have fewer fully mature B-cells than most people and are extremely susceptible to bacterial infections. The disease is caused by mutations in the gene encoding an enzyme called Bruton' s tyrosine kinase (Btk), which is involved in B-cell development. This enzyme is usually kept inactive until the B-cells are needed, but the molecular mechanism of this restraint remains to be discovered. Wang",380,128,0.3368
scientific_lay_summarisation-elife-norm,"state from which it only exits concomitant with the differentiation into a stalked cell. During this G1→S transition, the polar flagellum and pili of the swarmer cell are eliminated and replaced by the stalk that elaborates from the vacated cell pole. Upon sequential transcriptional activation of developmental factors during the cell cycle (Panis et al. , 2015), the nascent stalked cell re-establishes polarization and ultimately gives rise to an asymmetric pre-divisional cell that yield a swarmer and a stalked progeny. 10. 7554/eLife. 18647. 003Figure 1. Cell cycle profile and phylogeny of ZitP and CpaM. (A) Scheme depicting the polarized factors PopZ, ZitP and CpaM during the cell cycle of the dimorphic bacterium C. crescentus. (B) Pilus assembly pathways and global dependencies of the two master cell cycle regulators GcrA and CtrA on the expression of the polar factors PodJ, CpaE, ZitP, CpaM and CpaC that control pilus biogenesis. Red and black dashed lines highlight transcriptional activation and polar recruitment, respectively. (C) Schematic representation (drawn to scale) of ZitP (blue) and CpaM (yellow). ZnR: zinc finger domain; TM: transmembrane domain, C: cysteine. Arrowheads below each protein pinpoint the site of truncation due to transposon insertion in the coding sequence. The large triangle on top of ZitP shows the 2 amino acid residues deleted in the ZitPGAP variant and the small triangle depicts the position of residue 133 where the ZitP coding sequence is truncated in the ZitP1-133 variant. (D) Conservation of ZitP (blue), CpaM (yellow) and CpaC (purple) across the α-proteobacterial clades. The phylogenetic tree was built in CLC Main Workbench (http: //www. clcbio. com/products/clc-main-workbench/) from 16S RNA alignments based on the Neighbor Joining method (Juke Cantor substitution model) with 100 bootstrap replicates. Empty boxes mean that no ortholog was found in the genome. Scale bar, 0. 15 substitution per site. : http: //dx. . org/10. 7554/eLife. 18647. 003 The GcrA transcriptional regulator predominates in early S-phase (Holtzendorff et al. , 2004) (1A–B). It accumulates during the G1→S transition and activates expression of polarity factors that are required for pilus or flagellum biogenesis and cytokinetic components (Davis et al. , 2013; Fioravanti et al. , 2013; Murray et al. , 2013; Quon et al. , 1996; Viollier et al. , 2002b) (1A–B). Among GcrA target promoters, is the promoter controlling expression","Living cells become asymmetric for many different reasons and how they do so has been a long-standing question in biology. In some cells, the asymmetry arises because a given protein accumulates at one side of the cell. In particular, this process happens before some cells divide to produce two non-identical daughter cells that then go on to develop in very different ways – which is vital for the development of almost all multicellular organisms. The single-celled bacterium Caulobacter crescentus also undergoes this type of asymmetric division. The polarized Caulobacter cell produces two very different offsprings – a stationary cell and a nomadic cell that swims using a propeller-like structure, called a flagellum, and has projections called pili on its surface. Before it divides asymmetrically, the Caulobacter cell must",380,128,0.3368
scientific_lay_summarisation-elife-norm,"has been a barrier to study how cells use nutrients differently within tissues to support both normal and disease physiology. Cancer cell metabolism in culture can differ from the metabolism of tumors in vivo (Biancur et al. , 2017; Cantor et al. , 2017; Davidson et al. , 2016; Mayers and Vander Heiden, 2015; Muir et al. , 2017; Sellers et al. , 2019; Vande Voorde et al. , 2019). This can at least partially be ascribed to changes in cancer cell metabolism that are driven by different nutrients present in the extracellular environment; however, another major difference between cell culture and tumors is the presence of additional cell types within tumors that are absent from most culture systems. The presence of many different cell types complicates the ability to characterize cancer cell metabolism in tumors, particularly in cases where a minority of the tumor is composed of cancer cells. For instance, cancer cells are a minority cell type in pancreatic ductal adenocarcinoma (PDAC) tumors (Feig et al. , 2012), and an understanding of cell metabolism in these tumors requires de-convolution of cancer-specific and stroma-specific phenotypes. Furthermore, there is evidence that the metabolism of cancer cells and different stromal cells isolated from these tumors can be different from each other when studied in culture (Francescone et al. , 2018; Halbrook et al. , 2019; Sousa et al. , 2016), and it is unknown whether the metabolic programs used by different cell populations in culture are also used within PDAC tumors in vivo where environmental conditions are different. Studies of bulk tumor metabolism fail to capture information about metabolic heterogeneity with regard to different cell types (Xiao et al. , 2019), and existing approaches are limited in their ability to study functional metabolic phenotypes in different cell populations in intact tissue. A major limitation arises from the fact that metabolic reactions take place on time scales that are faster than the turnover of many metabolic intermediates, complicating metabolite analysis after tumor digestion and cell sorting (Shamir et al. , 2016). Furthermore, cell sorting exposes cells to conditions that are different from those experienced by cells in tissues and can change metabolism in many ways. For example, sorting can induce mechanical and oxidative stress and reduce the levels of certain metabolites (Binek","Tumors contain a mixture of many different types of cells, including cancer cells and non-cancer cells. The interactions between these two groups of cells affect how the cancer cells use nutrients, which, in turn, affects how fast these cells grow and divide. Furthermore, different cell types may use nutrients in diverse ways to make other molecules – known as metabolites – that the cell needs to survive. Fibroblasts are a subset of non-cancer cells that are typically found in tumors and can help them form. Separating fibroblasts from cancer cells in a tumor takes a lot longer than the chemical reactions in each cell of the tumor that produce and use up nutrients, also known as the cell’s metabolism. Therefore, measuring the levels of glucose (the sugar that",380,128,0.3368
dialogsum,"#Person1#: Are you ready to go shopping? #Person2#: Just a minute. I need to make a list of thinks that we need. #Person1#: Good idea. Have you written down potatoes, carrots, and onions? #Person2#: I don ' t have onions on my list. I ' ll add them. We should get some tea. Is green tea ok or should we get the same tea that we usually get? #Person1#: Let ' s get both. We need some coffee too. Is that on your list? #Person2#: Yes, it is. Here ' s my list. Is there anything that I ' Ve forgotten? #Person1#: I think you ' Ve got everything. I want to got some chocolate and some cheese. #Person2#: What kind of cheese do you want. #Person1#: I ' m not sure. I ' ll decide at the cheese counter, when I can see what they have. Have we got enough money? #Person2#: We don ' t have enough cash, so I ' ll take my credit card and we can pay with that. Where are the car keys? #Person1#: I ' Ve got them there. Shall I drive?",#Person1# and #Person2# talk about what to buy and make a list before going shopping. They don't have enough cash so #Person2#'ll take #Person2#'s credit card.,189,26,0.1376
dialogsum,"#Person1#: Hello, Mr. Benson, welcome to Beijing! Is this your first time to visit china? #Person2#: Oh, no, I'v already made several trips to Guangzhou, this is my first trip to Beijing though. It is a lot larger than I expected it would be. #Person1#: Yes, Beijing has been grown over the last few years, there are a lot of improvements and changes being made for the Olympics. What would you like to see changing be made for Olympic, what would you like to see when are you here? #Person2#: I hope to have time to visit great wall when I am here, I always want to go there, I think it would be a real shame by came all the way in Beijing and didn't make out the wall, do you think I have a chance to see it? #Person1#: I can pretty sure it can be arranged, the wall is a short distance from the city, but we could make arrangements for driver to take us out to visit the great wall during when our afternoon breaks, I also recommend you to visit Tian'an Men Square and city while you add it! #Person2#: Yes, that would be nice, would I have a tour guide to tour completely visit these places? #Person1#: Don't worry, I would be able to go along with you, over the next few days, if you have any questions or problems, I will be right here to help you out, I can be a translator and tour guide. #Person2#: Thank you very much. #Person1#: My pleasure, I hope your visit to Beijing is very enjoyable!","#Person1# asks Mr. Benson what he wants to visit in Beijing, and helps arrange the tour. They will visit some tourist attractions, such as the Great Wall and Tian'an Men Square. #Person1# is willing to be Mr. Benson's translator and tour guide.",270,42,0.1556
pubmed-summarization,"of the test teeth were taken ( figures 13 ) . immediately prior to surgery patients were asked about their personal reason for undergoing surgical root coverage : immediately prior to and 3 months after surgical therapy patients were asked to complete the ohip questionnaire ( ohip - g49 clinic version ) . one week 1 day after surgery patients were asked about postsurgical pain . pain intensity after surgery for ctg donor and recipient site were assessed separately using a visual analogue scale ( vas ) . three months after surgery all patients were questioned as of their opinion and impression of the performed ctg would the patient undergo this kind of surgery again ( yes / no ) . by how much has the stated reason of surgery ( ctg ) improved ( school grades : a [ very good ] to f [ insufficient ] ) . satisfaction with the result ( grade a [ very good ] to f [ insufficient ] ) . the surgical technique that was examined in this study has been described in detail before , therefore only a brief description is provided . local anesthesia was rendered as major palatinal nerve block at the palatal donor region and as infiltrations ( ultracain d - s forte , sanofi / aventis , hoechst , deutschland ) at the buccal aspect of the recession tooth . the denuded root surface was scaled and planed thoroughly until the surface was hard and smooth as probed by an explorer . by removing a tissue collar of 0.5 mm width around the recession the sulcus epithelium was excised . the resulting wound should facilitate vascularisation of the ctg particularly in the gingival margin area . thereafter a pouch ( envelope ) was prepared using a no.15c or mb69 blade : gingiva and mucosa were separated from the periosteum to provide nutrition for the ctg from the underlying periosteum and covering soft tissue . at the palate an incision was made 2 mm paramarginally in the premolar and first molar region . a second parallel incision was made 1 to 2 mm apart from the first , both their mesiodistal length measuring twice the recession width . both incisions converged into the palatal tissue to meet at","purpose . the aim of this prospective longitudinal clinical pilot study was the evaluation of the effect on the oral health impact profile ( ohip ) and patient - centered results of the envelope technique for connective tissue graft ( ctg ) . methods . sixteen patients ( 11 females ) 24 to 71 years of age ( 42.6 11.1 ) received ctg that had been harvested from the palate and grafted using the envelope technique . prior to and 3 months after surgery , all patients were examined clinically , completed the ohip - g49 questionnaire , and were asked to judge the results of surgery . results . mean baseline recession depth of 2.5 0.8 mm was reduced by 1.2 0.9 mm ( p < .001",380,128,0.3368
scientific_lay_summarisation-elife-norm,"impairing behavioral performance (Carcea et al. , 2017; Kuchibhotla et al. , 2017; Otazu et al. , 2009). The potential contribution of these cells to behavior remains to a large extent unknown and represents a major conceptual challenge to the field (Olshausen and Field, 2006). How do these non-classically responsive cells relate to behavioral task variables on single trials? While there are sophisticated approaches for dissecting the precise correlations between classically responsive cells and task structure (Erlich et al. , 2011; Jaramillo and Zador, 2011; Kiani and Shadlen, 2009; Murakami et al. , 2014; Raposo et al. , 2014), there is still a need for complementary and straightforward analytical tools for understanding any and all activity patterns encountered (Jaramillo and Zador, 2011; Raposo et al. , 2014; Rigotti et al. , 2013). Moreover, most behavioral tasks produce dynamic activity patterns throughout multiple neural circuits, but we lack unified methods to compare activity across different regions, and to determine to what extent these neurons might individually or collectively perform task-relevant computations. To address these limitations, we devised a novel trial-to-trial analysis using Bayesian inference that evaluates the extent to which relative spike timing in single-unit and ensemble responses encode behavioral task variables. We trained 15 rats on an audiomotor frequency recognition go/no-go task (Carcea et al. , 2017; Froemke et al. , 2013; King et al. , 2016; Martins and Froemke, 2015) that required them to nose poke to a single target tone for food reward and withhold from responding to other non-target tones (1A). Tones were 100 ms in duration presented sequentially once every 5–8 s at 70 dB sound pressure level (SPL); the target tone was 4 kHz and non-target tones ranged from 0. 5 to 32 kHz separated by one octave intervals. After a few weeks of training, rats had high hit rates to target tones and low false alarm rates to non-targets, leading to high d' values (mean performance shown in 1B; each individual rat included in this study shown in — 1). To correctly perform this task, animals must first recognize the stimulus and then execute an appropriate motor response. We hypothesized that two brain regions important for this behavior are the auditory cortex (AC) and frontal cortical area 2 (FR2). Many but not all auditory","Neurons encode information in the form of electrical signals called spikes. Certain neurons increase the rate at which they produce spikes under specific circumstances, e. g. , whenever an animal hears a particular sound. These neurons are said to be' classically responsive' . But not all neurons behave in this way. Others produce spikes at a variable rate that does not obviously relate to the animal' s behavior. These neurons are said to be' non-classically responsive' . They are often omitted from analyses, despite typically outnumbering their classically responsive counterparts. So, what are these neurons doing? To find out, Insanally et al. trained rats to respond to sounds. The animals learned to poke their nose into a window whenever they heard a specific tone, and to avoid responding",380,128,0.3368
pubmed-summarization,"can be formulated as a multiobjective design optimization problem in which one seeks to minimize investment , operation cost , and total production time , and , simultaneously , to maximize the revenue . recall that not much work has been reported in the literature on the multiobjective optimal design of a multiproduct batch plant . huang and wang introduced a fuzzy decision - making approach for multiobjective optimal design problem of a multiproduct batch plant . a monotonic increasing or decreasing membership function is used to define the degree of satisfaction for each objective function and the problem is then represented as an augmented minmax problem formulated as minlp models . to obtain a unique solution , presented the development of a two - stage methodology for multiobjective batch plant design and retrofit according to multiple criteria . the authors used a multiobjective genetic algorithm based on the combination of a single - objective genetic algorithm and a pareto sort procedure for proposing several plant structures and a discrete event simulator for evaluating the technical feasibility of the proposed configurations . in the case of multiple objectives , an optimum solution with respect to all objectives may not exist . in most cases , the objective functions are in conflict , because in order to decrease any of the objective functions , we need to increase other objective functions . recently , solimanpur et al . developed a sophisticated multiobjective integer programming model where the objectives considered were the maximization of total similarity between parts , the minimization of the total processing cost , the minimization of the total processing time and the minimization of the total investment needed for the acquisition of machines . the presence of multiple objectives in a problem usually gives rise to a family of nondominated solutions , largely known as pareto - optimal solutions , where each objective component of any solution along the pareto front can only be improved by degrading at least one of its other objective components . since none of the solutions in the nondominated set is absolutely better than any other , any one of them is then an acceptable solution . as it is difficult to choose any particular solution for a multiobjective optimization problem without iterative","optimal design problem are widely known by their multiple performance measures that are often competing with each other . in this paper , an optimal multiproduct batch chemical plant design is presented . the design is firstly formulated as a multiobjective optimization problem , to be solved using the well suited non dominating sorting genetic algorithm ( nsga - ii ) . the nsga - ii have capability to achieve fine tuning of variables in determining a set of non dominating solutions distributed along the pareto front in a single run of the algorithm . the nsga - ii ability to identify a set of optimal solutions provides the decision - maker dm with a complete picture of the optimal solution space to gain better and appropriate choices",380,128,0.3368
dialogsum,"#Person1#: Bruno Bistro, how may I help you? #Person2#: Yes, hello, I would like to make a reservation please. #Person1#: Certainly sir, For which day and time please? #Person2#: Tonight at seven. #Person1#: I'm sorry sir, but we are fully booked tonight until eight. #Person2#: In that case, eight o'clock is fine. #Person1#: Very well, and how many people will attend tonight? #Person2#: Four people. #Person1#: Lastly, may I please know what name I should make the reservation under? #Person2#: Mark.",#Person1# in Bruno Bistro helps Mark to make a reservation at eight tonight.,81,13,0.1605
pubmed-summarization,"the contributing causes of dn pathogenesis and progression are still poorly understood but chronic hyperglycemia and high blood pressure represent the main risk factors for disease onset . , high systemic blood pressure usually determines an increase of the intraglomerular pressure and glomerular filtration rate ( gfr ) which results in glomerular hyperfiltration . from the biochemical point of view , hyperglycemia per se sustains the accumulation of advanced glycation end products ( ages ) , altering the electronegativity of the cell ; additionally ages bind proteins of the extracellular matrix ( ecm ) inhibiting their degradation . ages accumulation can induce an increased production of reactive oxygen species ( ros ) and a transcriptional activation of different proinflammatory and profibrotic molecules , including tgf - beta . the high glucose - mediated induction of tgf - beta and the central role of this growth factor in dn progression represent the few defining constants in the pathogenesis of dn . the earliest clinical signs of dn include a slight but persistent urinary excretion of albumin ( microalbuminuria ) and a temporary increase of the glomerular filtration rate ( gfr ) . these clinical signs , along with the presence of hyperglycemia , are often considered sufficient indicators of dn . today , extensive evidence shows that dn is not the only type of renal damage that can be found in diabetic patients and kidney biopsy , although highly invasive , remains the diagnostic gold standard . the histological hallmarks of dn include hyperproliferation of the mesangial cells , thickening of the glomerular basement membrane ( gbm ) , podocyte effacement , tubulointerstitial fibrosis , and nodular accumulations of ecm ( kimmelstiel - wilson lesions ) in the glomerulus . given the high prevalence of type 2 diabetes ( t2d ) and the diagnostic limitations currently associated with kidney biopsy , there is an impending need for new , accurate , and easily accessible biomarkers of disease . in this review we will try to outline a system biology overview on dn by recapitulating the main annotations obtained at different levels of molecular investigation . only those studies investigating human samples will be described ; the murine models of dn in fact , although undergoing albuminuria , mesangial expansion , and","diabetic nephropathy ( dn ) , a microvascular complication occurring in approximately 2040% of patients with type 2 diabetes mellitus ( t2 dm ) , is characterized by the progressive impairment of glomerular filtration and the development of kimmelstiel - wilson lesions leading to end - stage renal failure ( esrd ) . the causes and molecular mechanisms mediating the onset of t2 dm chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients . we performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic , epigenetic , proteomic , and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression . the picture that emerges is",380,128,0.3368
pubmed-summarization,", ca , usa ) was used to design the pcr assay and iplex single - base extension primers for the multiplexed snp massextend assay . the snp genotypes were obtained according to the iplex protocol provided by sequenom massarray rs1000 ( sequenom . san diego , california , usa ) and the sequenom typer 4.0 software was used for data analysis . the chi - squared test was used to compare the differences in frequency distributions of genotypes and alleles between cases and controls . hardy - weinberg equilibrium was assessed using a pearson chi - squared test only among controls at the 1% level . odds ratios ( ors ) and corresponding 95% confidence intervals ( 95% ci ) were obtained by binary logistic regression analysis , which adjusted for age and sex . the possibility of sex differences was evaluated by a genotype test for each tsnp in males and females separately . we adopted the snp stats ( website software from ) to analyze the association of certain single - nucleotide polymorphism loci contributed to the glioblastoma risk under variant models . we used the akaike s information criterion ( aic ) and bayesian information criterion ( bic ) to select the best - fit model for each snp . all p values presented were calculated based on a 2-sided test , and p<0.05 was considered significant . from october 2011 to september 2012 we recruited 72 gbm patients into an on - going molecular epidemiological study at the department of neurosurgery of the tangdu hospital affiliated with the fourth military medical university in xian , china . tumor histological type and grade were determined based on the who criteria and we successfully genotyped 72 gbm cases for further study . as controls we randomly selected 320 unrelated healthy individuals from the medical center of tangdu hospital from june 2011 to july 2012 according to standard recruitment and exclusion criteria . detailed recruitment and exclusion criteria were used . subjects with chronic diseases and conditions involving vital organs such as the heart , lung , liver , kidney , and brain , and/or had severe endocrinological , metabolic , or nutritional diseases were excluded from this study . all of the control subjects were generally healthy","backgroundglioblastoma ( gbm ) is a highly invasive , aggressive , and incurable brain tumor . genetic factors play important roles in gbm risk . the aim of this study was to elucidate the influence of gene polymorphism on gbm susceptibility.material/methodsin this case - control study , we included 72 gbm patients and 320 healthy controls to analyze the association between 29 single - nucleotide polymorphisms and gbm cancer risk in the chinese han population . the single - nucleotide polymorphisms were determined by sequenom massarray rs1000 and statistical analysis was performed using spss software and snpstats software.resultsusing the 2 test , we found that rs2297440 and rs6010620 in rtel1 increased risk of gbm . in the recessive model , we also found that the genotypes cc of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"complex with molecular chaperones, including Hsp70, Hsp90 and TRiC/CCT (Shi et al. , 1998; Zou et al. , 1998; Neef et al. , 2014). At physiological concentrations monomeric Hsf1 does not bind appreciably to heat shock elements (nGAAn). In the activated state Hsf1 forms trimers or higher order oligomers and binds to its response elements in heat shock gene promoters (Clos et al. , 1990; Rabindran et al. , 1993). Currently, two models are discussed for the heat-induced activation of Hsf1: (1) Based on the observation that deletion or mutational alteration of HR-C leads to constitutive trimerization Wu and co-workers proposed that Hsf1 is a thermosensor itself and kept monomeric by intramolecular leucine zipper formation (Rabindran et al. , 1993). However, activation of human Hsf1 in human and insect cells and Xenopus oocytes occurs at different temperatures, arguing against an Hsf1 intrinsic mechanism of heat shock activation (Baler et al. , 1993; Clos et al. , 1993). (2) Owing to the fact that the large variety of Hsf1-inducing signals have in common to cause protein misfolding and in analogy to the regulation of the heat shock response in E. coli (Guisbert et al. , 2008), chaperones were proposed to prevent Hsf1 activation and to be titrated away from Hsf1 under stress conditions, resulting in heat shock response induction (Morimoto, 1998). Consistent with this hypothesis is the observation that inhibition of Hsp70, Hsp90 or TRiC/CCT or knock-down of their expression leads to the induction of the heat shock response (Powers and Workman, 2007; Powers et al. , 2008; Neef et al. , 2014; Whitesell et al. , 2003; Lee et al. , 2013; Abravaya et al. , 1992; Zou et al. , 1998). 10. 7554/eLife. 11576. 003Figure 1. Recombinant purified human Hsf1 is largely monomeric and trimerizes and acquires DNA binding competence upon heat shock. (A) Domain organization of human Hsf1 [modified from Anckar and Sistonen (2011) ]. (B) Size exclusion chromatography separates recombinant human Hsf1 in monomer, dimer and trimer/oligomer as indicated. (C) Blue native gel of the three peak indicated in panel B (monomer and dimer), monomeric Hsf1 after 10 min heat shock at 42°C (monomer HS); and trimeric/oligomeric Hsf1 purified under denaturing conditions and refolded into a DNA binding competent state (M, monomer; D, dimer; T, trimer; HO,","Cells cope with excessive heat, toxic compounds and other adverse environmental conditions by triggering an internal repair process called the heat shock response. In mammalian cells, a protein called Hsf1 is activated by stress and regulates the activity of a large set of target genes. These genes code for proteins that help the cell cope with the effects of stress, for example, by repairing or breaking down damaged proteins. Under normal conditions, Hsf1 exists as a single molecule, but when it is activated, three molecules come together to make a complex called a trimer that is able to bind to DNA and activate the target genes. Proteins are made of long chains that then fold into specific three-dimensional shapes. It is not known how Hsf1 is kept in",380,128,0.3368
pubmed-summarization,"patients presenting to the out - patient department of psychiatry , s.c.b . medical college , cuttack from july 2006 to june 2007 , diagnosed as schizophrenia using international classification of diseases 10 , clinical descriptions and diagnostic guidelines , ( icd-10 criteria ) and were in the acute phase were enrolled into the study . patients fulfilling the diagnostic criteria and who gave informed consent and were in the age group of 18 - 58 formed the study subjects . patients having co - morbid substance dependence , chronic medical illnesses , mental retardation or organic brain diseases formed the exclusion criteria . modified kuppuswamy scale : this scale is based on scoring obtained in three domains : ( i ) occupation of the head , ( ii ) education of the head and ( iii ) family income per month . based on the total score obtained , socio economic status is classified into lower ( < 5 ) , upper - lower ( 5 - 10 ) , lower - middle ( 11 - 15 ) upper middle ( 16 - 25 ) and upper ( 26 - 29)positive and negative syndrome scale ( panss ) ( kay et al . 1987 ) derived originally from the brief psychiatric rating scale ( bprs ) scale , panss has 7 items each for positive and negative symptoms and 16 items for measuring general psychopathology . all the 30 items are given a score ; from 1 ( complete absence of symptoms ) to 7 ( extreme severity of symptoms ) andworld health organisation quality of life scale _ brief version ( whoqol bref ( oriya version ) formed the study tools to collect individual patient information . who - qol - bref is based on 4-domain structure with six items in physical , psychological , social and environmental domain and two items from overall qol and general health . the instrument was translated into oriya and after a series of translations and back - translations ; oriya version was used after equivalence was established . modified kuppuswamy scale : this scale is based on scoring obtained in three domains : ( i ) occupation of the head , ( ii ) education of the head and ( iii","objective : to find the association of patient characteristic and psychopathology with quality of life in acute phase of schizophrenia.materials and methods : socio - demographic variables of patient , psychopathology and quality of life were assessed . spearman 's correlation coefficients were measured using spss version 15.0.results:quality of life of the patients varied in different domains . male gender , unmarried status and higher educational status predicted a poorer quality of life . the domains of physical and psychological well - being of who - qol were correlated with panss general and total scores whereas environmental and social health showed no correlation with panss scores.conclusion:domains of subjective quality of life in acute phase of schizophrenia are associated variedly with socio - demographic variables and symptomatology .",380,127,0.3342
dialogsum,"#Person1#: Dave, there's something I want to talk to you about. #Person2#: Zina, why are you whispering? #Person1#: I've been talking to WebTracker. I'm thinking of jumping ship. #Person2#: What? Are you serious? You'd defect to our archrival! ? #Person1#: Keep your voice down. We'll talk more later. Right now I need to see Vince. #Person2#: We definitely have to talk, Zina. And watch your back. Elvin is still mad about his nose. #Person1#: OK, but don't tell anyone what I said.",Zina tells Dave her idea of job-hopping to the rival company and Dave is stunned.,82,15,0.1829
scientific_lay_summarisation-elife-norm,"Maintaining attention at a task-relevant spatial location while making eye-movements necessitates a rapid, saccade-synchronized shift of attentional modulation from the neuronal population representing the task-relevant location before the saccade to the one representing it after the saccade. Currently, the precise time at which spatial attention becomes fully allocated to the task-relevant location after the saccade remains unclear. Using a fine-grained temporal analysis of human peri-saccadic detection performance in an attention task, we show that spatial attention is fully available at the task-relevant location within 30 milliseconds after the saccade. Subjects tracked the attentional target veridically throughout our task: i. e. they almost never responded to non-target stimuli. Spatial attention and saccadic processing therefore co-ordinate well to ensure that relevant locations are attentionally enhanced soon after the beginning of each eye fixation. The processing of vision and visuospatial attention mostly proceeds via retinotopic representations in the brain (Cavanagh et al. , 2010; Wurtz, 2008). Since each saccadic eye-movement leads to a change in the retinotopic representation of the visual scene, maintaining attention at a task-relevant spatial location across a saccade necessitates a rapid, saccade-synchronized shift of attentional modulation from the neuronal population representing the task-relevant location before the saccade to the one representing it after the saccade (Marino and Mazer, 2016; Yao et al. , 2016). Currently, perceptual measurements in humans suggest a neuronal attention shift that starts before the saccade and continues after the saccade ends (Rolfs et al. , 2011; Szinte et al. , 2015; Golomb et al. , 2008,2010a, 2011; Jonikaitis et al. , 2013). However, because these previous measurements used coarse temporal sampling and/or long-duration attentional probes, the precise time at which spatial attention becomes fully allocated to the task-relevant location after the saccade remains unclear. Here, using a fine-grained temporal analysis of human peri-saccadic detection performance in an attention task, we show that spatial attention is fully available at the task-relevant location within 30 milliseconds after the saccade. This rapid post-saccadic recovery of performance in our attention task indicates that retinotopic attentional shifts occur within the time required to recover from saccadic suppression of vision. Subjects almost never responded to the distractor change, indicating that they tracked the attentional target veridically throughout the task. Spatial attention and saccadic processing therefore co-ordinate well to ensure that relevant","When we look at a scene, our gaze does not move continuously across it. Instead, our eyes move discontinuously, shifting gaze rapidly from point to point to focus on different locations in the scene. These eye movements are known as saccades, and during them the brain temporarily and selectively stops processing visual information. In the brain, a particular area of a scene is represented by different neurons before and after a saccade. Paying attention to a relevant location in a scene across an eye movement therefore requires the brain to shift its attentional effects from the neurons that represented that location in the scene before the saccade to the set of neurons that do so after the saccade. Ideally, this shift should happen rapidly and be synchronized with",380,128,0.3368
scientific_lay_summarisation-elife-norm,"by RUNX TFs through allosteric regulation (Bravo et al. , 2001; Tahirov et al. , 2001). Thus, we hypothesized that RUNX1, together with CBFβ, might play a key role in mammary epithelial cell (MEC) lineage determination as a master regulatory TF and that the loss of this normal function might contribute to breast cancer development. There are two major epithelial cell lineages in the mammary gland (MG), luminal lineage (including ductal and alveolar luminal cells), and basal lineage (the mature cell type in the basal lineage is myoepithelial cell) (1A). These two types of MECs are produced by multipotent mammary stem cells (MaSCs, which are basal cells) during embryonic development or upon MEC transplantation to cleared mammary fat pads (Shackleton et al. , 2006; Stingl et al. , 2006; Spike et al. , 2012). In adult MGs, they appear to be maintained by both lineage-specific unipotent stem cells and multipotent basal MaSCs, based on lineage tracing studies (Van Keymeulen et al. , 2011; van Amerongen et al. , 2012; Rios et al. , 2014; Tao et al. , 2014; Wang et al. , 2014). The gene regulatory network that must be in place to orchestrate lineage specification and differentiation of stem cells into mature MEC types remains largely elusive, although a number of key TFs have been identified in recent years, for example, GATA3 has been shown as a master regulator for both ductal and alveolar luminal cells (Kouros-Mehr et al. , 2006; Asselin-Labat et al. , 2007); ELF5 was identified as a master regulator of alveolar cells (Oakes et al. , 2008; Choi et al. , 2009); SLUG (SNAIL2) was shown as a master regulator of MaSCs, and it could reprogram differentiated MECs to transplantable MaSCs, together with another TF, SOX9 (Guo et al. , 2012). In this work, we asked whether RUNX1 is an integral part of this transcription network and how its mutations contribute to breast tumorigenesis. By using genetic, cellular, and molecular approaches, we found that RUNX1 is a key regulator of estrogen receptor (ER) -positive mature ductal luminal cells, and that the loss of RUNX1 may contribute to the development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss. 10. 7554/eLife. 03881. 003Figure 1. Expression pattern of Runx1 in","Stem cells can develop into the many types of specialized cell found in the body. Several proteins regulate these transformations by switching on and off the expression of genes that are specific to different cell types. Disrupting these proteins can cause the development of cells to go awry and can lead to cancer. A protein called RUNX1 controls gene expression to direct the development of blood cells. Mutations in the gene encoding this protein have been linked to blood cancers and a particular type of breast cancer, which begins in the cells that line the ducts that carry milk towards the nipple. Mammary duct-lining cells develop from a pool of stem cells that produces breast tissue cells. Now van Bragt et al. have found that RUNX1 is expressed",380,128,0.3368
dialogsum,"#Person1#: Good afternoon, welcome to IBA. How can I be of service? #Person2#: I'd like to talk to somebody about the Group Account Deposit Service. #Person1#: This refers to the deposit business offered to the level 1 account of group companies. #Person2#: What is it used for? I mean, why bother to get this special account? #Person1#: Group companies can use this to make their arrangement of funds flexible, when dealing with their subsidiaries. #Person2#: I see, so this can really cut down on time and centralise management. Interesting...",#Person2# wants to know about the Group Account Deposit Service. #Person1# introduces it to #Person1#.,89,15,0.1685
pubmed-summarization,"active metabolites , pgd2 , pge2 , pgf2 , pgi2 , or thromboxane a2 via distinct synthases such as pgd synthase and pge synthase . two pgd synthases have been identified , lipocalin ( l - pgds ) and hematopoietic ( h - pgds ) . l - pgds and h - pgds are quite different from each other biochemically in terms of their amino acid sequence , tertiary structure , evolutional origin , chromosomal and cellular localization , and tissue distribution and immunologically in terms of their functional relevance . hematopoietic pgd synthase ( h - pgds ) was previously known as the spleen - type pgds or glutathione- ( gsh- ) requiring enzyme for the production of pgd2 in the peripheral tissues . h - pgds is characterized as a member of sigma class of glutathione s - transferase ( gst ) gene family that catalyze the conjugation of gsh to an electrophilic substrate . h - pgds is localized in antigen - presenting cells and mast cells of a variety of tissues and is involved in the activation and differentiation of mast cells . h - pgds isomerizes pgh2 to pgd2 selectively and effectively , whereas other gst isozymes catalyze the conversion of pgh2 nonselectively to produce pgd2 , pge2 , and pgf2. the high specificity of h - pgds for the production of pgd2 is attributed to the unique architecture of the catalytic pocket . the deep and wide catalytic cavity of h - pgds is striking in comparison with the narrow shallow cavities of other gsts . the unique 3 d architecture of the cleft leads to the putative substrate binding mode and its catalytic mechanism , responsible for the specific isomerization from pgh2 to pgd2 . h - pgds contributes to the production of the d and j series of prostanoids in the immune system and is involved in allergic inflammatory response . since h - pgds is present in mast cells , th2 cells , and other leukocytes , it is thought to be responsible for the bulk of pgd2 production during allergic responses . in mouse models of asthma and allergic disease , h - pgds has a substantial proinflammatory effect , regulating many hallmark characteristics including eosinophilia , airway hyperreactivity ,","pgd2 is formed from arachidonic acid by successive enzyme reactions : oxygenation of arachidonic acid to pgh2 , a common precursor of various prostanoids , catalyzed by cyclooxygenase , and isomerization of pgh2 to pgd2 by pgd synthases ( pgdss ) . pgd2 can be either pro- or anti - inflammatory depending on disease process and etiology . the anti - inflammatory and immunomodulatory attributes of pgds / pgd2 provide opportunities for development of novel therapeutic approaches for resistant infections and refractory inflammatory diseases . this paper highlights the role of pgd synthases and pgd2 in immune inflammatory response .",380,100,0.2632
scientific_lay_summarisation-elife-norm,"It is unclear whether the two hippocampal lobes convey similar or different activities and how they cooperate. Spatial discrimination of electric fields in anesthetized rats allowed us to compare the pathway-specific field potentials corresponding to the gamma-paced CA3 output (CA1 Schaffer potentials) and CA3 somatic inhibition within and between sides. Bilateral excitatory Schaffer gamma waves are generally larger and lead from the right hemisphere with only moderate covariation of amplitude, and drive CA1 pyramidal units more strongly than unilateral waves. CA3 waves lock to the ipsilateral Schaffer potentials, although bilateral coherence was weak. Notably, Schaffer activity may run laterally, as seen after the disruption of the connecting pathways. Thus, asymmetric operations promote the entrainment of CA3-autonomous gamma oscillators bilaterally, synchronizing lateralized gamma strings to converge optimally on CA1 targets. The findings support the view that interhippocampal connections integrate different aspects of information that flow through the left and right lobes. Lateralization of certain neural functions in vertebrates is thought to bear evolutionary advantages (Halpern et al. , 2005). Earlier studies have mainly focused on finding anatomical correlates to behavioral asymmetries, but there has been little insight gained into the functional mechanisms underlying the differential routing and integration of activity in bilateral networks. For example, fMRI studies have shown bilateral or lateral activation of the same structures when subject performs different tasks (Smith and Goodale, 2015; Lee et al. , 2016). The bilateral function in the hippocampus is largely unknown and it is unclear to what extent the two lobes convey similar or complementary information, and whether they do indeed work together. However, the existence of important bilateral connections between the same and different hippocampal subregions does suggest some degree of integration and cooperation. In rodents, hippocampal lateralization is observed during certain memory tasks (Klur et al. , 2009; Shipton et al. , 2014), in the expression of synaptic plasticity (Kohl et al. , 2011), or following environmental enrichment (Shinohara et al. , 2013). In the human, such lateralization was reported during sequence disambiguation (Kumaran and Maguire, 2006) and in cognitive navigation (Iaria et al. , 2003; Iglói et al. , 2015). Available data is however limited and it provides no mechanistic insights. Here we have used pathway-specific local field potentials (LFPs) (Herreras et al. , 2015) in anesthetized rats to","In humans and other backboned animals, the brain is divided into the left and right hemispheres, which are connected by several large bundles of nerve fibers. Thanks to these fiber tracts, sensory information from each side of the body can reach both sides of the brain. However, although many areas of the brain work with a counterpart on the opposite hemisphere to process this sensory information, they do not necessarily perform the same tasks, or perform them at the same time as their partner. The hippocampus is a brain region that helps to support navigation, to detect novelty, and to produce memories. In fact, our brains contain two hippocampi – one in each hemisphere. Previous studies of the hippocampus have tended to record from only one side of",380,128,0.3368
pubmed-summarization,"yeast cultures were grown in nutrient - rich ypd media ( 1% yeast extract , 2% peptone , and 2% dextrose ) at 30 on a rotary shaker unless otherwise noted . for induction of autophagy , cells were grown to mid - log phase ( a600 = 0.7 ) in ypd , collected by centrifugation ( 3000 rpm 5 min ) , washed with water , then resuspended in nitrogen starvation media ( 1.7 g / liter yeast nitrogen base without amino acids and without ammonium sulfate , plus 2% dextrose ) . for northern blot analysis of temperature - sensitive mutants , cultures were grown at 30 to an od600 of 0.7 and then incubated at 37 for 1 hr before rna extraction . spei cut atg31ses1 intergenic fragment ( pcr amplified with oligos ddo1281/-1282 , which added an artificial xhoi site ) into bluescript sk+ ( all oligos used are listed in supporting information , table s2 ) . two - step pcr mutagenesis was performed using pdd1232 as template and t7 and t3 primers with mutagenic primers ( ddo184/-1284 ; ddo183/-1285 , respectively ) to amplify the fragment containing the tdna deletion ; this fragment was then cloned into bluescript sk+ as above to create pdd1233 . direct - site - directed mutagenesis was performed on pdd1232 to create pdd1248 ( tdna b - box ) , pdd1249 ( tdna b - box mutant ) , pdd1261 ( tdna a - box mutant ) , and pdd1260 ( tdna::ecori bamhi linker ) , using ddo1391/-1392 , ddo1393/-1394 , ddo1474/-1475 , and ddo1466/-1467 primer sets , respectively . the b - box mutant had the invariant cytosine and following guanine bases changed to gc , and the a - box mutant scrambled the entire consensus . plasmids pdd1262 ( flipped orientation of the tdna ) and pdd1272 ( tdna::etc9 ) were created by cloning ecori bamhi - digested pcr - amplified fragments using ddo1468/-1469 ( flip ) , or ddo1534/-1535 ( etc9 ) , respectively , into ecori yeast genomic dna was used as pcr template . plasmid pdd1263 ( tdna::etc4 ) was constructed by directly ligating complementary oligonucleotides ( ddo1489/-1490 ) containing ecori yeast strains were generated from wild - type s. cerevisiae w303 - 1a","the major function of eukaryotic rna polymerase iii is to transcribe transfer rna , 5s ribosomal rna , and other small non - protein - coding rna molecules . assembly of the rna polymerase iii complex on chromosomal dna requires the sequential binding of transcription factor complexes tfiiic and tfiiib . recent evidence has suggested that in addition to producing rna transcripts , chromatin - assembled rna polymerase iii complexes may mediate additional nuclear functions that include chromatin boundary , nucleosome phasing , and general genome organization activities . this study provides evidence of another such extratranscriptional activity of assembled rna polymerase iii complexes , which is the ability to block progression of intergenic rna polymerase ii transcription . we demonstrate that the rna polymerase iii complex bound",380,128,0.3368
dialogsum,"#Person1#: Welcome to ABC's Campus Interview Series. I'm David Crystal. Tonight, we shall share the story of Vet, a senior at Lee High School. Vet, what was life like for you as a child? #Person2#: Life was fun. I was always very loved, even without my father around. I was somewhat of a troublemaker, but I have a lot of good memories to show for it. Being a child was the best time of my life. #Person1#: How have your childhood years affected who you are today? #Person2#: I was raised by very strong, supportive people. My mother and sisters have a lot to do with who I am. I also learned many lessons, good and bad, which have made me a strong adult. They have helped me realize what I need to do to be happy. My mother has always been the best person in my life. She has never let me down, and has always been very supportive. Whenever I needed a friend, she was one. My sisters have also been there for me. When my morn was getting her college degree, she would be out late, and my sisters stepped in and played morn. They are my best friends and give me great advice. #Person1#: What have been some of your biggest trials, and how have you overcome them? #Person2#: The biggest trial in my life was when I got pregnant sophomore year. It was a new road to travel. I didn't have to get over it, I had to accept it and learn to adapt. Another trial would be trying to get over the love of my life, my baby's father. We were engaged, but things went the other way. I had to learn to love myself more than I loved a man. #Person1#: Who helped you during your pregnancy? #Person2#: My morn and sisters were everything I needed them to be-a mother, sister, boyfriend, best friend and father. All my friends were there for me, I could cry to them whenever I needed to. I'm especially thankful for my morn. It was hard for her to deal with two pregnant children at the same time. The dad and his family were also there, which was a blessing #Person1#: When a bad situation comes up, what","Vet, a senior at Lee High School, share her childhood experience with David Crystal on ABC's Campus Interview Series. She tells David about how she has been affected by her childhood years, her hard time in pregnancy and how she goes through with it with her family and friends' help, and what she would do when confronted with a bad situation.",380,61,0.1605
dialogsum,"#Person1#: Well, humans could never make something like that. #Person2#: Those poor Egyptians slaves worked so hard and you want to give aliens all the credit! #Person1#: Be a little more open-minded, Stu! Don't believe everything you read in your history books! #Person2#: OK, but don't believe everything you see on The X-files, either! #Person1#: Speaking of The X-files, it's on right now!",#Person1# thinks it's aliens who built the pyramids while Stu believes it's Egyptians' work.,63,14,0.2222
dialogsum,"#Person1#: This is ridiculous! I can't believe you've been sleeping with someone else! How could you do this! You know what? I'm out of here! #Person2#: Wait! Doctor how is this possible? I haven't cheated on my boyfriend! #Person3#: I have something to confess. . . I'm sorry Veronica, I lied. #Person2#: Wait. . . what? What do do you mean? #Person3#: I lied. You aren't even pregnant. there's no bun in the oven. I was just so overwhelmed with jealousy that I couldn't help myself. Veronica I love you! #Person2#: What are you talking about! ! ! Who are you? #Person3#: It's me! Daniel, don't you remember me? From high school. I sat behind you every day in class! I used to go to every football game and watch you in the cheerleading squad! #Person2#: You are insane! We never even spoke! Why did you lie like that to my boyfriend? #Person3#: Because Veronica. . . It's not fair! I love you; I have since the first day we met! Everything was going fine until that jerk came into the picture and ruined everything! I went to med school and became a doctor for you! You always said how you wanted to marry a doctor! You will be mine now. . . one way or another. . . #Person1#: I heard everything, you lying bastard! Get your hands off her!",The doctor tells a lie to #Person1# and #Person2# that #Person2# is pregnant because the doctor is jealous of #Person2#'s boyfriend. The doctor sat behind #Person2# every day and watch her in the cheerleading squad from high school because he loves #Person2#.,231,42,0.1818
scientific_lay_summarisation-elife-norm,"Here, we demonstrate that Arabidopsis thaliana Formin 2 (AtFH2) localizes to plasmodesmata (PD) through its transmembrane domain and is required for normal intercellular trafficking. Although loss-of-function atfh2 mutants have no overt developmental defect, PD’s permeability and sensitivity to virus infection are increased in atfh2 plants. Interestingly, AtFH2 functions in a partially redundant manner with its closest homolog AtFH1, which also contains a PD localization signal. Strikingly, targeting of Class I formins to PD was also confirmed in rice, suggesting that the involvement of Class I formins in regulating actin dynamics at PD may be evolutionarily conserved in plants. In vitro biochemical analysis showed that AtFH2 fails to nucleate actin assembly but caps and stabilizes actin filaments. We also demonstrate that the interaction between AtFH2 and actin filaments is crucial for its function in vivo. These data allow us to propose that AtFH2 regulates PD' s permeability by anchoring actin filaments to PD. Plasmodesmata (PD) function as the intercellular channels in plants and are important for the growth and development of plants, as well as during their interaction with the surrounding environment (Cheval and Faulkner, 2018; Lee, 2015; Lucas and Lee, 2004; Maule, 2008; Maule et al. , 2011). The density and size of PD are developmentally controlled (Xu and Jackson, 2010), which allows the formation of spatial symplastic domains in order to establish tissue-specific developmental programs. The permeability of PD must be precisely regulated at specific times during plant growth and development. However, the mechanisms that tightly regulate the permeability of PD are largely unknown. The actin cytoskeleton has been implicated in intercellular communication via PD (Aaziz et al. , 2001; Chen et al. , 2010; Pitzalis and Heinlein, 2017; White and Barton, 2011). In support of this notion, actin and some actin-associated proteins were demonstrated to localize to PD (Deeks et al. , 2012; Faulkner et al. , 2009; Radford and White, 1998; Van Gestel et al. , 2003). However, due to technical problems, the existence of filamentous actin in PD remains controversial, as does the nature of its organization. This has been a barrier to our understanding of the function of the actin cytoskeleton in the regulation of cell-to-cell trafficking via PD. In addition, to date, most of the data regarding the function of actin at PD have","Plant cells communicate with each other via narrow channels embedded across adjacent cell walls. These channels, called plasmodesmata, allow molecules to pass between cells, thereby enabling plants to grow normally and develop tissues and organs. But plasmodesmata also serve as passageways that viruses can exploit to infect more and more cells. Given these pros and cons, plants must regulate how permeable their plasmodesmata are so they can transport necessary materials cell-to-cell while still defending against the spread of infection. Each cell within plants, animals, and fungi, contains a protein skeleton that helps to stabilize it. A threadlike fiber called actin filament, one of the key components that makes up the cell’s skeleton, presumably extends out to the plasmodesmata, which lie across the cell’s external wall. Previous research has",380,128,0.3368
pubmed-summarization,"there was no complication intraoperatively and desired anatomic conclusions were achieved [ no hypotony , uveitis , cystoid macular edema , iol dislocation , hyphema , and vitreous hemorrhage were seen at long - term follow - up ( 1 week - 6 month ) like mentioned about in the other studies . nevertheless , pupillary distortion was seen in one patient in group 1 and in two patients in group 2 . since aforementioned detachment was in the inferior retina with a shallow feature , it was just followed with no intervention in a 6 months follow - up . elevated iop were noted in four patients in group 1 and in five patients in group 2 1 week postoperatively . these increases were statistically significant for each group at 1 week ( p < 0.05 ) . all patients increased iop values were controlled adequately with a fix combination of hypotensive drop ( dorzolamide / timolol 2 times / day ) . when the treatment stopped just a few weeks later , there was no permanent increase of iop . there was no statistically significance when complications range compared between the two groups ( p = 0.067 ) . an implanted anterior chamber artisan intraocular lens when evaluating the cdvas in both groups , there was statistically significant increase when compared the preoperatively and for each 1 week , 1 , 3 , and 6 month values ( p < 0.05 ) . however , these increases were stabilized since 1 month visit . sixteen patients achieved the same final cdva values , four patients achieved poorer cdva values that were measured preoperatively in group 1 . eighteen patients achieved the same final cdva values , two patients achieved a poorer cdva that was measured preoperatively in group 2 . mean spherical equivalent ( se ) was 4.98 5.99d in group 1 and 4.87 6.01 in group 2 preoperatively . when evaluated postoperatively , se decreased to 0.25 1.87/0.25 1.75 in group 1 and 2 , respectively . p values of the best corrected visual acuity and intraocular pressure values at 6 months follow - up best corrected visual acuity and intraocular pressure values of each group at 6 months follow - up in this study , we","purpose : to compare the outcomes of anterior chamber and retropupillary implantation of iris - claw artisan intraocular lenses ( iol).design : prospective , randomized , single - blinded study.patients and methods : forty eyes of forty aphakic patients were enrolled . patients were randomized into two groups . each group includes twenty patients . group 1 received anterior chamber artisan iol implantation . group 2 received retropupillary artisan iol implantation . preoperative and postoperative corrected distance visual acuity ( cdva ) , intraocular pressure ( iop ) , and all complications were noted and compared at 6 months follow-up.results:each two groups obtained a significant improvement in cdva ( p < 0.05 ) . four patients in group 1 and five patients in group 2 had significant but",380,128,0.3368
dialogsum,"#Person1#: Welcome to our International Business Counter. How can I help? #Person2#: Hello. I'm trying to track down some documents due to arrive any day on our new L / C. #Person1#: Not a problem. Could you tell me you L / C number, please? #Person2#: It's TH 15699324873 0. #Person1#: OK, just checking for you. . . yes, they have arrived. How would you like me to handle them? #Person2#: Would it be possible to transfer them to IBA Bank? #Person1#: That's fine. I'll get on with that for you right now.",#Person1# helps #Person2# to track down some documents. #Person2# asks #Person1# to transfer them to IBA Bank.,93,17,0.1828
dialogsum,"#Person1#: Taxi. #Person2#: Get on, PLS. Where do you wanna go? #Person1#: Thank you. Pls hurry, I am late. Can I get to the Battery Park before 4? #Person2#: All right, Miss. I think we will get there if there are no delays on the way. #Person1#: How exactly do you out the car fare? #Person2#: According to the kilometer rate, the first five kilometers are 4 dollars and every kilometer extra costs 50 cents. #Person1#: Oh, I see. #Person2#: Here we are, Miss. #Person1#: Thank you. How much do I owe you? #Person2#: You owe me 19 dollars. #Person1#: That's 20 dollars. Keep the change! #Person2#: Thank you!",#Person1# takes the taxi in a hurry. #Person1# pays and tells #Person2# to keep the change.,109,16,0.1468
pubmed-summarization,"agents that act by inhibiting the reverse transcriptase ( rt ) of hiv-1 . unlike nrti , nvp does not act through a competitive mechanism , but by directly binding to the catalytic site of rt , leading to the inhibition of the dna polymerase , which is essential for rna and dna activities.13,14 nvp - xr was developed from a hydrophilic polymer called hypromellose 2208 , to allow a controlled and extended release of nvp in the intestinal tract.15 nvp - ir is very well absorbed in the digestive tract , with a bioavailability rate as high as 90% . compared with nvp - ir , nvp - xr is slowly absorbed in the digestive tract , with a bioavailability rate of 72%.12 the minimal plasmatic concentration of 2920 ng / ml achieved after a single dose of 400 mg of nvp - xr and the 24-hour time to maximum concentration , are compatible with a single daily intake using this formulation.12 nvp undergoes a biotransformation process involving cytochrome p450 to yield several hydroxylated metabolites . the efficacy and tolerance of nvp - xr have been assessed in two major clinical trials : the verxve16 and tranxition17 trials . verxve was a phase iii multinational , randomized , single - blinded parallel arms trial , comparing the efficacy and tolerance of nvp - xr ( 400 mg once - daily ) with nvp - ir ( 200 mg twice - daily ) ; each arm augmented with emtricitabine ( ftc ) and tenofovir ( tdf ) among 1011 adult patients ( 505 in the nvp - xr arm and 506 in the nvp - ir arm ) with hiv infection and nave to art drugs.16 the primary outcome of the study was a sustained virologic response at 48 months of treatment . sustained virologic response was defined by two consecutive hiv viral load < 50 copies / ml at least 2 weeks apart and without relapse or change in the art regimen.16 after 48 weeks of treatment , this study showed a noninferiority of once - daily nvp - xr 400 mg compared with twice - daily nvp - ir , for a predefined margin of 10% . the proportion of patients with sustained virologic response at 48 weeks",an extended - release formulation of nevirapine ( nvp - xr ) has been developed with the aim of simplifying antiretroviral treatment regimens and improving patients adherence with a single daily intake . the verxve and tranxition clinical trials have demonstrated the noninferiority of nvp - xr compared with nevirapine immediate - release ( nvp - ir ) on viral load after 24 and 48 months of treatment . the tolerance profiles of nvp - xr and nvp - ir are similar . simplifying the treatment dosage for nvp would likely improve adherence to antiretroviral treatments .,380,97,0.2553
dialogsum,"#Person1#: May I help you, sir? #Person2#: Yes, I have many things to buy. I would like to choose the cleaning milk first. #Person1#: All right. What is your type of skin? #Person2#: Dry. That's my problem. #Person1#: You can use this. It has special effect for keeping your face moisturized. It has this lotion, as a gift attached. #Person2#: Sounds good. What about shampoo? I would like to buy the product that prevents scurf. #Person1#: How about this one? It is well-known for the effect of removing scurf. #Person2#: Is it a newcomer? #Person1#: Yes, it is a new brand. #Person2#: I do not care the brand as long as it works well. #Person1#: Anything else? #Person2#: I want to buy the toothpaste, the brand of Jiajieshi. #Person1#: Yes, here you are.",#Person2# helps #Person1# to choose the cleansing milk for dry skin and shampoo to prevent scurf. #Person2# also buys a toothpaste.,133,21,0.1579
scientific_lay_summarisation-elife-norm,"Mutational activation of the BRAF proto-oncogene in melanocytes reliably produces benign nevi (pigmented ‘moles’), yet the same change is the most common driver mutation in melanoma. The reason nevi stop growing, and do not progress to melanoma, is widely attributed to a cell-autonomous process of ‘oncogene-induced senescence’. Using a mouse model of Braf-driven nevus formation, analyzing both proliferative dynamics and single-cell gene expression, we found no evidence that nevus cells are senescent, either compared with other skin cells, or other melanocytes. We also found that nevus size distributions could not be fit by any simple cell-autonomous model of growth arrest, yet were easily fit by models based on collective cell behavior, for example in which arresting cells release an arrest-promoting factor. We suggest that nevus growth arrest is more likely related to the cell interactions that mediate size control in normal tissues, than to any cell-autonomous, ‘oncogene-induced’ program of senescence. Activating BRAF mutations (e. g. BRAFV600E) are the most common oncogenic mutations in melanoma, seen in about 66% of cases (Davies et al. , 2002). Curiously, the same mutation is found in 89% of melanocytic nevi (Pollock et al. , 2003) —the benign, pigmented ‘moles’ found on the skin of most individuals. In animal studies, melanocyte-specific expression of BRAFV600E efficiently produces nevi, but only very rarely melanoma (Dankort et al. , 2009; Dhomen et al. , 2009; Patton et al. , 2005). The widely-accepted explanation is that transformed melanocytes undergo oncogene-induced senescence (OIS), arresting proliferation before additional oncogenic events can occur (e. g. Bennett, 2003; Huang et al. , 2017; Kaplon et al. , 2014; Michaloglou et al. , 2005). Nevus melanocytes are indeed growth-arrested, but the assumption that OIS is the cause remains untested, in part because of a lack of criteria to rigorously define OIS in vivo (Damsky and Bosenberg, 2017). Initially studied as a consequence of forced expression of oncogenes in cell cultures (Serrano et al. , 1997), OIS has come to be seen as a distinctive cellular stress response characterized by a phenotype of growth arrest, morphological and metabolic changes, chromatin alterations, and secretion of growth factors, chemokines, cytokines and proteases (Campisi and d' Adda di Fagagna, 2007; Gorgoulis et al. , 2019; Ito et al. , 2017; Kuilman et al. , 2010). Given an abundance","Melanocytes are pigment-producing cells found throughout the skin. Mutations that activate a gene called BRAF cause these cells to divide and produce melanocytic nevi, also known as “moles”. These mutations are oncogenic, meaning they can cause cancer. Indeed, BRAF is the most commonly mutated gene in melanoma, a deadly skin cancer that arises from melanocytes. Yet, moles hardly ever progress to melanoma. A proposed explanation for this behavior is that, once activated, BRAF initiates a process called “oncogene-induced senescence” in each melanocyte. This process, likened to premature aging, is thought to be what causes cells in a mole to quit dividing. Although this hypothesis is widely accepted, it has proved difficult to test directly. To investigate this notion, Ruiz-Vega et al. studied mice with hundreds of moles created",380,128,0.3368
dialogsum,"#Person1#: So what are you doing for Thanksgiving? #Person2#: Not much really. It's more of an American tradition, so back home we don't really celebrate it. In fact, I am not even sure of what exactly is being celebrated! #Person1#: Well you know, it's a time to get together with all your family and be thankful for everything! #Person2#: Yeah but, how did this holiday come to be? #Person1#: Well, the first settlers of Massachusetts arrived there because of religious persecution from England and King James. Once in the New World, they befriended an native named Squanto, who taught them how to harvest food from the area such as corn. #Person2#: And then what did happen? #Person1#: Well, they had enough harvests for the next winter and celebration . They decided to have a big feast for the natives, giving thanks the land, and everyone for the foods, healthy and new lives. #Person2#: Interesting! I am amazed how big and delicious thanksgiving dinners are! #Person1#: Come to my house for Thanksgiving! We are having turkey, pumpkin pie, mashed potatoes with gravy, and lots of stuffing! #Person2#: Count me in!",#Person1# asks about #Person2#'s plan for Thanksgiving but #Person2# doesn't celebrate it. Then #Person1# tells #Person2# the history of Thanksgiving and the way people celebrate it. #Person1# invites #Person2# to #Person1#'s house for Thanksgiving dinner.,189,35,0.1852
dialogsum,"#Person1#: I've received your letter of application and I see your current job is as a sales assistant at Ray Stones book shop? Why have you applied for this position? #Person2#: Well, I've really enjoyed my work at Ray Stones. I've always been interested in books and usually the customers are really nice. And I like trying to find books for them. #Person1#: So why do you want to leave? #Person2#: Because it's quite a small independent book shop. But EI books is a much bigger company. I read on your website. You have over 50 branches now and you're still growing, and I see you also have a website where people can order books. #Person1#: Well, it's true that we've grown quickly in recent years and it's nice to see you found out about the company. So would you describe yourself as ambitious? #Person2#: Um... I don't think so, but I'd like to be successful. #Person1#: And what are some of your main strengths? #Person2#: Ah, I work hard and I enjoy working with other people and uh, I can solve problems. You can always put your trust in me. #Person1#: That's good.",#Person2# used to work as a sales assistant at Ray Stones book shop but now applies for a job at EI books. #Person1# interviews #Person2# and asks #Person2#'s personality and main strengths.,194,32,0.1649
pubmed-summarization,"patients . in addition , training serves as a catalyst in active participation and performance of tasks by inducing interest and pleasure , providing immediately visual feedback on the result to enhance motor education ability9 . many recent researches of virtual reality games with higher accessibility reported that such games showed significant effects on voluntary control and coordination of children with cerebral palsy and increases in the motor ability of patients with parkinson disease10 . those types of games were also effective on recovery of upper limb functions and induced significant improvement in balance and walking of stroke patients , showing that the games can be used as an effective method of intervention11 , 12 . as a means of overcoming limitations of the existing intervention methods , virtual reality shows an availability it has to being applied in the rehabilitation of stroke patients . however , devices of virtual reality in previous studies are so large that they are difficult to be used in general social institutes or homes in terms of scale and cost . furthermore , they are targeted to a small number of patients . in this context , the purpose of this study was to perform treadmill exercise and virtual reality training exercise using nintendo wii , a device that can be easily used without regard to place or facility , in order to investigate the effects on balance and walking of stroke patients . all of the subjects were sufficiently explained of this study and voluntarily consented to their participation in the experiment . this study was approved by the research agency , and all participants provided written informed consent . those who could perform communication , comply with instructions in this study , perform balancing and walking independently , had no pain limiting execution of exercise , and had no disability in sight , hearing , and the vestibular organs were selected to be the subjects of this study . the forty stroke patients were randomly divided into two exercise program groups with one group using virtual reality training ( n=20 ) and another group using a walking exercise program using a treadmill ( n=20 ) . age for the virtual reality group , the age was 62.2 7.2 years old , the","[ purpose ] the purpose of this study is to investigate the effects of virtual reality training using nintendo wii on balance and walking for stroke patients . [ subjects and methods ] forty stroke patients with stroke were randomly divided into two exercise program groups : virtual reality training ( n=20 ) and treadmill ( n=20 ) . the subjects underwent their 40-minute exercise program three times a week for eight weeks . their balance and walking were measured before and after the complete program . we measured the left / right weight - bearing and the anterior / posterior weight - bearing for balance , as well as stance phase , swing phase , and cadence for walking . [ results ] for balance , both",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin intermediate, which promote formation of a transient, thioester-bonded HECT∼ubiquitin intermediate. Here we report that the second step of ligation is mediated by a distinct catalytic architecture established by both the HECT E3 and its covalently linked ubiquitin. The structure of a chemically trapped proxy for an E3∼ubiquitin-substrate intermediate reveals three-way interactions between ubiquitin and the bilobal HECT domain orienting the E3∼ubiquitin thioester bond for ligation, and restricting the location of the substrate-binding domain to prioritize target lysines for ubiquitination. The data allow visualization of an E2-to-E3-to-substrate ubiquitin transfer cascade, and show how HECT-specific ubiquitin interactions driving multiple reactions are repurposed by a major E3 conformational change to promote ligation. A prevailing mechanism for altering protein function involves post-translational modification by ubiquitin (Ub) via E1-E2-E3 trienzyme cascades. First, an E1 activating enzyme catalyzes formation of a transient E2∼Ub intermediate, which is linked by a thioester bond between Ub’s C-terminus and the catalytic cysteine of an E2 conjugating enzyme (here, ‘∼’ refers to a covalent protein–protein interaction linked by a thioester, oxyester, or isopeptide bond, ‘-’ refers to a noncovalent interaction, and ‘x’ refers to a crosslinked complex). E3s subsequently utilize one of two general mechanisms to adjoin the activated Ub C-terminus with targets. E3s in the RING family promote transfer of Ub’s C-terminus from the E2 catalytic cysteine to a substrate (Deshaies and Joazeiro, 2009). Notably, recent structural studies have revealed how isolated RING domains bind both E2 and Ub to optimally orient and activate the E2∼Ub intermediate for nucleophilic attack (Dou et al. , 2012; Plechanovová et al. , 2012; Pruneda et al. , 2012). Many ligases utilize a different mechanism possessing an active site cysteine participating directly in catalysis via a two-step mechanism. First, Ub is transferred from an E2∼Ub intermediate to the E3 catalytic cysteine to form a labile, thioester-linked E3∼Ub intermediate. Second, Ub is transferred from the E3 cysteine to a substrate’s primary amino group, which is typically from a lysine side-chain. This catalytic mechanism is common to many classes of E3s, including several","Ubiquitin is a small protein that can be covalently linked to other, ‘target’, proteins in a cell to influence their behavior. Ubiquitin can be linked to its targets either as single copies or as polyubiquitin chains in which several ubiquitin molecules are bound end-on-end to each other, with one end of the chain attached to the target protein. A multi-step cascade involving enzymes known as E1, E2, and E3 adds ubiquitin to its targets. These enzymes function in a manner like runners in a relay, with ubiquitin a baton that is passed from E1 to E2 to E3 to the target. The E3 enzyme is a ligase that catalyzes the formation of a new chemical bond between a ubiquitin and its target. There are approximately 600 different E3",380,128,0.3368
dialogsum,"#Person1#: What's up? You don't look too good. #Person2#: Yeah, my head hurts, that's all. I'Ve been in physics class all day. It's killer! #Person1#: I liked physics. It's all math, really. arcs, curves, velocity, cool stuff. #Person2#: Yeah, yeah, but today's lesson was all about the creation of the universe. #Person1#: A physics class about the creation of the universe? That's some pretty unscientific language there. Sounds more religious to me. #Person2#: It's all religion. Take the theory of the Big Bang. How is it possible that all of the stuff in the universe comes from an explosion? That's no better than Atlas carrying the globe on his back or African myths about turtles and stuff. #Person1#: Turtles? Whatever. . . Look, all that's required for the creation of matter an imbalance of particles and anti-particles. At least, that's what the math says. #Person2#: Math, sheath. What's the evidence? #Person1#: There is evidence! You know Edwin Hubble? He's the guy who in the early twentieth century was the first scientist to measure the drift of matter in the universe, thus advancing notions of an expanding universe. What would it be expanding from? Well, the Big Bang. . . DUH! #Person2#: Anyway, it's just a theory. Why do people go around touting theories? Where's the scientific rigor in that? #Person1#: Dude, don't equivocate. A theory only becomes a theory after withstanding rigorous testing. You slept through class, didn't you?",#Person1# and #Person2# discuss the creation of the universe. #Person2# thinks the theory of the Big Bang sounds religious and cannot understand how the universe comes from an explosion. #Person1# explains the imbalance of particles and anti-particles and provides the evidence.,239,41,0.1715
pubmed-summarization,"7 preoperatively to 9 at discharge and reached 11 at one year postoperatively . she was satisfied with the treatment although she had difficulty in climbing stair case without crutches . the cervical spondylotic myelopathy ( csm ) is not an uncommon condition in the spinal area , which follows a protracted clinical course consisting of a longer period of relatively stable symptoms punctuated by exacerbation of variable duration . for patients with moderate to severe symptoms , the surgical intervention should be considered as a possible procedure to prevent further neurologic deterioration and create a chance for recovery from myelopathy4512 ) . aku , with its sequel ochronosis is a rare disease caused by an inborn deficiency of hga oxidase . although there are symptoms that may give instant clue to the diagnosis like the urine turns to dark on exposure to air and discoloration on sclera , jowl , as well as in the underwear , the patients can often neglect the symptoms and appear at late in the course of disease24 ) . in few cases it may be neglected until fourth or fifth decade when the symptoms secondary to ochronosis develop and the patients report to physicians . the disease affecting the spine follows a chronological sequence , the patient usually first suffer from ochronotic spondylosis which is accompanied with the peripheral joint arthropathy1 ) , and it progresses to cervical spondylotic myelopathy which warrants surgical intervention . the initial complaints usually include low back or neck pain with stiffness , and occasionally sciatica resulting from disc protrusion6 ) . the characteristics of ochronotic spondylosis are multiple disc space narrowing , vacuum phenomenon and calcification in a water - like pattern due to the sparing of the central nucleus pulpous39 ) . current literature has rarely reported the involvement of the cervical spine and consequent spinal cord compression requiring surgical intervention . in the present case report , findings from the mri on the cervical region revealed that the redundant ligamentum flavum appeared to be the main cause behind the cord compression . this could be secondary to the fact that the hga could bind irreversibly by a process of polymerization and oxidation to connective tissue collagen . this prevents the collagen cross - link formation","ochronosis is a musculoskeletal manifestation of alkaptonuria , a rare hereditary metabolic disorder occurs due to the absence of homogentisic acid oxidase and leading to various systemic abnormalities related to deposition of homogentisic acid pigmentation ( ochronotic pigmentation ) . the present case reports the clinical features , radiographic findings , treatments and results of a cervical spondylotic myelopathy woman patient due to the ochronotic arthropathy of the cervical spine . the patient aged 62 years was presented with gait disturbance and hand clumsiness . physical examination , x - rays , computed tomography and lab results of the urine sample confirmed the presence of ochronosis with the involvement of the cervical spine . the patient underwent a modified cervical laminoplasty due to multi - segment spinal cord",380,128,0.3368
pubmed-summarization,"blunt trauma includes road traffic crash ( rtc ) , altercation , industrial / occupational accidents , sports , and falls . penetrating injuries are results of gunshots , missiles , stabbing , and explosions . pathological diseases such as tumors , osteomyelitis , cysts , osteoradionecrosis may also contribute to facial fracture . rtcs have been reported as the most frequent reason for facial fractures in nigeria , rural and developing world ; while altercations remains the leading causes in urban and developed countries . however , recent report on the war in afghanistan by breeze and associates have identified increasing facial fractures among british troops despite to protective armor worn and advances in on - field resuscitation and critical care that have increased survival in the battle field . falls are common in the very young and elderly . pattern of facial fracture is predicated on etiology , population density , socioeconomic , cultural , race , and time . facial fractures and other maxillofacial injuries have high clinical significant because the anatomical specificity of face provides protection to important vital organs such as the brain and eyes and others like the digestive and respiratory systems . the facial skeleton is one of the most complex arrangements of curving bony structures in the body and consists of bones of the mandible , maxilla , zygoma , bony walls of the nasal cavities , paranasal sinuses , and orbit . injuries to this region can result in serious dysfunctions of sight , smell , breathing ; eating and talking which impact negatively on the victim 's quality of life . moreover , owing to high premium placed on facial appearance in many societies esthetic disturbance could results in adverse psychological consequence . unfortunately , limited specialized manpower needed to treat this injuries and the considerable treatment cost imposes huge burden and demand on the ever dwindling healthcare recourses of developing nation like ours . owing to the forgoing , it is necessary to explore the etiology and pattern of fractures of facial skeleton . such periodic verification of the etiology of maxillofacial injuries will facilitates the assessment of proficiency of road safety measures such as speed limit , drunk driving , crash helmets , and seat belt laws .","background : facial fracture is gradually become a public health problem in our community due to the attendant morbidity and mortality . hence , the aim of this study was to determine the pattern of facial fracture in dental and maxillofacial surgery department of usmanu danfodiyo university teaching hospital . this cross - sectional study was undertaken to provide information regarding gender , age , etiology , and diagnosis of patients with maxillofacial fractures.materials and methods : a 1-year review of patients diagnosed and treated for facial fractures in usmanu danfodiyo university teaching hospital between january 2011 and december 2011 . the diagnosis was based on radiographic data and clinical examination . the main analysis outcome measures were etiology , age , gender , site , and treatment",380,128,0.3368
dialogsum,"#Person1#: I like this television very much. How much does it cost? #Person2#: It's the most expensive model in the shop. It costs five hundred pound. #Person3#: That's too expensive for us. We can't afford all that money. #Person2#: This model's less expensive than that one. It's only three hundred pound. But, of course, it's not as good as the expensive one. #Person1#: I don't like this model. The other model's more expensive, but it's worth the money. Can we buy it on instalments? #Person2#: Of course. You can pay a deposit of thirty pounds, and then forty pound a minth for three years. #Person1#: Do you like it, dear? #Person3#: I certainly do, but I don't like the price. you always want the best, but we can't afford it. Sometimes you think you're a millionaire! #Person1#: Millionaires don't buy things on instalments !","#Person1# and #Person3# are buying television at #Person2#'s shop. #Person1# prefers the most expensive model and thinks it's worth the money, but #Person3# thinks it's too expensive.",144,27,0.1875
scientific_lay_summarisation-elife-norm,"(ERV1, ERVK and ERVL), according to the infectious retroviruses they derive from (Stocking and Kozak, 2008). Non-LTR elements comprise Long and Short INterspersed Elements (LINEs and SINEs, 20% and 8% of the genome, respectively), and also consist of specific sub-families (Babushok et al. , 2007). The majority of transposons have accumulated nullifying mutations and truncations, but around 1–2% of LINEs and ERVs have intact sequences that embed the protein coding information necessary for their mobilization. Notably, ERVK elements show the greatest level of activity, which causes at least 10% of spontaneous mutations in laboratory mice (Maksakova et al. , 2006). To minimize their impact on genome fitness, multiple layers of control antagonize transposons at different steps of their life cycle (Zamudio and Bourc’his, 2010). Notably, restraining mechanisms can differ between cell types. In somatic cells and in the male differentiating germline, DNA methylation is the main transcriptional suppressor of LTR and non-LTR transposons. In these contexts, transposable elements are densely methylated (Rollins et al. , 2006; Smith et al. , 2012) and DNA hypomethylation leads to their de-repression (Bourc’his and Bestor, 2004; Walsh et al. , 1998). In contrast, the early germline and the early embryo manage to globally control their transposon burden without DNA methylation. These cells naturally undergo genome-wide loss of DNA methylation, likely as part of the acquisition of a pluripotent, flexible state (Seisenberger et al. , 2013). Moreover, genetic studies have demonstrated that mouse embryonic stem (ES) cells can use DNA methylation-independent mechanisms to silence transposons: knocking-out the three active DNA methyltransferases (Dnmt-tKO) does not yield significant de-repression of transposons, except Intracisternal A Particle (IAP) elements (Karimi et al. , 2011b; Matsui et al. , 2010) In fact, transposon control in ES cells seems to rely primarily on post-translational histone methylation, notably at lysine 9 of histone H3 (H3K9). H3K9 dimethylation (H3K9me2), which is deposited by the EHMT2/G9a and EHMT1/GLP lysine methyltransferases, directly and specifically represses class L ERVs (Maksakova et al. , 2013). H3K9 trimethylation (H3K9me3) can be catalyzed by the SETDB1 (also known as ESET) or the SUV39H enzymes. The SUV39H system targets H3K9me3 at evolutionary young LTR and non-LTR transposons, but Suv39h mutant ES cells principally up-regulate LINE1 elements (Bulut-Karslioglu et al. , 2014). In parallel, SETDB1, together with its associated co-repressor, the","Transposons are sequences of DNA with the ability to mobilize and jump from one position to another. In the human genome, the number of transposons far surpasses the number of genes. Furthermore, while transposons have been beneficial for the evolution of the human genome, they can also alter genes and cause cancer and genetic diseases. The danger posed by transposons has led to numerous mechanisms to keep them under control. In particular, a natural biochemical modification of the DNA molecule called “DNA methylation” plays an important role in keeping transposons inactive or silent. However, during the early development of an embryo, the DNA methylation marks are erased throughout the entire genome. This provides an opportunity for transposons to be active, and it is not clear how the genome",380,128,0.3368
dialogsum,"#Person1#: It is really exciting news. #Person2#: What news? #Person1#: You don't know? The company is going to replace these old computers with the latest ones. #Person2#: You know what we will get? #Person1#: We will all get a docking station on our own desk from which you can remove your laptop easily. And if you come back to office, you just reconnect your laptop with docking station. #Person2#: What docking station? #Person1#: This is a kind of socket mounted to your desk. The socket has all the wire connections of the company line and all the other office automation equipments, like fax, copier, a screen, printer and scanner, and it will be very convenient. #Person2#: Another big step forward in saving on our office equipment, I don't need a desktop anymore. A laptop is enough.",#Person1# tells #Person2# the news that the company is going to replace these old computers with the latest ones and they will all get a docking station.,136,27,0.1985
scientific_lay_summarisation-elife-norm,"The 14th–18th century pandemic of Yersinia pestis caused devastating disease outbreaks in Europe for almost 400 years. The reasons for plague’s persistence and abrupt disappearance in Europe are poorly understood, but could have been due to either the presence of now-extinct plague foci in Europe itself, or successive disease introductions from other locations. Here we present five Y. pestis genomes from one of the last European outbreaks of plague, from 1722 in Marseille, France. The lineage identified has not been found in any extant Y. pestis foci sampled to date, and has its ancestry in strains obtained from victims of the 14th century Black Death. These data suggest the existence of a previously uncharacterized historical plague focus that persisted for at least three centuries. We propose that this disease source may have been responsible for the many resurgences of plague in Europe following the Black Death. The bacterium Yersinia pestis is among the most virulent pathogens known to cause disease in humans. As the agent of plague it is an existing threat to public health as the cause of both emerging and re-emerging rodent-derived epidemics in many regions of the world (Duplantier et al. , 2005; Vogler et al. , 2011; Gage and Kosoy, 2005). This, and its confirmed involvement in three major historical pandemics, have made it the subject of intense study. The first pandemic, also known as the Justinian Plague, occurred from the 6th through the 8th centuries; the second pandemic spanned the 14th to the 18th centuries; and the third pandemic started in the 19th century and persists to the present day. Attempts to date the evolutionary history of Y. pestis using molecular clocks have been compromised by extensive variation in nucleotide substitution rates among lineages (Cui et al. , 2013; Wagner et al. , 2014), such that there is considerable uncertainty over how long this pathogen has caused epidemic disease in human populations. In addition, there has been lively debate as to whether or not it was the principal cause of the three historical pandemics (Cohn, 2008; Scott and Duncan, 2005). It is well established that extant lineages of Y. pestis circulated during the third pandemic (Achtman et al. , 2004; Morelli et al. , 2010), and various ancient DNA studies have now unequivocally demonstrated its","A bacterium called Yersina pestis is responsible for numerous human outbreaks of plague throughout history. It is carried by rats and other rodents and can spread to humans causing what we conventionally refer to as plague. The most notorious of these plague outbreaks – the Black Death – claimed millions of lives in Europe in the mid-14th century. Several other plague outbreaks emerged in Europe over the next 400 years. Then, there was a large gap before the plague re-emerged as threat in the 19th century and it continues to infect humans today, though on a smaller scale. Scientists have extensively studied Y. pestis to understand its origin and how it evolved to become such a deadly threat. These studies led to the assumption that the plague outbreaks",380,128,0.3368
dialogsum,"#Person1#: I need something to wash this down. Is there any juice in the fridge? #Person2#: What is that? It looks like something from a swamp! #Person1#: It's a green drink. It's supposed to be full of vitamins and minerals. #Person2#: You know, healthy eating doesn't have to make you gag. #Person1#: The sales lady said that even if I eat right, I wouldn't get enough vitamins. #Person2#: Have you ever tried it? Or are you just going to believe the sales lady? #Person1#: It's easier to drink this once a day than eat fruit and vegetables all day. #Person2#: It may take less time, but I don't know about easier. Yuck.",#Person1# bought a green drink that looks gross but is said to have many vitamins and minerals. #Person2# thinks it's hard to drink it.,112,24,0.2143
pubmed-summarization,"previously considered to be rare because a unilateral hydronephrosis may not produce symptoms , mild obstruction may not be identified and no systematic follow - up after vascular surgery was performed . however , it is now known that ureteral obstruction occurs in 1020% of all bypass operations . patients with ureteral obstruction are significantly more likely to have graft complications , including auf , compared with those without ureteral obstruction . in particular , delayed ureteral obstruction , as observed in the present case , appears to be a marker for current or impending graft complications . it is important to recognize the predisposing risk factors for auf , and the urologist should suspect auf in any patient with hematuria and the predisposing risk factors . the pathogenesis of auf is closely related to inflammatory or ischemic changes in the ureter , vessels or both . the predisposing factors from the outside of the ureter that could cause the pathogenesis are previous genitourinary or pelvic oncologic surgery , previous vascular surgery , radiotherapy and an underlying vascular disease . in addition , chronic ureteral stenting is a strong predisposing factor from the inside of the ureter . chronic ureteral stenting acts as a counter - brace to facilitate the transmission of arterial pulsations to a fragile ureter , producing pressure necrosis and resulting in fistula formation . in a previous study assessing a large patient cohort , 85 of 139 auf patients ( 61% ) had chronic ureteral catheterization prior to the fistula formation . auf in a patient who underwent vascular graft surgery is often located at the level of the proximal or distal anastomosis of the vascular graft . this is because anastomosis is most fragile in the artery . in the review of 139 auf cases , a significant portion of the fistulas originated at the level of the anastomosis of the vascular graft . consistent with this , the fistula in the present case was located at the level of the distal anastomosis . the treatment of auf in an arterial lesion is either via an open procedure or via an endovascular procedure . endovascular treatments are less invasive and safer than open procedures because they avoid direct procedures on areas damaged during previous radiation","artery ureteral fistula ( auf ) is a rare condition but there is an increase in the number of reported cases . it is frequently difficult to treat . a 63-year - old male who had undergone a dacron y - graft placement for an infrarenal aortic aneurysm 3 years earlier , presented with hematuria . contrast - enhanced computed tomography revealed a fistula located between the right common iliac artery and the right ureter at graft anastomosis . endovascular treatment using a covered stent was performed successfully .",380,89,0.2342
scientific_lay_summarisation-elife-norm,"et al. , 2015; Urnavicius et al. , 2018), how pulling forces are precisely regulated to achieve the appropriate spindle displacement remains incompletely understood. The budding yeast Saccharomyces cerevisiae provides an important model for studying spindle position regulation [for review see (Xiang, 2017) ]. During metaphase, the yeast spindle moves into the mother bud neck via dynein-dependent sliding of astral MT along the bud cortex (Adames and Cooper, 2000; Moore et al. , 2009; Yeh et al. , 2000). In the current model, dynein is recruited from the dynamic plus ends of astral MTs to cortical foci containing the attachment molecule Num1; once anchored, dynein uses its minus end-directed motor activity to walk along the MT lattice, generating pulling forces on astral MTs along the bud cortex, thereby moving the connected spindle into the bud neck (Lee et al. , 2005,2003; Markus et al. , 2011; Sheeman et al. , 2003). In contrast to the yeast model, studies in C. elegans embryos and mammalian cells show that cortically anchored dynein is able to mediate spindle movement by pulling on astral MTs in an apparent ‘end-on’ fashion (Guild et al. , 2017; Gusnowski and Srayko, 2011; Kiyomitsu and Cheeseman, 2012; Nguyen-Ngoc et al. , 2007; Redemann et al. , 2010; Schmidt et al. , 2017). Indeed, in vitro reconstitution studies using either bead-bound brain dynein or barrier-attached yeast dynein show that dynein can capture dynamic MT plus ends and generate pulling force on the captured MT (Hendricks et al. , 2012; Laan et al. , 2012). These experiments suggest that the particular geometry of the interaction between the barrier-attached dynein and the captured MT might promote MT shrinkage due to the barrier effect. Why ‘capture-shrinkage’ mechanism is not observed for Num1-based ‘cortical pulling’ has remained enigmatic. On the one hand, a classic study hinted that dynein pulls on the MT tips by inducing MT catastrophe at the cell cortex (Carminati and Stearns, 1997); on the other hand, a recent work suggested that dynein destabilizes astral MT plus ends regardless of their cortex interaction and that this activity might not be used for generating force for spindle movement (Estrem et al. , 2017). Additionally, the MT-cortex interactions described by Carminati and Stearns. (1997) occurred before or after the nuclei moved into the","Cells must divide so that organisms can grow, repair damaged tissues or reproduce. Before dividing, a cell creates two identical copies of its genetic information – one for each daughter. A molecular machine known as the mitotic spindle then moves each set of genetic material to where it will be needed when the daughter cells form. For the process to work properly, however, a motor protein known as dynein must correctly position the spindle by pulling it into place from the outskirts of the cell. When a baker’s yeast cell divides, it first forms a ‘bump’, which grows into a bud that will ultimately become another yeast. The spindle needs to be precisely placed at the midpoint between the original cell and the bud, so the genetic material",380,128,0.3368
scientific_lay_summarisation-elife-norm,"in Quasibacillus thermotolerans (Qs), an organism that does not encode any ferritins in its genome. We show that this encapsulin-based system self-assembles into a thermostable 42 nm 9. 6 MDa protein compartment with a novel T = 4 topology able to mineralize and store an exceptionally large quantity of iron. IMEF-systems are found in Firmicute genomes and their operon organization indicates a function in dynamic iron storage. To investigate the distribution of IMEF-systems in microbes, we carried out BLASTp searches using IMEF cargo proteins as queries and identified 71 operons in a range of Firmicutes including Qs (— 1a). The core operon consists of the encapsulin capsid protein and the IMEF cargo protein with 70% of operons also encoding a 2Fe-2S ferredoxin homologous to bacterioferritin-associated ferredoxins (Bfd). Bfd proteins are involved in the mobilization of iron under iron-limited conditions (Yao et al. , 2012). In addition, 31% of operons are associated with proteins similar to ferrochelatases involved in catalyzing the insertion of ferrous iron into protoporphyrins (Dailey et al. , 2000). The majority of IMEF-encoding genomes do not contain any ferritin or bacterioferritin genes (Supplementary file 1). Most IMEF genomes do however contain Dps-encoding genes. Overall, the operon organization of IMEF-systems and the lack of other known primary iron storage proteins indicate a function for IMEF-systems in dynamic iron storage similar to that of Ftn and Bfr. Using a recombinant system for the expression of the two-gene IMEF operon containing the IMEF cargo protein gene and the encapsulin capsid protein gene, we produced homogeneous IMEF cargo-loaded encapsulins (— 1b). Through single-particle cryo-EM analysis, we determined the structure of the Qs IMEF encapsulin shell at an overall resolution of 3. 85 Å (— 2a and Supplementary file 2). The IMEF encapsulin self-assembles into a 240-subunit icosahedral compartment with a diameter of 42 nm (1b and — 2a–d). The IMEF compartment is substantially larger than previously reported encapsulins and possesses a triangulation number of T = 4 instead of T = 1 (60 subunits, 24 nm) or T = 3 (180 subunits, 32 nm) and represents the largest encapsulin compartment reported to date (— 2e). The shell is composed of 12 pentameric and 30 hexameric capsomers occupying icosahedral vertices and faces, respectively. In contrast, T = 1 encapsulins consist of only 12","People often think of the cell as the basic unit of life. Despite this, individual cells are also subdivided into many compartments, called ‘organelles’ because they act like the internal organs of the cell. For example, organelles can break down nutrients, store information in the form of DNA, or help remove waste. Even bacterial cells, despite being smaller and simpler than most other cell types, contain organelle-like structures. These are tiny compartments, termed protein organelles, which are enclosed by ‘shells’ made from self-assembling proteins within the cell. Cells need iron to carry out the chemical reactions necessary for life. Iron is therefore an essential nutrient, but it can also be toxic if not stored properly inside the cell. Cells often solve this problem by locking iron away inside",380,128,0.3368
dialogsum,"#Person1#: Could I have my hair dyed? #Person2#: Certainly, which color do you want to dye it? #Person1#: I want the latest fashion, can you make some suggestions? #Person2#: Right now, many girls are dyeing there hair blond. #Person1#: I don't think that was suit me very well, blond is kind of erratic. #Person2#: What do you think about pink? #Person1#: Oh, no. I think it's better to be a natural chinese, with natural chinese hair. Have you got good brand of hair dye? #Person2#: Yes, we have several brands, which one do you prefer? #Person1#: I want the best one. #Person2#: First, you need a shampoo, it makes it easier for your hair to be dyed. Let's down your hair in the water, you hair will be fairly clean that way. #Person1#: After this dye job, it feels I look younger. #Person2#: You hair is definitely fresh and shiner looking.",#Person1# refuses #Person2#'s recommendation of either dyeing the hair blood or pink. #Person1# prefers a natural Chinese and chooses the best brand of hair dye. #Person1# thinks the dying makes #Person1# look younger.,151,33,0.2185
scientific_lay_summarisation-elife-norm,"ApoE4 genotype is the most prevalent and also clinically most important risk factor for late-onset Alzheimer’s disease (AD). Available evidence suggests that the root cause for this increased risk is a trafficking defect at the level of the early endosome. ApoE4 differs from the most common ApoE3 isoform by a single amino acid that increases its isoelectric point and promotes unfolding of ApoE4 upon endosomal vesicle acidification. We found that pharmacological and genetic inhibition of NHE6, the primary proton leak channel in the early endosome, in rodents completely reverses the ApoE4-induced recycling block of the ApoE receptor Apoer2/Lrp8 and the AMPA- and NMDA-type glutamate receptors that are regulated by, and co-endocytosed in a complex with, Apoer2. Moreover, NHE6 inhibition restores the Reelin-mediated modulation of excitatory synapses that is impaired by ApoE4. Our findings suggest a novel potential approach for the prevention of late-onset AD. Over the course of the last 30 years, we have learned much about the genetics of Alzheimer’s disease (AD), yet the pathological mechanisms that cause the onset of the disease and that define its progression culminating in massive neurodegeneration and debilitating dementia remain poorly understood. We know that amyloid-β (Aβ), an aggregation-prone proteolytic processing product that consists of juxtamembrane sequences and approximately 2/3 of the transmembrane segment of the larger amyloid precursor protein (APP), plays a central role early on, while during later stages of the disease – through mechanisms that are completely obscure – the microtubule-associated protein τ begins to form intraneuronal aggregates, that is the neurofibrillary tangles, that can spread transsynaptically (Selkoe and Hardy, 2016). It is this τ-aggregation, not the amyloid plaques, which occur early in the disease process, that is thought to be primarily responsible for the neuronal cell death and brain mass loss and that most closely tracks with dementia progression. Before they become visible as the telltale plaques and tangles that cement the AD diagnosis for the pathologist, Aβ and τ are present as smaller oligomeric aggregates that can directly and profoundly impair neuronal functions, by disrupting synaptic Ca2+ homeostasis (Kuchibhotla et al. , 2008). The resulting synaptic dysfunction is widely thought to represent the earliest stage of the AD pathogenic process and to be a major cause of its clinical manifestation as mild cognitive impairment (MCI) (Palop and Mucke,","Alzheimer’s disease is a degenerative condition that destroys connections between brain cells leading to memory loss, confusion and difficulties in thinking. Apolipoprotein E is a protein that carries fatty substances called lipids and cholesterol around the brain, and plays an important role in repair mechanisms. There are three major forms of Apolipoprotein E, and individuals who carry a version known as ApoE4 are up to 10 times more likely to develop Alzheimer’s disease than those who carry other variations. In nerve cells, or neurons, Apolipoprotein E binds to a specific family of receptors. One of these receptors, called Apoer2, is found in the synaptic gap between neurons, where it regulates their activities. Both Apolipoprotein E and Apoer2 are taken into the cell within compartments known as endosomal vesicles.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER) -associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway. Sterols, such as cholesterol in animals or ergosterol in yeast, are essential components of cellular membranes and their concentration to a large extent determines many of the membrane properties, such as fluidity and rigidity. Therefore, cells evolved sophisticated mechanisms to precisely regulate their sterol levels (Goldstein et al. , 2006; Brown and Goldstein, 2009). These are critical not only for adjusting membrane properties to diverse cellular environments but also for preventing the accumulation of free sterols, which is toxic both to individual cells and to whole organisms (Goldstein et al. , 2006; Espenshade and Hughes, 2007; Maxfield and van Meer, 2010). The regulation of cellular sterol levels occurs primarily during their biosynthesis in the endoplasmic reticulum (ER) by the mevalonate pathway (Espenshade and Hughes, 2007; Brown and Goldstein, 2009). This highly conserved pathway produces isoprenoids, precursors not only for sterols but also for other essential molecules such as dolichol or ubiquinone (1A; Goldstein and Brown, 1990). While a constant supply of these molecules is required, cells must avoid overaccumulation of sterols, a balance that is achieved by a number of feedback systems operating at the transcription, translation, and post-translational levels. Remarkably, decades of work demonstrated that many of these homeostatic control systems converge on the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), an enzyme involved in an early and rate-limiting step of the mevalonate pathway (Brown and Goldstein, 2009; Burg","All cells are enclosed by a membrane that is made up of fatty molecules called lipids and is studded with proteins. This membrane allows cells to detect and react to outside events. Since external conditions, such as temperature, can vary dramatically, membranes need to be able to adjust their properties. For example, lipids become more fluid as the temperature rises, so membranes respond to heat stress by incorporating molecules called sterols to increase their rigidity. In fact, sterols have profound effects on membrane properties and are essential to regulate a number of cellular processes. But high levels of sterols can become toxic, so it is essential that they are carefully controlled. Sterols, such as ergosterol in yeast or cholesterol in mammals, are synthesized in a tightly regulated multi-step",380,128,0.3368
pubmed-summarization,"whose ancestry was 6 standard deviations from the mean on one of the top ten eigenvectors . in the replication study we successfully determined genotypes for 46 snps that showed suggestive ( p < 10 ) or significant p values in the genome - wide meta - analysis of gwas1 and gwas2 , using a custom illumina goldengate assay . snp genotypes were subjected to quality control filters similar to those in gwas1 and gwas2 , as appropriate . for gwas2 , after quality control filtering of subjects and snp data and removal of genetic outliers , we compared allele frequencies of the remaining 495,821 snps in the final 418 cases and 2810 controls using the unadjusted cochran - armitage trend test implemented in plink and the adjusted cochran - armitage trend test implemented in eigensoft , in which both phenotypes and genotypes of subjects were adjusted for ancestry using the top ten eigenvectors . the unadjusted cochran - armitage trend tests and the adjusted cochran - armitage trend tests yielded genomic inflation factors of 1.054 and 1.050 , respectively , indicating that residual population stratification was negligible . odds ratios and 95% confidence limits were calculated by logistic regression analysis by use of plink . to fully assess association at the 24 novel suggestive loci , we imputed genotypes for each locus using mach , ver.1.0 based on patterns of haplotype variation in the 1000 genomes project european ancestry samples ( release aug 4 , 2010 ) . we retained imputed snps with r > 0.3 and minor allele frequency > 0.01 for further analyses . for the replication study , after quality control filtering , we compared allele frequencies for genotyped snps in the remaining 1377 patients and 1284 controls using the cochran - armitage trend test . odds ratios and 95% confidence limits were calculated by logistic regression analysis . to obtain combined ors and p values for gwas1 and gwas2 , and for the combined gwas1 , gwas2 , and replication studies , we performed meta - analysis using a cochran - mantel - haenszel test . a breslow - day test was used to test for heterogeneity of ors of the same snp in different study cohorts . calculation of linkage disequilibrium between snps in","in previous linkage and genome - wide association studies we identified 17 susceptibility loci for generalized vitiligo . by a second genome - wide association study , meta - analysis , and independent replication study , we have now identified 13 additional vitiligo - associated loci , including oca2-herc2 , a region of 16q24.3 containing mc1r , a region of chromosome 11q21 near tyr , several immunoregulatory loci including ifih1 , cd80 , clnk , bach2 , sla , casp7 , cd44 , ikzf4 , sh2b3 , and a region of 22q13.2 where the causal gene remains uncertain . functional pathway analysis shows that most vitiligo susceptibility loci encode immunoregulatory proteins or melanocyte components that likely mediate immune targeting and genetic relationships among vitiligo , malignant melanoma ,",380,128,0.3368
dialogsum,"#Person1#: Mom!? ? ? #Person2#: I know, sweetie. Just open wide. Don't talk. #Person1#: Mmm. . . #Person2#: Oh, you've got a fever. One-oh-one. . . time to break out the children's Tylenol. #Person1#: I have the chills. Can you turn on the heater? #Person2#: We're not turning on the heater in May! You need to take a bath. We'll heat you up and see if you can sweat this thing out.",#Person1# has a fever. #Person1#'s mom asks #Person1# to take a bath to sweat it out.,72,16,0.2222
dialogsum,"#Person1#: Is everything going well according to the plan? #Person2#: Our store will open two weeks before Christmas. #Person1#: I guess we should announce ourselves soon. Tell people we're coming. Put up a big sign. #Person2#: Sure. The minute they see the sign, they will be lining up. #Person1#: To show their anger. #Person2#: Yeah. They are lining up not to buy things but to show their anger. Because some people think chain stores all look the same. #Person1#: They'll hate us in the beginning. But we'll get them in the end.",#Person1# and #Person2# talk about the plan of announcing themselves in their store's open day and predict people's reactions.,92,19,0.2065
dialogsum,"#Person1#: Wow, it all looks so good. I'm not sure what to choose. #Person2#: I can recommend the spare ribs. They are very tasty here. #Person1#: Actually, I ate too much pork yesterday. I fancy a change. #Person2#: Ok why don't you order the braised fish then? #Person1#: That sounds like a good idea. It looks very big though. #Person2#: Don't worry. I'll help you eat it.",#Person2# recommends spare ribs but #Person1# fancy a change. #Person2# suggests eating braised fish.,67,14,0.209
dialogsum,"#Person1#: Who do you think should get the job? How about Mr. Becket? #Person2#: Mr. Becket? I'm not sure. He is a nice fellow, of course, and easy to get along with. But I doubt his professional expertise. I want someone who can get the job done.",#Person2# doesn't think Mr. Becket is qualified for the job,47,10,0.2128
pubmed-summarization,"be left to others began to be asked in the 1980s , especially in the usa , when many science - based markets were lost to japan , including very sophisticated areas such as dynamic access random memory , and the question was even raised whether the us semiconductor industry could survive at all . japan ( together with singapore , hong kong , and south korea ) was often quoted as a country that had been very successful economically , and captured science - based markets , but had supported applied research and product development rather than basic science . funding of basic science is important for society as a whole , but is not in the interest of any individual investor . those who make fundamental discoveries generally do not reap the benefits ; the laws of nature can not be protected and the applications are too long - term and unpredictable and the cultural and educational benefits do not generate direct profits . newton 's heirs ( if he had had any ) would be rich if it had been possible to patent the calculus and they received a royalty whenever it was used , but one can not patent laws of mathematics . if rutherford , who discovered the nucleus , could not foresee nuclear power , could a government committee do better ? who could have foreseen warm superconductors , fullerenes , or the world wide web ? human resource development in terms of ergonomics is really crouched for better , cleaner productivity . ergonomics developed into a recognized field during the second world war , when for the first time , technology and the human sciences were systematically applied in a coordinated manner . physiologists , psychologists , anthropologists , medical doctors , work scientists , and engineers together addressed these problems arising from the operation of complex military equipment . the results of this interdisciplinary approach appeared so promising that the cooperation was pursued after the war , in industry . interest in the approach grew rapidly , especially in europe and the united states , leading to the foundation in england of the first ever national ergonomics society in 1949 , which is when the term ergonomics was adopted . this was","ergonomics is becoming a subject of applying fundamentals on anthropocentric dimensions for holistic welfare . the so - called conflict between basic science and applied research finds one of its edges in ergonomics . be it cutting - edge technology or frontiers of scientific innovation all start from understanding basic scientific aptitude and skill , and the best way to get familiar with the situation is practicing basic science again and again at a regular basis . ergonomics is diversified in such paradigms that truly set an example of such harmony between two apparently never - ending straight lines . if the spirit of science is true human welfare , be it in the form of environmental development , machine development , technological advancement , human resource development",380,128,0.3368
dialogsum,"#Person1#: Hello. Nice to see you again. I heard you went into hospital for a few days to undergo surgery. I hope everything ' s OK. #Person2#: Yes, fine. I had something wrong with my stomach. I won ' t go into detail, but it wasn ' t serious. #Person1#: I really dislike going to a doctor or to a hospital. #Person2#: I think most people are a little nervous about it. I was really very, very nervous just before I had the operation, but the anaesthetist gave me an anaesthetic and the next thing I remember was waking up after the operation. #Person1#: It must have really hurt afterwards. #Person2#: Well, the nurse game me plenty of painkillers, but it did feel uncomfortable. I wasn ' t permitted to eat anything for 48 hours. That was the worse thing. #Person1#: I bet you were ready for a thick juicy steak when you got out of hospital. #Person2#: I certainly was! However, the doctor gave me a list of food I couldn ' t eat for another 72 hours, and steak was on the list! #Person1#: Is there any pain now? #Person2#: No, not at all. I stopped taking painkillers after a couple of days. #Person1#: Did they take good care of you in the hospital? #Person2#: Oh, yes. The nurse were very kind, though they were strict about what I could drink. In the end, I just drank water and nothing else. Everyone was very professional and I actually enjoyed some aspects of my stay.",#Person2# tells #Person1# about his experience in the hospital and says there isn't any pain now.,256,16,0.0625
pubmed-summarization,"idiopathic granulomatous mastitis ( igm ) is an uncommon disease which usually arises in premenopausal women shortly after their last childbirth . its etiology is unclear , however , breast - feeding and the use of oral contraceptives could exert an influence in its pathogenesis . very often clinical and radiological findings mimic multifocal breast cancer and the diagnosis is made by histopathology . etiopathogenesis of igm often involves an inflammatory mechanism which could be resolved by the administration of corticosteroids or methotrexate , negating the requirement complete surgical excision . cases of igm are related to the chronic use of selective inhibitors of serotonin reuptake ( ssri ) during antidepressant therapy are underestimated and should be treated with non - surgical therapeutic approaches . the postulated causes have included autoimmune diseases such as granulomatous thyroiditis , granulomatous prostatitis , granulomatous orchitis , immune response to local trauma , local irritants , undetected organisms such as viruses , mycotic , and parasitic infections , hyperprolactinemia , diabetes mellitus , alpha-1 antitrypsin and the use of oral contraceptives . interestingly , it has been reported that antipsychotic therapy can be associated with hyperprolactinemia and that the onset of breast enlargement can occur during chronic antidepressant therapy suggesting a possible side effect of ssri . in particular ssri could exert a perturbation in dopamine secretion , counteracting its role in repressing prolactin gene expression , leading finally to hyperprolactinemia and associated igm . in this regard , it seems worthy of noting the findings about a functional crosstalk between serotonin and dopamine receptors . in our opinion , surgical excision of the lesion is not necessary in cases of antidepressant therapy - related igm , and where possible , a conservative approach based on administration of an antiinflammatory therapy is favored . histopathological confirmation , combined with exclusion of malignancy and other causes of granulomatous disease , is of great importance in guiding clinical decision making and preventing inappropriate and unnecessary treatments . a retrospective study by erhan et al . reviewed delayed wound healing or recurrence after excisional biopsy , or those who have had an incisional biopsy only , if prolactin level was normal , reexcision and oral prednisone usage may be curative . in patients with a high prolactin","granulomatous mastitis is a rare benign inflammatory disease of the breast with multiple etiologies such as tuberculosis , sarcoidosis , foreign body reaction , and mycotic and parasitic infections . in contrast , idiopathic granulomatous mastitis ( igm ) is characterized by the presence of chronic granulomatous lobulitis in the absence of an obvious etiology . clinically and radiologically it may mimic breast carcinoma and so awareness of surgeons , pathologists , and radiologists is essential to avoid unnecessary mastectomies . cases of igm are reported during antidepressant therapy in patients also showing high levels of prolactinemia . in these cases , we believe that surgical excision must be avoided being replaced with a conservative management of the pathological condition based on a corticosteroid treatment .",380,126,0.3316
dialogsum,"#Person1#: Good morning. Mrs. Smith. #Person2#: Good morning! Can you help me, please? I'm looking for some books for my mother. #Person1#: Well, what kind of books does she like? #Person2#: She's very fond of detective stories? #Person1#: I see. Has she read any detective stories? #Person2#: Oh, yes! #Person1#: Do you know if she's read this one? #Person2#: I'm not sure, but she probably won't remember if she has! She's very forgetful! #Person1#: Ah! She has a bad memory. How old is she? #Person2#: She's eighty-seven. #Person1#: I suggest you take this book. It's very exciting. #Person2#: Thank you. That's a good idea. she likes exciting books. Can you suggest another one?",#Person2# asks #Person1# to recommend some detective stories for #Person1#'s mother.,113,11,0.0973
pubmed-summarization,"- translational modifications , the species - specific isoform , and detergent solubilization procedures . in addition to the fmn , fad , and nadph binding domains , cpr also contains a 60 amino acid hydrophobic n - terminal membrane anchoring region , which is essential for full activity with native redox partners , such as cytochrome p450 enzymes . a number of important crystal structures of cpr and several of its mutants have been produced , including those demonstrating important conformational changes that take place upon reduction and cyp binding . the first crystal structure of cpr was obtained using an n - terminally truncated sequence of the rat isoform . this structure demonstrated that the nadph fad binding domain also contained an important linker sequence that could help position the fmn and fad domains in close proximity for efficient electron transfer . the linker sequence distinguishes cpr from the closely related , single - domain ferrodoxin reductases . it is worthwhile to note that this particular n - terminally truncated construct was not able to support cyp reduction , even though it successfully reduced cytochrome c. more recent x - ray crystal structures have provided some insight into cyp the crystal structure of a cpr mutant with a four amino acid deletion in the hinge region between the fmn binding domain and the rest of the protein demonstrated remarkable flexibility in this region by crystallizing in three different conformations . although this particular mutant was not able to catalyze intramolecular electron transfer between the fad and fmn prosthetic groups , it was able to successfully reduce cyps , given enough reducing equivalents . the three different conformations observed suggest that cpr inherently possesses a high degree of conformational plasticity , especially in the c terminus of the hinge region , allowing it to efficiently interact with a variety of cyp isoforms and other enzymes . other structures obtained from protein x - ray crystallography and nmr have confirmed this conformational flexibility and the ability of cpr to transition between closed and open forms , which had also been predicted by computational molecular dynamics studies . another intriguing possibility is that subtle structural differences between cyp isoforms may regulate interaction with cpr and cytochrome b5 . seminal work examining","through their unique oxidative chemistry , cytochrome p450 monooxygenases ( cyps ) catalyze the elimination of most drugs and toxins from the human body . protein protein interactions play a critical role in this process . historically , the study of cyp protein interactions has focused on their electron transfer partners and allosteric mediators , cytochrome p450 reductase and cytochrome b5 . however , cyps can bind other proteins that also affect cyp function . some examples include the progesterone receptor membrane component 1 , damage resistance protein 1 , human and bovine serum albumin , and intestinal fatty acid binding protein , in addition to other cyp isoforms . furthermore , disruption of these interactions can lead to altered paths of metabolism and the production of toxic",380,128,0.3368
scientific_lay_summarisation-elife-norm,"all isoforms (Drep-2C-Term). Western blots from wild-type fly head extracts probed with Drep-2C-Term showed a double band (1C) of the size expected for Drep-2 isoforms (McQuilton et al. , 2012). We generated drep-2 mutants by FLP-mediated excision between FRT site-bearing transposons to explore the function of Drep-2. The transposons P (XP) d00223 and PBac (RB) e04659 were used for the deletion allele drep-2ex13 (1A). A second deletion allele, drep-2ex27, was established using transposon lines PBac (RB) e02920 and PBac (RB) e04659. All drep-2 exons are deleted in homozygous drep-2ex13 animals, while no other annotated transcription unit is affected. In the smaller intragenic deletion drep-2ex27, all drep-2 exons apart from the very small (12 bp) first exon are eliminated. Both Drep-2C-Term antibody bands were absent in head extracts of both mutants (1C), confirming the complete elimination of Drep-2 expression in these deletion alleles. Flies lacking drep-2 were viable and fertile but shorter-lived than the isogenic controls (— 2). Subsequently, we used the Drep-2C−Term antibody for wholemount immunostainings of Drosophila brains. The synaptic neuropil was strongly labeled throughout the brains of larvae (not shown) and adults (). In both drep-2 mutants, Drep-2C−Term staining in the CNS was completely abolished (drep-2ex13: 2A, B). 10. 7554/eLife. 03895. 006Figure 2. Synaptic Drep-2 staining in the CNS. (A–B) Confocal frontal sections of adult Drosophila brains. Anti-Drep-2C-Term and BrpNc82 immunostaining; the latter marks all synaptic active zones. Synaptic Drep-2C-Term signal is visible throughout the brain of wild-type flies (A). Complete loss of the anti-Drep-2C-Term staining can be observed in drep-2ex13 mutants (B). Scale bars: 20 µm. (C–E) Frontal sections of wild-type brains, anti-Drep-2C-Term, and BrpNc82 staining. Scale bars: 5 µm. (C) Posterior–dorsal detail showing strong Drep-2 staining in MB calyces (arrow). (D) Anterior frontal section with antennal lobes and MB lobes. (E) Ellipsoid body in the central complex and bulbs (lateral triangles) (E′: magnification of strong Drep-2 staining in bulbs). : http: //dx. . org/10. 7554/eLife. 03895. 006 As a Dff family member, Drep-2 has been suggested to be involved in the apoptotic regulation of DNA degradation (Inohara and Nuñez, 1999; Park and Park, 2012). However, neuronal cell bodies lacked Drep-2C−Term staining (). We produced synaptosome-like preparations by fractionation of the adult Drosophila CNS to biochemically confirm the association of Drep-2 with synapses (Owald et al. ,","Synapses are specialized structures that connect nerve cells to one another and allow information to be transmitted between the cells. Synapses are essential for learning and storing memories. Many proteins that regulate how signals are transmitted at synapses have already been studied. In this manner, much has been learned about their function in learning and memory. Cells can commit suicide by a process called apoptosis, also known as programmed cell death. Apoptosis is not only triggered in damaged cells but is also necessary for an organism to develop correctly. In fruit flies, the protein Drep-2 is a member of a family of proteins that degrade the DNA of cells that undergo apoptosis. Andlauer et al. found no evidence that Drep-2 plays a role in apoptosis, but have now",380,128,0.3368
dialogsum,"#Person1#: She is, like, mega-intense, isn't she? #Person2#: Ha, she is unstoppable. I'm learning so much from her. #Person1#: What's it like to work with her? #Person2#: She's demanding. But I like that. I mean, I know our timeline is tight. #Person1#: Tell me about it. #Person2#: You guys are working around the clock, I know. That guy Dave next to Zina never leaves. #Person1#: Vince wants us to have everything debugged and ready to go by the end of the month.",#Person2# tells #Person1# about a hard-working coworker. #Person2# acknowledges that #Person1# is working overtime as well.,82,16,0.1951
pubmed-summarization,"d - penicillamine has been known as one of the agents that are able to induce pemphigus ( 1,2 ) . n-(2-mercapto-2-methylpropionyl)-l - cysteine ] is a thiol compound contained two free sulfhydryl groups , whereas d - penicillamine has only one sulfhydryl radical ( 3 ) . while drug - induced pemphigus was not infrequently demonstrated in association with d - penicillamine , it has rarely been reported with bucillamine and has never been reported in rheumatoid arthritis ( ra ) and polymyositis ( pm ) overlap syndrome . hereby , we report a case of bucillamine - induced pemphigus vulgaris in a patient with ra and pm overlap syndrome . a 46-yr - old woman was referred to our rheumatology department due to polyarthralgia , and myalgia in may 2001 . soft tissue swelling and tenderness were bilaterally noted at the proximal interphalangeal and metacarpophalangeal joints with morning stiffness lasting at least 1 hr . proximal motor weakness on upper arms and legs has insidiously developed over three months and findings of magnetic resonance image on both thighs were compatible with myositis . in addition , elevated level of muscle enzymes including creatine kinase ( ck ) , aldolase , alanine aminotransferase ( ast and alt ) , and lactate dehydrogenase was shown . antinuclear antibody was positive at 1:80 of speckled pattern , and 1:2,560 of cytoplasmic pattern . auto - antibodies including anti - jo-1 , anti - rnp , anti - double stranded dna , anti - sm , and anti - ss - a / ss - b were absent . level of rheumatoid factor was 3,420 iu / ml , but level of c3 and c4 was 97.9 mg / dl ( normal range 79 - 152 mg / dl ) and 30.8 mg / dl ( normal range 16 - 38 mg / dl ) respectively . chest radiograph showed pattern of interstitial lung disease and pulmonary function test revealed significantly decreased dlco . she was diagnosed as ra and pm overlap , and had been treated with prednisolone , azathioprine and non - steroidal anti - inflammatory drug since may 2001 . myositis became silent over time with above regimen , however she had continuous synovitis and joint pain on right","bucillamine is a disease modifying anti - rheumatic drug , structurally similar to d - penicillamine . although d - penicillamine - induced pemphigus has been not infrequently demonstrated , pemphigus associated with bucillamine was rarely reported . we describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis ( ra ) and polymyositis ( pm ) overlap syndrome . pm and ra overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months . skin lesions including erythematous flaccid blisters on her chest , axillae , and back were occurred and were compatible with pemphigus vulgaris by typical pathology . withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions .",380,119,0.3132
dialogsum,"#Person1#: You're all set to leave. #Person2#: I can't believe it. #Person1#: What are your plans? #Person2#: I plan on going back to school. #Person1#: What will your major be? #Person2#: I'm not sure yet, but I plan to do good things. #Person1#: You don't have plans to end up back here, do you? #Person2#: I have no plans on being back. #Person1#: You don't belong here. #Person2#: That's true. #Person1#: Good luck with your life. #Person2#: I'm going to be fine.",#Person2#'s leaving and tells #Person1# #Person2#'s plan to go to school without coming back.,82,14,0.1707
dialogsum,"#Person1#: May I help you, sir? #Person2#: I need a hat. Would you show me some? #Person1#: Certainly, here you are. #Person2#: I like the black one. May I try it on? #Person1#: Of course. It fits you perfectly. #Person2#: Yes, I thinks so. How much is it? #Person1#: It's forty-five yuan. #Person2#: Can you make it much cheaper? #Person1#: Sorry, our prices are set.","#Person2# bargains for a hat, but #Person1# says the price is set.",65,12,0.1846
pubmed-summarization,". at the morphological level , ltp is generally associated with dendritic spine growth , whereas ltd can induce the removal of postsynaptic ampa receptors and loss of spines . it is thus not surprising that synaptic development , maintenance , and plasticity under normal physiological conditions are frequently associated with changes in the morphology and number of dendritic spines . in many neurodegenerative diseases , particularly those exhibiting cognitive impairments such as alzheimer 's disease ( ad ) and parkinson 's disease ( pd ) , changes in dendritic spine number and morphology are also found in other disease conditions such as autism , down syndrome , drug addiction , fragile x syndrome , and schizophrenia . it is worth emphasizing that degeneration of synapses and dendritic spines is one of the earliest features in those neurodegenerative disease conditions , prior to subsequent loss of neurons . interventions aimed to protect the nervous system from the ravages of these disease would therefore seem more effective when the synaptic and spine pathology are prevented as early as possible . in this review article , we will summarize recent advances in our understanding of the molecular mechanisms underlying synaptic and dendritic spine pathology in neurodegenerative diseases , particularly in ad and pd . the readers are referred to some excellent previous reviews on the observation of synaptic and dendritic spine pathology in neurological disorders . ad is the most common neurodegenerative disease and the leading cause of dementia in the elderly . decades of intensive research have uncovered amyloid plaque and neurofibrillary tangle ( nft ) as the pathological hallmarks , and soluble amyloid- ( a ) oligomers as the leading candidate for the causative agent of ad . however , the mechanistic link between amyloid plaque and nft and the mechanism by which a oligomer may cause cognitive impairments remains poorly defined , and there is no effective treatment for this devastating disease . substantial evidences have accumulated indicating that the memory deficits in ad patients do not correlate well with amyloid plaque burden ; instead , the loss of synaptic markers is a better predictor of clinical symptoms and disease progression . together with studies using animal ad models , these studies have lent support to the hypothesis that","synapses are sites of cell - cell contacts that transmit electrical or chemical signals in the brain . dendritic spines are protrusions on dendritic shaft where excitatory synapses are located . synapses and dendritic spines are dynamic structures whose plasticity is thought to underlie learning and memory . no wonder neurobiologists are intensively studying mechanisms governing the structural and functional plasticity of synapses and dendritic spines in an effort to understand and eventually treat neurological disorders manifesting learning and memory deficits . one of the best - studied brain disorders that prominently feature synaptic and dendritic spine pathology is alzheimer 's disease ( ad ) . recent studies have revealed molecular mechanisms underlying the synapse and spine pathology in ad , including a role for mislocalized tau in",380,128,0.3368
dialogsum,"#Person1#: Hey, let's eat out tonight. #Person2#: What's the occasion? You won the lottery? #Person1#: No. Just want to relax a little bit. You don't have to win the lottery to relax, do you? #Person2#: Well, I am kind of broke. #Person1#: Come on. It's on me. #Person2#: Really? It's very nice of you. #Person1#: Don't be silly. I'll take you anywhere you wanna go. #Person2#: Wonderful! You know what? I wish you wanted to relax everyday. #Person1#: Dream on!","#Person1# asks #Person2# to eat out tonight to relax. Since #Person2#'s kind of broke, #Person1# will treat today.",80,18,0.225
dialogsum,"#Person1#: Did you hear about the air crash that occurred in South America recently? It was quite a tragic accident! #Person2#: No, I didn't see anything in the news about it. What happened? #Person1#: A foreign airliner was attempting to land at night in a mountainous area in Argentina and flew into a hill! #Person2#: That sounds really terrible! Did anyone survive? #Person1#: No, everyone aboard, including the crew, was killed instantly. #Person2#: What were the circumstances? Were they bad weather, a fire, or engine failure? #Person1#: Apparently, there were some low clouds in the area, but mostly it was just miscommunication between the pilots and the traffic controllers. #Person2#: Weren't they both speaking in English, the official international aviation language? #Person1#: Yes they were, but the transmit ion from poor quality radios was slightly distorted and the accents of the Spanish speaking controllers was so strong that the pilots that the pilots misunderstood a vital instruction. #Person2#: How could a misunderstanding like that cause such a serious accident? #Person1#: The pilots were told to descend to 2-2,000 feet. The instruction actually meant 22,000 feet, but they thought they heard descend 2,000 feet. That's a huge difference, and it should have been confirmed, but it was not. Unfortunately, the terrain of the mountains in Norweija ascends to 2,000 feet. #Person2#: So the pilots did descend to the wrong altitude then, because they were following the air controllers instructions. #Person1#: Sadly enough, yes they did. It was a really bad mistake. Many people died as a result of the simply understanding. #Person2#: Wow, that's a powerful lesson on how important it can be to accurately communicate to each other.",#Person1# tells #Person2# about the air crash that occurred in South America recently which was caused by miscommunication between the pilots and the traffic controllers. #Person2# thinks it's important to accurately communicate with each other.,278,35,0.1259
scientific_lay_summarisation-elife-norm,"among visual objects (Fiser and Aslin, 2002; Bulf et al. , 2011; Kirkham et al. , 2002). Nine-month-old infants who were exposed to multi element visual scenes, showed greater interest in element pairs which co-occurred more frequently than in pairs which co-occurred less frequently. Moreover, the infants were sensitive to the predictability between elements of the pairs as manifested by the conditional probability relations between these elements (Fiser and Aslin, 2002). The ability to extract statistical patterns of visual stimuli was found even in younger age groups (Kirkham et al. , 2002); two-, five-, and eight-month-old infants were habituated to sequences of discrete visual stimuli whose ordering followed a statistical predictable pattern. Subsequently the infants were shown the previously encountered pattern alternating with a novel pattern of identical stimulus components. Infants of all age groups looked longer at the novel sequences providing evidence for the detection of visual statistical regularities at an early developmental stage. These results suggest that infants own powerful mechanisms for extracting the statistical properties of their sensory input without any instructions, explicit feedback, or intentional awareness (Lany and Saffran, 2013; Krogh et al. , 2012). The ability of infants to detect crossmodal statistical regularities within their sensory environment is less well understood, but some basic multisensory abilities, such as multisensory temporal synchrony detection seem to exist within the first month of life (Lewkowicz, 1992). In the next months the capability to perceive higher-level and more complex multisensory relations starts to develop. For example, at the age of six months infants were shown to perceive duration-based (Lewkowicz, 1992) and spatio-temporal based crossmodal relations (Scheier et al. , 2003). Furthermore, there is evidence that similar to adults, infants take advantage of crossmodal events in terms of a better discrimination and a faster responsiveness to bimodal compared to unimodal information (Bahrick et al. , 2004; Lewkowicz and Kraebel, 2004). First evidence for multisensory facilitation was found in eight-month-old infants as indicated by faster eye movements to spatially aligned auditory and visual cues compared to eye movements to each of these stimuli alone (Neil et al. , 2006). Moreover, other studies revealed multisensory benefits for perceptual learning in infants (Bahrick and Lickliter, 2000; Frank et al. , 2009). Five-month-old infants were habituated to either an audio-visual rhythm or the same","On a crowded city street, we automatically attribute the sounds of cars to the cars we see driving past, and not to the motorcycles or trucks on the same road. Similarly, we assign the voices we hear to the pedestrians around us, and not to the dogs those pedestrians are walking. As adults, we cope with these everyday challenges effortlessly, but how do infants first learn to match what they see with what they hear? When young animals are exposed to new stimuli, their brains undergo changes. Similar changes only occur in adult animals if they deliberately pay attention to the stimuli and if they are associated with rewards. Rohlf, Habets et al. therefore predicted that human infants would automatically learn to associate sights and sounds upon being",380,128,0.3368
scientific_lay_summarisation-elife-norm,"were numbered according to the B isoform and can be compared to ours by subtracting 44 residues from our numbering. Phosphorylation sites identified in Araki et al. , (2015) were numbered according to the A isoform and can be compared to ours by adding 15 residues to our numbering. The 5 residue PDZ ligand is located at the C-terminus. (B) PSD-95. The five major domains of PSD-95, including the approximate relationships of its three N-terminal PDZ domains are indicated (Cho et al. , 1992). : http: //dx. . org/10. 7554/eLife. 16813. 004 SynGAP, a postsynaptic GTPase activating protein, is unusually abundant in the PSD scaffold. One prominent alternatively spliced isoform, synGAP-α1 (Li et al. , 2001) contains a PDZ-domain ligand and binds to all three of the PDZ domains of PSD-95 (Kim et al. , 1998; Figures 1,2). Here we propose that association of synGAP-α1 with PDZ domains of PSD-95 contributes to regulation of docking of AMPARs within the PSD and, therefore, to regulation of its overall protein composition. This function is distinct from its function as a Ras/Rap GAP (Walkup et al. , 2015). We support this hypothesis by showing that phosphorylation by at least two protein kinases on several sites in the regulatory region of synGAP-α1 reduces the affinity of synGAP-α1’s PDZ-ligand for the three PDZ domains of PSD-95. One of these protein kinases is CaMKII, which is activated when synaptic plasticity is initiated by activation of NMDA-type glutamate receptors (NMDARs). The other is PLK2, a constitutively active kinase that is induced by neuronal activity and mediates homeostatic scaling (Seeburg et al. , 2005). We further show that binding of Ca2+/CaM to synGAP-α1 selectively reduces its affinity for PDZ3 of PSD-95. Finally, we show that reduction of the total amount of synGAP in heterozygous knockout mice alters the composition of PSDs in the mutant mice in a way that is most directly explained by reduced competition from synGAP-α1 for binding to PDZ domains of PSD-95. The PSD is an organized complex of signaling proteins attached to the postsynaptic membrane of excitatory glutamatergic synapses in the central nervous system. It comprises a network of scaffold proteins, the most prominent of which is PSD-95, a member of the MAGUK family (Membrane-Associated GUanylate Kinase-like proteins) (Kennedy, 2000; Sheng and Kim, 2011).","The formation of memories is believed to depend on the strengthening of connections, called synapses, between neurons in the brain. When neurons are activated together, their synaptic connections become permanently strengthened to record the memory. This strengthening is called activity-dependent long-term potentiation. As long-term potentiation develops, more protein receptors are added to the receiving side of the synapse. This allows the receiving neuron to produce a larger electrical response to the signaling chemicals it receives from the neuron on the sending side of the synapse. The addition of receptors is regulated by a set of enzymes held near the membrane of the synapse by a protein scaffold known as the postsynaptic density. A major scaffold protein called PSD-95 contains binding sites, known as PDZ domains, that hold protein",380,128,0.3368
pubmed-summarization,"in physical activity ( pha ) . the first two components can be measured opportunely with reasonable accuracy and have been fully studied in lean and obese subjects . there is actually no clear evidence that a low bmr is a factor in the development of obesity , even if the issue continues to be debated . the thermic effect of food , and more specifically the thermic effect of carbohydrate , has been shown to decrease in obese subjects . this decrease may , nevertheless , be secondary to obesity - related insulin resistance and is of too small magnitude to account for a major weight gain . nonexercise activity thermogenesis ( neat)the energy expended for everything we do that is not sleeping , eating , or sports - like exercise and pha , that is crucial for weight control , may be important in the physiology of weight change . we review the current concepts about energy expenditure and evaluate the pha in the context of this knowledge and the available literature . during pha , mechanical work associated with muscle contractions clearly requires energy . as a result of the associated loss of energy as heat during atp synthesis in the mitochondria and atp hydrolysis during muscular contraction , pha may thus have a major impact on the total 24-hour energy expenditure and energy balance . based on the possible means by which alterations in pha can impact on 24-hour energy expenditure and energy balance , the following hypotheses can be formulated . this response would induce to a lower energy expenditure for any given work load and would probably contribute to the realization of a positive energy balance in affected subjects . it was further shown to be similar in both lean and post - obese women . there is then little reason to suppose that this factor might be involved in body - weight gain . , nevertheless , showed that a common polymorphism of uncoupling protein 2 , a protein with close homology to the uncoupling protein of brown adipose tissue ubiquitously expressed in man , was associated with a lower energetic efficiency of muscle contractions . therefore , brown adipose tissue , where uncoupling protein 1 ( ucp1 ) activity uncouples mitochondrial respiration","we review the current concepts about energy expenditure and evaluate the physical activity ( pha ) in the context of this knowledge and the available literature . regular pha is correlated with low body weight and low body fat mass . the negative fat balance is probably secondary to this negative energy balance . nonexercise activity thermogenesis ( neat ) and physical activity , that is crucial for weight control , may be important in the physiology of weight change . an intriguing doubt that remains unresolved is whether changes in nutrient intake or body composition secondarily affect the spontaneous physical activity .",380,103,0.2711
dialogsum,"#Person1#: Good morning. Vane Theater, at your service. #Person2#: Hello. I'm thinking about watching a Chinese traditional opera with a foreign girl. What's on this weekend? #Person1#: Well, there will be charity performance on Saturday night. And also, there will be a solo concert by an opera star on Sunday night. #Person2#: It's a good thing that I have choices here. Can you tell me about the one on Saturday? #Person1#: Sure. It's to raise money for the homeless. #Person2#: What about the performance itself? #Person1#: Oh, it's a reserved opera named The Monkey Creates Havoc in Heaven. #Person2#: Wow, a story about the clever Monkey King. It's a classic and children's favorite. #Person1#: It surely is. And the cast is really the best. #Person2#: Wonderful! How much is the ticket? #Person1#: The price varies according to the seats. 300 for the front, 200 for the middle, and 50 for the back.",#Person2# is going to watch a Chinese opera with a girl. #Person1# introduces The Monkey Creates Havoc in Heaven and #Person2# is interested.,152,23,0.1513
pubmed-summarization,"serum opacity factor ( sof ) was first discovered in 1938 by the australians ward and rudd as a substance produced by group a streptococci that caused serum to become cloudy ( ) , hence its name . sof was found to act on a lipoprotein fraction of serum and various enzymatic activities were proposed to account for the opacity reaction of sof including those as a cholesterol esterase and apolipoproteinase or aspartic protease . subsequently , sof was found not to be a hydrolase but rather induced opacification of serum by binding to high - density lipoproteins ( hdls ) , displacing apolipoprotein a - i ( apo a - i ) and disrupting the structure of hdl resulting in the formation of large , lipid particles that cause serum to become opaque . sof is expressed by a variety of streptococci and staphylococci including both human and animal pathogens . sof is expressed by approximately 50% of the invasive isolates of the group a streptococcus , streptococcus pyogenes , an important human pathogen that colonizes the human skin and the oral cavity where it may stimulate mild to severe local inflammatory responses resulting in pharyngitis in the throat and impetigo in the skin . in susceptible hosts , these infections can lead to life - threatening complications such as sepsis , necrotizing fasciitis , and toxic shock , or to debilitating sequelae such as rheumatic fever and glomerulonephritis . the adhesion to and subsequent colonization of the host by s. pyogenes have been attributed to a number of surface exposed molecules including sof . furthermore , sof has been found to contribute to the pathogenesis of streptococcal infections in animal models and to evoke protective immune responses in humans and animals indicating its potential as a virulence determinant and vaccine candidate . sof is a unique protein exhibiting multiple functions including not only its ability to opacify serum but also an ability to bind to a variety of host proteins such as fibronectin , fibrinogen , and fibulin-1which are involved in bacterial adhesion . this paper will provide an overview of the methods of assaying for sof activity , the structure and function of sof , its prevalence and distribution in bacteria , its role in contributing to","serum opacity factor ( sof ) is a virulence determinant expressed by a variety of streptococcal and staphylococcal species including both human and animal pathogens . sof derives its name from its ability to opacify serum where it targets and disrupts the structure of high - density lipoproteins resulting in formation of large lipid vesicles that cause the serum to become cloudy . sof is a multifunctional protein and in addition to its opacification activity , it binds to a number of host proteins that mediate adhesion of streptococci to host cells , and it plays a role in resistance to phagocytosis in human blood . this article will provide an overview of the structure and function of sof , its role in the pathogenesis of streptococcal infections",380,128,0.3368
pubmed-summarization,"cortical and posterior subcapsular . investigations on possible risk factors for the development of cataract , showed positive correlation with myopia , diabetes , smoking , use of systemic corticosteroids , exposition to uv - b , and other environmental factors , to which has to be added genetic predisposition . however , it should be underlined that different degrees of correlation between distinct risk factors and the three types of cataract have been reported . prevalence studies of age - related cataracts are hampered by the absence of a uniform grading system for cataract opacities , by differing definitions of visual impairment , and by additional coexisting ocular pathologies causing loss of vision . nonetheless , the framingham eye study in 1977 reported that the proportion of people with age - related cataracts causing loss of vision of 20/30 ( 6/9 ) or worse was 15.5% for all ages and 45.9% for those older than 75 years . in the beaver dam eye study in 1992 , using a similar definition of loss of vision reported proportions were 38.8% for men and 45.9% for women older than 74 years . however , it is not clear if variations in frequency reflect methodological diversity or true differences between populations . interestingly , most of the cited studies analyzed the cataract prevalence in age groups which are substantially different from those of our two cases . one single study reported the prevalence of cataract at a younger age ( 40 years and older ) with identified risk factors for the three different histological types of cataract . this study showed age - specific rates of the different histological cataract type , by stratifying the population sample by age . prevalence of 1% ( cortical type ) , of 0.2% ( nuclear type ) and of 2.0% ( posterior subcapsular ) was reported in individuals between 40 and 49 years and a prevalence of 3.9% ( cortical type ) of 0.2% ( nuclear type ) and of 2.6% ( posterior subcapsular ) was reported in individuals between 50 and 59 years . here , we report two cases that both developed cataract before the age of 50 years on the side affected from the cluster headache and reviewed published similar cases and","cluster headache ( ch ) consists of attacks of severe , unilateral orbital / supraorbital / temporal pain , lasting for 15180 min , occurring once or more times a day , and associated with ipsilateral conjunctival injection , lacrimation and other symptoms . cataract is clouding of the lens of the eye causing a progressive and painless loss of vision . we describe the cases of two men ( not relative , but with the same last name , which originates from north - eastern italy ) that in young adult age , after years of suffering from chronic ch , developed cataract on the same side of the pain attacks . patient 1 was diagnosed as having cataract 18 years after the onset of episodic (",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Acoustic communication is fundamental to social interactions among animals, including humans. In fact, deficits in voice impair the quality of life for a large and diverse population of patients. Understanding the molecular genetic mechanisms of development and function in the vocal apparatus is thus an important challenge with relevance both to the basic biology of animal communication and to biomedicine. However, surprisingly little is known about the developmental biology of the mammalian larynx. Here, we used genetic fate mapping to chart the embryological origins of the tissues in the mouse larynx, and we describe the developmental etiology of laryngeal defects in mice with disruptions in cilia-mediated Hedgehog signaling. In addition, we show that mild laryngeal defects correlate with changes in the acoustic structure of vocalizations. Together, these data provide key new insights into the molecular genetics of form and function in the mammalian vocal apparatus. Vocal communication is fundamental to social interaction. Indeed, the voice is so crucial to our quality of life that the neurobiology of speech and language has been hotly studied for decades, as has the developmental biology of the ear. These bodies of work stand in surprising contrast to our still rudimentary understanding of the developmental biology of the organs of vocalization, the larynx and vocal folds. This is true despite the fact that most animal vocalizations, including human speech, are critically dependent upon the careful control of airflow though the larynx. In fact, larynx and vocal fold morphology and elasticity are key factors influencing vocalization even in animals with widely divergent mechanisms of sound production (e. g. audible vocalizations in humans, ultrasound in rodents). This deficit in our understanding of laryngeal and vocal fold development is significant, because many people who are capable of normal speech still cannot communicate due to defects in voice (e. g. problems with pitch, loudness, etc.). Some voice defects arise from acute insults, such as insufficient hydration of the vocal folds in laryngitis sicca or vocal fold hemorrhages resulting from blood vessel ruptures (Aronson and Bless, 2009). Other conditions are hereditary and chronic, such as those arising from mutations in genes encoding the extracellular matrix protein Elastin (Vaux et al. , 2003; Watts et al. , 2008). All of these conditions impact the voice, thereby impacting patients’ well-being. A wide","Nearly all animals communicate using sound. In many cases these sounds are in the form of a voice, which in mammals is generated by a specialized organ in the throat called the larynx. Millions of people throughout the world have voice defects that make it difficult for them to communicate. Such defects are distinct from speech defects such as stuttering, and instead result from an inability to control the pitch or volume of the voice. This has a huge impact because our voice is so central to our quality of life. A wide range of human birth defects that are caused by genetic mutations are known to result in voice problems. These include disorders in which the Hedgehog signaling pathway, which allows cells to exchange information, is defective.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"these leukaemias represent different diseases across bivalve species, they have been classically grouped under the same term because neoplastic cells share morphological features (Carballal et al. , 2015). Some HNs have been proven to have a clonal transmissible behaviour (Metzger et al. , 2015), in which neoplastic cells, most likely haemocytes (i. e. the cells that populate the haemolymph and play a role in the immune response), are likely to be transmitted through marine water. In late stages of the disease, leukaemic cells invade the surrounding tissues and, generally, animals die because of the infection (Carballal et al. , 2015), although remissions have also been described (Burioli et al. , 2019). Despite the observation that leukaemic cells are typically transmitted between individuals from the same species, on occasion they can infect and propagate across populations from a second, different bivalve species (Metzger et al. , 2016; Yonemitsu et al. , 2019). Hence, these cancers represent a potential threat for the ecology of the marine environment, which argues for the necessity of their identification and characterization for their monitoring and prevention. Here, we use multiplatform next-generation genome sequencing technologies, including Illumina short reads and Oxford Nanopore long reads, together with cytogenetics, electron microscopy, and cytohistological approaches to identify, characterize, and decipher the evolutionary origin of a new marine leukaemia that is transmitted between two different clam species that inhabit the Seas of Southern Europe, namely warty venus (Venus verrucosa) and striped venus (Chamelea gallina) (Video 1). We investigated the prevalence of HN in the warty venus clam (V. verrucosa), a saltwater bivalve found in the Atlantic Coast of Europe and the Mediterranean Sea. We collected 345 clam specimens from six sampling regions in the Atlantic and the Mediterranean coasts of Europe across five different countries, including Spain, Portugal, France, Ireland, and Croatia (1a; Supplementary file 1). Cytohistological examination identified HN-like tumours in eight specimens from two sampling points in Spain (1b–e; — 1). Three HN-positive specimens (ERVV17-2995, ERVV17-2997, and ERVV17-3193) were collected in Galicia, northwest of the Iberian Peninsula in the Atlantic Ocean, and another five specimens (EMVV18-373, EMVV18-376, EMVV18-391, EMVV18-395, and EMVV18-400) were collected in the Balearic Islands, bathed by the Mediterranean Sea (1a; Supplementary file 1). Four of these specimens (ERVV17-2995, ERVV17-3193, EMVV18-391, and EMVV18-395) showed a severe form","In humans and other animals, cancer cells divide excessively, forming tumours or flooding the blood, but they rarely spread to other individuals. However, some animals, including dogs, Tasmanian devils and bivalve molluscs like clams, cockles and mussels, can develop cancers that are transmitted from one individual to another. Despite these cancers being contagious, each one originates in a single animal, meaning that even when the cancer has spread to many individuals, its origins can be traced through its DNA. Cancer contagion is rare, but transmissible cancers seem to be particularly common in the oceans. In fact, 7 types of contagious cancer have been described in bivalve species so far. These cancers are known as ‘hemic neoplasias’, and are characterized by the uncontrolled division of blood-like cells, which can",380,128,0.3368
dialogsum,"#Person1#: May I have a word with you? #Person2#: Certainly. #Person1#: When will you be free? #Person2#: Come by any time. #Person1#: Shall I say around ten o'clock? #Person2#: Yes, I'll be waiting for you in my home by 10:00.","#Person1# suggests a meeting at 10, where #Person2# agrees.",40,9,0.225
scientific_lay_summarisation-elife-norm,"The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display ‘active’ histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a ‘bivalent’ chromatin state bearing simultaneous ‘active’ and ‘inactive’ chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G + C-rich DNA. A high CpG density alone is not sufficient for this effect, as A + T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G + C-richness are required for induction of signature chromatin structures at CGIs. CpG islands (CGIs) are stretches of atypical genomic DNA sequences that mark most gene promoters (Bird, 1986; Deaton and Bird, 2011). Though individually unique in nucleotide sequence, mammalian CGIs share two features that often correlate but can vary independently: a G + C-rich base composition (65% vs 40% for the bulk genome) and high density of the dinucleotide CpG (5–10-fold higher than the bulk genome). Whereas bulk genomic DNA is globally methylated, CGIs associated with promoters invariably lack DNA methylation. It has been proposed that CGIs function as generic platforms for gene regulation, probably via proteins that bind to CpG and influence chromatin modification (Blackledge and Klose, 2011; Deaton and Bird, 2011). This hypothesis has gained credence due to accumulating evidence that enrichment or depletion of specific chromatin marks at CGIs is linked to proteins that bind to unmethylated CpG. So far, all such proteins possess CXXC zinc finger domains that bind specifically to the CpG dyad in duplex DNA (Lee et al. , 2001). Cfp1, for example, is a CXXC domain-containing component of the Set1/COMPASS complex (Lee and Skalnik, 2005), which generates H3K4 methylation, a signature chromatin mark at non-methylated CGIs (Bernstein et al. , 2006; Guenther et al. , 2007). Accordingly, Cfp1 is concentrated at CGIs as determined by chromatin immunoprecipitation (ChIP) and its absence is associated with reduced H3K4 methylation","The building blocks of DNA are four molecules commonly named ‘A’, ‘T’, ‘C’ and ‘G’. The order of these DNA letters in a gene contains the instructions to make specific proteins or other molecules. Other stretches of DNA contain codes that direct the cell' s machinery to genes that need to be switched on or switched off. The start of a gene, for example, has a stretch of DNA called a promoter, which is where the molecular machinery that switches on the gene is assembled. A human cell can contain over two and half metres of DNA. To get this length to fit inside the cell, the DNA is wrapped tightly around proteins to form a structure called chromatin. However, this packing can make it difficult to access",380,128,0.3368
scientific_lay_summarisation-elife-norm,"mec-8 encodes a conserved RNA-binding protein involved in alternative splicing (Lundquist et al. , 1996; Spike et al. , 2002). We have shown that the contribution of MEC-8 in the resistance to this force arises, at least in part, through its control of FBN-1, a protein that shares several domains with vertebrate fibrillins and acts in the embryonic sheath. Notably, mutations in human fibrillin genes lead to connective tissue disorders including Marfan syndrome (Dietz et al. , 2005; Ramirez and Dietz, 2009; Ramirez and Sakai, 2010). In wild-type embryos at the 1. 5-fold stage of development, a shallow pit (∼2. 1 µm deep), termed the sensory depression, is detected in the region corresponding to the location of the future mouth (buccal cavity; 1A, Table 1; Sulston et al. , 1983). This morphological feature is relatively short-lived and is no longer visible in threefold-stage embryos (1A, 2C). In contrast, mec-8; sym-3 and mec-8; sym-4 embryos had a striking keyhole-shaped invagination in this region, which increased in depth between the 1. 5-fold (∼4. 3 µm) and 3-fold (∼9. 5 µm) stages (1A, Table 1). In contrast to wild-type L1 larvae, in which the pharynx and associated buccal capsule (terminal mouth part) extended to the anterior tip of the worm, mec-8; sym-3 and mec-8; sym-4 L1 larvae displayed what we have termed the ‘Pharynx ingressed’ (Pin) phenotype, in which the pharynx and buccal capsule are displaced toward the posterior end of the animal (1A). In Pin larvae, lateral anterior tissues appeared to fold over and surround the ingressed buccal capsule, thereby preventing double mutants from feeding (1A). Although these defects were observed at only low frequencies in sym-3, sym-4 and mec-8 single mutants, they were highly penetrant in mec-8; sym-3 and mec-8; sym-4 double mutants (1B, Supplementary file 1). 10. 7554/eLife. 06565. 003Figure 1. mec-8; sym-3 and mec-8; sym-4 mutants exhibit an abnormal ingression of the anterior epidermis. (A) Whereas wild-type 1. 5-fold embryos display only a shallow ingression of the anterior epidermis (sensory depression) and little or no ingression by the threefold stage, mec-8; sym-3 and mec-8; sym-4 (data not shown) mutants contain a deep keyhole-shaped ingression that increases in depth between the 1. 5-fold and 3-fold stages. mec-8; sym-3 and mec-8; sym-4 (data not shown) L1 larvae also contain an ingressed","For an animal embryo to develop, its cells must organize themselves into tissues and organs. For example, skin and the lining of internal organs—such as the lungs and gut—are made from cells called epithelial cells, which are tightly linked to form flat sheets. In a microscopic worm called Caenorhabditis elegans, the outermost layer of epithelial cells (called the epidermis) forms over the surface of the embryo early on in embryonic development. Shortly afterwards, the embryonic epidermis experiences powerful contractions along the surface of the embryo. The force generated by these contractions converts the embryo from an oval shape to a roughly cylindrical form. These contractions also squeeze the internal tissues and organs, which correspondingly elongate along with the epidermis. It has been known for decades that such ‘mechanical’",380,128,0.3368
scientific_lay_summarisation-elife-norm,"co-activators via its C-terminus, most notably to the CREB-binding protein (CBP) histone acetyltransferase or its p300 paralog (Mosimann et al. , 2009), resulting in the transcription of the linked Wnt target genes. Subsequent reversion to the OFF state (for example, by negative feedback from high Wnt signaling levels near Wnt-producing cells, or upon cessation of signaling) involves Groucho/TLE-dependent silencing, but also requires the Osa/ARID1 subunit of the BAF (also known as SWI/SNF) chromatin remodeling complex (Collins and Treisman, 2000) which binds to β-catenin through its BRG/BRM subunit (Barker et al. , 2001). Cancer genome sequencing has uncovered a widespread tumor suppressor role of the BAF complex, which guards against numerous cancers including colorectal cancer, with >20% of all cancers exhibiting at least one inactivating mutation in one of its subunits, most notably in ARID1A (Kadoch and Crabtree, 2015). Thus, it appears that failure of Wnt-inducible enhancers to respond to negative feedback imposed by the BAF complex strongly predisposes to cancer. How β-catenin overcomes Groucho/TLE-dependent repression remains unclear, especially since β-catenin and TLE bind to TCF simultaneously (Chodaparambil et al. , 2014). Therefore, the simplest model envisaging competition between β-catenin and TLE cannot explain this switch, which implies that co-factors are required. One of these is Pygo, a chromatin reader binding to histone H3 tail methylated at lysine 4 (H3K4m) via its C-terminal PHD finger (Fiedler et al. , 2008). In Drosophila where Pygo was discovered as an essential co-factor for activated Armadillo, its main function appears to be to assist Armadillo in overcoming Groucho-dependent repression (Mieszczanek et al. , 2008). We recently discovered that Pygo associates with TCF enhancers via its highly conserved N-terminal NPF motif that binds directly to the ChiLS complex, composed of a dimer of Chip/LDB (LIM domain-binding protein) and a tetramer of SSDP (single-stranded DNA-binding protein, also known as SSBP). Notably, ChiLS also binds to other enhancer-bound NPF factors such as Osa/ARID1 and RUNX, and to the C-terminal WD40 domain of Groucho/TLE, and thus forms the core module of a multiprotein complex termed ‘Wnt enhanceosome’ (Fiedler et al. , 2015). We proposed that Pygo renders this complex Wnt-responsive by capturing Armadillo/β-catenin through the Legless adaptor (whose orthologs in humans are BCL9 and B9L, also known as BCL9-2) (Kramps et al. , 2002; Städeli and Basler, 2005).","In every animal, different cells must be able to communicate with each other to make sure that the body is correctly formed and maintained. Animal cells have many ways of communicating, but one important and well-studied mechanism involves a signaling molecule called Wnt that is released by some cells and received by others. The Wnt molecule and its effects are similar in all animals, and over-active Wnt signaling in humans contributes to a number of diseases including various cancers. The Wnt signal is carried from the surface of the receiving cell to the DNA in its nucleus via a protein called β-catenin. The β-catenin protein then helps to switch on a large number of genes. However, to do this β-catenin must interact with an assembly of other proteins",380,128,0.3368
pubmed-summarization,"hek293 cells stably expressing human glp-1 receptor and a 3x - cre luciferase reporter were grown at 37c in 5% co2 in dulbecco 's modified eagle 's medium-31053 ( invitrogen , carlsbad , ca ) supplemented with 0.5% fbs , 2 mmol / l l - glutamine , 50 units / ml penicillin , 50 g / ml streptomycin , and 20 mmol / l hepes . for compound testing , cells were plated into 96-well poly - d - lysine , white opaque microplates . compounds were solubilized in dmso , diluted in medium containing 0.1% bsa fraction v substituted for 0.5% fbs , and added to cells . after a 5-h incubation , cells were harvested in steadylite plus lysis reagent ( perkin elmer , waltham , ma ) , and luciferase activity was measured according to the manufacturer 's instructions using an envision 2104 multilabel reader . data are expressed as a percentage of maximum stimulation induced by the glp-1 ( 736 ) amide peptide ( bachem , torrance , ca ) . two hours before compound testing , cells were resuspended in the aforementioned medium and plated in 96-well half area , solid black microplates . cells were assayed for camp using the camp dynamic 2 kit with homogenous time - resolved fluorescence technology ( cisbio , bedford , ma ) . fluorescence was measured according to the manufacturer 's instructions using an envision 2,104 multilabel reader . data are expressed as nm camp of the final assay solution induced by the glp-1 receptor agonists . animals were maintained in accordance with the institutional animal use and care committee of eli lilly and company and the guide for the use and care of laboratory animals by the national institutes of health . for animal treatment , compounds were solubilized in dosing solution containing 10% ethanol / solutol , 20% polyethylene glycol-400 , and 70% pbs ( ph 7.4 ) . male sd rats were purchased from harlan ( indianapolis , in ) and group - housed three per cage in polycarbonate cages with filter tops . rats were maintained on a 12:12 h light - dark cycle ( lights on at 6:00 a.m. ) at 21c and received 2014 teklad global diet ( harlan , indianapolis","objectivethe clinical effectiveness of parenterally - administered glucagon - like peptide-1 ( glp-1 ) mimetics to improve glucose control in patients suffering from type 2 diabetes strongly supports discovery pursuits aimed at identifying and developing orally active , small molecule glp-1 receptor agonists . the purpose of these studies was to identify and characterize novel nonpeptide agonists of the glp-1 receptor.research design and methodsscreening using cells expressing the glp-1 receptor and insulin secretion assays with rodent and human islets were used to identify novel molecules . the intravenous glucose tolerance test ( ivgtt ) and hyperglycemic clamp characterized the insulinotropic effects of compounds in vivo.resultsnovel low molecular weight pyrimidine - based compounds that activate the glp-1 receptor and stimulate glucose - dependent insulin secretion are described . these",380,128,0.3368
pubmed-summarization,"agenesis of the inferior vena cava ( ivc ) as a cause of recurrent deep vein thrombosis ( dvt ) is uncommon . a 33-year - old male with no family history of thrombophilia , who had experienced multiple recurrent episodes of dvt over a 15-year period of unknown cause , was admitted into our hospital because of cellulitis in the right leg . congenital absence of the ivc could be a rare risk factor for idiopathic dvt , especially in young individuals . venous thromboembolism ( vte ) , which includes deep vein thrombosis ( dvt ) and pulmonary embolism , has an incidence of 1 to 3 per 1000 individuals per year in western populations.1 congenital anomalies of the inferior vena cava ( ivc ) are uncommon , and have been associated with the development of venous thrombosis of the lower limbs.2 congenital anomalies of the ivc has been reported as a risk factor for dvt , especially in individuals < 30 years old , and a concomitant thrombophilic disorder has been found in such individuals.3 we report a case of recurrent dvt in a 33-year - old man with agenesis of the ivc . the patient had experienced recurring episodes of idiopathic dvt in the right leg for 15 years . a 33-year - old man was admitted to the internal medicine department , holy family hospital , nazareth , israel , because of cellulitis in the right leg . one week prior to his admission , he complained about pain and increased local heat in the left ankle and thumb of the right leg . the patient had no history of previous trauma , surgery , insect bites , dysuria , or joint symptoms , and no family history of thrombophilia . he reported that he had ( a ) rheumatic fever without any complications when he was 19 years old , which was treated with penicillin , ( b ) been hospitalized when he was 23 years old because of infected skin ulcers on the right calf , for which he was treated by parenteral antibiotics , and ( c ) recurrent episodes of idiopathic dvt for the last 15 years . he also reported that he had not been treated with warfarin , but","background : agenesis of the inferior vena cava ( ivc ) as a cause of recurrent deep vein thrombosis ( dvt ) is uncommon.case:a 33-year - old male with no family history of thrombophilia , who had experienced multiple recurrent episodes of dvt over a 15-year period of unknown cause , was admitted into our hospital because of cellulitis in the right leg . computer tomography with contrast of the abdomen showed an absence of ivc.conclusion:congenital absence of the ivc could be a rare risk factor for idiopathic dvt , especially in young individuals .",380,95,0.25
dialogsum,"#Person1#: I think the car we saw yesterday would be a good deal. What do you think? #Person2#: Yes, but I think you should ask someone to take a look at it just to be sure. #Person1#: My friend Jack knows cars and he helped me do the check this morning. #Person2#: It was smart of you to think ahead. Have you and the salesman agreed on a price? #Person1#: Yes, he finally agreed to accept the discounted price I asked. #Person2#: Then have you thought about how to pay? #Person1#: Well, I've saved up enough money to pay cash for this car. #Person2#: Good. Let me go with you to make the payment and drive the car home for you. #Person1#: Thank you. That would make it much easier for me. #Person2#: You're welcome. Let's go take care of that right now.",#Person1# and #Person2# think the car is a good deal. #Person1#'s friend Jack helped to check it and the salesman agreed on a discount. #Person2#'ll go with #Person1# to pay.,143,30,0.2098
dialogsum,"#Person1#: Hey, John. Nice car. #Person2#: Thanks. I finally got rid of that old Nissan that got me through college. #Person1#: What is this, the new Ford? #Person2#: No, it's last year's model. #Person1#: True. How much did you pay? #Person2#: $ 14, 500. It only has 10, 000 miles on it, so it's like a new car. #Person1#: Does that mean you're not going to take the train to work anymore? #Person2#: Well, sometimes, I think it'll be nice to drive to work instead. We'll see. Want to go for a ride? #Person1#: Yeah, sure. #Person2#: Come on.","John buys a Ford for $14,500 and will drive to work. John will take #Person1# for a ride.",99,18,0.1818
dialogsum,"#Person1#: Jenny, I was wondering if you, um. . . are you busy this Friday? #Person2#: Yes, Friday I have a class right after work. #Person1#: Oh. What about Saturday? Are you free then? #Person2#: Saturday my parents are coming to town. What's up? #Person1#: What about tonight? Do you have plans tonight? #Person2#: No. Did you want to go do something? #Person1#: Yes! Yes! I want to take you to dinner. #Person2#: Oh! That sounds great! How about six o'clock?",Jenny's unavailable on Friday and Saturday so #Person1# invites her to dinner tonight.,81,13,0.1605
scientific_lay_summarisation-elife-norm,"can be essentially abolished by the opioid receptor antagonist naloxone (Valentino and Dingledine, 1982). VTA-DA neurons were identified based on Ih currents (1A) and tyrosine hydroxylase (TH) staining (1B). Details of the identification method are given in the ‘Materials and methods’ section. Using original recordings of spontaneous firing (left panel of 2A) and the time course of spontaneous firing (middle panel of 2A) in VTA-DA neurons for comparison, we could see that morphine (10 μM) increased the frequency of spontaneous firing in VTA-DA neurons. The average frequency of spontaneous firing increased from 1. 0 ± 0. 3 Hz before to 1. 4 ± 0. 4 Hz for 10–15 min after morphine application (n = 6 cells from five rats, paired t test, p < 0. 05, compared to control before morphine, right panel of 2A). In order to determine the role of glutamatergic input in the morphine-induced increase in the spontaneous firing frequency of VTA-DA neurons, we observed the influence of the N-methyl-D-aspartic acid (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) (50 μM) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6,7-Dinitroquinoxalie-2,3-dione (DNQX) (10 μM) on the effect of morphine. In the presence of APV and DNQX, morphine no longer increased spontaneous firing frequency (2B). The average frequency of spontaneous firing was 0. 7 ± 0. 1 Hz before and 0. 8 ± 0. 1 Hz for 10–15 min after morphine application in the presence of APV and DNQX (n = 6 cells from five rats, paired t test, p > 0. 05, compared to control with APV and DNQX before morphine, right panel of 2B). These results suggest that the morphine-induced increase in the spontaneous firing frequency of VTA-DA neurons requires AMPA and NMDA receptor-mediated glutamatergic input, consistent with a recent report using the NMDA antagonist APV and the AMPA receptor antagonist 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) in in vivo experiments (Jalabert et al. , 2011). 10. 7554/eLife. 09275. 003Figure 1. Identification of VTA-DA neurons in rats. (A) Electrophysiological properties of VTA-DA neurons. Left panel: representative traces showing a large hyperpolarization-activated current (Ih) in whole-cell voltage-clamp recording. Holding potential: −70 mV. Right panel: representative traces showing a large voltage ‘sag’ when hyperpolarized in whole-cell current-clamp recording. Holding current: 0 pA. (B) Immunohistochemical labeling of identified VTA-DA neurons. Panel 1: images of a Lucifer yellow-labeled","Morphine is one of the most commonly used drugs for the treatment of severe pain. It is derived from opium, which is extracted from poppies, and binds to the same receptors in the brain as the body' s own naturally produced painkillers. As well as providing pain relief, morphine can act directly on the brain' s reward system to trigger a state of euphoria, and can therefore be highly addictive. One of the key components of the brain' s reward circuit that morphine affects is called the ventral tegmental area (VTA). The activity of the VTA is regulated by the combined efforts of two groups of cells: excitatory glutamatergic neurons that increase VTA activity and inhibitory interneuronsthat reduce the activity of the VTA. Morphine inhibits the interneurons, thereby",380,128,0.3368
pubmed-summarization,"showed pd - associated peritonitis : the white blood cell ( wbc ) count of the peritoneal effluent was 1,620/mm with a neutrophil predominance ( 90% ) . his hemoglobin was 9.9 g / dl , wbc count was 14.510/l , and c - reactive protein was 12.53 mg / dl ( normal : < 0.8 mg / dl ) . after the peritoneal fluid was sent for bacterial culture , a single 1 g / d dose of cefazolin and a single 1 g / d dose of ceftazidime were given intraperitoneally . two peritoneal fluid samples were inoculated into a bactec plus aerobic / f culture bottle ( becton dickinson diagnostic instrument system , drogheda , ireland ) and incubated in a bact / alert 3d blood culture system ( biomerieux , marcy l`etoile , france ) . culture of the peritoneal dialysate revealed streptococcus mitis , which was susceptible to levofloxacin , clindamycin , vancomycin , and tetracycline . the peritoneal wbc count decreased to 30/mm , and the patients clinical condition improved on the 5 day after starting intraperitoneal cefazolin and ceftazidime . however , he complained of abdominal pain and turbid peritoneal effluent 3 days after termination of intraperitoneal antibiotics . the wbc count of the peritoneal effluents was 2,140/mm with a neutrophil predominance ( 80% ) . we restarted intraperitoneal cefazolin and ceftazidime , and repeated culture of the peritoneal dialysate revealed s. mitis . according to the international society for peritoneal dialysis guidelines , we recommended removal of the pd catheter , but he refused our recommendation . therefore , we maintained intraperitoneal antibiotics , and the patient improved after intraperitoneal antibiotics for 2 weeks ; however , the patient experienced turbid peritoneal effluent 10 days after cessation of the second round of intraperitoneal antibiotics . the wbc count of the peritoneal effluents was 2,080/mm with a neutrophil predominance ( 85% ) , and repeated culture of the peritoneal dialysate revealed r. mucilaginosa . the peritoneal wbc count decreased to 8/mm , and abdominal pain disappeared on the 3 day after starting intraperitoneal cefazolin and ceftazidime . the patients condition improved , and he was discharged after a 2-week course of intraperitoneal antibiotics ( . x - ray showed a poorly defined ,","rothia muciliaginosa ( r. mucilaginosa ) is a facultative , gram - positive coccus that is considered to be part of the normal flora of the mouth and respiratory tract . there are sporadic reports of the organism causing endocarditis in patients with heart valve abnormalities , as well as meningitis , septicemia , and pneumonia associated with intravenous drug abuse . however , it is an unusual pathogen in cases of peritoneal dialysis ( pd)-associated peritonitis . although r. mucilaginosa is generally susceptible to penicillin , ampicillin , cefotaxime , imipenem , rifampicin , and glycopeptides , there are no guidelines for the treatment of pd - associated peritonitis . herein , we report a case of pd - associated peritonitis due to r. mucilaginosa that was",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. To understand how MITF regulates transcription, we used tandem affinity purification and mass spectrometry to define a comprehensive MITF interactome identifying novel cofactors involved in transcription, DNA replication and repair, and chromatin organisation. We show that MITF interacts with a PBAF chromatin remodelling complex comprising BRG1 and CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. Combinations of MITF, SOX10, TFAP2A, and YY1 bind between two BRG1-occupied nucleosomes thus defining both a signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of the regulatory elements they occupy. BRG1 also regulates the dynamics of MITF genomic occupancy. MITF-BRG1 interplay thus plays an essential role in transcription regulation in melanoma. Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper (bHLH-Zip) factor, regulates specification, survival, and proliferation of normal melanocytes, and controls proliferation, migration and invasion of melanoma cells (Goding, 2000; Widlund and Fisher, 2003; Steingrimsson et al. , 2004). The level of functional MITF expression determines many of the proliferation and invasion properties of melanoma cells (Hoek and Goding, 2010) and siRNA-mediated MITF silencing induces senescence in several melanoma lines (Strub et al. , 2011). We previously reported a genome wide analysis of MITF target genes in 501Mel melanoma cells (Strub et al. , 2011). Chromatin immunoprecipitation coupled to deep sequencing (ChIP-seq) identified MITF binding sites and integration with RNA-seq following siRNA-mediated MITF knockdown showed that MITF directly and positively regulates genes involved in DNA replication and repair and mitosis. In contrast, MITF represses genes involved in melanoma invasion. To better understand the molecular function of MITF, we used tandem affinity purification to isolate MITF from 501Mel melanoma cells and mass spectrometry to identify its interacting partners. We report here the first comprehensive characterisation of the MITF interactome and we show that MITF interacts physically and functionally with a novel form of the PBAF chromatin-remodelling complex specific for neural crest derived cells comprising both BRG1 and CHD7. We also show that MITF and SOX10 recruit BRG1/PBAF to the nucleosomes flanking critical enhancer elements in the melanocyte lineage. Using 501Mel melanoma","Melanocytes are pigment-producing cells found primarily in the skin. Many of the genes that help these cells to develop are also thought to affect the development of melanomas: an aggressive form of skin cancer that originates in these cells. One such gene encodes a protein called MITF. This protein binds to DNA and regulates genes that control the development, survival, and spread of melanocytes; it is also linked to the invasive properties of melanomas. The MITF protein works together with partner proteins to control numerous genes, activating some while inhibiting others, by binding to nearby stretches of DNA that act as regulatory elements. Its interactions are therefore widespread and complex. Now, Laurette, Strub et al. have used techniques called tandem affinity purification and mass spectrometry to identify the",380,128,0.3368
dialogsum,"#Person1#: I was thinking about cooking dinner tonight. #Person2#: What do you want to make? #Person1#: I'm not exactly sure. #Person2#: I wouldn't mind a Beef Bowl. #Person1#: How do I make that? #Person2#: All it has is rice and beef. #Person1#: That sounds easy. But How do I make it? #Person2#: First, you need to make some white rice. #Person1#: Then what do I do? #Person2#: Then, you need to cut up some beef and mix it with sauce. #Person1#: Is there anything else I need to do? #Person2#: Then all you need to do is cook it and enjoy it.",#Person2# suggests having a Beef Bowl for dinner and tells #Person1# how to make it.,102,15,0.1471
pubmed-summarization,"screened molecular mechanics ( mm ) charges or simple empirical damping corrections . such screened mm charges are typically parametrized for qm / mm applications and may be not directly applicable in full mm calculations , e.g. , to reproduce the attractive sapt electrostatic energy in a stacked benzene benzene conformation , unless an explicit term for interactions of the valence charge densities is included , as in the model recently proposed by wang and truhlar . in this study , the charge is revisited , implemented , and extensively tested in the context of the amoeba force field and using a new parametrization strategy . the charge penetration corrected amoeba point multipole model ( multipoles + cp ) is developed using a comprehensive set of small molecule complexes , and the parameters are determined for h , c , n , o , p , s , f , cl , and br to cover the elements commonly found in organic and biological molecules . to facilitate model development in this and future studies , a new database of sapt2 + decomposed quantum mechanical energies constructed for 101 small molecule pairs , each at 7 different intermolecular distances ( the s1017 database ) , is presented . in order to systematically examine the electrostatic and other components of intermolecular forces , the s101 and s1017 databases of homo- and heterodimers of common organic molecules have been constructed . the first 66 pairs , which cover the majority of the typical organic interactions of h , c , n , and o atoms , are taken from the s66 database from hobza et al . in addition , 15 complexes containing halogen atoms ( f , cl , and br ) , six complexes containing sulfur , and four complexes containing phosphorus have been added . furthermore , 10 monomer water complexes , which encompass amino acid side chain analogs ( including the charged ones ) missing in the s66 data set , have also been added , yielding a total of 101 pairs . to construct the s1017 database , definitions of the intermolecular distance vectors from the s668 database of hobza et al . were used . unlike s668 , each of the 101 model complexes were placed","classical molecular mechanics force fields typically model interatomic electrostatic interactions with point charges or multipole expansions , which can fail for atoms in close contact due to the lack of a description of penetration effects between their electron clouds . these short - range penetration effects can be significant and are essential for accurate modeling of intermolecular interactions . in this work we report parametrization of an empirical charge charge function previously reported ( piquemalj .- p . ; j. phys . chem . a2003 , 107 , 1035326313624 ) to correct for the missing penetration term in standard molecular mechanics force fields . for this purpose , we have developed a database ( s1017 ) of 101 unique molecular dimers , each at 7 different intermolecular distances",380,128,0.3368
pubmed-summarization,", and for providing a broad range of social and health services to their residents . documenting disparities between geographical areas with the lowest and highest cvd rates moreover , a spatial - temporal analysis should help identify geographical areas or regions which not only have high rates of cvd mortality but have also experienced slower mortality reductions , indicating the need for urgent action for cvd prevention and control . the aim of our study is to examine changes in the extent of geographical disparities in cvd mortality among 9 census regions , 50 states and the district of columbia , and 3,141 counties of the united states between 1969 and 2011 . using small - area national vital statistics mortality and census data , we model variations in county - level cvd mortality rates as a function of area deprivation , urbanization , racial / ethnic composition , smoking , obesity , physical inactivity , diabetes , and health care access . additionally , we use the national longitudinal mortality study ( nlms ) to model regional and state - level disparities in cvd mortality risks after adjusting for individual - level socioeconomic and demographic characteristics . to analyze geographical disparities in cvd mortality over time , we used the national vital statistics mortality database , which has been the cornerstone of health and disease monitoring among sociodemograhic groups and geographical areas in the us for over a century.[3 - 9,17 ] the national mortality database is based on information from death certificates of every death occurring in the united states each year . while the national mortality database provides the number of deaths ( numerator data ) by year , age , sex , race , geographic area , and cause of death , the corresponding population statistics developed by the us census bureau serve as the denominator for computing mortality rates.[6 - 9,17,18 ] the mainland united states consists of 50 states and the district of columbia , which are grouped into 9 census regions as shown in . states are divided into counties , and the number of counties varies by state . in all , there are 3,143 counties in the united states . in our study , cvd mortality rates were computed annually","objectives : this study examined trends in geographical disparities in cardiovascular - disease ( cvd ) mortality in the united states between 1969 and 2011.methods:national vital statistics data and the national longitudinal mortality study were used to estimate regional , state , and county - level disparities in cvd mortality over time . log - linear , weighted least squares , and cox regression were used to analyze mortality trends and differentials.results:during 1969 - 2011 , cvd mortality rates declined fastest in new england and mid - atlantic regions and slowest in the southeast and southwestern regions . in 1969 , the mortality rate was 9% higher in the southeast than in new england , but the differential increased to 48% in 2011 . in 2011 , southeastern",380,128,0.3368
dialogsum,"#Person1#: I hear that the Students' Union is going to take new members. #Person2#: Really? Can I join it? #Person1#: Of course you can if you like it. #Person2#: How can I join it? #Person1#: There will be an information session about the Students' Union this Tuesday. You can apply for it then. #Person2#: OK, thank you.",#Person2# wants to join the Students' Union and #Person1# suggests checking the information session.,57,14,0.2456
scientific_lay_summarisation-elife-norm,"of the genomic RNA into two large polyproteins that are extensively auto-proteolytically processed by viral proteases to give rise to 16 processing end-products, termed non-structural proteins (nsps) 1–16. Nsp1 is rapidly cleaved from the polyproteins and not considered an integral component of the coronaviral RTC, but interferes with host cell translation by inducing degradation of cellular mRNAs (Huang et al. , 2011; Züst et al. , 2007; Lokugamage et al. , 2015). Although it has not yet been formally demonstrated, the remaining nsps (nsp2-16) are thought to comprise the RTC and harbor multiple enzymes and functions, such as de-ubiquitination, proteases, helicase, polymerase, exo- and endonuclease, and N7- and 2’O-methyltransferases (Thiel et al. , 2003; Snijder et al. , 2003; Decroly et al. , 2008; Barretto et al. , 2005; Lindner et al. , 2005; Athmer et al. , 2017). Many of these functions have been studied using reverse genetic approaches, which revealed their importance in virus-host interactions (Kindler et al. , 2017; Züst et al. , 2011; Eckerle et al. , 2007; Deng et al. , 2017; Zhang et al. , 2015). In most cases, phenotypes were described via loss-of-function mutagenesis. However, in the context of virus infection, the specific interactions of RTC components with host cell factors remain largely unknown. A number of individual host cell proteins have been shown to impact coronavirus replication by using various screening methods, such as genome-wide siRNA, kinome, and yeast-two-hybrid screens (Verheije et al. , 2008; Reggiori et al. , 2010; de Wilde et al. , 2015; Wong et al. , 2015; Pfefferle et al. , 2011). Likewise, genome-wide CRISPR-based screens have been applied to other positive-stranded RNA viruses, such as flaviviruses, and identified critical host proteins required for replication (Marceau et al. , 2016; Zhang et al. , 2016). Some of these proteins were described in the context of distinct ER processes, such as N-linked glycosylation, ER-associated protein degradation (ERAD), and signal peptide insertion and processing. Although individual proteins identified by these screens may interact with viral replication complexes, they likely constitute only a small fraction of the global replicase microenvironment. To capture the full breadth of host cell proteins and cellular pathways that are spatially associated with viral RTCs, we employed a proximity-based labeling approach involving a promiscuous E. coli-derived biotin","Coronaviruses can infect the nose and throat and are a main cause of the common cold. Infections are usually mild and short-lived, but sometimes they can turn nasty. In 2002 and 2012, two dangerous new coronaviruses emerged and caused diseases known as SARS and MERS. These viruses caused much more serious symptoms and in some cases proved deadly. The question is, why are some coronaviruses more dangerous than others? Scientists know that the body' s response to virus infection can make a difference to whether someone had mild or severe disease. So, to understand why some coronaviruses cause a cold and others kill, they also need to learn how people react to virus infection. Coronaviruses hijack membranes inside cells and turn them into virus factories. Within these factories,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"independently bind to inaccessible instances of their motifs, induce chromatin accessibility, and activate endoderm-specific gene expression. The only notable distinction between the two factors was that HNF4A required more copies of its motif to bind. When expressed together, co-binding could only be explained in a minority of cases by sequential FOXA1 and HNF4A activity. Instead, most co-bound sites required concurrent co-expression of both factors, which suggests cooperativity between these TFs at certain repressive genomic locations. We suggest that our findings present an alternative to the PFH that eliminates the categorical distinction between PFs and non-PFs and instead posits that the energy required to pioneer occluded sites (‘pioneer activity’) comes from the affinity of interaction between TFs and DNA. We tested predictions of the PFH using FOXA1 as a model endoderm PF and HNF4A as a model non-PF. Because PFs are defined by their behavior in ectopic settings, we expressed FOXA1 and HNF4A in mesoderm-derived K562 lymphoblast cells. These cells express neither FOXA1 nor HNF4A and present a different complement of chromatin and cofactors. Thus, any ectopic signature that we observe is due primarily to the TFs themselves. We focused only on the initial response to TF expression to capture primary mechanisms of TF behavior and not the secondary effects that can lead to cellular conversion and that may confound our analyses. To perform these experiments, we created lentiviruses that inducibly express either FOXA1 or HNF4A (1A). We created cassettes in which a doxycycline-inducible promoter drives either FOXA1 or HNF4A and cloned these cassettes separately into a lentiviral vector (Meerbrey et al. , 2011) that constitutively expresses green fluorescent protein (GFP). Although PFs are typically expressed at supraphysiological levels (Ng et al. , 2021; Davis et al. , 1987), we infected K562 cells with each vector at a multiplicity of infection (MOI) of 1 to limit the degree of nonspecific effects. We then used flow cytometry to sort single cells and selected FOXA1 and HNF4A clones that had similar GFP levels to ensure that our clones carried a similar transgene load. Finally, we performed both doxycycline titration induction and time-course experiments to identify the minimum doxycycline concentration and treatment time for robust TF activity. We observed that 0. 5 µg/ml doxycycline for 24 hr was the minimal treatment condition that allowed","Cells only use a fraction of their genetic information to make the proteins they need. The rest is carefully packaged away and tightly bundled in structures called nucleosomes. This physically shields the DNA from being accessed by transcription factors – the molecular actors that can read genes and kickstart the protein production process. Effectively, the genetic sequences inside nucleosomes are being silenced. However, during development, transcription factors must overcome this nucleosome barrier and activate silent genes to program cells. The pioneer factor hypothesis describes how this may be possible: first, ‘pioneer’ transcription factors can bind to and ‘open up’ nucleosomes to make target genes accessible. Then, non-pioneer factors can access the genetic sequence and recruit cofactors that begin copying the now-exposed genetic information. The widely accepted theory is",380,128,0.3368
pubmed-summarization,"the number of yearly deaths from melanoma continues to increase , and the overall melanoma mortality rate is one of the few cancer mortality rates not on the decline . these realities combined with increasing evidence of the lack of efficacy of the abcde criteria have necessitated ongoing efforts to enhance the earlier clinical detection of melanoma . most approaches to melanoma diagnosis have included some predominant emphasis or combination of emphases on recognition of changing lesions , recognition of outlier ( ugly - duckling ) lesions , and specific melanoma characteristics , with the most utilized criteria being the abcde criteria ( a for asymmetry , b for border irregularity , d for 6 mm diameter , and e for evolving lesions ) . many recently published strategies have rejected the diameter criterion as well as abandoned all or portions of the abcde mnemonic . many of these proposed strategies , including the d for dark proposal i offered , have also added emphasis on recognition of darkness as a particular feature of concern in pigmented lesions . i have recently reviewed the compelling rationale for both an increased emphasis on darkness and rejection of the diameter criterion in the clinical diagnosis of melanoma . the georgia approach to melanoma diagnosis uniquely incorporates many elements of these strategies in a complementary manner to increase the sensitivity of diagnosis of early melanoma ( ) . in their review of melanoma diagnosis , marghoob and scope discuss the concepts of a screening examination to identify lesions of possible concern and then the specific lesion assessment that follows . this distinction is important because the screening examination determines the sensitivity of melanoma recognition , and it is the screening examination that really describes how most practitioners examine patients and how patients examine each other . first , the georgia approach places increased emphasis on the screening examination by initial , distinct discussion and clarification of its function . second , the approach includes both of the two screening strategies that have been used in most melanoma educational materials , change and ugly duckling identification . third , the approach adds the easily perceived , easily communicated , highly sensitive , specific ( compared to change and ugly duckling identification ) screening feature","current clinical approaches to melanoma diagnosis have not been associated with a decrease in mortality from this cancer . the components of the new approach presented are , first , a screening examination to look for any lesion that stands out because of being dark , different , or changing ; second , when a single lesion is recognized to be of concern for any reason , that lesion is then evaluated in more detail utilizing the abcde criteria , with the d signifying dark and not 6 mm diameter in this mnemonic ; and , third , additional discussion of the ugly duckling sign and of the recognition of nodular melanomas . since the georgia society of dermatology and dermatologic surgery was the first state or national",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of system xc− inhibition. Finally, we found that resistance to system xc− inhibition is correlated with dramatically increased expression of AKR1C family members that regulate the detoxification of oxidative lipid breakdown products, providing potential insight into the downstream consequences of system xc− inhibition, and the execution mechanism of ferroptosis. Erastin and SAS were previously shown to trigger ferroptosis in human HT-1080 fibrosarcoma cells grown on two-dimensional substrates with atmospheric levels of oxygen (i. e. , 21% oxygen) (Dixon et al. , 2012). We endeavored to generalize and validate the lethality of erastin towards cancer cells in several ways. First, we tested whether the same effects were observed in other cell types using a ‘modulatory profiling’ strategy (Wolpaw et al. , 2011; Dixon et al. , 2012). This method allows for the simplified detection and presentation of small molecule combination effects on cell viability (modulatory effect, Me < 0, sensitization; Me = 0, no effect; Me > 0, rescue). We observed that in five different human cancer cell lines, cell death induced by either erastin or SAS was rescued by the same canonical ferroptosis inhibitors: the iron chelator ciclopirox olamine (CPX), the lipophilic antioxidants trolox and ferrostatin-1 (Fer-1), the MEK inhibitor U0126, the protein synthesis inhibitor cycloheximide (CHX) and the reducing agent beta-mercaptoethanol (β-ME) (Dixon et al. , 2012; 1A, B). Thus, the ferroptotic death phenotype, whether induced by erastin or SAS, was similar in all cell lines tested. The inhibition of cell death by β-ME indicates that cell death most likely involves inhibition of system xc− function, as β-ME treatment can generate mixed disulfides taken up by other transporters, thereby circumventing the need for system xc− function (Ishii et al. , 1981). 10. 7554/eLife. 02523. 003Figure 1. Cell death is triggered by erastin and related compounds in different cell lines under a variety of physiological conditions. (A and B) Modulatory effect (Me) profiles of erastin- and SAS-induced death in five different cell lines (143B, BJeHLT, BJeLR, Calu-1, and HT-1080) in response to six different cell death inhibitors (U0126, Trolox, Fer-1, CPX, CHX, β–ME) or the vehicle DMSO. Me >0 indicates rescue from cell death. (C and D) Relative viability of MCTSs formed over 72 hr from HT-1080 (C) or Calu-1 (D) cells in response to erastin, RSL3 or staurosporine (STS)","Sugars, fats, amino acids, and other nutrients cannot simply diffuse into the cell. Rather, they must be transported across the cell membrane by specific proteins that stretch from one side of the cell membrane to the other. One such ‘transporter’—system xc−—is of special interest. This transporter imports one molecule of cystine from outside the cell in exchange for one molecule of glutamate from inside the cell. Cystine, a variant of the amino acid cysteine, is essential for synthesizing new proteins and for preventing the accumulation of toxic species inside the cell. Not surprisingly, many cancer cells are dependent upon the transport activity of system xc− for growth and survival. Drugs that can inhibit system xc− could therefore be part of potential treatments for cancer and other diseases. Dixon,",380,128,0.3368
dialogsum,"#Person1#: So what do you usually do in your free time? #Person2#: At the moment, I'm spending most of my free time learning German. I also enjoy playing the violin. How about you? #Person1#: I go to the sports club and do some exercise once a week.","#Person2# learns German when free, while #Person1# does exercises.",47,9,0.1915
dialogsum,"#Person1#: I haven't had much exercise lately. My only recreation has been watching TV or going to the movies. What do you do for recreation? #Person2#: In summer I like playing tennis instead of swimming and boating, and my favorite sport in the winter is skating.",#Person1# and #Person2# are sharing their recreations together.,46,8,0.1739
scientific_lay_summarisation-elife-norm,", 2017; Liu et al. , 2018; Zhang et al. , 2016). In the NAc, a significant reduction of myelin basic protein (MBP) was detected in all defeated mice, regardless of their behavioral responses (control, 3. 6 ± 0. 4%; susceptible, 2. 4 ± 0. 3%; resilient 2. 0 ± 0. 3%; 1D–E). However, no significant differences were detected in the length of myelinated segments measured by MBP immunoreactivity (1F–H) or in myelin thickness (1I–K) among groups. Pearson coefficients correlation showed no significant correlation between the length of MBP-covered segments and social interaction ratio in either control or defeated group (control, r = −0. 2242, p=0. 5934, defeated, r = −0. 3483, p-0. 3240, 1G–H). Altogether, these results suggest that myelination in the NAc uniformly responds to stress and does not distinguish susceptibility and resilience following CSDS. In contrast, the mPFC displayed a unique myelination phenotype following CSDS. While the levels of MBP did not significantly differ between susceptible and resilient mice (control, 6. 2 ± 0. 5%; susceptible, 6. 1 ± 0. 9%; resilient, 5. 3 ± 0. 8%; 2A–B), the length of myelinated segments indicated by MBP immunoreactivity showed a significant positive correlation with social interaction in defeated mice (2C–E). Importantly, such correlation was not detected in the control (unstressed) group, suggesting that changes in the length of myelinated segments represent an adaptive response to the social defeat stress. To more accurately quantify internodal length, we conducted immunohistochemical analysis using antibodies specific for the contactin-associated protein (Caspr), which marks the paranodal regions (2F). Also in this case, a significant positive correlation between internodal length and social interaction ratio was detected only in the defeated mice, with shorter internodal lengths identified in susceptible mice (2G–H). Myelin was also thinner in the susceptible - but not in the resilient – mice, compared to controls (2I–K). Therefore, region-specific myelination differences in the mPFC could -at least in part- explain the behavioral differences between susceptible and resilient mice in response to stress. To determine whether reduced myelin content in the mPFC of susceptible mice was limited to the internodal length, we further performed a detailed quantitative immunohistochemical analysis on oligodendrocyte lineage cells. No significant difference in the overall number of OLIG2+ cells was detected (3A, C), thereby ruling out decreased survival of","High levels of stress do not have the same effect on everybody: some individuals can show resilience and recover quickly, while other struggle to cope. Scientists have started to investigate how these differences may find their origin in biological processes, mainly by focusing on the role of neurons. However, neurons represent only one type of brain cells, and there is increasing evidence that interactions between neuronal and non-neuronal cells play an important role in the response to stress. Oligodendrocytes are a common type of non-neuronal cells which shield and feed nerve cells. In particular, their membrane constitutes the myelin sheath, a protective coating that insulates neurons and allows them to better communicate with each other using electric signals. Bonnefil et al. explored whether differences in oligodendrocytes could affect",380,128,0.3368
dialogsum,"#Person1#: What are you reading? #Person2#: It is a book written by a guy who was born without arms or legs. #Person1#: What? So, how does he get around? #Person2#: He can actually walk pretty well, but he can't move that fast. He also has an assistant who helps him. He is actually quite successful. #Person1#: He must have worked pretty hard. #Person2#: Yeah. He travels around the world and gives speeches to young people. He's changed many people's lives. Even when nothing seemed possible, he stayed positive and put in even more effort.",#Person2# tells #Person1# about how a guy who was born without arms or legs manages to get around and stay positive.,94,21,0.2234
pubmed-summarization,"renal transplantation is the unique curative option for patients suffering from end - stage renal disease , but to date the evolution of each patient after transplantation can not be predicted . in the past decades , acute graft rejection has decreased dramatically as a result of the introduction of immunosuppressive drugs . however , immunosuppressive drugs carry undesired and severe side effects such as infections , malignancies , and metabolic disorders which may threaten patient 's life . yet , chronic rejection is still the main cause of long - term graft loss . the holy grail of organ transplantation is to maintain long - term graft function without immunosuppressive treatment , namely , operational tolerance ( ot ) . however , ot is a rare event in kidney transplanted patients , as only about 0.03% of cases are estimated to be in such state . thus , despite the efforts made in the past , there is still a clear need to find new strategies to achieve long - term tolerance and to investigate the immunological mechanisms that may be implicated in the process of ot . among the actors implicated in the mechanisms of the immune response , b and t lymphocytes are the main characters that lead to graft rejection . in this play , b lymphocytes have a dual key role since they present antigens of the donor to t cells in addition to secreting antibodies that can lead to acute rejection or , later in time , chronic rejection . nevertheless , a sparse b cell subset has been attributed immune regulatory functions which conveys that not all b cells play on the rejection side . although it was first described in 1974 it was not until 2000 that this population was named regulatory b cells ( breg ) . in the last decade , the regulatory role played by breg has been highlighted by many authors in autoimmune diseases such as systemic lupus erythematosus ( sle ) , rheumatoid arthritis , and pathologies that promote antineutrophil cytoplasmic antibodies and also in allograft tolerance in organ transplantation . the current general consensus is that breg develop their function mainly via the secretion of il-10 . however , a complete phenotype signature , development pathway","regulatory b cells ( breg ) are in the spotlight for their role in immune homeostasis maintenance and tolerance achievement as in the last years the correlation with functional and increased breg numbers in autoimmune diseases and transplantation has been extensively proven . their study is , however , in its infancy with still little knowledge and consensus on their origin , phenotype , and mechanism of action . all this hampers the pursuit of an effective breg induction method for therapeutic purposes . in this review we aim to summarize the studies on human breg and their implication in kidney transplantation and to further discuss the issues surrounding therapeutic applications of this cell subset .",380,116,0.3053
dialogsum,"#Person1#: You have been here for how long? Four months now? #Person2#: Yeah, about. #Person1#: Do you know Chinese better now? #Person2#: Oh, definitely. I remember, when I first arrived in Guangzhou, my girlfriend was haggling with a sales clerk over the price of a mobile phone. #Person1#: Oh, yeah. Many Chinese like to bargain. It happens almost everywhere. #Person2#: I mean, I understand that. But the speed of the conversation got faster and faster, until it seemed to me that they would fight. My perception of the tone was that it was a violent shouting match. The truth was that it was a perfectly normal conversation. #Person1#: A shouting match? You're so funny. You must be exaggerating. I don't believe it. #Person2#: I am not exaggerating at all. I'm telling you the truth. That was how I felt at that time. #Person1#: Yes, perhaps. Chinese usually don't notice that sort of thing. Maybe it's quite natural to us. #Person2#: Yes, absolutely true.",#Person2# has been in China for 4 months and knows Chinese better now. Then #Person2# and #Person1# talk about the feeling of bargaining between Chinese.,163,25,0.1534
dialogsum,"#Person1#: What forms should I fill out to collect unemployment? #Person2#: You need to fill out a special form to apply for unemployment benefits. #Person1#: Where do I get the application form for unemployment benefits? #Person2#: You can call the Employment Development Office and request a form. #Person1#: What information will I need to provide to apply for unemployment? #Person2#: Be prepared to provide your employer's name and address and what dates you worked. #Person1#: What else will the Employment Development Office need? #Person2#: You need to be prepared to show that your unemployment is not your fault. If you have a termination notice, that would be great. #Person1#: What will happen next? #Person2#: The Employment Development Office will call you for an interview.","#Person2# tells #Person1# to call the Employment Development Office to request a form, and provide the employer's information and prove the unemployment is not #Person1#'s fault.",124,26,0.2097
scientific_lay_summarisation-elife-norm,"from normal locomotion and light touch responses (Babcock et al. , 2009; Tracey et al. , 2003). When a larva is challenged with a sub-threshold temperature (38°C or below), only light touch behaviors occur, whereas higher thermal stimuli result in aversive rolling behavior (Babcock et al. , 2009). Peripheral class IV multi-dendritic neurons (class IV neurons) are the nociceptive sensory neurons that innervate the larval barrier epidermis by tiling over it (Gao et al. , 1999; Grueber et al. , 2003) and mediate the perception of noxious stimuli (Hwang et al. , 2007). For genetic manipulations within class IV neurons, ppk1. 9-GAL4 has been used widely as the 1. 9 kb promoter fragment of pickpocket1 driving Gal4 selectively labels class IV nociceptive sensory neurons in the periphery (Ainsley et al. , 2003). When the barrier epidermis is damaged by 254 nm UV light, larvae display both thermal allodynia and thermal hyperalgesia (Babcock et al. , 2009). This does not model sunburn because UV-C light does not penetrate the Earth’s atmosphere, however, it has proven useful for dissecting the molecular genetics of nociceptive sensitization (Im and Galko, 2011). What conserved factors are capable of sensitizing nociceptive sensory neurons in both flies and mammals? Known molecular mediators include but are not limited to cytokines, like TNF (Babcock et al. , 2009; Wheeler et al. , 2014), neuropeptides, metabolites, ions, and lipids (Gold and Gebhart, 2010; Julius and Basbaum, 2001). In addition, Hedgehog (Hh) signaling mediates nociceptive sensitization in Drosophila larvae (Babcock et al. , 2011). Hh signaling regulates developmental proliferation and cancer (Fietz et al. , 1995; Goodrich et al. , 1997) and had not previously been suspected of regulating sensory physiology. The main signal-transducing component of the Hh pathway, smoothened, and its downstream signaling components, such as the transcriptional regulator Cubitus interruptus and a target gene engrailed, are required in class IV neurons for both thermal allodynia and hyperalgesia following UV irradiation (Babcock et al. , 2011). In mammals, pharmacologically blocking Smoothened reverses the development of morphine analgesic tolerance in inflammatory or neuropathic pain models suggesting that the Smoothened/Hh pathway does regulate analgesia (Babcock et al. , 2011). Interactions between the Hh and SP pathways in regulating nociception have not been investigated in either vertebrates or Drosophila. Transient receptor potential (TRP)","Injured animals from humans to insects become extra sensitive to sensations such as touch and heat. This hypersensitivity is thought to protect areas of injury or inflammation while they heal, but it is not clear how it comes about. Now, Im et al. have addressed this question by assessing pain in fruit flies after tissue damage. The experiments used ultraviolet radiation to essentially cause ‘localized sunburn’ to fruit fly larvae. Electrical impulses were then recorded from the larvae’s pain-detecting neurons and the larvae were analyzed for behaviors that indicate pain responses (for example, rolling). Im et al. found that tissue injury lowers the threshold at which temperature causes pain in fruit fly larvae. Further experiments using mutant flies that lacked genes involved in two signaling pathways showed that",380,128,0.3368
dialogsum,"#Person1#: How did you get around over there? Did you rent cars? #Person2#: No, that would be too expensive. We used the train system. We bought a special pass called a Enrail pass. It lets people use the train wherever they want, as often as they want. #Person1#: I've heard about Enrail passes. So those Europeans really depend on trains a lot. #Person2#: Yes, they do. I wish we Americans had a better train system. #Person1#: I know. Our train system is lousy. And besides, Americans love their cars too much. #Person2#: I agree. And probably the automobile companies are too powerful. They never allowed the government to develop trains. #Person1#: It's too bad for the environment. So much pollution from cars. #Person2#: Americans love cars for different reasons, I think. One reason is that we are very individualistic. And cars are a very individual way of getting around. Americans like the freedom of driving around by themselves. They don't want to ride in a train or bus with a group of people. #Person1#: Yes, I agree. I think it is a cultural characteristic. It would be very hard to get us Americans to change this. But you know what? Probably, in the future, Americans will have to change. #Person2#: Why do you say ' have to '? #Person1#: Because the earth's environment can't tolerate cars forever. I think cars are already causing global warming. When the problem gets more serious, world governments will have to start limiting car use. #Person2#: Maybe you're right. They will have to develop alternative transportation. But it will be hard in America. Too many people are used to cars. Even in our movies cars are very important. #Person1#: Wow! I didn't notice the time. It's almost noon. I have to get home. #Person2#: Do you want me to give you a ride? #Person1#: No, no problem. I have my car in the parking ramp around the corner. #Person2#: Alright. Well, I'll stay here and have another coffee. Nice running into you. #Person1#: See you around.","#Person2# tells #Person1# #Person2# takes Enrail to get here. #Person2# hopes Americans had a better train system, but #Person1# says the train system is lousy and Americans like going out by car, which are harmful to the environment. #Person2# agrees and says alternative transportation should be developed though it will be hard in America.",341,54,0.1584
dialogsum,"#Person1#: May I help you? #Person2#: Yes, I would like to exchange some money. #Person1#: what currency would you like to trade in? #Person2#: I would like to exchange Chinese RMB for American dollars. Do you accept $ 100 bills? #Person1#: No problem, we can accept any denomination. How much would you like to exchange today? #Person2#: Well, that depends on the rate. How much is the RMB trading at today? #Person1#: It's a shame you didn't come a little earlier, the exchange rate was reset yesterday afternoon. The American dollar is now worth 7.45 RMB. It was much lower yeasterday. If you would like to sell RMB, we can give you a rate of 7.35. Will that be all right? #Person2#: I guess, here, give me 5, 000 RMB worth please. I might as well exchange a little extra. Who knows what the exchange rate will be tomorrow!","#Person2# wants to exchange some RMB for American dollars and asks the rate. #Person1# gives #Person2# a rate of 7.35 and #Person2# wants to exchange 5, 000 RMB.",149,28,0.1879
dialogsum,"#Person1#: Hi Rose, what are you busy with right now? #Person2#: Hi Jack, I'm working on these documents. The manager wants them for half an hour. #Person1#: Well, Rose. #Person2#: Is there something any need? #Person1#: Are your free this weekend? #Person2#: Yes, I have nothing to do. #Person1#: Great, Is it convenient if i visit you this weekend? #Person2#: I beg your pardon? #Person1#: I'd like to call on you this weekend. I just want to a drop in for a chat. #Person2#: Really? well, ok, you're welcome. #Person1#: Is 5 PM. Saturday a good time for you? #Person2#: Hmm, how about seven? I can treat you to dinner. #Person1#: Sure, that would be great. I'll bring the wine. #Person2#: OK. Then I'll be expecting you. #Person1#: I'll be there on time.",Jack asks Rose if he can visit her this weekend for a chat. Rose agrees and will treat him to dinner. Jack will bring wine.,133,25,0.188
scientific_lay_summarisation-elife-norm,"The resection of DNA strand with a 5´ end at double-strand breaks is an essential step in recombinational DNA repair. RecJ, a member of DHH family proteins, is the only 5´ nuclease involved in the RecF recombination pathway. Here, we report the crystal structures of Deinococcus radiodurans RecJ in complex with deoxythymidine monophosphate (dTMP), ssDNA, the C-terminal region of single-stranded DNA-binding protein (SSB-Ct) and a mechanistic insight into the RecF pathway. A terminal 5´-phosphate-binding pocket above the active site determines the 5´-3´ polarity of the deoxy-exonuclease of RecJ; a helical gateway at the entrance to the active site admits ssDNA only; and the continuous stacking interactions between protein and nine nucleotides ensure the processive end resection. The active site of RecJ in the N-terminal domain contains two divalent cations that coordinate the nucleophilic water. The ssDNA makes a 180° turn at the scissile phosphate. The C-terminal domain of RecJ binds the SSB-Ct, which explains how RecJ and SSB work together to efficiently process broken DNA ends for homologous recombination. DNA double-strand breaks (DSBs) are the most lethal form of DNA damage due to the free DNA ends. DSBs can be repaired by homologous recombination (HR), which requires a pre-aligned homologous sequence prior to ligation. DNA end resection degrades the 5´ strand of a DSB end and is one of the earliest and most important processes in HR repair (Symington and Gautier, 2011). In bacteria DSBs are predominantly repaired by either the RecBCD or the RecF pathways. Compared with the RecBCD pathway, the RecF pathway is highly conserved across eubacteria and shows functional homology in the eukaryotic HR process. For example, RecA resembles yeast Rad51 protein with regard to the catalysis of DNA strand invasion and change reactions (Cox and Lehman, 1982). RecO is capable of annealing single-stranded DNA-binding (SSB) protein-coated ssDNA and facilitates RecA loading (Kantake et al. , 2002), a property that is shared with the yeast Rad52 protein. The RecBC complex contains both helicase and nuclease activities. In contrast, the RecF pathway requires RecJ, a 5´-3´ exonuclease, together with RecQ helicase and SSB protein to initiate DSB end resection (Courcelle and Hanawalt, 1999; Han et al. , 2006; Handa et al. , 2009; Morimatsu and Kowalczykowski, 2014). Deinococcus radiodurans is extremely resistant to DNA-damaging agents, such as ionizing","DNA encodes information that cells need to create the molecules and proteins that are essential for life. It is therefore vital that damaged DNA is repaired rapidly and accurately. Some DNA-damaging agents, such as gamma radiation, break both strands of the DNA double helix, which can be fatal to cells if not repaired quickly and accurately. One important pathway in charge of repairing such double-strand breaks is called the homologous recombination repair pathway. The first stage of this repair involves cutting away part of one of the DNA strands at the break. This exposes a single-stranded stretch of the partner strand, which can be used for the repair. One organism that is highly resistant to having its DNA damaged by radiation is the bacterium Deinococcus radiodurans. In this",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. , 2011; Sato and Kornberg, 2002). The cytonemes that mediate the exchange of these proteins contain the Dpp receptor Thickveins (Tkv) or the FGF receptor Breathless (Btl), extending from the basal surface of the ASP cells and synapsing with Dpp- or FGF-producing disc cells, respectively (Roy et al. , 2014). The ASP lies underneath the basement membrane that envelops the wing disc (Guha et al. , 2009), and although the space they traverse has not been analyzed, it presumably has characteristics of prototypical extracellular matrix (ECM, reviewed in Broadie et al. , 2011). The number and distribution of ASP cytonemes depend on the production of Dpp and FGF in the disc and on their respective receptors in the ASP, but it is not known whether the cells between the producing and receiving cells (henceforth called' intermediate cells' ) also contribute to cytoneme-mediated signaling. Possible candidates that might have roles in these intermediate cells that we tested include components of the planar cell polarity (PCP) system, heparan sulfate proteoglycans (HSPGs) and integrins. PCP is an aspect of cell polarity that establishes a singular, shared bipolar orientation across an epithelial sheet (reviewed in Goodrich and Strutt, 2011). In the insect cuticle, it is responsible for the coordinated and consistent orientation of hairs and bristles. PCP is also manifested in the asymmetric subcellular localization of proteins such as Frizzled (Fz, a seven-pass transmembrane protein), Dishevelled (Dsh) and Diego (Dgo, cytosolic proteins) to one side and Van Gogh (Vang, a four-pass transmembrane protein) and Prickle (Pk, a cytosolic protein) to the other. Fz, Dsh, Dgo, Vang and Pk are constituents of the core PCP pathway in Drosophila, and all are required for planar orientation and polarization. Absent any one and the hairs and bristles lack normal polarity. In Drosophila genetic mosaics, cells to one side of PCP mutant cells also have abnormal planar polarity (Casal et al. , 2002; Taylor et al. , 1998; Vinson and Adler, 1987), leading to the idea that PCP involves a system of cell-cell interactions that coordinate the polarity of neighboring cells and propagate orientation long-range. PCP components also have other roles. Studies of cells deficient for components of the PCP system in Drosophila (Djiane et al. , 2005; Harumoto et al. , 2010) and mouse (Tao et","The embryos of animals develop in a controlled manner that ensures that their tissues and organs form properly and at the right time. These processes depend on molecules called morphogens that are distributed throughout the embryo in specific ways and that are dispersed via extensions that protrude from the surfaces of cells. These extensions, called cytonemes, transport the morphogens across the distances that separate cells and transfer these molecules to target cells via direct contact. However, it was not known how cytonemes navigate to their targets. The fruit fly Drosophila is commonly used to investigate how animals develop organs and tissues. Previous studies have shown that the development of one of the fly’s organs – the air sac primordium –relies on morphogens transported by cytonemes. Now, Huang and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Life-long lack of growth hormone (GH) action can produce remarkable extension of longevity in mice. Here we report that GH treatment limited to a few weeks during development influences the lifespan of long-lived Ames dwarf and normal littermate control mice in a genotype and sex-specific manner. Studies in a separate cohort of Ames dwarf mice show that this short period of the GH exposure during early development produces persistent phenotypic, metabolic and molecular changes that are evident in late adult life. These effects may represent mechanisms responsible for reduced longevity of dwarf mice exposed to GH treatment early in life. Our data suggest that developmental programming of aging importantly contributes to (and perhaps explains) the well documented developmental origins of adult disease. Epidemiological studies of individuals born or conceived during the ‘Dutch famine’ led to an appreciation of the impact of early-life events on adult health, and this important concept was formalized as the ‘Barker hypothesis’ (Barker, 1997). Low birth weight infants born to undernourished mothers were found to have increased risk for hypertension, cardiovascular disease and diabetes in later life (Huxley et al. , 2002; Xiao et al. , 2010). Furthermore, recent studies have shown that maternal over-nutrition and obesity are also strongly associated with adult metabolic dysfunction in the offspring (Curhan et al. , 1996; Levin and Govek, 1998). This evidence linked early growth status and nutrient signals to the development of diseases in adult life, and now this concept has been formulated as the Developmental Origins of Health and Diseases (Hanson and Gluckman, 2014; Sinclair et al. , 2007). It should be noted that the impact of reduced nutrient availability, and the resulting slower growth and development is not always detrimental. Moderate reduction of food or protein intake during pregnancy of female rats and mice lead to improved metabolic status and extended longevity of offspring (Hales et al. , 1996; Jennings et al. , 1999; Ozanne and Hales, 2004). We have shown that a modest reduction of nutrient availability during the pre-weaning period produced by increasing the number of pups in a litter increased longevity of UM-HET3 mice (Sun et al. , 2009a). Likely, the mechanisms of the effects of both under- and over-nutrition on adult disease, aging and longevity include alternations in hormonal signaling. Hepatic responsiveness","For decades, research has shown that early-life events that happen when animals, including humans, are developing as embryos can later influence how those animals look and behave as adults. However, little is known about if the hormones that drive an animal’s growth shortly after its birth have long-lasting effects too. For example, do growth hormones influence how quickly an animal will age, how healthy it is during adulthood, and how long it will go on to live? Sun et al. now show that increasing the levels of growth hormones in young mice for just six weeks can have a long-lasting effect on the animals’ lifespans. The experiments involved normal mice and dwarf mice, which are smaller and live for longer. From when they were one week old until",380,128,0.3368
scientific_lay_summarisation-elife-norm,"factors, five of which are members of the σ70 family and recognize similarly positioned promoter elements using the counterparts of σ70 domains 2 and 4. Most alternative σ factors exhibit highly restricted promoter specificity (Koo et al. , 2009b; Rhodius et al. , 2013). Thus, genes that are responsive to disparate physiological inputs often carry two or more promoters that are recognized by distinct σ factors (Wade et al. , 2006; Gama-Castro et al. , 2008; Cho et al. , 2014). Although σ factors were historically identified as promoter specificity factors, it has become clear that their roles are not limited to the initiation phase of transcription. In particular, multiple studies have shown that the release of σ from the transcription complex is not required for entry into the elongation phase of transcription (reviewed in Mooney et al. , 2005; Perdue and Roberts, 2011). Furthermore, the functional properties of a transcription elongation complex (TEC) containing σ differ from the properties of a TEC that does not contain σ. For example, TEC-associated σ70 can induce transcription pausing by engaging promoter −10-like sequence elements within transcribed regions (Ring et al. , 1996; Brodolin et al. , 2004; Nickels et al. , 2004; Hatoum and Roberts, 2008; Deighan et al. , 2011; Perdue and Roberts, 2011), a phenomenon that was first uncovered in the context of the bacteriophage λ late gene promoter (reviewed in Roberts et al. , 1998; Perdue and Roberts, 2011). This pausing occurs due to an interaction between the −10-like element and domain 2 of TEC-associated σ70 (the same domain of σ70 that binds the promoter −10 element during transcription initiation). In addition, the presence or absence of σ can alter the accessibility of the TEC to elongation factors, including the λ Q protein and RfaH (Roberts et al. , 1998; Nickels et al. , 2002,2006; Sevostyanova et al. , 2008), and can influence the ability of RNAP to reinitiate transcription at certain promoters (Bar-Nahum and Nudler, 2001). Initial-transcribed-region −10-like elements, such as those associated with the λ late promoters and the late promoters of other lambdoid phages, induce early elongation pausing because they are recognized by TECs that have not yet released the σ70 that was used during initiation (Marr et al. , 2001; Mukhopadhyay et al. , 2001;","Proteins are made following instructions that are encoded by sections of DNA called genes. In the first step of protein production, an enzyme called RNA polymerase uses the gene as a template to make molecules of messenger ribonucleic acid (mRNA). This process—known as transcription—starts when RNA polymerase binds to a site at the start of a gene. The enzyme then moves along the DNA, assembling the mRNA as it goes. This stage of transcription is known as elongation and continues until the RNA polymerase reaches the end of the gene. In bacteria, RNA polymerase needs a family of proteins called sigma factors to help it identify and bind to the start sites associated with the genes that will be transcribed. In the well studied bacterium known as E.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"approaches to circumvent some of the intrinsic technical biases associated with each of the previously used methods to systematically investigate the clonal organization of PC lineages in the cerebral cortex. Our results provide a detailed quantitative assessment of the neurogenic fate of individual VZ progenitor cells that reveal a large diversity of PC lineage configurations. These findings support a stochastic model of cortical neurogenesis through which a limited number of progenitor cell identities could generate the diverse of cytoarchitectonical patterns observed in the neocortex. To study the cellular mechanisms underlying the generation of PCs in the neocortex, we analyzed the output and organization of neuronal lineages generated by individual progenitor cells. To this end, we first used replication-deficient retroviral vectors that integrate indiscriminately in mitotic cells but only identify cell lineages with fluorescent proteins following Cre-dependent recombination (Ciceri et al. , 2013). To specifically label PC lineages, we injected a very low titer cocktail of conditional reporter retroviruses (rv: : dio-Gfp and rv: : dio-mCherry) into the lateral ventricle of Neurod6Cre/+ mouse embryos (also known as Nex-Cre), in which Cre expression is confined to postmitotic PCs (Goebbels et al. , 2006) (1a). Using this approach, we achieved sparse labeling and avoided biasing the tagging of progenitor cells by the expression of specific genetic markers (Cepko et al. , 2000). To identify the developmental stage at which progenitor cells become neurogenic in the cortex, we injected retroviruses at different embryonic days (E9. 5 to E14. 5) and analyzed the organization of individual PC clusters at postnatal day (P) 21 (1a). Since a single copy of the viral vector is stably integrated into the host genome, retroviral infection leads to the labeling of only one of the two daughter cells resulting from the division of the infected progenitor cell. Consequently, infection of progenitor cells in the ventricular zone (VZ) of the pallium labels PC lineages in three main configurations depending of the mode of division of the infected progenitor (1b): (1) a large cluster containing more than one lineage, which results from the infection of a self-renewing progenitor cell dividing symmetrically; (2) a single lineage, which results from the infection of a progenitor cell undergoing its last symmetric division; and (3) a partial lineage, which results from a neurogenic division of a","Recognizable by its deep outer folds in humans, the cerebral cortex is a region of the mammalian brain which handles complex processes such as conscious perception or decision-making. It is organized in several layers that contain different types of ‘excitatory’ neurons which can activate other cells. The various areas of the cortex have different characteristics as they contain various proportions of each kind of neurons. Stem cells are cells capable to divide and create various types of specialized cells. The excitatory neurons in the cortex are created during development by stem cells known as radial glial cells. These cells divide several times, giving rise to different types of neurons in sucessive divisions, presumably thanks to internal molecular clocks. In the cortex, it is generally assumed that an individual",380,128,0.3368
scientific_lay_summarisation-elife-norm,"control. Error bars represent + SEM of three biological replicates, each with three technical repeats. (E) 22Rv1 proliferation as in (C). (F) LNCaP proliferation as in (C). (G) VCaP proliferation as in (C) alongside expression of shRNA-resistant wild-type (WT) PRMT5, catalytically inactive PRMT5 (G365A/R368A), or vector control (Vector). Error bars represent + SEM of three biological replicates, each with three technical repeats. : http: //dx. . org/10. 7554/eLife. 13964. 00310. 7554/eLife. 13964. 004Figure 1— 1. PRMT5 knockdown in prostate cancer cells. (A) Western blot of candidate ERG interactors from 1A, as presented in 1B. (B) Left panel: western blot for FLAG-PRMT5 and GFP-ERG constructs after immunoprecipitation of FLAG-PRMT5 in 293 cells. Right panel: western blot for HA-ERG and V5-PRMT5 after immunoprecipitation of HA-ERG from PC3 cells. (C) Top panel: schematic representation of four ERG deletion mutants. ERG FL: full-length ERG; ERG△NTD: ERG lacking N-terminal domain; ERG△CTD: ERG lacking C-terminal domain; ERG△PNT: ERG lacking pointed domain. Bottom left panel: western blot of noted proteins from WCEs of 293 cells expressing FLAG-PRMT5 and either ERG construct. Bottom right panel: Western blot of FLAG-PRMT5 IP from 293 cells. (D) VCaP, LNCaP and 22Rv1 cells targeted by PRMT5 knockdown using three shRNA sequences (sh1, sh2, sh3) or NTC shRNA. Cells were left either treated or untreated with 100ng/ml doxycycline (Dox) for 7,4 and 5 days respectively to induce shRNA expression. Western blots were analyzed for levels of PRMT5, total histone H4, AR and GAPDH as loading control. (E) Top panel: waterfall plot of Achilles cell line panel sensitivity to knockdown of PRMT5 using PRMT5 shRNA#1 (Kryukov et al. , 2016). Prostate cancer cell lines are in red and ERG status is noted. Bottom panel: replotting of the data, colored for MTAP status—red arrows indicate the locations of the prostate cancer cell lines noted in the top panel. : http: //dx. . org/10. 7554/eLife. 13964. 004 We next narrowed the shRNA screen hit list by focusing on candidates more likely to be ERG interacting proteins. We immunoprecipitated ERG from VCaP cells, and then identified co-immunoprecipitated proteins by mass spectrometry (Materials and methods). Identified proteins (Supplementary file 2) included AR and DNA-PKcs, previously known ERG interactors (Brenner et al. , 2011; Yu et al. , 2010). Eight of the VCaP-selective shRNA screen hits that also co-immunoprecipitated","Prostate cancers are among the most common types of cancer in men, which, like other cancers, are driven by genetic mutations. Roughly half of all prostate cancers contain a genetic change that incorrectly fuses two genes together, causing the cells to produce abnormally high levels of a protein called ERG. ERG is a transcription factor, a protein that binds to specific sequences of DNA to influence the activity of nearby genes. ERG represses genes that help to prevent prostate cancers from growing, and so promotes prostate cancer development. Like most other transcription factors, ERG is difficult to target with drugs and no therapies that directly prevent the activity of ERG currently exist. Mounir et al. wanted to find out whether ERG cooperates with other proteins to cause prostate",380,128,0.3368
dialogsum,"#Person1#: Mr. Green, I'd like to introduce you to Mr. Brown. #Person2#: How do you do, Mr. Brown? It's a pleasure to get to know you. #Person1#: My pleasure, Mr. Green. I look forward to an excellent relationship with your company. #Person2#: I propose a toast to the health of everyone here and to the success of our negotiation. #Person1#: Okay, let's make a toast.",Mr. Green and Mr. Brown greet each other and make a toast.,65,12,0.1846
dialogsum,#Person1#: Hey Mike. What are you doing? #Person2#: Nothing much. What are you up to? #Person1#: I was just concerned about Sam. He hasn't been himself lately. #Person2#: He took the civil service exam and failed. #Person1#: That sucks. He must feel depressed. #Person2#: Yeah. He's been sitting in his room everyday for the last 4 days. #Person1#: Why don't we take him out? We can try to take his mind off of it. In the least show him that we're there for him. #Person2#: That's a great idea. Why don't you call him. I already talked to him a couple of times and it might be good for him to hear from somebody else. #Person1#: Ok. I'll call you back after I'm done. #Person2#: Sounds good.,Sam failed in the civil service exam and feels depressed. Mike already talked to Sam several times and #Person1# will call Sam.,127,22,0.1732
scientific_lay_summarisation-elife-norm,"appeared to induce a necrotic phenotype (1B–D). Indeed, electron microscopy verified that staurosporine-treated Wt cells, but not DKO cells, exhibited hallmarks of apoptosis including nuclear condensation with maintenance of plasma membrane integrity, while ionomycin induced a purely necrotic phenotype that showed rupture of the plasma membrane and dispersion of the nucleus, which was not seen in DKO cells (1E). By comparison, analysis of apoptotic cell death with annexin V (phosphatidylserine externalization in the plasma membrane) and necrotic death with propidium iodide (PI, plasma membrane opening/rupture) staining in cultured MEFs showed an apoptotic profile with staurosporine treatment, while ionomycin induced a necrotic phenotype; H2O2 had an intermediate profile of both forms (— 1A–D). Apoptosis leads to annexin V staining prior to PI staining, while necrosis causes simultaneous annexin V and PI staining. Molecular markers also confirmed a uniform apoptotic profile in Wt MEFs treated with staurosporine, such that caspase cleavage was observed and cell death was inhibited with z-Vad (pan-caspase inhibitor) but not by disabling the MPTP in MEFs from Ppif (CypD) -null mice (— 1E–H). By comparison, ionomycin-induced cell death in Wt MEFs did not appreciably involve caspase activation nor was it affected by caspase inhibition, while inhibiting MPTP function by deletion of the Ppif gene–reduced cell death, suggesting mitochondrial-dependent necrosis (— 1E–H). Using these conditions, DKO MEFs were completely refractory to H2O2- and ionomycin-induced necrosis as assessed with annexin V and PI labeling (1F, G; compare with — 1C, D), but all deaths were restored in DKO MEFs containing a stably integrated Bax or Bak viral–based expression cassette, or acutely by infection with a recombinant Bax encoding adenovirus, collectively indicating that there is not an unrelated defect in the DKO MEFs (1H, I). Reconstitution with Bax and Bak produced an equal or slightly lower level of protein compared with endogenous protein content in Wt cells (data not shown). 10. 7554/eLife. 00772. 003Figure 1. Bax/Bak1 DKO MEFs are resistant to a necrotic-like cell death. (A) – (C) MultiTox-Fluor multiplex cytotoxicity assay, which measures membrane (mem) integrity loss induced death, for different time points in cultures of Wt and Bax/Bak1 DKO MEFs treated with staurosporine (St), H2O2, ionomycin (Iono) for different time points. (D) Propidium iodide (PI) inclusion to assess membrane integrity following methyl methanesulfonate (MMS) for different time points. (E)","In all multicellular plants and animals, cells are continuously dying and being replaced. There are a number of different types of cell death, but two of the best studied are apoptosis and necrosis. Apoptosis, sometimes referred to as ‘cell suicide’, is a form of programmed cell death that is generally beneficial to the organism. Necrosis, however, occurs whenever cells are damaged—for example, due to a lack of oxygen—and can trigger harmful inflammation in surrounding tissue. Although the processes leading up to apoptosis and necrosis are very different, they both involve regulated changes in mitochondria—the organelles that supply cells with chemical energy. Mitochondria have a distinctive appearance, being enclosed by two membranes, the innermost of which is highly folded. During apoptosis, large pores form in the outer membranes of",380,128,0.3368
dialogsum,#Person1#: What games do you like? #Person2#: I like word games. #Person1#: How about a game of bridge? #Person2#: I don't like it at all. #Person1#: What about guessing games? #Person2#: I'm not one for the games. #Person1#: Let's play other game. #Person2#: What about playing go? #Person1#: OK.,#Person2# likes word games. #Person1# and #Person2# are going to play go.,49,12,0.2449
pubmed-summarization,"was 70.0 24.2 min , and the mean duration of anesthesia was 87.5 25.4 min ( table 2 ) . median intraoperative bis was 80.5 ( interquartile range [ q1-q3 ] , 8094 ) , and the median rss score was 2 ( q1-q3 , 13 ) . four desaturation events occurred intraoperatively , but the patients soon recovered with respiration encouragement or elevation of the mandible in the surgical field without mask bagging or additional airway management . postoperative complications were evaluated during hospitalization and at the outpatient clinic follow - up ( table 3 ) . no patient received analgesics while in the pacu , but five patients required pain control on the ward . according to the nurse 's records , four patients complained of sore throat during hospitalization . symptomatic hypocalcemia occurred in one patient , which was medically corrected during hospitalization without subsequent complications . transient voice color change was observed in one patient who had recovered by the follow - up examination . the major advantages of general anesthesia are total loss of awareness , stable operative field , and a controlled airway . however , general anesthesia prolongs postoperative recovery and can lead to hemodynamic instability during anesthetic induction . in contrast , local anesthesia with mac results in a faster postoperative recovery , no throat or vocal cord irritation , and avoidance of muscle relaxant use . however , it can be challenging to control the sedation level to meet the surgeons ' and patients ' requirements and while simultaneously maintaining proper oxygenation . the ideal properties of sedative agents include rapid onset , easy titration , high clearance , and minimal side effects , particularly a lack of hemodynamic impairment or respiratory depression . however , no definitive data are available for sedative drugs used during thyroidectomy under local or regional anesthesia . snyder et al . , reported about patients who received local anesthesia with mac and boluses of midazolam , propofol , or fentanyl citrate for supplemental analgesia . another study administered incremental doses of midazolam and fentanyl citrate to patients under mac with regional anesthesia only when required . this single or repeated bolus technique can induce an unstable plasma / effect - site concentration , consequently leading","because the current trend favors minimally invasive surgery for thyroid disease , increasing interest has developed for thyroidectomy under local anesthesia with monitored anesthesia care ( mac ) . here , we retrospectively reviewed 18 cases of thyroidectomy performed under local anesthesia with mac in a single center . all of the procedures were performed by a single surgeon , using local lidocaine infiltration around the incisional site and propofol plus remifentanil target - controlled infusion . sore throat ( 4/18 ) , hypocalcemia ( 1/18 ) , and transient voice color change ( 1/18 ) were observed , but the patients recovered during the follow - up period . no cases of postoperative nausea and vomiting , hematoma , wound problems , or vocal cord paralysis were",380,128,0.3368
pubmed-summarization,"cyanotic cardiac diseases those were not present in our patient . the remaining possible etiological factor for secondary hoa in our case was the huge pelvic malignancy which was excised previously . the surgery for these kinds of pathologies may be planned as single or staged procedures . blepharoplasty with excessive skin excision is usually required both for better cosmesis and to reduce the tissue bulk . no complications were encountered during surgery , but bleeding was more than any other lid surgery . the profound inflammatory reaction in the tissue might be the cause of this excessive bleeding . hoa may not be always primary , particularly in patients with negative family history . in cases of findings with abnormal fibroproliferative and inflammatory changes , detailed systemic examination and investigations both using serologic and imaging modalities the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .","a 52-year - old male patient presented to our hospital with a history of secondary hypertrophic osteoarthropathy ( hoa ) associated with an abdominal neoplasia and blepharoptosis . he had finger clubbing , hyperhidrosis , and hypertrichosis . he also had a recent history of extensive abdominal surgery with a pathology report of myelolipoma . routine blood work was unremarkable . upper eyelid reconstruction with blepharoplasty , upper eyelid wedge resection , and brow suspension was performed to address his eyelid concerns . by this case report , we would like to attract notice that the eyelid involvement may be a part of hoa and to emphasize the importance of systemic and pathologic evaluation in failed blepharoptosis surgery .",291,119,0.4089
dialogsum,"#Person1#: Where's Mrs. Johnson? #Person2#: Just call her Lisa, Mary. She's cooking dinner. #Person1#: I see. Can I sit down? #Person2#: Of course! Make yourself at home. #Person1#: Thank you, Mr. Johnson. #Person2#: Please, just call me Tom. #Person1#: Okay, Tom. #Person2#: Where's Cindy? #Person1#: She's upstairs in my room. #Person2#: Can you tell her to come downstairs? We're about to have dinner.",Mary is visiting Johnson's family. Mr. Johnson asks Mary to tell Cindy to come downstairs.,63,15,0.2381
dialogsum,"#Person1#: I'm Sue from Daily Magazine. We're doing a study of transport service in this area. Can you answer some questions? #Person2#: How long will it take? I'm in a hurry. #Person1#: It takes only a few minutes. #Person2#: Yes. OK. #Person1#: Do you live near the place of your work? #Person2#: Oh, no, I don't. #Person1#: Do you live one to five kilometers from your job, or six to ten, or more than ten kilometers? #Person2#: More than ten. Fourteen or fifteen. #Person1#: And, how do you go to work? #Person2#: By train. #Person1#: Do your family members always use public transport? #Person2#: Yes, they go to work or school by bus. #Person1#: Thank you very much, sir. #Person2#: You are welcome.",#Person2# answers some questions from Sue from Daily Magazine for a study of transport service in the area.,123,18,0.1463
dialogsum,"#Person1#: Hello, Jane. #Person2#: Hi, Harry. Did you have a good summer holiday? #Person1#: Sure. I went for my holiday on my uncle's farm. #Person2#: Really? What interesting things did you do there? #Person1#: I helped get in some rice, take care of the fruit garden and drive the tractor. #Person2#: Drive a tractor? #Person1#: Yes. It was easy to learn. Did you go away for your holiday, Jane? #Person2#: Oh, no. I just stayed at home. My mother has been in hospital. I had to look after her and help do some cooking and washing at home. #Person1#: I'm sorry. Oh, it's late. I must be off now. Bye bye.",Harry and Jane talk about their summer holiday. Harry went to his uncle's farm while Jane stayed at home.,111,19,0.1712
pubmed-summarization,"functional interactions and compensation among genes for decades and has recently been exploited for the development of new genotype - selective anticancer agents , identification of novel therapeutic targets for cancer treatment , and characterization of genes associated with treatment response . for example , if gene a in 1b is mutated , small interfering rna ( sirna ) or small molecules targeting the genes x , y , or z would likely induce synthetic lethality in cells with an abberant a but not in the cells with a wild - type a. therefore , using paired isogenic cell lines with and without abberant a , one can screen for sirna or compounds that specifically kill the cells with an abberant a. concept and models of synthetic lethal interactions . ( a ) synthetic lethality between genes a and b. a and b represent wild types , while a and b represent mutants . synthetic lethality refers to a lethal phenotype observed only in the combination group of a and b. ( b ) an essential survival function is regulated by two pathways conducted by a , b , c and x , y , x , respectively . a functional change in either of these pathways is insufficient to induce viability changes . however , the simultaneous presence of mutations or dysfunctions in both pathways , such as a mutation in a and any mutation in x , y , or z , induces lethal phenotype . thus , a is synthetic lethal with x , y , and z , and vice versa . ( c ) an essential survival function is regulated by pathway a alone , in which a2 is a multiprotein complex composed of x , y , and z ; and a3 has homologues of , and . synthetic lethality may exist among x , y , and z and among a3 , , and . several models of interactions among genes and/or proteins have been proposed to account for synthetic lethality , including the components of parallel pathways that together regulate an essential biological function , the presence of homologous genes or protein isomers derived from the same ancestral gene ( paralogs ) , subunits of an essential multiprotein complex , and components","the concept of synthetic lethality ( the creation of a lethal phenotype from the combined effects of mutations in two or more genes ) has recently been exploited in various efforts to develop new genotype - selective anticancer therapeutics . these efforts include screening for novel anticancer agents , identifying novel therapeutic targets , characterizing mechanisms of resistance to targeted therapy , and improving efficacies through the rational design of combination therapy . this review discusses recent developments in synthetic lethality anticancer therapeutics , including poly adp - ribose polymerase inhibitors for brca1- and brca2-mutant cancers , checkpoint inhibitors for p53 mutant cancers , and small molecule agents targeting ras gene mutant cancers . because cancers are caused by mutations in multiple genes and abnormalities in multiple signaling",380,128,0.3368
dialogsum,"#Person1#: Are you busy this week? #Person2#: Yes. This morning I need to write a business report and this afternoon at 1:30, I'll discuss the report with the general manager. #Person1#: What's your schedule for tomorrow? #Person2#: I'm attending the sales meeting at 9 o'clock and in the afternoon at 3:00, I'm seeing Mr. .Black, the marketing manager. #Person1#: What about Wednesday? #Person2#: I've got an appointment at 8:30 with Mr. Anderson, the bank manager. In the afternoon, I'm taking the 4:45 flight to Hong Kong for the conference. #Person1#: The conference is on Thursday, right? #Person2#: Oh, yes. At 10 o'clock in the morning and 2 o'clock in the afternoon. After the conference, I'll be free. I'll be enjoying my weekend in Hong Kong.",#Person1# tells #Person2# about #Person1#'s busy work schedule this week.,125,10,0.08
dialogsum,"#Person1#: So Alex, you're off to the Olympic stadium then? #Person2#: Yes, I should get there just in time for the women's 400m relay. #Person1#: Wow, that should be really exciting, especially with so many famous athletes there. #Person2#: Yes, I'm also going to watch the triple jump and the high jump. #Person1#: Well have a good time. Get me some autographs if you can. #Person2#: Ok, I'll try my best.",Alex's off to the Olympic stadium to watch some games.,71,10,0.1408
pubmed-summarization,"nasopharyngeal carcinoma ( npc ) is an endemic disease within specific regions in the world . the highest incidence is found among southern chinese people , especially those of cantonese origin , whereas among caucasians from north american and other western countries it is sporadic . radiation therapy ( rt ) , alone or combined with chemotherapy , is a paramount approach as initial treatment option for npc . distant metastasis , however , remains one of the major problems after radical treatment in patients with locally advanced disease . we report a case of a 68-year - old patient with advanced npc who developed intrathoracic endotracheal metastasis after rt . we believe this to be the first reported case of intrathoracic endotracheal metastasis in an npc patient . a 68-year - old man presented at our in - patient department on september 21 , 2004 , with a 3-month history of headache and hearing loss . computed tomography ( ct ) revealed a nasopharyngeal mass extending into the left parapharyngeal space , left carotid sheath , and skull base . an enlarged cervical lymph node , about 2 2 cm , was found in the left level ii . pathology showed nasopharyngeal undifferentiated nonkeratinizing carcinoma . according to the 2002 american joint committee on cancer staging system , the patient received an initial dose of 66 gy by conventional rt and a boost dose of 10 gy by three - dimensional conformal radiation therapy ( 3d - crt ) to the primary site . prophylactic radiation was given to his bilateral neck with doses of 63.3 gy to the upper neck and 50 gy to the lower neck . however , 2 months later , a metastatic nodule about 1.5 1.1 cm was found in the left lower lobe of the lung . he received 4 cycles of chemotherapy with vinorelbine and cisplatin , 2 cycles of chemotherapy with docetaxel and cisplatin , and a 3d - crt dose of 66 gy to the nodule in 33 fractions over 6.5 weeks . thirty - four months after the initial rt , the patient presented with a cough and hemoptysis . ct showed the presence of an enlarged lymph node measuring approximately 1.5 1.5 cm in the para - aortic","intrathoracic endotracheal metastasis from a very distant site is extremely rare . we report the first case of such a disease in a 68-year - old man with nasopharyngeal carcinoma who presented with a cough and hemoptysis 34 months after finishing radiotherapy . prior to tracheal metastasis , he developed a solitary metastasis in the lung and underwent chemotherapy followed by radiotherapy . computed tomography showed the presence of an enlarged lymph node in the para - aortic arch . fiberoptic bronchoscopy revealed an endotracheal tumor 1 cm above the carina . histological and immunohistochemical analyses confirmed its nasopharyngeal origin . he was treated with conventional radiotherapy and three - dimensional conformal radiotherapy ; complete tumor remission was achieved . he died of nonmalignant disease with no signs",380,128,0.3368
dialogsum,"#Person1#: I remember you said that you like China because it has cheap beers. #Person2#: Yes, unbelievably cheap. Carlsborg is less than $ 1. #Person1#: Why do you drink? I mean, where does drinking get you? #Person2#: It's fashionable. #Person1#: Come on, you don't even know that blinds following is a sign of immaturity. #Person2#: Mary, it's not about the blind following. What matter is I enjoy in drinking. It's like when you get off of work. You're so tired. You need to get relaxed. You can't just turn on the TV and keep watch the programs until you fall asleep. You need to make your after work time more fun. #Person1#: How? By drinking? #Person2#: Drinking is just part of it. I mean, you have a bunch of friends coming by and having fun. You drink and talk. And the more you drink, the more you talk. It makes me so relaxed. #Person1#: When did you begin to drink? #Person2#: It's a long time ago. When I first went to a bar to pick up girls there, I saw the most beautiful girl sitting and sipping a coke. Then I went up to her and said'can I buy you a drink? ' #Person1#: And then? #Person2#: Then I talked to her and got her number. You know what? When you don't know what to say? Just drink. #Person1#: So you get drunk every day?",#Person1# tells Mary #Person1# likes drinking because drinking is fashionable and relaxing. #Person1# also shares with Mary #Person1#'s first experience of drinking.,235,22,0.0936
dialogsum,"#Person1#: I know I'm a blabbermouth, but what do you think she should do, John? #Person2#: Honey, we're in the museum now. We're not here to discuss your coworker's love life. We're here to enjoy the great paintings by Picasso! #Person1#: I know! But it's really important to her! Her whole life could be ruined by this man! #Person2#: You're making a federal case out of it. One unhealthy love affair can't ruin anything. It could even make your life more interesting. #Person1#: Are you serious, John? #Person2#: All I'm trying to say is that life is. . . like. . . er. . . this painting.",#Person1# still thinks about #Person1#'s coworker's love life when visiting a museum but John thinks they should focus on the paintings.,107,21,0.1963
scientific_lay_summarisation-elife-norm,"transcriptionally controls a large network of genes (>300), many of which are involved in virulence (Fields et al. , 1989; Behlau and Miller, 1993; Belden and Miller, 1994; Gunn and Miller, 1996; Guo et al. , 1997; Bearson et al. , 1998; Guo et al. , 1998; Adams et al. , 2001; Bader et al. , 2003; Dalebroux et al. , 2014). Precise PhoPQ-mediated gene regulation is essential for salmonellae infection as strains with null or constitutively active mutations in PhoPQ are highly attenuated for virulence in animals and humans (Fields et al. , 1989; Galán and Curtiss, 1989; Miller et al. , 1989; Miller and Mekalanos, 1990). The PhoQ PD is a member of the PAS-fold and PDC-fold domain families (Cho et al. , 2006; Cheung et al. , 2008; Cheung and Hendrickson, 2010). Unlike other PDC-sensors, which bind small ligands in a defined binding pocket or PhoQ PD homologs found in environmental bacteria, the PhoQ PD from bacteria that primarily interact with animals has no apparent binding pocket due to an occluding structural element: α-helices 4 and 5 (Cho et al. , 2006; Prost et al. , 2007; Cheung et al. , 2008; Prost et al. , 2008). Acidic residues on α4 and α5 and β-strands 5 and 6 in the PhoQ PD form a structural scaffold for binding antimicrobial peptides, as well as the divalent cations Mg2+, Mn2+, and Ca2+ (Waldburger and Sauer, 1996; Bader et al. , 2005; Cho et al. , 2006; Prost et al. , 2008). PhoQ kinase activity is repressed and phosphatase activity is dominant at millimolar or greater concentrations of divalent cations (Garcia Vescovi et al. , 1996; Castelli et al. , 2000; Montagne et al. , 2001), presumably due to divalent cation salt-bridges formed between the PD acidic patch and inner membrane phospholipids (Cho et al. , 2006). Additionally, PhoQ activity is repressed by feedback inhibition involving the small inner membrane protein, MgrB (Lippa and Goulian, 2009). Conversely, bacterial growth in sub-millimolar divalent cation conditions results in PhoQ activation and increased kinase activity (Garcia Vescovi et al. , 1996), presumably due to disruption of salt-bridges between the PhoQ PD and inner membrane. However, the macrophage phagosome has a magnesium concentration of approximately one millimolar and a calcium concentration of approximately 500","Salmonella bacteria cause illnesses in humans, such as food poisoning and typhoid fever. In response to a Salmonella infection, immune cells known as macrophages detect and engulf the bacteria. The conditions inside the macrophage (which include an acidic pH and high levels of antimicrobial molecules) can destroy some bacteria. However, Salmonella bacteria (which are also called salmonellae) can sense and counteract these hostile conditions; this allows them to remodel their surface to survive and reproduce inside macrophages and continue to cause disease. A protein known as PhoQ, which is found on the surface of Salmonella bacteria, is a sensor that detects when the bacterium is inside a macrophage and so needs to boost its defenses. The PhoQ sensor is able to respond to acidity, the absence of divalent",380,128,0.3368
scientific_lay_summarisation-elife-norm,"soils (Meng et al. , 2012; Rosenzweig et al. , 2012), and phenazine production by P. fluorescens can contribute to scab control (Arseneault et al. , 2015; Arseneault et al. , 2013; Arseneault et al. , 2016). Differences between soil microbial populations that enable effective pathogen suppression are routinely assessed using amplicon sequencing (Fierer, 2017; Rosenzweig et al. , 2012). However, the heterogeneity of the P. fluorescens group limits the usefulness of these methods for observing changes at the species or even the genus level. To effectively determine the relationship between the soil Pseudomonas population and disease suppression, it is important to accurately survey genotypic and phenotypic variability at the level of individual isolates, and to determine how this variation is linked to agriculturally relevant environmental changes (Mauchline and Malone, 2017). To investigate the genetic bases for S. scabies inhibition by P. fluorescens and to assess whether the scab-suppressive effects of irrigation derive from increased populations of biocontrol genotypes in the soil or on the plant, we focused on the Pseudomonas population from a potato field susceptible to potato scab. We first employed a phenotype-genotype correlation analysis across P. fluorescens strains isolated from a single potato field. We hypothesized that an unbiased correlation analysis would identify genetic loci and biosynthetic gene clusters (BGCs) that may be overlooked by screening for bioactive small molecules or by focusing on the biosynthetic repertoire of a limited number of strains. Here, we correlated phylogeny, phenotypes, specialized metabolism, and accessory genome loci, then investigated the importance of strong correlations by genetic manipulation of selected wild isolates. In total, 432 Pseudomonas strains were phenotyped (with 69 whole genomes sequenced). This approach also enabled us to answer a number of ancillary questions: how diverse is the P. fluorescens population from a single field location? Do the phenotypes associated with a P. fluorescens strain correlate with its biosynthetic capacity? What does irrigation do to both the population structure of the P. fluorescens group and to the wider bacterial community? Using this approach, we identify the P. fluorescens genes, gene clusters, and natural products that are required for potato pathogen suppression in vitro. We use this data to inform the discovery that the cyclic lipopeptide (CLP) tensin is a key determinant of in planta pathogen suppression by a Pseudomonas","Potato scab and blight are two major diseases which can cause heavy crop losses. They are caused, respectively, by the bacterium Streptomyces scabies and an oomycete (a fungus-like organism) known as Phytophthora infestans. Fighting these disease-causing microorganisms can involve crop management techniques – for example, ensuring that a field is well irrigated helps to keep S. scabies at bay. Harnessing biological control agents can also offer ways to control disease while respecting the environment. Biocontrol bacteria, such as Pseudomonas, can produce compounds that keep S. scabies and P. infestans in check. However, the identity of these molecules and how irrigation can influence Pseudomonas population remains unknown. To examine these questions, Pacheco-Moreno et al. sampled and isolated hundreds of Pseudomonas strains from a commercial potato field, closely examining the",380,128,0.3368
pubmed-summarization,"injuries in classical ballet are common and often challenging to treat for a number of reasons . many practitioners do not understand the physical demands of the sport or the terminology describing the common mechanisms of over use . classical ballet dancers subject themselves to repetitive loads that require progressive training over hundreds of hours both increasing the risk of overuse injury and complicating rehabilitation that involves any rest from dance . the ability to dance en pointe ( on the tips of the toes ) for instance , requires progressive development of the kinetic chain from the back to the toes , any disruption of which may result in overuse injury anywhere in the chain . foot and ankle injuries that are more common in classical ballet are both anterior and posterior ankle impingement , flexor hallucis longus tendonitis , and stress fractures at the base of the second metatarsal and fibula . this article will address the diagnosis and treatment of anterior ankle impingement including when performers should return to dance . successful treatment of injuries in classical ballet starts with an understanding of the basic positions and common movements which can lead to overuse injury . the five basic positions involve maximum turnout of the hips to achieve the foot position . inadequate hip turnout results in excessive knee or ankle external rotation and rolling in of the ankle to achieve the desired foot position ( . 1 ) . rolling in excessively stretches the medial ankle and compresses the anterior lateral ankle which can contribute to anterior impingement . pli ( . 2 ) is the common dance movement contributing to anterior impingement and the rolled in position of the foot exaggerates the lateral compressive forces worsening the problem . 2pli resulting in compressive force to anterior ankle right foot demonstrates excessive pronation of ankle in attempt to exaggerate turnout pli resulting in compressive force to anterior ankle anterior impingement in athletes is either secondary to hypertrophied soft tissue interposed in the anterior ankle joint or proliferation of osteophytes ( . 3 ) that limit the open space between the anterior lip of the tibia and the dorsal talar neck . different theories have been proposed to account for the pathologic changes . because impingement often","anterior impingement is a common problem in dancers occurring primarily secondary to the repetitive forced ankle dorsiflexion inherent in ballet . symptoms generally occur progressively and may respond to conservative treatment including addressing biomechanical faults that contribute to the problem . as impingement progresses , movements essential to ballet may become impossible and arthroscopic ankle surgery is often effective for both diagnosis and treatment , allowing athletes to return to dance .",380,72,0.1895
dialogsum,"#Person1#: Did you hear the news? #Person2#: What happened? #Person1#: Our cousin went into labor and had her baby last week. #Person2#: She did? Why didn't anyone tell me? #Person1#: I would've thought that somebody would have told you. #Person2#: No, I had no idea. #Person1#: Well, she did, her baby was 8 pounds 6 ounces. #Person2#: Oh my God, that's great! #Person1#: Are you going to go and visit her and the baby? #Person2#: I think that I might. #Person1#: Good! I just thought I'd let you know. #Person2#: Thanks for telling me.",#Person1# tells #Person2# their cousin went into labor and had her baby. #Person2# plans to have a visit.,94,18,0.1915
dialogsum,"#Person1#: I think I want to go back to school, Paul. #Person2#: Well, that's a nice idea, Cindy. But what would you study? #Person1#: I'm not sure. I've always been interested in psychology. I think I'd do really well. #Person2#: Uh-huh, it's not that I don't believe in you, sweetheart. You were always a good student, but it's different when you're an adult going back to school. #Person1#: Well, I don't think I would have any problems making friends. Lots of older folks get a second BA degree later in life, just like I would be doing and besides I've always been young at heart. I'm sure I'd get along with the other students. And I think I'd be an even better rider and test taker now. Then when I went to college in my late teens and early 20s. #Person2#: Yeah, but that's not what I'm worried about honey. Have you given any thought to what you do when you graduate? #Person1#: I suppose I'd look for a job. #Person2#: And what do you know about jobs in the field of psychology? #Person1#: Not too much I guess, but I could start small and work my way to the top. #Person2#: That sounds like something a person might say about a big company on the Wall Street. Psychology is different. There just aren't that many jobs in that field right now and the ones that are out there don't pay much unless you have a PhD. I mean, we have 2 kids to feed, you know?","Cindy wants to go back to school to get a second BA in psychology, but Paul is worried there aren't that many jobs in this field while they have 2 kids to feed.",257,33,0.1284
dialogsum,"#Person1#: My English teacher suggested that I come in and borrow one of these English-Chinese dictionaries. #Person2#: Of course, Mr. Jackson. You are welcome to use our dictionaries. But they may not be taken from this room. Wouldn't it be better if you have one of your own?",Jackson wants to borrow a dictionary but #Person2# advises him to have one of his own.,48,16,0.3333
scientific_lay_summarisation-elife-norm,"Some anaerobic bacteria use insoluble minerals as terminal electron acceptors and discovering the ways in which electrons move through the membrane barrier to the exterior acceptor forms an active field of research with implications for both bacterial physiology and bioenergy. A previous study suggested that Shewanella oneidensis MR-1 utilizes a small, polar, redox active molecule that serves as an electron shuttle between the bacteria and insoluble acceptors, but the shuttle itself has never been identified. Through isolation and synthesis, we identify it as ACNQ (2-amino-3-carboxy-1,4-naphthoquinone), a soluble analog of menaquinone. ACNQ is derived from DHNA (1,4-dihydroxy-2-naphthoic acid) in a non-enzymatic process that frustrated genetic approaches to identify the shuttle. Both ACNQ and DHNA restore reduction of AQDS under anaerobic growth in menaquinone-deficient mutants. Bioelectrochemistry analyses reveal that ACNQ (−0. 32 VAg/AgCl) contributes to the extracellular electron transfer (EET) as an electron shuttle, without altering menaquinone generation or EET related cytochrome c expression. Life is powered by redox reactions. It survives on the energy released as electrons move from the substrates that are oxidized to terminal electron acceptors (TEAs). The redox reactions that support life embrace a huge variety of substrates, intermediates, and acceptors as different environments demand different tactics. Anaerobic bacteria with an insoluble TEA face an especially demanding challenge as they must move electrons from inside their cells where the life-sustaining redox reactions occur, to outside the cell where the TEA resides. One solution to this transfer is an ‘electron shuttle’ – a redox active, diffusible molecule that shuttles electrons between a bacterial cell and a TEA (Brutinel and Gralnick, 2012; Gralnick and Newman, 2007). Shewanella oneidensis MR-1 has been a model organism for studying extracellular electron shuttles since it was discovered by Myers and Nealson in 1988 for its ability to use an array of insoluble, extracellular TEAs (Myers and Nealson, 1988). In 2000 Newman and Kolter provided evidence for an extracellular electron shuttle in MR-1 by demonstrating that strains with a defect in menaquinone (MK) biosynthesis could not grow anaerobically with some TEAs, unless nearby wild type MR-1 provided a ‘quinone-like’ extracellular electron shuttle that functioned as a public good (Newman and Kolter, 2000). While their study suggested the existence of an electron shuttle, it did not identify it, and additional attempts at identification led to conflicting","In order to survive, we break down food through a series of chemical reactions that release energy to power our cells. In these metabolic reactions, small electrically charged particles called electrons are removed from the food molecule, and transferred, via a series of reactions, to a terminal electron acceptor. For humans and many other organisms, oxygen is the terminal electron acceptor. Bacteria generate energy through a similar series of chemical reactions, but many species of bacteria live in environments where oxygen is absent. Some bacteria solve this problem by transferring the electrons released in their metabolic reactions to acceptor compounds in the external environment. These species must therefore employ a small molecule ‘shuttle’ to carry the electrons to the acceptor. Previous work has shown the bacterial strain Shewanella",380,128,0.3368
dialogsum,"#Person1#: Do you have cold medicine? #Person2#: Yes, but do you have a prescription with you? #Person1#: No, I don't. #Person2#: I'm afraid you can't buy any medicine without a prescription from a doctor. #Person1#: I have a headache. Is there anything I can buy without a prescription? #Person2#: Then you can buy Aspirin. #Person1#: I will take the Aspirin then. And have you a small first-aid kit? #Person2#: Yes, here this is. #Person1#: I'll take it too. #Person2#: Thank you and take care.","#Person1# has a headache but isn't allowed to buy any medicine without a prescription, so #Person1# purchases Aspirin and a small first-aid kit with #Person2#'s assistance.",84,26,0.3095
scientific_lay_summarisation-elife-norm,"have a centriole-associated fraction and a fraction that spreads out into the PCM, such as ‘Pericentrin/D-PLP’ (Martinez-Campos et al. , 2004; Zimmerman et al. , 2004; Fu and Glover, 2012; Lawo et al. , 2012; Mennella et al. , 2012) and ‘DSpd-2/Cep192’ (Pelletier et al. , 2004; Dix and Raff, 2007; Gomez-Ferreria et al. , 2007; Giansanti et al. , 2008; Zhu et al. , 2008; Joukov et al. , 2010; Decker et al. , 2011; Joukov et al. , 2014), (3) proteins that reside in the PCM, such as ‘Cnn/Cdk5Rap2’ (Megraw et al. , 1999; Lucas and Raff, 2007; Fong et al. , 2008; Barr et al. , 2010; Conduit et al. , 2010), ‘DGp71WD/NEDD1’ (Haren et al. , 2006,2009; Lüders et al. , 2006; Manning et al. , 2010), and ‘γ-tubulin’ (Sunkel et al. , 1995; Hannak et al. , 2002), and (4) mitotic protein kinases, such as ‘Polo/Plk1’ and ‘Aurora A’ (Barr and Gergely, 2007; Petronczki et al. , 2008). In recent super-resolution microscopy studies, several of these proteins appeared to be highly organized around interphase centrioles, but the organisation of proteins within the extended mitotic PCM was much less apparent (Fu and Glover, 2012; Lawo et al. , 2012; Mennella et al. , 2012; Sonnen et al. , 2012). It has long been thought that the mitotic PCM is assembled on an underlying scaffold structure (Dictenberg et al. , 1998; Schnackenberg et al. , 1998). We recently showed that Drosophila Centrosomin (Cnn) can form such a scaffold around centrioles and that this scaffold is assembled from the inside out (Conduit et al. , 2014): Cnn molecules continuously incorporate into the scaffold around the centrioles and the scaffold then fluxes slowly outward, away from the centrioles. This inside out assembly mechanism could be important, as it potentially allows the assembly of the mitotic PCM to be regulated by the centrioles. Many PCM proteins, however, can be recruited to mitotic centrosomes in the absence of Cnn, albeit at reduced levels (Lucas and Raff, 2007), suggesting that at least one other protein must be able to form a scaffold around centrioles that can recruit other PCM components. We reasoned that such a scaffold might also be assembled from the inside out. To identify such a protein (s), we analyzed","Long protein filaments called microtubules perform a range of roles inside cells—for example, they give the cell its shape and help to divide its genetic material during cell division. In animal cells, microtubules emerge from structures called centrosomes. These contain two cylindrical structures called centrioles that are surrounded by a matrix of pericentriolar material made from several hundred different proteins. Problems with centrosomes have been linked to several disorders, including cancer. In the fruit fly Drosophila, it was long thought that the pericentriolar material assembles on an underlying ‘scaffold’, the composition of which had remained unclear. A protein called Centrosomin was a good candidate molecule, as it is required to maintain the proper structure of the pericentriolar material. In addition, Centrosomin molecules continuously spread away from the centrioles",380,128,0.3368
pubmed-summarization,"indeed , the ten leading companies newly marketed compounds increased their revenues by only ~10 % , and the average innovation deficit was ~1.31.8 new chemical entities per year ( drews 2003 ) . as the time from drug discovery to launch is currently ~12 years and costs ~$750 million / drug , the pharmaceutical industry is determined to reduce both the cost and time scale of this process ; it is , therefore , understandable that the strategies adopted by these companies are those which provide information in advance of costly clinical trials . a significant obstacle to this is determining the properties of a drug that facilitate its delivery to , and uptake by , target tissues and/or cells to avoid unsuccessful but nonetheless expensive clinical trials . the bioavailability of drugs and hence their ability to interact with their targets can be summarized by four notions grouped under the acronym adme , which stands for absorption , distribution , metabolism , and excretion . each of these notions involves a particular aspect of the physiological interactions between body tissues and drugs , which explain drug bioavailability . to circumvent the inherent difficulty linked to adme - related problems , lipinski and collaborators produced a set of rules to identify the optimum physicochemical properties required for an oral compound to achieve maximum bioavailability , i.e. to cross all biological barriers before reaching its target . they studied all marketed drugs and deduced similarities or common important properties of all the different active compounds . in this context the first rule is based on the lipophilic index of drugs ( octanol water partitioning : log p < 5 ) . the second rule is based on the drugs molecular weight ( mw ) , which must be < 500 . the third and fourth rules are based on the nature of the charge on the drugs ( number of hydrogen - bond donors , i.e. number of oh + nh bonds < 5 ; and number of hydrogen bond acceptors , i.e. number of o + n atoms < 10 ) . together , these rules define the 90th percentile of the physicochemical properties drugs should have to achieve the greatest bioavailability ( lipinski et al . 2001 )","with a predicted 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm by 2015 , and a current death toll of 1 out of 8 deaths worldwide , improving treatment and/or drug design is an essential focus of cancer research . multi - drug resistance is the leading cause of chemotherapeutic failure , and delivery of anticancer drugs to the inside of cancerous cells is another major challenge . fifteen years ago , in a completely different field in which improving drug delivery is the objective , the bioavailability of oral compounds , christopher lipinski formulated some rules that are still used by the pharmaceutical industry as rules of thumb to improve drug delivery to their target . although lipinski s rules were not",380,128,0.3368
pubmed-summarization,"polycystic ovary syndrome ( pcos ) , the most common female endocrine disorder , is a heterogeneous endocrine and metabolic disorder , affecting 6 - 10% of women of reproductive age ( 1 ) . features of pcos may manifest at any age , ranging from childhood ( premature puberty ) , teenage years ( hirsutism , menstrual abnormalities ) , early adulthood and middle life ( infertility , glucose intolerance ) to later life ( diabetes mellitus and cardiovascular diseases ) ( 2 ) . several of these features increase the risk of cardiovascular diseases ( cvd ) in women ( 3 ) and the prevalence of hypertension in women with pcos is about 40% in comparison with a prevalence of about 25.8 in the general population ( 4 ) . pcos is also associated with a higher risk of myocardial infarction ( relative risk ) ( 5 ) and with a compromised cardiovascular profile independent from obesity in young women ( 6 ) . hyperandrogenism and insulin resistance or deficiency was linked to pcos , as early as 1921 , when achard and thiers published their classic description of a bearded woman with diabetes ( 7 ) . the polycystic ovary syndrome was then called the stein - leventhal syndrome , which was first described in 1935 . originally , diagnosis required pathognomonic ovarian findings and the clinical triad of hirsutism , amenorrhea and obesity ( 8) . experimental induction of a polycystic ovarian syndrome ( pcos ) in rodents by brower in 1996 was made possible by the use of a single intramuscular ( i.m . ) the rats ceased ovulation and developed characteristics of human pcos , including large cystic follicles in the ovaries and altered concentrations of luteinizing hormone ( 9 ) . roman chamomile or chamaemelum nobile ( l. ) , ( synonym anthemis nobilis l. from asteraceae family ) , is a perennial herb cultivated in western europe and north africa . in traditional medicine , chamomile flowers are used as an anti - spasmolytic and anti - inflammatory tea for stomach disorders . in women , the antispasmodic effects of chamomile ease menstrual cramps and lessen the possibility of premature labor . chamomile extract 's stimulating effect on leukocytes ( macrophages and","introductionpolycystic ovary syndrome ( pcos ) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction . presently , little is known about the primary factors that initiate pcos . chamomile flowers are used in alternative medicine for its anti - spasmolytic and anti - inflammatory effects . antispasmodic properties of chamomile ease menstrual cramps and lessen the possibility of premature labor . this medicinal herb also stimulates menstruation . in this study , we evaluated the effects of chamomile alcoholic - extract on the biochemical and clinical parameters in a rat model of pcos.materials and methodsestrous cyclicity of 30 virgin adult cycling rats was monitored by vaginal smears obtained between 0800 and 1200 hours . after about 4 days , each rat received an i.m .",380,128,0.3368
dialogsum,"#Person1#: Come in, please. #Person2#: Good morning! I am Anna Lu. I've come for an interview which was arranged. #Person1#: Oh, I see. I am Jack White, Personnel Manager. Take a seat, please. #Person2#: Glad to meet you, Mr. White. #Person1#: Miss Lu, have you got any experience in restaurant service? #Person2#: Yes. Since I entered college, I have been working at a fast food restaurant as a part-time waitress. #Person1#: For how long? #Person2#: 3 years. #Person1#: Our restaurant receives a lot of foreign customers. Can you serve them in English? #Person2#: That's why I applied for this job. Now I am studying Hotel English in my college, and I am quite familiar with the western courtesy and restaurant etiquette. I am sure my public relation skills will leave a strong impression on your customers. #Person1#: You must know our working hours are very long and overtime work is frequent. #Person2#: I don't mind that. #Person1#: I think I will give you a 3 months ' trial. The salary for this period is 800 yuan a month with no bonus. After that period if we both feel satisfied, a formal contract would be signed. #Person2#: When am I supposed to start working? #Person1#: Next monday. Bring your resume and diploma with you. #Person2#: Yes, I will. Thank you, Mr. White. Goodbye! #Person1#: Goodbye!",Anna Lu comes to Mr. White to apply for a job in a restaurant and shares her previous working experience as a part-time waitress. Mr. White'll give her a 3 months' trial.,224,32,0.1429
pubmed-summarization,"trypanosoma cruzi is an obligate intracellular parasite that is responsible for chagas disease , which affects 1618 million people in latin america . this parasite has a complex biphasic life cycle in which four developmental forms alternate between the reduviid beetle vector ( epimastigotes and metacyclic trypomastigotes ) and the mammalian host ( amastigotes and bloodstream trypomastigotes ) . transmission is initiated in the reduviid beetle vector , which becomes infected by taking up circulating trypomastigotes during a blood meal . after trypomastigotes differentiate to epimastigotes in the insect gut lumen , the parasite divides by binary fission before migrating along the hindgut and rectum , where they transform to metacyclic trypomastigotes . these trypomastigotes are released near the bite wound with the insect feces during the next blood meal . following its introduction into mammalian blood , the trypomastigotes penetrate nonphagocytic and phagocytic cells through a parasitophorous vacuole to start the intracellular cycle . in this stage amastigotes develop into nondividing bloodstream trypomastigotes that can either initiate another round of infection to propagate to different organs or can be taken up by the insect vector to complete the life cycle . throughout its life cycle , t. cruzi survives under a wide range of environmental conditions that induce complex morphological changes among parasite stages . in addition to the four main developmental forms , it is possible to observe intermediate forms ( ifs ) that seem to follow the same differentiation path , independent of whether they exist in a vertebrate or in an invertebrate host . intermediate forms appear transiently during the differentiation of epimastigotes into metacyclic trypomastigotes ( metacyclogenesis ) in the triatomine , the differentiation of metacyclic trypomastigotes ( primary amastigogenesis ) , and tissue - derived trypomastigotes ( secondary amastigogenesis ) into amastigotes and also into bloodstream trypomastigotes inside the mammalian host cell . adaptation of t. cruzi to diverse environments found in the different hosts undoubtedly induces a complex regulation of gene expression that apparently precedes the morphological changes observed during parasite transformation . several researchers have studied some of the factors that represent physiological stress for the parasite and have demonstrated that temperature , nutritional conditions , and ph stimulate morphological differentiation during amastigogenesis . the vast majority of the information regarding in","trypanosoma cruzi undergoes a biphasic life cycle that consists of four alternate developmental stages . in vitro conditions to obtain a synchronic transformation and efficient rates of pure intermediate forms ( ifs ) , which are indispensable for further biochemical , biological , and molecular studies , have not been reported . in the present study , we established an improved method to obtain ifs from secondary amastigogenesis . during the transformation kinetics , we observed progressive decreases in the size of the parasite body , undulating membrane and flagellum that were concomitant with nucleus remodeling and kinetoplast displacement . in addition , a gradual reduction in parasite movement and acquisition of the amastigote - specific ssp4 antigen were observed . therefore , our results showed that the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"specific RBPs is sufficient or required for the induction of mesenchymal state transitions or is merely one of many downstream manifestations of the EMT. Furthermore, although many splicing changes occur during EMT, only a small number of specific splicing events are known to functionally contribute to EMT including changes in the splicing of CD44, FGFR2 and Exo70 (Brown et al. , 2011; Lu et al. , 2013; Warzecha et al. , 2009). Here, we have undertaken a comprehensive approach to identify genes that regulate the EMT in breast cancer and found that genes whose protein products participate in AS regulate the transition to mesenchymal- and stem-like cell states. In prior work, we described a genetically defined, experimental model of breast cancer, derived from introducing vectors expressing the telomerase catalytic subunit, the SV40 large-T and small-t antigens, and an H-Ras oncoprotein into human mammary epithelial cells (HMLER cells) (Elenbaas et al. , 2001). Subsequent work demonstrated that the CD44 cell surface antigen is a surrogate marker for the EMT cell state change in this model (Chaffer et al. , 2011; Chaffer et al. , 2013). Thus, we separated the CD44-high and -low populations of HMLER cells by fluorescence-activated cell sorting (FACS) and confirmed that the CD44-low cells displayed epithelial properties, as measured by levels of EMT marker expression (— 1A). The highly purified CD44-low cell population remained in the epithelial cell state for at least 4 weeks in the experimental conditions. In contrast, the CD44-high HMLER cells showed elevated expression of mesenchymal markers and a greater propensity to form mammospheres, an in vitro surrogate assay for the stemness of mammary epithelial cells (— 1B, C). To study inducers of the EMT and stem-like cell state, we performed a genome scale open-reading frame (ORF) screen to identify genes that convert the HMLER cells from the CD44-low state to the CD44-high state. Each ORF in the human ORFeome library collection 8. 1 (Yang et al. , 2011) was tagged with a unique 24-nucleotide barcode and introduced into FACS purified CD44-low HMLER cells by lentiviral-mediated gene transfer. Following 7 days in culture, we purified the newly arising CD44-high HMLER cells by FACS and identified ORFs enriched in these cells by massively parallel sequencing (1A). We found that the consistency between the biological replicates of","As the human body develops, countless cells change from one state into another. Two important cell states are known as epithelial and mesenchymal. Cells in the epithelial state tend to be tightly connected and form barriers, like skin cells. Mesenchymal state cells are loosely organized, move around more and make up connective tissues. Some cells alternate between these states via an epithelial-to-mesenchymal transition (EMT for short) and back again. Without this transition, certain organs would not develop and wounds would not heal. Yet, cancer cells also use this transition to spread to distant sites of the body. Such cancers are often the most aggressive, and therefore the most deadly. The epithelial-to-mesenchymal transition is dynamically regulated in a reversible manner. For example, the genes for some proteins might only",380,128,0.3368
pubmed-summarization,"microarray data is deposited at the ncbi gene expression omnibus ( geo ) database under geo series accession number gse52552 ( ) . to gain insight in the mechanisms of complement resistance in m. catarrhalis , the transcriptional response of m. catarrhalis strain bbh18 , a complement resistant isolate , , upon exposure to 10% pooled normal human serum ( nhs ) was analyzed by microarray expression profiling . this concentration was chosen because test experiments demonstrated that a m. catarrhalis bbh18 gene deletion mutant lacking the key complement resistance factor uspa2h was rapidly killed in 10% nhs ( data not shown ) . to reduce the effect of day to day variation , two fully independent microarray expression profiling experiments were performed , indicated hereafter as experiments a and b ( table 1 ) . m. catarrhalis bbh18 was pre - cultured overnight on brain heart infusion ( bhi ) agar plates at 37 c in an atmosphere containing 5% co2 . bacteria were harvested from plates and resuspended in pbs supplemented with 0.15% gelatin ( pbs - g ) . next , 5 ml bhi medium was inoculated to an od600 nm of ~ 0.075 and cultured until mid - log phase ( od600 nm of ~ 1.0 ) , obtaining cultures with a density of 6 10 cfu / ml . of this culture , 4 ml was harvested by centrifugation , washed in 16 ml pbs - g , and resuspended in 20 ml pbs - g with 0.2 mm mgcl2 and 1 mm cacl2 ( ca and mg ) . 5.5 ml of this suspension was mixed with 5.5 ml of either pbs - g ( ca and mg ) ( control ; experiment a ; n = 3 , experiment b ; n = 2 ) or with 20% pooled nhs ( gti diagnostics ) in pbs - g ( ca and mg ) ( experiment a ; n = 3 , experiment b ; n = 3 ) and incubated at 37 c with agitation ( 200 rpm ) . after 0 , 30 ( experiment a only ) , and 60 min , a 3.5 ml aliquot was taken , harvested by centrifugation , and immediately treated with 1 ml of rnaprotect","the complement system is an important part of the innate defense against invading pathogens ( blom et al . , 2009 ; ) . the ability to resist complement - mediated killing is considered to be an important virulence trait for the human - restricted respiratory tract pathogen moraxella catarrhalis , as most disease - associated m. catarrhalis isolates are complement - resistant ( wirth et al . , 2007 ; ) . here we provide a detailed overview of the experimental methods that we have used to study the molecular basis of m. catarrhalis complement - resistance by transcriptome profiling of the bacterium upon exposure to 10% normal human serum ( nhs ) , associated with the study of de vries et al . published in molecular",380,128,0.3368
pubmed-summarization,"first nemertine alkaloid to be isolated and identified , anabaseine , occurs in relatively large concentrations in the intertidal pacific nemertine paranemertes peregrina . the peregrine ( wandering ) designation refers to the relatively unique foraging behavior of this moderately large ( > 15 cm ) species : it glides along the exposed surface of mud flats at low tide searching for annelid worms in full view of potential predators such as seagulls , raccoons and other large predators . several thousand worms were collected and an alkaloid fraction was obtained from the ethanolic extract , much as described by king . because more than a gram of alkaloid was isolated , it was possible to obtain a homogeneous picrate salt , even though in relatively small yield . after conversion back to the free base , nuclear magnetic resonance and mass spectrometric analyses indicated that the alkaloid was anabaseine , a previously synthesized compound that had not been reported as a natural product . this was corroborated by comparison of the chemical and toxicological properties of natural and synthetic samples . anabaseine is chemically similar to the tobacco alkaloid , anabasine , but possesses an imine double bond in the otherwise saturated piperidine ring ( . 2 ) . imine - enamine tautomerism constrains the -carbon to lie within the same plane as the -carbon and the imine nitrogen . this electronic conjugation strongly favors the two rings of anabaseine being approximately co - planar with respect to each other . this contrasts with nicotine and anabasine , whose respective pyrrolidine and piperidine rings are oriented approximately at right angles in their preferred conformations . anabaseine was first prepared as an intermediate in the synthesis of anabasine by two austrian tobacco chemists . a mixed aldol - like condensation reaction between nicotinic acid ethyl ester and n - benzoyl piperidone yielded the expected diketone , which rearranged in the presence of concentrated hydrochloride acid at high temperature to anabaseine hydrochloride . conversion of the salt to the free base , extraction of the free base with organic solvent and purification by distillation , the method reported by spath and mamoli or column chromatography generally provided anabaseine in relatively low yields . 251 ) obtained in this manner exists as","nemertines are a phylum of carnivorous marine worms that possess a variety of alkaloidal , peptidic or proteinaceous toxins that serve as chemical defenses against potential predators . the hoplonemertines additionally envenomate their prey with a mixture of proboscis alkaloids delivered with the help of a calcareous stylet that punctures the skin of the victim . anabaseine , the first of these alkaloids to be identified , stimulates a wide variety of animal nicotinic acetylcholine receptors ( achrs ) , especially the neuromuscular [ e.g. , 121 ( embryogenic ) or 121 ( adult ) ] and 7 achrs that are inhibited by the snake peptide -bungarotoxin . a synthetic derivative , 3-(2,4-dimethoxybenzylidene)-anabaseine ( dmxba ; also called gts-21 ) , improves memory in experimental animals and humans",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Nef-deficient strains of HIV-1 often do not develop AIDS for over 10 years even if untreated (these patients are referred to as ‘long-term non-progressors’ or ‘slow progressors’) (Deacon et al. , 1995; Kirchhoff et al. , 1995; Gorry et al. , 2007). Inhibition of Nef thus holds the promise to have a similarly beneficial effect. To date, however, this potential has not been realized mainly because Nef has no enzymatic activity and its mechanisms of action are insufficiently understood. At the cellular level, Nef has been ascribed multiple functions, of which the best characterized and most critical for pathogenesis is the downregulation of CD4 from the surface of infected cells (Guy et al. , 1987; Garcia and Miller, 1991; Carl et al. , 2000; Glushakova et al. , 2001). CD4 is a transmembrane protein that acts as a co-receptor in both the host’s immune response and the initial binding of HIV-1 to their target cells (Bowers et al. , 1997). Nef-induced CD4 downregulation interferes with the immune system (Skowronski et al. , 1993), prevents superinfection (Benson et al. , 1993) and promotes virion release (Lama et al. , 1999; Ross et al. , 1999), all of which contribute to enhanced HIV-1 propagation. HIV-1 Nef is a small, polymorphic protein of 200–215 amino acids having a myristoylated N-terminus. X-ray crystallography (Lee et al. , 1996; Arold et al. , 1997; Horenkamp et al. , 2011; Jia et al. , 2012) and NMR (Grzesiek et al. , 1996a, 1997) have shown that Nef has a folded core (residues 55–65 and 84–203), with flexible N-terminal (residues 1–54) and C-terminal (residues 204–206) segments, and a central flexible loop (residues 149–179) (residue numbers correspond to the NL4-3 strain of HIV-1). CD4 downregulation depends on both Nef myristoylation (Aiken et al. , 1994) and specific residues in the loop, including Leu164 and Leu165 (Bresnahan et al. , 1998; Craig et al. , 1998; Greenberg et al. , 1998; Janvier et al. , 2003), which are in a sequence context fitting the [DE]XXXL[LI] motif for dileucine-based sorting signals (Bonifacino and Traub, 2003), and the diacidic motif, Asp174-Asp175 (Aiken et al. , 1996; Lindwasser et al. , 2008). Myristoylation allows recruitment of Nef from the cytosol to the inner leaflet of the plasma membrane (Yu and Felsted, 1992)","Infection by a pathogen, such as a bacterium or virus, activates both the innate immune response—which is immediate but not specific to the pathogen—and the adaptive immune response, which is stronger and specific to the pathogen. White blood cells called CD4+ T helper cells play an important role in the early stages of the adaptive immune response by helping to activate and regulate other white blood cells that go on to eradicate the pathogen. HIV-1 is a retrovirus that infects immune cells that have the CD4 receptor on their surface, including CD4+ T helper cells. As the number of worker CD4+ T helper cells falls, the adaptive immune response gradually weakens, and the HIV-1 infected individual becomes increasingly susceptible to infection and disease. An individual is said to",380,128,0.3368
dialogsum,"#Person1#: I need to purchase some business cards. #Person2#: No problem. How many are you thinking about? #Person1#: I think 2, 000 would be fine. #Person2#: If you'll just fill out this form, please. #Person1#: I want the new cards to be exactly like this card. #Person2#: We can do that very easily. #Person1#: . . . Okay, I'm done. Here's the form and my old card. #Person2#: Great. Your order will take only one week. #Person1#: You know, I think it would be better if I could pick it up in three days. #Person2#: We can do that. It'll just cost you extra.","#Person1# needs 2,000 business cards to be exactly like an old card. #Person2# can do that in three days with extra pay.",104,22,0.2115
dialogsum,"#Person1#: Welcome! #Person2#: Would you give me a bottle of beer, please? #Person1#: With ice, sir? #Person2#: No, ice will spoil the taste. #Person1#: Anything else, sir? #Person2#: Yes. Something non-alcoholic, please. #Person1#: Fruit juice, milk or mineral water? #Person2#: A glass of juice please. #Person1#: Coming up immediately.",#Person2# orders beer and juice with #Person1#'s assistance.,49,8,0.1633
pubmed-summarization,"the national tb prevalence survey in eritrea was conducted from february through october 2005 ( 6 ) . in 40 selected villages , a census ( which included information about sex and age ) was taken of 875 persons in each village . all persons > 15 years of age were asked to provide a morning and a spot sputum sample . persons who had 2 positive sputum samples were informed about the test results and referred for treatment . those who had 1 positive sputum sample were referred to a nearby healthcare facility for further smear examination . if results of smear examination were negative , thoracic radiographs were taken and evaluated by 2 experienced radiologists . the case definition for a sputum smear positive case was at least 2 sputum specimens positive for acid - fast bacilli by ziehl - neelsen staining and microscopy or at least 1 sputum specimen positive for acid - fast bacilli and radiographic abnormalities consistent with active pulmonary tb ( classification of the national tuberculosis control program in eritrea ) . using the prevalence estimate obtained from the survey and 2 different models , we calculated the cdr for 2004 . in model 1 , described by styblo , cdr = ( notification rate / prevalence rate ) / ( 0.5 + 0.83 [ notification rate / prevalence rate ] ) ( 7,8 ) . in model 2 , described by dye et al . , cdr = ( notification rate / prevalence rate ) / ( [ notification rate / prevalence rate ] + 0.5 ) ( 9,10 ) . we then compared the calculated cdr with the cdr estimated by the world health organization ( who ) to evaluate whether comparable conclusions about tb case detection would be obtained . a total of 38,047 persons were included in the prevalence survey . of those > 15 years of age , 18,152 ( 94.6% ) provided at least 1 sputum sample ( ) . the prevalence of new smear - positive tb was estimated at 90/100,000 ( 95% confidence interval [ ci ] 35145/100,000 ) in persons > 15 years of age . in 2005 , 44.7% of the eritrean population was < 15 years of age ( 11 ) , which","we used results from a national tuberculosis prevalence survey in eritrea to calculate case detection rate ( cdr ) and compared it with the published cdr . the cdr obtained from the survey was 40% , whereas the cdr published by the world health organization was 3 lower ( 14% ) .",380,52,0.1368
dialogsum,"#Person1#: Excuse me. Can you tell me the way to the Public Library? #Person2#: The Public Library? But there are so many public libraries in London. Which one do you want to go to? #Person1#: The nearest one. #Person2#: That's rather far away, too. You'd better take a bus. Take the No. 7 bus to the zoo, then change to the No. 9 bus and get off at the end. #Person1#: And where's the No. 7 bus-stop, please? #Person2#: Go straight down the street, and turn left at the traffic lights. Then take the second turning on the right, and you'll find the bus-stop near the corner. You can't miss it. #Person1#: Thank you very much. #Person2#: Not at all.",#Person2# tells #Person1# how to get to the nearest public library.,120,11,0.0917
dialogsum,"#Person1#: Good morning, sir. Is there anything I can do for you? #Person2#: Yes, I would like to have a suit made to measure. #Person1#: Sure. How do you like your suit? #Person2#: I want a single breasted suit. Here is the cloth.",#Person1# helps #Person2# have a suit made to measure.,43,9,0.2093
dialogsum,"#Person1#: You are still a student? #Person2#: Yes, but I will graduate from the Shanghai Finance and Trade school next month. #Person1#: Are you sure you can be a successful cashier? #Person2#: I'm sure. You know my major is statistics and I get excellent records in all of the courses I have taken. #Person1#: That's only for your theory foundation. I am afraid if you have ever handled large amounts of cash before? #Person2#: Yes, my father runs a business so I have opportunity to work in the finance department every holiday. #Person1#: Good. I think you'll make a good cashier. #Person2#: Thank you.",#Person2# tells #Person1# #Person2#'s obtained excellent records as well as practical experience. #Person1# thinks #Person2# will be a successful cashier.,104,20,0.1923
dialogsum,"#Person1#: Hi, Francis, how was your business trip? #Person2#: It was a nightmare. #Person1#: What ' s up? #Person2#: Actually, the business trip itself was very successful. We arrived on time, we had nice conversations and we settled some important issues for the next year. #Person1#: Sounds quite fruitful, why do you call it still a nightmare then? #Person2#: Well, the air line lost my luggage on the return flight and then I lost my carry on bag when I was tackling with the officers in charge. I left the airport three hours later than I expected and then I was caught in a traffic jam. When I finally got home, I was totally exhausted. But I found the elevator was out of service due to a blackout. #Person1#: This is really a sad story. Did they trace back your luggage? #Person2#: I am still waiting for their call. #Person1#: Take it easy, all sufferings have their reward.","Although the business conversation was successful, Francis thinks the trip was a nightmare because he was unlucky to lose his luggage on the return flight.",158,25,0.1582
pubmed-summarization,", usa ) , biotinylated goat anti - rabbit secondary antibody ( transduction laboratories , usa ) , urea , gsh , sod , and catalase kits ( biodiagnostic , egypt ) , and creatinine ( humen , germany ) were purchased . adult male wistar rats weighing about 250350 g were obtained from the animal research centre , giza , egypt . animals were kept in standard housing conditions in cages and were left to acclimatize for one week . this work was conducted in the pharmacology department , faculty of medicine , el - minia university , egypt , and the animal experimental protocol was approved by the faculty board . rats were randomly assigned into 6 groups ( n = 6 each ) as follows . group i received vehicle ( 1% carboxymethylcellulose ) for 15 days and ip saline at day 11 . group ii was treated with dld ( 25 mg / kg / d orally ) for 15 days and ip saline at day 11 . group iii was treated with dhd ( 50 mg / kg / d orally ) and ip saline at day 11 . group iv was treated with vehicle for 15 days and dox ( 15 mg / kg ) at day 11 . group v was treated with dld ( 25 mg / kg / d orally ) for 15 days + ip injection of dox ( 15 mg / kg ) at day 11 . group vi was treated with dhd ( 50 mg / kg / d orally ) for 15 days + ip injection of dox ( 15 mg / kg ) at day 11 . the doses of dox and dia were based on the previous studies . group i received vehicle ( 1% carboxymethylcellulose ) for 15 days and ip saline at day 11 . group ii was treated with dld ( 25 mg / kg / d orally ) for 15 days and ip saline at day 11 . group iii was treated with dhd ( 50 mg / kg / d orally ) and ip saline at day 11 . group iv was treated with vehicle for 15 days and dox ( 15 mg / kg ) at day 11 .","nephrotoxicity is one of the limiting factors for using doxorubicin ( dox ) . interleukin 1 has major role in dox - induced nephrotoxicity , so we investigated the effect of interleukin 1 receptor antagonist diacerein ( dia ) on dox - induced nephrotoxicity . dia ( 25 and 50 mg / kg / day ) was administered orally to rats for 15 days , in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of dox ( 15 mg / kg ) at the 11th day . we measured levels of serum urea , creatinine , renal reduced glutathione ( gsh ) , malondialdehyde ( mda ) , total nitrites ( nox ) , catalase , and superoxide dismutase ( sod ) . in",380,128,0.3368
pubmed-summarization,"the stress challenge ( nature , intensity , and duration of threat ) , as well as individual subject characteristics ( sex , age , stress history ) , will be critical for delineating individualized therapeutic approaches for the future . in doing so , we hope to provide guidance on significant gaps in our knowledge that remain to be filled and some possible pathways for the future . although we focus largely on the link between stress and negative affective states , such as depression and anxiety , the same processes are probably involved in risk for other forms of psychopathology as well . the first step in understanding neuroimmune mechanisms of stress and their eventual role in stress - related health outcomes is to define what is meant by , most studies have focused on intercellular signaling factors , such as cytokines , chemokines , and the many species of prostaglandins , whose primary roles were initially defined within an immunologically relevant context . demonstration that such intercellular mediators are often invoked by stress challenges in which there is no apparent tissue damage or other immunological insult suggests a natural role for these agents in mediating stress outcomes . however , the identification and interpretation of such findings can be quite difficult because there are literally dozens of inflammatory signaling factors that can be simultaneously regulated ; cytokines often have redundant biological action with one another ; and nearly all cytokines have pleiotropic functions . even more troublesome is the fact that actions of cytokines can manifest as generally pro- or anti - inflammatory , depending upon the presence of other signaling molecules and the context in which they are induced . in addition to these conceptual issues surrounding the identification and interpretation of cytokine action , there are also technical considerations surrounding the assessments of cytokines and other immune mediators . because immune - related factors are expressed at appreciably low quantities in the normal central nervous system ( cns ) , the techniques to detect and measure such cytokines , particularly in early studies , have often been inadequate to yield precise results . for instance , many studies have utilized gross tissue dissections ( or micropunches ) that aggregate cytokine measures over large anatomical areas","the relationship between stress challenges and adverse health outcomes , particularly for the development of affective disorders , is now well established . the highly conserved neuroimmune mechanisms through which responses to stressors are transcribed into effects on males and females have recently garnered much attention from researchers and clinicians alike . the use of animal models , from mice to guinea pigs to primates , has greatly increased our understanding of these mechanisms on the molecular , cellular , and behavioral levels , and research in humans has identified particular brain regions and connections of interest , as well as associations between stress - induced inflammation and psychiatric disorders . this review brings together findings from multiple species in order to better understand how the mechanisms of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"As the biodiversity crisis continues, we must redouble efforts to understand and curb pressures pushing species closer to extinction. One major driver is the unsustainable trade of wildlife. Trade in internationally regulated species gains the most research attention, but this only accounts for a minority of traded species and we risk failing to appreciate the scale and impacts of unregulated legal trade. Despite being legal, trade puts pressure on wild species via direct collection, introduced pathogens, and invasive species. Smaller species-rich vertebrates, such as reptiles, fish, and amphibians, may be particularly vulnerable to trading because of gaps in regulations, small distributions, and demand of novel species. Here, we combine data from five sources: online web searches in six languages, Convention on International Trade in Endangered Species (CITES) trade database, Law Enforcement Management Information System (LEMIS) trade inventory, IUCN assessments, and a recent literature review, to characterise the global trade in amphibians, and also map use by purpose including meat, pets, medicinal, and for research. We show that 1215 species are being traded (17% of amphibian species), almost three times previous recorded numbers, 345 are threatened, and 100 Data Deficient or unassessed. Traded species origin hotspots include South America, China, and Central Africa; sources indicate 42% of amphibians are taken from the wild. Newly described species can be rapidly traded (mean time lag of 6. 5 years), including threatened and unassessed species. The scale and limited regulation of the amphibian trade, paired with the triptych of connected pressures (collection, pathogens, invasive species), warrants a re-examination of the wildlife trade status quo, application of the precautionary principle in regard to wildlife trade, and a renewed push to achieve global biodiversity goals. At the close of a ‘decade of biodiversity’, we have failed to meet any of the Aichi targets designed to safeguard biodiversity (CBD, 2020). One important driver of biodiversity loss is unsustainable wildlife exploitation (IPBES, 2019). Countering illegal wildlife trade is critical to limiting biodiversity loss; however, focusing solely on illegal wildlife trade can miss a potentially greater issue: that of legal wildlife trade. Gaps in trade regulations in terms of species covered by international regulation such as by the Convention on International Trade in Endangered Species (CITES) leave groups like amphibians and reptiles among the most frequently traded animals (Herrel","In the last few decades, exotic pets have become much more common. In the UK in 2008, reptiles and amphibians were more popular than dogs, with over eight million in captivity. But while almost all pet cats and dogs are born and bred in captivity, exotic pets are often taken from the wild, putting species and their habitats at risk. An international trade agreement called the Convention on International Trade in Endangered Species (CITES) strives to prevent unsustainable animal trade. But to get CITES protection, species depend on data showing that wildlife trade threatens their survival. In addition, their range countries need to first propose them to be listed. For most wild animal species, there are no data on population size or population decline. In the case of",380,128,0.3368
dialogsum,"#Person1#: What do you expect to be doing five years from now? What are your medium-term career goals? #Person2#: I would like to be in a managerial role, ideally working do6ely with external clients. I have worked in client-facing roles for more than two years and I enjoy the challenge of keeping the customer satisfied. I think Ifs something I'm good at. Finally, I'd like to be on the right career path towards eventually becoming a senior manger within the company. I'm very aware that these are ambitious goals, however I fell through hard work and dedication they achievable.",#Person2# wants a managerial role for a medium-term career goal and wants to become a senior manager eventually.,99,18,0.1818
dialogsum,"#Person1#: Excuse me. Mr. Emory? #Person2#: Yes, Ms. Rodriguez? How can I help you? #Person1#: I wanted to see if I could arrange a meeting with you to discuss recruitment. #Person2#: Absolutely. I've been wanting to meet with you about that. Let me just get my book.",Ms. Rodriguez arranges a meeting with Mr. Emory to discuss recruitment.,47,11,0.234
pubmed-summarization,"the information gathered during pre - marketing drug development is inevitably incomplete with regard to possible adverse reactions . this is mainly due to : animal testing is insufficient to predict human safety;patients enrolled in clinical trials are selected and limited in number;the conditions of use are different from those in clinical practice;the period of testing is limited . animal testing is insufficient to predict human safety ; patients enrolled in clinical trials are selected and limited in number ; the conditions of use are different from those in clinical practice ; the period of testing is limited . clinical trials often lack important information about rare but serious adverse reactions , chronic toxicity , use in special groups ( such as children , women , elderly or pregnant ) or interactions with other drugs . therefore , post - marketing surveillance activities are important to allow the early detection of unexpected and/or serious adverse reactions . it is estimated that only 6 - 10% of all adrs are reported : this underestimation is a major problem . although the extent of under - reporting is widely variable depending on the estimates , it is certain that the number of reported adrs represents only a small percentage of the total number of occurring adrs . adrs have a great impact on public health and represent a significant economic burden on both healthcare systems and society . in fact , it is estimated that in the united states , the total cost of adrs may be comparable to that of diabetes , as well as it represents the fourth leading cause of death by disease . in the european union ( eu ) , it is estimated that 5% of all hospital admissions are due to adrs , which are the fifth leading cause of hospital death : approximately 197,000 deaths per year in the eu are caused by adrs , and the total cost to the society of adrs in the eu is about 79 billion . based on these alarming data , on july 21 , 2012 , a new eu pharmacovigilance legislation came into force in order to strengthen and rationalize the eu pharmacovigilance system , with the overall objectives of better protection of public health , ensuring","introduction : spontaneous reporting of adverse drug reactions ( adrs ) is the basis of pharmacovigilance . in fact , adrs are associated with a high degree of morbidity and mortality . however , underreporting by all healthcare professionals remains the major problem in italy and in the rest of the world . the dissemination of pharmacovigilance knowledge among italian healthcare professionals , and the new pharmacovigilance regulations may promote the early detection and reporting of adrs . this review examines the legislative framework concerning the pharmacovigilance in italy.materials and methods : the information was collected from scientific articles and the websites of the italian ministry of health and the italian medicines agency ( agenzia italiana del farmaco , aifa).results : the pharmacovigilance system , both in italy",380,128,0.3368
scientific_lay_summarisation-elife-norm,"mice were re-exposed to the light compartment 24 hr later and we assessed their crossover latency to enter the dark compartment (Reactivation session). Immediately after they entered the dark compartment, the mice were returned to their home cage and crossover latency was assessed 48 hr later (post-reactivation long-term memory test, PR-LTM). The control group (treated with vehicle, VEH) displayed significantly increased crossover latency in Reactivation (398. 9 ± 48. 31 s) compared to Training (19. 7 ± 1. 68 s), indicating that the mice formed and retrieved IA memory (1A). Interestingly, the VEH group displayed further and significantly increased crossover latency at PR-LTM (1553. 5 ± 193. 81 s) compared to Reactivation, suggesting that memory retrieval enhanced IA memory in our experimental condition. This ability of retrieval to enhance memories is consistent with previous work (Gordon, 1981). 10. 7554/eLife. 02736. 003Figure 1. Memory retrieval can enhance inhibitory avoidance memory in a manner that is blocked by inhibiting protein synthesis. (A) Re-exposure to the light compartment until mice entered the dark compartment at 1 d after training. The VEH group showed enhancement of inhibitory avoidance (IA) memory (n = 10). The ANI group showed disruption of reactivated IA memory (n = 9). (B) At 3 d after training, a similar pattern was observed (VEH, n = 8; ANI, n = 12). (C) At 7 d after Reactivation (VEH, n = 8; ANI, n = 8). (D) Re-exposure to the light compartment for 3 min, but not 0 min (NR), led to IA memory enhancement (0 min: VEH, n = 8, ANI, n = 8; 3 min: VEH, n = 8, ANI, n = 9). (E) Positive correlation of crossover latency between the Reactivation and PR-LTM sessions (n = 96, r2 = 0. 646). (F) Re-exposure to the dark compartment for 3 min following re-exposure to the light compartment. The VEH group showed long-term extinction of IA memory, while ANI blocked this (VEH, n = 10; ANI, n = 10). (G) CREB-mediated transcription is required for memory reconsolidation in the protocol used in 1A (WT/VEH, n = 9; WT/TAM, n = 9; CREBIR/VEH, n = 9; CREBIR/TAM, n = 9). ANI: anisomycin; CREB: cAMP responsive element binding protein; CREBIR: inducible CREB repressor (CREBIR) transgenic mice; IA: inhibitory avoidance; NR: non-reactivated; PR-LTM: post-reactivation","Video cameras allow us to record events as they happen. When we look back at a video clip, what we see is an exact replica of what was originally recorded. We tend to assume that our memories work in a similar manner. However, recent research suggests that our memories may be more malleable than we realize. Once a memory has been reactivated, it goes through a process known as reconsolidation that can make it stronger or weaker, or that can change its content. Now, Fukushima et al. have carried out a series of experiments which shed light on the process of memory reconsolidation. Mice were trained to remember a negative event, and later tested on their memory of this event. Some of the mice were also given a",380,128,0.3368
scientific_lay_summarisation-elife-norm,"(H+); metabolites, such as inorganic phosphate (Pi), or lactate; and reactive oxygen species (Allen et al. , 2008). For example, high-frequency stimulation (HFS) of nerve or muscle raises the level of extracellular K+ or [K+]o, which may mediate fatigue by depolarizing muscle membrane, inactivating Nav1. 4 voltage-gated sodium channels at the NMJ, and consequently blocking the production of muscle action potentials (APs; Cairns et al. , 2015) This mechanism may also underlie the muscle weakness observed in patients with hyperkalemic periodic paralysis, a neuromuscular disorder caused by dominant mutations in the Scna4 gene encoding the Nav1. 4 channel and characterized by episodic muscle stiffness and weakness (Cannon, 2015). In addition to presynaptic nerve terminals and muscle endplates, terminal or perisynaptic Schwann cells (TPSCs) reside at the NMJ. TPSCs are a non-myelinating Schwann cell subtype that influence the regeneration of injured peripheral motor axons (Son et al. , 1996), maintain developing synapses (Reddy et al. , 2003), and participate in synaptic pruning (Smith et al. , 2013). TPSCs also respond to neural activity by increasing cytosolic Ca2+ levels (Jahromi et al. , 1992; Reist and Smith, 1992) and are therefore functionally similar to other perisynaptic glial cells, such as astrocytes and enteric glia. In addition to responding to neurotransmitter released during neural activity by mobilizing Ca2+, astrocytes regulate the concentration of extracellular metabolites produced by activity through the expression of various ion channels and transporters (Olsen et al. , 2015; Boscia et al. , 2016; Weller et al. , 2016). Therefore, TPSCs, as the perisynaptic glia of the NMJ, likely act to modulate the concentrations of these ions at the NMJ and thereby regulate muscle fatigue. In astrocytes, activity-induced Ca2+ signaling is largely mediated by neurotransmitter-mediated stimulation of Gq G-protein coupled receptors (GPCRs), leading to the release of Ca2+ from the endoplasmic reticulum (ER) through the second messenger inositol-1,4, 5-triphosphate (IP3; Volterra et al. , 2014). Astrocytic Ca2+ signaling in turn modulates synaptic transmission and contributes to functional hyperemia, although each of these effects remains controversial (Agulhon et al. , 2010; Bonder and McCarthy, 2014). The interpretation of these effects is complicated by the observation that the mechanisms contributing to activity-induced Ca2+ signaling in the fine processes of astrocytes are distinct from those underlying this signal in the cell body (Bazargani","A muscle that contracts over and over again will become tired. This can sometimes occur after vigorous exercise, but abnormal muscle fatigue is also a feature of various clinical disorders. These include conditions that affect muscles directly, such as muscular dystrophy, as well as disorders of the motor nerves that control muscles, such as Guillain-Barré syndrome. Nerves make contact with muscles at specialized sites called neuromuscular junctions. Failing to send the correct signals to the muscles at these junctions can lead to muscle fatigue. Studies to date have focused on the role of nerve cells and muscle cells in these communication failures. But there is also a third cell type present at the neuromuscular junction, known as the terminal/perisynaptic Schwann cell (TPSC). Stimulating motor nerves in a way",380,128,0.3368
pubmed-summarization,", no more ects were given in view of a plateau of clinical response . on mental status examination , she only had blunted affect with no other active psychopathology at the end of the course of ect . it is recommended that catatonia should be managed with high doses of benzodiazepines ( i.e. , lorazepam or other benzodiazepines ) or ect , in addition to the treatment of underlying medical and psychiatric disorder with specific treatment . however , the literature with regard to the use of ect in adolescents is limited . in a review of the published literature from 1985 to 2009 , the authors located 31 reports , which described 59 cases of catatonia in children and adolescents treated with ect . majority of the patients described in the literature who were treated with ect were males ( 57% ) . the age range of patients varied from 6 to 19 years with only three patients less than 11 years of age . most of the cases were diagnosed with mood disorders ( 47.5% ) and this was followed by schizophrenia ( 27.1% ) , pervasive developmental disorder ( 13.5% ) , organic catatonia ( 5% ) , psychotic disorders other than schizophrenia ( 5% ) and one case ( 1.7% ) each of idiopathic catatonia and familial catatonia with seizures . in terms of response to ect , the data suggested that 45 patients ( 76.27% ) had a favorable response , 3 ( 5% ) cases had a partial response and in one case there was no response to ect . the authors cautioned that while interpreting the efficacy data it is important to remember that there may a potential bias for reporting only those cases , which show improvement with ect . in another review , authors noted that bilateral ( bitemporal or bifrontal ) ect has better efficacy than the unilateral ect . further , it is suggested that if a patient responds partially to lorazepam it should be used concurrently with ect for a better outcome in the acute management of catatonia . we carried out a search in pubmed and could locate 10 reports of use of ect in adolescents with catatonia published after the review of consoli et al","there is lot of skepticism about the use of electroconvulsive therapy ( ect ) in children and adolescents . however , available literature suggests that use of ect can be at times life - saving in adolescents , especially those presenting with severe catatonia . we treated a 16-year - old female who presented to us with catatonia with a course of nine ects , with which she showed marked improvement . review of the literature suggests that ect should be considered as the second line treatment in the management of catatonia in adolescents .",380,95,0.25
dialogsum,"#Person1#: Hello, Parker. How's everything? #Person2#: Can't complain. And you? #Person1#: Business is booming. I understand you want to meet up with me next week. How's your schedule look? #Person2#: Let me see. I can come out and see you first thing Wednesday. #Person1#: Great.",#Person1# and Parker will meet next Wednesday.,45,7,0.1556
dialogsum,"#Person1#: How are Zina's new programmers working out? #Person2#: I hate to admit it, but they're good. And fast. The Filipino kid is a genius. #Person1#: So you'll make the Stars. com deadline, and have us up and running next week? #Person2#: It'll be close, but we'll make it. #Person1#: Good. After Stars. com starts paying us, we won't need Vikam's cash anymore. #Person2#: And if we don't need them, we won't need Zina, either.",#Person1# and #Person2# talk about how their company is working and the possible changes.,75,14,0.1867
scientific_lay_summarisation-elife-norm,"fungal LysM effector proteins that scavenge soluble chitin fragments, thus preventing recognition by plant PRRs, suggests that mechanisms releasing these soluble fragments from fungal cell walls must exist (de Jonge et al. , 2010). Most often, however, it is an open question whether soluble ligand presentation to eukaryotic host PRRs is the result of spontaneous decomposition of the microbial extracellular matrix during infection or, alternatively, whether host-derived factors contribute to the generation of immunogenic ligands for PRR activation. For example, only monomers of bacterial flagellin induce immune responses through human TLR5 whereas filamentous flagella, in which the immunogenic flagellin structure is buried and thus is not accessible to TLR5, do not (Smith et al. , 2003). It was proposed that a number of circumstances cause flagellin monomer release from intact flagella. For instance, Caulobacter crescentus deliberately ejects its flagellum once it is no longer required for the bacterial life cycle (Jenal and Stephens, 2002). Moreover, during infection, Pseudomonas aeruginosa produces rhamnolipids which act as surfactants and cause flagellin shedding from intact flagella, resulting in a more pronounced immune response (Gerstel et al. , 2009). Alternatively, host factors such as proteases or environmental conditions such as pH, temperature, or bile salts have been proposed to mediate shearing of flagella from bacterial surfaces (Ramos et al. , 2004). Likewise, recognition of PGN by intracellular receptors, such as mammalian NOD1 and NOD2, or by plasma membrane receptors, such as mammalian TLR2 or plant LYM1, LYM3 and CERK1 (Müller-Anstett et al. , 2010; Sorbara and Philpott, 2011; Willmann et al. , 2011), is facilitated by soluble ligands. Animal lysozymes have been implicated in PGN hydrolysis, bacterial lysis, and host immunity (Callewaert and Michiels, 2010), probably through partial PGN degradation and generation of soluble ligands for PGN sensors (Cho et al. , 2005; Dziarski and Gupta, 2010; Davis et al. , 2011). In plants, knowledge of the mode of release of immunogenic fragments from microbial extracellular structures and their contribution to plant immunity is lacking. We here describe a plant enzyme activity (LYS1) that hydrolyzes β (1,4) linkages between N-acetylmuramic acid and N-acetylglucosamine residues in PGN and between N-acetylglucosamine residues in chitooligosaccharides, thus closely resembling metazoan lysozymes (EC 3. 2. 1. 17). Importantly, PGN breakdown products produced by LYS1 are immunogenic in plants, and LYS1","The immune response of plants and animals is triggered when cells detect small molecules that are present on the surface of the bacteria or fragments of peptidoglycans—the polymers that are a major component of the bacterial cell wall. The mechanisms by which small molecules trigger the immune response in plants have been widely studied in the model plant Arabidopsis thaliana, but less is known about the ways in which peptidoglycan fragments can initiate an immune response. Proteins called lysozymes are known to break peptidoglycans into smaller pieces in animals. Plants do not produce lysozymes, but they do produce other enzymes such as chitinases that have similar properties. Now Liu, Grabherr, et al. have shown that a chitinase called LYS1 acts as an enzyme that catalyzes the breakdown of",380,128,0.3368
dialogsum,"#Person1#: What in the world is that smell? #Person2#: The aroma of roasting coffee beans. #Person1#: Smells like you're baking something. What are those? #Person2#: Green beans. They pop and turn brown when you roast them. #Person1#: Cool! But isn't that a hot air popcorn popper? #Person2#: This machine roasts the beans just right. If you roast them too long, or the temperature is too hot. . . #Person1#: The beans will burn. I know. I've tasted burnt coffee before. . . yuck!",#Person2# is roasting coffee beans with a popcorn popper. #Person2# tells #Person1# this machine roasts the beans just right.,83,19,0.2289
scientific_lay_summarisation-elife-norm,"Toretsky and Wright, 2014). Characterization of the physical, structural, dynamical, and functional properties of these crowded environments remains challenging due to the dearth of appropriate tools that are needed to investigate the complexity and heterogeneity of these environments on the nanoscale. One example of a crowded environment is the pore of the NPC, which mediates bidirectional traffic between the cytoplasm and the nucleoplasm of eukaryotic cells. The translocation passageway of the NPC is occupied by hundreds of intrinsically disordered polypeptides (Lim et al. , 2008; Peleg and Lim, 2010; Suntharalingam and Wente, 2003), 50–100 nuclear transport receptors (NTRs) (Lowe et al. , 2015; Tokunaga et al. , 2008), and protein and nucleic acid cargo complexes moving in opposite directions. NTRs are classified as importins or exportins, reflecting their ability to carry cargos into or out of the nucleus, respectively (for reviews, see [Chook and Süel, 2011; Güttler and Görlich, 2011; Jamali et al. , 2011; Stewart, 2007; Wente and Rout, 2010]). On the nuclear side, RanGTP promotes disassembly of NTR/cargo import complexes, freeing the cargo and allowing NTRs to diffuse back to the cytoplasm (Chook and Blobel, 2001; Izaurralde et al. , 1997; Rexach and Blobel, 1995; Siomi et al. , 1997). NTR/cargo/RanGTP export complexes are disassembled on the cytoplasmic side after GTP hydrolysis, which results from interactions with RanGAP and a Ran-binding protein (RanBP) (Bischoff and Görlich, 1997; Bischoff et al. , 1994; Güttler and Görlich, 2011; Kutay et al. , 1997a; Okamura et al. , 2015). Many of these assembly and disassembly reactions are coordinated to occur at the cytoplasmic and nucleoplasmic exits of the NPC’s central pore (Sun et al. , 2013; Sun et al. , 2008). Exactly how cargo complexes are specifically recognized and yet rapidly migrate in milliseconds (Dange et al. , 2008; Grünwald and Singer, 2010; Kubitscheck et al. , 2005; Tu et al. , 2013; Yang et al. , 2004; Yang and Musser, 2006a) through the NPC’s crowded environment remains enigmatic. NPCs are large (~60–120 MDa) structures with octagonal rotational symmetry. They are comprised of ~30 different nuclear pore proteins (nucleoporins, or Nups), each of which are thought to be present in an integer multiple of eight copies (Cronshaw et al. , 2002; Fahrenkrog and Aebi, 2003; Mi et al. , 2015; Ori","Most of the genetic material inside an animal cell is enclosed within a compartment called the nucleus. This compartment is separated from the rest of the cell by the nuclear envelope, a double-membrane structure containing thousands of pores that selectively allow certain molecules (collectively referred to as cargo) to enter and exit the nucleus. The movement of cargo through the pores is controlled by large groups of proteins called nuclear pore complexes. The pore is at the center of the complex and is filled by a selective barrier made of an extensive network of flexible proteins known as the FG-network. Other proteins known as nuclear transport receptors bind to the proteins in the FG-network and carry cargos through the barrier. The properties of the nuclear pore barrier and",380,128,0.3368
dialogsum,"#Person1#: I'm fed up with sitting on packing cases, Joe. Don't you think we should buy at least two chairs? #Person2#: Do you know how much new chairs cost? One cheap comfortable armchair is eighty pounds. #Person1#: Yes, I know. It's terrible. But I have an idea. Why don't we look for chairs at a street market? I've always wanted to see one. #Person2#: All right. Which one shall we go to? #Person1#: Portobello Road, I think. There are a lot of secondhand things there. And we'll have to go tomorrow. It's only open on Saturdays. #Person2#: What time do you want to go? Not too early. I hope. #Person1#: The guidebook says the market is open from nine to six. It's a very popular market, so we'd better be there when it opens. #Person2#: Right. I'll set the alarm.",#Person1# wants to sit on chairs instead of packing cases but Joe thinks new chairs are expensive. They decide to have a look at the street market tomorrow.,140,28,0.2
scientific_lay_summarisation-elife-norm,"Hippocampal pyramidal neurons and interneurons have received much attention related to the contextual fear memory process in the mammalian brain (Lamsa and Lau, 2019; Roy et al. , 2017; Xia et al. , 2017; Zhu et al. , 2014). In vivo animal and human studies have found dynamic morphological and molecular changes in astrocytes during hippocampus-based contextual or spatial memory processes (Choi et al. , 2016; Sagi et al. , 2012), indicating the functional involvement of astrocytes in memory processes. However, as to whether and how astrocyte activity regulates contextual fear memory remains unclear. It has been demonstrated that channelrhodopsin-2 (ChR2) expression is nontoxic, safe, stable, and functional (Aravanis et al. , 2007; Cardin et al. , 2010; Deisseroth, 2011; Doroudchi et al. , 2011; Zhang et al. , 2006). At present, ChR2 is widely used to explore the role of glia in regulating rodent behavior and circuits by precisely manipulating their Ca2+ signaling (Bang et al. , 2016; Figueiredo et al. , 2011; Gourine et al. , 2010; Nam et al. , 2016; Perea et al. , 2014; Yamashita et al. , 2014). Our previous work showed that the [Ca2+]i elevation induced by ChR2 in astrocytes is entirely from the extracellular space (Yang et al. , 2015). Due to its proximity to the plasma membrane where exocytosis occurs, transmembrane Ca2+ influx may be more efficient in inducing gliotransmitter release than Ca2+ release from intracellular stores (Chen et al. , 2013; Tan et al. , 2017; Yang et al. , 2015). Rats are well-adapted to the natural environment and are generally considered to perform well in learning and memory tasks (Crawley, 2007). The rat brain is relatively large, so injury from optical fibers is relatively small, thus photostimulation can be delivered specifically to the hippocampus. To clarify the exact role of astrocytes in fear memory and fear-related anxiety, we generated transgenic rats with astrocyte-specific ChR2 expression. We found that the optogenetic activation of astrocytes in CA1 within a critical time window after fear conditioning disrupted memory consolidation and persistently reduced contextual fear memory and fear-related anxiety. Conversely, reducing astrocyte Ca2+ activity increased fear memory. Notably, our data revealed that the gliotransmitter adenosine and adenosine A1 receptors (A1Rs) were responsible for the fear memory attenuation and anxiolytic effect. Furthermore, intraperitoneal (i.","Memory is the record of what we learn over time and is essential to our survival. But not all memories are helpful. Repeatedly recalling a traumatic event – such as an assault – can be harmful. About 1 in 3 people who experience severe trauma go on to develop post-traumatic stress disorder (PTSD), in which they re-live the traumatic event in the form of flashbacks and nightmares. Others develop panic disorder, phobias or depression. Preventing this chain of events is challenging because fear memories form rapidly and last a long time. Current treatments involve re-exposing individuals to the traumatic event. This could be real-life exposure in the case of a phobia. Or it could involve visualizing the event, in the case of PTSD. Controlled re-exposure can help individuals",380,128,0.3368
scientific_lay_summarisation-elife-norm,"IL-22 (Cupedo et al. , 2009) and contribute to host defence against pathogens, particularly in the gut (Sonnenberg et al. , 2011). The multi-functional roles of ILCs in disease development and pathogenesis (Buonocore et al. , 2010), as well as host defence (Moro et al. , 2010; Neill et al. , 2010; Sonnenberg et al. , 2011) and repair (Monticelli et al. , 2011) have been the focus of much interest. Polyfunctional ILCs have also been described that do not fall into distinct ILC1 or ILC3 phenotypes but express both ILC1 and ILC3 lineage defining transcription factors Tbet and RORγt and secrete multiple cytokines such IL-17A, IL-22 as well as IFNγ (Buonocore et al. , 2010). We previously identified a critical role for a phenotypically distinct population of IL-23R+ RORγt+ CD4- NKp46- ILCs in the development of innate intestinal inflammation in Rag-/- mice following Helicobacter hepaticus infection or αCD40 stimulation (Buonocore et al. , 2010). Similar ILC populations were enriched in the colonic mucosa of patients with inflammatory bowel disease (IBD) (Geremia et al. , 2011), implicating IL-23-responsive, RORγt expressing ILCs in the pathogenesis of inflammatory gut disease in mice and humans. However, it remains unclear how ILCs, that are numerically sparse in vivo can initiate inflammatory processes that lead to colitis. Despite advances in understanding of the functions of ILCs, little is known about their location in tissue at different stages of the inflammatory response, and how putative structural and cytokine-mediated functions are co-ordinated. Since its description in 2006 (Uhlig et al. , 2006), the induction of colitis by injecting agonistic anti-CD40 antibody has become an important tool to assess ILC-driven acute colitis (Buonocore et al. , 2010; Vonarbourg et al. , 2010; Fuchs et al. , 2013; Kim et al. , 2013; Song et al. , 2015). By contrast with other models, anti-CD40 induced colitis follows discrete phases at well-defined time points following initiation, offering the opportunity to probe the role of leukocytes in the development and amplification of the inflammatory response. Experiments have demonstrated that intestinal inflammation was mediated via Thy1+ ILCs in a rorc dependent manner, making it an ideal system to study how ILCs contribute to pathogenesis (Buonocore et al. , 2010). A recent study investigating potential biomarkers for anti-IL-23 therapy described similar changes in","Crohn’s disease and ulcerative colitis are diseases in which the body’s own immune system causes inflammation of the large intestine. These autoimmune diseases can be severely debilitating and difficult to treat. However an improved understanding of the factors that contribute to the intestinal inflammation may lead to new and effective treatments. Immune cells called innate lymphoid cells were discovered recently, and shown quickly to play a role in host defense, tissue repair and inflammation regulation. Several groups of innate lymphoid cells are now known; each group is characterized by the genes that control the cell’s development and the small proteins (called cytokines) that the cells release. One group of innate lymphoid cells, the ILC3s, are generally found in the intestinal tract, albeit in small numbers. Given that innate",380,128,0.3368
dialogsum,"#Person1#: Room service. What can I do for you? #Person2#: I find the sheet in my room is so stained. Would you please help us change it for a clean one? #Person1#: I am sorry. sir. Someone will there in a moment. #Person2#: All right. Please be quick about it. #Person1#: Yes, sir. I assure you it would never happen again.",#Person2# asks #Person1# to change the stained sheet for a clean one.,61,12,0.1967
pubmed-summarization,"academy of medical sciences of ukraine and trial registration ( registered eudract no . 2013 - 002442 - 37 ) . after providing written informed consent , each patient was grafted with a rhciii - mpc implant consisting of rhciii ( 8% wt / vol ; from fibrogen , inc , san francisco , usa),17 mpc ( 4% wt / vol ) and poly(ethylene glycol ) diacrylate ( 1.37% wt / vol)11 by anterior lamellar corneal transplantation . patient 1 , an 80-year - old male , suffered an alkali burn to his right eye resulting in a persistent corneal ulcer resistant to conventional medical treatment and bandage contact lens wear . he suffered from pain , tearing , and photophobia due to the inability of the corneal epithelium to stably adhere to the underlying damaged and vascularized stroma . patient 1 s best corrected visual acuity ( bcva ) was 6/600 , i.e. , near blindness . patient 2 was a 72-year - old female with a previously rejected penetrating human cornea graft in her left eye , which was combined with cataract extraction and intraocular lens ( iol ) implantation . she suffered from corneal ulceration , which was unresponsive to medical treatment and bandage contact lens wear , and had the same symptoms as patient 1 , with only light perception , i.e. , effectively blind . patient 3 was a 52-year - old male who suffered from recurrent corneal erosions following an acid burn . his symptoms were similar to those of the other two patients . during the chronic stage of the burn , he received excimer laser phototherapeutic keratectomy and a human amniotic membrane ( ham ) graft for ocular surface healing . he has also had a cataract phacoemulsification and was implanted with an iol one year after the injury . all three patients needed surgery to treat the ulceration , restore corneal integrity , alleviate the associated pain and discomfort , and to improve vision . based on literature review all were considered high - risk patients for limbal epithelial graft rejection as well as penetrating or lamellar cornea graft rejection and failure . each patient s pathologic cornea was initially cut with a 45-mm - diameter trephine ( depending on lesion","corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues . in this early observational study , we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure . these patients suffered from corneal ulcers and recurrent erosions preoperatively . the implants provided relief from pain and discomfort , restored corneal integrity by promoting endogenous regeneration of corneal tissues , and improved vision in two of three patients . such implants could in the future be alternatives to donor corneas for high - risk patients , and therefore , merits further testing in a clinical trial .",380,122,0.3211
dialogsum,"#Person1#: What do you reading, Linda? #Person2#: I'm reading a novel, The Mill on the Floss, written by the one of my favorite famous novelists, Gorge Alias. #Person1#: What's it about? #Person2#: It's meanly about relationship between a brother and a sister, who live in the mill on the river floss. It describe there are childhood and disputes cause them to separate, the book ends with them ha #Person1#: Is it difficult to understand? #Person2#: Not really, i would consider it easy. #Person1#: Besides novels, any other types literary works that you indulgence. #Person2#: I really like short stories. #Person1#: Have you read anything else besides literature? #Person2#: Certainly I have. I like to read books on vary subjects, and i can read everything I can get my hands on in my spare time. I don't want to idle away and waste my time. #Person1#: I agree. People who don't read are no better often people who can't read. I also agree that books are like food for the mind.",Linda tells #Person1# she's reading a novel and she also likes short stories. Both she and #Person1# agree that books are like food for the mind.,170,26,0.1529
dialogsum,#Person1#: I need to find somewhere to park. #Person2#: Off campus or on campus? #Person1#: I need to find a space on campus. #Person2#: Why don't you park in the parking structure for students? #Person1#: Where is the parking structure at? #Person2#: It's on the west side of the campus. #Person1#: Do you know if the parking structure is full or not? #Person2#: It was empty last time I went up there. #Person1#: How long ago was that? #Person2#: I went up there early this morning. #Person1#: Do you think it'll be full now? #Person2#: It might be. You'll have to go see for yourself.,#Person1# needs to park the car on campus. #Person2# suggests the parking structure for students and asks #Person1# to see if it's full.,105,23,0.219
dialogsum,"#Person1#: Well, if it isn't the teacher's pet! #Person2#: Stop it. Teacher doesn't treat me any different than she does everyone else. #Person1#: You can't prove that by me. I saw the score on your report. #Person2#: Hey, I worked hard on that report and I deserve the grade I got. #Person1#: It just happened to be the highest grade in the class. #Person2#: You're just jealous because you didn't do as well as you thought you did. Admit it. #Person1#: I worked hard too. But she always gives me a lower grade. #Person2#: If you think that she is not fair with your work then you should talk to her in person instead of stewing over it.",#Person2# gets the highest grade. #Person1# thinks the teacher treats #Person2# better. #Person2# thinks #Person1#'s jealous and suggests #Person1# talk to the teacher.,118,23,0.1949
dialogsum,"#Person1#: Mr. : Are you Mary Lin? #Person2#: Yes. #Person1#: Mr. : I'm Mr. Rogers, your homeroom teacher. #Person2#: Where should I sit? #Person1#: Mr. : Why don't you sit behind Brad? #Person2#: Who's Brad? #Person1#: Mr. : He's that guy in the blue shirt. #Person2#: When does the first period begin, by the way? #Person1#: Mr. : As soon as the bell rings after the morning announcement.",Mr. Rogers asks Mary Lin to sit behind Brad and says the first period will begin when the bell rings.,68,20,0.2941
pubmed-summarization,"these patients . the proportion of phrynoderma cases in the present study is less compared to other studies where it was found to be 1.3% , 3% , and 5% . these studies were conducted in the middle of last century . the decline in the proportion of phrynoderma patients over the past few decades therefore , nutrition seems to play an important role in the pathogenesis of phrynoderma . in many studies including the present one , the family history of phrynoderma was very low ( 0% , 3.57% , and 5% ) . the absence of the disease in siblings who are also taking the same diet suggests the role of other factors in the manifestation of phrynoderma . the distribution and site of onset of lesions indicate importance of pressure and friction in the development of lesions . the incidence of phrynoderma is higher in the cooler months of the year , as is documented in the present study . the flare up of the disease duirng winter may be due to follicular prominence , which generally occurs in otherwise normal children during cold weather . the typical case of phrynoderma presents with bilaterally symmetrical discrete , keratotic , follicular , brown or skin colored , acuminate papules with central keratinous plug localized to elbows , knees , buttocks , and extensor extremities . in generalized disease these distinct clinical features help in differentiating phrynoderma from other common follicular keratotic disorders such as keratosis pilaris , lichen spinulosis , pityriasis rubra pilaris , and follicular lichen planus . although the occurrence of phrynoderma has been related to nutritional status of the patient , in the present study , the signs and symptoms of nutritional deficiency the ocular manifestations of vit a deficiency in patients with phrynoderma have been reported to be 5% . it has also been demonstrated that the incidence of phrynoderma is less where the prevalence of signs of vit a deficiency is high and vice versa . extremely low levels of serum vit a , 0.1 mol / l ( normal , 1.4 - 4 mol / l ) has been reported secondary to vit a malabsorption , following small bowel bypass surgery for obesity , colectomy , and in pancreatic insufficiency . diet","background : phrynoderma is a type of follicular hyperkeratosis . various nutritional deficiency disorders have been implicated in the etiology of phrynoderma.aim:to determine clinical features of phrynoderma and its association with nutritional deficiency signs.materials and methods : a cross - sectional descriptive study of 125 consecutive patients with phrynoderma attending the outpatient department ( opd ) of dermatology was conducted in a tertiary care hospital . in all patients , a detailed history was taken and cutaneous examination findings such as distribution , sites of involvement , morphology of the lesions , and signs of nutritional deficiencies were noted.results:the proportion of patients with phrynoderma attending the opd was 0.51% . there were 79 males and 46 females . age of the patients was in the range of 3",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Heart regeneration is limited in adult mammals but occurs naturally in adult zebrafish through the activation of cardiomyocyte division. Several components of the cardiac injury microenvironment have been identified, yet no factor on its own is known to stimulate overt myocardial hyperplasia in a mature, uninjured animal. In this study, we find evidence that Neuregulin1 (Nrg1), previously shown to have mitogenic effects on mammalian cardiomyocytes, is sharply induced in perivascular cells after injury to the adult zebrafish heart. Inhibition of Erbb2, an Nrg1 co-receptor, disrupts cardiomyocyte proliferation in response to injury, whereas myocardial Nrg1 overexpression enhances this proliferation. In uninjured zebrafish, the reactivation of Nrg1 expression induces cardiomyocyte dedifferentiation, overt muscle hyperplasia, epicardial activation, increased vascularization, and causes cardiomegaly through persistent addition of wall myocardium. Our findings identify Nrg1 as a potent, induced mitogen for the endogenous adult heart regeneration program. Myocardial infarction (MI) is a common injury that causes permanent loss of hundreds of millions of cardiac muscle cells, increasing susceptibility to heart failure and sudden death. Major goals of regenerative medicine are methodologies to enhance cardiomyocyte recovery after MI and to restore cardiac function to patients with heart failure. Although there has been much investment in candidate cardiac stem cell populations over the past decade (Laflamme and Murry, 2011; Behfar et al. , 2014), many promising alternative strategies for heart regeneration have emerged, including activation of cardiomyocyte division, reprogramming of non-muscle cells into cardiomyocyte-like cells, and delivery of stem cell-derived cardiomyocytes (Bersell et al. , 2009; Qian et al. , 2012; Shiba et al. , 2012; Song et al. , 2012; Chong et al. , 2014). Heart regeneration occurs naturally after extreme tissue damage in non-mammalian vertebrates like zebrafish (Poss et al. , 2002). New myocardium is created through division of spared cardiomyocytes, and lineage-tracing experiments have not yielded evidence for a stem cell contribution (Jopling et al. , 2010; Kikuchi et al. , 2010). Zebrafish regenerate after injuries that deplete 60% or more of their cardiomyocytes, suggesting broad potential of most or all cardiomyocytes to participate in regeneration in these animals (Wang et al. , 2011). By contrast, cardiomyocyte division is robust through early postnatal life in mice and can enable regeneration, but by the adult stage is profoundly reduced (Porrello et al. , 2011). Factors that","Heart attacks—which are a major cause of death in humans—occur when a blocked blood vessel stops blood from flowing to the heart. This causes many heart muscle cells to die, which can result in permanent damage that makes survivors more susceptible to heart failure in the future. A major goal of regenerative medicine is to develop therapies that can improve the recovery of heart muscle cells after a heart attack and restore normal heart activity to patients with heart failure. Unlike the human heart, the heart of an adult zebrafish is able to regenerate even after extensive damage. After an injury, the remaining heart muscle cells divide to replace the lost heart muscle, but it is not clear how this works. A protein called Neuregulin1 (or Nrg1 for",380,128,0.3368
pubmed-summarization,"abdominal pain and nausea and was found to have elevated liver enzymes , in a pattern suggesting damage to the biliary tree ( ast 52 u / l , alt 86 u / l , alkaline phosphatase 405 u / l , ggt 604 u / l , total bilirubin 5 ct scanning of the abdomen demonstrated generalized mottling of the liver , compatible with postembolization edema with a substantial decrease in tumor burden and 2 significant lesions remaining . the patient 's liver enzymes remained elevated over the following 6 months until she developed significant right upper quadrant pain . ct 9 months after y treatment revealed a very inhomogeneous liver texture and a large biloma traversing segments 5 and 8 of the liver , measuring 8.5 6.5 5.5 cm . this was initially noted 10 months after y treatment and was slightly progressive on the 14-month scan ( . 1 ) . imaging also demonstrated multiple subcentimeter right hepatic lesions raising concern for metastatic disease , some of which had not previously been seen . due to radiographic evidence of progressive disease , everolimus 10 mg once daily was initiated , and the patient continued on this for 36 months with stabilization of the disease . her liver enzymes remained unchanged over this time , with elevated hepatobiliary enzymes and borderline - elevated hepatocellular enzymes . at 25 months after initiation of everolimus therapy , progressive disease was noted in 2 solitary hepatic lesions and was treated with radiofrequency ablation . due to disease control in the remainder of the hepatic parenchyma , everolimus was resumed after radiofrequency ablation . thirty - five months after initiation of everolimus therapy , radiographic note was made of the advanced cirrhotic appearance of the liver ( . 1 ) and the increase in size of a left hepatic lesion . there was no evidence of portal hypertension . due to the radiographic evidence of progressive disease and the cirrhotic appearance of the liver , everolimus therapy was interrupted and a liver biopsy to further characterize the nature of the parenchymal disease was performed . a single 18-gauge core was obtained from the left lobe of the liver in order to avoid the biloma involving the right lobe . the biopsy demonstrated","backgroundmanagement options for pancreatic neuroendocrine tumors ( pnets ) metastatic to the liver include surgical , ablative , cytotoxic , and radioisotope approaches . one potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 ( 90y ) microspheres . 90y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver . it appears to be well tolerated ; however , there is no randomized controlled trial reporting long - term toxicities . previous retrospective reports have described biliary damage as a potential complication of therapy with 90y and chemoembolization ; however , the long - term sequelae of 90y treatment are poorly understood.case presentationwe present the case of a 65-year - old caucasian woman who suffered biliary damage following 90y administration",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2016; Travers et al. , 2016). One approach to a deeper understanding of cardiac population biology is through single-cell genomics, including single-cell RNA sequencing (scRNA-seq). Single-cell methods have the power to overcome the limitations of bulk cell analyses, where insights into complex cell system dynamics are lost (Tanay and Regev, 2017). The rich data generated by single-cell methods allow new computational frameworks for inferring cell dynamics and causality, unencumbered by strict a priori notions of cell identity, hierarchy, trajectory and markers. Here, we present the first comprehensive analysis of cellular lineage heterogeneity, dynamics and intercellular communication among immune and stromal (non-CM) cells in healthy and injured adult mouse hearts using scRNA-seq. Clustering analysis of >30,000 cells identified over 30 cell populations across the total non-CM fraction and enriched (Pdgfra-GFP+) fibroblast lineage cells. These populations comprised most of the known cell types and their dynamics after injury, as well as novel cell types and their intermediates. We describe a novel population of activated fibroblasts present in both sham and injured hearts expressing a strong anti-Wingless-related integration site (WNT) transcriptome signature, a putative pre-proliferative state, and three novel myofibroblast subtypes expressing pro-fibrotic or anti-fibrotic (including anti-WNT) signatures. We were also able to distinguish the major tissue-resident and infiltrating Mo/MΦ, and numerous minor populations. Overall, our data reveal dynamic, multi-dimensional lineage trajectories in the injured heart. This deep resource will provide novel insights into the inflammatory and fibrotic cascades in the injured mouse heart that may suggest novel molecular or cellular targets for enhancing heart repair and regeneration in man. We performed single-cell expression profiling on the total cardiac interstitial cell population (TIP) using the 10x Genomics Chromium platform, from hearts of 8 weeks old male PdgfraGFP/+ mice at days 3 and 7 post-sham or MI surgery. To enrich for cells relevant to cardiac ischemic injury and repair, we isolated TIP cells from dissected ventricles and interventricular septum, excluding cells of the atria, annulus fibrosus and atrioventricular valves (— 1A). Transcriptional profiles of 13,331 cells were captured after quality control filtering (sham: 5,723; MI-day 3: 3,875; MI-day 7: 3,733). To identify cells with distinct lineage identities and transcriptional states, we performed unbiased clustering on an aggregate of cells using the Seurat R package (Butler et al. , 2018), with cell populations visualized in","In our bodies, heart attacks lead to cell death and inflammation. This is then followed by a healing phase where the organ repairs itself. There are many types of heart cells, from muscle and pacemaker cells that help to create the beating motion, to so-called fibroblasts that act as a supporting network. Yet, it is still unclear how individual cells participate in the heart' s response to injury. All cells possess the same genetic information, but they turn on or off different genes depending on the specific tasks that they need to perform. Spotting which genes are activated in individual cells can therefore provide clues about their exact roles in the body. Until recently, technological limitations meant that this information was difficult to access, because it was only",380,128,0.3368
dialogsum,"#Person1#: Have you heard about the new Iphone? #Person2#: Yes, I heard it's supposed to come out in June. Are you thinking about getting one? #Person1#: I'd like to. It's not only a cell phone, but a camera, PDA and MP3 player all in one.",#Person1# tells #Person2# #Person1# is thinking about getting the new iPhone.,45,11,0.2444
dialogsum,"#Person1#: Well, that's why you'r here. My source for big TV sets overcharged me on the last shipment, so I need someone new. I wanted to meet you to see if we can work together. I think #Person2#: I agree. #Person1#: Fine, but before you agree, don't you need to know what you're agreeing to? #Person2#: I guess you're right. But like you said, you called me here to check me out. I've been doing the same. #Person1#: Ha, ha, ha! That's fair. How did I do? #Person2#: Quite good, actually. I'm pretty sure you're demanding, but fair and honest. I feel we can work together. #Person1#: Good, well, here's what I need from you. Are you ready? #Person2#: Shoot! #Person1#: Well, I know you work for someone else, but as your client, please, we have to get this straight between us. I'm your client, not your company. As your client, I expect you to be square with me at all times. Can you do that? #Person2#: I don't see a problem. #Person1#: Good! Do you have any questions?",#Person1#'s source for big TV sets overcharged #Person1# on the last shipment so #Person1# asks #Person2# if they can work together. #Person1# expects #Person2# to be square with #Person1# at all times. #Person2# agrees.,179,34,0.1899
dialogsum,"#Person1#: Excuse me. I'm looking for Bluemingdails. Could you tell me how to get there? #Person2#: Sure. It's very close actually. You go straight down this road. Then you turn left, at the next junction. #Person1#: Left the next junction. Ok. #Person2#: Bluemingdails is on the corner of that block. You see it as you turn left. Seriously, You can't miss it. It's enormous. #Person1#: Thanks very much.","#Person1#'s looking for Bluemingdails, and #Person2# tells #Person1# how to get there.",68,12,0.1765
dialogsum,"#Person1#: Good morning everyone. Thank you for attending the meeting today. I'm sure you all have a copy of the agenda. So let's get started with the first issue. #Person2#: We're here today to present to you the results of our marketing research regarding the consumer behavior. #Person1#: I would like to begin by introducing our foreign guests to our stuff on your left, we have Mr. Brown, who is Vice President of Sales. Next to him is Ms. Arts, Director of Marketing for the Atlas Company. In the back row is Dr. Barolo, who is visiting from Italy. Thank you all for coming here. #Person2#: I am glad to see everyone is here and on time. Let's get started! Susan, toss out some of your ideas.","#Person1# and #Person2# are hosting a meeting about the results of marketing research. They first introduce their guests, and then start the meeting.",127,23,0.1811
scientific_lay_summarisation-elife-norm,"Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias – decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis. The prosthetic group heme plays a key role in proteins (hemoproteins) with diverse cellular functions, including oxygen binding (hemoglobin and myoglobin), electron transfer (cytochromes), protection from oxidative stress (catalases and peroxidases), and generation of second messengers (nitric oxide synthase and guanylate cyclase) (Ponka, 1999). With few exceptions (Kořený et al. , 2012), it is essential for viability in all 3 domains of life. Heme is composed of a heterocyclic tetrapyrrole called a porphyrin coordinated to a central iron atom (some researchers classify the entire heme molecule as a porphyrin, but this term is reserved for the organic ring alone here). Although naturally occurring auxotrophs have been reported (Rao et al. , 2005; Gruss et al. , 2012), heme is usually synthesized from the precursor 5-aminolevulinic acid (ALA) through a series of enzyme-catalyzed reactions. In non-photosynthetic eukaryotes, ALA is produced in the mitochondria via condensation of glycine and succinyl CoA by ALA synthase (ALAS). This is the first and typically rate-limiting step in the heme biosynthesis pathway, which proceeds in the cytoplasm before returning to the mitochondria (Layer et al. , 2010). Like ALAS, the enzymes catalyzing the 7 remaining reactions in the pathway are tightly regulated by ubiquitous and tissue-specific mechanisms (Ponka, 1997; Balwani and Desnick, 2012). Inherited, loss-of-function mutations in any of the heme biosynthesis enzymes downstream of ALAS (or gain-of-function mutations in ALAS) cause a group of diseases collectively","Porphyrias are rare diseases that involve ring-shaped molecules called porphyrins accumulating in various parts of the body. Porphyrins are produced as part of the normal process that makes an important molecule called heme, which is required to transport oxygen. However, high levels of porphyrins can be toxic. For example, porphyrins deposited in the skin can cause swelling and blistering when the skin is exposed to bright light. Other disease symptoms include neurological issues ranging from anxiety and confusion to seizures or paralysis. It has been speculated that porphyrias may have affected several historical figures, including the artist Vincent van Gogh. In addition to their role in heme production, porphyrins also have other roles. For example, they are used as pigments in the wing feathers of some owls. Researchers",380,128,0.3368
dialogsum,"#Person1#: How much is this? #Person2#: You mean the large one or the small one? #Person1#: The large one. #Person2#: They're on special this week. They've been reduced to five dollars. #Person1#: Is this the only kind you have? #Person2#: No. We have some that are different in style but not in color. They're over there. Do you see the sign? #Person1#: Oh, yes. I think I'll look at those over there before I decide. #Person2#: Very well. Just take your time.","#Person1# is shopping. #Person2# serves #Person1#, showing the goods #Person1# is interested in.",82,13,0.1585
scientific_lay_summarisation-elife-norm,"Cnidarians possess remarkable powers of regeneration, but the cellular and molecular mechanisms underlying this capability are unclear. Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation, forming a blastema at the oral pole within 24 hr. This process is necessary for head regeneration. Knocking down Piwi1, Vasa, Pl10 or Ncol1 expressed by blastema cells inhibited regeneration but not blastema formation. EdU pulse-chase experiments and in vivo tracking of individual transgenic Piwi1+ stem cells showed that the cellular source for blastema formation is migration of stem cells from a remote area. Surprisingly, no blastema developed at the aboral pole after stolon removal. Instead, polyps transformed into stolons and then budded polyps. Hence, distinct mechanisms act to regenerate different body parts in Hydractinia. This model, where stem cell behavior can be monitored in vivo at single cell resolution, offers new insights for regenerative biology. Cnidarians are renowned for their remarkable ability to regenerate any missing body part. Classical work on the freshwater polyp Hydra has shown that both head and foot regeneration can occur without a significant contribution from cell proliferation (i. e. , through morphallaxis) (Park et al. , 1970; Marcum and Campbell, 1978a, 1978b; Cummings and Bode, 1984; Dübel and Schaller, 1990; Holstein et al. , 1991). In planarians, by contrast, proliferation of pluripotent stem cells (called neoblasts) and formation of a mass of undifferentiated cells (called blastema) are required for head, tail, and pharynx regeneration (Reddien and Sanchez Alvarado, 2004; Baguñà, 2012; Reddien, 2013; Adler et al. , 2014). The establishment of a blastema in regeneration has been observed in other taxa including annelid worms (Bely, 2014) and echinoderms (Candia Carnevali, 2006; Kondo and Akasaka, 2010), but the nature of the cells involved is unclear. Urodele amphibians are the only vertebrate tetrapods that can regenerate amputated limbs as adults. They are similar to planarians in their requirement for cell proliferation and blastema formation to complete regeneration, but the cellular source for urodele regeneration is different. In newts, dedifferentiation of cells in the stump provides progenitor cells, but in the axolotl, resident stem cells fulfill the same task (Sandoval-Guzman et al. , 2014). Furthermore, amphibian blastema cells are lineage restricted rather than being pluripotent (Kragl et al. , 2009). The ability to","Although all animals are capable of regenerating damaged tissue to some extent, a few—including jellyfish, coral, and their relatives—are able to regenerate entire lost body parts. Closely related species may have very different regeneration capabilities. This has led some researchers to propose that higher animals, such as mammals, still possess the ancient genes that allow entire body parts to regenerate, but that somehow the genes have been disabled during their evolution. Studying animals that can regenerate large parts of their bodies may therefore help scientists understand what prevents others, including humans, from doing so. An animal that is particularly useful for studies into regeneration is called Hydractinia echinata. These tiny marine animals make their homes on the shells of hermit crabs. They are small, transparent and stay fixed",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses. Collectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention. Positive-strand RNA viruses replicate at membranous structures that accommodate the viral replication complex and facilitate RNA synthesis in the cytosol of infected host cells (Romero-Brey and Bartenschlager, 2016; Romero-Brey et al. , 2012; Cortese et al. , 2017; Knoops et al. , 2008; Miorin et al. , 2013). Rewiring host endomembranes is hypothesized to provide a privileged microenvironment physically separated from the cytosol, thereby ensuring adequate concentrations of macromolecules for viral RNA synthesis, preventing recognition of replication intermediates such as double-stranded RNA (dsRNA) by cytosolic innate immune receptors (Overby et al. , 2010; Neufeldt et al. , 2016), and providing a platform that facilitates molecular interactions with host cell proteins. Ultrastructural studies have reported the origin, nature, and extent of membrane modifications induced by coronaviruses (order Nidovirales, family Coronaviridae), which materialize as an ER-derived network of interconnected double-membrane vesicles (DMVs) and convoluted membranes (CM) in perinuclear regions of infected cells to which the viral replication/transcription complex (RTC) is anchored (Knoops et al. , 2008; Ulasli et al. , 2010; Oudshoorn et al. , 2017). The RTC is generated by translation of the genomic RNA into two large polyproteins that are extensively auto-proteolytically processed by viral proteases to give rise to 16 processing end-products, termed non-structural proteins (nsps) 1–16. Nsp1 is rapidly cleaved from the polyproteins and not considered an integral component of the coronaviral RTC, but interferes with host cell","Coronaviruses can infect the nose and throat and are a main cause of the common cold. Infections are usually mild and short-lived, but sometimes they can turn nasty. In 2002 and 2012, two dangerous new coronaviruses emerged and caused diseases known as SARS and MERS. These viruses caused much more serious symptoms and in some cases proved deadly. The question is, why are some coronaviruses more dangerous than others? Scientists know that the body' s response to virus infection can make a difference to whether someone had mild or severe disease. So, to understand why some coronaviruses cause a cold and others kill, they also need to learn how people react to virus infection. Coronaviruses hijack membranes inside cells and turn them into virus factories. Within these factories,",380,128,0.3368
dialogsum,"#Person1#: Where is it? #Person2#: I'm going to the Golden hotel. #Person1#: Get in, please. #Person2#: Thank you. I have an appointment with an important client at 10 o'clock. #Person1#: Don't worry, you'll be there plenty of time. That is it. 7. 15$, please. #Person2#: Thank you. here's 10$, just give me 1$ back , please.",#Person2#'s going to the Golden hotel for an appointment with an important client at 10. #Person1# drives #Person2# there.,56,19,0.3393
scientific_lay_summarisation-elife-norm,"map the distribution of transcriptionally engaged Pol II genome-wide, we performed global run-on sequencing (GRO-seq) experiments using nuclei from three stages of wild-type animals (embryos, starved L1 larvae, and L3 larvae) and dosage-compensation-defective embryos. In GRO-seq reactions, engaged polymerases are allowed to transcribe (run-on) short distances (100 nucleotides) and incorporate affinity tags into their nascent RNAs under conditions that prohibit new initiation (Core et al. , 2008). Tagged transcripts are affinity purified, amplified, sequenced, and aligned to the genome to map engaged Pol II (1A–E). 10. 7554/eLife. 00808. 003Figure 1. Genome-wide annotation of Caenorhabditis elegans transcription start sites. (A) – (E) Examples of newly annotated transcription start sites (TSSs) for protein-coding genes, non-coding RNA genes, and multigenic transcription units called operons identified using the combination of GRO-seq and GRO-cap. Red arrows demark the WormBase (WB) gene models. Dashed vertical lines show the WB gene starts. The GRO-seq signal is in reads per kilobase per million (RPKM). For protein coding genes, the GRO-seq signal was averaged across 25 bp windows with a 25 bp step. The GRO-cap signal is in reads per million (RPM). TAP+ is the signal from capped mRNAs, and TAP− is the background. For (D) and (E), the GRO-cap signal is the TAP+ signal after subtracting the TAP− signal. (A) TSS for a trans-spliced gene. The TSS maps 981 bp upstream of the WB start, with a continuous intervening GRO-seq signal. (B) TSS for the polycistronc microRNA cluster mir-54-56 maps 158 bp upstream of the primary transcript start. (C) TSS for a non-trans-spliced gene. The TSS from GRO-cap and GRO-seq aligns with the WB start site. (D) Identification of the operon TSS shows the operon includes an additional gene, tag-175. The TSS for the operon maps 781 bp upstream of tag-175. (E) TSSs for genes in operons that also use independent promoters, including the TSS for a snoRNA gene within the intron of a gene. vha-10 mRNA is trans-spliced with an SL2 RNA, indicating processing from a polycistronic RNA and an SL1 RNA, indicating transcription from an independent promoter. (F) Heat maps show that TSSs vastly improve gene models. The GRO-seq signal from embryos was plotted, one gene per row, for each of 4246 genes relative to the WB start (left) or the new TSS (right). The genes","In many species, including humans, females have two X chromosomes whereas males have only one. To ensure that females do not end up with a double dose of the proteins encoded by genes on the X chromosome, animals employ a strategy called dosage compensation to control the expression of X-linked genes. The mechanisms underlying dosage compensation vary between species, but they typically involve a regulatory complex that binds to the X chromosomes of one sex to modify gene expression. In the nematode worm Caenorhabditis elegans—which consists of hermaphrodites (XX) and males (XO) —this regulatory complex, called the dosage compensation complex (DCC), binds to both X chromosomes of XX individuals, reducing gene expression from each by 50%. DCC shares many subunits with a protein complex called condensin, which regulates",380,128,0.3368
scientific_lay_summarisation-elife-norm,"binds the opposite site (Dziembowski et al. , 2007; Makino et al. , 2015) (1A). The catalytic subunits, which may function redundantly in certain contexts, mediate RNA degradation and/or processing (Kilchert et al. , 2016). Unlike Dis3L and Exosc10, which are strictly exoribonucleases, Dis3 is also an endoribonuclease (Lebreton et al. , 2008; Tomecki and Dziembowski, 2010). The core subunits, except Exosc1, are considered to confer structural integrity (Liu et al. , 2006). 10. 7554/eLife. 17877. 003Figure 1. Exosc8 or Exosc9 downregulation disrupts protein-protein interactions within the exosome complex. (A) Crystal structure and model of the human exosome complex (Liu et al. , 2006). Solid line, direct interactions; Dashed line, indirect interactions. (B) Real-time RT-PCR analysis of mRNA expression (mean ± SE, 3 independent replicates) in G1E-ER-GATA-1 cells 48 hr post-infection with either Exosc8 or Exosc9 shRNA expressing retrovirus. Values normalized to 18S expression and relative to the control. (C) Left: representative image of a semi-quantitative Western blot of Exosc2 co-immunoprecipitated with anti-Exosc3 antibody in G1E-ER-GATA-1 whole cell lysates prepared 48 hr post-Exosc8 or Exosc9 knockdown. Right: densitometric analysis of band intensity relative to the input for each knockdown condition (mean ± SE, 3 independent replicates). Statistical analysis of control and treatment conditions was conducted with the Student’s T-test. *p<0. 05, **p<0. 01, ***p<0. 001. Source data is available in —source data 1. : http: //dx. . org/10. 7554/eLife. 17877. 00310. 7554/eLife. 17877. 004Figure 1—source data 1. This Excel spreadsheet contains the values of each independent replicate for data presented as histograms (mean ± SE) in . Sheet 1: 1B mRNA expression of Exosc8 and Exosc9 normalized to 18S. Sheet 2: 1C densitometric analysis of Exosc2 immunoblots (pull down/input) from an Exosc3 immunoprecipitation 48 hr after Exosc8 or Exosc9 knockdown. : http: //dx. . org/10. 7554/eLife. 17877. 00410. 7554/eLife. 17877. 005Figure 1— 1. The RNA binding exosome complex component Exosc3 suppresses erythroid maturation. (A) qRT-PCR analysis of Exosc3 mRNA in primary erythroid precursor cells 72 hr post-infection with shRNA-expressing retrovirus (mean ± SE, 5 biological replicates). Values are normalized to 18S expression and relative to the control. (B) Erythroid maturation analyzed by flow cytometric quantitation CD71 and Ter119 staining 72 hr post-Exosc3 knockdown in primary erythroid precursor cells. Representative flow cytometry plots, with the R1-R5 gates denoted (5 biological replicates).","Red blood cells supply an animal’s tissues with the oxygen they need to survive. These cells circulate for a certain amount of time before they die. To replenish the red blood cells that are lost, first a protein called stem cell factor (SCF) instructs stem cells and precursor cells to proliferate, and a second protein, known as erythropoietin, then signals to these cells to differentiate into mature red blood cells. It is important to maintain this balance between these two processes because too much proliferation can lead to cancer while too much differentiation will exhaust the supply of stem cells. Previous work has shown that a collection of proteins called the exosome complex can block steps leading towards mature red blood cells. The exosome complex controls several processes",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2005; Umezawa et al. , 2006; Golldack et al. , 2011). However, downstream signalling pathways that inhibit cell proliferation remain largely unknown; therefore, it remains to be established whether plants deploy central signalling pathway (s) that induce cell cycle arrest upon exposure to multiple stresses. DNA damage also arrests the cell cycle to allow DNA repair to occur before DNA replication or mitosis begins (Harper and Elledge, 2007; Ciccia and Elledge, 2010; Hu et al. , 2016). The programmed response to DNA damage is therefore crucial to maintain genome integrity. DNA damage is sensed by two kinases, ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR) (Abraham, 2001; Garcia et al. , 2003; Culligan et al. , 2004). ATM is activated by double-strand breaks (DSBs), whereas ATR senses single-strand breaks (SSBs) and stalled replication forks (Bensimon et al. , 2011; Flynn and Zou, 2011). In animals, ATM phosphorylates the checkpoint kinase CHK2, which stabilizes the transcription factor p53 and induces expression of the CDK inhibitor p21, resulting in cell cycle arrest at G1/S phase (Donjerkovic and Scott, 2000; Bartek and Lukas, 2001; Cheng and Chen, 2010). CHK1, which is phosphorylated by ATR, and CHK2 also activate the G2/M-phase checkpoint by phosphorylating CDC25 phosphatases (Karlsson-Rosenthal and Millar, 2006; Perry and Kornbluth, 2007). In contrast, while plants possess ATM and ATR, they lack functional orthologues for p21, p53, CDC25 or CHK1/2. Instead, a plant-specific NAC-type transcription factor, SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), is phosphorylated and activated by ATM and ATR, and triggers DNA damage responses (DDRs) (Yoshiyama et al. , 2009; Yoshiyama et al. , 2013; Sjogren et al. , 2015; Yoshiyama et al. , 2017). A previous study demonstrated that in Arabidopsis, SOG1 regulates the expression of almost all genes induced by DSBs (Yoshiyama et al. , 2009), causes G2 arrest in the meristem, enhances the transition from cell division to endoreplication (a repeated cycle of DNA replication without mitosis), and triggers stem cell death (Furukawa et al. , 2010; Adachi et al. , 2011). Expression of CDK inhibitors, such as SMR5 and SMR7, is directly induced by SOG1 (Yin et al. , 2014; Ogita et al. , 2018); however, their induction also occurs in DSB-tolerant Arabidopsis mutants, suggesting that it is not sufficient to arrest the cell cycle (Chen","During environmental stresses, such as high light or a drought, plants do not have the opportunity to up and leave. Instead, they need to buy time and energy by pausing their growth, which means stopping their cells from dividing. In this case, the cell cycle, a series of stages during which a cell prepares itself for division, must be halted. If the genetic information in cells is damaged, often under the influence of the environment, plants stop their cell cycle in the step just before division. However, it is still unclear how this process takes place, and which proteins participate in it. Researchers also do not know whether environmental stresses can directly trigger this mechanism. To investigate, Takahashi et al. conducted a series of genetic experiments on a",380,128,0.3368
dialogsum,"#Person1#: Stephanie! Did you just get to school? But you were up and about when I left the dorm this morning! That was about an hour and a half ago. This happens all the time! Why do you always take so long to get ready the morning? #Person2#: It's a skill. What can I say? I don't know why, I just have a long routine. #Person1#: Please explain because it makes no sense to me. How can a girl's routine be so complicated? You get up, you shower, you get dressed, you brush your teeth, you're out the door. Half an hour, tops. #Person2#: Jacob, you have the luxury of having a haircut that rarely needs styling. I don't. I have to set aside about an hour and a half to get ready in the mornings. Every day, I wake up and head straight for the shower. Every second day, I wash my hair. If it's a hair-washing day, I frequently need to wash my hair twice because it gets really oily. Then I usually put in a conditioner and have to rinse that out too. Because my hair is so long, I seldom manage to take a shower in under twenty minutes. Afterwards, I often put on a pot of coffee and get dressed while I wait for it to brew. I take a long time to get dressed in the morning. Every now and then I remember to choose my outfit the night before, but usually I do it in the morning. In all, getting dressed takes about half an hour, at which time my hair is now semi-dry so then I have to style my hair. From time to time I'll put my hair up, but oftentimes I bloody it straight. And then, because of the texture of my hair, I regularly have to flat-iron it to keep it from frizzing. That's another twenty minutes or so. After that, I have my daily makeup routine. #Person1#: True, I hardly ever see you without your hair done and your makeup on, even when you show up to class in sweatpants. Tell me, how long does it take you to choose that outfit in the morning? #Person2#: Not funny.","Jacob cannot understand why Stephanie needs 1.5 hours to get ready in the morning, so Stephanie explains her long and complex morning routine including washing her hair, choosing her outfit, getting herself dressed, styling her hair, and doing makeup.",370,39,0.1054
dialogsum,"#Person1#: It's my first visit to Prague, I'll be here for three days for a conference, then I have a day on my own to do some sightseeing before I head back home. What do you suggest I see when I'm here? #Person2#: There are many interesting places you should be sure to see. One problem is transportation, however. Because the city is very old, the roads are narrow and congested. If you only have three or four days to visit, you don't want to spend them waiting in traffic in a cab. I suggest you take the subway. #Person1#: The subway? But is there a subway station next to my hotel? I have to go between the conference center and the hotel several times a day. . . #Person2#: No worries, there's a subway station at the conference center itself, and a shuttle from your hotel to the conference center that takes only 5 minutes. When you do your personal sightseeing, you can first take the shuttle to the conference center, then hop on the metro. #Person1#: Is it expensive to ride on the underground? #Person2#: You can get a daily pass that will allow you to travel unlimited for the whole day for about 6 dollars. Otherwise, you can pay by trip, which is about 50 cents to 2 dollars each trip, depending on how far you go. #Person1#: Is it easy to get lost? #Person2#: No, no. . . . it's very hard to get lost. There are two lines, one that goes in a circle, the other that is straight. If you get lost, there are always subway attendants that can help you find your way.","It is #Person1#'s first visit to Prague. #Person2# states a transportation problem within the city before giving advice to #Person1# in several interesting places, and gives a guide of taking the subway in the city, as well as suggests a daily pass for subway taking.",280,45,0.1607
dialogsum,"#Person1#: Here's Copellini's, my cousin's store. #Person2#: Sounds like an Italian name with an ' i ' at the end. #Person1#: Admit it. You just think of Mussolini. #Person2#: No, I'm an art lover, so I think more of Bellini and Botticelli! #Person1#: Ah, yes. The Italians do love the sensual forms of the human body. #Person2#: Don't we all. . . hey! Your cousin sells gift items? #Person1#: Yeah-all from Italy. See all the saints? They're important to Roman Catholics.",#Person1# introduces #Person2# to #Person1#'s cousin's store. #Person2# thinks the name sounds like Italian and finds some gift items in the store.,81,22,0.2716
pubmed-summarization,"5 ' t7-ex1a-6 primer 5'aaacgacggccagtgaatacgactcactataggcgccagacgccgaggatggcc3 ' ) and three 3 ' primers ( 3 ' ex 5-a 993 - 1 cat tgc tgg cct ggt tct cc ; 3 ' ex 5-a 993 - 2 cat tgc tgg cct ggt tct ctt ; 3 ' ex 5-a 993 - 3 cat tgc tgg cct agt tct ctt ) . pcr reaction was mixed with 25 l of hotstart pcr reagents ( qiagen , ca ) , 5 ng-0.5 g of genomic dna , 5 l of 15 m 5'primer , 5 l of 15 m 3'primer mix and h2o to a 50 l final volume . the reaction was cycled at 95c for 10 minutes , 96c for 35 seconds , 65c for 45 seconds , 72c for 3 minutes , 4 cycle ; 96c for 30 seconds , 60c for 40 seconds , 72c for 3 minutes , 19 cycles and 96c for 30 seconds , 55c for 40 seconds , 72c for 2 minutes , 9 cycles . one l of pcr product from each sample was analyzed using a bioanalyzer on dna7500 chip ( agilent biotechnology ) . the pcr products were then precipitated with etoh at room temperature and re - suspended in depc - treated h2o at 0.1 g/l concentration . in vitro transcription ( ivt ) for each sample , the following reaction mixture was made : 4 l of each 75 mm ntp ( a , g , c and utp ) , 4 l reaction buffer , 4 l enzyme mix ( rnase inhibitor and t7 phage polymerase ) and 1 g purified pcr product in 16 l depc - treated h2o . amplified rna was then purified using trizol reagent according to manufacture instruction ( gibcobrl ) and re - suspended in 40 l of depc water . rna concentrations were estimated by using a bioanalyzer on rna 6000 chip ( agilent biotechnology ) . fluorescence - labeled single strand cdna was generated by reverse transcription ( rt ) and used for hybridization . in the rt reaction , 4 l of first strand buffer , 1 l random hexmer ( 8 g/l ; boehringer mannheim ) , 2 l 10 low t - dntp ( 5 mm a , c","detection of unknown single nucleotide polymorphism ( snp ) relies on large scale sequencing expeditions of genomic fragments or complex high - throughput chip technology . we describe a simplified strategy for fluorimetric detection of known and unknown snp by proportional hybridization to oligonucleotide arrays based on optimization of the established principle of signal loss or gain that requires a drastically reduced number of matched or mismatched probes . the array consists of two sets of 18-mer oligonucleotide probes . one set includes overlapping oligos with 4-nucleotide tiling representing an arbitrarily selected "" consensus "" sequence ( consensus - oligos ) , the other includes oligos specific for known snp within the same genomic region ( variant - oligos ) . fluorescence - labeled dna amplified from a",380,128,0.3368
dialogsum,"#Person1#: You will never guess where my family is going for summer vacation. #Person2#: Let me try. It has to be somewhere amazing, and far away. . . Egypt? #Person1#: How in the world did you guess that? Did someone tell you already? #Person2#: Yes. I overheard your mom and my mom talking in the grocery store. #Person1#: I want to ride a camel and definitely see the pyramids! #Person2#: I wish our family took outrageous summer vacations like yours. #Person1#: It helps that my dad is an archaeologist. #Person2#: We'll get to go fishing at the river. I hate fish.",#Person1#'s family will go to Egypt for summer vacation while #Person2#'s family will go fishing though #Person2# hates fish.,101,19,0.1881
pubmed-summarization,"sarcopenia is present in approximately 513% of persons over the age of 60 years and defined as the loss of skeletal muscle mass and strength with progressive decline in mobility and function . the pathogenesis of sarcopenia is associated with many intrinsic and extrinsic factors , including proinflammatory cytokine accumulation , oxidative stress , mitochondrial dysfunction , insulin resistance , and aging - related loss of anabolic hormones and motor neuron end plates . the loss of skeletal muscle results from an imbalance of protein metabolism , which is the dynamic balance between protein degradation and protein synthesis . the protein degradation systems in skeletal muscle are modulated by a coordinated network of signaling pathways activated or suppressed by hormones and cytokines ; therefore , catabolism is stimulated by a variety of proinflammatory cytokines , glucocorticoids , and reactive oxygen species ( ros ) . it is important to note that impaired cellular immune function combined with low - grade inflammation represents a continuous impact in aging process . although aging is associated with prolonged inflammatory activity that is mainly attributed to progressively worsening muscle weakness , it is unclear whether these processes are cross - talked . molecular signals and pathways connecting inflammatory system and muscle degeneration may be the key to reveal the interactions responsible for the progression of sarcopenia . the interplay seems to exist between the mass loss of skeletal muscle and elevated systemic inflammation ( ) . sarcopenia is a complex process with a subclinical state of inflammation driven by proinflammatory cytokines and oxidative stress , which increases the infiltration of immune cells into injured muscles . in turn , inflammation aggravates muscle loss and fat accumulation in the aging skeletal muscle and further decreases muscle function and physical activity . the increase in chronic inflammation response associated with high - level proinflammatory mediators as the extension of age has been considered as one of the diagnostic hallmarks and a significant contributor to aging - related atrophy of skeletal muscle . the transcription factor , nuclear factor-b ( nf-b ) , has been considered as an important mediator underlying the relationship between inflammation and aging . the correlation between inflammation and sarcopenia exists as a possible linkage describing the effect of inflammation on the balance","sarcopenia has been defined as the aging - related disease with the declined mass , strength , and function of skeletal muscle , which is the major cause of frailty and falls in elders . the activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia . several proinflammatory cytokines , especially interleukin-6 ( il-6 ) and tumor necrosis factor - alpha ( tnf- ) , play crucial roles in modulation of inflammatory signaling pathway during the aging - related loss of skeletal muscle . micrornas ( mirnas ) have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines . in this paper , we have systematically",380,128,0.3368
dialogsum,"#Person1#: I'd like to buy a house about 300m with a garden. Can you help me? #Person2#: Sure. We've helped more than ten thousand people buy and sell houses. We're the No. 1 realtor in this community. I recommend this house ( He points at a picture ). #Person1#: Where is it? #Person2#: On a hill to the east of the Tarsus river. You have a good view of the beautiful sunrise and sunset. You can't find a better home to live in. #Person1#: How many rooms are there? #Person2#: Eight rooms, a roomy kitchen, two modem bathrooms, a lovely dining room, a gorgeous living room and three sweet bedrooms. All are built with first-rate materials. #Person1#: How much is it? #Person2#: 6 million. You needn't pay the whole price at one time. You just pay 50 % in cash. We'll process the legal documents for you and then you can borrow the other 50 % from a bank and repay it in installments. We ask for only 1 % as commission. #Person1#: OK. How much is the deposit? #Person2#: Ten thousand.","#Person1# wants to buy a house about 300m with a garden. #Person2# recommends a house and tells #Person1# about its location, rooms, price, and the deposit.",182,26,0.1429
pubmed-summarization,") . comparisons between the different lymphoma subgroups were made using one way anova or the tukey correction of this test where normality failed , and where relevant by the student 's t - test or the mann - whitney rank sum test where normality failed . characteristics of the study population including treatment duration and mean follow - up duration are presented in table 1 . the bl subgroup was divided between those treated in earlier years with protocols ( comp ) that did not include anthracyclines ( 7/12 patients ) , and those that were treated more recently ( 5/12 patients ) with protocols ( lmb , nci ) containing anthracyclines . these two subgroups did not differ significantly with regard to age at diagnoses ( 6.7 3.7 ; 8.30 5.1 years , resp . , p = .52 ) or age at follow - up ( 21.2 4.2 ; 16.1 5.8 years , p = .1 ) . the mean dose of doxorubicin ( adriamycin ) , for the group as a whole was 25 mg / m per treatment , leading to a cumulative dose of 150 mg / m or a total cumulative dose of 225250 mg . all participants underwent evaluation which included an interview to assess functional class ( new york heart association ( nyha ) ) , physical examination , 12-lead ecg , and echocardiography . cardiovascular physical examination , ecg , and echocardiography were performed by 2 senior staff pediatric cardiologists ( a. lorber and y. braver ) . analyses of ecg and echocardiography images were then undertaken in a blinded manner by different investigators ( m. friedberg and i. solt ) . stroke volume was calculated by multiplying the aortic valve area , measured from the 2-dimensional echocardiographic long axis view of the internal aortic diameter at valvular level , with the velocity time integral ( vti ) of aortic flow . cardiac index ( ci ) was then calculated by multiplying this value by heart rate , and dividing the product by body surface area . mitral regurgitation was graded according to the routine clinical gradation used in the lab as none , trivial , mild , moderate or severe . normal values were defined as being within 2","objectives . we studied long - term effects of therapy for childhood lymphoma on cardiac function . design and patients . we prospectively evaluated 45 survivors of childhood lymphoma , using clinical parameters , electrocardiography and echocardiography . further comparisons were made between lymphoma subgroups and between males and females . results . mean age at diagnosis was 9.1 years . mean followup duration was 10.9 years . the nyha functional class was i in 43 patients and ii in 2 patients . a prolonged qtc interval ( > 0.44 msec ) was found in 8 patients . left ventricular ( lv ) systolic function and compliance were normal ( lv shortening fraction 40 5.6% ; cardiac index 2.84 1.13 l / min / m2 ; e /",380,128,0.3368
dialogsum,"#Person1#: Where did you get assigned to go this time around? #Person2#: They asked me to go to Paris to check on the new office that was just established there. And you? #Person1#: Hong Kong again. I would like to go somewhere different for a change. #Person2#: Teach me Cantonese and I'll pull some strings to get a trade with you next time around. #Person1#: If you really want to learn, remind me when you get back from your business trip. #Person2#: You're on. #Person1#: When do you leave? #Person2#: I'm scheduled to fly out on the tenth.","#Person1# and #Person2# shares where they got assigned to go. #Person2# asks #Person1# to teach #Person2# Cantonese, and #Person1# agrees.",98,20,0.2041
pubmed-summarization,"tha among medicare patients having a primary tha with m - pe , m - m , and c - c tha bearings . the 2005 to 2007 100% medicare inpatient claim files were used to perform a matched cohort analysis in three separate cohorts of tha patients ( m - pe , m - m , c - c ) . patients in each tha cohort were matched by age , gender , and us census region to the comparison or m - m hip resurfacing arthroplasty procedures ( which have a separate icd-9-cm procedure code ) were excluded from the analysis . each m - m patient and c - c patient ( case ) were matched to three m - pe patients ( control ) , while each c - c patient ( case ) was matched to three m - m patients ( control ) . case patient , the eligible pool of controls consisted of those patients who were within 3 years in age of the case patient and who were at least 65 years old . if more eligible controls were available than the three required per case , controls closest in age were selected first . eligible controls were also of the same gender and resided in the same us census region . all cases and controls had to be enrolled in both part a and part b of medicare . patients who received their medicare health benefits through a health maintenance organization were excluded because their healthcare expenses were not submitted to the centers for medicare and medicaid services ( cms ) for payment and , therefore , claims from these beneficiaries were not available from the database . primary tha patients were identified using international classification of diseases , 9th rev , clinical modification ( icd-9-cm ) procedure code 81.51 from the inpatient claims records and grouped into three bearing cohorts based on their corresponding icd-9-cm optional procedure modifier bearing codes ( 00.74 for m - pe , 00.75 for m - m , 00.76 for c - c ) . using each patient s unique de - identified beneficiary i d , the patients were tracked longitudinally with revision tha or selected complications as end points . the selected complications","backgroundto address the long - term problems of bearing surface wear and osteolysis associated with conventional metal - polyethylene ( m - pe ) total hip arthroplasty ( tha ) , metal - metal ( m - m ) , and ceramic - ceramic ( c - c ) bearings have been introduced . these bearing surfaces are associated with unique risks and benefits and higher costs . however the relative risks of these three bearings in an older population is unknown.questions/purposeswe compared the short - term risk of complication and revision tha among medicare patients having a primary tha with metal - polyethylene ( m - pe ) , metal - metal ( m - m ) , and ceramic - ceramic ( c - c )",380,128,0.3368
pubmed-summarization,"64 monoamine oxidase inhibitors of the training and test set were built and energy minimized using smart minimize module from the cerius . the catalyst model treats molecular structures as templates comprising chemical functions localized in space that will bind effectively with complementary functions on the respective binding proteins . the most relevant chemical features are extracted from a small set of compounds that cover a broad range of activity . the best searching procedure was applied to select representative conformers within 20 kcal / mol from the global minimum . the conformational model of the training set was used for hypothesis ( pharmacophore ) generation within catalyst , which aims to identify the best 3-dimensional arrangement of chemical functions explaining the activity variations among the compounds in the training set . the automatic generation procedure using the hypogen algorithm in catalyst was adopted for generation of the hypotheses . in order to obtain a reliable model , which adequately describes the interaction of ligands with high predictability , the method recommends a collection of training set with biological activity covering 45 orders of magnitude for the training set . the pharmacophore / hypotheses are described by a set of functional features such as hydrophobic , hydrogen - bond donor , hydrogen - bond acceptor , and positive and negative ionizable sites distributed over a 3d space . the statistical relevance of the obtained hypotheses is assessed on the basis of their cost relative to the null hypothesis and their correlation coefficient . pharmacophore generation was carried out with the 64 monoamine oxidase - a inhibitors ( table 1 ) by setting the default parameters in the automatic generation procedure in catalyst such as function weight 0.302 , mapping coefficient 0 , resolution 10 pm ( due to smaller size of the inhibitor set considered for the study ) , and activity uncertainty 3 . as uncertainty in the catalyst paradigm indicates an activity value lying somewhere in the interval from activity divided by to activity multiplied by . hypotheses approximating the pharmacophore of the mao - a inhibitors are described as a set of aromatic hydrophobic , hydrogen - bond acceptor , hydrogen bond acceptor lipid , positively and negatively ionizable sites distributed within a 3d space . the","flavoprotein monoamine oxidase is located on the outer membrane of mitochondria . it catalyzes oxidative deamination of monoamine neurotransmitters such as serotonin , norepinephrine and dopamine and hence is a target enzyme for antidepressant drugs . mao ( mono amine oxidase ) has two isoforms , namely mao - a and mao - b . mao - a isoform has higher affinity for serotonin and norepinephrine , while ; mao - b preferentially deaminates phenylethylamine and benzylamine . these important properties determine the clinical importance of mao inhibitors . selective mao - a inhibitors are used in the treatment of neurological disorders such as depression . in this article we have developed a hypogen pharmacophore for a set of 64 coumarin analogs and tried to analyze the intermolecular",380,128,0.3368
scientific_lay_summarisation-elife-norm,"intra-transcript interactions will predominate, but as the local density of mRNAs increases, inter-transcript interactions become more likely. Previously, we described an example involving the Drosophila oskar (osk) mRNA, in which control elements on one transcript influenced translation of another transcript (Reveal et al. , 2010). osk mRNA is expressed during oogenesis, and is subject to multiple forms of post-transcriptional control. Following transcription in the nurse cells of each egg chamber, osk mRNA is transported through cytoplasmic connections to the transcriptionally-silent oocyte. Eventually, as oogenesis proceeds, osk mRNA localizes to the posterior pole of the oocyte, and only then does Osk protein begin to accumulate. Translation of osk mRNA is highly regulated: repression prevents premature translation from unlocalized mRNA, and activation turns on translation of the localized mRNA (Kim-Ha et al. , 1995; Markussen et al. , 1995; Rongo et al. , 1995). Both types of regulation rely on binding sites for Bruno (Bru) (Reveal et al. , 2010; Kim-Ha et al. , 1995; Webster et al. , 1997; Reveal et al. , 2011). These sites, BREs and others, reside in two clusters - the AB and C regions - near the opposite ends of the 3’ UTR (1A). All the BREs contribute to translational repression (Kim-Ha et al. , 1995), and the C region BREs also play a role in translational activation (Reveal et al. , 2010). Strikingly, defects in either repression (from mutation of all BREs in osk ABC BRE-) or activation (from mutation of the C BREs in osk C BRE-) can be rescued by the presence of another osk mRNA, one that itself cannot make Osk protein but has all regulatory elements intact (Reveal et al. , 2010). 10. 7554/eLife. 10965. 003Figure 1. Rescue of osk expression in trans is not limited to Bru-dependent regulation. (A) Diagram of the osk mRNA showing sites of mutations discussed in the text. The UTRs are shown as thick lines and the coding region as a rectangle. Because two different start codons are used, portions of the 5’ region can be both UTR and coding region. Not all the mutations at the 3’ end of the mRNA are shown. (B) Embryonic patterning assays to monitor osk activity. For the upper panel, the only source of osk mRNA was a genomic osk","Genes encode the instructions needed to make proteins and other molecules. To make a protein, the DNA within a gene is copied to produce molecules of messenger ribonucleic acid (mRNA) that are then used as templates to build proteins via a process called translation. This process – which involves protein machines called ribosomes binding to the start of the mRNA – is tightly regulated to control the amounts of particular proteins in cells. For example, in fruit fly ovaries, a protein called Bruno both represses and activates the translation of a gene known as oskar. To achieve this, Bruno binds to regions near the end of the oskar RNA known as Bruno response elements. It is not clear how Bruno acts to control translation. However, because ribosomes begin",380,128,0.3368
scientific_lay_summarisation-elife-norm,"which account for less than 5% of ELKS (Kaeser et al. , 2009; Liu et al. , 2014). In addition, ELKS C-terminal variants determine RIM-binding: the B-isoforms are prominently expressed in the brain and contain the RIM binding site, whereas A-isoforms are expressed outside the brain and lack RIM binding (Wang et al. , 2002; Kaeser et al. , 2009). 10. 7554/eLife. 14862. 003Figure 1. ELKS1α and ELKS2α are co-expressed at excitatory synapses. (A) Schematic of ELKS protein structure. Arrows: transcriptional start sites of α- and β-ELKS, CCA-D: coiled-coil regions A - D (ELKS1: CCA1MYG…SKI208, CCB 209TIW…ENN358, CCC 359MLR…EAT696, CCD697LEA…EEE988; ELKS2: CCA1MYG…ARM204, CCB205SVL…ENI362, CCC363HLR…NIE656, CCD657DDS…DEE917, B: PDZ-binding sequence (ELKS1: 989GIWA992, ELKS2: 918GIWA921) of the ELKS-B C-terminal splice variant. Binding regions for interacting active zone proteins are indicated with black bars. (B) Sample images and quantification of ELKS1α (left) and ELKS2α (right) expression levels at excitatory and inhibitory synapses. VGAT or GAD2 (red, inhibitory synapses) and VGluT1 (blue, excitatory synapses) staining was used to define regions of interest (ROIs), respectively (control n = 4 independent cultures, cDKO n = 4,10 images were averaged per culture). All data are means ± SEM; *p≤0. 05 as determined by Student' s t test. (C) Sample images (top) and correlation of expression levels of ELKS1α and ELKS2α (bottom) at excitatory (left) and inhibitory (right) synapses. Arrowheads indicate example puncta used to define ROIs. Data points represent the fluorescent intensity of ELKS1α within an ROI plotted against the ELKS2α signal in the same ROI. Within a single channel, individual puncta are normalized to the average intensity across all puncta (excitatory synapses: 329 ROIs/30 images/3 independent cultures; inhibitory synapses: 250/30/3). ρ: Spearman rank correlation between ELKS1α and ELKS2α. : http: //dx. . org/10. 7554/eLife. 14862. 00310. 7554/eLife. 14862. 004Figure 1— 1. ELKS antibody specificity. (A) Western blot for testing specificity of ELKS2α (1029, top) and ELKS1α (E-1, middle) antibodies against samples of HEK293T cells transfected with ELKS1αB or ELKS2αB cDNAs. The ELKS2α specific antibodies were raised in rabbits to a non-conserved sequence between ELKS1 and ELKS2 (109LSHTDVLSYTDQ120), the E-1 antibody is commercially available. β-actin was used as a loading control. (B) Western blot testing reactivity of ELKS2α (top) and ELKS1α (middle) in cultured cDKO and control hippocampal neurons and whole brain homogenate. β-actin was used as a","Nerve cells in the brain communicate with one another at connections known as synapses: one nerve cell releases signaling molecules called neurotransmitters into the synapse, which are then sensed by the second cell. For the brain to work correctly, it is important that the nerve cells control when and how much neurotransmitter they release. Nerve cells package neurotransmitters into small packets called vesicles. These vesicles can be released at the so-called active zones of each synapse, though only a small subset of vesicles at a synapse are releasable. Many proteins at the active zone control the release of vesicles to influence how nerve cells communicate with each another. ELKS is one of the proteins found at the active zones of nerve cells that release either of the two",380,128,0.3368
pubmed-summarization,"the in vitro ageing of human diploid fibroblasts ( hdfs ) , first described by hayflick and moorhead , has become a classical experimental model to study cellular ageing . hdfs have a limited ability to divide when cultured in vitro . normally after about 50 cell divisions , hdfs enter a state of irreversible proliferative arrest , termed as replicative senescence or cellular senescence . cells with less than 10 passages were considered young cells with high proliferative ability while cultures at 1020 passages have entered an intermediate state or pre - senescence , and cultures of over 25 passages with no detectable doubling in cell numbers for 2 weeks were considered as senescent cells . senescent cells have been shown to accumulate with age in human tissues and , thus , have been suggested to contribute to organismal ageing . reactive oxygen species ( ros ) were implicated in replicative senescence and ageing . during physiological metabolism , endogenous ros which include superoxide anion , hydrogen peroxide , hydroxyl radicals , and singlet oxygen accumulation of oxidatively damaged cellular macromolecules is suggested to account for the free radical theory of ageing . upon entering the state of senescence the cell size or volume is increased with accumulation of cellular debris and intracellular vesicles , many of which are lysosomes . it has been reported that senescent fibroblasts became flattened and more irregular in shape with increased expression of senescence marker such as senescence associated -galactosidase ( sa--gal ) . both in vitro and in vivo studies have shown the increase in percentage of cells positive for sa--gal with cumulative population doublings ( cpds ) and age . nevertheless , the mechanisms that are responsible for the continuous cell growth and increased in sa--gal expression in senescent cells have not been well elucidated . cell cycle checkpoints sense damage of the dna structure and elicit complex cellular repair response . the checkpoints maintain cell cycle arrest while the repair takes place followed by cell cycle progression once repair is completed . cells undergo permanent cell cycle arrest and apoptosis if the dna can not be repaired adequately . a permanent cell cycle arrest occurs with cells remaining in g0/g1 phase during senescence . besides oxidative dna damage accumulation ,","this study determined the molecular mechanisms of tocotrienol - rich fraction ( trf ) in preventing cellular senescence of human diploid fibroblasts ( hdfs ) . primary culture of hdfs at various passages were incubated with 0.5 mg / ml trf for 24 h. telomere shortening with decreased telomerase activity was observed in senescent hdfs while the levels of damaged dna and number of cells in g0/g1 phase were increased and s phase cells were decreased . incubation with trf reversed the morphology of senescent hdfs to resemble that of young cells with decreased activity of sa--gal , damaged dna , and cells in g0/g1 phase while cells in the s phase were increased . elongated telomere length and restoration of telomerase activity were observed in trf -",380,128,0.3368
dialogsum,"#Person1#: Will you tell me the situation? #Person2#: I was in my friend's room, talking for an hour or so. #Person1#: And then? #Person2#: I came back to my room and found my suitcase was open and my camera and five hundred dollars in cash inside the wallet were gone. #Person1#: I'm afraid you must give up the cash. Are you insured? #Person2#: Yes, this is my overseas travel accident insurance card. #Person1#: I'll make a report for you and please claim this to the insurance company with this report.",#Person2# tells #Person1# how #Person2#'s camera and money were gone. #Person1# will make a report for #Person2# to claim to the insurance company.,90,23,0.2556
dialogsum,"#Person1#: Hello, this is the International Youth Hotel. How can I help you? #Person2#: oh, yes. I want to check whether you still have any vacancies. I need three single rooms for next Monday. #Person1#: ok. There're vacancies. Since the peak season is coming, it's advisable to book soon. Would you like to make a reservation now? #Person2#: yes, please. Do you take credit cards? #Person1#: yes, we accept all major credit cards. #Person2#: and how about Internet access? #Person1#: there's free Internet access in the lobby. #Person2#: is it available in the rooms? #Person1#: Unfortunately not. #Person2#: that's OK. Is breakfast included? #Person1#: yes, breakfast is included and parking is available. #Person2#: fantastic. Thank you very much. #Person1#: you're welcome. And we have 24 hour reception. Please don't hesitate to call anytime if you have any further questions.",#Person2# calls #Person1# to book three single rooms using credit cards.,139,11,0.0791
scientific_lay_summarisation-elife-norm,"contraction. This contraction leads to the circumferential constriction of the embryo and its conversion to a tapered cylindrical (fusiform) shape that is ∼250 µm long (about five times the length of the egg shell; Costa et al. , 1997; Priess and Hirsh, 1986). As a consequence of constriction at the epidermal surface and contractions by body wall muscles (Williams and Waterston, 1994; Chisholm and Hardin, 2005), tissues and organs inside the embryo are thought to experience squeezing forces and to elongate in conjunction with the outer layers of the embryo. Notably, the apical ECM (aECM) of the embryonic epidermis, termed the embryonic sheath, is required to prevent excessive constriction and deformation of the epidermis by actomyosin ring contraction (Priess and Hirsh, 1986). Although critical for development, the molecular composition and related physical properties of the embryonic sheath remain poorly characterized. Despite a growing interest in mechanical aspects of development and morphogenesis (Guillot and Lecuit, 2013; Heisenberg and Bellaiche, 2013), the interplay between mechanical forces and the physical properties and structure of tissues have been difficult to characterize. This is due in part to an incomplete description of mechanical forces in living embryos. In addition, genetic redundancy has likely impeded progress toward fully understanding the molecular control of tissue and organismal morphogenesis (Thomas, 1993; Pickett and Meeks-Wagner, 1995; Tautz, 2000; Herman and Yochem, 2005; Bussey et al. , 2006). Here we describe a morphological defect that results from the failure of the anterior epidermis to maintain its proper shape while experiencing an inward-directed pulling force exerted by the developing pharynx (foregut) as it undergoes elongation. This defect occurs at a low frequency in single mutants of mec-8, sym-3 and sym-4, but at a high frequency in mec-8; sym-3 and mec-8; sym-4 double mutants, indicating that this process is redundantly controlled (Davies et al. , 1999; Yochem et al. , 2004). Whereas sym-3 and sym-4 encode conserved proteins with predicted roles in vesicular trafficking (Yochem et al. , 2004; also see ‘Discussion’), mec-8 encodes a conserved RNA-binding protein involved in alternative splicing (Lundquist et al. , 1996; Spike et al. , 2002). We have shown that the contribution of MEC-8 in the resistance to this force arises, at least in part, through its control of FBN-1, a protein that shares several domains","For an animal embryo to develop, its cells must organize themselves into tissues and organs. For example, skin and the lining of internal organs—such as the lungs and gut—are made from cells called epithelial cells, which are tightly linked to form flat sheets. In a microscopic worm called Caenorhabditis elegans, the outermost layer of epithelial cells (called the epidermis) forms over the surface of the embryo early on in embryonic development. Shortly afterwards, the embryonic epidermis experiences powerful contractions along the surface of the embryo. The force generated by these contractions converts the embryo from an oval shape to a roughly cylindrical form. These contractions also squeeze the internal tissues and organs, which correspondingly elongate along with the epidermis. It has been known for decades that such ‘mechanical’",380,128,0.3368
dialogsum,#Person1#: I just heard that you won the long-distance race. Congratulations on your victory. #Person2#: Thank you. #Person1#: So it is really worth your great effort. And hope you can keep the record you've made today. #Person2#: I will try my best.,#Person1# congratulates #Person2# as #Person2# won the long-distance race.,42,9,0.2143
dialogsum,"#Person1#: I am trying to see if I can afford to purchase a home that I wish to buy. #Person2#: We can that out right now. How much do you earn annually? #Person1#: My wife and I earned one hundred and fifty thousand dollars last year. #Person2#: How many years have you held your current position? #Person1#: I have been at my current job for 10 years. #Person2#: Is there any extra income that you receive other than salary? #Person1#: I collect one thousand dollars a month from a rental property. #Person2#: Have you ever figured out your credit score? #Person1#: I try not to think about it! #Person2#: Adding in your expenses, I calculate that you can spend three hundred thousand on a house.",#Person2# helps #Person1# to out whether #Person1# can afford to purchase a home that #Person1# wishes to buy.,125,18,0.144
scientific_lay_summarisation-elife-norm,"The nucleolus is a membrane-less organelle formed through liquid-liquid phase separation of its components from the surrounding nucleoplasm. Here, we show that nucleophosmin (NPM1) integrates within the nucleolus via a multi-modal mechanism involving multivalent interactions with proteins containing arginine-rich linear motifs (R-motifs) and ribosomal RNA (rRNA). Importantly, these R-motifs are found in canonical nucleolar localization signals. Based on a novel combination of biophysical approaches, we propose a model for the molecular organization within liquid-like droplets formed by the N-terminal domain of NPM1 and R-motif peptides, thus providing insights into the structural organization of the nucleolus. We identify multivalency of acidic tracts and folded nucleic acid binding domains, mediated by N-terminal domain oligomerization, as structural features required for phase separation of NPM1 with other nucleolar components in vitro and for localization within mammalian nucleoli. We propose that one mechanism of nucleolar localization involves phase separation of proteins within the nucleolus. The nucleolus, a membrane-less organelle, is the site of ribosome biogenesis and a cellular stress sensor (Boisvert et al. , 2007). Nucleoli contain three substructures: the fibrillar centers (FCs) and dense fibrillar component (DFC) are engulfed in the granular component (GC) (Boisvert et al. , 2007), which exhibits ATP-dependent liquid-like features (Brangwynne et al. , 2011). Ribosomal RNA (rRNA) genes are transcribed between the FC and DFC, and rRNAs are processed while migrating into the GC, wherein they assemble with ribosomal proteins to form pre-ribosomal particles (Boisvert et al. , 2007). Nucleophosmin (NPM1, also known as B23), a highly abundant marker of the GC, functions as a nucleolar chaperone and plays a role in cellular stress responses (Colombo et al. , 2011). While appreciated (Brangwynne et al. , 2011; Chen and Huang, 2001; Negi and Olson, 2006; Weber and Brangwynne, 2015), the molecular basis of the GC’s fluidity is unknown. While Npm1 loss is embryonic lethal in mice, mouse fibroblasts derived from Npm1-/-/Trp53-/- embryos readily proliferate in culture (Colombo et al. , 2005), indicating that NPM1 is dispensible for ribosome biogenesis. However, NPM1 is known to influence ribosome biogenesis, genome stability and tumor suppression (Lindstrom, 2011) and to participate in responses to cellular stresses, including DNA damage (Lee et al. , 2005), chemotoxicity (Chan, 1992; Yao et al. , 2010b), and oxidative stress (Paron et al. , 2004). Furthermore, NPM1 depletion","Inside cells, machines called ribosomes assemble proteins from building blocks known as amino acids. Cells can alter the numbers of ribosomes they produce to match the cell’s demand for new proteins. For instance, when cells grow they require a lot of new proteins and therefore more ribosomes are produced. However, when cells face harsh conditions that cause stress (e. g. exposure to UV radiation or a harmful chemical) they generally stop growing and therefore need fewer ribosomes. In human and other eukaryotic cells, ribosomes are assembled in a structure called the nucleolus. However, because the nucleolus is not separated from the rest of the cell by a membrane, it was not clear how it is able to accumulate large quantities of the proteins and other molecules needed to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"i. e. chemotaxis, thermotaxis, or rheotaxis (Cosson et al. , 2008; Morisawa, 2008; Yanagimachi et al. , 2013). Instead, many fishes deposit sperm directly onto the eggs. For fertilization, sperm must search for the narrow entrance to a cone-shaped funnel in the egg coat – the micropyle – that provides access to the egg membrane. Sperm reach the micropyle probably by haptic interactions with tethered molecules that line the egg surface and the opening or interior of the micropyle (Iwamatsu et al. , 1997; Ohta and Iwamatsu, 1983; Yanagimachi et al. , 2013). At surfaces, sperm swim with their flagellum slightly inclined, which pushes the head against the wall and stabilizes sperm at the surface (Denissenko et al. , 2012; Elgeti et al. , 2010). Thus, fish sperm motility might be governed by specific hydrodynamic and haptic interactions with the egg surface and the micropyle. Although the principal targets of a CNGK-mediated hyperpolarization – the Na+/H+ exchanger and CatSper – are absent in fish, vertebrate orthologues of the sperm CNGK channel are present in various fish genomes (1A). Here, we study the function of the CNGK channel in sperm of the freshwater fish Danio rerio (DrCNGK). The DrCNGK channel constitutes the principal K+ channel in D. rerio sperm. Unexpectedly, cyclic nucleotides neither regulate CNGK channel activity nor sperm motility; instead, intracellular alkalization, a key mechanism to control sperm function in many species, strongly activates CNGK and, thereby, triggers a Ca2+ signal and a motility response. Although its mechanism of activation is entirely different compared to sea urchin sperm, the principal CNGK function, namely to provide a hyperpolarization that triggers a Ca2+ signal, is conserved. Our results show that sperm signalling among aquatic species shows unique variations that probably represent adaptations to vastly different ionic milieus and fertilization habits. 10. 7554/eLife. 07624. 003Figure 1. Identification of DrCNGK channel homologues and of a K+ channel in D. rerio sperm. (A) Phylogenetic tree (Page, 1996) of various ion channel families. The CNGK channel family exists in protozoa (dark blue), marine invertebrates and fish (medium blue), and freshwater fish (light blue). The HCN, CNG, and KCNH channel families are highlighted in green; voltage-gated Nav and Cav channels are highlighted in yellow; and voltage-gated Kv channels are highlighted in red. The following ion channel sequences","Mammalian sperm cells fertilize egg cells inside the female’s body; while for fish and other marine animals it is common for fertilization to take place outside in the environment. In general, sperm cells become attracted to egg cells by various chemical or physical signals. Sperm detect these cues and generate electrical signals that control their own movements and eventually guide sperm to the egg. In 2009, researchers identified a potassium ion channel, called CNGK, that starts the electrical signal in the sperm cells of sea urchins. This channel is activated by signalling molecules inside cells, called ‘cyclic nucleotides’, and its activity ultimately leads to calcium ions flowing into the sperm cell’s tail. This influx of calcium ions in turn controls the beating of the tail and, thereby, steers",380,128,0.3368
pubmed-summarization,"epidemiology survey of diabetes , hypertension , obesity and endocrine diseases ( turdep - ii ) , a population - based study , which was included randomly assigned 26,499 adult people from 270 urban and 270 rural centers . the field survey was performed between january and june 2010 , with a participation rate of 85% . the study was approved by the local ethical board ( istanbul medical faculty ethical committee , 16.4.2008/699 ) . people with known dm or other systemic diseases who had hs - crp levels of 10 mg / l ( 95.2 nmol / l ) or above were excluded from this study due to a possible infection . all biochemical tests including glucose , insulin , and lipid profile were measured in fasting blood samples using roche diagnostics modular autoanalyzer system ( roche diagnostics , germany ) in the central biochemistry laboratory of istanbul medical faculty . concentration of hs - crp was analyzed by immunoturbidimetric assay ( roche / hitachi 912 , modular p analyzers : acn 210 ; crpl3 tina - quant c - reactive protein gen . 3 ) and hba1c by turbidimetric inhibition immunoassay ; both the system and the laboratory have been regularly certified ( roche diagnostics tq hba1c gen . 3 ; ngsp certificate of traceability ; september 2010 - 2011 ) . a detailed medical history of each participant was obtained , and measurements of anthropometry ( height , weight , waist , and hip circumference ) and systolic and diastolic blood pressure ( sbp , dbp ) were done . body mass index ( bmi ) , homa - ir (= fasting glucose fasting insulin/405 ) , and non - hdl - cholesterol (= total cholesterol hdl - cholesterol ) were calculated accordingly . glomerular filtration rate ( egfr ) was estimated using chronic kidney disease epidemiology collaboration ckd - epi equation . risk factors for dm were evaluated using chi - square test ; mean values by sex were compared using nonparametric mann - whitney u test . homogeneity of variance and normal distribution of variables were tested by kolmogorov - smirnov test . pearson correlation coefficients ( r values ) were calculated to assess the association between hs - crp and other laboratory parameters","fasting plasma glucose ( fpg ) and hemoglobin a1c ( hba1c ) have been used to diagnose new - onset diabetes mellitus ( dm ) in order to simplify the diagnostic tests compared with the 2-hour oral glucose tolerance test ( ogtt ; 2-hpg ) . we aimed to identify optimal cut - off points of high sensitive c - reactive protein ( hs - crp ) in new - onset dm people based on fpg , 2-hpg , or hba1c methods . data derived from recent population - based survey in turkey ( turdep - ii ) . the study included 26,499 adult people ( 63% women , response rate 85% ) . the mean serum concentration of hs - crp in women was higher than in",380,128,0.3368
dialogsum,"#Person1#: Look! This picture of Mom in her cap and gown. #Person2#: Isn't it lovely! That's when she got her Master's Degree from Miami University. #Person1#: Yes, we are very proud of her. #Person2#: Oh, that's a nice one of all of you together. Do you have the negative? May I have a copy? #Person1#: Surely, I'll have one made for you. You want a print? #Person2#: No. I'd like a slide, I have a new projector. #Person1#: I'd like to see that myself. #Person2#: Have a wallet size print made for me, too. #Person1#: Certainly.",#Person2# thinks the picture is lovely and asks #Person1# to give a slide and a wallet-size print.,96,17,0.1771
dialogsum,"#Person1#: Could you show me how to operate this fax machine? I am going to receive some urgent fax from a company. #Person2#: Of course. Let me check it. Firstly, don't be frustrated about all the buttons on it. #Person1#: That's right. #Person2#: After overcoming these buttons, you should check whether there is any paper in the machine, you must make sure this. #Person1#: I couldn't agree more. #Person2#: And then prepare what you want to receive. If you want to send a photograph, you must copy one. #Person1#: What can I do next? #Person2#: The next thing you should do is to wait. The sender will give you the fax. #Person1#: Look. Some of the faxes come through blurred. What is wrong with it? #Person2#: Maybe we should call its after-service man.",#Person2# shows #Person1# how to operate the fax machine but some of the faxes come through blurred. #Person2# suggests calling the after-service man.,133,23,0.1729
dialogsum,"#Person1#: Professor, excuse me, but I need to leave early. #Person2#: What seems to be the problem? #Person1#: I am not feeling well. #Person2#: What is bothering you? #Person1#: I think I am beginning to have an asthma attack. #Person2#: Would you like someone to walk you over to the Student Health Center? #Person1#: No, I think that I should just go home because I have some medicine there. #Person2#: Do you need a ride home? #Person1#: I live in the dorms across the street, so I'll be OK. #Person2#: OK, then, hope you feel better soon. Check your e-mail for missed assignments.",#Person1# wants to leave early because #Person1# has an asthma attack. #Person2# agrees and reminds #Person1# of checking the email for missed assignments.,103,23,0.2233
dialogsum,"#Person1#: I Don't know how they do it! Our competitors have undercut us by 10 % percent on the price of our latest model. There is no way will be able to compete against that. We're barely breaking even with the present prices. #Person2#: These price wars are disastrous for our bottom line. If they're charging 10 % less than we are, we've got to find a way to lower our price while keeping our profit. #Person1#: Profits are almost nonexistent now, we can't beat their price. How do they keep their price so low? #Person2#: We can try to lower our cost of production then. We need a price that we can compete with, something comparable with the competition. #Person1#: You really think we can make it? I don't have much faith in our ability to lower the price again. We're no match for them, the competition will beat us hands down.","#Person1# and #Person2# are worried that they cannot compete against their competitors in terms of price. #Person2# suggests lowering their cost of production, but #Person1# thinks it's hard.",153,28,0.183
dialogsum,"#Person1#: Have you gone to school today? #Person2#: I went to school today. Did you go to school? #Person1#: I couldn't go to school today, I was sick. #Person2#: That's horrible. I'd be happy to give you the assignments from English class. #Person1#: Thank you very much, that's kind of you. #Person2#: Don't mention it. #Person1#: When you miss a day of school, I'll be happy to give you the English assignments. #Person2#: That is greatly appreciated and I hope you feel well enough to go to school tomorrow.",#Person1# couldn't go to school for the illness. #Person2#'ll give #Person1# the assignments from English classes.,89,16,0.1798
dialogsum,"#Person1#: Have you ever taken history 231? #Person2#: Yeah, last term. #Person1#: Who was the professor? #Person2#: Professor Johnson. #Person1#: I have him this semester. What do you think of him? #Person2#: He's a terrible instructor and demands a lot. But fortunately, we can get high scores easily in his class. #Person1#: What did you end up getting? #Person2#: I got an A, but none of my test scores were that high. So I don't know how I got such a good score. #Person1#: Really? I was about to give it up. After hearing your experience, I think I will continue to stay in the class. #Person2#: You will get a better grade than your test scores. #Person1#: Thanks for the information. I feel relieved now.",#Person2# tells #Person1# Professor Johnson is a terrible instructor but students' final scores will be higher than expected. #Person1# feels relieved and decides to stay in the class.,126,28,0.2222
pubmed-summarization,"categorical variables . for all compliant patients , overall treatment time was calculated from the day of initiation of cancer - directed therapy to completion of treatment . further , to study the pattern of non - compliance , patients were divided into early non - compliance ( patients that were non - compliant during the investigation and staging work up period ) , mid - course non - compliance ( patients non - compliant after complete diagnostic work up and treatment decision , but before radiation delivery ) , and late non - compliance ( patients non - compliant during radiation delivery ) . in this cohort of 47 patients , treatment decision taken at the multi - disciplinary clinic was for radical treatment in 68% ( 32/47 patients ) , whereas the remaining 32% ( 15/47 patients ) were planned to receive palliative treatment . radical treatment included either radical radiation with or without chemotherapy in 55% ( 26/47 ) of the patients or surgery followed by postoperative radiotherapy in 13% ( 6/47 ) of the patients . in this retrospective analysis , patient and treatment characteristics the salient features were that majority ( 42/47 ) of the elderly hnscc presented in loco - regionally advanced stage ( iii iv ) , the most common site of malignancy was oropharynx ( 21/47 ) , followed by oral cavity ( 11/47 ) , larynx ( 9/47 ) , and hypopharynx ( 6/47 ) . with regard to age distribution , 72% ( 34/47 ) of the patients were between the age group of 6574 years , whereas ( 13/47 ) 28% were 75 or older . general condition was fair in most of the elderly patients ( 38/47 ) ; only ( 5/47 ) of the elderly patients were in good general condition , while the remaining ( 4/47 ) were in poor general condition . out of the 47 elderly patients , analysis of compliance to treatment decision revealed that 62% ( 29/47 ) of the elderly hnscc patients were compliant to cancer - directed therapy , whereas 38% ( 18/47 ) of the patients were not able to complete the stipulated treatment . for all compliant patients , overall treatment time was calculated from the day of","backgroundtreatment compliance of elderly patients to intensive multi - modality cancer therapy can be challenging and has not been adequately addressed in developing countries . the present study evaluated compliance of elderly head and neck carcinomas patients to cancer - directed therapy.methodsforty-seven elderly hnscc patients were evaluated in the present study . patients were assessed as per stage and site of disease , general condition , performance status , and any pre - existing co - morbidities . compliance was defined as patients who were able to complete cancer therapy as intended at primary clinic . non - compliance to therapy was stratified as early , mid- and late - course non - compliance . statistical analysis was done using stata 9.1 software , chi - square /",380,128,0.3368
dialogsum,#Person1#: I would like to order a suit made to my own measure. #Person2#: I share the same opinion. You are over-weight so it's hard for you to buy clothes. #Person1#: Maybe I should try to lose weight. #Person2#: Here is one tailor's shop. Why not order one here?,#Person1# would like to order a suit since #Person1# is overweight. #Person2# recommends a tailor shop.,49,16,0.3265
dialogsum,"#Person1#: Hello, I've got to get up early tomorrow, so please give me a wake-up call. #Person2#: Of course. We can give you a call anytime you like. #Person1#: Actually, I need two calls, one at 7 and the other at 7 fifteen. #Person2#: Your wish is our command. Expect a call at 7, and another one at 7 fifteen. #Person1#: Wait a minute! I don't like 7 fifteen, now that I think about it. Change it to 7 thirty. #Person2#: The second call is now changed to 7 thirty. Is there anything else we can help you with? #Person1#: Nothing that I can think of right now. If something comes up, though, I'll call you. #Person2#: We're here all night long if you need anything.","#Person1# is calling #Person2# to arrange wake-up calls for tomorrow, at 7 and 7:30, respectively.",126,15,0.119
dialogsum,"#Person1#: How long will it take us to drive to London? #Person2#: I think it's a distance of 180 kilometers from here to London, so it should be a two-hour drive on the motorway. #Person1#: That's unless there is a traffic jam. It could take three hours. #Person2#: You're right. We will be able to travel at high speeds at the beginning and end of the journey, because we will be in built-up area. #Person1#: So, shall we allow three hours to cover the distance? #Person2#: Ok. You haven't seen my company car, have you? #Person1#: No. let me take a look. . . It's longer than my car. #Person2#: I think it's over five meters long. I can't remember exactly. It has a maximum speed of over 200 kilometers an hour. #Person1#: Wow! That's fast! I don't think we will be traveling that fast on the motorway. #Person2#: We can't. if we went that fast, we would break the speed limit.","#Person1# discusses with #Person2# about how long it takes to drive to London, taking account of the distance, traffic jams, and speed.",162,22,0.1358
pubmed-summarization,"infection22 . if colony count of catheter were 5 times more than blood sample , blood stream infection were established720 . . statistical analysis was performed with independent sample t - test and chi - square tests . a hundred and fifty patients with end - stage renal disease were assessed for eligibility . the study was a prospective , randomized , controlled clinical trial ( iranian clinical registration number 138811182370n6 ) , and conducted at two tertiary - care urban medical center . patients with end - stage renal disease from december 2009 to march 2010 were included in the study . inclusion criteria included age more than 18 , being dialyzed with central tunneled catheter , med comp ( only if placed in the internal jugular vein ) , with a maximum time of one month post catheterization , dialysis 3 times a week and having accepted to participate in the study . exclusion criteria were allergy to cefotaxime , antibiotic treatment within 2 weeks prior to enrollment , patients requiring a surrogate decision maker , catheters with blood flow rates less than 300 ml / min , or requiring frequent thrombolytic solution dwells in the catheter lumen because of malfunction . at the beginning of the study 38 patients were eligible to participate in the study , but 30 of them were consented ( 20.6% ) . enrolled patients were randomly assigned by using a block computerized randomization protocol into two groups of 15 patients . in intervention group , we used cefotaxime , at a concentration of 10 mg / ml as the experimental antibiotic lock solution . solutions were prepared by dissolving sterile cefotaxime sodium powder in normal saline for injection to reach a concentration of 10 mg / ml for cefotaxime . then mixture of 1.5 cc cefotaxime ( 10 mg / ml ) and 1.5 cc heparin solution ( 5,000 u / ml ) ( ce / hs ) , was prepared in a syringe using aseptic precautions to fill 1.6 ml in the venous and 1.4 ml in the arterial lumen of the catheter at the end of each dialysis session ( exact volume of each venous and arterial port so that cefotaxime would not inter the blood stream , preventing its","background : chronic hemodialysis patients frequently require vascular access through central venous catheters ( cvcs ) . the most significant complication of these catheters is infection . this risk can be lowered by the use of an antibiotic - heparin lock . this study focuses on hemodialysis patients using tunneled - cuffed catheters ( tcc ) , to assess the rate of catheter - related infections ( cri ) in catheter - restricted filling with cefotaxime and heparin in end stage renal disease patients.methods:a double - blind randomized study was conducted to compare 5000 u / ml heparin plus10 mg / ml cefotaxime ( ce / hs ) as catheter - lock solutions , with heparin ( 5000 u / ml ) alone . a total of 30",380,128,0.3368
dialogsum,"#Person1#: Flora, when you were little, what did you like to do? #Person2#: When I was small and I was at junior high school, I used to like playing soccer with my friends, actually in Kenya. What's different from other countries is we used to make our own soccer ball to play. So it was very easy. #Person1#: Wow, how did you make the soccer balls? #Person2#: We used to collect like plastic and paper and bind them with string to make something round. So it was like...you didn't have to spend any money. #Person1#: Wow, that's ingenious! That's great! So were you a good soccer player? #Person2#: Not really. I used to like playing soccer, but I was not very good actually, to tell the truth. #Person1#: Yeah, like me. I wasn't a very good athlete. I mean, I like sports, but I was never very good. Uhm, so do you play soccer in Japan? #Person2#: Sometimes. Right now actually I'm not playing anymore, because the work in the bank takes up much of my time.",Flora and friends used to make their own soccer ball to play in Kenya but Flora couldn't play well. #Person1# likes sports but #Person1# isn't a good athlete. Flora doesn't play soccer now because of her busywork.,177,37,0.209
dialogsum,"#Person1#: Oh!!! I have a horrible toothache. #Person2#: You should go to the dentist. #Person1#: I hate dentists. #Person2#: Well, suffer then. If you have a toothache, you have to go to the dentist. #Person1#: It always hurts. I hate going. #Person2#: Stop being such a baby. If it really hurts that much, just let them knock you out. #Person1#: O. K ., O. K ., I ' ll go. #Person2#: Good. You feel better after you do.",#Person1# has a toothache. #Person2# persuades #Person1# into seeing a dentist.,78,11,0.141
dialogsum,"#Person1#: I don't know what to do. I can't seem to get anyone in the hospital to listen to my complaints and this outdated equipment is dangerous. Just look at it. #Person2#: Hmm, uh, are you trying to say that it presents a health hazard? #Person1#: Yes, I am. The head technician in the lab tried to persuade the hospital administration to replace it, but they are trying to cut costs. #Person2#: You are pregnant, aren't you? #Person1#: Yes, I am. I made an effort to get my supervisor to transfer me to another department, but he urged me not to complain too loudly. Because the administration is more likely to replace me than an X-ray equipment, I'm afraid to refuse to work. But I'm more afraid to expose my unborn child to the radiation. #Person2#: I see what you mean. Well, as your union representative, I have to warn you that it would take quite a while to force management to replace the old machines and attempt to get you transferred may or may not be successful. #Person1#: Oh, what am I supposed to do then? #Person2#: Workers have the legal right to refuse certain unsafe work assignments under two federal laws, the Occupation or Safety and Health Act and the National Labor Relations Act. But the requirements of either of the Acts may be difficult to meet. #Person1#: Do you think I have a good case? #Person2#: If you do lose your job, the union will fight to get it back for you along with back pay, your lost income. But you have to be prepared for a long wait, maybe after two years.",#Person1# complains that the hospital administration isn't willing to replace the dangerous outdated equipment and transfer #Person1# to another department. #Person2# tells #Person1# workers have legal rights to refuse unsafe works and the union will fight for her if she loses her job but she needs to prepare for a long wait.,276,52,0.1884
scientific_lay_summarisation-elife-norm,"Native PKD2-L1 channel subunits are present in primary cilia and other restricted cellular spaces. Here we investigate the mechanism for the channel' s unusual regulation by external calcium, and rationalize this behavior to its specialized function. We report that the human PKD2-L1 selectivity filter is partially selective to calcium ions (Ca2+) moving into the cell, but blocked by high internal Ca2+concentrations, a unique feature of this transient receptor potential (TRP) channel family member. Surprisingly, we find that the C-terminal EF-hands and coiled-coil domains do not contribute to PKD2-L1 Ca2+-induced potentiation and inactivation. We propose a model in which prolonged channel activity results in calcium accumulation, triggering outward-moving Ca2+ ions to block PKD2-L1 in a high-affinity interaction with the innermost acidic residue (D523) of the selectivity filter and subsequent long-term channel inactivation. This response rectifies Ca2+ flow, enabling Ca2+ to enter but not leave small compartments such as the cilium. Polycystic kidney disease proteins (PKDs), or polycystins (PC), are divided into two distinct gene families. The four PKD1 members (PKD1, PKD1-L1, PKD1-L2, PKD1-L3) are large proteins (~1700–4300 amino acids) with 11 putative transmembrane segments (TM) and a large autocleaved N-terminal extracellular domain. In contrast, the three PKD2 members are often included in the TRP ion channel family because they have 6 TM domains and a putative selectivity filter loop between TM5 and TM6 (Ramsey et al. , 2006). These include PKD2, (PC2, TRPP1; formerly TRPP2), PKD2-L1 (PC2-L1, TRPP2; formerly TRPP3) and PKD2-L2 (PC2-L2, TRPP3, formerly TRPP5) (Wu et al. , 2010). Members of the PKD1 and PKD2-subfamilies are often reported to associate in the plasma membrane, although the nature of these complexes is not understood. PKD1 + PKD2 were purported to form mechanosensitive ion channels in the primary cilia of kidney collecting duct epithelia (Nauli and Zhou, 2004; Nauli et al. , 2003), a hypothesis that has recently been challenged (DeCaen et al. , 2013; Delling et al. , 2016). In humans, autosomal dominant polycystic kidney disease (ADPKD) is associated with loss-of-function mutations in genes that encode for either PKD1 or PKD2 (Wu and Somlo, 2000). Complete loss of either Pkd1 or Pkd2 in mice results in embryonic lethality with defects in formation of the kidney, pancreas and heart (Boulter et al. , 2001; Lu et al. , 1997; Kim et","Most of our cells have a single tiny-hair like structure called a primary cilium that projects outwards from the cell surface. Many cilia contain an ion channel protein called PKD2-L1 that allows calcium ions to pass through the membrane that surrounds each cell. There are many different calcium channels and they are found in a variety of locations in cells to control the levels of calcium ions within various cell compartments. Channels on the cell surface allow calcium ions from the external environment to enter a compartment called the cytoplasm. Under normal conditions, calcium ions always flow into cells because they are much more abundant outside the cell than inside. Despite the absence of a membrane barrier between cilia and cytoplasm, calcium ions are maintained at a higher",380,128,0.3368
pubmed-summarization,"we make observations and based upon these observations we make empirical predictions . in the engineering sciences this is often be reduced to formulae and mathematical modelling which can be used predictively to design newer and better engineered products however orthodox medicine has been struggling to develop such methodology . despite the huge amounts of investment made in the life sciences systems biologists compile models of organs e.g. of the heart and other organs , in their efforts to understand the complexity of organ function and of associated cellular and molecular biologies . it is the equivalent of knowing the most intricate details of a computer - the hardware - yet not having the software to make it work . moreover , if there is no understanding of the mechanisms which the body uses to regulate its function and to recover from dysfunction or infection how can it be possible to assess whether a patient 's recovery is due to a medicine , medical procedure , or to the natural processes of recovery ? modern medicine evolved from the growth of the chemical industry and the massive increase of chemical research which yielded chemicals of ever greater complexity and biological significance . aspirin and paracetamol were developed which reduce the temperature of a fever and reduce the severity of headaches . such chemical discoveries were followed by drugs which reduce the symptoms of almost all conceivable diseases , and upon which huge swathes of the population are increasingly dependent , yet the burden of healthcare on society continues to increase . the cost of treating disease has grown by more than ten times since the mid-1970 's . this leads us to question basic assumptions upon which modern biomedicine is based e.g. : how accurate are biomarker techniques?it is increasingly understood that many medical conditions are polygenic and multi - systemic . the degree of coiling or uncoiling of proteins is associated with the onset of diabetes , cystic fibrosis , alzheimer 's disease , etc . accordingly , the measurement of the level of a single protein / biomarker may be a flawed concept.how accurate is a doctor 's diagnosis?the ability of the gp to provide an accurate diagnosis is questionable . many diseases are poorly defined and are","the cost of diagnosing and treating disease continues to rise inexorably . almost every new test adds to the complexity and cost of healthcare . there is a need for better and less expensive screening , diagnostic and scanning techniques . medical scanning technologies are based upon the body 's response to an external stimulus e.g. heat , ultrasound , x - rays , magnetic resonance , etc . biomarker and histopathology tests have inherent limitations because diseases are often polygenic and/or influence the function of multiple physiological systems . the results are compared with expected norms . this makes it difficult to diagnose the onset of disease . such techniques measure only what the clinician wants or expects to see . a technique which can provide more",380,128,0.3368
dialogsum,"#Person1#: Hey, Dave. Can we talk for a minute? #Person2#: Sure about what? I'm kind of busy, but yeah ... #Person1#: Well, ....um, well, I'm not sure what to say, but um ... #Person2#: Come on. come on. #Person1#: Well, ... #Person2#: What is it? I've never known my sister to be at a loss for words. #Person1#: Well, you know Dave. I've got to be honest. I'm getting really, really concerned about your drinking. #Person2#: What are you talking about? #Person1#: Well, uh, it's ... #Person2#: Can't a person just have a few drinks without people getting on their case? I mean, first, Dad, then you! #Person1#: Dave, Dave. No seriously. Listen, Dave. You're my brother. I love you, but you've had two DUIs, you lost your last job because you showed up drunk, your girlfriend's going to dump you because you're drinking too much. Dave. #Person2#: You don't understand. I have it under control. #Person1#: Dave, you don't. #Person2#: That was the old me. #Person1#: Dave. You got your last DUI three weeks ago. You can't keep doing this. Dave, you're going to kill someone. #Person2#: I thought ... #Person1#: You might kill yourself. #Person2#: I thought siblings there, were there to support each other, and that's not what you're doing right now. #Person1#: Dave. I love you, and I'm trying to help you. I really care about you. And these friends that you hang out with ... they're not friends. A friend is a person who is honest and frank with you, not these so-called buddies you've got that encourage you to go and buy booze for any old party. #Person2#: You just know them like I don't. I mean ... #Person1#: I know them well enough. Come on. Wake up. These guys are dragging you down. #Person2#: I've had enough. #Person1#: No, no. Listen. The truth hurts; it stings. Listen. I know. I've seen what's happening to you, and look, there's ... #Person2#: You don't understand. #Person1#: You know what? AA. Alcoholics Anonymous. You can go there and you can meet with other people, and they can help you be sober. #Person2#: That's for people who have problems. #Person1#: You've got problems, Dave. AA. There's no membership fees, anyone can attend, the meetings are very confidential.","#Person1# tries to persuade Dave not to drink with his friends anymore and to go to Alcoholics Anonymous because #Person1#, as Dave's sister, is worried about him after he had two DUIs and lost his last job and his girlfriend. Dave refuses #Person1#'s suggestions and doesn't want to talk about it anymore.",380,52,0.1368
scientific_lay_summarisation-elife-norm,"Host antiviral proteins engage in evolutionary arms races with viruses, in which both sides rapidly evolve at interaction interfaces to gain or evade immune defense. For example, primate TRIM5α uses its rapidly evolving ‘v1’ loop to bind retroviral capsids, and single mutations in this loop can dramatically improve retroviral restriction. However, it is unknown whether such gains of viral restriction are rare, or if they incur loss of pre-existing function against other viruses. Using deep mutational scanning, we comprehensively measured how single mutations in the TRIM5α v1 loop affect restriction of divergent retroviruses. Unexpectedly, we found that the majority of mutations increase weak antiviral function. Moreover, most random mutations do not disrupt potent viral restriction, even when it is newly acquired via a single adaptive substitution. Our results indicate that TRIM5α’s adaptive landscape is remarkably broad and mutationally resilient, maximizing its chances of success in evolutionary arms races with retroviruses. Mammalian genomes combat the persistent threat of viruses by encoding a battery of cell-intrinsic antiviral proteins, termed restriction factors, that recognize and inhibit viral replication within host cells. The potency of restriction factors places selective pressure on viruses to evade recognition in order to complete replication (Duggal and Emerman, 2012). In turn, viral escape spurs adaptation of restriction factors, by selecting for variants that re-establish viral recognition and thereby restriction (McCarthy et al. , 2015). Mutual antagonism between viruses and their hosts thus drives cycles of recurrent adaptation, in prey-predator-like genetic arms races (Van Valen, 1973). These arms races result in the rapid evolution of restriction factors, which accumulate amino acid mutations at their virus-binding interfaces at a higher than expected rate (Daugherty and Malik, 2012). Numerous restriction factors, including TRIM5α (Sawyer et al. , 2005), APOBEC3G (Sawyer et al. , 2004), and MxA (Mitchell et al. , 2012), evolve rapidly as a result of arms races with target viruses. The resulting divergence between restriction factor orthologs can result in cross-species barriers to viral infection (Compton and Emerman, 2013; Kirmaier et al. , 2010). Such barriers led to the initial identification of TRIM5α, during a screen for proteins that prevented HIV-1 (human immunodeficiency virus) from efficiently replicating in rhesus macaque cells (Stremlau et al. , 2004). Rhesus TRIM5α could potently restrict HIV-1, whereas the virus almost completely escapes TRIM5α-mediated inhibition","The evolutionary battle between viruses and the immune system is essentially a high-stakes arms race. The immune system makes antiviral proteins, called restriction factors, which can stop the virus from replicating. In response, viruses evolve to evade the effects of restriction factors. To counter this, restriction factors evolve too, and the cycle continues. The challenge for the immune system is that mammals do not evolve as fast as viruses. How then, in the face of this disadvantage, can the immune system hope to keep pace with viral evolution? One human antiviral protein that seems to have struggled to keep up is TRIM5α. In rhesus macaques, it is very effective at stopping the replication of HIV-1 and related viruses. But in humans, it is not effective at all. But",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Trisomy, the presence of a third copy of one chromosome, is deleterious and results in inviable or defective progeny if passed through the germ line. Random segregation of an extra chromosome is predicted to result in a high frequency of trisomic offspring from a trisomic parent. Caenorhabditis elegans with trisomy of the X chromosome, however, have far fewer trisomic offspring than expected. We found that the extra X chromosome was preferentially eliminated during anaphase I of female meiosis. We utilized a mutant with a specific defect in pairing of the X chromosome as a model to investigate the apparent bias against univalent inheritance. First, univalents lagged during anaphase I and their movement was biased toward the cortex and future polar body. Second, late-lagging univalents were frequently captured by the ingressing polar body contractile ring. The asymmetry of female meiosis can thus partially correct pre-existing trisomy. During female meiosis, a G2 oocyte containing four genome copies undergoes two asymmetric cell divisions depositing one genome in a single haploid egg, while the other three genomes are segregated into polar bodies. These divisions are mediated by meiotic spindles that are asymmetrically positioned against the oocyte cortex with the pole-to-pole axis of the spindle perpendicular to the cortex. Both the inheritance of only one of the four genome copies and the distinct perpendicular positioning of the meiotic spindle are remarkably conserved among animal phyla suggesting a selective advantage (Maro and Verlhac, 2002; Fabritius et al. , 2011a; Maddox et al. , 2012). Several advantages of asymmetric meiosis have been suggested previously, yet none are applicable to all animals. Asymmetric meiotic spindle positioning maximizes the volume of a single egg, helps prevent interference with the meiotic spindle by the sperm aster (McNally et al. , 2012), and preserves predetermined embryonic polarity gradients. Here, we suggest a previously unrecognized advantage of asymmetric meiosis, the ability of meiotic spindles to correct trisomy by preferentially depositing the extra chromosome copy into a polar body. Accurate segregation of homologous chromosomes to opposite spindle poles depends on a physical attachment, or chiasma, between homologous chromosomes. A chiasma consists of a crossover, which holds the two homologous chromosomes together in a bivalent so that kinetochores can be properly oriented toward opposite poles (Moore and Orr-Weaver, 1998; Miller et al. , 2013).","Inside cells, DNA is found packaged into structures called chromosomes. Most human and animal cells contain two sets of chromosomes, one inherited from each parent. Chromosomes from one set pair up with the equivalent chromosome from the other set. However, egg and sperm cells only contain one copy of each chromosome, so that when the egg is fertilized, the resulting cell again has two sets of chromosomes. If there are either more or fewer than two copies of a chromosome in the fertilized cell, this can cause birth defects and conditions such as Down syndrome. An egg cell develops from a cell called an oocyte via a process called meiosis. The oocyte first duplicates its DNA so that it contains four copies of each chromosome. The oocyte then",380,128,0.3368
pubmed-summarization,"the wnt signaling pathway is known to play a key role in regulating cellular differentiation , proliferation , survival , and apoptosis . wnt proteins are a highly conserved family of secreted lipid - modified cysteine - rich glycoproteins that activate signaling cascades inside the cell by binding to a member of the frizzled ( fz ) family of g - protein - coupled receptors on the extracellular matrix . there are 19 members of vertebrate wnts , which can be grouped into two main classes based on their ability to stabilize cytosolic -catenin : canonical and noncanonical pathway . recent works have also shown that certain wnt ligands , like wnt5a , are able to activate more than only one wnt signaling pathway , so the strictly binary classification is becoming more and more outdated . malfunctioning of wnt signaling pathway is related to several diseases like osteoporosis , crohn 's disease , alzheimer 's disease , schizophrenia , and especially cancer . the ligand wnt3a belongs to -catenin dependent ( canonical ) wnt signaling , which binds to frizzled transmembrane receptors . subsequently the low - density lipoprotein receptor - related protein 5 ( lrp5 ) or lrp6 receptor complex activates cytoplasmic disheveled proteins , which trigger the inhibition of glycogen synthase kinase 3 ( gsk-3 ) . the protooncoprotein -catenin accumulates in the cytoplasm as a consequence of the disassembly of the destruction complex that is formed by adenomatosis polyposis coli ( apc ) , axin , and gsk-3. thus , -catenin can be translocated into the nucleus where it activates the transcription of target genes mediated by t - cell specific transcription factor ( tcf)/lymphoid - enhancing factor ( lef ) . these genes are responsible to regulate essential physiological processes in embryonic and adult development such as cell proliferation , differentiation , morphogenesis , and cell adhesion . with the indication of proliferation , there is a complex interplay between the canonical wnt signaling and the cell cycle . the wnt/-catenin signaling pathway is significant in stimulating progression of g1-phase by inhibiting gsk-3 , which regulates cell cycle effectors and growth regulators . one direct target gene of the wnt/-catenin signaling pathway is the protooncogene myc , which was identified as a wnt target in","the wnt signaling pathway has been associated with many essential cell processes . this study aims to examine the effects of wnt signaling on proliferation of cultured hek293 t cells . cells were incubated with wnt3a , and the activation of the wnt pathway was followed by analysis of the level of the -catenin protein and of the expression levels of the target genes myc and ccnd1 . the level of -catenin protein increased up to fourfold . while the mrna levels of c - myc and cyclin d1 increased slightly , the protein levels increased up to a factor of 1.5 . remarkably , mtt and brdu assays showed different results when measuring the proliferation rate of wnt3a stimulated hek293 t cells . in the brdu assays",380,128,0.3368
dialogsum,"#Person1#: Hi Bob, how's business? #Person2#: Just okay. #Person1#: Okay, enough small talk. Let's get down to business. #Person2#: Good idea. #Person1#: Since we're good friends, you don't have to pay me. #Person2#: No, I can't accept it. Business is business.",#Person1# gets down to business with #Person2#.,41,7,0.1707
dialogsum,"#Person1#: I have to get to Chicago by tomorrow and you're telling me that there are no flights? #Person2#: I'm very sorry, sir. I could put you on a waiting list, but you would be wise to check out other means of travel. #Person1#: You mean like a bus? Have you ever traveled for ten hours on a bus before? #Person2#: I have not sir. But I do have a number for a very comfortable bus that goes to Chicago every hour from here. #Person1#: Alright, give me the number. But put me on that waiting list as well. #Person2#: Here is the number, and your name is on the waiting list. #Person1#: How many people are on the waiting list right now? #Person2#: Right now I show that there are 176 people on the list. And you are number 176.","#Person2# tells #Person1# there're no flights to Chicago. #Person2# advises #Person1# to be put on the waiting list, or travel by bus.",141,22,0.156
dialogsum,"#Person1#: Hello, fire service. #Person2#: Oh, I'm ringing because I think there's a fire in the house opposite. Smoke is coming out of the upstairs windows. #Person1#: Can you give me your name and address and telephone number, please? #Person2#: Yes, Hank Cousins, 17 Mallett Street, Alford. #Person1#: I'm sorry. Can you spell Mallett, please? #Person2#: Yes. M-A-double L-E-double T. The telephone number is 6943168. The fire's in number 18 just across the road. #Person1#: Is anyone in the house? #Person2#: No they've gone on holiday. They went to the Mediterranean last Saturday, for two weeks. #Person1#: All right, we'll get there immediately. #Person2#: What shall I do? Shall I warn the neighbours? #Person1#: Yes, you'd better tell the people living next door, at number 16 and number 20. But don't go into the house.",Hank Cousins calls #Person1# because he thinks there's a fire in the house opposite. #Person2# asks him to warn the people living next door.,135,24,0.1778
dialogsum,"#Person1#: This week's program Up Your Street takes you to Harrogate, a small town in Yorkshire. Harrogate became a fashionable resort during Victorian times, when people came to take a bath in the mineral waters. Today, few people come to visit the town for its mineral waters. Instead, Harrogate has become a popular town for people to retire to. Its clean air, attractive parks, and the absence of any industry, make this an ideal spot for people looking for a quiet life. Now, to tell us more about Harrogate, I have with me Tom Percival, President of the Chamber of Commerce. Tom, one of the things visitor notices about Harrogate is the large area of open park land right down into the middle of the town. Can you tell us more about it? #Person2#: Yes, certainly. The area is called the Stray. #Person1#: Why the Stray? #Person2#: It's called that because in the old days, people let their cattle stray on the area, which was common land. #Person1#: Oh, I see. #Person2#: Then, we've changes in farming and in land ownership. The Stray became part of the land owned by Harrogate. #Person1#: And is it protected? #Person2#: Oh, yes, indeed. As a special law, no one can build anything on the stray. It's protected forever. #Person1#: So it will always be park land? #Person2#: That's right. As you can see, some of the Stray is used for sports fields. #Person1#: I believe it looks lovely in the spring. #Person2#: Yes, it does. There're spring flowers on the old trees, and people visit the town just to see the flowers.",#Person1# introduces a small town Harrogate. People come for its mineral waters in the past and now this town becomes a place for people to retire to. Then #Person1# invites Tom to introduce a large area of open parkland called the Stray in Harrogate.,269,44,0.1636
pubmed-summarization,"ureteropelvic junction ( upj ) obstruction has been classically treated through the standard open approach with outstanding results . since anderson - hynes ( ah ) reported the first dismembered pyeloplasty , a great number of authors have published excellent results , with overall success rates of 90 - 100% . their technique respected the basic principles of the open classical approach while providing less morbidity and faster recovery . since then , transperitoneal and retroperitoneal approaches have been described and advocated by several authors , with excellent results . in order to ease laparoscopic repair and decrease surgical time , many alternative time saving maneuvers and even robot assistance have been developed . these alternative techniques helped in bringing the operative time close to that of open surgery and made laparoscopic pyeloplasty a more desirable alternative . we evaluated the transmesocolic technique as a way to reduce operative time and facilitate repair by avoiding colon displacement and compare it with conventional retrocolic laparoscopic pyeloplasty ( rlp ) in cases of left sided ureteropelvic junction obstruction ( upjo ) . between september 2006 and may 2012 , a total 130 laparoscopic pyeloplasties were performed . only left sided pelvi - ureteric junction obstruction were enrolled for study . a total of 38 transmesocolic laparoscopic pyeloplasty ( tmp ) and 41 left sided rlp were performed . the data were recorded in a prospective manner that included age , pelvic volume , presence of stone [ 1a and b ] , aberrant vessel , [ 1b ] operative time , analgesics requirement ( paracetamol 15 mg / kg body weight for children more than 10 kg of weight and 7.5 mg / kg body weight for children less than 10 kg of weight ) , time to accept oral feeds , drain removal . a dismembered ah pyeloplasty was performed in all patients . double j stent ( djs ) was placed in 73.68% of patients in tmp group while 82.92% patients in rlp group . based on pelvic volume , patients were divided into three groups : group 1 : less than 50 ml ( 16 patients in rlp and 24 patients in tmp)group ii : 50 - 100 ml ( 14 patients in rlp and 10 patients in tmp)group","objective : this prospective randomized study was designed to evaluate the feasibility and outcome of transmesocolic laparoscopic pyeloplasty ( tmp ) and compare it with retrocolic laparoscopic pyeloplasty ( rlp ) in pediatric and adolescent patients.materials and methods : between september 2006 to may 2012 , data of pediatric and adolescent patients undergoing laparoscopic pyeloplasty were recorded in a prospective manner . data included age , pelvic volume , presence of stones , aberrant vessels , operative time , analgesics requirement and time to accept oral feeds and drain removal . patients with left side pelviureteric junction obstruction with any size of pelvic volume , with or without renal stones and aberrant vessels were included in the study . patients were assigned into two groups by simple randomization",380,128,0.3368
pubmed-summarization,"covering almost the entire front teeth . her past medical history revealed that the patient was hypertensive for last 2 years and was under medication ( amlodipine 10 mg , once daily ) . the lesion was asymptomatic , but the patient complained it to be severely interfering with mastication , speech , and oral hygiene practice resulting in functional and aesthetic problem . on intraoral examination , the lesion was a well - circumscribed exophytic sessile spherical mass of 1.5 inches diameter with color same as that of the surrounding oral mucosa with the scattered erythema [ ] . the lesion was extended from distal surface of upper right canine to distal surface of upper left central incisor crossing the midline . poor oral hygiene status of the patient was assessed from the presence of local irritating factors contributing to the mild inflammatory component of the gingival enlargement . pre - operative clinical presentation of amlodipine induced plasma cell granuloma of gingiva complete hemogram showed all blood counts to be within the normal limits . intraoral periapical radiograph and orthopantomogram in the region of aigo showed generalized advanced horizontal bone loss around all teeth resulting in pathologic migration the lesion was biopsied under local anesthesia . the area was sutured and the specimen submitted for histopathological examination . as the extraction of all the remaining teeth with poor prognosis was planned substitution of amlodipine was not considered . planned extraction of remaining mandibular teeth was carried out in subsequent appointment . following healing period of 2 months complete denture prosthesis histopathological examination using hematoxylin and eosin stain , revealed proliferative parakeratinized stratified squamous epithelium , connective tissue with sheets of plasma cells intermixed with scattered small lymphocytes . high power microscopy : h and e staining shows sheets of plasma cells intermixed with scattered small lymphocytes immunohistochemical study of the biopsy material revealed the polyclonal plasma cell infiltrate uniformly positive for cd138 , a marker for plasmacytoid cells [ ] and kappa light chain [ ] and weak expression was noted for the lambda light chain . absence of findings from common tetrad of multiple myeloma ( crab : c = calcium ( elevated ) , r = renal failure , a = anemia , b = bone lesions","drug - induced gingival overgrowth ( digo ) can be a serious concern for both patients and clinicians . digo is a well - documented side - effect of some pharmacologic agents , including , but not limited to , calcium channel blockers , phenytoin , and cyclosporine . plasma cell granulomas ( pseudotumors ) are exceedingly rare , non - neoplastic , reactive tumor - like proliferation , primarily composed of plasma cells that manifest primarily in the lungs , but may occur in various anatomic locations . intraoral plasma cell granulomas involving the lip , oral mucosa , tongue , and gingiva have been reported in the past . this is the first case report of amlodipine induced plasma cell granuloma of the gingiva in the",380,128,0.3368
dialogsum,#Person1#: I want to get a snack at the cafeteria. #Person2#: What are you going to buy? #Person1#: I may just get some chips. #Person2#: I'm probably going to buy something too. #Person1#: What do you want to get? #Person2#: I want some sort of candy. #Person1#: What kind do you want? #Person2#: I want some chocolate. #Person1#: What kind of chocolate? #Person2#: I'm going to get a Snickers or a Kit Kat. #Person1#: I don't think they sell Kit Kats. #Person2#: I'll just get a Snickers then.,#Person1# wants to get a snack at the cafeteria. #Person2# also wants to go and they discuss what to buy.,88,20,0.2273
scientific_lay_summarisation-elife-norm,"A key challenge in antibiotic stewardship is figuring out how to use antibiotics therapeutically without promoting the evolution of antibiotic resistance. Here, we demonstrate proof of concept for an adjunctive therapy that allows intravenous antibiotic treatment without driving the evolution and onward transmission of resistance. We repurposed the FDA-approved bile acid sequestrant cholestyramine, which we show binds the antibiotic daptomycin, as an ‘anti-antibiotic’ to disable systemically-administered daptomycin reaching the gut. We hypothesized that adjunctive cholestyramine could enable therapeutic daptomycin treatment in the bloodstream, while preventing transmissible resistance emergence in opportunistic pathogens colonizing the gastrointestinal tract. We tested this idea in a mouse model of Enterococcus faecium gastrointestinal tract colonization. In mice treated with daptomycin, adjunctive cholestyramine therapy reduced the fecal shedding of daptomycin-resistant E. faecium by up to 80-fold. These results provide proof of concept for an approach that could reduce the spread of antibiotic resistance for important hospital pathogens. Vancomycin-resistant Enterococcus faecium (VR E. faecium) is an important cause of antibiotic-resistant infections in healthcare settings (Arias and Murray, 2012; García-Solache and Rice, 2019; O' Driscoll and Crank, 2015). The antibiotic daptomycin is one of the few remaining first-line therapies for VRE infection (O' Driscoll and Crank, 2015), but daptomycin-resistance is spreading in VRE populations (Judge et al. , 2012; Kamboj et al. , 2011; Kinnear et al. , 2019; Woods et al. , 2018). Therapeutic daptomycin use is thought to be a key driver of resistance (Kinnear et al. , 2020; Woods et al. , 2018). Managing the evolution of daptomycin-resistance in healthcare settings is crucial to future control of VRE infections. E. faecium is an opportunistic pathogen that colonizes the human GI tract asymptomatically, spreads via fecal-oral transmission, and causes symptomatic infections when introduced to sites like the bloodstream or the urinary tract (Arias and Murray, 2012). E. faecium colonizing the gut may be exposed to daptomycin during therapeutic use, potentially contributing to the transmission of daptomycin-resistant E. faecium. Daptomycin is administered intravenously to treat infections caused by pathogens including VRE and Staphylococcus aureus. Daptomycin is primarily eliminated by the kidneys, but 5–10% of the dose enters the intestines through biliary excretion (Woodworth et al. , 1992). We hypothesize that this therapeutically unnecessary intestinal daptomycin exposure could drive resistance evolution in E. faecium colonizing the gut. Increased resistance","Antibiotics are essential for treating infections. But their use can inadvertently lead to the emergence of antibiotic-resistant bacteria that do not respond to antibiotic drugs, making infections with these bacteria difficult or impossible to treat. Finding ways to prevent antibiotic resistance is critical to preserving the effectiveness of antibiotics. Many bacteria that cause infections in hospitals live in the intestines, where they are harmless. But these bacteria can cause life-threatening infections when they get into the bloodstream. When patients with bloodstream infections receive antibiotics, the bacteria in their intestines are also exposed to the drugs. This can kill off all antibiotic-susceptible bacteria, leaving behind only bacteria that have mutations that allow them to survive the drugs. These drug-resistant bacteria can then spread to other patients causing hard-to-treat infections.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"sensory epithelia of the inner ear in all vertebrates each hair cell is surrounded and separated from its neighbours by intervening supporting cells. Hair cells derive their name from the organised bundle of projections from the apical poles. They are mechanotransducers that convert motion into electrical signals. Supporting cells play a role in maintaining the physiological environment necessary for hair cell function and survival, and also repair the lesions in the epithelium when hair cells die. In non-mammalian vertebrates, hair cells lost from the auditory or vestibular sensory epithelia are replaced spontaneously by new ones (Collado et al. , 2008; Rubel et al. , 2013). These nascent hair cells are derived from supporting cells. Initially, new hair cells arise from direct, non-mitotic transdifferentiation (phenotypic conversion) of supporting cells into hair cells (Cafaro et al. , 2007; Taylor and Forge, 2005). Other supporting cells re-enter the cell cycle, the daughter cells giving rise to hair and supporting cells (Burns and Stone, 2017; Cafaro et al. , 2007; Collado et al. , 2008; Rubel et al. , 2013). There is no regeneration in the adult mammalian auditory system. However, there is a limited capacity to regenerate hair cells in vivo in the mammalian vestibular system (Forge et al. , 1993; 1998; Lopez et al. , 1997; Kawamoto et al. , 2009). These hair cells arise by direct phenotypic conversion of supporting cells (Li and Forge, 1997; Lin et al. , 2011). We recently reported the presence of cells bearing immature hair bundles in the vestibular system of elderly people (Taylor et al. , 2015). This suggests that a capacity to regenerate hair cells may exist at a very low level throughout life in humans. During development, supporting cells and hair cells are derived from the same homogeneous population of precursor cells following a terminal mitotic event (Kelley, 2006). The mosaic patterning of hair and supporting cells develops by lateral inhibition mediated by the Notch signalling pathway (Kiernan, 2013). In cells differentiating as hair cells the basic helix-loop-helix transcription factor Atonal homolog 1 (Atoh1) is transiently expressed and has been shown to be necessary for sensory precursors to differentiate into hair cells (Bermingham et al. , 1999; Kelley, 2006; Woods et al. , 2004). The nascent hair cells express the Notch ligand Delta1","The inner ear contains our balance system (the vestibular system) and our hearing organ (the cochlea). Their sensing units, the hair cells, detect movement or sound waves. A loss of hair cells is a major cause of inner ear disorders, such as dizziness, imbalance and deafness. When hair cells die, supporting cells that surround them close the ‘wound’ to repair the tissue. In fish, amphibians, reptiles and birds, the supporting cells can replace lost hair cells, but in mammals – including humans – hair cells are unable to regenerate in the cochlea, so hearing loss is permanent. However, previous research has shown that in certain mammals, spontaneous replacement of lost hair cells in the vestibular system can occur, but not enough to lead to a full recovery. Scientists",380,128,0.3368
dialogsum,"#Person1#: How's your job search going? #Person2#: I only started looking for a job a few days ago. #Person1#: have you finished compiling your resume? #Person2#: yes, I was precise with every word in my resume. Do you think it's good or not? #Person1#: that's good. Don't forget to design the format. An attractive format is as important as the content. #Person2#: absolutely, I've highlighted all my strengths and the resume is clear and easy to read. #Person1#: good. How about your cover letter? #Person2#: a cover letter? I've never thought about that. Won't a CV do for my job application? #Person1#: no, a CV is not enough. You should also attach it with a cover letter. Don't overlook it. You're faced with fierce competition in the job market. If your cover letter cannot stand out in the pile of #Person2#: sounds reasonable. Even if I'm the right one for the job, many people are applying for the same vacancy at the same time, so I should try my best to catch the Human Resources manager's attention. #Person1#: yes, you're right. All your preparation efforts are to help you land a job interview. #Person2#: got it. I'll start right now.",#Person1# has finished compiling the resume with a clear format. #Person2# advises #Person1# to attach it with a cover letter. #Person1# thinks it is a good idea to catch the Human Resources manager's attention.,200,34,0.17
dialogsum,"#Person1#: Good morning, Miss Smith. I'm sorry to trouble you. #Person2#: Good morning, not at all. Please be seated. What can I do for you? #Person1#: It's about my son. #Person2#: He isn't in trouble. I hope he's doing well in all his lessons. He'll do well in the exams. #Person1#: Except in Chinese. I'm afraid. He says that he is a little weak in Chinese. #Person2#: Is he? I'm sorry to hear that. #Person1#: That's why I've come to see you. I'm worried about his Chinese. He may fall behind the others when he comes back. #Person2#: What do you mean? #Person1#: We'll go back to London for a holiday for two months. We haven't been back for three years. #Person2#: I see. I think that maybe his Chinese teacher can give him some homework to do during the holiday. He won't fall too far behind the others when he comes back.",#Person1#'s worried that #Person1#'s son might fall behind in Chinese because they'll go to London for two months. Miss Smith suggests that more Chinese homework may be helpful.,153,28,0.183
dialogsum,"#Person1#: I'd like to order dinner. #Person2#: What would you like? #Person1#: I'd like to order a bottle of champagne, lobster tail, and filet mignon, medium rare. #Person2#: I'm sorry. We're currently out of filet mignon. May I suggest the porterhouse instead? #Person1#: I'd prefer the filet, but the porterhouse will do. #Person2#: And may I suggest chocolate-covered strawberries with the champagne? #Person1#: Normally, I would take you up on that suggestion, but just the champagne will do for tonight. #Person2#: Okay, no strawberries. Room service will be charged to your amenities account. Is that all right? #Person1#: That's fine. #Person2#: It will be up shortly. Enjoy your food, sir.","Since the filet mignon #Person1# orders isn't available, #Person2# suggests the porterhouse and chocolate-covered strawberries with the champagne. #Person1#'ll go for the porterhouse and prefers just the champagne.",110,28,0.2545
dialogsum,"#Person1#: How's it going? #Person2#: I'm in a good mood today, actually. How about you? #Person1#: To be honest, I'm a bit fed up. #Person2#: What's wrong? #Person1#: There's a girl in my company that I really like but I always get shy when she is around. #Person2#: I see! Do you want to ask her out? #Person1#: Sure, but how? #Person2#: You can ask her out for a drink after work. #Person1#: But for what reasons? She doesn't even know who I am. #Person2#: Then you've got a lot of homework to do. You need to get her notice first. #Person1#: Easier said than done. #Person2#: You can start by meeting her at the bus stop and saying hello to her. #Person1#: But I always get tongue-tied when I see her. #Person2#: That's something you need to overcome. Men should make the first move as most of the girls prefer being chased. #Person1#: I see. I'll try. #Person2#: Good luck.",#Person1#'s fed up because he gets shy whenever the girl he likes is around. #Person2# encourages #Person1# to ask her out for a drink. #Person1# will try.,161,27,0.1677
dialogsum,"#Person1#: Mom, I don't want to eat vegetables. Can I have dessert now? I love chocolate cake! #Person2#: You can have some fruit for dessert. If you eat an apple, I might let you have a small piece of chocolate cake.",#Person1# wants to have dessert. #Person2# gives a requirement.,41,9,0.2195
scientific_lay_summarisation-elife-norm,"be important for its role in trafficking (Misko et al. , 2010). Although loss of both Drp1 and MFN2 impair mitochondrial trafficking, a careful comparison of the phenotypes associated with loss of Drosophila Drp1, Mitofusin or Marf, would be useful as the suggested mechanisms by which they impair transport seem very different. In addition to their roles in fission and fusion, Drp1, Mfns and Opa1 have been implicated in a variety of other processes. For example, Drp1 has been shown to facilitate the induction of apoptosis (Frank et al. , 2001) whereas Opa1 was shown to affect the stability of cristae junction in inner mitochondrial membrane (Frezza et al. , 2006). Finally, Mfn2 also tethers mitochondria to the endoplasmic reticulum (ER) to mediate Ca2+ uptake (de Brito and Scorrano, 2008). However, the molecular mechanisms underlying these non-canonical functions are less well studied. In an unbiased screen designed to identify essential genes that affect neuronal function (Yamamoto et al. , 2014), we identified the first mutant allelic series of Marf in Drosophila. Here we exploit these mutants to determine how loss of Marf affects mitochondrial transport when compared to Drp1 loss. Surprisingly, we observe NMJ defects only in Marf mutants but not in Drp1 mutants. These defects are regulated non-cell autonomously by steroid-hormones produced in ring glands (RG), a major endocrine organ in insects. Through expression of human MFN1 or MFN2 in Marf mutant RG, we show that MFN1 and MFN2 have both distinct and complementary roles. Through a forward genetic screen on the Drosophila X-chromosome (Yamamoto et al. , 2014) we isolated seven independent lethal alleles of Marf that affect electroretinogram (ERG) recordings in homozygous mutant clones (1A, C, — 1). The on- and off-transients (1A, red arrows) of the ERG are a read-out of synaptic transmission between photoreceptors (PR) and postsynaptic cells, while the amplitude of the depolarization (1A, green bracket) is a measure of the function of the phototransduction cascade (Wang and Montell, 2007). The Marf mutations vary in strength (1A, E and — 1B), providing an allelic series. ERG recordings in homozygous mutant eye clones reveal a reduction in on- and off-transients as well as loss of amplitude in one day old flies (1A). The ERG recordings differ from Drp1 mutants that only exhibit a loss of","Mitochondria are the main source of energy for cells. These vital and highly dynamic organelles continually change shape by fusing with each other and splitting apart to create new mitochondria, repairing and replacing those damaged by cell stress. For nerve impulses to be transmitted across the gaps (called synapses) between nerve cells, mitochondria need to supply the very ends of the nerve fibers with energy. To do this, the mitochondria must be transported from the main body of the nerve cell to the tips of the nerve fibers. This may not happen if mitochondria are the wrong shape, size or damaged. While searching for genetic mutations that disrupt nerve function in the fruit fly Drosophila, Sandoval et al. spotted mutations in a gene called Marf. Further investigations revealed",380,128,0.3368
scientific_lay_summarisation-elife-norm,"which can interfere with reproducibility and exploratory data analysis. The creation of synthetic datasets can substantially overcome replicability issues, as this method creates a new dataset that mimics an original dataset by preserving its statistical properties and relationships between variables (Little, 1993; Reiter, 2005b; Reiter, 2005a; Reiter and Raghunathan, 2007; Rubin, 1993). Synthetic datasets also reduce disclosure risk to essentially zero, as no complete casewise record in the new dataset represents a real individual (Duncan and Elliot, 2011). Synthetic datasets also allow researchers to fit exploratory models in the synthetic datasets, which the data custodians can verify in the original data. Finally, synthetic datasets enable readers and reviewers to better understand the data, as they can recreate the reported analyses and explore data distributions, variance, outliers, and means. Synthetic datasets were originally developed for sharing sensitive population-level data (for a summary, see Bonnéry et al. , 2019). The use of synthetic data for sharing sensitive information is beginning to emerge in the biobehavioural sciences (e. g. , Arslan et al. , 2018; Newbury et al. , 2018); however, this approach is not widely known in the field. Given the benefits of synthetic data, the purpose of this article is to introduce this concept using examples and an accompanying R script. The R script and datasets to reproduce the analyses described in this paper are available online at https: //github. com/dsquintana/synthpop-primer (Quintana, 2019; copy archived at https: //github. com/elifesciences-publications/synthpop-primer). This website also includes a link to a RStudio Server instance of the primary analysis and results, which recreates the complete computational environment used for this manuscript (i. e. , the R version and R package versions used) and facilitates straightforward reproducibility of the analysis described in this article via any modern web browser. Van Cappellen et al. (2016) investigated the impact of oxytocin administration on self-reported spirituality and deposited the raw study data online (https: //osf. io/rk2x7/). In a between-participants design, volunteers were randomly assigned to self-administer an intranasal oxytocin (N = 41) or intranasal placebo spray (N = 42). Approximately forty minutes after receiving the nasal spray, participants were asked “Right now, would you say that spirituality is important in your life? ”. The reported outcome from an ANCOVA suggested that when accounting for religious affiliation, participants who self-administered the","It is becoming increasingly common for scientists to share their data with other researchers. This makes it possible to independently verify reported results, which increases trust in research. Sometimes it is not possible to share certain datasets because they include sensitive information about individuals. In psychology and medicine, scientists have tried to remove identifying information from datasets before sharing them by, for example, adding minor artificial errors. But, even when researchers take these steps, it may still be possible to identify individuals, and the introduction of artificial errors can make it harder to verify the original results. One potential alternative to sharing sensitive data is to create ‘synthetic datasets’. Synthetic datasets mimic original datasets by maintaining the statistical properties of the data but without matching the original recorded",380,128,0.3368
dialogsum,"#Person1#: Tom has grown six inches within a year. #Person2#: He has reached puberty. His mind and body both will change a lot. #Person1#: Yeah, do you see his Adam's apple? It becomes bigger. #Person2#: Time is flying. I still remember everything when he was a child.",#Person1# and #Person2# talk about Tom's change over time.,47,9,0.1915
dialogsum,"#Person1#: So you are to leave all of us. How can you do that? What shall we do without you? #Person2#: Don't worry. I'll be back in five or six days. #Person1#: What are you going to do there? #Person2#: Some people are in great need of help after the flood. Being a doctor, I have the responsibility to help those in trouble. #Person1#: That's true. But you often go to those dangerous places and we are all worried about your safety, mum. #Person2#: Don't be so troubled. I'm a doctor. I know how to care for myself. What worries me is your life and study at school. Are you used to the life in the school? #Person1#: Yes. But many classmates have their mothers or fathers pick them up after school. I have to go and come all by myself. #Person2#: I'm sorry, dear. I'll ask your father to be back when I'm away. Maybe he can manage a few days off from his manager. I must go right now. The bus is waiting out over there. Bye-bye.",#Person2#'ll help those people who suffered from the flood as a doctor. #Person1#'s worried about #Person2# and says other children have their parents pick them up. #Person1#'ll ask #Person2#'s dad to take some days off.,179,35,0.1955
dialogsum,"#Person1#: The children have been playing in the mountains for a long time. Why haven't they come back? I am really worried about them. #Person2#: Look at the sky. Black clouds are gathering and strong winds are blowing. It seems a heavy rain will fall soon. #Person1#: They haven't brought anything to protect themselves. They will be caught in the rain I think. #Person2#: Don't be worried too much about them. Anyhow, they're old enough now. They ought to be able to take care of themselves. #Person1#: I'm afraid they will catch a cold if they are caught in the rain. You see it's a little cold now. #Person2#: Shall we bring some umbrellas or raincoats for them? #Person1#: How can you find them since we don't know where they are? #Person2#: Well, we can only stay home and wait for them.",#Person1# is worried about the children who are playing in the mountains because it seems heavy rain will fall soon. #Person2# thinks they can take care of themselves.,142,28,0.1972
dialogsum,"#Person1#: Well, you know what, don't do it, 'cause the minute you do, they lose all respect for you. #Person2#: Well, it's not like that. We just e-mail, it's really nothing. On top of which I am definitely thinking about stopping because it's getting... #Person1#: Out of hand. #Person2#: Confusing. But not, because it's nothing. #Person1#: Where'd you meet him? #Person2#: Oh, listen, I can't even remember. Ok, on my birthday, I wandered into over 30 rooms, for a joke, sort of and he was there, and we started chatting... #Person1#: About what? #Person2#: Oh, books, and music, how much we both love New York. Harmless, harmless, meaningless. Bouquets of sharpened pencils. Oh. #Person1#: Excuse me? #Person2#: Forget it. We don't talk about anything personal, so I don't know his name or what he does or where he lives exactly. So it'll be really easy for me to stop seeing him, because I'm not...","#Person2# tells #Person1# that #Person2# just email with the man. Then #Person2# recalls the day they met. Because they chatted about nothing personal, #Person2# thinks it'll be easy to stop seeing him.",154,32,0.2078
dialogsum,"#Person1#: Where do you live, Kim? #Person2#: I live in an apartment downtown. #Person1#: Oh, that's convenient, but . . . how much crime is there? #Person2#: Not much. But there is a lot of traffic. I can't stand the noise sometimes! Where do you live? #Person1#: . I have a house in the suburbs. #Person2#: Oh, I bet it's really quiet. But is there much to do there? #Person1#: No, not much. In fact, nothing ever really happens. That's the trouble. #Person2#: Hey. Let's trade places one weekend! #Person1#: OK. Great idea!",Kim lives in an apartment downtown while #Person1# has a house in the suburbs. They decide to trade places one weekend.,93,21,0.2258
dialogsum,"#Person1#: Hi, Sarah. How's your speech for Professor Grey's class next Monday? #Person2#: Actually, I'm a bit worried. #Person1#: Why should you? What's going on? #Person2#: You know, what I chose to talk about is British history. #Person1#: Really? That is a big topic. #Person2#: Yes. There are so many things to cover. I just can't see how to do it in a 3 minute speech.",Sarah tells #Person1# that she's worried about her speech because she doesn't know how to cover so many things about British history in 3 minutes.,66,25,0.3788
scientific_lay_summarisation-elife-norm,"soil theory) (Paget, 1889; Ribatti et al. , 2006; Erler and Weaver, 2009; Comen, 2012). To create such a niche, tumor cells either directly alter the microenvironment, or instruct local or recruited stromal cells to do so. In the context of breast cancer, recent studies have shown that the cross-talk and interaction of the tumor cells with their surrounding microenvironment is necessary for tumor progression (Tlsty and Coussens, 2006; Polyak et al. , 2009; Dvorak et al. , 2011; Boudreau et al. , 2012; Conklin and Keely, 2012; Fordyce et al. , 2012). In addition, the nature of the tumor microenvironment or gene expression profile of the stromal cells has been used to define human breast cancer types (Bergamaschi et al. , 2008; Finak et al. , 2008; Conklin et al. , 2011). Recent studies have also demonstrated that treatment outcome depends on the tumor microenvironment (vascularization, oxygenation, recruited normal cells, etc; Chauhan et al. , 2011; Jacobetz et al. , 2013). The extracellular matrix (ECM) is the complex scaffold of proteins that provides the architectural support for cell and tissue organization (Hynes and Naba, 2012). Cells are in turn able to adhere to the extracellular matrix via different types of receptors including the integrins (Hynes, 2002; Geiger and Yamada, 2011). In addition to providing biophysical cues, the ECM provides biochemical signals that are major regulators of cell proliferation, survival, migration, and invasion. (Hynes, 2009). Pathologists have used excessive ECM deposition (desmoplasia) as a marker of tumors with poor prognosis long before the complexity of the ECM was even deciphered (Anastassiades and Pryce, 1974). Despite its great importance in physiological (development, aging) and pathological processes such as cancer, the extracellular matrix remains underexplored (Wilson, 2010). To define the composition of extracellular matrices of tissues and tumors, we have developed a proteomics-based method to enrich and identify ECM proteins and coupled it with a bioinformatic annotation of the ‘matrisome’ defined as the ensemble of ECM and ECM-associated proteins (Naba et al. , 2012). Using this approach, we characterized the extracellular matrices of normal murine tissues (e. g. , lung and colon) and demonstrated that each of these comprises over 100 proteins. In this study, we apply this proteomics approach to study the composition of the ECMs of poorly and highly metastatic","Metastasis is the process whereby tumor cells spread within the body and is the cause of most deaths from cancer. This complex process involves several steps: first the cancer cells invade the tissues that surround the tumor; second, the cancer cells enter the blood stream and travel throughout the body; and third, the cancer cells seed the growth of new tumors in distant organs. Within tissues, the extracellular matrix forms a complex scaffold of proteins that surrounds cells, to support and organize them: it also provides signals that control how much cells can multiply, how likely cells are to stick together or migrate, and even a cell’s chances of survival. Pathologists have used an accumulation of extracellular matrix proteins in tumors as a sign that the outcome of",380,128,0.3368
pubmed-summarization,", dyrk4 ) , which are part of the cmgc superfamily and share structural similarity of the catalytic domain and a small sequence nearby , the so - called dyrk homology box ( dh - box ) . although dyrks are serine / threonine kinases , autophosphorylation occurs at a conserved tyrosine residue of the activation loop . this autophosphorylation is constitutive and seems to be not related to regulation . in the light of its involvement in ds and other neurodegenerative disorders , the inhibition of dyrk1a with small chemical inhibitors has been suggested as a therapeutic strategy . selective dyrk1a inhibitors would also be valuable tools for the investigation of the role of dyrk1a in physiological and pathobiochemical processes . to date , most protein kinase inhibitors exert their activity by competing with atp in the binding pocket of the kinase . since atp binding sites of protein kinases share a common structure with subtle differences , selectivity with regard to closely related kinases is not easily achieved . when selective dyrk1a inhibitors are to be developed , special attention should therefore be devoted to other members of the cmgc superfamily , consisting of cdks , mapkinases ( such as erks ) , gsk-3 , and cdc - like kinases . the structures and properties of dyrk1a inhibitors have been summarized in recent reviews . a well established dyrk1a inhibitor is the -carboline alkaloid harmine ( 1 , chart 1 ) , which however also shows high affinity for serotonine and tryptamine receptor binding sites , acts as monoamine oxidase a ( mao a ) inhibitor , and also inhibits clks and therefore is inappropriate for use as a cellular chemical probe . epigallocatechin 3-gallate ( egcg ) is a polyphenolic constituent of green tea reported to inhibit dyrk1a in a non - atp - competitive manner , but it is chemically reactive and also interacts with numerous intracellular signaling pathways by other mechanisms . the benzothiazole derivative indy showed potent inhibition of dyrk1a and related kinases ( dyrk1b , dyrk2 , dyrk3 , clk1 , clk4 , ck1 , and pim1 ) . a prodrug of this compound , proindy ( 2 ) , has been shown to protect xenopus tadpoles that overexpress dyrk1a against head malformation","the protein kinase dyrk1a has been suggested to act as one of the intracellular regulators contributing to neurological alterations found in individuals with down syndrome . for an assessment of the role of dyrk1a , selective synthetic inhibitors are valuable pharmacological tools . however , the dyrk1a inhibitors described in the literature so far either are not sufficiently selective or have not been tested against closely related kinases from the dyrk and the clk protein kinase families . the aim of this study was the identification of dyrk1a inhibitors exhibiting selectivity versus the structurally and functionally closely related dyrk and clk isoforms . structure modification of the screening hit 11h - indolo[3,2-c]quinoline-6-carboxylic acid revealed structure activity relationships for kinase inhibition and enabled the design of 10-iodo - substituted",380,128,0.3368
dialogsum,"#Person1#: Glad you're back. How did the conference go, Chris? #Person2#: Uh, it was good. All the topic were interesting and the speakers were really good. The organization was a lot better this year, as well. I think having smaller number of people there made a big difference. You know you can make decisions a lot more quickly. #Person1#: Then how was the hotel? #Person2#: Ah, that was probably the only thing that people really complained about. The food in the restaurant wasn't very good and the service was slow. If we go back to the same hotel again, we'll have to find another restaurant. #Person1#: You're right. Anyway, I want to get a cup of coffee. Do you want to come? #Person2#: I'm done with coffee. I think I'll just go and have a cup of tea.",Chris compliments the conference on the topics and speakers as well as the better organizations and smaller size but complains about the hotel restaurant to #Person1#.,138,26,0.1884
scientific_lay_summarisation-elife-norm,"some of these cells fail to invaginate, and if so, how they shut off the auto-regulatory control of trh. In this article, we first show that trh plays a critical role in maintaining the invaginated structure but not in initiating invagination. Second, we reveal that the tracheal placode cells initiating trh expression later become either tracheal or epidermal cells, and the maintenance of trh expression is tightly associated with the change from the epithelial sheet to the invaginated structure. On the basis of our findings, we propose that the transcriptional coordination of trh expression, tracheal cell fate specification and invaginated structures during epithelial invagination ensures that only the invaginated cells are canalized robustly into the tracheal fate. We previously reported that mitosis can drive tracheal invagination, alone or in combination with EGFR signaling (Kondo and Hayashi, 2013). Although all embryonic cells undergo multiple cell divisions, mitosis-induced invagination occurs only in the tracheal placode. Non-tracheal epidermal cells quickly recover their flat epithelial architecture after mitosis, suggesting that the tracheal placode cells possess a special ability to couple mitosis with invagination and tubule formation (Kondo and Hayashi, 2013). Since trh is considered a master regulator of tracheal morphogenesis (Isaac and Andrew, 1996; Wilk et al. , 1996), we reasoned that trh is involved in this mitosis-induced invagination. Previous studies showed that in trh mutants, the tracheal tissue is completely missing in late-stage embryos, and no invagination occurs (Isaac and Andrew, 1996; Wilk et al. , 1996; Younossi-Hartenstein and Hartenstein, 1993). However, in the stage-10 tracheal placode, di-phosphorylated ERK, a hallmark of EGFR activation, was detected even in trh mutants (— 1) (Ogura et al. , 2018), suggesting that some early tracheal development processes were taking place. Live imaging of trh1 (an EMS-induced missense allele) mutants at single-cell resolution revealed an unexpected finding: apical constriction forming a tracheal pit appeared in the center of the placode region, followed by mitosis in the pit cells and rapid, deep invagination as seen in the control, although the onset of invagination was delayed (1B, C). Over the next 90 min, the invaginated structure gradually returned to the surface epidermal layer and merged with these cells to form a segmental furrow, leaving no trace of the tracheal structure (1C). Consistent with this live imaging analysis of trh1,","Cells in developing organs have two important decisions to make: where to be and what cell type to become. If cells end up in the wrong places, they can stop an organ from working, so it is vital that one decision depends upon the other. The so-called progenitor cells responsible for forming the trachea, for example, can either become part of a flat sheet or part of a tube. The cells on the sheet need to become epidermal cells, while the cells in the tube need to become tracheal cells. Work on fruit flies found that a gene called' trachealess' plays an important role in this process. Without it, developing flies cannot make a trachea at all. At the start of trachea development, some of the cells form",380,128,0.3368
scientific_lay_summarisation-elife-norm,"biophysical multi-protein solution studies naturally complement super-resolution fluorescence imaging and co-localization studies of live cells (Sherman et al. , 2011; Houtman et al. , 2006; Coussens et al. , 2013; Barda-Saad et al. , 2010). But, unfortunately, traditional SV is limited in several ways by optical detection systems that generally require the use of micromolar concentrations of purified proteins. 10. 7554/eLife. 17812. 003Figure 1. Concentration profiles in a sedimentation velocity experiment. Two different macromolecular components are depicted (blue and red) reversibly forming a complex (magenta). As a result of centrifugal force at 200,000–300,000 g, macromolecules sediment at a rate determined by their mass, density, and Stokes radius (or translational friction coefficient) (Svedberg and Rinde, 1924). The velocity of sedimentation normalized relative to the centrifugal field strength is expressed in the molecular sedimentation coefficient s. With time, transport clears the region of the solution column closest to the center of rotation and a moving front is formed -- the sedimentation boundary – that separates the cleared zone from a zone of constant concentration named the solution plateau region. While the boundary moves with time (dashed vs solid line), the concentration in the plateau region continuously decreases, solely due the radial geometry of sedimentation resulting in an increase in intermolecular distances (for a detailed description, see Schuck et al. , 2015). If protein interactions cause complexes to form, these generally sediment faster and therefore migrate through a bath of slower sedimenting free constituent components. This allows association/dissociation reactions to continuously occur in a way that reflects equilibrium and kinetic properties of the interaction, at the same time as the complex boundaries are hydrodynamically resolved (Schuck, 2010). The temporal evolution of the boundary shapes is governed by macromolecular diffusion and polydispersity, and the latter can be extracted by mathematical modeling of experimental data in form of sedimentation coefficient distributions (Schuck, 2000). : http: //dx. . org/10. 7554/eLife. 17812. 003 Recently, analytical ultracentrifugation was enhanced by the availability of a commercial fluorescence optical detection system (FDS), that uses confocal detection radially scanning the sample in the spinning rotor (MacGregor et al. , 2004) (2a). After accounting for characteristic data features, the FDS allows highly quantitative analyses of the sedimentation process (Zhao et al. , 2013b), extending the sensitivity of SV by several orders of","Many proteins in cells combine to form molecular machines or complexes that carry out specific processes inside cells. Analytical ultracentrifugation is a technique commonly used to explore the physical properties of proteins and their complexes and in this way to gain insights into the biological roles of these molecules. The technique involves spinning a sample containing the molecules to generate a strong centrifugal force, while monitoring the movement of the molecules. Under these conditions, molecules with different sizes and masses sink – or “sediment” – at different rates, so individual proteins and their complexes can be clearly distinguished. Analytical ultracentrifugation was recently extended to make it possible to detect fluorescent tags added on to proteins. This advance allowed researchers to study more dilute samples or complexes that are",380,128,0.3368
pubmed-summarization,"pacific islander were designated as high - risk minorities . using the defined high - risk factors , the population meeting ada screening criteria was determined . this included any patient 45 years of age or any overweight patient < 45 years with at least one additional high - risk factor ( 5 ) . the number of eligible patients screened was determined . because screening for patients < 45 years should be triggered by the presence of at least one high - risk factor in addition to obesity , a separate analysis of patients in this category was conducted . multivariable logistic regression was used to estimate adjusted odds ratios ( ors ) , predicted probabilities , and 95% ci for relationships between diabetes screening and patient and visit characteristics . predicted probabilities were calculated using the margins command in stata and calculating the effects at the average of the covariates . predicted probabilities were produced from a fitted logistic regression model where the outcome was whether a subject would receive diabetes screening . therefore , from this model , one can calculate the probability of receiving diabetes screening at any given level of covariates . additional models predicted fpg screening for patients with high - risk and non high - risk ethnic status and for the subsample of obese patients < 45 years with an additional risk factor . as a sensitivity analysis the presence of prediabetes and pcos was given in low numbers in the sample and was not used in analyses . this study was approved by the university of wisconsin - madison health sciences institutional review board . the methods used in this study were adapted from methods described previously ( 6 ) . in brief , patients included were 20 years of age on 1 january 2005 and had at least one family practice or internal medicine visit to the physician group in each of the 3 study years , 2005 , 2006 , and 2007 , in addition to a yearly visit in each of the 2 preceding years , 2003 and 2004 . a 3-year period from 2005 to 2007 was chosen based on ada recommendations to screen every 3 years ( 5 ) . data from years 2003 and 2004 were","objectiveethnicity has been identified as a risk factor not only for having type 2 diabetes but for increased morbidity and mortality with the disease . current american diabetes association ( ada ) guidelines advocate screening high - risk minorities for diabetes . this study investigates the effect of minority status on diabetes screening practices in an ambulatory , insured population presenting for yearly health care.research design and methodsthis is a retrospective population based study of patients in a large , midwestern , academic group practice . included patients were insured , had 1 primary care visit yearly from 2003 to 2007 , and did not have diabetes but met ada criteria for screening . odds ratios ( ors ) , 95% confidence intervals ( ci ) , and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"a platform for efficient reconstruction of axonal morphology. We demonstrate the utility of this system by reconstructing the extensive, brain-wide axonal arborizations of diverse projection neurons in the motor cortex within a single mouse brain. To image the axonal arbors of individual neurons, we constructed a platform for fast, automated, volumetric fluorescence imaging at sub-micron resolution. This system is based on a two-photon laser scanning microscope integrated with a vibrating microtome (1a), and was optimized for high-fidelity mosaic imaging in three dimensions. 10. 7554/eLife. 10566. 003Figure 1. Schematic of imaging system. (a) Schematic of apparatus for automated volumetric two-photon tomography. (b) To image large volumes of tissue, a collection of three-dimensional image stacks (tiles) covering the full volume of the tissue sample was acquired serially. Tiles overlapped in all three dimensions to aid in image registration and ensure coverage of the full volume. (c) The active imaging region is determined for each section by first tracing the perimeter of the tissue block and then filling in any tiles internal to the traced region. (d) Flow chart illustrating the tasks performed during data acquisition. : http: //dx. . org/10. 7554/eLife. 10566. 00310. 7554/eLife. 10566. 004Figure 1— 1. Point spread function measurement. (a) Empirically-measured point spread function measured using 200-nm fluorescent polystyrene beads. : http: //dx. . org/10. 7554/eLife. 10566. 004 To achieve high imaging speeds, we used a resonant scanning galvanometer, a piezoelectric motor-mounted objective for fast Z-scanning, and high excitation power. This approach allowed us to image up to 16 million voxels/s (>50 mm3/day) with signal-to-noise ratios (SNRs) sufficient for axonal reconstruction. This fast-scanning microscope represents a 16–48× increase in speed over conventional laser-scanning microscopy systems (Pologruto et al. , 2003). The system is comprised primarily of commercially-available hardware and custom control software (freely available at github. com/TeravoxelTwoPhotonTomography) and operates as follows: (1) the entire volume of space addressable by the stage system is partitioned into overlapping 3D tiles, each corresponding to a single image stack (1b); (2) tiles intersecting the exposed surface of the sample are marked for imaging (1c); (3) an image stack corresponding to each marked tile is acquired; (4) the integrated vibratome removes a portion of the imaged volume; (5) the precise surface plane of the remaining tissue is determined; and (6) this sequence of events","Nerve cells or neurons transmit electrical impulses to each other over long distances. These signals travel through highly branching nerve fibers called axons, which are about one hundred times thinner than a human hair, and can extend across the entire brain. Tracing the axon of a neuron from start to end can help to explain how individual neurons and brain areas communicate signals over long distances. A mouse brain contains approximately 70 million neurons, and tracing the axons of many neurons within a brain is a challenging problem. Tackling this problem requires a method for imaging entire brains in high enough detail to unambiguously resolve and follow axons from individual neurons across the brain. Economo, Clack et al. now demonstrate such a method for three-dimensional imaging of tissue",380,128,0.3368
pubmed-summarization,"in the past 15 years , green fluorescent protein ( gfp ) has changed from a nearly unknown protein to a commonly used molecular imaging tool in biology , chemistry , genetics , and medicine . in 2006 , more than 10 000 papers gfps and gfp - like proteins ( i.e. , chromoproteins and fluorescent proteins ) are particularly useful due to their stability and the fact that the chromophore ( see ) is formed in an autocatalytic cyclization of the 65syg67 sequence that does not require a cofactor . this means that unlike most other bioluminescent reporters , gfp fluoresces in the absence of any other proteins , substrates , or cofactors . furthermore , it appears that fusion of gfp to a protein does not alter the function or location of the protein . by changing residue 66 and/or the amino acid residues around the chromophore (n1c1c2c3 ) and (c1c2c3c4 ) dihedral angles of the gfp chromophore . in the protein , r1 is gly67 and r2 is ser65 , and in hbdi , an often - used model compound , r1 = r2 = ch3 . in one - bond flips ( -obf ) the dihedral rotation occurs around the torsional angle , in a -obf it is around the dihedral angle , and in a positively correlated hula - twist ( + ht ) the and dihedral angles concertedly rotate in the same direction ( as shown above ) , while in a negatively correlated hula twist ( ht ) they concertedly rotate in opposite directions . a plot of the and dihedrals for a perfectly correlated negative ht will have a slope of 1 . if the chromophore cavity is complementary with a planar chromophore , then the and best fit line will pass through the origin and all the and angles will be centered around the origin . a nonzero intercept along the or axis ( see , for example , ) or and dihedrals centered in quadrant ii ( > 0 ; < 0 ) or quadrant iv ( < 0 ; > 0 ; see , for example , ) are indications of a cavity that is not complementary with a planar chromophore . the fluorescent emission of the chromophore within","green fluorescent protein ( gfp ) and gfp - like fluorescent proteins owe their photophysical properties to an autocatalytically formed intrinsic chromophore . according to quantum mechanical calculations , the excited state of chromophore model systems has significant dihedral freedom , which may lead to fluorescence quenching intersystem crossing . molecular dynamics simulations with freely rotating chromophoric dihedrals were performed on green , yellow , and blue fluorescent proteins in order to model the dihedral freedom available to the chromophore in the excited state . most current theories suggest that a restriction in the rotational freedom of the fluorescent protein chromophore will lead to an increase in fluorescence brightness and/or quantum yield . according to our calculations , the dihedral freedom of the systems studied ( bfp >",380,128,0.3368
dialogsum,"#Person1#: Excuse me, what time do you expect to land in Berlin? #Person2#: We should be there by 5 this afternoon. #Person1#: Do you have any idea how long it will take to clean customs? #Person2#: Well, it all depends on traffic from other arriving aircraft.",#Person1# asks #Person2# about the time of arrival and the duration of customs clearance.,46,14,0.3043
dialogsum,"#Person1#: Now I've collected all your personal information. #Person2#: Then when will you exchange the CD for another one? #Person1#: After I give the information to the shop manager we will solve your problem. Please don't worry. #Person2#: But when? Could you tell me the deadline? I don't want to be bothered by it all the time. #Person1#: Um, I promised the day after tomorrow. #Person2#: Then I will be here in your shop on that day to get a new CD. #Person1#: OK, if you have any other questions, please let me know. Or you can call my number anytime.",#Person2# wants a CD exchange very much and urges #Person1# to give a deadline for the next exchange. #Person1# promises the day after tomorrow.,101,24,0.2376
pubmed-summarization,"v1v3 and v6 of the 16s rrna gene were amplified from all samples . pcr products were sequenced using 454 high throughput sequencing . using quantitative insights into microbial ecology pipeline the composition , richness and diversity of microbial communities were determined and compared between d - irritable bowel syndrome and hc . the results were the fact that the contribution of bacterial groups to the composition of the intestinal microbiota differed between d - irritable bowel syndrome and hc . d - irritable bowel syndrome patients had significantly higher levels of enterobacteriaceae ( p=0.003 ) and lower levels of faecalibacterium genera ( p=0.04 ) compared to hc . beta - diversity values demonstrated significantly lower levels of unifrac distances in hc compared to d - irritable bowel syndrome patients . the richness of 16s rrna sequences was significantly decreased in d - irritable bowel syndrome patients ( p<0.04 ) . their 16s rrna sequence data demonstrated that a community - level intestinal microbiota in d - irritable bowel syndrome is associated with significant increase , which is detrimental and decreases beneficial bacterial groups , and a reduction in microbial richness . suggest that altered intestinal microbiota contributes to the symptoms of irritable bowel syndrome through increased levels of organic acids . in fecal samples , irritable bowel syndrome patients had significantly higher numbers of veillonella and lactobacillus than healthy controls . furthermore , in irritable bowel syndrome patients with high acetic acid or propionic acid levels the symptoms were more severe , they presented negative emotions and an impaired quality of life . the results are in accordance with the concept that the gut microbiota interacts with higher brain centers that influence the sensory , motor and immune system of the gut . the bacterial overgrowth in the small intestinal observed in a subset of irritable bowel syndrome patients shows quantitative changes in the small bowel microbiota . data are lacking on qualitative changes in the gut microbiota in irritable bowel syndrome patients . the concepts identified here may lead to the development of novel therapeutic strategies for irritable bowel syndrome using manipulation of the intestinal microbiota . dysbiosis of the intestinal microbiota in irritable bowel syndrome has been detected on several levels : the overall community appears to","after acute infectious gastroenteritis , up to thirty percent of patients present prolonged gastrointestinal symptoms and a part of those affected patients can have the diagnostic criteria for postinfectious irritable bowel syndrome.treatment is symptom directed rather than curative and includes agents prescribed for the treatment of irritable bowel syndrome in general . prophylaxis or early treatment of acute bacterial diarrhea may reduce the risk of postinfectious irritable bowel syndrome development by reducing the occurrence , duration , and severity of the chronic inflammation and mucosal alterations ( all these believed to play an important role in disease persistence ) . probiotic treatment is effective in restoring the intestinal microbiota in patients with irritable bowel syndrome and in animal models there are improvements of postinfectious irritable bowel syndrome .",380,128,0.3368
dialogsum,"#Person1#: I am going to celebrate my birthday with you all in a night club this year, what do you say? #Person2#: Fantastic! I enjoy clubbing, especially those clubs with live bands. The only fly in the ointment is that the air is bad, full of smoke, and the music is too loud, so conversations are not really possible. Once I nearly got burnt by a cigarette. #Person1#: How did that happen? #Person2#: A wild dancer dropped it on my left foot and said nothing about it. If I had drunk enough and I would have had the bold to punch him in the face. #Person1#: Sounds cool! But that is not what a lady should do. People are easy to lose head in a night club and being drunk.",#Person1# wants to celebrate #Person1#'s birthday in nightclubs. #Person2# enjoys the clubs excluding the bad air and #Person2# nearly got burnt in a nightclub once.,130,25,0.1923
scientific_lay_summarisation-elife-norm,"al. , 2006). The expression patterns of these two opsins form opposing and overlapping gradients along the dorsal-ventral axis, resulting in a majority of cones expressing both opsins (herein either ‘mixed cones’ or M+S+) (Applebury et al. , 2000; Ng et al. , 2001; Wang et al. , 2011). Thus, S-opsin enrichment in the ventral retina better detects short-wavelength light from the sky, and M-opsin in the dorsal retina perceives the ground (e. g. , a grassy field) (Baden et al. , 2013; Gouras and Ekesten, 2004; Osorio and Vorobyev, 2005; Szél et al. , 1992), while co-expression of both opsins (herein either mixed cones or M+S+) (Röhlich et al. , 1994) broadens the spectral range of individual cones and improves perception under varying conditions of ambient light (Chang et al. , 2013). This unusual opsin expression pattern poses a challenge for color-coding, particularly so for mixed cones. However, it has been discovered that a small population of cones only expresses S-opsin (‘true S-cones’, or S+M-). These true S-cones are thought to be evenly distributed across the retina (Franke et al. , 2019; Haverkamp et al. , 2005; Szatko et al. , 2019; Wang et al. , 2011) and to be critical for encoding color, especially in the dorsal retina where they are quasi-evenly distributed in a sea of cones expressing only M-opsin (M+S-), a pattern akin to mammalian retinas in general (Haverkamp et al. , 2005; Wang et al. , 2011). Nonetheless, subsequent physiological studies revealed that color-opponent retinal ganglion cells (RGCs) are more abundant in the dorsal-ventral transition zone (Chang et al. , 2013) and the ventral retina (Joesch and Meister, 2016). Recent large scale two-photon imaging results further demonstrated that color opponent cells were mostly located in the ventral retina (Szatko et al. , 2019). Intriguingly, a behavior-based mouse study demonstrated that their ability to distinguish color is also restricted to the ventral retina (Denman et al. , 2018). These results prompt us to study, at the single-cell level and across the whole retina, the spatial distributions of cone types with different opsin expression configurations and, more importantly, with regard to S-cone bipolar cell connections in order to better understand the anatomical base for the unique color-coding scheme of the mouse retina. In mouse retina, the gradients","Many primates, including humans, can see color better than most other mammals. This difference is due to the variety of light-detecting proteins – called opsins – that are produced in the eye by cells known as cones. While humans have three, mice only have two different opsins, known as S and M, which detect blue/UV and green light, respectively. Mouse cones produce either S-opsins, M-opsins or both. Fewer than 10 percent of cone cells in mice produce just the S-opsin, and these cells are essential for color vision. Mice are commonly used in scientific research, and so their vision has been well studied. However, previous research has produced conflicting results. Some studies report that cone cells that contain only S-opsin are evenly spread out across the retina. Other",380,128,0.3368
dialogsum,"#Person1#: My shirt needs ironing. Could you please help me with that, Mary? #Person2#: No way. Do it yourself. #Person1#: Please, I promise this is the last time. #Person2#: OK, I'll iron your shirt for you, but only if you make me a cup of coffee.",Mary won't iron #Person1#'s shirt unless he makes coffee for her.,46,11,0.2391
pubmed-summarization,"a 36-year - old man presented with an incidental hepatic mass . the mass was slightly hyperintense in t2-weighted image with several poorly defined bright foci , and isointense in t1-weighted image , and arterial enhancement and slight washout on late dynamic phase . on mri , no gross fat or hemorrhage was noted in the tumor ( . macroscopically , the specimen comprised a huge mass , measuring 10 cm in size , with a cut surface showing a dark - green color and focal areas of congestion ( . microscopically , the nuclei of tumor cells were slightly larger than those of the nontumor hepatocytes . moderate mononuclear inflammatory cell infiltrates were found around abnormally shaped blood vessels . in the cytoplasm of the tumor cells , dark - brown colored granular pigment was observed ( . 6b ) , mimicking dubin - johnson - like pigment . additionally , diffuse immunoexpression of saa ( . the patient has been followed up for a period of 3 years with no evidence of local recurrence or metastasis after operation . a 46-year - old man showed a hepatic mass found during a routine check - up . his past history was unremarkable and he had no history of alcohol or drug abuse . laboratory findings were all within normal ranges , including aspartate aminotransferase , alanine aminotransferase , -glutamyltransferase , lactate dehydrogenase , total bilirubin , and total protein . hepatitis b surface antigen and antihepatitis c virus antibody were negative , but anti - hbs antibody was positive . serum levels of -fetoprotein and protein - induced by vitamin k absence or antagonist ii were normal . liver dynamic computed tomography ( ct ) showed an arterial enhancing 6-cm sized lesion without washout in portal and delayed phase . gadobenate dimeglumine ( gd - bopta ) enhanced magnetic resonance imaging ( mri ) showed slight hyposignal intensity in t1-weighted image , and arterial enhancement without washout on portal phase . in 3-hour delayed hepatobiliary phase , the lesion was hypointense . in t2-weighted image , however , there was a focal washout area within the enhancing mass , which may suggest hcc ( . right lobectomy was performed and the specimen revealed a multilobular mass measuring 75 cm","hepatocellular adenoma ( hca ) is an uncommon benign hepatic tumor , and the use of oral contraceptives is known to contribute to the development of hca . recently , a genotype and phenotype classification system for hca was suggested , and malignant transformation to hepatocellular carcinoma ( hcc ) was shown to be strongly associated with activating mutations in -catenin . here , we report three cases of hca in korean patients : 7-cm , inflammatory and -catenin - activated hca with hcc transformation in a 46-year - old man ; 13-cm , -catenin - activated hca with cytological atypia in a 23-year - old woman ; and 10-cm , pigmented , inflammatory and -catenin - activated hca in a 36-year - old man . all cases",380,128,0.3368
dialogsum,"#Person1#: I need to get my internet fixed. #Person2#: What's the problem with your internet? #Person1#: It won't connect. #Person2#: How long has this been happening? #Person1#: This problem has been happening for a few days now. #Person2#: The internet doesn't come up at all? #Person1#: It just won't connect to a webpage, but it will pop up. #Person2#: There's obviously a problem with your connection. #Person1#: I'm going to need someone to come and fix it for me. #Person2#: I can send somebody right now to fix it. #Person1#: How long will it take for them to get here? #Person2#: They'll be there in about an hour.",#Person1#'s internet hasn't been able to connect to a webpage for a few days. #Person2# will send someone to fix it.,108,21,0.1944
dialogsum,"#Person1#: Doctor, can you give me some suggestions on how to stay healthy? #Person2#: Well, first of all, you need to make sure that you eat the right foods. #Person1#: What are the best foods to eat? #Person2#: You should emphasize fresh fruits and vegetables, along with whole grains and protein. #Person1#: What should I avoid? #Person2#: You need to avoid highly fatty and greasy foods. You should also avoid too much sugar and caffeine. #Person1#: What else is important to stay healthy? #Person2#: You need to get plenty of exercise every day. If you smoke, you need to stop. #Person1#: Is it OK to drink alcohol? #Person2#: Actually, studies have shown that people who have one-half a glass of alcohol per day do better than those who don't drink.","#Person1# consults the doctor about how to stay healthy and the doctor suggests #Person1# eat the right food, get plenty of exercise, and it is ok to drink alcohol.",130,29,0.2231
dialogsum,"#Person1#: Hello, Mrs. White. Do you feel better today? #Person2#: Oh, much better. Thank you. #Person1#: Can I ask you some questions now? #Person2#: Certainly. #Person1#: First, do you remember what the driver looks like? #Person2#: Yes. He looked quite old and not very tall. Oh, and he had thick lips. #Person1#: OK. When the accident happened, where were you going? #Person2#: I was walking fast to a bank and pay a bill for my son. #Person1#: I see. After the driver knocked you down, he got out of his car and looked at you, didn't he? #Person2#: Yes, he did. I was bleeding, so he looked scared and then hurried back to the car. #Person1#: Do you remember his clothes? #Person2#: Yes. He wore a blue T-shirt, gray trousers. #Person1#: OK. I think I have enough information now. Thank you. #Person2#: You're welcome.",Mrs. White feels better today. Then she tells #Person1# the details about her car accident and the looking and dressing of the driver.,144,23,0.1597
scientific_lay_summarisation-elife-norm,"GRN. We found an overrepresentation of copy-number aberrations and point mutations in genes dating back to early metazoan ancestors. Point mutations disrupted key master regulators that evolved in early in the metazoan lineage, suggesting a primary role in the uncoupling of the subnetworks regulating multicellularity and the fundamental core of cellular processes dating back to single-celled organisms. CNAs were involved in a complementary mechanism of dysregulation, generally disrupting the downstream targets of each of these subnetworks. These results indicate that both point mutations and CNAs contribute to the dysregulation of multicellularity in cancer, but do so in different ways, impacting regions of transcriptional networks with distinct roles in the regulation of multicellularity. Finally, we show how our approach of integration of sequence conservation and transcriptome data with annotated regulatory associations provides a framework for identifying important driver mutations and prioritizing compounds for targeted therapy, at the level of both patient populations and individual tumors. We investigated the association between the evolutionary ages of genes and the frequency of copy-number aberrations (CNAs) and point mutations across tumor cohorts (The Cancer Genome Atlas Network, 2017a; The Cancer Genome Atlas Network, 2017b). We collected CNA and point mutation data from 10256 and 9926 patients, respectively, from The Cancer Genome Atlas across 30 tumor types (see Materials and methods). We selected a subset of genes that were consistently amplified or deleted in at least 10% of patients of each tumor cohort, and genes with either missense or loss-of-function (LoF) mutations in at least three patients and with a higher rate of occurrence than synonymous mutations (— 1) (see Materials and methods). Human genes were classified by their evolutionary age using phylostratigraphy (Domazet-Loso and Tautz, 2010), resulting in 16 phylogenetic groups (phylostrata) (— 2), ranging from genes found in unicellular ancestors (Phylostrata 1–3) (6,719 UC genes), to genes found in early metazoans (Phylostrata 4–9) (7,939 EM genes), and mammal-specific genes (Phylostrata 10–16) (2,660 MM genes) (— 3) (Trigos et al. , 2017). We calculated the fraction of genes in each phylostratum with recurrent CNAs and point mutations, accounting for differences in CNA and mutation rates between tumor cohorts by ranking each phylostratum by the fraction of genes altered (1A, B). We found an increasing trend of enrichment of CNAs starting from the earliest UC genes","Cancers arise when harmful changes happen in the genetic information of certain cells. These ‘mutations’ are different from person to person, but overall, they disrupt healthy cells in similar ways. In particular, cancer cells tend to lose features that help cells work together in the body. Researchers have suggested that cancers may emerge when cells stop being able to cooperate with each other as part of an organism. Our bodies still rely on old genes that were present in our earliest, single-cell ancestors. However, we also have newer genes that evolved when the organisms in our lineage started to have more than one cell. A complex network of signals exists to ensure that both sets of genes work together smoothly, and previous studies have suggested that cancers may",380,128,0.3368
dialogsum,"#Person1#: Dad, may I have a room of my own? #Person2#: Oh, honey, I'm so sorry, we don't have enough space for you to have your own room. #Person1#: Dad, but I don't want to share a room with Peter. He snores every night. #Person2#: Honey, you can ask him to be quite. Otherwise you may punish him and tell him to stand out of the room, right? #Person1#: Alright. Maybe it's the only way to do it.",#Person1# asks to have #Person1#'s room because Peter snores. #Person1#'s dad says they don't have enough space and suggests #Person1# ask Peter to be quiet.,78,25,0.3205
pubmed-summarization,"representing the other . mondrian 's so - called abstract plasticism generated paintings that seem as far removed from nature as they possibly could be ( taylor , 2002a , 2004 ) . they consist of elements primary colors and straight lines that never occur in a pure form in the natural world . in contrast to mondrian 's simplicity , pollock 's abstract expressionism speaks of complexity a tangled web of intricate paint splatters . whereas mondrian 's patterns are traditionally described as artificial and geometric , pollock 's are natural and organic ( taylor , 2011 ) . but if pollock 's patterns celebrate nature 's organic shapes , what shapes would these be ? since the 1970s many of nature 's patterns have been shown to be fractal ( mandelbrot , 1982 ; barnsley , 1993 ; gouyet , 1996 ) . in contrast to the smoothness of artificial lines , fractals consist of patterns that recur on finer and finer scales , building scale - invariant shapes of immense complexity . even the most common fractal objects , such as the tree shown in , contrast sharply with the simplicity of artificial shapes . an important parameter for quantifying a fractal pattern 's visual complexity is the fractal dimension , d. this parameter describes how the patterns occurring at different magnifications combine to build the resulting fractal shape ( mandelbrot , 1982 ) . for euclidean shapes , dimension is described by familiar integer values for a smooth line ( containing no fractal structure ) d has a value of 1 , whilst for a completely filled area ( again containing no fractal structure ) its value is 2 . however , the repeating patterns of a fractal line cause the line to begin to occupy space . as a consequence , its d value lies between 1 and 2 . by increasing the amount of fine structure in the fractal mix of repeating patterns , the d value moves closer to 2 ( mandelbrot , 1982 ; taylor and sprott , 2008 ) . thus , for fractals described by a low d value , the small content of fine structure builds a very smooth , sparse shape . however , for fractals with a","fractals have been very successful in quantifying the visual complexity exhibited by many natural patterns , and have captured the imagination of scientists and artists alike . our research has shown that the poured patterns of the american abstract painter jackson pollock are also fractal . this discovery raises an intriguing possibility are the visual characteristics of fractals responsible for the long - term appeal of pollock 's work ? to address this question , we have conducted 10 years of scientific investigation of human response to fractals and here we present , for the first time , a review of this research that examines the inter - relationship between the various results . the investigations include eye tracking , visual preference , skin conductance , and eeg",380,128,0.3368
scientific_lay_summarisation-elife-norm,"synaptic strength in the LA after fear conditioning. Auditory fear conditioning elicits LTP-like effects in LA neurons (Rogan and LeDoux, 1995; Rogan et al. , 1997) and elicits presynaptic enhancement of inputs arriving in the LA from the medial geniculate nucleus of the thalamus and cortex (McKernan and Shinnick-Gallagher, 1997; Tsvetkov et al. , 2002; Zinebi et al. , 2002). Dopamine is a potent modulator of plasticity in the LA. In the anesthetized rat, odor-evoked potentials in the LA are potentiated following pairing with a footshock that is dependent on dopamine receptor activation (Rosenkranz and Grace, 2002). In addition, dopamine signaling modulates local inhibitory networks in the LA (Loretan et al. , 2004), facilitates LTP induction through suppression of feedforward inhibition (Bissiere et al. , 2003), and regulates intrinsic excitability of principal neurons (Yamamoto et al. , 2007). Consistent with the modulation of fear-evoked plasticity in the LA, suppression of dopamine signaling attenuates acquisition of conditioned fear memory (Borowski and Kokkinidis, 1996; Lamont and Kokkinidis, 1998; Guarraci et al. , 1999,2000; Greba et al. , 2001) and fear memory expression (Nader and LeDoux, 1999). Subsets of dopamine neurons are activated by aversive stimuli (Schultz and Romo, 1987; Guarraci and Kapp, 1999; Brischoux et al. , 2009) and undergo plasticity following an aversive experience (Lammel et al. , 2011) or fear conditioning (Guarraci and Kapp, 1999; Brischoux et al. , 2009; Gore et al. , 2014). NMDAR signaling in dopamine neurons regulates both synaptic plasticity (Bonci and Malenka, 1999) and phasic activation of these cells (Overton and Clark, 1997), and disruption of NMDARs in dopamine neurons of mice results in the development of behavioral correlates of generalized fear and anxiety following an aversive experience (Zweifel et al. , 2011). These results suggest a potential link between cell autonomous functions of this receptor in dopamine neurons and the disruption of fear coding in the amygdala that may be an underlying cause of fear generalization. Here we demonstrate that mice lacking NMDARs in dopamine neurons have deficits in cued fear discrimination and that this deficit is associated with altered fear coding in the LA. Contrary to our initial hypothesis, fear generalization in DAT-NR1 KO mice was not associated with a non-specific increased activation of LA neurons to a non-US predictive conditioned stimulus (CS−),","When we experience a situation that causes us to feel fearful, the brain processes information about the events that led up to it. This information is encoded by groups of nerve cells called neurons in a region of the brain called the lateral amygdala. The nerve cells communicate with each other through chemicals called neurotransmitters. At a junction between two neurons—called a synapse—neurotransmitters are released from one cell and influence the activity of the other cell. Long-term changes in the strength of these communications in response to specific cues underlie the formation of memories about fearful events. When these changes occur incorrectly they can lead to memories about particular events becoming inaccurate, which can lead to fear being associated with related, but non-threatening, situations. This ‘generalization’ of fear",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Correct orientation of the mitotic spindle in stem cells underlies organogenesis. Spindle abnormalities correlate with cancer progression in germ line-derived tumors. We discover a macromolecular complex between the scaffolding protein Gravin/AKAP12 and the mitotic kinases, Aurora A and Plk1, that is down regulated in human seminoma. Depletion of Gravin correlates with an increased mitotic index and disorganization of seminiferous tubules. Biochemical, super-resolution imaging, and enzymology approaches establish that this Gravin scaffold accumulates at the mother spindle pole during metaphase. Manipulating elements of the Gravin-Aurora A-Plk1 axis prompts mitotic delay and prevents appropriate assembly of astral microtubules to promote spindle misorientation. These pathological responses are conserved in seminiferous tubules from Gravin−/− mice where an overabundance of Oct3/4 positive germ line stem cells displays randomized orientation of mitotic spindles. Thus, we propose that Gravin-mediated recruitment of Aurora A and Plk1 to the mother (oldest) spindle pole contributes to the fidelity of symmetric cell division. Mitotic cell division is a process whereby genetic material is duplicated, separated, and packaged to yield two daughter cells (Nigg and Raff, 2009). This process relies heavily on the spatial and temporal synchronization of protein kinase activity at the mitotic spindle, a macromolecular machine that segregates the chromosomes and guides them towards the daughter cells (Lowery et al. , 2004; Nigg and Stearns, 2011; Langeberg and Scott, 2015). Correct orientation of the mitotic spindle during cell division combined with local kinase signaling is crucial for cell fate determination, tissue organization, and development (Yamashita et al. , 2007; Lesage et al. , 2010; Gillies and Cabernard, 2011; Kiyomitsu and Cheeseman, 2012; Pelletier and Yamashita, 2012; Joukov et al. , 2014). The mitotic spindle is constrained by two spindle poles that nucleate microtubules. The mother spindle pole contains the oldest centriole and remains anchored near the stem-cell niche, while the daughter spindle pole migrates to the opposite side of the cell to complete spindle formation (Yamashita et al. , 2007; Izumi and Kaneko, 2012). Recently, a spindle orientation complex has been identified at the mother spindle pole containing protein components that promote maturation (Yamashita et al. , 2007; Izumi and Kaneko, 2012; Chen et al. , 2014). Several disease-linked genes encode these proteins and their loss causes mitotic delays and spindle misorientation phenotypes (Buchman et al. , 2010; Gruber et","The genetic material inside our cells is contained within structures called chromosomes. When a cell divides, these chromosomes are copied and then must be correctly divided between the two daughter cells so that each cell has a complete set of genetic material. The correct separation of the chromosomes depends on a structure called the mitotic spindle whose location in the cell also determines where the point of division will be. Two structures called centrioles are associated with the mitotic spindle and help to organize and direct cell division. The cell carefully controls how these structures are inherited by the daughter cells. For example, when a stem cell divides to produce one stem cell and one cell of a different type, the older centriole can be inherited by the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"sinus-associated macrophages and IFNγ precommitted CD8 T cells and NK cells is important for mounting rapid Th1-like and NK cell responses against acute infection by Pseudomonas aeroguinosa, Salmonella typhimurium and Toxoplasma gondii (Coombes et al. , 2012; Kastenmüller et al. , 2012). IL17 is a cytokine with roles in anti-bacterial and anti-fungal defense that is made abundantly by effector T cells at epithelial surfaces (Littman and Rudensky, 2010). Whether IL17 is produced rapidly during responses to subcapsular sinus-invaders in LNs is unclear. In recent work, our group and others identified populations of innate-like (pre-formed effector) lymphocytes that are enriched near the SCS in peripheral LNs and are pre-committed to produce IL17 (Do et al. , 2010; Doisne et al. , 2009; Gray et al. , 2012; Roark et al. , 2013). These cells express high amounts of the chemokine receptors Ccr6 and Cxcr6 as well as the cytokine receptor IL7R, and they include a majority of αβ T cells but also considerable numbers of γδ T cells as well as non-T cells (Gray et al. , 2012). Within the IL17-committed γδ T cell population a major subset expresses a Vγ4-containing TCR (according to the nomenclature of [Heilig and Tonegawa, 1986]), and undergoes expansion in response to challenge with imiquimod or complete Freund’s adjuvant (Gray et al. , 2013; Ramirez-Valle et al. , 2015; Roark et al. , 2013). In previous work, we found that innate-like lymphocytes isolated from peripheral LNs were heavily coated with CD169+ macrophage-derived membrane fragments (‘blebs’) (Gray et al. , 2012). This observation suggested there may be strong adhesive interactions between these cells and the CD169+ macrophages. CD169 is the founding member of the Siglec family of sialic acid-binding lectins (Crocker et al. , 2007; Macauley et al. , 2014). Although CD169 is a defining feature of LN SCS macrophages and targeting antigens to CD169 can promote antibody responses (Macauley et al. , 2014), the function of CD169 on these cells is not fully understood. Pre-enrichment of innate-like lymphocytes near LN sinuses is thought to be important for allowing very rapid responses against lymph-borne invaders (Gray et al. , 2012; Kastenmüller et al. , 2012). Despite this, it is not known whether IL17-committed innate-like lymphocytes in LNs respond rapidly upon pathogen challenge, and little is understood about","The lymphatic system is a network of vessels and a vital part of our immune system. Amongst other things, the lymphatic system carries microbes that have entered the body – for example via to a cut or mosquito bite – to small, oval-shaped organs called lymph nodes. The lymph nodes are packed with immune cells that can be activated to help fight off infections, however certain microbes actually replicate inside the lymph nodes themselves. Lymph nodes protect themselves from these infections by having some pre-armed immune cells that are ready to respond rapidly as soon as an invading microbe is detected. These cells, referred to as innate-like lymphocytes, position themselves at the exposed surfaces of the lymph node – the locations where microbes are most likely to enter",380,128,0.3368
pubmed-summarization,"of recent mass spectrometry - based proteomic studies on the molecular fate of mitochondrial enzymes in senescent fibres . this paper briefly outlines the proposed role of mitochondria in cellular senescence and recent achievements of mitochondrial proteomics and then focuses on findings from proteomic profiling studies of aged skeletal muscle preparations and the identification of mitochondrial elements as potential markers of fibre aging . mitochondria are the primary site for energy generation via oxidative phosphorylation and play a key role in protein transport , intermediary metabolism , cell cycle progression , calcium signaling , and the regulation of apoptosis . proteomic cataloguing studies of this crucial organelle suggest the existence of approximately 1,500 mitochondrial proteins , whereby altered expression levels within the mitochondrial proteome are critical factors for normal development and numerous diseases . changes in mitochondria have long been associated with playing an integral role during natural aging , and the pharmacological application of antioxidants for counteracting mitochondria - specific symptoms of senescence is being extensively studied . interestingly , the mitochondrial theory of aging also encompasses the mechanisms that may lead to cellular senescence in contractile tissues . altered levels of mitochondrial activity in aged muscle tissues have been well established and extensively reviewed . the detrimental accumulation of mitochondrial dna deletions and mutations on the genetic level and deficiencies in the mitochondrial electron transport chain on the biochemical level are clearly associated with muscle aging . the pathological consequences of an age - related decline in mitochondrial function are the impairment of essential atp - dependent cellular processes and amplified oxidative stress in senescent tissues due to the increased release of reactive oxygen species from the mitochondrial respiratory chain . in general , senescent muscle tissues are exposed to an enhanced production of mitochondrial reactive oxygen species , increased mitochondrial apoptotic susceptibility , disturbed mitochondrial bioenergetic functions , and a reduced transcriptional drive for mitochondrial biogenesis . although these functional impairments clearly occur in skeletal muscle mitochondria during aging , biochemical studies have also demonstrated considerable age - related changes in the abundance and posttranslational modifications of key mitochondrial enzymes . proteomics is concerned with the large - scale and high - throughput identification and characterization of the global protein constellation of a given biological entity ,","mitochondria are of central importance for energy generation in skeletal muscles . expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis , fibre maturation , and various neuromuscular pathologies , as well as natural fibre aging . mass spectrometry - based proteomics suggests itself as a convenient large - scale and high - throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease . this paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles . changes in the abundance , biochemical activity , subcellular localization , and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc–Brn1b and linc–Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr−/− neonates, whereas linc–Brn1b−/− mutants displayed distinct abnormalities in the generation of upper layer II–IV neurons in the neocortex. This study demonstrates that lncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of lncRNA molecules. Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs), which are emerging as key regulators of cellular processes (Rinn and Chang, 2012; Mercer and Mattick, 2013). Gain- and loss-of-function approaches in cell-based in vitro systems have been useful in uncovering important roles for lncRNAs, such as modulating chromatin states, maintaining cellular identity (i. e. pluripotency) and regulating cell cycle and translation (Tsai et al. , 2010; Guttman et al. , 2011; Wang et al. , 2011; Yoon et al. , 2012). Genome-wide association and expression profiling studies in humans have also identified correlations between lncRNA mutation, misregulation and disease states (Visel et al. , 2010; Cabili et al. , 2011; Brunner et al. , 2012). Yet, direct in vivo, genetic evidence of the functional significance of lncRNAs as a class of transcripts remains elusive. Functional studies in knockout mouse models have provided compelling evidence for the requirement and sufficiency of particular transcripts for organ development and function. However, small and large-scale efforts have focused primarily on protein coding genes, leaving long noncoding RNAs vastly understudied (Edwards et al. , 2011; White et al. , 2013). Of the few lncRNA mutant mice generated to date, most involved previously studied and classic examples of lncRNAs (e. g. , Xist, H19, Kcn11ot1, Malat1) (Anguera et al. , 2011; Gomez et al. , 2013; Gordon et al. , 2010; Moseley et al.","The mammalian genome is comprised of DNA sequences that contain the templates for proteins, and other DNA sequences that do not code for proteins. The coding DNA sequences are transcribed to make messenger RNA molecules, which are then translated to make proteins. Researchers have known for many years that some of the noncoding DNA sequences are also transcribed to make other types of RNA molecules, such as transfer and ribosomal RNA. However, the true breadth and diversity of the roles played by these other RNA molecules have only recently begun to be fully appreciated. Mammalian genomes contain thousands of noncoding DNA sequences that are transcribed. Recent in vitro studies suggest that the resulting long noncoding RNA molecules can act as regulators of transcription, translation, and cell cycle. In",380,128,0.3368
dialogsum,"#Person1#: You took an optional course this semester, didn't you? How's it going? #Person2#: Terrible! It seems like the more the professor talks, the less I understand. #Person1#: If I were you, I would take a different course. There are five optional courses, aren't there?",#Person2# thinks the optional course is terrible. #Person1# suggests taking a different course.,45,13,0.2889
dialogsum,"#Person1#: Is there a medication you can prescribe to help me with my problem? #Person2#: There are various choices of blood pressure medication that we can try. #Person1#: What is available? #Person2#: We could start with Hydrochlorothiazide, which is a diuretic. #Person1#: Are there many side effects? #Person2#: There really are not many side effects. You need to drink a lot of water when you take this pill. #Person1#: Is that the only medication I need to take? #Person2#: It might be, but for a while I also want you to take an ACE inhibitor, Lisinopril. #Person1#: What are the side effects of that drug? #Person2#: You may have a little bit of a dry cough, but you will feel much better.",#Person2# prescribes some blood pressure medications such as Hydrochlorothiazide and Lisinopril to help #Person1# with the problem. #Person2# also explains the side effects.,122,23,0.1885
scientific_lay_summarisation-elife-norm,"combination of nacroprismatic microstructure and aragonitic mineralogy is observed in freshwater unionoid mussels but also in marine trigonioids and anomalodesmatans (Appendix 1, section 2). Stable isotope analyses for all of the samples yielded average δ18O and δ13C values of −5. 3 ± 0. 4 and −11. 1 ± 0. 6 ‰ for Havnø, −6. 1 ± 1. 0 and −11. 9 ± 1. 7 ‰ for Peştera Ungurească and −9. 3 ± 0. 5 and −10. 6 ± 1. 6 ‰ for Hornstaad, respectively (Appendix 1, section 3. 3). The consistently low δ18O and δ13C values of shells from Peştera Ungurească and Hornstaad indicate a local freshwater origin for the shells (Keith et al. , 1964; Leng and Lewis, 2016), whereas the δ18O values at Havnø suggest some mixing of marine water or changes in the atmospheric circulation, with precipitations slightly enriched in 18O compared to present day over the region. Our interpretations are broadly supported by the average annual δ18O values of modern local precipitations for the sites (WaterIsotopes. org, 2018). The isotope data therefore suggest that the shells were locally sourced (Keith et al. , 1964). The absence of recrystallization observed by SEM was consistent with the concentration, composition and relatively low D/L values for all the amino acids analysed (e. g. alanine D/L ~0. 1 for Peştera Ungueraşca, ~0. 2 for Havnø and Hornstaad), except for sample HorA. This supports a non-fossil origin for the shells used to make the double-buttons, that is the makers used ‘fresh’ or recently dead mollusc shells. However, the extent of degradation for HorA was significantly higher and both D/L and concentration values showed a clear ‘burning’ signal (Crisp, 2013; Demarchi et al. , 2011). The amino acid composition was similar to that of freshwater bivalves (Unio, Margaritifera) present in the reference database of Demarchi et al. (2014), although HorA and PesB appeared to be rather different from the other double-buttons (Appendix 1, section 3. 4). We characterized the proteomes preserved within the seven double-buttons and performed bioinformatic searches (PEAKS 8. 5, Bioinformatics Solutions Inc [Ma et al. , 2003]) of the product ion spectra against both a Protein sequences and an Expressed Sequence Tags (ESTs) database, restricting the taxonomy to Mollusca (see Methods section). This resulted in the identification of 1973","Just like people do today, prehistoric humans liked to adorn themselves with beautiful objects. Shells, from creatures like clams and snails, were used to decorate clothing or worn as jewelry at least as far back as 100,000 years ago. Later people used shells as the raw materials to make beads or bracelets. Learning where the shells came from may help scientists understand why prehistoric people chose certain shells and not others. It may also offer clues about how they used natural resources and the cultural significance of these objects. But identifying the shells is difficult because they lose many of their original distinctive features when worked into ornaments. New tools that use DNA or proteins to identify the raw materials used to craft ancient artifacts have emerged that",380,128,0.3368
pubmed-summarization,"and uyghur . the study protocol was approved by the ethics committee of people 's hospital of xinjiang uyghur autonomous region . informed consent was obtained from all subjects before data collection . in our study site , all the data collection was performed by the same staff group from department of endocrinology in people 's hospital of xinjiang uyghur autonomous region . they were trained according to a standard protocol that made them familiar with the specific tools and methods used . venous blood samples were drawn after an overnight fast of at least 8 h and centrifuged on the spot after collection . serum 25(oh)d levels and thyroid parameters , serum tsh , and the levels of tgab and tpoab were measured with a roche electrochemiluminometric analyzer ( e601 ) , with an interassay variance of < 10% . it is generally agreed that serum 25(oh)d levels of 20 to 30 ng / ml should be considered as representative of vitamin d insufficiency , whereas serum 25(oh)d levels of < 20 ng / ml should be considered as an indicative of vitamin d deficiency . serum tpoab of > 35 iu / ml and/or tgab of > 116 iu / ml were considered autoantibody positivity ( roche ) . continuous variables are presented as means standard deviation for continuous normally distributed variables and median ( interquartile range ) for the nonnormally distributed variables . student 's t - test and mann - whitney u test were used for comparison of mean values between groups . linear regression analysis was used to examine the relationship between log - transformed tgab / tpoab titer and age , ethnicity , 25(oh)d , and other biochemical variables . all calculations were performed using spss 19.0 for windows ( chicago , il , usa ) . a probability ( p ) value of < 0.05 was considered statistically significant for all tests . a total of 1,714 subjects ( 969 han and 745 uyghur ) including 1,197 females ( 652 han and 545 uyghur ) and 517 males ( 317 han and 200 uyghur ) were enrolled in this study . the mean level of total serum 25(oh)d was 16.55 8.53 ng / ml . vitamin d deficiency and insufficiency were noted in","objectives . some evidence has pointed out that vitamin d plays a significant role in reducing the incidence of autoimmune diseases , especially autoimmune thyroid diseases . the authors aimed to examine the relationship between circulating 25-hydroxyvitamin d and thyroid autoantibody in a population - based health survey of xinjiang chinese population . subjects and methods . a total of 1714 chinese adults were analyzed . 25(oh)d , anti - thyroid antibodies , and thyroid function were measured . results . the prevalence of vitamin d insufficiency was 28.3% in hans and 9.3% in uyghurs , and the prevalence of vitamin d deficiency was 61.6% in hans and 87.6% in uyghurs . overall prevalence of tgab positivity was 6.2% ( 0.9% males ; 5.3% females ) . in",380,128,0.3368
pubmed-summarization,"a dilution of 1/100 . nanosign hbs poc strips were used to screen serum samples from 297 individuals at risk of hbv in local clinical settings ( health fairs and outreach events ) in parallel with soc serologic testing for hbsag through a commercial laboratory ( quest diagnostics eia ; madison , nj , usa ) . trained technicians under the supervision of a pharmacist or physician performed and read the results of the poc tests . the 37 samples tested included hbv genotypes a ( n = 4 ) , b ( n = 4 ) , c ( n = 6 ) , d ( n = 4 ) , e ( n = 8) , f ( n = 4 ) and g ( n = 7 ) . two hbv genotype c samples were the divergent subgenotype c4 , found only in indigenous australians , which has a surface gene region most closely related to hbv genotype j 7 . all 37 samples tested positive for hbsag using the poc strips ( sensitivity 100% ) . hbsag - negative samples did not produce any signal ( specificity 100% ) , even when samples were seropositive for hepatitis a virus or hepatitis c virus . testing serially diluted serum samples ( .1a ) showed that the poc strips reliably detected hbsag at a concentration of at least 50 iu / ml for all genotypes and at lower concentrations for some genotypes . we acknowledge that this detection limit is similar to or slightly higher than most hbsag enzyme immunoassays 3 ; however , poc strips appear to be sensitive enough to detect hbsag levels in serum from chronically infected patients across a range of genotypes . nanosign hbs poc test strip results for a panel of serum samples with known hbv genotypes ( panel a ) and for eight samples with a determinant mutations ( panel b ) . hbsag titres measured by elecsys hbsag ii assay are indicated under each strip in iu / ml . the assay control band is on the right of each strip with the sample band on the left . common hbsag variants surface ( s)d144e and sg145r , in particular , showed clear reactivity . this is notable because the","early identification of chronic hepatitis b is important for optimal disease management and prevention of transmission . cost and lack of access to commercial hepatitis b surface antigen ( hbsag ) immunoassays can compromise the effectiveness of hbv screening in resource - limited settings and among marginalized populations . high - quality point - of - care ( poc ) testing may improve hbv diagnosis in these situations . currently available poc hbsag assays are often limited in sensitivity . we evaluated the nanosign hbs poc chromatographic immunoassay for its ability to detect hbsag of different genotypes and with substitutions in the a determinant . thirty - seven serum samples from patients with hbv infection , covering hbv genotypes a g , were assessed for hbsag titre with",380,128,0.3368
pubmed-summarization,"can be treated easily by endoureteral catheterization or percutaneous nephrostomy which allows rapid normalization of renal function in most cases and further administration of effective systemic chemotherapy . survival after the onset of distant metastases is relatively short , poulakis et al . in 2001 reported a patient with breast cancer and urinary bladder involvement still alive at five years from diagnosis . hence , appropriate treatment and follow - up may improve the prognosis of patients with bladder metastases .","breast carcinoma is the most common nondermatologic cancer diagnosis in women . common metastatic sites include lymph nodes , lung , liver , and bone . breast carcinoma metastatic to the bladder has been reported only sporadically . most patients were symptomatic breast cancer with evidence of disseminated disease at the time of diagnosis . metastasis usually occurred many years after diagnosis , and the prognosis was poor . we report a case of breast caricinoma metastasizing to the urinary bladder and retroperitoneum , which presented initially with acute renal failure . patient was treated with bilateral per cuteneous nephrostomies and chemotherapy . starting from this clinical case we review the available literature on this issue . patients with breast cancer presenting with urinary symptoms should be examined",81,128,1.5802
pubmed-summarization,"ewing 's sarcoma family of tumors are a group of small round - cell neoplasms , which include ewing 's sarcoma ( ews ) , primitive neuroectodermal tumor ( pnet ) , askins tumor , pnet of the bone , and extraosseous ewing 's sarcoma ( ess ) . ewing 's sarcoma / peripheral primitive neuroectodermal tumor , presumed to be neuroectodermal in origin , most often occurs in the bone and soft tissues of children and young adults . the intracranial extraosseous ewing 's sarcoma ( cns - ess ) is extremely rare and often misdiagnosed as central nervous system pnet ( c - pnet ) or as other primary intracranial neoplasms . an 11-year - old female presented with a history of headache for one year , which increased in intensity over the last one month . she had repeated episodes of vomiting for one month and a left temporal scalp swelling , which was gradually increasing in size . on examination there was bilateral papilledema , but no other focal neurological deficits were detected . the left temporal scalp swelling was mildly tender , firm , immobile , and non - pulsatile with ill - defined margins . the computed tomography scan ( ct scan ) of the brain showed a rounded , well - defined , heterogeneously hyperdense , enhancing lesion in the left temporoparietal region , with a mass effect and destruction of the left temporal bone , extending into the scalp , suggesting the possibility of a meningioma . no evidence of calcification was noted within the lesion [ ] . magnetic resonance imaging ( mri ) of the brain showed a left temporal lesion , hypointense on t1 , heterointense on t2 , with heterogeneous enhancement [ ] . a significant mass effect was detected with a midline shift to the right , of 15 mm . preoperative ct scan of the brain showed a rounded , well - defined , heterogeneously hyperdense , enhancing lesion in the left temporoparietal region , with a mass effect and destruction of the left temporal bone extending into the scalp , suggesting the possibility of meningioma . no evidence of calcification was noted within the lesion preoperative mri of the brain showed a left temporal lesion","ewing 's sarcoma / peripheral primitive neuroectodermal tumors occur most often in bone and soft tissues of children and young adults . the intracranial manifestation of the disease is rare , and when present , this is often misdiagnosed with other varieties of primary brain tumors . we report such a case of extraosseous ewing 's sarcoma , which was initially suspected to be a case of meningioma in an 11-year - old girl .",380,75,0.1974
scientific_lay_summarisation-elife-norm,"The eQTLs summary-level data were obtained from eQTLGen Consortium (https: //www. eqtlgen. org/) or GTEx Consortium V8 (https: //gtexportal. org/), the details of which are presented in Supplementary file 1—Table 1. We identified common (minor allele frequency [MAF] >1%) eQTLs single-nucleotide polymorphisms (SNPs) significantly (p < 5. 0 × 10−8) associated with the expression of HMGCR or PCSK9 in blood, and the expression of NPC1L1 in adipose subcutaneous tissue as there are no eQTLs in blood or other tissues available at a significance level for NPC1L1. Only cis-eQTLs were included to generate genetic instruments in this study, which were defined as eQTLs within 1 Mb on either side of the encoded gene. Secondly, to validate the observed association using the eQTLs as an instrument, we additionally proposed an instrument by selecting SNPs within 100 kb windows from target gene of each drug that was associated with LDL cholesterol level at a genome-wide significance level (p < 5. 0 × 10−8) to proxy the exposure of lipid-lowering drugs. A GWAS summary data of LDL cholesterol levels from the Global Lipids Genetics Consortium (GLGC) with a sample size of 173,082 were used to identify these SNPs, where only common SNPs (MAF >1%) were included (Willer et al. , 2013; Supplementary file 1—Table 1). Seven SNPs within 100 kb windows from HMGCR gene were selected for proxying HMGCR inhibitors, 12 SNPs from PCSK9 gene identified for PCSK9 inhibitors, and 3 SNPs from NPC1L1 gene selected for NPC1L1 inhibitor. To maximize the strength of the instrument for each drug, SNPs used as instruments were allowed to be in low weak linkage disequilibrium (r2 < 0. 30) with each other. GWAS summary-level data for COVID-19 outcomes were obtained from the COVID-19 Host Genetics Initiative V4 with a sample size of 1,299,010 for COVID-19 susceptibility, 908,494 for COVID-19 hospitalization, and 626,151 for COVID-19 severe disease, respectively (https: //www. covid19hg. org/; COVID-19 Host Genetics Initiative, 2020; Supplementary file 1—Table 1). The study population was restricted to individuals with European ancestry, including meta-analyses of GWASs containing up to 22 cohorts from 11 countries. GWAS from these cohorts used a model adjusted for age, sex, age × age, age × sex, genetic principal components, and study-specific covariates. A COVID-19 case was confirmed by lab or self-reported infections, or electronic","The virus SARS-CoV-2 has caused millions of infections and deaths during the COVID-19 pandemic, but as of December 2021, no new drugs targeted to SARS-CoV-2 specifically exist. Thus, it is important to identify existing drugs that can reduce the infection and mortality of this virus, since repurposing old drugs is faster and cheaper than developing new ones. Fats, such as cholesterol, can play an important role in viral infections, meaning that drugs intended to lower the levels of fats in the blood could have a protective effect against SARS-CoV-2. To test this hypothesis, Huang, Xiao, et al. carried out a Mendelian randomization study to investigate if there is a link between drugs that lower fats and outcomes of SARS-CoV-2 infection, including susceptibility, hospitalization, and severe disease. This approach",380,128,0.3368
pubmed-summarization,"large elastic arteries in the central region and medium - sized muscular arteries have two functions , i.e. , they act as low resistance conduits and as flow pulsation buffers ( 1 ) . moreover , a reduction in buffering capacity may increase systolic blood pressure ( bp ) , left ventricular afterload , and pulsatile flow in capillary beds and reduce the diastolic contribution to blood flow in the coronary artery ( 2 ) . arterial stiffness is determined by the properties of the arterial wall matrix and by vascular smooth muscle tone , and may be changed immediately by an alteration in vascular smooth muscle tone caused by exercise ( 3 ) . exercise training - induced alterations in arterial stiffness would be of great benefit to those with coronary artery disease ( cad ) , and would potentially reduce myocardial oxygen demand and ischemic symptoms ( 4 ) . in the present study , we investigated the effect of short - duration exercise on arterial stiffness in patients with coronary artery disease , by repeatedly measuring brachial - ankle ( ba ) pulse wave velocity ( pwv ) ; an established non - invasive means of assessing arterial stiffness . fifty patients that underwent percutaneous coronary intervention ( cad group ) and 50 patients without a history of cardiovascular disease ( control group ) who were referred for treadmill testing by physicians mostly due to atypical chest pain , were prospectively enrolled . patients who were positive for myocardial ischemia on treadmill tests or those with comorbid conditions that limited exercise were excluded to ensure adequate exercise duration . thus , patients with residual ischemia after pci was excluded from cad group and patients with overt clinical coronary artery disease was excluded from control group . brachial - ankle pwv was measured using an automatic pwv measurement system ( form - pwv / abi , colin , komaki , japan ) in both brachia and ankles before treadmill exercise testing . this instrument simultaneously records bapwv , and brachial and ankle blood pressures on left and right sides , and provides an electrocardiogram and heart sounds . after baseline measurements , each subject performed symptom limited treadmill exercise testing according to the bruce protocol . at 10","arterial stiffness is an important contributor to the development of cardiovascular disease . we investigated the effect of short duration exercise using the treadmill test on arterial stiffness in the presence of coronary artery disease . we enrolled patients with and without coronary artery diseases ( cad and control group , 50 patients each ) referred for treadmill testing . brachial - ankle pulse wave velocity ( bapwv ) were measured before and after treadmill testing . values of bapwv were significantly reduced at 10 min after exercise in both groups , more in the cad group than in the control group ( baseline bapwv and post - exercise change [ cm / sec ] : 1,527245 and -132155 in the cad group , 1,439202 and -7793 in",380,128,0.3368
pubmed-summarization,"fundamental concepts in psychology and philosophy of the mind are the notion of sensation and perception . when a stimulus produces an effect on different sensory receptors it induces sensation . subsequent interpretation and organization of this sensory stimulus produce a meaningful experience of the world and of one 's perception . although in most cases perception is conscious , perception without awareness does exist , that is , the interpretation of semantic stimuli . normally wakefulness and awareness are related ; one has to be awake ; that is , there has to be a certain level of consciousness to be aware of something ; that is , there is content in consciousness . in states of deep sleep , anesthesia , and coma there is little or no wakefulness and hence no awareness . in drowsiness and light sleep however , in certain states , dissociations exist between wakefulness and awareness , such as in the vegetative state , when there is wakefulness presumably without awareness ( eyes open , brain shut ) . in the dream state there is awareness ( content in consciousness ) with decreased wakefulness ( level of consciousness ) . dreams are succession of images , ideas , emotions , and perceptions without sensations that occur involuntarily in the mind predominantly during rapid eye movement ( rem ) sleep . nonpulsatile subjective tinnitus is considered a phantom perception , the conscious awareness of a percept in the absence of an external stimulus . it is characterized by the perception that the phantom sound comes from an external sound source , even though the sound might be pulled from memory . this is reminiscent of a dream state , when there is awareness , with stimuli attributed to the external world but generated internally . whereas tinnitus can be considered a simple phantom percept , dreams could be considered complex phantom percepts , like hallucinations and hallucinosis . however , in contrast to hallucinations and hallucinosis that occur during wakefulness , dreams occur during certain stages of sleep . stimulus - evoked auditory cortical activation does not necessarily produce conscious auditory perception , and auditory perception is possible in the absence of auditory input : more than 80% of people with normal hearing perceive","there are pathophysiological , clinical , and treatment analogies between phantom limb pain and phantom sound ( i.e. , tinnitus ) . phantom limb pain commonly is absent in dreams , and the question arises whether this is also the case for tinnitus . a questionnaire was given to 78 consecutive tinnitus patients seen at a specialized tinnitus clinic . seventy - six patients remembered their dreams and of these 74 claim not to perceive tinnitus during their dreams ( 97% ) . this can be most easily explained by a predictive bayesian brain model . that is , during the awake state the brain constantly makes predictions about the environment . tinnitus is hypothesized to be the result of a prediction error due to deafferentation , and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The ancestral condition from which humans evolved is critical for understanding the adaptive origin of bipedal locomotion. The 4. 4 million-year-old hominin partial skeleton attributed to Ardipithecus ramidus preserves a foot that purportedly shares morphometric affinities with monkeys, but this interpretation remains controversial. Here I show that the foot of Ar. ramidus is most similar to living chimpanzee and gorilla species among a large sample of anthropoid primates. The foot morphology of Ar. ramidus suggests that the evolutionary precursor of hominin bipedalism was African ape-like terrestrial quadrupedalism and climbing. The elongation of the midfoot and phalangeal reduction in Ar. ramidus relative to the African apes is consistent with hypotheses of increased propulsive capabilities associated with an early form of bipedalism. This study provides evidence that the modern human foot was derived from an ancestral form adapted to terrestrial plantigrade quadrupedalism. Terrestrial bipedalism is widely regarded as a shared-derived characteristic of the hominin clade and understanding its evolution is one of the central foci of biological anthropology (Darwin, 1871; Wasburn, 1967; Fleagle et al. , 1981; Richmond et al. , 2001; Gebo, 1996; Begun, 2004; Lovejoy et al. , 2009a; White et al. , 2015). There are numerous adaptive explanations for the origin of bipedalism (Darwin, 1871; Hewes, 1961; Lovejoy, 1981; Rose, 1991; Washburn, 1960; Hunt, 1996) that are inherently difficult to test directly (Smith and Wood, 2017), but each of them depends on alternative hypothetical models for the morphology and locomotor behavior of the human-chimpanzee last common ancestor (LCA; Richmond et al. , 2001). Hypotheses for the locomotor behavior of the LCA include vertical climbing (Stern, 1975; Prost, 1980; Fleagle et al. , 1981), terrestrial knuckle-walking (Wasburn, 1967; Gebo, 1992; Gebo, 1996; Pilbeam, 1996; Richmond and Strait, 2000; Richmond et al. , 2001; Begun, 2004; Inouye and Shea, 2004), below-branch suspension (Keith, 1923; Tuttle, 1969; Young et al. , 2015), arboreal bipedality (Thorpe et al. , 2007), and more generalized quadrupedalism with slow, deliberate climbing (Lovejoy et al. , 2009a; White et al. , 2009; White et al. , 2015). These behavioral hypotheses make different assumptions about whether the LCA was adapted to arboreality or terrestriality (Wasburn, 1967; Gebo, 1996; Gebo, 1992; Schmitt, 2003; Crompton et al. , 2010). No matter the specific elements of the proposed behavioral hypothesis for","Walking on two legs is considered to be one of the first steps towards becoming human. While some animals are also able to walk on two legs, such as kangaroos, birds, and some rodents, the way they move is nevertheless quite distinct to the way humans walk. How animals evolve traits is influenced by the characteristics of their ancestors. But what exactly was the common ancestor of humans and chimpanzees like? Most primates are suited for a life in the trees. But some also have skeletal characteristics associated with living on the ground. For example, the feet of chimpanzees and gorillas show adaptations that suit life on the ground, such as walking on the sole of the foot with a heel first foot posture. So far, it was",380,128,0.3368
dialogsum,"#Person1#: Steward! #Person2#: Yes, ma'am? #Person1#: May I have a magazine or something? #Person2#: Certainly. Just a moment. I'll be right back with one. Which do you prefer, one in English or in Chinese? #Person1#: One in English, please. #Person2#: All right, ma'am.",Steward will bring #Person1# a magazine in English.,43,8,0.186
scientific_lay_summarisation-elife-norm,"velocity and are highly sensitive to contrast (O’Carroll 1993, Wiederman et al. , 2008,2013). One identified STMD, CSTMD1, responds selectively to a small, moving target, even when embedded within natural scenes (Wiederman and O' Carroll, 2011). CSTMD1 also exhibits a sophisticated form of selective attention. The neuronal response to the presentation of two simultaneously moving targets does not simply result in either neuronal summation or inhibition. Instead, CSTMD1 responds in a winner-takes-all manner, selecting a single target as if the distracter does not even exist (Wiederman and O' Carroll, 2013). We mapped CSTMD1’s receptive field by measuring spiking activity in response to a single, black, square target (1. 5°x1. 5°) moving along trajectories at varying spatial locations in the visual field. In one region, a gridded array (10 × 10) of short, vertical, target trajectories evoke weak neuronal responses (1A). For each short 200 ms trajectory, we plot mean spike rate over a 100 ms analysis window (from 50 to 150 ms). This colormap represents the spiking activity in response to short trajectories for each of the 100 corresponding spatial locations. In comparison, we present an identical square target moved along long, vertical trajectories (1B, Video 1) and segment responses at the same corresponding spatial locations as the short paths in 1A (mean spike rate over 100 ms bins). This reveals higher overall spiking activity in response to the long, continuous target trajectories. Here we investigate this effect of stimulus history by separating trajectories into components; a primer and a probe. Each elicit responses when presented alone, however, the probe’s initial response is affected by the gain induced by a preceding primer (1C). We note that neuronal responses build slowly over hundreds of milliseconds - a property we have previously termed facilitation (Nordström et al. , 2011). For the primer & probe condition (where a primer always precedes the probe stimulus) responses to the probe are facilitated (green region, cf. black with blue time courses). This facilitatory effect is not simply due to slow kinetics, as both responses have a rapid decay time course when the stimulus ends (Dunbier et al. , 2012). 10. 7554/eLife. 26478. 003Figure 1. CSTMD1’s receptive field mapped with drifting targets. (A) Small targets (black squares, 1. 5°x1. 5°) move along short trajectories (200 ms) that","Catching a ball requires a person to track the speed and direction of a small moving target often against a cluttered and varying background. Predatory insects, like dragonflies, face a similar challenge when they pursue their prey through the air. The task is made a little easier, however, by the fact that most moving targets tend to follow predictable trajectories. Indeed, animals are also better at tracking targets that follow smooth continuous trajectories, suggesting that brains have evolved to exploit the normal behavior of visual stimuli to reduce their workload To find out how this process works, Wiederman, Fabian et al. studied the brains of dragonflies as they watched a black square intended to mimic prey. Brain cells called Small Target Motion Detectors (or STMD neurons for short)",380,128,0.3368
scientific_lay_summarisation-elife-norm,"UV-reflective surface wax consisted of very long-chain methyl ketones and aldehydes, which have not been previously identified as major wax components. Comparative transcriptomics identified a gene encoding a member of the elongation of very long-chain fatty acids (ELOVL) protein family, whose expression was strongly correlated with the distribution of very long-chain methyl ketones on the surface of dragonflies. Notably, chemically synthesized 2-pentacosanone, the major component of the surface wax, spontaneously formed scale-like fine structures that strongly reflected UV light. These results provide a previously undescribed molecular and structural basis for wax-based body color change and UV reflection that has ecological and applied relevance. We compared the wax-based body color changes and UV reflection patterns of adult insects of O. albistylum using a high-sensitivity camera with a UV filter. UV reflection was hardly detected on the body surface of immature males and females (1B, D, G and I; Video 1). As sexual maturation proceeded, males accumulated whitish wax, mainly on their dorsal abdomen, which strongly reflected UV (1C, F, H and K; Video 1). It should be noted that in mature females, UV-reflective whitish wax was secreted on the ventral abdomen only (1D, F, I and K; Video 1). As adult aging proceeded further, not only males but also females developed pruinose wax on the entire body surface (1A), which resulted in considerable UV reflection even in females. Optical measurements of reflectance on both the dorsal and ventral abdominal regions were used for quantitative evaluation of sex- and stage-dependent changes in the adult insects of O. albistylum. Immature males and females mainly reflected light of above 500 nm in wavelength, and did not exhibit remarkable UV reflection (2A and D; — 1A and D; —source data 1; —source data 2). In mature males, reflectance increased, in particular of light of wavelengths below 600 nm, resulting in strong UV reflection on the dorsal abdomen and moderate UV reflection on the ventral abdomen (2B; — 1B; —source data 3; —source data 4). In mature females, by contrast, moderate UV reflection was observed on the ventral abdomen only (2E; — 1E; —source data 3; —source data 4). In aged males and females, reflectance increased to some extent on both the dorsal and the ventral sides of the abdomen (2C and F; — 1C and","Humans have often looked to nature for answers to problems. Living things has evolved for millions of years to deal with life’s challenges, and so engineers and inventors faced with similar challenges can also take inspiration from the natural world. Several plants and animals, for instance, reflect ultraviolet light. This ability may protect them from some of the damaging effects of sunlight; materials with similar properties would have a range of uses, including as coatings on windows that protect our homes and furniture or as cosmetics that protect ourselves in the same way. Some dragonflies – including the white-tailed skimmer, which is particularly common in Japan – are partly coated with a wax that reflects both ultraviolet and visible light. These insects can also see ultraviolet light, which",380,128,0.3368
scientific_lay_summarisation-elife-norm,"rates of biochemical processes (Block, 2007). During the mechanochemical cycle, each kinesin head transitions between one or more states that are strongly bound to the MT (the ATP-containing state, and also the no-nucleotide state), and one or more states that are weakly bound to the MT (the ADP-containing state) (Block, 2007). A simplified version of this cycle (1A) may arbitrarily be taken to begin with the one-head-bound (1-HB), ATP-waiting state [α], where the nucleotide-free front head is strongly bound to the MT while the rear, ADP-bound tethered head remains unbound (Hackney, 1994; Asenjo and Sosa, 2009; Guydosh and Block, 2009; Toprak et al. , 2009). Following ATP binding to the MT-bound head, the NL of its motor domain undergoes a structural reconfiguration and forms a β-sheet with the head, in a process termed NL docking (Rice et al. , 1999; Schnitzer et al. , 2000; Rosenfeld et al. , 2001; Asenjo et al. , 2006; Tomishige et al. , 2006; Khalil et al. , 2008; Sindelar and Downing, 2010; Clancy et al. , 2011). NL docking shifts the position of the tethered head towards the MT plus-end, beyond the position of the bound head [β1, β2]. Recent work has suggested that NL docking may occur in two stages: first, ATP binding induces a load-dependent mechanical transition, leading to partial NL docking [β1], whereas subsequent ATP hydrolysis completes the docking and enables the tethered head to bind the MT [β2] (Milic et al. , 2014). Once the bound head hydrolyzes ATP, fully docks its NL, and the tethered head binds the MT, the motor enters a mechanically strained, two-heads-bound (2-HB) state [γ] (Rice et al. , 1999; Rosenfeld et al. , 2003; Block, 2007; Yildiz et al. , 2008; Gennerich and Vale, 2009; Clancy et al. , 2011). Finally, rear-head release (Klumpp et al. , 2004) completes the step and returns the motor to its initial 1-HB waiting state [α], primed to begin the cycle anew, after having translocated forward by one step (8. 2 nm) along the MT. The processivity of kinesin—evinced by the ability of a single dimer to undergo >100 consecutive stepping cycles before dissociation—relies upon a tight coordination of the biochemical and mechanical events, collectively known as gating mechanisms (Block, 2007). 10. 7554/eLife. 07403. 003Figure 1. A","In cells, molecules are moved from one location to another by motor proteins. Kinesins are a large family of such motors that transport their cargos along long filaments known as microtubules. Most kinesin molecules are formed from two identical protein chains. Each chain has a motor region at one end (called the head) that can attach to microtubules. The other end of each protein chain wraps around its partner to form a common stalk region (called the tail) that links to the cargo being carried. The two kinesin heads are connected to the tail via a ‘neck linker’ region, and they advance along the microtubule in strict alternation, similar to the way our legs move when walking. During each step, the front head remains tightly associated with the",380,128,0.3368
dialogsum,"#Person1#: How many people are there in your family? #Person2#: My immediate family is quite small. It's just my older step-brother, my mom, my step-dad and me. how about you? #Person1#: I have a large family. I have three older sisters, my twin sister, a younger brother, and parents. #Person2#: I didn't know you were a twin! Are you identical or fraternal? #Person1#: We're identical. I mean, we look exactly the same, but we are complete opposites when it comes to everything else. #Person2#: Interesting. It must be great having a twin sister. Are you best friends, too? #Person1#: We used to be really close, but that all changed once she moved to Shanghai. How about your family? You didn't mention to your biological father. #Person2#: I don't know much about him. He died when I was just a baby. Even though I don't have a blood relationship with my step-father and step-brother, I consider them to be my real family. #Person1#: What about your step-brother's mother? Does he keep in touch with her? #Person2#: No, she also died when my step-brother was little. My mother and my step-father met each other shortly after my father died and became good friends. They ended up getting married a few years later. #Person1#: Sounds like it was meant to be.","#Person2# has a step-brother, a step-dad, and #Person2#'s mom. #Person2#'s mom and #Person2#'s step-father met after #Person2#'s father died and got married later. #Person1# has a big family including an identical sister who looks the same as #Person1# but is different from #Person1# in every aspect.",218,46,0.211
pubmed-summarization,"therapy can improve outcomes . eculizumab ( soliris ) was approved by food and drug administration ( fda ) in september 2011 for patients refractory to pex . mortality rate before that was 67% and has gone down a lot where four out of five patients are able to come off dialysis . to note , end - stage renal disease was the major cause of death in people surviving initial hospitalization with ahus ( 5 ) . it has always been a dilemma to differentiate ahus from ttp . in the past , traditionally , ttp is the diagnosis when there is an involvement of central nervous system ( cns ) , and ahus is the diagnosis when renal impairment is predominant . now it is known that both these entities are in fact different disorders with distinct characteristics . therefore , clinically , patients with ttp may have renal dysfunction and those with ahus may develop cns manifestations . even though , it is now possible to differentiate these two disorders , we still do not have the capability to differentiate them at presentation . hence , initial treatment for both these disorders is same , that is , pex therapy . although a severe deficiency of the adamts13 protease ( < 510% ) and documented mutations of complement proteins are not required for the diagnosis of acquired ttp and ahus , respectively , both findings in the appropriate clinical context serve to confirm the clinical diagnosis . , the two conditions were found to be secondary to completely different mechanisms as explained above . eculizumab was approved by fda in 2011 for ahus and has become the gold standard therapy for this . but it still remains a challenge to differentiate them and the decision has to be made on clinical judgment . adamts13 can differentiate in most of the conditions but takes days to weeks to come back depending on the location . meanwhile , starting therapy as soon as possible is really necessary to improve survival outcomes . c3 , c4 , and ch50 can not be used because they are very non - specific and can be abnormal in a lot of situations . ttp seems to cause more severe thrombocytopenia , and ahus","thrombotic thrombocytopenic purpura ( ttp ) is a rare multisystem microvascular disorder , which is characterized by pentad of thrombocytopenia , microangiopathic hemolytic anemia , and organ dysfunction due to occlusive thrombi . the proposed pathophysiology involves an imbalance between unusually large von willebrand factor multimers and the cleaving protease adamts13 . acute pancreatitis is a well - described consequence of ttp , but ttp secondary to acute pancreatitis is a rare phenomenon . we present a patient who developed ttp due to post - ercp pancreatitis with hematologic , cardiovascular , pulmonary , and renal complications and is the first case of this kind . despite early initiation of therapy , the patient did not recover making it among the 10% of cases of ttp that prove",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142, we utilized a novel reporter and a loss-of-function mouse allele that we have recently generated. In this study, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Genetic ablation of miR-142 caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterized a network of miR-142-3p targets which collectively control actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal hemostasis. microRNAs (miRNAs) are single-stranded RNA molecules of 22 nucleotides in length, processed from endogenous hairpin transcripts. miRNAs provide cells with a sequence-based silencing mechanism through base-pairing of a minimal recognition sequence, called the miRNA ‘seed’ (Bartel, 2009; Carthew and Sontheimer, 2009; Fabian et al. , 2010). miRNAs control hematopoiesis and the function of both lymphoid and myeloid progeny (Chen and Lodish, 2005; Lawrie, 2007; Garzon and Croce, 2008; Navarro and Lieberman, 2010). For example, in vivo studies uncovered roles for miR-451 in erythropoiesis (Patrick et al. , 2010; Rasmussen et al. , 2010; Yu et al. , 2010), for miR-223 in granulopoiesis (Johnnidis et al. , 2008), for miR-150 in the commitment of multipotent myeloerythroid progenitors (Lu et al. , 2008), and for miR-155 in the mammalian immune system (Rodriguez et al. , 2007; Thai et al. , 2007; Mann et al. , 2010; O' Connell et al. , 2010,2007). Megakaryocytes (MKs) display a distinctive miRNA expression pattern (Garzon et al. , 2006; Opalinska et al. , 2010; Xu et al. , 2012). However, functional genetic studies dissecting the role of miRNA in megakaryopoiesis are still limited. In the present work, we focused on miR-142, a hematopoietic-specific miRNA, which resides in a genomic locus that was previously associated with t (8; 17) translocation in B-cell leukemia (Gauwerky et al. , 1989). Pioneering experimental evidence has suggested miR-142 involvement in lymphocyte","DNA carries all the information needed for life. This includes the codes required for making proteins, as well as instructions on when, where, and how much of these proteins need to be produced. There are a number of ways by which cells control protein manufacturing, one of which is based on small RNAs called microRNAs. Before proteins are assembled, the DNA molecule is copied into a temporary replica dubbed messenger RNA. microRNAs are able to recognize specific messenger RNA molecules and block protein production. microRNAs serve a very important regulatory role in our bodies and are involved in virtually all cellular processes, including the production of all classes of blood and immune cells. Platelets seal injuries and prevent excessive bleeding by creating a clot at the location of",380,128,0.3368
dialogsum,"#Person1#: This business of having to be a role model, where you can never relax, hang loose, can you? #Person2#: Well, I can't exactly go to hang with my friends at some of the places we used to go to, and just basically raise hell and have a whole bunch of fun. I can't do that any more because it's not good for the public to see that. It's not good for me. #Person1#: Your father said you have the ability to be one of the biggest influences in history, not just golf, humanity. What do you think of that? #Person2#: I think that is more important than just my golf. I think my golf is merely a vehicle to influence people #Person1#: How? #Person2#: How? Oh, so many kids look up to role models, so I can help out kids in a positive way, I can influence their lives in a positive way, and I think that's what it's about. #Person1#: I mean you are only 21, what's the goal? Where do you go? #Person2#: Keep winning. #Person1#: But you know, at a certain point, doesn't lose its thing...? #Person2#: Winning never gets old and having fun never gets old either. And you always have fun. #Person1#: And playing these tournaments is with all the apprehension and everything, still fun? #Person2#: Always. The day it's not fun is the day I quit And it's been fan since I was in the high chair. And it's fun today.",#Person2# can't hang out with friends like before because what #Person2# does will influence the kids and #Person2# tells #Person1# that #Person2#'s goal is to keep winning because winning never gets old just like having fun.,248,36,0.1452
pubmed-summarization,"many stroke patients with stroke have a balance problems while standing because they tend to put their weight on their non - paralyzed lower limb to increase swing of their upper body1 . falling accidents due to such decline in balance ability is on the increase annually . even when there is no injury from falling , frequent falling can sufficiently disrupt physical and social activities2 . because deterioration of muscular strength and balance ability increases the risk of falling , it is significantly important to perform exercises to promote upper limb muscular strength and training for balance3 . regular exercise of walking and for muscular strength and balance may increase muscular strength and balance to prevent falling of patients4 . walking , in particular , is known to be a safe type of aerobic exercise for patients , having the merit that it can be performed gradually by considering appropriate intensity , frequency , period , and phases of exercise for abilities of each patient5 . recently efficiency of walking training using a treadmill has attracted more attention as when such training has been reported to have better effects than walking on even ground . some researchers reported that walking on a treadmill is effective in improving balance and walking ability6 , 7 . with recent developments of relevant computer programs , new methods of rehabilitation exercise such exercises can increase interest and participation of patients in treatment and improve their significant functions by enabling them to perform various forms of tasks appropriate for goals of individual patients in virtual reality . virtual reality indicates a type of interactive simulation using computer hardware and software , in which users can have close - to - reality experiences8 . virtual reality training using visual feedback enables the participants to undergo the training while seeing their movements with their own eyes , a feature that helps them adjust their inaccurate body center caused by body image damage suffered by most stroke patients . in addition , training serves as a catalyst in active participation and performance of tasks by inducing interest and pleasure , providing immediately visual feedback on the result to enhance motor education ability9 . many recent researches of virtual reality games with higher accessibility reported that such games","[ purpose ] the purpose of this study is to investigate the effects of virtual reality training using nintendo wii on balance and walking for stroke patients . [ subjects and methods ] forty stroke patients with stroke were randomly divided into two exercise program groups : virtual reality training ( n=20 ) and treadmill ( n=20 ) . the subjects underwent their 40-minute exercise program three times a week for eight weeks . their balance and walking were measured before and after the complete program . we measured the left / right weight - bearing and the anterior / posterior weight - bearing for balance , as well as stance phase , swing phase , and cadence for walking . [ results ] for balance , both",380,128,0.3368
dialogsum,"#Person1#: You like living in New York, don't you? #Person2#: Oh, I love it. It's so convenient. I can take the bus to work or the subway or a taxi. And there's so much to do. #Person1#: I know what you mean. I'd like to live in the city, but living in the suburbs is better for Michelle. Trees, grass. There are a lot of good things about suburban living. #Person2#: I grew up in suburbs, remember? So I know. But, as a working woman, I think New York has all the conveniences, including the best tomatoes. #Person1#: The truth is, Michelle has lived in suburbs for more than ten years. It is very hard for her to leave her friends. #Person2#: I don't think so. Michelle is at the right age. There are lots of things for her here. #Person1#: But I'm afraid that she cannot adapt herself to the new environment. #Person2#: Don't worry. It is never too late to learn or change. #Person1#: OK, I will think about it.",#Person2# loves living in New York because it's convenient but #Person1# is afraid that Michelle cannot adapt herself to the city life. #Person2# assures #Person1# Michelle is at the right age.,172,31,0.1802
dialogsum,"#Person1#: Hey, is your sister coming to dinner tonight? #Person2#: No, she isn't. She has to work late on Fridays. #Person1#: Well, did you invite our neighbor Don? #Person2#: Nope. He's out of town this week. #Person1#: So does that mean it's just us for dinner? #Person2#: Yeah. Is that a problem? #Person1#: No... It's just that we always have dinner together. I was hoping that we could have some company for once. #Person2#: Well, I'm sorry to let you down. But I did make pizza, so I hope you can at least appreciate that.",#Person1# is down because #Person2#'s sister and Don cannot come to dinner. #Person2# comforts #Person1# with pizza.,95,17,0.1789
pubmed-summarization,"regulation of gene expression is fundamental for the coordinate synthesis , assembly and localization of the macromolecular structures of cells . this is achieved by a multi - step program that is highly interconnected and regulated at diverse levels ( . it starts in the nucleus , where transcription factors bind to specific dna sequences proximal to the genes they regulate and recruit rna polymerases for rna synthesis . as soon as rna precursors are formed , they get covered by a host of proteins forming ribonucleoprotein complexes . messenger rna - binding proteins ( mrbps ) associate with nascent mrna precursors and mediate diverse rna processing reactions including 5-end capping , splicing , editing , 3-end cleavage and polyadenylation . the transcripts are subsequently exported through nuclear pores to the cytoplasm where they may undergo localization to subcellular regions by complexes consisting of motor proteins and rbps or by the signal recognition particle . the transcripts assemble with translation factors and ribosomes for protein synthesis , which is controlled by global or transcript - specific mechanisms . the fate and location of proteins can be further controlled through modification of specific amino acids , cleavage by site - specific proteases and degradation through the proteasome . see text for details . besides many classical biochemical and genetic studies that revealed factors involved in and regulating these diverse steps in the gene expression program , the recent development of genome - wide analysis tools like dna microarrays allowed fundamental new insights into the systems architecture of gene regulatory programs . for instance , dna microarrays have been extensively used to study transcriptional programs by comparing steady - state rna levels between diverse cell types and stages , and by the mapping of binding sites for dna - associated proteins through chromatin immunoprecipitation ( so - called chip - chip assays ) . integration of these data allowed the description of complex transcriptional regulatory networks , involving large sets of genes that control coherent global responses in physiological and developmental programs . in contrast , less is known about the systems architecture that underlies the post - transcriptional steps in the gene expression program ( although many rna regulatory processes also occur co - transcriptionally , we further classify them as","abstract.post-transcriptional regulation of gene expression plays important roles in diverse cellular processes such as development , metabolism and cancer progression . whereas many classical studies explored the mechanistics and physiological impact on specific mrna substrates , the recent development of genome - wide analysis tools enables the study of post - transcriptional gene regulation on a global scale . importantly , these studies revealed distinct programs of rna regulation , suggesting a complex and versatile post - transcriptional regulatory network . this network is controlled by specific rna - binding proteins and/or non - coding rnas , which bind to specific sequence or structural elements in the rnas and thereby regulate subsets of mrnas that partly encode functionally related proteins . it will be a future challenge to",380,128,0.3368
dialogsum,"#Person1#: Can I help you? #Person2#: Yes, I'd like to read some articles that are on reserve about British culture. #Person1#: Professor Grand's class? #Person2#: That's right. How could you know? #Person1#: Let's just say you are not the first person coming in asking for those articles. #Person2#: Oh, well, seeing as how I haven't read any of them yet, it doesn't really matterwhich one you give me first. #Person1#: I'm afraid I can't give you any of them at the moment. They've all been checked out. #Person2#: You're joking, all of them? #Person1#: Every month. I've asked professor Grand twice already to bring in additional copies of the articles, but no sooner do I place them on the shelves than they are gone. See that girl in the black sweater? She's been waiting for half an hour for those same articles to be returned. #Person2#: And here's me. I went out of my way to free out the whole afternoon to read. #Person1#: I'm sorry, but there is not a whole lot I can do about it. All I can suggest is that you come in first thing tomorrow morning and try again. We open at eight.",#Person2# wants to read some articles for Professor Grand's class. #Person1# says they have all been checked out and suggests that #Person1# come in first thing tomorrow morning and try again.,198,31,0.1566
dialogsum,"#Person1#: Yeah, but you guys don't stay with the same classmates all day, right? #Person2#: Right. The people in your math class might not be the people you have science with. #Person1#: So, you sent out invitations to your whole graduating class? #Person2#: Yep. And the date is set for homecoming night. #Person1#: I thought homecoming was a high school dance. #Person2#: It's a football game the school team plays at home. The dance and reunions are usually that night, too.",#Person2# tells #Person1# about sending out invitations to the whole graduating class for the homecoming night.,81,16,0.1975
pubmed-summarization,"major depressive disorder ( mdd ) is the most common mood disorder with a significant effect on the progression of medical conditions.1 factors accompanying depression , such as patients ' failure to look after their health , inability to adapt to their environment , social dissociation , chronic stresses of life , cigarette smoking , reduced physical activity , inappropriate nutrition and poor compliance with medical advice , make depression one of the risk factors of noncommunicable diseases.2 in addition to the effect of depression on lifestyle , the direct effect of depression on metabolic factors has been shown in many studies.3 recently , a relationship has been observed between depression and serum levels of lipoproteins and apolipoproteins ( apo ) , which are known risk factors of obesity and cardiovascular diseases.4 one theory of this relationship suggests a disturbance in function of the serotonergic system . in addition , metabolic changes in patients with mdd are due to genetic changes in the coding of serum lipoproteins.5 other theories describe changes in interleukin 2 , number of total tcells , melatonin and other cytokines in depressed patients.6 - 8 despite these studies , controversy exists about the relationship between depression and the lipid profile . studies have shown different results for the level of apo a one of the highdensity lipoprotein cholesterol ( hdlc ) subgroups , and of apo b the major protein of lowdensity lipoprotein cholesterol ( ldlc ) , in patients with mdd.4,9,10 sevincok and sarandol showed that the serum level of apo a in depressed patients was lower than that in control group.4,9 another study showed no significant difference in the serum levels of apolipoproteins between depressed patients and the control group.11 the lack of evidence and controversial results of previous studies led us design this study to compare the serum levels of apolipoproteins in depressed patients and normal individuals . a population of 153 patients with mdd ( 63 women , 90 men , aged 2147 years ) in 2007 were included in this case control study . all the patients were diagnosed with mdd according to the structured clinical interview ( scidi ) for diagnostic and statistical manual of mental disorders , fourth edition ( dsmiv ) . relatives of hospitalized patients and hospital","objective : to investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease.introduction:little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein.methods:this case control study included 153 patients with major depressive disorder who fulfilled the criteria of the diagnostic and statistical manual of mental disorders , fourth edition ( dsmiv ) , and 147 healthy individuals . all participants completed a demographic questionnaire and hamilton rating scale for depression . anthropometric characteristics were recorded . blood samples were taken and total cholesterol , high and lowdensity lipoproteins and apolipoproteins a and b were measured . to analyze the data , ttest , 2 test , pearson correlation test and",380,128,0.3368
dialogsum,"#Person1#: are you still coming to my place for dinner tomorrow night? #Person2#: of course. Is the dinner still on? #Person1#: yes, I was just wondering how you and your roommate were planning on coming to my place. #Person2#: we were planning on walking both ways since the weather is still nice. #Person1#: that's what I thought you would do. Listen, I live in a bit of a rough neighborhood. It's just down the street from all the bars. You probably don't want to be walking around after dark. #Person2#: it can't be that bad. #Person1#: I wish it wasn't, but there is actually a lot of crime and prostitution around here. #Person2#: really? I never would have guessed. The criminals must only come out in the evenings, because I've never noticed anything strange when I've been at your house in the daytime. #Person1#: do me a favor, and take a taxi. It'd make me feel a lot better. #Person2#: ok, we will. How do you get around in the evenings? #Person1#: when I first moved in, I walked everywhere. But within a week, I had my purse stolen, just a block away from the police station! Now, I always take public transportation. #Person2#: has anything else happened to you? #Person1#: nothing else has happened to me, but I have seen quite a few fights on the streets after the bars close. #Person2#: well, we'll be careful. Thanks for letting me know.",#Person2# plans to walk to #Person1#'s home with roommates but #Person1# advises to take a taxi because the neighborhood is not safe enough. #Person1# also shares #Person1#'s personal experience of having the purse stolen and witnessing fights on the streets.,242,40,0.1653
scientific_lay_summarisation-elife-norm,"Subcellular asymmetry directed by the planar cell polarity (PCP) signaling pathway orients numerous morphogenetic events in both invertebrates and vertebrates. Here, we describe a morphogenetic movement in which the intertwined socket and shaft cells of the Drosophila anterior wing margin mechanosensory bristles undergo PCP-directed apical rotation, inducing twisting that results in a helical structure of defined chirality. We show that the Frizzled/Vang PCP signaling module coordinates polarity among and between bristles and surrounding cells to direct this rotation. Furthermore, we show that dynamic interplay between two isoforms of the Prickle protein determines right- or left-handed bristle morphogenesis. We provide evidence that, Frizzled/Vang signaling couples to the Fat/Dachsous PCP directional signal in opposite directions depending on whether Pkpk or Pksple predominates. Dynamic interplay between Pk isoforms is likely to be an important determinant of PCP outcomes in diverse contexts. Similar mechanisms may orient other lateralizing morphogenetic processes. PCP signaling controls the polarization of cells within the plane of an epithelium, orienting asymmetric cellular structures, cell divisions and cell migration. In flies, PCP signaling controls the orientation of trichomes (hairs) on the adult cuticle, orientation of ommatidia in the eye, and orientation of cell divisions, though the full range of phenotypic outputs has not been explored. While much focus has been placed on mechanistic studies in flies, medically important developmental defects and physiological processes in vertebrates are also under control of PCP signaling, motivating mechanistic studies in flies that might inform similar studies in vertebrates. Defects in the core PCP mechanism result in open neural tube defects, conotruncal heart defects, deafness, situs inversus and heterotaxy (reviewed in Butler and Wallingford, 2017; Henderson et al. , 2018; Blum and Ott, 2018). PCP is also believed to participate in both early and late stages of cancer progression and in wound healing. PCP polarizes skin and hair, the ependyma and renal tubules. Paralogs of the PCP component Prickle are mutated in an epilepsy-ataxia syndrome (Tao et al. , 2011; Mei et al. , 2013; Bassuk et al. , 2008; Ehaideb et al. , 2014; Paemka et al. , 2015). Mutations in ‘global’ PCP components have been associated with a human disorder of neuronal migration and proliferation (Zakaria et al. , 2014) and in developmental renal disorders (Zhang et al. , 2019). Work in Drosophila indicates","Our right and left hands are mirror images of each other and cannot be precisely superimposed. This property, known as chirality, is vital for many tissues and organs to form correctly in humans and other animals. For example, fruit flies have hair-like sensory organs on the edges of their wings known as bristles. One of the cells in each bristle forms a shaft that generally tilts away from the main body of the fly and is anchored in place by another cell known as the socket. A signaling pathway known as PCP signaling controls the directions in which many chiral tissues and organs in animals form. The pathway contains two signaling modules: the global module collects “directional” information about the orientation of the body and sends it to",380,128,0.3368
dialogsum,"#Person1#: Shall we sing with a karaoke? #Person2#: Great idea! I do it every so often. #Person1#: For us, karaoke is becoming a popular entertainment. #Person2#: Yep. If you are a good singer, your audience will feel comfortable, right? #Person1#: I can not agree with you more. And if you are an awful one, that will be funny. #Person2#: I remembered Tom is always out of tune. We burst into laughter. #Person1#: Is that true? Shall we invite him to join with us? #Person2#: So tricky!","#Person1# and #Person2# plan to sing karaoke, and #Person1# wants to invite Tom because tom is funny.",86,17,0.1977
dialogsum,"#Person1#: Do you like the apartment? #Person2#: I absolutely love the apartment. #Person1#: Everything is okay? #Person2#: I do have one problem with the apartment. #Person1#: What ' s the problem? #Person2#: I don ' t like all those stains in the carpet. #Person1#: We will have the carpet cleaned before you move into the apartment. #Person2#: I did not know that. #Person1#: I assure you that we will, and if there are any more problems, feel free to tell me. #Person2#: That was the only thing that I saw wrong with the apartment. #Person1#: I ' m glad to know that you think the apartment is so nice. #Person2#: It ' s absolutely incredible. I ' ll take it.",#Person2# loves the apartment but doesn't like all those stains in the carpet. #Person1# promises to clean the stains so #Person2# will take it.,120,24,0.2
scientific_lay_summarisation-elife-norm,"The TIM22 complex mediates the import of hydrophobic carrier proteins into the mitochondrial inner membrane. While the TIM22 machinery has been well characterised in yeast, the human complex remains poorly characterised. Here, we identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it’s C-terminus exposed to the intermembrane space. Tim29 is required for the stability of the TIM22 complex and functions in the assembly of hTim22. Furthermore, Tim29 contacts the Translocase of the Outer Mitochondrial Membrane, TOM complex, enabling a mechanism for transport of hydrophobic carrier substrates across the aqueous intermembrane space. Identification of Tim29 highlights the significance of analysing mitochondrial import systems across phylogenetic boundaries, which can reveal novel components and mechanisms in higher organisms. Mitochondria cannot be created de novo and pre-existing mitochondria are used as templates for mitochondrial biogenesis. This genesis requires the ~1500 different mitochondrial proteins to be imported via dynamic translocation machines to one of four subcompartments of the organelle – outer and inner membrane, intermembrane space and matrix (Chacinska et al. , 2009; Stojanovski et al. , 2012; Dolezal et al. , 2006; Harbauer et al. , 2014; Neupert and Herrmann, 2007; Baker et al. , 2014). The Translocase of the Outer Membrane (TOM) complex is described as the general entry gate to mitochondria and provides a passageway through which precursors can cross the outer membrane. The mitochondrial inner membrane contains two translocase machines that are responsible for the import of a large fraction of the mitochondrial proteome; the Translocase of the Inner Membrane 23 (TIM23) complex and the Translocase of the Inner Membrane 22 (TIM22) complex. The TIM23 complex typically transports proteins that possess a matrix-targeting N-terminal presequence (Chacinska et al. , 2009; Neupert and Herrmann, 2007; Wagner et al. , 2009; Mokranjac and Neupert, 2010), while the TIM22 complex mediates the inner membrane insertion of multi-transmembrane spanning proteins that contain internal targeting elements (Chacinska et al. , 2009; Neupert and Herrmann, 2007; Rehling et al. , 2004; Koehler, 2004). Substrates of the TIM22 complex include the mitochondrial carrier family, such as the ADP/ATP carrier (AAC) and the phosphate carrier (PiC), and multispanning inner membrane proteins like, Tim17 and Tim23 (subunits of the TIM23 complex) and Tim22 itself (pore","Mitochondria are like tiny bean-shaped “power stations” that provide our cells with the vast majority of the energy that they need. These structures, however, are not self-sufficient and instead rely on proteins and chemicals that are imported from elsewhere in the cell. Two layers of membrane enclose the mitochondria, and transporting proteins across the inner and outer membranes requires large molecular machines embedded within the membranes. One such complex, the TIM22 complex, organizes tunnel-like carrier proteins that in turn ferry chemicals across the inner membrane to fuel metabolism. The TIM22 complex is vitally important as it allows mitochondria to adapt their metabolism – that is, how and when they generate energy – to match the cell’s needs during development. Yet, while the TIM22 complex has been studied extensively",380,128,0.3368
dialogsum,"#Person1#: Medicine Industry, this is Peter Bush speaking, can I help you? #Person2#: Good afternoon, could you connect this call with Mr. Brown, please #Person1#: May I know who's calling? #Person2#: This is Li Ping of ABC computer company limited. I'm calling on our Mr. Wilson the general manager of our company. #Person1#: I'm sorry, Mrs. Li, Mr. Brown is now in a meeting.May I have your number, and ask him to call you back later? #Person2#: I'm afraid Mr. Wilson would like to speak to Mr. Brown right now.He ' s got an urgent matter to discuss with Mr. Brown without delay. #Person1#: Ok, then would you please hold the line? Mr. Li, the line is through, Mr. Brown is ready answering the call, go ahead. #Person2#: Thank you for your assistance, Mr. Bush. #Person1#: You are welcome.",Mrs. Li phones Medicine Industry since Mr. Wilson's got an urgent matter to discuss with Mr. Brown. Mr. Bush helps with it.,139,22,0.1583
pubmed-summarization,"it consists of a pair of cylindrically shaped centrioles surrounded by fibrous pericentriolar material . before or during dna replication in s phase , the centrioles split , and each cylinder serves as a template for the assembly of a new daughter centriole . before mitosis , when cells contain two pairs of centrioles , each pair serves as a nucleation center for microtubules of the spindle apparatus . defects in centrosome assembly or in centrosome separation can result in defective nucleation of spindle microtubules , and in several cases , in the formation of monopolar spindles and mitotic arrest ( sunkel et al . several years ago , evidence was published that defective centrosome assembly can prevent cells from entering s phase . in particular , removal of the centrosome by microsurgery or by laser ablation resulted in a cell cycle arrest , as did inhibition or silencing of several centrosome - associated proteins , such as dynactin , parp-3 , centriolin , or akap450 ( hinchcliffe et al . , 2001 ; khodjakov and rieder , 2001 ; quintyne and schroer , 2002 ; augustin et al . , 2003 ; gromley et al . , 2003 ; keryer et al the mechanism leading to this centrosome - dependent cell cycle arrest in g1 phase has been unclear ; it was proposed that a checkpoint control would prevent those cells with imperfect centrosomes from continuing the cell cycle , to prevent the assembly of defective spindles later in mitosis ( murray , 2001 ) . in this study , we followed cell cycle progress after inhibition of centrosome assembly by depleting the pericentriolar proteins pericentriolar material 1 ( pcm-1 ) and pericentrin . these proteins have been shown to be necessary for the assembly of other centrosomal constituents ( dictenberg et al . , 1998 ; dammermann and merdes , 2002 ; kubo and tsukita , 2003 ) . we found that depletion of pcm-1 or pericentrin activates the p38-dependent stress pathway and the p53-dependent cell cycle checkpoint . we have previously shown that depletion of the protein pcm-1 leads to defects in the assembly of the centrosomal components centrin , ninein , and pericentrin , and to an altered organization of the microtubule network in interphase cells","previous evidence has indicated that an intact centrosome is essential for cell cycle progress and that elimination of the centrosome or depletion of individual centrosome proteins prevents the entry into s phase . to investigate the molecular mechanisms of centrosome - dependent cell cycle progress , we performed rna silencing experiments of two centrosome - associated proteins , pericentriolar material 1 ( pcm-1 ) and pericentrin , in primary human fibroblasts . we found that cells depleted of pcm-1 or pericentrin show lower levels of markers for s phase and cell proliferation , including cyclin a , ki-67 , proliferating cell nuclear antigen , minichromosome maintenance deficient 3 , and phosphorylated retinoblastoma protein . also , the percentage of cells undergoing dna replication was reduced by > 50%",380,128,0.3368
dialogsum,"#Person1#: Linda, would you care for some candies or cookies? #Person2#: No, don't try to tend me. I'm becoming chubby, and I have to slender down. #Person1#: You are not really chubby. You are actually thin enough. #Person2#: I don't think so. I know I've put on weight this winter. #Person1#: So you are watching your weight, aren't you? #Person2#: Yes, to tell you the truth. I am on the diet.",#Person1# invites Linda for some candies or cookies. Linda refuses because she is on the diet.,71,16,0.2254
dialogsum,"#Person1#: We have a variety of trousers. Which one do you like best? #Person2#: I want to buy one to match my shirt. Can you give me some advice? #Person1#: What about this one? #Person2#: Yes,they seem to be my size and go with my shirt quite well. I will take it.",#Person2# buys a pair of trousers with #Person1#'s assistance.,52,9,0.1731
scientific_lay_summarisation-elife-norm,"media (1. 6% agar, USP grade, Thermo Fisher Scientific) with revised Hutner’s trace elements (Kropat et al. , 2011) at 22°C in low light (~10–20 µmol photons m−2 s−1). Lines harboring the ClpP1 repressible gene were maintained in the media supplemented with 100 µg ml−1 spectinomycin (Sigma). Lines harboring a mutagenic cassette disrupting the MARS1 gene were maintained in the media supplemented with 20 µg ml−1 paromomycin (Sigma). Lines harboring a MARS1 transgene construct were maintained in the same conditions with solid media supplemented with 20 µg ml−1 hygromycin (Thermo Fisher Scientific). Sulfur-depleted TAP liquid and agar pates were prepared as previously described (Davies et al. , 1994). Generally, during liquid growth, no antibiotic was supplemented. For the experiments shown in — 2A–C, TAP liquid cultures and agar plates were supplemented with 5 µg/ml or 0. 2 µg/ml tunicamycin (EMD Millipore), respectively. All strains used in this study are listed in Table 1. The cpUPR reporter strain (CrPW1) was generated by nuclear transformation of the C. reinhardtii ClpP1 repressible strain (DCH16; Ramundo et al. , 2014), using 300 ng of Nde1-linearized pPW3217 plasmid Table 2 for plasmids used in this study). Nde1 and all the other restriction enzymes described in this publication were purchased from NEB. The nuclear transformation was carried out via electroporation as described below (section on ‘Insertional mutagenesis’). Transformants isolated on TAP agar plates containing 20 µg ml−1 hygromycin and tested by Flag immunoblot analysis upon ClpP1 repression and exposure to HL. As previously observed (Ramundo et al. , 2014; Ramundo et al. , 2013), during random insertion of a construct with regulatory regions in its promoter, less than 10% of the hygromycin resistant transformants preserved the correct gene expression pattern of the downstream coding sequence. Among them, we selected CrPW1 for further studies. The pPW3217 plasmid, containing a minimum region of the VIPP2 gene promoter, its 5’ untranslated region and its first exonexon intrintrone yellow fluorescent protein coding sequence (YFP CDS), C-terminally appended to a triple Flag epitepitope the 3’ untranslated region of the RBCS2 gene, was generated by In-Fusion cloning (Clontech). The VIPP2 genomic fragment was amplified from genogenomic with primers SR510 and SR502 (see Table 3 for primers used in this study). The YFP CDS fused to a 3x-Flag epitope was amplified from pLM005","Life on Earth crucially depends on photosynthesis, the process by which energy stored in sunlight is harnessed to convert carbon dioxide into sugars and oxygen. In plants and algae, photosynthesis occurs in specialized cellular compartments called chloroplasts. Inside chloroplasts, complex molecular machines absorb light and channel its energy into the appropriate chemical reactions. These machines are composed of proteins that need to be assembled and maintained. However, proteins can become damaged, and when this occurs, they must be recognized, removed, and replaced. When exposed to bright light, the photosynthetic machinery is pushed into overdrive and protein damage is accelerated. In response, the chloroplast sends an alarm signal to activate a protective system called the “chloroplast unfolded protein response”, or cpUPR for short. The cpUPR leads to the production",380,128,0.3368
dialogsum,"#Person1#: hi, Natasha, how's life? #Person2#: great. My family came to visit me. #Person1#: oh, you must be very happy. How many people are there in your family? #Person2#: my immediate family is very large. It's my mother, my father, my two older brothers, my younger sister and me. #Person1#: I have a small family. They are my parents, my younger brother and me. #Person2#: I thought you were the only child in the family. Didn't China practice the only-child policy in the early 1980s? #Person1#: yes, it did. But my parents are ethnic minority people. It's a preferential policy for an ethnic minority family to have two children. #Person2#: interesting. What do you think about families with only one child? #Person1#: the child must feel very longly. My younger brother is 10 years younger than me. Before he was born, I used to be the only child and always dreamed that I would have a younger sister or brother one day. #Person2#: do you get along well with each other? #Person1#: yes, we are very close. He is 12 years old and very smart. He always makes us laugh a lot. #Person2#: you are very lucky to have such a nice family. #Person1#: thank you.",Natasha tells #Person1# her family came to visit her. Then they talk about their family. Natasha's immediate family is very large. #Person1# has a small family including a 12-year-old brother.,206,30,0.1456
dialogsum,"#Person1#: How time flies! The winter holidays are coming next week. #Person2#: Yes, do you have any plans? #Person1#: Certainly. I want to go to Egypt. What about you? #Person2#: I'm afraid I can go nowhere. I failed my English exam. You know my parents are so strict with me. #Person1#: Bad luck! #Person2#: I see. Is Egypt an African country? Is it far? #Person1#: Yes, it's in Africa and quite far. But it's not only the Pyramids that I want to see but the Aswan Dam. #Person2#: You want to see? #Person1#: Of course. I'll go there by boat on the Nile. #Person2#: That'll be wonderful and interesting. How will you get there? #Person1#: By air - by flight No. CA808. My sister works on it. And then I'll be treated as a king! #Person2#: Don't be so proud. I'll be off now. I wish you a good trip. #Person1#: Oh, sorry. I didn't mean that. I don't want to hurt you...","#Person1# is going to Egypt to see Pyramid and Aswan Dam by flight during the winter holidays, while #Person2# cannot go anywhere because #Person2# failed the English exam.",163,28,0.1718
dialogsum,"#Person1#: May I help you, sir? #Person2#: Yes, please. I want to buy a personal gift for my brother. He's taking a trip to South America. #Person1#: Is he going by ship or plane? #Person2#: He,s flying. My gift will have to be something light in weight. What can you suggest? #Person1#: What about this tie? It's made of pure silk. #Person2#: My sister already gave him one. I'd like something unusual. Let me look around...oh, that clock looks nice, but... #Person1#: Hey,here is a gift for the man who has everything. #Person2#: Oh,a folding toothbrush! That's a wonderful idea! I'll take it.",#Person1# helps #Person2# to choose a gift for his brother and #Person1#'ll take a folding toothbrush.,103,16,0.1553
dialogsum,"#Person1#: Carmen, please help me. I'm going on a trip to San Francisco for 6 days with my parents, and I have 4 suitcases. #Person2#: Four suitcases? Why do you need so much? #Person1#: I just started taking all my favorite clothes out of the cupboard, and, well, it just happened. #Person2#: OK. Let's talk about this. First of all, San Francisco is full of hills and you'll be walking a lot, so these leather shoes have to go. So do these beach shoes. You should bring the hiking shoes instead. #Person1#: You're right. #Person2#: Now, let's see what we can arrange with two skirts, this black one and this dark green one, a yellow blouse, one gray, one light blue. Take a narrow belt and a wide one, and you're set for anything. #Person1#: Hey, you're working magic. #Person2#: A pair of jeans. And you're ready, except for underwear. #Person1#: You're so great. In just a few minutes, you've solved my problem.",#Person1# got over-packed for a trip to San Francisco so Carmen's helping #Person1# take out unnecessary items.,163,17,0.1043
dialogsum,"#Person1#: May I help you? #Person2#: Give me six-piece chicken nuggets, a large fries, and a large coke. #Person1#: You will need to wait a few minutes for fries. They're still in the fryer. #Person2#: That's fine. #Person1#: Your total comes to 7 dollars. #Person2#: Here's 20. #Person1#: Thank you. Your cash back is 13 dollars. Pull into a parking states, and we'll bring you your fries in two minutes. #Person2#: Thanks.",#Person2# buys some food and drink in the parking lot with #Person1#'s assistance.,72,13,0.1806
pubmed-summarization,"the detection and quantification of tumour - specific rearrangements are important issues in cancer research and in clinical diagnosis of tumours . in particular , its significance became obvious for haematological malignancies that exhibit characteristic translocations in specific tumour subgroups . although gene rearrangements are typical for haematological malignancies , they also may occur in solid tumours as characteristic changes . this has been shown for ret / ptc rearrangements in papillary thyroid carcinoma ( ptc ) that fuse the ret proto - oncogene to a variety of constitutively expressed partner genes ( for review see zitzelsberger ) . this was further improved by the development of fluorescence in situ hybridization ( fish ) techniques that allows a cytogenetic analysis of rearrangements on metaphase spreads as well as on interphase cell nuclei . multicolour fish approaches such as spectral karyotyping ( sky ) allowed a more detailed analysis of cytogenetic aberrations , in particular in the case of complex and hidden rearrangements . the analysis of interphase nuclei by fish has the advantage that gene rearrangements can be investigated at single cell level in nonproliferating cells . an evaluation of fish signals is usually performed by visual inspection directly from the microscopic image . in this case , cell numbers for further statistical analysis and a possible bias of the investigator towards positivity or negativity of fish signals indicating the rearrangement are major limitations . in order to analyse a statistically relevant number of cells , an automatic scanning system for fluorescence spot counting using a fully motorized fluorescence microscope with an eight - slide scanning stage and a high - resolution ccd camera driven by the metacyte software ( metasystems , altlussheim , germany ) has been established and optimized . to demonstrate routine application of the scanning system , the ret / ptc rearrangement in papillary thyroid carcinomas has been scored with a probe set that produces split fish signals if a gene rearrangement is present . therefore , the parameters of the scanning system had to be optimized using cell culture models as positive and negative controls . the aims of the present study were to establish such optimised scanning parameters and to characterise chromosomal and ret / ptc rearrangements in a ptc cohort . primary cell","structural genomic rearrangements are frequent findings in human cancers . therefore , papillary thyroid carcinomas ( ptcs ) were investigated for chromosomal aberrations and rearrangements of the ret proto - oncogene . for this purpose , primary cultures from 23 ptc have been established and metaphase preparations were analysed by spectral karyotyping ( sky ) . in addition , interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation ( fish ) for the presence of ret / ptc rearrangements using ret - specific dna probes . sky analysis of ptc revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20 , 21 , and 22 . fish analysis for ret / ptc rearrangements showed prevalence of this",380,128,0.3368
pubmed-summarization,"supported by nci 2p50 ca09825806 , nci u01 ca168394 , stand up to cancer / aacr dream team translational cancer research grant su2c - aacr - dt0209 , tcga gdac grant ( nih / nci u24 ca143883 ) to gbm ; mdacc uterine spore career development award ( nci p50ca098258 ) to lwt .","pik3r1 ( encoding the p85 subunit of phosphatidylinositol 3-kinase ) is the 11th most frequently mutated gene across tumors . we recently reported neomorphic p85 mutants that induce signaling cascades not predicted by the canonical functions of p85 , suggesting the need to functionally annotate specific mutations in cancer genes for effective genome - informed personalized therapy .",54,58,1.0741
scientific_lay_summarisation-elife-norm,"(Ranger et al. , 2013), and behavioural state (Slater et al. , 2006) influence noxious-evoked responses, large sample sizes are often required to account for between-subject variability (Anand et al. , 2004; Ancora et al. , 2013; Hartley et al. , 2018; Kabataş et al. , 2016; Sindhur et al. , 2020; Taddio et al. , 2006). In adult studies, cross-over trial designs are often used to minimise sample sizes by reducing between-subject variability (Cooper et al. , 2016). However, this approach may not be appropriate when studying pain in neonates as painful medical procedures can only be performed when clinically necessary and within-subject variables that influence pain can change dramatically across sequential test occasions. One approach used to balance demographic characteristics or other prognostic factors across treatment groups in clinical trials is to stratify neonates across treatment arms and to adjust for these factors in the statistical analysis (McEntegart, 2003). While this can improve comparability across groups for recognised factors, many unknown variables likely influence pain sensitivity, and a more nuanced approach to account for individual differences in noxious-evoked sensitivity could be more effective in reducing sample sizes. In analgesic studies performed in adults, individual pain thresholds can be identified by applying graded increments of experimental stimulus intensity until pain is reported by the participants. This can be used to stratify treatment groups (Demant et al. , 2014; Smith et al. , 2017; Vollert et al. , 2017) or statistically correct for variability in baseline pain thresholds (Lane et al. , 2010; Sanga et al. , 2013). In neonates, application of graded non-noxious stimuli such as von Frey hairs has previously been used to identify limb reflex withdrawal thresholds (Andrews and Fitzgerald, 2002; Andrews and Fitzgerald, 1999; Andrews and Fitzgerald, 1994; Kühne et al. , 2012), but these have not been used as a baseline measure in analgesic clinical trials. In the absence of a validated objective biomarker of pain (Davis et al. , 2020), electroencephalography (EEG) -derived measures of brain activity may provide a valuable surrogate marker of pain by measuring the noxious-evoked activation of the cortex. In adults, brain activity during painful procedures is strongly correlated with verbal reports (Coghill et al. , 2017); and in neonates, a template of noxious-evoked brain activity that discriminates between noxious","Hospitalized newborns often undergo medical procedures, like blood tests, without pain relief. This can cause the baby to experience short-term distress that may have negative consequences later in life. However, testing the effects of pain relief in newborns is challenging because, unlike adults, they cannot report how much pain they are experiencing. One way to overcome this is to record the brain activity of newborns during a painful procedure and to see how these signals are modified following pain relief. Randomized controlled trials are the gold standard for these kinds of medical assessments, but require a high number of participants to account for individual differences in how babies respond to pain. Finding ways to reduce the size of pain control studies could lead to faster development of pain",380,128,0.3368
pubmed-summarization,"case of damaged blood vessels in inflamed tissues . chronic inflammation may lead to hypoxia of variable severity in the damaged tissues and , accordingly , to increased production of polyclonal erythroid progenitors and red blood cells in an effort to improve cell and tissue oxygenation . conversely , hypoxia can lead to increased production of inflammatory cytokines : individuals with mountain sickness present with elevated levels of inflammatory cytokines in peripheral blood , and healthy volunteers exposed to a hypoxic environment ( three nights in high altitude above 3400 meters ) presented with a high level of interleukin- ( il- ) 6 . patients with chuvash polycythemia associated with homozygous germline mutation in the von hippel - lindau ( vhl ) gene , a major actor of the hypoxia sensing pathway , present with elevated levels of tumor necrosis factor- ( tnf- ) and interferon- ( ifn- ) . inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis also provide evidence of cross talk between hypoxia and inflammation . in rheumatoid arthritis , hypoxia - inducible factor- ( hif- ) 2 is the hif isoform that plays a major role in inflammation , notably by inducing expression of il-6 and tnf- . importantly , hif-1 plays an essential role in survival and function of myeloid cells during inflammation . if the initial injury persists , the inflammation response and associated chronic stimulation of hematopoiesis are prolonged , and the risk of dna alteration increases in cells from the damaged tissues or / and in overstimulated hematopoietic progenitors . over time the acquisition of genetic defects in the inflamed tissues or / and hematopoietic progenitors may eventually lead to the development of solid cancer or / and clonal hematopoiesis and hematological malignancy ( ) . in fact , all types of solid and blood cancers , including mpns , are accompanied by some degree of chronic inflammation chronic inflammation is an early event in many types of cancers and in certain lymphoma but in mpns , the possibility that chronic inflammation precedes the acquisition of the main mpn mutations is a new subject of research . whatever its chronology , chronic inflammation facilitates further dna alteration in cancer and adjacent cells , and targeting inflammation and its causes should","myeloproliferative neoplasms ( mpns ) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages . recent advances in the biology of mpns have greatly facilitated their molecular diagnosis since most patients present with mutation(s ) in the jak2 , mpl , or calr genes . yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of mpns are not fully elucidated . importantly , chronic inflammation has long been associated with mpn disease and some of the symptoms and complications can be linked to inflammation . moreover , the jak inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the just-noticeable difference (JND). The PSE corresponded to the speed at which the two scenes were perceived as moving equally fast. Therefore, PSEs higher than the actual speed of the reference scene indicated speed underestimation, whereas PSEs lower than the speed of the reference scene indicated speed overestimation. The JND corresponded to the smallest detectable difference between two different speeds. High JNDs indicated low discrimination sensitivity, whereas low JNDs indicated high discrimination sensitivity. 10. 7554/eLife. 00031. 003Figure 1. Experimental design and time course of trials. (A) Experiments 1 and 3: for each trial, the first scene was presented for 700 ms, which included a 100-ms fade-in phase at the beginning and a 100-ms fade-out phase at the end. The second scene was presented 300 ms after the end of the first scene and had the same temporal structure as the first one. Participants had to fixate a central cross for the whole duration of the trial. The order of presentation of the reference and test scene was randomized. (B) Experiments 2 and 4: three driving sessions (i. e. , one per target speed) were performed in random order for experiment 2, and one session for experiment 4. Before each test session, the drivers performed a training phase in which a numerical feedback indicated the driving speed when it did not match the target speed (white digits at the bottom of the screen, left panel). In each training phase, the drivers had to drive a total of 5 min at target speed. In addition, at the beginning of each test trial, the scene was shown for 7 s moving at target speed with clear visibility (memory refresher). : http: //dx. . org/10. 7554/eLife. 00031. 003 The contrast of the scene was reduced either in a distance-dependent manner, as would happen in natural fog, or in a distance-independent manner, as has been done in previous experiments. The difference between these two types of contrast reduction is represented in 2B and C. Moderate and severe levels of reduction were implemented for each type of contrast alteration. Importantly, for each level of reduction, the overall visual contrast was the same for distance-dependent and distance-independent alteration (Root mean square [RMS] contrast = 0. 31 for moderate visibility reduction and 0. 19 for severe visibility reduction,","The ways people respond to conditions of reduced visibility is a central topic in vision research. Notably, it has been shown that people tend to underestimate speeds when visibility is reduced equally at all distances, as for example, when driving with a fogged up windshield. But what happens when the visibility decreases as you look further into the distance, as happens when driving in fog? Fortunately, as new research reveals, people tend to overestimate their speed when driving in fog-like conditions, and show a natural tendency to drive at a slower pace. Pretto et al. performed a series of experiments involving experienced drivers and high-quality virtual reality simulations. In one experiment, drivers were presented with two driving scenes and asked to guess which scene was moving faster. In",380,128,0.3368
dialogsum,"#Person1#: Good morning, City Taxi. #Person2#: Good morning. I'd like to book a taxi to the airport for Saturday morning, please. #Person1#: Where from? #Person2#: I'm at Garden Hotel in Union Street. There will be three of us sharing. How much will it be? #Person1#: About 60 dollars. #Person2#: 60 dollars? Each of between us? #Person1#: Oh, that's all together. What time do you want to leave? #Person2#: Seven in the morning. #Person1#: Right! We'll pick you up at your hotel at seven then. #Person2#: Thank you very much. Goodbye.",#Person1# helps #Person2# to book a taxi to the airport on Saturday morning for 60 dollars.,90,16,0.1778
scientific_lay_summarisation-elife-norm,"MalQ are involved in the degradation of the glycogen particle to Glc1P (Colleoni et al. , 1999; Seibold and Eikmanns, 2007; Wilson et al. , 2010). Finally, the very large majority of circulating C. trachomatis strains contain a 7. 5 kb plasmid. Loss of this plasmid is associated with decreased GlgA expression and impaired glycogen accumulation (Carlson et al. , 2008). 10. 7554/eLife. 12552. 003Figure 1. Glycogen accumulation in C. trachomatis inclusions. (A) Glycogen metabolism in bacteria. In green: glycogen synthesis. In blue: glycogen degradation. Glc1P is the substrate of GlgC for ADP-Glc synthesis. GlgA (glycogen synthase) produces linear glycogen chains via α-1,4 glycosidic bonds, and the branching enzyme (GlgB) introduces branches through α-1,6 linkages. Glycogen depolymerization in Glc1P is the result of the activity of GlgP (glycogen phosphorylase), GlgX (debranching enzyme) and MalQ (4-α-glucanotransferase). The phosphoglucomutase MrsA converts Glc1P to Glc6P. The arrows point to the site within the polysaccharide that is subjected to enzymatic activity. Genes for all these enzymes are present in C. trachomatis. (B) HeLa cells were infected for 30 hr with C. trachomatis. Glycogen was visualized by TEM after PATAg stain. Grey arrows point at glycogen. Green arrows point at examples of EBs and red arrows at RBs. The picture on the bottom shows an enlargement of the boxed region containing three EBs. Scale bars: 1 µm (top), 200 nm (bottom). (C, D) Cells were Glc-deprived 48 hr prior to infection. 10 mg/ml Glc were added 24 hpi and cells were (C) fixed immediately or (D) 4 hr after Glc administration. Note that no glycogen is detectable in the bacteria while it is highly abundant in the inclusion lumen. Scale bar: 1 µm. : http: //dx. . org/10. 7554/eLife. 12552. 00310. 7554/eLife. 12552. 004Figure 1— 1. Relocation of glycogen stores to the inclusion during infection. Cells were (A) non-infected, or infected with C. trachomatis for (B) 24 hr or (C) 48 hr, fixed in PFA and processed for PAS stain. (D) Enlargement of the boxed region in (B) Note that glycogen particles (white arrowheads) are still detected in cells infected for 24 hr but not later, while inclusion glycogen content strongly increases with infection time. Black arrowheads point to examples of inclusions. Scale bar: 10 µm. : http: //dx. . org/10. 7554/eLife. 12552. 00410. 7554/eLife.","Chlamydia trachomatis is the most common sexually transmitted bacteria that causes disease. Infections often do not produce any obvious symptoms, but can lead to infertility or other severe problems if left untreated. This microbe is also the leading cause of blindness by an infectious agent. The bacteria grow in the human body by infecting host cells. Inside these cells, the bacteria are found inside compartments known as inclusions, which protect them from the host’s defense responses and enable them to create a comfortable environment for themselves. However, this comes at a cost because the bacteria lose immediate access to the nutrients in the rest of the host cell. Thus, C. trachomatis has developed ways to import these nutrients into inclusions, and, more generally, to take the control of",380,128,0.3368
dialogsum,"#Person1#: Can you fix the time for the next meeting, Alex? How about June twelfth that's after the trade exhibition? #Person2#: I thought something was happening on that day, Rebecca. #Person1#: Oh, yes. You're right. The people from head office are coming. #Person2#: What time does the airplane arrive? Can we have the meeting in the morning? #Person1#: No, it's all arranged. I'm meeting them at 10:30, so I won't be available at all that day. #Person2#: Well, let's have the meeting earlier in June then. The trade exhibition finishes on the third, doesn't it? #Person1#: Yes, but we need John's sales report for the meeting. How is it going? #Person2#: I'm afraid John hasn't started yet. The figures won't be in place till next week. #Person1#: Will it be ready early in June? #Person2#: Well, not really. He told me that he will finish them by June tenth. #Person1#: So we're looking at the week starting the seventeenth. How about 2 o'clock on that day? #Person2#: I think that's OK. Let's meet here again then.",Rebecca and Alex try to fix the time for the next meeting. They need John's sales report which won't be finished until June tenth. They finally decide to meet at 2 o'clock on June 17th.,176,35,0.1989
dialogsum,"#Person1#: Would you like to drink some coffee? #Person2#: No, thanks. I have some trouble with my heart, my doctor recommend I to drink less. #Person1#: Would you like to try some watermelon juice? It tastes good. #Person2#: All right",#Person1# help #Person2# order drinks.,40,5,0.125
dialogsum,"#Person1#: Mark? What were you up to yesterday? I called you, but there wasn't anybody home. #Person2#: We went out to the stadium. Bob hadn't been to a game for a few weeks. #Person1#: How'd it go? Did we win? #Person2#: Nope, lost again. But, it was a good game.",Mark tells #Person1# that he went to the stadium for a game yesterday.,50,13,0.26
scientific_lay_summarisation-elife-norm,"1983). Furthermore, a combination of meropenem and Clav showed significant bactericidal activity against drug-resistant strains of Mtb (Hugonnet et al. , 2009). In view of this, there is an imminent need to investigate the mechanisms of action of β-lactams in combination with Clav against Mtb, and the potential development of resistance by the pathogen against this combination. In other bacteria, β-lactams directly interact with enzymes involved in PG synthesis. This is likely to result in killing of the pathogen through multiple mechanisms, including the induction of autolysin pathway, holin: antiholin pathway, DNA damage, and alterations in physiology (e. g. TCA cycle and oxidative stress) (Tomasz, 1974; Rice et al. , 2003; Miller et al. , 2004; Kohanski et al. , 2007; Lobritz et al. , 2015). The complex effects of β-lactams on both PG biosynthesis and other processes indicate that the response to β-lactams could be mediated either through direct sensing of β-lactam molecules or by their effects on bacterial physiology. In Staphylococcus aureus, a transmembrane protease (BlaR1) senses β-lactam concentrations by direct binding through an extracellular domain, which activates its intra-cytoplasmic proteolytic domain resulting in cleavage of the β-lactamase repressor, BlaI, and induction of β-lactamase expression (Gregory et al. , 1997). It has been shown that Mtb expresses a homolog of BlaR1 (encoded by Rv1845c, blaR), which modulates the activity of BlaC by regulating the BlaI repressor in a manner analogous to S. aureus BlaR1-BlaI couple (Sala et al. , 2009). However, BlaR orthologues in all mycobacterial species lack the extracellular sensor domain involved in binding with β-lactams (Sala et al. , 2009), indicating that mechanisms of antibiotic sensing and BlaC regulation are likely to be distinct in Mtb. Furthermore, how β-lactams influence mycobacterial physiology (e. g. redox balance and primary metabolism) remains unknown. Therefore, insights on how the presence of β-lactams is conveyed in Mtb to activate appropriate adaptation response are key to combating resistance and developing novel therapies. In this work, we generated a system-scale understanding of how AG affects mycobacterial physiology. Exploiting a range of technologies, we explained mechanistically that the efficacy of AG is partly dependent upon the redox physiology of Mtb. Furthermore, we have rationally described the role of a redox-responsive transcription factor, WhiB4, in regulating the tolerance of Mtb to AG during infection.","A bacterium called Mycobacterium tuberculosis causes tuberculosis in humans. Multiple antibiotics are available to treat this infection, yet around one million people still die from tuberculosis each year. One of the reasons that the number of deaths is so high is because many M. tuberculosis cells have become resistant to these drugs. Therefore, new drug treatments are urgently needed to tackle the disease. When cells are under stress – for example, when a bacterial cell is exposed to an antibiotic – they can increase the production of chemicals known as reactive oxygen species. These chemicals are vital to many processes in cells, but if their levels get too high they can kill cells by damaging DNA and other molecules. To prevent this damage, bacterial cells produce molecules, such",380,128,0.3368
dialogsum,"#Person1#: Hi, Ben. Here are the top ten of this week's top chart. #Person2#: Oh, great! #Person1#: Which is your favorite in this ten? #Person2#: I like No. 4. #Person1#: You mean Sweet Heart. #Person2#: Yes. In fact, I think it's much better than this week's No. 1. #Person1#: What do you think about Cold Wind? #Person2#: I like it as well, but I don't think it's as good as Sweet Heart. #Person1#: So No. 4 is your favorite. Which one don't you like? #Person2#: Well. I don't like Your Lips very much. #Person1#: Why? #Person2#: I think it's too slow makes me sleepy. In fact, it's the worst in this week's top ten, if you ask me. #Person1#: Really? But it's my favorite.",#Person1# and #Person2# are talking about the top ten of this week's top chart. #Person2# likes No.4 best while #Person1#'s favorite is Your Lips.,124,24,0.1935
scientific_lay_summarisation-elife-norm,"When pathogens enter the host, sensing of environmental cues activates the expression of virulence genes. Opposite transition of pathogens from activating to non-activating conditions is poorly understood. Interestingly, variability in the expression of virulence genes upon infection enhances colonization. In order to systematically detect the role of phenotypic variability in enteropathogenic E. coli (EPEC), an important human pathogen, both in virulence activating and non-activating conditions, we employed the ScanLag methodology. The analysis revealed a bimodal growth rate. Mathematical modeling combined with experimental analysis showed that this bimodality is mediated by a hysteretic memory-switch that results in the stable co-existence of non-virulent and hyper-virulent subpopulations, even after many generations of growth in non-activating conditions. We identified the per operon as the key component of the hysteretic switch. This unique hysteretic memory switch may result in persistent infection and enhanced host-to-host spreading. Bacterial populations spontaneously differentiate into distinct phenotypic states (Avery, 2006; Dubnau and Losick, 2006). This variability has been described as a bet-hedging strategy that results in subpopulations that will survive under unpredictable stress (Fraser and Kaern, 2009). It has also been suggested that phenotypic variability is a ‘division of labor’ strategy: essentially, the bacterial population diversifies in order to utilize nutrients more efficiently or to allow invasion and colonization of diverse niches in the host (Ackermann et al. , 2008). Diversification upon infection is also related to antigenic variation, which is a key strategy to eluding the acquired immune response of the host (Kamada et al. , 2015; Stewart et al. , 2011). The role of phase-variation mechanisms in phenotypic diversification through reversible genetic changes is well established (see for example, Casadesús and Low, 2013; McClain et al. , 1991; Silverman and Simon, 1980). Diversification processes, not linked to DNA alteration have been attributed to noise in gene expression that can be further amplified by regulatory motifs such as excitatory dynamics (Süel et al. , 2006) positive feedback leading to bi-stability (Ozbudak et al. , 2004) and ultrasensitivity (Temme et al. , 2008; Rotem et al. , 2010; Levine et al. , 2012). Interestingly, phenotypic diversification in microorganisms is frequently accompanied by growth rate variability. One striking example is that of bacterial persistence under antibiotic treatment (Lewis, 2000) mediated by growth rate bimodality (Balaban et al. , 2004; Brauner et","Bacteria typically cope with harsh and changing environments by activating specific genes or accumulating those mutations that change genes in a beneficial way. Recently, it was also shown that the levels of gene activity can vary between otherwise identical bacteria in a single population. This provides an alternative strategy to deal with stressful conditions because it generates sub-groups of bacteria that potentially already adapted to different environments. Bacteria that enter the human body face many challenges, and this kind of pre-adaptation could help them to invade humans and overcome the immune system. However, this hypothesis had not previously been tested in a bacterium called enteropathogenic E. coli, which infects the intestines and is responsible for the deaths of many infants worldwide. Ronin et al. show that cells in",380,128,0.3368
dialogsum,"#Person1#: Oh, I'm exhausted. #Person2#: Why are you so tired? What did you do today? #Person1#: There were so many things to do. #Person2#: Did you do all those things all yourself? #Person1#: Oh, yes. I had to. I had to check the new products. I had to hold the meeting with the department managers. I had to listen to their reports and give my comments. That's my job, you know. #Person2#: Well, it sounds like you really had to do all those things. But you shouldn't work too hard. Do you know what you should do at the moment? #Person1#: What? #Person2#: Take some time off. #Person1#: Go on holiday? #Person2#: To relax yourself. How about having a trip this weekend? #Person1#: And to have a picnic? #Person2#: Yes. #Person1#: Great!",#Person2# advises #Person1# to have a picnic on the weekend to be free from exhausting work.,132,16,0.1212
dialogsum,"#Person1#: Good morning, Madam! Can I help you? #Person2#: Well, I'd like to buy a watch. #Person1#: Oh, look at these two watches, aren't they lovely? #Person2#: Yeah. But I think I'd prefer. . . #Person1#: How about this one? It's graceful in style. #Person2#: Mm, yes, but I think I like that one better. It's made of gold, isn't it? #Person1#: Sure. #Person2#: How much is it? #Person1#: 500 dollars, Madam. #Person2#: I wonder if it keeps good time. #Person1#: Surely. As this is the latest model, and you can also set the alarm. #Person2#: How do I set it? #Person1#: Just do like this. Very simple. #Person2#: All right. this suits my taste best. I'II take It.",#Person2# wants to buy a watch. She prefers a gold watch. #Person1# shows how to set the alarm and #Person2# buys it.,119,22,0.1849
dialogsum,"#Person1#: Isn't he the best instructor? I think he's so hot. Wow! I really feel energized, don't you? #Person2#: I swear, I'm going to kill you for this. #Person1#: What's wrong? Didn't you think it was fun? ! #Person2#: Oh, yeah! I had a blast! I love sweating like a pig with a bunch of pot bellies who all smell bad. Sorry, I'm just not into this health kick. #Person1#: Oh, no, get off it. It wasn't such a killer class. You just have to get into it. Like they say, no pain, no gain. #Person2#: I am wiped out. Thank you. #Person1#: Look, next time get yourself some comfy shoes. You're gonna come back again with me, aren't you? #Person2#: Never! But thank you for inviting me. #Person1#: Come on. You'll feel better after we hit the showers.","#Person1# thinks the instructor's the best, but #Person2# isn't into this health kick. #Person1# advises #Person2# to get comfy shoes but #Person2# doesn't want to come back again.",139,28,0.2014
dialogsum,"#Person1#: What do you do in summer? #Person2#: I love going out into the countryside for walks or bike ride. I love being out in the fresh summer air. How about you? #Person1#: I don't often go for walks, but I either play sports outside-you know, tennis or badminton-or just sit in the sunshine and read a good book. #Person2#: What do you do in winter? #Person1#: Well, I play sports indoors quite often. If I'm feeling lazy, I just watch a film at home. I prefer summer to winter. #Person2#: I think most people do. I like wearing nice, colorful clothes in summer, you know, a nice dress or skirt. It's too cold for those kinds of clothes in winter. #Person1#: Yes. I like wearing shorts in summer. My legs would freeze! #Person2#: Do you think we'll have a nice summer this year? #Person1#: Thanks to global warming, it could be hotter than ever!","In summer, #Person2# loves going for walks in the countryside while #Person1# enjoys playing sports outside. In winter, #Person1# plays sports indoors often or watch films at home. They both prefer summer to winter.",155,34,0.2194
dialogsum,"#Person1#: Help! That man stole my bag! #Person2#: Don't chase him. It's dangerous because the train is moving and you could fall in front of it. I'll call the police. You should go to tell the man at the ticket counter what happened. The counter is next to the parking lot. #Person1#: Thanks. Could you drive me home? My car keys were in my bag. #Person2#: Of course. Was your wallet in your bag too? #Person1#: No, luckily my wallet is in my pocket. Oh no, I just remembered my camera was in my bag!","#Person1# tells #Person2# #Person1#'s bag was stolen, and #Person2# suggests going to tell the man at the ticket counter.",95,19,0.2
scientific_lay_summarisation-elife-norm,"only in jawless vertebrates, whereas Immunoglobulin (Ig) genes are only in jawed vertebrates. However, both jawed and jawless vertebrates have a lymphocyte-based adaptive immune system suggesting that the genetic programs necessary for lymphocyte development originated in a common ancestor before the antigen receptor genes. Cytidine deaminases are expressed by lymphocytes in both jawed and jawless vertebrates and may have originated in a common ancestor; activation-induced cytidine deaminase (AID) and cytosine deaminase (CDA). Structures of prototypic VLRB (Top, PDB: 3e6j) and IgG (Bottom, PDB: 1Igt) are shown to the right, along with cartoons of their secreted forms. Regions of antigen recognition are shaded in blue or green. In red are the concave antigen binding residues of VLR and the complementarity determining regions (CDRs) of Ig. : http: //dx. . org/10. 7554/eLife. 07467. 003 The germline VLRB gene is incomplete because the invariant 5′ and 3′ coding sequences are separated by non-coding intervening sequences (Pancer et al. , 2004). Several of the hundreds of leucine rich repeat (LRR) -encoding genes flanking the VRLB gene are copied into the gene to generate an in-frame, functional VLRB gene during lymphocyte development (Nagawa et al. , 2007; Rogozin et al. , 2007; Alder et al. , 2008). This generates a VLRB repertoire with diversity comparable to Igs (Alder et al. , 2005). VLRB encodes for single-chain, crescent-shaped proteins that bind to antigens with a concave surface composed of multiple LRR β-strands and a C-terminal variable loop (LRRCT) (Kim et al. , 2007; Han et al. , 2008; Herrin et al. , 2008; Velikovsky et al. , 2009; Kirchdoerfer et al. , 2012; Deng et al. , 2013; Luo et al. , 2013). In contrast, Igs consist of a heavy and a light chain, each of which contributes three complementarity determining region loops to form a structurally distinct antigen-binding site (). To probe the VLRB response to IAV, we collected blood from lamprey larvae immunized three times with inactivated, purified prototypic H1N1 PR8 IAV. Polyclonal VLRB primarily migrates on an SDS-PAGE gel as disulfide-linked multimers under non-reducing conditions and as monomers in the presence of reducing agents (Alder et al. , 2008; Herrin et al. , 2008). As seen previously (Alder et al. , 2005), monitoring plasma VLRB by immunoblotting revealed that unlike mammalian Ig, where","Influenza viruses infect ten of millions of people each year. To conquer a flu infection, the human immune system develops antibodies that hasten recovery and prevent future flu infections. Unfortunately, flu is constantly changing in response to the human immune response, and antibodies induced by previous infection or vaccination provide partial protection, at best, against new strains. An ideal flu vaccine would stimulate the immune system to produce antibodies that protect against all future strains of influenza. Most human antibodies that are induced by influenza target a part of the virus called the hemagglutinin, which attaches the virus to cells to start a flu infection. Some hemagglutinin-specific antibodies recognize many strains of influenza, but individuals do not produce enough of these antibodies to prevent infections with new strains.",380,128,0.3368
dialogsum,"#Person1#: Welcome. #Person2#: Hi, John. Hey, you've done a good job decorating this place. Really nice. #Person1#: Thanks. I'm glad you like it. Can I get you a drink? #Person2#: No, thanks. Let's go to prepare dinner. I am getting hungry. #Person1#: Here is the kitchen. I will chop the onions. Could you take the meat out of the fridge? It's in a yellow plastic container. #Person2#: Wow. This smells good. #Person1#: Could you slice those potatoes for me please? #Person2#: What are we having? #Person1#: My special dumplings. Sweet and sour pork with pineapple beef with onions and green peppers, eggplant and soy sauce and a few side dishes like tomatoes with sugar. #Person2#: Sounds wonderful. #Person1#: I'll start preparing the meat stuffing. #Person2#: I wish I had the recipe and could you tell me what's in this? #Person1#: I will tell you after dinner.",#Person2# comes to John's house and admires the decoration. They will have John's special dumplings for dinner and #Person2# helps John prepare it.,146,23,0.1575
dialogsum,"#Person1#: Hello, I'd like some information about trips to Katmandu. #Person2#: Well, how can I help you? #Person1#: I hear there is a special kind of bus with sleeping rooms. #Person2#: Yes,that's true. #Person1#: How many people travel on the bus? #Person2#: Well, the bus sleeps ten. Usually there are eight travelers, two drivers, and a girl to act as your tour guide. #Person1#: So, we sleep comfortably on the bus. #Person2#: Yes. It's fully equipped for cooking, and weather permitting it's got a shower system that we set up outside every evening. #Person1#: We leave from London? #Person2#: Yes, and return to London. #Person1#: Is there anything special we need to bring? #Person2#: Oh, we give everyone a list of suitable clothes and all the things to bring. Of course, space is limited. #Person1#: Oh, yes, I understand that. Now can you tell me about the deadline for booking? #Person2#: Well, it depends. Usually six or eight months before your travel. Could you come in and we can go over the details? #Person1#: OK. I'll come and see you next Wednesday. #Person2#: OK, thanks for calling.",#Person1# calls to know some information about trips to Katmandu and a special kind of bus with sleeping rooms. #Person1# will go to meet #Person2# next Wednesday for details.,187,29,0.1551
scientific_lay_summarisation-elife-norm,"(Richard Clark et al. , 2004; Babiloni et al. , 2006). Increased anteriorization of beta band power (15–30 Hz) has been associated with effortful compensatory mechanisms (Gola et al. , 2013) in response to intensified levels of neural noise, that is, decreased temporal autocorrelation of the EEG signal as revealed by flatter 1/f slopes (Voytek et al. , 2015). Importantly, age-related variability in fMRI and EEG seems to be independent to a substantial degree (Kumral et al. , 2020). The challenge of predicting at the single-subject level from such heterogenous neuroimaging modalities governed by distinct data-generating mechanisms has been recently addressed with model-stacking techniques (Rahim et al. , 2015; Karrer et al. , 2019; Liem et al. , 2017). Rahim et al. , 2015 enhanced classification in Alzheimer’s disease by combining fMRI and PET using a stacking approach (Wolpert, 1992), such that the stacked models used input data from different modalities. Liem et al. , 2017 have then applied this approach to age-prediction and found that combining anatomical MRI with fMRI significantly helped reduce errors while facilitating detection of cognitive impairment. This suggests that stacked prediction might also enable combining MRI with electrophysiology. Yet, this idea faces one important obstacle related to the clinical reality of data collection. It is often not practical to do multimodal assessments for all patients. Scanners may be overbooked, patients may not be in the condition to undergo MRI and acute demand in intensive care units may dominate priorities. Incomplete and missing data is, therefore, inevitable and has to be handled to unleash the full potential of multimodal predictive models. To tackle this challenge, we set out to build a stacking model for predicting age from electrophysiology and MRI such that any subject was included if some data was available for at least one modality. We, therefore, call it opportunistic stacking model. At this point, there are very few multimodal databases providing access to electrophysiology alongside MRI and fMRI. The Leipzig Mind-Brain-Body (LEMON) dataset (Babayan et al. , 2019) includes high-quality research-EEG with MRI and fMRI for 154 young subjects and 75 elderly subjects. The dataset used in the present study is curated by the Cam-CAN (Shafto et al. , 2014; Taylor et al. , 2017) and was specifically designed for studying the neural correlates","How old are you? What about your body, and your brain? People are used to answering this question by counting the years since birth. However, biological age could also be measured by looking at the integrity of the DNA in cells or by measuring the levels of proteins in the blood. Whether one goes by chronological age or biological age, each is simply an indicator of general health – but people with the same chronological age may have different biological ages, and vice versa. There are different imaging techniques that can be used to study the brain. A method called MRI reveals the brain’s structure and the different types of tissue present, like white and grey matter. Functional MRIs (fMRIs for short) measure activity across different brain regions,",380,128,0.3368
dialogsum,"#Person1#: May I help you? #Person2#: My daughter. She is missing. I don't know where she is. #Person1#: What dose she look like? #Person2#: She has blond hair and blue eyes. #Person1#: What was she wearing? #Person2#: She has a yellow dress on and red sneakers. #Person1#: When did you last see her? #Person2#: I just saw her down the street. I don't know where she is. #Person1#: How long has it been? #Person2#: Oh, it's been uh... fifteen minutes.",#Person2#'s daughter is missing for fifteen minutes. #Person2# tells her appearance characters to #Person1#.,80,14,0.175
scientific_lay_summarisation-elife-norm,"Since both neutral and selective processes govern codon usage bias, the balance between selection, mutational bias and drift is crucial in shaping the codon usage of each species (Bulmer, 1991). Importantly, although the selective advantage offered by alternative synonymous codons is considered to be moderate, it was recently demonstrated that selection can still shape codon usage patterns in vertebrates even with their small effective population sizes (Doherty and McInerney, 2013). Notably, the differential usage of codons represents the evolution of the ‘demand’ aspect of translation, namely the codon usage of all expressed genes. Yet, the adaptation mechanisms of the ‘supply’, namely the expression level of each tRNA type that is loaded with an amino acid, are not fully understood. While ribosomal genes do not exhibit appreciable changes in response to environmental alterations (Müller and Wittmann-Liebold, 1997; Itoh et al. , 1999; Wolf et al. , 2001), tRNA genes may provide an important source of evolutionary plasticity for fine tuning translation. tRNAs constitute a fundamental component in the process of translation, linking codons to their corresponding amino acids (Widmann et al. , 2010). tRNA genes are classified into gene families according to their anticodon, with each gene family containing between one and several copies scattered throughout the genome. Importantly, it has been experimentally observed for Saccharomyces cerevisiae (Tuller et al. , 2010) and Escherichia coli (Dong et al. , 1996) that the cellular concentrations of each tRNA family in the cell (i. e. , the tRNA pool) correlate with its genomic tRNA copy number (Percudani et al. , 1997; Kanaya et al. , 1999). Notably, the rate-limiting step of polypeptide elongation is the recruitment of a tRNA that matches the translated codon (Varenne et al. , 1984). Thus, the translation efficiency is defined as the extent to which the tRNA pool can accommodate the transcriptome (Sharp and Li, 1987; Dos Reis et al. , 2004; Stoletzki and Eyre-Walker, 2007), thereby affecting protein production and accuracy. In general, highly expressed genes exhibit a marked codon usage bias toward ‘optimal’ codons, whose corresponding tRNA gene copy number is high (Sharp and Li, 1986a, 1986b). The evolutionary force that acts to maintain optimal translation efficiency of such genes was coined ‘translational selection’ (Dos Reis et al. , 2004). It was previously suggested that translational","Genes contain the blueprints for the proteins that are essential for countless biological functions and processes, and the path that leads from a particular gene to the corresponding protein is long and complex. The genetic information stored in the DNA must first be transcribed to produce a messenger RNA molecule, which then has to be translated to produce a string of amino acids that fold to form a protein. The translation step is performed by a molecular machine called the ribosome, with transfer RNA molecules bringing the amino acids that are needed to make the protein. The information in messenger RNA is stored as a series of letters, with groups of three letters called codons representing the different amino acids. Since there are four letters—A, C, G and",380,128,0.3368
dialogsum,"#Person1#: Hello? This is John Smith. Can I speak to Mr. White, please? #Person2#: This is Mr. White speaking. #Person1#: Hi. I understand that you have a house for sale, haven ' t you? #Person2#: Yes. #Person1#: I ' d like to know more about it. #Person2#: Can you come to my office this afternoon at 3 o ' clock? #Person1#: OK. I will be there. #Person2#: Thank you for calling. Goodbye. #Person1#: Bye.",John Smith will come to Mr. White's office to talk about the house for sale.,74,15,0.2027
scientific_lay_summarisation-elife-norm,"genes may be acquired by species not previously adapted to a particular niche (Tasse et al. , 2010; Hehemann et al. , 2010). The movement of microbes to new environments has been shown to increase both the rate and impact of HGT, and HGT is most frequent for genes under positive selection (Niehus et al. , 2015). In moving to a new environment, microbes can face novel abiotic conditions (temperature, moisture, salinity, pH, and nutrients) and novel biotic challenges and opportunities resulting from the presence of microbial neighbors. Evaluating HGT within the context of microbial communities could provide new insights concerning the extent, mechanisms, and ecological impact of this important process. Advances in genome sequencing have begun to provide a glimpse into HGT within environmentally, medically and economically important microbiomes (McDaniel et al. , 2010; Andam et al. , 2015). For example, extensive gene sharing has been observed throughout the commensal human microbiome, including sharing of genes that enable nutrient acquisition from novel food sources (Hehemann et al. , 2010; Smillie et al. , 2011), and pathogenicity islands and antibiotic resistance genes in pathogenic microbes (McCarthy et al. , 2014; Hiramatsu et al. , 2001; Forsberg et al. , 2012). There is evidence of extensive HGT in other natural habitats, such as soil (Coombs and Barkay, 2004; Heuer and Smalla, 2012) and aquatic environments (McDaniel et al. , 2010; Frischer et al. , 1994). Although these studies offer valuable insights into the frequency and potential impact of genes that can be transferred in microbial communities, the complexity of these systems makes difficult any further examination of the effects of these HGT events on their evolution and ecology. The microbial communities of fermented foods experience strong selection as a result of growing in novel, human-made environments. Previous work has demonstrated that HGT can be a major driver of adaptation in food systems and other human-managed environments (Andam et al. , 2015; Rossi et al. , 2014). Prior analysis of microbial species from cheese has revealed several instances of HGT in this environment. Lactic acid bacteria (LAB) such as Lactobacillus and Lactococcus, which are used in the initial fermentation of milk, are known to harbor antibiotic resistance genes and may be reservoirs for transfer to pathogenic enterococci (Wang et al. , 2006;","From the depths of the ocean to the lining of the human gut, almost every environment on Earth is home to a unique community of microorganisms referred to as a microbiome. Within these communities, unrelated microorganisms can exchange genetic information through a process known as horizontal gene transfer. For example, genes linked to antibiotic resistance are often transferred between different microorganisms, which can create increasingly drug resistant microbes and has important implications for human health. Horizontal gene transfer has been studied for almost 100 years, but examining it directly is challenging because, almost by definition, it requires studying a community of microbes rather than one microbe in isolation. As such, researchers are looking for simple models of microbial communities that can be easily manipulated in experiments. Bonham et",380,128,0.3368
scientific_lay_summarisation-elife-norm,"that encode distance metrics between landmarks (Howard et al. , 2014; Morgan et al. , 2011) and directions to goals (Chadwick et al. , 2015) can be read out directly from functional magnetic resonance imaging (fMRI) data in the entorhinal cortex. The hippocampal formation also encodes non-spatial relationships between objects. When these objects can be laid out in a continuous dimension such as time, hippocampal codes extracted from neuronal ensembles (Rubin et al. , 2015) or fMRI voxel patterns (Ezzyat and Davachi, 2014) reflect proximity along this dimension. fMRI signals also appear to reflect veridical angles when two-dimensional abstract spaces are formed from continuous dimensions (Constantinescu et al. , 2016; Tavares et al. , 2015). However, many relationships that are encoded by the hippocampal formation reflect associations or relationships between discrete objects (Horner et al. , 2015; Schapiro et al. , 2013,2012; Wimmer and Shohamy, 2012). To be a useful source of knowledge, many associations must be organised within an associative structure, but it is unclear how such structures might be represented in the absence of a continuous organising dimension such as space or time. Highly complex relational structures are often learnt implicitly i. e. unintentionally and without explicit awareness (Cleeremans et al. , 1998; Reber, 1989; Seger and Augart, 1994). Neurally, implicitly acquired relational knowledge can be reflected as increases in neural similarity for pairwise associations in the temporal cortex (Schapiro et al. , 2012) or for members of a temporal community structure (Schapiro et al. , 2013). However, it is unclear whether map- or graph-like knowledge structures might be encoded non-consciously, i. e. without subjects being aware of relationships between objects. Here, we explicitly tested this notion using a fMRI adaptation paradigm that allowed us to quantify the relationships between object representations in a neuronal representational space following an implicit learning paradigm. We presented human participants with sequences of objects where stimulus transitions were drawn from random walks along a graph structure. Within the hippocampal-entorhinal system, a map-like organisation of the relationships between object representations could be extracted from fMRI adaptation data acquired on the subsequent day. In this map, associative distance between objects formed a metric that allowed us to extract organising dimensions. This suggests that the brain can automatically organise abstract relational information into map-like structures","To help us navigate, the brain encodes information about the positions of landmarks in space in a series of maps. These maps are housed by two neighbouring brain regions called the hippocampus and entorhinal cortex. These regions also encode information about non-spatial relationships, for example, between two events that often occur close together in time. However, it was not known whether such non-spatial relationships may also be encoded as a map. To address this question, Garvert et al. showed volunteers a series of objects on a screen. Unbeknown to the volunteers, the order of the objects was not entirely random. Instead, each object could only follow certain others. The objects were thus connected to one another by a network of non-spatial relationships, broadly comparable to the spatial relationships",380,128,0.3368
dialogsum,"#Person1#: Now please tell me something about your past work achievements. #Person2#: All right, madam. When I was sales manager at the Beijing Friendship Store. I succeeded in raising the yearly sales volume by 25 percent and profit margins from 50 percent to 80 percent. #Person1#: That is quite an achievement! Do you consider it your most rewarding work experience? #Person2#: I don't think so. I'll create further achievement in the future. #Person1#: Have you received any honors? #Person2#: Yes. I got the title of Advance Worker in 2006. #Person1#: Do you have any publications? #Person2#: Yes. I wrote a thesis entitled On Interpersonal Relations in the Socialist Market Economy and it was published in China Daily.",#Person2# tells #Person1# #Person2#'s past work achievements and #Person2# received the title of Advance Worker and published a thesis in China Daily.,117,22,0.188
pubmed-summarization,", where the rate of cam resistance is high . we retrospectively investigated the h. pylori eradication rate over time in 750 patients , who had been diagnosed as h. pylori - infected by at least one positive result from culture test , microscopy or c - urea breath test ( ubt ) . the 750 patients had received the triple therapy based on a ppi ( omeprazole ( opz ) 20 mg or lansoprazole ( lpz ) 30 mg or rabeprazole ( rpz ) 10 mg twice as day ) , ampc ( 750 mg twice as day ) , and cam ( 200 mg or 400 mg twice a day ) at nagoya city university hospital from january , 1997 until december , 2008 . successful eradication was determined by performing a ubt following the first month after eradication , and <2.5 was defined as successful eradication . we also investigated the relationship between the eradication rate and the h. pylori cam primary resistance ( from the flat dilution method , mic > 8 g / ml ) in four terms detected at nagoya city university hospital from january 1997 until december 2008 . terms were divided as follows ; term 1 : 19972000 , before eradication therapy was approved and covered by insurance in japan ; term 2 : 20012003 , the first half of period when only omeprazole and lansoprazole were approved , term 3 : 20042006 , the latter half of period when only omeprazole and lansoprazole were approved ; term 4 : 20072008 , after rabeprazole was approved . the eradication rate by type of ppi was evaluated as well . the kruskal - wallis test and 491 men and 259 women with the average age of 56.1 14.2 years were enrolled in the study . the classification of disorders were gastric ulcers ( 258/750 , 34.4% ) , duodenal ulcers ( 188/750 25.1% ) , gastroduodenal ulcers ( 57/750 , 7.6% ) , other gastrointestinal disorders ( 247/750 , 32.9% ) . the patients with gastrointestinal disorders mainly comprised patients with atrophic gastritis or patients having undergone endoscopic treatment for a gastric tumor . 709 patients were tested by ubt to determine whether the h. pylori was eradicated , and successful eradication was","a triple therapy based on a proton pump inhibitor ( ppi ) , amoxicillin ( ampc ) , and clarithromycin ( cam ) is recommended as a first - line therapy for helicobacter pylori ( h. pylori ) eradication and is widely used in japan . however , a decline in eradication rate associated with an increase in prevalence of cam resistance is viewed as a problem . we investigated cam resistance and eradication rates over time retrospectively in 750 patients who had undergone the triple therapy as first - line eradication therapy at nagoya city university hospital from 1995 to 2008 , divided into four terms ( term 1 : 19972000 , term 2 : 20012003 , term 3 : 20042006 , term 4 : 20072008 )",380,128,0.3368
scientific_lay_summarisation-elife-norm,"CD8+ T cells produce IFN-γ in response to parasitized erythroblasts in an antigen-specific manner. These results suggest that parasitized erythroblasts are the targets of CD8+ T cells. In this study, we investigated the effector mechanism of CD8+ T cells against blood-stage malaria in detail. Splenic CD8+ T cells activated during malaria express Fas ligand (FasL) and interact with Fas-expressing parasitized erythroblasts. As a result, phosphatidylserine (PS) is externalized to the outer leaflet of the cell membrane, leading to enhanced phagocytosis of the parasitized cells. Thus, CD8+ T cells expressing FasL contribute to the immune response to blood-stage malaria by making parasitized cells susceptible to phagocytosis. C57BL/6 mice infected with PyNL exhibited peak parasitemia of up to 30% and recovered from the infection. However, those depleted of CD8+ T cells showed significantly greater parasitemia and died from the infection (1A, — 1C). BALB/c mice depleted of CD8+ T cells showed similar results (— 1D), indicating that CD8+ T cells play an essential role in protecting mice against blood-stage malaria. CD4+ T cells are known to be important in the protective immune response to blood-stage malaria (Suss et al. , 1988; Kumar et al. , 1989; Podoba and Stevenson, 1991; Good and Doolan, 1999), and we confirmed that CD4+-T-cell-depleted mice displayed greater parasitemia and a higher mortality rate (1A). However, the course of infection clearly differed in CD8+-T-cell-depleted and CD4+-T-cell-depleted mice. Although mice depleted of CD8+ T cells suffered from much greater parasitemia from the early phase to its peak, the survivors eliminated the parasites similar to the control mice, whereas the CD4+-T-cell-depleted survivors took longer to recover from infection. This suggests that CD4+ and CD8+ T cells have different effector mechanisms for parasite clearance, and that the protective immunity mediated by CD8+ T cells is important in controlling infection during the early phase, within the period of peak parasitemia. Therefore, the following analyses were conducted 7–8 days after infection, when the CD8+ T cells might be activated in response to the parasite, and 16–18 days after infection, when the parasites begin to be eliminated. 10. 7554/eLife. 04232. 003Figure 1. CD8+ T cells and FasL protect against infection with P. yoelii NL (PyNL). (A) Daily parasitemia and survival rates of C57BL/6 mice depleted of CD8+ or CD4+ T cells after infection with","The immune system consists of several different types of cell that work together to prevent infection and disease. For example, immune cells called cytotoxic CD8+ T cells kill tumor cells or other cells that are infected. To do so, the CD8+ T cells must recognize certain molecules on the surface of the tumor or infected cells and bind to them. Malaria is an infectious disease caused by the Plasmodium parasite, which is transferred between individuals by mosquitoes. The parasite is able to evade the immune system—so much so that it is not well understood how the immune system tries to respond to stop the infection. This has made it difficult to develop a vaccine that protects against malaria. During the latter stages of a malaria infection, the parasite",380,128,0.3368
dialogsum,"#Person1#: Well, what do you think is the reason most people do so badly at reaching goals? #Person2#: They lose focus. Everybody's life is busy. There is so much happening in everybody's life. That what happens is they might have a goal and then something will get in the way of that. Maybe their goal is that they want to go on a holiday every year and they put in their leave form with their boss and their boss may ask them to wait for another month and then for another month. That is, so different things get in their way and people don't stand up for their goals. They don't struggle for them. They let other forces push them around a little bit. Also, a lot of people don't set goals; they think they do. But it's either a dream of very loose goal. So when they have to make a decision about a necessary action in their life the goal is so far back in their mind that they don't act in its best interest. Also because people will sit down and say 'oh, here are my goals' and forget all about them. Revisiting them every week is a good way. They stay at the top of your mind so you can take actions based on them.",#Person1# asks #Person2# why most people cannot reach goals. #Person2# says it is because people lose focus or do not set goals.,219,22,0.1005
scientific_lay_summarisation-elife-norm,"(Papaxanthis et al. , 1998b; Gentili et al. , 2007). Furthermore, upward/downward direction-dependent kinematics could also arise from the complex dynamics of the peripheral neuromuscular system. For example, the firing properties of extensor motoneurons (pulling the arm downwards when upright) are known to obey different rules from those of flexor motoneurons (pulling upwards when uptight; Cotel et al. , 2009; Wilson et al. , 2015). In addition, muscle force production generated by eccentric contraction (elongation, e. g. downward movements for flexors) is also known to obey differing rules from concentric contraction (e. g. upward movement for flexors; for a review see Enoka, 1996). Because of these asymmetrical neuromuscular peripheral properties, upward/downward kinematic asymmetries cannot necessarily be attributed to gravity effort optimality (i. e. , minimization of muscular force to elevate and lower the arm). Thus, a solid test of the effort optimization hypothesis has been lacking. Here, we explicitly distinguish between the compensation and effort optimization hypotheses with two critical experiments. First, we contrast predictions of optimal control models that either compensate or take advantage of gravity force effects. Then, we quantitatively compare these predictions with actual kinematic features of arm movements in multiple directions. Second, in order to discard a possible influence of peripheral neuromuscular mechanisms, we measure how differences in upward versus downward arm movement kinematics are influenced by the lack of gravity during the zero-G phase of parabolic flight. If directional asymmetries originate from asymmetric firing of flexor/extensor motoneurons, they should persist in the absence of gravity because motoneurons properties are not expected to change during the short zero-G phase of a parabolic flight (Ishihara et al. , 1996,2002; for a review see Nagatomo et al. , 2014). On the other hand, if they originate from eccentric versus concentric force production differences, directional asymmetries should cease to exist instantly in 0g because movement dynamics no longer differ for upward and downward movements (Enoka, 1996). Alternatively, however, if directional asymmetries originate from neural planning processes that take advantage of the internal model of gravity, following a gradual recalibration of the gravity internal model, directional asymmetries should progressively decrease towards new optimal zero-G values (McIntyre et al. , 2001; Izawa et al. , 2008; Snaterse et al. , 2011). In support of the effort optimization hypothesis, we show that","Many of the activities of humans and other animals require the limbs to be moved in a coordinated manner. For a movement to be successful, the brain must generate muscle contractions that take into account factors in the environment that might affect the movement. One such prominent environmental feature is gravity, and it is broadly believed that the brain develops and uses an internal representation of gravity to anticipate its effects on the limbs. How an internal representation of gravity helps limb movements to be made successfully is not known. Theorists have proposed that the brain could use the internal model of gravity to predict how to compensate for its mechanical effects – or, on the contrary, take advantage of them. Flying a plane in a “parabolic” arc",380,128,0.3368
dialogsum,"#Person1#: I have some good news for you. #Person2#: What's that? #Person1#: Jenny is getting married. #Person2#: Great! Who's the bridegroom? #Person1#: Tom, that lucky guy. #Person2#: The guy always hands the girls in a line. When did he propose? #Person1#: Last week, It said that he fell in love with Jenny at Mrs. Whit's party last Monday as soon as he saw her. #Person2#: My gosh! How romantic! When's the big day? #Person1#: July 4, the National Holiday. #Person2#: Will it be a church wedding or a civil ceremony? #Person1#: Jenny plans to hold it in church. #Person2#: Who is the best man? #Person1#: Guess! #Person2#: Nobody is OK, but you! #Person1#: You know, Tom is my best friend and he asked me to be his best man. #Person2#: Did you promise him? #Person1#: Yes, I did.",#Person1# tells #Person2# that Jenny and Tom are getting married and #Person1# will be the best man.,138,17,0.1232
scientific_lay_summarisation-elife-norm,"UPR induces pro-apoptotic pathways, thereby placing the network at the center life-or-death decisions that affect the progression of numerous diseases (Bi et al. , 2005; Feldman et al. , 2005; Lin et al. , 2007; Lu et al. , 2014; Vidal et al. , 2012; Walter and Ron, 2011; Zhang and Kaufman, 2008). IRE1 drives the most conserved branch of the UPR, which exhibits remarkably similar mechanistic aspects shared between yeast and mammals (Aragón et al. , 2009; Korennykh et al. , 2009; Li et al. , 2010). In mammals, IRE1 exists in two isoforms, α and β. IRE1α is ubiquitously expressed, whereas IRE1β expression is restricted to gastrointestinal and respiratory tracts (Bertolotti et al. , 2001; Tsuru et al. , 2013). Both IRE1 orthologs are trans-membrane kinase/nucleases that oligomerize in the ER-membrane in response to ER stress (Aragón et al. , 2009; Li et al. , 2010). Oligomerization is crucial for IRE1 activation as it allows for trans-autophosphorylation and allosteric activation of its endonuclease domain, which for IRE1α then initiates the unconventional splicing of the XBP1 mRNA (Aragón et al. , 2009; Cox et al. , 1993; Cox and Walter, 1996; Korennykh et al. , 2009; Li et al. , 2010; Sidrauski and Walter, 1997; Yoshida et al. , 1998; Yoshida et al. , 2001). Spliced XBP1 mRNA encodes the transcription factor XBP1s, which activates the transcription of several target genes involved in restoring ER homeostasis (Acosta-Alvear et al. , 2007; Lee et al. , 2003). While the XBP1 mRNA is the only known splicing target of IRE1, active IRE1 can also cleave ER-localized mRNAs in a process known as regulated IRE1-dependent decay of messenger RNAs (RIDD), which serves to limit the amount of client proteins entering the ER, thus helping alleviate the folding stress (Hollien et al. , 2009; Hollien and Weissman, 2006). Two alternative models are used to describe how IRE1’s lumenal domain senses ER stress: a recent model where unfolded proteins act directly as activating ligands and an earlier model where IRE1 lumenal domain is indirectly activated through dissociation of the ER-chaperone BiP. The direct activation model emerged from the crystal structure of the core lumenal domain (cLD) from S. cerevisiae IRE1 (yIRE1; ‘y’ for yeast), where yIRE1 cLD dimers join via a 2-fold symmetric interface","Proteins are long string-like molecules that fold into specific three-dimensional shapes. Most proteins that a cell uses to communicate with its environment are folded within a part of the cell called the endoplasmic reticulum. Dedicated sensor proteins in this cellular compartment track this process to make sure that it continues to meet the cell’s demand for protein folding. If it cannot meet the demand, unfolded or poorly folded proteins build up, which stresses the cell. IRE1 is a sensor protein that detects stress in the endoplasmic reticulum. It is found in a range of organisms from yeast to humans, where it spans the membrane that encloses the endoplasmic reticulum. When unfolded proteins accumulate, IRE1 proteins come together and form so-called oligomers. The IRE1 oligomers then become active and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"adults, and as similar to that of their fathers as their mothers (Yatsunenko et al. , 2012). Moreover, mothers and fathers shared more similar bacterial communities in their guts compared to unrelated individuals living in other households (Yatsunenko et al. , 2012), indicating that a shared environment or lifestyle (e. g. , contact with same microbial sources or diet) affects the similarity of the fecal microbiota. Family members may also share intestinal bacteria with their household pets (Caugant et al. , 1984). Because we leave microbes from our bodies on the surfaces we touch (Fierer et al. , 2010; Flores et al. , 2011) and at least a moderate level of microbial exchange is facilitated by direct contact, it is conceivable that our body site-associated microbial communities are shaped in part by our surroundings and those we contact on a daily basis. Whether similar patterns to those mentioned exist within non-gut body sites, whether body sites respond differently to factors such as cohabitation and family structure, and how these patterns change with host age remain unknown. To test the hypothesis that more microbes are shared between individuals who share a greater number of potential microbial sources, we examined the extent to which microbiota are shared among members of households composed of cohabiting heterosexual adults with and without children (offspring), and with and without dogs. If our hypothesis were supported, then cohabiting family members would have microbiota more similar to each other than to members of different households. Furthermore, cohabiting couples with either children or dogs would share more microbial taxa in one or more of their body habitats than those without either, because such households contain, in addition to a shared environment, additional shared sources of potentially unique microbes with which couples are in close contact. We sampled 159 individuals comprising 17 families with cohabiting children aged 6 months to 18 years, 17 families with one or more dogs but no children, 8 families with both children and dogs, and 18 families with neither children nor dogs. Each family consisted of at least two cohabiting adults (which we define as ‘partners’ or ‘couples’) between the ages of 26 and 87 years, and all children included in this study were biologically related to and cohabited with the focal couple. Sampling was","The human body is home to many different microorganisms, with a range of bacteria, fungi and archaea living on the skin, in the intestine and at various other sites in the body. While many of these microorganisms are beneficial to their human hosts, we know very little about most of them. Early research focused primarily on comparing the microorganisms found in healthy individuals with those found in individuals suffering from a particular illness. More recently researchers have become interested in more general issues, such as understanding how these collections of microorganisms, which are also known as the human microbiota or the human microbiome, become established, and exploring the causes of similarities and differences between the microbiota of individuals. We now know that the communities of microorganisms found in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"pausing (Toulokhonov et al. , 2001; Artsimovitch and Landick, 2002; Yakhnin et al. , 2016; Zhang and Landick, 2016). Despite its crucial role in cellular information processing, the biophysical mechanism of pausing remains incompletely defined. Multiple pause mechanisms exist, but most pauses that mediate gene regulation are triggered initially by sequence-specific interactions of DNA and RNA with RNAP. An increasingly accepted view is that these initial interactions interrupt the nucleotide addition cycle by promoting entry of RNAP into a state termed the elemental pause (Landick, 2006), creating an elemental paused elongation complex (ePEC; 1B). The ePEC can then rearrange into long-lived pause states by backtracking (reverse translocation of RNA and DNA), by pause hairpin (PH) formation in the RNA exit channel that alters RNAP conformation (at least in bacteria), or by interactions of diffusible regulators with the ePEC. Recent cryoEM structures of artificially assembled PECs suggest the ePEC is half-translocated with a tilted RNA–DNA hybrid, meaning that the RNA but not the DNA is translocated and the next template base is still sequestered in the downstream DNA duplex (Kang et al. , 2018a; Guo et al. , 2018; Vos et al. , 2018). The hairpin-stabilized PEC is additionally inhibited by a rotation of the swivel module (including the clamp, shelf, and SI3) that inhibits trigger-loop folding (Kang et al. , 2018a; Guo et al. , 2018). High-throughput sequencing of nascent RNAs from bacteria (NET-seq) reveals a consensus elemental pause sequence conserved among diverse bacterial RNAPs and mammalian RNAPII whose effects on pausing in vitro are consistent with a block in template DNA translocation sometimes accompanied by modest backtracking (Larson et al. , 2014; Vvedenskaya et al. , 2014; Imashimizu et al. , 2015). Although earlier work establishes contributions of multiple pause signal components (upstream RNA, RNA–DNA hybrid, downstream fork junction, and downstream DNA) to hairpin-stabilized pausing (Chan and Landick, 1993; Wang et al. , 1995; Chan et al. , 1997), the definition of the consensus elemental pause signal has varied and it is unknown if the discrete components affect a common step in the elemental pause mechanism. Additionally, questions remain about the structure and properties of the ePEC. A longstanding debate is whether the ePEC is an on-pathway state unable to translocate DNA or RNA in a largely unchanged RNAP","The information a cell needs to create a specific protein is encoded in a sequence of precisely organized DNA ‘letters’. Unlocking these instructions requires an enzyme known as RNA polymerase (RNAP for short), which reads the DNA segment and faithfully copies the information to form a strand of RNA. This molecule then relays the genetic message to the machinery that pieces together a protein. An RNAP works by reading a DNA segment and building a matching RNA strand at the same time. The enzyme clamps onto DNA, and threads it letter-by-letter through its reading and building site. For each DNA letter that RNAP reads, the enzyme adds a matching RNA building block onto the budding RNA strand, with DNA and RNA segments then being moved away from the",380,128,0.3368
dialogsum,"#Person1#: Hello, Mr. Brown. How are you? #Person2#: Fine, thanks, Mrs. Downs. How is your boy, Mike? #Person1#: He is a bit tired. You know, he goes to school at eight o'clock every morning. He doesn't get home until after four. Then he does his homework after tea. It often takes him a couple of hours to finish it. #Person2#: Poor boy. They work hard at school nowadays, don't they? Does he like it? #Person1#: You mean the school? Yes, he does. He likes his teachers and classmates. #Person2#: Does he go to school by bus? #Person1#: No, he walks. He likes walking. He meets some of his friends at the corner and they go together. #Person2#: What does he do when it rains? #Person1#: My husband takes him in the car. He passes the school on the way to the office.",Mr. Brown and Mrs. Downs are talking about Mike. Mike works hard at school and likes the school.,142,18,0.1268
dialogsum,"#Person1#: I'm afraid I have to return this sweater. #Person2#: May I ask if there's anything wrong with it? #Person1#: You see, there is a run at the neck. #Person2#: Oh, sorry. But do you want to change it for another one? #Person1#: No, thank you. #Person2#: Okay, I am really sorry, I'll have it returned.",#Person1# wants to return the sweater because there is a run. #Person2# apologizes and agrees.,56,15,0.2679
scientific_lay_summarisation-elife-norm,"2016). These findings are highly relevant in the context of the ‘reproducibility crisis’ (Baker, 2016; von Herrath et al. , 2019) as well as having ethical implications for the use of animals in research that is not of optimum quality (Prescott and Lidster, 2017). Non-alcoholic fatty liver disease (NAFLD) is a highly active field of animal research (Brenner, 2018; Farrell et al. , 2019). NAFLD is a common condition characterised by increased liver fat (hepatic steatosis) that may progress to inflammation in the form of non-alcoholic steatohepatitis (NASH) and fibrosis (Sanyal, 2019). Cirrhosis, end-stage liver disease, and hepatocellular carcinoma develop in a small proportion of patients. However, due to the high prevalence of obesity, NAFLD is the second most common indication for liver transplant in the United States (Younossi et al. , 2018), predicted to overtake hepatitis C virus. NAFLD is intricately related with insulin resistance and therefore usually coexists with other features of the metabolic syndrome, such as type 2 diabetes and its recognised complications including cerebrovascular disease, coronary artery disease, and chronic kidney disease (Byrne and Targher, 2015). There are currently no approved pharmacological therapies for NAFLD (Chalasani et al. , 2018). Several Phase three trials are ongoing (Ratziu et al. , 2019), but many interventions that appeared to have substantial efficacy in preclinical models have failed to be replicated in humans (Budas et al. , 2016; Harrison et al. , 2018; STELLAR-3 and STELLAR-4 Investigators et al. , 2020; Sanyal et al. , 2014). These studies have used a wide range of preclinical NAFLD models, including genetically modified animals (e. g. leptin deficient ob/ob mice), hypercaloric diets (e. g. high-fat diet), and toxic insults (e. g. streptozocin injections), all of which may be used in varying combinations and with different parameters (Anstee and Goldin, 2006). It is not known if, or which of, these variables influence treatment response to therapeutic agents in preclinical models of NAFLD, and which models are better predictors of response in humans. Therefore, we performed a meta-analysis of interventional rodent studies of NAFLD to describe which drug classes were associated with improvement in NAFLD and whether any study characteristics (or biases) were linked to the magnitude of effect. We used random-effects meta-analysis to estimate the mean difference (MD) in hepatic triglyceride (TG) content","Obesity and diabetes are increasingly common diseases that can lead to other complications such as fatty liver disease. Fatty liver disease affects one in five people and is caused by a built-up of fat in the liver, which can result in scarring of the liver tissue and other serious complications. There is currently no cure for fatty liver disease. Drugs that have been effective in treating the condition in mice, lack efficacy in humans. To better understand why this is the case, Hunter, de Gracia Hahn, Duret, Im et al. conducted a review of over 5,000 published studies, analysing over 600 experiments. Hunter et al. asked which drugs improved fatty liver in mice the most and if they had the same effect in humans. They also tested whether",380,128,0.3368
dialogsum,"#Person1#: Hi, Mr. Bridges. How are you this morning? #Person2#: Terrible. I'll have a cup of coffee and some toast, please. I do not want sugar in my coffee. #Person1#: All right. I'm sorry to hear you're not in a good mood. What happened? #Person2#: Well, my car won't start. I'm already late to work. My dog ran away this morning, and I had to find him. Also, it's raining and my hat is wet. But you know me, I always have bad Mondays. I had a great weekend, but this morning is awful! #Person1#: I'm going to give you your coffee for free today. You have had such a bad morning! #Person2#: Wow, thanks! I feel a little bit better already. Are you sure you can give me free coffee? #Person1#: Yes, it's no problem. We have extra coffee. You come into this coffee shop every day! I hope your day gets better.",Mr. Bridges orders coffee and some toast and tells #Person1# about his bad morning. #Person1# gives Mr. Bridges the coffee for free to cheer him up.,154,26,0.1688
pubmed-summarization,"= 11 ) was first introduced for aqueous angiography at 10 mm hg followed by fluorescein aqueous angiography in the same eye as previously done in cows ( saraswathy s , et al . alternatively , 3-kd fixable and fluorescent dextrans ( life technologies , carlsbad , ca , usa ; diluted to 2.5 mg / ml in bss ) were used ( n = 2 ) at 10 mm hg . the eyes were placed in front of the spectralis hra+oct ( heidelberg engineering , heidelberg , germany ; fluorescein capture mode : excitation wavelength = 486 nm and transmission filter set at > 500 nm ; icg capture mode : excitation wavelength = 786 nm and transmission filter set at > 800 nm ) with fluorescent images taken with a 55 lens using a 25-diopter focus . confocal scanning laser ophthalmoscopic ( cslo ) infrared images were taken to center the eye . prior to tracer application , cslo fluorescent angiographic images using the fluorescein or icg capture mode were taken to provide a standard pretracer intensity background image , which appeared black . subsequent fluorescein or icg capture mode images were taken at various time points in various positions or face - on after tracer introduction . to prevent image signal intensity saturation over time during prolonged imaging sessions , the laser sensitivity setting on the spectralis was adjusted with each image to set the central fluorescent signal in the anterior chamber to just under signal saturation . after aqueous angiography with fluorescent dextrans for 2 minutes in human eyes ( n = 2 ) , the intracameral fluorescent dextran solution was exchanged with 4% paraformaldehyde ( pfa ) for 15 minutes at 10 mm hg . the entire globe was then placed in 4% pfa for an additional 15 minutes of fixation . wedges including the angle were cut from angiographically positive and negative regions , dehydrated through ethanol steps , brought through xylenes , and paraffin embedded . five - micrometer - thick sections were cut on a leitz 1512 microtome ( leica biosystems , vista , ca , usa ) onto superfrost plus slides ( vwr , radnor , pa , usa ) and air dried . slides were mounted with a 4,6-diamidino-2-phenylindole (","purposeto assess the ability of trabecular micro - bypass stents to improve aqueous humor outflow ( aho ) in regions initially devoid of aho as assessed by aqueous angiography.methodsenucleated human eyes ( 14 total from 7 males and 3 females [ ages 5284 ] ) were obtained from an eye bank within 48 hours of death . eyes were oriented by inferior oblique insertion , and aqueous angiography was performed with indocyanine green ( icg ; 0.4% ) or fluorescein ( 2.5% ) at 10 mm hg . with an angiographer , infrared and fluorescent images were acquired . concurrent anterior segment optical coherence tomography ( oct ) was performed , and fixable fluorescent dextrans were introduced into the eye for histologic analysis of angiographically positive and negative",380,128,0.3368
pubmed-summarization,"small areas of the solid , insular pattern as seen in jgct . the unusual facet in this case is the clinical presentation of an unsuspected gct in a seven - day - old neonate . a 76-year - old woman presented with a growth at the umbilicus and bowel obstruction . ct scan showed a complex mass arising from the anterior bladder wall / dome of the bladder ( (a ) ) . with the clinical suspicion of a urachal carcinoma , the patient was taken to the operating room where she underwent a partial cystectomy and anterior abdominal wall mesh reconstruction . the mass was smooth and solid cystic ( (b ) ) , with extension from the bladder 's dome to the umbilicus . at microscopic examination , sheets of spindle cells in focal retiform - like areas with uniform grooved nuclei were identified ( (c ) ) . immunohistochemical analysis found the mass to be positive to vimentin , with focal positivity to inhibin a ( (d ) ) and cytokeratin . an incidental pelvic mass was detected in a 64-year woman with a past history of total abdominal hysterectomy and bilateral salpingooophrectomy for a gct 16 years prior . a ct scan confirmed the presence of a large heterogenous solid - cystic pelvic mass ( (a ) ) . the preoperative diagnosis of this mass included abscess , gastrointestinal stromal tumor , and extracolonic mass . she underwent laparotomy with pelvic washings for cytology and en - bloc resection of the left ovarian mass . on gross examination , necrosis reminiscent of colonic adenocarcinoma admixed with diffuse , microfollicular , and cords of neoplastic cells were observed ( (b ) ) . deeper sections confirmed the presence of the glandular neoplasm originating from a diverticular outpouching of the overlying colonic mucosa , confirming the presence of colonic adenocarcinoma arising in a diverticulum of the large bowel . this was further supported by immunohistochemistry that confirmed the two components of this collision tumour with inhibin positivity in the gct component ( (c ) ) and cytokeratin positivity in the adenocarcinoma component ( (d ) ) . a 45-year - old woman presented to the emergency room with a two - year history of menorrhagia and acute","background . granulosa cell tumors ( gcts ) , representing ~2% of ovarian tumours , are poorly understood neoplasms with unpredictable and undetermined biological behaviour . design . 5 unusual presentations of gct and a retrospective 14-year ( 19972011 ) surgical pathology review based on patient sex , age , tumour type and concurrent pathology findings are presented to discuss the myths and realities of gcts in the context of relevant evidence - based literature . results . the 5 index cases included ( 1 ) a 5 month - old boy with a left testicular mass , ( 2 ) a 7-day - old neonate with a large complex cystic mass in the abdomen , ( 3 ) a 76-year - old woman with an umbilical mass",380,128,0.3368
dialogsum,"#Person1#: Have you got your invitation yet? #Person2#: My invitation? No, I haven't. My invitation to what? #Person1#: The house warming party. #Person2#: Whose house warming party is it? #Person1#: Tom and Bill Smith. They are both working now you know? And they've bought a new house. #Person2#: Oh, they have? I didn't know. I haven't seen Tom lately. #Person1#: It's out in the suburbs. #Person2#: Have you seen the house? #Person1#: Yes, I have. I went out with them last weekend. #Person2#: Is it nice? #Person1#: Yes, it is. There are three bedrooms, a living room, a dining room, and a big kitchen. #Person2#: There's also a garden. #Person1#: Well, that does sound nice. Have they moved in yet? #Person2#: They are moving today. Tom's taken the day off. He's rented a truck, and they should have all their furniture in the house tonight. #Person1#: When are they going to have the party? #Person2#: Next Saturday night. You should get your invitation today or tomorrow. #Person1#: Wow, that would be something to look forward to.",#Person1# tells #Person2# about Tom and Bill Smith's new house in the suburbs and thinks #Person2# will get the invitation to the house warming party.,176,25,0.142
scientific_lay_summarisation-elife-norm,"Each of the olfactory sensory neurons (OSNs) chooses to express a single G protein-coupled olfactory receptor (OR) from a pool of hundreds. Here, we show the receptor transporting protein (RTP) family members play a dual role in both normal OR trafficking and determining OR gene choice probabilities. Rtp1 and Rtp2 double knockout mice (RTP1,2DKO) show OR trafficking defects and decreased OSN activation. Surprisingly, we discovered a small subset of the ORs are expressed in larger numbers of OSNs despite the presence of fewer total OSNs in RTP1,2DKO. Unlike typical ORs, some overrepresented ORs show robust cell surface expression in heterologous cells without the co-expression of RTPs. We present a model in which developing OSNs exhibit unstable OR expression until they choose to express an OR that exits the ER or undergo cell death. Our study sheds light on the new link between OR protein trafficking and OR transcriptional regulation. Seven transmembrane G-protein coupled receptors (GPCRs), are diverse and the largest superfamily of receptors. Their roles are well established in sensing various stimuli including odorants, tastants, light, hormones, neurotransmitters and proteins. Some GPCRs require the presence of specific accessory proteins such as chaperones, vesicular targeting molecules and co-receptors for their cell surface expression (Lu et al. , 2003; Salahpour et al. , 2004; Dey and Matsunami, 2011; Wu et al. , 2003). Mammalian olfactory receptors (ORs), which are GPCRs (Buck and Axel, 1991), are retained in the ER when expressed in non-olfactory cells. RTP1 (Receptor Transporting Protein 1) and RTP2 (Receptor Transporting Protein 2), both single transmembrane proteins strongly and exclusively expressed in the peripheral olfactory organs (Lu et al. , 2003; Saito et al. , 2004; Zhuang and Matsunami, 2008; Gimelbrant et al. , 1999), greatly enhance the trafficking of ORs to the cell surface of heterologous cells. However, the role played by the RTPs in vivo remains unclear. The mouse genome encodes over one thousand intact OR genes (Niimura et al. , 2014), which are expressed in a singular and monoallelic fashion in each olfactory sensory neuron (OSN) (Shykind et al. , 2004; Chess et al. , 1994; Serizawa et al. , 2000; Malnic et al. , 1999). Each OR is not chosen at random; rather, OSNs express different ORs with dramatically varying probabilities (Khan et al. , 2011;","Olfaction, or the sense of smell, is perhaps the most complicated and least understood of the five basic senses. Olfactory neurons in the nose can detect and distinguish between tens of thousands of different odor producing substances. They do so by using hundreds of unique sensors called olfactory receptors, each of which responds to a specific type of odor. During development, each olfactory neuron “chooses” to produce only one type of olfactory receptor. Once the neuron recognizes that the functional receptor is being generated and transported to the cell surface, it will stop making all the other olfactory receptors. Chaperone proteins are responsible for transporting many olfactory receptors to the cell surface. To investigate how the loss of these chaperones affects how the olfactory system develops, Sharma et",380,128,0.3368
dialogsum,"#Person1#: What are some of the problems of doing a part-time job as a college student? #Person2#: Schoolwork suffers. Because I don't have as much time to study as when I didn't have a part-time job. I have had to give up things I enjoy, like sleep and football. I can't get into the social life because I have to work right after class. Some of my Mends have stopped calling me. I also miss TV. #Person1#: What do you do in a day? #Person2#: I get up at seven to make an 8:00 a. m. class. I have classes till 1:30. And then, I drive to the supermarket where I work. I work till 7:00 p. m. And then I drive to my home and eat dinner. After I take a shower and rest for a half hour, it's about nine. This gives me only a couple of hours to study. My eyes start to close well before I go to bed at eleven.",#Person2# discusses with #Person1# about the problems of doing a part-time job as a student and tells #Person1# #Person2#'s daily routine.,165,21,0.1273
dialogsum,"#Person1#: What are your plans for this weekend? #Person2#: I'd like to hire a bike. I think it would be a good idea to do some cycling on Sunday. #Person1#: If the weather's fine. #Person2#: I am sure it will be. It's been good so far this weekend. #Person1#: I know a good place to hire bikes if you want. #Person2#: Thanks. That would be really helpful. #Person1#: But remember, be careful when you ride a bike. The traffic in Beijing can be dangerous.",#Person2# is planning to do some cycling on Sunday. #Person1# recommends a place to hire bikes and reminds #Person2# to be cautious.,84,22,0.2619
pubmed-summarization,"though the stylet was withdrawn . finally , the frova intubating introducer with its tip modified as much as a 60 angle , similar to the mcgrath mac video laryngoscope , was inserted through the vocal cords ( figs . 1 and 2 ) . the frova intubating introducer was used as a railroad for the ett , and there was no difficulty advancing the ett under vision with the video laryngoscope ( . correct placement of the ett was further confirmed by auscultation and end - tidal co2 detection . we applied the mcgrath mac video laryngoscope and frova intubating introducer for endotracheal intubation in this case of a difficult airway and showed that the strategy was effective and successful . fiber - optic intubation is currently the gold standard for elective difficult airway management , but alternatives are described in the literature . the intubation techniques described include : airtraq optical laryngoscopy ( prodol meditec sa , vizcaya , spain ) , video laryngoscopy , non - fiber - optic intubation via lma , fiber - optic intubation via lma , and a paraglossal approach with tube advancement over a gum - elastic bougie . we chose a mcgrath mac video laryngoscope and malleable stylet because the mcgrath mac video laryngoscope provides a good view of the glottis , and a malleable stylet helps direct the ett to the glottis . as a precaution for a failed intubation , we also prepared a frova intubating introducer and fiber - optic bronchoscope for combined use , and an lma in case of a difficult mask ventilation according to the difficult airway guidelines . it is important to have backup airway management plans because it takes less than 10 min for patients with a difficult airway to become hypoxic . at our first attempt , insertion of the 60 angled malleable styletted ett failed because the tube tip could be seen posterior to the arytenoids . external laryngeal pressure and withdrawal of the blade to lessen tilting of the laryngeal axis and to reduce the introducing angle may have been helpful . however , these maneuvers did not work in our case . the tube tip reached the glottis , but there was considerable resistance advancing the ett through the","patients with pierre robin syndrome are characterized by micrognathia , retrognathia , glossoptosis , and respiratory obstruction and are prone to have a difficult - to - intubate airway . the mcgrath mac video laryngoscope provides a better view of the glottis than a macintosh laryngoscope , but it is not easy to insert an endotracheal tube through the vocal cords because a video laryngoscope has a much greater curvature than that of a conventional direct laryngoscope and an endotracheal tube has a different curvature . the frova intubating introducer is used as a railroad for an endotracheal tube in cases of a difficult airway . we thought that a combination of these two devices would make it easy to insert an endotracheal tube through the vocal cords",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and R3/R4d innervation takes place in the EB during pupal development. Strong CadN immunolabeling shows EB morphological changes (dashed lines) between 16 hr and 48 hr APF (hours after puparium formation). R2/R4m axons (red arrows) extend into the developing EB earlier than R3/R4d axons (green arrows and arrowheads), as can be observed between 16 and 24 hr APF since R2/R4m axons exhibit dense elaboration and co-localization with strong CadN staining prior to R3/R4d axons. R axon projections and elaborations appear complete between 40 and 48 hr APF, and the overall organization of R axons after 48 hr APF shows no difference when compared to the adult brain. (E) Schematics highlight changes in EB morphology (strong CadN staining in dark blue and weak CadN staining in light blue), sequential innervation of the EB by pb-eb-gall dendrites (immunostaining in — 1K and L), R2/R4m and R3/R4 axons during early pupal stages. Scale bars are 50 μm in panels B and D; 20 μm in panel C. : http: //dx. . org/10. 7554/eLife. 25328. 00310. 7554/eLife. 25328. 004Figure 1— 1. R neuron axons and pb-eb-gall dendrites have different morphologies and closely associate with each other in the developing and adult brain. (A–F’) Single-cell MARCM clones show the diverse morphologies of ring neuron axons and pb-eb-gall neuron dendrites in the EB (frontal views in A–F, dorsal views in A’–F’). (G) Schematic depicting a dendritic arbor from a single pb-eb-gall neuron (red) overlapping with axons from multiple types of R neuron. Only axons from one R4m (yellow) and one R3 (blue) are shown here as examples. (H) R19G02-GAL4 was used to express pre-synaptic (Syt-GFP) and dendritic (DenMark) markers in small-field pb-eb-gall neurons. Syt-GFP, but not DenMark, was enriched in the gall, demonstrating that these gall projections are largely pre-synaptic. PB and EB projections were filled by both Syt-GFP and DenMark, suggesting that these projections include both pre- and post-synaptic terminals. (I–J) Native GFP fluorescence is reconstituted between pb-eb-gall dendrites and R neuron axons (R1/R3/R4d in panel I, R2/R4m in panel J) in GRASP (GFP reconstitution across synaptic partners) experiments. CD4-spGFP1-10 was expressed in R1/R3/R4d and R2/R4m neurons by R15B07-GAL4 and EB1-GAL4, respectively. CD4-spGFP11 and mCherry were expressed in pb-eb-gall neurons by R19G02-lexA in both cases. No GFP fluorescence was observed in control animals in which","The human brain contains around one hundred billion nerve cells, or neurons, which are interconnected and organized into distinct layers within different brain regions. Electrical impulses pass along a cable-like part of each neuron, known as the axon, to reach other neurons in different layers of various brain structures. The brain of a fruit fly contains fewer neurons – about 100 thousand in total – but it still establishes precise connections among neurons in different brain layers. In both flies and humans, axons grow along set paths to reach their targets by following guidance cues. Many of these cues are conserved between insects and mammals, including proteins belonging to the semaphorin family. These proteins work together to steer growing axons towards their proper targets and repel them away",380,128,0.3368
dialogsum,"#Person1#: Where do you want to go? #Person2#: I am going to the Capital Hotel. #Person1#: Get in. I will take you there. #Person2#: About how much it will cost? #Person1#: $ 50. #Person2#: On the meter? #Person1#: Ye, of course. #Person2#: OK. let's go.",#Person1# takes #Person2# to the Capital Hotel for $50.,45,9,0.2
pubmed-summarization,"residual spores were not completely killed after a 30-minute exposure to chlorine dioxide at a relative humidity of 20% to 40% , whereas all spores were killed after a 15-minute exposure to chlorine dioxide with the addition of prehumidification at a relative humidity of 70% to 75% ( 21 ) . the amount of contamination , level of cleanliness of surfaces , and relative humidity will contribute to peracetic acid vapor s effectiveness as a sporicide ( 24 ) . the sporicidal property of ozone is affected by relative humidity : as relative humidity decreases , the time required for killing organisms increases ( 27 ) . decontamination of buildings from intentional release of b. anthracis is a new problem , and no accumulated scientific knowledge exists on the subject . two areas of prior scientific research may be relevant : food processing and laboratory decontamination . with modification based on further study , direct information on killing b. anthracis spores in foods by cooking is scarce , and the complexity of food matrices precludes easy extrapolation of the laboratory data into nonfood matrices . however , information on inactivating spores of bacterial species more resistant to environmental conditions than b. anthracis can provide guidance . the spores of clostridium botulinum are more resistant to heat inactivation than are b. anthracis spores ( 4 ) . the commercial retort process of canning achieves a 12-log reduction of c. botulinum spores , and by extension , should achieve a similar killing rate for b. anthracis spores . further research in this area is needed . historically , formaldehyde solution or gas has been used both as a disinfectant and chemical sterilant . formaldehyde was used to disinfect as early as the late 1880s and is still used to reprocess hemodialyzers for reuse on the same patient and to decontaminate biologic safety cabinets and laboratories ( 3537 ) . formaldehyde gas has been used for fumigation in the poultry industry and for disinfection of biologic safety cabinets and laboratories ( 38,39 ) . data from controlled experiments with b. globigii nctc 10073 spores have demonstrated the effect of humidity on formaldehyde concentration ( mg / m ) to obtain a > 8-log reduction in viable spores ( 15 ) . / l","after the intentional release of bacillus anthracis through the u.s . postal service in the fall of 2001 , many environments were contaminated with b. anthracis spores , and frequent inquiries were made regarding the science of destroying these spores . we conducted a survey of the literature that had potential application to the inactivation of b. anthracis spores . this article provides a tabular summary of the results .",380,70,0.1842
pubmed-summarization,"a hundred and fifty patients with end - stage renal disease were assessed for eligibility . the study was a prospective , randomized , controlled clinical trial ( iranian clinical registration number 138811182370n6 ) , and conducted at two tertiary - care urban medical center . patients with end - stage renal disease from december 2009 to march 2010 were included in the study . inclusion criteria included age more than 18 , being dialyzed with central tunneled catheter , med comp ( only if placed in the internal jugular vein ) , with a maximum time of one month post catheterization , dialysis 3 times a week and having accepted to participate in the study . exclusion criteria were allergy to cefotaxime , antibiotic treatment within 2 weeks prior to enrollment , patients requiring a surrogate decision maker , catheters with blood flow rates less than 300 ml / min , or requiring frequent thrombolytic solution dwells in the catheter lumen because of malfunction . at the beginning of the study 38 patients were eligible to participate in the study , but 30 of them were consented ( 20.6% ) . enrolled patients were randomly assigned by using a block computerized randomization protocol into two groups of 15 patients . in intervention group , we used cefotaxime , at a concentration of 10 mg / ml as the experimental antibiotic lock solution . solutions were prepared by dissolving sterile cefotaxime sodium powder in normal saline for injection to reach a concentration of 10 mg / ml for cefotaxime . then mixture of 1.5 cc cefotaxime ( 10 mg / ml ) and 1.5 cc heparin solution ( 5,000 u / ml ) ( ce / hs ) , was prepared in a syringe using aseptic precautions to fill 1.6 ml in the venous and 1.4 ml in the arterial lumen of the catheter at the end of each dialysis session ( exact volume of each venous and arterial port so that cefotaxime would not inter the blood stream , preventing its systemic effect and microbial resistance ) . in control group we just filled 1.6 ml and 1.4 ml of standard heparin solution ( hs ; 5,000 u / ml ) in the venous and arterial lumens respectively .","background : chronic hemodialysis patients frequently require vascular access through central venous catheters ( cvcs ) . the most significant complication of these catheters is infection . this risk can be lowered by the use of an antibiotic - heparin lock . this study focuses on hemodialysis patients using tunneled - cuffed catheters ( tcc ) , to assess the rate of catheter - related infections ( cri ) in catheter - restricted filling with cefotaxime and heparin in end stage renal disease patients.methods:a double - blind randomized study was conducted to compare 5000 u / ml heparin plus10 mg / ml cefotaxime ( ce / hs ) as catheter - lock solutions , with heparin ( 5000 u / ml ) alone . a total of 30",380,128,0.3368
scientific_lay_summarisation-elife-norm,"been appreciated that individuals who preferentially accumulate WAT in subcutaneous regions are at a relatively lower risk for developing insulin resistance when compared to equally obese individuals with central (visceral) adiposity (Kissebah et al. , 1982; Krotkiewski et al. , 1983). It is now widely believed that visceral and subcutaneous WAT depots represent fundamentally distinct types of WAT (Karastergiou et al. , 2013; Lee et al. , 2013; Macotela et al. , 2012; Yamamoto et al. , 2010). Indeed, visceral and subcutaneous WAT depots emanate from distinct developmental lineages (Chau et al. , 2014). Importantly, another clear determinant of metabolic health in obesity is manner in which individual WAT depots expand and ‘remodel’ (Hepler and Gupta, 2017; Lee et al. , 2010). WAT ‘remodeling’ associated with obesity can be described as both quantitative and qualitative changes in adipocyte numbers and stromal-vascular cell composition. Pathological WAT expansion is characterized by the presence of enlarged adipocytes, excessive macrophage accumulation, and fibrosis (Divoux et al. , 2010; Gustafson et al. , 2009; Hardy et al. , 2011; Klöting and Blüher, 2014; Sun et al. , 2013). The prevailing hypothesis is that as ‘overworked’ fat cells reach their storage capacity, adipocyte death, inflammation, and fibrosis ensue (Hepler and Gupta, 2017; Sun et al. , 2011). This is often associated with the deleterious accumulation of lipids in the liver, skeletal muscle, pancreas, and heart (termed ‘lipotoxicity’) (Unger and Scherer, 2010). Healthy WAT expansion occurs when adipose tissue expands through adipocyte hyperplasia (increase in adipocyte number through de novo differentiation) (Denis and Obin, 2013; Kim et al. , 2014; Klöting et al. , 2010). This is associated with a lower degree of chronic tissue inflammation and fibrosis. These adipose phenotypes of the ‘metabolically healthy’ obese tightly correlate with sustained insulin sensitivity in these patients. To date, the factors dictating a healthy vs. unhealthy WAT expansion in obesity remain poorly defined. In particular, the array of cell types within the adipose stromal-vascular compartment contributing to the remodeling of WAT in obesity has remained largely undefined. The growing appreciation for the casual link between adipose tissue distribution and remodeling with systemic metabolic health has sparked considerable interest in defining the adipocyte precursors giving rise to fat cells in adults and the mechanisms controlling their differentiation in vivo (Hepler","Fat tissue, also known as white adipose tissue, specializes in storing excess calories. Much of this storage happens under the skin, but fat tissue can also build up inside the abdomen and surround organs, where it is known as ‘visceral’ fat. When visceral fat tissue is unhealthy, it may help diseases such as diabetes and heart disease to develop. Unhealthy fat tissue contains enlarged fat cells, which may die from overwork. The stress this places on the surrounding tissue activates the immune system, causing inflammation and the build-up of collagen fibers around the cells (a condition known as fibrosis). Not all people develop this type of unhealthy fat tissue, but we do not yet understand why. In many tissues, blood vessels serve as a home for several types",380,128,0.3368
pubmed-summarization,"in 9 biopsies , of the classic mn cases , fresh frozen tissue for if was not available in 8 and in 2 there were no glomeruli in the tissue submitted for if . however , ihc done on paraffin fixed tissues showed granular positivity of c4d along the glomerular basement membrane ( gbm ) in 100% cases . all the control groups including 15 cases of mcd , 3 cases of diabetic nephropathy and 2 cases of amyloidosis were negative for c4d . c4d is a degradation product of complement factor c4 , which is activated during the classical , as well as lectin pathway of complement cascade . the classical pathway of complement is activated by conformational changes in ig molecules , after binding to specific antigens . c4b is then cleaved by c3bina in the presence of c4b binding proteins into c4c and c4d . antibodies dissociate naturally because of relatively weak hydrostatic and van der waals forces between antigens and antibodies , whereas covalent bond of c4d has a much longer half - life . therefore , detection of c4d is regarded as an indirect sign , a footprint of complement activation . the use of ihc to detect the c4d complement degradation product in kidney disease has sparked considerable clinical interest recently . c4d positivity in peritubular capillaries is a diagnostic marker for antibody mediated rejection as incorporated by banff 2007 . the literature on its use in glomerulonephritis , recently the role of c4d was highlighted in diagnosis and pathogenesis of iga nephropathy , mpgn and mn . the other studies on c4d in mn has have shown near 100% positivity similar to what was observed by us in this study . the original description of the pathogenesis of mn includes role of 4 auto antigens like m type phospholipase a2 receptor , aldose reductase , manganese superoxide dismutase , membrane metalloendopeptidase . c4d is only an extension of our understanding of complement activation in immune complex glomerulonephritis . its presence can also be extrapolated in the form of ihc for diagnostic purpose , which is an added advantage . it is well known that mcd is not an immune complex disorder and occurs due to podocyte effacement . negativity of c4d in diabetic","background : membranous nephropathy ( mn ) is the most common cause of nephropathy in adults . the diagnosis is based on characteristic light microscopic , electron microscope and immunofluorescence ( if ) findings . in early mn , the light microscopic findings may be difficult to differentiate from minimal chain disease . in the absence of fresh frozen tissue for if , immunohistochemistry with c4d aids in the diagnosis.materials and methods : a total 48 cases of mn diagnosed on renal biopsy were analyzed . the formalin fixed paraffin embedded tissues were stained with routine hematoxylin and eosin stains along with periodic acid - schiff and silver methenamine stains to highlight the basement membrane . fresh frozen tissues were available for if in 40 cases . immunostaining",380,128,0.3368
scientific_lay_summarisation-elife-norm,"largest known risk factors for mental illness. Recently, a mouse model has been developed which reproduces the human form of DISC1 truncation (Shen et al. , 2008). Those Disc1 mice allow to directly examine the impact of a depression- and schizophrenia-related risk gene mutation on behaviour and the activity of neuronal networks involved in the control of cognitive functions. We find that Disc1 mice show increased immobility during the tail-suspension (TST) and forced swim test broadly accepted as depression-related behavioural changes in rodents (Porsolt et al. , 1977; Steru et al. , 1985). This behavioural phenotype correlates with abnormalities in the synchrony of low-gamma oscillations (30–50 Hz) in the prelimbic cortex (PrlC), which have been implicated in supporting encoding of information (Fries et al. , 2007). Moreover, we provide evidence that network malfunction is related by a profound defect of FS-INs, including reduced numbers of FS-INs as well as alterations in their synaptic connections. Thus, our study provides a correlative link between behavioural alterations in Disc1 mice and the possible underlying cellular and synaptic mechanisms. To investigate the effect of truncated Disc1 on potential depression- or schizophrenia-like phenotypes of Disc1 mice we conducted a comprehensive analysis covering a wide spectrum of behavioural deficits characteristic for psychiatric syndromes (, refer to Table 1 for a summary of values). We probed depression-related traits using highly validated tests for anhedonia (LeGates et al. , 2012) and behavioural despair (Porsolt et al. , 1977; Steru et al. , 1985) in rodents. Disc1 mice showed no deficit in sucrose preference, which is used to quantify anhedonia (1A). However, in the TST and forced swim test, in which animals exhibit epochs of immobility that are thought to reflect states of behavioural despair intersected by periods of active escape, Disc1 mice showed longer periods of immobility (1B, C). Behavioural variability among individuals was high and therefore resulted in a moderately but significantly enhanced mean immobility by 35% in the TST and by 18% in the forced swim test of Disc1 mice (TST: p = 0. 015,22 Disc1 and 14 control mice; forced swimming: p = 0. 049,22 and 20 mice; Cohen' s d of 0. 82 and 0. 65 corresponding to a strong and moderate effect size, respectively [Table 1]). Both genotypes reached similar movement speeds in","Our thoughts and emotions are produced and processed by complex networks of neurons inside our brains. Signals are sent from one neuron to another via chemical messengers, and pass through the neuron as an electrical signal. The electrical signals produced by a brain region often show steady rhythms, or oscillations. In the brains of many people diagnosed with certain mental disorders, such as schizophrenia and major depression, these oscillations are disrupted, but how these changes in rhythm are linked to defects in the networks of neurons behind the electrical activity is not well understood. Studies of a family in Scotland over several decades revealed that a gene called DISC1 was shortened in family members who had been diagnosed with mental illnesses. Recently, scientists have been able to create",380,128,0.3368
dialogsum,"#Person1#: Which service offered by your bank do you use most? #Person2#: I use several services. Of course, I deposit and withdraw money quite often. I often use my ATM card to take money out of my current account. I use my bank to exchange money from once currency to another. I often travel abroad, you see. #Person1#: Do you ever ask you bank for traveller's cheques? They are much safer than carrying lots of cash around. #Person2#: I sometimes use traveller's cheques, but sometimes I travel to countries where they are hard to exchange for cash. #Person1#: Do you use your bank to pay your utility bills? I use direct debit. #Person2#: Yes, I do. It save me a lot of time. I also have standing orders for my subscriptions to magazines. #Person1#: That's good idea. You don't need to worry about missing an issue of a magazine if you do that. I suppose you have a mortgage too. #Person2#: Yes. My bank offers very good terms and conditions on mortgage. There's a lot of competition between banks nowadays. Each one is trying to offer better conditions and services than the others. #Person1#: I have a deposit account with my bank. There are some restrictions on withdrawing money, but the interest rate is much higher. #Person2#: I don't have one. I prefer to buy shares. My bank also provides a share trading service. It's cheap and easy to use. #Person1#: That's great. But I prefer to put my money somewhere where the returns are more certain.",#Person2# talks about the bank services #Person2# usually uses. Then #Person1# and #Person2# discuss the usages of direct debit in their life. #Person1# also has a deposit account but #Person2# prefers to buy shares.,257,34,0.1323
dialogsum,"#Person1#: Where are you feeling the pain? #Person2#: I can ' t stand up! My stomach is killing me! #Person1#: Can you put your hand where it hurts the most? #Person2#: It hurts smack in the middle of my gut! #Person1#: Did this just come on suddenly? #Person2#: I felt OK until an hour or so ago, and then I just doubled over. #Person1#: Have you exercised strenuously or played sports recently? #Person2#: No, and I don ' t usually get a lot of stomachaches. #Person1#: We need to get you to an emergency room to see what the problem is. #Person2#: I think that that is the best way to out what is causing this. Thank you.",#Person2# has a stomachache and #Person1# tries to diagnose through interrogation. #Person1# decides to take #Person2# to an emergency room.,118,20,0.1695
pubmed-summarization,"and guanidines and have a lower affinity for 2-aminoimidazolines such as clonidine . the i2 receptors are mitochondrial , not g - protein coupled , and allosteric binding sites , possibly with a modulatory function , on monoamine oxidase - a and -b ( mao - a and -b ) . these enzymes are found in the neurons and astroglia cells and have a critical role in the inactivation of neurotransmitters . thereby , the i2 receptors may be useful as a therapeutic agent in various neurological diseases in which neurodegeneration is observed . besides , it is known that these subtypes contribute to reduce body temperature , exert control over central noradrenergic and hypothalamic - pituitary - adrenal axis activity , and regulate the small intestinal motility . more remarkably , it has been shown that the i2 receptors take part in the antinociception in several acute and chronic pain models and the ligands acting on the i2 receptors may be assessed as novel analgesics . the imidazoline-3 ( i3 ) receptors whose biological importance investigated further , are present in the pancreatic beta islet cells and modulate insulin secretion . we focus on the i2 receptor subtypes in this educational forum because involvement of this subtype in antinociception is well determined . pain modulation is a highly complex process , including numerous interacting peripheral and central mechanisms . the activation of the peripheral nociceptors or mediators that are released by the damaged tissue is required for the perception of pain . the activation - triggered signal is conveyed with the afferent transmission to the spinal cord with a and c nerve fibers and transmission parts through the dorsal horn ( dh ) to the higher centers via parallel ascending pain pathways . the impulses originated from the brain stem nuclei , descend to the spinal level and affect the transmission of pain signals at the dh . the relative balance between descending inhibition and facilitation can be changed by the type and intensity of the stimulus and also by the time following an injury . this complex process is regulated by the interaction of various chemicals and receptors over an extensive network from the periphery to the cns . the rate of participation of the chemicals and receptor","pain is an unpleasant experience and effects daily routine negatively . although there are various drugs , many of them are not entirely successful in relieving pain , since pain modulation is a complex process involving numerous mediators and receptors . therefore , it is a rational approach to identify the factors involved in the complex process and develop new agents that act on these pain producing mechanisms . in this respect , the involvement of the imidazoline receptors in pain modulation has drawn attention in recent years . in this review , it is aimed to focus on the imidazoline receptors and their ligands which contribute to the pain modulation . it is demonstrated that imidazoline-2 ( i2 ) receptors are steady new drug targets for analgesics",380,128,0.3368
scientific_lay_summarisation-elife-norm,"PCR and sequencing protocols (Charlop-Powers et al. , 2014). The entire dataset representing 185 biomes was clustered into operational taxonomic units (OTUs) at a sequence distance of 5%. Despite millions of unique sequencing reads yielding a predicted Chao1 OTU estimate of greater than 350,000 for each domain, rarefaction analysis suggests that we have not yet saturated the sequence space of either domain (1A, C). 10. 7554/eLife. 05048. 003Figure 1. Global abundance and comparative distribution of AD/KS sequences. The global abundance (A and C), sample-to-sample variation (B and D), and geographic distribution (E, F, G, and H) of adenylation domains (AD) and ketosynthase domains (KS) were assessed by pyro-sequencing of amplicons generated using degenerate primers targeting AD and KS domains found in 185 soils/sediments from around the world. (A and C) Global AD (A) or KS (C) domain diversity estimates were obtained by rarefying the global OTU table (de novo clustering at 95%) for AD and KS sequences and calculating the average Chao1 diversity metric at each sampling depth. (B and D) The ecological distance (i. e. , Jaccard dissimilarity) between AD (B) or KS (D) domain populations sequenced from each metagenome was determined as a function of the great circle distance between sample collection sites (km). Insets show local relationships (<500 km) in more detail. (E and F) All sample collection sites are shown on each world map and lines are used to connect sample sites that share at least the indicated fraction (3%, 10%) of AD (E) or KS (F) OTUs. (G and H) Biome-specific relationships within domain OTU populations sequenced from geographically proximal samples assessed by Jaccard similarity. Samples were collected from (G) Atlantic forest, saline or cerrado environments or from the (H) New Mexican desert topsoils or hot springs sediments. : http: //dx. . org/10. 7554/eLife. 05048. 003 The first question we sought to address with this data was how biosynthetic sequence composition varies by geographic distance. To do this we calculated the pairwise Jaccard distances between AD/KS sequence sets derived from each sampling site and used these metrics to compare samples. The Jaccard distance, a widely used metric for comparing the fraction of shared OTUs between samples, was chosen over alternative metrics due to its simplicity and to the lack of a comprehensive reference phylogenetic tree","Many of the most useful medicinal drugs—including antibiotics and cancer drugs—are derived from bacteria living in the soil that produce these chemicals as part of their natural life cycle. Many of these chemicals have been found by culturing bacteria in the laboratory, but this approach is limited because it only provides access to the chemicals produced by the small fraction of bacteria species that we can culture in this way. Also, many bacteria do not produce as many different chemicals when they are grown under these artificial conditions, instead of their natural environment. This suggests that bacteria living in the environment are likely to provide an additional source of new chemicals that could have medicinal benefits. Here, Charlop-Powers et al. tackle this issue by employing a high-throughput genetic",380,128,0.3368
dialogsum,"#Person1#: good afternoon. ' ginger's restaurant '. May I help you? #Person2#: yes. I'd like to book a table for Friday evening please. #Person1#: certainly. For how many people? #Person2#: we'll be eight or nine people. Could we book a private room? #Person1#: I'll just check. At what time on Friday evening? #Person2#: about 7:30. #Person1#: yes. That's fine. We can book you a private room for up to ten people at that time. Could you give me your name please? #Person2#: my name is Jenkins. My phone number is 7539738 2. that's confirmed then. 7:30 on Friday. #Person1#: yes. Do you intend to order a la carte or will you be having our seafood buffet? #Person2#: oh, we'd like the buffet please. We'Ve heard it's very good.",Jenkins books a private room at ginger's restaurant for Friday evening. Jenkins gives his number and says he would like the buffet.,128,22,0.1719
pubmed-summarization,"microbiological confirmation of bacterial infection is rarely achieved in children with acute lower - respiratory - tract infections ( alrtis ) because of the inability to obtain material from the infection site ( ie , the lung ) . treatment is , therefore , mostly empirical , which irrevocably leads to overtreatment and sometimes undertreatment . sputum induction with nebulized hypertonic saline can help adequately produce sputum in children who are otherwise unable to do so . sputum induction is routinely used to obtain samples for microbial cultures in pediatric illnesses such as cystic fibrosis and tuberculosis . it may also be useful in establishing a causative diagnosis of alrti in otherwise healthy children . the purpose of this study was to determine the effectiveness of sputum induction in obtaining good quality sputum in children with clinically suspected alrti in the everyday , busy general hospital setting . a prospective study in 2 large regional hospitals ( jeroen bosch hospital and mxima medical centre ) in the netherlands was conducted between october 2009 and october 2011 . children aged 6 months to 18 years presenting with suspected alrti were eligible for inclusion . suspected alrti was a clinical diagnosis of the attending physician , with tachypnea and 1 of the following symptoms : dyspnea , fever , cough , and/or abdominal pain . exclusion criteria for participation were a recent severe asthma exacerbation , oxygen saturation 92% , anatomical airway abnormalities , and the use of -blockers or diuretics blood inflammation parameters ( ie , leukocyte count and c - reactive protein [ crp ] level ) , blood culture , and chest x - ray were performed before initiation of the study procedure as part of routine diagnostics . sputum induction was performed with hypertonic saline ( nacl 5.8% ) inhalation using a nebulizing device with oxygen flow . when a patient was unable to expectorate sputum after induction , a sterile suction catheter was used to obtain secretions from the oropharynx . specimens were considered of good quality if < 25 squamous epithelial cells and > 25 leukocytes were present per low - power field ( 10x lens objective ) . sputum samples were cultured for 48 hours using routine microbiological procedures . a concomitant nasopharyngeal lavage sample",we prospectively studied the feasibility and effectiveness of sputum induction in obtaining good quality sputum and its subsequent bacterial yield in children with clinically suspected acute lower - respiratory - tract infection ( alrti ) . good quality sputum was collected in 89/98 ( 91% ) patients . sputum cultures revealed 1 bacterial pathogens in 22 cases ( 25% ) . adverse events were infrequent and mild ( 6% ) . sputum induction is feasible in young children and leads to an increased number of etiological diagnoses of alrti .,380,90,0.2368
dialogsum,"#Person1#: Hello, IMPF Bank, how can I help you? #Person2#: I need to report a missing Bank Card and Book. #Person1#: OK Sir. Could you tell me the account holder's name, the account number, the amount in the account and your PIN number, please? #Person2#: Well, the account's in my name. Patrick Dean, that's D-E-A-N. The account number is 15273478841. There was about 20, 000 RMB inside. #Person1#: OK, Sir. Almost there, I just need your PIN number. When we issue you with a new card and book we would recommend that you change your PIN number. It's a very simple procedure. #Person2#: OK, it's 672910.",#Person1# helps Patrick Dean to deal with his missing bank card and book.,106,13,0.1226
dialogsum,"#Person1#: The boss announces the pay raise today, right? How much do you think we'll get? #Person2#: No idea. Your guess is as good as mine. #Person1#: It better be more than last year. #Person2#: Well, anything is better than nothing. Wait and see.",#Person1# and #Person2# guess how much the pay raise is.,44,10,0.2273
scientific_lay_summarisation-elife-norm,"a reduction in the amplitude of excitatory but not inhibitory inputs to abGCs, suggesting that microglia are essential for proper integration of abGCs in adult circuits. We labeled cohorts of abGCs born using lentiviral injection into the RMS (Consiglio et al. , 2004; Livneh and Mizrahi, 2012) of adult 8–12 week old mice. To visualize interactions between microglia and abGCs, we performed time-lapse in vivo two-photon imaging of the dendrites of dTomato-labeled abGCs in the external plexiform layer (EPL) of the OB over the first four weeks after injection in CX3CR1-GFP +/- mice, in which microglia are labeled with GFP (Video 1, 1A). Consistent with previous observations (Nimmerjahn et al. , 2005; Tremblay et al. , 2010), we found that microglial processes were highly motile and occasionally appeared in close proximity to labeled dendritic spines (Video 2, 1B). To quantify whether microglia preferentially interact with dendritic spines (defined as colocalization of a microglial process with at least 5% of the area of a spine head, see Materials and methods, Analysis of microglia-spine interactions) on abGCs compared to encountering them by chance during the course of continuous motility, we compared the frequency of interactions between microglial processes and spine heads in the actual imaging data with the frequency of interactions in a series of images in which the microglia channel was arbitrarily shifted with respect to the dendritic imaging channel (‘Offsets’). Microglia exhibited an impressive degree of motility, interacting with 38. 5% of abGC dendritic spines classified as ‘mushroom’ spines (1C) and 27. 2% of spines classified as ‘filopodial’ spines (1H) during the course of our 30–90 min imaging sessions, which was not significantly different from the offset data (p=0. 13 and p=0. 39, respectively) (1D, I). However, we found that microglia interacted significantly more often with individual mushroom spines than predicted by chance (Data: mean 0. 15 ± 0. 00039 interactions/10 min vs. Offsets: mean 0. 12 ± 0. 016 interactions/10 min, p=0. 048) (1E) though the length of individual interactions was not significantly greater (p=0. 96) (1F). In contrast, microglia did not interact with filopodial spines at levels above chance (1I–L). Microglia did not cover significantly more of the spine than predicted by chance during interactions with either spine type (Mushroom: p=0. 72, Filopodial: p=0. 84) (1G, L). These","The brain has its own population of resident immune cells known as microglia, which defend against infections and are involved in conditions such as Alzheimer’s, Parkinson’s and other diseases. In the last decade, new studies have suggested that these cells also sculpt brain circuits during early development. They can ‘eat’ weak connections between neurons, and help strong ones to mature. Most of brain ‘wiring’ happens during development, when the majority of neurons is born and connects together. However, a few brain areas can incorporate new neurons during adulthood into existing circuits. In mice for example, this process takes place in the olfactory bulb, the area that first processes smells: it is believed that new neurons connecting to existing ones helps to detect new odors. It is unclear, however,",380,128,0.3368
dialogsum,"#Person1#: Have you seen the new show that everyone's talking about? #Person2#: It's called stranger things, I watched it this weekend and it was so cool. #Person1#: I haven't seen it yet, but yeah, everyone is talking about it, what's it about? #Person2#: Well, it's sort of a science fiction tale about a boy who gets caught in the upside down. The opposite world of ours. There are monsters and spiders action and even comedy. The coolest part is that most of the actors are kids our age, you should check it out.",#Person1# and #Person2# are talking about the new show called stranger things. #Person2# recommends it to #Person1#.,93,17,0.1828
dialogsum,"#Person1#: What upsets you? #Person2#: My parents called. As usual, they reminded me again that I should have a plan to marry by my late 20s. Easier set than done. Who should I marry? I have no time to go on a date. #Person1#: It is not your mother finding one for you? #Person2#: I will find one myself, of course. I'm a modern girl. #Person1#: Perhaps you can try the three minutes date, the latest type. #Person2#: You mean dozens of the opposite sex meet each other for three minutes in a dimly bar serving alcohol, I hate that idea. #Person1#: No, there is an updated version, three minutes video date. I know an online dating website providing such service with a microphone and webcam, you can sigh for it. You can be face-to-face with a guy talking for maximum three minutes. #Person2#: I don't think it makes sense. Three minutes is such a short time. #Person1#: I think you can find out if there is a possibility of romance within the first second of meeting someone, so-called love at first sight. #Person2#: Anyway, I don't want to post my face up for sale on the internet like that. #Person1#: Don't worry. There are many other options using the internet as dating methods. Some sites operate at international standard even have got certifications. #Person2#: Of course, for these sites, you have to pay a membership fee. But all in all, it is more serious and professional. The chance of meeting a good and serious person who does not play games is higher. #Person1#: I don't want to post my personal information on the internet. I'm not knowing who is reading it.","#Person2# is upset because her parents urge her to get married. #Person1# suggests she use the internet as dating methods, but #Person2# doesn't want to post her personal information on the internet.",282,32,0.1135
scientific_lay_summarisation-elife-norm,"HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high. HIV infection is known to result in extensive T cell depletion in lymph node environments (Sanchez et al. , 2015), where infection is most robust (Brenchley et al. , 2004; Doitsh et al. , 2010; Doitsh et al. , 2014; Finkel et al. , 1995; Galloway et al. , 2015; Mattapallil et al. , 2005). Depletion of HIV infectable target cells, in addition to onset of immune control, is thought to account for the decreased replication ratio of HIV from an initial peak in early infection (Bonhoeffer et al. , 1997; Nowak and May, 2000; Perelson, 2002; Phillips, 1996; Quiñones-Mateu and Arts, 2006; Ribeiro et al. , 2010; Wodarz and Levy, 2007). This is consistent with observations that individuals are most infectious in the initial, acute stage of infection, where the target cell population is relatively intact and produces high viral loads (Hollingsworth et al. , 2008; Wawer et al. , 2005). T-cell death occurs by several mechanisms, which are either directly or indirectly mediated by HIV infection. Accumulation of incompletely reverse transcribed HIV transcripts is sensed by interferon-γ–inducible protein 16 (Monroe et al. , 2014) and leads to pyroptotic death of incompletely infected cells by initiating a cellular defence program involving the activation of caspase 1 (Doitsh et al. , 2010; Doitsh et al. , 2014; Galloway et al. , 2015). HIV proteins Tat and Env have also been shown","The HIVvirus infects cells of the immune system. Once inside, it hijacks the cellular molecular machineries to make more copies of itself, which are then transmitted to new host cells. HIV eventually kills most cells it infects, either in the steps leading to the infection of the cell, or after the cell is already producing virus. HIV can spread between cells in two ways, known as cell-free or cell-to-cell. In the first, individual viruses are released from infected cells and move randomly through the body in the hope of finding new cells to infect. In the second, infected cells interact directly with uninfected cells. The second method is often much more successful at infecting new cells since they are exposed to multiple virus particles. HIV infections can be",380,128,0.3368
scientific_lay_summarisation-elife-norm,"membrane potential, while the equivalent results in patch clamp-controlled experiments are remarkably inconsistent. During whole cell patch clamp of cardiac myocytes, activation of PKAs has been reported to duplicate results with dyes (Despa et al. , 2005), to mildly stimulate pump currents under all experimental conditions (Kockskamper et al. , 2000), to have no effect (Ishizuka and Berlin, 1993; Main et al. , 1997; Fine et al. , 2013), or to inhibit pump currents via an oxidative mechanism (Galougahi et al. , 2013). One analysis suggests that phosphorylation by PKA inhibits pump activity in the absence of Ca, but overcomes an inhibitory action of Ca and thereby enhances pump activity, albeit modestly, in the presence of cytoplasmic Ca (Gao et al. , 1996). Results for PKCs are similarly complex and presumably reflect complexities of PKC signaling in cardiac myocytes. Both small stimulatory effects (Gao et al. , 1999; Han et al. , 2006) and inhibitory effects (White et al. , 2009) are reported, the latter occurring through oxidative stress signaling mechanisms. Na/K pumps are evidently regulated by trafficking mechanisms in some cell types (Al-Khalili et al. , 2003; Liu and Shapiro, 2007; Lecuona et al. , 2009; Alves et al. , 2015), but there is little support for physiological regulation of cardiac pumps by these mechanisms. Nonconventional endocytic mechanisms can remove pumps from the sarcolemma during reperfusion injury (Lin et al. , 2013). Other mechanisms proposed to regulate the activity of Na/K pumps in cardiac myocytes include redox-dependent glutathionylation of the beta subunits of Na/K pumps (Liu et al. , 2012) and the modulation of phospholemman function by palmitoylation (Tulloch et al. , 2011). Given this background, we initiated a new analysis of pump regulation in murine myocytes, starting with the observation that Na/K pump currents can run down during whole-cell patch clamp experiments. Attempting to stop and/or reverse this run-down, it became evident that a brief elevation of cytoplasmic Ca via reverse Na/Ca exchange had substantially larger effects on pump activity than the activation of either PKAs or PKCs. As described here, the stimulatory effects of transient Ca elevation, usually associated with spontaneous beating, occur as an apparent increase of the cytoplasmic Na affinity of Na/K pumps, the same functional effect proposed to occur with PKA activation (Despa et","All animal cells have pumps in their outer membrane that continuously pump out sodium ions and bring in potassium ions. As a result, the concentration of sodium ions inside cells is low in comparison to the concentration outside, and vice versa for potassium ions. These differences between inside and outside concentrations are a source of energy for cells to do a variety of important tasks, similar to using energy that is stored in a reservoir formed by a dam. When cells allow ions to move in the direction they naturally move, similar to water moving over a dam, they carry out two important roles. First, they generate electrical signals that are the basis of all fast communication in nerves and muscles. Second, they can force important molecules to",380,128,0.3368
dialogsum,#Person1#: It's quiet everywhere in winter. #Person2#: Yes. I like winter. #Person1#: Me too. #Person2#: It's snowing heavily. What about taking a walk? #Person1#: That's a good idea. Let's go! #Person2#: What a heavy snow! Look! The water is frozen. #Person1#: Take care! Don't slip on the ground. #Person2#: I've got it. I like the feeling of stepping on the ice. #Person1#: Yes. Very wonderful. #Person2#: There is a snowman over there. #Person1#: How lovely it is!,#Person1# and #Person2# take a walk on a snowy day. They enjoy the scenery.,77,14,0.1818
dialogsum,"#Person1#: I'm exhausted. My new exercise class is so hard, #Person2#: I think it is easy. I could work in your class with no problem. #Person1#: You thing so? #Person2#: Oh, without a doubt. When is the next class? #Person1#: Tomorrow morning. Try it. #Person2#: No problem. #Person1#: Are you going to this class this morning? #Person2#: Of course, easy. No sweat. #Person1#: You're no able to move after this class. #Person2#: Are you kidding me? It's going to be up a piece of cake. #Person1#: You want to bet? #Person2#: Yeah, what't the bet? #Person1#: I bet I can go one hour in your class this morning and not feel a thing.",#Person1# feels exhausted about #Person1#'s exercise class while #Person2# thinks it's easy and wants to have a try.,113,18,0.1593
pubmed-summarization,"as small as 30 nm in diameter using stimulation emission depletion fluorescence microscopy . the results indicate that raft lipids , but not non - raft lipids , are indeed preferentially trapped , albeit for short distances ( < 20 nm ) and for short periods ( 10 - 20 ms ) . homofret measurements , combining frap , emission anisotropy , and theoretical model fitting to test models of lateral organization in the membrane , were used determine the degree of clustering of glycosylphosphatidylinositol ( gpi)-anchored proteins in the plasma membrane . the formation of gpi - anchored protein nanoclusters ( of ~4 molecules or even less ) is an active process involving both actin and myosin , and these nanoclusters are nonrandomly distributed into larger domains of < 450 nm . additionally , high - speed single - particle tracking ( 50 khz ) revealed that gpi - anchored proteins , along with other membrane proteins , undergo rapid hop diffusion between 40 nm actin - regulated compartments , with a compartment dwell time of 1 - 3 ms on average . however , when gpi - anchored proteins were deliberately cross - linked by gold or quantum dot particles , they underwent transient confinement or stall ( stimulation - induced temporary arrest of lateral diffusion ) from a cholesterol - dependent nanodomain in a src family kinase mediated manner [ 17 - 19 ] . a recent study identified a transmembrane protein ( carboxyl - terminal src kinase [ csk]-binding protein ) involved in the linkage between the particle - cross - linked gpi - anchored protein , thy1 , and the cytoskeleton ( ) . thy-1 crosslinking by streptavidin - coated quantum dots aggregates gpi lipid tails in the outer leaflet of the plasma membrane in a cholesterol - dependent manner . carboxyl - terminal src kinase ( csk)-binding protein ( cbp ) , a transmembrane protein , is recruited to or captured by thy-1 clusters along with src - family kinase substrates ( ks ) . cbp or ks ( or both ) are phosphorylated by src - family kinases ( sfk ) , enabling cbp to bind to actin filaments via an ebp50-erm ( ezrin / radixin / moesin - binding phosphoprotein 50-ezrin /","evidence in support of the classical lipid raft hypothesis has remained elusive . data suggests that transmembrane proteins and the actin - containing cortical cytoskeleton can organize lipids into short - lived nanoscale assemblies that can be assembled into larger domains under certain conditions . this supports an evolving view in which interactions between lipids , cholesterol , and proteins create and maintain lateral heterogeneity in the cell membrane .",380,70,0.1842
scientific_lay_summarisation-elife-norm,"physiology of SLC7A8, we generated null Slc7a8 knockout mice (Slc7a8−/−) (Font-LLitjós, 2009) and (— 1A). Here, we describe the detection of a hypoacusic phenotype in the Slc7a8−/− mouse model and demonstrate that novel loss-of-function SLC7A8 mutations constitute a primary cause in the development of ARHL in a cohort of elderly people from two isolated villages in Italy. SLC7A8 is highly expressed in the kidney, intestine and brain, and neither full-length nor truncated SLC7A8 protein were detected in membrane samples of Slc7a8−/− mice (1A). The Allen Brain Atlas (Allen Institute for Brain Science, 2004) localizes mouse brain SLC7A8 to the cortical subplate, cerebellum, thalamus and olfactory bulb. Our results showed that SLC7A8 protein was localized to the plasma membrane of neuronal axons in different brain regions such as, the choroid plexus, subfornical organ, cerebral cortex and hypothalamus by immunohistochemistry (— 2A). This specific localization in the brain pointed to the possibility that the absence of the transporter could potentially lead to neurological disorders. Behavioral screening showed that absence of SLC7A8 in mice does not affect either learning or memory (— 3). In contrast, a significant reduction in latency was observed in the rotarod acceleration test indicating impairment in motor coordination in Slc7a8−/− mice (— 3G). Reaffirming poorer motor coordination performance in the Slc7a8−/− mice, an increased exposure to shock on the treadmill was also observed (— 3B). Interestingly, a marked impairment was observed in the pre-pulse inhibition of acoustic startle response, which assesses the response to a high intensity acoustic stimulus (pulse) and its inhibition by a weaker pre-pulse. The response to a 120 dB single-pulse was significantly reduced in Slc7a8−/− mice (1B). The higher threshold required for responding to the acoustic stimulus in the PPI tests in Slc7a8−/− animals could potentially be indicative of a hearing impairment or to a defect in the stress response signaling. Response to stress is modulated by the hypothalamic-pituitary-adrenal axis via the release of corticosterone from the adrenal cortex (Smith and Vale, 2006). As SLC7A8 is expressed in the murine pituitary gland (— 2A and S3H), plasma corticosterone levels under stressing conditions were analyzed. No differences were observed in corticosterone levels at either basal conditions, nor under restraint stress in the Slc7a8−/− group, indicating a normal stress response in the absence of SLC7A8 (— 3I).","Age-related hearing loss affects about one in three individuals between the ages of 65 and 74. The first symptom is difficulty hearing high-pitched sounds like children’s voices. The disease starts gradually and worsens over time. Changes in the ear, the nerve that connects it to the brain, or the brain itself can cause hearing loss. Sometimes all three play a role. Genetics, exposure to noise, disease, and aging may all contribute. The condition is so complex it is difficult for scientists to pinpoint a primary suspect or develop treatments. Now, Guarch, Font-Llitjós et al. show that errors in a protein called SLC7A8 cause age-related hearing loss in mice and humans. The SLC7A8 protein acts like a door that allows amino acids – the building blocks of proteins –",380,128,0.3368
pubmed-summarization,"the right and left sides was done , to ascertain , if certain joints were more prone to disease processes , based on functional inequalities . this study was approved by the ethics committee of sdm college of dental sciences , karnataka , india . fifteen patients in the age group of 20 - 60 years ( 11 females and 4 males ) were selected for this study , out of a referral pool of patients from the oral medicine , rheumatology and orthopaedics clinics . patients with a diagnosis of ra according to the american rheumatism association 's revised criteria for rheumatoid arthritis . only patients over the age of 18 patients with joint involvement other than the tmj / hand ( mcp ) and wrist joint were not included . patients with myofascial pain , tmj ankylosis , headache , patients with known history of previous trauma , cervical spondylosis and pregnant females were not included . detailed case history as per the questionnaire was taken . as the patients were known ra patients , the primary focus was to ascertain the onset , duration , site , type of symptoms like pain , limited / altered movement of the hands and jaw etc . clinical assessment of tmj for function and range ( deviation / limitation ) of movement , pain in the joint proper or while biting , audible or palpable clicking of joints were recorded . examination of the mouth was carried out at the same time as the clinical examination of the joint . examination of hand / wrist joints for soft tissue swelling , pain , limitation of movement , tenderness to palpation , difficulty in performing simple functions like writing or picking up objects and deformities was done . in all cases , laboratory tests involving erythrocyte sedimentation rate ( esr - westergren 's method ) and ra test using the rhelax rf slide test kit ( tulip , india ) was used in this study for the determination of rheumatoid factor . radiographic evaluation of the tmj was carried out using the conventional projections , transcranial and opg and advanced computed tomography ( ct ) . transcranial views of right and left tm joints of all patients were taken using siemens","background : a review of literature revealed that , although the involvement of temporomandibular joint ( tmj ) in rheumatoid arthritis ( ra ) patients is not uncommon , variation in presentation persist . comparative studies of bony changes in the right and left tmj with the right and left peripheral hand ( metacarpophalangeal - mcp)/wrist joints have not been done , to the best of our knowledge.materials and methods : in this cross - sectional study , the temporomandibular and hand ( mcp ) and wrist joints of fifteen rheumatoid arthritis patients were evaluated with questionnaires , clinical and lab assessment and radiographically using conventional radiographs and computed tomography . students t - test was applied for the statistical analysis of the data obtained and a p",380,128,0.3368
pubmed-summarization,"obesity stigma and negative stereotypes of obese people are widespread and damaging to the health , dignity , human rights , and quality of life of obese individuals . standard media and biomedical depictions of obese individuals contribute to this stigmatization by positing that obesity incidence is nearly entirely dependent on individualistic actions . furthermore , obese individuals ' may occupy numerous intersecting social roles and identities based on their gender , class , race , and other social positions . biomedical and media depictions invariably refer to obesity as a crisis or epidemic . obesity 's multifactorial and multilevel etiology is reduced to an energy balance model of causation , which inadequately explains weight trajectories . despite the oft - reported inefficacy of weight loss dieting , public health interventions may be unsuccessful due to a narrow focus on weight loss , an overly simplistic notion of how obese individuals live ; experience their bodies ; the contexts they inhabit ; and the opportunities available to them in seeking wellness , happiness , and a full life . furthermore , while health is posited as the ultimate goal , these projects frequently focus on weight and deem fatness or higher weights as necessarily pathological . this is especially important given that the populations often targeted by such campaigns may differ culturally and socioeconomically from dominant groups . these diverse factors may affect their lifeways , priorities , and health conceptualizations in manners which may require in - depth exploration to produce truly beneficial and sensitive programming . qualitative social scientists , such as anthropologists or sociologists , trained in methods such as ethnography , may be uniquely suited to explore the lived experiences of obese individuals . they may aid in developing a public health strategy that is suited to the priorities and lifestyles of all individuals and is implemented in a manner consistent with a salutogenic , positive , and holistic understanding of health promotion . this paper discusses the potential for in - depth , qualitative social science research to concretely contribute to program delivery . even within the expanding fields of critical obesity research , as warin and gunson note , the compiling of actual obese people 's experiences and perspectives has been limited . through","obesity is viewed as a major public health concern , and obesity stigma is pervasive . such marginalization renders obese persons a special population . weight bias arises in part due to popular sources ' attribution of obesity causation to individual lifestyle factors . this may not accurately reflect the experiences of obese individuals or their perspectives on health and quality of life . a powerful role may exist for applied social scientists , such as anthropologists or sociologists , in exploring the lived and embodied experiences of this largely discredited population . this novel research may aid in public health intervention planning . through these studies , applied social scientists could help develop a nonstigmatizing , salutogenic approach to public health that accurately reflects the health priorities",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2013). These observations raise the possibility that alternate mechanisms may be active in symmetrically dividing eukaryotic cells. The fission yeast Schizosaccharomyces pombe is an excellent model system for investigating RLS and aging phenotypes in symmetrically dividing eukaryotic cells. Fission yeast cells are cylindrical, grow by linear extension, and divide via medial fission. After cell division, the two sibling cells each inherit one pre-existing cell tip (old-pole). The new tip is formed at the site of septation (new-pole). Immediately after division, new growth is localized at the old-pole end of the cell. Activation of growth at the new-pole cell tip occurs ~30% through the cell cycle (generally halfway through G2). This transition from monopolar to bipolar growth is known as new end take-off (NETO) (Mitchison and Nurse, 1985; Sveiczer et al. , 1996; Martin and Chang, 2005). Prior studies of fission yeast have yielded conflicting results regarding cellular aging. Several papers reported aging phenotypes akin to those observed in budding yeast (e. g. , mother cells become larger, divide more slowly, and have less healthy offspring as they age) (Erjavec et al. , 2008; Barker and Walmsley, 1999). However, a recent report used colony lineage analysis to conclude that protein aggregates are not asymmetrically distributed, and that inheriting the old cell pole or the old spindle pole body during cell division does not lead to a decline in cell health (Coelho et al. , 2013). However, this report tracked the first 7–8 cell divisions of microcolonies on agar plates and thus could not observe the RLS of single cells (Coelho et al. , 2013). The controversy between these studies may partially stem from the difficulty in tracking visually identical cells for dozens of generations. Replicative lifespan assays require the separation of cells after every division. This is traditionally done via manual micro-dissection of sibling cells on agar plates, a laborious process that is especially difficult and error-prone for symmetrically dividing fission yeast. Extrinsic effects related to using a solid agar surface may confound observations made under these conditions (Mei and Brenner, 2015). Finally, recent work using high-throughput microfluidic devices to study individual budding yeast and bacterial cells (Lee et al. , 2012; Crane et al. , 2014; Wang et al. , 2010; Liu et al. , 2015; Jo et al. ,","As the cells in our bodies age, their ability to carry out their normal processes also degrades. Ultimately, this causes tissues to deteriorate. How rapidly a cell ages depends on the genes encoded in its DNA, and can also be affected by certain drug treatments. Cells reproduce by dividing to form two new cells. One common approach used to study cellular aging is to follow how genetic modifications and drug treatments alter how many offspring a cell produces before it dies. So far, most of these studies have been performed using budding yeast cells, which reproduce by dividing asymmetrically to form two differently sized cells. Little is known about aging in cells that divide symmetrically. Another type of yeast, called fission yeast, divides symmetrically. Furthermore, many of the",380,128,0.3368
dialogsum,"#Person1#: Hello, Macy Agency. #Person2#: Good morning. I'd like to book a return ticket from London to Paris on Monday, July 14th, please. #Person1#: Yes, Madam. We have a flight at 14: 30, Is that suitable? #Person2#: Oh, that's fine. And how much will that cost, please? #Person1#: The price is $ 420 for the return flight. #Person2#: Good. Which airport does the flight leave from? #Person1#: It leaves from Heathrow Airport. Check in time is one hour before departure. #Person2#: My name is Susan Smith. Can I pick up the ticket tomorrow morning? #Person1#: Sure, we'll have it ready soon, so come whenever you like after that. #Person2#: Thank you. #Person1#: You are welcome.",Susan Smith phones Macy Agency to book a return ticket from London to Paris on July 14th at 14: 30 with #Person1#'s assistance.,115,23,0.2
scientific_lay_summarisation-elife-norm,"move in a variety of non-directional manners collectively referred to as dwelling (Gray et al. , 2005; von Stetina et al. , 2006; Gallagher et al. , 2013; Gjorgjieva et al. , 2014). During lethargus, C. elegans prominently exhibit quiescence—the complete absence of dynamic muscle contraction. Alternating bouts of locomotion and quiescence comprise the simple architecture of C. elegans sleep (Raizen et al. , 2008; Iwanir et al. , 2013). In a previous study, we have shown that the durations of these bouts are correlated (Iwanir et al. , 2013), but the mechanisms underlying this process of routine stabilization were not examined. In this study, we analyze the behavioral responses of sleeping nematodes under undisturbed, weakly disturbed, and strongly disturbed conditions. To do so, we continuously assayed the locomotion of C. elegans from the mid fourth intermolt stage (L4int), through the fourth lethargus stage (L4leth), and into the mid young adult stage (YA). We found that weak photo- or mechano-stimulation transiently skewed the dynamics of bouts while preserving the characteristic pairwise correlations. Thus, under unperturbed or weakly perturbed conditions, homeostatic compensation manifested as a transient extension of quiescence bouts (and shortening of motion bouts under some conditions) in response to prolonged motion. This form of compensation under low noise conditions, termed micro-homeostasis (Iwanir et al. , 2013; Nelson and Raizen, 2013), required the function of the neuropeptide Y (NPY) receptor homolog, NPR-1. In contrast, strong stimuli induced a qualitatively different homeostatic response: the animals moved continuously for several minutes, after which quiescence monotonically returned to its baseline level. Compensation for the motion induced by a strong stimulus manifested as an upshift in the baseline fraction of time spent in quiescence, rather than a transient extension of quiescence bouts. The homeostatic responses to strong stimuli required the function of the DAF-16/FOXO in neurons (see also Driver et al. , 2013) but not the function of NPR-1. Conversely, micro-homeostasis was not abolished in daf-16 mutants. In addition, we show that neuropeptidergic signaling is not strictly required for maintaining high levels of mean quiescence during lethargus. The loss of function of UNC-31/CAPS, a calcium-dependent activator protein required for dense core vesicle exocytosis (Avery et al. , 1993; Charlie et al. , 2006), resulted in a minor reduction of overall quiescence. In contrast, quiescence","The regenerative properties of sleep are required by all animals, with even the simplest animal, the nematode Caenorhabditis elegans, displaying a sleep-like state called lethargus. During development, nematodes must pass through four larval stages en route to adulthood, and the end of each stage is preceded by a period of lethargus lasting 2 to 3 hr. Human sleep is divided into distinct stages that recur in a prescribed order throughout the night. Nematodes, on the other hand, simply experience alternating periods of activity and stillness as they sleep. Nevertheless, in both species, any disruptions to sleep automatically lead to adjustments of the rest of the sleep cycle to compensate for the disturbance and to ensure that the organism gets an adequate amount of sleep overall. To date, it",380,128,0.3368
dialogsum,"#Person1#: Are you going out Ann? But supper will be ready in a minute. #Person2#: I'm going to Mary's house for dinner this evening. I told you so this morning daddy. #Person1#: Sorry, I forgot about it. So you were going to her birthday party? #Person2#: Yes, and Jenny and Laura will be there, too. We were all good friends when we were at school you know? #Person1#: Yes, and now all of you have graduated from University. Where does Mary work? #Person2#: In the East Photo nearby as a photographer, you can go and have your picture taken there someday. #Person1#: Ok, see you.",Ann will go to Mary's house to attend her birthday party. Ann tells #Person1# Mary works as a photographer.,105,19,0.181
pubmed-summarization,", 2003 ) . in zebrafish , crip2 is reported to be a target of wnt3a signaling and regulates smooth muscle cell differentiation ( kihara et al . , 2011 ) and the development of cardiac neural crest cells during early embryogenesis ( sun et al . , 2008 ) . however , the direct role of crip2 in the av valve formation has not yet been elucidated . zebrafish is a useful animal model for studying development of the heart and other circulation systems , including blood and lymphatic vessels ( kim and kim , 2014 , kim et al . , 2012a ; 2013a ; 2013b ; ) because the embryos are transparent and a multitude of transgenic lines that express fluorescent proteins in tissue- and cell - specific manners are readily available . in zebra - fish , the heart can be observed under a dissecting microscope soon after formation of the primitive heart tube . the heart starts beating at 24 h post - fertilization ( hpf ) , heart looping begins at 36 hpf , functional valves are formed by 48 hpf , and heart valve development is complete by approximately 55 hpf ( stainier et al . , 2002 ) . in this study , we found that crip2 expression in the avc endocardial cells , but not in the avc myocardial cells , in late heart development is critical for heart valve development in zebrafish embryos . furthermore , crip2-deficient embryos showed markedly increased expression of the has2 and versican a genes , which are responsible for the synthesis of versican a and hyaluronan . we provide data that crip2 expressed in the avc endothelial cells plays an important role in cardiac valve formation by suppressing genes involved in the synthesis of versican a and hyaluronan , which are essential ecm components in the cardiac jelly and endocardial cushion . zebrafish ( danio rerio ) were raised and maintained at 28.5c , and embryos were staged as described in a previous study ( kimmel et al . , 1995 ) . embryos were obtained from spontaneous spawnings and the embryos were manually dechorionated at appropriate stages by using watchmaker s forceps and then fixed using 4% paraformaldehyde in phosphate - buffered saline .","the initial step of atrioventricular ( av ) valve development involves the deposition of extracellular matrix ( ecm ) components of the endocardial cushion and the endocardialmesenchymal transition . while the appropriately regulated expression of the major ecm components , versican and hyaluronan , that form the endocardial cushion is important for heart valve development , the underlying mechanism that regulates ecm gene expression remains unclear . we found that zebrafish crip2 expression is restricted to a subset of cells in the av canal ( avc ) endocardium at 55 hours post - fertilization ( hpf ) . knockdown of crip2 induced a heart - looping defect in zebrafish embryos , although the development of cardiac chambers appeared to be normal . in the avc of crip2-deficient embryos",380,128,0.3368
dialogsum,"#Person1#: Thanks for the advice, Mr. Macmillan. I'll keep it in mind. I had better head off though. I'm meeting my husband for dinner. #Person2#: Sure, I'm heading out myself. Enjoy your evening. #Person1#: Thanks, sir. You too. Drive safely, I hear there's a lot ice on the roads. #Person2#: Thanks for the warning! See you tomorrow!",#Person1# thanks Mr. Macmillan for his advice. They say goodbye to each other.,57,13,0.2281
scientific_lay_summarisation-elife-norm,"the expression of cholesterol and steroid biosynthesis genes. For each of the Mondo pathway members MondoA, ChREBP and Mlx one single orthologue is present in the zebrafish genome (GRCz11/danRer11). We cloned the full cDNAs for zebrafish MondoA and ChREBP (GenBank Accession KF713493 [mondoa], KF713494 [chrebp]) based on the (partially) predicted sequences. Phylogenetic analysis showed that zebrafish mondoa, chrebp and mlx cluster with their mammalian and chicken homologs (1A) and revealed a high level of protein sequence conservation between zebrafish and human orthologs (1B), especially of the glucose-sensing module (GSM) specific to the Mondo family and of the DNA binding bHLH/Zip domains. This finding suggests that the functions of these proteins are conserved. To examine whether the zebrafish Mondo pathway factors function similarly in the regulation of gene transcription as their mammalian orthologs, we studied the pathway in zebrafish PAC2 cells (Lin et al. , 1994). All three Mondo pathway factors are expressed in these cells (— 1A). To monitor Mondo signaling, we generated a luciferase reporter gene construct driven by two ChoREs fitting the mammalian consensus (Ma et al. , 2006) and a TATA box minimal promoter (1C). This construct was active in HepG2 cells, a mammalian cell culture model commonly used for Mondo pathway studies (Kim et al. , 1996; Yu and Luo, 2009; — 1B). In PAC2 cells, bioluminescence equally increased in a dose-dependent manner upon glucose treatment (1C). No significant changes in bioluminescence levels were detected upon glucose treatment in cells expressing a constitutively active luciferase reporter (pGL3-Control; 1D), excluding a general unspecific increase in transcriptional activity by glucose treatment. We next tested whether overexpression of Mondo pathway members enhances glucose induced pathway activity. Transient overexpression of MondoA and Mlx activated transcription from the reporter also under low glucose conditions (1E), as shown by the increased bioluminescence compared with transfection of the 2xChoRE reporter alone (p≤0. 001). Overexpression of the MondoA and Mlx factors together led to an even more pronounced effect on bioluminescence (p≤0. 01), revealing synergistic effects. High glucose levels caused significant reporter gene induction in control cells (p≤0. 01; 1E). Importantly, strong glucose induction of the reporter was also shown by cells overexpressing either Mlx (p≤0. 01) or MondoA (p≤0. 001) alone as well as both factors together (p≤0. 001; 1E). An unrelated control","In most animals, a protein called MondoA closely monitors the amount of glucose in the body, as this type of sugar is the fuel required for many life processes. Glucose levels also act as a proxy for the availability of other important nutrients. Once MondoA has detected glucose molecules, it turns genetic programmes on and off depending on the needs of the cell. So far, these mechanisms have mainly been studied in adult cells. However, recent studies have shown that proteins that monitor nutrient availability, and their associated pathways, can control early development. MondoA had not been studied in this context before, so Weger et al. decided to investigate its role in embryonic development. The experiments used embryos from zebrafish, a small freshwater fish whose early development is",380,128,0.3368
dialogsum,"#Person1#: Have you got any specific proposal about the terms of payment? #Person2#: I wonder if we can make payment for this order by documentary collection. #Person1#: I'm sorry to say the only term of payment we can accept is 100 % irrevocable letter of credit payable against shipping documents. #Person2#: But our order this time is very large. To open an L / C for such a large amount at a bank is costly. Can you be a bit more flexible and bend the rule a little? #Person1#: I'm afraid not. We insist on a letter of credit, because as seller, we also have the problem of funds being tied up. #Person2#: To be frank, a letter of credit would increase the cost of my import. When I open a letter of credit with a bank, I have to pay a deposit. That will tie up my money and add to my cost. #Person1#: Consult your bank and see if they will reduce the required deposit to a minimum.",#Person2# wants to make payment for the order by documentary collection to decrease the cost of the import but #Person1# refuses and suggests consulting #Person2#'s bank and seeing if they will reduce the required deposit to a minimum.,170,38,0.2235
dialogsum,"#Person1#: Hi, John, how was your vacation? #Person2#: Awesome, we went to Australia and New Zealand. #Person1#: That must have been wonderful. Do anything interesting? #Person2#: Well, we went bungee jumping when we were in Australia. #Person1#: Wow! Isn't that dangerous? #Person2#: A little, but the rush was worth it. #Person1#: Tell me about it. #Person2#: We jumped off a bridge and fell 500 feet before the bungee cord caught us. #Person1#: 500 feet! I would never be able to do that. #Person2#: Yeah, it was scary, but exhilarating.","John tells #Person1# about his vacation in Australia and New Zealand, especially the bungee jumping.",89,15,0.1685
dialogsum,"#Person1#: What can I help you with today? #Person2#: My washing machine isn't working. #Person1#: What's the problem? #Person2#: The water will not drain. #Person1#: Is there anything else wrong with it? #Person2#: No, that's it. #Person1#: I can come down and fix that for you if you'd like. #Person2#: When will you be able to fix it? #Person1#: How does this afternoon at 2 thirty sound to you? #Person2#: That would be perfect. #Person1#: Alright, so I'll see you then? #Person2#: See you then.",#Person2#'s washing machine isn't working. #Person1# will come down to fix it this afternoon at 2 thirty.,85,17,0.2
scientific_lay_summarisation-elife-norm,"Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity. Trauma, burns, ischemia, strenuous exercise, all induce a sterile inflammatory response. It is likely that this response evolved to clear cell debris, promote tissue repair and maintain tissue sterility (Zelenay and Reis e Sousa, 2013; Eming et al. , 2014) but, if uncontrolled, it can lead to (aseptic) shock and, in some cases, death (Rock et al. , 2010). The prevailing notion is that sterile inflammation is initiated by pro-inflammatory signals that are released by damaged cells. These include intracellular components that are exposed when cells lose their membrane integrity, such as ATP, uric acid, RNA and DNA, collectively known as damage-associated molecular patterns (DAMPs) (Rock et al. , 2010; Zelenay and Reis e Sousa, 2013). The universe of DAMPs and their receptors, as well as the mechanisms regulating DAMP responses, remains underexplored. This is partly because early research in this area was tainted by issues of microbial contamination (Beg, 2002) and because immunologists have often focussed on sterile inflammation from the narrow perspective of adaptive immunity (Matzinger, 1994; Land et al. , 1994). However, it is probable that responses to DAMPs, like responses to microbes, pre-date the vertebrate evolution of T and B cells and have an early metazoan origin, much like the clearance of dead cells (Krysko et al. , 2011; Hochreiter-Hufford and Ravichandran, 2013; Eming et al. , 2014). Therefore, the study of invertebrate responses to DAMPs","All animals must be able to detect and repair injuries quickly. To do this, the body triggers a process called inflammation at the site of injury to remove dead and damaged cells, keep the area free from infection and trigger repair. However, if an area becomes excessively inflamed, or remains inflamed for a long period of time, it can contribute to diseases like cancer and Alzheimer’s disease. Inflammation starts when the body detects molecules that are released when cells die or are damaged to the extent that they become leaky. Actin, which is a protein that usually provides structural support to the cell, is one molecule that is sensed by the immune system in mammals when released from dying cells. However, it is not clear whether released actin",380,128,0.3368
dialogsum,"#Person1#: Hello, is that the Peace Restaurant? #Person2#: Yes. May I help you? #Person1#: Yes. I'd like a table for six at 7:00 this evening. Can you arrange it for us? #Person2#: Just a minute. I'll check if there is any availability. I'm sorry, sir. There isn't any table left for 7:00, but we can give you one at 8: 00. Would you like to make a reservation at that time? #Person1#: Let me see. It seems a little late. #Person2#: Usually, the restaurant will be quieter at that time. #Person1#: OK. I'll change the time to 8: 00. #Person2#: Very good, sir. A table for 6 at 8: 00 this evening. May I have your name, please? #Person1#: It's John. #Person2#: Thank you very much. Bye.",John calls to book a table at 7:00 but #Person2# can only give him one at 8:00. John changes the time to 8:00.,127,23,0.1811
dialogsum,"#Person1#: How long have you been in this company? #Person2#: I came two years ago after I graduated from college. This is my first job. #Person1#: You must have found much difference between working in company and studying in college. #Person2#: Of course! Everyday, there is a deadline to meet. Bosses watching and testing me all the time, not liking in college, handed in paper months later and tested on schedule. It is so busy. But anyway, I have trying my best to be a good employee. #Person1#: Well, you've adapted yourself very well. Everyone in our office thinks you've made a great progress in the past two years. What is your secret? #Person2#: It is so encouraging to hear this remark. The secret is to make plans. Write down your goals, short-term and long-term and make detail plans for a week or a month. Then just work hard.",#Person2# tells #Person1# about the difference between working in a company and studying in college and reveals the secret of making progress.,149,22,0.1477
dialogsum,"#Person1#: How old is Keith? #Person2#: He's 21. how old is James? #Person1#: He's a year older than Keith, but he looks younger. #Person2#: How's your father? #Person1#: He's fine. He retired last week. It's turning going in his life. Now he can relax and enjoy his retirement. #Person2#: He can spend more time with his grandchildren. #Person1#: Oh, I don't think he wants to. He wants to travel to several different countries around the world. #Person2#: So, he wants to have a more active retirement. Good idea! #Person1#: How do you want to spend your old age? #Person2#: In the same way, probably.",#Person1# and #Person2# are talking about their families' ages. #Person2#'s father wants to travel around the world after retirement.,104,19,0.1827
dialogsum,"#Person1#: So, have you seen all three The Lord of the Rings movies? #Person2#: Yes, but I didn't really like the third one at all. #Person1#: That's the Return of the King, right? #Person2#: Yeah. Even though the customs were brilliant, I didn't think it was as good as the first two. What did you think? #Person1#: I thought the special effects were amazing, but I got a bit confused. The plot was too complicated for me. #Person2#: Did you read the books before you watched the movies? #Person1#: No. did you? #Person2#: Yes, I've read them many times. I think it's much easier to follow for people who were already familiar with all the characters. #Person1#: Yes, trying to keep track of all the characters was quite confusing for me. #Person2#: I also think that it was much better in the theatre than at home. #Person1#: Most movies are. Another problem for me was the film was dubbed in German with English subtitles. #Person2#: That happens a lot in non-English speaking countries. #Person1#: I heard that The Return of the King was nominated for 11 Oscars. #Person2#: Actually, they not only had 11 nominations, but they won 11 Oscars, too!",#Person2# thinks that the third one of The Lord of the Rings movies was not as good as the first two. #Person1# didn't read the books before watching the movies so #Person1# got a bit confused.,201,36,0.1791
scientific_lay_summarisation-elife-norm,"(voxel or single unit) may participate in ensembles responding to more than one feature, so it is also possible that a particular element that appears not to distinguish specific features of different outcomes is in fact coding independent features that co-vary with each outcome' s value. So how can we address whether the OFC signals features of impending outcomes vs value independent of those features? One way is to strip away or ‘block’ the value portion of the outcome during learning, while leaving unblocked—free to enter into associations—the outcome' s unique sensory and other features. This can be done by pairing a ‘target’ cue with a rewarding outcome in the presence of a cue that has been previously trained to predict a differently-flavored, but similarly-valued outcome. When this is done, the previously conditioned cue predicts the general value that is common to the two outcomes, but does not predict the unique features that distinguish the new outcome (note features are not limited to sensory properties, but might include the outcome timing, location, temperature, size, number, etc). As a result, the target cue acquires associations with the unique features of the new outcome but not with its general or common currency value (Rescorla, 1999; Burke et al. , 2008). If OFC neurons represent only a general or common currency value, divorced from features, then they should respond no more to such a target cue than to a completely blocked cue (Kamin, 1969). However, if OFC neurons represent outcome features, independent of value, then they should respond to the target cue just as they do to a cue that has been explicitly unblocked by increasing the amount of the outcome delivered. Indeed, both pure value and outcome expectancy accounts of OFC function would predict neural activity to such an unblocked cue, but only an outcome expectancy account predicts encoding of the target cue signaling a valueless change in outcome flavor. We recorded single–unit activity in the OFC in six rats during an odor-based unblocking task (1A). Prior to implantation with electrodes rats were trained to sample an odor in a central port following house light illumination and then respond to a reward well below for two drops of Nestlé' s flavored milk (chocolate or vanilla, counterbalanced). This training was meant to establish","Imagine you are at a restaurant and the waiter offers you a choice of cheesecake or fruit salad for dessert. When making your choice it is likely that you will consider the features of these desserts, such as their taste, their sweetness or how healthy they are. However, when you decide which dessert to have, you will pick the one that you judge to have the highest value for you at that moment in time. In this sense, ‘value’ is a subjective concept that varies from person to person, while ‘features’ remain relatively static. It is generally agreed that the orbitofrontal cortex (OFC) is involved in making these sorts of decisions, but its role is still a topic of debate. According to one theory the neurons in the",380,128,0.3368
dialogsum,"#Person1#: Doctor, I slipped and fell on my way to school. The ground is so slippery from the snow. It seems I can't move my left arm now. #Person2#: Let me see. Roll up your sleeve, please. Um. . . it's swollen and red here. I'm afraid we'll need to take an X-ray to see if it's broken. #Person1#: What if it's broken? #Person2#: Then we'll put you in a cast. #Person1#: What do you mean by a cast? #Person2#: Well, we apply tape and plaster to from a solid enclosure to protect the bones from moving. In this way they will heal properly. Take it easy. It won't hurt you. Let me see. The X-ray picture indicates that your humerus is broken in two places. And you'll have to wear the cast for three weeks. You'll need to come back in two weeks, so I can have another look.",The doctor asks #Person1# to take an X-ray and the doctor puts #Person1# in a cast because the X-ray picture shows that #Person1#'s humerus is broken.,150,26,0.1733
dialogsum,"#Person1#: Hi I am Jane, pleased to meet you. #Person2#: Hi Jay. I'm glad to be here for the interview. #Person1#: Did you have problems finding these place? #Person2#: Not at all. But the traffic was not easy and it took me hours to find a parking space. #Person1#: Traffic is always being difficult these days. #Person2#: It would have been so much easier if a train or a subway line went through here. #Person1#: Yes, you're definitely right. Well, why don't we start by telling me about your previous work experience?",Jane comes for an interview. #Person2# and Jane have a casual talk about the traffic before the interview starts.,92,19,0.2065
dialogsum,"#Person1#: What is this big box at the front door? #Person2#: Oh. I don't know what to do. I joined this club a long time ago and I didn't read the fine print. #Person1#: What did you get yourself into? #Person2#: I didn't realize that I have to buy something from them every six months. #Person1#: So, what's in the box? A fridge? #Person2#: It's a curio cabinet. The only thing is I don't even own those kinds of little keepsakes. #Person1#: I guess you'll read the fine print next time, won't you! #Person2#: Don't rub it in. Where am I going to put this huge thing?","#Person2# tells #Person1# #Person2# joined a club without reading the fine print, so #Person2# has to buy something from them every six months.",107,23,0.215
dialogsum,"#Person1#: I've never been to a restaurant like this before. #Person2#: It's really different, isn't it? #Person1#: That's a good word to describe it. #Person2#: I hope you're hungry because the pizza here is huge as well as to die for. #Person1#: I am hungry. I think I could eat a lot by myself. #Person2#: Well, let's order one for a starter. #Person1#: I'm in the mood for a Californian pizza. #Person2#: That happens to be my favorite. Waiter, I think we're ready to order.",#Person2# takes #Person1# to an unusual restaurant and they decide to order a Californian pizza.,85,15,0.1765
pubmed-summarization,"this 41-year - old housewife , educated up to sixth standard , hailing from middle socioeconomic status , with nil contributory family history , and suffering from hypertension and myopia in left eye ( + 0.75 ) and hypermetropia in right eye ( 0.75 ) , reported to outpatient clinic with history of 10-years duration characterized by unpleasant , frequent , and distressing doubts related to dirt and contamination . these resulted in performance of long , nonfunctional repetitive activities like cleaning and saying same words again and again . it was also reported both by husband and the patient herself that these symptoms have a seasonal pattern appearing in october and complete resolution in april - may . this seasonal pattern was so well - recognized that no treatment was taken for initial 3 - 4 years as they considered it an effect of change of season and that symptoms would disappear once the winter is over . no associated stress or precipitating factor was identified that might lead to reoccurrence of these symptoms every year in winter . gradually over the years she noted that the severity of her illness increased and was causing socio - occupational dysfunctions . therefore , this year she reported for psychiatric treatment at the beginning of october . on mental state examinations she had obsessions of contamination , compulsions for washing , and assurance seeking . the severity of symptoms was assessed by administrating yale brown obsessive compulsive scale ( y - bocs ) . the total y bocs score was 30 ( obsessions score 17 and compulsions score 13 ) , other routine investigations were within normal limit . other than ocd in subsequent follow - ups , patient was also diagnosed as having cervical spondylitis . she was on fluoxetine 20 mg once daily for 1month , but did not show much improvement . therefore , keeping in view the seasonal variation in the pattern of oc symptoms , she was also considered for phototherapy . she was also taken up for exposure and response prevention ( erp ) therapy twice a week for 1hour , where therapist assisted the patient in exposure . her y - bocs score came down to 8 ( 5 for obsession and 3 for",a case of obsessive - compulsive disorder ( ocd ) with seasonal variation in symptoms of 10-years duration is reported because of its rarity . the phenomenology of the observed disorder was obsessions related to dirt and contamination resulting in washing compulsions with onset in october and complete resolution in april - may every year . the patient responded to phototherapy along with exposure and response prevention therapy and pharmacotherapy .,380,71,0.1868
pubmed-summarization,"ductal adenocarcinoma of the prostate was first reported by melicow and pachter in 1967 as an endometrial carcinoma prostatic utricle . since then , ductal adenocarcinoma of the prostate has been found to account for 0.27.5% of all prostate carcinomas . a 73-year - old man was referred to our hospital due to an elevated prostate - specific antigen ( psa ) level of 23.4 ng / ml . he had no remarkable medical history . the hematological and biochemical data showed no abnormal findings aside from the elevated psa levels . in february 2016 , a prostate needle biopsy detected gleason score 4 + 4 adenocarcinoma in his left prostate . computed tomography ( ct ) and magnetic resonance imaging ( mri ) showed a higher density on his left peripheral zone ( 1a , b ) . in may 2016 , radical prostatectomy with lymph node resection histologically , there were many large , clear - edged cells and cancer cells with low differentiation forming a circular shape . based on these findings , ductal adenocarcinoma and gleason score 4 + 4 = 8 acinar adenocarcinoma with positive surgical margin were diagnosed . the patient has not experienced recurrence or biochemical recurrence in the 10 months since radical prostatectomy . histologically , there were many large , clear - edged cells and cancer cells with low differentiation forming a circular shape . based on these findings , ductal adenocarcinoma and gleason score 4 + 4 = 8 acinar adenocarcinoma with positive surgical margin were diagnosed . no adverse perioperative events were observed . the patient has not experienced recurrence or biochemical recurrence in the 10 months since radical prostatectomy . ductal adenocarcinoma of the prostate was first reported as endometrial carcinoma of the prostatic utricle in 1967 . recent studies have suggested that ductal adenocarcinoma of the prostate developed from the ductal epithelium , based on findings from immunohistochemical and electron microscope analyses . histologically , ductal adenocarcinoma of the prostate is characterized by high cylindrical epithelium collate papillary or etat cribriform . the histological differences between ductal adenocarcinoma and acinar adenocarcinoma are thought to be clear . in this case , although the prostate needle biopsy showed acinar adenocarcinoma , the surgical specimens showed ductal adenocarcinoma .",ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate . a 73-year - old male was referred to our hospital for the further examination of an elevated prostate - specific antigen level of 23.4 ng / ml . radical prostatectomy ( rp ) was performed based on the diagnosis obtained by a prostate needle biopsy . the rp specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration . we herein report a rare case of ductal adenocarcinoma of the prostate .,380,85,0.2237
dialogsum,"#Person1#: Did your company go union? I heard that many companies in out industry are being unionized, so It's getting harder and harder to compete on a level playing field. #Person2#: Yes, we're hopping on the bandwagon and signing up for the union. Mostly people are pretty happy about it... I guess it depends on if you are in management or in the labor force. #Person1#: Management isn't looking on the labor unions too favorably, I'd guess. I don't blame them... labor unions can really put the squeeze on the executives. #Person2#: Sure... but it's probably better for the workers, because the union's whole purpose is to look out for the little guys. The only way that the little guys can take on the big bosses is if they unite. Labor unions are all about getting a voice for the underdog.",#Person1# and #Person2# are talking about labor unions. They agree that management isn't looking on them too favorably but it's probably better for workers.,141,24,0.1702
dialogsum,"#Person1#: I think you know already that I want to discuss the represention for your alarm clocks. #Person2#: Yes, Mr. Bergeron. You mentioned that in your letter. To tell you the truth, your proposal surprised us. #Person1#: Is that so? Anyhow I want to go over the details with you in person, so you can give my suggestion thorough consideration. Our firm specializes in this line of business. We have six sales representatives, who are on the road all the time, covering the whole of the European market. #Person2#: Do you sell direct to shops? #Person1#: Yes, we specialize in handling clocks and watches of all sorts. We have well established channels of distribution and we canvass the retailers direct, without any middlemen. #Person2#: Do you keep a stock of these things? #Person1#: In some cases, such as the wristwatches, which always have a steady market, we keep a stock in London and act as distributors as well as agents. Generally, however, we pass on the orders of our clients to the manufacturers for supply. We are paid for our service, of course. #Person2#: That is, your commission. #Person1#: Yes, our commission is very reasonable. We usually get a 10 % commission of the amount on every deal. #Person2#: Our agents in other areas usually get a 3-5 % commission. #Person1#: The European market is not familiar with your products. You have competitors from Japan and other continental countries. At the beginning of our campaign, there is sales resistance to overcome, we must send out salesmen to do a lot of traveling and spend a considerable amount of money on advertising in news - papers and TV programs. A 10 % commission will not leave us much. #Person2#: According to your estimate, what is the maximum annual turn - over you can fulfill, in round figures, of course? #Person1#: We will always do our utmost to enlarge the business, as our remuneration increases with the turnover, but we will not be able to guarantee anything, at least not to begin with. #Person2#: We appreciate very much your intention to push the sale of our products. But our suggestion to you, Mr. Bergeron, as a preliminary step, is to do a little research into the market... #Person1#: Do you mean to",Mr. Bergeron wants to get the European market sales agency of Mrs. Miller's clocks and wants a commission of 10%. Mrs. Miller thinks Mr. Bergeron's team has no idea about the annual turnover so she refuses Mr. Bergeron's suggestion but will still carry on their business relationship without the agreement and will give Mr. Bergeron a 5 % commission on every transaction. They will discuss the matter again at the next Fair.,380,72,0.1895
dialogsum,"#Person1#: Did you see the fashion awards last night? #Person2#: I sat through about half of it but they lost me after that. #Person1#: Not interested? #Person2#: Not really, to be honest. Some of what they call fashion looks terrible to me. #Person1#: But they are showing what will be all the rage next year. #Person2#: All the rage with whom? I never see anyone wearing these designs on the street. #Person1#: Did you know that fashion is cyclical? #Person2#: What, it keeps coming back? #Person1#: Precisely! For example, Flares were popular for a while, then went out of fashion. Now we can start to see them coming back in again. #Person2#: Flares? #Person1#: They're also known as bell-bottoms. They are a type of trousers. #Person2#: It's too complicated. I'll just stick to the plain clothes. #Person1#: That's fine, but then you'll always look plain.",#Person1# and #Person2# are talking about the fashion awards last night. #Person2# thinks some of them look terrible. #Person1# tells #Person2# that fashion is cyclical but #Person2#'d rather stick to the plain clothes.,145,33,0.2276
scientific_lay_summarisation-elife-norm,"et al. , 2018; Winter et al. , 2017). While most mammalian tissues express three BET factors (Brd2, Brd3, Brd4) (Uhlén et al. , 2015), many studies have implicated Brd4 as most important for widespread changes in transcription after BET inactivation (Muhar et al. , 2018; Zheng et al. , 2021; Zuber et al. , 2011). These broad genome-wide expression defects are due to the important roles of Brd4 in both transcription initiation and elongation. Brd4 contributes to recruitment of the transcription coactivator Mediator to enhancers and promoters and cooperates with Mediator in forming nuclear condensates at actively transcribed regions (Bhagwat et al. , 2016; Han et al. , 2020; Sabari et al. , 2018). Brd4 is also important for productive transcription elongation, but it is unclear what mechanisms are involved. Brd4 associates with the positive transcription elongation factor b (P-TEFb), but no global defects in P-TEFb recruitment to chromatin were observed following inactivation of Brd4 or all BET factors (Muhar et al. , 2018; Winter et al. , 2017). Proposed alternative mechanisms of elongation control include release of P-TEFb inhibition, histone chaperone activity, or direct kinase activity (Devaiah et al. , 2012; Itzen et al. , 2014; Kanno et al. , 2014). Finally, Brd4 was shown to affect preinitiation complex (PIC) formation at promoters, although its roles in later stages of transcription are believed to be dominant (Kanno et al. , 2014; Winter et al. , 2017). TFIID is a conserved Pol II factor that, in yeast, regulates transcription of almost all Pol II-transcribed genes (Donczew and Hahn, 2018; Huisinga and Pugh, 2004; Warfield et al. , 2017). TFIID comprises TBP (TATA binding protein) and 13–14 Tafs (TBP-associated factors). TFIID acts as a TBP-DNA loading factor, a promoter recognition factor and a molecular scaffold guiding PIC assembly (Patel et al. , 2020). Recruitment of metazoan TFIID to promoters is thought to be aided by interactions between two Taf subunits and chromatin marks that are enriched at the +1 nucleosome. The human Taf1 double BD and Taf3 PHD domain recognize acetylated histone H4 tails and trimethylated histone H3 lysine 4, respectively (Jacobson et al. , 2000; van Ingen et al. , 2008). In contrast, Taf1 and Taf3 in budding yeast are missing both of these chromatin readers as well as","When a healthy cell creates new proteins, it activates a standard two-step biological manufacturing process. Firstly, DNA is transcribed from a specific gene to generate a strand of messenger RNA, or mRNA. Next, this mRNA molecule is translated to create the final protein product. This process of converting DNA into mRNA is supported by a series of helper proteins, including proteins from the bromodomain and extra-terminal domain (BET) family. Cancer cells can become ‘addicted’ to the process of converting DNA into RNA, leading to the overproduction of mRNA molecules, uncontrolled cell growth and tumor formation. Knocking out BET helper proteins could potentially bring cancer cells under control by halting transcription and preventing tumor growth. However, the precise ways in which BET helper proteins regulate transcription are currently poorly",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2013). However, the role of PTBP2 in differentiating neurons is not understood. PTBP1 and PTBP2 are encoded by paralogous genes and are very similar in peptide sequence, especially in their four RNA recognition motifs (RRMs), giving them similar RNA-binding properties (Oberstrass et al. , 2005). The best-characterized function of the two PTB proteins is in the regulation of alternative splicing patterns. PTBP1 and PTBP2 bind to CU-rich regulatory sequences within or adjacent to many alternative exons to repress or activate their splicing, or sometimes to cause intron retention (Xue et al. , 2009; Llorian et al. , 2010; Kafasla et al. , 2012; Keppetipola et al. , 2012). However the two proteins differ in their splicing regulatory activities. Some exons, such as exon 8A of the CaV1. 2 calcium channel transcript (Cacna1c), are more strongly repressed by PTBP1 than PTBP2, whereas other exons, such as exon 18 of the PSD95 transcript (Dlg4), are affected by both proteins (Markovtsov et al. , 2000; Tang et al. , 2011; Zheng et al. , 2012). Neither the mechanisms underlying the different responses of exons to the two PTB proteins, nor the roles of their partially overlapping splicing programs in neuronal development are known. To identify roles of PTBP2 in the developing mouse brain, we used conditional gene targeting. We show that the loss of PTBP2 leads to a catastrophic failure in neuronal maturation and to the misexpression of many protein isoforms affecting neurite growth, synapse formation and synaptic transmission. We find that PTBP2 and the program of splicing it controls are critical to both embryonic and postnatal brain development. PTBP2 is induced as nestin-positive neuronal progenitors exit mitosis and begin to differentiate (Boutz et al. , 2007). This can be seen in the embryonic cortex and olfactory bulb where proliferating cells in the subventricular zone are stained for nestin, but more mature cells populating the outer cortical layers have lost nestin expression but gained PTBP2 immunoreactivity (1A). To investigate the function of PTBP2 in the developing brain, we generated a conditional null allele carrying loxP sites flanking exon 4 of the Ptbp2 gene (Ptbp2loxP) (1B). In targeted tissues, Cre-mediated deletion of exon 4 introduces a reading frame shift to render the allele null. Correct targeting in ES cells and germ line transmission","Cells within the developing brain undergo an extended period of maturation. A neuronal progenitor cell must first migrate to the proper place within the brain and then develop long extensions that become the axon and dendrites used by the mature neuron to communicate with other cells. Finally, the synapses that connect neurons with other neurons must be established. Multiple mechanisms are needed to ensure that all the proteins involved in this process are expressed when and where they are needed. The production of a protein begins with a region of DNA being transcribed to produce an RNA transcript that consists of segments called exons separated by segments called introns. This transcript then undergoes a process called splicing that involves the introns being removed and the exons being joined",380,128,0.3368
pubmed-summarization,"that is grounded in the unique experiences of primigravid and multigravid women . there are a few studies that investigated the quality of commissioning mothers experiences such as their anxiety and stress . since the number of spouses treated by art such as surrogacy is growing worldwide , it is crucial to understand their emotional and psychological reactions toward surrogacy during the 9 months of the waiting period . this is the first qualitative study in iran , which assessed the experiences of commissioning mothers . with their diverse culture and social contexts , developing countries demand much more context - dependent studies this study has aimed to explore and explain the nature of concerns ( experiences ) of commissioning mothers . the aim of this study was to explore and explain the nature of concerns ( experiences ) of commissioning mothers . the aim of this study was to explore and explain the nature of concerns ( experiences ) of commissioning mothers . content analysis is a research method that has come into wide use in health studies in recent years . this type of design is usually appropriate when an existing theory or research literature on a phenomenon is limited . royan research centre consists of six departments ( endocrinology and female infertility , epidemiology and reproductive health , reproductive genetics , reproductive imaging , andrology , and embryology ) and one clinic actively working on different aspects of infertility and the development of new methods for infertility treatment . our participants were first - time commissioning mothers , during the waiting period ( pregnancy of the surrogate mother ) or after that ( child rearing period ) . they had to be able to speak persian and willing to participate in the research . participants were selected from gestational surrogacy cases ( the conceptions were with own gametes ) , as gestational surrogacy is more prevalent in iran than partial surrogacy and we had a better access to them . women who were in a waiting list for finding a surrogate by the infertility centers or those who were waiting to know the result of embryo implantation and the women whose embryo was aborted after implantation were not included in this study . it means for selection","background : there are a few studies about commissioning mothers understanding from the surrogacy during 9 months of waiting for delivery in iran and other countries . this study was conducted with an aim to explore and explain the nature of concerns ( experiences ) of commissioning mothers.materials and methods : a qualitative design with a conventional content analysis approach was used to gather and analyze the experiences of commissioning mothers . they were selected from royan research centre and other infertility centers in iran . after purposive sampling for the selection of the participants , unstructured interviews were held for data collection . twenty - four unstructured interviews were conducted with 12 commissioning mothers , 2 surrogate mothers , and 2 infertility center social workers who directly",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Under high light, oxygenic photosynthetic organisms avoid photodamage by thermally dissipating absorbed energy, which is called nonphotochemical quenching. In green algae, a chlorophyll and carotenoid-binding protein, light-harvesting complex stress-related (LHCSR3), detects excess energy via a pH drop and serves as a quenching site. Using a combined in vivo and in vitro approach, we investigated quenching within LHCSR3 from Chlamydomonas reinhardtii. In vitro two distinct quenching processes, individually controlled by pH and zeaxanthin, were identified within LHCSR3. The pH-dependent quenching was removed within a mutant LHCSR3 that lacks the residues that are protonated to sense the pH drop. Observation of quenching in zeaxanthin-enriched LHCSR3 even at neutral pH demonstrated zeaxanthin-dependent quenching, which also occurs in other light-harvesting complexes. Either pH- or zeaxanthin-dependent quenching prevented the formation of damaging reactive oxygen species, and thus the two quenching processes may together provide different induction and recovery kinetics for photoprotection in a changing environment. Sunlight is the essential source of energy for most photosynthetic organisms, yet sunlight in excess of the organism’s photosynthetic capacity can generate reactive oxygen species (ROS) that lead to cellular damage. To avoid damage, plants respond to high light (HL) by activating photophysical pathways that safely convert excess energy to heat, which is known as nonphotochemical quenching (NPQ) (Rochaix, 2014). While NPQ allows for healthy growth, it also limits the overall photosynthetic efficiency under many conditions. If NPQ were optimized for biomass, yields would improve dramatically, potentially by up to 30% (Kromdijk et al. , 2016; Zhu et al. , 2010). However, critical information to guide optimization is still lacking, including the molecular origin of NPQ and the mechanism of regulation. Green algae is a sustainable alternative for biofuels and livestock feed (Lum et al. , 2013; Wijffels and Barbosa, 2010). In Chlamydomonas (C.) reinhardtii, the model organism for green algae, light-harvesting complex stress-related (LHCSR) is the key gene product for NPQ. LHCSR contains chlorophyll (Chl) and carotenoid (Car) held within its protein scaffold. Two isoforms of LHCSR, LHCSR1 and LHCSR3, are active in NPQ, although LHCSR3 is accumulated at higher levels and so has the major role (Dinc et al. , 2016; Maruyama et al. , 2014; Peers et al. , 2009; Tokutsu and Minagawa, 2013). While the photophysical mechanism of quenching in light-harvesting complexes has not been determined,","Green plants and algae rely on sunlight to transform light energy into chemical energy in a process known as photosynthesis. However, too much light can damage plants. Green plants prevent this by converting the extra absorbed light into heat. Both the absorption and the dissipation of sunlight into heat occur within so called light harvesting complexes. These are protein structures that contain pigments such as chlorophyll and carotenoids. The process of photoprotection starts when the excess of absorbed light generates protons (elementary particles with a positive charge) faster than they can be used. This causes a change in the pH (a measure of the concentration of protons in a solution), which in turn, modifies the shape of proteins and the chemical identity of the carotenoids. However, it is",380,128,0.3368
pubmed-summarization,"soft tissue sarcomas are very rare tumors ; however , there are many histologic subtypes . among those subtypes , furthermore , among sarcomas originating within the retroperitoneum , which constitute 1015% of all soft tissue sarcomas , liposarcomas are the most common histologic type , accounting for 41% of these tumors . liposarcomas are generally located in the head , neck , trunk , mediastinum , upper and lower extremities , gastrointestinal tract , and retroperitoneum . they commonly occur in patients aged 4060 years , and men and women are equally affected . the dimensions and weight of liposarcomas are variable ; those over 20 kg are called herein , we report a giant retroperitoneal liposarcoma weighing 25.0 kg , encasing the entire left kidney and adherent to adjacent structures which was successfully removed with kidney and aorta preserving . the patient had not experienced any symptoms , such as abdominal pain , nausea , vomiting , constipation , dyspepsia , or dyspnea . the patient was admitted to the hospital and underwent contrast - enhanced computed tomography ( ct ) of the abdomen . the scan revealed a huge fatty mass originating from the retroperitoneum probably indicative of retroperitoneal liposarcoma . the spleen was pushed anteriorly and the small bowel was deviated to the right side of the intra - abdominal space by the mass ( . 1 ) . because the patient was old , we decided to attempt organ - preserving surgery for the removal of the tumor to minimize the morbidity . adherence of the mass to the diaphragm , stomach , spleen , pancreas , and aorta could be observed . the greatest difficulty was that the tumor was encasing the entire left kidney and adherent to the aorta . although the entire left kidney was encased with the huge tumor , neither the renal parenchyma nor the ureter was invaded . we successfully performed a salvage of the left kidney by wide excision and separated the tumor from the aorta by shaving it away , thus preserving both kidney and the aorta . the specimen measured 45.0 30.0 11.0 cm and weighted 25.0 kg ( . 2 ) . microscopic examination showed a combined type of liposarcoma ( tumor component : well","retroperitoneal liposarcoma is a rare tumor . the dimension and weight of liposarcoma are variable ; those over 20 kg are called giant liposarcoma. herein , we report giant retroperitoneal liposarcoma measuring 45 cm in diameter and 25 kg in weight encasing the entire left kidney and adherent to adjacent structures . a 71-year - old woman presented for a regular checkup . image study revealed a huge mass probably indicative of retroperitoneal liposarcoma encasing the entire left kidney and adherent to adjacent structures . we performed an organ - preserving surgical removal . the pathologic report was liposarcoma . at postoperative month 16 , a follow - up ct revealed a locally recurrent tumor . the patient underwent surgical removal of the newly discovered mass . after",380,128,0.3368
scientific_lay_summarisation-elife-norm,"PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory in wild-type mice, and PKMζ-null mice recruit compensatory mechanisms. We find that whereas PKMζ persistently increases in LTP maintenance in wild-type mice, PKCι/λ, a gene-product closely related to PKMζ, persistently increases in LTP maintenance in PKMζ-null mice. Using a pharmacogenetic approach, we find PKMζ-antisense in hippocampus blocks late-LTP and spatial long-term memory in wild-type mice, but not in PKMζ-null mice without the target mRNA. Conversely, a PKCι/λ-antagonist disrupts late-LTP and spatial memory in PKMζ-null mice but not in wild-type mice. Thus, whereas PKMζ is essential for wild-type LTP and long-term memory, persistent PKCι/λ activation compensates for PKMζ loss in PKMζ-null mice. LTP and long-term memory can be divided into two mechanistically distinct phases—a transient induction and a persistent maintenance (Malinow et al. , 1988). Induction is thought to rely solely on post-translational modifications. Maintenance requires new protein synthesis soon after strong synaptic stimulation or learning, and these newly synthesized proteins are believed to sustain the synaptic potentiation or behavioral modification (Kandel and Schwartz, 1982). Although numerous signal transduction molecules are important for LTP and long-term memory, most have been implicated in induction, with many participating in either the initial transient potentiation or the mechanisms for upregulating new protein synthesis (Sanes and Lichtman, 1999). In contrast, few molecules have been implicated in maintenance. Such a maintenance molecule would be both: 1) a product of de novo protein synthesis sufficient to enhance synaptic transmission and 2) a necessary component of the mechanism sustaining synaptic potentiation and long-term memory, as shown by inhibition of the molecule reversing sustained synaptic potentiation and erasing long-term memory. One hypothesis for a molecular mechanism of maintenance involves the persistent increase in an autonomously active PKC isoform, PKMζ (Sacktor, 2011). LTP and long-term memory maintenance may depend upon the function of PKMζ because data suggest the kinase possesses the two essential properties of a maintenance molecule. First, PKMζ is produced in LTP by new protein synthesis and is sufficient to potentiate synaptic transmission. PKMζ is generated from a PKMζ","How are long-term memories stored in the brain? The formation of memories is believed to depend on the strengthening of connections between neurons. During learning, neurons produce an enzyme called PKMzeta (or PKMζ), which is thought to be responsible for maintaining the newly strengthened connections. Inhibitors of PKMzeta, such as a drug called ZIP, disrupt long-term memories. This suggests that the brain may be like a computer hard disc in that its stored information — its memories — could be erased. However, recent experiments on genetically engineered mice have thrown the role of PKMzeta into question. Knockout mice that lack the gene for PKMzeta can still strengthen connections between neurons and can still learn and remember. Moreover, ZIP still works to reverse the strengthening and to erase long-term",380,128,0.3368
dialogsum,"#Person1#: Do you like this dress, madam? #Person2#: I like the colour very much. It's a lovely dress, but it's too small for me. #Person1#: What about this one? It's a lovely dress. It's very smart. Short skirts are in fashion now. Would you like to try it? #Person2#: All right. I'm afraid this green dress is too small for me as well. It's smaller than the blue one. I don't like the colour either. It doesn't suit me at all. I think the blue dress is prettier. Co #Person1#: I'm afraid I haven't got a larger dress. This is the largest dress in the shop.",#Person1# recommends several dresses for #Person2# but they are too small. #Person1# hasn't got larger dresses.,106,16,0.1509
scientific_lay_summarisation-elife-norm,"delayed coupling between resting-state brain activity and a visceral organ, the stomach. The stomach continuously produces a slow electrical rhythm (0. 05 Hz, one cycle every 20 s) that can be non-invasively measured (electrogastrogram, EGG [Koch and Stern, 2004]). The gastric basal rhythm is continuously (Bozler, 1945) and intrinsically (Suzuki et al. , 1986) generated in the stomach wall by a network of specialized cells, the interstitial cells of Cajal (Sanders et al. , 2014), which form synapse-like connections not only with gastric smooth muscle but also with afferent sensory neurons (Powley and Phillips, 2011). The stomach is an interesting candidate for large-scale brain coordination for several reasons. First, visceral inputs can reach a number of cortical targets (Critchley and Harrison, 2013; Park and Tallon-Baudry, 2014). Second, gastric frequency (~0. 05 Hz) falls within the range of BOLD fluctuations that are used to define RSNs and that are free from known cardiac and respiratory artifacts (Glerean et al. , 2012). Finally, the amplitude of alpha rhythm, the dominant rhythm in the human brain at rest, depends on the phase of gastric rhythm (Richter et al. , 2017). We simultaneously recorded brain activity with fMRI and stomach activity with EGG (1a) in 30 human participants at rest with open eyes. We then determined the regions in which spontaneous fluctuations in brain activity were phase synchronized with gastric basal rhythm; we refer to these regions as the gastric network. We first determined gastric frequency (1b) in each participant as the frequency of the largest spectral peak within the normogastric range (0. 033–0. 066 Hz). The mean EGG peak frequency across the 30 participants was 0. 047 Hz (±SD 0. 003, range 0. 041–0. 053). EGG peak frequency measured inside and outside the scanner did not differ (EGG outside the scanner measured in 29 of the 30 participants, mean 0. 046 Hz ± SD 0. 006; two-sided paired t-test, t (28) =0. 35, p=0. 725 Bayes Factor <0. 001, indicating decisive evidence for the null hypothesis). In each participant and at each voxel, we quantified the degree of phase synchrony between the EGG signal and BOLD time series filtered around gastric frequency (1c). We computed the phase-locking value (PLV) (Lachaux et al. , 1999), a measure widely used in electrophysiology that varies between","The brain is always active. Even when it is not receiving sensory input, it generates its own spontaneous activity. This activity shapes how we interpret future sensory signals and creates our inner mental world. Moreover, this spontaneous activity is not random. When a healthy volunteer lies inside a brain scanner without performing any task, his or her brain shows predictable patterns of activity. Specific groups of brain regions – often with related roles – become active at the same time as one another. Each set of regions is referred to as a resting state network. Of course, the brain does not operate in isolation from the rest of the body. Our internal organs continuously send signals to the brain via the spinal cord and cranial nerves. Specialized cells",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of the hypoxic cells were radial glia (GFAP+) and a smaller percentage (28. 3 ± 9. 5%) were early intermediate progenitor cells (Tbr2+/Dcx-) (1C, D) in close proximity to the SGZ. In contrast, none of the hypoxic cells (0%) expressed the neuroblast marker doublecortin (DCX, 1C, D). 10. 7554/eLife. 08722. 003Figure 1. Detection of hypoxia and oxidative stress in SGZ niches of the adult DG. (A) Schematic diagram of experimental design. (B) Immunostaining with pimonidazole hydrochloride marks hypoxic areas (white arrows) within the adult SGZ (scale bar: 20 μm). (C) Pimonidazole-positive cells colocalized with stem cell marker GFAP (red, top row), intermediate progenitor marker Tbr2 (blue, middle row) but not with neuroblast marker DCX (blue, bottom row). The enlargement in the rightmost panel in the top row indicates a hypoxic neural stem cell (green) that colocalizes with a GFAP+ radial glial cell (yellow). A smaller fraction of early progenitors (Tbr2+) also were pimonidazole-positive (middle row, rightmost panel). Scale bar: 15μm left panel, 5 μm right panel. (D) Quantification of SGZ cells types expressing pimonidazole. (E) Oxidized 8-deoxyguanosine (8OHdG), a marker of oxidized nucleic acids, was not detected in GFAP positive neural stem cells, but in Tbr2- and DCX-expressing intermediate progenitors and neuroblasts (scale bar: 25 μm). (F) Quantification of SGZ cell types expressing oxidized 8-deoxyguanosine. For all quantifications data are plotted as mean ± SD. : http: //dx. . org/10. 7554/eLife. 08722. 003 Shortly after their generation, proliferating intermediate precursors translocate away from the proximal domain and into the intermediate domain (Fuentealba et al. , 2012). Thus, we hypothesized that migration away from hypoxic zones might result in oxidative damage as diagrammed in 1A. Oxidative byproducts were highly localized in cells within the SGZ as assayed by 8-oxo-7,8-dihydro-2' -deoxyguanosine (8-OHdG) labeling, an established biomarker of nucleic acid oxidative damage (1E). Interestingly, phenotypic analysis revealed that 74. 6 ± 5. 8% of the 8-OHdG positive cells were late intermediate progenitors (Tbr2+/DCX+) and 29. 2 ± 12. 2% were neuroblasts (DCX+ only) (1E, F). Thus, a subset of newborn cells in the SGZ undergoes oxidative damage during their early migration and differentiation. The most critical survival period for adult-generated dentate granule cells occurs during the first few days post mitosis, as they differentiate from late intermediate progenitors to neuroblasts (Dayer et al.","The hippocampus is a region in the mammalian brain that has been implicated in the formation of new memories. This process involves the birth of new neurons, which are created at a rate of ∼4000 a day in the hippocampus of a young adult mouse. Yet only a fraction of these cells survive to form mature neurons. These cells die in two main waves – the first occurs days after they form, and the second several weeks later when as immature neurons they integrate into the brain. During this later wave, new neurons become active and survive if they connect with other nerve cells and die if they don’t. But little is known about what causes the earlier wave of cell death. The tissues that contain the precursors",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a splicing program that suppresses adipose tissue thermogenesis. Together, these data provide quantitative analysis of gene expression at exon-level resolution in obesity and identify a novel mechanism that contributes to the regulation of adipose tissue function and the maintenance of normal glycemia. Alternative pre-mRNA splicing is an important mechanism that increases the complexity of the transcriptome (Pan et al. , 2008; Wang et al. , 2008) and expands the diversity and function of the proteome (Nilsen and Graveley, 2010; Yang et al. , 2016). Indeed, differences in pre-mRNA splicing can contribute to the specialization of different cell types within the body (Vaquero-Garcia et al. , 2016). The regulation of alternative pre-mRNA splicing is therefore an important aspect of cellular differentiation. Indeed, processes that regulate pre-mRNA splicing represent potential mechanisms that can control cell function. Recent studies have identified changes in pre-mRNA splicing associated with autism (Irimia et al. , 2014; Weyn-Vanhentenryck et al. , 2014), cardiac hypertrophy (Mirtschink et al. , 2015), embryonic stem cell re-programming (Han et al. , 2013a), tumorigenesis (Oltean and Bates, 2014; Hsu et al. , 2015; Koh et al. , 2015), and the regulation of signal transduction pathways (Gupta et al. , 1996; Tournier et al. , 1999; Maimon et al. , 2014; Martinez et al. , 2015). Moreover, alternative pre-mRNA splicing associated with pathogenesis represents a tractable target for the development of new therapies (Daguenet et al. , 2015). The role of alternative pre-mRNA splicing in metabolism is unclear. We studied pre-mRNA splicing in adipocytes to investigate whether adipocyte function may be regulated by changes in pre-mRNA splicing. Adipose tissue is critically important for whole body metabolic regulation because it acts as both an endocrine","The process of building a protein from the information encoded in a gene begins when the gene is copied to form a pre-messenger RNA molecule. This molecule is then edited to produce a final messenger RNA that is “translated” to form the protein. Different segments of the pre-messenger RNA molecule can be removed to create different messenger RNAs. This “alternative splicing” enables a single gene to produce multiple protein variants, allowing a diverse range of processes to be performed by cells. Fat cells store energy in the form of fats and can release this energy as heat in a process called thermogenesis. This helps to regulate the body’s metabolism and prevent obesity. Vernia et al. now find that that feeding mice a high-fat diet causes widespread changes in",380,128,0.3368
dialogsum,"#Person1#: Can you recognize that woman, Millie? #Person2#: I think I can, Kate. It must be Karen Marsh, the actress. #Person1#: I thought so. Who's that beside her? #Person2#: That must be Conrad Reeves. #Person1#: Conrad Reeves, the actor? It can't be. Let me have another look. I think you're right! Isn't he her third husband? #Person2#: No, He must be her fourth or fifth. #Person1#: Doesn't Karen Marsh look old! #Person2#: She does, doesn't she! I read she's twenty-nine, but she must be at least forty. #Person1#: I'm sure she is. #Person2#: She was a famous actress when I was still a schoolgirl. #Person1#: That was a long time ago, wasn't it? #Person2#: Not that long ago! I'm not more than twenty-nine myself.",#Person1# and #Person2# recognize Kate and Kate is with Conrad. They are amazed that Kate looks so young.,124,18,0.1452
scientific_lay_summarisation-elife-norm,"of the subdomains leading to ADP and phosphate release or dissociation from actin upon ATP binding could only be studied in silico (Cecchini et al. , 2008,2010; Sweeney and Houdusse, 2010; Preller and Holmes, 2013). The experimental challenge in revealing such structural dynamics has been largely of spatiotemporal origin, since they are likely on the Ångstrom scale and may be very transient. Similarly, there has been considerable interest in directly revealing the motion of the individual heads as myosin steps along actin in an attempt to unravel the origins of efficient motion on the nanoscale. Single molecule studies employing optical trapping (Mehta et al. , 1999; Rief et al. , 2000) and fluorescence imaging (Forkey et al. , 2003; Yildiz et al. , 2003; Snyder et al. , 2004; Warshaw et al. , 2005) have either reported periods of increased flexibility, (Veigel et al. , 2002; Dunn and Spudich, 2007; Beausang et al. , 2013) or partitioning of the step into sub-events (Veigel et al. , 2002; Uemura et al. , 2004; Cappello et al. , 2007; Sellers and Veigel, 2010). All resulting models involve a forward aiming power stroke followed by a Brownian search mechanism (Veigel et al. , 2002; Okada et al. , 2007; Shiroguchi and Kinosita, 2007; Karagiannis et al. , 2014). The power stroke of the attached head contributes only partially to the step by moving the pivot point that facilitates Brownian rotation of the unbound head. The bias towards the next binding site is believed to be provided by the recovery stroke and its stability, but how unidirectional stepping is achieved in the presence of such a large and mostly random motion remains unclear (Shiroguchi et al. , 2011). The first passage time of the translocating head is expected to be on the order of 100 µs, (Veigel et al. , 2002; Hinczewski et al. , 2013) although the head spends tens of ms in the unbound state given the maximum rates of ATP hydrolysis and binding to actin (Veigel et al. , 2002; Dunn and Spudich, 2007; Beausang et al. , 2013). Any technique aiming to visualize the structural dynamics of the motor domain or the motion of the unattached head would thus have to achieve simultaneous millisecond temporal and nanometer spatial precision. Optical","Cells use motor proteins that to move organelles and other cargos from one place to another. The myosins are a family of motor proteins that pull cargo along filaments made of another protein called actin. The ‘head’ end of myosin attaches to the actin filament and the ‘tail’ end binds to the cargo. The head and tail are connected by a flexible linker that allows the protein to change shape. The tails of two myosin molecules bind together to form a two-headed motor that can move along an actin filament by taking 74 nm steps. At the start of each step, both heads are attached to the actin with one in front of the other. The leading head remains attached while the rear head detaches from actin and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and protein levels (1A) with PHF1, a crucial component facilitating PHT1 post-translational regulation and its targeting to the PM (Gonzalez et al. , 2005; Bayle et al. , 2011) (1A). The root tip surrounds and protects the meristem, while also acting as the initial contact point between the roots and soil. In order to visualize Pi in plants, pulses of radioactive tracer were applied by immersing the whole root system in 33Pi solution. When fed to plantlets, 33Pi accumulation was observed at the extremity of the root tip (1B), including the meristematic zone (1C). 10. 7554/eLife. 14577. 003Figure 1. Active Pi transporters are localized in the root cap. (A) Reporter lines expressing transcriptional and translational fusions for the high affinity transporters expressed in the root (PHT1; 1 and PHT1; 4) are localized in the root cap, in addition to PHF1, a major post-translational regulator required for PHT1 targeting to the plasma membrane. Scale bars: 50 μm. (B) Accumulation of 33P in the root tip of Arabidopsis plantlets. Whole roots were immersed in 33P-enriched solution for 1 day. (C) Pi accumulation in the root tip is abolished by targeted ablation with 5FC in the Q0171>>FCY-UPP line. The short pulse of 33Pi applied to the WT and Q0171>>FCY-UPP lines was revealed by a live radioisotope microimaging system. Light transmission and 33P images are merged. 33P content is represented as color intensity. Scale bar: 100 μm. : http: //dx. . org/10. 7554/eLife. 14577. 00310. 7554/eLife. 14577. 004Figure 1— 1. Assay for Pi translocation to the root tip. (A) 33P (200 kBq) was initially applied to the middle of the root in a zone isolated from the medium by Vaseline. (B) The presence of 33P in the root tip is observed 30 min later by the live radioisotope microimaging system. Presented image is a magnified view of the box in (A). Scale bar: 200 μm. : http: //dx. . org/10. 7554/eLife. 14577. 00410. 7554/eLife. 14577. 005Figure 1— 2. Conditional negative marker expression in the root cap. (A) Enzymatic transformation of 5-Fluorocytosine (5-FC) into toxic 5-Fluoro-UMP by FCY and UPP enzymes. (B) Transactivation system used to express a conditional negative marker in the root cap. The Q0171 transgenic line contains a GAL4 activator gene (in T-DNA) driven by a minimal promoter (enhancer trap), which is","All plants need phosphate to grow because it is a major component of DNA and many other biological molecules. Most of the Earth’s soil is poor in phosphate, and so farmland is routinely supplemented with fertilizers to provide crops with this essential nutrient. However, phosphate fertilizers are becoming scarce and their quality is expected to decline in the near future. Plant biologists must therefore determine how to adapt plants to a restricted supply of this resource, in order to sustain high crop yields for the growing world population. Plants are known to absorb phosphate through specific protein-based transporters located in the cells that make up the outer layer of roots. These proteins are highly concentrated at the root tip, and while this specialized tissue is well-known for perceiving",380,128,0.3368
dialogsum,"#Person1#: Hello. Dr. Brown's Dental Office. How can I help you? #Person2#: Hi, this is Susan Smith. I'm calling about my appointment with Doctor Brown today at 3 #Person1#: What happened? #Person2#: I got the flu. I have a fever and a headache. Can I cancel my appointment? #Person1#: Sure, you can, but you'll be charged for $ 10. #Person2#: Oh, there's a charge? Why? #Person1#: This is for the delayed cancellation. Because this time is reserved for you. If you are unable to keep an appointment, you should notify us 48 hours in advance. Otherwise, the charge will be made. #Person2#: I see. That's ok. I'll pay. #Person1#: Thanks for your understanding. Do you want to make another appointment? #Person2#: No. Not right now. When I feel better I'll call you again. #Person1#: Ok. Take care. #Person2#: Thank you.",Susan phones to cancel her appointment with Dr. Brown because she got the flu. #Person1# tells her she'll be charged for $10 for the delayed cancellation.,140,26,0.1857
scientific_lay_summarisation-elife-norm,"pools, as well as between dimer and oligomer. These equilibria are independent of fission. Fission signals shift these equilibria toward stable oligomerization at targeted fission sites on the OMM. While few studies address the order of events during Drp1 recruitment, de novo assembly is often tacitly assumed (Otera et al. , 2013; Elgass et al. , 2015; Labbé et al. , 2014). Here, we show evidence supporting targeted equilibrium. We observe that mitochondrially-bound Drp1 oligomers mature into stable oligomers through a series of merging events. Some of these Drp1 oligomers are motile—capable of translocating on the mitochondrial surface before engaging in fission. Notably, not all mitochondrially-bound Drp1 oligomers engage in fission. Using ionomycin treatment to induce mitochondrial fission, we show that actin polymerization precedes Drp1 oligomerization, and that actin enriches with Drp1 at fission sites. Inhibition of actin polymerization, INF2 or myosin II decreases ionomycin-induced Drp1 accumulation and mitochondrial fission. Biochemically, actin filaments bind Drp1 directly and enhance its GTPase activity, suggesting that actin filaments can organize Drp1 into a productive oligomer. These results suggest that actin promotes fission by facilitating productive oligomerization of Drp1 on the OMM. To monitor Drp1 dynamics in live cells, we developed a U2OS cell line stably expressing GFP-Drp1 with partial shRNA suppression of endogenous Drp1 (gDrp-U2OS). By quantitative western blotting, gDrp-U2OS cells maintain 1. 64-fold total Drp1 levels compared to control U2OS cells, with 56% endogenous Drp1 and 44% GFP-Drp1 (— 1A, B). Mitochondrial morphology appears similar between control U2OS and gDrp-U2OS cells (not shown). We also developed a live-cell assay to measure mitochondrial fission rate, in which peripheral cellular regions are imaged over 10 min for dynamics of a fluorescent mitochondrial marker. Fission events are scored based on stable separation of the marker, and similar fission rates are obtained with either a matrix marker or an OMM marker (— 1C). Using this assay, the fission rates of control U2OS and gDrp1-U2OS cells are statistically similar (1. 26 ± 1. 01 versus 1. 51 ± 0. 69 fission events per mm mitochondrion per min, p = 0. 49) (— 1D). Additionally, a second clone displaying undetectable endogenous Drp1 levels and GFP-Drp1 levels ~3. 5-fold higher than control Drp1 levels displays similar mitochondrial fission frequency to control cells (, — 1E–G), suggesting that GFP-Drp1 functionally","Inside cells, structures called mitochondria supply the energy needed to carry out the processes that sustain life. Mitochondria constantly divide (a process known as fission) or fuse together, which helps to keep them in good working condition and well distributed around the cell. Several neurological disorders, including Parkinson’s disease and Alzheimer’s, are associated with problems that affect mitochondrial fission. Many different molecules work together to help mitochondria divide, including a protein called Drp1. A number of Drp1 molecules can associate with each other to form an “oligomer” in the shape of a ring around a mitochondrion. The ring then constricts to split the mitochondrion in two. It is often assumed that Drp1 molecules are recruited to the mitochondria immediately before fission and then form the oligomer ring. However,",380,128,0.3368
dialogsum,"#Person1#: Hello, Could you please connect me to Mr. Cook's office? It is on Line Three. #Person2#: I'm afraid you've got the wrong extension number. #Person1#: Oh. Then I don't know what his number is. Can you check it for me? #Person2#: OK. Hold on, please. #Person1#: OK. Thank you. #Person2#: Mr. Cook is on Line Six. I'll put you through. #Person1#: Thank you. You helped me a lot. #Person2#: You are welcome.",#Person2# helps #Person1# to connect to Mr. Cook who is on Line Six.,73,13,0.1781
pubmed-summarization,"primitive neuroectodermal tumors ( pnets ) are highly malignant embryonal neoplasms of bone and soft tissues accounting for 4%17% of all pediatric soft tissue tumors . metastasis at presentation is quite common , with central pnets metastasizing to cranium and leptomeninges while peripheral pnets ( ppnets ) disseminating to lungs , bone , liver , and lymph nodes . primary pulmonary pnet is known to metastasize to pancreas , adrenal gland and ovaries while it metastasizing to brain is exceedingly rare . a 29-year - old female presented with a cough and right - sided chest pain of 1-month duration . computed tomography scan of chest [ ] showed an 11.3 cm 11 cm 10 cm soft tissue mass lesion in right perihilar region with the loss of fat planes with esophagus , aorta , and diaphragm without chest wall or pleural involvement . biopsy showed atypical round to oval cells with scanty cytoplasm intermixed with respiratory epithelium [ ] . immunohistochemistry ( ihc ) was positive for neuron - specific enolase ( nse ) [ ] , synaptophysin , chromogranin , cd 99 , and vimentin . smooth muscle actin ( sma ) , epithelial membrane antigen ( ema ) , cytokeratin ( ck ) , leukocyte common antigen ( lca ) , cd 20 , cd 45 , thyroid transcription factor ( ttf-1 ) and desmin were negative , confirming the diagnosis of pnet lung . computed tomography scan ( axial section ) of thorax showing a large heterogeneously enhancing soft tissue mass lesion in the right perihilar region involving right lower lobe extending into the mediastinum with loss of fat planes with esophagus , aorta , and right crus of the diaphragm . there is no chest wall or pleural involvement biopsy from lung lesion showing small round cells with scanty cytoplasm with condensed chromatin and inconspicuous nucleoli ( h and e , 200 ) immunohistochemistry picture from lung lesion showing tumor cells positive for neuron specific enolase ( 200 ) magnetic resonance imaging ( mri ) brain and positron emission tomography scan showed localized disease . received chemotherapy vincristine , adriamycin , and cyclophosphamide alternating with ifosfamide plus etoposide ( vac / ie ) resulting in partial response ( pr ) to therapy . conformal radiotherapy","primitive neuroectodermal tumors ( pnets ) are highly malignant neoplasms of embryonal origin manifesting in children and adolescents , rarely seen in adults . carcinoma lung with hemorrhagic metastasis to the brain is very common , but primary lung pnet with hemorrhagic brain metastasis is extremely uncommon . we hereby report a 29-year - old female diagnosed as pnet lung was treated with vincristine , adriamycin , and cyclophosphamide alternating with ifosfamide plus etoposide followed by radiotherapy ( rt ) . after 9 months , she developed hemorrhagic brain metastasis from pnet lung confirmed from tissue immunohistology postcraniotomy . received palliative whole brain rt followed by oral pazopanib resulting in significant improvement in performance status . a thorough review of literature reveals that our case may be the",380,128,0.3368
dialogsum,"#Person1#: I want to send some money to Nanchang. Is it handled here? #Person2#: Yes, sir. How much would you like to remit? #Person1#: I want to remit 1, 200 yuan to my brother in Nanchang. #Person2#: No problem. Do you want the money to go by M / T or T / T? #Person1#: What's the difference? #Person2#: If you take M / T, it will take a longer time for your brother to receive the money. #Person1#: OK. I'll take T / T. #Person2#: Would you please fill in this application form? #Person1#: All right. Here it is. #Person2#: For 1, 200 yuan to Nanchang, the commission is 12 yuan. #Person1#: Here you are. Thanks. #Person2#: You are welcome. #Person1#: Bye-bye.","#Person1# wants to remit 1, 200 yuan to Nanchang by T / T and #Person2# tells that the commission is 12 yuan",123,22,0.1789
pubmed-summarization,"comprehensive supervision and administration of work safety and coalmines of the whole country . china has made mandatory provisions focusing on the implementation of safety standards , risk forecasting , accident reporting , accident accountability and other aspects through the development of relevant laws and regulations , departmental regulations and safety standards . the saws is law - based administration to strengthen the comprehensive supervision and administration of work safety and coal mines of the whole country . the saws collects information from provinces , cities and local data sources , including details regarding fatal accidents with more than three deaths and non - fatal injuries , and associated economic losses . the information of work safety accidents and coalmine incidents are required to report from enterprise involved to the regional agency and provincial department , and then finally submitted to the saws . after conducting an investigation , the saws announces the findings and determines about penalty . in this study , the data covered most industries except the military forces and private enterprises . additionally , we checked statistical year - book of road traffic accidents and public literature to information and details . the analysis was conducted using the registered data with more than 10 deaths per incident . major accidents in transportation involved victim who was the operator , passenger , or a pedestrian stuck in or on the side of the road . after extraction , details including types of the event , year , region , number of deaths and injuries , causes of accidents were transformed into spss v13.0 ( chicago , il , usa ) . we performed analysis on the frequency of accidents and deaths , the trend , geographic distribution and type of major accidents . we analyzed the geographic distribution using hierarchical cluster analysis , focused on the frequency of accidents and deaths . incidence of major accident shows the occurrence probability of any person , and major accident mortality shows the dying probability . the incidence and mortality of major accident are defined as follows : incidence = number of major accident/ ( total national population106)mortality = number of death/ ( total national population 106 ) data from the state saws corresponding to the period 20032012 were used","background : this study provides a national profile of major work safety accidents in china , which cause more than 10 fatalities per accident , intended to provide scientific basis for prevention measures and strategies to reduce major work safety accidents and deaths.methods:data from 20032012 census of major work safety accidents were collected from state administration of work safety system ( saws ) . published literature and statistical yearbook were also included to implement information . we analyzed the frequency of accidents and deaths , trend , geographic distribution and injury types . additionally , we discussed the severity and urgency of emergency rescue by types of accidents.results:a total of 877 major work safety accidents were reported , resulting in 16,795 deaths and 9,183 injuries . the numbers",380,128,0.3368
dialogsum,"#Person1#: Look at the catalogue, John. I think I want to get this red blouse #Person2#: Don't you have one like this in blue? #Person1#: Yah, but it doesn't have a red one. #Person2#: Do you need every color in the rainbow? #Person1#: Yes! #Person2#: Ze ze ze ... Women!",#Person1# tells John that she wants blouses in different colors.,50,10,0.2
dialogsum,"#Person1#: Can I help you? #Person2#: I'd like to buy a ticket to Casablanca on flight US125 tomorrow. #Person1#: Hold on, please. It will take off at 14:00 tomorrow. The price is $ 110. #Person2#: Well, I want to stay under $ 100. #Person1#: I am sorry Sir. We won't give any discount in busy seasons. The price is the same.",#Person2# wishes to buy a flight ticket at a low price but #Person1# won't offer a discount in busy seasons.,61,20,0.3279
scientific_lay_summarisation-elife-norm,"into eggs for future embryo formation and not all of these components contribute to the flies’ decision to produce eggs (Piper et al. , 2014; Mirth et al. , 2019; Wu et al. , 2020). This means that high protein diets might drive mothers to produce eggs at a faster rate than they can support if the diet contains insufficient levels of the other components that are required to make eggs. In this scenario, the macronutrients would have an indirect effect on lifespan by changing the availability of another limiting nutrient that is required for somatic maintenance. If true, this would move the focus of mechanistic studies away from the direct effects of protein, TOR, and proteostasis, towards some other component of nutritional physiology. Distinguishing between these possible causes of death is important since it would fundamentally change our understanding of the way diet alters lifespan. It also has the important knock-on effect that we could change the way we design diets for longer life. For instance, supplementing high protein diets with key limiting nutrients would be as beneficial as restricting dietary protein or treating with pharmacological suppressors of TOR. Of the many studies that have examined the effects of dietary protein and carbohydrate on lifespan and reproduction in Drosophila, most have done so by varying dietary yeast and sugar proportions, where yeast is the flies’ natural source of protein (Mair et al. , 2005; Lee et al. , 2008; Skorupa et al. , 2008). However, yeast also contains all of the flies’ other essential macro and micronutrients whose relative proportions can change, and thus possibly interact with protein and carbohydrates to dictate life-history outcomes. We have previously found that depriving adult female flies of a source of sterols, an essential micronutrient for insects, imposes a minor cost on reproduction, but a substantial (>50%) cost to lifespan (Piper et al. , 2014; Wu et al. , 2020). These data indicate that yeast sterol levels may contribute to the effects on lifespan of protein and carbohydrate. To investigate the interactions between dietary protein, carbohydrate, and sterols systematically, we have used the design principles of the geometric framework for nutrition (Simpson and Raubenheimer, 2012; Simpson and Raubenheimer, 1993) and a completely defined (holidic) diet that allows us to control the levels of","For the past fifteen years, animal studies have consistently shown that a low-protein, high-carbohydrate (‘carbs’) diet can extend the lifespan of many organisms, but at the cost of the number of offspring an individual can produce. Yet, it is still unclear what the best dietary balance is, and how these effects arise. One potential explanation could be that reproduction damages the body: low levels of proteins would therefore prolong life by lowering the reproductive output. Here, Zanco et al. examined the possibility that protein intake in fruit flies could instead be acting indirectly by changing the levels of a fat-like molecule called cholesterol, which is used to maintain the body and to support reproduction. To test this idea, groups of fruit flies were fed high levels of proteins.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"syllabic rate (Luo and Poeppel, 2007; Kayser et al. , 2009; Szymanski et al. , 2011; Zoefel and VanRullen, 2015). It has therefore been suggested that entrainment reflects a key mechanism underlying hearing by facilitating the parsing of individual syllables through adjusting the sensory gain relative to fluctuations in the acoustic energy (Giraud and Poeppel, 2012; Peelle and Davis, 2012; Ding and Simon, 2014). Crucially, because some regions that track the specific acoustic rhythm of speech are sensitive to speech intelligibility, neural synchronization is not only driven by changes in the acoustic cue of the auditory stimuli, but also reflects cortical encoding and processing of the auditory signal (Peelle et al. , 2013; Ding and Simon, 2014). Speech tracking is therefore an invaluable tool to probe regions that interface speech perception and comprehension (Poeppel et al. , 2008; Gross et al. , 2013; Peelle et al. , 2013). Does the occipital cortex of EB people synchronize to speech rhythm? Is this putative synchronization of neural activity to speech influenced by comprehension? Addressing these questions would provide novel insights into the functional organization of speech processing rooted in the occipital cortex of EB people. In the current study, we investigated whether neuronal populations in blind occipital cortex synchronize to rhythmic dynamics of speech, by relating the amplitude fluctuations in speech to electromagnetic dynamics recorded from the participant’s brain. To this end, we quantified the local brain activity and directed connectivity in a group of early blind (EB; n = 17) and sighted individuals (SI; n = 16) using magnetoencephalography (MEG) while participants listened to short narrations from audiobooks. If the occipital cortex of the blind entrains to speech rhythms, this will support the idea that this region processes low-level acoustic features relevant for understanding language. We further tested whether the putative synchronization of occipital responses in EB people benefits from linguistic information or only relates to acoustic information. To separate linguistic and acoustic processes, we relied on a noise-vocoding manipulation. This method spectrally distorted the speech signal in order to impair intelligibility gradually, but systematically preserves the slow amplitude fluctuations responsible for speech rhythm (Shannon et al. , 1995; Peelle and Davis, 2012). Furthermore, to go beyond differences in the local encoding of speech rhythm in the occipital cortex, we also","Scientists once thought that certain parts of the brain were hard-wired to process information from specific senses or to perform specific tasks. For example, some had concluded that language processing is built into certain parts of the brain, because the way the brain responds to language is remarkably similar in different people even from very early on in life. Yet other studies with individuals who were born blind emphasize that experience also shapes the way the brain works. In people who are born blind, parts of the brain that typically interpret visual information in sighted people are often put to other uses. Now, van Ackeren et al. show that people who became blind early in life are able to repurpose parts of the brain that are more typically",380,128,0.3368
scientific_lay_summarisation-elife-norm,"technique has several advantages (Soto et al. , 1994) over the serial-section electron microscopy method that was used previously to determine the structures of spindles in cdc25. 22 fission yeast and budding yeast cells (Ding et al. , 1993; Winey et al. , 1995). We use the analyses of the EM spindle reconstructions to build computational models of the spindle. These models imply that the fission yeast spindle architectures organise a limited supply of structural components to increase their resistance to compressive forces, thus demonstrating a direct link between the morphology of a mitotic spindle and its function. We also investigate the effects of external mechanical reinforcement (Pickett-Heaps et al. , 1997; Mitchison et al. , 2005; Brangwynne et al. , 2006) on the forces that the spindle can bear during its elongation. We began by using the very uniform mitotic progression of cells containing GFP-labelled tubulin (1A; Video 1,2) to assign ET reconstructions to a specific time during mitosis. Our ET reconstructions confirmed that the spindle is composed of two opposing arrays of pole-nucleated microtubules that interdigitate at the spindle midzone (1B; Videos 3–5). A similar gross spindle organisation was observed in previous serial-section reconstructions of cdc25. 22 fission yeast cells (Ding et al. , 1993) and the related budding yeast spindle (Winey et al. , 1995). 10. 7554/eLife. 03398. 003Figure 1. The Architecture and Dynamics of the Fission Yeast Spindle. (A) Fission yeast cell expressing GFP-labelled tubulin. The dashed red line shows cell outline at mitotic entry. Interval between frames = 1 min, scale bar = 0. 5 μm. (B) ET reconstructions of three anaphase B spindles. Microtubules are coloured according to the pole from which they originate. Dashes represent the approximate locations of the cross-sections shown in C. (C) Longitudinal and transverse spindle architecture. Diagrams on the left show the contour length and number of microtubules within each spindle. Black arrowheads mark the three anaphase B spindles depicted in B. Circle-and-stick diagrams on the right represent cross-sections near to the poles and midzone of each spindle. Microtubule radii are drawn to scale. Black lines are drawn between neighbouring anti-parallel microtubules. (D) Raw electron tomographic images of second-longest anaphase B spindle shown in C. Microtubules are marked by yellow arrows. Scale bar = 25 nm. (E) Histograms of","Before a cell divides to form two new cells, it duplicates its entire set of chromosomes. These chromosomes need to be equally distributed between the new cells—if cells receive too many or too few chromosomes, it can cause developmental defects or cancer. In cells that have a nucleus, a structure called the mitotic spindle ensures that chromosomes are partitioned equally between the dividing cells. The spindle consists of long, thin protein fibers called microtubules, which grow from small structures known as centrosomes that are present on either side of a cell. While some of the microtubules from each centrosome overlap in the middle of the spindle in a region called the spindle midzone, another set of microtubules attaches to the chromosomes, allowing the spindle to pull each of",380,128,0.3368
pubmed-summarization,"force measurements on a scaled hair - bundle model respected the physiological character of the liquid flow . the finite - element method provided approximate solutions to partial differential equations reflecting the hair bundle 's geometry . the velocity variable of the liquid was substituted by the time derivative of the displacement ; fluid pressure was approximated by linear shape functions and the displacements of liquid and solid by quadratic ones . the hydrodynamic forces between stereocilia were estimated analytically by solving the stefan - reynolds equations under the lubrication approximation , which is valid when the gaps between adjacent stereocilia are much smaller than their diameter . stochastic simulations based on these results were performed for a system of linearly coupled dynamic variables following a langevin description with gaussian white noise at room temperature . the integration procedure was validated by choosing time steps small enough to assure that the results were independent of the increment . we tested the effects of inertia and of the estimated top - connecter stiffness and confirmed the validity of our conclusions for mammalian hair bundles . dual - beam differential interferometry was used to record stereociliary motions with sub - nanometre spatial and sub - millisecond temporal resolution . fourier analysis of the records was performed with the multitaper method to obtain coherence spectra as well as stiffness and drag coefficients . these results were used to verify the predictions of the numerical model and to measure directly the relative mode of motion between stereocilia .","the detection of sound begins when energy derived from an acoustic stimulus deflects the hair bundles atop hair cells1 . as hair bundles move , the viscous friction between stereocilia and the surrounding liquid poses a fundamental physical challenge to the earfs high sensitivity and sharp frequency selectivity . part of the solution to this problem lies in the active process that uses energy for frequency - selective sound amplification2,3 . here we demonstrate that a complementary part of the solution involves the fluid - structure interaction between stereocilia and the liquid within the hair bundle . using force measurement on a dynamically scaled model , finite - element analysis , analytical estimation of hydrodynamic forces , stochastic simulation , and high - resolution interferometric measurement of hair",254,128,0.5039
dialogsum,"#Person1#: Hello, Lucy. When are you going off to Beijing? #Person2#: This evening. #Person1#: How are you getting there, by air or by train? #Person2#: By train. It leaves at 5:00 and arrives in Beijing at 7:10 tomorrow morning. #Person1#: Oh, only 14 hours. Is anybody seeing you off this evening? #Person2#: Yes, my parents are going with me to the station to see me off. #Person1#: That's good! How long are you staying in Beijing for your holiday? #Person2#: Only four days. Well, I must be off now. See you when I get back. #Person1#: OK. Good luck and have a good trip! #Person2#: Thanks. Goodbye!",#Person1# asks Lucy's plan for leaving for Beijing and Lucy tells #Person1# the details and her parents will see her off.,107,21,0.1963
dialogsum,"#Person1#: The restaurant across the street hired a new Chinese chef, so I ordered some Chinese food there for this evening. #Person2#: Good. I love Chinese food. What did you order? #Person1#: Something hot and spicy. They look very inviting on the menu. You are going to love them. #Person2#: Maybe we can find a place to learn some Chinese cooking. I hear there's a place in Chinatown where you can take some courses. Are you interested? #Person1#: I'm not sure. I don't enjoy cooking that much. As long as we can order it from a restaurant, we don't have to learn to do it by ourselves. #Person2#: You are right. But I just want to know how they prepare food and make it taste so different.",#Person1# ordered some Chinese food for this evening. #Person2# suggests finding a place to learn some Chinese cooking but #Person1# prefers just ordering from a restaurant.,127,26,0.2047
dialogsum,"#Person1#: Hey! That food was terrific. I can't eat another bite. Are you sure you don't want another dish? #Person2#: No, I'm full. My stomach isn't growling at me any more. #Person1#: I know what you mean. I'm so full that I can burst. Shall we go then? #Person2#: I'm all set. Thank you for the dinner, Jack. #Person1#: You are welcome.","Jack and #Person2# are both full, then #Person2# thanks Jack for the dinner.",62,13,0.2097
scientific_lay_summarisation-elife-norm,"phase (Yao et al. , 2008). Expression of the transcription factor PU. 1 determines lymphoid versus myeloid hematopoietic cell lineages (Kueh et al. , 2013; Laslo et al. , 2006). Adipocyte differentiation is controlled by differential expression of C/EBP and PPARγ proteins (Park et al. , 2012). Regulation by positive feedback is a hallmark of bistable systems, and in all of the above cases, the transcription factors act in one or more positive feedback circuits. In some systems, positive feedback is generated by two transcription factors that mutually repress each other’s expression. In these scenarios, cells in one state continually express a transcription factor that represses a second transcription factor, and when these cells transit to another state, they continually express the second transcription factor, which represses its antagonist. Fate restriction in hematopoietic, neural, pancreatic, and muscle cell lineages is regulated by such double-negative feedback circuits (Briscoe et al. , 2000; Laslo et al. , 2006; Olguin et al. , 2007; Schaffer et al. , 2010). Most examples of this type of bistable mechanism have transcription factors that act specifically within a handful of cell states limited to a single tissue or organ system. One remarkable exception to this rule is found in Drosophila. There, two ETS-domain transcription factors act in a wide assortment of cell types across the body and across the life cycle. Yan and Pointed (Pnt) act downstream of signals mediated by receptor tyrosine kinases (RTKs) that regulate cell differentiation, migration, and division in tissues ranging from ovarian follicular cells, dorsal and ventral neuroectoderm, embryonic mesoderm, the embryonic trachea, and the post-embryonic compound eye (Dumstrei et al. , 1998; Gabay et al. , 1996; Halfon et al. , 2000; Jurgens et al. , 1984; Morimoto et al. , 1996; O' Neill et al. , 1994; Ohshiro et al. , 2002; Yao et al. , 2008) It is thought that Yan and Pnt control such diverse cell states by acting in concert with tissue-specific transcription factors to regulate transcription of appropriate target genes. For instance, transcription of even-skipped occurs in mesoderm only if Yan/Pnt act in combination with Tinman and Twist proteins (Halfon et al. , 2000), whereas transcription of prospero (pros) in the eye only occurs if Yan/Pnt act in combination with Lozenge, Sine Oculis, and Glass","As animal cells develop, they pass through different states to mature into specific cell types. For some cells, this development depends on the cell’s ability to switch between two stable states, a property called bistability. Many bistable systems operate during development and often feature proteins called transcription factors that regulate a few cell states in specific tissues. These proteins activate or repress a range of target genes, and cells can adjust the levels of the transcription factors to bring about transitions between states. In fruit flies, two transcription factors, called Yan and Pnt, regulate numerous processes throughout development. In the developing embryo of a fruit fly, Yan and Pnt are regulated by signals induced by a receptor called EGFR. When EGFR is activated, Pnt is produced and Yan",380,128,0.3368
scientific_lay_summarisation-elife-norm,"between mammalian sickness sleep and invertebrate SIS was recently reviewed (Davis and Raizen, 2016). Nematode SIS is a distinct sleep state from a larval sleep state known as developmentally timed sleep (DTS) (Trojanowski et al. , 2015), which is regulated by a homolog of the core circadian protein PERIOD (Monsalve et al. , 2011). In the absence of stress, nematodes experience sleep only when they transition between larval stages but do not sleep in the adult stage. Since C. elegans does not have an identifiable circadian rhythm of sleep, adult nematodes are an ideal system to study SIS in the absence of the circadian and homeostatic effects of animals that require daily sleep. The mechanism of SIS is poorly-understood, yet a few common themes have emerged from studies across phylogeny. The acute illness can occur outside of the brain yet affect behavior, suggesting that communication occurs between non-neural and neural tissues. Cytokine signaling is involved. For example, in mammals, the cytokines interleukin-1 beta and tumor necrosis factor alpha, whose levels increase during an infectious challenge, are each sufficient to induce sleep when injected into the brain (reviewed in (Krueger, 2008). In nematodes (Van Buskirk and Sternberg, 2007), arthropods (Foltenyi et al. , 2007), and mammals (Kushikata et al. , 1998; Kramer et al. , 2001), signaling by epidermal growth factor (EGF) is sufficient to induce sleep behavior and, at least in nematodes, EGF signaling is necessary for SIS (Hill et al. , 2014). These cytokines act on central nervous system (CNS) neurons, which then induce sleep. In mammals, CNS neurons that regulate sleep reside in the hypothalamus (Saper et al. , 2005b). In C. elegans, the target for EGF action is a single interneuron called ALA (Van Buskirk and Sternberg, 2007), whose developmental program has similarities to the developmental program of mammalian neuroendocrine cells (Van Buskirk and Sternberg, 2010). With EGF activation, ALA depolarizes to release neuropeptides encoded by the gene flp-13 (FMRFamide-Like Peptide-13) to promote sleep (Nelson et al. , 2014). FLP-13 peptides are characterized by an amidated Arginine-Phenylalanine (RFamide) motif at their C-termini. RFamide neuropeptides are involved in many physiological functions in both invertebrates (López-Vera et al. , 2008; Peymen et al. , 2014), and vertebrates (Rőszer and Bánfalvi, 2012; Kim, 2016). In fruit flies, several RFamide neuropeptides","People often feel fatigued and sleepy when they are sick. Other animals also show signs of sleepiness when ill – they stop eating, move less, and are less responsive to changes in their environment. Sickness-induced sleep helps both people and other animals to recover, and many scientists believe that this type of sleep is different than nightly sleep. Studies of sickness-induced sleep have made use of a simple worm with a simple nervous system. In this worm, a single nerve cell releases chemicals that cause the worm to fall asleep in response to illness. Animals exposed to one of these chemicals, called FLP-13, fall asleep even when they are not sick. As such, scientists would like to know which cells in the nervous system FLP-13 interacts with, what",380,128,0.3368
dialogsum,"#Person1#: Why did you buy a second hand car for me? It is so disappointing. I thought you'd have bought me a new one. #Person2#: Don't be so angry my darling, I wanted to buy a new car for you, but I haven't got enough money at the moment. So when I got to the car market, I changed my mind. #Person1#: I feel so ashamed to drive such an old car. You know all my friends have good cars and beautiful houses. I really envy them. #Person2#: I am sorry for that. Please forgive me, I can promise you that if my business grows better for 3 more years, I'll surely make a fortune, then I'll buy you the most expensive car and a beautiful house with a nice, big garden and in the garden, there will be a fountain and a swimming pool. #Person1#: OK. That's enough. Thank you for the crazy ideas, but for the moment, let's see what we can do to make this car look better.",#Person2# buys a second-hand car for #Person1# and #Person1# feels angry. #Person2# apologizes and says #Person2# will buy a beautiful car for #Person1# when #Person2# becomes rich. #Person1# forgives #Person2#.,171,30,0.1754
dialogsum,"#Person1#: Tom, is Jenny crying? #Person2#: Can you take he away from me? #Person1#: I ' m just coming for that. #Person2#: She kept bothering me. #Person1#: She ' s your sister. What she asked was only duck soup for you. Why can ' t you be good to her? #Person2#: But I am her brother, not her servant.",Tom asks #Person1# to take Jenny away because she bothers him.,59,11,0.1864
dialogsum,"#Person1#: Hello there, welcome to Wine World. Let me know if I can help you out at all. #Person2#: Um, yes, please, I could really use some help. I'm going over to my boss'house for dinner tonight and don't know what kind of wine I should bring. #Person1#: OK, do you know what kind of food will be served? #Person2#: Well, his wife is Japanese. He said she makes really good sushi. #Person1#: Hmm, that's a bit of a challenge. Sushi is notoriously difficult to pair with wine. Well, let's see. have to be a white wine, of course. #Person2#: Why? Wouldn't a red wine go well with sushi? #Person1#: No, I don't think so. Sushi is a very delicately flavored food, and red wine would be a jarring contrast. You need a white wine, which has more subtle flavors, to complement the fish. #Person2#: I see. So should I get a bottle of Chardonnay? That's a white wine, right? #Person1#: Yes, Chardonnay is a white wine, but I'm not sure it'd be your best bet. Chardonnay is one of the more fullbodied whites, and tends to be a bit oaky. I'd suggest that you go for something brighter, like this Sauvignon Blanc from New Zealand. #Person2#: Sauvignon Blanc? What's that? #Person1#: That's another varietal, or type of grape, just like Chardonnay. #Person2#: Let's see. The label says it's got 'attractive citrus and grassy aromas that give way to crisp, mineral flavors and a bonedry finish. Serve chilled. ' Oh, no, how long will it take to chill the wine? I'm on my way to the dinner now. #Person1#: It's OK, don't worry, we'll just choose a wine from the cooler. We don't have quite as extensive a selection over here, but. . . this Rhone Valley white would be lovely. #Person2#: All right. What varietal is that? #Person1#: Well, this is a French wine, so they don't always specify the varietal on the label. The French believe that the soil a grape is grown in is one of the most important factors in the final flavor of the wine. This wine is probably a blend of a few different types of grapes, mostly Viognier, I'd guess. #Person2#: And you think this is a good wine? #Person1#: Yes, this is","#Person2# is going over to the home of #Person2#'s boss whose wife is Japanese, so #Person2# wants to buy a bottle of wine. #Person2# wants Chardonnay but it is denied by #Person1#. #Person1# recommends Sauvignon Blanc but it is denied by #Person2#. At last #Person2# decides on Rhone Valley white.",380,50,0.1316
scientific_lay_summarisation-elife-norm,"their data while filtering these artifacts generates a consensus that retrotransposition does occur in developing brain but at a much lower rate consistent with prior single-cell studies (Evrony et al. , 2012; Evrony et al. , 2015), thereby constraining the range of possible functional roles for retrotransposition in the brain. Our discussion of the challenges in single-cell sequencing may provide a useful framework for the design and analysis of single-cell genomics studies. Upton et al. isolated single neuronal cells from postmortem human brains and amplified their genomes using the MALBAC method (Zong et al. , 2012). They then profiled human-specific L1 elements (L1Hs) using their RC-seq method (Shukla et al. , 2013; Upton et al. , 2015) that captures and amplifies both the 5' and 3' ends of L1Hs elements via oligonucleotide hybridization and PCR, hence providing sequence data that identify L1Hs insertion sites in the genome. Although whole genome amplification methods have remarkable abilities to amplify picogram quantities of DNA from a single cell into microgram quantities, chimeric DNA molecules falsely linking unrelated DNA fragments are well known to arise during single-cell genome amplification (Macaulay and Voet, 2014). Chimera artifacts also arise during ligation and PCR steps of sequencing library preparation (Kircher et al. , 2012; Quail et al. , 2008), processes integral to the RC-seq method. Chimeric sequences can create a DNA fragment connecting a LINE element to an unrelated portion of the genome, creating the appearance of biological LINE mobilization (— 1A–B). Sequence analysis of Upton et al.' s putative PCR-validated candidates (Table S2 of Upton et al.) demonstrates that more than half of them (7 of 13) are chimera artifacts that could not have been generated by the process of L1 mobilization (Supplementary file 1). Some chimeras originated immediately downstream of germline L1Hs/L1Pa elements that are incapable of retrotransposition, because the L1 elements are truncated, are from an old, inactive L1 subfamily, or contain numerous inactivating mutations (1B; Supplementary file 1). In other cases, L1 5' and 3' junction chimeras originating from distinct L1 elements were misinterpreted as two ends of the same L1 (Figures 1B–C; Supplementary file 1). Some candidates lack poly-A tails (1C; Supplementary file 1), a key feature of retrotransposon insertions. Although the remaining 6/13 PCR-validated insertions lack clear evidence of being chimeras,","The human brain harbors perhaps the most diverse collection of cells among any organ in the body, consisting of neurons and other cells with many different shapes and behaviors. The mechanisms that create this diversity have been a long-standing area of investigation. While neurons can become more diverse through changes in the activity of genes during development and in response to experiences, it has been speculated that genetic differences among neurons may also play a role. The complete set of genes found in an individual is known as its genome. It is often assumed that each cell in an individual' s brain has an identical genome. However, mutations accumulate in cells during the lifetime of an individual such that every brain cell may in fact contain a unique",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2012). While this forms the major feedback loop of the mammalian molecular clock, the overall mechanism also depends on additional feedback loops driven by ROR and REV-ERBα/β (Preitner et al. , 2002; Sato et al. , 2004; Ueda et al. , 2005; Cho et al. , 2012). Significant progress has been made in identifying the core clock genes and the functions of their protein products in the clock mechanism, yet it is clear from other studies, including mutagenesis screens, that additional genes are necessary for a fully functional circadian clock (Takahashi, 2004). We previously identified at least 13 loci in mice that affect circadian behavior through complex epistatic interactions (Shimomura et al. , 2001), indicating that there are other clock-relevant genes in the mammalian genome. By extension, it is possible that the variance in circadian behavior observed in the human population results from polymorphisms in non-core circadian clock genes. Thus, identifying these genes is important for both mechanistic understanding and translational application. The quantitative trait locus (QTL) approach has been successfully applied to detect loci that associate with phenotypes of interest. An important application of QTL analysis is the identification of loci that modify the function and/or expression of a particular gene (Nadeau and Topol, 2006). A major obstacle, however, has been the cloning of these genes—particularly those underlying behavioral QTLs (Nadeau and Frankel, 2000). To overcome this challenge, several approaches have been proposed, yet it remains difficult to obtain a mapping resolution suitable for gene cloning by the positional candidate method (Darvasi and Soller, 1995; Churchill et al. , 2004; Valdar et al. , 2006). To date there are few examples of behavioral QTLs having been cloned using high-resolution mapping strategies (Yalcin et al. , 2004; Watanabe et al. , 2007; Tomida et al. , 2009). Because classical inbred laboratory mouse strains are derived from a limited number of progenitor species and the genomes of inbred strains are an admixture of different domesticated stocks (Wade et al. , 2002; Frazer et al. , 2007; Yang et al. , 2011), polymorphisms at the Soc locus may be ancestral. If so, other inbred strains that share identity by descent with the Soc locus should also suppress Clock. To test this hypothesis, we characterized 14 additional laboratory inbred strains by crossing to","Circadian rhythms are biochemical, physiological and behavioral processes that follow a 24-hr cycle, responding primarily to the periods of light and dark, and they have been observed in bacteria, fungi, plants and animals. The circadian clock that drives these rhythms—which dictate our sleep patterns and other processes—involves a set of genes and proteins that participate in a collection of positive and negative feedback loops. Previous research has mainly focused on identifying core clock genes—that is, genes that make up the molecular clock—and studying the functions of these genes and the proteins they code for. However, it has become clear that other clock genes are also involved in circadian behavior, and it has been proposed that polymorphisms in these non-core clock genes could contribute to the variations in circadian",380,128,0.3368
dialogsum,"#Person1#: I got something really special in the mail today. It's about classes to help you set up your own Internet business. Doesn't that sound fun? #Person2#: Oh, gosh! I don't know, just how much are these classes? #Person1#: $500 for 5 classes. But they guarantee that you'll have your business set up on a website before your done. #Person2#: Don't you think that's a lot of money? What kind of business would you start anyway? #Person1#: Well, you know how everyone loves my homemade candy? I'm going to start selling it on the web. I'm going to call it www.sweettooth.com. #Person2#: Well, good luck, you know it just might turn out to be a sweet investment.",#Person1# wants to take classes helping people set up internet businesses. #Person2# thinks the classes are expensive and it's a sweet investment.,117,22,0.188
dialogsum,"#Person1#: Hello, Jason, there is going to be a screening of Final Destination 3 at our campus cinema tomorrow. I plan to go to see it. #Person2#: Is it a horror movie? #Person1#: Yeah, I love horror movies. Would you like to go with me tomorrow? #Person2#: No way. I will be scared out of my wits. #Person1#: That's funny, I didn't know a big fellow like you could be so soft and timid on the inside. #Person2#: Hey, how would you like to taste my fist? #Person1#: Alright, all joking aside, what kinds of moves do you like? #Person2#: Um, let me see, romance, comedy. documentary, action, science fiction, animated and so on. #Person1#: That is to say, you like all genres except for horror movies. #Person2#: Yeah. It seems like we don't speak the same language as far as movies are concerned. #Person1#: Not quite. I also greatly enjoy romance and comedy. #Person2#: The Notebook is this type of movie. #Person1#: Really? I haven't heard of it. #Person2#: Well then, this could be a nice opportunity to enjoy it together. I bet you'd love it. #Person1#: Ok. I can't wait to see it. Let's go!",#Person1# invites Jason to watch a horror movie with #Person1#. Jason refuses because he doesn't want to be scared. They discuss the genres they like and decide to watch a romantic comedy called The Notebook.,197,35,0.1777
scientific_lay_summarisation-elife-norm,"about the size of organelle abundance fluctuations, leading to the surprising conclusion that the cell tolerates the maximum level of variability in Golgi apparatus and vacuole abundances generated by their biogenesis pathways. Second, for organelles where competing processes could contribute to organelle production but whose relative quantitative importance was unknown—the peroxisome—we used the model and experiment to infer that budding yeast cells switch from de novo synthesis dominated peroxisome production when grown in glucose-containing medium to fission dominated production in oleic acid-containing medium. Our theory of organelle biogenesis is very simple, but despite its simplicity we can gain mechanistic insight into the processes underlying organelle biogenesis. Though our framework suppresses details that could be relevant to organelle copy number regulation, such as when organelles share and thus compete for common biogenesis factors—as in the case of mitochondria and peroxisomes, which share fission factors in common for example—or when different processes affecting organelle copy number interact, such as the Golgi checkpoint regulating the progression of the mammalian cell cycle in which organelle biogenesis and decay would be coupled (Sutterlin, et al. , 2002), it is easily extendable to account for such effects. We therefore anticipate it will be a useful framework in which to analyze the pathways underlying organelle creation and destruction and subcellular structures more generally. To evaluate the relative importance of different biophysical pathways in shaping organelle abundances, we constructed a mathematical model of organelle abundance dynamics (1A). As the average number of organelles is typically small, we formulated a model consisting of four coupled stochastic processes, each parameterized by an associated rate constant: 10. 7554/eLife. 02678. 003Figure 1. A stochastic model of organelle abundance dynamics. (A) Organelle abundances are governed by four distinct biophysical processes: (i) de novo synthesis (kde novo, with units per time); (ii) fission (kfission, with units per organelle per time); (iii) fusion (kfusion, with units per organelle squared per time); and (iv) decay (γ, with units per organelle per time). (B) Sample trajectory generated by a Gillespie simulation of the model depicted in (A) in which the parameters are chosen to allow de novo synthesis to dominate over fission, fusion, and decay. (C) Sample trajectory as in (B), but with parameters chosen to allow fission to dominate over de novo synthesis, fusion, and decay.","Any cell that has a nucleus also contains various other organelles, such as the mitochondria that generate energy inside the cells. Like the nucleus, most of these organelles are enclosed within a membrane. Unlike the nucleus, however, there can be two or more copies of other types of organelles in a healthy cell. How do the numbers of the different organelles in a cell change? The copy number for a given organelle can be increased in two ways: by the synthesis of new organelles, or the fission of an existing organelle to form two new organelles. Conversely, the number of organelles can also be decreased in two ways: an organelle can decay, or two organelles can fuse to form one new organelle. The steady state for a given",380,128,0.3368
pubmed-summarization,"of art after conservative treatment remains anecdotal . the purpose of this study was to evaluate the outcomes of coh - ivf in infertile patients after conservative treatment for bot . a retrospective review of ivf records from january 1999 to july 2005 revealed 10 attempted ivf cycles in five patients who had been previously diagnosed with bot and had had conservative treatment to preserve fertility . bot has the histological characteristics of ovarian tumors : 1 ) epithelial proliferation with the formation of a papillary configuration , 2 ) demonstration of atypical epithelial activity , 3 ) mild or moderate atypical nuclei , and 4 ) the absence of stromal invasion , which distinguishes it from invasive carcinoma ( . conservative treatment is defined as preservation of the uterus and at least a portion of one ovary . in cases where the diagnosis of bot was made intraoperatively , staging was made according to the international federation of gynecology and obstetrics ( figo ) classification based on ipsilateral pelvic and paraaortic lymph node dissections , peritoneal cytology , omentectomy , and multiple peritoneal biopsies . after conservative surgery , a gynecological oncologist followed all patients every 3 months during the first year and thereafter every 6 months with a physical examination , serum ca-125 levels and transvaginal ultrasound . the main outcome measures were pregnancy outcomes such as clinical pregnancy rate ( cpr ) , implantation rate ( ir ) and live birth rate ( lbr ) after coh - ivf , and the recurrence of bot during the follow - up period . approval from the institutional review board was not obtained because this study was a retrospective case observational study . coh was performed with gonadotropin - releasing hormone agonist ( gnrh - a ) long protocol or flare - up protocol using human menopausal gonadotropin ( menogon , ferring , germany ) or recombinant follicle - stimulating hormone ( puregon , organon , netherland ) . for the long protocol , patients underwent pituitary desensitization with gnrh - a ( suprefact , hoechst , germany ) from the previous menstrual mid - luteal phase , and gonadotropins were administered after pituitary down regulation and continued up to hcg ( pregnyl , organon , netherland ) administration","to evaluate the outcomes of controlled ovarian hyperstimulation ( coh)-in vitro fertilization ( ivf ) such as clinical pregnancy rate ( cpr ) , implantation rate ( ir ) and live birth rate ( lbr ) for infertile patients with borderline ovarian tumor ( bot ) after conservative treatment , 10 ivf cycles in five patients from january 1999 to july 2005 were analyzed . at the time of diagnosis with bot , the mean age of patients was 30.0 yr ( range , 22 - 40 ) . for 8 cycles out of 10 attempted ivf cycles , except for 2 cancellation cycles , the mean number of oocytes retrieved was 5.6 ( range , 2 - 16 ) with a mean fertilization rate of 74.4% .",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Transporters from bacteria to humans contain inverted repeat domains thought to arise evolutionarily from the fusion of smaller membrane protein genes. Association between these domains forms the functional unit that enables transporters to adopt distinct conformations necessary for function. The small multidrug resistance (SMR) family provides an ideal system to explore the role of mutations in altering conformational preference since transporters from this family consist of antiparallel dimers that resemble the inverted repeats present in larger transporters. Here, we show using NMR spectroscopy how a single conservative mutation introduced into an SMR dimer is sufficient to change the resting conformation and function in bacteria. These results underscore the dynamic energy landscape for transporters and demonstrate how conservative mutations can influence structure and function. Membrane transport proteins catalyze the movement of ions and molecules across the membrane by binding substrates on one side of the bilayer and undergoing conformational changes (Jardetzky, 1966; Zhang et al. , 2016). Structural and functional experiments have shown support for the alternating access model in which a transporter samples at least two different conformations that expose the substrate to the inside and outside environment of the cell membrane. The presence of inverted structural repeats within a single polypeptide chain is widespread in membrane protein transporters (Shimizu et al. , 2004; Forrest and biology, 2013) and has been proposed as a mechanism to enable alternating access exchange (Forrest et al. , 2008). Proteins with structural repeats are thought to arise evolutionarily from the fusion of smaller membrane protein genes, such as three or four transmembrane (TM) domain transporters that associate into oligomers to achieve the functional state (Xu et al. , 2014; Bay and Turner, 2009). One class of these proteins is the small multidrug resistance (SMR) family (Schuldiner, 2014; Schuldiner, 2009; Paulsen et al. , 1996) found in bacteria and archaea that contain four TM domains and assemble into antiparallel homodimers or heterodimers which resemble the inverted repeat structure in larger transporters. Homodimer transporters such as the multidrug efflux pump EmrE are able to insert into two opposing directions in the membrane (i. e. dual topology) whereas heterodimers are comprised of two genes that each insert into the membrane in a single orientation (i. e. single topology). The latter form the paired SMR (pSMR) subfamily and","Cells are bound by a thin membrane layer that protects the cell’s interior from the outside environment. Within this layer are various transporter proteins that control which substances are allowed in and out of the cell. These transporters actively move substances across the membrane by loading cargo on one side of the layer, then changing their structure to release it on the other side. Membrane transporters are typically made up of multiple repeating units. In more complex transporters, the genetic sequence for each of these structural units is fused together into a single gene that codes for the protein. It is thought that the repeated pattern evolved from smaller membrane protein genes that had duplicated and fused together. But, what are the evolutionary advantages of having more complex",380,128,0.3368
dialogsum,"#Person1#: Excuse me, sir. Which would you like? A Chinese or a western meal? #Person2#: Chinese food, please. #Person1#: Please put down the table in front of you. Here, like this. #Person2#: Oh, thank you. That's very kind of you. #Person1#: It's my pleasure. What would you like to drink? Tea, coffee, orange juice? #Person2#: Do you have any soybean milk? #Person1#: Yes, here you are. We also have some very nice orange juice. Would you like to try some? #Person2#: Thanks a lot. Just a small cup, please. By the way, how long does the flight take? And can I have a seat beside a window? I'd like to enjoy the scenery outside. #Person1#: About 6 hours, and it lands at 8:00 PM. I'll ask someone to see if you can change seats.","#Person2# chooses a Chinese meal, soybean milk, and a small cup of orange juice on the plane. He asks #Person1# about the duration of the flight and requests to change his seat.",134,32,0.2388
scientific_lay_summarisation-elife-norm,"the zebrafish retina is ‘cone rich’ like the human retina. Second, about 70% of human genes have at least one ortholog in zebrafish (Howe et al. , 2013). Moreover, all RP-associated genes listed in RetNet (https: //sph. uth. edu/retnet/) have conserved zebrafish orthologs. Third, the zebrafish retinal system develops quickly being fairly mature by day five of development (Brockerhoff et al. , 1995; Moyano et al. , 2013; Schmitt and Dowling, 1999). Fourth, zebrafish are amendable to large-scale chemical screening due to their high fecundity rate, small size, and ease of visualizing and quantifying a variety of phenotypes (Mathias et al. , 2012; Zon and Peterson, 2005). To streamline such screens, we developed a high-throughput plate reader-based method for quantifying reporter gene expression in vivo (‘ARQiv’; Walker et al. , 2012). Recently, we adapted the ARQiv system to human stem-cell-derived retinal organoids (Vergara et al. , 2017) to enable cross-species PDD. To realize full throughput potential, ARQiv was combined with robotics-based automation to create ‘ARQiv-HTS’ (Wang et al. , 2015b; White et al. , 2016). Here, to identify neuroprotective compounds promoting rod photoreceptor survival, ARQiv-HTS was used to perform a large-scale chemical screen in a transgenic zebrafish model enabling inducible rod photoreceptor cell death (Walker et al. , 2012; White et al. , 2017). In these fish, YFP-NTR (a yellow fluorescent protein-nitroreductase bacterial enzyme fusion protein) is selectively expressed in rod photoreceptors. NTR expression enables inducible ablation of rod cells upon exposure to prodrug substrates, such as metronidazole (Mtz), which are thought to cause apoptosis through activated metabolites that cause DNA damage (Curado et al. , 2007; White and Mumm, 2013). Close to 3000 largely human-approved drugs were tested across six concentrations (i. e. using qHTS principles, Inglese et al. , 2006) in more than 350,000 zebrafish larvae. Statistically, 113 hits were identified as hits and 42 of the top performing compounds advanced through confirmation and orthogonal assays. Eleven compounds passed all secondary tests and moved forward as lead drug candidates. Validation tests in an orthogonal series of mouse RP models followed, reasoning that drugs effective across species and/or independent of disease mutation may translate better clinically. All leads were screened in primary mouse photoreceptor cell cultures and a subset of leads was evaluated in retinal explants from the retinal","Photoreceptors are the cells responsible for vision. They are part of the retina: the light-sensing tissue at the back of the eye. They come in two types: rods and cones. Rods specialise in night vision, while cones specialise in daytime colour vision. The death of these cells can cause a disease, called retinitis pigmentosa, that leads to vision loss. Symptoms often start in childhood with a gradual loss of night vision. Later on, loss of cone photoreceptors can lead to total blindness. Unfortunately, there are no treatments available that protect photoreceptor cells from dying. Research has identified drugs that can protect photoreceptors in animal models, but these drugs have failed in humans. The classic way to look for new treatments is to find drugs that target molecules implicated",380,128,0.3368
dialogsum,"#Person1#: What do you mean his grandmothers are already dead? Wait a minute, you don't think he's avoiding me, do you? #Person2#: Well you know, claiming that your grandmother is sick is the classic excuse used to get out of doing something. #Person1#: Oh man, I hate rejection. It really makes you feel terrible, especially when you really liked the person. #Person2#: Is there anything I can do to help? Just remember that I'm there for you if you want to talk about it.",#Person1# is upset due to the rejection of a boy. #Person2# comforts her.,84,13,0.1548
scientific_lay_summarisation-elife-norm,"algal-fungal interactions. Nannochloropsis oceanica cells flocculated in dense clusters around M. elongata mycelium when they were incubated together (1A and B). After 6 days co-cultivation, scanning electron microscopy (SEM) revealed a wall-to-wall fungal-algal interface between the organisms grown in co-culture, (1C) with the morphology of N. oceanica cells differing from those of cells grown in the absence of fungus. Specifically, SEM images showed that N. oceanica cells incubated alone in f/2 medium have a smooth outer layer (1D and — 1A), which was fragmented or lacking after co-culture with M. elongata AG77 and fibrous extensions underneath the smooth outer layer were exposed (1E and — 1B). While it is possible that the fibrous extensions have been elicited by the contact with the fungus, remnant pieces of the outer coat covering the underlying extensions are evident in our observations (1E and F and — 1B). Therefore, it seems likely that these extensions are present underneath the outer smooth layer. In addition, the fibrous extensions appeared to contribute to anchoring the algae to hyphae and irregular tube-like extensions were formed between the two interacting cell types (1F). Further SEM revealed that the fibrous extensions only were exposed in N. oceanica cells that were in physical contact with live fungal hyphae. N. oceanica cells maintained a smooth outer wall covering (— 1) when they were co-cultured without physical contact with live fungi, and when they were co-cultured with M. elongata mycelium that had been killed in a 65°C water bath. We demonstrated that a combination of enzymes, including 4% fungal hemicellulase and 2% driselase, could partially digest the outer smooth cell wall layer of N. oceanica and expose the fibrous extensions to mimic the morphological change observed during the physical interaction between live M. elongata and N. oceanica cells (— 2). To test whether nutrient, that is carbon or nitrogen exchange underlies the interaction between M. elongata and N. oceanica, we conducted a series of tracer experiments using reciprocally 14C- and 15N-labeled algal and fungal partners. For carbon exchange assays, algal cells were labeled with [14C]-sodium bicarbonate and were co-cultivated with actively growing non-labeled fungal hyphae for 1 week in flasks. Conversely, fungal hyphae were grown in either [14C]-glucose- or [14C]-acetate-containing medium for labelling. Labeled fungi were then co-incubated with non-labeled algal cells","Yeast, molds and other fungi are found in most environments across the world. Many of the fungi that live on land today form relationships called symbioses with other microbes. Some of these relationships, like those formed with green algae, are beneficial and involve the exchange carbon, nitrogen and other important nutrients. Algae first evolved in the sea and it has been suggested that symbioses with fungi may have helped some algae to leave the water and to colonize the land more than 500 million years ago. A fungus called Mortierella elongata grows as a network of filaments in soils and produces large quantities of oils that have various industrial uses. While the details of Mortierella’s life in the wild are still not certain, the fungus is thought to",380,128,0.3368
pubmed-summarization,"functional gastrointestinal disorder ( fgid ) is one of the commonest digestive disease entities , which is characterized by recurrent gastrointestinal symptoms with no identifiable organic pathology . in recent years , a bio - psycho - social pathophysiological model has been implicated for the pathogenesis of fgid , which emphasizes the importance of biological , social , environmental and psychological factors in development of fgid.1 this paper aimed to review the epidemiology , mechanism and psychological intervention of fgids . the observations on the association between psychological disorders and fgid used to be considered conflicting , and it was generally regarded as biased observations that were limited to more severe patients seen in referral center setting . an early study conducted in a gastroenterology clinic reported a very high lifetime prevalence of generalized anxiety disorder of 34% in newly referred irritable bowel syndrome ( ibs ) patients.2 in another study that involved patients with anxiety or depressive disorders , ibs symptoms were found to be associated with severity of anxiety and depressive symptoms . however , patients with depression in remission had no associated ibs symptoms.3 in a study of primary care patients referred for endoscopy , however , there was no difference between patients with functional or organic dyspepsia in the prevalence or risk of mental distress as determined by questionnaire.4 talley et al5 reported that dyspepsia patients who present for investigation were more likely to be neurotic , anxious , and depressed than non - dyspepsia controls . using the gold standard diagnostic method with psychiatrist - conducted structured clinical interview for diagnostic statistical manual of mental disorders - iv axis i disorders , we have reported that anxiety disorders are diagnosed in 38% of patients with functional dyspepsia compared with 4% in the general population.6 depression , anxiety , phobia and somatization are strongly correlated with severity of dyspeptic symptoms in a group of patients from tertiary center.7 somatization is more commonly seen in patients with co - morbid fgid and psychological disorder.8 it has also been observed that ibs patients with psychiatric morbidity are characterized by low rectal distension pain thresholds , high rates of healthcare consultations , interpersonal problems and sexual abuse.9 in recent years , there are mounting evidence showing that similar association","functional gastrointestinal disorder ( fgid ) is one of the commonest digestive diseases worldwide and leads to significant morbidity and burden on healthcare resource . the putative bio - psycho - social pathophysiological model for fgid underscores the importance of psychological distress in the pathogenesis of fgid . concomitant psychological disorders , notably anxiety and depressive disorders , are strongly associated with fgid and these psychological co - morbidities correlate with severity of fgid symptoms . early life adversity such as sexual and physical abuse is more commonly reported in patients with fgid . there is mounting evidence showing that psychological disorders are commonly associated with abnormal central processing of visceral noxious stimuli . the possible causal link between psychological disorders and fgid involves functional abnormalities in various",380,128,0.3368
dialogsum,"#Person1#: Hey Mike, good to have you back. You look exhausted. #Person2#: Hi, Mary. Yeah. I'm totally beat. I can barely keep my eyes open. #Person1#: Was it a rough trip? #Person2#: Well, it was actually pretty productive. But all the flying really got to me. #Person1#: Oh, jet lag. #Person2#: Yep. I flew from Beijing to Boston for a meeting and then got on a plane to go to the trade fair in Frankfurt. Then back to Beijing before catching a train back here to Shanghai. #Person1#: Wow, that's a lot of traveling. No wonder you're exhausted. #Person2#: The worst thing was adjusting to the time zones. It's so hard to get used to the difference. #Person1#: Yeah, it's hard. You know jet lag only hits if you travel east west or west east. You could fly from Germany to Cape Town in South Africa and you wouldn't feel a thing. #Person2#: Right, because it's all in the same time zone. Unfortunately for me, all my travel was between different time zones. I've got to say, I'm really suffering. Why is jet lag so nasty? #Person1#: I know what you mean. Well, you'll be OK once you get some rest.",Mike tells Mary that all the flying makes him exhausted and it is very hard to get used to the difference between different time zones. Mary suggests that Mike gets some rest.,201,32,0.1592
pubmed-summarization,"pain originates from a musculoskeletal cause . when a mediastinal mass such as a thymic carcinoma invades the chest wall , pleura , or heart , patients frequently present with chest pain.3 our case illustrates several considerations in the initial evaluation of chest pain . first , chest ct was needed more than emergent coronary angiography because of the characteristics of the chest pain , which was sharp and had lasted for a month . although a few cases of thymic cyst and malignancy have been documented,4 - 7 there has been no report that echocardiography detected an extracardiac mediastinal mass in the course of evaluating chest pain . thymic carcinoma is a heterogeneous group of aggressive and epithelial malignancies , and its incidence is rare . most patients present with cough , dyspnea , or chest pain . while these symptoms are being evaluated , the malignancy is often incidentally detected by chest radiographs or ct scan.3 when an anterior mediastinal mass shows the presence of an irregular contour , necrotic or cystic component , heterogeneous enhancement , lymphadenopathy , and great vessel invasion on a ct scan , the mass is likely to be a thymic carcinoma.8 mediastinal tumors , including thymoma , thymic carcinoma , and seminoma have been incidentally detected by thallium-201 ( tl 201 ) imaging.9 considering that the mediastinal mass is adjacent to the cardiac chamber , echocardiography can evaluate a mediastinal mass like a ct scan or tl 201 uptake . the mediastinal mass can distort or partially displace one or more cardiac chambers , and an anterior mediastinal mass can compress the right heart chamber , which can be shown by echocardiography.5 it has been reported that thymic cancer was detected by echocardiography presenting as cardiac tamponade or supra vena cava ( svc ) echocardiography is useful for the evaluation of chest pain in emergency circumstances and can detect a mediastinal mass because mediastinal masses are just adjacent to the heart ; however , the diagnosis of an extracardiac mass can be missed . therefore , it is important to look outside the heart in addition to the heart itself in the assessment of chest pain .",we report a case of thymic carcinoma that was initially detected by echocardiography in an 80-year - old male who visited the emergency room for chest pain and had a history of myocardial infarction and percutaneous coronary intervention . transthoracic echocardiography showed a huge extracardiac mass that was located in the anterior mediastinum and was diagnosed as a thymic carcinoma by biopsy .,365,63,0.1726
scientific_lay_summarisation-elife-norm,"large (~60–120 MDa) structures with octagonal rotational symmetry. They are comprised of ~30 different nuclear pore proteins (nucleoporins, or Nups), each of which are thought to be present in an integer multiple of eight copies (Cronshaw et al. , 2002; Fahrenkrog and Aebi, 2003; Mi et al. , 2015; Ori et al. , 2013; Rout and Aitchison, 2001). The vertebrate NPC has an outer diameter of ~120 nm, and extends ~200 nm along the transport axis (Fahrenkrog and Aebi, 2003; Stoffler et al. , 1999). Eight flexible filaments extend ~50 nm into the cytoplasm, and an additional eight filaments extend ~75 nm into the nucleoplasm and terminate in a ring to form the nuclear basket (Fahrenkrog and Aebi, 2003; Stoffler et al. , 2003). In humans, the hourglass-shaped central pore has a minimum diameter of ~50 nm and a length of ~85 nm (Maimon et al. , 2012). Within this large pore and decorating its openings is a network of ~200–250 intrinsically disordered polypeptides, which generates a permeability barrier impeding macromolecular transport (Lim et al. , 2008; Ori et al. , 2013; Peleg and Lim, 2010; Suntharalingam and Wente, 2003) and which is particularly selective against larger cargos (Mohr et al. , 2009; Popken et al. , 2015; Ribbeck and Görlich, 2001; Timney et al. , 2016). These disordered polypeptides contain, in total, 3000–4000 phenylalanine-glycine (FG) repeats to which NTRs transiently bind as they carry cargos through NPCs (Cronshaw et al. , 2002; Denning et al. , 2003; Rout et al. , 2000; Strawn et al. , 2004; Tran and Wente, 2006). We term this assembly of intrinsically disordered FG-containing polypeptides the FG-network. Each FG-containing nucleoporin (FG-Nup) has a globular anchor domain that is embedded in or attached to the NPC scaffold, and thus, it acts as an anchor point for the flexible and mobile FG-domain. The FG-repeat motifs are separated by short (~10–20 amino acid residues), largely hydrophilic segments (Denning and Rexach, 2007; Yamada et al. , 2010). The FG-domains do not form readily recognizable secondary structures, but rather are more appropriately described as flexible polymers with alternating hydrophobic and hydrophilic domains (Lim et al. , 2006; Yamada et al. , 2010). The FG-network is sufficiently fluid and mobile that it is rapidly displaced by transporting cargos, which can","Most of the genetic material inside an animal cell is enclosed within a compartment called the nucleus. This compartment is separated from the rest of the cell by the nuclear envelope, a double-membrane structure containing thousands of pores that selectively allow certain molecules (collectively referred to as cargo) to enter and exit the nucleus. The movement of cargo through the pores is controlled by large groups of proteins called nuclear pore complexes. The pore is at the center of the complex and is filled by a selective barrier made of an extensive network of flexible proteins known as the FG-network. Other proteins known as nuclear transport receptors bind to the proteins in the FG-network and carry cargos through the barrier. The properties of the nuclear pore barrier and",380,128,0.3368
dialogsum,"#Person1#: Hi, I think I was supposed to call for my test results today. #Person2#: If you go onto our website and put in your password, you can access your test results. #Person1#: Are you saying that there weren't any problems? #Person2#: I will always have you come in for a discussion if there is a major problem. #Person1#: Will I be able to read the results on the website and understand them? #Person2#: Yes, if you go there, you can see what each test is about. #Person1#: How will I know what the numbers mean? #Person2#: You can see your results and how they compare to the normal range. #Person1#: How can I see test results from tests I have taken before? #Person2#: We put all of your test results up in the same place. Just check the dates for what you need.",#Person1# comes to get #Person1#'s test results. #Person2# advises #Person1# to access to the results on the website and offers guidance about how to read the results.,144,27,0.1875
dialogsum,"#Person1#: Can you tell me how to reach the bank,please? #Person2#: Which bank? There are two: the Allied Irish Bank and the Bank of Ireland. #Person1#: I have an AIB pass card and I want to get money from the bank. #Person2#: You need to go to the Allied Irish Bank which is near the local shopping center, Dunnes Stores. #Person1#: How do I get there? I have no knowledge of this area. #Person2#: Cross the road and turn left at the other side. Walk a long the footpath until you reach the traffic lights. You will see a shopping center on the right hand side. Walk across the road and turn right after the shopping center. Keep going straight for about 100 metres and the bank is to your left. #Person1#: It sounds a little bit difficult. How far is it from here? #Person2#: It's not so difficult. It's about five minutes' walk from here. I can draw a map for you if you wish. #Person1#: Oh, I would really appreciate that.",#Person2# shows #Person1# the ways to the Allied Irish Bank. #Person1# feels it's difficult and #Person2# draws a map for #Person1#.,173,21,0.1214
scientific_lay_summarisation-elife-norm,"which can vary between transcript isoforms (de Klerk and' tHoen, 2015; Ingolia et al. , 2011; Sterne-Weiler et al. , 2013). Classic examples of translational control include upstream ORFs (uORF) -mediated translational control of yeast GCN4 (Hinnebusch, 2005), protein binding such as the iron regulatory protein (Gray and Hentze, 1994), and the action of micro-RNAs (Nottrott et al. , 2006; Wilczynska and Bushell, 2015) or DEAD-box proteins such as eIF4A and Ded1 (Chuang et al. , 1997; Hinnebusch and Lorsch, 2012; Sen et al. , 2015). Alternative 5′ leader sequences, uORFs, and select tandem 3′ untranslated region (UTR) isoforms have been demonstrated to influence protein production (Brar et al. , 2012; Hinnebusch, 2005; Ingolia et al. , 2011; Mayr and Bartel, 2009; Sandberg et al. , 2008; Zhang et al. , 2012). Any of these features may in principle be different between transcript isoforms, but the prevalence and dynamic range of isoform-specific translational control across the human genome is currently unknown. Previous work measuring genome-wide translation in human cells has focused largely on the relationship between gene-level mRNA abundance and protein levels, which is blind to the contribution of transcript isoforms. Ribosome profiling is not well-suited for measuring transcript isoform-specific translation, primarily due to the short ~30 bp length of ribosome-protected fragments (Ingolia, 2014). Prior attempts to characterize isoform-specific translation have measured the effects of 5′ end diversity in yeast (Arribere and Gilbert, 2013) and 3′ end diversity in mouse cells (Spies et al. , 2013), or splicing differences between cytoplasmic and aggregate polysomal mRNAs (Maslon et al. , 2014; Sterne-Weiler et al. , 2013). However, sequencing just the ends of transcripts cannot distinguish between transcript isoforms of the same gene harboring degenerate termini. In addition, aggregating polysome fractions averages lowly- and highly-ribosome-associated messages. Therefore, a different strategy is required to understand how the diversity of the human transcriptome impacts translational output. Here, we adapt a classic approach of polysome profiling coupled with global gene expression analysis (Arava et al. , 2003) to measure transcript-isoform specific translation using deep sequencing, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). By using high gradient resolution and sequencing depth, this approach yields polysome profiles for over 60,000 individual transcript isoforms representing almost 14,000 protein coding genes. We observe frequent intron retention on","To produce a protein, a gene’s DNA is first copied to make molecules of messenger RNA (mRNA). The mRNAs pass through a molecular machine known as the ribosome, which translates the genetic code to make a protein. Not all of an mRNA is translated to make a protein; the “untranslated” regions play crucial roles in regulating how much of the protein is produced. In animals, plants and other eukaryotes, many mRNAs are made up of small pieces that are “spliced” together. During this process, proteins are deposited on the mRNA to mark the splice junctions, which are then cleared when the mRNA is translated. Many different mRNAs can be produced from the same gene by splicing different combinations of RNA pieces. Each of these mRNA “isoforms” can, in",380,128,0.3368
dialogsum,"#Person1#: I made a reservation earlier this week, but I have to cancel it. #Person2#: No problem, sir. Just tell me your name, phone number, and date of reservation. #Person1#: Great! I'm Rudy Randolph, 818-555-1234, and my reservation was for April 9 to 15. #Person2#: Okay, sir, let me hit the delete button, and your reservation will be cancelled. #Person1#: That was nice and fast. Thanks. #Person2#: Not at all.",Rudy asks #Person1# to cancel his reservation for April 9 to 15.,70,12,0.1714
dialogsum,"#Person1#: We are going to put on a performance. #Person2#: Really? When? #Person1#: On May 4. We have been preparing for it for two months. #Person2#: Where are you going to put it on? In your school? #Person1#: No. At the People's Theatre. #Person2#: If I remember correctly, you put it on at the Youth Square last year. #Person1#: Yeah. But it is under repair now. #Person2#: But why are you doing that? To collect money for repairing the Youth Square? #Person1#: No. We want to collect money and send it to Project Hope. #Person2#: That sounds like a good idea. Good luck to you. #Person1#: Thanks a lot.",#Person1# tells #Person2# they are going to put on a performance at the People's Theatre to collect money for Project Hope.,109,21,0.1927
scientific_lay_summarisation-elife-norm,"position 302/303 causes the movement disorder DYT1 primary dystonia (Ozelius et al. , 1997; Breakefield et al. , 2008). Mammalian TorsinA has been assigned to a variety of possible functions including nuclear envelope (NE) organization, synaptic vesicle transport and turnover, operation of the secretory pathway, protein degradation, cytoskeletal organization and transport via NE budding (Vander Heyden et al. , 2009; Granata and Warner, 2010; Jokhi et al. , 2013). While LAP1 and LULL1 were first considered as Torsin substrates (Naismith et al. , 2009), they are now being proposed as possible activators of Torsin (Zhao et al. , 2013). To better understand the function of LAP1 in relation to Torsin, we set out to determine its structure. Our data suggest that LAP1 and LULL1 can both form heterohexameric ring assemblies with Torsin, whereby Torsin is activated through an arginine finger at amino acid (aa) R563 of LAP1 (R449 of LULL1). Thus LAP1 and LULL1 each have dual roles, namely the targeting and activation of Torsins. The conserved luminal domain of LAP1 (aa356–583) was recombinantly expressed, purified, and set up for crystallization. Because the protein failed to yield crystals alone, we produced a camelid single domain (VHH) antibody fragment, VHH-BS1, against LAP1 as a crystallization chaperone. The complex of VHH-BS1 and LAP1 yielded well-diffracting crystals (Table 1). The structure was solved using molecular replacement with VHH as the search model (for details, see ‘Materials and methods’). In the asymmetric unit we find two LAP1 molecules related by a non-crystallographic symmetry axis, each identically bound by one VHH. The final structure is completely built, except for four N-terminal residues in LAP1, which seem disordered in the crystal (six N-terminal residues in the second LAP1 copy). 10. 7554/eLife. 03239. 003Table 1. X-ray data collection and refinement statisticsDOI: http: //dx. . org/10. 7554/eLife. 03239. 003ProteinHuman LAP1356–583-VHH-BS1 complexPDB ID4TVSData collection Space groupP21 a, b, c (Å) 69. 79,74. 02,85. 43 α, ß, γ (°) 90,108. 8,90 Wavelength (Å) 1. 2548 Resolution range (Å) *66. 1–1. 60 (1. 66–1. 60) Total reflections630,312 (46,516) Unique reflections105,976 (10,195) Completeness (%) 97. 6 (94. 3) Redundancy5. 9 (4. 6) Rsym (%) 9. 1 (141. 2) Rp. i. m. (%) 4. 0 (68. 6) I/σ12. 5 (1. 1) CC1/2 (%) 99. 8 (54. 7) Refinement Resolution range (Å) 66. 1–1.","Cells are filled with activity—proteins must be folded into intricate shapes and unfolded, complex molecules must be built and taken apart—and all this activity requires energy. Cells use a molecule called ATP as a source of energy, with the energy being released when enzymes called ATPases remove a phosphate group from the ATP molecule. There are many different ATPases, and when one of them does not work properly, the consequences can be severe. A single mutation in the gene for an ATPase called TorsinA, for example, can lead to a painful and severely disabling disorder called primary dystonia. However, scientists have yet to discover what the TorsinA enzyme does in cells and how mutated TorsinA causes primary dystonia. It is known that the TorsinA enzyme is found in",380,128,0.3368
pubmed-summarization,"men and 14 women between 26 and 87 years old ( median 65 years ) . out of these 51 patients , 23 ( 45.1% ) manifested thoracic symptoms ( dysphagia , dyspnea , thoracic pain ) , 22 ( 43.1% ) reported nonspecific signs and symptoms ( fever and weight loss ) , and 6 ( 11.8% ) were asymptomatic . the forwarding physicians included 22 ( 43.1% ) oncologists , 18 ( 35.3% ) clinical pulmonologists and thoracic surgeons , and 11 ( 21.6% ) others ( general clinicians , digestive surgeons , and cardiologists ) . it should be highlighted that out of the 51 eus performed for mediastinal assessment purposes , 23 ( 45.1% ) happened in the final four years of the research period , and these cases were mostly referred by pulmonologists and thoracic surgeons . endoscopic alterations ( extrinsic compression ) were found in 24 ( 47.1% ) patients , three of whom already displayed esophageal stenosis . in group 1 ( with previously known malignant disease , forwarded for mediastinal staging ) , 17 patients were included , 9 with primary lung tumors , 4 with breast tumors , 2 with kidney tumors , 1 with a colon tumor , and 1 with a bladder tumor . out of these 17 patients , a previous pet scan had been done in only 4 , all of whom were considered the diameter of the punctured lesions ranged from 1.1 to 6.8 cm , with an average of 3.7 cm . their location ( mountain , 1997)9 corresponded to stations 2r ( 2 cases ) , 2l ( 1 ) , 4r ( 1 ) , 4l ( 2 ) , # 5 ( 1 ) , # 6 ( 1 ) , # 7 ( 3 ) , # 8 ( 2 ) , 10r ( 1 ) , and 10l ( 3 ) . eus - fna demonstrated metastatic involvement in 15 out of 17 ( 88.2% ) patients in group 1 . the respective lymph node stations sampled by eus were the paraesophageal ( # 8 ) and the left hilar ( 10l ) . both cases were later submitted to classical cervical mediastinoscopy , which identified metastases in lower paratracheal",objectives : to disseminate transesophageal ultrasound - guided fine needle aspiration ( eus - fna ) as an alternative to investigate mediastinal tumoral lesions because it is an underused modality that has been available in brazil for more than 15 years.methods:descriptive analysis of a single endoscopy service 's experience since 1997 in the accomplishment of eus - fna for mediastinal staging of previously known malignancies ( group 1 ) or diagnostic definition of suspect lymph nodes and masses ( group 2).results : eus - fna was performed in 51 patients between 26 and 87 years of age . the diameter of the lesions ranged between 1.1 and 9.8 cm ( mean 3.9 cm ) . their location corresponded to the following stations : higher paratracheal ( 4 cases,380,128,0.3368
scientific_lay_summarisation-elife-norm,"Adaptation is a salient property of sensory processing. All adaptational or gain control mechanisms face the challenge of obtaining a reliable estimate of the property of the input to be adapted to and obtaining this estimate sufficiently rapidly to be useful. Here, we explore how the primate retina balances the need to change gain rapidly and reliably when photons arrive rarely at individual rod photoreceptors. We find that the weakest backgrounds that decrease the gain of the retinal output signals are similar to those that increase human behavioral threshold, and identify a novel site of gain control in the retinal circuitry. Thus, surprisingly, the gain of retinal signals begins to decrease essentially as soon as background lights are detectable; under these conditions, gain control does not rely on a highly averaged estimate of the photon count, but instead signals from individual photon absorptions trigger changes in gain. Sensory systems encode an enormous range of input signals—for example, a rock concert is ∼1012 times louder than a just detectable whisper. Maintaining sensitivity as inputs change requires adaptational mechanisms that adjust the gain or amplification of neural signals to match their limited dynamic range to the range of the input signals a cell receives. Such gain control mechanisms operate under challenging conditions as the inputs they encounter can vary rapidly in time and locally in the space of possible stimuli. For example, visual neurons can experience >1000-fold changes in input a few times a second as the eyes move to explore a typical scene (Frazor and Geisler, 2006). Standard cameras fail to capture the full structure of such scenes because they employ a single global gain control in the form of an exposure setting, which is often poorly matched to the brightest and dimmest regions of a scene. Sensory gain controls are clearly more sophisticated. Effective gain control requires balancing the need to be rapid and local with the need to be accurate (reviewed by Rieke and Rudd, 2009). This is an example of the classic change detection problem: how many samples from a signal distribution are needed to determine whether or not the distribution has changed (Buracas et al. , 1998; Deneve, 2008; Wark et al. , 2009)? Gain control mechanisms operating near absolute visual threshold exemplify this problem. Human behavioral","To process the sights and sounds around us, our senses must be attuned to a huge range of signals: from barely audible whispers to deafening rock concerts, and from dim glimmers of light to bright spotlights. Sensory neurons face the challenge of encoding this huge range of inputs within their much more restricted response range. Thus, neurons in our eyes and ears must continually adjust their gain or sensitivity to match changes in the light and sound inputs. These gain control processes must operate rapidly to keep up with the ever-changing input signals, but must also operate accurately so as not to distort the inputs. The trade-off between rapid and accurate gain control can be illustrated by considering how the retina processes information at low light levels. There",380,128,0.3368
dialogsum,#Person1#: I decided to go for this kind of life. #Person2#: Try to keep cool. It's not an easy take. #Person1#: I know. I always hope for the best and prepare for the worst. #Person2#: Then you will be in line for a doom.,#Person2# thinks it's hard for #Person1# to go for this kind of life.,44,13,0.2955
dialogsum,"#Person1#: I've got some bad news about the bike you lent me. #Person2#: What's that? #Person1#: I fell on the way to school, and your bike got scratched. I'm really sorry. #Person2#: Don't worry about it. It's not new, it already has a few scratches. Did you get hurt? #Person1#: No, thank you. #Person2#: That's the most important thing. #Person1#: It's kind of you to say. I feel a little stupid. #Person2#: Forget about it. #Person1#: When you lent me the bike, it looked brand new, almost anyway. #Person2#: Maybe, but really I have fallen a couple of times and it's been hit once or twice as well. #Person1#: I appreciate that, thank you.",#Person1# apologizes to #Person2# for getting #Person2#'s bike scratched. #Person2# comforts #Person1# for it's not a new bike.,114,18,0.1579
dialogsum,"#Person1#: Can I help you? #Person2#: I hope so. I'm looking for some material for a paper I'm writing, and I'm not quite sure where to look. #Person1#: I'll certainly try to help you. What topic is your paper on? #Person2#: My paper is on the influence of television on children. #Person1#: There are several possible sources you might use for that topic. I suggest you use the computer and the computer will give you a list of every scientific journal that talks about children and television. #Person2#: Thank you for you help.",#Person1#'s assisting #Person2# in finding some material for a paper on the influence of television on children.,93,17,0.1828
scientific_lay_summarisation-elife-norm,"However, recent evidence showed that it was possible to reduce the RT considerably before any decline in movement accuracy was observed. For example, when individuals were placed under strict time constraints, movement accuracy and task success decreased only after the RT was shortened by ~80 ms (Haith et al. , 2016). Similarly, startle by a loud acoustic stimulus could evoke initiation of a fully prepared action ~70 ms earlier than typically observed (Valls-SoleSolé et al. , 1999; Carlsen et al. , 2004). These findings suggest that the RT includes some additional time that is not required for computing the upcoming response, raising the possibility that other factors might also influence the RT. An additional clue that the RT does not strictly represent computation time comes from evidence that the RT is influenced by context. This was illustrated in a recent study examining the planning of intentionally curved reaches (Wong et al. , 2016). In this study, the RTs of simple point-to-point reaches were observed to be shorter than those of more complex curved movements, consistent with the idea that RT reflects computation time. However, when point-to-point movements were interleaved among curved reaches, the RTs of those point-to-point reaches were surprisingly prolonged by ~90 ms, matching the RTs of the curved reaches. A similar contextual effect has been observed during mental rotation: during a letter discrimination task, identifying letters that were presented upright occurred at much shorter RTs when all the letters were upright compared to when other letters in the same block of trials were rotated (Ilan and Miller, 1994). These data suggest that RTs might be subject to experience-dependent biases – akin to other movement parameters such as speed or direction (Diedrichsen et al. , 2010; Verstynen and Sabes, 2011; Hammerbeck et al. , 2014; Huang et al. , 2011) – rather than arising strictly from the outcome of computational requirements. That is, RTs may be subject to habit in the sense that an RT of a given magnitude may become more likely to be generated in the future simply because it has been generated in the past, regardless of current task requirements. Here we present results from two experiments which demonstrate that the RT is subject to experience-dependent effects. In the first experiment – a target-interception task –","Often, we need to make split-second decisions, be it to avoid an accident, outwit someone in an argument or to win a game. The time that it takes to respond to a signal, i. e. , the reaction time, might be the crucial factor to help us succeed or even survive. Many people assume that the reaction time represents the time needed to prepare an action, and to respond sooner one must ‘think faster’. However, what really happens in the brain is not well understood. While more complex tasks seem to require longer reaction times, recent evidence suggests that determining when an action begins may not depend on how long it takes to decide which specific action should be taken. Indeed, reaction times may be shortened without changing",380,128,0.3368
pubmed-summarization,"oregon . a study - specific certificate of confidentiality was also obtained to protect the study findings from forced disclosure of identifiable information . detailed information on the development of the test set is published elsewhere ( 9 ) . briefly , test set cases were identified from biopsy specimens obtained from mammography registries with linkages to breast pathology and/or tumor registries in vermont and new hampshire ( 10 ) . samples were chosen from cases biopsied between january 1 , 2000 and december 31 , 2007 . a consensus process was undertaken by three experienced breast pathologists to come to a final reference diagnosis for each case in the test set , which is described elsewhere ( 12 ) . using a random stratified approach , patient cases were assigned into one of four test sets , which contained 60 cases each ( 240 total unique cases ) and represented the following diagnostic categories : benign without atypia ( 30% ) , atypia ( 30% ) , ductal carcinoma in situ ( 30% ) and invasive cancer ( 10% ) . this distribution resulted in an oversampling of more atypia and ductal carcinoma in situ cases , which would help quantify the diagnostic challenges to be included in the educational intervention . pathologists were recruited to participate from eight geographically diverse states ( ak , me , mn , nm , nh , or , wa , vt ) via email , telephone , and street mail . all practicing pathologists in these states were invited to participate . to be eligible for participation , pathologists interpret breast biopsies as part of their practice , have been signing out breast biopsies for at least one year post residency or fellowship , and intend to continue interpreting breast biopsies for at least one year post enrollment . all participating physicians completed a brief 10-minute survey that assessed their demographic characteristics ( age , sex ) , training and clinical experiences ( fellowship , case load , interpretive volume , years interpreting , academic affiliations ) , and perceptions of how challenging breast pathology is to interpret . two hundred and fifty - two pathologists of 389 eligible participants ( 65% ) agreed to take part in the study . among","we examined how pathologists process their perceptions of how their interpretations on diagnoses for breast pathology cases agree with a reference standard . to accomplish this , we created an individualized self - directed continuing medical education program that showed pathologists interpreting breast specimens how their interpretations on a test set compared to a reference diagnosis developed by a consensus panel of experienced breast pathologists . after interpreting a test set of 60 cases , 92 participating pathologists were asked to estimate how their interpretations compared to the standard for benign without atypia , atypia , ductal carcinoma in situ and invasive cancer . we then asked pathologists their thoughts about learning about differences in their perceptions compared to actual agreement . overall , participants tended to overestimate",380,128,0.3368
scientific_lay_summarisation-elife-norm,"have enabled analysis of the neural crest GRN at a global level, helping to clarify lineage trajectories and elucidate key biological processes therein, ranging from proliferation to differentiation (Williams et al. , 2019). These approaches have opened the way to extensive functional analysis of important nodes within the GRN, particularly at early stages of neural crest development, which are less well-studied. Neural crest formation begins at the gastrula stage, with establishment of the presumptive neural ectoderm bordering the non-neural ectoderm. Quantitative gene expression analysis of gastrula stage chick embryos has revealed a surprisingly high degree of overlap of multiple transcription factors associated with diverse cell types within single cells in the early neural plate border region, ranging from markers characteristic of the neural crest (Pax7), to neural (Sox2) and placodal (Six1) cell types (Roellig et al. , 2017). This is consistent with the possibility that cells in the neural plate border are transcriptionally primed toward multiple cell fates, rather than committed to a particular lineage. What then leads to cell lineage commitment and specification toward neural crest rather than alternative fates, and to their subsequent ability to initiate migration from the neural tube? One possibility is that previously unidentified transcriptional and epigenetic regulators play a critical role in these processes. In this study, we used scRNA-seq to identify novel transcription factors and chromatin remodelers expressed in neural crest cells of the early chick embryo. We first describe the single-cell transcriptome of early migrating neural crest cells emerging from the hindbrain, with a focus on identifying new transcriptional regulators. One of the genes uncovered in the neural crest cluster was Hmga1, a non-histone chromatin remodeler that has known roles in tumor metastasis (Resar et al. , 2018), but has been understudied in development. We first characterized the expression and function of Hmga1 during neural crest development using in situ Hybridization Chain Reaction (HCR) and observed Hmga1 transcripts enriched in the neural crest, with the onset of expression preceding neural crest specification in the neural plate border. To test its functional role in neural crest development, we used plasmid- and protein-based CRISPR-Cas9 strategies to knock out Hmga1 in neural crest progenitors with temporal precision. The results demonstrate an early role for Hmga1 in neural crest lineage specification in a Pax7-dependent manner, resulting","The neural plate is a structure that serves as the basis for the brain and central nervous system during the development of animals with a backbone. In particular, the tissues at the border of the neural plate become the neural crest, a group of highly mobile cells that can specialize to form nerves and parts of the face. The exact molecular mechanisms that allow the crest to emerge are still unknown. The protein Hmga1 alters how genes are packaged and organized inside cells, which in turn influences how genes are switched on and off. Here, Gandhi et al. studied how Hmga1 helps to shape the neural crest in developing chicken embryos. To do so, they harnessed a genetic tool called CRISPR-Cas9, and deleted the gene that encodes Hmga1",380,128,0.3368
scientific_lay_summarisation-elife-norm,"orthologue of the Ras GTPase activating protein (RasGAP) Neurofibromin (NF1), a tumour suppressor that is mutated in the genetic disorder Neurofibromatosis type 1 (Xu et al. , 1990), is a key regulator of both macropinocytosis and phagocytosis. To generate fresh axenic strains for sequencing, we cultured wildtype D. discoideum cells in HL5 growth medium after washing them free of food bacteria. This medium supports the growth of axenic strains such as Ax2 and AX4, but wildtype cells arrest their growth and ultimately die. In order to minimize the number of irrelevant background mutations we avoided mutagenesis and found that spontaneous mutants that are able to grow and proliferate arise frequently among these growth-arrested populations. We selected several independent mutants and sequenced the genomes of three after clonal isolation, along with that of the parental DdB strain, which was chosen because it was also parent to the established axenic laboratory strains (Bloomfield et al. , 2008). At first, other than two large duplications that do not correlate with axenicity (— 1), we could only identify one mutation affecting coding sequence in any of these strains relative to their parent, a seven basepair deletion in strain HM559 (Table 1). We noted that the reference genome sequence (Eichinger et al. , 2005), derived from the axenic mutant strain AX4, also differs from its parent DdB in the same gene model (annotated as DDB_G0279251). Further analysis demonstrated that AX4 has lost almost nine kilobases of this region on chromosome 3, resulting in the deletion of most of the coding sequence of a large gene encoding a homologue of the Ras GTPase-activating protein (RasGAP) Neurofibromin (NF1), as well as part of the upstream gene (1A), with a short segment of extraneous sequence inserted. The 7 bp deletion mutation in HM559 lies within the C-terminal region of this NF1 homologue, and we found that another established axenic mutant, Ax2, has exactly the same deletion-insertion mutation as AX4 (— 2; Table 1). 10. 7554/eLife. 04940. 003Table 1. Mutations in the axeB gene in Dictyostelium discoideum axenic mutantsDOI: http: //dx. . org/10. 7554/eLife. 04940. 003StrainMutationEffect on Dd NF1 proteinPosition in human NF1 proteinAx2c. -1954_6926delinsCM000150. 2: 1390060_1390808Deletion to amino acid 2309to 2358AX4c. -1954_6926delinsCM000150. 2: 1390060_1390808Deletion to amino acid 2309to 2358HM557c. 226_230delDeletion, frameshift66HM587c. 1015A > TNonsense315HM591c. 3033_3040delDeletion, frameshift∼1060 (in insertion","Dictyostelium amoebae are microbes that feed on bacteria living in the soil. They are unusual in that the amoebae can survive and grow in a single-celled form, but when food is scarce, many individual cells can gather together to form a simple multicellular organism. To feed on bacteria, the amoebae use a process called phagocytosis, which starts with the membrane that surrounds the cell growing outwards to completely surround the bacteria. This leads to the bacteria entering the amoeba within a membrane compartment called a vesicle, where they are broken down into small molecules by enzymes. The cells can also take up fluids and dissolved molecules using a similar process called macropinocytosis. With its short and relatively simple lifestyle, Dictyostelium is often used in research to study phagocytosis,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Protein–protein interactions are fundamental to many biological processes. Experimental screens have identified tens of thousands of interactions, and structural biology has provided detailed functional insight for select 3D protein complexes. An alternative rich source of information about protein interactions is the evolutionary sequence record. Building on earlier work, we show that analysis of correlated evolutionary sequence changes across proteins identifies residues that are close in space with sufficient accuracy to determine the three-dimensional structure of the protein complexes. We evaluate prediction performance in blinded tests on 76 complexes of known 3D structure, predict protein–protein contacts in 32 complexes of unknown structure, and demonstrate how evolutionary couplings can be used to distinguish between interacting and non-interacting protein pairs in a large complex. With the current growth of sequences, we expect that the method can be generalized to genome-wide elucidation of protein–protein interaction networks and used for interaction predictions at residue resolution. A large part of biological research is concerned with the identity, dynamics, and specificity of protein interactions. There have been impressive advances in the three-dimensional (3D) structure determination of protein complexes which has been significantly extended by homology-inferred 3D models (Mosca et al. , 2012; Webb et al. , 2014) (Hart et al. , 2006; Zhang et al. , 2012). However, there is still little, or no, 3D information for ∼80% of the currently known protein interactions in bacteria, yeast, or human, amounting to at least ∼30,000/∼6000 incompletely characterized interactions in human and Escherichia coli, respectively (Mosca et al. , 2012; Rajagopala et al. , 2014). With the rapid rise in our knowledge of genetic variation at the sequence level, there is an increased interest in linking sequence changes to changes in molecular interactions, but current experimental methods cannot match the increase in the demand for residue-level information of these interactions. One way to address the knowledge gap of protein interactions has been the use of hybrid, computational–experimental approaches that typically combine 3D structural information at varying resolutions, homology models, and other methods (de Juan et al. , 2013), with force field-based approaches such as RosettaDock, residue cross-linking, and data-driven approaches that incorporate various sources of biological information (Kortemme and Baker, 2002; Dominguez et al. , 2003; Kortemme and Baker, 2004; Kortemme et al. , 2004; Svensson et al. ,","DNA is often referred to as the ‘blueprint of life’, as this molecule contains the instructions that are required to build a living organism from a single cell. But these instructions largely play out through the proteins that DNA encodes; and most proteins do not work alone. Instead they come together in different combinations, or complexes, and a single protein may participate in many complexes with different activities. Proteins are so small that it is difficult to get clear information about what they look like. Visualizing protein complexes is even harder. Most protein–protein interactions remain poorly understood, even in the best-studied organisms such as humans, yeast, and bacteria. Proteins are made from smaller molecules, called amino acids, strung together one after the other. The order in which different",380,128,0.3368
scientific_lay_summarisation-elife-norm,"As superfamily 2 (SF2) -type translocases, chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA. Yet how they move DNA around the histone core has not been clear. Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleosomal DNA at superhelix location 2 (SHL2). Using canonical and variant 601 nucleosomes, we find that the Saccharomyces cerevisiae Chd1 remodeler decreased DNA twist at SHL2 in nucleotide-free and ADP-bound states, and increased twist with transition state analogs. These differences in DNA twist allow the open state of the ATPase to pull in ~1 base pair (bp) by stabilizing a small DNA bulge, and closure of the ATPase to shift the DNA bulge toward the dyad. We propose that such formation and elimination of twist defects underlie the mechanism of nucleosome sliding by CHD-, ISWI-, and SWI/SNF-type remodelers. Chromatin remodelers are members of the extensive superfamily 2 (SF2) group of ATPase motors found in all kingdoms of life (Flaus and Owen-Hughes, 2001; Flaus et al. , 2006). SF2 ATPases possess a bi-lobed architecture, with a central ATP-binding pocket defined by two RecA-like domains (reviewed in Singleton et al. , 2007). The occupancy of the central pocket – whether empty, ADP-bound or ATP-bound – determines the preferred conformation for the two lobes of the motor. Like the architecturally similar SF1 ATPases, both lobes of the motor coordinate in binding to DNA or RNA, with conformational changes driven by cycles of ATP binding and hydrolysis enabling many SF2 enzymes to translocate in an inchworm fashion along nucleic acids (Singleton et al. , 2007). Chromatin remodelers are specialized for altering the organization of DNA on the nucleosome. Canonical nucleosomes consist of two copies each of the four core histones (H2A, H2B, H3, and H4) wrapped by ~146 base pairs (bp) of duplex DNA (reviewed in McGinty and Tan, 2015). Several chromatin remodelers have been shown to ratchet DNA past the histone core in single bp steps, known as nucleosome sliding, which is consistent with the basic inchworm mechanism of DNA translocation (Deindl et al. , 2013; Harada et al. , 2016). One of the earliest models for nucleosome motion suggested that DNA could be shifted past the histone core by","DNA is shaped like a spiral staircase, twisting around itself to create a double helix. This results in a long string-like molecule that needs to be carefully packaged to fit inside the cells of organisms as diverse as fungi or humans. This packaging process starts when a portion of DNA tightly wraps around a spool-like core of proteins called histones. The resulting structure is known as a nucleosome. Like the beads on a necklace, nucleosomes exist at regular intervals along DNA. The DNA sequence around the histones cannot be accessed by a cell, and so the nucleosomes need to be ‘shifted’ along DNA to free up the genetic information. Enzymes known as chromatin remodelers perform this role by binding to a nucleosome, and then using energy to fuel",380,128,0.3368
dialogsum,"#Person1#: Hey, you. Can't you be a bit faster? You make the whole group wait for you. #Person2#: How can you blame it on me? I'm having trouble in operating this kind of machine. It is designed for you right handers. #Person1#: You always complain about these machines. But you are not the only one using your left hand. #Person2#: Really? I don't know any others who are the same as me. #Person1#: To tell you the truth, I'm also left-handed. #Person2#: You? #Person1#: Yeah. You should spend some time getting suited to it in advance. Then you can do it quickly. #Person2#: Is that what you have done? #Person1#: Yes. In fact, it pays to use both hands. #Person2#: OK, I will try.",#Person2#'s left-handed and works slowly. #Person1# tells #Person2# #Person1#'s also left-handed and asks #Person2# to get suited to the work in advance instead of complaining about the machines.,124,28,0.2258
dialogsum,"#Person1#: How may I help you? #Person2#: Hi, I would like to rent a car. #Person1#: Sure, did you make a reservation? #Person2#: No, I decided to rent one when I got off the plane just now, is that OK? #Person1#: Of course. I was just checking, so how many days do you need the car for? #Person2#: Can I just do 4 days for now and make the rent longer through a phone call later? #Person1#: In that case, I suggest you go for 7 days, which will give you a 20% discount and if you choose to return the car after 5 days, you can get the rest of your money back. #Person2#: OK, I will do that. Can I return the car at the train station? #Person1#: Yes, you can.",#Person2# rents a car for 7 days with #Person1#'s suggestions.,133,10,0.0752
dialogsum,"#Person1#: Good morning, can I help you? #Person2#: Yes, I'd like to know something about the weather in Arizona in the coming week. #Person1#: Well, it will be fairly hot and there will be much rain. #Person2#: I see. Thanks very much for your help.",#Person2# tells #Person1# the weather in Arizona in the next week.,45,11,0.2444
dialogsum,"#Person1#: I need to buy some fruit. #Person2#: All the fruit are pretty fresh here. #Person1#: How much are the pears? #Person2#: They're four yuan per kilo. #Person1#: Give me one kilo of those, please. Do you have any fresh plums? #Person2#: Yes, we do. They are eight yuan per kilo. #Person1#: It's a bit too expensive. We can get it for six yuan in the shop next here. #Person2#: Take much and you can have them six yuan per kilo. #Person1#: Sounds reasonable. I'll take three kilos. #Person2#: OK. It's 22 yuan #Person1#: Here you are.",#Person1# buys some pears and plums in #Person2#'s store after #Person2# agrees to give a discount.,97,16,0.1649
scientific_lay_summarisation-elife-norm,"The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response of T cells to foreign antigens. Signal transduction by the T cell receptor (TCR) triggers the activation of three non-receptor tyrosine kinases: Lck, ZAP-70, and Itk (Smith-Garvin et al. , 2009; Weiss and Littman, 1994). A notable feature of this pathway is a strict hierarchy in kinase activation, which is accompanied by highly specific phosphorylation of substrates by each kinase (). T cells must mount a strong and sustained response upon encountering a foreign peptide antigen bound to a major histocompatibility complex (MHC) molecule on an antigen-presenting cell, without launching an immune reaction against self-antigens. The origin of this selectivity is not well understood, and it cannot be explained by the modest differences in affinities between self and foreign peptide antigens for the T cell receptor (Palmer and Naeher, 2009). The pattern of tyrosine kinase activity downstream of the T cell receptor is implicated in a kinetic proofreading mechanism that has been posited to underlie the fidelity of the T cell response (Chakraborty and Weiss, 2014; McKeithan, 1995). In such a mechanism, complexes formed between the T cell receptor and antigens must be sufficiently long-lived to propagate a biochemical signal through the sequential steps of kinase activation and substrate phosphorylation within the T cell. 10. 7554/eLife. 20105. 003Figure 1. T cell receptor-proximal signaling. (A) Initiating events in T cell receptor signaling (based on Au-Yeung et al. , 2009). (B) Ordered kinase activation and substrate phosphorylation by","A class of enzymes known as tyrosine kinases relay signals in cells by adding phosphate groups onto specific sites (called' tyrosine residues' ) in other proteins. Most tyrosine kinases can phosphorylate many targets (or' substrates' ); they can also phosphorylate and thereby activate themselves, when given the right signal. Many tyrosine kinases select their substrates on the basis of their location; once recruited to and activated at a specific site, these enzymes will typically phosphorylate many nearby proteins. A tyrosine kinase called ZAP-70 is found in immune cells known as T cells. ZAP-70 works together with another kinase called Lck to activate T cells, which enables the cells to mount an immune response when they encounter foreign molecules. This pathway is precisely controlled, with Lck activated first, followed",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Although many high-risk mucosal and cutaneous human papillomaviruses (HPVs) theoretically have the potential to synthesize L1 isoforms differing in length, previous seroepidemiological studies only focused on the short L1 variants, co-assembling with L2 to infectious virions. Using the multimammate mouse Mastomys coucha as preclinical model, this is the first study demonstrating seroconversion against different L1 isoforms during the natural course of papillomavirus infection. Intriguingly, positivity with the cutaneous MnPV was accompanied by a strong seroresponse against a longer L1 isoform, but to our surprise, the raised antibodies were non-neutralizing. Only after a delay of around 4 months, protecting antibodies against the short L1 appeared, enabling the virus to successfully establish an infection. This argues for a novel humoral immune escape mechanism that may also have important implications on the interpretation of epidemiological data in terms of seropositivity and protection of PV infections in general. Human Papillomaviruses (HPVs) are widely distributed in nature and more than 220 types were sequenced up to date (PaVE: Papillomavirus Episteme). They cannot only be divided in mucosal and cutaneous types (Bzhalava et al. , 2013), but also whether the infection is acquired, for example via sexual intercourse (as for high-risk genital HPVs) (Gravitt and Winer, 2017) or whether a commensal cohabitation (as for cutaneous HPVs) occurred shortly after birth (Antonsson et al. , 2003; Weissenborn et al. , 2009). Depending on environmental factors (e. g. chronic UV exposure) (Rollison et al. , 2019; Uberoi et al. , 2016), the individual immune status (e. g. systemic immunosuppression) (Reusser et al. , 2015; Vinzón and Rösl, 2015) or genetic predispositions (e. g. EVER1/2 mutations in Epidermodysplasia verruciformis patients) (de Jong et al. , 2018), commensal cutaneous papillomaviruses can induce hyperproliferative lesions (e. g. actinic keratosis) which may progress to squamous cell carcinomas (SCCs) (Hasche et al. , 2018). The African multimammate rodent Mastomys coucha represents a unique model system to investigate the consequences of a natural PV infection in the context of skin carcinogenesis (Hasche and Rösl, 2019). The animals become infected with Mastomys natalensis papillomavirus (MnPV) soon after birth (Schäfer et al. , 2011) and seroconversion against viral proteins can be detected shortly afterwards (Schäfer et al. , 2010). MnPV is a typical cutaneous PV that resembles human β-types by lacking an E5 open-reading frame (ORF)","Cancer is not one disease but rather a collection of disorders. As such there are many reasons why someone may develop cancer during their lifetime, including the individual’s family history, lifestyle and habits. Infections with certain viruses can also lead to cancer and human papillomaviruses are viruses that establish long-term infections that may result in cancers including cervical and anal cancer, and the most common form of cancer worldwide, non-melanoma skin cancer. The human papillomavirus, or HPV for short, is made up of DNA surrounded by a protective shell, which contains many repeats of a protein called L1. These L1 proteins stick to the surfaces of human cells, allowing the virus to get access inside, where it can replicate before spreading to new cells. The immune system responds",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Decision-making behavior is often characterized by substantial variability, but its source remains unclear. We developed a visual accumulation of evidence task designed to quantify sources of noise and to be performed during voluntary head restraint, enabling cellular resolution imaging in future studies. Rats accumulated discrete numbers of flashes presented to the left and right visual hemifields and indicated the side that had the greater number of flashes. Using a signal-detection theory-based model, we found that the standard deviation in their internal estimate of flash number scaled linearly with the number of flashes. This indicates a major source of noise that, surprisingly, is not consistent with the widely used' drift-diffusion modeling' (DDM) approach but is instead closely related to proposed models of numerical cognition and counting. We speculate that this form of noise could be important in accumulation of evidence tasks generally. Subjects performing perceptual decision-making tasks display a large amount of trial-to-trial behavioral variability. Determining the sources of this variability could provide insight into the neural mechanisms of decision-making and produce more accurate predictions of behavior. It has been proposed that behavioral variability is caused in part by noise accruing during the process of evidence accumulation. This noise may have a variety of origins depending on the behavioral task. It can be inherent in the natural world, produced by the signal detection limits of sensory organs themselves (Barlow and Levick, 1969), or it may reflect the variability of neural responses in the brain at different stages of processing. Previous studies have attempted to trace the sources of noise using a combination of behavioral and neurophysiological approaches. At the behavioral level, many models of the evidence accumulation process are known as ‘drift-diffusion’ models (DDMs), because a major component of the noise is modeled as diffusion noise in the accumulator, i. e. , noise that is independent for each time point (Bogacz et al. , 2006; Smith and Ratcliff, 2004, but see Zariwala et al. , 2013). A recent study by Brunton and colleagues (Brunton et al. , 2013) developed an accumulation of evidence task, which they modeled with a DDM-like process, to isolate different sources of noise. In their task, evidence was delivered in randomly timed but precisely known pulses: two randomly generated streams of discrete auditory clicks were presented from","Perceptual decision-making, i. e. making choices based on observed evidence, is rarely perfect. Humans and other animals tend to respond correctly on some trials and incorrectly on others. For over a century, this variability has been used to study the basis of decision-making. Most behavioral models assume that random fluctuations or' noise' in the decision-making process is the primary source of variability and errors. However, the nature of this noise is unclear and the subject of intense scrutiny. To investigate the sources of the behavioral variability during decision-making, Scott, Constantinople et al. trained rats to perform a visual' accumulation of evidence' task. The animals counted flashes of light that appeared on either their left or their right. Up to 15 flashes occurred on each side, in a random",380,128,0.3368
dialogsum,"#Person1#: Well, the salad's almost ready. How's the beef going? I'm starving. #Person2#: So am I. The beef looks just about ready. Just one minute ... ow! #Person1#: What's the matter? #Person2#: Oh, my finger, I burned my finger! #Person1#: Oh, wait, I'll get some ice and put it on your finger. #Person2#: OK. #Person1#: There. #Person2#: Ah, ah, much better. The ice really works. #Person1#: How does it feel? #Person2#: Oh, I feel good. Thanks. Let's eat.","#Person2# burned #Person2#'s finger when preparing the beef, and #Person1# puts some ice on #Person2#'s finger.",78,16,0.2051
pubmed-summarization,"gold glucometer with glucose reagent strips using the finger prick method . saliva samples were collected in the morning between 9 am and 12 pm . before collecting the saliva samples , they were asked to spit into the graduated disposable collecting cup at the end of every minute for 5 minutes and the average was calculated to estimate the unstimulated whole salivary flow rate . salivary ph was estimated by placing the gc saliva ph strip for 10 seconds in the saliva sample , which was then removed and matched with the color - coded table provided along with the kit . pipettes provided along with the kit were used to draw saliva sample from the collecting cup and 3 drops added over the 3 slots of the strips . after 2 minutes , the color change was matched with the color - coded table scores provided by the manufacturer . decayed missing filled teeth ( dmft ) index was recorded to assess the status of teeth . using a micropipette , 10 l of saliva was drawn from the disposable collecting cup and added into a cuvette to which 1000 l of glucose oxidase peroxidase enzyme reagent was added ; the sample was then incubated at 37c for 10 minutes . similarly , 10 l of standard glucose solution was drawn into a cuvette to which 1000 l of enzyme reagent was added , and the sample was incubated at 37c for 10 minutes . the optical absorbance readings were recorded using the digital photocolorimeter using the green filter with a peak of 540 nm wavelength [ ] . armamentarium used to assess unstimulated whole salivary glucose uwsg was calculated using the formula : salivary glucose in mg / dl = absorbance of sample concentration of standard / absorbance of standard concentration of the standard glucose was 100 mg / dl statistical analysis was done using contingency coefficient analysis , independent samples t - test , multivariate analysis of variance ( manova ) , and correlations using pearson coefficient . the statistical package for the social sciences ( spss ) for windows ( spss , version 16.0 , chicago , spss inc . ) was used for statistical analysis . sixty patients previously diagnosed with type 2 dm","aims and objectives : the purpose of this study was to estimate and assess any correlation between random capillary blood glucose ( rcbg ) and unstimulated whole salivary glucose ( uwsg ) , as well as to estimate various salivary parameters , such as flow rate , ph , buffering capacity , and the influence of these factors on the oral health status in type 2 diabetes mellitus ( dm).materials and methods : sixty individuals suffering from type 2 dm and 40 healthy individuals in the age group of 3060 years were included in the study . rcbg was estimated using glucometer and uwsg was estimated using photocolorimeter . salivary parameters such as flow rate , ph , and buffering capacity were assessed using gc saliva kit .",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and maternofoetal transmission, laboratory contamination, transmission through transfusion) (Musso and Gubler, 2016). The most common clinical manifestations include rash, fever, arthralgia, and conjunctivitis (Musso and Gubler, 2016) but a large proportion of infections are asymptomatic or trigger mild symptoms that can remain unnoticed. Nevertheless, the virus may be involved in many severe neurological complications, including Guillain-Barre syndrome (Cao-Lormeau et al. , 2016) and microcephaly in newborns (Schuler-Faccini et al. , 2015). These complications and the impressive speed of its geographically propagation make the Zika pandemic a public health threat (Who, 2016). This reinforces the urgent need to characterize the different facets of virus transmission and to evaluate its dispersal capacity. We address this here by estimating the key parameters of ZIKV transmission, including the basic reproduction number (R0), based on previous epidemics in the Pacific islands. Defined as the average number of secondary cases caused by one typical infected individual in an entirely susceptible population, the basic reproduction number (R0) is a central parameter in epidemiology used to quantify the magnitude of ongoing outbreaks and it provides insight when designing control interventions (Diekmann et al. , 2010). It is nevertheless complex to estimate (Diekmann et al. , 2010; van den Driessche and Watmough, 2002), and therefore, care must be taken when extrapolating the results obtained in a specific setting, using a specific mathematical model. In the present study, we explore the variability of R0 using two models in several settings that had Zika epidemics in different years and that vary in population size (Yap, Micronesia 2007, Tahiti and Moorea, French Polynesia 2013–2014, and New Caledonia 2014). These three countries were successively affected by the virus, resulting in the first significant human outbreaks and they differ in several ways, including population size and location specific features. Hence, the comparison of their parameter estimates can be highly informative on the intrinsic variability of R0. For each setting, we compare two compartmental models using different parameters defining the mosquito populations. Both models are considered in a stochastic framework, a necessary layer of complexity given the small population size and recent Bayesian inference techniques (Andrieu et al. , 2010) are used for parameter estimation. We use mathematical transmission models and data from surveillance systems and seroprevalence surveys for several ZIKV outbreaks in Pacific islands","Zika virus is an infectious disease primarily transmitted between people by mosquitoes. While most people develop mild flu-like symptoms, infection during pregnancy can interfere with how the baby’s head and brain develop. Until recently, the virus had only been seen sporadically in Africa and Asia, but since 2007, outbreaks have been recorded on several Pacific islands. In 2015, the Zika virus reached the Americas, and within six months over 1. 5 million cases had been reported in Brazil alone. There is an urgent need to understand how the Zika virus moves within a population in order to help policymakers, and public health professionals, plan treatment and control of outbreaks of the disease. Researchers often use predictive models to estimate how a disease will spread. A parameter commonly calculated",380,128,0.3368
pubmed-summarization,"the small sizes of the nanoparticles and large surface to volume ratio put the nanoparticles in a position for tremendous and wide applications essentially in biomedicine . though the small sizes of engineered nanoparticles have been linked with highly desirable properties ( mechanical , electrical , and chemical ) for specific uses , yet these same desirable properties are also likely to be associated with unwanted biological / toxicological reactivity . although metal nanoparticles have received increasing attention due to their widespread medical , consumer , industrial , and military applications , studies have correlated particle size of some metal - based nanoparticles ( e.g. , ag , au , and cu ) with toxicity , even if the same material is relatively inert in its bulk form . indeed , there are increasing concerns about the safety of nanoparticles for human health and environment , highlighting the need for further investigations on the safety of metal nanoparticles . moreover , data on the safety / toxicity profiles of metal nanoparticles are scarce . perhaps , the fears of health risks may not be completely unfounded , if the small sizes and the large surface area to volume ratio as well as the chemical reactivity and/or biological activity of the nanoparticles are to be considered . also there are studies revealing the potential of nanoparticles to alter normal physiology by interacting with biomolecules in living cells thereby causing adverse effects at the cellular , subcellular , and protein levels . furthermore , nanoparticles enter the human body through ingestion , inhalation , and skin contact or genitourinary tract and become deposited in vital organs such as brain , liver , or kidneys . studies have shown that nanoparticles may change or damage cellular processes by passing through cellular membranes to interact with biomolecules leading to dna and protein damage or cross the blood - brain barrier to cause neurotoxicity . these factors underscore the urgent need for investigations aimed at establishing the influence of nanoparticles on biochemical parameters . the present study determined the effect of the oral administration of silver nanoparticle on some biochemical parameters in wistar rats . alanine aminotransferase ( alt ) , aspartate aminotransferase ( ast ) , and alkaline phosphatase ( alp ) assay kits","background . silver nanoparticles have found wider and increasing biomedical applications due to their broad antimicrobial characteristics . however , toxicity of nanoparticles is a subject of continued controversy , thus necessitating further studies in this direction . objectives . this study investigated the biochemical effects of silver nanoparticles in wistar rats . materials and methods . forty male rats were randomly distributed into eight experimental groups of five . group a served as the control and received distilled water . groups b to h were orally exposed to varying concentrations of silver nanoparticles ( agnps ) at 100 , 1000 , and 5000 mg / kg daily for 7 , 14 , and 21 days alternately . following cessation of treatments , rats were sacrificed and the",380,128,0.3368
dialogsum,"#Person1#: Jane, what would you do if you were on vacation overseas and lost all your money and credit cards? #Person2#: Well, I guess I'd probably sell my watch and camera... Or I might get a job as a waitress somewhere till I made enough money to buy a plane ticket to return home.",Jane tells #Person1# what she would do if she lost all money and cards abroad.,54,15,0.2778
dialogsum,"#Person1#: I'm free on Sunday. I'd like to take a look in Beijing City, could you tell me where to go? #Person2#: Sure, no problem. I'll ring to have a city tour. on sunday morning we can go to the Great Wall, then we can go to the summer palace in the afternoon. In the evening we can have typical dinner in restaurant in Beijing. Quanjude, a restaurant serving roast ducks. However if you don't like above trips, we can go some famous places outside of Beijing. #Person1#: Any place will be fine. you make the decision. #Person2#: What time shall we start? #Person1#: I will pick you up at your hotel at eight in the morning. #Person2#: Ok, then see you in sunday morning.","#Person1# invites #Person2# to take a look in Beijing City together. #Person2# suggests going to the Great Wall, the summer palace, and Quanjude.",125,23,0.184
dialogsum,"#Person1#: Oh, damn. There ' s another traffic jam on the highway. #Person2#: How can there be a traffic jam on a 16 - lane highway every day? #Person1#: There are just too many people, and too many cars. #Person2#: I wonder if there was an accident. #Person1#: No, they just said it too many people were trying to get off at the Capitol exits. #Person2#: Well, let ' s put on some music. We ' re going to be stuck in this for a while. #Person1#: All right, what do you want to listen to? #Person2#: How about some Beatles? #Person1#: Yeah, all right.",#Person1# and #Person2# encounter a traffic jam. They put on some music because they're going to be stuck for a while.,105,21,0.2
scientific_lay_summarisation-elife-norm,"Hair follicle (HF) development is orchestrated by coordinated signals from adjacent epithelial and mesenchymal cells. In humans this process only occurs during embryogenesis and viable strategies to induce new HFs in adult skin are lacking. Here, we reveal that activation of Hedgehog (Hh) signaling in adjacent epithelial and stromal cells induces new HFs in adult, unwounded dorsal mouse skin. Formation of de novo HFs recapitulated embryonic HF development, and mature follicles produced hair co-occurring with epithelial tumors. In contrast, Hh-pathway activation in epithelial or stromal cells alone resulted in tumor formation or stromal cell condensation respectively, without induction of new HFs. Provocatively, adjacent epithelial-stromal Hh-pathway activation induced de novo HFs also in hairless paw skin, divorced from confounding effects of pre-existing niche signals in haired skin. Altogether, cell-type-specific modulation of a single pathway is sufficient to reactivate embryonic programs in adult tissues, thereby inducing complex epithelial structures even without wounding. The number and pattern of hair follicles (HFs) are specified before birth in humans. In the mouse this is true for most body areas such as back skin (Alonso and Rosenfield, 2003; Millar, 2002; Paus and Cotsarelis, 1999). HF morphogenesis requires Hedgehog (Hh) and Wnt/β-catenin signaling and becomes first morphologically visible at embryonic day 14. 5 (E14. 5) in mice (Chiang et al. , 1999; Gat et al. , 1998; Lo Celso et al. , 2004; St-Jacques et al. , 1998). At this stage, the embryonic hair germ has formed, consisting of an epithelial placode and a dermal condensate, whose epithelial-mesenchymal crosstalk is essential for further HF development (Hardy, 1992; Schmidt-Ullrich and Paus, 2005). De novo HF formation in adult skin has been observed in combination with wounding in rabbits, mice, and humans (Breedis, 1954; Ito et al. , 2007; Kligman and Strauss, 1956; Lim et al. , 2018), and in unwounded skin as a response to forced epithelial Wnt/β-catenin signaling in mice (Gat et al. , 1998; Lo Celso et al. , 2004). Two decades after the initial discovery that Wnt/β-catenin-pathway activation results in ectopic HFs (Gat et al. , 1998), it is still the only known approach to induce de novo HFs in adult unwounded skin. Accordingly, it remains a major clinical challenge to generate replacement skin with hair, urging the search for new ways to achieve HF","We are born with all the hair follicles that we will ever have in our life. These structures are maintained by different types of cells (such as keratinocytes and fibroblasts) that work together to create hair. Follicles form in the embryo thanks to complex molecular signals, which include a molecular cascade known as the Hedgehog signaling pathway. After birth however, these molecular signals are shut down to avoid conflicting messages – inappropriate activation of Hedgehog signaling in adult skin, for instance, leads to tumors. This means that our skin loses the ability to make new hair follicles, and if skin is severely damaged it cannot regrow hair or produce the associated sebaceous glands that keep skin moisturized. Being able to create new hair follicles in adult skin would",380,128,0.3368
pubmed-summarization,"who were unable to stop treatment and therefore needed constant hormone replacement therapy . those patients whose clinical profiles matched both of the following were classified as tch : ( a ) the thyroid imaging examination indicated the location and morphology of the thyroid to be normal and ( b ) the thyroid remained functional for more than 6 months after treatment was stopped and the thyroid function test would continue to be performed monthly . data were analyzed using spss 13.0 , and the relationship between the multiplicity of factors and the results of the second diagnosis were analyzed with multiple logistic regression analysis . a total of 1210 patients ( 659 males and 551 females ) were confirmed as potential ch cases among 930 612 newborns . of these the incidence of ch and hyperthyroxinemia was 60.0/100 000 ( 1/1665 ) and 69.9/100 000 ( 1/1430 ) , respectively , with the total being 120.0/100 000 ( 1/769 ) . in the 1210 confirmed patients , 391 patients ( 32.2% of the total including 331 hyperthyroxinemia patients and 60 patients with congenital hypothyroidism ) were lost to follow - up , and thus 819 patients took part in the study . from december 2009 to december 2013 , 273 patients were followed - up for more than 2 years , and 68 patients were diagnosed with pch , 126 patients were diagnosed with tch , and 78 patients were still under review ( ) . based on screening of the population at the present time , the incidence of pch was 15/100 000 ( 1/6673 ) , the incidence of tch was 29.5/100 000 ( 1/3385 ) , and the ratio of pch to tch is approximately 1:2 . distribution of permanent and transient ch in 273 patients followed - up for more than 2 years . in 194 patients ( 68 with pch and 126 with tch ) with clear diagnosis of the disease , multiple logistic regression analysis was performed . the final diagnosis was considered as the dependent variable ( pch / tch , 0/1 ) , and the gender , gestational age , birth weight , and tsh and ft4 values at screening and diagnosis were considered as independent variables . the results indicate","background . a newborn screening program ( nsp ) for congenital hypothyroidism ( ch ) was carried out in guangxi in order to understand the incidence of ch and the factors interrelated to major types of ch in this region of china . methods . during 2009 to 2013 , data from 930 612 newborns attending nsp in guangxi were collected . patients were classified with either permanent ch ( pch ) or transient ch ( tch ) after 2 years of progressive study . results . a total of 1210 patients were confirmed with ch with an incidence of 1/769 , including 68 pch and 126 tch cases with incidences of 1/6673 and 1/3385 , respectively . the frequency of thyroid stimulating hormone values greater than 5",380,128,0.3368
dialogsum,"#Person1#: Hello. I want to purchase an old music box. #Person2#: We have a good variety. What decade would you like? #Person1#: I was hoping I could find something made in the'20s. #Person2#: There are six on this table. #Person1#: I hope at least one of them has dancing figures. #Person2#: Many people like the dancing figures. Two of our boxes have the figures. #Person1#: So hard to choose. I think I'll take this one. #Person2#: That one will bring you many hours of pleasure. #Person1#: Does a warranty come with this music box? #Person2#: I'm sorry, but if it breaks down, you're on your own. #Person1#: I just thought I would ask. #Person2#: When you buy a Model T, you can't expect a warranty.","#Person1# chooses an old music box with dancing figures from #Person2#, and #Person2# tells #Person1# there is no warranty.",125,19,0.152
dialogsum,"#Person1#: Hey, Wen! Welcome to D. C. ! Glad you came out to visit! #Person2#: Thanks for inviting me. Actually, I've never been anywhere with so many black people before. It's different. #Person1#: Howard is eighty percent black. But there are whites, and even Asians here. Thankfully, it's also coed. #Person2#: Great! Is your, too? #Person1#: Sorry, nope. But the Alpha Phi Alpha's are throwing a party tonight. #Person2#: That's a black fraternity, right? So we should see some dancing!",Wen thinks D.C. is different with so many black people. #Person1# invites Wen to a black fraternity party.,80,18,0.225
pubmed-summarization,"severity of disease of hospitalized patients has increased over the past decade , and advanced techniques have allowed such patients to stay alive . it is well - known that advances in medicine and biomedical technology have created the likelihood for medical treatment to be continued beyond a point , of which it offers no advantage to the patient and may lengthen suffering . it is widely recognized that continued care may not always be advantageous , and this concept has given rise to frequent limitation of life support treatment ( lst ) . the concept of limitation of lst which includes do - not - resuscitate ( dnr ) and withdrawal of lst ( wlst ) has examined medical practices to avoid use of treatment which lengthen the patient 's life and does not improve the patient 's outcomes . in north america and europe , 2865% of all pediatric intensive care unit ( picu ) in contrast to the west , where limitation proceeds up to 90% of deaths ; the rate in india is 2250% , in iran 6.7% , and in saudi arabia 34% . different cultures , religions , philosophic , legal , and professional attitudes may in part explain these differences . in the context of pakistan , the cost of intensive care is high and affordable only by middle - high income groups . . we could not find any published reports from pakistan on patterns of mortality among critically ill children in picu . therefore , our aim was to conduct a retrospective review on mortality patterns over a 6-year period in a picu and to compare the results with published data from other countries . we retrospectively reviewed the medical records for all children aged 1-month to 16 years old admitted in the picu from january 2007 to december 2012 . the picu is a tertiary care private - sector teaching hospital in karachi , the most populous city of pakistan . it is a 4- bedded closed , multidisciplinary , medical - surgical unit with about 350 admissions per year . trends of mortality were categorized into 4 groups : ( 1 ) failed cardiopulmonary resuscitation ( cpr ) , ( 2 ) dnr , ( 3 ) brain death","background and aim : advances in biomedical technology have made medical treatment to be continued beyond a point , at which it does not confer an advantage but may increase the suffering of patients . in such cases , continuation of care may not always be useful , and this has given rise to the concept of limitation of life - sustaining treatment . our aim was to study mortality patterns over a 6-year period in a pediatric intensive care unit ( picu ) in a developing country and to compare the results with published data from other countries.materials and methods : retrospective cohort study was conducted in a picu of a tertiary care hospital in pakistan . data were drawn from the medical records of children aged",380,128,0.3368
dialogsum,"#Person1#: What are you going to have for breakfast? #Person2#: I just have some cereal each morning. #Person1#: You're supposed to always have a hearty breakfast. #Person2#: I don't always have time to make breakfast. #Person1#: It's easy to make a quick breakfast. #Person2#: What do you have for breakfast? #Person1#: When I need to make a quick breakfast, I just make some oatmeal, toast, and OJ. #Person2#: That's a good idea. #Person1#: It's not time consuming at all. #Person2#: It doesn't take much time to make? #Person1#: Would you like me to make something? #Person2#: Why don't you make me some oatmeal and toast?",#Person2# doesn't have time to make breakfast. #Person1# suggests some easy examples and is asked by #Person2# to make some.,105,20,0.1905
dialogsum,"#Person1#: Are you ready to visit grandma in Springfield? #Person2#: Yes. I just have to get the picture that I drew for her. #Person1#: Great. Let's put it in this box, so it stays nice and flat. #Person2#: I used the colored pencils that she got me for my birthday to make it, too! She will be happy about that. #Person1#: Yes, she will. She loves your artwork! I wish I had time to bake a cake. #Person2#: She would have liked that. You are the best baker, Mom.",#Person1# and #Person2# will visit grandma in Springfield. #Person2# brings the picture #Person2# drew for grandma.,89,16,0.1798
pubmed-summarization,"test , chi - square test , mann - whitney u - test , or the fisher exact test , as appropriate . data were analyzed via a repeated - measures analysis of variance with a bonferroni correction . statistical significance was set at 0.05 ( two - sided ) for all of the tests . this study comprised 106 eyes of 104 patients ( 70 males and 34 females ) , with a mean age of 55.4 16.7 years ( range , 20 to 85 years ) . the time between onset of rd ( defined by the onset of early signs and symptoms , including flashes and floaters ) and surgery was 15.4 34.7 days ( range , 4 to 75 days ) . the time of rd evolution was 35.8 26.9 months ( range , 1 to 120 months ) . the mean duration of follow - up was 18.0 8.7 months ( range , 12 to 60 months ) . ten of the eyes ( 9.4% ) have had previous ocular surgery ( an anterior vitrectomy in six eyes , a penetrating keratoplasty in one eye and refractive surgery in two of the eyes ) . cataract surgery was performed on 16 eyes in our hospital and surgery was performed on the remaining 90 eyes in another hospital . there were no sclera tunnel incisions and no iris - fixated or anterior chamber lenses . a superior incision was made in four of the eyes ( 3.8% ) and 60 eyes ( 56.5% ) had a temporal incision . the incisional approach for 42 of these eyes ( 39.6% ) was ill - defined . the location of the iol was in the ciliary sulcus in six eyes , scleral fixation in four eyes , and in the bag in the remaining eyes . univariate analysis did not show any statistically significant differences between the baseline visual acuity and the following variables : gender ; age ; laterality ; the time of rd evolution ; the duration of symptoms ; lower iop ; iol location ; lens capsule status ; identification of a retinal break ; number of retinal breaks ; location of retinal breaks ; and type of surgery . a smaller extension of the",purposeto evaluate the clinical features and surgical outcomes for primary rhegmatogenous retinal detachments ( rds ) in patients with pseudophakia after phacoemulsification.methodsthe medical records of patients with pseudophakia after phacoemulsification and intraocular lens implantation who had undergone surgery for primary rhegmatogenous rds with a minimum duration of follow - up of 12 months were reviewed retrospectively.resultsa total of 104 patients were enrolled in this study and 106 eyes were analyzed . post - operative retinal attachment was achieved in 87 of the eyes ( 82.1% ) and the final visual acuities ( logarithm of the minimum angle of resolution ) were improved to 0.65 0.49 from the baseline measurement of 1.51 1.14 ( p < 0.001 ) . re - operations were performed in 24 of the eyes,380,128,0.3368
scientific_lay_summarisation-elife-norm,"treatment for a neurodevelopmental disorder based on this principle has yet been approved. A second issue with the unidimensionality of the E/I imbalance model is that it lumps together all excitatory and inhibitory neural circuit components. In 1B, we show a schematic diagram of a generic neural circuit with excitatory components colored red and inhibitory components colored blue. The E/I imbalance model implies that varying any of the excitatory components, such as the strength of recurrent excitatory synapses or the input resistances of excitatory neurons, would have the same overall effect on circuit function. In contrast, theorists have found that these equivalences often do not hold even in very simple circuit models (Wilson and Cowan, 1972). Third, because the standard E/I imbalance model is given in terms of circuit components, not circuit function, it does not specify which aspect of a neural circuit’s activity should be maintained for healthy performance. For example, it leaves unclear which of neuronal firing rates, synchrony, or reliability of responses might be altered if E/I balance is upset. To motivate our study, we began by investigating which circuit activity properties are altered in a model brain disorder. We re-analyzed published in vivo two-photon Ca2+ imaging data we previously recorded from somatosensory cortex in Fmr1 knockout mice (Gonçalves et al. , 2013), a well-studied animal model for fragile-X syndrome (The Dutch-Belgian Fragile X Consortium, 1994). We compared the data from wild-type (WT) mice with Fmr1 KO mice, across three different developmental time points: just before (P9–11) and after (P14–16) the critical period for heightened activity-dependent synaptic plasticity in L2/3 barrel cortex, and a more mature timepoint (P30–40). Example ΔF/F raster plots from each group are shown in 1C, top left. We binned the data into 1 s timebins (originally imaged at 4 Hz), then transformed each neuron’s timeseries of ΔF/F values into a probabilistic sequence of binary ON/OFF values by assuming a Poisson firing model (Materials and methods). We then summarized the neural population activity from each animal with three statistics: the mean ON probability across all recorded neurons, the standard deviation (s. d.) in ON probability across neurons, and the mean correlation between all pairs of neurons (1C, bar charts right and scatter plots lower left). Together these measures capture both the statistics of the","In many brain disorders, from autism to schizophrenia, the anatomy of the brain appears remarkably unchanged. This implies that the problem may reside in how neurons communicate with one another. Unfortunately, neuroscientists know little about how brain activity might differ from normal in these disorders, or how specific changes in activity give rise to symptoms. One leading theory, first proposed over a decade ago, is that these disorders reflect an imbalance in the activity of excitatory and inhibitory neurons. Excitatory neurons activate their targets, whereas inhibitory neurons suppress or silence them. While studies in mice have lent support to this theory, they have not yet culminated in new treatments for brain disorders. One limitation of the excitation-inhibition imbalance theory is that it is one-dimensional. It assumes that there",380,128,0.3368
dialogsum,"#Person1#: Hello. This is Hamilton's Heating and cooling service. Can I help you? #Person2#: Yes. My home freezer is not working properly. #Person1#: What's the problem? #Person2#: It keeps running all the time, never stopping. And it makes a strange sound. All the ice cream inside it melted. #Person1#: Maybe the compressor is going bad. #Person2#: Can you send the technician to check it out? #Person1#: Sure. But there is a minimum charge of $ 60 for a service visit. If your freezer needs parts, there will be an additional charge. #Person2#: Okay. I'll pay the charges. #Person1#: All right. let me check our technician's schedules. I'll call you back and let you know what time we can send a service technician to your house. What is your phone number? #Person2#: My number is 627-555-1234. #Person1#: Okay. I'll call you right back. #Person2#: Thank you. Good bye. #Person1#: Bye.",#Person2# phones to have #Person2#'s home freezer checked out. #Person1# agrees to send a service technician and will charge #Person2# for the service visit.,149,24,0.1611
dialogsum,"#Person1#: My doctor says that I need a blood test. #Person2#: I can help you with that. Just have a seat and roll up your left sleeve. #Person1#: What are you taking my blood for? #Person2#: Your doctor has requested a check of your white blood count. #Person1#: What information does that give him? #Person2#: If your white blood cell count is off, it could signal an infection somewhere in your body. #Person1#: Is a blood test painful? #Person2#: I am putting a tourniquet on your arm to plump up the vein. It will only feel like a little pin prick. #Person1#: Oh, my God, that hurts! #Person2#: That was it! Thank you for coming in today.",#Person1# needs to do a blood test and #Person2# helps take #Person1#'s blood to check #Person1#'s white blood count. #Person1# thinks it hurts to take blood.,117,26,0.2222
pubmed-summarization,"personal / patient - centered decision . a study conducted in saudi arabia by aziz1 on 1,046 patients has demonstrated that ramadan fasting itself does not pose a risk to human metabolism or health , but conversely has beneficial health effects on physiological parameters ( eg , an opportunity to lose weight ) and on chronic disease prevention . this study has demonstrated that this goal can be achieved only by optimal pre - ramadan assessment and diabetes education.1 similar observations were reported in other studies as well.68 however , in 2003 , laarijani et al9 demonstrated a slight decrease in fasting serum glucose among healthy subjects during ramadan fasting . a similar finding has also been demonstrated by aziz1 in the ramadan study , with the lowest prevalence of hypoglycemia ( 4.58% ) . contrary to these facts , different studies conducted in the past during ramadan fasting have demonstrated high prevalence of hypoglycemia during ramadan fasting ( up to 21.7%).1018 however , these studies were mostly observational in nature , and patients were not selected before ramadan for extensive diabetes self - management education ( dsme ) , counseling , assessment for hba1c / creatinine , and alteration of therapy . hence in other words , it can be concluded , in general , that blood glucose levels fall during ramadan fasting in diabetic and nondiabetic subjects , and prevention of hypoglycemia with medication adjustments / alterations are the basic strategies to manage diabetes during ramadan fasting . with this literature background , the current review focuses on a class of medications which does not cause hypoglycemia , both in general and during ramadan fasting . one of them is dpp-4 inhibitors , and the drug available in the market is vildagliptin . we will focus on the pathophysiology of type 2 diabetes , dpp-4 inhibitors , and the role of vildagliptin during ramadan fasting . dpp-4 inhibitors are the new oral antidiabetic agents ( including vildagliptin sitagliptin , saxagliptin , linagliptin , alogliptin and other agents as well which are under extensive research ) . these agents / drugs reduce serum glucose concentrations and improve the glycemic control by augmenting the effects of incretins ; hence this strategy is also called incretin based therapy for diabetes management","diabetes management during ramadan fasting is challenging to the physician in terms of minimizing the risk of hypoglycemia . as compared to oral hypoglycemic agents ( ohas ) and sulfonylureas ( sus ) , which carry a higher and significant risk of hypoglycemia , newer antidiabetic agents such as dipeptidyl peptidase-4 ( dpp-4 ) inhibitors have demonstrated lower risk of hypoglycemia during ramadan fasting , with better patient compliance . in addition to diabetes education and pre - ramadan assessments , the physician should also consider use of dpp-4 inhibitors ( such as vildagliptin ) during ramadan fasting to minimize the risk of hypoglycemia in type 2 diabetic subjects . severe episodes of hypoglycemia have been demonstrated in recent research and clinical trials with ohas / sus .",380,128,0.3368
dialogsum,"#Person1#: Hello, excuse me! #Person2#: Hello! Is there anything I can help you with? #Person1#: Yes. I wanna know where I can get on the bus going downtown. #Person2#: Go straight then turn right, and you will see a big bus station there. #Person1#: Ok, I see. Thank you! #Person2#: You are welcome!",#Person2# tells #Person1# how to get to the bus station.,53,10,0.1887
scientific_lay_summarisation-elife-norm,"Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system. Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder, mainly caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2), a protein involved in transcriptional regulation (Amir et al. , 1999; Wan et al. , 1999; Xiang et al. , 2000). RTT patients show regression of head growth followed by various neurological symptoms including seizures, mental retardation, stereotypic hand-wringing movements, breathing irregularities, ataxia and autistic behavior (Rett, 1966). Mouse models with Mecp2 mutations display similar neurological phenotypes, and have been quite critical in defining the pathophysiology of RTT. Mecp2Null/y mice grow normally until 4–6 weeks of age, after which they display RTT-like symptoms such as reduced mobility, hindlimb clasping, abnormal breathing patterns and premature death (Chen et al. , 2001; Guy et al. , 2001). Similarly, mice engineered to express twice the endogenous levels of MeCP2 (Mecp2Tg1) are characterized by seizures, forepaw clasping, hypoactivity, increased aggression, and around 30% die by one year of age (Collins et al. , 2004; Jugloff et al. , 2008; Luikenhuis et al. , 2004). Loss or doubling of MeCP2 in primary mouse hippocampal neurons results in reduction or enhancement of synaptic response respectively, primarily due to the number of glutamatergic synapses formed (Chao et al. , 2007). Furthermore, restoring MeCP2 levels rescued neurological defects associated with loss of MeCP2 the extent of which depends on timing of activation and dynamic variation in MeCP2 levels (Giacometti et","Rett syndrome is a progressive brain disorder. Individuals with the condition (who are typically girls) grow normally until they are 6-18 months old and then developmentally regress, with symptoms including anxiety, impaired coordination, seizures and breathing problems. Rett syndrome is caused by mutations in the gene that encodes a protein called MeCP2. Researchers know that MeCP2 is vital for “excitatory” neurons in the brain to communicate with (and activate) their neighbors. Neurons that lack MeCP2 tend to make fewer of the connections across which they communicate – called synapses – with others. Many researchers who study Rett syndrome use male mice that lack the MeCP2 protein. This mouse model mimics the symptoms seen in Rett patients, but at a faster and more severe rate. These studies have shown",380,128,0.3368
dialogsum,#Person1#: My goodness. She is thirty seconds faster than the world records in five thousand meters race. #Person2#: Excuse me. What did you say? #Person1#: A chinese girl has broken the world record in the Olympic Games #Person2#: That's incredible. I cann't believe it. #Person1#: You have to. It's sure. #Person2#: How amazing!,#Person1# and #Person2# think it is incredible that a Chinese girl has broken the world record.,53,16,0.3019
scientific_lay_summarisation-elife-norm,"secondary metabolites in green tissues of many solanaceous plants, including tobacco (Nicotiana spp.), pepper (Capsicum annuum) and wolfberry (Lycium chinense) (Jassbi et al. , 2006; Lee et al. , 2008; Heiling et al. , 2010). DTGs consist of a 17-hydroxygeranyllinalool aglycone that is decorated at the C3 and C17 hydroxyl positions by glucose, which in turn is modified by glucose, rhamnose and malonyl moieties, in various combinations (1A and — 1). So far, 46 different DTGs (21 chemical formulas and several structural isomers) have been characterized in Nicotiana attenuata, an ecological model plant with a rich portfolio of specialized metabolites; however, the glycoside Lyciumoside IV and its malonylated products, Nicotianoside I and Nicotianoside II, constitute more than 80% of the DTG pool (Poreddy et al. , 2015). In N. attenuata, DTGs function in resistance against the specialist herbivore, tobacco hornworm (Manduca sexta) (Lou and Baldwin, 2003; Jassbi et al. , 2008; Heiling et al. , 2010). The malonylated DTGs are particularly strongly induced by M. sexta feeding and jasmonate signaling (Heiling et al. , 2010). The malonyl moieties of DTGs are lost from the DTGs soon after their ingestion by M. sexta larvae due to the alkaline environment of M. sexta oral secretions and midgut (Poreddy et al. , 2015). This observation rules out a central role for malonylation of DTGs in antiherbivore defense, and suggests that other arenas need to be explored for potential functions mediated by this malonylation. Specialized metabolites are primarily thought to function in mediating an organism’s ecological interactions, to help optimize Darwinian fitness. Many are produced in response to particular ecological interactions, such as those that are induced in response to specific attackers. However, many secondary metabolites have effects on growth and development which are more specific than those that might result from resource trade-offs between growth and putative defense metabolites (Züst and Agrawal, 2017). For example, the insect feeding-induced glucosinolate breakdown product, indole-3-carbinol, arrests growth by interacting with the auxin receptor Transport Inhibitor Response (TIR1) as an auxin antagonist (Katz et al. , 2015). Arabidopsis glucosinolates are also thought to modulate plant biomass, flowering time and the circadian clock, and inhibit root growth (Kerwin et al. , 2011; Jensen et al. , 2015; Francisco et al. , 2016; Malinovsky et al. , 2017). Hyper-accumulation","Plants produce tens of thousands of molecules called secondary metabolites that are thought to help them cope with threats from their environment, such as attack by insects or ultraviolet radiation from the sun. Wild coyote tobacco plants produce large amounts of a particular class of secondary metabolite known as DTGs. Insects feeding on tobacco plants containing DTGs cause less damage and produce fewer offspring Plants modify many secondary metabolites by attaching tags known as malonyl groups to them. Enzymes called malonyl transferases take a malonyl group from another substrate and attach it to the secondary metabolite. This process can be repeated so that an individual secondary metabolite molecule may have many malonyl groups attached to it. Previous studies have shown that insects feeding on tobacco plants trigger more",380,128,0.3368
dialogsum,"#Person1#: How do you shoot pool? #Person2#: You have 16 balls on the table, 7 solid colored, 7 striped colored, a black 8 ball, and the white ball. #Person1#: And? #Person2#: You hit the white ball with your cue. The white ball hits the colored balls. And you want to get the colored balls into the pockets. #Person1#: How do you know whether you should hit the solid or the striped one? #Person2#: At the beginning, it does not matter, but once someone gets one ball in, it is set. #Person1#: Can I get the black ball in? #Person2#: The black ball has to be the final ball in the pockets. #Person1#: Let's go and try now!",#Person2# introduces the rules of shooting pool to #Person1#. And they are going to try now.,117,16,0.1368
scientific_lay_summarisation-elife-norm,"Adam et al. , 2012; Cheng et al. , 2012). The substrates are unfolded and translocated in an ATP-dependent process into a secluded chamber formed by the ATPase and protease domains. Finally, the unfolded substrates inside the chamber can be degraded into small peptide fragments (Gottesman, 2003; Baker and Sauer, 2006). The ATP-dependent translocation process of substrates into the hexameric chamber has been well characterized (Lin et al. , 2016; Su et al. , 2016). Structures of different N-terminal fragments of LonA had been reported (Li et al. , 2005; Duman and Löwe, 2010; Li et al. , 2010; Chen et al. , 2019), including Escherichia coli (EcLon), Mycobacterium avium complex (MacLon), and Bacillus subtilis (BsLon). However, no structural study has been conducted to analyze substrate interactions by the NTD either in isolation or in the context of full-length LonA. Here we address the question of substrate recognition and discrimination by the NTD of LonA using nuclear magnetic resonance (NMR) spectroscopy. To understand how LonA selectively recognizes protein substrates being in damaged states, we have used a thermal stable LonA isolated from Meiothermus taiwanensis (termed MtaLonA henceforth), which allows temperature cycling experiments to be used for switching the populations of protein substrates in the folded and unfolded states. In this work, five various protein substrates have been employed for NMR experiments, which include (1) Ig2 (domains 5 and 6 of the gelation factor from Dictyostelium discoideum [Hsu et al. , 2009], hereafter abbreviated as Ig2) with an immunoglobulin (Ig) fold forming a dimer that is natively folded up to 40°C; (2) α-casein, which is an intrinsically disordered protein with no tertiary structure; (3) native lysozyme with four disulfide bridges and reduced lysozyme forming loose and flexible aggregates; (4) Ig2D5 (domain 5 of the gelation factor from D. discoideum), which is used for characterization of substrate conformation selection by the NTD; and (5) a degron-tagged Ig2D5 designed to identify the residues of degrons that can be recognized and bound by the NTD. Our results show that the presence of MtaLonA NTD is required to degrade damaged proteins and native proteins with degrons, but it does not play an active role in mediating the degradation by LonA of an intrinsically disordered substrate, α-casein. Here we report the crystal structure of an N-terminal","There are many different types of protein which each have different roles in biology. Most proteins are surrounded by water and are folded so that their water-attracting regions are on the outside and more fat-like regions, which repel water, are on the inside. When a protein becomes damaged or is assembled incorrectly, some of the fat-like regions end up on the outside of the protein and become exposed to water. This can prevent the protein from performing its role and harm the cell instead. LonA proteases are responsible for dismantling and recycling these harmful proteins, as well as proteins that have been labelled for destruction. They do this by unfolding the unwanted protein and transporting it into an enclosed chamber made of six LonA molecules. Once inside the",380,128,0.3368
dialogsum,"#Person1#: Miss Wang, would you mind my asking you a personal question? #Person2#: No , not at all. Go ahead. #Person1#: Are you married? #Person2#: Yes. Is that so important? #Person1#: Frankly yes. We like to employ married people. By the way, do you have any children? #Person2#: Yes, I have a three-year-old son.",Miss Wang is married and #Person1# likes employing married people.,54,10,0.1852
pubmed-summarization,"up a decision model , so testing and matching of new sample can follow . what if in a scenario where a handful of unknown voiceprints are collected , but we wish to obtain some information about them ? such scenarios may include but not limited to security surveillance problems where a list of voice traces are captured from a monitored area , how many unique speakers there are , their ages , and genders , and from their speech accents which ethnic backgrounds these people belong to ; customer - service applications where callers will be automatically classified from their tones to categories of their needs and emotions . it was only until recently , voice classification ( vc ) that attempts to determine if a speaker should be classified to a particular characteristic group rather than to a particular individual has gained popularity . vc can help complement the security of vv and vi systems too . in an example of a voice biometric system is being compromised ; through hacking , the content of a voiceprint b is modified to that of another voiceprint ( let us say a ) that has a higher access authority . because the database of the voiceprints just like an encrypted list of passwords in a file system is accessed individually , each voiceprint is protected independently ; allowing the existence of two same voiceprints goes undetected . so an imposter with b can cheat gaining a restricted access right by matching b to a in a vi system . vc could be used to prevent this fraud by checking how many unique items there are in different groups . if extra voiceprints suddenly emerge or have gone missing from a group , the integrities of the voiceprints must have changed . for developing a vc system , several approaches have been studied , such as artificial neural networks ( ann ) , support vector machines ( svms ) , hidden markov models ( hmms ) and gaussian mixture models ( gmms ) . they have been used heavily for training up a model with predefined voice samples for voice recognition . table 1 shows a summary of the techniques by which majority of research works used . these techniques generally","voice biometrics has a long history in biosecurity applications such as verification and identification based on characteristics of the human voice . the other application called voice classification which has its important role in grouping unlabelled voice samples , however , has not been widely studied in research . lately voice classification is found useful in phone monitoring , classifying speakers ' gender , ethnicity and emotion states , and so forth . in this paper , a collection of computational algorithms are proposed to support voice classification ; the algorithms are a combination of hierarchical clustering , dynamic time wrap transform , discrete wavelet transform , and decision tree . the proposed algorithms are relatively more transparent and interpretable than the existing ones , though many techniques",380,128,0.3368
pubmed-summarization,"tennis elbow ( te ) is not an inflammation of the outside portion of the elbow but rather is the degeneration of the extensor tendon of the humeral lateral epicondyle ( le ) due to microscopic injuries . common symptoms include pain , tenderness over the le , pain upon gripping , and dorsiflexion against resistance of the wrist , middle finger , or both1,2,3,4,5 . conservative treatments such as nonsteroidal anti - inflammatory drugs , local steroid injections , strengthening exercises , stretching , taping , ultrasound ( us ) , iontophoresis , laser , acupuncture , and massage are usually used6,7,8,9,10,11 . meanwhile , surgical intervention is required for cases of te when conservative management is deemed ineffective12 . one non - invasive treatment for te - associated pain is extracorporeal shock wave therapy ( eswt ) . although the underlying mechanism of eswt is not completely clear , it likely involves hyperstimulation analgesia ; it alleviates pain as a result of moderate - to - intense sensory input that is usually applied at the site of greatest discomfort . . however , there is a lack of comparative studies of the analgesic effects of various electrotherapy methods on chronic te . therefore , the present study compared the analgesic effects of eswt and us therapy in patients with chronic te . this study was performed in the department of physiotherapy mining in jaworzno , poland . the exclusion criteria were local soft - tissue infection , malignant disease , pacemaker , epileptic disorders , rheumatoid arthritis , diabetes mellitus , neurological abnormalities , infectious diseases , cardiovascular disease , lung or endocrine disease , skin ulcerations , reduced range of motion at the elbow , previous surgical intervention of the te , previous conservative treatment of the te 6 months before start of the study , and history of local corticosteroid injection 6 months before the study . the inclusion criteria were age > 18 years , pain in the lateral epicondyle of the humerus persisting longer than 12 months ( table 1table 1.baseline characteristicscharacteristicseswt groupus grouppatients ( n)2525occupation : physical worker / white - collar worker ( n)19/715/10age ( yr)47.9 4.4 * 49.0 4.5*duration of symptoms ( months)14.9 2.1 * 15.1 1.9*dominant arm ( right /","[ purpose ] this study compared the analgesic effects of extracorporeal shock wave therapy with those of ultrasound therapy in patients with chronic tennis elbow . [ subjects ] fifty patients with tennis elbow were randomized to receive extracorporeal shock wave therapy or ultrasound therapy . [ methods ] the extracorporeal shock wave therapy group received 5 treatments once per week . meanwhile , the ultrasound group received 10 treatments 3 times per week . pain was assessed using the visual analogue scale during grip strength evaluation , palpation of the lateral epicondyle , thomsen test , and chair test . resting pain was also recorded . the scores were recorded and compared within and between groups pre - treatment , immediately post - treatment , and 3",380,128,0.3368
scientific_lay_summarisation-elife-norm,"weak 5HT staining as a joint higher order cortical area complex and have termed it HO-5HT. The 5HTstaining revealed that this region contains the higher order visual areas surrounding V1 (Wang and Burkhalter, 2007), the retrosplenial cortex (RSC) medially, and the ventral posterior temporal cortex laterally. The accurate distribution of staining across cortical layers can only be estimated using tangential sections. However, using P7 sagittal section, we confirmed in layer 4 that the caudal 5HT-positive cortical area (corresponding to V1) and the anteriorly adjacent 5HT-negative area between V1 and S1 (corresponding to HO-5HT) appears larger in ne-Emx2 brains than in wt ones (1B). Next, we labeled TCAs projecting to V1 by filling the dLG with crystals of the lipophilic neuronal tracer DiI. On the P7 sagittal sections that were derived from five different medial to lateral levels, anterograde DiI labeling in the cortex revealed that TCAs from the dLG terminate in a smaller region in wt than in ne-Emx2 brains (— 1). Across genotypes, the DiI staining revealed a sharp border with adjacent cortical tissues that did not receive TCAs input from the dLG (— 1). This finding is consistent with the 5HT staining and indicates a well-defined border between V1 neighboring higher order areas that is anteriorly shifted in ne-Emx2 brains. 10. 7554/eLife. 11416. 003Figure 1. Increased V1 and higher order sensory area sizes in ne-Emx2 cortices (A) Serotonin (5HT) staining on postnatal day (P) 7 tangential sections of the flattened cortex reveals targeting patterns of TCAs revealing primary sensory area borders and the border of the neocortex to the ECT. 5HT staining is not detectable in the region containing the retosplenial cortex and the higher order sensory areas surrounding V1 (HO-5HT). In Emx2-overexpressing brains (ne-Emx2), V1 and HO-5HT appear larger (compare dotted outlines in higher magnification images), compared to wt brains. (B) Targeting of TCAs in cortical layer 4 (L4) was revealed on P7 sagittal cortex sections by 5HT staining, whereas L4 genetic area borders were revealed by in situ hybridization for Rorb. In ne-Emx2 brains, the V1 border shifts anteriorly. Higher order areas surrounding V1 are characterized by low 5HT/Rorb staining (between arrowheads, HO-5HT and HO-Rorb), which in ne-Emx2 brains appear overall larger (compare area between arrowheads). (C) In L5, an expansion (see arrows) of corticotectal projection","The neocortex is the most recently evolved part of the human brain. It is associated with higher thought processes, including language and the processing of information from our senses. Anatomically, the neocortex is organised into different regions called ‘primary areas’ and ‘higher order areas’, and perturbations to this organisation are associated with disorders such as autism. There are many more higher order areas than primary areas in a mammalian brain. But, while primary areas are known to be specified by developmental genes in the embryo, little is known about how the development of higher order areas is controlled. Recent findings suggested that primary areas might themselves influence the emergence of higher order areas via a series of developmental events. Now, Zembrzycki, Stocker et al. have investigated the developmental",380,128,0.3368
pubmed-summarization,"projected population of 3.7 million people based on 2006 census made up of two ethnic groups namely , hausa and fulani . sokoto town , the capital of sokoto state , has a population of approximately 2.5 million . the population is largely rural with farming , cattle rearing , and fishing as the predominant occupations ( > 80% ) . the diagnosis of fracture was based on clinical history , signs and symptoms , visual findings , manual examination , and correct interpretation of plain radiographs . the pattern of facial fracture is determined according to the fractures of mandible , midface , and alveolar bone . fractures of the middle third of the facial skeleton were classified according to the le fort classification . fractures including the base of the skull and frontal bone were not included in the present study . closed reduction and dental wiring with arch bars , direct wires , and eyelet wires combine with mandibulomaxillary fixation ( mmf ) were routine mode of treatment for mandibular fractures . open reduction and internal fixation ( orif ) with intraosseous wire of mandibular fractures were employed when indicated . fractures of the maxillae / le fort fractures were reduced and fixed by eyelets / arch bars combined with mmf and with / without suspension wires . stable zygomatic complex fractures were reduced ( elevated ) intraorally , and unstable ones were supported by antral packs . all patients were placed on oral or intravenous antibiotics for 5 - 7 days except those with established infections who had their antibiotics regimen appropriately extended . data analyses for age , sex , etiology , site of fracture , and treatment given were performed using analyse - it for microsoft excel 2012 . pearson 's chi - square test was used to compare the frequency distribution and statistical significance was set at p 0.05 . there was an overwhelming male dominance in all age groups ( male : female ( m : f ) = 19:1 , odds ratio = 380 ) [ table 1 ] . the most susceptible age group was 21 - 30 years ( 47.5% ) and the least were 0 - 10 years and 51 - 60 years ( 2.5% ) [ ]","background : facial fracture is gradually become a public health problem in our community due to the attendant morbidity and mortality . hence , the aim of this study was to determine the pattern of facial fracture in dental and maxillofacial surgery department of usmanu danfodiyo university teaching hospital . this cross - sectional study was undertaken to provide information regarding gender , age , etiology , and diagnosis of patients with maxillofacial fractures.materials and methods : a 1-year review of patients diagnosed and treated for facial fractures in usmanu danfodiyo university teaching hospital between january 2011 and december 2011 . the diagnosis was based on radiographic data and clinical examination . the main analysis outcome measures were etiology , age , gender , site , and treatment",380,128,0.3368
pubmed-summarization,"for a more complete study we also carried out the effect of solvent on the pes using the polarizable continuum model ( pcm ) . all calculations were performed with the gaussian03w program , running on a pentium iv personal computer . we used restricted and unrestricted b3lyp gradient corrected exchange - correlation functional in combination with the 6 - 311+g * * basis set [ 25 - 27 ] . in our computational investigation , we determined the location of the minima and transition structures of the singlet state surfaces . for equilibrium geometries and transition states , we carried out irc calculations to confirm that the transition stats connect to right minima . zero - point vibrational energy corrections ( zpve ) were estimated at the same theory level at which optimization was carried out and etotal was calculated as eopt ( optimization energy at equilibrium geometry ) + zpve . basis set superposition error ( bsse ) corrections were used to obtain more reasonable total energies in fragmentation reaction ( pathway 3 ) . subsequently , the polarizable continuum model ( pcm ) was applied considering water , ethanol , and cyclohexane as solvents ( = 78.3553 , 24.852 , and 2.0165 , respectively ) . all calculations were performed with the gaussian03w program , running on a pentium iv personal computer . we used restricted and unrestricted b3lyp gradient corrected exchange - correlation functional in combination with the 6 - 311+g * * basis set [ 25 - 27 ] . in our computational investigation , we determined the location of the minima and transition structures of the singlet state surfaces . for equilibrium geometries and transition states , we carried out irc calculations to confirm that the transition stats connect to right minima . zero - point vibrational energy corrections ( zpve ) were estimated at the same theory level at which optimization was carried out and etotal was calculated as eopt ( optimization energy at equilibrium geometry ) + zpve . basis set superposition error ( bsse ) corrections were used to obtain more reasonable total energies in fragmentation reaction ( pathway 3 ) . subsequently , the polarizable continuum model ( pcm ) was applied considering water , ethanol , and cyclohexane as","backgroundchrysanthemic acid ( cha ) is a major product from the photodecomposition of pyrethrin which is an important class of pesticide compounds.in the following paper , hybrid density functional theory ( dft ) calculations of the potential energy surface ( pes ) for three possible channels decomposition of chrysanthemic acid ( cis - trans isomerization , rearrangement and fragmentation ) have been carried at the b3lyp/6 - 311+g * * level of theory . dft was employed to optimize the geometry parameters of the reactants , transition states , intermediates and products based on detailed potential energy surfaces ( pes).resultsour results suggest that all three pathways of cha are endothermic . dft calculations revealed that the activation barriers for cis - trans isomerization are low , leading to",380,128,0.3368
dialogsum,"#Person1#: What dances do you like? #Person2#: I love to dance the fast music. #Person1#: Then you must be interested in disco. #Person2#: Yes, it's my favorite. #Person1#: Oh, it's a disco. Let's dance. #Person2#: You're a good dancer. #Person1#: Thank you. Now they are playing a rumba. Would you have a try? #Person2#: Sorry. I feel like sitting out the next dance. #Person1#: OK. Let's get something to drink. #Person2#: Good idea.","#Person2# likes disco, so #Person1# and #Person2# dance the disco. They decide not to dance the rumba.",73,17,0.2329
dialogsum,"#Person1#: What kind of jobs are becoming popular in your country? #Person2#: As in many countries, there's been a big growth in anything related to computers. Young people are attracted to that field in particular. There's also been a big growth in education. #Person1#: There's been a growth in that field in my country too. A lot of people want to learn practical and professional skills. #Person2#: The interesting thing is that many of the teachers are not actually trained teachers. They are usually professionals who are taking a break from their jobs to pass on skills to others. #Person1#: I noticed that too. What are the people learning? #Person2#: In my country, they are usually studying something business-related, such as marketing, management techniques, and human resource management. #Person1#: I think that jobs in the leisure industry will become more popular in the future. #Person2#: That trend has already begun in my country. In particular, there's a big demand for people to work in fitness centers. Which kinds of jobs are less in demand? #Person1#: Those in traditional fields, such as agriculture and heavy industry. Younger people are not interested in doing those jobs and other countries have industries that can produce things much cheaper. #Person2#: Yes. My country is certainly expanding in the service and hi-tech sectors, but contracting in the heavy industry and primary industry sectors. However, our car and aircraft manufacturers are doing very well. #Person1#: They are well known for high quality, that's why.","There is growth in computers and education in #Person1#'s and #Person2#'s countries. In #Person2#'s country, people usually study business-related things, and service and hi-tech sectors are expanding. #Person1# thinks the leisure industry will become popular and younger people are not interested in traditional fields.",248,44,0.1774
scientific_lay_summarisation-elife-norm,"As the closest unicellular relatives of animals, choanoflagellates serve as useful model organisms for understanding the evolution of animal multicellularity. An important factor in animal evolution was the increasing ocean oxygen levels in the Precambrian, which are thought to have influenced the emergence of complex multicellular life. As a first step in addressing these conditions, we study here the response of the colony-forming choanoflagellate Salpingoeca rosetta to oxygen gradients. Using a microfluidic device that allows spatio-temporal variations in oxygen concentrations, we report the discovery that S. rosetta displays positive aerotaxis. Analysis of the spatial population distributions provides evidence for logarithmic sensing of oxygen, which enhances sensing in low oxygen neighborhoods. Analysis of search strategy models on the experimental colony trajectories finds that choanoflagellate aerotaxis is consistent with stochastic navigation, the statistics of which are captured using an effective continuous version based on classical run-and-tumble chemotaxis. Taxis, the physical migration towards preferred or away from undesired conditions, is a feature shared by virtually all motile organisms. Taxis comes in many forms, and in common is an underlying field of attractant (or repellent) and an ability to react and navigate along gradients of this field. Bacteria do chemotaxis towards nutrients (Adler, 1969; Berg, 1993) and away from toxins (Tso and Adler, 1974). Algae do phototaxis towards light (Yoshimura and Kamiya, 2001; Drescher et al. , 2010) and gyrotaxis along gravitational potentials (Kessler, 1985). Chemotaxis provides a mechanism for the recognition and attraction of gametes (Vogel et al. , 1982) and for complex behavioural patterns such as in the slime mould Dictyostelium discoideum, where cAMP-driven chemotaxis is a critical part of the formation of the multicellular stage of the life cycle (Bonner, 1947). Aerotaxis, defined as oxygen-dependent migration, is well-characterized in bacteria (Taylor et al. , 1999), but is poorly studied in more complex organisms. This is despite the essentiality of oxygen for all aerobic life, and the important role that Precambrian oxygen levels played in the emergence and evolution of multicellular animal life (Nursall, 1959). One group of aquatic heterotrophic protists, the choanoflagellates, are of particular interest for the study of how multicellularity evolved. Choanoflagellates are a class of unicellular microorganisms that are the closest relatives of the animals (Lang et al. , 2002). This relationship was first proposed by James-Clark in","Most animals are made up of millions of cells, yet all animals evolved from ancestors that spent their whole lives as single cells. Today the closest single-celled relatives of animals are a group of aquatic organisms called choanoflagellates. Certain species of choanoflagellates can also form swimming colonies. This kind of multicellularity might resemble that seen in the earliest of animals. As such, studies into modern-day choanoflagellates can give insights into how the first animals to evolve might have behaved. Many organisms can find their way towards favorable areas using different strategies. For instance, bacteria can bias their tumbling to gradually swim towards food, and algae can turn and move directly towards light. While choanoflagellates require oxygen, it was not known if they could also actively navigate towards it,",380,128,0.3368
dialogsum,"#Person1#: Hey. Why did you take that money? You are such a cheater! I should send you to jail! #Person2#: I am not cheating. When you pass go, you collect $ 200, Everyone knows that! #Person1#: Well you can't just take the money. You have to ask the bank for money. And I'm the banker. #Person2#: Banker? #Person1#: Yes. . . #Person2#: Can I have my $ 200 please? #Person1#: Sure. Here you are, $ 200, Thank you, please come again! Now it's my turn to roll the dice.",#Person1# and #Person2# are playing a game. #Person1# thinks #Person2# should ask #Person1# for money instead of just taking it.,89,20,0.2247
scientific_lay_summarisation-elife-norm,"cortical and limbic areas (Veening et al. , 2010; Fuxe et al. , 2012; Ludwig and Stern, 2015; Brown et al. , 2020). Indeed, this mechanism seems likely to work in concert with limited/targeted release from centrally projecting axon collaterals of OT neurons, as has been effectively demonstrated in several extrahypothalamic areas to date (Knobloch et al. , 2012; Eliava et al. , 2016; Oettl et al. , 2016). In the current study, we use a combination of electrophysiological and subcellular optical recording techniques to evaluate dendritic physiology of OT-MCNs. Somatic activity was induced with a reproducible train of action potential-like voltage pulses delivered to the soma, and calcium influx induced by this somatic activity was quantified using high frequency two-photon line scans across the proximal and distal dendrite. The results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes. We further report that acute hyperosmotic challenge preferentially reduces activity-induced calcium influx in distal vs. proximal OT-MCN dendrites, while acute hypoosmotic challenge increases it. Extensive control experiments indicate these effects are likely mediated by modulation of a previously unidentified osmosensitive channel expressed along the dendritic membrane. Finally, we report that that activity-induced calcium influx in the distal dendrites of OT-MCNs is also preferentially and robustly inhibited, absent any change in osmolarity, by activation of dendritic GABAA receptors. Collectively, these results significantly increase our understanding of the mechanisms through which OT-MCNs are likely to dynamically regulate the relationship between somatic activity and calcium-dependent dendritic release of OT into the CNS. All experiments for this study were performed in an OT-reporter mouse line designed to selectively expresses a red fluorescent protein (tdTomato) in oxytocinergic neurons (1A, see Materials and methods). In order to validate specificity and selectivity of this reporter in the PVN, we used immunohistochemical techniques to evaluate co-expression of tdTomato and neurophysin 1 (NP1, an OT carrier protein found in oxytocinergic neurons, 1B). Overall, we found that a strong majority of tdTomato expressing neurons in the PVN were immunoreactive for NP1 (92. 8 ± 0. 8% across all animals tested, 93. 2 ± 1. 0% in males, and 92. 4 ± 0. 5% in females, n = four animals total, two male, two female, 2838 total tdTomato-positive PVN neurons evaluated, 1352 from males, and 1486 from","Oxytocin is often referred to as a ‘love hormone’ because it can be released during activities such as hugging, snuggling, or sex. Reality, of course, can be a bit more complicated. In the brain, oxytocin can have powerful and diverse effects on mood, stress, anxiety, and social interactions. In the body it helps regulate fluid balance, promotes contractions during childbirth, and stimulates the letdown of milk during breastfeeding. Much of the oxytocin produced in both humans and rodents comes from oxytocin-synthetizing magnocellular neurons located in an area of the brain called the hypothalamus. These very specialized neurons have separate, but overlapping, mechanisms for releasing oxytocin into the brain and into the rest of the body. This means that while certain signals cause the neurons to release oxytocin into",380,128,0.3368
dialogsum,"#Person1#: How do you do, Mr. Smith ? This is Lili. I'm calling to thank you for the wonderful dinner we had yesterday . I enjoyed it very much. #Person2#: You're welcome. I'd like you to join us for dinner again sometime. #Person1#: Thank you, Mr. Smith. I'm returning to China today. #Person2#: Today? #Person1#: Yes. I appreciate all help and in particular, all the time that you've spent on my account during my stay here. #Person2#: Don't mention it. I am pleased to help you. #Person1#: If there's anything that I can help you in the future, please let me know. #Person2#: I'll do that. Thank you. Have a safe trip home.",Lili phones Mr. Smith to tell him she's returning to China today and expresses her gratitude for the dinner and his help.,113,22,0.1947
pubmed-summarization,"with a shallow depression , termed the canyon the canyon region was proposed as the docking site for the other component proteins , and , indeed , later crystallographic studies revealed that the regulatory component does occupy a portion of the canyon in hydroxylase regulatory protein complexes of ph , toluene-4-monooxygenase ( t4mo , another four - component bmm ) , and , very recently , smmo ( 1b ) . regulatory protein complex of smmo ( pdb i d 4gam ) : ( a ) the hydroxylase mmoh showing the canyon , and ( b ) mmoh in complex with the regulatory protein mmob . there is another mmob molecule binding to the canyon on the other side of mmoh . mmoh -subunit is colored in green , -subunit in blue , -subunit in yellow , and mmob in purple . there is no crystal structure available for the hydroxylase reductase complex of any bmm enzyme . by using the zero - length cross - linker 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide ( edc ) , a chemical cross - linking study of smmo isolated from methylosinus trichosporium ob3b revealed that the reductase , mmor , cross - linked to the -subunit of the hydroxylase mmoh , and that the regulatory component , mmob , cross - linked to the -subunit . a different result was obtained , however , using smmo isolated from methylococcus capsulatus ( bath ) , where either the full - length mmor or its fd cross - linked to the -subunit using the same cross - linker , edc . further attempts to determine the binding site by identifying cross - linked residues failed . the two identified fd cross - linking sites , glu-56 and glu-91 , cross - linked to the n - terminal amino group of mmoh -subunit , which is not observed in the crystal structure of mmoh owing to disorder . because the mmor binding site on mmoh is obscure , it was unclear how the regulatory protein and the reductase might interact in the complete enzyme system . simulations of steady - state oxidase and oxygenase activities of smmo as a function of component protein concentrations favored a non - competitive model , whereby mmor and mmob bind at distinct sites on mmoh","the hydroxylation or epoxidation of hydrocarbons by bacterial multicomponent monooxygenases ( bmms ) requires the interplay of three or four protein components . how component protein interactions control catalysis , however , is not well understood . in particular , the binding sites of the reductase components on the surface of their cognate hydroxylases and the role(s ) that the regulatory proteins play during intermolecular electron transfer leading to the hydroxylase reduction have been enigmatic . here we determine the reductase binding site on the hydroxylase of a bmm enzyme , soluble methane monooxygenase ( smmo ) from methylococcus capsulatus ( bath ) . we present evidence that the ferredoxin domain of the reductase binds to the canyon region of the hydroxylase , previously determined to be the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"dynein heavy chain (DHC) or the dynactin subunit p150 (— 1F–G). To prevent cortical recruitment of NuMA by the endogenous LGN-Gαi complex, we depleted LGN by RNAi (1A middle, 1B t = 0: 00; — 1H). We then continuously illuminated the cortical region next to one of spindle poles (indicated by red circles in Figures) with a 488 nm laser to induce NuMA-RFP-Nano targeting. Light illumination induced the asymmetric cortical accumulation of NuMA-RFP-Nano within a few minutes (1B–C), which subsequently recruited DHC-SNAP and p150-SNAP (1B–C; — 2A–C). The level of light-induced cortical NuMA is about three times higher than that of endogenous NuMA in metaphase, but similar to that in anaphase (— 1I–J). Importantly, following asymmetric NuMA-RFP-Nano targeting, the mitotic spindle was gradually displaced toward the light-illuminated region in 82. 4% of cells (n = 17, 1B, D–E, and Video 2), whereas spindle displacement and cortical dynein recruitment was never observed by targeting RFP-Nano alone (n = 6, 1D and — 2D). Additionally, we found that light-induced repositioning of cortical NuMA is sufficient to drive spindle rotational re-orientation (1F and Video 3), and that light-induced NuMA targeting also causes spindle displacement in 71. 4% of Gαi (1 + 2 + 3) depleted cells (n = 7, — 2E–F). These results indicate that light-induced cortical recruitment of the Dynein-Dynactin-NuMA (DDN) complex is sufficient, and that LGN/Gαi are dispensable for generating cortical spindle-pulling forces in human cells. Cortical pulling forces are supposed to be generated by dynein-based motility on astral microtubules and/or astral microtubule depolymerization coupled with cortical anchorage (Grill and Hyman, 2005). To understand the contributions of astral microtubules to the spindle movement caused by light-induced cortical NuMA, we disrupted or stabilized astral microtubules using the microtubule-targeting drugs, nocodazole or taxol, respectively. In control cells, the metaphase spindle contains visible astral microtubules (2A, left) and is displaced following light-induced NuMA-RFP-Nano targeting (2B, D–E). In contrast, when astral microtubules were selectively disrupted by treatment with 30 nM nocodazole (2A, middle), the spindle was no longer displaced in 56% of cells (n = 5/9 cells), and only partially displaced in the remaining 44% of cells (n = 4/9) (2C–E), despite presence of cortical dynein (2C t = 5: 30). This suggests that astral microtubules are required for spindle pulling by the light-induced cortical","Almost every time a cell divides, it must share copies of its genetic material between two new daughter cells. A large molecular machine called the mitotic spindle makes this happen. The spindle is made of protein filaments known as microtubules that radiate out from two points at opposite ends of the cell. Some of these filaments attach to the genetic material in the center of the cell; some extend in the other direction and anchor the spindle to the cell membrane. The anchoring filaments – also known as astral microtubules – can position the mitotic spindle, which controls whether the cell splits straight down the middle (to give two identically sized cells) or off-center (which gives cells of different sizes). The force required to move the spindle comes",380,128,0.3368
dialogsum,"#Person1#: I can't decide whether to go to university or get a job. What do you think? #Person2#: Well, if I were you, I'd go on studying. #Person1#: But I don't even know what to study. #Person2#: If I had the chance again, I'd study computer. You're good at science subject. #Person1#: That's what my parents want me to do. #Person2#: You should take their advice. They know what's the best for you. #Person1#: But my friends will have jobs and lots of fun while I spend all my time studying. #Person2#: But if you go to university, you'll still have time for fun. #Person1#: What you say makes sense. But you know, I still have to ask my parents for pocket money and I hate to do so at this age. #Person2#: If you try to find a part time job, you will have some money, too. #Person1#: You're right. Thank you for the advice.",#Person2# gives some advice to #Person1# about deciding between studying or working. #Person2# suggests finding a part time job while studying since #Person1# hates asking parents for pocket money.,156,29,0.1859
scientific_lay_summarisation-elife-norm,"The ‘pitchers’ of carnivorous pitcher plants are exquisite examples of convergent evolution. An open question is whether the living communities housed in pitchers also converge in structure or function. Using samples from more than 330 field-collected pitchers of eight species of Southeast Asian Nepenthes and six species of North American Sarracenia, we demonstrate that the pitcher microcosms, or miniature ecosystems with complex communities, are strikingly similar. Compared to communities from surrounding habitats, pitcher communities house fewer species. While communities associated with the two genera contain different microbial organisms and arthropods, the species are predominantly from the same phylogenetic clades. Microbiomes from both genera are enriched in degradation pathways and have high abundances of key degradation enzymes. Moreover, in a manipulative field experiment, Nepenthes pitchers placed in a North American bog assembled Sarracenia-like communities. An understanding of the convergent interactions in pitcher microcosms facilitates identification of selective pressures shaping the communities. Similar selective pressures in geographically distant habitats can cause unrelated organisms to converge in both morphological and functional traits. Pitchers of carnivorous plants have evolved repeatedly and independently to have the same shapes and insect-trapping functions in Southeast Asia, North America, and Australia (Albert et al. , 1992). Similar selective pressures can also cause the independent emergence of multispecies interactions with parallel physiological or ecological functions, defined as ‘convergent interactions’ (Bittleston et al. , 2016b). The concept of convergent interactions was developed in detail in Bittleston et al. (2016b), and can be used as a tool to better understand forces influencing interspecific relationships. Here, we investigate whether convergent interactions can be identified between different, independently evolved pitcher plant genera and the arthropods and microbes housed within their pitchers. We hypothesize that the microbial communities formed within the fluids of distantly-related pitcher plant species possess similar community structures and functions, and we test this hypothesis by comparing the bacterial and eukaryotic communities living within the plant-held waters (phytotelmata) of pitcher plants from two genera in different plant orders, Nepenthes (family Nepenthaceae, order Caryophyllales) native to Southeast Asia and Sarracenia (family Sarraceniaceae, order Ericales) native to North America. Microbial communities are complex, and even apparently simple habitats house orders of magnitude more microbial species than plant or animal species (Horner-Devine et al. , 2004). Parsing the principles shaping microbial community structure and","The ecosystems found across the Earth, including in forests, lakes and prairies, consist of communities of plants, animals and microbes. How these organisms interact with each other determines which ones grow and thrive. We still do not understand how communities form: why different species exist where they do, and what enables them to survive in different locations. This knowledge is particularly limited with regard to communities of microbes because they are hard to see and count. Pitcher plants are an ideal system for studying how communities and ecosystems assemble. The pitcher-shaped leaves of these plants each contain small aquatic communities of microbes and arthropods (including insects and mites) that can be relatively easily studied. Because unrelated groups of plants have evolved pitchers at different times and on different",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of the elusive ligands for this RTK. ALK and the related LTK share similarity in their membrane proximal ECD in the form of a glycine-rich domain that is ∼250 amino acids in length (1A, GR depicted in grey). This domain contains multiple runs of up to eight glycine residues, and is unique to ALK and LTK within the human genome. The importance of the GR in ALK has been highlighted in Drosophila studies, where four independent point mutations leading to exchange of single glycine residues result in complete loss of function in vivo (Englund et al. , 2003) (— 1). The similarity between ALK and LTK within the GR is ∼70%, with amino acid identity of 55%, containing a total of 51 conserved glycine residues (1B). Given this similarity, and the important role of the glycine-rich domain for function in Drosophila, we hypothesized that FAM150A and FAM150B, which were recently reported as ligands for LTK (Zhang et al. , 2014) may act as ligands for ALK. 10. 7554/eLife. 09811. 003Figure 1. FAM150A and FAM150B activate ALK. (A) Schematic overview of human anaplastic lymphoma kinase (ALK) and leukocyte tyrosine kinase (LTK) protein domain structures. ALK and LTK share a membrane proximal extracellular glycine-rich region (GR, grey), transmembrane and an intracellular tyrosine kinase domain (red). In addition, the extracellular region of ALK contains two MAM domains (purple) and an LDLa-motif (yellow). (B) Alignments of the GR of ALK and LTK, conserved runs of glycine residues are highlighted in bold with red asterisks. (C) Neurite outgrowth in PC12 cells expressing either vector control, FAM150A, FAM150B, ALK, FAM150A and ALK, FAM150B and ALK or ALK-F1174L quantified in (D). Experiments were performed in triplicate and each sample within an experiment was performed in duplicate (error bars indicate SD). (E) Whole cell lysates from PC12 cells expressing either vector control, FAM150A, ALK, FAM150A and ALK or ALK-F1174L were analyzed by immunoblot analysis of ALK, pALK-Y1604 (arrowheads), FAM150A and ERK1/2. Pan-ERK was employed for equal loading. (F) Whole cell lysates from PC12 cells expressing either vector control, FAM150B, ALK, FAM150B and ALK or ALK-F1174L were analyzed by immunoblot analysis of ALK, pALK-Y1604 (arrowheads), HA (FAM150B) and pERK1/2. Pan-ERK was employed for equal loading. : http: //dx. . org/10. 7554/eLife. 09811. 00310. 7554/eLife. 09811. 004Figure 1— 1. Glycine","Cells have receptor proteins on their surface that enable them to detect changes in their environment and communicate with other cells. Signal molecules bind to a segment of the receptor called the extracellular domain that faces out from the cell. This can result in the activation of another domain in the receptor that is just inside the cell, which, in turn, activates signaling pathways that relay the information around the cell. However, these communication systems are often disrupted in cancer cells. This helps the cells to override the strict growth controls imposed upon them by other (healthy) cells in the body. The gene that encodes a receptor protein called Anaplastic Lymphoma Kinase (or ALK for short) is often mutated in some types of human cancer so that the",380,128,0.3368
pubmed-summarization,"in an era of finite resources and ever - increasing medical possibilities , every health care system faces challenges in determining which new health technologies , including medical devices , should be introduced into clinical practice.1 while technology can improve safety2 and have other benefits , it can also bring new risks35 and contribute to the increasing cost of care.6,7 ideally , health organizations should have a systematic process both to gather relevant scientific information about a technology s safety and effectiveness and to decide whether the technology is suitable for the local setting . however , several studies have concluded that the decision - making process for the adoption of new technologies could be improved at the institutional level.810 the international network of agencies for health technology assessment defines health technology assessment ( hta ) as : the systematic evaluation of properties , effects , and/or impacts of health care technology . it may address the direct , intended consequences of technologies as well as their indirect , unintended consequences . its main purpose is to inform technology - related policymaking in health care.11 hta reports from various international , national , and provincial agencies provide comprehensive , objective , evidence - informed analyses about the safety , clinical effectiveness , cost - effectiveness , and the broader impact of health technologies , including devices , drugs , and procedures . despite the exponential growth in the numbers and the types of hta reports over the past decade and their documented impact on health care,1215 it has been observed that recommendations are not put into practice as often as their envisioned potential.1618 there are several possible reasons for this . first , local decision makers may be unaware of the wealth of hta information available to them.19,20 second , external hta agencies may not be able to consider operational factors that are critical for local decision - making , such as local needs , financial impact , and the presence of local alternatives , trained personnel , or sufficient resources . third , health care organizations may lack a systematic process by which to integrate and translate context - free hta reports with context - sensitive considerations , particularly as decision making on technology adoption at the local level","purposeintroducing new health technologies , including medical devices , into a local setting in a safe , effective , and transparent manner is a complex process , involving many disciplines and players within an organization . decision making should be systematic , consistent , and transparent . it should involve translating and integrating scientific evidence , such as health technology assessment ( hta ) reports , with context - sensitive evidence to develop recommendations on whether and under what conditions a new technology will be introduced . however , the development of a program to support such decision making can require considerable time and resources . an alternative is to adapt a preexisting program to the new setting.materials and methodswe describe a framework for adapting the local hta",380,128,0.3368
scientific_lay_summarisation-elife-norm,"increase in their expression level is relatively low compared to other insects (Benoit et al. , 2011) In the present work, we studied how the major Chagas disease vector Rhodnius prolixus copes with the excess of heat associated to blood-feeding. We performed real-time thermography and measured HSP expression, to analyse the extent to which these bugs are exposed to heat stress during feeding. Based on these results, we then performed a morpho-functional analysis of the R. prolixus head to gain insights on its structural organisation and how it could be implicated in heat management. Finally, we used synchrotron-based high-resolution X-ray imaging to see how the ingestion pumps work and to assess their role in blood displacement inside the insect. Based on the results obtained during this study, we propose a 3-D (three-dimensional) model of the R. prolixus head, as well as the existence of a countercurrent heat exchange mechanism through which this species can protect itself against heat stress during blood-feeding. To understand how R. prolixus manages the heat flow associated with the ingestion of a blood-meal, we first performed a real-time thermographic analysis of the dynamics of body warming during the entire feeding process (1A; SI Video 1). Before the blood intake, Tb = Ta for all body parts of the insect. But once the insect started to feed, the different parts of its body did not exhibit the same temperature (i. e. heterothermy) (2A–B). Indeed, while the temperature of the proboscis (Tp) was high and close to the temperature of the blood, that of the abdomen (Tabd) was close to the ambient temperature, whereas the temperature of the head (Th) and that of the thorax (Tth) remained intermediate. Thus, a marked thermal gradient was established along the insect body: Tp >Th > Tth>Tabd. Interestingly, Tp and Th oscillated during feeding, certainly in concordance with the variations in the activity of the ingestion pumps, while Tth and Tab did not, remaining stable during the entire blood intake. These results show that R. prolixus is able to minimise the amount of heat reaching the abdomen during feeding (2A–B). We then characterised regional heterothermy in R. prolixus by establishing different combinations of both ambient and blood temperature, to see how the temperature of the different parts of the body would be","Many insect species have adopted the blood of birds and mammals as their main or even only food. Yet, blood is not freely available in nature, but it circulates inside vessels hidden under the skin of animals much bigger than the insect and capable of defending themselves from getting bitten. To succeed in getting a meal, blood-sucking insects must be able to feed quickly and take in as much blood as possible. Each time that they do this, a huge amount of warm fluid enters their body in just a few minutes. The blood temperature can be up to 20° or 25°C warmer than the insect itself. Moreover, an insect called a kissing bug may ingest up to 10 times its own weight in only fifteen minutes. The",380,128,0.3368
pubmed-summarization,"placed in the right upper quadrant to avoid the liver . a 12-mm trocar was placed five fingerbreadths above the umbilicus , just to the right of midline . next , a 5-mm trocar was placed in the left lower quadrant approximately two fingerbreadths below the umbilicus in the midclavicular line . a 12-mm port was then placed under direct vision in the left midclavicular line approximately five fingerbreadths above the umbilicus . a 12-mm port was placed in the right upper quadrant in the midclavicular line , and a 5-mm port was placed in the right upper quadrant one fingerbreadth below the costal margin in the midaxillary line [ ] . exploration revealed extensive adhesions as a result of her previous open procedures . at this point , the stomach was identified and noted to be severely adhered to the liver , which was , in turn , adherent to the abdominal wall . the stomach was mobilized , the band was identified , and the band buckle was cut and removed . the previous fundoplication was taken down using a 3.5-mm depth 45-mm length stapler , and the greater curvature and short gastric vessels were divided using a harmonic scalpel . after performing the dissection all the way to the angle of his and exposing the left crux of the diaphragm , a 34-french bougie was placed into the stomach with the tip of the bougie sitting in the proximal duodenum . the formation of the gastric sleeve with a 4.8-mm depth 45-mm length stapler was started from a point 5 cm proximal to the pylorus muscle and directed toward the angle of his [ ] . eight total firings were used , thus dividing the stomach completely and forming a gastric tube over the 34-french bougie . at the most proximal aspect of the stomach , several dense adhesions to the diaphragm were encountered and eventually taken down . following the formation of the gastric tube , the staple line was oversewn with 2 - 0 absorbable suture using an endo stitch ( covidien inc . , after submerging the gastric tube underwater , air was pumped into the scope , and subsequently no leak was appreciated . before removal of the last trocar , the detached","while several equivalent alternatives are available in the bariatric algorithm , more recently the laparoscopic sleeve gastrectomy ( sg ) has been gaining traction as an effective means of weight loss in patients with morbid obesity . we present the case of a 39-year - old woman with situs inversus totalis , who was taken to the operating room for laparoscopic sg . the patient had previously undergone a failed open gastric banding procedure 20 months earlier . awareness of the inherited condition before performing the operation allows for advanced planning and preparation . subsequent modifications to the standard trocar placement help make the procedure more technically feasible . to our knowledge , this is the first published report of a laparoscopic sg after open gastric banding in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"toxic gain of function of SOD1. An effective understanding of the role of individual metals (Cu and Zn) would require studying SOD1 variants containing only one metal (Cu or Zn) in addition to a variant that contains none. We have therefore prepared an apo (metal free) protein, which serves the latter purpose. For the former, we have generated two single metal containing mutants of SOD1, viz. H121F (only Zn, no Cu) and H72F (only Cu, no Zn), which are situated near the key loop VII (H121F) and loop IV (H72F) at the protein structure (1a). Using computational analysis based on a statistical mechanical model and detailed in vitro experiments, we propose here a ‘Co-factor derived membrane association model’ of SOD1 aggregation and its possible implication in ALS. We demonstrate that differential metal binding and membrane assisted conformational changes can work in concert to attenuate the rate and propensity of aggregation. While apo (no metal) protein and H72F mutant (no Zn) experience strong membrane interaction, the WT (both metals) protein and H121F (no Cu) mutant do not show significant binding. We further find that membrane-induced aggregates of H72F and apo protein showed significantly higher toxicity in terms of cell death and model membrane deformation when compared to WT and H121F mutant. We finally check the validity of this model to ALS using computational and experimental studies. For the computational validation, we show, using 15 ALS disease mutants, that the distance between the mutation site and Zn correlates well with the membrane binding energy and patient survival time after disease diagnosis, while Cu site does not seem to have any prominent role. For the experimental study, we use two well-studied disease mutants (G37R where mutational site is close to the Cu pocket and I113T where mutational site is near Zn pocket) to show that the model accounts well for their membrane binding/aggregation, correlating well with their disease onset phenotypes. This model puts forward a mechanism that Zn pocket destabilization (either by metal content variation or by mutational stress near Zn center) is the driving force behind the toxic gain of function of SOD1 mediated by the process of membrane association. The large size of SOD1 (151 residues) precludes a detailed characterization of the conformational landscape, the role of ions in determining the","Amyotrophic lateral sclerosis, or ALS, is an incurable neurodegenerative disease in which a person slowly loses specialized nerve cells that control voluntary movement. It is not fully understood what causes this fatal disease. However, it is suspected that clumps, or aggregates, of a protein called SOD1 in nerve cells may play a crucial role. More than 140 mutations in the gene for SOD1 have been linked to ALS, with varying degrees of severity. But it is still unclear how these mutations cause SOD1 aggregation or how different mutations influence the survival rate of the disease. The protein SOD1 contains a copper ion and a zinc ion, and it is possible that mutations that affect how these two ions bind to SOD1 influences the severity of the disease. To",380,128,0.3368
dialogsum,"#Person1#: the dinner was really good. It knocked my socks off. #Person2#: that's very kind of you to say so. Let's try some after-dinner wines. #Person1#: great. Sweet wines are my favorite. They always make a great finish to a decisions meal. #Person2#: do you prefer brandy or ports. #Person1#: port, please. #Person2#: excellent choice. I love its smooth flavor. #Person1#: the port is exquisite. It must have spent years aging in barrels. Am I right? #Person2#: yes. You always have a good nose for wines. #Person1#: next time we are about to dinner we should try some Canadian ice wine. #Person2#: oh, what's that? #Person1#: it's made from naturally frozen grapes. #Person2#: why not? It sounds great. #Person1#: oh, here's to your health. #Person2#: thanks. Cheers. #Person1#: cheers.",#Person1# and #Person2# try port wines after dinner. #Person1# likes the port and #Person2# invites #Person1# to try Canadian ice wine next time.,129,23,0.1783
scientific_lay_summarisation-elife-norm,"The segregation of eukaryotic chromosomes during mitosis requires their extensive folding into units of manageable size for the mitotic spindle. Here, we report on how phosphorylation at serine 10 of histone H3 (H3 S10) contributes to this process. Using a fluorescence-based assay to study local compaction of the chromatin fiber in living yeast cells, we show that chromosome condensation entails two temporally and mechanistically distinct processes. Initially, nucleosome-nucleosome interaction triggered by H3 S10 phosphorylation and deacetylation of histone H4 promote short-range compaction of chromatin during early anaphase. Independently, condensin mediates the axial contraction of chromosome arms, a process peaking later in anaphase. Whereas defects in chromatin compaction have no observable effect on axial contraction and condensin inactivation does not affect short-range chromatin compaction, inactivation of both pathways causes synergistic defects in chromosome segregation and cell viability. Furthermore, both pathways rely at least partially on the deacetylase Hst2, suggesting that this protein helps coordinating chromatin compaction and axial contraction to properly shape mitotic chromosomes. The DNA molecule at the core of any eukaryotic chromosome is a hundred to million times longer than the average diameter of the cell that hosts it. Thus, cells need to fold their genetic material in order to fit it in the interphase nucleus; they need to pack it further during mitosis, in order to move sister-chromatids safely and symmetrically apart. Furthermore, chromatin folding must be dynamic to allow transcription and replication during interphase, and such that exceptionally large chromosomes can hyper-condense during anaphase in order to fit the size of the spindle and prevent chromosome missegregation (Neurohr et al. , 2011; Titos et al. , 2014). Moreover, mitotic condensation also facilitates the decatenation of sister chromatids during their separation (Charbin et al. , 2014), and might help to ‘cleanse’ chromosomes from transcription, replication and cohesion factors (Yanagida, 2009). This is thought to ‘reset’ the transcriptional state of genes, and prevent displaced factors from interfering with chromosome segregation. However, despite their importance for chromosome segregation, the events ensuring the mitotic condensation of chromosomes are still only partially understood. Early studies made evident that nucleosomes play a critical role in DNA packaging. In favor of the idea that they play specific roles in chromatin condensation, histone H3 is phosphorylated by aurora B throughout mitosis on a serine at","DNA in humans, yeast and other eukaryotic organisms is packaged in structures called chromosomes. When a cell divides these chromosomes are copied and then the matching pairs are separated so that each daughter cell has a full set of its genome. To enable these events to take place, the DNA must become more tightly packed so that the chromosomes become rigid units with projections called arms. Any failure in this chromosome “condensation” leads to the loss of chromosomes during cell division. Within a chromosome, sections of DNA are wrapped around groups of proteins to make a series of linked units called nucleosomes, which resemble beads on a string. These units and other scaffold proteins together make a structure called chromatin and establish the overall shape of the chromosome.",380,128,0.3368
dialogsum,"#Person1#: Hi, Mark! I heard you just had an interview for a new job? How did it go? #Person2#: I think I did well. They said they'd make a decision by this Friday. #Person1#: This Friday? It looks like they want to hire the person as quickly as possible.",Mark will get the result of the interview and #Person1# thinks it's quick.,49,13,0.2653
scientific_lay_summarisation-elife-norm,"(Kim et al. , 2007; Kloss et al. , 1998; Emery et al. , 1998; Stanewsky et al. , 1998; Ceriani et al. , 1999; Hunter-Ensor et al. , 1996; Syed et al. , 2011). Without these repressors, CLK/CYC-mediated transcription begins again restarting the daily cycle of transcription. In the Drosophila brain, this molecular clock resides in a neural network of ~150 neurons. These neurons are divided into seven subgroups including three groups of dorsal neurons (DNs; DN1, DN2, and DN3), three groups of lateral neurons (ventral and dorsal lateral neurons; large and small LNvs and LNds, respectively) and the lateral posterior neurons (LPNs) with discrete behavior functions; reviewed in (Peschel and Helfrich-Förster, 2011). These neurons make up a small portion of the Drosophila brain (~0. 1%) and head (~0. 05%). As a result, it is difficult to profile these specialized neurons as part of studies that focus on Drosophila brain and head tissues (Hughes et al. , 2012; Rodriguez et al. , 2013). To learn more about the function of these neurons within the circadian neuronal circuit, three subgroups (DN1s, LNds, and LNvs) of these neurons as well as one non-circadian outgroup (Dopaminergic or tyrosine-hydroxylase (TH) expressing neurons) were labeled with GFP using neuron-specific drivers and manually isolated (Abruzzi et al. , 2015; Abruzzi et al. , 2017). Illumina RNA-seq datasets from these neurons were analyzed to examine the global mRNA landscape at the transcription level. This analysis revealed many cycling transcripts whose abundance changes with time of day that were not identified in previous studies of brain or head tissues (McDonald and Rosbash, 2001; Claridge-Chang et al. , 2001; Wijnen et al. , 2006; Rodriguez et al. , 2013). In addition, many neuron-specific transcripts including novel circadian neuropeptides were revealed. Besides transcriptional level gene regulation, post-transcriptional level regulation, such as alternative pre-mRNA splicing, is also known to be essential for the normal functioning of the nervous system. Alternative pre-mRNA splicing (AS) is a major gene regulatory mechanism that enables a single gene locus to produce populations of often functionally distinct mRNAs in a tissue- or cell-type-specific manner, greatly diversifying the metazoan transcriptome. The nervous system is well recognized to exhibit extraordinarily complex and diverse AS patterns in a variety of metazoan organisms (Li et al. , 2007; Wang","The life of nearly all creatures on Earth follows the rhythm of day and night. For example, in fruit flies, darkness and light dictate when the insects feed, rest, move or mate. This is possible thanks to the circadian clock, an internal program which is synchronized with the environment to tell cells in the body when to perform certain roles. In fruit flies, the structure that keeps the body clock ticking is formed of about 150 ‘circadian neurons’, which are divided into several subgroups. In these cells, a complex genetic programis at work, with networks of genes being ‘switched on’ in a cyclical way. To understand how this program works, scientists need to know which genes are turned on and when, as well as which proteins are created",380,128,0.3368
pubmed-summarization,"there are approximately 287,000 preventable maternal deaths annually , of which 99% occur in developing countries . as a sentinel event , maternal death is also a prime indicator in evaluating the quality of a nation 's health care delivery systems . mothers are pivotal to the social , economic , and cultural development of a community ; maintaining their health elevates the physical , psychological , and social well - being of their children and families and , by extension , society as a whole . for this reason , improving maternal health has been proposed by the world health organization ( who ) as one of their eight millennium development goals ( mdg ) . however , in countries with few maternal deaths , this approach fails to provide comprehensive information , leaving policy makers to react based on current rather than past statistics . to facilitate the development of precautionary measures and safer environments that minimize maternal deaths , it is essential that near miss data are recorded and analyzed . the who defines an individual having experienced severe acute maternal morbidity ( samm ) ( i.e. , near miss ) as a woman who nearly died but survived a complication that occurred during pregnancy , childbirth or within 42 days of termination of pregnancy . in fact , maternal near miss includes those cases in which a woman nearly died but survived during pregnancy or during 42 days after the delivery . using near miss data in maternal death prevention planning first , because the number of near miss cases exceeds maternal death cases , near miss is a better predicate for preventive planning . second , because the mother survives a near miss , she can provide valuable details on what she experienced . lastly , because near miss is one step removed from death , obtaining any information about the event could prove useful in preventing maternal death . the prevalence of maternal near miss varies among different countries based on health care quality and availability . nevertheless , in a systematic review using disease - specific criteria , near miss rates have been reported to be between 0.6% and 14.98% . from a global perspective , iran has been notably successful in reducing","this prospective study aimed to estimate the incidence and associated factors of severe maternal morbidity in southeast iran . during a 9-month period in 2013 , all women referring to eight hospitals for termination of pregnancy as well as women admitted during 42 days after the termination of pregnancy were enrolled into the study . maternal near miss conditions were defined based on say et al . 's recommendations . five hundred and one cases of maternal near miss and 19,908 live births occurred in the study period , yielding a maternal near miss ratio of 25.2 per 1000 live births . this rate was 7.5 and 105 per 1000 in private and tertiary care settings , respectively . the rate of maternal death in near miss cases",380,128,0.3368
pubmed-summarization,"oral infections of geotrichum candidum are clinically similar to candidiasis and commonly associated with diabetes mellitus and hiv infection , . cases of dissemination and fungemia are reported in patients with chronic and acute myeloid leukemia , , , , , , . old women post - partum with isolated renal calculi and renal fungal bezoar attributed to geotrichum candidum and to illustrate the diagnostic dilemmas . old women presented with history of left flank pain and intermittent fever since 15 days . she was evaluated elsewhere with contrast enhanced computerized tomography ( ct ) scan which revealed contracted left kidney with 2 calculi in the lower and middle calyx of 89 mm each with intrapelvic mass and multiple air pockets in the renal pelvis ( . 2 ) . she had undergone cytoscopy and left dj stenting elsewhere but continued to have fever and flank pain when she was presented to us . after routine investigation , patient was started on 3rd generation cephalosporin and she underwent left percutaneous nephrolithotripsy ( pcnl ) which revealed brownish gray material with 2 calculi . gross specimen consists of multiple irregular gray brown tissue bits , largest measuring 0.5 cm0.5 cm and cut portion showed gray brown areas . section showed fungal ball containing aggregates of macerated , distorted fungal hyphae with some showing acute angle branching surrounded by cell debris and neutrophils . both urine and biopsy material sent to mycology laboratory for culture investigation were inoculated on sabourauds dextrose agar ( hi - media laboratories ltd . , mumbai ) and incubated at 37 c and 28 c which grew a rapidly growing fungus with flat , white to creamy having a smooth texture later becoming hairy consistent with geotrichum candidum ( . geotrichum candidum was morphologically identified by the presence of true hyphae , hyaline smooth , one - celled , subglobose to cylindrical , slimy arthroconidia and the lack of blastoconidia . the arthroconidia vary in size and germinate at one end giving a hockey stick appearance ( . 4 ) . biochemical identification was carried out in the mycology laboratory , kasturba medical college , manipal using both conventional and api 20c yeast identification system ( biomerieux inc . ) . it was further differentiated from trichosporon",geotrichum candidum is yeast like fungi that cause infections in immunocompromised patients . we report a case of renal fungal ball with geotrichum candidum in a 27 yr . old women post - partum . this case to our knowledge is the first case of renal fungal bezoar due to geotrichum candidum reported in india .,380,56,0.1474
dialogsum,"#Person1#: Hi, Jennie. How do you like the university? #Person2#: Hello, Bob. I like it very much. #Person1#: Have you started your classes yet? #Person2#: I have been to two lectures, chemistry and history. #Person1#: Well, how were they? #Person2#: They were very large. I'm not used to 300 students in class. #Person1#: My lectures have been large too. #Person2#: Have you been to your English class yet? #Person1#: Yes, it was quite small, there were only about 20 students in it. #Person2#: My classes are so far apart, the campus is sure big. #Person1#: It sure is, my morning classes are in different buildings. I have to run between them. Otherwise, I'll be late. #Person2#: I guess we'll get used to it.","Jennie and Bob have been to lectures at university and some classes are large, so they think the campus is big.",123,21,0.1707
dialogsum,"#Person1#: People are funny. #Person2#: They sure are. #Person1#: Did you hear about the pilot? #Person2#: The one that stole a small plane? #Person1#: Yes, he stole a plane in Canada and flew into the U. S. #Person2#: Did they catch him? #Person1#: Yes. After two U. S. fighter jets followed him for an hour, he landed on a highway. #Person2#: Did he crash? #Person1#: No, he just landed the plane and walked to a restaurant. #Person2#: Did the cops find out why he flew into the U. S. ? #Person1#: His life sucked. He was hoping a fighter jet would shoot him down. #Person2#: Poor guy.",#Person1# and #Person2# are talking about a pilot who stole a plane in Canada and hoped a fighter jet would shoot him down.,107,23,0.215
dialogsum,"#Person1#: Did a lot of people attend the lecture? #Person2#: Well, yes and no. #Person1#: What do you mean? #Person2#: You see, the classroom was quite full at the beginning. Almost all the seats were occupied. But after the short rest, almost one-third of the audience left. #Person1#: Terrible! That was a very rude thing. I should have been there. I had told the students to behave themselves. I do hope Professor Black was not angry. #Person2#: What do you mean? He wasn't even there. #Person1#: What? Professor Black did not come? #Person2#: No, his lecture is Thursday next week, not this Thursday. #Person1#: Oh, yes, of course. How silly of me!","#Person1# feels terrible knowing one-third of the students left during the class, then #Person2# says it's because the lecture isn't today.",112,21,0.1875
scientific_lay_summarisation-elife-norm,"could be fundamental to many addictive behaviors, compulsive disorders, and psychopathologies. A simple account for goal neglect is that the cognitive processes leading to goal selection have, in such cases, poor access to knowledge about expected outcomes and their value. One way to assess an animal’s knowledge of outcome values is through reinforcer devaluation in the devaluation task. Although the subjective value of a food or fluid outcome is influenced by many factors, such as probability, magnitude, and the effort required to obtain it, the devaluation task isolates a different and independent aspect of subjective value: an outcome’s worth at a particular moment based on the individual’s current state. In one version of this task, monkeys first learn that some objects are associated with one kind of food (food 1), while other objects are associated with a different food (food 2). Next, a selective satiation procedure temporarily devalues one food type, and monkeys are given a series of choice tests in which food-1 objects are pitted against food-2 objects. If monkeys can update the value of expected outcomes and link this information to their goal choices, they will shift these choices away from objects associated with the devalued food, a phenomenon called the devaluation effect. Other kinds of visual stimuli can be substituted for physical objects in these experiments, as in the present experiment. The key question for the present study is when various brain areas make their contribution to the devaluation effect. By inactivating the amygdala of monkeys either before or after the selective satiation procedure, Wellman et al. (2005) showed that neurons in the amygdala need to be active during the satiation procedure for normal value updating to occur. Specifically, inactivation of the amygdala before selective satiation disrupted devaluation effects, whereas inactivation after satiation, but before the choice phase of the experiment, had no effect. Thus, the amygdala is essential for value updating but, once that has occurred, it is no longer essential for making goal choices based on those valuations. In addition to the amygdala, the orbitofrontal cortex (OFC) makes a necessary contribution to devaluation effects in monkeys (Izquierdo et al. , 2004; Machado and Bachevalier, 2007; Baxter et al. , 2009; Rudebeck et al. , 2013). Further, functional interaction of the amygdala and OFC is required","Everyone knows that somehow, somewhere, the brain translates knowledge into action. In some people, however, knowledge and action become disconnected. These people behave in a way that either ignores or contradicts the knowledge that they have. They know what to do and can explain it to others, but – when the time comes to act – they do something else, something wrong. Murray et al. have now investigated how a brain region called the orbitofrontal cortex helps to link knowledge and action in macaque monkeys, which, unlike rodents, have all of the main brain areas that make up the orbitofrontal cortex of humans. The monkeys learned to associate images with different types of food, and then performed a task where they chose between two images in order to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50o kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface. African Animal Trypanosomiasis is one of the major constraints on the productivity of pastoralists in sub-Saharan Africa and can be caused by infection by a range of trypanosome species (Shaw, 2004), while infections of humans are caused by only two subspecies of Trypanosoma brucei (Laveran, 1902; Pays and Vanhollebeke, 2009). The disease is persistent as the host immune system is usually unable to clear the infection. This is due to the trypanosome having evolved a population survival strategy based on autoregulation of parasitaemia and antigenic variation (MacGregor et al. , 2011; Horn, 2014). The trypanosomes also internalize and degrade surface bound immunoglobulin (Pal et al. , 2003; Engstler et al. , 2007), increasing the survival of an individual cell and thereby increasing the likelihood of transmission. Both of these strategies require a densely packed cell surface coat of variant surface glycoprotein (VSG) that acts as a barrier, preventing access of host immunoglobulins to the plasma membrane (Schwede and Carrington, 2010). This coat also undergoes antigenic variation through expression of a single VSG gene from a genomic repertoire of hundreds (Horn, 2014). Although the VSG coat restricts immunoglobulin access, it must be permissive for receptor-mediated binding and uptake of macromolecular ligands. T. brucei, and the closely related T. congolense, have receptors for both transferrin (TfR) for iron (Steverding et al. , 1994; Schell et al. , 1991; Jackson et","African Trypanosomes are a group of single-celled parasites that are a major concern for livestock farmers in sub-Saharan Africa. They are carried by the tsetse fly and can cause disease in domestic livestock that diminishes productivity through reduced growth, and may ultimately lead to death. The parasites are coated in a dense layer of protein that help them evade the host’s immune system by preventing immune cells from identifying them. Humans have evolved immunity to many trypanosome species by exploiting a weakness in their lifestyle. Trypanosomes need to get haem—a molecule found in the protein haemoglobin—from their host to survive. In blood plasma, haemoglobin is found associated with a carrier protein called haptoglobin. To acquire haem, the parasites have a protein called HpHbR that binds to these haptoglobin-haemoglobin",380,128,0.3368
dialogsum,"#Person1#: Can you speak English? #Person2#: Yes I can. I speak it very well. #Person1#: Where did you learn it? #Person2#: I lived in England when I was a child. #Person1#: What else can you speak? #Person2#: Well, I know a little Italian.",#Person2# can speak English and a little Italian.,43,8,0.186
scientific_lay_summarisation-elife-norm,"and sub-national studies (). Southern and Tropical Latin America appeared to have higher levels than the other sub-regions (). The total cholesterol prevalence estimates were informed by 68 studies (129,123 individuals) overall. The pooled prevalence since 2005 was 21% for total cholesterol ≥240 mg/dl and 34% for total cholesterol ≥200 mg/dl (Table 1). There was a positive trend with time, signalling an increase yet weak evidence supported this observation (). National studies were evenly distributed; Southern and Tropical Latin America seemed to have higher estimates (). The overall sample for LDL-Cholesterol was 61 studies (86,854 subjects). Since 2005, the pooled mean was 120 mg/dl (Table 1). There was a non-significant decreasing trend (). National studies seemed to report lower means, and there was not a clear geographic distribution (). Overall, LDL-Cholesterol prevalence estimates were informed by 29 studies (42,900 individuals). The pooled prevalence of high LDL-cholesterol since 2005 was 21% for LDL-Cholesterol ≥160 mg/dl and 40% for LDL-Cholesterol ≥130 mg/dl (Table 1), and such estimates have slightly increased (). National studies were evenly distributed along the other studies (). Southern and Tropical Latin America appeared to have higher estimates (). The HDL-Cholesterol mean estimates benefited from 84 studies (121,282 subjects). The pooled mean since 2005 was 47 mg/dl (Table 1). The time trend of mean HDL-Cholesterol was negative yet non-significant (). National studies were evenly distributed; Southern and Tropical Latin America seemed to show higher means (). The HDL-Cholesterol prevalence estimates were based on 34 studies (55,164 individuals) overall. The pooled prevalence since 2005 was 48% for HDL-Cholesterol ≤40 mg/dl in men and ≤50 mg/dl in women (Table 1). The prevalence of low HDL-Cholesterol had a negative trend, yet not strong evidence supported this finding (). National studies were evenly distributed; Central Latin America seemed to have higher rates of low HDL-Cholesterol (). There were 84 studies (121,009 people) included in the mean triglycerides analysis. The pooled mean was 139 mg/dl since 2005 (Table 1). The mean levels of triglycerides have slightly increased (). Estimates from national studies did not show a strong pattern (). Estimates from Andean and Central Latin America appeared to be higher than those from Southern and Tropical Latin America (). Data from 70 studies (109,935 people) informed the triglycerides prevalence estimates overall. The pooled prevalence","Cholesterol and triglycerides are fatty substances found in the blood. They are crucial components of cell membranes and important for a variety of processes in the body. But, too much, or too little blood fat can damage the blood vessels. For example, high levels of fat in the blood can clog arteries, which can increase the chances of heart disease, heart attacks and strokes. Fat starts to build up if ‘bad’ fats, such as triglycerides and LDL cholesterol, are too high. But it can also happen if levels of' good' fats, like HDL cholesterol, are too low. The causes of, and treatments for, these different types of dyslipidaemia (or fat levels outside normal ranges) are not the same. So, to plan interventions effectively, public health authorities need to",380,128,0.3368
pubmed-summarization,"gonadotropin - releasing hormone ( gnrh ) controls the production of gonadotropins , there - by having an orchestrating effect on the reproductive hormone cascade and spermatogenesis ( 1 ) . active immunization against gnrh has successfully suppressed the secretion of gonadotropins and decreased sperm production , follicular development , ovulation and conception in male and female mammals ( 2 , 3 ) . therefore , it can be used as an alternative for castration and fertility control in farm animals , companion animals and wildlife species ( 46 ) . application of gnrh vaccination in humans has been suggested for controlling fertility - related endocrine disorders and gonadal steroid - dependent diseases ( 7 ) . active immunization of adult animals against gnrh causes the loss of synthesis and secretion of gonadotropins and cessation of gonadal function as long as the antibody titers remain elevated ( 8) . it has been reported that cow urine contains all beneficial elements such as chemical properties , potentialities and constituents that are capable of removing all the ill effects and imbalances of body caused by various infectious agents and toxicants . in this way , it ensures a protection against various ailments including the most dreaded diseases like cancer , diabetes , hepatitis etc . kamdhenu ark ( distilled cow urine ) has been reported as a strong immunomodulator and bioenhancer by various researchers ( 10 , 11 ) . experimental studies of rangasamy and kaliappan revealed the protective effects of cow urine on haematological , serum biochemical parameters and immune status of broilers ( 12 ) . the present study attempts to evaluate the effects of gnrh - bsa immunization on gonado - somatic indices ( gsi ) and sperm parameters in male mice and to examine the modulatory role of kamdhenu ark following the immunization . sixty adult male mice , mus musculus , of parke 's strain ( p ) , weighing 305 g were used in the study . the mice in group i served as the controls , receiving intraperitoneal phosphate buffered saline ( pbs ) injections ( 100 l ) on the 1 , 30 , 60 and 90 days , while the mice in group ii were immunized by gnrh - bsa conjugate ( 50/0.2/35","backgroundactive immunization against gnrh decreases the secretion of gonadotropins and causes cessation of gonadal function , thereby , inducing infertility . based on the immunoenhancing activity of kamdhenu ark ( distilled cow urine ) , this study was performed to evaluate its effects on the gonadosomatic indices ( gsi ) and sperm parameters in male mice receiving a gnrh contraceptive vaccine.methodssixty adult male mice of parke 's strain were divided into three groups of twenty . group i served as the controls , while group ii was immunized by gnrh - bsa conjugate ( 50/0.2/35 g / ml / g bw ) by four intraperitoneal injections at different intervals on days 1 , 30 , 60 and 90 . however , group iii was supplemented daily by oral",380,128,0.3368
scientific_lay_summarisation-elife-norm,"A polymorphism in the autophagy gene Atg16l1 is associated with susceptibility to inflammatory bowel disease (IBD); however, it remains unclear how autophagy contributes to intestinal immune homeostasis. Here, we demonstrate that autophagy is essential for maintenance of balanced CD4+ T cell responses in the intestine. Selective deletion of Atg16l1 in T cells in mice resulted in spontaneous intestinal inflammation that was characterized by aberrant type 2 responses to dietary and microbiota antigens, and by a loss of Foxp3+ Treg cells. Specific ablation of Atg16l1 in Foxp3+ Treg cells in mice demonstrated that autophagy directly promotes their survival and metabolic adaptation in the intestine. Moreover, we also identify an unexpected role for autophagy in directly limiting mucosal TH2 cell expansion. These findings provide new insights into the reciprocal control of distinct intestinal TH cell responses by autophagy, with important implications for understanding and treatment of chronic inflammatory disorders. Crohn’s disease (CD) and ulcerative colitis (UC) are the two most common forms of inflammatory bowel disease (IBD), characterized by chronic inflammation of the gastrointestinal tract. IBD is a complex multifactorial disease that emerges on a background of many genetic and environmental factors (Maloy and Powrie, 2011). In recent years, tremendous efforts have been undertaken to identify the genetic factors that influence susceptibility to IBD. In particular, genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 150 distinct loci that influence IBD susceptibility, many of which have revealed novel pathways in disease pathogenesis (Van Limbergen et al. , 2014). Among these, a single-nucleotide polymorphism (SNP) in the essential macroautophagy (hereafter called' autophagy' ) gene ATG16L1 was associated with an increased risk of CD (Hampe et al. , 2007; Rioux et al. , 2007). A recent study showed that the IBD predisposing T300A mutation in the coding region of ATG16L1 led to increased degradation of ATG16L1 protein and reduced autophagy (Murthy et al. , 2014), indicating that decreased autophagy may contribute to IBD development. Polymorphisms in several other autophagy-related genes, including IRGM, LRRK2 and SMURF1, are also linked to IBD susceptibility (Van Limbergen et al. , 2014), suggesting that changes in the autophagy pathway alter intestinal homeostasis and predispose to chronic intestinal inflammation. Autophagy is a highly conserved cellular process that targets cytoplasmic components for lysosomal degradation and maintains homeostasis by recycling damaged","The gut presents a puzzle to our immune system. Immune cells must rapidly respond to antigens produced by harmful bacteria, but food and the beneficial bacteria that inhabit the gut also produce antigens that our immune system must tolerate. Inappropriate immune responses in the gut can lead to inflammatory bowel disease, a debilitating disease with no current cure. We do not fully understand why these harmful inflammatory responses arise, but we know that genetic factors are important. Mutations in genes that affect a process known as autophagy – a pathway that breaks down and recycles unwanted material inside cells – make inflammatory bowel disease more likely to develop, but exactly how they do so remains unclear. T helper cells are crucial controllers of intestinal immune responses and changes",380,128,0.3368
pubmed-summarization,"in a cohort of peruvian hiv - patients on haart using the homa - ir . moreover , we described the prevalence of ms according to the criteria proposed by the national cholesterol education program s adult treatment panel iii report . the study was approved by the institutional review board of the universidad peruana cayetano heredia and of the hospital nacional cayetano heredia . authors take complete responsibility for the integrity of the data and the accuracy of the data analysis . a cross - sectional study of adult patients with hiv infection on haart was carried out between june and october 2012 at the institute of tropical medicine alexander patients recruited were adults over 18 years of age diagnosed with hiv infection on haart . we excluded patients with a known history of carbohydrate metabolism disorders ( igt , t2 dm ) , diseases that alter insulin sensitivity ( cushing syndrome , acromegaly , polycystic ovary syndrome ) , use of corticosteroids , and pregnancy . we obtained clinical records that included the following variables : age , gender , family history of diabetes in a first degree relative , smoking , blood pressure , weight , height , bmi , waist circumference , regimen and duration of haart . we obtained a fasting serum sample to measure levels of glucose , insulin , and lipids . insulin level determination was performed using the immunoradiometric assay based on the separation of antibody - coated tube ( ins - irma diasource - belgium ) . this method has a detection limit , defined as the concentration resulting in two standard deviations above the average link of the zero calibrator , 1 uiu / ml . the coefficient of variation intra - assay and inter - assay were 1.5 % and 6.5 % respectively . hyperglycemia was considered as a fasting glucose value 100 mg / dl . total cholesterol , high - density lipoprotein cholesterol ( hdl - c ) , and triglycerides were determined by enzymatic method . low - density lipoprotein cholesterol ( ldl - c ) was calculated according to the friedewald formula . the presence of ir was determined by the homa mathematical model using the following formula : [ insulin ( u / ml","backgroundthe highly active antiretroviral therapy ( haart ) has altered the course of hiv infection , transforming it from a fatal illness to a chronic condition , reducing morbidity and mortality . however , this therapy has led to an increased incidence of metabolic problems such as insulin resistance , dyslipidemia , lipodystrophy and impaired glucose metabolism.the objectives of this study are to determine the prevalence of insulin resistance ( ir ) in a cohort of human immunodeficiency virus ( hiv)-infected patients on highly active antiretroviral therapy ( haart ) and to investigate the potentially associated factors.methodswe conducted a cross - sectional study including 219 adult patients with hiv on haart . ir was determined through the homeostasis model assessment ( homa - ir ) mathematical model ,",380,128,0.3368
dialogsum,#Person1#: Mrs. Schmidt! What's happening! #Person2#: You'll never guess what happened today! I went to the doctor after work and the doctor told me. . . #Person1#: And the doctor told you to start listening to Bach? #Person2#: No. . . He told me I'm pregnant! #Person1#: Congratulations! #Person2#: And so I bought all these books on having kids and. . . #Person1#: And they said you should play classical music? #Person2#: How did you know! They say listening to classical music can make your baby smarter!,Mrs. Schmidt tells #Person1# that she's pregnant so she started reading books on having kids and listening to classical music.,87,20,0.2299
dialogsum,"#Person1#: Did you set your clock forward for daylight savings time? #Person2#: What? Why do we have to do that? #Person1#: Well, at the start of the spring we usually have more daylight in the mornings and less in the afternoon. This is basically due to our position on the planet and the rotation of the earth. In any case, to take better advantage of the daylight available, we compensate by moving our clocks forward one hour. #Person2#: I see. That ' s convenient! I never understood things like this, such as GMT. I never know what time zone we are in or when to change my clock! #Person1#: That just stands for Greenwich Mean Time. Here in California, we are in Pacific Standard Time, that is eight time zones west of Greenwich. Remember when we were in Beijing? Well, then we were in China Standard Time, and that ' s eight time zones east of Greenwich! #Person2#: That ' s why it was so weird traveling from Beijing to LA! Because of the huge time difference, even though we left Beijing at noon and flew for more than eight hours, we still arrived in LA the same day at noon! It ' s like we went back in time!",#Person1# tells #Person2# to set the clock forward which is a convention to take better advantage of the daylight due to their position on the earth. #Person1# also helps #Person2# understand the time zone and time difference.,210,37,0.1762
scientific_lay_summarisation-elife-norm,"The innervation of the mammary gland is controlled by brain-derived neurotrophic factor (BDNF), and sexually dimorphic sequestering of BDNF by the truncated form of TrkB (TrkB. T1) directs male-specific axonal pruning in mice. It is unknown whether other cues modulate these processes. We detected specific, non-dimorphic, expression of Semaphorin family members in the mouse mammary gland, which signal through PlexinA4. PlexinA4 deletion in both female and male embryos caused developmental hyperinnervation of the gland, which could be reduced by genetic co-reduction of BDNF. Moreover, in males, PlexinA4 ablation delayed axonal pruning, independently of the initial levels of innervation. In support of this, in vitro reduction of BDNF induced axonal hypersensitivity to PlexinA4 signaling. Overall, our study shows that precise sensory innervation of the mammary gland is regulated by the balance between trophic and repulsive signaling. Upon inhibition of trophic signaling, these repulsive factors may promote axonal pruning. During development of the peripheral nervous system, specific neuronal connections are being established to ensure its proper function. Sensory neurons of the dorsal root ganglia (DRG) initially extend their axons toward their targets by responding to attractive and repulsive cues expressed in the extracellular environment along their trajectory (Kolodkin and Tessier-Lavigne, 2011). Once axons reach the targets, limiting amounts of neurotrophic factors control target innervation by regulating axonal growth, neuronal cell death, and pruning (Huang and Reichardt, 2001). Brain-derived neurotrophic factor (BDNF) acts as a survival factor for specific subsets of sensory neurons during development (Kirstein and Fariñas, 2002), and regulates mechanosensation (Carroll et al. , 1998). During early development of the mammary gland, BDNF is required to establish and maintain sensory innervation in both female and male embryos. In males only, at later stages of development, sequestering of BDNF by a truncated form of TrkB (TrkB. T1) results in elimination of the axons innervating the gland. This elimination is not blocked in the Bax knockout (KO), suggesting that it occurs through axonal pruning rather than cell death (Liu et al. , 2012). As a result, a sexually dimorphic pattern of mammary gland sensory innervations is formed. Whether other cues operate in concert with BDNF, both in females and males, is unknown. The Semaphorins belong to a large family of secreted and membrane-bound guidance cues. The 27 family members are divided into 8","Almost every action an animal can perform in its life will rely on its nervous system being wired correctly. Before the animal is born, nerve cells next to the spinal cord send out long fibers – called axons – to connect with different parts of its body. These nerves will help relay sensations to the brain. The ends of the nerve fibers follow trails of signals that guide them to the correct targets. When the axon arrives in the right place, it can receive further signals called neurotrophic factors. These signals keep the axon alive, but they are in short supply. Not every axon will receive the signal, and, without it, the nerve fiber dies back. This phenomenon, known as pruning, helps to make sure that nervous system",380,128,0.3368
dialogsum,"#Person1#: Are you interested in history? #Person2#: Yes, I am. I enjoyed studying it at school, though I had trouble remembering all the dates, so my teacher never gave me good marks. #Person1#: I love history, but I'Ve always thought that learning the reasons behind events is more important than remembering exactly when they happened. #Person2#: I wish you had been my history teacher! I might have got better marks! #Person1#: Some people say that history repeats itself. #Person2#: What does that mean? The same events never happen twice, do they? #Person1#: The idea is that the people and dates change, but the reason why things happen stay the same. #Person2#: I see. I think I'd agree with that statement. People often seem to make the same mistakes over and over again.",#Person1# says history repeats itself. #Person2# agrees with the statement because people often make the same mistakes over and over again.,132,21,0.1591
dialogsum,"#Person1#: Help! Help! #Person2#: What's the trouble, ma'am? #Person1#: I was taking a walk when a young man came at me from nowhere and snatched the bag off my hands and ran away. #Person2#: What did the young man look like? #Person1#: Well, he's young, tall and thin. #Person2#: To which direction did he run? #Person1#: Let me see. . . my right arm. . . oh, to the east.",#Person2# was robbed and she describes the robber's appearance and the running direction to #Person1#.,70,15,0.2143
scientific_lay_summarisation-elife-norm,"methylation (Bheda et al. , 2020; D' Urso et al. , 2016; Kundu et al. , 2007; Light et al. , 2010; Tan-Wong et al. , 2009). In mammals, interferon-induced transcriptional memory (Gialitakis et al. , 2010; Kamada et al. , 2018; Light et al. , 2013) and inflammation-induced Aim2 gene transcriptional memory (Naik et al. , 2017) also rely on chromatin structure and histone modifications. On the other hand, DNA demethylation has been observed to associate with transcriptional memory of the Tat gene during glucocorticoid induction (Thomassin et al. , 2001) and the IL2 gene during T cell activation (Murayama et al. , 2006), but whether DNA demethylation plays a causal role in transcriptional memory regulation remains unclear. In summary, transcriptional memory enhances the future response to a previously experienced stimulus, providing a mechanism for cells to adapt to environmental changes. Several critical and intriguing questions regarding transcriptional memory need to be explored. Why do only a small fraction of genes induced by the same stimuli exhibit transcriptional memory? What differentiates genes with or without transcriptional memory effects? What are the characteristics of epigenetic modules governing transcriptional memory? The proinflammatory cytokine TNF-α plays a vital role in the pathogenesis of chronic inflammatory diseases (Reimold, 2003; Schett et al. , 2013). TNF-α activates the transcription factor NF-κB, which is essential for inflammatory responses (Duh et al. , 1989; Lowenthal et al. , 1989; Osborn et al. , 1989; Taniguchi and Karin, 2018). Canonical NF-κB contains p65 and p50 and binds to genomic regions termed κB sites to activate target genes (Hayden and Ghosh, 2008; Sen and Baltimore, 1986; Zhang et al. , 2017). We previously reported that short-term TNF-α treatment activates the methylated IL32 gene in the absence of demethylation and that long-term TNF-α treatment induces DNA demethylation of the IL32 promoter and CpG island, which depends on p65 and TET enzymes (Zhao et al. , 2019). However, whether any NF-κB target gene exhibits transcriptional memory in response to TNF-α induction is unknown. By combining reporter assays and genome-wide analysis, we found that the proinflammatory cytokine TNF-α can induce transcriptional memory effects in several target genes. These genes are associated with p65 peaks induced by TNF-α treatment. Interestingly, these regions are heavily methylated in cells naïve to TNF-α signaling and","Genes are the instruction manuals of life and contain the information needed to build the building blocks that keep cells alive. To read these instructions, cells use specific signals that activate genes. The process, known as gene expression, is tightly controlled and for the most part, fairly stable. But gene expression can be modified in various ways. Epigenetics is a broad term for describing reversible changes made to genes to switch them on and off. Sometimes, certain genes even develop a kind of ‘transcriptional memory’ where over time, their expression is enhanced and speeds up with repeated activation signals. But this may also have harmful effects. For example, the signalling molecule called tumour necrosis factor α (TNF-α) is an essential part of the immune system. But it is",380,128,0.3368
scientific_lay_summarisation-elife-norm,"(Fox) family transcription factors are excellent candidates for establishing chromatin accessibility at chondrogenic enhancers. In the endoderm lineage, HNF3/FoxA binds closed chromatin at enhancers and makes these more accessible (Cirillo et al. , 2002). Foxd3 has been similarly proposed to establish chromatin accessibility in the early neural crest lineage (Lukoseviciute et al. , 2018). In mouse, loss of Foxc1 results in widespread cartilage and bone defects (Kume et al. , 1998), including impaired tracheal and rib cartilages (Hong et al. , 1999), loss of calvarial bone due to premature ossification (Rice et al. , 2003; Sun et al. , 2013; Vivatbutsiri et al. , 2008), syngnathia (Inman et al. , 2013), and disruption of endochondral bone maturation (Yoshida et al. , 2015). In zebrafish, loss of both Foxc1 paralogs (foxc1a and foxc1b) results in severe reductions of dorsal cartilages of the upper face, which are preceded by reduced expression of several Sox9 targets, including col2a1a, acana, matn1, and matn4 (Xu et al. , 2018). Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) using a Sox9 antibody in dissected mouse rib and nose cartilage revealed enrichment of Fox binding motifs within Sox9-bound cis-regulatory sequences near chondrogenic genes (Ohba et al. , 2015). Here, we use profiling of chromatin accessibility in wild-type and mutant zebrafish facial cartilages and find that Foxc1 paralogs are required for accessibility and activity of a number of cartilage enhancers. These findings support a model in which Foxc1 promotes chondrogenesis by establishing selective accessibility of cartilage enhancers in CNCC-derived mesenchyme. In order to identify potential cis-regulatory elements important for facial cartilage development, we performed a genome-wide analysis of chromatin accessibility in chondrocytes from 72 hr post-fertilization (hpf) zebrafish. We labeled chondrocytes by co-expression of sox10: Dsred and col2a1a: GFP transgenes (1A) and isolated double-positive and control double-negative cells by fluorescence-activated cell sorting (FACS). We then subjected these cells to a modified ‘micro’ version of the assay for transposase-accessible chromatin followed by next-generation sequencing (µATACseq). In order to focus on potential distal cis-regulatory elements, we excluded accessible regions within 1 kb upstream or 0. 5 kb downstream of transcription start sites. This analysis yielded 33,679 distal accessible elements, with 5736 elements over-enriched in chondrocytes and 8955 elements under-enriched in chondrocytes (1B, C). As confirmation of sequence quality, the cartilage-specific R2","Animals with backbones (or vertebrates) have body shape determined, in part, by their skeletons. These emerge in the embryo in the form of cartilage structures that will then get replaced by bone during development. The neural crest is a group of embryonic cells that can become different tissues. In the head, it forms the cartilage scaffold for some of the facial bones and the base of the skull. During this process, a protein called Sox9 is required for neural crest cells to morph into cartilage. This transcription factor binds to regulatory sequences in the genome to turn cartilage genes on. But Sox9 is also required to form non-cartilage tissues in organs such as the liver, lung, and kidneys. How, then, does Sox9 only turn on the genes required",380,128,0.3368
pubmed-summarization,"and human coronary artery wall using mri , thus , potentially directing vivo mr vessel wall imaging techniques for characterizing coronary atherosclerotic plaques . initially , to derive optimal protocol for ex vivo coronary artery wall imaging , 10 fresh porcine hearts ( weighted from 500 g to 750 g ) were prospectively studied with mri on the day of explanation . , the heart was flushed with water to clear clots within the chambers and coronary arteries , and then , a three - way tube was inserted into the left main coronary artery through the left coronary sinus and fixed in order to inject the contrast . to null the lumen and improve the contrast between the wall and lumen , 20 ml of diluted mri contrast medium containing iron - oxide particles ferucarbotran ( resovist , spio , bayer schering pharma , berlin , germany ) was injected into the lad via the three - way tube , mimicking black blood technique . the optimal proportion of mr contrast agent and saline solution was 1% vs. 99% ( 17 ) . the porcine heart was imaged by using the signa 1.5 t hd mr scanner ( ge medical systems ) . to investigate optimal coronary vessel wall delineation , three different surface coils were respectively used as described in table 1 ( temporomandibular surface coil , eight - channel head surface coil and knee coil ) . the 3-planar imaging was used for the localization and 3d steady state free precession ( ssfp ) sequence was used to delineate lad with repeat time ( tr ) 7.5 ms , echo time ( te ) 3.1 ms , field of view ( fov ) 12 12 cm , slice thickness 3.0 mm , slice space 1.5 mm , matrix 256 192 , number of excitations ( nex ) 1 ( . , 10 ml saline solution was injected into the left coronary artery via a three - way tube . then , 2d spin - echo t1-weighted image ( t1wi ) with fat saturation was performed respectively with temporomandibular surface coil , eight - channel head surface coil and knee coil using the same parameters ( tr 440 ms , te 21 ms , fov 12 9 cm","objectiveto optimize the mr imaging protocol for coronary arterial wall depiction in vitro and characterize the coronary atherosclerotic plaques.materials and methodsmri examination was prospectively performed in ten porcine hearts in order to optimize the mr imaging protocol . various surface coils were used for coronary arterial wall imaging with the same parameters . then , the image parameters were further optimized for high - resolution coronary wall imaging . the signal - noise ratio ( snr ) and contrast - noise ratio ( cnr ) of images were measured . finally , 8 human cadaver hearts with coronary atherosclerotic plaques were prospectively performed with mri examination using optimized protocol in order to characterize the coronary atherosclerotic plaques.resultsthe snr and cnr of mr image with temporomandibular coil were the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"N-myristoylation is a ubiquitous class of protein lipidation across eukaryotes and N-myristoyl transferase (NMT) has been proposed as an attractive drug target in several pathogens. Myristoylation often primes for subsequent palmitoylation and stable membrane attachment, however, growing evidence suggests additional regulatory roles for myristoylation on proteins. Here we describe the myristoylated proteome of Toxoplasma gondii using chemoproteomic methods and show that a small-molecule NMT inhibitor developed against related Plasmodium spp. is also functional in Toxoplasma. We identify myristoylation on a transmembrane protein, the microneme protein 7 (MIC7), which enters the secretory pathway in an unconventional fashion with the myristoylated N-terminus facing the lumen of the micronemes. MIC7 and its myristoylation play a crucial role in the initial steps of invasion, likely during the interaction with and penetration of the host cell. Myristoylation of secreted eukaryotic proteins represents a substantial expansion of the functional repertoire of this co-translational modification. Toxoplasmosis currently affects approximately one third of the world’s population (Robert-Gangneux and Dardé, 2012). It is caused by the obligate protozoan parasite Toxoplasma gondii originating from the phylum Apicomplexa. While the majority of human infections are asymptomatic, the disease manifests its severity in immunocompromised individuals, such as those receiving chemotherapy and transplants or in HIV/AIDS patients (Montoya and Liesenfeld, 2004). Key steps in the successful propagation of Toxoplasma infection in the acute phase are orchestrated cycles of invasion and egress of tachyzoites from host cells (Black and Boothroyd, 2000). These crucial processes are regulated by several post-translational modifications (PTMs), such as phosphorylation (Gaji et al. , 2015; Jacot and Soldati-Favre, 2012; Lourido et al. , 2010; Treeck et al. , 2014), ubiquitination (Silmon de Monerri et al. , 2015), and also protein lipidation, such as palmitoylation and myristoylation (Alonso et al. , 2012; Frénal et al. , 2014). While the extent of protein palmitoylation in Toxoplasma has been investigated (Caballero et al. , 2016; Foe et al. , 2015), the myristoylated proteome remains largely uncharacterised. N-myristoylation is an irreversible, predominantly co-translational covalent addition of myristic acid to an N-terminal glycine (Boutin, 1997; Gordon et al. , 1991). Functionally, myristoylation often primes proteins for subsequent palmitoylation and a stable protein-membrane association (Martin et al. , 2011; Wright et al. , 2010), however, it has also been shown to facilitate protein-protein interactions (PPIs) (Chow","A microscopic parasite known as Toxoplasma gondii infects around 30% of the human population. Most infections remain asymptomatic, but in people with a compromised immune system, developing fetuses and people infected with particular virulent strains of the parasite, infection can be fatal. T. gondii is closely related to other parasites that also infect humans, including the one that causes malaria. These parasites have complex lifecycles that involve successive rounds of invading the cells of their hosts, growing and then exiting these cells. Signaling proteins found at specific locations within parasite cells regulate the ability of the parasites to interact with and invade host cells. Sometimes these signaling proteins are attached to membranes using lipid anchors, for example through a molecule called myristic acid. An enzyme called NMT can",380,128,0.3368
dialogsum,#Person1#: What kinds of things do you like to do? #Person2#: I've always liked to draw and paint. #Person1#: I didn't know you knew how to draw and paint. #Person2#: I do it every once in a while. #Person1#: How long have you known how to do that? #Person2#: I first learned how to do it in high school. #Person1#: Did you take some sort of art class or something? #Person2#: That was my favorite class. #Person1#: You have got to be talented. #Person2#: Thanks. #Person1#: If only I was talented. #Person2#: You have a talent. You just don't know what it is yet.,#Person2# has liked to draw and paint since hight school. #Person1# thinks #Person2# has a talent and wishes to have a talent too.,104,23,0.2212
pubmed-summarization,"from the supplementary material or web site of these articles . together with the newest data from ensembl , refseq , lncrnadb , gencode and the old versions of noncode data , literature data were processed through a standard pipeline for each species . all of the input data were processed into bed or gtf formats based on one assembly version , for example , hg38 for human and mm10 for mouse.combination . all of the normalized data files were combined together using the cuffcompare program in the cufinks suite ( 22 ) . after eliminating redundancy , every new transcript i d and the accompanying resources were extracted.filtering protein - coding rna . firstly , the rna was compared with the coding rna in refseq and ensembl , and the = and c transcripts were excluded . secondly , the rna was filtered through the coding - non - coding index ( cnci ) ( 23 ) program and only the rnas considered non - coding by cnci were kept.information retrieval . we assigned each transcript a name according to the criterion of noncode v4 and extracted basic information such as location ( 24 ) , exons , length , assembly sequence , source , etc.advanced annotation . advanced annotations included expression profiles , predicted functions , conservation , disease information , etc . human expression profiles were collected from 16 tissues of the human bodymap 2.0 data ( ena archive : erp000546 ) and eight cell lines ( geo accession no . gse30554 ) , while mouse data was collected from six different tissues ( ena archive : erp000591 ) . functions for the lncrna genes were predicted by lnc - gfp ( 25 ) , a coding non - coding co - expression network ( 26,27 ) based global function predictor.web presence . more annotation information has been added and a more user - friendly interface has been introduced . all of the input data were processed into bed or gtf formats based on one assembly version , for example , hg38 for human and mm10 for mouse . all of the normalized data files were combined together using the cuffcompare program in the cufinks suite ( 22 ) . after eliminating redundancy , firstly , the","noncode ( ) is an interactive database that aims to present the most complete collection and annotation of non - coding rnas , especially long non - coding rnas ( lncrnas ) . the recently reduced cost of rna sequencing has produced an explosion of newly identified data . revolutionary third - generation sequencing methods have also contributed to more accurate annotations . accumulative experimental data also provides more comprehensive knowledge of lncrna functions . in this update , noncode has added six new species , bringing the total to 16 species altogether . the lncrnas in noncode have increased from 210 831 to 527,336 . for human and mouse , the lncrna numbers are 167,150 and 130,558 , respectively . noncode 2016 has also introduced three important",380,128,0.3368
dialogsum,"#Person1#: How is everything going with your girlfriend? #Person2#: Didn't I tell you? It's over! #Person1#: Oh, I am sorry to hear that. I did't know that you had split up. What happened? #Person2#: It was a few things. The first thing that happened was that we were supposed to go out for a romantic dinner for our one year anniversary, but she stood me up! #Person1#: Really! Did she tell you why she didn't show up? #Person2#: No, but I ended up finding out later that night when I saw her drinking with another man at a club near my home! #Person1#: What was she thinking? Did you confront her about it when you saw her? #Person2#: I wanted to, but I knew that if I spoke to her, I'd just blow up at her, so I decided to just go home. I called her later that the night, but she didn't answer the phone. #Person1#: I can't believe she would do that to you. It's so dishonest-and rude! #Person2#: I know. I still haven't heard from her. The good thing is that I'm so angry with her that I don't feel sad about not having her around. #Person1#: I bet you that she regrets what she's done. You are such a good catch! She really lost out, didn't she? #Person2#: I guess so. #Person1#: So I don't think you'll have a problem finding another girlfriend. There are plenty of fish in the sea!",#Person2# split up with his girlfriend because his girlfriend stood him up and drank with another man on their anniversary. #Person1# thinks his girlfriend will regret and #Person2# will find another girlfriend.,245,32,0.1306
dialogsum,"#Person1#: Hi, I'm Mike. I just moved in next door. #Person2#: Oh hi, come on in. I'm Barbara. Would you like something to drink? #Person1#: Thanks, some tea would be nice. I really like your tea set. Where did you get it? #Person2#: Oh, there is a supermarket not far from here. I bought it on sale. But there is also a teahouse around the corner. #Person1#: It's a nice neighborhood here. #Person2#: Yeah, you can get to the bus and the underground train stations within 10 minute's walk. There's a bookstore, a gym and many restaurants along the street. #Person1#: There's a gym nearby? I really want to go to a gym as soon as possible. #Person2#: Well. If you want, we can go together sometime. Actually I was thinking of going this afternoon. If you like, you can join me. #Person1#: That would be wonderful.",Mike moved into Barbara's next door and comes to visit Barbara. Barbara tells Mike about the neighborhood. They decide to go to the gym this afternoon.,147,26,0.1769
scientific_lay_summarisation-elife-norm,"The unfolded protein response (UPR) adjusts the cell’s protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α’s ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD’s MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1’s activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization. Protein-folding homeostasis is critical for proper cell function. Accordingly, cells evolved surveillance mechanisms to monitor protein-folding status and elicit adaptive responses to adjust protein-folding capacity according to need (Balchin et al. , 2016; Bukau et al. , 2006; Walter and Ron, 2011). In the endoplasmic reticulum (ER), where the majority of transmembrane and soluble secretory proteins fold and mature, protein-folding homeostasis is ensured by a network of signaling pathways collectively known as the unfolded protein response (UPR) (Walter and Ron, 2011). In metazoans, perturbations leading to the accumulation of mis- or unfolded proteins in the ER are recognized as ‘ER stress’ by three unique ER-resident UPR sensors, IRE1, PERK and ATF6 (Cox et al. , 1993; Cox and Walter, 1996; Harding et al. , 2000; Niwa et al. , 1999; Sidrauski and Walter, 1997; Tirasophon et al. , 2000; Walter and Ron, 2011; Yoshida et al. , 1998; Yoshida et al. , 2001). These sensors transmit information about the protein-folding status in the ER and drive gene expression programs that modulate both the protein-folding load and folding capacity of the ER. If ER stress remains unmitigated, the UPR induces pro-apoptotic pathways, thereby placing the network at the center life-or-death decisions that affect the progression of numerous diseases (Bi et al. , 2005; Feldman et al. , 2005; Lin et al. , 2007; Lu et al. , 2014; Vidal et al. , 2012; Walter and Ron, 2011; Zhang","Proteins are long string-like molecules that fold into specific three-dimensional shapes. Most proteins that a cell uses to communicate with its environment are folded within a part of the cell called the endoplasmic reticulum. Dedicated sensor proteins in this cellular compartment track this process to make sure that it continues to meet the cell’s demand for protein folding. If it cannot meet the demand, unfolded or poorly folded proteins build up, which stresses the cell. IRE1 is a sensor protein that detects stress in the endoplasmic reticulum. It is found in a range of organisms from yeast to humans, where it spans the membrane that encloses the endoplasmic reticulum. When unfolded proteins accumulate, IRE1 proteins come together and form so-called oligomers. The IRE1 oligomers then become active and",380,128,0.3368
pubmed-summarization,"helicobacter pylori have infected nearly half of the world s population . in the developing countries , more than 90% of adults are typically infected during their early childhood , and once acquired the infection would last for several decades ( 1 ) . helicobacter pylori infection is the main cause of gastritis and persistent chronic inflammation may lead to peptic ulcers or gastric cancer ( 2 - 4 ) . helicobacter pylori gastritis is associated with the expression of various cytokines and immune cells infiltration ( 1 ) . it is recently demonstrated that il-17 , il-8 and il-18 are associated with h. pylori - related gastritis diseases ( 5 - 7 ) . recently , it is found that il-17 , a pro - inflammatory cytokine that can recruit neutrophils by inducing the production of cxc chemokines , plays a vital role in the inflammatory response to the h. pylori - related diseases ( 8) . furthermore , it is also reported that il-17 , il-8 , and il-18 are important to maintain the chronic gastric inflammation in the mongolian gerbils model induced by the h. pylori ( 8 - 10 ) . considering that up - regulation of il-17 , il-8 and il-18 plays a crucial role in h. pylori infection , it was explored that the expression of il-17 , il-8 and il-18 in peripheral blood may be involved in the inflammatory response to h. pylori . the current study aimed to obtain evidence regarding the association between serum levels of il-17 , il-8 and il-18 and the stomach pathological changes induced by h. pylori infection in mongolian gerbils . three - week - old male specific pathogen - free mongolian gerbils were purchased from wenzhou medical university animal experiment center / china ( approximately 25 g ) . they were kept in polypropylene cages on saw dust bedding in groups of two per cage , and caged under a ld 12:12 cycle . the animals used in the current study were cared for according to the institutional guidelines . the experimental protocol was approved by the animal care and use committee of wenzhou medical university / china . the bacteria were cultivated in columbia agar ( oxoid england ) with 10% sheep blood ( wenzhou","background : persistent helicobacter pylori infection confers an increased risk for serious illnesses such as peptic ulcers and gastric cancer . various cytokines are involved in the regulation of inflammatory immune response in h. pylori - infected gastric mucosa.objectives:the current study aimed to obtain evidence regarding the association between il-17 , il-8 and il-18 expression in peripheral blood and h. pylori infection in mongolian gerbils.materials and methods : mongolian gerbils were inoculated with h. pylori by a metal stomach catheter . after sacrifice , their gastric mucosae were examined in macroscopic , histological and electron microscopy levels . in addition , enzyme linked immunosorbent assay ( elisa ) assay was performed on the il-17 , il-8 and il-18 cytokines in the blood samples.results:serum levels of il-17 , il-8",380,128,0.3368
dialogsum,"#Person1#: I lost my dog. Can you help me look for him? #Person2#: Yes, of course. When was the last time you saw him? #Person1#: I tide him up right here as I went to grab some coffee. When I came back outside, he was gone. #Person2#: OK, what does he look like? #Person1#: He's white with black spots He's around 40 pounds and has short hair. His name is Milo and he always comes when he's called. #Person2#: I'll take the streets going to the right and you take the streets going to the left. Meet me back in front of the coffee shop in 10 minutes. If we don't find him, we can take my car to look farther out. #Person1#: Do you think I should call the police? #Person2#: I doubt if they'll have time to help, but I don't think will need them. Look over there in that Park 2 blocks down. #Person1#: It's Milo! Quick! Let's run over there! #Person2#: Let's go.",#Person1# lost the dog and describes to #Person2# what it looks like. #Person2# helps to look for the dog.,167,19,0.1138
scientific_lay_summarisation-elife-norm,"et al. , 2008). This small cytoplasmic protein possesses an alpha-helical SNARE-binding domain known as the central helix (CH), which is broadly conserved among metazoa (Pabst et al. , 2000; Reim et al. , 2001; Bracher et al. , 2002; Chen et al. , 2002; Brose, 2008). The CH domain of mCpx1 is flanked on its N-terminus by a stable alpha helix called the accessory helix (AH) (Pabst et al. , 2000; Chen et al. , 2002), and this domain has subsequently been shown to play an inhibitory role in mammalian, fly, and nematode synapses (Xue et al. , 2007,2009; Yang et al. , 2010; Martin et al. , 2011; Cho et al. , 2014; Trimbuch et al. , 2014). However, the primary sequence of the AH domain is poorly conserved, and its secondary structure has only been investigated in rodent complexin. A wide variety of models for AH function have been proposed including direct binding to SNAREs or other proteins (Giraudo et al. , 2009; Lu et al. , 2010; Yang et al. , 2010; Kummel et al. , 2011; Bykhovskaia et al. , 2013; Cho et al. , 2014), electrostatic interactions with membranes (Trimbuch et al. , 2014), and direct effects on the CH and its SNARE binding through secondary structure interactions (Chen et al. , 2002). Do all of these mechanisms contribute to AH domain function? If the AH domain binds specifically to another protein, why is it so poorly conserved relative to the CH domain? To investigate the mechanism of AH action and its conservation across phylogeny, we examined the AH domain structure and function in the Caenorhabditis elegans mCpx1/2 ortholog CPX-1 using both in vitro and in vivo approaches. While worm and mouse AH domains are two of the most divergent among published complexin sequences, the two domains could be exchanged without impairing function in vivo. Further, the recombinant worm AH formed a highly stable alpha helix in solution similar to the mouse AH. Abolishing the hydrophobic character of the worm or mouse AH domain had little effect, whereas disrupting helix stability and invasion of helical structure into the CH severely impaired complexin inhibitory function. Moreover, replacing the AH with an artificial helical sequence fully restored inhibitory function. Remarkably, this sequence was functional despite large","The nervous system sends information around the body in the form of electrical signals that travel through cells called neurons. These signals cannot pass across the small gaps—called synapses—that separate neighboring neurons. Instead, when electrical signals reach the synapse, chemicals called neurotransmitters are released across the gap and trigger an electrical signal in the next neuron. Neurotransmitters are stored within neurons in small envelopes of membrane known as synaptic vesicles. They are released when the vesicles fuse with the membrane that surrounds the neuron. This fusion process must be tightly controlled to ensure that information is passed between the neurons at the right time. Complexin is a small protein that controls vesicle fusion by binding to a group of proteins called the SNARE complex. It contains two structured",380,128,0.3368
pubmed-summarization,"can be activated by a myriad of cellular stress stimuli such as heavy metals , organic solvents , uv and ionizing irradiation . once the cellular stress response is initiated two cytosolic regulatory units of nox , p47 , p67 , and the small g protein rac translocate to the membrane and associate with cytochrome b558 ( consisting of two subunits gp91phox ( nox2 ) and p22phox ) , which acts as a central docking site for complex formation . emerging evidence has linked nox enzymes to oxidative stress that may contribute to disease progression . the radicals generated from nox activation are capable of modulating various redox - sensitive signaling pathways involved in the activation of mitogen - activated protein kinases ( mapks ) and transcription factors ( nf-b ) causing regulation of nox activation to be complex . oxidative stress can be generated endogenously , as well as promoted exogenously by multiple environmental factors . uv is known to damage dna and other intracellular proteins through direct and indirect mechanisms . uv exists in three forms uva ( 400320 nm ) , uvb ( 320290 nm ) , and uvc ( 290100 nm ) . uva and uvb are the most biologically significant , with uvc being most absorbed by ozone . uv is known to directly induce the cross - linking of neighboring pyrimidines to form pyrimidine dimers in dna that result in mutagenic dna lesions . however , uv is known to promote ros generation that can damage a large number of intracellular proteins and can indirectly damage dna . high levels of ros are detrimental and can cause damage to various biomolecules , which include the fatty acid side chains of membrane lipids that form reactive organic products such as malondialdehyde and 4-hydroxynonenal , both of which can generate dna adducts and point mutations . lipid peroxidation not only affects dna stability , but can also alter lipid membrane proteins that are involved in signal transduction pathways to promote constitutive activation and downstream cellular proliferation . furthermore , previous studies have shown that products of lipid peroxidation served as intermediates in the activation of signaling pathways that involved phospholipase a2 and the mapk pathway , both associated with uv - induced carcinogenesis . although there","the formation of reactive oxygen species ( ros ) is a result of incomplete reduction of molecular oxygen during cellular metabolism . although ros has been shown to act as signaling molecules , it is known that these reactive molecules can act as prooxidants causing damage to dna , proteins , and lipids , which over time can lead to disease propagation and ultimately cell death . thus , restoring the protective antioxidant capacity of the cell has become an important target in therapeutic intervention . in addition , a clearer understanding of the disease stage and molecular events that contribute to ros generation during tumor promotion can lead to novel approaches to enhance target specificity in cancer progression . this paper will focus on not only the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"against these tags, permitting biochemical experiments. Fluorescent tags also facilitate imaging in unfixed tissue or live animals. The most commonly used method of in vivo protein tagging is to introduce a transgene that contains a cDNA with a terminal epitope tag sequence that is expressed using an exogenous promoter (Bischof et al. , 2013). Although this may permit the determination of the subcellular localization of the protein, it does not allow assessment of the native expression pattern. It may also affect the distribution and function of the protein, because the transgene is typically not expressed at the endogenous level. An alternative is to tag the genomic locus using a genomic transgene, rather than a cDNA, because native regulatory elements then control the expression patterns and levels (Venken et al. , 2008; Ejsmont et al. , 2009). This genomic transgene can be integrated by a site-specific integrase into a defined docking site to minimize chromosomal position effects on the expression of the transgene. The tagged genomic transgene allows the analysis of the spatial and temporal patterns of expression of the protein, but does not provide a means to alter the expression of the endogenous copy of the gene. Finally, the most effective and informative strategy is to tag genes in their endogenous locations (Venken et al. , 2011b). A large collection of such GFP tagged genes would permit numerous powerful genetic and biochemical applications in addition to determining expression patterns and protein distributions. These include efficient immunoprecipitations with anti-GFP nanoantibody followed by mass spectroscopy (Neumüller et al. , 2012), ChIP sequencing (Nègre et al. , 2011), iGFPi (Neumüller et al. , 2012) and deGradFP mediated protein degradation (Caussinus et al. , 2011; Urban et al. , 2014). To tag numerous endogenous genes in Drosophila, protein trapping methods were previously developed based on screening untargeted insertions of transposable elements carrying a protein trap cassette. The first such protein trap vectors used P-elements, piggyBacs and piggyBacs with an internal P-element sequence (Morin et al. , 2001; Buszczak et al. , 2007; Quiñones-Coello et al. , 2007; Aleksic et al. , 2009). Only a small percentage of the transpositions function as protein traps, because the insertion must be within the intron between two protein-coding exons, as well as being in the right orientation and","In the last few decades, technical advances in altering the genes of organisms have led to many discoveries about how genes work. For example, it is now possible to add a specific DNA sequence to a gene so that the protein it makes will carry a ‘tag’ that enables us to track it in cells. One such tag is called green fluorescent protein (GFP) and it is often used to study other proteins in living cells because it produces green fluorescence that can be detected under a microscope. It is labor intensive to add tags to individual genes, so this limits the number of proteins that can be studied in this way. In 2011, researchers developed a new method that can easily tag many genes in fruit flies.",380,128,0.3368
pubmed-summarization,"many people throughout the world live with a variety of clinical conditions , including stroke , spinal trauma , cerebral palsy , and multiple sclerosis . unfortunately , these conditions frequently present with motor deficits , which greatly reduce the quality of life for those affected . mental practice with motor imagery ( mi ) is currently considered a promising additional treatment to improve motor functions repetitive cognitive training exercise , during which the patient imagines performing a task or body movement without actual physical activity , has been shown to modulate the cerebral perfusion and neural activity in specific brain regions . interestingly , it has been suggested that the combination of robot - assisted training devices and brain - controlled limb assistive technology may help to induce neural plasticity , resulting in motor function improvement . despite recording noninvasively and on the same time scale as the sensorimotor control of the brain , more specifically , these signals are usually collected from multiple electrodes ( or channels ) , which are inevitably contaminated by the noise from biological , environmental , and instrumental origins . dimensionality reduction plays a key role in many fields of data analysis . using this method , data from a high - dimensional space can be represented by vectors in a reduced , low - dimensional space in order to simplify problems without degrading performance . one of the most popular dimensionality reduction methods is principle component analysis ( pca ) , which is theoretically guaranteed to discover the dimensionality of the subspace and produce a compact representation if the data is embedded in a linear subspace . in many real world problems , however , there is no evidence that the data is actually sampled from a linear subspace . various manifold learning techniques , including isomap , locally linear embedding ( lle ) , and laplacian eigenmaps , have been proposed to reduce the dimensionality of fixed training sets in ways that maximally preserve certain interpoint relationships . unfortunately , these methods do not generally provide a functional mapping between the high- and low - dimensional spaces that is valid both on and off the training data . spectral regression ( sr ) , based on regression and spectral graph analysis","motor imagery electroencephalography ( eeg ) has been successfully used in locomotor rehabilitation programs . while the noise - assisted multivariate empirical mode decomposition ( na - memd ) algorithm has been utilized to extract task - specific frequency bands from all channels in the same scale as the intrinsic mode functions ( imfs ) , identifying and extracting the specific imfs that contain significant information remain difficult . in this paper , a novel method has been developed to identify the information - bearing components in a low - dimensional subspace without prior knowledge . our method trains a gaussian mixture model ( gmm ) of the composite data , which is comprised of the imfs from both the original signal and noise , by employing kernel",380,128,0.3368
pubmed-summarization,"colon cancer develops as a result of the pathologic transformation of normal colonic epithelium to adenomatous polyp , which ultimately leads to invasive cancer . tumor induction and progression are characterized by accumulation of multiple genetic and epigenetic alterations , that confer a selective reproductive advantage to a clone , within a genetically unstable heterogeneous cell population . the survival and the expansion of the neoplastic cell clone are supported by the surrounding tissue that sustains and favours these conditions . tumor - associated stroma actively fuels the colon cancer progression . among the tumor - associated cells are endothelial cells and pericytes that form the neo - vasculature . in turn , the newly formed angiogenic blood vessels supply tumor cells with nutrients and oxygen . in addition , mesenchymal cells are present in the stroma at earlier tumor stages , suggesting a co - evolution between stromal and cancer cells that leads to clonal expansion and metastasis . chronic inflammation , such as inflammatory bowel disease may predispose to malignancy and tumor progression . the chronic inflammatory microenvironment consists of immune , inflammatory and stromal cells , all of which produce cytokines , growth factors and adhesion molecules that may sustain tumor growth , its progression and spreading . the cytokines and growth factors produced by cancer cells function to create optimal growth conditions within the tumor microenvironment , while cytokines secreted by stromal cells may influence the behaviour of malignant cells . pro - inflammatory cytokines ( il-6 , il-1 ) , growth factors ( such as vegf , tgf--1 , -2 , -3 ) and their cognate receptors either in cancer and in stromal cells , influence not only primary gene transcription , but activate several pathways that cooperate to the aberrant clone survival , tumor expansion and metastasis . in addition , alteration of microenvironmental factors induced by hypoxia , represents an hallmark of cancer progression . in this review , we discuss the role played by mirna in colon cancer initiation and progression , especially in the context of the synergism existing among hypoxic condition , expression of il-6 pro - inflammatory cytokine and up - regulation of vegfa165 . we report that this cooperation could act on the neoplastic cell , also by","the influence of the microenvironment through the various steps of cancer progression is signed by different cytokines and growth factors , that could directly affect cell proliferation and survival , either in cancer and stromal cells . in colon cancer progression , the cooperation between hypoxia , il-6 and vegf - a165 could regulate the dna repair capacity of the cell , whose impairment is the first step of colon cancer development . this cooperation redirects the activity of proteins involved in the metabolic shift and cell death , affecting the cell fate . the pathways triggered by micro environmental factors could modulate cancer - related gene transcription , affecting also small non coding mrna , micrornas . micrornas have emerged as key post - transcriptional regulators of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of transcription start site) with high, medium or low expression in S2 cells (data from [Cherbas et al. , 2011]). (D) Venn diagram showing overlap of the common regions from three biological replicates (S1-3-5) with two additional, independent biological replicates (A1 and A2) using a different Atro antibody (4H6). Only the peaks at the major chromosome arms (heterochromatin are excluded) are compared, and thus, only 1275 peaks are used in S1-3-5 for this analysis instead of 1377 peaks. (E) Example overlap of Atro ChIP-seq peaks at the engrailed (en) locus. Atro #1–3 are the triplicates Atro ChIP-seq data; IgG #1–3 are the corresponding IgG ChIP-seq controls for the Atro ChIP-seq data. Atro (4H6) #1–2 are the independent Atro ChIP replicates (shown in D). (F) Top 10 GO-term enrichment hits of the Atro ChIP-seq data. GO-term enrichments were done with PANTHER overrepresentation test with default parameters and Bonferroni correction (Mi et al. , 2016). : http: //dx. . org/10. 7554/eLife. 23084. 00310. 7554/eLife. 23084. 004Figure 1—source data 1. PANTHER GO-Term enrichment results (Mi et al. , 2016) for 1F. : http: //dx. . org/10. 7554/eLife. 23084. 00410. 7554/eLife. 23084. 005Figure 1—source data 2. Overlap of ChIP data sets with the three classes defined in PCA analysis of Atro peaks (modENCODE (downloaded from http: //intermine. modencode. org/) and CBP [Philip et al. , 2015]) for — 1B. : http: //dx. . org/10. 7554/eLife. 23084. 00510. 7554/eLife. 23084. 006Figure 1— 1. Principal component analysis of Atro peaks. (A) Score plot showing the first two components from principal component analysis using enrichment of all factors mapped by modENCODE (S2 cells) within Atro-binding regions. The Atro-binding regions are colored according to the three classes defined by hierarchical clustering. R2X values represent the fraction of the total variation explained by each component. (B) The mean scaled enrichment values for each factor withing the three classes. All factors with enrichment values below 0. 4 in all classes were excluded. : http: //dx. . org/10. 7554/eLife. 23084. 006 Trl was initially discovered to bind to the promoter of Ultrabithorax (Ubx) to activate transcription of Ubx in vitro (Biggin and Tjian, 1988). Trl is also required in transcriptional repression. This is supported by three pieces of evidence: First, Trl binds to Polycomb response elements, DNA sequences where Polycomb group","Cells with the same genetic information can look and behave differently to each other. This is because they can control the activity of their genes, changing the effects the genes have in the cell. Regulating genes in this way is important in allowing cells to adapt to their surroundings and to perform different tasks. Proteins called transcription factors control the activity of genes through other proteins called transcriptional co-activators and co-repressors. Atrophins are a group of co-repressors found in many animals including humans and fruit flies. Atrophins suppress the activity of certain genes, reducing the effects that they have in the cell. Losing Atrophin from cells can lead to severe diseases, but how Atrophin causes these effects is currently not well understood. Yeung et al. examined which genes",380,128,0.3368
pubmed-summarization,"term , to predict instances of genes that potentially could give rise to more than one protein . annotated protein coding genes were extracted from completely sequenced prokaryotic genomes in the genome database of ncbi . all alternative orfs , potentially encoding 100 amino acids or more , were extracted from each gene sequence using perl scripts and the bioperl application programming interface ( api ) ( 3 ) . using the standard genetic code , the in silico translated amino acid sequence of each alternative orf was searched for similarity in completely sequenced prokaryotic genomes ( 4 ) and for conserved domains and motifs using cdd ( 5 ) , pfam ( 6 ) , cog ( 7 ) , kog ( 8) , smart ( 9 ) and uniprot . ( 10 ) . hierarchical clustering using the software hcluster_sg developed as part of the treefam project ( 11 ) was used to build sequence families with the alternate orfs . blast e - values were normalized from 0 to 100 ( with 100 corresponding to e - value 0.0 ) . the resulting information was stored in a relational database built with microsoft sql server 2005 . release 1.0 ( september 2007 ) contains approximately 1.5 million annotated genes from 481 organisms and about 3 million alternate orfs . of these 942 856 ( 33% ) occur in frame 1 , 621 306 ( 21% ) in frame 2 , 322 284 ( 11% ) in frame 3 , 350 805 ( 12% ) in frame + 2 and 675 525 ( 23% ) in frame + 3 . the following are provided for each alternate orf sequence : ( i ) conserved domains and motifs including cdd ( 5 ) , pfam ( 6 ) , cog ( 7 ) , kog ( 8) , smart ( 9 ) and uniprot . ( 10 ) and ( ii ) blast results with annotated sequences in completely sequenced prokaryotic genomes and alternate orfs identified in alterorf . the cross genera conservation of some alternate orfs suggests that they might represent new protein families or domains and hierarchical clustering ( 11 ) was used to build sequence families from conserved alternate orfs . the alterorf database can be",alterorf is a searchable database that contains information regarding alternate open reading frames ( orfs ) for over 1.5 million genes in 481 prokaryotic genomes . the objective of the database is to provide a platform for improving genome annotation and to serve as an aid for the identification of prokaryotic genes that potentially encode proteins in more than one reading frame . the alterorf database can be accessed through a web interface at www.alterorf.cl,380,75,0.1974
dialogsum,"#Person1#: Would you like a piece of birthday cake? #Person2#: No, thanks, I'll pass. It looks very tempting though. #Person1#: I thought strawberry cake with cream cheese frosting was your favorite? #Person2#: It is. I'm on a diet and strawberry cream cheese cake is not on it. #Person1#: A diet? What for? You are in great shape. #Person2#: I went to the doctor the other day. My cholesterol is up. #Person1#: Oooo. This sounds serious. #Person2#: Not too serious. But he gave me a strict diet to help bring it down.",#Person2# refuses the cake for #Person2# is on a diet to control cholesterol.,91,13,0.1429
pubmed-summarization,"( 30.4% ) , 4042 ( 42% ) , 7182 ( 33.5% ) , 7576 ( 30.1% ) , 6034 ( 32.6% ) , 4063 ( 42.5% ) , 2524 ( 32.6% ) , and 235 ( 25.2% ) ; prevalence of anti - hbs antibody positivity was in turn 4456 ( 32.9% ) , 8345 ( 40.3% ) , 15162 ( 44.8%),12944 ( 42.5% ) , 12.497 ( 39.7% ) , 12.947 ( 43.9% ) , 8689 ( 51% ) , and 10687 ( 52.3% ) ; prevalence of anti - hiv antibody positivity was in turn 15 ( 0.1% ) , 56 ( 0.7% ) , 120 ( 0.6% ) , 127 ( 0.4% ) , 15 ( 0.05% ) , 16 ( 0.06% ) , 52 ( 0.3% ) , and 6 ( 1% ) ; prevalence of anti - hcv antibody positivity was in turn 181(1% ) , 388 ( 2.1% ) , 704 ( 2.2% ) , 559 ( 1.5% ) , 397 ( 1% ) , 349 ( 1.5% ) , 161 ( 1.9% ) , and 132 ( 0.7% ) ( table 2 ) . prevalence of chronic hepatitis b ( hbv ) virus infection shows variation among regions . in the world , africa and a part of asia are high endemic regions for hbsag ( 8% ) , whereas southern europe and north and south america ( except for some regions of amazon , brazil and peru ) are considered low endemic regions ( < 2% ) 6 . the most common way for transmission changes according to the endemicity of hbv infection . perinatal transmission is the primary way of transmission of hbv in high endemic regions , whereas sexual intercourse between high risk adults and shared needles among intravenous drug users are the main ways of transmission of hbv in low endemic regions 7 . moreover , prevalence of hbv and hcv carriers changes according to the age , socio - economic status and occupational groups . the incidence of hepatitis b defined by the world health organization for the european union countries is 1.49 per100000 people , whereas the incidence of hcv is 8.7 per 100000 people 8 . in the national studies on hbsag positivity , prevalence","distribution of hbv , hcv and hiv results of the inpatients or outpatients , who had been treated for various diagnoses in diyarbakr training and research hospital between 2005 and 2012 , among years was investigated.files of the patients , who had been treated as inpatient or outpatient 992 . to any diagnosis between 01/01/2005 and 31/12/2012 in the clinics or policlinics of diyarbakr 581 due training and research hospital , were retrospectively reviewed using patient file database . serum samples ( 235.534 for hbsag , 196.727 for anti - hbs antibody , 98.497 for hbeag , 97.417 for anti - hbe antibody , 225.483 for hcv and 138.923 for hiv ) of these patients , which had been processed in microbiology laboratory , were studied by chemiluminescence",380,128,0.3368
pubmed-summarization,"5 months and ks lesions regressed . the patient received 30 sessions of irradiation on the skin lesions resulting in complete regression . proliferation of spindle cells arranged in a whorled and fascicular pattern with slit - like spaces containing red blood cell extravasation ( hematoxylin and eosin40 ) follicular hyperplasia with prominent vascular proliferation , hyalinization and few tight concentric layers of lymphocytes , arranged in onion skin appearance ( hematoxylin and eosin100 ) castleman 's disease is divided into localized and multicentric type and histologically , almost the entire multicentric variants are pc type . the standard curative treatment of localized cd is surgical excision with a 5-year survival rate of 100% and excellent prognosis . additionally , corticosteroids , chemotherapic agents and radiation therapy are the other modalities for the treatment of mcd . in 2003 , boller et al . , reported simultaneous of mcd and ks in a 17-year - old patient after treatment with cyclosporine for nephropathy . in addition , de rosa et al . described a woman affected by mcd and complicated by ks . they discussed that mcd and ks might be presented in a same immunologically patient or ks was a consequence of immunosuppression . our patient shared many similarities to the previous literature reports and demonstrated mcd findings such as fever , anorexia , weight loss , peripheral and mediastinal lymphadenopathy , and also hepatosplenomegaly . he had simultaneously violaceous papules and plaques over both legs and the histopathology findings were consistent with co - existence of mcd and ks . notably , mcd has been reported in adults usually before age 30 and shows an association with hhv-8 and hiv infections . in contrast , our patient was a 77-year - old man and compared with the prior literature findings , he had hhv-8 and hiv - negative serology . co - incidence of mcd with ks in our case report can be interpreted that mcd may be complicated by ks or the latter is a manifestation of mcd . finally , mcd should be kept in mind as a differential diagnosis in a patient with ks . mcd should be kept in mind as a differential diagnosis in a patient with ks .","castleman 's disease ( cd ) or giant lymph node hyperplasia is a rare disorder that can be unicentric or multicentric . multicentric castleman 's disease ( mcd ) is manifested by generalized lymphadenopathy , hepatosplenomegaly , polyclonal hypergammaglobulinemia , hematological abnormality , and constitutional symptoms . human herpesvirus 8 ( hhv-8 ) infection is present in nearly 100% mcd associated with hiv-1 infection , but in about 50% of cases of hiv negative . herein , we report a 77-year - old man with systemic involvement and skin lesions on the anterior aspect of both legs in the previous site of saphenous vein angioplasty . co - existence of mcd with kaposi 's sarcoma ( ks ) led us to present this rare case .",376,126,0.3351
pubmed-summarization,"and had no history of exposure to known ototoxic drugs . all monkeys were treated in the same way ( e.g. , diet and cage status ) . they were maintained in individual cages in a controlled environment of 120 cm ( h ) 80 cm ( w ) 75 cm ( d ) . the front , roof , and walls were composed of organic glass , whereas the bottom of the cage was composed of metal net . the monkeys were routinely released into a semi - closed environment that had environmental enrichment objects , such as toys , branches and climbing materials , mirrors , and tvs , as well as other objects . in the abi surgical procedure , general anesthesia was induced via intramuscular injections of ketamine ( 15 mg / kg , gutian pharmaceutical co. , ltd . , china ) , midazolam ( 0.5 mg / kg , enhua pharmaceutical co. , ltd . , china ) and atropine ( 0.02 mg / kg , jinyao amino acid co. , ltd . , orotracheal intubation was performed after an intravenous ( iv ) injection of fentanyl ( 0.001 mg / kg , astrazeneca ltd . , uk ) and rocuronium ( 0.3 mg / kg , n.v . organon , the netherlands ) . lumbar puncture and urethral catheterization were performed prior to surgery . during the surgery , the electrocardiogram , blood pressure , pulse rate , spo2 , end - tidal carbon dioxide partial pressure and temperature were monitored . for the magnetic resonance imaging ( mri ) , computed tomography ( ct ) scanning , auditory brainstem response ( abr ) , electrical abr ( eabr ) or lumbar puncture , the monkeys were initially anesthetized with intramuscular ketamine ( 15 mg / kg ) , midazolam ( 0.5 mg / kg ) and atropine ( 0.02 mg / kg ) . all of these experiments were performed under iv propofol ( propoflo , abbott laboratories , usa ) anesthesia with an initial bolus of 1.5 mg / kg and a continuous infusion of 0.5 mgkgmin . the electrode pad was comprised by medical silicone , slightly elliptical , and measured 12 mm 4 mm 2 mm . the 24","background : the auditory brainstem implants ( abis ) have been used to treat deafness for patients with neurofibromatosis type 2 and nontumor patients . the lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device . this study aimed to establish an animal model of abi in adult rhesus macaque monkey ( macaca mulatta).methods : six adult rhesus macaque monkeys ( m. mulatta ) were included . under general anesthesia , a multichannel abi was implanted into the lateral recess of the fourth ventricle through the modified suboccipital - retrosigmoid ( rs ) approach . the electrical auditory brainstem response ( eabr ) waves were tested to ensure the optimal implant site . after the operation , the eabr and",380,128,0.3368
dialogsum,"#Person1#: What are the requirements to apply for the position? #Person2#: Your major must be computer. #Person1#: Do you think my educational background suits this position? #Person2#: Yes, I'm quite satisfied with your qualifications. #Person1#: Does this job require that new employees take any kind of training course? #Person2#: Generally speaking, training new members is usually necessary. We offer our new employees a one-week training course. #Person1#: Could you tell something about the job? #Person2#: Yes, of course. You will be responsible for the designing and developing new products and also be in charge of the evaluation of the software programs including complex software systems to ensure product features and operation complaints. #Person1#: Oh, I see. I believe I can do the job well.","#Person2# tells #Person1# the requirements to apply for a position, whether new employees need training, and what #Person1# needs to do in this position.",124,24,0.1935
dialogsum,"#Person1#: Hello? I would like to speak to Mr. Lee. #Person2#: This is Lee speaking. #Person1#: This is Linda, your old friend. #Person2#: Oh, how are you, Linda? I'm glad you called. #Person1#: Mr. Smith wrote to me that you were coming to our city. May I see you at your hotel right away? #Person2#: Please hold on a moment. I have to check my schedule. Yes, that's ail fight. #Person1#: Great. I'll be there in haft an hour. #Person2#: All right, I'll be expecting you. #Person1#: Oh, I almost forgot. What's your room number? #Person2#: It's the No. 311 on the second floor. Please call me if you can't find me. #Person1#: I'll do that. See you later.",Linda calls to Mr. Lee because she wants to visit Lee. Mr. Lee gladly agrees.,119,15,0.1261
scientific_lay_summarisation-elife-norm,"When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35: 01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35: 01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8+ T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B*35: 01 do not directly activate CD8+ T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8+ T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8+ T cell activation, mediated by the binding of empty HLA-I to CD8. The major histocompatibility complex class I (MHC-I) molecules play a crucial role in adaptive immune responses by presenting antigenic peptides to CD8+ T cells, which enables the immune system to detect transformed or infected cells that display peptides from foreign or mutated self-proteins. Peptides are an integral component of MHC-I molecules. In the MHC-I antigen presentation process, peptides are mainly produced in the cytosol by proteasome and then translocated to the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). Peptides are loaded to MHC-I peptide binding groove with the assistance of several ER chaperones, ERp57, calreticulin and tapasin. There are several quality control components to ensure that most cell surface MHC-I molecules are filled with optimal peptide. However, under certain pathophysiological conditions, MHC-I peptide-deficient or open conformers are also detected on the cell surface. Prior evidence suggests that peptide-deficient conformers of MHC-I molecules appear on the cell surface of activated lymphoid cells (Madrigal et al. , 1991; Schnabl et al. , 1990), TAP-deficient cells (Ljunggren et al. , 1990; Ortiz-Navarrete and Hämmerling, 1991) or EBV transformed B cells (Madrigal et al. , 1991). Although the presence of peptide-deficient conformers of MHC-I molecules on the cell surface under certain conditions is established, their functions are poorly understood. In the past few years, peptide-deficient conformers of MHC-I molecules of some allotypes have been shown to be","The immune system keeps tabs on everything that happens in our body, looking for potential signs of threat. To alert it to any problems, almost every cell produces specific proteins on its surface called human leukocyte antigens class I, or HLA-I for short. These HLA-I molecules are bound to small protein fragments called peptides that have been exported from within the cell and are presented to the cells of the immune system for scanning. When cells are healthy, the peptides all stem from normal proteins. But, if the cell has become infected or cancerous, it contains foreign or abnormal peptides. Some of the HLA-I molecules, however, are empty. These antigens are unstable, and their role is unclear. Now, Geng et al. investigated this further by studying blood samples",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and sentential boundaries are not cued by prosodic features or by the transitional probability between words. The neural responses on the time scales of phrases and sentences have been taken as strong evidence that the brain applies grammatical rules to group words into chunks (Ding et al. , 2017; Martin and Doumas, 2017). Challenging this rule-based chunking interpretation, it has been argued that neural responses at the phrasal and sentential rates may not reflect neural construction of multi-word chunks based on rules and can instead be explained by neural tracking of properties of individual words alone (Frank and Yang, 2018). In the English materials used in Ding et al. (2017), for example, all sentences have the same structure of adjective+noun+verb+noun, for example ‘new plans gave hope’. Therefore, neural activity tracking lexical properties, such as part of speech information or lexical semantic information that distinguishes objects and actions, may appear to track sentences and phrases. For example, neural activity tracking verbs will occur at the sentence rate, since there is one verb per sentence. Consistent with this lexical property model, it has been shown that apparent neural tracking of sentences could be observed if the neural response independently represents each word using multidimensional features learned by statistical analysis of large corpora (Frank and Yang, 2018). In other words, neural populations that are tuned to lexical features of individual words may show activity that apparently tracks sentence structures. Furthermore, it is well established that the neural response to a word depends on the context and the response amplitude is smaller if the word is semantically related to previous words (Kutas and Federmeier, 2011; Lau et al. , 2008). In general, words within the same sentence are more related than words from neighboring sentences. Therefore, for a context-dependent neural response, its amplitude is expected to be stronger at the beginning of a sentence, leading to apparent neural tracking of sentences. This model considers semantic relatedness between consecutive words, but it does not consider the sentence structure: Semantic relatedness is evaluated the same way within and across sentence boundaries. Apparent sentence tracking behavior is generated since words within a sentence are more closely related. The lexical property model and semantic relatedness model do not assume chunk-level representations and therefore provide different explanations for sentential/phrasal-rate","From digital personal assistants like Siri and Alexa to customer service chatbots, computers are slowly learning to talk to us. But as anyone who has interacted with them will appreciate, the results are often imperfect. Each time we speak or write, we use grammatical rules to combine words in a specific order. These rules enable us to produce new sentences that we have never seen or heard before, and to understand the sentences of others. But computer scientists adopt a different strategy when training computers to use language. Instead of grammar, they provide the computers with vast numbers of example sentences and phrases. The computers then use this input to calculate how likely for one word to follow another in a given context."" The sky is blue"" is",380,128,0.3368
dialogsum,"#Person1#: My goodness! What happened? You have blood on your face. #Person2#: Oh, don't worry. I just killed a pigeon. #Person1#: How could you have the heart to kill it ? We only have one! #Person2#: It spoiled my painting!",#Person2# tells #Person1# #Person2# killed a pigeon because it spoiled #Person2#'s painting.,40,12,0.3
scientific_lay_summarisation-elife-norm,"org/10. 7554/eLife. 02726. 003 To determine the single input response, the PFC neuronal response to VTA stimulation was first measured by recording Ca2+ transients. Most DA neurons are spontaneously active with firing patterns that range from regular tonic firing (1–5 Hz) to phasic firing (40–50 Hz) (Robinson et al. , 2004; Grace and Bunney, 1984a; Grace and Bunney, 1984b). In addition, salient events such as experiencing a novel environment or receiving a reward-associated signal, evoke phasic firing in the VTA (Schultz, 2007; Horvitz, 2000). The PFC activity evoked by VTA stimulation in these physiological ranges was therefore examined. When low frequency VTA microstimulation was used (1 Hz–10 Hz, tonic range), Ca2+ transients in the PFC neurons were evoked and decayed within 5 s. This steep increase and short decay is comparable with the reported response to sensory input observed in cortical neurons of anesthetized animals (Ohki et al. , 2005). In contrast, high frequency VTA stimulation (40–50 Hz, phasic range) evoked substantially elongated Ca2+ transients that lasted 20–30 s and then returned to the original baseline (). In addition, these Ca2+ transients of the PFC neurons reached a peak relatively slowly, 6–7 s after stimulation. Furthermore, high frequency VTA stimulation robustly evoked Ca2+ transients in all tested animals, whereas low frequency VTA stimulation did not as only about half of the animals tested showed detectable Ca2+ transients in the PFC. Importantly, these long-lasting Ca2+ transients were only detected in awake and not in anesthetized mice (1E, F), possibly because of the potential inhibition of voltage-gated calcium channels by isoflurane (Herring et al. , 2009; Study, 1994). This result highlights the advantage of a system using awake animals to elucidate dopamine regulation of neuronal responses in the PFC. 10. 7554/eLife. 02726. 004Figure 2. Ca2+ transients in response to ventral tegmental area (VTA) stimulation. (A) The left panel shows the population average of Ca2+ transients across the cells of a single animal. The right panel shows the Ca2+ transients of each single neuron using a color map according to its dF/F value. A train of 10 pulses was applied at each frequency of VTA stimulation (1,5, 10,20,30,40, and 50 Hz). (B) Population average of Ca2+ transients across eight animals. VTA electrical stimulation was applied at the 30 s time point (red arrowhead).","Around 120 years ago, Ivan Pavlov unintentionally sparked a new field of psychology research. He did so by noting that his dogs had learned to associate the sound of the bell that he rang before feeding them with the food itself, such that they would salivate upon hearing the bell even when there was no food present. This form of learning—now known as associative learning—has since been demonstrated in species from honeybees to humans. For the brain to associate two events, such as the sound of a bell and the delivery of food, it must encode the first event and keep that information available or ‘on-line’ until the occurrence of the second event, at which point the two can be linked together. This process takes place in part",380,128,0.3368
dialogsum,"#Person1#: I have made up my mind. I am getting a tattoo. #Person2#: Really? Are you sure? #Person1#: Yeah! Why not? They are trendy and look great! I want to get a dragon on my arm or maybe a tiger on my back. #Person2#: Yeah but, it is something that you will have forever! They use indelible ink that can only be removed with laser treatment. On top of all that, I have heard it hurts a lot! #Person1#: Really? #Person2#: Of course! They use this machine with a needle that pokes your skin and inserts the ink. #Person1#: Oh, I didn't know that! I thought they just paint it on your skin or something. #Person2#: I think you should reconsider and do some more research about tattoos. Also, find out where the nearest tattoo parlor is and make sure they used sterilized needles, and that the place is hygienic. #Person1#: Maybe I should just get a tongue piercing!",#Person1# wants to get a tattoo but #Person2# suggests #Person1# reconsider it because it hurts a lot and a tattoo is hard to be removed.,159,25,0.1572
dialogsum,#Person1#: The country is strong only in appearance. Don't you think so? #Person2#: Yes. In fact there are quite a large number of people who have no food to eat and no place to live in. #Person1#: You can say that again. The government must open it's eyes to the fact.,#Person1# and #Person2# agree that this country is strong only in appearance.,51,12,0.2353
pubmed-summarization,"consciousness and orientation to person , location , and time . at discharge , vital parameters were stable with pulse of 86 bpm and bp of 130/80 mm hg . in our case , addition of antibiotic linezolid ( 600 mg twice daily ) for the treatment of acute onset pneumonia in a patient receiving serotonergic antidepressant , escitalopram ( 10 mg / day ) for depressive disorder since 2 months , temporally led to the constellation of the neurological and mental state features in the absence of other cns pathology led to the diagnosis of ss . we ruled out the possibility of other drug interactions , as none of them ( paracetamol , etophylline , guaiphenesin , ambroxol ) possess either adrenergic or serotonergic properties supplemented by literature search . linezolid is a totally synthetic compound that was initially synthesized as a reversible maoi class antidepressant . due to its weak , nonspecific mao inhibition , concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine ( > 100 mg / day ) may increase the risk of ss . it is believed to act through early inhibition of protein synthesis via binding to the 23s portion of the 50s ribosomal bacterial rrna subunit inducing conformational structural changes and preventing trna to enter and functionally bind to the ribosome therefore inhibiting mrna translation . its oral bioavailability is nearly equal to intravenous administration , with plasma half - life of 4 - 6 h. peak serum concentrations attain about 20 mcg / ml on 600 mg twice daily dosing in adults . linezolid is metabolized via oxidation procedure in a way independent of cytochrome p450 ( cyp-450 ) ; consequently there is no possible pharmacokinetic mechanism of interaction between linezolid and other medication metabolized through cyp450 pathways . although 80% of the dose of linezolid appears in the urine , dose modification has not been currently recommended in renal insufficiency as serum concentrations and half - life of the drug are not appreciably affected . however , linezolid and its breakdown products are eliminated by dialysis ; the drug should be administered after hemodialysis . linezolid is generally well - tolerated , with some minor side - effects like gastrointestinal disturbances , headache , and rashes .","linezolid is a synthetic antimicrobial agent of the oxazolidinone class with weak , nonspecific inhibitor of monoamine oxidase enzymes . concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine ( > 100 mg / day ) may induce serotonin syndrome ( ss ) . we present a case report of near - fatal adverse interaction between linezolid and escitalopram inducing ss in a 65-year - old woman with sepsis , under empirical antibiotic treatment . this report also summarizes the current relevant literature as identified via pubmed , embase , and psycinfo , supplemented with a manual search of cross references .",380,104,0.2737
scientific_lay_summarisation-elife-norm,"For example immune cells utilize adhesion-independent migration during tissue surveillance (Lammermann et al. , 2008), while endothelial cells utilize polymerization-driven protrusion during angiogenesis (Lamalice et al. , 2007). Recent evidence indicates that physical confinement in a non-adhesive environment may drive a change of migration modes. In particular, contractility and extracellular pressure can drive a switch from polymerization/adhesion-based to bleb/friction-based motilities known as the mesenchymal-to-amoeboid transition (MAT) (Bergert et al. , 2015; Liu et al. , 2015; Ruprecht et al. , 2015). Cancer cells are known to be highly contractile, making them prone to blebbing (Bergert et al. , 2012), while tumors are known to be sites of high turgor pressure (Jain, 1987), both properties being conducive to MAT. Indeed, intravital imaging revealed that melanoma and breast cancer cells migrate by blebbing in live mice (Tozluoglu et al. , 2013). Thus, metastatic cancer cells are hypothesized to be susceptible to MAT in vivo, with the plasticity of their migration modes and lack of specificity in adhesion contributing to their high invasivity and difficulty targeting (Lammermann and Sixt, 2009). Polymerization-driven mesenchymal migration and bleb-based amoeboid migration are mechanistically distinct. In mesenchymal migration, actin polymerization initiated by localized activation of a filament-nucleating factor drives the formation of actin networks or bundles that mediate lamellipodial or filopodial membrane protrusion (Skau and Waterman, 2015). In contrast, in blebbing cells, membrane protrusion is mediated by myosin II contractility-induced hydrostatic pressure that drives a bubbling-out of the plasma membrane at a site of local weakness in the cortical actin cytoskeleton (Charras et al. , 2005; Charras and Paluch, 2008). While the molecular mechanisms mediating polymerization-based protrusion and contractility-induced pressure are reasonably well understood, the molecules responsible for local changes in the actin cortex that allow bleb formation are not known. It is hypothesized that blebs could form either by local down-regulation of membrane-cytoskeleton linkers such as those of the ezrin/radixin/moesin family (Estecha et al. , 2009; Lorentzen et al. , 2011), or by local weakening of sites in the cortical actin network itself (Charras et al. , 2006). Indeed, experiments using actin depolymerizing drugs have shown cortex integrity to be an important factor in regulating blebbing (Charras et al. , 2006). Local inhomogeneity in cortical integrity could be mediated by regulation of actin filament number or organization.","Cells within an animal have to be able to move both during development and later stages of life. For example, white blood cells have to move around the body and into tissues to fight off infections. Normally, cell movement is heavily controlled and will only happen when it is necessary to keep an animal healthy. However, cancer cells can bypass these controls and ‘metastasize’, or spread to new sites in the body. Cells can move in several different ways: on the one hand, cells can use ‘mesenchymal’ movement, in which the skeleton-like scaffolding of molecules within a cell rearranges to push the cell forward. On the other hand, cells can employ ‘amoeboid’ movement, in which they squeeze their way forward by building up pressure in the cell. Although",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance. All procedures were approved by the Weizmann Institute IACUC. Five male C57BL/6 mice aged 8-12 weeks at the start were used in this study. Mice were housed with 1-4 cage-mates in cages with running wheels, and underwent two surgical procedures under isoflurane anesthesia (1. 5-2% volume). First, we injected into the CA1,400 nL of the viral vector AAV2/5-CaMKIIα-GCaMP6s or AAV2/5-CaMKIIα-GCaMP6f (~2 × 1013 particles per ml, packed by University of North Carolina Vector Core) (Chen et al. , 2013). Stereotatic coordinates were: -1. 9 mm anterio-posterior, -1. 4 mm mediolateral, -1. 6 mm dorsoventral from bregma. The second surgery, which took place at least one week after the viral injection, was the implantation of a glass guide tube directly above the CA1. We used a trephine drill to remove a circular part of the skull centered posterio-lateral to the viral injection site. We removed the dura and cortex above the CA1 by suction with a 29 gauge blunt needle while constantly washing the exposed tissue with sterile PBS. We then implanted an optical guide tube with its window just dorsal to, but not within, area CA1, and sealed the space between the skull and guide tube using 1. 5% agarose in PBS. The exposed areas of the skull were then sealed with Metabond (Parkell, Edgewood, NY) and dental acrylic. For time-lapse imaging in freely behaving mice using an integrated miniature","The ability to recall the timing of events is an important feature of long-term memory. Episodic memory, the mental account of “what” happened, “where” and “when”, depends on a region of a brain called the hippocampus. Certain neurons in the hippocampus, called place-cells, are known to capture information about the locations an animal has visited so that a specific pattern of place cell activity marks each location an animal visits. However, it is not clear how the brain can mark the relationship between the timing of different events. Some studies have documented gradual changes in the activity patterns of the place cells over time, which could help mark time. If these changes are specific to a particular environment then they would not allow animals to associate in memory",380,128,0.3368
scientific_lay_summarisation-elife-norm,"focus on the homologous adhesion proteins α-catenin (Kobielak and Fuchs, 2004) and vinculin (Ziegler et al. , 2006), which are major ABP components found in adherens junctions (α-catenin and vinculin) and focal adhesions (vinculin) that are critical for the force-dependent strengthening of cellular adhesion and mechanotransduction (Dumbauld et al. , 2013; Yonemura et al. , 2010). Vinculin is a strictly auto-inhibited globular protein that must engage with multiple adhesion partners to be activated and bind F-actin (Johnson and Craig, 1995), stabilizing adhesion through incompletely defined mechanisms. On the other hand, α-catenin exists in two distinct populations maintained in dynamic equilibrium in the cell (Drees et al. , 2005). It serves as a central component of the membrane-anchored heterotrimeric α-catenin–β-catenin–cadherin complex (the ‘cadherin-catenin complex’) at adherens junctions, which lacks F-actin-binding activity in traditional assays when isolated (Yamada et al. , 2005). It also forms a soluble homodimer with constitutive modest F-actin-binding activity, thought to play a role in the generation and maintenance of actin bundles by cross-linking filaments and inhibiting ARP2/3 binding, thereby suppressing branched-actin formation (Drees et al. , 2005). The structural mechanisms by which forces transmitted through the actin cytoskeleton modulate the complex networks of binding interactions formed by α-catenin and vinculin during adhesion maturation remain unknown. Both proteins are entirely α-helical (Bakolitsa et al. , 2004; Rangarajan and Izard, 2013) and are composed of a large N-terminal ‘head’ domain, which engages in protein-protein interactions with other adhesion molecules (Kobielak and Fuchs, 2004; Ziegler et al. , 2006) and a smaller C-terminal 5-helix bundle F-actin binding ‘tail’ domain (Bakolitsa et al. , 1999; Ishiyama et al. , 2013; — 1, Helices H1–H5), connected by a flexible linker. The isolated actin-binding domains (ABDs), which we utilize in our study, retain their structures and actin-binding activities (Bakolitsa et al. , 1999; Ishiyama et al. , 2013), engaging a similar site on the filament surface (Hansen et al. , 2013; Janssen et al. , 2006; Kim et al. , 2016; Thompson et al. , 2014). Recent single-molecule force-spectroscopy studies reported that both α-catenin in the cadherin-catenin complex (Buckley et al. , 2014) and vinculin (Huang et al. , 2017) form catch bonds with F-actin, characterized by increased bond lifetime when moderate forces around 10 pN are applied across the ABP-actin interface. These","All of the cells in our bodies rely on cues from their surrounding environment to alter their behavior. As well sending each other chemical signals, such as hormones, cells can also detect pressure and physical forces applied by the cells around them. These physical interactions are coordinated by a network of proteins called the cytoskeleton, which provide the internal scaffold that maintains a cell’s shape. However, it is not well understood how forces transmitted through the cytoskeleton are converted into mechanical signals that control cell behavior. The cytoskeleton is primarily made up protein filaments called actin, which are frequently under tension from external and internal forces that push and pull on the cell. Many proteins bind directly to actin, including adhesion proteins that allow the cell to ‘stick’",380,128,0.3368
dialogsum,"#Person1#: Why don't we get you some shirts? #Person2#: I want to leave. We've already been here two hours. #Person1#: But we should get you some shirts while we're here. You need summer shirts. #Person2#: I would rather buy them somewhere else. #Person1#: Why? They have everything here. #Person2#: I don't like shopping in malls. I like shopping on the street. There is more variety. #Person1#: Let's just look and see what they have. #Person2#: Alright. #Person1#: What about these shirts? Do you see anything you like? #Person2#: The styles here are too boring for me. I told you. I like street shopping. #Person1#: Oh, come on! Don't be so sour. These are beautiful shirts. I know if we don't buy some today, you will never go shopping by yourself. #Person2#: Sure I would. #Person1#: Here. Look at this shirt. Try it on. #Person2#: Do they have it in LARGE. #Person1#: I don't know. Let me look on the rack. Here is one. LARGE. Try it on. #Person2#: Where is the fitting room? I don't see it. #Person1#: The fitting rooms are over there. #Person2#: Okay, I will try it on. #Person1#: It looks good on you. #Person2#: I look like a nerd. #Person1#: No, it looks great. Why are you always like this when you're shopping? You know it looks good. #Person2#: Well, I don't think it's the best style for me. #Person1#: I think we'll buy this one. And I want you to try on this one too. #Person2#: Alright. Alright. #Person1#: You should be happy I want you to look good. If I let you shop for yourself, you would never buy anything. #Person2#: Yes, maybe. But I like street shopping. There is more variety. I'm sorry. I just don't like malls.","#Person1# wants to buy shirts for #Person2# in the malls and asks #Person2# to try on some, but #Person2# keeps thinking they make him look no good because #Person2# prefers street shopping.",295,32,0.1085
dialogsum,"#Person1#: Here you are at last! You're half an hour late, you know. #Person2#: I'm awfully sorry to have kept you waiting for so long. #Person1#: What happened? #Person2#: My watch stopped and I didn't know. I certainly need to buy a better one.",#Person2# tells #Person1# #Person2# is late because of #Person2#'s stopped watch.,44,11,0.25
dialogsum,"#Person1#: Hi, where will you go? #Person2#: I will go to the bookstore. #Person1#: What book actually do you look for? #Person2#: I look for an English grammar book written by Batties Simon. #Person1#: Why do you want to buy a grammar book? #Person2#: I will go to America next year, so I should study English well. #Person1#: May I come with you to the bookstore? #Person2#: Of course, you can. Will you also buy a book? #Person1#: Yes, I want to buy a novel. #Person2#: Do you like reading a novel? #Person1#: Of course. I have many novels in my house. #Person2#: Wow, that's very interesting. Let's go now.",#Person2# will go to the bookstore for an English grammar book and #Person1# will go together for a novel.,110,19,0.1727
dialogsum,"#Person1#: Hi, Jack. Long time no see! #Person2#: Yeah. How's everything going? #Person1#: Not bad. At least I am still alive. #Person2#: Just alive? I guess you are some lucky guy. I heard you are going out with Jane. #Person1#: Where did you get that idea? #Person2#: Oh, come on. Jane is a very nice girl, someone you meet only once till lifetime. #Person1#: You are right. I am not boasting, but she is really as beautiful as she is intelligent. #Person2#: Well, I really envy you for finding such a nice girl.",Jack envies that #Person1# should date with Jane who is a nice girl.,93,13,0.1398
scientific_lay_summarisation-elife-norm,"to be home to ~86,000 PWID (Ambekar et al. , 2019) with HIV prevalence ranging from 13. 5% to 35. 8% (Mehta et al. , 2015; Lucas et al. , 2015) and HCV prevalence ranging from 42. 4% to 90% (Solomon et al. , 2015; Solomon et al. , 2019a; Solomon et al. , 2019b). With the exception of index participants, all participants were recruited via a name generator network referral methodology. Participants completed a baseline assessment and were invited to complete semi-annual follow-up visits. This manuscript presents baseline data from this cohort. Recruitment of the cohort was initiated with two indexes in November 2017—eight more indexes were included later to account for variability in type of drug injected, marital status, and zip code of residence/injection. All 10 indexes were selected from a cross-sectional sample of PWID in New Delhi accrued for an evaluation assessment of a cluster-randomized trial (ClinicalTrials. gov Identifier: NCT01686750) (Solomon et al. , 2019b). When a participant enrolled in the Spatial Network Study, whether the initial 10 indexes or subsequent recruits, they were asked to recall the names of people with whom they injected in the prior month (regardless of whether they shared injection paraphernalia). In addition, they were asked to provide identifying information about each named network member (e. g. , scar on left hand, one finger missing on right hand) and a factoid about each named partner (e. g. , ‘his wife’s name is Priyanka’). Each participant was then provided with a referral card for each named injection partner and was asked to invite them to participate in the study. When these recruits visited the study site, their name and identifying information were compared against the information previously provided. If the information matched, they were enrolled and asked to name, describe, and recruit people with whom they injected in the prior month (recruit’s egocentric network and the index’s sociometric network). Recruitment continued until the desired sample size (~2500) was reached. Biometric data (fingerprint scans) was used to identify duplicates and establish cross-network linkages (if the same participant was recruited by two different participants). The fingerprint scans were converted to unique hexadecimal codes and stored as described previously (Solomon et al. , 2019b) —no images were stored. The eligibility criteria varied depending on if the","Understanding the social and spatial relationships that connect people is a key element to stop the spread of infectious diseases. These networks are particularly relevant to combat epidemics among populations that are hard to reach with public health interventions. Network-based approaches, for example, can help to stop HIV or hepatitis C from spreading amongst populations that use injectable drugs. Yet how social and geographic connections such as acquaintances, injection partners, or preferred drug use places impact the risk of infection is still poorly mapped out. To address this question, Clipman et al. focused on people who inject drugs in New Delhi, India, a population heavily impacted by HIV and hepatitis C. Over 2500 people were recruited, each participant inviting their injection partners to also take part. The volunteers",380,128,0.3368
dialogsum,"#Person1#: Wow, American football is more exciting than I thought. #Person2#: You're in America now, my British friend. We just call it football. #Person1#: Oh, right. So, I can't quite follow what's going on. . . who's winning? #Person2#: The Giants are up by three points because of the field goal they kicked, but the Redskins have the ball and there pretty close to the end zone. #Person1#: Wow! What a hit! #Person2#: Yeah, he tackled him so hard his helmet came off. #Person1#: Is he ok? #Person2#: It looks like it, he's getting up. #Person1#: I guess he hit him too hard ; the referee just called a penalty on the home team. #Person2#: The Giants? #Person1#: Yeah. #Person2#: Well, here we go again. #Person1#: What happened? Why did everyone get so quiet? #Person2#: The Redskin's quarterback just threw a touchdown pass for seven points. We're losing again.",#Person1# and #Person2# are watching a football game between the Giants and the Redskin. They take the Giants' side but finally the Redskin win by a touchdown pass.,149,28,0.1879
scientific_lay_summarisation-elife-norm,"Flows generated by ensembles of flagella are crucial to development, motility and sensing, but the mechanisms behind this striking coordination remain unclear. We present novel experiments in which two micropipette-held somatic cells of Volvox carteri, with distinct intrinsic beating frequencies, are studied by high-speed imaging as a function of their separation and orientation. Analysis of time series shows that the interflagellar coupling, constrained by lack of connections between cells to be hydrodynamical, exhibits a spatial dependence consistent with theory. At close spacings it produces robust synchrony for thousands of beats, while at increasing separations synchrony is degraded by stochastic processes. Manipulation of the relative flagellar orientation reveals in-phase and antiphase states, consistent with dynamical theories. Flagellar tracking with exquisite precision reveals waveform changes that result from hydrodynamic coupling. This study proves unequivocally that flagella coupled solely through a fluid can achieve robust synchrony despite differences in their intrinsic properties. Despite the elegance and apparent simplicity of the eukaryotic flagellum and its shorter ciliary version, the collective motions exhibited by groups of these organelles and the resultant fluid flows are far from trivial. For example, the unicellular biflagellate alga Chlamydomonas reinhardtii executes diffusive ‘run-and-turn’ locomotion (Goldstein et al. , 2009; Polin et al. , 2009) through stochastic switching between synchronized and unsynchronized swimming gaits—a process which could enhance searching efficiency and assist in the avoidance of predators (Stocker and Durham, 2009). Ensembles of cilia and flagella exhibit stunning temporal coordination, generating flows that transport mucus and expel pathogens (Button et al. , 2012), establish the left-right asymmetry in developing mammalian embryos (Nonaka et al. , 2002), and transport ova in human fallopian tubes (Lyons et al. , 2006). The origin of flagellar synchronization has been the subject of intense theoretical investigation for many decades. One of the earliest experimental results was Rothschild' s qualitative observation (Rothschild, 1949) that the flagella of bull spermatozoa tend to synchronize when they swim close to one another, coupled only through the fluid surrounding them. Much more recent observations of self-organised vortex arrays of swimming sea urchin spermatazoa near surfaces (Riedel et al. , 2005) provide further evidence for synchrony mediated purely by hydrodynamic coupling. Motivated by Rothschild' s observation, Taylor (Taylor, 1951) developed a mathematical model in which two laterally infinite, inextensible sheets with prescribed","Sperm cells, as well as many bacteria and algae, propel themselves using whip-like appendages called flagella. Similar, shorter structures called cilia are also found on the surface of many cells, where they perform roles such as moving liquids over the cell. Each cilium or flagellum beats at its own characteristic rhythm, but there are many situations where cilia or flagella must synchronize their beating with other nearby cells. For example, an egg cell is swept along the Fallopian tube by the coordinated beating of the cilia lining the tube. Bull sperm cells are also known to synchronize the beating of their flagella when swimming close to each other. It has been suggested that the movement of the fluid surrounding the beating flagella could be the source of this",380,128,0.3368
scientific_lay_summarisation-elife-norm,"depression and epilepsy. Despite great interest (Mueller et al. , 2014), the cellular influence of TMS has yet to be ascertained since the precise effects of TMS at the level of a single neuron are very difficult to gauge, particularly in humans. The neural architecture of the brain means the neural processes which receive and transform most synaptic inputs, the dendrites, extend into the upper layers where TMS would be most effective. Since dendrites can shape synaptic input to be greater or less than their linear sum (Polsky et al. , 2004; Losonczy and Magee, 2006; Larkum et al. , 2009) thereby altering the firing properties of the neuron (Larkum et al. , 1999), the active properties of dendrites have attracted attention and have been linked to cognitive processes and feature selectivity (Lavzin et al. , 2012; Xu et al. , 2012; Smith et al. , 2013; Cichon and Gan, 2015). Furthermore, it has been suggested that active dendritic processing underlies a more general principle of cortical operation that facilitates parallel associations between different cortical regions and the thalamus (Larkum, 2013) which is controlled by dendritic inhibition (Palmer et al. , 2012; Lovett-Barron and Losonczy, 2014). Establishing the validity of this hypothesis will have important ramifications for understanding brain function as a whole. TMS presents a most promising way to study the causal relationship between active dendritic properties and cognition but only if its effect on dendrites can be understood and ultimately controlled. Using an optical fiber imaging approach, here we present a study examining the effect of TMS on sensory-evoked dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex. We find that TMS suppresses dendritic Ca2+ activity evoked by tactile stimulation and that this suppression can be abolished by blocking GABAB receptors and excitatory transmission in the upper layers of the cortex. We uncover the cellular mechanisms underlying TMS-evoked inhibition, demonstrating that TMS of the rat brain activates long-range fibers that leads to the activation of dendrite-targeting inhibitory neurons in the upper cortical layers which in-turn suppress dendritic Ca2+ activity. Since indirect brain stimulation shows immense promise in treating many neurological disorders, such as epilepsy (Berenyi et al. , 2012), this study not only illustrates the cellular mechanisms underlying TMS but also highlights dendrites as potential targets","The brain’s billions of neurons communicate with one another using electrical signals. Applying a magnetic field to a small area of the scalp can temporarily disrupt these signals by inducing small electrical currents in the brain tissue underneath. The currents interfere with the brain’s own electrical signals and temporarily disrupt the activity of the stimulated brain region. This technique, which is known as transcranial magnetic stimulation, is often used to investigate the roles of specific brain regions. By examining what happens when a region is briefly taken ‘offline’, it is possible to deduce what that area normally does. Transcranial magnetic stimulation is also used to treat brain disorders ranging from epilepsy to schizophrenia without the need for surgery or drugs. But despite its widespread usage, little is known",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The amylase gene (AMY), which codes for a starch-digesting enzyme in animals, underwent several gene copy number gains in humans (Perry et al. , 2007), dogs (Axelsson et al. , 2013), and mice (Schibler et al. , 1982), possibly along with increased starch consumption during the evolution of these species. Here, we present comprehensive evidence for AMY copy number expansions that independently occurred in several mammalian species which consume diets rich in starch. We also provide correlative evidence that AMY gene duplications may be an essential first step for amylase to be expressed in saliva. Our findings underscore the overall importance of gene copy number amplification as a flexible and fast evolutionary mechanism that can independently occur in different branches of the phylogeny. Diet has been a significant adaptive force in shaping human and nonhuman primate variation (Hardy et al. , 2015; Milton, 1981; Zhang et al. , 2002). One of the best-described examples of diet-related adaptation is the expansion of the copy number of the amylase gene in concordance with the increase of starch consumption in the human lineage (Perry et al. , 2007), likely postdating the human Neanderthal split (Inchley et al. , 2016). A gene duplication in the ancestor of Old World monkeys and great apes initially led to the formation of two amylase genes (AMY2A and AMY2B) with pancreas-specific expression (Samuelson et al. , 1990). Then, a subsequent gene duplication in the ancestor of great apes led to the formation of AMY1 which gained salivary gland-specific expression (Meisler and Ting, 1993). In the human lineage, further gene copy number gains of AMY1 led to increased expression of the AMY1 enzyme in human saliva (Perry et al. , 2007). Gene copy numbers of both AMY1 and AMY2 vary in different human populations (Carpenter et al. , 2015; Usher et al. , 2015), the former correlating with the extent of traditional starch consumption in these communities (Perry et al. , 2007). While the evolution of the amylase locus in the human lineage is well described, its evolution in other mammals is less well understood. Some studies have produced intriguing findings. For example, it was shown that mice, rats, and pigs express substantial levels of amylase in their saliva (Boehlke et al. , 2015; Janiak, 2016) In addition, the","Many mammals can digest starch by using an enzyme called amylase, but different species eat different amounts of starchy foods. Amylase is released by the pancreas, and in certain species such as humans, it is also created by the glands that produce saliva, allowing the enzyme to be present in the mouth. There, amylase can start to break down starch, releasing a sweet taste that helps the animal to detect starchy foods. Curiously, humans have multiple copies of the gene that codes for the enzyme, but the exact number varies between people. Previous research has found that populations with more copies also eat more starch; if this correlation also existed in other species, it could help to understand how diets influence and shape genetic information. In addition, it",380,128,0.3368
dialogsum,"#Person1#: I am so happy to know that the promotion campaign for our new product is very successful. We just made a record sale this season. #Person2#: That is very encouraging news. I heard that the marketing department has done a three months research, they sent the feedback information to the research and development center by the end of every month. That is to say, the R&D center redesigned the product twice before it was launched into the market. #Person1#: It is not an easy job. How do you like the advertisement for the new product? #Person2#: That is the best one I have seen. I am sure our target customers, young people will love it. #Person1#: Certainly.",#Person1# and #Person2# are talking about their successful new product which made a record sale and there is much efforts behind it.,118,22,0.1864
dialogsum,"#Person1#: Brian, a company called me for an interview. #Person2#: That's great! You need to prepare for it. #Person1#: How? #Person2#: Get your hair done at a good hair saloon. Tell them you are going for a job interview. #Person1#: Okay. #Person2#: Buy an expensive suit. #Person1#: How expensive? #Person2#: The more expensive, the better. #Person1#: I can't afford too expensive, maybe $ 50 to $ 70? #Person2#: That'll do it. The best way is to find the dressing color code of the company. #Person1#: How? #Person2#: If you know somebody at the company, ask them. If not, dark color will be fine. #Person1#: Is a white blouse okay? #Person2#: Yeah, fine. And dressing shoes. #Person1#: Black? #Person2#: Black is good. #Person1#: White pantyhose? #Person2#: No. Dark or skin colored. #Person1#: Jewelry? #Person2#: Necklace, ring, and earrings are all fine. But don't wear too many pieces of jewelry. #Person1#: How about make up? #Person2#: Not much make up. #Person1#: Perfume? #Person2#: Yes, some. But be aware that different people may like different scents.",#Person1# is going to take an interview. Brian gives #Person1# suggestions on appearance and dressing style.,173,16,0.0925
dialogsum,"#Person1#: Let's decide what to order. #Person2#: I'll have a hamburger. #Person1#: The works? #Person2#: No, just tomatoes, please. And large fries. #Person1#: Anything to drink? #Person2#: A small cola. #Person1#: I'll have a sandwich and small fries. Would you like to have some desserts? #Person2#: Apple pie is my favorite dessert. #Person1#: I'd like to have an ice cream",#Person2# and #Person1# talk about what to order.,60,8,0.1333
dialogsum,"#Person1#: Excuse me. Do you know how to get to the mall? #Person2#: Sure, I used to work there. Go straight for about a mile, then turn left at the light. The mall will be on the right. #Person1#: Do you know the address? #Person2#: Yes, the address is 541 Main street. #Person1#: Can you write it down for me please? #Person2#: No problem. #Person1#: Is it faster if I take Highland avenue? #Person2#: No, that way is longer. There are more stop lights on that street. #Person1#: I think you're right. Thank you.",#Person2# tells #Person1# how to get the mall efficiently and writes down the address.,94,14,0.1489
dialogsum,"#Person1#: Excuse me, sir, could you please tell me the way to Aidan Bookstore? #Person2#: Yes, of course. Would you like to walk there or take a bus? #Person1#: Er. . . Is it far from here? #Person2#: It's just about ten minutes'walk. Go along this street, on the third cross you'll find it on your left. #Person1#: Then I'll walk. Many thanks. #Person2#: Not at all.",#Person2# tells #Person1# how to walk to the Aidan Bookstore.,67,10,0.1493
pubmed-summarization,"in all patients , with the exception of one , who underwent wedge resection . the nsclc histologic type was adenocarcinoma in 7 patients ( 58.3% ) , squamous cell carcinoma in 3 ( 25% ) , and adenosquamous cell carcinoma in 2 . lymph node metastases were present in 7 patients , and were staged n1 in 3 patients and n2 in 4 . these included headaches in 4 , visual disturbances in 1 , slurred speech in 1 , motor weakness in 1 , and gait disturbances in 1 . treatment for brain lesions included 5 craniotomies , 7 stereotactic radiosurgery ( srs ) , and 11 wbrt . as modality to increase local control , either craniotomy or srs was applied , and the decision on modality selection was made on an individual bases considering the advantages and the disadvantages of each modality . craniotomy was favored if the lesions were rather superficially located and were causing distressing neurologic symptoms and signs , while srs was favored if the lesions were in deep and eloquent areas . further local treatment for the brain lesions was not performed in two patients following wbrt , who were with very small sized metastatic lesions . treatment for brain lesions was carried out prior to that for pulmonary lesions in 7 patients , one of whom underwent craniotomy and wbrt at another hospital . gross total removal of metastatic tumors was verified in all patients who underwent craniotomy at our institution . srs was conducted with linear accelerator - based radiosurgery system in 1 patient , and gamma - knife unit in 6 patients . survival was estimated by the kaplan - meier method , with the date on which treatment on cerebral or pulmonary lesion was initiated as the starting point , and the date of death or last follow - up as the end point . a p value of less than 0.05 ( p<0.05 ) was considered to be statistically significant . all analyses were performed using the spss software package ( spss for windows , release 11.0 , standard version ) . pulmonary resection included pneumonectomy in 1 patient , bilobectomy in 4 , lobectomy in 6 , and wedge resection in 1 . mediastinoscopic lymph node","this study is a retrospective examination of our experiences with patients who underwent treatment of isolated synchronous brain metastases coupled with primary non - small cell lung cancer . from january 1995 to june 2004 , 12 patients presented with isolated synchronous brain metastases coupled with primary non - small cell lung cancer . the patient was comprised of 8 men and 4 women . the median age was 52 yr , in a range of 32 to 75 yr . median follow - up duration was 10.6 months , in a range of 2 to 55.8 months . recurrence developed in 7 patients , and the median interval from 1st treatment to recurrence was 4.5 months ( 2.8 - 6.5 months ) . the overall 1-yr survival",380,128,0.3368
dialogsum,"#Person1#: Hello! Tomorrow I'm going to need a wake-up call. #Person2#: Not a problem. What time shall we call you? #Person1#: I always hit the snooze button, so give me two calls, one at 7 and another at 7 fifteen. #Person2#: It'll be our pleasure. We'll call you at 7 and then at 7 fifteen. #Person1#: Oops, cancel that. Change the second call to 7 thirty will you, please? #Person2#: No sooner said than done. Can I help you with anything else? #Person1#: No, that's about it for now. Thanks. #Person2#: Okay, sir. Have a pleasant evening.","#Person1# asks #Person2# to give #Person1# two wake-up calls, one at 7:00 and another at 7:30, tomorrow morning.",97,18,0.1856
pubmed-summarization,", tex , from october 1 , 2005 through september 30 , 2008 . all women routinely received serum hiv testing at their initial prenatal visit and at time of presentation to labor and delivery for delivery via the opt - out approach with the abbott commander hiv ab hiv-1/hiv-2 ( rdna ) eia ( abbott laboratories , abbott park , ill ) . hiv test results performed at the time of delivery were analyzed in this study . a woman was considered hiv negative if eia testing was negative . positive test results were confirmed with the fluorognost immunofluorescent assay ( ifa ) hiv-1 ( sanochemia corp , stamford , conn , usa ) . women were considered to be falsely positive if eia results were positive and the ifa was negative . women delivered in this time period were identified through the obstetric operations database and linked to the pathology database for hiv , hepatitis b surface antigen ( hbsag ) , and rapid plasma reagin ( rpr ) results . maternal characteristics , including race , parity , age , singleton versus multiple gestation , and a diagnoses of diabetes or hypertension were obtained using the obstetrics operations database . laboratory results drawn 28 days prior to delivery through seven days after delivery were included . the study was approved by the institutional review board at the university of texas southwestern medical center . categorical data were reported as frequencies , and statistical significance was determined using analysis . statistical analyses were performed using sas , version 9.2 ( sas institute , cary , nc ) . a total of 47,794 women were identified who delivered during the study time frame . compared to hiv negative patients , false positive patients were more likely to be nulliparous ( 43% versus 31% , p < 0.001 ) and younger ( mean age 23.9 5.7 versus 26.2 5.9 , p < 0.001 ) . hiv positive patients were significantly older than false positive patients ( 27.4 versus 23.9 , p < 0.001 ) and hiv negative patients ( 27.4 versus 26.2 , p = 0.012 ) . of the 47,794 women , 47,391 ( 99% ) were hiv negative , 145 ( 0.3% ) had a false positive test","objective . to examine risk factors for false positive hiv enzyme immunoassay ( eia ) testing at delivery . study design . a review of pregnant women who delivered at parkland hospital between 2005 and 2008 was performed . patients routinely received serum hiv eia testing at delivery , with positive results confirmed through immunofluorescent testing . demographics , hiv , hepatitis b surface antigen ( hbsag ) , and rapid plasma reagin ( rpr ) results were obtained . statistical analyses included pearson 's chi - square and student 's t - test . results . of 47,794 patients , 47,391 ( 99% ) tested negative , 145 ( 0.3% ) falsely positive , 172 ( 0.4% ) positive , and 86 ( 0.2% ) equivocal or",380,128,0.3368
dialogsum,"#Person1#: Good morning, and welcome to Live Tech. It is my honor to make this presentation for you. Let me begin by explaining some of our digital cameras'selling points. You will see immediately that they are very stylish, but what you can't see is the cutting-edge technology inside. All of our cameras are light, compact, and easy to use. #Person2#: Can I take a look at one of those? #Person1#: Be my guest. Live Tech's digital cameras combine point-and-shoot simplicity with the ability to easily turn pictures into great-looking prints. Furthermore, it allows users to transfer pictures to a computer while the camera recharges. #Person2#: Can I take a picture of you? Seeing is believing. #Person1#: Sure, Just push the button, like. . . #Person2#: I think I can this out. Let's see if this works as advertised. Say'cheese!' #Person1#: I think you will find these are the best digital cameras on the market today. #Person2#: I think the quality of the photos will speak for themselves.",#Person1# is making a presentation about digital cameras' selling points and explains the advantages and functions to #Person2#. #Person2# takes a picture and thinks the quality of the photos will speak for themselves.,167,33,0.1976
scientific_lay_summarisation-elife-norm,"the Cannabis sativa plant, and multiple animal and clinical studies suggest its efficacy relieving chronic pain (De Vry et al. , 2004; Harris et al. , 2016; King et al. , 2017; Ueberall et al. , 2019; Williams et al. , 2008), although controversial results have been obtained in human clinical trials (Stockings et al. , 2018). However, THC has important side effects including cognitive deficits and anxiety (Célérier et al. , 2006; Kasten et al. , 2017; Puighermanal et al. , 2013). This work investigates the effects of natural THC in a mouse model of endometriosis that reproduces the ectopic endometrial growths and some of the behavioral alterations of clinical endometriosis. Our data show that THC is effective inhibiting hypersensitivity in the caudal abdominal area without inducing tolerance, as well as reducing the pain unpleasantness associated with endometriosis. Notably, THC also prevents the cognitive impairment observed in mice with ectopic endometrium without modifying anxiety-like behavior at this particular dose. Interestingly, THC shows efficacy limiting the development of ectopic endometrium, revealing disease-modifying effects of this natural cannabinoid. Our first aim was to characterize a novel experimental procedure to evaluate at the same time nociceptive, cognitive and emotional manifestations of endometriosis pain in female mice. Mice were subjected to a surgical implantation of endometrial tissue in the peritoneal wall of the abdominal compartment or to a sham procedure. Mice receiving ectopic endometrial implants developed persistent mechanical hypersensitivity in the caudal abdominal area, whereas sham mice recovered their baseline sensitivity and showed significant differences in comparison to endometriosis mice since the second week of implantation (1a and — 1). To test whether mechanical hypersensitivity of endometriosis mice was specific to this abdominal region, nociceptive responses were also measured in the hind paw. In this distant area, mechanical sensitivity remained unaltered, indicating that pain sensitization did not generalize to other sites (1b and — 2). To discern whether increased nociception was accompanied by a component of negative affect, a measure of pain unpleasantness was taken on day 14 after the surgeries (1c). Endometriosis mice showed increased nocifensive behaviors to mechanical stimuli when compared with sham mice. Similarly, endometriosis mice exhibited enhanced anxiety-like behavior reflected in lower percentages of time and entries to the open arms of the elevated plus maze (1d). Total arm","Endometriosis is a common disease in women caused by tissue that lines the uterus growing outside the uterine cavity on to other organs in the pelvis. This can cause a variety of symptoms including chronic pelvic pain, infertility, and pain during menstruation or sexual intercourse. These symptoms may contribute to anxiety, depression, loss of working ability and a reduced quality of life. Currently available treatments for endometriosis, including hormonal therapy and surgery, have a limited effect and can produce unwanted side effects. For example, women who undergo surgery to remove the growths may experience post-surgical pain or a recurrence. As a result, women with endometriosis often rely on self-management strategies like dietary changes or exercise. Although cannabis consumption has a large number of potential side effects and can",380,128,0.3368
pubmed-summarization,"advanced ckd subgroups , including those on hemodialysis , to compare the predictive value of r2chads2 for stroke and other thrombosis against those of chads and cha2ds2vasc and to determine the risk of developing stroke , transient ischemic attack ( tia ) , and other thrombosis in patients with egfr < 30 ml / min . this is a 10-year retrospective analysis of all patients admitted to metropolitan hospital center ( mhc ) in new york city with a diagnosis of non - valvular af . the 2013 icd-9-cm diagnosis code 427.31 was used to screen all hospital admissions and outpatient visits . inclusion criteria were any adult patient , age above 18 , admitted to mhc , with a documented non - valvular af diagnosis and at least 1-year follow - up from the time of the diagnosis . one hundred and forty - six were excluded after af was ruled out by review of their ekg and 78 after a documentation of valvular af was discovered . in addition , 464 patients were excluded for lack of follow - up of at least 1 year from the time of af diagnosis . the remaining 524 patients with atrial fibrillation were then analyzed and any occurrence of a primary endpoint was documented . we calculated the risk for a primary endpoint by recording the variables of interest that are present 1 year prior to the incidence of the endpoint . for patients who did not have an endpoint , we calculated their risk by recording the variables of interest present in the last recorded visit in our hospital . eleven variables were evaluated as potential confounders of the ckd and stroke relationship : age , sex , race / ethnicity , presence of congestive heart failure ( chf ) , hypertension , diabetes , prior stroke , history of vascular disease and anticoagulation treatment . race / ethnicity is categorized as hispanic , african american or others , including caucasian . chf is defined as a documented left ventricular ejection fraction of < 40% , hypertension ( htn ) as mean systolic blood pressure > 160 mmhg , vascular disease as the presence of peripheral arterial disease , carotid artery disease , or coronary arterial disease . treatment was","backgroundthe r2chads2 is a new prediction rule for stroke risk in atrial fibrillation ( af ) patients wherein r stands for renal risk . however , it was created from a cohort that excluded patients with advanced renal failure ( defined as glomerular filtration rate of < 30 ml / min ) . our study extends the use of r2chads2 to patients with advanced renal failure and aims to compare its predictive power against the currently used chads and cha2ds2vasc.methodsthis retrospective cohort study analyzed the 1-year risk for stroke of the 524 patients with af at metropolitan hospital center . auc and c statistics were calculated using three groups : ( i ) the entire cohort including patients with advanced renal failure , ( ii ) a cohort",380,128,0.3368
pubmed-summarization,"site - specific insertions , at the foldback tip and dna transpositional integration at the intercoil end of the detached dte . it will be examined in this review how fbi dna mediation of transposition can be extended to different classes and families of rtes . readers are suggested to refer to many good reviews available on the classification , structures , genetic contents , and function of the gene products and on the mechanisms of transposition with excellent diagrammatic illustrations . this review will minimize duplicate descriptions and focus on the mechanistic features that are relevant to the application of fbi dna to the mechanisms of dna transposition . to build the basis for comparison and understand transposition mechanisms , it is necessary to consider te structures based on the presence or absence of the following factors : 1 ) rna intermediates before transposition , 2 ) tirs or ltrs , 3 ) transposase or reverse transcriptase ( rt ) and other proteins related to autonomous or non - autonomous transposition , 4 ) tsd , and 5 ) other features , like dna replication modes , hairpin structure , and enhancers . transposition of dtes involves direct movement of the dte intermediate either by a simple cut - and - paste mechanism , as in tn5 , tn7 , and tn10 , or by replicative transposition , in which case one copy stays in the original site and a daughter dte copy appears in a distant location . step - wise description of the transposition events includes the requirement and pairing of both dte ends , binding of the transposase proteins to the terminal sequences , double - strand breaks ( dsbs ) of the dte terminals and target ends , ligation of the 3'-oh donor end and the 5'-p target end , and gap repair of the single - strand gaps on the target that were generated by dsb . in the case of the mu bacteriophage , the gap can be repaired while the entire transposon gets replicated in a cointegrate mechanism . transposition of rtes involves an rna intermediate that is reverse - transcribed by rt into a cdna . this double - stranded linear dna functions as the direct precursor for integration by an","foldback intercoil ( fbi ) dna is formed by the folding back at one point of a non - helical parallel track of double - stranded dna at as sharp as 180 and the intertwining of two double helixes within each other 's major groove to form an intercoil with a diameter of 2.2 nm . fbi dna has been suggested to mediate intra - molecular homologous recombination of a deletion and inversion . inter - molecular homologous recombination , known as site - specific insertion , on the other hand , is mediated by the direct perpendicular approach of the fbi dna tip , as the attp site , onto the target dna , as the attb site . transposition of dna transposons involves the pairing of",380,128,0.3368
pubmed-summarization,"and according to 12 studies conducted in australia , the maximum changes of the reliability was 3.1 percent of personal well- being and in australia and other world regions , cronbach 's alpha coefficient was 0.70- 0.85(16).the correlation between the questions was 30%-55% and the sum of questions correlation was at least 50% in pwi - a version ( 10 ) . all the questions of personal well - being index- cognitive disability were translated and revised based on ( comqol ) and pwi protocol . then , the translated text was back translated , and the two forms were compared . finally , the translated text was revised and given to several professors holding a phd in psychology ; and their professional suggestions were included in the translations . to identify the face validity and initial survey , the persian version of the personal well - being index- cognitive disability scale in this study , we gathered the total sample size is 200 of mentally retarded students in north of tehran ( districts 1 , 2 , 3 ) and the sample size was determined according to previous research ( 11 - 12 ) and also sample size for preliminary evaluation of reliability and validity test . data were analyzed by cronbach 's alpha coefficient for internal consistency and linear multivariate regression for construct validity ( since this scale has seven items and each item measures comments and feedback of the person about one area of personal well - being , the designers ( 16 ) of this scale believe that the individual score in each area plays an important role in the distribution of overall life satisfaction scores ( the first single item and separated from the other seven items ) . therefore , the designers have recommended linear multivariate regression analysis for validity assessment in which individual score in single item of overall life satisfaction as the dependent variable and the seven items scales as prediction variables are considered ) . after obtaining an authorization for the study from tehran 's exceptional education organization , we referred to sayyad shirazi girl 's exceptional school and piroozi boy 's exceptional school located in north of tehran . in these schools , a total of 200 mentally retarded students","objectivehaving a good quality of life has always been desirable for humans , and the concept of a good life and the ways of achieving it have become important over the years . personal wellbeing is the mental component of quality of life . thus , the current study was conducted to assess the reliability and validity of the personal well - being index- cognitive disability on mentally retarded students.method200 mentally retarded students in north districts of tehran ( districts 1 , 2 and 3 ) were selected by systematic random sampling . the collected data using personal well - being index- cognitive disability was analyzed by cronbach 's alpha coefficient for internal consistency and linear multivariate regression for construct validity.resultsresults confirmed the reliability and validity for the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu) /Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models. The liver is known to possess high capacity for regeneration upon injury. In acutely injured or surgically resected livers, regeneration is usually achieved by proliferation and hypertrophy of residual hepatocytes (Fausto and Campbell, 2003; Miyaoka et al. , 2012). By contrast, under chronic or severe liver injury that impairs the proliferation of hepatocytes, liver progenitor cell (LPC) has been postulated to contribute to liver regeneration by differentiating into hepatocytes and biliary epithelial cells (BECs), also known as cholangiocytes (Thorgeirsson, 1996; Fausto, 2004; Miyajima et al. , 2014). This response is known as ductular reaction (DR), in which LPC/biliary cell with BEC marker expression proliferates from the portal areas of injured livers, forming pseudo-ductular structures. DRs are frequently observed in human chronic liver diseases and rodent models including fatty liver disease and cholangiopathy (Shafritz and Dabeva, 2002; Roskams et al. , 2003; Gouw et al. , 2011; Wood et al. , 2014). In zebrafish models, biliary cells have been reported to contribute to regenerating hepatocytes after substantial loss of hepatocytes (Choi et al. , 2014). In mouse models, accumulating evidence by in vitro assay or transplantation experiments of biliary cells supports the presence of potential LPC with clonogenicity and bi-lineage differentiation capacity in the biliary compartment (Suzuki et al. , 2008a; Okabe et al. , 2009; Dorrell et al. , 2011; Lu et al. , 2015). In addition, a recent","Bile is a green to yellow liquid that the body uses to break down and digest fatty molecules. The substance is produced by the liver, and then it is collected and transported to the small bowel by a series of tubes known as the bile duct. When the liver is damaged, the ‘biliary’ cells that line the duct orchestrate the repair of the organ. In fact, the duct often reorganizes itself differently depending on the type of disease the liver is experiencing. For example, the biliary cells can form thin tube-like structures that deeply invade liver tissues, or they can grow into several robust pipes near the existing bile duct. However, it remains largely unknown which protein – or proteins – drive these different types of remodeling. Miura",380,128,0.3368
scientific_lay_summarisation-elife-norm,"thymic selection (Ebert et al. , 2008), or in the absence of the signal amplifying kinase Itk (IL-2 inducible T cell kinase) (Singleton et al. , 2011). To determine cSMAC properties, we have used stimulated emission depletion (STED) super-resolution microscopy and correlative light electron microscopy (CLEM). The cSMAC was composed of multiple complexes of supramolecular dimensions and associated with extensive membrane undulations. To investigate cSMAC function, we have systematically manipulated the localization of three adaptor proteins in live primary T cells: LAT (Balagopalan et al. , 2015) is an integral component of the cSMAC. SLP-76 (SH2 domain-containing leucocyte protein of 76 kD) (Koretzky et al. , 2006) is associated with it only during the first minute of T cell activation (Roybal et al. , 2015). Grb2 (growth factor receptor-bound 2) (Jang et al. , 2009) association with the cSMAC is less prevalent (Roybal et al. , 2015). Interface recruitment of all three adaptors was diminished upon attenuation of T cell activation by costimulation blockade and Itk-deficiency as was IL-2 secretion, a critical T cell effector function. By fusing these adaptors with various protein domains with a strong interface localization preference we brought them back to the interface under the attenuated T cell activation conditions and restored cSMAC formation. Such restoration enhanced IL-2 secretion but only when executed to the extent and with dynamics seen under full stimulus conditions. To investigate the function of µm scale protein accumulation at the center of the T cell: APC interface, we first cataloged protein localization events that were consistently associated with efficient T cell activation. We attenuated T cell activation through costimulation blockade (Singleton et al. , 2009; Wülfing et al. , 2002) and Itk deficiency. The 5C. C7 T cell receptor (TCR) recognizes the moth cytochrome C (MCC) 89–103 peptide presented by I-Ek. In the restimulation of in vitro primed 5C. C7 T cells with CH27 B cell lymphoma APCs and MCC peptide IL-2 amounts in the supernatant were reduced upon blockade of the CD28 ligands CD80 and CD86 (‘costimulation blockade’) and in T cells from Itk knock out 5C. C7 TCR transgenic mice, in particular at lower peptide concentrations (1A). As IL-2 amounts in T cell culture supernatants are determined by the difference between IL-2 generation and consumption we also determined IL-2","Cells receive dozens of signals at different times and in different places. Integrating incoming information and deciding how to respond is no easy task. Signaling molecules on the cell surface pass messages inwards using chemical messengers that interact in complicated networks within the cell. One way to unravel the complexity of these networks is to look at specific groups of signaling molecules in test tubes to see how they interact. But the interior of a living cell is a very different environment. Molecules inside cells are tightly packed and, under certain conditions, they interact with each other by the thousands. They form structures known as ‘supramolecular complexes’, which changes their behavior. One such supramolecular complex is the ‘central supramolecular activation cluster’, or cSMAC for short. It forms under",380,128,0.3368
dialogsum,"#Person1#: Tom, today is already July fifth. You are leaving for London in 5 days. Have you booked a flight ticket? #Person2#: Yes, I did that this morning. #Person1#: Will you go to the airport by bus or by taxi? #Person2#: Jim will go to the airport that morning to give me a lift.","Tom tells #Person1# he already booked the flight, and Jim will take him to the airport.",54,16,0.2963
scientific_lay_summarisation-elife-norm,"mediate host-parasite interactions (Collins et al. , 2016), and allow metastatic parasite transmission in host tissues (Brehm and Koziol, 2014). How stem cells may regulate regeneration in parasites such as tapeworms is largely unexplored and the subject of this study. We use H. diminuta, to investigate the molecular basis of tapeworm regeneration. We have established and refined experimental tools such as transcriptomics, in vitro parasite culture, whole-mount and fluorescent RNA in situ hybridization (WISH and FISH), cycling-cell tracing with thymidine analogs, RNA interference (RNAi), and cell transplantation, all described in this work. We determine that the ability to regenerate is regionally limited to the neck of adult H. diminuta. However, regeneration from the neck is finite without signals from the tapeworm head. Using RNA sequencing (RNA-seq), we identify and characterize various markers of the somatic cycling-cell population, which includes tapeworm stem cells. Using RNAi, we functionally validate molecular regulators of growth and regeneration. However, our analyses failed to uncover a neck-specific stem cell population that explains the regional regenerative ability displayed by H. diminuta. Instead, we show that cells from both regeneration-competent and regeneration-incompetent regions of H. diminuta have stem cell ability and can restore viability to lethally irradiated tapeworms. Our results show that extrinsic signals present in the tapeworm neck, rather than specialized stem cells, confer region-specific regenerative ability in this tapeworm. The anatomy of adult H. diminuta consists of a head with four suckers, an unsegmented neck, and a body with thousands of proglottids/segments that grow and mature in an anterior-to-posterior direction (Roberts, 1980; Rozario and Newmark, 2015) (1a). What regions of the tapeworm body are competent to regenerate? In order to test regeneration competency, it is necessary to grow tapeworms in vitro instead of in the intestine, where the suckers are required to maintain parasites in vivo. We established H. diminuta in vitro culture conditions modified from Schiller' s method (Schiller, 1965) and tested the regeneration competence of 1 cm amputated fragments (1b–c). The anterior-most fragments (head+neck+body) were competent to regenerate, confirming in vivo observations using amputation and transplantation (Read, 1967; Goodchild, 1958). Anterior fragments that were first decapitated (neck+body) were also competent to regenerate. In contrast, ‘body only’ fragments failed to regenerate proglottids. All amputated fragments could grow in length (1d), differentiate mature reproductive structures, and","Many worms have remarkable abilities to regrow and repair their bodies. The parasitic tapeworms, for example, can reach lengths of several meters and grow much more quickly than tissues in humans and other complex animals. This growth allows tapeworms to counteract the continual loss of the segments that make up their bodies, known as proglottids – a process that happens throughout their lives. The capacity to regenerate thousands of lost body segments and maintain an overall body length suggests that tapeworms have groups of stem cells in their body which can grow and divide to produce the new body parts. Yet, regeneration in tapeworms has not been closely studied. Rozario et al. have now examined Hymenolepsis diminuta, the rat tapeworm, and identified the neck of the tapeworm as",380,128,0.3368
scientific_lay_summarisation-elife-norm,"when density increases while for wood ants (Hönicke et al. , 2015) and mass raiding ants (John et al. , 2009) the speed remains constant when density increases. However, the range of densities tested was large enough to observe traffic jams only in the study conducted with fire ants traveling in tunnels (Gravish et al. , 2015). The highest densities as well as the estimated occupancy (fraction of area covered by ants), recorded in leaf-cutting ants (Burd et al. , 2002), wood ants (Hönicke et al. , 2015) and mass raiding ants (John et al. , 2009) were relatively low: 0. 8 ants. cm−2 (occupancy 0. 20), 0. 6 ants. cm−2 (0. 13) and 0. 3 ants. cm−2 (0. 10) and not sufficiently high to generate a traffic jam as ants never exceeded the capacity of the trail, that is the maximum value of the flow allowed by the trail width. Here, we investigated if ants succeed in maintaining a smooth traffic flow and avoid traffic congestion under the widest possible range of densities. We used the European supercolony of Argentine ants Linepithema humile, which is a major pest around the world and the largest recorded society of multicellular organisms (Giraud et al. , 2002). In our experiment, a colony was connected to a food source using a bridge (1B). To manipulate density, we used a combination of bridges of different widths (5,10 and 20 mm) and experimental colonies of different sizes (from 400 to 25,600 ants). We conducted a total of 170 experiments. The flow q and the density k were recorded on each experiment every second for one hour giving us 612,000 flow/density (non-independent) observations pairs. We succeeded in generating large variations of density (from 0 to 18 ants. cm−2) and occupancy (from 0 to 0. 8). We first studied ant traffic at a macroscopic level. The flow of ants q heading in both directions was plotted as a function of density in 2A. The flow q increased with the density k to a certain point and then it remained constant. We analyzed the relationship between k and q using three different macroscopic traffic functions (Greenshields et al. , 1935; Pipes, 1953; Underwood, 1960) (2B). All the parameters of the functions were fitted using a nonlinear least squares","Humans and ants are among the few species that engage in two-way traffic. Maintaining a smooth and efficient traffic flow while avoiding collisions is challenging for humans. Yet ants seem to be masters of traffic management. They can efficiently move back and forth between their nests and food without overtaking or passing each other, forming a steady stream of traffic. Few studies have looked at how ants maintain such a smooth flow even as the number of ants on a path increases. Now, Poissonnier, Motsch et al. have designed an experiment to investigate whether ants can maintain their steady stream of traffic when their path to food gets more crowded. This involved manipulating the density of ants using a combination of different sized colonies (ranging from 400 to",380,128,0.3368
dialogsum,"#Person1#: Would you like to come by and play bridge? #Person2#: Well, let's see. Why don't we go dancing for a change? We haven't done that for a long time. #Person1#: Well, to tell the truth, I don't really feel like it tonight. I had a pretty hard day and I'm sort of tired. #Person2#: Hmm. Well, in that case, we could go to the movies. #Person1#: Oh, we always go to the movies. Can't we do something different? #Person2#: Well, do you have any suggestions? #Person1#: Let's see. How do you feel about playing bridge? #Person2#: It's OK with me, but we don't have any beer and things. #Person1#: Well, shall I call Janet and ask her and Tom to come over, and I'll go to the store and buy some stuff. #Person2#: OK. #Person1#: Hello, Janet. It's me. . . Oh, fine. Just fine. Say, Janet, I was wondering if you and Tom were doing anything tonight. . . No? Well. would you like to come by our place and play a few hands of bridge?",#Person1# invites #Person2# to come by and play bridge. #Person2# at first wants to do something else but ultimately agrees. Then #Person1# calls Janet and Tom to come.,178,28,0.1573
dialogsum,"#Person1#: I think we have everything in the contract. Shall we sign it? #Person2#: Wait a minute. I think we have missed an important point. We should include an arbitration clause in the contract. #Person1#: I believe we can solve disputes through an amicable negotiation. #Person2#: I hope so. too. But I still think the provision of arbitration is of great importance to both of us. #Person1#: All right. I agree with you. But where do we hold arbitration? #Person2#: I suggest the arbitration be held in a third country. #Person1#: It sounds reasonable. The clause should be like this - any disputes arising from the execution of this contract shall be settled in a friendly way. If no settlement can be reached through consul - nation and conciliation, the disputes shall be submitted for arbitration by a mutually nominated arbitrator. The arbitrator's decision on the dispute is final and binding on the both parties. #Person2#: Ok.",#Person1# and #Person2# are adding an arbitration clause in the contract before they sign it and #Person2# suggests the arbitration be held in a third country.,157,26,0.1656
scientific_lay_summarisation-elife-norm,"include lipid-derived molecules like endocannabinoids (Ohno-Shosaku and Kano, 2014), gases like nitric oxide (Hardingham et al. , 2013), neurotransmitters (Koch and Magnusson, 2009; Regehr et al. , 2009), neurotrophins (Zweifel et al. , 2005), and other signaling factors like TGF-β and Wnt (Poon et al. , 2013; Salinas, 2005; Sanyal et al. , 2004; Speese and Budnik, 2007). Adhesion complexes that provide direct contacts across the synaptic cleft also participate in retrograde signaling (Futai et al. , 2007; Gottmann, 2008; Hu et al. , 2012; Mozer and Sandstrom, 2012; Peixoto et al. , 2012; Vitureira et al. , 2012). Although retrograde signaling is a key modulator of synaptic function, little is known about how postsynaptic exocytosis is regulated and coordinated. Components of a postsynaptic SNARE complex have been recently identified in mammalian dendrites. The t-SNAREs Syntaxin 3 (Stx3) and SNAP-47 are required for regulated AMPA receptor exocytosis during long term potentiation, while the v-SNARE synaptobrevin-2 regulates both activity-dependent and constitutive AMPAR trafficking (Jurado et al. , 2013). Stx4 has also been implicated in activity-dependent AMPAR exocytosis (Kennedy et al. , 2010). In Drosophila, a Ca2+-dependent retrograde signaling pathway relies on the postsynaptic Ca2+ sensor Syt4. Syt4 vesicles fuse with the postsynaptic membrane in an activity-dependent fashion (Yoshihara et al. , 2005), and loss of Syt4 leads to abnormal development and function of the NMJ. Syt4 null animals have smaller synaptic arbors, indicating a defect in synaptic growth, and also fail to exhibit several forms of synaptic plasticity seen in control animals, including robust enhancement of presynaptic release in response to high frequency stimulation, and rapid budding of synaptic boutons in response to strong neuronal stimulation (Barber et al. , 2009; Korkut et al. , 2013; Piccioli and Littleton, 2014; Yoshihara et al. , 2005). However, a detailed understanding of how the postsynaptic cell regulates constitutive and activity-dependent signaling of multiple retrograde pathways is lacking. In addition to exocytosis, it is likely that many cellular processes including vesicle trafficking and polarized transport of protein and transcript are specialized to facilitate postsynaptic signaling. Identifying such regulatory mechanisms is crucial for understanding synaptic development and function. We conducted a candidate-based transgenic RNAi screen to identify regulators of postsynaptic exocytosis at the Drosophila NMJ, a model for studying glutamatergic synapse growth and plasticity (Harris","Synapses are connections that allow a neuron to communicate with a neighboring cell (often another neuron). When an electrical impulse traveling down the “presynaptic” neuron reaches the synapse, it causes the neuron to release molecules called neurotransmitters. These molecules then bind to receptors on the surface of the other “postsynaptic” cell and cause that cell to respond in a particular way. Communication between the two cells at the synapse can also go in the opposite direction, with the postsynaptic cell signaling to the presynaptic cell. Such “retrograde” signals typically regulate the properties of the synaptic connection, such as changing the strength or shape of the synapse, or altering which proteins are present there. While a lot is known about how a presynaptic neuron communicates with the postsynaptic cell,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Signal propagation from the cell membrane to a promoter can induce gene expression. To examine signal transmission through sub-cellular compartments and its effect on transcription levels in individual cells within a population, we used the Wnt/β-catenin signaling pathway as a model system. Wnt signaling orchestrates a response through nuclear accumulation of β-catenin in the cell population. However, quantitative live-cell measurements in individual cells showed variability in nuclear β-catenin accumulation, which could occur in two waves, followed by slow clearance. Nuclear accumulation dynamics were initially rapid, cell cycle independent and differed substantially from LiCl stimulation, presumed to mimic Wnt signaling. β-catenin levels increased simultaneously at adherens junctions and the centrosome, and a membrane-centrosome transport system was revealed. Correlating β-catenin nuclear dynamics to cyclin D1 transcriptional activation showed that the nuclear accumulation rate of change of the signaling factor, and not actual protein levels, correlated with the transcriptional output of the pathway. Imaging of gene expression in individual cells using quantitative microscopy has become a central experimental approach for unraveling the dynamic aspects of mRNA transcription (Darzacq et al. , 2009; Coulon et al. , 2013; Hager et al. , 2009), and for examining various events of gene expression in real time (Darzacq et al. , 2007; Huranová et al. , 2010; Brody et al. , 2011; Martins et al. , 2011; Yao et al. , 2006; Mueller et al. , 2010). Cells govern specific transcriptional responses to various stimuli by use of signaling pathways and transducing factors that relay the signal to the promoters of induced target genes (Purvis and Lahav, 2013; Carmo-Fonseca et al. , 2002). Studies of transcription factor dynamics in single cells in response to signaling have revealed dynamic aspects of transcription factor nuclear translocation and modulation (Kalo and Shav-Tal, 2013; Yissachar et al. , 2013; Lahav et al. , 2004; Loewer et al. , 2010; Nelson et al. , 2004; Vartiainen et al. , 2007). This study centers on the dynamics of the Wnt/β-catenin signaling pathway and its control of cyclin D1 gene expression, as a model system for examining the dissemination of a signal in the cell and the transcriptional response it elicits. The Wnt/β-catenin canonical signaling pathway is activated by the binding of the Wnt ligand to plasma membrane receptors, thereby triggering downstream events that","Cells in an animal’s body must communicate with one another to coordinate many processes that are essential to life. One way that cells do this is by releasing molecules that bind to receptors located on the surface of others cells; this binding then triggers a signaling pathway in the receiving cell that passes information from the surface of the cell to its interior. The last stage of these pathways typically involves specific genes being activated, which changes the cell’s overall activity. Wnt is one protein that animal cells release to control how nearby cells grow and divide. One arm of the Wnt signaling pathway involves a protein called β-catenin. In the absence of a Wnt signal, there is little β-catenin in the cell. When Wnt binds to its",380,128,0.3368
dialogsum,"#Person1#: Dad, I'd like a pair of Adidas tennis shoes. #Person2#: Adidas? They're expensive. They're for the Chicago Bulls. #Person1#: No, all the guys as well as girls are wearing Adidas. #Person2#: But none of us ever had Adidas and we used to play quite well.",#Person1# is asking #Person1#'s dad for a pair of Adidas tennis shoes.,46,12,0.2609
scientific_lay_summarisation-elife-norm,"brought together to subsequently seam and result in a single continuous epithelial layer (Jacinto et al. , 2001). Dorsal closure in Drosophila melanogaster (Diptera: Drosophilidae) is a classical model system to study epithelial fusion (Jacinto et al. , 2000). This process is promoted by the mechanical action of different players: a contractile actomyosin cable forming at the leading edge of the epidermal flanks, the extraembryonic amnioserosa which covers the dorsal opening and generates contractile forces during epidermal flank advancement, and the eventual seaming of the epidermis through a mechanism involving microtubule-based cellular protrusions (Eltsov et al. , 2015; Hutson et al. , 2003; Kiehart et al. , 2000; Saias et al. , 2015). Genetically, the c-Jun N-terminal kinase (JNK) pathway and the transforming growth factor beta (TGF-β) family gene decapentaplegic (dpp) play an essential regulatory role in the process (Fernández et al. , 2007; Glise and Noselli, 1997; Jacinto et al. , 2002; Knust, 1997). The expression of dpp localizes to the leading edge of the epidermal flanks and depends on the activity of the D. melanogaster JNK gene (basket, bsk). Embryos lacking bsk activity show downregulation of dpp at the epidermal leading edge, failure of dorsal closure progression, and a dorsal-open phenotype in the larval cuticle (Glise and Noselli, 1997; Sluss et al. , 1996). At the molecular level, activation of the JNK/Dpp signaling pathways promotes the formation and maintenance of the actomyosin cable at the epidermal leading edge (Ducuing et al. , 2015) and, thus, progression of the opposing epidermal flanks toward the dorsal midline where they meet. At the final stage of dorsal closure, the opposing epidermal flanks ‘zipper’ or ‘seam’ through the action of microtubules that align toward the dorsal opening and promote the formation of filopodial protrusions at both epidermal leading edges (Jacinto et al. , 2002; Jankovics and Brunner, 2006; Millard and Martin, 2008). Dorsal closure is a conserved morphogenetic process that occurs in all insects (Chapman, 1998). Although in D. melanogaster it involves two tissues, the embryonic epidermis and the extraembryonic amnioserosa, in most insects it involves three: the embryonic epidermis, an extraembryonic amnion, and a separate extraembryonic serosa (Panfilio, 2008; Schmidt-Ott and Kwan, 2016). These complex anatomical differences raise the question whether the mechanisms responsible for epithelial fusion in a simple two-tissue","For a single fertilized egg to become an animal with many millions of cells, complex networks of genes must control the different stages of development. These gene networks create all the patterns needed to form different parts of the body. Changes to these patterns can create new species, with different sizes, body shapes, colors and lifestyles. Researchers often examine how evolution can create new species by altering gene networks to change patterns of development. Yet, some differences in development may not directly result from changes to gene networks. Other causes could include how the tissues are organized to begin with. One way to better understand this kind of difference is to compare developmental processes between two or more related species. Dorsal closure, for example, is a stage in",380,128,0.3368
dialogsum,"#Person1#: If you can choose, will you marry a foreigner or a Chinese? #Person2#: Why? Did tom pop the question? #Person1#: Not yet. But I wonder if I can get my parents' consent. #Person2#: Let me guess, your parents want you to marry a Chinese man, right? #Person1#: You are right. It is giving me a real headache. I feel like I'm between a rock and a hard place. #Person2#: I used to have the same problem when I was with my ex. #Person1#: Oh, how did you deal with it? #Person2#: I just let it go and continued dating with my Korean boyfriend. But finally we broke up. #Person1#: Oh, it's a pity. What was the matter? #Person2#: Simple. We had personality clashes and there were too many cultural differences. #Person1#: Like what? #Person2#: He hoped to live in the Korean way and asked me to give up working and stay at home to take care of the family. #Person1#: Oh, I see. In their culture women should put family first. #Person2#: Yes, he said it would be better for me and for the whole family. But I simply can not quit working. #Person1#: So that's why it's hard to have a happy marriage with a foreigner. #Person2#: Not really. There are many successful mixed marriage around us.",That #Person1#'s parents want #Person1# to marry a Chinese man makes #Person1# headache. #Person2# used to have the problem when with a Korean boyfriend but broke up. #Person1# thinks it's hard to have a mixed marriage but #Person2# says there're many successful examples.,219,43,0.1963
dialogsum,"#Person1#: It's weekend again, I'm glad I can arrange for my personal matters. #Person2#: What do you mean by that? #Person1#: Oh, that means I can do whatever I like without few interruptions. #Person2#: You've been always active and versatile. It seems that you are interested in everything. #Person1#: Oh, really? I just have lots of hobbies in my spare time ; such as going to the concert, painting, handwriting, reading novels and reading fashion magazines. What about yours? #Person2#: I have fewer hobbies than yours. That's why I find campus life a bit dull and uninteresting. #Person1#: Oh, you can't think like that. We young people should try our best to learn new things and accept new ideas. You like taking photos and going to photography shows, why not practise the technique and catch something unforgeable? #Person2#: That's a good suggestion. It's fine today. Maybe I can take photos on the scenery of the lake at sunset. It must be fantastic. #Person1#: I quite agree with you. With our hobbies, our life can be more colorful and exciting. #Person2#: And I can concentrate on my study after the relaxation over the weekend. #Person1#: Yes, it's a good habit to have a life-long hobby. Those who practise calligraphy and Qigong always live longer.",#Person1# has lots of hobbies while #Person2# has fewer and finds campus life uninteresting. #Person1# knows #Person2# likes taking photos and suggests #Person2# practice the technique. They agree hobbies make their life more colorful and help them concentrate on their studies.,213,41,0.1925
dialogsum,"#Person1#: Hi, can I help you? #Person2#: No, thanks. I'm just looking. #Person1#: All right. If you need any help, just let me know. My name is Greg. #Person2#: Sure, I'll let you know if I need anything. Hm, this mattress is very firm. Jack will probably like it. #Person1#: Did you find something you like? #Person2#: Yes, this mattress is very good. It's pretty firm. The mattress I'm now sleeping on is saggy. #Person1#: You are right. This is very good brand. It doesn't sag easily and we offer a lifetime warranty, so you don't have to worry about its quality. #Person2#: Does it come with a frame? #Person1#: Unfortunately, it doesn't. However we can give you a 10 % discount on the frame. We also offer a very good financing plan. There is no payment no interest until next June. #Person2#: That's an attractive plan. I'll think about it.",#Person2#'s mattress is saggy. Greg recommends one with a lifetime warranty and offers a 10% frame discount and a financing plan.,151,21,0.1391
scientific_lay_summarisation-elife-norm,"(Zikherman et al. , 2012). The most prominent characteristic of GFPhi reporter B cells is decreased surface IgM BCR relative to GFPlo cells. Goodnow and colleagues first suggested that IgM downregulation may mark autoreactive B cells in the normal mature repertoire shortly after they reported selective downregulation of IgM in the IgHEL (hen egg lysozyme) BCR Tg/soluble HEL Tg model system of B cell autoreactivity (Goodnow et al. , 1988; Goodnow et al. , 1989). Indeed, multiple studies in mice and humans have identified naturally occurring IgD+IgMlo cells as autoreactive and ‘anergic’ or functionally unresponsive (Duty et al. , 2009; Kirchenbaum et al. , 2014; Quách et al. , 2011; Zikherman et al. , 2012). These results corroborate observations with several BCR transgenic model systems (Cambier et al. , 2007). However, whether or how IgM downregulation might constrain autoreactivity remains unclear because naturally-occurring autoreactive B cells maintain high expression of the IgD BCR isotype (Zikherman et al. , 2012). IgM and IgD are splice isoforms of a common precursor heavy chain mRNA (Moore et al. , 1981). While they differ in their Fc domains, both BCR isotypes contain the same antigen-binding domain, as well as identical 3-amino acid cytoplasmic tails, and they pair with Igα/β in order to initiate the canonical BCR signaling cascade (Blum et al. , 1993; Radaev et al. , 2010). However, the expression pattern of the isotypes differs; IgM expression begins as soon as heavy and light chains recombine early in B cell development, and persists until class switch recombination occurs following B cell activation (Chen and Cerutti, 2010). IgD is uniquely co-expressed with IgM during a narrow developmental window on late transitional and mature naïve Fo B cells as a result of alternate splicing regulated by the zinc-finger protein ZFP318 (Enders et al. , 2014; Pioli et al. , 2014). This suggests that IgD may play a critical role specifically in mature naïve B cells. Initial characterization of IgM- and IgD-deficient mice revealed only mild phenotypes and substantial redundancy; each isotype could mediate B cell development, initiate antibody responses to T-dependent and -independent immunization, and induce normal levels of steady-state serum IgG (Lutz et al. , 1998; Nitschke et al. , 1993; Roes and Rajewsky, 1993). This is consistent with prior studies in BCR transgenic","To defend an organism against invaders such as viruses and bacteria, cells of the immune system need to recognize and respond to foreign microbes. However, these immune cells must also avoid attacking ‘self’ – for example, the healthy tissues of the body – as this could lead to autoimmune disease. B cells are a type of immune cell that is essential in order to produce antibodies, protective proteins that can identify and defend against a broad range of germs: in addition, certain antibodies can also recognize ‘self’. When a B cell first develops, it places its antibody on its surface and uses this protein as a receptor (termed ‘B cell receptor’) to sense its surroundings. Prior to mounting an immune response, B cells carry two closely related versions",380,128,0.3368
scientific_lay_summarisation-elife-norm,"HCT116 (PTEN -/-) ] cells. We found near-significant or significant differences of total lysate β-Arrestin1 and ARHGAP21 between PTEN-expressing and -deficient cells [Caco-2 vs ShPTEN (1A, B) and HCT116 vs PTEN -/- cells (—supplements 1 and 2) ]. To infer subcellular localization of β-Arrestin1 and ARHGAP21, we performed membrane fractionation studies and normalized each protein’s densitometry value against its total lysate level, to investigate relative proportions of β-Arrestin1 and ARHGAP21 associated with membrane. We found greater β-Arrestin1 but lower ARHGAP21 levels in Caco-2 than in ShPTEN membrane fractions (1C, D). As β-Arrestins are known to localize to activated lysophosphatidic acid receptors [LPARs] (Urs et al. , 2005; Li et al. , 2009) that are expressed in Caco-2 and HCT116 cell membranes (Yun et al. , 2005), we investigated effects of PTEN on lysophosphatidic acid (LPA) -induced membrane recruitment of β-Arrestin1. We found greater LPA-mediated membrane enrichment of β-Arrestin1 in Caco-2 and HCT116 cells than in PTEN-deficient ShPTEN or PTEN -/- HCT116 (PTEN -/-) subclones (1E, F; —supplements 3 and 4). We next used confocal microscopy to determine PTEN effects on β-Arrestin1 subcellular distribution in whole cells. We expressed the β-Arrestin1-mCherry fusion protein and mCherry only controls in PTEN-expressing and -deficient cells. We assessed colocalization with Alexa 488-labeled wheat germ agglutinin (WGA), a widely used fluorescent probe for cell and Golgi complex membranes (Crossman et al. , 2015) by confocal microscopy. β-Arrestin1-mCherry was predominantly cytosolic in vehicle only (VO) -treated cells, in accord with cytosolic accumulation of unlabelled β-Arrestin1 in fractionation studies. On treatment with LPA, the β-Arrestin1-mCherry fusion protein colocalized with WGA at the plasma membrane in PTEN-expressing Caco-2 and HCT116 control cells (1G; — 5). Line scanning analysis revealed overlap of β-Arrestin1-mCherry and Alexa 488 fluorescence signals in plasma membrane peaks in PTEN-expressing Caco-2 and HCT116 cells after LPA treatment (1G; — 5). While LPA had limited effects in ShPTEN cells that have residual low level PTEN (1G), this treatment had no effects on β-Arrestin1-mCherry subcellular distribution in PTEN-null (PTEN -/-) cells (— 5). mCherry only did not localize at the plasma membrane (data shown for control PTEN-expressing HCT116 and PTEN -/- cells only; — 6). To exclude a non-specific effect of PTEN on ligand-mediated protein translocation to the cell membrane, we investigated 1,25 (OH) 2D3-mediated membrane localization of","The protein PTEN helps to organize cells in the body to form complex structures. In particular, it collects signals from a cells’ surroundings and changes where cells divide so new cells are produced in the right places. The control of cell division by PTEN is also thought to help limit the progression and spread of cancer. PTEN can interact with another protein called β-Arrestin1, which behaves as a so-called scaffolding protein – in other words, one that helps groups of proteins to interact with each other. β-Arrestin1 has been found to control cell division via a series of other proteins, including ARHGAP21 and Cdc42. The relationship between PTEN and these other proteins in dividing cells is still not fully understood. Javadi, Deevi et al. studied PTEN in human",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the slipping points (Delhaye et al. , 2016). We hypothesized that information about these local deformations is carried by tactile afferents that inform the central nervous system about the contact state. Single-unit recordings of primary tactile afferents, both in humans and monkeys, have shown that type I afferents respond strongly to local skin deformation (Johansson et al. , 1982; Sripati et al. , 2006; Saal et al. , 2017). Those responses contain information about local geometric features such as edge orientation (Pruszynski and Johansson, 2014; Suresh et al. , 2016; Delhaye et al. , 2019). The most common stimuli used to evoke deformation of the skin are indentations and scanning with embossed geometric patterns or textures. Applying such stimuli makes it possible to relate the strength or the timing of the response to the topography or the statistics of the stimulus itself, but does not provide a mechanistic understanding of the nature of the response with respect to the local skin deformation at the mechanoreceptors themselves. Moreover, it is mostly unknown how tactile afferents respond to surface strains, that is, strains acting tangentially to the surface (as opposed to features indented perpendicularly to the skin surface). Afferent recordings in the hairy skin of the human hand have shown that afferents of all types strongly respond to local skin stretch and that the fast-adapting type I (FA-I) afferents also strongly respond when the stretch is released (Edin, 1992; Edin, 2004). Slowly-adapting type II (SA-II) afferents are also known to be sensitive to skin stretch, but relating their response to the exact local stretch pattern is complex given the large size of their receptive fields. How glabrous skin afferents, that is, those engaged in the contact with objects during manipulation, respond to local skin strain has, to our knowledge, never been studied. This is mainly due to the difficulties of applying well-controlled mechanical stimuli and measuring the strain at the same time. To address this, we took advantage of a recently developed imaging system that can measure fingertip skin strain through a transparent material during tangential loading of the fingertip until slip occurs (Delhaye et al. , 2014; Delhaye et al. , 2016). While recording local strains with this system, we simultaneously recorded the activity of human tactile afferents innervating the fingertip","Each fingertip hosts thousands of nerve fibers that allow us to handle objects with great dexterity. These fibers relay the amount of friction between the skin and the item, and the brain uses this sensory feedback to adjust the grip as necessary. Yet, exactly how tactile nerve fibers encode information about friction remains largely unknown. Previous research has suggested that friction might not be recorded per se in nerve signals to the brain. Instead, fibers in the finger pad might be responding to localized ‘partial slips’ that indicate an impending loss of grip. Indeed, when lifting an object, fingertips are loaded with a tangential force that puts strain on the skin, resulting in subtle local deformations. Nerve fibers might be able to detect these skin changes, prompting the",380,128,0.3368
dialogsum,"#Person1#: Please pull your vehicle over to the side of the road. Please roll down your window. #Person2#: What's the matter, sir? #Person1#: Have you been drinking? #Person2#: No, I haven't, sir. #Person1#: Really? But I can smell alcohol on your breath. Blow to the breathalyzer, please. #Person2#: But sir, I didn't drink at all. #Person1#: If you refuse the blow, you'll receive a ticket and your vehicle will be impounded. #Person2#: OK, I will blow. #Person1#: Your BAC exceeds legal limit. #Person2#: But I. . . #Person1#: I'll have to write you a ticket and impound your vehicle. #Person2#: Oh, no!",#Person1# writes a ticket and impounds #Person2#'s vehicle because #Person2#'s BAC exceeds the legal limit.,102,15,0.1471
scientific_lay_summarisation-elife-norm,"multiple generally conserved sub-complexes can be recognized that perform specific roles. Outer kinetochore sub-complexes together form an interface with microtubules and serve as a platform for spindle assembly checkpoint signaling, coupling chromosome-microtubule interactions with cell cycle progression. Inner kinetochore sub-complexes direct assembly of the outer kinetochore. Several kinetochore subcomplexes together assemble into a Constitutive Centromere-Associated Network (CCAN; also known as the Ctf19 complex in budding yeast) (reviewed in McAinsh and Meraldi (2011); Westermann and Schleiffer (2013) ) As its name implies, the CCAN/Ctf19 complex is bound to centromeric chromatin throughout the mitotic or meiotic cell division program. In meiotic G2/prophase of budding yeast, when recombination occurs, only the Ctf19 and Mis12/MIND (Mtw1 including Nnf1-Nsl1-Dsn1) kinetochore complexes are bound to the centromere (Meyer et al. , 2015; Miller et al. , 2012). The Ctf19 complex exerts long range effects by promoting cohesin enrichment throughout the ~20–50 kb surrounding pericentromere despite being restricted to the core ~125 bp centromere sequence (Eckert et al. , 2007; Fernius and Marston, 2009; Ng et al. , 2009). It does so by targeting the Scc2/4 cohesin loader to the centromere, from where cohesin spreads into the pericentromere (Fernius et al. , 2013). These characteristics make the Ctf19 complex a particularly good candidate for mediating kinetochore-derived recombination suppression. Here we show that both cohesin-independent suppression of DSB formation and cohesin-dependent repair pathway choice underlie a central role for the Ctf19 complex in suppression of CO formation in the pericentromere. To understand how pericentromeric COs are prevented, we used a fluorescent CO reporter assay (Thacker et al. , 2011) (1A) to measure recombination rates within a pericentromere (around CEN8, the centromere of chromosome VIII) or, as a control, on a chromosome arm interval of equivalent size on chromosome VIII of budding yeast (1B, C). In wild-type cells, map distance, a measure of CO frequency, was 7. 5 cM within the arm interval but only 0. 04 cM within the pericentromere interval. In cells lacking the synaptonemal component, Zip1, map distance within the pericentromeric interval rose to ~2 cM (1B), in agreement with previous observations (Chen et al. , 2008), while we observed a modest decrease in map distance within the chromosomal arm region (1C). Thus, the fluorescent reporter assay can report on pericentromeric CO formation. 10. 7554/eLife. 10850.","The cells of animals, plants and many other organisms store most of their DNA inside the cell nucleus, packaged into structures called chromosomes. Most cells contain two copies of each chromosome – one inherited from each parent. However, sex cells (such as egg cells and sperm cells) contain just one copy of every chromosome, so that when they fuse, the new cell that is formed contains the full set. Sex cells form in a process called meiosis, where a cell containing two copies of every chromosome duplicates its genetic material and then divides to form four new cells, each of which contains one copy of each chromosome. During meiosis, different versions of the same chromosome are able to swap sections of their DNA in a process called crossover.",380,128,0.3368
dialogsum,"#Person1#: Hello, how are you? I am Jack. #Person2#: Hello, I am Amy. #Person1#: What brings you here? #Person2#: I saw that your Corollas are on sale. #Person1#: Yes, it is really a good deal. $ 1, 000 discount. I've never seen a sale as good as this one. #Person2#: Tell me about Corollas. #Person1#: Sure. It has 1. 8 liter engine. This one comes with all power options, air condition, CD player, full size spare tire, automatic transmission and ABC. The window price is $ 17, 000, and I can give You for $ 16. 000. #Person2#: Sounds good. How about $ 15, 000? #Person1#: You must be kidding! You cannot get that price anywhere. #Person2#: I am serious. $ 15, 000. #Person1#: Can you put down a $ 2, 000 deposit, and I'll talk to my manager, see what we can do. #Person2#: No. Just talk to your manager and let me know. #Person1#: Okay, I'll be right back. . . Congratulations! The manager approved the final price $ 15, 000. #Person2#: The price is fine if you give me free security system and free carpet mats. #Person1#: You are really tough. You got a deal. #Person2#: Thanks!",Amy saw Corollas are on sale and Jack says the Corolla has all power options and it costs $16000. Amy wants it $15000 and the manager agrees.,200,27,0.135
scientific_lay_summarisation-elife-norm,"as contact with the lymph node stromal cell network or short-term encounters with resident dendritic cells (Miller et al. , 2004; Bajénoff et al. , 2006; Khan et al. , 2011). Whereas the basic signaling mechanisms for cell-intrinsic induction of random motility have been previously explored in fibroblasts and neuroblastoma cells (Petrie et al. , 2009), it remains unclear if such mechanisms apply in T cells. Upon T cell recognition of cognate antigen, TCR engagement results in an elevated cytosolic Ca2+ concentration that acts as a ‘STOP’ signal to halt motility and anchor the T cell to the site of antigen presentation (Donnadieu et al. , 1994; Negulescu et al. , 1996; Dustin et al. , 1997; Bhakta et al. , 2005; Moreau et al. , 2015). The predominant mechanism for increasing cytosolic Ca2+ in T cells is through store-operated Ca2+ entry (SOCE), which is mediated by the molecular components STIM1 and Orai1. TCR stimulation triggers depletion of intracellular Ca2+ stores in the endoplasmic reticulum (ER), resulting in translocation of the ER-resident Ca2+ sensor STIM1 to specialized ER-plasma membrane (PM) junctions where Orai1 channels aggregate into puncta and activate to allow sustained Ca2+ influx (Liou et al. , 2005; Roos et al. , 2005; Zhang et al. , 2005; Luik et al. , 2006; Vig et al. , 2006; Zhang et al. , 2006; Calloway et al. , 2009; Wu et al. , 2014). Orai1 channel activity is crucial for immune function, as human mutations in Orai1 result in severe combined immunodeficiency (SCID) (Feske et al. , 2006). Additional roles of Orai1 have been defined in chemotaxis to certain chemokines and T cell homing to lymph nodes (Greenberg et al. , 2013); actin cytoskeleton rearrangement (Schaff et al. , 2010; Dixit et al. , 2011; Babich and Burkhardt, 2013; Hartzell et al. , 2016); migration during shear flow (Schaff et al. , 2010; Dixit et al. , 2011); lipid metabolism (Maus et al. , 2017); and dendritic spine maturation in neurons (Korkotian et al. , 2017). However, despite their contributions to other aspects of T cell function, no role has been identified for Orai1 channels in T-cell motility patterns underlying scanning behavior. In this study, we use human and mouse T cells to assess the role of Orai1 and Ca2+","To help protect the body from disease, small immune cells called T lymphocytes move rapidly, searching for signs of infection. These signs are antigens – processed pieces of proteins from invading bacteria and viruses – which are displayed on the surface of so-called antigen-presenting cells. To visit as many different antigen-presenting cells as possible, T cells move quickly from one to the next in an apparently random manner. How T cells are programmed to move in this way is largely unknown. The entry of calcium ions into cells triggers characteristic actions in many cells throughout the body. In T cells, calcium ions enter through Orai1 proteins that form calcium channels on the cell surface. Now, Dong, Othy et al. have asked whether calcium signals guide moving T cells",380,128,0.3368
dialogsum,"#Person1#: Nice to meet you, sir. I come from New Times Clothes Company. We learnt that your exhibits on the Trade Fair in Shanghai this month were marvelous. Would you please quote the price? #Person2#: Before we discuss the price, may I ask you what kind of exhibits you are interested in? #Person1#: Your summer clothes for white-collar and men's jackets. #Person2#: Can you give us a rough idea of the quantity you require? It is generally known that the price varies according to the quantity. #Person1#: That is to say, 10000 sets for the one of white-collar and 5000 for men's jackets. #Person2#: In that case, our offer for the white-collar series is US $ 200, and the other is US $ 300 per set. #Person1#: Do you quote CIF or FOB? #Person2#: We usually quote on a CIF basis and a commission of five percent for you. You will find our price is most competitive. #Person1#: What are your terms of payment? #Person2#: Letter of credit at sight. #Person1#: Another question. Could you tell me the earliest possible time of shipment? #Person2#: Within a month after your letter of credit reaches us. #Person1#: Well, I got all the point. All the decision will be made since I get the approval from my supervisor. #Person2#: OK! I expect you to accept our general terms and conditions of trade. We believe that through our cooperation, large transactions will be brought to speedy conclusion.","#Person1# has a great interest in #Person2#'s exhibits in Shanghai. #Person1# orders 10000 sets for the one of white-collar and 5000 for men's jackets. They discuss the price, terms of payment, and the earliest possible time of shipment.",243,38,0.1564
scientific_lay_summarisation-elife-norm,"β-oxidation and glutamine consumption (Vats et al. , 2006; Jha et al. , 2015). Importantly, such metabolic shifts critically support macrophage activation. Increased glycolytic flux in M1 macrophages is coupled to de novo lipogenesis, which enables ER and Golgi expansion and production of high levels of inflammatory cytokines (Everts et al. , 2014). Another consequence of enhanced glycolysis is accumulation of the TCA cycle metabolite succinate, leading to stabilization of the transcription factor HIF-1α and transcriptional induction of Il1b and other target genes in the M1 macrophage (Tannahill et al. , 2013). How oxidative metabolism boosts M2 activation is not clear, but glutamine metabolism fuels production of UDP-GlcNAC, an important modification of multiple M2 markers (Jha et al. , 2015). Consistent with the idea that macrophage activation is supported by metabolic shifts, recent studies indicate that macrophage polarizing signals impinge on metabolic signaling pathways. Polarizing signals like LPS and IL-4 regulate the activity of Akt, mTORC1, and AMPK (Everts et al. , 2014; Byles et al. , 2013; Cheng et al. , 2014; Weichhart et al. , 2008), presumably to coordinate metabolic processes that critically underlie macrophage polarization. Limited studies indicate that perturbing the activity of these metabolic regulators impairs macrophage metabolism and activation (Everts et al. , 2014; Cheng et al. , 2014). For example, Akt mediates enhanced glycolysis to support lipid synthesis and inflammatory cytokine secretion in M1 macrophages (Everts et al. , 2014). Akt similarly stimulates glucose-fueled lipid synthesis in growing and proliferating cells, where lipids are used to build cellular membranes (Robey and Hay, 2009). Therefore, M1 macrophages co-opt a metabolic process (Akt-dependent lipogenesis) in order to coordinate a macrophage-specific function (inflammatory cytokine secretion). In general, however, how polarizing signals control metabolic shifts, and the full implications of this for control of macrophage activation, remains poorly understood. Here we show that integration of the Akt-mTORC1 pathway into IL-4 signaling allows for selective control of some M2 responses. Control is exerted at the level of Acly, a key enzyme in Ac-CoA production, thereby modulating histone acetylation and transcriptional induction of a subset of M2 genes. Consistent with its role as an important metabolic sensor, the Akt-mTORC1 pathway couples metabolic input to such gene-specific control. Our findings also reveal subsets of the M2 response, including chemokine production and","Macrophages are immune cells that are found in most of the tissues of the body. Exactly what the macrophages do depends on which tissue they are in, and the state of the tissue. For example, M2 macrophages can multiply in numbers, heal wounds or help to fight off parasites depending on the signals they receive from their environment. Conversely, when macrophages sense pathogens such as bacteria they can also become M1 macrophages, which produce inflammatory molecules that help kill the invading bacteria. As a macrophage transforms into a more specialized state, its metabolism – the set of chemical reactions the cell performs in order to survive and thrive – also changes. This shift appears to play an important role in activating the macrophages and determining how they’ll specialize.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Malaria inflicts an enormous burden on global human health. The emergence of parasite resistance to front-line drugs has prompted a renewed focus on the repositioning of clinically approved drugs as potential anti-malarial therapies. Antibiotics that inhibit protein translation are promising candidates for repositioning. We have solved the cryo-EM structure of the cytoplasmic ribosome from the human malaria parasite, Plasmodium falciparum, in complex with emetine at 3. 2 Å resolution. Emetine is an anti-protozoan drug used in the treatment of ameobiasis that also displays potent anti-malarial activity. Emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin, thereby delivering its therapeutic effect by blocking mRNA/tRNA translocation. As the first cryo-EM structure that visualizes an antibiotic bound to any ribosome at atomic resolution, this establishes cryo-EM as a powerful tool for screening and guiding the design of drugs that target parasite translation machinery. Malaria is responsible for an estimated 627,000 annual deaths worldwide, with the majority of victims being children under 5 years of age (WHO, 2012). At present there is no licensed malaria vaccine and parasites have developed resistance to all front-line anti-malarial drugs. As such, there is an urgent need for novel therapeutics that can be used as monotherapies or as partner drugs for combinatorial regimes (Kremsner and Krishna, 2004). An alternative to novel candidates is the repurposing or repositioning of clinically approved drugs that can be used in combination with known anti-malarials, such as chloroquine, antifolates, and artemisinin, to increase their useable lifespan by reducing resistance (Grimberg and Mehlotra, 2011). The etiological agents for malaria are a family of unicellular protozoan pathogens of the genus Plasmodium. The parasite has a complex two-host lifecycle with a sexual stage occurring in the mosquito vector and an asexual stage in the human host. It is during the asexual blood stage that disease symptoms in humans first appear, including those associated with severe malaria, and it is often at this stage that the need for clinical intervention becomes apparent (Miller et al. , 2002). Much of malaria pathology is the result of exponential growth of the parasite within erythrocytes, and given the critical role that protein synthesis plays in this, the translational machinery is an attractive drug target. Protein translation in the parasite","Each year, malaria kills more than 600,000 people, mostly children younger than 5 years old. Humans who have been bitten by mosquitoes infected with malaria-causing parasites become ill as the parasites rapidly multiply in blood cells. Although there are several drugs that are currently used to treat malaria, the parasites are rapidly developing resistance to them, setting off an urgent hunt for new malaria drugs. Developing new antimalarial medications from scratch is likely to take decades—too long to combat the current public health threat posed by emerging strains of drug-resistant parasites. To speed up the process, scientists are investigating whether drugs developed for other illnesses may also act as therapies for malaria, either when used alone or in combination with existing malaria drugs. Certain antibiotics—including one called emetine—have",380,128,0.3368
pubmed-summarization,"developed to correct casting defects in the fitting surface and reduce the abutment / implant misfit . despite various prosthetic and technical improvements , laboratory procedures used in the fabrication of implant - supported prostheses , especially casting and porcelain baking , this study evaluated the effect of cast rectifiers on the misfit of cast ucla abutments compared to premachined ucla abutments . the influence of casting and porcelain baking on the marginal misfit of these components was also investigated . two groups of components were analyzed : test group ( n=10 ) castable plastic non - hexed ucla abutments ( 055021;conexo sistemas de prtese ; so paulo , sp , brazil ) ; control group ( n=10 ) non - hexed premachined ucla abutments ( 055022 ; conexo sistemas de prtese , so paulo , sp , brazil ) ( 1a ) . the components of both groups were individually positioned over an implant analogue ( 013020 ; conexo sistema de prteses , so paulo , sp , brazil ) and sectioned with a diamond bur ( 34570 ; microdont , so paulo , sp , brazil ) at low speed under water cooling until they were 8 mm in height , keeping the cylindrical shape . the abutments were secured to the sprues and fixated in a sprue former . a silicone - casting ring was adapted to the sprue former and the investment was poured ( bellavest t ; bego , bremen , germany ) . four silicone rings were used , each one containing 5 ucla abutments , adding up to 20 components ( 10 per group ) . the patterns were induction cast : abutments of the test group with a nickel - chromium alloy ( wiron 99 ; bego , bremen , germany ) , and abutments of the control group with a palladium - silver alloy ( williams w1 ; ivoclar vivadent , amherst , ny , usa ) . castings were allowed bench cool and were then divested and cleaned with air abrasion . during this process , implant analogues were joined to the abutments to reduce the risk of damage to the abutment / implant interface ( 1b ) . fitting surfaces of the castings made with plastic patterns ( test","objectives : this study assessed the effect of cast rectifiers on the marginal misfit of cast ucla abutments compared to premachined ucla abutments . the influence of casting and porcelain baking on the marginal misfit of these components was also investigated.methods:two groups were analyzed : test group 10 cast ucla abutments , finished with cast rectifier and submitted to ceramic application ; control group 10 premachined ucla abutments , cast with noble metal alloy and submitted to ceramic application . vertical misfit measurements were performed under light microscopy . in the test group , measurements were performed before and after the use of cast rectifiers , and after ceramic application . in the control group , measurements were performed before and after casting , and after ceramic application",380,128,0.3368
dialogsum,"#Person1#: Jeanne, can I ask you a question? #Person2#: Go ahead. #Person1#: If you could go anywhere in the world, where would you go? #Person2#: That's a good question, Tim! I would go to Japan, China, or France. Too bad I have no money to buy a ticket!",Tim asks Jeanne where would she go if she could go anywhere.,48,12,0.25
dialogsum,"#Person1#: Hello, Pineapple Computer Company. This is Janice Shaw, the secretary of Nova. May I ask who is calling? #Person2#: Good morning. This is Dan. Could I speak to Nova? #Person1#: I feel so sorry that Nova has gone on her business trip. #Person2#: Really? When will she come back? #Person1#: Maybe next weekend. She only mentioned this before she left. #Person2#: Well, the reason why I am calling is to tell her that our appointment in next month will have to be postponed. And the exact time for this meeting will be discussed after she comes back. #Person1#: Wait a minute. I have to leave a memo here. Anything else? #Person2#: The file for the meeting needs to be retyped and please send it to us as soon as possible. #Person1#: Dan, don't worry. I will tell her everything as soon as she comes back.",Dan calls to speak to Nova but Nova is unavailable. Janice will help to inform Nova that Dan intends to postpone their appointment and the file for the meeting needs to be retyped.,146,33,0.226
scientific_lay_summarisation-elife-norm,"and Spradling, 2010; Zhang and Kalderon, 2001). A comprehensive re-evaluation, which included the analysis of all FSC lineages, without any prior assumptions about their behavior, showed that individual FSCs were frequently lost or duplicated (Reilein et al. , 2017) and that FSC differentiation to an FC was not temporally coupled to, or dependent upon division of the same FSC (Reilein et al. , 2018). These characteristics of maintenance by population asymmetry, together with independent cell division and cell differentiation events and decisions, are shared by two very important and intensively studied types of mammalian epithelial stem cell, in the gut and in the epidermis (Jones, 2010; Mesa et al. , 2018; Ritsma et al. , 2014; Rompolas et al. , 2016). The re-evaluation of FSC lineages and appreciation of population asymmetry as the governing principle not only highlighted FSCs as a suitable model for many types of mammalian stem cells but also drastically revised evaluation of the number, location and behavior of FSCs (Reilein et al. , 2017), as summarized below. Production of 5–6 ‘founder’ FCs (the first FCs to associate with a germline cyst to seed the FC epithelium) per budding cycle is accomplished by 14–16 FSCs, arranged in three anterior-posterior (AP) rings anterior to the border of strong Fas3 protein expression, near the mid-point of the germarium (1A–D; Hayashi et al. , 2020; Reilein et al. , 2017; Reilein et al. , 2018). These FSCs also produce a second cell type known as an Escort Cell (EC) (Hayashi et al. , 2020; Reilein et al. , 2017). ECs are quiescent cells anterior to the FSC domain (1A) that envelop and support the differentiation of developing germline cysts (Decotto and Spradling, 2005; Kirilly et al. , 2011). FCs, which first encapsulate region 2b germline cysts and are defined by continued association with a single cyst, derive directly from the posterior (‘layer 1’) FSCs, whereas ECs derive directly from anterior FSCs in layers 2 or 3 (Reilein et al. , 2017). Each FSC lineage (marked descendants of a single FSC) exhibits stochastic behaviors, including extinction or amplification and production of FCs, ECs or both. A single FSC lineage can include both ECs and FCs because FSCs can divide and can exchange AP locations over time. FSCs also exhibit extensive radial","Adult organisms contain a variety of cells that are routinely replaced using adult stem cells which can generate the cells of a specific tissue. These stem cells are often clustered into small groups, where combinations of chemical signals from nearby cells can encourage each stem cell to divide or ‘differentiate’ into another type of cell. These different signals must somehow balance stem cell division and differentiation to maintain the size and shape of the community. The ovary of an adult fruit fly contains a group of adult stem cells called follicle stem cells, or FSCs for short. FSCs support the continual production of eggs by supplying two types of cell from opposite faces of the stem cell cluster: dividing follicle cells emerge from the back of the cluster",380,128,0.3368
scientific_lay_summarisation-elife-norm,"TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18. Collagens are the most abundant secretory proteins, comprising 25–30% of the human body dry weight (Pataridis et al. , 2008). They are required for cell attachment, tissue organization and remodeling, and for the differentiation of chondrocytes to produce mineralized bones (Gelse et al. , 2003; Wilson et al. , 2011). There are at least 28 different kinds of collagens, composed of homo or hetero trimers of polypeptide chains coiled around each other to form a triple helix (Shoulders and Raines, 2009). These unbendable triple helices, which can be up to 450 nm long, as in the case of Collagen VII, are too big to fit into the conventional transport carriers of the secretory pathway that have been identified thus far (Malhotra and Erlmann, 2011). How are these bulky proteins exported from the ER? While the debate on the trafficking of collagen-like molecules across the Golgi stack goes unabated, new data are beginning to unravel the mechanism by which collagens are exported from the ER. A protein called TANGO1 has been identified for its requirement in the export of Procollagen VII (PC VII) from the ER in tissue culture cells (Saito et al. , 2009). The knockout of TANGO1 in mice results in the production of a pup that dies at birth due to defective bone mineralization. The cause is a block in the secretion of multiple collagens needed for the","Collagens are long proteins that join individual cells together to build tissues and organs. They also provide strength and elasticity to bones, tendons, and blood vessels. Like many other proteins, collagens are produced inside cells: they are folded in a compartment called the endoplasmic reticulum, and then packaged and transported to another compartment called the Golgi. Collagens are then directed from the Golgi to their final destination, which is typically the outside of the cell. Small proteins travel from the endoplasmic reticulum to the Golgi inside packages called vesicles. However it is not clear how large proteins like collagens are transported between these two compartments. It is known that a protein called TANGO1 is needed to direct a collagen called Procollagen VII to the outside of the cells.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"inhibitory neurons in the upper cortical layers which in-turn suppress dendritic Ca2+ activity. Since indirect brain stimulation shows immense promise in treating many neurological disorders, such as epilepsy (Berenyi et al. , 2012), this study not only illustrates the cellular mechanisms underlying TMS but also highlights dendrites as potential targets for therapeutic approaches. We recorded the Ca2+ activity in populations of layer 5 (L5) pyramidal neuron dendrites in the hindlimb somatosensory cortex of urethane anesthetized rats using a custom-made fiber optic' periscope' in vivo (Murayama et al. , 2007) oriented horizontally for use in tandem with a TMS coil (1A, — 1A). Pyramidal neurons located approximately 800 μm below the cortical surface were loaded with the Ca2+ indicator Oregon Green BAPTA1 AM (OGB1 AM; 1A inset and see' Materials and methods' ). Using this approach, large dendritic Ca2+ responses to brief hindpaw stimulation (100 V, 1 ms) were reliably evoked after 70 min loading with OGB1 AM (— 1B). To investigate the effects of TMS on evoked cortical network activity, the TMS coil was positioned just above the craniotomy (1A) and a single brief TMS pulse was evoked together with the stimulation of the hindpaw (1B) greater than 70 min post loading with OGB1 AM. TMS caused a significant decrease in the hindpaw-evoked dendritic Ca2+ response when triggered 50 ms before hindpaw stimulation (1C and — 2A), both in the maximum amplitude (control, 7. 3 ± 1. 5 △F/F versus TMS, 5. 0 ± 1. 1 △F/F, n = 17, p<0. 05) and integral (control, 4. 3 ± 0. 9 △F/F•s versus TMS, 2. 4 ± 0. 6 △F/F•s; n = 17; p<0. 001, 1D). Further, the size of the coil (— 2B) and the type of hindpaw stimulation (— 2C) did not influence the results, whereas the distance of the coil from the cortical region of interest influenced the effectiveness of the TMS inhibition on the dendritic sensory responses (— 3). 10. 7554/eLife. 13598. 003Figure 1. TMS inhibits sensory evoked Ca2+ activity in layer 5 dendrites. (A) Schematic of the experimental design. Layer 5 pyramidal neurons were bulk loaded with OGB1-AM and dendritic Ca2+ activity was recorded using a flat-periscope configured horizontally and inserted underneath the TMS coil from the side. The TMS coil was placed above the dendrites","The brain’s billions of neurons communicate with one another using electrical signals. Applying a magnetic field to a small area of the scalp can temporarily disrupt these signals by inducing small electrical currents in the brain tissue underneath. The currents interfere with the brain’s own electrical signals and temporarily disrupt the activity of the stimulated brain region. This technique, which is known as transcranial magnetic stimulation, is often used to investigate the roles of specific brain regions. By examining what happens when a region is briefly taken ‘offline’, it is possible to deduce what that area normally does. Transcranial magnetic stimulation is also used to treat brain disorders ranging from epilepsy to schizophrenia without the need for surgery or drugs. But despite its widespread usage, little is known",380,128,0.3368
scientific_lay_summarisation-elife-norm,"at least a two fold increase (1B) using TargetScan 7. 1 (Lewis et al. , 2005) to identify potential targeting to the mRNAs SCN5A, SCN1B, and KCND3. Ultimately, we identified miR-34b and −34c as the only miRNAs predicted to target not just one of these ion channel genes, but notably target all three collectively (1C). Notably, we also observed 14 miRNAs decreased greater than two fold (1B). However, a loss in miRNA expression is not consistent with the role of KChIP2 as a transcriptional repressor, and also would not lead to a decrease in ion channel mRNA expression. Real-time qPCR was used to confirm the array results, showing elevation in the mature transcripts for miR-34b and −34c (1D). Importantly, we also performed overexpression of three different cardiac KChIP2 isoforms which reduced the expression of miRs-34b/c (1D). Together, these changes are consistent with the novel idea that KChIP2 behaves as a transcriptional repressor. 10. 7554/eLife. 17304. 003Figure 1. miR-34 regulation linked to changes in KChIP2 expression. (A) Results of miRNA microarray showing the log2 of the fold changes in miR expression following 72 hr of KChIP2 siRNA treatment. Arrow identifies miR-34b and −34c amongst the panel of altered miRNAs. Analysis of miRNAs for mRNA targets using TargetScan 7. 1 was restricted to those above two fold induction (dashed line) (B) Tables showing the list of those miRNAs showing at least a two fold increase or decrease following KChIP2 silencing. (C) Alignment of the 3’-UTR of SCN5A, SCN1B, and KCND3 genes with miRs-34b/c from rat, showing hybridization of the seed region. Grayed letters indicate variation in sequence between miR-34b and −34c. A single site of interaction is indicated for SCN5A and SCN1B while two sites exist for KCND3. (D) Real-time qPCR analysis showing percent change of miR-34b/c expression from control cells in NRVM transfected with KChIP2. 3 (n = 5), KChIP2. 6 (n = 6), KChIP2. 4 (n = 4), or KChIP2 siRNA (n = 4–5). (E) Cytosolic, membrane, and nuclear fractions of native adult rat heart tissue. KChIP2 nuclear localization was assessed by using lactate dehydrogenase (LDH), Serca2a, and Lamin-B as cytoplasmic, membrane, and nuclear markers respectively. (F) Representative z-stack images of adult rat ventricular myocyte. Nuclear stained regions (DAPI, blue) show the absence of cytosolic protein LDH (green), while KChIP2","The heart pumps blood throughout the body to provide oxygen and nourishment. To do so, proteins in the heart create electrical signals that tell the heart muscles to contract in a coordinated manner. Heart disease can cause cells to lose control of the production or activity of these proteins, creating disorganized electrical signals called arrhythmias that interfere with the heart’s ability to pump. Sometimes these arrhythmias lead to sudden death. Researchers do not know exactly what triggers these changes in the heart’s normal electrical rhythms. This has made it difficult to develop strategies to prevent these disruptions or to fix them when they occur. By studying rat and human heart cells, Nassal et al. now show that a protein called KChIP2 stops working properly during heart disease. Most",380,128,0.3368
pubmed-summarization,"the surveyed races were flat races on turf and dirt tracks held by the jra from january 1st , 2002 , to december 31st , 2010 . the race lengths were 1,200 , 1,400 , 1,600 , 1,800 and 2,000 m on turf and 1,000 , 1,200 , 1,400 , 1,700 and 1,800 m on dirt . these were the respective top 5 races in terms of their number of starters . the base of a dirt track is a layer of mountain sand packed firmly and then covered with loose sand ( 9 cm ) to absorb the touchdown impact . only the final time data from firm or standard condition tracks were used in this study because track condition affects the final time and the firm and standard conditions had the most data . the final time is that officially recorded by the jra , which is measured on video in time increments of one - tenth of a second . the horses were divided by gender , with one group being females and the other being males & geldings ; male horses and geldings were grouped together because of the relatively low number of geldings belonging to the jra . the racing speed of each horse was calculated by dividing the race distance ( m ) by the horse s final time ( sec ) . average speeds per month for each age and distance condition were calculated for each gender group when there were 30 or more starters per month for each age and distance condition in each gender group . the average weight carried per month by each age group was calculated for each gender group when there were 30 or more starters per month for each age group in each gender group . in descending order , the greatest number of turf race starters were found in the 1,200 m , 1,800 m , 2,000 m , 1,600 m and 1,400 m races ( table 1table 1.distribution of gender and distance for starters on flat turf racesdistance ( m)gender1,2001,4001,6001,8002,000males & geldings22,0248,76116,00621,51422,013females24,2278,31011,00913,1008,962total46,25117,07127,01534,61430,975 ) . the greatest number of starters for dirt races , in descending order , were found in the 1,200 m , 1,800 m , 1,700 m , 1,400 m and 1,000 m","abstractthe running performance of thoroughbred racehorses has been reported to peak when they are between 4 and 5 years old . however , changes in their racing speed by month or season have not been reported . the purposes of this study were to reveal the average racing speed of thoroughbreds , and observe changes in their average speed with age . the surveyed races were flat races on turf and dirt tracks with firm or standard track conditions held by the japan racing association from january 1st , 2002 to december 31st , 2010 . the racing speed of each horse was calculated by dividing the race distance ( m ) by the horse s final time ( sec ) . average speeds per month for each",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Exposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behavior (‘susceptible’) and those who escaped the deleterious effect to stress (‘resilient’). Myelin protein content in the nucleus accumbens was reduced in all mice exposed to stress, whereas decreased myelin thickness and internodal length were detected only in the medial prefrontal cortex (mPFC) of susceptible mice, with fewer mature oligodendrocytes and decreased heterochromatic histone marks. Focal demyelination in the mPFC was sufficient to decrease social preference, which was restored following new myelin formation. Together these data highlight the functional role of mPFC myelination as critical determinant of the avoidance response to traumatic social experiences. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor' s assessment is that all the issues have been addressed (see decision letter). Exposure to stress increases the risk of developing affective disorders such as depression and post-traumatic stress disorder. While stress leads to maladaptive behavioral responses in a subset of humans, others are capable of coping and remain resilient. Differences in the behavioral response to stress can also be detected in experimental mouse models, thereby highlighting the degree of conservation of this response. However, the cellular and molecular basis underlying resilience or susceptibility to negative experiences remains poorly defined. We and others have previously reported that animal models of psychosocial stressors, such as social isolation (Liu et al. , 2012; Liu et al. , 2016; Makinodan et al. , 2016; Makinodan et al. , 2017; Makinodan et al. , 2012), chronic social defeat stress (CSDS) (Cathomas et al. , 2019; Lehmann et al. , 2017), and chronic variable stress (Liu et al. , 2018), lead to transcriptional, translational, or ultrastructural changes in oligodendrocytes and myelination. Here we tested the hypothesis that myelinating glia serves a causal role in behavioral susceptibility or resilience following stress exposure. We examined social behaviors, ultrastructural changes in myelination as well as epigenetic modifications in oligodendrocytes in brain regions","High levels of stress do not have the same effect on everybody: some individuals can show resilience and recover quickly, while other struggle to cope. Scientists have started to investigate how these differences may find their origin in biological processes, mainly by focusing on the role of neurons. However, neurons represent only one type of brain cells, and there is increasing evidence that interactions between neuronal and non-neuronal cells play an important role in the response to stress. Oligodendrocytes are a common type of non-neuronal cells which shield and feed nerve cells. In particular, their membrane constitutes the myelin sheath, a protective coating that insulates neurons and allows them to better communicate with each other using electric signals. Bonnefil et al. explored whether differences in oligodendrocytes could affect",380,128,0.3368
dialogsum,"#Person1#: Do you sometimes feel overwhelmed by your work? #Person2#: Of course! It is the No. 1 stressor in my life. You know job stress has become a very common problem these days. So we must learn to cope with it. #Person1#: Totally agree. What is your solution? #Person2#: Well, there are two causes of job stress. One is employee characteristic and the other is company condition. So if we want to manage job stress, both we and the companies should do something. For me, I am trying to balance work and leisure time. You know, all work and no play make Jack a dull boy. #Person1#: You seem to have a very relaxed outlook. #Person2#: It is necessary. Positive attitude helps to prevent stress. #Person1#: But I don ' t think we can change our working condition. Anyway, we are not the bosses. #Person2#: I heard some companies are providing stress management training and making changes inside them, like avoiding unrealistic deadlines and organizing relaxation activities. Our boss is a smart person. He will be learning from that if he would like to an efficient and healthy team.","#Person1# asks #Person2# about job stress. Then #Person2# explains that two causes of job stress are employee characteristic and company condition, and provides some solutions to each cause.",189,28,0.1481
dialogsum,"#Person1#: It's so relaxing, taking a walk in the country. The air is so fresh and clean. #Person2#: Would you like to live in the country? I'm not sure I'd like it. #Person1#: I can see a lot of advantage and disadvantage. The problem is that, for me, each advantage has its own disadvantage. #Person2#: What do you mean? #Person1#: Well, I hate the noise in the city, but I love being around lost of people. The problem is that you can't have lots of people and have peace and quiet. The tow just don't go together. #Person2#: I see what you mean. I love being far away from a city, but I hate being so far away department stores and sports facilities. #Person1#: People can't have it both ways. If you live in the country, it is often less convenient. If you live in a city, it is noisy, buy there's more to do. #Person2#: I would love to be surrounded by hills and streams. They're so much better to look at than concrete, rows of parked cars and tall buildings. #Person1#: I would love to hear the birds singing and feel the fresh breeze on my face. When the wind blows in the city, you get dust in your mouth and in your eyes. #Person2#: The view from the hill is so beautiful and relaxing. There's so sign of pollution. The village looks so peaceful. #Person1#: Just remember that in that village there's nothing to do. There's not even a pub or restaurant. There's just one small shop with a poor selection of goods. #Person2#: You're right. I would have to travel to the city at least once a week to go shopping and see friends. I would hate living in the country!","#Person1# and #Person2# are talking about the advantages and disadvantages of living in the country. For #Person1# each thing has two sides and people cannot have them both. They both like the peaceful life in the country, but it isn't convenient for distant stores and facilities.",295,46,0.1559
dialogsum,"#Person1#: Hi, Francis, how was your business trip? #Person2#: It was a nightmare. #Person1#: What's up? #Person2#: Actually, the business trip itself was very successful. We arrived on time, we had nice conversations and we settled some important issues for the next year. #Person1#: Sounds quite fruitful, why do you call it still a nightmare then? #Person2#: Well, the air line lost my luggage on the return flight and then I lost my carry on bag when I was tackling with the officers in charge. I left the airport three hours later than I expected and then I was caught in a traffic jam. When I finally got home, I was totally exhausted. But I found the elevator was out of service due to a blackout. #Person1#: This is really a sad story. Did they trace back your luggage? #Person2#: I am still waiting for their call. #Person1#: Take it easy, all sufferings have their reward.",#Person2# tells #Person1# the business trip was a nightmare because he lost his luggage and carry-on bag. He was also caught in a traffic jam and found the elevator was out of service.,156,33,0.2115
dialogsum,"#Person1#: Have you been registered yet, sir? #Person2#: No, I haven't been registered. #Person1#: Are you a medical or surgical case? #Person2#: I'm a medical case. #Person1#: Do you have your medical history sheet with you? #Person2#: Yes, here you are. #Person1#: Please fill in this admission card. Well, how long do you expect to stay in the hospital? #Person2#: The doctor told me to stay about one month. #Person1#: But there're no beds available now. Two patients will be discharged this afternoon, so you'll have to wait until then. #Person2#: Well, when they leave the hospital, give me a call and I'll come back. #Person1#: Certainly. See you in the afternoon.",#Person2# applies to stay in the hospital but there're no beds available. #Person2# requests #Person1# to call him when the bed's available.,112,22,0.1964
scientific_lay_summarisation-elife-norm,"shown). Treatment with purified Bacillus cereus sphingomyelinase (SM) for 30 s enhanced the anti-ceramide staining along the PM. Permeabilization with the pore-forming toxin streptolysin O (SLO) had a similar effect, rapidly increasing the anti-ceramide reactivity at the cell periphery (1A, B). These results suggested that injury with SLO or exposure to SM triggered the formation of ceramide-enriched structures that might represent PM invaginations or intracellular vesicles. 10. 7554/eLife. 00926. 003Figure 1. Caveolae-like vesicles accumulate in cells exposed to SLO and sphingomyelinase. (A) Cryo-immuno EM with anti-ceramide in NRK cells untreated or exposed to SLO or SM for 30 s. Bars: 100 nm. Arrows: patches of ceramide staining near the PM. (B) Quantification of anti-ceramide label in cells treated as in (A). All gold particles (2522–6876) within an area of 200 nm along the PM were counted in 14–31 cell sections. Data represent mean ± SEM of gold particles/cell section. *p=0. 023, ***p<0. 001. The results are representative of two independent experiments. (C) TEM of NRK cells exposed or not to SLO+Ca2+ or SM in the presence of BSA-gold. Arrows: <80 nm vesicles with BSA-gold. Arrowheads: merged vesicles. Bars: 100 nm. (D) Quantification of vesicles with BSA-gold in control, SLO or SM-treated cells after 30 s. All vesicles containing BSA-gold (191–485) were counted in 20 cell sections/sample. Data represent mean ± SEM of BSA-gold-containing vesicles/cell section. ***p<0. 001. The results are representative of two independent experiments. (E) Numbers of BSA-gold positive <80 nm and >80 nm vesicles over time in SLO treated cells. Data represent mean ± SEM of vesicles/cell section. *p=0. 033, **p=0. 004, ***p<0. 001 (comparison with <80 nm vesicles in the same time point). (F) Average area of BSA-gold positive vesicles over time. Data represent mean ± SEM of vesicle area/cell section. ***p<0. 001 (comparison with 30 s time point). (G) BSA-gold particles detected within <80 nm and >80 nm vesicles over time. Data represent mean ± SEM of gold particles. **p=0. 0019 (comparison with <80 nm vesicles in the same time point). From (E) to (G), all gold-containing vesicles (73–142) were quantified in 14–47 cell sections. (H) TEM of NRK cells untreated (control) or treated with ASM in the presence of BSA-gold as an endocytic tracer. Arrows point to <80 nm vesicles containing BSA-gold; arrowheads point to","Cells must be able to rapidly repair damage to their outer membranes. This is particularly important in the case of muscle cells, which are vulnerable to damage, and the failure of these cells to repair their outer membranes leads to the muscle wastage seen in muscular dystrophy. Researchers do not fully understand how cells repair membrane, but one popular theory is that they use the membranes of specialized vesicles to ‘patch’ areas that have been damaged. A group of proteins called caveolins have also been implicated in membrane repair but, again, the details have not been worked out. These proteins are best known for their role in the formation of caveolae — small pouches formed by invaginated sections of the plasma membrane. Now, Corrotte et al. have obtained",380,128,0.3368
dialogsum,"#Person1#: It's almost Christmas. What are you doing this weekend? #Person2#: Nothing special, just working. Why do you ask? #Person1#: Well, I still haven't finished my Christmas shopping. Do you want to go shopping with me this weekend? #Person2#: I'd like to, but I'm not sure if I can. Work has been really busy lately. Why don't we go on Friday instead? #Person1#: Friday's not good. I think the stores will be very crowded and I have to work. #Person2#: OK, then let's try to go this weekend. I should know if I can go by Friday. Is it OK if I call you then? #Person1#: Yeah, that's fine. #Person2#: What's your number? #Person1#: 233-331-8828. Let me give you my email address too. It's Tom861@gmail. com #Person2#: OK, I'll talk to you soon. #Person1#: OK.","Tom invites #Person2# to do Chrismas shopping on Friday night, but #Person2# isn't sure if #Person2# will be available. Tom gives #Person2# his contact information and #Person2#'ll tell him then.",135,30,0.2222
pubmed-summarization,"superficial global muscles . although many studies on the effect of the abdominal hollowing exercise in rehabilitation programs have been performed , none have examined the combined effect of the abdominal hollowing exercise and curl - up exercise on an unstable surface . therefore , the purpose of this study was to investigate the effects of the abdominal hollowing exercise on trunk muscle activity during the curl - up exercise on an unstable surface by measuring electromyography ( emg ) activity . fourteen healthy subjects ( nine males , five females ) volunteered to participate in this study ( table 1table 1.summary of anthropometric characteristics and neck disability index of the study participantscharacteristiccontrol group(n = 13)mnp group(n = 14)gender ( n , male)66age ( years ) , mean ( sd)20.6 1.620.6 1.5height ( cm ) , mean ( sd)167 . 6.9168.0 8.0weight ( kg ) , mean ( sd)60.7 10.761.0 12.4neck disability index ( ndi ) ( % ) , mean ( sd)3.3 2.616.9 7.1*mnp : mild neck pain ; sd : standard deviation . all subjects were in good health and reported no history of neurological and/or respiratory diseases . none of them had undergone institutional care for any pathological back conditions during the preceding year . * significant difference between the two groups ( p < 0.05 ) emg data were collected using a biopac mp150wsw data acquisition system ( biopac systems , inc . , surface electrode pairs were oriented along the line of action of the underlying muscle fibers on the right side : ra , centered 2 cm lateral and caudal to the umbilicus ; tra , centered 2 cm cephalad to the pubic bone , just lateral to the midline , and parallel to the superior pubic ramus ; external oblique ( eo ) , centered over the tip of the eighth rib diagonally ; and internal oblique ( io ) , centered 2 cm proximal to the midpoint from the anterior superior iliac spine ( asis ) to the symphysis pubis diagonally11 . the maximum voluntary isometric contraction ( mvic ) of each muscle was measured using the maneuver suggested by kendall et al.12 for normalization . the subjects were instructed on how to perform the curl - up and abdominal hollowing exercises","[ purpose ] the purpose of this study was to investigate the effects of the abdominal hollowing exercise on trunk muscle activity during the curl - up exercise on an unstable surface by measuring electromyography ( emg ) activity . [ subjects ] fourteen young healthy adults ( nine male , five female ) voluntarily participated in this study . [ methods ] each subject was asked to perform a curl - up exercise on two supporting surfaces ( stable and unstable surfaces ) combined with the abdominal hollowing exercise on an unstable surface . the muscle activities of the rectus abdominis ( ra ) , external oblique ( eo ) , internal oblique ( io ) , and transverse abdominis ( tra ) were measured using surface",380,128,0.3368
scientific_lay_summarisation-elife-norm,"been identified at the mother spindle pole containing protein components that promote maturation (Yamashita et al. , 2007; Izumi and Kaneko, 2012; Chen et al. , 2014). Several disease-linked genes encode these proteins and their loss causes mitotic delays and spindle misorientation phenotypes (Buchman et al. , 2010; Gruber et al. , 2011; Tan et al. , 2014; Chen et al. , 2014; Kim and Rhee, 2014). Spindle orientation defects that promote an imbalance between symmetric and asymmetric cell divisions have been implicated in the progression of germ line-derived cancers such as teratomas, seminomas, and ovarian carcinomas (Neumüller and Knoblich, 2009). These cancers can be exacerbated by mislocalization or misregulation of mitogenic and mitotic protein kinase cascades (Carnegie et al. , 2009; Scott and Pawson, 2009). The A-kinase anchoring protein Gravin/AKAP12/SSeCKS has been implicated in the control of mitotic progression (Xia et al. , 2001; Gelman, 2010; Canton et al. , 2012; Canton and Scott, 2013). We now report that Gravin is depleted in proliferating germ line-derived tumors from several patients diagnosed with testicular seminoma. Mechanistic studies show that Gravin is required to spatially coordinate the activities of Aurora A and polo-like kinase 1 (Plk1), two kinases that act in concert to promote spindle orientation. Mutation or amplification of Gravin has been linked to melanoma, prostate, and ovarian cancers, yet nothing is known about the role of this kinase-anchoring protein in solid tumors (Xia et al. , 2001; Bateman et al. , 2015; Finger et al. , 2015). Testicular germ line tumors are the most frequently diagnosed solid cancers in men aged 15–40 years. Currently, 200,000 men develop seminoma annually (Fung et al. , 2007; Burum-Auensen et al. , 2010; Singh et al. , 2011). Although seminoma screening and treatment is well understood, much less is known about the molecular events in germ line stem cells that underlie oncogenesis. Surprisingly, immunoblot analysis of clinical samples from three seminoma patients detected a 9. 15-fold reduction in Gravin protein compared to adjacent tissue (1A, B). Interestingly, the loss of Gravin was accompanied by a decrease in two essential cell cycle regulator kinases, Aurora A and Plk1 (1A, mid panels, and 1B). Similar trends were observed in four additional clinical samples from seminoma patients (— 1A). 10. 7554/eLife. 09384. 003Figure 1. Loss of","The genetic material inside our cells is contained within structures called chromosomes. When a cell divides, these chromosomes are copied and then must be correctly divided between the two daughter cells so that each cell has a complete set of genetic material. The correct separation of the chromosomes depends on a structure called the mitotic spindle whose location in the cell also determines where the point of division will be. Two structures called centrioles are associated with the mitotic spindle and help to organize and direct cell division. The cell carefully controls how these structures are inherited by the daughter cells. For example, when a stem cell divides to produce one stem cell and one cell of a different type, the older centriole can be inherited by the",380,128,0.3368
pubmed-summarization,"were saudi adults of 18 years of age or more , with a definite first stroke . the clinical diagnosis was made by the admitting physician and reviewed independently by two members of the study group ( em and mn ) . the ct brain scans were reviewed by two observers , a radiologist ( ka ) and a physician ( mn ) to determine the pathological type of the stroke . the reliability of the method was confirmed by assessing a random 10% sample of the radiographs without knowledge of prior reports . survival duration was estimated from the date of onset of stroke to the date of death or last contact . kaplan - meier analysis was used with log - rank procedure to compare unadjusted survival . cox proportional hazard analysis was used to investigate the effect of each prognostic factor on survival . in all data analysis , the bmdp statistical software package was used ( university of california press , berkeley , 1991 ) . there were 106 males and 68 females with a male to female ratio of 1.56:1 . hypertension , diabetes mellitus and heart disease were found in 54 ( 31% ) , 49 ( 33% ) and 57 ( 28% ) of patients respectively . at the time of analysis , 126 patients , 72.4% of all patients , were alive . over the follow up period , 19 patients ( 10.9% ) died within 2 weeks , 32 patients ( 18.4% ) died within 4 weeks and 38 patients ( 21.8% ) died within 24 weeks . while the median survival has not been reached , the lower 95% confidence limit for the median survival was estimated at 103.14 weeks . kaplan - meier survival curve for all patients in the study is shown in . figures 2a , 2b and 2c show the survival curves of the patients who presented with or without coma , heart disease and age below and above 60 years consecutively . unadjusted analysis of survival as a function of various variables is shown in table 1 . a logistic regression analysis to examine the adjusted effect of these variables to estimate their independent influence on survival overall survival of patients with stroke survival of","background : prognosis of stroke has been studied in various population . factors adversely affecting short term survival include impaired consciousness , leg weakness and increasing age.aim of the study : in this study , the prognostic effects of age , sex , hypertension , diabetes mellitus and presentation in coma on the survival pattern of stroke patients presenting to a referral hospital , are reviewed.methodology:the medical records of all patients hospitalized with definite stroke at king fahd specialist hospital , buraidah , for the period between june 1986 and june 1991 , were reviewed . the cranial ct scans were also reviewed.results:one hundred and seventy four patients , 106 males and 68 females , with a mean age of 64 years who had definite stroke were studied",380,128,0.3368
dialogsum,"#Person1#: Hey, check out this new game I bought today. #Person2#: Wow! It's a trivia game all about the Academy Awards. #Person1#: I know you love the Oscars. This game has some great questions about all types of movies. #Person2#: Does it have questions about foreign language films? There's hardly any American films worth watching. #Person1#: Yes. In fact, one of the categories is on foreign language films.",#Person1# and #Person2# talk about the new trivia game #Person1# bought today.,68,12,0.1765
scientific_lay_summarisation-elife-norm,"2004). NPC2 transports the cholesterol to the lysosomal membrane where it transfers its cholesterol to membrane-embedded NPC1 (Wang et al. , 2010). Designated a hydrophobic handoff, this transfer occurs in such a way that hydrophobic cholesterol is shielded from the aqueous environment (Kwon et al. , 2009). NPC1 is an intrinsic membrane protein of 1278 amino acids that contains 13 membrane spanning helices separated by hydrophilic loops and 19 potential N-linked glycosylation sites (Davies and Ioannou, 2000) (see ). NPC2 transfers its cholesterol to the N-terminal domain (NTD) of NPC1, which is the hydrophilic sequence of 239 amino acids that projects into the lysosomal lumen after the signal peptide is cleaved (Infante et al. , 2008a; 2008b). NPC2 binds to the second luminal loop of NPC1, an event that may precede the cholesterol transfer to the NTD (Deffieu and Pfeffer, 2011). Mutations that abolish the function of either NPC2 or NPC1 lead to cholesterol accumulation in lysosomes and cause the fatal Niemann-Pick C disease (Pentchev, 2004; Dixit et al. , 2011). 10. 7554/eLife. 12177. 003Figure 1. Domain structure of human Niemann-Pick C1 (NPC1). The predicted topology of the polytopic protein is based on the data of Davies and Ioannou (2000). Each of the five known functional domains of the protein are shown in a different color. The locations of three loss-of-function mutations referred to in the manuscript are indicated. aa, amino acid; NTD, N-terminal domain. : http: //dx. . org/10. 7554/eLife. 12177. 003 After its transfer to NPC1, cholesterol leaves the lysosome by a mechanism that is poorly understood. Some of the cholesterol reaches the endoplasmic reticulum (ER) where it has two actions. First, it binds to Scap, an ER protein that regulates the cleavage and activation of membrane-bound sterol regulatory element-binding proteins (SREBPs). Cholesterol binding to Scap prevents the protease-mediated release and nuclear entry of the active fragment of SREBPs, thereby blocking cholesterol synthesis and uptake from LDL (Horton et al. , 2002). When excess cholesterol reaches the ER, it is esterified with a long chain fatty acid through the action of acyl-coenzyme A cholesterol acyltransferase (ACAT), which converts the cholesterol to its storage form as cholesteryl esters (Brown et al. , 1975). Lysosome-derived cholesterol also reaches the plasma membrane where it fills three distinguishable pools, thereby assuring membrane","Cholesterol is a type of fat molecule and is a vital component of animal cell membranes. It is taken up into cells within particles called low density lipoproteins (LDLs) that are then digested in cell compartments known as lysosomes to release the cholesterol. Then, the cholesterol leaves the lysosome with the help of a transport protein called NPC1. Mutations in the gene that encodes NPC1 lead to the accumulation of cholesterol in lysosomes; this can cause a devastating illness that affects the brain, liver and other organs. The NPC1 protein also plays a crucial role in allowing Ebola viruses to infect animal cells and multiply. U18666A is a drug that blocks the movement of cholesterol out of lysosomes and also inhibits Ebola virus infections, but it was not",380,128,0.3368
dialogsum,"#Person1#: I left a suitcase on the train to London the other day. #Person2#: Can you describe it, sir? #Person1#: It's a small blue case and it's got a zip. There's a label on the handle with my name and address on it. #Person2#: Is this case yours? #Person1#: No, that's not mine. #Person2#: What about this one? This one's got a label. #Person1#: Let me see it. #Person2#: What's you name and address? #Person1#: David Hall, 83, Bridge Street. #Person2#: That's right. D. N. Hall. 83. Bridge Street. Three pound and fifty pence please. #Person1#: Here you are. #Person2#: Thank you. #Person1#: Hey! #Person2#: What's the matter? #Person1#: This case doesn't belong to me! You've given me the wrong case!",#Person1# asks #Person2# to find #Person1#'s suitcase. #Person2# asks #Person1# to tell more information but #Person2# still gives #Person1# the wrong suitcase.,121,22,0.1818
dialogsum,"#Person1#: We like your product, and are interested in placing an order with you as soon as possible. #Person2#: Well, we can proceed with the order until after the Christmas holidays. Our factories will be closed for another week. #Person1#: That's all right. We will send you a purchase order in one week. I hope you will be able to take care of it. #Person2#: No problem. Once we get your purchase order, we will begin the execution of the order right away. #Person1#: Thanks. We need the products in less than one month, because we have a big deal with another company. By the way, will payment against delivery be OK? #Person2#: That will be fine. And I can promise you that you'll get the goods about two weeks after we get your purchase order.",#Person1# will send #Person2# a purchase order and #Person2# will begin the execution immediately and will finish in two weeks after receiving it.,136,23,0.1691
scientific_lay_summarisation-elife-norm,"2006; Scorrano et al. , 2002) and outer membrane permeability (Gross et al. , 1999; Li et al. , 1998; Luo et al. , 1998; Walensky et al. , 2006; Wang et al. , 1996). cBid associates with the multidomain Bcl-2 proteins Bax and Bak through its BH3-domain at the outer mitochondrial membrane (OMM), triggering mitochondrial outer membrane pores (MOMP) (Gross et al. , 1999; Li et al. , 1998; Luo et al. , 1998; Walensky et al. , 2006; Wang et al. , 1996). Bid’s role in regulating cristae structure has been limited to in vitro studies focusing on isolated mitochondria and cBid. cBid’s interaction with the mitochondrial membrane is stabilized in part through an interaction with MTCH2 as well as cBid’s membrane binding domain (MBD), consisting of alpha-helices 4,5, and 6 (Tae-Hyoung Kim, Yongge Zhao, Wen-Xing Ding, Kim et al. , 2004). Alpha-helix-6 partially embeds within the membrane (Oh et al. , 2005), and has been shown to be necessary for apoptotic cristae reorganization (Cogliati et al. , 2013). In addition to its apoptotic function, Bid is also known to be involved in the regulation of other essential cellular processes such as DNA damage and metabolism, acting as rheostat for cell health (Reviewed in Giménez-Cassina and Danial, 2015; Hardwick et al. , 2012; Zinkel et al. , 2006). Interestingly, full-length Bid can also localize to the mitochondria (Maryanovich et al. , 2012; Wang et al. , 2014). The role for this association and the consequence for mitochondrial function as well as implication for human disease have not been explored. We reveal a new role for full-length Bid in the regulation of mitochondrial cristae under homeostatic conditions in an approach that integrates cell biology with human genetic studies (). We observe that loss of Bid impairs proper cristae formation in the absence of an apoptotic stimulus both in myeloid cells and left ventricular (LV) cardiomyocytes. This function is independent of Bid’s caspase-8 cleavage site (D59A), and BH3-domain. We demonstrate decreased respiration in Bid-/- cells and decreased respiration coupled with decreased ATP production in LV fibers. These deformations become more pronounced in the heart when it is exposed to various cardiac stressors including Epinephrine and Doxorubicin, in both cases leading to decreased LV function in Bid-/- mice. In the case","Cells contain specialized structures called mitochondria, which help to convert fuel into energy. These tiny energy factories have a unique double membrane, with a smooth outer and a folded inner lining. The folds, called cristae, provide a scaffold for the molecular machinery that produces chemical energy that the cell can use. The cristae are dynamic, and can change shape, condensing to increase energy output. Mitochondria also play a role in cell death. In certain situations, cristae can widen and release the proteins held within their folds. This can trigger a program of self-destruction in the cell. A family of proteins called Bcl-2 control such a ‘programmed cell death’ through the release of mitochondrial proteins. Some family members, including a protein called Bid, can reorganize cristae to regulate this",380,128,0.3368
dialogsum,"#Person1#: Do you offer a course in business management? #Person2#: Yes, we do. #Person1#: How many nights a week is it? #Person2#: It's 3 nights a week, Monday, Tuesday and Thursday. #Person1#: And how long does the course last? #Person2#: It lasts for 9 months. #Person1#: When does it start? #Person2#: The next beginning class starts on October 25th. #Person1#: What time is the class? #Person2#: From 7 to 9 o'clock. #Person1#: How much does it cost? #Person2#: It costs 125 dollars a month. #Person1#: Yes, that's all right. I want to enroll in the course. #Person2#: Thank you, please fill out this form for us. #Person1#: Do you want me to fill it out now? #Person2#: Yes , please. we need a record of you enducation and your work experiences.",#Person1# asks #Person2# about a business management course and decides to enroll.,131,12,0.0916
pubmed-summarization,"students use of test preparation and test taking strategies . each scale contains eight items except one which has five ( 77 items in total ) . for each of the 77 items , students were requested to darken the bubble containing the letter that corresponds to how well the statement describes them on a five - scale ranging from not at all like me ( scale : 1 ) to very much like me ( scale : 5 ) . this questionnaire is a diagnostic tool to find out the learning problems in ten different domains , so the overall score is not calculated12 . validity and reliability of the persian version were confirmed in previous studies.13 for the intervention group , different components of strategic learning like attitude , motivation , time management , anxiety , concentra - tion , study aids , etc . were taught during the semester in two - hour weekly sessions ( 16 sessions in total ) . the course was held as a workshop and all the students actively participated in the program . at the beginning of each session , the students presented written and oral reports about the application of the learning strategies which were introduced in the previous discussion . in each session the lecturer provided some explanation about the subject by an example and then , a discussion was held about the importance of using the learning guidelines . since the students were aware of each session 's topic and had to do some study about the topics before each session , they actively participated in the discussion . the lecturer had to provide the information and data during the discussion and conclude the topic at the end of each session while defining the assignments and resources for the next session . in the second session of the course , each student was informed about his pre - course score and became aware of his / her weaknesses . in the control group , students attended clinical physiology lectures and case presentations presented by a physiology professor . students were evaluated based on a portfolio , self - evaluation questionnaire and their progress in lassi test . portfolio was consisted of monitoring forms about the implementation of each","background : it has been demonstrated that educational programs that focus on study skills could improve learning strategies and academic success of university students . due to the important role of such supportive programs aimed at the fresh students , this survey was carried out to investigate the effectiveness of an optional course of learning and study skills on learning and study skills of second year medical students.methods:this quasi - experimental research was performed on 32 eligible medical students in isfahan university of medical sciences , who chose the optional course of learning and study skills . both of intervention and control groups completed learning and study strategies inventory ( lassi ) at the beginning and the end of semester . students in the intervention group studied different",380,128,0.3368
pubmed-summarization,"schwannoma may arise from any peripheral nerve and is often found in the chest wall and posterior mediastinum . however , case reports of intrapulmonary schwannoma are extremely rare . a 38-year - old man was referred to our institution because of an abnormal shadow found incidentally on the chest x - ray . the plain chest x - ray showed a mass lesion in the left middle zone . chest computed tomography ( ct ) showed a round and homogeneous mass 25 18 mm in size with a well - defined margin in the lingular segment of the left upper lobe ( . 18-fluorodeoxy - glucose ( fdg ) positron - emission tomography ( pet ) showed no accumulation in the tumor ( . the ct and fdg - pet findings suggested the possibility of a benign tumor or a low - grade malignancy . as a malignant tumor could not be definitively ruled out , we performed lingular segmentectomy. . 1 a computed tomography shows a mass with well - defined margins in the lingular segment of the left upper lobe . b 18-fluorodeoxy - glucose ( fdg ) positron - emission tomography ( pet ) showed no accumulation in the tumor a computed tomography shows a mass with well - defined margins in the lingular segment of the left upper lobe . b 18-fluorodeoxy - glucose ( fdg ) positron - emission tomography ( pet ) showed no accumulation in the tumor macroscopic examination of the resected specimen showed a well - demarcated round tumor in the lung , without any evidence of invasion of the surrounding tissues . microscopic examination revealed proliferation of elongated tumor cells having spindle - shaped nuclei , with cellular palisading ( . immunohistochemical staining demonstrated positive staining of the tumor cells for s-100 protein and bcl2 , but negative staining for cd34 and desmin . the histopathological diagnosis was intrapulmonary schwannoma. . 2 a macroscopic examination of the specimen showed a round , well - demarcated tumor in the lung , without invasion of the surrounding tissues . b microscopic examination revealed elongated tumor cells with spindle - shaped nuclei a macroscopic examination of the specimen showed a round , well - demarcated tumor in the lung , without invasion of","a 38-year - old man without any symptoms was admitted to our institution because of an abnormal shadow found incidentally on a chest x - ray . chest computed tomography showed a round mass in the lingular segment of the left upper lobe . lingular segmentectomy was performed , and the histopathological diagnosis was intrapulmonary schwannoma . immunohistochemical staining revealed a positive result for s-100 protein and negative results for cd34 and desmin . we report this case of intrapulmonary schwannoma , which is extremely rare .",380,87,0.2289
pubmed-summarization,"( fiu ) . participants were instructed to refrain from smoking , consuming any food and beverages except water , and doing any unusual exercise for at least 8 hours prior to their blood collection . the purpose and protocol of the study were explained to the subjects , and their written consent , either in spanish or english , was obtained prior to the commencement of the study . seven participants reported not having diabetes but were reclassified because their lab results classified them as having t2d according to american diabetes association ( ada ) standards . for the data analysis , subjects with caloric intakes > 5000 kcals ( n = 2 ) and missing a1c levels ( n = 2 ) were excluded . for two participants , we were unable to perform a1c analysis . in total , we included only the data from subjects with t2d ( n = 179 ) who were aged 30 years and older . a sociodemographic questionnaire was given to each participant to complete , which included questions related to age , gender , smoking status , medications for diabetes , htn , and cholesterol . height and weight were measured using a seca balance scale ( seca corp , columbia , md , usa ) . body mass index ( bmi ) was calculated as weight in kg / height in m. bp was measured twice then averaged in participants in a sitting position after a 15-minute rest using a random zero sphygmomanometer ( tycos 5090 - 02 welch allyn pocket aneroid sphygmomanometer , arden , nc , usa ) and a stethoscope ( littmann cardiology , 3 m , st paul , mn , usa ) . htn was defined as follows : systolic bp 140 mm hg systolic or diastolic bp 90 mm hg or using antihypertensive treatment.11 dietary intake was measured using a validated semiquantitative food frequency questionnaire ( ffq ) developed by willett et al.12 this ffq has also been validated by nath and huffman13 exclusively for the cuban american population . participants self - reported average consumption of specified amounts of various foods over the past year and chose from frequency responses ranging from never to six or more servings per day . in","purpose : to investigate to what degree the presence of hypertension ( htn ) and poor glycemic control ( gc ) influences the likelihood of having microalbuminuria ( mau ) among cuban americans with type 2 diabetes ( t2d).methods : a cross - sectional study conducted in cuban americans ( n = 179 ) with t2d . participants were recruited from a randomly generated mailing list purchased from knowledge - base marketing , inc . blood pressure ( bp ) was measured twice and averaged using an adult size cuff . glycosylated hemoglobin ( a1c ) levels were measured from whole blood samples with the roche tina - quant method . first morning urine samples were collected from each participant to determine mau by a semiquantitative assay (",380,128,0.3368
dialogsum,"#Person1#: Look, it's full of traffic here. Is this the shopping district? #Person2#: Yes, it is. There are a lot of stores, restaurants, and theaters near here. #Person1#: What is the largest building on the left? #Person2#: That's Honor Department Store. They sell clothing, furniture, food-almost everything. #Person1#: Do you like purchasing everything in the supermarket? It's very convenient and saves a lot of time. Now I just want to buy some clothes there. #Person2#: Wait a minute please. I'd like to recommend some better stores for man's clothes. Look, there, next to the bank, is a man's clothing store building. And there are also some good stores on Park Street. #Person1#: Are they far from here? #Person2#: No, it's just three blocks straight ahead. #Person1#: Ok, maybe I can shop around by myself. Thanks a lot for your help. #Person2#: That's my pleasure. Go ahead.",#Person2# introduces the shopping district to #Person1# and recommends some better stores for man's clothes to #Person1#. #Person1#'ll shop around by himself.,146,22,0.1507
scientific_lay_summarisation-elife-norm,"signaling events have been proposed to account for the effectiveness of peripherally restricted opioids, including inhibition of voltage-gated Na+ channels (Gold and Levine, 1996), inhibition of HCN channels (Ingram and Williams, 1994), activation of several classes of K+ channels (Cunha et al. , 2010; Nockemann et al. , 2013; Baillie et al. , 2015), and, importantly, again the inhibition of TRPV1 channels (Vetter et al. , 2006; Endres-Becker et al. , 2007; Spahn et al. , 2013) However, despite the plethora of proposed targets, the magnitude and the interplay of these individual effects has not been determined. Furthermore, many of these ion channels are not inhibited by µOR activation per se, but rather their upregulation or sensitization by the cAMP/PKA pathway is blocked by µOR signaling. It is therefore unclear, how much each of these targets contributes to the overall effect of opioids on peripheral nerve endings, and how this contribution may vary during shifts from resting to inflamed states (and back). Further, it is unclear, and perhaps even unlikely, that all important downstream targets of µORs have already been identified. Recently, TRPM3 channels (Oberwinkler and Philipp, 2014) were described in primary nociceptive neurons (Nealen et al. , 2003; Lechner et al. , 2009; Vriens et al. , 2011; Straub et al. , 2013a, 2013b; Held et al. , 2015; Usoskin et al. , 2015) and it was shown that these divalent-permeable cation channels (Grimm et al. , 2003; Oberwinkler et al. , 2005; Wagner et al. , 2010) play an important role in noxious heat sensation since these channels are intrinsically thermosensitive (Vriens et al. , 2011). Activation of TRPM3 leads to release of pro-inflammatory CGRP from peripheral nociceptor nerve terminals (Held et al. , 2015), while TRPM3-deficient animals show severe defects in the development of inflammatory hyperalgesia (Vriens et al. , 2011). In this context, it is interesting that inhibitors of TRPM3 channels have been identified that exhibit strong anti-nociceptive properties (Straub et al. , 2013b; Chen et al. , 2014; Suzuki et al. , 2016; Krügel et al. , 2017). Hence, TRPM3 channels in peripheral nociceptors have pro-nociceptive and pro-inflammatory properties, making them an interesting target to study the mechanism of peripheral nociception and inflammation. Here, we demonstrate that TRPM3 channels in primary nociceptive neurons are rapidly","There are very few treatments available for people suffering from strong or long-lasting pain. Currently, substances called opioids – which include the well-known drug morphine – are the strongest painkillers. However, these drugs also cause harmful side effects, which makes them less useful. Like all drugs, opioids mediate their effects by interacting with molecules in the body. In the case of opioids, these interacting molecules belong to a group of receptor proteins called G-protein coupled receptors (or GPCRs for short). These opioid receptors are widely distributed in the nerve cells and brain regions that detect and transmit pain signals. It was poorly understood how activation of opioid receptors reduces the activity of pain-sensing nerve cells, however several lines of evidence had suggested that a protein called TRPM3 might",380,128,0.3368
pubmed-summarization,"the function of sensory receptors ( nrec ) in the movement control , muscle coordination and perception of the space position of temporo - mandibular joint ( tmj ) is fundamental although the presence of nrec in the tmj is still debated : some authors have reported on the lack of nervous fibers in the articular disk 1,2 , while florid innervation of tmj has been reported in several studies on animal models and in human 3 - 6 which suggested that 6 the concentration of sensory receptors within tmj is higher in the areas supporting higher strong tensions during articular movements ( chewing , biting , speaking ) . in discordance , other authors disclosed the presence of mechanical nrec in the articular disk of human tmj 7,8 also distinguishing receptors in capsulated and uncapsulated on the bases of morphological features . the aim of this study is to ascertain the presence and the distribution of nrec in human tmj by using of immunohistochemical investigations in healthy and pathological tmj such as arthritis and arthrosis . the study was approved by the bioethics committee of the department of odontology and surgery of university of bari . 10 samples of capsular and pericapsular soft tissues with the disk were obtained from healthy patients ( six men and four women with a mean age of 39 years ) who suffered surgery of tmj because of accidental trauma of the temporo - mandibular region ; the remaining 7 cases ( four men and three women with a mean age of 57 years ) were patients surgically treated for severe degenerative lesions of tmj ( chronic arthritis and arthrosis ) . all specimens were immediately fixed in neutral buffered formalin and embedded in paraffin ; 5 micron thick sections were cut and stained with haematoxylin - eosin , pas , gomori 's reticulin and azan - mallory trichrome ; consecutive sections were used for the immunohistochemical detection of the antigens listed in table 1 . all the antibodies used are commercially avalaible from dako italia spa , milan , italy ( glial fibrillary acidic protein = gfap ; myelin basic protein = mbp ; neurofilaments = nf ; neuron specific enolase = nse ; synaptophysin ; s-100 protein = s-100 ) and from","aim : a study was performed on the articular disk and periarticular tissues of the temporo - mandibular joint ( tmj ) with immunohistochemical techniques to give evidence to the presence of neuroreceptors ( nrec ) in these sites . methods : the study was carried out on tissue samples obtained from 10 subjects without tmj disease and from 7 patients with severe tmj arthritis and arthrosis . we use antibodies directed against following antigens : gliofibrillary acidic protein ( gfap ) , leu-7 , myelin basic protein ( mbp ) , neurofilaments 68 kd ( nf ) , neuron specific enolase ( nse ) , s-100 protein ( s-100 ) and synaptophysin ( syn ) . results : this study revealed that ruffini's - like , pacini's",380,128,0.3368
dialogsum,"#Person1#: After you go back to your country, I think I will invite you to my home someday. #Person2#: Thank you! I would love to! #Person1#: What's the weather like in your country? I suppose it must be warmer than here. #Person2#: Oh, yes. We have rather mild winters. It always has much sunshine in winter. But it was very foggy when I left two days ago. I knew it would be colder here, but I thought there would be a lot of snow. #Person1#: We don't have much snow in winter in Beijing. In fact, we haven't had any so far this winter. The winter is rather long, but the cold is generally not severe. The temperature seldom gets as low as ten below zero Centigrade. #Person2#: What is the temperature today, do you know? #Person1#: About freezing point, I think. But the morning's forecast said that we are going to have a very cold spell in the next few days - and the temperature will probably drop to 10 or 15 degrees below zero. #Person2#: Oh, I'm very lucky that my wife let me take a heavy overcoat. #Person1#: It is considerate of your wife. #Person2#: Yes, she is. By the way, what is the best season in Beijing? #Person1#: Fall is the best season in Beijing. It's neither hot nor cold. The sky is clear and blue. There's hardly any wind, only a slight breeze which is hardly noticeable. And we have plenty of sunshine too. #Person2#: Really? Then I will come to Beijing in the fall next time. #Person1#: Good, you are welcome.",#Person1# and #Person2# talk about the different winter weather in #Person2#'s country and Beijing. They also talk about today's temperature and the best season in Beijing. #Person1# welcomes #Person2# to come to Beijing in the fall.,267,36,0.1348
scientific_lay_summarisation-elife-norm,"it is important to understand how these different factors contribute to screening effectiveness at departure and arrival. During screening initiatives for influenza A/H1N1p, MERS-CoV, SARS-CoV and Ebola virus, large numbers of travellers were detained for in-depth assessment, but few or no cases were ultimately detected (Table 1). Although fever is the symptom most commonly measured during screening, it might not be detected in all infected individuals for several reasons. First, those with recent exposure may not yet have progressed to a symptomatic stage (Pitman et al. , 2005; Mabey et al. , 2014). Second, travellers might be symptomatic but not febrile; the probability a symptomatic patient will have a fever varies by pathogen (Donnelly et al. , 2004; Cao et al. , 2009; Louie et al. , 2009; Assiri et al. , 2013; Cowling et al. , 2013; Gao et al. , 2013; Gong et al. , 2014; Sun et al. , 2014; WHO Ebola Response Team, 2014). Third, the sensitivity of non-contact infrared thermometers (the devices most often used for airport fever screening) is limited, so passengers with fever may pass through symptom screening undetected (Hausfater et al. , 2008; Bitar et al. , 2009; Nishiura and Kamiya, 2011). Fourth, passengers may conceal fever and other symptoms during screening using antipyretic drugs (Nishiura and Kamiya, 2011). At the same time, fever is notoriously non-specific as a symptom, leading to high opportunity costs from detaining travellers with non-target illnesses (Anderson et al. , 2004; Gunaratnam et al. , 2014; Mabey et al. , 2014). 10. 7554/eLife. 05564. 003Table 1. Airport screening measures during past disease outbreaksDOI: http: //dx. . org/10. 7554/eLife. 05564. 003PathogenDateLocationDirectionScreenedDetainedPositiveSourceInfluenza A/H1N1p27 April–22 June 2009Auckland, New ZealandInbound456,5184064 (Hale et al. , 2012) 28 April–18 June 2009Sydney, AustraliaInbound625,14758453 (Gunaratnam et al. , 2014) 28 April–18 June 2009Tokyo, JapanInbound471,73380515 (Nishiura and Kamiya, 2011) SARS Co-V5 April–16 June 2003AustraliaInbound1,840,0007940 (Samaan et al. , 2004) 31 March–31 May 2003SingaporeInbound442,9731760 (Wilder-Smith et al. , 2003) 14 May–5 July 2003Toronto, CanadaInbound349,75412640 (St John et al. , 2005) 14 May–5 July 2003Toronto, CanadaOutbound495,4924110 (St John et al. , 2005) MERS Co-V24 September 2012–15 October 2013EnglandInboundNR772 (Thomas et al. , 2014) Ebola virusAugust–September 2014Guinea, Liberia, Sierra LeoneOutbound36,000770 (Centers for Disease Control and Prevention, 2014a) 11 October–22 October 2014United StatesInbound76230 (Apuzzo and Fernandez, 2014; CBS, 2014) Self-reporting","International air travel has contributed to the spread of several recent disease epidemics. For example, travelers infected with severe acute respiratory syndrome (or SARS) in 2003 carried the disease around globe. One infected air traveler can carry a disease to a new continent: in 2014, a man infected with Ebola in West Africa flew to the United States and infected two healthcare workers in Dallas during treatment. Efforts to prevent the spread of SARS, Ebola and other disease outbreaks have included screening air passengers for infection prior to boarding, or immediately after arrival. In these situations, infrared thermometers are often used to check for symptoms of fever and passengers may be asked to fill out questionnaires to assess their risk of exposure to the disease. However, the effectiveness",380,128,0.3368
pubmed-summarization,"through her hospitalization . as her reticulocyte count was also inappropriately low at the time ( 0.012 e6/l ) , her worsening thrombocytopenia was felt most likely to be due to myelosuppression from hydroxyurea . consequently , in addition to halting the hydroxyurea , she also received epoetin alfa ( 40,000 units sq ) for marrow stimulation . despite holding hydroxyurea and the dose of epoetin , she required an additional 4 units of phenotype - matched rbcs ( 1 unit hd 5 , 1 unit hd 8 , 2 units hd 12 ) during the hospitalization to maintain her hemoglobin level . although immune hemolysis was suspected at the time , no additional antibodies were identified ( table 1 ) . after her pain improved , she was discharged on hospital day 12 with a hemoglobin of 9.1 g / dl and a platelet count of 20,000 cells / ul ( a discharge lactate dehydrogenase ( ldh ) and total bilirubin were not performed ) . at her first outpatient follow - up , 6 days after discharge ( about 7 days from her last red cell transfusion ) , she reported new symptoms of fatigue , shortness of breath , and worsening pain . her hemoglobin at this visit was 2.7 g / dl , and platelet count was 20,000 cells / ul . of note , her reticulocyte percent was below the level of detection ( < 0.4% ) despite an erythropoietin level that was elevated at 132 miu / ml ( reference : 3.7 - 31.5 miu / ml ) . her laboratory results were consistent with intravascular red cell hemolysis : ldh was > 2500 u / l ( ref : 100 - 190 u / l , her baseline was 342 u / l ) , haptoglobin was 18 mg / dl ( ref : 30 - 200 mg / dl ) , and her total bilirubin was 5.0 mg / dl ( ref : 0.2 - 1.0 mg / dl ) with hemoglobinuria detected on urine screen . there was no evidence of disseminated intravascular coagulation , and no schistocytes were observed on her peripheral smear . her dat was now strongly positive , with 3 + polyspecific ahg , 1 + igg","in patients with sickle cell disease , hyperhemolysis is a rare but life - threatening complication of transfusion . in this case report , we describe a 61 year - old woman with hemoglobin sickle cell ( sc ) disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion . she was found to have a warm and a clinically - significant cold autoantibody . severe anemia ( hb 2.7 g / dl ) with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy , which demonstrated extensive bone marrow necrosis . despite treatment , the bone marrow failure did not improve and the patient died on hospital day 38 . this case illustrates the potential risks of transfusion in a patient with sickle cell disease ,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"in the nucleus to prepare for nuclear export, its RBD might immediately interact with RanGTP on CRM1 (because of proximity and high affinity) and dissociate its own NES before animal RanBP1 is exported. One may argue that NES may play a role in recruiting animal RanBP1 to CRM1. However, RanBP1-RanGTP-CRM1 complex displayed much higher affinity than NES-CRM1-RanGTP complex in yeast (Maurer et al. , 2001); thus, the recruiting purpose seems unnecessary and unlikely. It should be noted that there are about ten residues between RBD and NES, which are insufficient to cover the distance (about 70 Å) between RBD and NES in space. Therefore in theory, the NES and RBD of animal RanBP1 would not bind to CRM1-RanGTP simultaneously. It is fascinating as to why animal RanBP1 requires an extra NES while fungi RanBP1 does not; what factor (s) prevents animal RBD from dissociating its own NES during its nuclear export; whether the NES of animal RanBP1 functions in cargo dissociation by direct competition with NES of cargo; and how animal RBD and NES binding to CRM1-RanGTP is regulated in time and space in cells. Intrigued by these long-standing questions, we performed biochemical, biophysical, and cellular studies on RanBP1 and related proteins. Our work not only solved those puzzles, but also discovered unexpected animal RanBP1 nuclear export and cargo dissociation mechanisms distinctive from those in the yeast. In yeast, RanBP1, RanGTP and CRM1 form a tight complex whereby RanBP1 forces H9 loop of CRM1 to allosterically close NES binding groove and dissociate NES. In order to visualize the mode of animal RanBP1’s binding to RanGTP-CRM1, we first attempted to solve the crystal structure of complex formed by mouse RanBP1 (mRanBP1), human RanGTP (hRanGTP) and human CRM1 (hCRM1). However, although the yeast complex formed readily as expected, the equivalent complex with animal proteins hardly formed under similar conditions (1A). The human and yeast Ran protein shares 83% sequence identity and are often used interchangeably (Koyama and Matsuura, 2010; Sun et al. , 2013). When RanBP1, RanGTP and CRM1 were mixed at 5: 3: 1 molar ratio and passed through a size exclusion chromatography column, the yeast proteins formed stable complex and were co-eluted, but not the case for the animal proteins (— 2). Interestingly, a greater amount of animal complex was","Plant, animal and fungal cells all store their DNA inside the cell’s nucleus. Small molecules can freely cross the membrane that surrounds the nucleus, but pores in the membrane control when larger molecules enter or leave. This transport process is an essential part of healthy cell behavior. To leave the nucleus, large molecules need to carry a coded sequence called a nuclear export signal. In yeast cells, which are often used to study cell biology, this sequence allows cargo to bind to a groove in so-called molecular cargo vehicles, such as a protein called CRM1. A protein called RanGTP binds to CRM1 to supply the energy needed to transport molecules across the membrane. Outside of the nucleus, another protein called RanBP1 closes up the groove in the CRM1",380,128,0.3368
dialogsum,"#Person1#: You asked Beth to be here around 7:00, didn't you? #Person2#: Yes, what time is it now? #Person1#: It's almost 8.I wonder what happened? #Person2#: Um, she might have forgotten the time. Why don't I call and see if she's on her way. 'A few minutes later.', I got her voicemail so she must not have turned on her cellphone. #Person1#: I hope she didn't have a problem on the road. Her car could have broken down or something. #Person2#: Of course she may have simply forgotten and done something else today. #Person1#: No, she couldn't have forgotten. I just talked to her about it yesterday. I guess we should start to order without her.",#Person1# and #Person2# are waiting for Beth. They discuss the possible reasons for her being late.,116,16,0.1379
pubmed-summarization,"we compared monthly listeriosis data from england and wales with temperature records from 1989 through 2007 to determine the influence of various potential predictors on the number of listeriosis cases . uk health protection agency ( hpa ) data listing total monthly cases of human listeriosis in england and wales during 19902007 ( 4,5 ) are aggregate . all age categories and regions were included and were collated by the hpa centre for infections from voluntary reporting by microbiology laboratories and from referrals of cultures . these publicly available data were also validated by the hpa , and in our analysis we used revised figures based on that validation . our analysis covered the period from 1990 , when active surveillance of listeriosis began , through 2007 . undated cases that could not be assigned to a particular month were excluded from analysis . we used the uk met office mean monthly area temperature time series for 19892007 and 30-year means averaged during 19611990 ( 6 ) . exploratory linear regression analyses suggested a positive correlation between the number of listeriosis cases and the monthly mean uk ambient temperature , as well as suggesting a change in this relationship after 2000 ( p = 0.001 ; , panel a ) . however , residual variability was not constant , and the monthly counts are likely to be overdispersed due to clustering of cases ( 3 ) . the data were fitted again by using a negative binomial generalized linear model with a logarithmic link function , a common model for time series of foodborne illness cases ( 7,8 ) . to separate seasonality of listeriosis rates from dependence on temperature , we considered the 30-year mean monthly temperatures from 19611990 , as well as monthly temperature anomalies ( observed mean temperature minus 30-year mean ) . to determine whether temperatures could have a delayed effect on listeriosis incidence , we also included mean and anomaly temperature variables lagged by 1 or more months . to allow for 2 break points at which the incidence of listeriosis may have suddenly changed , dummy variables were used to represent periods before , between , and after the months in which these increases might have occurred . a best - fit model was","the monthly incidence of listeriosis infections in england and wales had 2 sudden increases during april 2001 ( 41% ) and march 2003 ( 48% ) . although no causative association is demonstrated , these increases correspond to key dates relating to the onset and aftermath of the 2001 foot and mouth disease outbreak in the united kingdom .",380,59,0.1553
dialogsum,"#Person1#: Mrs. Lee, I'Ve stayed here for almost a week. And I really must leave tomorrow. #Person2#: Please feel free to stay as long as you want. You know you're always welcome here. #Person1#: Thank you. You'Ve been so nice to me. #Person2#: Is there anything else I can do for you before your leave? #Person1#: No, thanks. You'Ve done a lot for me already. Thank you for everything. #Person2#: Don't mention it. I'Ve really enjoyed your company.",#Person1# says her farewells to Mrs. Lee and thanks to her for the hospitality.,78,14,0.1795
pubmed-summarization,"acyl - coa thioesterases ( acots ) represent a group of enzymes that metabolise acyl - coa esters to their corresponding non - esterified fatty acid and coenzyme a ( coash ) . in addition to ' acyl - coa thioesterases ' , these enzymes also have been described as ' acyl - coa hydrolases ' , ' acyl - coa thioester hydrolases ' and ' deacylases ' . the reaction catalysed by acot enzymes is very important during fatty acid metabolism . as such acyl - coa thioesterase expression is widespread and activity is detectable within many tissues and cell types . acot activity helps to regulate cellular pools , as well as proper ratios , of activated fatty acyl - coas ( acyl - coa esters ) , free fatty acids ( non - esterified fatty acids ) and coash . these enzymes are found within a number of subcellular locations , including peroxisomes , mitochondria and the cytosol . peroxisomal and mitochondrial acots are thought to play a major role in fatty acid degradation via -oxidation , which provides energy through the citric acid cycle , as well as in ketone body formation . in order for a fatty acid to be transported into the peroxisome for -oxidation , it must first be activated to its coenzyme a ester by acyl - coa synthetases . some acyl - coa esters undergo -oxidation much more slowly than others -- which can effectively sequester large amounts of coash and limit the activity of acyl - coa synthetases and the rate of subsequent fatty acid -oxidation . under these conditions , acots may act to increase the levels of free coash , thereby restoring fatty acid -oxidation . mammalian acots are capable of metabolising a wide variety of compounds , including short- , medium- and long - chain acyl - coas . they can also metabolise polyunsaturated fatty acyl - coas , branched - chain acyl - coas and aromatic - acyl - coas . these compounds are not only utilised during -oxidation and fatty acid degradation , but also have roles in inflammation , ion channel opening , signal transduction , lipid biosynthesis and gene regulation . ten human acot genes have been identified to date , compared with","the acyl - coa thioesterase gene ( acot ) family encodes enzymes that catalyse the hydrolysis of acyl - coa thioester compounds , also known as activated fatty acids , to their corresponding non - esterified ( free ) fatty acid and coenzyme a ( coash ) . these enzymes play a very important role in lipid metabolism by maintaining cellular levels and proper ratios of free and activated fatty acids , as well as coash . within the acyl - coa family there are two distinct subgroups , type i and type ii . despite catalysing the same reaction , the two groups are not structurally similar and do not share sequence homology , strongly suggesting convergent evolution . this suggestion is further supported if one compares",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Many ‘non-enveloped’ viruses, including hepatitis A virus (HAV), are released non-lytically from infected cells as infectious, quasi-enveloped virions cloaked in host membranes. Quasi-enveloped HAV (eHAV) mediates stealthy cell-to-cell spread within the liver, whereas stable naked virions shed in feces are optimized for environmental transmission. eHAV lacks virus-encoded surface proteins, and how it enters cells is unknown. We show both virion types enter by clathrin- and dynamin-dependent endocytosis, facilitated by integrin β1, and traffic through early and late endosomes. Uncoating of naked virions occurs in late endosomes, whereas eHAV undergoes ALIX-dependent trafficking to lysosomes where the quasi-envelope is enzymatically degraded and uncoating ensues coincident with breaching of endolysosomal membranes. Neither virion requires PLA2G16, a phospholipase essential for entry of other picornaviruses. Thus naked and quasi-enveloped virions enter via similar endocytic pathways, but uncoat in different compartments and release their genomes to the cytosol in a manner mechanistically distinct from other Picornaviridae. The presence or absence of an external lipid envelope has featured strongly in the systematic classification of animal viruses for decades. However, many viruses that have previously been considered to be ‘non-enveloped’ are now known to be released non-lytically from infected cells in a ‘quasi-enveloped’ form, enclosed in small extracellular vesicles (EVs) devoid of virus-encoded surface proteins. This phenomenon was recognized first among members of the Picornaviridae, including hepatitis A virus (HAV, genus Hepatovirus) (Feng et al. , 2013), poliovirus and coxsackievirus B (genus Enterovirus) (Bird et al. , 2014; Chen et al. , 2015; Jackson et al. , 2005; Robinson et al. , 2014), but it has been demonstrated also for hepatitis E virus (Hepeviridae), rotaviruses (Reoviridae), and noroviruses (Caliciviridae) (Nagashima et al. , 2017; Santiana et al. , 2018). The size of the virus-containing EVs varies widely among different viruses, as does the number of virus capsids enclosed in each vesicle, most likely reflecting different mechanisms of biogenesis. However, these membrane-wrapped, quasi-enveloped virions share the capacity to infect cells, and contribute to pathogenesis either by cloaking capsids in membranes such that they are sequestered from the host immune system, or possibly by increasing the number of viral genomes delivered to newly infected cells, thereby facilitating genetic complementation (Chen et al. , 2015; Feng et al. , 2013). HAV provides a prime example of viral quasi-envelopment. An ancient pathogen","The Hepatitis A virus is a common cause of liver disease in humans. It is unable to multiply on its own so it needs to enter the cells of its host and hijack them to make new virus particles. Infected human cells produce two different types of Hepatitis A particles. The first, known as ‘naked’ virus particles, consist of molecules of ribonucleic acid (or RNA for short) that are surrounded by a protein shell. Naked virus particles are shed in the feces of infected individuals and are very stable, allowing the virus to spread in the environment to find new hosts. At the same time, a second type of particle, known as the ‘quasi-enveloped’ virus, circulates in the blood of the infected individual. In a quasi-enveloped particle, the",380,128,0.3368
dialogsum,"#Person1#: Is that Anne Shaw? #Person2#: Yes, speaking? #Person1#: Hello, it is Eric from London. #Person2#: Hello, Eric. How can I help you? #Person1#: I'm fixing up on next project team meeting, and I just want to check some possible dates with you. #Person2#: Fine, let me just get my diary. Ok, which dates are you looking at? #Person1#: I've spoken to the others, and they prefer either the third week of May or the second week of June. #Person2#: Yeah, both of the weeks are pretty clear at the moment except for the 11th of June. #Person1#: Right, I've got that. #Person2#: So where is the meeting taking place this time? #Person1#: It was going to be in London. But I spoke to Carlos in Mexico City and he suggested Chicago. He thinks it will be more convenient for most of the team. #Person2#: He's probably right. It'll certainly be much easier for me as well. Because I can fly from Toronto, and I'm sure you can find a meeting room somewhere near the airport. #Person1#: That's a good idea. I'll check up some hotels in that area and get back to you towards the end of the week. #Person2#: Fine, but I'm not in the office on Friday. #Person1#: Ok, I'll call you later in the afternoon on Thursday. #Person2#: No problem. Bye.",Eric calls Anne Shaw to fix up the time and place for the next project team meeting. Anne tells Eric her available dates and says she prefers to meet in Chicago. Eric will check up some hotels and contact Anne again soon.,225,42,0.1867
scientific_lay_summarisation-elife-norm,"classification to reveal conformations of the complex that exist simultaneously in solution. In the work described here, we obtained and analyzed cryo-EM images of the bovine mitochondrial ATP synthase. 3D classification of the images resulted in seven distinct maps of the enzyme, each showing the complex in a different conformation. By averaging the density for the proton-translocating a subunit from the seven maps, we generated a map segment that shows α-helices clearly. Analysis of evolutionary covariance in the sequence of the a subunit (Göbel et al. , 1994) allowed the entire a subunit polypeptide to be traced through the density map. The resulting atomic model for the a subunit was fitted into the maps for the different rotational states, suggesting a path for protons through the enzyme and supporting the Brownian ratchet mechanism for the generation of rotation (Junge et al. , 1997; 2005), and thereby ATP synthesis, in ATP synthases. The FO regions of all seven maps also revealed a remarkable feature not resolved previously in cryo-EM maps of ATP synthases (Baker et al. , 2012; Allegretti et al. , 2015; Lau et al. , 2008; Rubinstein et al. , 2003). The feature appears to consist of an elongated membrane-embedded density, possibly an α-helix, that extends from the rotor-distal portion of FO to the c8-ring. The orientation of this density would cause it to pass through the inter-membrane space of the mitochondrion (1B and C, orange arrow). While not identified in the previous cryo-EM map of the enzyme at 18 Å resolution, the structure is consistent with a poorly-resolved ridge along the surface of the FO region seen in the earlier map (Baker et al. , 2012). Because it extends from the bent end of the FO region, this feature may correspond to the soluble part of the e subunit. Indeed, a similar structure was observed in single particle EM of negatively stained ATP synthase dimers from bovine heart mitochondria, and was proposed to be interacting e subunits (Minauro-Sanmiguel et al. , 2005). However, in the present structure the feature is not positioned to interact between dimers of the enzyme and its role in the complex remains unclear. In order to improve the signal-to-noise ratio for the FO region of the complex, the membrane regions from the seven different","A molecule called adenosine triphosphate (ATP) is the energy currency in cells. Most of the ATP used by cells is made by the membrane-embedded enzyme ATP synthase. This enzyme is found in membranes inside specialized compartments known as mitochondria. ATP synthase is made up of many protein subunits that work together as a molecular machine. Hydrogen ions flow across the membrane through the ATP synthase, turning a rotor structure within the enzyme, which leads to the production of ATP. It is not known how the transport of hydrogen ions causes rotation of the rotor. Some researchers have proposed that the enzyme works as a ratchet that is driven by the random Brownian motion of the rotor. That is, the rotational position of the rotor fluctuates randomly, but a",380,128,0.3368
pubmed-summarization,"( 00.74 for m - pe , 00.75 for m - m , 00.76 for c - c ) . using each patient s unique de - identified beneficiary i d , the patients were tracked longitudinally with revision tha or selected complications as end points . the selected complications included deep venous thrombosis ( dvt ) , dislocation , infection , and mechanical loosening . dvt was identified using the icd-9-cm diagnosis codes 451.1 , 451.2 , 451.81 , 451.9 , 453.1 , 453.2 , 453.4 , 453.8 , and 453.9 , while tha dislocation was identified using any occurrence of icd-9 diagnosis codes 718.35 , 835 , or 996.42 . infection and mechanical loosening were identified using icd-9 diagnosis codes 996.66 and 996.41 , respectively . an overall cohort of 36,423 tha patients with m - pe bearings were identified , along with 17,789 tha patients with m - m bearings and 2,835 tha patients with c - c bearings , from which the matched cohorts were derived . the mean age of all tha recipients included in the study was 74.5 years ( sd = 6.4 years ) . multivariate cox proportional - hazards models were constructed to compare complication and revision tha risk among cohorts , adjusting for medical comorbidities , race , socioeconomic status , and hospital factors . the medicare buy - in status was used as an identifier of patients whose medicare premiums and deductibles were subsidized by the state ( eg , medicaid ) and were used as a proxy for the patient s socioeconomic status . to account for the health status of each patient , the charlson comorbidity index was used as a measure of comorbid illness . for this analysis , the charlson index values were grouped into the following previously validated categories : 0 ( none ) , 1 to 2 ( low ) , 3 to 4 ( moderate ) , and 5 or more ( high ) . among younger medicare patients ( aged 6569 years ) , m - m bearings accounted for 35% of tha bearings and c - c bearings accounted for 8% . among older medicare patients ( older than 80 years ) , among female patients , 67% had m -","backgroundto address the long - term problems of bearing surface wear and osteolysis associated with conventional metal - polyethylene ( m - pe ) total hip arthroplasty ( tha ) , metal - metal ( m - m ) , and ceramic - ceramic ( c - c ) bearings have been introduced . these bearing surfaces are associated with unique risks and benefits and higher costs . however the relative risks of these three bearings in an older population is unknown.questions/purposeswe compared the short - term risk of complication and revision tha among medicare patients having a primary tha with metal - polyethylene ( m - pe ) , metal - metal ( m - m ) , and ceramic - ceramic ( c - c )",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2009; Wang et al. , 2015). It has also been shown that microglial phagocytosis decays over the course of AD (Hickman et al. , 2008; Koellhoffer et al. , 2017; Orre et al. , 2014a; Solito and Sastre, 2012; Zuroff et al. , 2017). Along these lines, Aβ clearance was found reduced in sporadic AD and it is assumed to be a key factor in the pathogenesis (Mawuenyega et al. , 2010; Saido, 1998; Wildsmith et al. , 2013). Importantly, Aβ clearance defects in AD microglia are reversible (Daria et al. , 2017; Krabbe et al. , 2013) and enhancing microglial phagocytic function has been explored as a therapeutic approach since substantial reduction of Aβ burden in mice appears to correlate with cognitive benefits (Bacskai et al. , 2001; Bard et al. , 2000; Bohrmann et al. , 2012; Janus et al. , 2000; Lathuilière et al. , 2016; Morgan et al. , 2000; Nicoll et al. , 2006; Nicoll et al. , 2003; Schenk et al. , 1999; Schlepckow et al. , 2020; Sevigny et al. , 2016; Wilcock et al. , 2004). However, when and how microglia change along AD progression is still not clear. Thus, understanding molecular alterations of microglia at different stages of AD is crucial and a pre-requisite for developing safe and efficacious therapy. Transcriptional expression profiles of microglia were previously revealed under physiological, neurodegenerative or neuroinflammatory conditions (Butovsky et al. , 2014; Galatro et al. , 2017; Gosselin et al. , 2017; Götzl et al. , 2019; Grabert et al. , 2016; Holtman et al. , 2015; Kamphuis et al. , 2016; Krasemann et al. , 2017; Mazaheri et al. , 2017; Orre et al. , 2014a; Orre et al. , 2014b; Wang et al. , 2015; Yin et al. , 2017). Transcriptional signatures were also recently reported at single-cell resolution, demonstrating regional and functional heterogeneity of brain myeloid cells (Hammond et al. , 2019; Jordão et al. , 2019; Keren-Shaul et al. , 2017; Mathys et al. , 2017; Sala Frigerio et al. , 2019; Zhou et al. , 2020). In neurodegenerative mouse models, two major profiles have been proposed along the spectrum of microglial alterations. One is the homeostatic microglial signature that occurs under physiological conditions and is characterized by the","Alzheimer’s disease is a progressive, irreversible brain disorder. Patients with Alzheimer’s have problems with memory and other mental skills, which lead to more severe cognitive decline and, eventually, premature death. This is due to increasing numbers of nerve cells in the brain dying over time. A distinctive feature of Alzheimer’s is the abnormally high accumulation of a protein called amyloid-β, which forms distinctive clumps in the brain termed ‘plaques’. The brain has a type of cells called the microglia that identify infections, toxic material and damaged cells, and prevent these from building up by clearing them away. In Alzheimer’s disease, however, the microglia do not work properly, which is thought to contribute to the accumulation of amyloid-β plaques. This means that people with mutations in the genes important",380,128,0.3368
dialogsum,"#Person1#: Hi, what're you reading? #Person2#: An old book Death on the Nile. Have you read it? #Person1#: Not yet, but I saw the movie. Could I borrow it when you finish reading? #Person2#: Sure. But you need to be patient.",#Person1# wants to borrow the book that #Person2# is reading.,41,10,0.2439
dialogsum,"#Person1#: Would you like to order anything else? #Person2#: No, I'm good. All we need now is our check. #Person1#: The waitress is walking over here with our check even as we speak. #Person2#: I have never had bad service at this restaurant, but this time was really exceptional. #Person1#: Yes, she really went out of her way to make this a pleasant dining experience. #Person2#: Let's take a look at our bill. The total price for our dinner is $ 36. 00. #Person1#: How much money should we leave for a tip? #Person2#: I know that 15 % is a normal tip, but I really thought that this waitress went out of her way for us. What do you think about tipping her 20 %? #Person1#: She definitely deserves 20 % for a tip. #Person2#: So we can add her tip of $ 7. 20 to the bill of $ 36. 00 and the total will be $ 43. 20. #Person1#: Yes, what a wonderful meal! #Person2#: It absolutely was a great meal. We'll have to return here for lunch sometime.",#Person1# and #Person2# agree they had a great meal and their waitress deserves 20% for a tip because she went out of her way for them.,182,26,0.1429
scientific_lay_summarisation-elife-norm,"hybridization has been extremely limited. Loss-of-function studies have clearly shown that some Grs are required for the responses to certain bitter compounds. For example, Gr93a is required for the behavioral and physiological response to caffeine; Gr8a is required for response to L-canavanine; Gr66a, Gr33a and Gr32a are broadly required for the response to several bitter tastants (Lee et al. , 2009; 2010; 2012; Moon et al. , 2006; Moon et al. , 2009). However, the roles of individual Grs in bitter response have been difficult to discern in detail, in part because of the coexpression of bitter receptors and in part because of the difficulty of expressing bitter receptors in conventional expression systems such as cultured cells or oocytes (Liman et al. , 2014). In vivo expression studies provide a complementary approach for analysis of Gr function. Here, we analyze eight bitter Grs, most of which have not been functionally studied before. We express them in a natural laboratory: in bitter neurons of the labellum that either do or do not express them endogenously, which we refer to as overexpression or ectopic expression, respectively. Specifically, we express individual Grs in four different bitter neurons, three of wild type and one of a Gr mutant, and we measure the effects of their expression using electrophysiology and a panel of 21 bitter tastants. From an analysis of ~600 receptor-neuron-tastant combinations (n≥27,000 total recordings) we find several surprising results. While expression of Grs led to increases in many responses, expression of some Grs led to decreases in certain responses. Conversely, the deletion of one Gr from a neuron led to novel responses not observed in wild type. Overexpression of a Gr in some neurons led not only to increased responses but also to novel responses. A recurrent theme was that the expression of the same Gr in different neurons led to strikingly different results. Taken together, our findings provide support for a model in which bitter Grs interact, exhibiting competition, inhibition, or activation in different contexts. The results may have profound evolutionary implications: they suggest a rich source of means by which the taste system can evolve novel, increased, or decreased responses to new environmental opportunities and dangers, or modulate its response to accommodate changes in the internal state of the fly. To","Insects and other animals use their sense of taste to tell if their food is safe to eat. Plant toxins, for example, often have a bitter flavor that animals can detect and avoid. Fruit flies have many bitter-sensitive nerve cells, but it is not known how the receptors on these nerve cells signal the detection of bitter-flavored compounds. Delventhal and Carlson have now used fruit flies to investigate how taste receptors of the so-called Gustatory receptor family detect bitter flavors. The experimental approach involved genetically modifying four different types of nerve cells that sense bitter compounds so that they produced higher levels of particular taste receptors than normal. Then, the flies were exposed to a range of bitter compounds while the electrical activity of each cell was measured.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"HEK cell lines were engineered to express fluorescent sensors that are specific to ppGalNAc-T2 or ppGalNAc-T3 activity (Song et al. , 2014). For each sensor, glycosylation of its isozyme-specific target site prevents furin protease from removing a blocking domain (1A). Thus, fluorescence increases upon ppGalNAc-transferase inhibition because removal of the blocking domain allows dimerization of a fluorogen activating protein domain so that it binds and activates the fluorescence of malachite green. They are ratiometric because the sensor backbone contains a green fluorescent protein as an internal control for expression. Each sensor showed clear activation after mutation of its glycan acceptor sites and these mutated constructs served as positive controls in the screen (1B, ∆glycan). The T3 sensor exhibited a background level of activation due to incomplete glycosylation (Song et al. , 2014) but this was considered advantageous for the possible identification of enzyme activators along with the desired inhibitors. Consistent with our previous report (Song et al. , 2014), sensor expression in HEK cell lines depleted of either ppGalNAc-T2 or T3 via zinc finger nuclease editing resulted in specific activation of the corresponding sensor confirming their isozyme selectivity (1B, HEK∆T2, HEK∆T3). Our screen included compounds based on structural diversity (21,710 compounds in total) with 6 hr treatments at 10 µM prior to flow cytometry to assay MG and GFP fluorescence on a cell-by-cell basis (1C). Each compound was tested in duplicate and against both sensors (—source data 1). Because each sensor requires essentially identical cellular reactions- the only difference being which ppGalNAc-transferase isoform modifies the sensor- most off-target hits (such as sugar nucleotide transporters, extending enzymes, or furin) will alter both sensors, whereas directly acting, isoform-specific candidates will be sensor-specific. Using cut-off parameters for the MG/GFP ratios that excluded >99% of the compounds (Q ≥ 3 or Q ≤ −2. 5), the screen yielded 72 sensor-specific hits with 18 increasing and 35 decreasing the T2 sensor fluorescence and 11 increasing and 8 decreasing the T3 sensor fluorescence (1D). 10. 7554/eLife. 24051. 003Figure 1. Screen for modulators of ppGalNAc-T2/T3. (A) Diagram showing sensor design and the linker sequences used. O-glycosylation of the linker masks the furin site but if an inhibitor blocks the ppGalNAc-transferase then furin cleaves the linker releasing the blocking domain (BD) allowing fluorescent activating protein (FAP) dimerization and","Complex cascades of interactions between different molecules regulate every process in the body. Enzymes are critical for this, because they act as ‘catalysts’ to speed up chemical reactions in a cell. Each type of enzyme has a specific role. The enzyme ppGalNAc-T3, for example, attaches sugar molecules onto certain proteins via a process called glycosylation. This modification fine-tunes the activity of the proteins. The enzyme ppGalNAc-T3 is implicated in at least two medically important pathways. It increases the amount of the hormone FGF23, which regulates phosphate levels in the bloodstream. Hormones are messenger molecules that regulate most processes that are crucial for life, and too much or too little of a hormone can lead to diseases. High levels of FGF23, for example, can cause serious and often fatal",380,128,0.3368
pubmed-summarization,"due to a nonreassuring fetal heart rate tracing , delivery by a cesarean section was performed . apgar scores were 5 , 7 , and 9 at 1 , 5 , and 10 min and neonatal weight was 720 g. on the pathology report the amniotic membranes were described as dull , thin , delicate , and green tinged . the placenta weighed 170 g with signs of acute vasculitis , funisitis , and chorioamnionitis . in recent years nipt is becoming increasingly popular . even in patients not at high risk of fetal aneuploidy some providers are offering nipt 1 . however , nipt is unable to evaluate placental dysfunction , and can not be used for determination of risk for preterm delivery , fetal growth restriction , preeclampsia , placental abruption , intrauterine fetal demise , and perinatal death . additionally , prohibitive cost has been identified as a major hurdle in the more routine use of nipt in low risk patients 3 . in a costconsequence analysis in belgium , the authors concluded that the price of nipt needs to be lowered substantially due to the government 's limited resources for universal reimbursement 4 . in our patient due to a normal first trimester serum screen , the second trimester screen was not obtained initially . however , due to the ultrasound findings , we obtained the second trimester serum screen and all four analytes on the quad screen were abnormal indicating that iugr was probably related to placental pathology . due to the abnormal quad screen results intensive maternal and fetal monitoring was initiated which allowed us to deliver a live fetus in a timely fashion . while nipt may be the most accurate screening for certain aneuploidies , the american college of obstetricians and gynecologists and the society of maternalfetal medicine caution that its use is solely for fetal aneuploidy and that nipt should not be part of routine laboratory assessment , but instead should be an informed patient choice for women at high risk of fetal aneuploidy 5 . in patients who are at risk of placentalbased pregnancy complications the integrated screen may be a better option for assessment of fetal chromosomal abnormalities , placental function , and fetal risks associated with placental dysfunction","key clinical messagenoninvasive prenatal testing ( nipt ) is becoming increasingly popular with some offering it as a primary screen option in all patients in place of serum screening . serum screening offers insight into placental function , which nipt does not . abnormal levels of analytes in the serum screen have been associated with pregnancy complications .",380,58,0.1526
dialogsum,"#Person1#: Could you please tell me how I can go job-hunting in the web? #Person2#: Generally speaking, job seekers can enter the websites either of job agencies or of some units for job advertisements. #Person1#: How should I contact them? #Person2#: You can e-mail your application materials for application to the websites of job agencies for enrollment in their database. #Person1#: Can I get a quick reply from the sites? #Person2#: Yes, usually it takes a short time, but you have to await the choice of the units for a while.","#Person2# tells #Person1# how to go job-hunting in the web, how to contact the units, and how quickly will one get a reply.",91,23,0.2527
scientific_lay_summarisation-elife-norm,"histone demethylase activity toward lysine 27 on histone H3 (H3K27), as well as demethylase-independent functions in establishment of enhancer regions (Hong et al. , 2007; Lan et al. , 2007; Wang et al. , 2017). KDM6A mutations are found in a variety of human cancers, including multiple myeloma, renal cell carcinoma, bladder carcinoma, acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), prostate cancer, and medulloblastoma (Jones et al. , 2012; Ntziachristos et al. , 2014; Van der Meulen et al. , 2014; van Haaften et al. , 2009). KDM6A has been mechanistically implicated as a tumor suppressor in ALL (Ntziachristos et al. , 2014; Van der Meulen et al. , 2015), AML (Gozdecka et al. , 2018), and lung cancer (Wu et al. , 2018), and also plays important developmental roles, especially in the heart (Lee et al. , 2012; Welstead et al. , 2012) and blood (Beyaz et al. , 2017; Thieme et al. , 2013). Because KDM6A functions primarily as a chromatin regulator, these studies imply that the epigenetic sequelae of KDM6A loss contribute to tumor initiation or progression. Here, we delete Kdm6a specifically in the male germ line of the mouse, and evaluate gene regulatory and phenotypic effects in genetically wild type offspring. We find that offspring of Kdm6a male germline knockouts exhibit an increased incidence of tumors, and that this effect is enhanced when Kdm6a is deleted in the germ line in two successive generations. Because these effects are provoked by a single genetic lesion in the parent, we were able to define specific epigenetic changes resulting from this manipulation. We find widespread perturbation of H3K27 methylation state in the Kdm6a mutant male germ line, as well as increased levels of DNA methylation at specific loci. Some of the changes in DNA methylation observed in the mutant germ line are retained in somatic tissue of wild type progeny, and may affect the transcriptional regulation of genes involved in cancer susceptibility. We designed a breeding strategy to produce genetically wild type male offspring from a Kdm6a mutant male germ line. We generated a germline-specific Kdm6a conditional knockout (Kdm6a cKO) in male mice by crossing a Cre recombinase driven by the Ddx4 (Mvh) promoter (Gallardo et al. , 2007) to a conditional allele of Kdm6a (Welstead et al.","Many diseases, such as certain cancers, run in families. Often, this is because several related individuals inherit a version of a gene that is faulty and causes the condition. But in a number of families with high rates of cancer, scientists are unable to pinpoint such disease-causing gene versions. Instead, it is possible that individuals inherit healthy genes that are not read and interpreted correctly by the cells. This could be because of epigenetic changes, modifications that do not alter the genetic code but can instead turn genes on or off temporarily by adding or removing certain marks on the genetic information. For a long time, researchers thought that epigenetic changes could not be passed from one generation to the next, but recent studies have revealed this is",380,128,0.3368
scientific_lay_summarisation-elife-norm,"evident in developmental modularity. Whereas the medial cerebellum develops early, the lateral cerebellum develops later in tandem with cerebral association areas (Tiemeier et al. , 2010; Altman and Bayer, 1997). We investigate the extent to which mammalian lateral cerebellar hemispheres evolved in coordination with the rest of the cerebellum, whether they are correlated with measures of domain-general cognitive performance, and what patterns underlie their evolutionary diversification. We primarily focus on the relative measure of lateral to medial cerebellar volume to account for the functional, connectional, and developmental modularity of the cerebellum (see more details in Materials and Methods). Volumetric measurements of cerebellar partitions were used because cerebellar volume is a nearly linear function of its number of neurons (Herculano-Houzel, 2010), and by extension, its relative investment in particular information processing loops (Herculano-Houzel, 2010). Phylogenetic scaling of lateral to medial cerebellar volume indicates a positive scaling trend (F = 294. 6, p<0. 001, λ = 0. 945) with a slope that is higher than unity (95% confidence interval: 1. 167: 1. 478) (). Residuals were considered as measures of ‘relative lateral to medial cerebellar size’ (or ‘lateral-medial cerebellar reorganization’). The ratio of the observed to the predicted values range from 2. 3 to 4. 4 in apes, cetaceans and pinnipeds, from 0. 6 to 0. 7 in feliformes, and from 0. 2 to 0. 3 in artiodactyls. Phylogenetic regression analysis also demonstrated that lateral-medial cerebellar reorganization is a significant predictor of domain-general cognition in primates (F = 15. 670, p=0. 001, ) The evolutionary history of lateral-medial cerebellar reorganization was quantified using a Bayesian reversible-jump Ornstein-Uhlenbeck (‘OU’) approach (Uyeda and Harmon, 2014) (). This analysis indicates five shifts in mean value with a posterior probability (‘PP’) >0. 8. These regime shifts occurred at the root branches of the apes, the cetartiodactyls, the cetaceans (note that our sample includes toothed whales only), the pinnipeds, and the feliformes (, — 1). The signal-to-noise ratio of this estimated pattern is 52. 34, demonstrating that the analysis has high effect size and high power. Phylogenetic analysis of covariance (Smaers and Rohlf, 2016) indicates that these shifts represent significant differences in the intercept of lateral to medial cerebellar scaling (i. e. grade shifts; Table 1). Specifically, apes, toothed whales and pinnipeds are not significantly different from","The brains of mammals consist of the same basic structures, but each of these structures varies from one species to the next. A given structure may be larger in one species than another, for example. It may contain different numbers or sizes of cells. It may even have different connections to other brain regions. By comparing individual brain structures between species, we can map how the mammalian brain has evolved. Smaers et al. have now done this for the cerebellum, a structure at the back of the brain. The mammalian cerebellum consists of three main areas: the vermis, paravermis, and the lateral hemispheres. Smaers et al. show that in apes, dolphins and seals, the lateral hemispheres are unusually large relative to the cerebellum as a whole. This could",380,128,0.3368
pubmed-summarization,"diluted propofol for sedation in patients undergoing ercp were significantly less than when using undiluted propofol . however , patients in that study were sedated using only clinical assessment.6 therefore , our aim of this study was to determine and compare the clinical efficacy of propofol deep sedation using either clinical assessment or the narcotrend index as a guide for depth of sedation in patients undergoing ercp . a total of 176 consecutive patients from a tertiary care teaching hospital , siriraj hospital , bangkok , thailand , were eligible for the study . exclusion criteria included any clinical evidence of severe liver disease , and patients who had american society of anesthesiologists ( asa ) physical status iv or v. this present study was approved by the institutional review board of the faculty of medicine siriraj hospital . all the enrolled patients provided written informed consent to undergo the procedures and to participate in the study . the primary outcome variable of the study was the successful completion of the endoscopic procedure . the secondary outcome variables were the total dose of propofol used during the procedure , recovery time , patient tolerance and satisfaction , endoscopist satisfaction , and complications during and immediately after procedure . the amount of propofol used was compared as total dose , dose / kg , or dose / kg / h . recovery time was defined as the time after the end of procedure to patient awakening . , 52 patients were sedated using clinical assessment with depth of sedation assessed with the use of the modified observer s assessment of alertness/ sedation ( moaa / s ) scale.12 in group n , 48 sedated patients were sedated using the narcotrend system . the anesthetic personnel who sedated the patients relied exclusively on the narcotrend index in determining the propofol dose given to the patients . however , patient observation might have played a role in the decision making if the patient was clinically sedated inadequately . however , all patients in both groups were monitored with the narcotrend system , but the patients in group c were not sedated using the narcotrend . additionally , the anesthetic personnel who sedated the patients in group c did not see the narcotrend index",introductionmoderate to deep sedation is generally used for endoscopic retrograde cholangiopancreatography ( ercp ) . the depth of sedation is usually judged by clinical assessment and electroencephalography - guided monitoring . the aim of this study was to compare the clinical efficacy of clinical assessment and narcotrendtm monitoring during deep - sedated ercp.methodsone hundred patients who underwent ercp in a single year were randomly assigned to either group c or group n. patients in group c ( 52 ) were sedated using the modified observer s assessment of alertness / sedation ( moaa / s ) scale . patients in group n ( 48 ) were sedated using the narcotrendtm system . the moaa / s scale 1 or 2 and the narcotrendtm index 4756 to 5764 were,380,128,0.3368
dialogsum,"#Person1#: I am an eloquent speaker in the classroom. But when I face a stranger outside, I get tongue-tied and nothing comes out. #Person2#: You should pay close attention to your manner of speaking. Speech is a reflection of personality, you know. You should reflect confidence by speaking in a low voice, loud enough to be heard without being aggressive or overpowering. #Person1#: I will go out of my way to catch the attention of the interviewer. #Person2#: Your speech should not call attention to itself, but should reveal your individuality and ability. #Person1#: I'm very shy. I think I might shake in my boots at the moment I meet the interviewer. #Person2#: You'd better overcome your nervousness. it is considered an indication that you lack self-confidence. #Person1#: Another problem is that I dare not look into their eyes whenever I meet strangers, especially foreigners. #Person2#: In China, it is impolite to look into the senior speakers eyes while speaking. But in Western countries it is the opposite. Eye contact gives a strong feeling of sincerity. Looking downwards or sideways shows that you are either insincere or absent-minded. #Person1#: Is there anything else that I should pay attention to in an interview? #Person2#: Yes. Don't eat onions or garlic before you come. If you do you'll have bad breath. #Person1#: I'll remember to bring gum with me. #Person2#: You should never chew gum or smoke during an interview, even if you are allowed to do so. #Person1#: I remember now. Your advice is very helpful.","#Person2# gives #Person1# interview advice, including speaking in a confident manner, not to eat garlic, and never chewing gum. #Person2# thinks #Person1# is nervous because #Person1# lacks self-confidence.",255,28,0.1098
scientific_lay_summarisation-elife-norm,"The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resulted in increased numbers of chromosome aberrations and γH2AX foci in non-transformed MCF10A human mammary epithelial cells. However, such increases were almost completely eliminated in isogenic cells with CASP3 gene ablation. Furthermore, we show that endonuclease G, an apoptotic nuclease downstream of Caspase-3, is directly responsible for Myc-induced genetic instability. Genetic ablation of either CASP3 or ENDOG prevented Myc-induced oncogenic transformation of MCF10A cells. Taken together, we believe that Caspase-3 plays a critical, unexpected role in mediating Myc-induced genetic instability and transformation in mammalian cells. One of the hallmarks of cancer is increased genomic instability (Hanahan and Weinberg, 2011). In addition to DNA replication errors and /or mutations induced by exposure to DNA damaging agents, over-expression of oncogenes have been shown to induce genomic instability (Bartkova et al. , 2005; Gorgoulis et al. , 2005). One such oncogene is Myc. As one of the most widely studied oncogenes in cancer biology, it is mutated or over-expressed in multiple types of cancer (Pelengaris et al. , 2002). Myc is involved in driving cellular proliferation and promoting stem cell self-renewal under normal circumstances. When myc is overexpressed in a cell, it can cause increased genomic instability and promote carcinogenesis (Karlsson et al. , 2003; Ray et al. , 2006). Despite numerous studies, the mechanisms involved in myc-induced genomic instability and transformation remain controversial. There are conflicting reports on the mechanism of myc-induced genomic instability and transformation. Several studies suggest that myc-induced genomic instability and carcinogenesis is a result of an overabundance of reactive oxygen species (ROS) (Vafa et al. , 2002; Felsher and Bishop, 1999). However, it has also been reported that myc overexpression can cause DNA damage and transformation in the absence of ROS (Ray et al. , 2006). Over-expression of myc has been shown to induce apoptosis (Evan et al. , 1992; Harrington et al. , 1994). Until recently, apoptosis has been widely recognized as an anti-carcinogenic process based on the assumption that it is utilized by the host to eliminate damaged cells, including those suffering DNA damage (Hanahan and Weinberg, 2011; Reed, 1999). However, there has","Healthy cells can become cancerous if their DNA is damaged and not repaired properly, leading to changes in the DNA known as mutations. The cells tend to accumulate more and more mutations – a phenomenon known as genomic instability – as they transition into cancer cells. A protein called Myc is known to promote genomic instability and contributes to many types of cancers. However, high levels of Myc proteins in a cell can also activate proteins that trigger a process called apoptosis, which makes the cell commit suicide. This role does not appear to fit with the cancer-promoting properties of Myc because apoptosis is generally thought to protect against cancer by helping to remove damaged cells from the body. Two of the proteins that Myc activates are known",380,128,0.3368
scientific_lay_summarisation-elife-norm,"an obligatory process in vivo. What regulates the switch from closed to open conformation? One model proposes that AP2 can open by simply binding the peptide motifs of cargo proteins and phosphatidylinositol 4,5-bisphosphate (PIP2) on the plasma membrane (Honing et al. , 2005; Kelly et al. , 2014). Alternatively, AP2 might require association with clathrin and phosphatidylinositol-3-phosphate to bind cargo at the plasma membrane (Rapoport et al. , 1997). Another model suggests that the open form of AP2 is induced by phosphorylation (Fingerhut et al. , 2001; Olusanya et al. , 2001; Conner and Schmid, 2002; Ricotta et al. , 2002; Honing et al. , 2005). Alternatively it is possible that the complex is activated by one of the many other clathrin-associated proteins. The most likely of these proteins would be one that precedes AP2 at sites of endocytosis. Examples include Epidermal growth factor receptor substrate 15 (Eps15), intersectin, and most recently, Fer/CIP4 Homology domain only (FCHo) proteins (Syp1p in yeast) (Stimpson et al. , 2009; Taylor et al. , 2011). The role of FCHo at endocytic sites is poorly defined. In syp1 mutants, which encodes the yeast homolog of FCHo, endocytic patches are less frequent, but still progress to coated pits (Reider et al. , 2009; Stimpson et al. , 2009). When FCHo proteins were knocked down in tissue culture cells, AP2 failed to bind membrane (Henne et al. , 2010). However, others found that knockdown of FCHo did not prevent AP2 association with the membrane (Umasankar et al. , 2012) but that there is an increased tendency for endocytic events to abort (Cocucci et al. , 2012) with flat clathrin plaques forming rather than clathrin-coated pits (Mulkearns and Cooper, 2012). These studies suggest that FCHo might regulate AP2 during the formation of a clathrin-coated pit. On the other hand, there is evidence that FCHo may be acting in a parallel endocytic pathway with ESCRT0 in Caenorhabditis elegans (Mayers et al. , 2013). In fish, FCHo appears to act in BMP signaling during development (Umasankar et al. , 2012). Thus it is unclear whether FCHo proteins function via AP2 or in parallel to AP2 in clathrin coat assembly, or in an entirely unrelated pathway. Here, we report that FCHo directly activates AP2 by promoting the open conformation. In FCHo","All cells are enveloped by a plasma membrane. To interact with the outside world, cells constantly recycle the molecules found in, or on, this barrier. This is accomplished by drawing in small patches of the membrane containing these ‘cargo’ molecules via a process called endocytosis. The predominant method of endocytosis involves coating the tiny membrane pouches with a scaffold-like structure made of clathrin molecules. However, clathrin requires a set of four proteins (known as the adaptor protein-2 complex) to connect the membrane and cargo to the clathrin cage. Previous studies have suggested that the adaptor protein-2 complex may exist in at least two forms: one in which the binding sites for membrane and cargo are hidden, and another where these sites are exposed. These structures were proposed to",380,128,0.3368
dialogsum,"#Person1#: Hey Carol, what's new? #Person2#: Not much, just catching up on a TV show I like to watch. Sometimes it's nice to come home after a long day at work and relax. #Person1#: I know what you mean. In fact, I wouldn't mind some relaxation time myself. #Person2#: You look like you had a long day, too. Did you just get home from work? #Person1#: No, I just returned home from an overseas business trip. I spent the last 24 hours in airports, and on airplanes. Luckily, I have the next 2 days off, it's a rare opportunity. #Person2#: So what are you going to do, since you finally have time to yourself? #Person1#: When I can I like to go to the beach. I go for a swim, dry off and lay in the sun with a good book to read. #Person2#: That sounds very peaceful, it's nice to be alone sometimes. Of course, there is nothing better than hanging out with your friends. #Person1#: That's true, actually if you're not doing anything tomorrow. You could come out with me and my friends we're going to have lunch, and then go see a movie. #Person2#: I would love to, I don't work tomorrow either. #Person1#: Great, well, I'll let you watch your TV show and I'll go to my room to send some emails to my boss. #Person2#: Don't be silly, you work too hard. Sit down and watch the show with me, relax. #Person1#: I guess that's the best thing to do.",Carol is watching a TV show and #Person1# just comes back from an overseas business trip. #Person1#'ll have two days off. #Person1# invites Carol to join them for lunch and movie tomorrow and Carol invites #Person1# to watch the TV show together tonight.,255,43,0.1686
dialogsum,"#Person1#: Would you like some tea or coffee? #Person2#: No, thank you. It's very late now. They will keep me awake the whole night. #Person1#: Then, what about some water? #Person2#: Yes, please. #Person1#: Don't work too late since you are not in good health. You should be careful with your health. #Person2#: I know, but I have to finish these reports tonight. Our manager will use them at the meeting tomorrow morning. #Person1#: Can I help you with something? #Person2#: No, I'm afraid you can't. Just turn down the TV a little so that it's not so noisy. #Person1#: I will. I do hope that you will finish the reports soon and get some sleep. #Person2#: Don't worry. It won't take me too long.",#Person2# cares about #Person1# and #Person2# only wants a cup of water because it is late and #Person1# has to finish the reports.,125,23,0.184
dialogsum,"#Person1#: Mom, I just finished my paper. Can you proofread it before I hand it in? #Person2#: Sure, let's take a look. Sweetie, this is terrific. Your ideas are so original. #Person1#: Thanks. #Person2#: I can tell you worked hard on it. #Person1#: I really did! I started thinking about what I wanted to say three weeks ago. #Person2#: Well, it was definitely worth all the time. #Person1#: Let's just hope my teacher agrees.",Mom helps #Person2# proofread the paper and thinks it is terrific.,74,11,0.1486
dialogsum,"#Person1#: Can you tell me where I can park? #Person2#: Are you driving a motorcycle or an automobile? #Person1#: I drive an automobile. #Person2#: Fine. You can either park in the student lot or on the street. Do you know what a handicapped space is? #Person1#: Yes, I have seen those spots. #Person2#: Well, when you see the blue spots with the handicapped logo, do not park there unless you have a special permit. Are you going to be parking in the daytime or the evening? #Person1#: I park in the evenings. #Person2#: Then you also need to be aware of the time limits on the street signs. Have you seen those signs? #Person1#: Yes, I have seen those signs. #Person2#: The signs always tell you how long you can park there and on what days. Do you know how to read the curb colors? #Person1#: Yes, I know what the curb colors mean. #Person2#: Well, just as long as you realize that red means no parking and white means loading and unloading, I think you know what you need to know.",#Person2# tells #Person1# when and where to park the automobile in the evenings and reminds #Person1# to be aware of the time limits on the street signs and the curb colors.,182,31,0.1703
scientific_lay_summarisation-elife-norm,"fetal hydrops, and the ultimate nonviability of the fetus (Chitayat et al. , 1993; Greenberg et al. , 1988; Horn et al. , 2000; Konstantinidou et al. , 2008; Trajkovski et al. , 2002). Interestingly, mounting evidence indicates that Greenberg skeletal dysplasia results from the inheritance of two mutant LBR alleles that when heterozygous cause Pelger-Huët anomaly (Konstantinidou et al. , 2008; Oosterwijk et al. , 2003), indicating that the two diseases represent different allelic states of the same chromosomal lesion. However, it is unclear whether these diseases are caused by structural changes in the nuclear lamina, or whether they are diseases of cholesterol metabolism (Clayton et al. , 2010; Olins et al. , 2010; Wassif et al. , 2007; Waterham et al. , 2003; Worman and Bonne, 2007). 10. 7554/eLife. 16011. 004Table 1. Diseases-associated LBR mutations used in this study. : http: //dx. . org/10. 7554/eLife. 16011. 004LBR variantMutationPhenotypeReferenceN547Dc. 1639A>GHeterozygous - No PhenotypeClayton et al. , 2010p. N547DHomozygous - Greenberg DysplasiaKonstantinidou et al. , 2008R583Qc. 1748G>AHeterozygous - No PhenotypeClayton et al. , 2010p. R583QHomozygous - Greenberg Dysplasia1402TΔc. 1402delTHeterozygous - Phenotype UnknownClayton et al. , 2010p. Y468TfsX475Homozygous - Greenberg Dysplasia1600*c. 1599-1605TCTTCTA→CTAGAAGHeterozygous - Pelger-Huët AnomalyWaterham et al. , 2003p. X534Homozygous - Greenberg Dysplasia In this study, we show that LBR is essential for cholesterol synthesis. Using a human cell culture model, we demonstrate that it is this function that is perturbed by LBR mutations associated with Pelger-Huët anomaly and Greenberg skeletal dysplasia, suggesting a loss-of-function mechanism for these congenital disorders. Unexpectedly, disease-causing mutations involving C-terminal truncations of LBR lead to their rapid degradation in the nuclear envelope (NE). Such LBR mutants appear to be dislocated from the INM directly into the nucleoplasm, unlike traditional substrates of the ER-associated degradation (ERAD) machinery, which are eliminated in the cytosol after their dislocation from the ER (Claessen et al. , 2012; Vembar and Brodsky, 2008). Metabolically unstable LBR mutant proteins will therefore be informative for future studies aimed at elucidating mechanisms of protein quality control at the nuclear envelope of mammalian cells, a site that was previously experimentally inaccessible due to the absence of suitable model substrates. In order to clarify the cellular function of LBR both in cholesterol metabolism and as a structural component of the nuclear lamina, we used the CRISPR/Cas9 system","In humans, mutations in the gene that encodes a protein called Lamin B receptor can lead to diseases ranging from harmless anomalies of blood cells to fatal developmental defects. The severity of the disease depends on the nature of the specific mutation, and whether one or both copies of the gene are affected. Lamin B receptor – or LBR for short – is found at the envelope that surrounds the cell’s nucleus and was previously proposed to anchor this envelope to an underlying scaffold to provide it with support. LBR can also catalyze a chemical reaction involved in producing cholesterol – an essential component of cell membranes. However, this enzymatic activity was assumed to be less important because a second enzyme named TM7SF2 can perform the same reaction.",380,128,0.3368
dialogsum,"#Person1#: What upsets you? #Person2#: My parents called. As usual, they reminded me again that I should have a plan to marry by my late 20s. Easier said then done. Who should I marry? I have no time to go on a date. #Person1#: It is not your mother finding one for you? #Person2#: I will find one myself, of course. I'm a modern girl. #Person1#: Perhaps you can try the three minutes date, the latest type. #Person2#: You mean dozens of the opposite sex meet each other for three minutes in a dimly bar serving alcohol, I hate that idea. #Person1#: No, there is an updated virgin, three minutes video date. I know an online dating website providing such service with a microphone and webcam, you can sigh for it. You can be face-to-face with a guy talking for maximum three minutes. #Person2#: I don't think it makes sense. Three minutes is such a short time. #Person1#: I think you can find out if there is a possibility of romance within the first second of meeting someone, so-called love at first sight. #Person2#: Anyway, I don't want to post my face up for sale on the internet like that. #Person1#: Don't worry. There are many other options using the internet as dating methods. Some sites operate at international standard even have got certifications. Of course, for these sites, you have to pay a membership fee. But all in all, it is more serious and professional. The chance of meeting a good and serious person who does not play games is higher. #Person2#: I don't want to post my personal information on the internet. I'm not knowing who is reading it.",#Person2# is upset because #Person2#'s parents reminded #Person2# to have a plan to marry. #Person1# advises #Person2# to try the three-minute video date but #Person2# doesn't want to post personal information online.,281,32,0.1139
pubmed-summarization,"polycystic ovary syndrome ( pcos ) which was first reported in 1935 is known as one of the most common endocrine hormones disorders in the women of the reproductive age afflicting as many as % 10 of them . the name of this syndrome has been derived from the appearance of the ovaries of the afflicted women ( an ovary of enlarged size and full of cysts ) . these cysts are in the form of follicles filled with liquid sacs full of developed ovum . due to the lack of a set of standard and unified diagnostic criteria , the rate of prevalence of this syndrome reported in the different studies is varied . some studies which used sonography as their diagnostic criteria found that the prevalence of pcos ranged between 21% and 22% respectively . on the contrary , in some other studies using oligomenerrhea and hyperandrogenemia manifestations as the pcos 's diagnostic criteria , this syndrome accounts for 30 - 40% of the common causes of infertility resulting from ovary dysfunctions . in addition , pcos is considered as the most leading cause of ovary disorders . as recent studies indicate , a person may have pcos without showing one or some of the above - mentioned symptoms , some other symptoms and signs which can be enumerated for pcos are as follows : increased androgenic hormones , metabolic syndrome ( insulin resistance ) , fat - related disorders , type 2 diabetes , cardiovascular disease , endometrial cancer and blood pressure . the patients with pcos also suffer from anxiety and depression some symptoms which are believed to be mostly a result of disorders occurred in the reproduction cycle which is naturally completed by releasing an ovum every month . the exact cause of pcos is not yet completely known , however , some factors such as insulin resistance / hyperinsulinaemeia , obesity , heredity and genetics factors , environmental factors such as exposure to high levels of masculinizing hormones , embryonic life cycle - related factors , hyperandrogenemia , gonadotropins secreting and functioning , hyperprolactinemia , hypothyroidism or thyroid - related dysfunctions , diet all may play a part in developing pcos . according to previous studies , the eating habits are not different between","background : polycystic ovary syndrome ( pcos ) is the most common endocrine disorder in reproductive women . nearly 10% of young women in this period involved . although factors such as insulin resistance , hyper insulinemia , obesity and dietary are suggested to be associated with pcos , cause of pcos is not completely understood . dairy products ( a key component of the usual diet ) of participants can also affect the factors of this disease and may have beneficial effects on treatment of pcos . however , research in this area is scarce . the purpose of this study was to evaluate the relationship between dairy products consumption and pcos.methods:this descriptive cross - sectional study of 400 women was conducted in shahid beheshti hospital of",380,128,0.3368
dialogsum,"#Person1#: Good morning. #Person2#: Good morning. May I help you? #Person1#: I want to place a long-distance call to London. Is this the right counter? #Person2#: Yes. Here's a booking form. Please write down the number you wish to call, the name of the person you want to talk to, and your own name for our reference. #Person1#: All right. Can you tell me when I will be able to get through? #Person2#: It's hard to say. It depends on how busy the lines are. Please take a seat over there. We'll try to put you through as soon as possible. #Person1#: Thank you.",#Person1# wants to place a long-distance call and #Person2# asks #Person1# to write down the number in a booking form.,104,20,0.1923
scientific_lay_summarisation-elife-norm,"Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. Marfan syndrome is a systemic connective tissue disorder caused by mutations in FBN1, the gene encoding extracellular matrix protein fibrillin-1. A major cause of mortality in Marfan patients is aortic dissection and rupture. In Marfan mice, multiple phenotypic manifestations, including aortic aneurysm, developmental lung emphysema, mitral valve disease, and skeletal muscle myopathy, correlate with enhanced transforming growth factor beta (TGFβ) signaling, while treatment with either TGFβ neutralizing antibody (NAb) or the angiotensin-II type 1 receptor (AT1R) blocker (ARB) losartan can ameliorate these phenotypes, in association with evidence of reduced TGFβ signaling (Neptune et al. , 2003; Ng et al. , 2004; Habashi et al. , 2006; Cohn et al. , 2007; Cook et al. , 2015). Both canonical (Smad2/3) and noncanonical (ERK1/2) TGFβ-dependent signaling cascades have been shown to be activated in the aortas of Marfan mice, while selective inhibition of extracellular signal-regulated kinase (ERK1/2) activation using RDEA119 (refametinib) rescues aortic growth and aortic wall architecture in Marfan mice (Habashi et al. , 2011; Holm et al. , 2011). Calcium channel blockers (CCBs) are a class of blood pressure lowering medications that block movement of calcium into cells from the extracellular space. There are several sub-classes of CCB based on chemical structure, including dihydropyridines (e. g. , amlodipine) and non-dihydropyridines, which include both phenylalkylamines (e. g. , verapamil) and benzothiazepines (e. g. , diltiazem). CCBs are currently considered an alternative therapeutic strategy for Marfan patients intolerant of β-blockers, due to their ability to reduce contractility","Marfan syndrome is a disorder that affects the body' s connective tissues, which maintain the structure of the body and support organs and other tissues. People with Marfan syndrome have connective tissues that can stretch more than those of other people, which put them at increased risk of a life-threatening tear in their aorta (the main artery in the body), muscle weakness and other problems. A cell communication pathway called TGFβ signaling is involved in cell growth and many other important processes. TGFβ signaling is more active in patients with Marfan syndrome due to mutations in a gene called FBN1. Drugs that block TGFβ signaling—which are also used to treat high blood pressure—can reduce the symptoms of the disorder. Unfortunately, not all people with Marfan disease can tolerate",380,128,0.3368
dialogsum,"#Person1#: I'd like to have a couple of complete sets of paper money and coins. #Person2#: Yeah. You can take them home and either use them as a gift or keep them as mementoes. #Person1#: Ah, where can I find old paper money and coins used before and after 1949? #Person2#: I'd suggest that you go to the Philately Store in Nanjing Road East, where the items are authentic and the prices are reasonable. #Person1#: Good. Sorry to have troubled you so much, Miss. #Person2#: You're always welcome. Anything else can I do for you, sir? #Person1#: No, thanks. I did not notice it has been dark outside. I think it is time to dinner. #Person2#: I guess it is. The restaurant is on the second floor. Please enjoy your dinner, sir!",#Person2# suggests #Person1# go to the Philately Store to find old paper money and coins used before and after 1949.,132,20,0.1515
dialogsum,"#Person1#: John, it's 7:30. I wonder how much later they are going to be? #Person2#: Oh, you know Terry and Susan. They never arrive on time. #Person1#: Yes, but half an hour late! My dinner will be ruined. #Person2#: Oh, maybe they got stuck in traffic. You know what the traffic is like at this time of day. #Person1#: Yes, but they said they were taking the subway so they wouldn't get caught in traffic. #Person2#: Well, they shouldn't be late then. Why don't you give them a call and see if they've left. Maybe they forgot about the invitation. #Person1#: They couldn't have forgotten about it. I was just talking to Susan last night. Anyway, let me just check if they are in. Their number is 2143556.",#Person1# complains to John that Terry and Susan arrive late for dinner. John suggests #Person1# give a call to them to check if they're in.,128,25,0.1953
dialogsum,"#Person1#: Why are you looking so upset? What's the problem? #Person2#: I have to write a long article and I just can't come up with any ideas. And I have to hand it in tomorrow. #Person1#: That shouldn't be too difficult. Remember those pictures you showed me last week? #Person2#: Sure. I've got them here. #Person1#: Why don't you write about your impressions of the pyramids in Egypt? #Person2#: Sounds like a good idea. I can also tell about our visit to North Africa and all of the historical places we visited. #Person1#: Well, now that you are feeling better about this, I think I'll be on my way. I have to finish my article, too. #Person2#: Thanks. Once organized, it won't be so difficult.",#Person2#'s stuck on an article. #Person1# suggests writing about the impressions of the pyramids. #Person2# thinks it's a good idea.,125,20,0.16
dialogsum,"#Person1#: Do you have a double room for tonight? #Person2#: With an ocean view? #Person1#: Without is fine. #Person2#: A double room without a view for just one night? #Person1#: That's right. #Person2#: Yes, we do. #Person1#: By the way, what's the rate for a single room?",#Person2# helps #Person1# book a double room.,47,7,0.1489
scientific_lay_summarisation-elife-norm,"averaging of the F1Fo ATP synthase dimers in situ revealed an angle of 86° between the monomers (Davies et al. , 2012). Coarse-grained molecular dynamic simulations have indicated that the shape of the F1Fo ATP synthase dimer alone is sufficient to deform the lipid bilayer and drive the self-assembly of the F1Fo ATP synthase dimers into rows (Davies et al. , 2012). However, a recent single-particle cryo-EM map of detergent solubilised, bovine F1Fo ATP synthase monomers found the detergent micelle around the Fo domain was bent leading to the suggestion that the monomer alone could deform lipid bilayers (Baker et al. , 2012). Electron cryo-crystallography and electron cryo-tomography allow the structure of membrane-embedded proteins to be investigated in a lipid environment (Fujiyoshi and Unwin, 2008; Davies and Daum, 2013). To determine the structure of membrane-embedded bovine heart F1Fo ATP synthase, we generated 2D crystals of intact and active bovine heart F1Fo ATP synthase using the synthetic lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). By a combination of subtomogram averaging and electron crystallography of tomographic slices, we determined the in situ structure and packing of the enzyme complex in 2D crystals. The oblique orientation of individual complexes in the membrane results in a zigzag arrangement of the lipid bilayer, which perfectly matches the observed bend in the detergent micelle of the isolated complex (Baker et al. , 2012). Our results demonstrate that the transmembrane region of bovine mitochondrial F1Fo ATP synthase monomer is sufficient to bend the lipid bilayer. This membrane deformation is likely to be a prerequisite for the self-association of F1Fo ATP synthases into dimers and dimers into rows, as observed in mitochondrial cristae. Monomeric mitochondrial F1Fo ATP synthase was purified from bovine heart muscle tissue by sucrose density gradient centrifugation and ion-exchange chromatography. For 2D crystallisation, fractions exhibiting high oligomycin-sensitive ATPase activity (>95%) and a high content of native lipids (>100 lipid molecules per F1Fo ATP synthase) were mixed with synthetic DMPC. When the detergent was removed by dialysis, abundant crystalline vesicles formed that were stable for weeks (— 1). Analysis by SDS-PAGE and mass spectrometry confirmed that the crystalline vesicles contained all subunits of the bovine F1Fo ATP synthase, including the small Fo subunits e, f, g, A6L, DAPIT, and the 6. 8-kDa protein (— 2). ATPase assays and blue-native PAGE","Cells use a molecule called adenosine triphosphate (or ATP for short) to power many processes that are vital for life. Animals, plants, and fungi primarily make their ATP in a specialised compartment called the mitochondrion, which is found inside their cells. The mitochondrion is often referred to as the powerhouse of cells as it captures and stores the energy that animals gain from eating food in the molecule ATP. Other enzymes in the cell break apart ATP to release the stored energy, which they use to power various cellular processes. The interior architecture of the mitochondrion includes a highly folded inner membrane where electrical energy is transformed into chemical energy. The tight folding of the inner membrane is thought to make this process more efficient. An enzyme named",380,128,0.3368
dialogsum,"#Person1#: I think that you look very cute today. #Person2#: Is that right? This is a brand new outfit. #Person1#: What store did you get it from? #Person2#: I went to Macy's and picked it out. #Person1#: I love your outfit right now. #Person2#: Well, I think you look nice today too. #Person1#: Thanks. I found these new shoes earlier at the store. #Person2#: I think that those are some really nice shoes. What kind are they? #Person1#: These are Chucks. #Person2#: Your shoes look really nice. How much did you get them for? #Person1#: They only cost me about forty dollars. #Person2#: I'm going to go get a pair for myself.",#Person1# and #Person2# admire each other's outfit today and talk about dressing. #Person1# compliments #Person2#'s outfit and #Person2# praises #Person1#'s shoes.,112,21,0.1875
dialogsum,"#Person1#: Is April Fools Day on Friday or Saturday this year? #Person2#: I'm almost certain it's on Thursday. #Person1#: My god, I thought it was on the weekend. I was going to play a joke on my girlfriend and then invite her to a restaurant. #Person2#: Why can't you invite her out on Thursday? #Person1#: Because I have an exam on Friday. #Person2#: Well, you could invite her out on the weekend to celebrate this interesting an late April Fools Day. #Person1#: I guess I'll have to do that.","#Person2# tells #Person1# April Fool's Day is on Thursday this year. #Person1# wanted to play a joke on his girlfriend, but he has an exam on Friday, so #Person2# suggests he do it on the weekend.",89,36,0.4045
dialogsum,"#Person1#: Can you tell me something about financial aid? #Person2#: What exactly? #Person1#: How to apply for it? #Person2#: In your first letter, that is, when you apply for admission, you should also tell them you need their financial aid. #Person1#: Then. . . #Person2#: If the aid is available, they will give you two or more application forms, One is for admission, the others are for the aid. #Person1#: What if not? #Person2#: They will tell you the aid is impossible.","#Person2# tells #Person1# when #Person1# applies for admission, #Person1# should also tell them #Person1# needs financial aids.",82,17,0.2073
dialogsum,#Person1#: I am so sorry that I must be off now. My girlfriend told me I must arrive at her home in ten minutes or she will break up with me. #Person2#: She can cope with it. Don't be such a wimp!,#Person1# must be off to meet #Person1#'s girlfriend.,42,8,0.1905
pubmed-summarization,"to review the current knowledge about nonpharmacologic approaches in the prevention and early treatment of type 2 diabetes . this study reviewed the research reports dealing with nonpharmacologic interventions aimed at preventing type 2 diabetes with early lifestyle interventions . the results from the randomized controlled trials all show that people with impaired glucose tolerance who received enhanced lifestyle advice had significantly lower ( on average 50% reduced ) incidence of type 2 diabetes compared with those allocated to receive usual care . individuals who were able to correct their lifestyle habits as recommended for usual healthy life patterns were mostly protected against type 2 diabetes . thus , compelling evidence exists that most of the cases of type 2 diabetes can be prevented or at least the onset of the disease can be significantly delayed . randomized controlled trials have unequivocally demonstrated that lifestyle management is highly efficient in the prevention and also in the early management of type 2 diabetes . this evidence of lifestyle modification in diabetes prevention is stronger than for most other multifactorial diseases . in the early randomized intervention study in malmhus , sweden ( 19 ) , lower rates of type 2 diabetes was found in igt men randomized to dietary intervention compared with those who received no therapy . more recently , several trials have tested the efficacy of lifestyle intervention in prevention of type 2 diabetes . the feasibility of diet and exercise intervention in men with igt was assessed in another study in malm , sweden ( 20 ) . because the reference group comprised of men who did not want to join the intervention , the groups were not randomly assigned . the lifestyle intervention aimed at reducing the intake of refined sugar , simple carbohydrates , fat , saturated fat , energy , and alcohol and an increase in the intake of complex carbohydrates and vegetables . physical activity training consisted of two weekly 60-min sessions with various dynamic activities . by the end of the 5-year study period , 11 and 29% of the men in the intervention group and reference group had developed type 2 diabetes , respectively . overall , the progression to diabetes in these swedish men was relatively low , even in the","objectiveto review the current knowledge about nonpharmacologic approaches in the prevention and early treatment of type 2 diabetes.research design and methodsthis study reviewed the research reports dealing with nonpharmacologic interventions aimed at preventing type 2 diabetes with early lifestyle interventions.resultsthe results from the randomized controlled trials all show that people with impaired glucose tolerance who received enhanced lifestyle advice had significantly lower ( on average 50% reduced ) incidence of type 2 diabetes compared with those allocated to receive usual care . individuals who were able to correct their lifestyle habits as recommended for usual healthy life patterns were mostly protected against type 2 diabetes . thus , compelling evidence exists that most of the cases of type 2 diabetes can be prevented or at least the onset",380,128,0.3368
dialogsum,"#Person1#: Did you take these pictures? They are very good. #Person2#: Yes, I think they turned out very well too. I like to bring my camera with me wherever I go. That way if I see something attractive I can snap a picture of it. #Person1#: Carrying a big camera around is too much trouble for me. #Person2#: My camera is really small enough. Here let me show you. #Person1#: That is a compact camera. But you must know a lot about photography to get such professional looking results. #Person2#: Not necessarily. This camera is simple to work. #Person1#: Does this model come with a flash attachment for indoor shots? #Person2#: Better than that. It has a built-in electronic flash and an automatic focus too. I don't even have to worry about focusing. #Person1#: That's what I need. When I take pictures, they usually come out blurry because I don't adjust the lenses properly. And I hate photos that are out of focus. Is a camera like yours very expensive? #Person2#: Less than you'd expect. Why don't you check the prices that Headfields demonstrates? This model was on sale there last week. #Person1#: I think I will. It certainly won't hurt to take a look.",#Person1# is impressed by #Person2#'s pictures. #Person2# is experienced in photographs and introduces basic functions and advantages of the compact camera to #Person1#. #Person2#advises #Person1# to check camera prices that Headfields demonstrates.,205,32,0.1561
dialogsum,"#Person1#: Yikes! What was that noise? #Person2#: I had to blow my nose. #Person1#: Did you have to blow right next to the phone? #Person2#: Did you hear that? #Person1#: Of course I heard that. I thought a plane had crashed into your house. #Person2#: It wasn't that loud. #Person1#: I will blow my nose sometime for you, and you'll see. #Person2#: Okay. I'll take your word for it. #Person1#: I thought you had an elephant in your house. #Person2#: You're funny. #Person1#: What did you say? I think I've gone deaf. #Person2#: I'm going into the bathroom to blow my nose. I'll be right back.",#Person1# complains that the noise of #Person2#'s blowing nose was very loud. #Person2#'ll go into the bathroom to blow the nose.,106,21,0.1981
pubmed-summarization,"conventional laparoscopic surgery requires the placement of multiple ports through the abdominal wall , with the aims of maintaining adequate internal spacing of instruments to reduce clashing and facilitating tissue manipulation for dissection . these multiple transabdominal punctures are associated with morbidity and risks such as herniation , bleeding , and damage to internal organs , as well as decreased cosmesis . laparoendoscopic single - site ( less ) surgery has been developed to overcome the port - related complications of laparoscopic surgery , to minimize morbidity , and to maximize cosmetic outcome . less surgery is performed through a single keyhole incision , typically at the umbilicus , allowing the completion of several urologic procedures with the use of familiar laparoscopic instruments and skills . since raman et al . first reported less nephrectomy ( less - n ) in 2007 , subsequent studies have demonstrated that less - n is safe and feasible with outcomes equivalent to those of conventional laparoscopic nephrectomy for both benign and malignant kidney diseases . the skill of surgeons at high - volume surgery centers has now reached a sufficient level such that less partial nephrectomy of small selected renal masses yields results comparable to those of conventional partial nephrectomy . however , the passage of all of the instruments through a single access point promotes instrument clashing and maneuverability problems , loss of triangulation , and unfamiliar working angles , even for surgeons skilled at less surgeries , and these limitations have prevented these procedures from entering mainstream clinical practice . furthermore , when the need for bleeding control , increased traction , or a suture arises , it can become necessary to apply an additional port or convert to conventional laparoscopy . these limitations are encountered not only by novices but also by experienced surgeons during complicated or difficult cases . to facilitate less techniques and overcome the learning curve for novices , magnetic anchoring and guidance systems ( magss ) these devices harness magnetic forces to steer and operate completely insertable intracorporeal instruments via externally controlled magnets . the devices are typically inserted through an already established entry site into the peritoneal cavity and are then coupled via magnetic attraction across the body wall to a handheld external component .","purposemagnetic anchoring devices may reduce the number of port sites needed in laparoscopic surgery . in this study , we prospectively assessed the feasibility of using a magnetic anchoring and guidance system ( mags ) in laparoendoscopic single - site ( less ) surgery performed by novices.materials and methodsa total of 10 less simple nephrectomies were performed with or without mags in a nonsurvival porcine model by 6 operators with no previous less surgery experience . after installation of the homemade single port , an intra - abdominal magnet was fixed to the renal parenchyma with suturing and stabilized by an external magnet placed on the flank so that the position of the kidney could be easily changed by moving the external handheld magnet . the length of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"003Figure 1. Two Sla1 SH3 domains and a Pan1 PRD domain share a crucial role for cell growth. (A) Spatial-temporal recruitment of endocytic proteins. Endocytic proteins are grouped into several modules (Lu et al. , 2016) as indicated. Pan1 and End3 appear after the mid coat module proteins but slightly before Sla1 and Las17 appear (Sun et al. , 2015). * Note that proteins of the WASP-Myosin module arrive at endocytic sites with different timing. Las17 arrives with a similar timing to Sla1, while the remaining components of the WASP-Myosin module arrive later (Sun et al. , 2006). (B) Synthetic genetic interaction between sla1W41AW108A and pan1∆PRD. Cell growth of indicated yeast strains was compared by spotting serial dilutions of liquid cultures on plates at 25°C, or 30°C or 37°C. (C-E) Analysis of sla1W41A-W108A-GFP dynamics. (F-H) Analysis of pan1∆PRD-GFP dynamics. C and F, Maximum fluorescence intensity of GFP-tagged patch proteins at endocytic sites (also see — 1D and E). (D and G) Lifetime (mean ± SD) of GFP-tagged proteins. E and H, Radial kymograph representations (for explanation, please see — 2) of GFP-tagged proteins. The scale bars are 20 s. : http: //dx. . org/10. 7554/eLife. 29140. 00310. 7554/eLife. 29140. 004Figure 1— 1. Characterization of sla1W41AW108A and pan1∆PRD mutant cells. (A) Domain structures of Pan1, End3 and Sla1. EH, Eps15 homology; CC, coiled-coil domain; PRD, proline rich domain; SH3, Src homology 3; SHD1, Sla1 homology domain 1; SHD2, Sla1 homology domain 2; CBM, clathrin-binding motif; SR repeats, LxxQxTG repeats. (B) Examining cell growth of indicated yeast strains by spotting serial dilutions of liquid cultures on plate at 30°C. (C) Immunoblot analysis of whole-cell extracts from indicated yeast cells. PGK (phosphoglycerate kinase) serves as a loading control. (D) Single frame from a movie in which SLA1-GFP PAN1-mCherry cells and sla1W41AW108A-GFP cells were simultaneously imaged in the GFP channel. PAN1-mCherry was used to identify wild-type cells. (E) Single frame from a movie in which PAN1-GFP SLA1-mCherry cells and pan1∆PRD-GFP cells were simultaneously imaged in the GFP channel. SLA1-mCherry was used to identify wild-type cells. The scale bars on cell pictures are 2 µm. : http: //dx. . org/10. 7554/eLife. 29140. 00410. 7554/eLife. 29140. 005Figure 1— 2. Flowchart for scheme used to generate radial kymograph of fluorescently labeled-proteins in a movie. Radial kymograph is","Actin is one of the most abundant proteins in yeast, mammalian and other eukaryotic cells. It assembles into long chains known as filaments that the cell uses to generate forces for various purposes. For example, actin filaments are needed to pull part of the membrane surrounding the cell inwards to bring molecules from the external environment into the cell by a process called endocytosis. In yeast, a member of the WASP family of proteins promotes the assembly of actin filaments around the site where endocytosis will occur. To achieve this, WASP interacts with several other proteins including WIP and myosin, a motor protein that moves along actin filaments to generate mechanical forces. However, it was not clear how these proteins work together to trigger actin filaments to assemble",380,128,0.3368
scientific_lay_summarisation-elife-norm,"A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms. We have investigated how microRNAs (miRNAs) contribute to core clock and clock-controlled gene expression using mice in which miRNA biogenesis can be inactivated in the liver. While the hepatic core clock was surprisingly resilient to miRNA loss, whole transcriptome sequencing uncovered widespread effects on clock output gene expression. Cyclic transcription paired with miRNA-mediated regulation was thus identified as a frequent phenomenon that affected up to 30% of the rhythmic transcriptome and served to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation. However, only few mRNA rhythms were actually generated by miRNAs. Overall, our study suggests that miRNAs function to adapt clock-driven gene expression to tissue-specific requirements. Finally, we pinpoint several miRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to miRNA regulation. Circadian clocks orchestrate daily oscillations in mammalian behaviour, physiology, and gene expression. In mammals, a master pacemaker in the brain' s suprachiasmatic nucleus (SCN) synchronises subsidiary oscillators present in most peripheral cell types (reviewed in Dibner et al. , 2010; Mohawk et al. , 2012). Timekeeping by peripheral and SCN clocks relies on negative transcriptional feedback loops that engender oscillatory gene expression. In the core loop, BMAL1: CLOCK transcription factor heterodimers drive the expression of repressors, encoded by the Period (Per1,2) and Cryptochrome (Cry1,2) genes. PER: CRY protein complexes subsequently accumulate in the nucleus and repress BMAL1: CLOCK-mediated transcription. Due to their instability, repressor protein and mRNA abundance rapidly drops below the threshold required for autorepression, clearing the way for a new cycle. The mechanisms that control the stability of clock proteins have been studied to considerable extent and frequently involve post-translational protein modifications that control proteasomal degradation (e. g. , Yagita et al. , 2002; Eide et al. , 2005; Shirogane et al. , 2005; reviewed in Mehra et al. , 2009; Chong et al. , 2012). It is less well understood how the decay of core clock mRNAs is controlled (reviewed in Kojima et al. , 2011; Lim and Allada, 2013). Cyclically expressed transcription factors such as BMAL1: CLOCK (Panda et al. , 2002; Rey et al. , 2011) or REV-ERBα/β (Ueda et al. , 2002; Le Martelot","The rising and setting of the sun have long driven the schedules of humans and other mammals. This 24-hr cycle influences many behavioural and physiological changes, including alertness, body temperature, and sleep. A region in the brain acts as a master clock that regulates these daily cycles, which are called circadian rhythms. Signals from the brain' s master clock turn on and off ‘core clock genes’ in cells, which trigger cycles that cause some proteins to be produced in a circadian rhythm. The rhythm is specialized to a particular tissue or organ, and may help them to carry out their designated daily tasks. However, circadian rhythms might also be produced in other ways that do not involve these genes. Messenger RNA (mRNA) molecules have a central role in",380,128,0.3368
dialogsum,"#Person1#: Mr. Crabby, I'm pleased to see you. #Person2#: I'Ve looked over your resume, Ms. Jane. I see you'Ve already have quite a lot of experience in secretary work, could you tell me something about your talent with that company? #Person1#: Oh, yes, I worked there for two years, just graduated from college. #Person2#: En? #Person1#: It was a good company to work for, I enjoyed my time with them. #Person2#: You like that work? #Person1#: Yes, I like it very much, the work was not very demanding, and the people I work with were friendly. #Person2#: Why do you want to leave the company? #Person1#: Because it is an age of challenges, I must accept the new challenge in my life.",Mr. Crabby is interviewing Ms. Jane and asks her about her talent with the previous company. Jane says she left the company because she must accept the new challenge.,122,29,0.2377
dialogsum,"#Person1#: John, it ' s time to get up. #Person2#: It can ' t be time to get up yet. #Person1#: It is. Hurry up! You ' ll be late for school. #Person2#: What ' s the time? #Person1#: It ' s nearly half past seven. #Person2#: My watch says ten past. #Person1#: It ' s slow. Hurry up! The bus goes at twenty to eight. #Person2#: Are you sure half past seven? #Person1#: Positive. I ' ll put the radio on. #Person2#: It ' s only seven o ' clock. Your watch is fast. #Person1#: No, it isn ' t. It ' s stopped. I forgot to wind it up last night. #Person2#: I could have stayed in bed for another half hour.",#Person1# asks John to get up otherwise he'll be late for school. It turns out that #Person1#'s watch is stopped and it's still early.,124,24,0.1935
dialogsum,"#Person1#: Good morning, this is Bird's Bicycle Rental. #Person2#: Good morning. A friend of mine suggested I call up to hire some bikes. #Person1#: Oh yes, a lot of people do so these days. #Person2#: Yes, we're just on a holiday here for a few days and they said it would be a good idea to see the island by bike. #Person1#: Well, it certainly is, and most People rent a motorbike because you can get around faster and even go to the beach if you like. #Person2#: If I wanted to hire 2 motorbikes tomorrow morning for 2 days, would there be any problem? #Person1#: None at all. May I have your name please? #Person2#: It's Green, Arthur Green. #Person1#: And your telephone number? #Person2#: I'm at the Holidays Sun Hotel. My number is 0708112. I'm in room 1203. By the way, is your bike rental shop at No.100 Tecum Street? #Person1#: That's right. #Person2#: Thank you. Bye.",Arthur Green calls Bird's Bicycle Rental to hire 2 motorbikes tomorrow morning for 2 days to see the island.,159,19,0.1195
dialogsum,"#Person1#: Have you seen Harry? #Person2#: No. As far as I can remember he was supposed to be on a business trip to Lisbon. #Person1#: Yes, but he was supposed to be back by now. #Person2#: Maybe you'll call his home.",#Person1# is looking for Harry. #Person2# advises #Person1# to call his home.,41,12,0.2927
pubmed-summarization,"the protocol - based software program is capable of storing and manipulating data on a theoretical basis . the sinpe analyzer module is used to create reports , graphs , and statistics summarizing the main findings . a specific protocol for laryngeal disorders among the master ent protocol available in sinpe was used for the analysis ; only patients diagnosed with vocal fold polyps were analyzed . in total , the inclusion criteria were as follows : a diagnosis of polyps , clinical laryngoscopy , and intraoperative confirmation of the diagnosis by anatomopathology . exclusion criteria were as follows : a diagnosis of infiltrative processes or storage disease ( vocal polyps not identified upon anatomopathologic examination ) . of the 245 patients who underwent surgery during the study period , 93 ( 36.61% of lesions ) with vocal polyps and an indication for microsurgery were evaluated . these 93 patients were classified into 2 groups according to the physical and histological characteristics of the lesions : ( a ) those with angiomatous polyps ( n = 63 , 67.75% ) and ( b ) those with gelatinous polyps ( n = 30 , 32.25% ) . comparisons between the 2 groups were made according to 12 anatomic and surgical parameters based on the polyp characteristics . parameters 18 refer to the intrinsic characteristics of the polyps ( table 1 ) , parameters 9 and 10 refer to polyp - associated lesions ( table 2 ) , and parameters 11 and 12 refer to the treatment strategy ( table 3 ) . the protocols were performed on the day before surgery after the pre - anesthetic consultation , and supplemented during the postoperative follow - up . endolaryngeal microsurgeries were performed in the operating room of the same institution using suspension laryngoscopy ( sl ) by 3 doctors from the laryngology and voice service department . during sl , statistical analyses were performed using the chi - square test to compare the variables discussed above , and the significance level was set at p < 0.05 . all 93 patients underwent laryngeal surgery due to a diagnosis of polyps of the vocal folds during the period february 2010 to february 2011 . of these , 63 ( 64.74% ) had angiomatous","summary introduction : dysphonia is the main symptom of lesions that affect the vocal tract . many of those lesions may require surgical treatment . polyps are one of the most common forms of vocal cord lesions and the most prevalent indication for laryngeal microsurgery . there are different types of polyps , and their different characteristics can indicate different prognosis and treatments . aim : to conduct a comparative study of polypoid lesions ( angiomatous and gelatinous ) in patients undergoing laryngeal microsurgery via an electronic protocol . method : we prospectively evaluated 93 patients diagnosed with vocal fold polyps ; the polyps were classified as angiomatous or gelatinous . results : in total , 93 patients undergoing laryngeal microsurgery were diagnosed with vocal fold polyps .",380,128,0.3368
dialogsum,"#Person1#: Hello. #Person2#: Is this Mr. Smith's office? #Person1#: Yes, it is. #Person2#: Is he there? #Person1#: I'm sorry, he isn't. He's at a meeting this morning. #Person2#: What time will he be back? #Person1#: He'll be back after two o'clock but he'll only be in the office for an hour. #Person2#: Can I reach him in the conference room? #Person1#: I'm sorry, but they aren't taking any calls. Can I take message for you? #Person2#: This is Anne Lucas in the accounts office. I would like a word with him, please. #Person1#: I can ask him to call you after the meeting. Can I have your number? #Person2#: Yes, it's 488 -6361. He can reach me there until three o'clock.",Anne calls Mr. Smith but he is unavailable. #Person1# helps Anne leave a message and keeps Anne's number for Mr. Smith to call back.,121,24,0.1983
pubmed-summarization,". a retrospective study by erhan et al . reviewed delayed wound healing or recurrence after excisional biopsy , or those who have had an incisional biopsy only , if prolactin level was normal , reexcision and oral prednisone usage may be curative . in patients with a high prolactin level and who had recurrence , medical treatment to control prolactin levels this study seems , therefore , to underline an unexpected and underestimated prognostic value of blood prolactin levels , which could exert an interesting role in the recurrence of igm . as hyperprolactinemia can be induced by ssri , whose chronic use can cause gm , in these particular cases the ideal management of patients is not surgical excision , given that lesions are not malignant , but are probably caused by an hypersecretion of prolactin by the pituitary gland related to alteration of serotonin / dopamine metabolism . if this pathogenetic hypothesis is validated it could be reasonable to propose a suspension of ssri therapy to monitor the evolution of breast lesions , which would regress spontaneously , or alternatively , a therapy aimed to control prolactin blood levels and/or to modulate inflammation could be achieved . igm raises important diagnostic and therapeutic dilemmas , as more than 50% of the reported cases are initially mistaken for breast carcinoma . occasionally some patients may be subjected to mastectomy as a consequence of a false positive fine - needle aspiration cytology ( fnac ) result , as has been previously reported . the practice of performing mastectomy merely on the basis of triple assessment ( clinical , mammographic , and fnac findings consistent with malignancy ) , therefore , does not seem to be necessarily justified . in this paper we emphasize the importance of diagnosis of igm , which in the non malignant forms should not be treated surgically . in particular we draw attention to cases of igm related to antidepressant ( ssri ) therapy , postulating that these clinical scenarios must also be approached conservatively .","granulomatous mastitis is a rare benign inflammatory disease of the breast with multiple etiologies such as tuberculosis , sarcoidosis , foreign body reaction , and mycotic and parasitic infections . in contrast , idiopathic granulomatous mastitis ( igm ) is characterized by the presence of chronic granulomatous lobulitis in the absence of an obvious etiology . clinically and radiologically it may mimic breast carcinoma and so awareness of surgeons , pathologists , and radiologists is essential to avoid unnecessary mastectomies . cases of igm are reported during antidepressant therapy in patients also showing high levels of prolactinemia . in these cases , we believe that surgical excision must be avoided being replaced with a conservative management of the pathological condition based on a corticosteroid treatment .",341,126,0.3695
scientific_lay_summarisation-elife-norm,"to analysis following genetic perturbation, at varying developmental stages, or with intact samples. Indeed, even for well-known synaptic organizers like Neurexin and Neuroligin (Chia et al. , 2013), studies investigating their function were rarely carried out in an intact system with a resolution sufficient to reveal their detailed functions in synaptogenesis between defined neuronal types. As such, there is a need to examine CNS synapses in the intact brain, at the level of light microscopy in a system with sufficient complexity to reflect features of the CNS, but tractable enough to dissect connectivity and function using genetic tools. Current work in Drosophila has sought to fulfill this need (Kremer et al. , 2010; Christiansen et al. , 2011; Berger-Muller et al. , 2013; Chen et al. , 2014). The Drosophila olfactory system contains complex circuits that transform chemosensory input to the regulation of behavioral output. Olfactory information is received by first-order olfactory receptor neurons (ORNs) and is transmitted by ORN axons to the antennal lobe, the first olfactory processing center in the brain. There, the information is conveyed to the dendrites of second-order projection neurons (PNs) through class-specific ORN–PN synapses. PN axons carry signals to higher-order brain centers (Vosshall and Stocker, 2007). The local interneurons (LNs) innervate the antennal lobe extensively with their dendrites (Chou et al. , 2010) and are involved in transforming ORN input to PN output (Wilson, 2013). These three groups of neurons have extensive interconnectivity and indeed, the antennal lobe has emerged as a model neural circuit for investigating the general principles of information processing (Wang, 2012; Wilson, 2013; Twick et al. , 2014). While many antennal lobe neurons have been examined electrophysiologically (Wilson, 2013), there has been little analysis of their synaptic architecture: how many connections are made, where they are made in relation to other neurons in the circuit, and what molecules are required for their organization. Electron microscopy has been used to probe different genetic conditions (Acebes and Ferrus, 2001; Acebes et al. , 2011) but could not definitively assign glomerular identity or cell type for individual synapses, highlighting the need for structural analysis at the level of light microscopy in three dimensions. Knowledge about synaptic organization is critical to understand how sensory information is received, processed, and relayed by this circuit. Thus,","Just as progress in science relies on researchers communicating their findings to other people working in their field, our bodies rely on neurons being able to communicate with other neurons. This is where structures called synapses come in: synapses allow signals to be passed from one neuron to another. Neurons and synapses process information by forming circuits in the brain, but relatively little is known about how synapses develop or how they are organized within circuits. Mosca and Luo have now examined a neural circuit in the fruit fly (Drosophila) that receives sensory information about smells in the environment, and then converts this information to signals which can be understood by other parts of the brain. This particular circuit has previously been identified as a good model of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and/or osteoclast function (Kasper et al. , 2005; Kornak et al. , 2001; Lange et al. , 2006; Undiagnosed Diseases Network et al. , 2019; Pressey et al. , 2010). In particular, osteopetrosis, a disease characterized by dense and brittle bones, is the most common disease associated with CLC-7 mutation, with more than 50 distinct pathogenic mutations identified to date (Chalhoub et al. , 2003; Cleiren et al. , 2001; Kasper et al. , 2005; Kornak et al. , 2001; Lange et al. , 2006; Sartelet et al. , 2014; Schulz et al. , 2010; Weinert et al. , 2010). Extensive structural and functional characterization of prokaryotic and eukaryotic CLC channels and transporters have established a framework for Cl-/H+ exchange and identified several key residues that participate in the transport cycle (Accardi et al. , 2004; Accardi and Miller, 2004; Accardi et al. , 2005; Basilio et al. , 2014; Chavan et al. , 2020; Dutzler et al. , 2002; Dutzler et al. , 2003; Feng et al. , 2010; Feng et al. , 2012; Jayaram et al. , 2008; Park et al. , 2017; Park and MacKinnon, 2018; Picollo et al. , 2012; Wang et al. , 2019; Zdebik et al. , 2008). Within the Cl--conduction pathway, the gating glutamate (Glugate) that is conserved in CLC transporters is proposed to oscillate between at least four different conformations (Chavan et al. , 2020; Dutzler et al. , 2002; Dutzler et al. , 2003; Feng et al. , 2010). The movement and changes in the protonation state of Glugate are coupled to the binding and release of Cl- ions in the highly conserved external and central binding sites (Picollo et al. , 2012). Near the center of the transporter, the anion and H+-conduction pathways diverge with the anion pathway passing through the internal binding site before reaching the cytosol, while the H+-conduction pathway passes through a hydrophobic gap before reaching a conserved internal glutamate (Gluin) (Accardi and Miller, 2004; Accardi et al. , 2005; Chavan et al. , 2020; Leisle et al. , 2020; Lim and Miller, 2009; Zdebik et al. , 2008). This conserved Gluin is dispensable for coupled transport and water molecules has been proposed to mediate H+ transport through the hydrophobic gap (Feng et al. , 2010; Han","Inside the cells of mammals, acidic compartments called lysosomes are responsible for breaking down large molecules and worn-out cells parts so their components can be used again. Similar to lysosomes, specialized cells called osteoclasts require an acidic environment to degrade tissues in the bone. Both osteoclasts and lysosomes rely on a two-component protein complex to help them digest molecules. Mutations in the genes for both proteins are directly linked to human diseases including neurodegeneration and osteopetrosis – a disease characterized by dense and brittle bones. For the main protein in this complex, called CLC-7, to remain stable and perform its roles, it requires an accessory subunit known as OSTM1. CLC-7 is a transporter that funnels electrically charged particles into and out of the lysosome, which helps to maintain",380,128,0.3368
pubmed-summarization,"efficacious in the management of various conditions associated with neuropathic pain , including phn . demirkaya and colleagues revealed 1 g i.v . mg sulfate is effective in the treatment of migraine attacks and collins and colleagues reported that 70 mg / kg magnesium sulphate infusions in 4 hours for 5 days reduced pain in patients with complex regional pain syndrome . whether intravenous administration of magnesium can achieve a sufficient concentration in the cerebrospinal fluid to block nmda receptors is unclear and studies have reported on the limited efficacy of magnesium when administered via the intravenous route . furthermore , even if the dose of intravenously administered magnesium is not sufficient to present toxicity , patients are still at risk of magnesium overdose . neuraxial administration of magnesium is an "" off - label "" use , and the safety of this technique in human subjects is still undetermined . however , animal studies showed that intrathecally administered magnesium was free of neurotoxicity , and recent studies have demonstrated the safety of magnesium administration via the epidural or intrathecal route in humans . in fact , the exact site of action of epidurally administered magnesium ( i.e. , spinal or supraspinal ) remains unclear . however , comparison with previous reports regarding intravenous magnesium administration suggested that the low dose epidural magnesium used in our patient was unlikely to result in systemic effects . in conclusion , tfemi showed a favourable result in the treatment of intractable allodynia associated with phn . this study was performed in only a single case , and further investigations are required to determine the efficacy of tfemi in the management of allodynia in patients with phn .","although postherpetic neuralgia ( phn ) is a common chronic pain syndrome , the pathophysiology of this disorder is not well known and management is often very difficult . n - methyl - d - aspartate ( nmda ) receptor antagonists are known to be effective in phn , and magnesium , a physiological blocker of nmda receptors , is widely used to treat various chronic pain disorders . here , we present a case of the phn refractory to conventional treatment , which was treated successfully with transforaminal epidural injection of magnesium sulphate at the affected dermatome .",284,99,0.3486
scientific_lay_summarisation-elife-norm,"life (Nursall, 1959). One group of aquatic heterotrophic protists, the choanoflagellates, are of particular interest for the study of how multicellularity evolved. Choanoflagellates are a class of unicellular microorganisms that are the closest relatives of the animals (Lang et al. , 2002). This relationship was first proposed by James-Clark in 1866 (James-Clark, 1866), on the basis of the resemblance between choanoflagellates and the choanocytes of sponges. The sister relationship between choanoflagellates and animals was further confirmed in the genomic era by molecular evidence (King et al. , 2008). All choanoflagellates share the same basic unicell structure: a prolate cell body with a single beating flagellum that is surrounded by a collar of microvilli. The beating of the flagellum creates a current in the surrounding fluid that guides suspended prey such as bacteria through the collar (Pettitt and Orme, 2002) where they can be caught and ultimately phagocytosed. The flagellar current also has the effect of causing the choanoflagellate cell to swim. The choanoflagellate Salpingoeca rosetta can form colonies through incomplete cytokinesis (Fairclough et al. , 2010). In the presence of certain bacteria (Dayel et al. , 2011; Levin et al. , 2014), these colonies have an eponymous rosette-like shape as shown in . The colony morphology is variable, and the constituent flagella beat independently of one another (Kirkegaard et al. , 2016). The random and independent flagellar motion argues against there being any coordination between cells in a colony, and as yet no evidence of any form of taxis for choanoflagellate colonies has been reported. 10. 7554/eLife. 18109. 003Figure 1. Micrograph of S. rosetta colonies (left) with schematic illustration (right, collars in blue). Scale bar: 50 µm. Cell body diameters are ~5 µm. : http: //dx. . org/10. 7554/eLife. 18109. 003 The geometry, flagella independence and lack of taxis observed in S. rosetta colonies contrast with other lineages, such as the Volvocales, a group of green algae (Goldstein, 2015). Phototaxis is clearly observable in both unicellular (Chlamydomonas) (Yoshimura and Kamiya, 2001) and colonial (Volvox) (Drescher et al. , 2010) species, in order to maintain optimum light levels for photosynthesis. Volvocalean phototaxis is deterministic, requiring precise tuning between the internal biochemical timescales and the rotation period of the organism as a whole. Although S. rosetta colonies also rotate around an internal","Most animals are made up of millions of cells, yet all animals evolved from ancestors that spent their whole lives as single cells. Today the closest single-celled relatives of animals are a group of aquatic organisms called choanoflagellates. Certain species of choanoflagellates can also form swimming colonies. This kind of multicellularity might resemble that seen in the earliest of animals. As such, studies into modern-day choanoflagellates can give insights into how the first animals to evolve might have behaved. Many organisms can find their way towards favorable areas using different strategies. For instance, bacteria can bias their tumbling to gradually swim towards food, and algae can turn and move directly towards light. While choanoflagellates require oxygen, it was not known if they could also actively navigate towards it,",380,128,0.3368
dialogsum,"#Person1#: Joy Chain elementary school, please. #Person2#: Will do. #Person1#: How frustrating! The bus is still not coming. #Person2#: Ma'am, take your kid to school? #Person1#: Yes. I am in a hurry. Please take a shortcut. #Person2#: No problem. Don't worry, the taxi is faster than the bus. #Person1#: The traffic is terrible on Monday morning. It takes us almost 1 hour to get to school. #Person2#: My son is the same. But he always makes an early start in the morning, and enjoys listening to the English programmer Let's talk in English on the way. #Person1#: That's wonderful. He is killing two birds with one stone. Sir, please turn right at the next corner. And stop at the taxi stand. #Person2#: OK! #Person1#: What is the fare? #Person2#: It's 14. 5 Yuan. #Person1#: Keep the change! #Person2#: Thanks, Ma'am.","#Person1# takes #Person2#'s taxi frustratedly to take her kids to school due to the terrible traffic on Monday morning, then #Person1# and #Person2# talk about taking kids to school.",140,29,0.2071
dialogsum,"#Person1#: Did you listen to the weather report this morning? #Person2#: Yes, I did. It will be cloudy in the afternoon. I hope that it won't rain. #Person1#: Have you made the sandwiches yet? #Person2#: No, I haven't. I'll start right away. Did you get the soft drinks? #Person1#: Yes, I did. They are in the refrigerator. #Person2#: Would you put plastic knives and forks in the picnic basket? And don't forget the paper plates and napkins. #Person1#: Oh, Nancy called a while ago. She told me that she would like to bring something for the picnic. #Person2#: I'll call her right away and ask her to bring a bottle of wine.",#Person1# and #Person2# talk about the weather and are preparing for the picnic in the afternoon.,112,16,0.1429
scientific_lay_summarisation-elife-norm,"2009; Ribi et al. , 1983). Although ‘Coley’s toxin’ is currently not used for cancer treatment because of its toxicities, accumulating evidence has revealed that his theory was correct and the notion that the enhanced host immune systems by endotoxin could attack some cancer cells has advanced to cancer immunotherapy. However, whether endotoxin has a direct function in attacking cancer cells remains controversial, while the interest in endotoxin as a cancer therapeutic agent waned, despite of many reports for favorable outcomes. A cytokine-like small secreted protein, SCGB3A2 (secretoglobin 3A2, also known as UGRP1 and HIN-2), was previously identified that is abundantly and specifically expressed in non-ciliated airway epithelial (club) cells of the trachea, bronchus, and bronchioles (Niimi et al. , 2001) and revealing that SCGB3A2 functions to suppress lung inflammation and fibrosis (Cai and Kimura, 2015; Cai et al. , 2014; Chiba et al. , 2006; Kido et al. , 2014; Kurotani et al. , 2011; Yoneda et al. , 2016). Although specific expression of SCGB3A2 in lung epithelial cells and its role in inflammation may imply a possible important function for SCGB3A2 in the clearance of pathogens, its role in host defense, if any, has not been studied. In addition, while fibrosis is closely related to tumor development (Coussens and Werb, 2002; Trinchieri, 2012) and SCGB3A2 functions as an anti-fibrotic agent, the role of SCGB3A2 in lung cancer development is unknown. To determine whether SCGB3A2 has any influence on cancer cell growth, CCK8 (cell counting kit 8) assay was performed using murine Lewis lung carcinoma (LLC) cells. The proliferation of LLC cells was markedly suppressed by mouse recombinant SCGB3A2 (1A). This in vitro effect of SCGB3A2 was also observed in vivo in the LLC cells intravenous metastasis model using wild-type C57BL/6 mice in conjunction with administration of SCGB3A2 (1B–1E). To confirm the tumor growth inhibition roles of SCGB3A2 in vivo, Scgb3a2-null mice were subjected to the metastasis model (Kido et al. , 2014). Mice null for Scgb3a2 developed far greater numbers of lung surface tumors than wild-type littermates when LLC cells were intravenously injected (1F). Furthermore, administration of recombinant mouse SCGB3A2 to Scgb3a2-null mice clearly rescued the Scgb3a2-null phenotypes of LLC cell lung metastasis (1G–1I). These results indicate the importance of SCGB3A2 in the suppression of LLC cell tumor","Inflammation serves to kill invading bacteria and viruses. Certain molecules on the surface of the microbes can trigger an inflammatory cascade, and one example of such a molecule is lipopolysaccharide (LPS). Cells can react to LPS by triggering a process called pyroptosis that causes the cell to burst and die. The released cell contents attract blood and lymphatic cells that in turn kill the LPS-producing bacteria. This prevents the bacteria from multiplying and spreading. LPS was used in the very early days of medicine to treat cancer, although it has fallen out of favor because it causes severe side effects, such as a hyperinflammatory response (sepsis) that can result in death. It was not known exactly how LPS kills cancer cells, which has limited its use. Yokoyama et",380,128,0.3368
scientific_lay_summarisation-elife-norm,"preventing excessive inflammation. Pathogenic bacterial species are often defined by unique virulence factors that enable host colonization and determine the severity of host disease symptoms. Much less well known are the unique factors produced by anti-inflammatory bacterial species, which likely play a key role in establishing host-bacterial mutualism and maintaining intestinal homeostasis. One such factor is the zwitterionic polysaccharide, PSA, produced by the human symbiont Bacteroidetes fragilis, that induces a toleragenic T cell profile and protects against intestinal inflammation (Mazmanian et al. , 2008; Mazmanian et al. , 2005; Round and Mazmanian, 2010). The anti-inflammatory properties of Lactobacillus rhamnosus have been attributed to secreted proteins p75 and p40 (Yan et al. , 2007), and Faecalibacterium prausnitzii secretes an anti-inflammatory 15 kDa protein called microbial anti-inflammatory molecule or MAM (Yan et al. , 2007; Quévrain et al. , 2016; Sokol et al. , 2008; Carlsson et al. , 2013; Martín et al. , 2014). These secreted proteins reduce inflammation in mouse models of colitis (Yan et al. , 2011), which suggests their therapeutic potential, but we do not yet understand how these proteins aid the bacteria that produce them. Investigating the bacterial fitness benefits for producing anti-inflammatory activities is critical for developing approaches to promote membership of these immunoregulatory bacterial species in chronic inflammatory diseases like IBD and to use bacterial immune modulators as therapeutics to shape microbiota composition. The investigation of microbiota-derived immunomodulatory factors is challenging because their effects on the host are subtler then those of disease-causing toxins and they are produced by complex and genetically intractable microbial consortia. We used the zebrafish, Danio rerio, as a high-throughput, gnotobiotic model vertebrate system to identify individual bacterial products with immunomodulatory properties and understand how those products promote host-bacterial mutualism. Zebrafish have long been used as a vertebrate model for developmental biology because of their optical transparency, high fecundity, and rapid early development (Grunwald and Eisen, 2002). Zebrafish embryos develop ex-utero within their protective chorions and first encounter environmental microbes when they hatch as larvae between 2 and 3 days post fertilization (dpf). By 5 dpf the animals have a fully functional digestive tract that is colonized with bacteria (Bates et al. , 2006; Stephens et al. , 2016; Wallace et al. , 2005). The larvae are also equipped with a","Animals, including humans, harbor vast numbers of bacteria inside our digestive tracts. But rather than wage constant war, we have learned to coexist peacefully, and many of these bacteria are important to keep us healthy. Our immune system controls the number of bacteria, but in some diseases, this balance fails, and immune cells called neutrophils start a defense response. However, such attacks also cause inflammation in our guts, which can damage the tissues and organs. Understanding the delicate balance between immune cells and individual bacteria in humans remains a challenge. Our gut bacteria live in complex communities with many species of microorganisms. Using animals like zebrafish can help to find out if gut bacteria are able to prevent such inflammation. These fish can grow under sterile conditions in",380,128,0.3368
pubmed-summarization,"biomechanical details that underlie gait and balance abnormalities and seek improved methods to direct targeted rehabilitation interventions . , a physiatrist from the cleveland clinic , noted that many of the currently used clinician - administered measures of gait , including the timed 25-foot walk ( t25fw ) , the 6-minute and 2-minute walk tests ( 2mwt , 6mwt ) , and the timed up and go ( tug ) test , can detect changes in gait speed or endurance but do not detect visually obvious improvements in gait quality , or assess important contributors to gait changes such as reduced cognitive function , visual function , upper body trunk control , spasticity , or sensation . although this limits their utility for guiding selection of specific interventions , these simple clinician - administered measures are still recommended for screening individuals for gait impairment and for standardized assessment of performance over time . susan bennett , pt , ed d from the university of buffalo , described some of the more sophisticated clinician - administered measures of balance , such as the berg balance scale ( bbs ) , the functional reach test , and the recently developed 4-square - step test and mini - best test . these measures can differentiate between people with ms who fall from those who do not ( bbs , 4-square - step test ) and can provide information to guide rehabilitation . dr . bennett also emphasized the utility of the trunk control test for assessing balance in nonambulatory patients for whom postural control of the trunk is essential for safe and independent transfers . , from the university of illinois at chicago , noted that self - reported measures , also known as patient reported outcome measures ( proms ) , have recently attracted attention from government agencies , including the national institutes of health and food and drug administration , because these measures capture directly from patients how they feel or function without interpretation by others . self - reported measures of gait and balance can ascertain patients ' quality of life , balance confidence , fear of falling , circumstances surrounding fall events , and other important information that can not be determined by clinical testing or physical instrumentation .","gait and balance measures have particular potential as outcome measures in multiple sclerosis ( ms ) because , of the many hallmarks of ms disability , gait and balance dysfunction are present throughout the course of the disease , impact many aspects of a person 's life , and progress over time . to highlight the importance and relevance of gait and balance measures in ms , explore novel measurements of gait and balance in ms , and discuss how gait , balance , and fall measures can best be used and developed in clinical and research settings , the 1st international symposium on gait and balance in multiple sclerosis was held in portland , oregon , usa on october 1 , 2011 . this meeting brought together",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The role of the hippocampus in spatial cognition is incontrovertible yet controversial. Place cells, initially thought to be location-specifiers, turn out to respond promiscuously to a wide range of stimuli. Here we test the idea, which we have recently demonstrated in a computational model, that the hippocampal place cells may ultimately be interested in a space' s topological qualities (its connectivity) more than its geometry (distances and angles); such higher-order functioning would be more consistent with other known hippocampal functions. We recorded place cell activity in rats exploring morphing linear tracks that allowed us to dissociate the geometry of the track from its topology. The resulting place fields preserved the relative sequence of places visited along the track but did not vary with the metrical features of the track or the direction of the rat' s movement. These results suggest a reinterpretation of previous studies and new directions for future experiments. When O' Keefe and Dostrovsky discovered that the firing of hippocampal place cells correlates strongly with the position of the rat with respect to discrete locations within the environment (the cell' s place field) (O' Keefe and Dostrovsky, 1971), they launched decades of intensive research into how place cells contribute to an internal map of the environment (Best et al. , 2001). That there is a considerable gulf between place cell firing and a cognitive spatial map, however, has become only clearer with time. Place cells appear to respond to a perplexing array of stimuli, from visual cues to head direction, goal planning, color changes, shape changes, and olfactory, vestibular and kinesthetic inputs, and discrepancies between the expected and actual location of a target (Harnad, 1994; Frank et al. , 2000; Wood et al. , 2000); recent work has shown that both spatial and nonspatial cell types in the entorhinal cortex provide myriad inputs to the hippocampus (Ideker et al. , 2011). The fascination with place cell promiscuity, however, has tended to distract from the fact that cognition is the work not of individual neurons but of large ensembles of cells (Ludvig, 1999; Fenton et al. , 2008). The nature of the information embedded in the place cell ensemble code and transmitted to downstream neurons has been largely ignored, along with the consequences for the type of spatial properties","The hippocampus is one of the most easily recognizable structures in the brain owing to its characteristic seahorse-like shape. Brain imaging studies in the 1990s famously showed the hippocampus to be larger in London taxi drivers than in other people, suggesting that it plays a role in spatial navigation. This was consistent with previous findings in rodents, which had shown that the hippocampus is active when animals find their way through mazes. Electrode recordings have revealed that whenever an animal is in a specific location of a particular environment (for example, in the back left-hand corner of a small room with white walls) one or a small number of cells within the hippocampus will fire to encode that location. When the animal moves to a new location within",380,128,0.3368
dialogsum,"#Person1#: How do you spend your spare time? Are you interested in sports? #Person2#: I have many hobbies, I like almost all kinds of sports and I also like to listen to pop songs. #Person1#: Do you think you are introverted or extroverted? #Person2#: I think I am extroverted.","#Person2# tells #Person1# #Person2#'s hobbies, and #Person2#'s extroverted.",49,8,0.1633
dialogsum,"#Person1#: Are you a smoker? #Person2#: Yes, I'm afraid I am. My husband is a smoker too. #Person1#: Would you describe yourself as being a heavy smoker? #Person2#: No. But my husband smokes 20 or more a day. #Person1#: When did you begin to smoke? #Person2#: I had my first cigarette when I was 17. #Person1#: Might I ask if you have tried to give up smoking? #Person2#: Yes. Twice.",#Person2# tells #Person1# about #Person2#'s smoking habits and history.,70,9,0.1286
scientific_lay_summarisation-elife-norm,"ATPase (Morita et al. , 2010), VPS4A/B, which contains a microtubule interacting and transport (MIT) domain that binds to MIT interacting motifs (MIM) of ESCRT-IIIs (Obita et al. , 2007; Stuchell-Brereton et al. , 2007). The final scission process is believed to be associated with VPS4 working on ESCRT-IIIs, but the mechanism is still unresolved. In some models, the ESCRT-IIIs provide the motive force for scission and the VPS4 is required after scission to recycle the ESCRT-IIIs for subsequent scissions (Lata et al. , 2008; Wollert et al. , 2009). In other models, the VPS4 is actively engaging the ESCRT-IIIs prior or during scission by actively remodeling ESCRT-IIIs in order to force scission (Saksena et al. , 2009), by rearranging ESCRT-IIIs as part of the pathway toward scission (Cashikar et al. , 2014), or by binding to ESCRT dome structures in order to add rigidity necessary for scission (Fabrikant et al. , 2009). ESCRT complexes are hijacked by HIV to enable separation of the viral particle from the host cell plasma membrane. The production of enveloped HIV-1 at the plasma membrane occurs with the recruitment of the structural protein Gag at individual assembly sites. The carboxyl terminus of Gag has a motif that is essential for recruitment of ESCRTs. First, Gag recruits the ‘early’ factors like ESCRT-I/TSG101 and ALIX which contribute to subsequent recruitment of ESCRT-III proteins. The ESCRT-IIIs then polymerize into structures that are believed to constrict the neck and drive membrane fission. HIV release appears to require fewer members of the ESCRT family than other processes. Redundancy likely makes many variants, such as CHMP5, CHMP6 and CHMP7, only conditionally necessary (Morita et al. , 2011). ESCRT-IIIs that are essential for assembly of HIV-1 include CHMP2 (either A or B variant) and CHMP4B, which are recruited to site of budding with other proteins such as ESCRT-I/TSG101 and ALIX which interact with Gag (Morita et al. , 2011). The reduced number of required ESCRTs makes HIV assembly an approachable system for studying the biophysics of ESCRT-mediated membrane scission. Prior to viral particle separation from a host cell, a roughly spherical particle is formed (Martin-Serrano et al. , 2003), but the topological pathway and timing of events to reaching the Gag sphere has not previously been followed in vivo. The order","Viruses need to be able to enter and leave the cells of their hosts to multiply and spread infections. Once inside the cell, many viruses, including the HIV virus, hijack the cell’s genetic material to produce more HIV particles and release them back into the surroundings. As the new viruses leave the cell, they wrap themselves in the membrane of their host cell. The shell of HIV consists of thousands of copies of a protein called Gag, which helps to release the viruses. Gag aggregates inside of the host cell membrane, which then begins to bulge outwards forming a spherical bud that subsequently pinches off. These released virus particles are now able to infect other cells. Both assembling and budding of the virus particles requires the help of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"timed, rapidly produced acoustic elements and frequency sweeps of bird vocalizations (Elemans et al. , 2004,2008) used for territorial defense and mate attraction (Collins, 2004). SFMs in the Oyster toadfish swimbladder and rattlesnake tailshaker both set the fundamental frequency of the produced sound by rhythmically contracting the swimbladder and shaking tail rattles respectively (Rome et al. , 1996). Other muscles have been suggested to be of the superfast phenotype, such as some extraocular or limb muscles (Fuxjager et al. , 2016), but non-isometric mechanical tests are lacking to classify them as such. Taken together, SFMs seem a commonly occurring muscle phenotype that interestingly so far has been established only in motor systems involving sound production and control. Force modulation in vertebrate skeletal muscles is precisely timed via the highly conserved excitation-contraction coupling (ECC) pathway that consists of several sequential steps whose individual kinetics affect the maximally attainable force modulation speed. In brief, firing of a motor neuron first triggers the release of intracellular calcium ions (Ca2+) stored in the sarcoplasmic reticulum (SR). Subsequent binding of Ca2+ to troponin in sarcomeres triggers the exposure of binding sites for the motor protein myosin along actin filaments, allowing the cyclical binding and unbinding of myosin motor head domains to actin, forming actomyosin crossbridges that generate force. Finally, force decreases when SR Ca2+-ATPases (SERCA) pump Ca2+ back into the SR, consecutively lowering the cytoplasmic free Ca2+ concentration ([Ca2+]i) and returning thin filament inhibition thus preventing further crossbridge formation. Extensive study of SFMs in the oyster toadfish (Opsanus tao) swimbladder has demonstrated that no single step in the ECC pathway is rate-limiting, but that multiple hallmark traits have adapted to allow superfast cycling rates. In swimbladder SFMs, a far greater proportion of cellular volume is dedicated to SR compared to locomotory muscles, which increases the number and density of SERCA pumps (Rome et al. , 1999). Furthermore small, ribbon-like myofibrils (Appelt et al. , 1991) greatly reduce diffusion distances for Ca2+. Together, these adaptations lead to the shortest [Ca2+]i transient times observed in any muscle (Rome et al. , 1996). Additionally, the rate of actomyosin crossbridge detachment in SFM of the toadfish swimbladder is extremely fast, which is necessary to ensure a rapid force drop after the return of actin filament inhibition (Rome et al.","Across animals, different muscle types have evolved to perform vastly different tasks at different speeds. For example, tortoise leg muscles move slowly over several seconds, while the flight muscles of a hummingbird move quickly dozens of times per second. The speed record holders among vertebrates are the so-called superfast muscles, which can move up to 250 times per second. Superfast muscles power the alarming rattle of rattlesnakes, courtship calls in fish, rapid echolocation calls in bats and the elaborate vocal gymnastics of songbirds. Thus these extreme muscles are all around us and are always involved in sound production. Did superfast muscles evolve from a common ancestor? And how do different superfast muscles achieve their extreme behavior? To answer these questions, Mead et al. studied the systems known to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF) –1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC–HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC–HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies. MYC oncogenes (c-, L-, and N-) encode a family of related transcription factors that are overexpressed in a majority of cancers and responsible for ~100,000 cancer-related deaths in the United States each year (Schaub et al. , 2018). Capable of acting as both transcriptional activators and repressors, MYC proteins (hereafter' MYC' ) dimerize with their obligate partner MAX (Blackwood and Eisenman, 1991) to bind and regulate the expression of thousands of genes connected to the cell cycle, protein synthesis, metabolism, genome stability, apoptosis, and angiogenesis (Tansey, 2014). Fueled by reports that experimental inactivation of MYC promotes tumor regression in mice (Alimova et al. , 2019; Beaulieu et al. , 2019; Giuriato et al. , 2006; Jain, 2002; Soucek et al. , 2013), there is considerable interest in the idea that MYC inhibitors could form the basis of broadly effective anticancer therapies. MYC itself, however, is widely viewed as undruggable (Dang et al. , 2017), meaning that effective strategies to pharmacologically inhibit MYC will most likely come from targeting the co-factors with which it interacts to drive and sustain the malignant state (Brockmann et al. , 2013; Bryan et al. , 2020). The interactome of MYC has been extensively interrogated (reviewed by Baluapuri et al. , 2020). One effective strategy for prioritizing which of these interaction partners to study has been to focus on those that interact with conserved segments of the MYC protein, which are referred to as ‘MYC boxes’ (Mb) (Meyer","Tumours form when cells lose control of their growth. Usually, cells produce signals that control how much and how often they divide. But if these signals become faulty, cells may grow too quickly or multiply too often. For example, a group of proteins known as MYC proteins activate growth genes in a cell, but too much of these proteins causes cells to grow uncontrollably. With one third of all cancer deaths linked to excess MYC proteins, these molecules could be key targets for anti-cancer drugs. However, current treatments fail to target these proteins. One option for treating cancers linked to MYC proteins could be to target proteins that work alongside MYC proteins, such as the protein HCF-1, which can attach to MYC proteins. To test if HCF-1 could",380,128,0.3368
dialogsum,"#Person1#: Peter, listen to the lyrics of this song. #Person2#: What's so special about this song? #Person1#: It's from the musical that is so popular in New York right now. Do you like it? #Person2#: Not very much. It sounds too emotional to me. #Person1#: That's why it is so popular. It was recorded by Barbara Tutin. I've heard that when she sang this song on stage the opening night, she created quite a sensation. #Person2#: I'm afraid my association with Broadway musicals is rather limited. #Person1#: Well, then, you need an introduction. The school drama club is putting on a musical production. How about going together? #Person2#: I have a better idea. Let's go to a jazz concert and I'll give you an education in jazz.","#Person1# wants to interest Peter in musicals by inviting him to the school drama club, but Peter prefers giving #Person1# an education in jazz.",127,24,0.189
dialogsum,"#Person1#: My computer isn't running at the same speed it used to be, it is testing my patience everyday. Can you tell me how to make it run faster? #Person2#: If you want to speed up your system, you'Ve got to clean it up first. #Person1#: How? #Person2#: You need to free your disk space. The simplest way is to use a Disk-Cleanup tool to remove temporary files and in store programs that you no longer use. Things should be fine next time you start. You also need to control what starts up. There is a program calls Start-up Delayer, It can help to set after how much time programs should be loaded after Windows boosts. For example, you can choose to set your Fox Mail program to load 30 seconds after Windows starts up. #Person1#: Very useful advice, I will try them right now.",#Person2# advises #Person1# to use a Disk-Cleanup tool to remove temporary files and in-store programs that are no longer used and control what starts up in order to speed up the computer system.,145,33,0.2276
scientific_lay_summarisation-elife-norm,"The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. Cellular signaling systems have evolved complex circuitry involving multiple layers of regulation, making their comprehensive characterization a major challenge. Forward genetics in model organisms has been a general and unbiased way to identify new components in signaling pathways and to map their connectivity. However, since signaling pathways have often diverged between humans and these simpler model systems, their analysis in human cells becomes an important goal. Indeed, our ability to identify the best therapeutic strategy or to predict the effectiveness of drugs targeting specific proteins is often hampered by an incomplete understanding of signaling circuitry in human cells (Lito et al. , 2013). Recent methodological advances have enabled the interrogation of biological processes in human cells through powerful genome-wide screens that overcome many of the limitations associated with previous platforms (Carette et al. , 2009; Gilbert et al. , 2014; Shalem et al. , 2014; Wang et al. , 2014). Yet, inferring functional relationships in complex pathways from such screens remains a major obstacle that has only recently began to be addressed (Bassik et al. , 2013; Blomen et al. , 2015; Parnas et al. , 2015; Wang et al. , 2015). Genetics has long relied on the use of sensitized backgrounds, modifier screens and synthetic effects to uncover the myriad layers","When an embryo is developing, its cells must communicate with one another to coordinate the processes that shape the body’s tissues and organs. Cells often communicate by releasing signaling molecules that engage with proteins called receptors on the surface of other cells. This triggers a series of events that sends the signal along a “pathway” of biochemical reactions inside the receiving cell and leads to the activation of genes. One such signaling pathway is triggered by the WNT proteins and is used extensively in all animals. The WNT pathway instructs cells to grow and divide, establishes the identity of specific cell types and maintains populations of stem cells that can regenerate tissues in adulthood as well. The WNT pathway must be carefully regulated because various types of cancer",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2008; Korennykh et al. , 2009) that stack onto each other with an axial rotation via IF2C and IF3C to form filaments with a helical arrangement of seven Ire1 dimers per turn (Korennykh et al. , 2009; Walter and Ron, 2011). The lumenal and cytosolic domain filaments predicted by the crystal structures have a different pitch and thus for steric reasons cannot be collinear. Instead, a two-dimensional arrangement of the two filaments, featuring ∼20–30 Ire1 molecules, provides a model for the higher-order assembly in vivo (Korennykh et al. , 2009; 1B). This model is compatible with the size of Ire1 foci observed by fluorescence microscopy (Aragón et al. , 2009) and is sterically feasible despite the twists of the filaments on either side of the planar membrane, owing to the flexibility and length (>100 Å) of the linker domains on either side of the membrane, which can relieve the strain. Alternatively and not mutually exclusive, Ire1 clusters may be dynamic, such that constant rearrangements of the Ire1 molecules in clusters sustain transient intermittent oligomerization events on either side of the membrane. 10. 7554/eLife. 05031. 003Figure 1. Oligomerization of Ire1' s cytosolic domain is required for UPR signaling but not for Ire1 cluster formation or HAC1 mRNA recruitment. (A) Schematic of S. cerevisiae Ire1. The ER-lumenal portion of Ire1 is divided in an N-terminal domain (I, gray), a core lumenal—ER-stress-sensing—domain (cLD, light blue), and BiP binding domain (V, dark green), which is tethered via a transmembrane (TM, orange) stretch to Ire1' s cytosolic portion that is composed of a linker (L, brown), a kinase (K, ochre), and an RNase (R, purple) domain (Walter and Ron, 2011). The activation loop (light green) and the αF–αEF (pink) loop protrude from the kinase domain (Lee et al. , 2008; Korennykh et al. , 2009). (B) A model architecture of a 24mer Ire1 cluster after oligomerization on either side of the ER membrane. Left: oligomerization via ER-lumenal interfaces IF1L (tan) and IF2L (steel blue) (top) and via cytosolic interfaces IF1C (indian red), IF2C (sea green), and IF3C (plum) (bottom). The 24 Ire1 molecules are labeled (A–H) A′–H′, and A′′–H′′. IF1C-mediated back-to-back dimers are between A & B and C & D, etc. IF2C, is formed between Ire1 molecules A and D, C","Proteins are built based on instructions in template molecules called messenger RNAs (or mRNAs), which are copied from the DNA of genes. As they are made, proteins must fold into a specific three-dimensional shape and some proteins pass into a compartment in the cell, called the endoplasmic reticulum, in which they fold. So-called molecular chaperone proteins assist this folding process. From the endoplasmic reticulum, most proteins travel to other destinations within or outside of the cell. If the molecular chaperones in the endoplasmic reticulum are overwhelmed by their protein folding task, unfolded proteins accumulate; a situation that can be harmful to the cell. In eukaryotic cells including yeast, a sensor protein called Ire1 detects when unfolded proteins build up in the endoplasmic reticulum. As a result, the Ire1",380,128,0.3368
dialogsum,"#Person1#: What can I do to help you? #Person2#: I have some extra help with my project. What would you prefer to help me with, typing or xeroxing? #Person1#: I could do some typing for you. #Person2#: That is very kind of you to offer to do that. Can you start with the pages on the table? #Person1#: Sure I will get to do that right now. #Person2#: I like your positive attitude. How many years have you been employed here? #Person1#: I have worked here long time. #Person2#: We have a really interesting project coming up. Would you want to join us on it? #Person1#: I'm not sure. Let me think about it. #Person2#: OK. I will mention how great you were about helping me today. I appreciate your help.","#Person1# helps #Person2# do some typing in #Person2#'s project. Then #Person2# invites #Person1# to join them on an interesting project, and #Person1# will think about it.",131,26,0.1985
scientific_lay_summarisation-elife-norm,"2015). Excitotoxic damage is thought to be initiated by mito-Ca2+ overload and subsequent ROS production (Böttger and Schacht, 2013; Wang et al. , 2018). Mechanistically, precisely how ribbon size is established during development or altered under pathological conditions is not fully understood. One known way to regulate ribbon size is through its main structural component Ribeye (Schmitz et al. , 2000). Perhaps unsurprisingly, previous work has shown that overexpression or depletion of Ribeye in hair cells can increase or decrease ribbon size respectively (Becker et al. , 2018; Jean et al. , 2018; Lv et al. , 2016; Sheets, 2017; Sheets et al. , 2011). Ribeye is a splice variant of the transcriptional co-repressor Carboxyl-terminal binding protein 2 (CtBP2) – a splice variant that is unique to vertebrate evolution (Schmitz et al. , 2000). Ribeye contains a unique A-domain and a B-domain that is nearly identical to full-length CtBP2. The B-domain contains a nicotinamide adenine dinucleotide (NAD+, NADH or NAD (H) ) binding site (Magupalli et al. , 2008; Schmitz et al. , 2000). NAD (H) redox is linked to mitochondrial metabolism (Srivastava, 2016). Because CtBPs are able to bind and detect NAD+ and NADH levels, they are thought to function as metabolic biosensors (Stankiewicz et al. , 2014). For example, previous work has demonstrated that changes in NAD (H) redox can impact CtBP oligomerization and its transcriptional activity (Fjeld et al. , 2003; Thio et al. , 2004). Interestingly, in vitro work has shown that both NAD+ and NADH can also promote interactions between Ribeye domains (Magupalli et al. , 2008). Whether NAD+ or NADH can impact Ribeye interactions and ribbon formation or stability has not been confirmed in vivo. In neurons, it is well established that during presynaptic activity, mitochondria clear and store Ca2+ at the presynapse (Devine and Kittler, 2018). Additionally, presynaptic activity and mito-Ca2+ can couple together to influence cellular bioenergetics, including NAD (H) redox homeostasis (reviewed in: Kann and Kovács, 2007; Llorente-Folch et al. , 2015). Based on these studies, we hypothesized that Ca2+ influx through CaV1. 3 channels may regulate mito-Ca2+, which in turn could regulate NAD (H) redox. Changes to cellular bioenergetics and NAD (H) redox could function to control Ribeye interactions and ribbon formation or impact ribbon-synapse function and stability. To study","Hearing depends upon specialized cells deep within the ear called hair cells. These cells take their name from the bundles of hair-like fibers found on their surface, which move when sound waves enter the ear. This movement activates the hair cells, which send signals to nearby neurons at contact points called synapses. Hair cells must send messages to their synaptic partners rapidly and continuously in order for humans to follow complex streams of sound, such as speech. This requires large amounts of energy, which are produced by compartments inside the hair cells called mitochondria. Wong et al. show that mitochondria, which are often described as the ‘power plants’ of cells, are critical for hair cell synapses to form and work correctly. But rather than studying hair cells in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"excretion comes from undigested protein fractions and endogenous tissue losses such as digestive enzyme secretions and desquamation of intestinal cells, which accounts for 17% of the N intake (Dourmad et al. , 1999). Only approximately 30% of P is retained in a grower-finisher pig on a cereal-soybean meal-based diet. In total, 70% of ingested P is excreted either through the feces or urine (Dourmad et al. , 1999). The N and P from animal excreta pollute the water, soil, or air of intensive pig production sites (Osada et al. , 2011; Philippe et al. , 2011; Carter and Kim, 2013). Surface water becomes eutrophic following excessive P and N inputs, thereby causing overgrowth of blue-green algae and death of aquatic animals (Jongbloed and Lenis, 1998; Poulsen, 2000). Considering all these aspects, improving nutrient utilization in feed is of great significance to maximize feed grain utilization as well as for environmental conservation. Non-starch polysaccharides (NSPs) are primarily present in plant cell walls (McDougall et al. , 1996; Sarkar et al. , 2009). In cereal grains, arabinoxylans and β-glucans are found in the cell walls of the protein-rich aleurone layer and starchy endosperm and can act as a barrier to nutrient hydrolysis and absorption (Bacic and Stone, 1981). Similarly, the cell wall polysaccharides of soybean, canola seed, and peas may also be responsible for this nutrient-encapsulating effect (Omogbenigun et al. , 2004). Therefore, NSPs are the main anti-nutrient factors of cereal and bran (Fangel et al. , 2012; Sarkar et al. , 2009). Due to a lack of endogenous NSP-degrading enzymes (NSPases), pigs are inherently incapable of digesting NSPs (Hooda et al. , 2010), but can partially degrade this material through the action of the natural microbial community in their intestinal tract. High-P emission from monogastric animals such as pigs and poultry arises from their poor physiological ability to hydrolyze plant phytates, which account for up to 80% of P in common cereal grains, oil seed meals, and by-products (Ravindran et al. , 1994). Phytates are negatively charged saturated cyclic acids that can bind to positively charged molecules in the diet such as minerals and protein, thereby reducing nutrient digestibility and increasing discharge of the unabsorbed nutrients to the environment (Dersjant-Li et al. , 2015). Various methods have been employed to address","The bodily waste that pigs produce contains high levels of chemicals that can damage the environment, such as nitrogen and phosphorus. For example, when excessive amounts of these two compounds make their way into the water, they can cause blue-green algae to grow too much, which asphyxiates other life in the water. Pigs produce a lot of nitrogen and phosphorus because they cannot efficiently digest their food. In particular, the animals lack the enzymes required to break down two types of molecules present in their feedstuff: phytates and non-starch polysaccharides (NSPs). Zhang, Li et al. take four microbial genes which code for the enzymes needed to digest NSPs and phytates, and they add these DNA sequences into the genomes of pigs. The animals then produce enzymes in their",380,128,0.3368
dialogsum,"#Person1#: Excuse me. #Person2#: Yes? What can I do for you? #Person1#: I just checked in, and there's a problem with my room. #Person2#: And what is the problem? #Person1#: I asked for a non-smoking room, and I don't have one. My room smells like cigarette smoke. I can't stand it. Could you change my room, please? #Person2#: Let me see. . . I'm sorry, but we don't have any more non-smoking rooms. We won't charge you for your room tonight. #Person1#: Thank you. #Person2#: I'm very sorry about this. #Person1#: That's OK. Thanks for your help.","#Person1# tells #Person2# that #Person1# asked for a non-smoking room, but #Person1#'s room smells like cigarette smoke. #Person2# doesn't have any non-smoking rooms so they won't charge #Person1# for tonight.",97,30,0.3093
scientific_lay_summarisation-elife-norm,"a common ancestor (Hoffman et al. , 2015). We also show that the two Wtf4 proteins assemble into distinct aggregated forms. Wtf4poison forms toxic aggregates that are dispersed throughout the cytoplasm. The Wtf4antidote forms aggregates that are recruited to the vacuole and vacuole-associated inclusions and are largely non-toxic. When the two Wtf4 proteins are expressed together, the Wtf4antidote and Wtf4poison co-assemble and are trafficked to the vacuole. This work adds to our understanding of how wtf meiotic drivers work. In addition, the conserved function of Wtf4poison’s toxicity and the fact that the Wtf4antidote exploits conserved aggregate management processes suggests that wtf genes represent good candidates for gene drive systems. The wtf4 meiotic driver used in this work is from S. kambucha, an isolate that is almost identical (99. 5% DNA sequence identity) to the commonly studied lab isolate of S. pombe (Rhind et al. , 2011; Singh and Klar, 2002). Our previous work demonstrated that the Wtf4antidote localizes to a region within the spores that inherit the wtf4 gene. The Wtf4poison protein, however, is found in all four spores and throughout the sac (ascus) that holds them (Nuckolls et al. , 2017). Here, we explored the localization of these proteins in greater depth to gain insight into their mechanisms. We used fluorescently tagged alleles of wtf4 to visualize the proteins. The two Wtf4 proteins have different translational start sites and thus different N-termini (1A, — 1A). We took advantage of this feature to visualize the proteins separately. For the Wtf4antidote, we used an allele with an mCherry tag immediately upstream of the first start codon. This mCherry-wtf4 allele tags only the Wtf4antidote (mCherry-Wtf4antidote) but still encodes an untagged Wtf4poison. We previously demonstrated that this allele is fully functional (Nuckolls et al. , 2017). To visualize Wtf4poison, we used the wtf4poison-GFP allele. This separation-of-function allele encodes only a C-terminally tagged poison but no Wtf4antidote protein. We previously demonstrated that this tagged allele is functional but has a slightly weaker phenotype than an untagged wtf4poison separation-of-function allele (Nuckolls et al. , 2017). We integrated the tagged alleles at the ade6 locus in separate haploid S. pombe strains. We then crossed those two haploid strains to create heterozygous mCherry-wtf4/wtf4poison-GFP diploids and induced these diploids to undergo meiosis. We imaged the asci using both","Meiotic drivers are genes that break the normal rules of inheritance. Usually, a gene has a 50% chance of passing on to the next generation. Meiotic drivers force their way into the next generation by poisoning the gametes (the sex cells that combine to form a zygote) that do not carry them. Harnessing the power of genetic drivers could allow scientists to spread beneficial genes across populations. One group of meiotic drivers found in fission yeast is called the' with transposon fission yeast' , or' wtf' gene family. The wtf drivers act during the production of spores, which are the fission yeast equivalent of sperm, and they encode both a poison that can destroy the spores and its antidote. The poison spreads through the sac holding the spores,",380,128,0.3368
dialogsum,"#Person1#: what do you hope to do when you finish university? #Person2#: I'd like to go into management. I'Ve applied for several jobs already and I'm hopeful that I'll get some job offers. How about you? #Person1#: after I graduate, I have to do some more studies to pass exams to become a lawyer. I think I'Ve got a good chance of passing. There's a possibility of getting a job with a law firm in London, provide #Person2#: we both have to overcome several obstacles if we are to achieve our ambitions. #Person1#: if life were easy, then we'd achieve our ambition quickly and then get bored. #Person2#: unfortunately, it's inevitable that some people are going to work hard yet not succeed. #Person1#: that's why ambition need to be realistic. You can't achieve something that's totally unrealistic. #Person2#: as long as you plan carefully, most thing are possible. It's always good to have a backup plan in case things go wrong. #Person1#: I think it's important to be successful in a field you are truly interested in, not something that other people force you to be interested it. #Person2#: my father wanted me to become a doctor, but I knew it would be impossible for me to be successful in that field. #Person1#: I hope my parents don't try to interfere in my choice of career.",#Person1# and #Person2# discuss their ambitions after graduation. They think they should plan carefully and have realistic ambitions. They also think it important to do something they're truly interested in.,226,30,0.1327
scientific_lay_summarisation-elife-norm,"and synthesize the wealth of experimental data on this process. Methodological advances now enable simulations to capture millisecond timescale processes for proteins with less than 100 residues (Lindorff-Larsen et al. , 2011). For example, it is now possible to capture the binding or release of small molecules (Buch et al. , 2011; Bowman and Geissler, 2012; Silva et al. , 2011; Plattner and Noé, 2015; Tiwary et al. , 2015) and peptides (Plattner et al. , 2017; Zhou et al. , 2017) from small proteins. Impressive simulations on the ANTON supercomputer have revealed critical conformational dynamics of G proteins in their inactive and active states, elucidating the role of domain opening in GDP unbinding (Dror et al. , 2015; Yao et al. , 2016). However, even this specialized hardware could not capture the entire process of G protein activation and GDP release due to the size of the Gα subunit (>300 residues) and the slow kinetics of GDP dissociation (~10−3 min−1) (Chidiac et al. , 1999; Ross, 2008; Mukhopadhyay and Ross, 1999). Here, we introduce an approach to capture rare or long-timescale events, such as GDP release, and reveal the mechanism of Gα activation. As a test of this methodology, we apply it to Gαq, which has one of the slowest GDP release rates (Chidiac et al. , 1999) and is frequently mutated in uveal melanoma (Van Raamsdonk et al. , 2009; Van Raamsdonk et al. , 2010). To highlight aspects of the activation mechanism that we propose are general to all G proteins, we focus our analysis on the behavior of secondary structure elements and amino acids that are conserved across Gα domains. Our approach first combines two powerful sampling methods, metadynamics (Laio and Parrinello, 2002) and Markov state models (MSMs), (Bowman et al. , 2014) to observe GDP release and identify the rate-limiting step for this slow process. Then we use our recently developed CARDS method (Singh and Bowman, 2017), which quantifies correlations between both the structure and disorder of different regions of a protein, to identify the allosteric network connecting the GPCR- and nucleotide-binding sites. The resulting model is consistent with a wealth of experimental data and leads to a number of predictions, described below. Taken together, our results provide the most comprehensive model of G protein","Cells communicate with each other by exchanging chemical signals, which allow them to coordinate their activities and relay important information about their environment. Often, cells secrete specific signals into their surroundings, which are then picked up by a receiving cell that has the right receptors to recognize the message. Once the signal attaches to the receptor, its shape or activity changes, which in turn triggers cascades inside the cell to convey the signal, much like a circuit would. A group of proteins called heterotrimeric G-proteins play an important role in these pathways. They act as molecular switches inside the cells to help transmit signals from the outside of the cell to the inside. The proteins are made up of three parts, one of which is G-alpha. When G-alpha",380,128,0.3368
dialogsum,"#Person1#: Hi, Judy. How did you go about changing your course? You did history of art originally, didn't you? #Person2#: No, my parents persuaded me that English would be more useful, so I took their advice. But I really didn't enjoy it and tried to change to history of art. But the course was full. The course tutor told me about the fine art.",Judy wants to change her course from English to history of art but it was full.,64,16,0.25
dialogsum,"#Person1#: Taxi, Taxi. #Person2#: Yes, madam. where are you going? #Person1#: I am going to the Chinese Consulate General at 520, 12th Ave. #Person2#: Get on, please. #Person1#: Thank you. Can we get there in half an hour, sir? #Person2#: I am not sure, madam. Generally we can. but look at the traffic. It's the rush hour at noon. ' #Person1#: I am leaving for Boston at l #Person2#: Goodness me. We are really in a hurry.",#Person1# takes a taxi to the Chinese Consulate General and hurries #Person2# to arrive there within half an hour.,77,19,0.2468
dialogsum,"#Person1#: My dear, it's five flights up! #Person2#: That's all right. We'll get used to it. Besides, it is quiet up there. We're little further away from the street and traffic noise and there's no one living over us. #Person1#: Is the place well-furnished? #Person2#: Yes, it's pretty bright in there and big enough for our children to play. #Person1#: What about the kitchen? #Person2#: The stove and refrigerator are in good working order, and I don't see any loose electric wiring that could cause fires. #Person1#: Are the plumbing all right? #Person2#: The plumbing seems OK, too. The toilet flushes and the shower has hot and cold water, and the sinks don't seem to leak. #Person1#: The place is OK. Let's go there and have a look at it again.",#Person1# and #Person2# are evaluating a house which is far from the street. They check the equipment of the house and think it is ok.,131,25,0.1908
pubmed-summarization,"cycles of chemotherapy patient started passing urine per urethra and nephrostomy output decreased . after nephrostomy removal patient 's serum creatinine remained static at 1.6 mg% and usg showed no hydronephrosis . metastases to urinary bladder are rare , accounting for less than 2% of all bladder tumors , these are mostly found in advanced stages with peritoneal dissemination . information pertaining to bladder metastases is derived largely from autopsy studies , and known primary sites of origin in descending frequency are gastric cancer , malignant melanoma , breast and lung . potential mechanisms contributing to the appearance of secondary bladder tumors could be due to minute viable tumor emboli that pass through the pulmonary circulation without establishing a lung metastasis and subsequently reach the urinary bladder by hematogenous transport . other possible routes are extension from retroperitoneal involvement or dissemination through the lymphatic or arterial circulation . the relative infrequency of primary adenocarcinoma of the bladder causes the dilemma whether bladder adenocarcinoma represents a primary or secondary process . if the adjacent mucosa contains polypoid formation , brunn 's nests , or glandular or mucous metaplasia , a primary bladder lesion is likely . cytokeratin , ck-7 , ck-18 , ck-19 , ck-20 are useful screening markers for the recognition of epithelial differentiation . other specific markers that are commonly used are er/ pr for endometrial and breast carcinoma , ca 19 - 9 for pancreatobiliary malignancy , prostate specific antigen ( psa ) for prostate , thyroglobulin for thyroid , uroplakin iii for urothelium , and heppar i for hepatocellular . in a retrospective study bates and baithun found 282 secondary urinary bladder metastases in a series of 6289 bladder tumors ( about 4.5% of all bladder tumors detected ) . seven cases of primary breast cancer were found ; bladder metastases were detected post - mortem in six of these seven cases and all of them had metastasized widely . postobstructive renal failure in breast cancer patients can be treated easily by endoureteral catheterization or percutaneous nephrostomy which allows rapid normalization of renal function in most cases and further administration of effective systemic chemotherapy . survival after the onset of distant metastases is relatively short , poulakis et al . in 2001 reported a patient with breast","breast carcinoma is the most common nondermatologic cancer diagnosis in women . common metastatic sites include lymph nodes , lung , liver , and bone . breast carcinoma metastatic to the bladder has been reported only sporadically . most patients were symptomatic breast cancer with evidence of disseminated disease at the time of diagnosis . metastasis usually occurred many years after diagnosis , and the prognosis was poor . we report a case of breast caricinoma metastasizing to the urinary bladder and retroperitoneum , which presented initially with acute renal failure . patient was treated with bilateral per cuteneous nephrostomies and chemotherapy . starting from this clinical case we review the available literature on this issue . patients with breast cancer presenting with urinary symptoms should be examined",380,128,0.3368
scientific_lay_summarisation-elife-norm,"large-scale changes, such as loss of heterozygosity (LOH) (Coste et al. , 2006; Dunkel and Morschhauser, 2011), copy-number variation (CNV), including short segmental CNV, and whole chromosome aneuploidy (Selmecki et al. , 2010) accompanied by point mutations. While we understand some aspects of the molecular basis of resistance, we understand less about the mechanisms that drive the evolution of drug resistance and overall pathogenicity in C. albicans. It is challenging to use forward genetic approaches in C. albicans due to its diploid genome and lack of a complete sexual cycle. Although C. albicans has conserved the genomic elements needed for mating, mating occurs instead through rare mating-competent haploids (Hickman et al. , 2013) or via a parasexual cycle consisting of mating of diploid strains to form tetraploids followed by chromosome loss to regenerate diploids (Bennett and Johnson, 2005). An alternative approach is to use isolates sampled consecutively from the same patient to study the changes in the frequency of variants in natural populations under selection for drug resistance. Studies in evolved isolates have implicated multiple mechanisms in drug resistance, but have focused on large-scale aberrations such as aneuploidies and LOH (Selmecki et al. , 2008; 2009) or candidate genes (Perea et al. , 2001; White et al. , 2002), and do not comprehensively chart the genetic basis of adaptation. Here, we used genome sequencing of isolates sampled consecutively from patients that were clinically treated with fluconazole to systematically analyze the genetic dynamics that accompany the appearance of drug resistance during oral candidiasis in human HIV patients. Most isolates from each individual patient were highly related, suggesting a clonal population structure and facilitating the identification of variation. Because each clinical sample was purified from a single colony, we cannot assess the population structure at any single time point. Instead, we have measured the occurrence of single-nucleotide polymorphisms (SNPs), CNV, and LOH events in each isolate and then compared them between isolates from the same patient and across patients' series. Consistent with previous studies, we found that LOH events were recurrent across patients' series and were associated with increased drug resistance. To identify SNPs with likely functional impact in the context of substantial genetic diversity, we focused on those events that were both persistent across isolates within a patient and were recurrent","Nearly all humans are infected with the fungus Candida albicans. In most people, the infection does not produce any symptoms because their immune system is able to counteract the fungus' attempts to spread around the body. However, if the balance between fungal attack and body defence fails, the fungus is able to spread, which can lead to serious disease that is fatal in 42% of cases. How does C. albicans outcompete the body' s defences to cause disease? This is a pertinent question because the most effective antifungal medicines—including the drug fluconazole—do not kill the fungus; they only stop it from growing. This gives the fungus time to develop resistance to the drug by becoming able to quickly replace the fungal proteins the drug destroys, or to efficiently",380,128,0.3368
dialogsum,"#Person1#: Tom, can you get the vegetables out of the fridge, please? #Person2#: Lettuce and carrots? #Person1#: We need carrots, but not lettuce. And can you see the peppers? #Person2#: Yes. #Person1#: Two of those as well. We'll cut them into small pieces. #Person2#: Fine. Shall I turn the cooker on? #Person1#: Yes, nice and hot, please. #Person2#: 190 degrees? #Person1#: Put it at 220 for now, and then we can change it to 200 later. #Person2#: OK, the vegetables are ready? #Person1#: Good. We can roast them together with the fish. #Person2#: How long will it take? #Person1#: Will cook it hot for 15 minutes, and then 25 minutes at a lower temperature. So in 40 minutes, it'll be ready. #Person2#: Great. I'm going to watch TV for a few minutes. #Person1#: Actually, can you do this little bit of washing up? I'm going to make a dessert. #Person2#: OK.","#Person1# asks Tom to get the carrots out of the fridge, cut the peppers, put the cooker at 220 and wash something up.",151,23,0.1523
scientific_lay_summarisation-elife-norm,"al. , 2013; Ito, 2013), and imaging (Wu et al. , 2011; Keller et al. , 2008) and tracking (Amat et al. , 2014; Bao, 2006; Santella et al. , 2010) large numbers of cells in developing embryos. Multiple LSFM implementations now obviate the problems of motion blur and photo damage in worm embryos (Wu et al. , 2011; Wu et al. , 2013; Kumar et al. , 2014; 2015), and also offer sufficient spatiotemporal resolution (sub-μm in all three spatial dimensions, sub-second volumetric imaging [Wu et al. , 2013; Kumar et al. , 2014]) that subcellular morphology may be observed over the entire 14-hour period of embryogenesis. Despite these advances, morphological changes still pose problems when trying to follow individual cells, or when combining data from multiple embryos. To address these problems, we have generated a nematode strain that expresses fluorescent markers within specific cells, and designed software that uses these markers to computationally' untwist' the embryo, resulting in straightened volumes that significantly ease the tracking of developmental events in later embryonic stages (described briefly in a preliminary conference proceeding [Christensen, 2015]). Our open-source software is based on the NIH’s Medical Image Processing, Analysis, and Visualization (MIPAV [McAuliffe, 2001; Haak et al. , 2015]) platform, implemented as a standalone plugin (http: //mipav. cit. nih. gov/plugin_jws/mipav_worm_plugin. php). Computational untwisting algorithms have previously been used to straighten images of L1 larval worms for use in tracking nuclear position (Peng et al. , 2008; Long et al. , 2009) in both two and three dimensions, but to our knowledge, these algorithms are not suitable for the nematode embryo. In addition to the untwisting capability, our plugin includes the ability to annotate and track 3D positions over time, allowing semi-automated quantification of cell and neurite positions in twisted (and untwisted) embryos. The positional data so derived also facilitate comparison and combination of information from multiple embryos, allowing us to create a composite model of development. We demonstrate the capabilities of our method by computationally untwisting eight nematode embryos; tracking the position of seam cell nuclei, the canal-associated neuron (CAN), ALA, and AIY neuron cell bodies, and the growing neurites of the ALA neuron in the untwisted reference frame; and combining the data from multiple embryos to model the time-evolution of all these elements","Understanding how the brain and nervous system develops from a few cells into complex, interconnected networks is a key goal for neuroscientists. Although researchers have identified many of the genes involved in this process, how these work together to form an entire brain remains unknown. A simple worm called Caenorhabiditis elegans is commonly used to study brain development because it has only about 300 neurons, simplifying the study of its nervous system. The worms are easy to grow in the laboratory and are transparent, allowing scientists to observe how living worms develop using a microscope. Researchers have learned a great deal about the initial growth of the nervous system in C. elegans embryos. However, it has been difficult to study the embryos once their muscles have formed because",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2017; Sanborn et al. , 2015; Wutz et al. , 2017). The two-sided loop extrusion model explains the emergence of TADs and their ‘corner peaks’ (or ‘dots’) and ‘stripes’ (sometimes called ‘lines’, ‘tracks’ or ‘flames’) in Hi-C maps as an average collective effect of multiple cohesins dynamically extruding chromatin loops and stopping at the CTCF boundaries (Fudenberg et al. , 2016; Sanborn et al. , 2015; reviewed in Fudenberg et al. , 2017). Existing models for loop extrusion during interphase have assumed LEFs with two mobile subunits, whether they be active or inactive (Alipour and Marko, 2012; Benedetti et al. , 2017; Brackley et al. , 2017; Fudenberg et al. , 2016; Sanborn et al. , 2015; Yamamoto and Schiessel, 2017). While it is clear that a one-sided LEF will necessarily leave an unlooped gap between its initial loading site and one of the CTCF boundary elements, the extent to which one-sided loop extrusion can recapitulate the experimental observations remains entirely unexplored. In bacteria, SMC complexes and homologs play an important role in the maintenance of proper chromosome organization and efficient chromosomal segregation (Britton et al. , 1998; Jensen and Shapiro, 1999; Moriya et al. , 1998; Sullivan et al. , 2009 and others). In Bacillus subtilis and Caulobacter crescentus, the circular chromosome exhibits enhanced contact frequency between its two chromosomal arms (often called ‘replichores’), as shown by Hi-C (Le et al. , 2013; Marbouty et al. , 2015). This signal is dependent on the bacterial SMC complex (bSMC) (Marbouty et al. , 2015; Wang et al. , 2015). Experiments show that bSMC is loaded at a bacterial parS site near the origin of replication, and then, while bridging the two arms, actively and processively moves along the chromosome, thus juxtaposing or ‘zipping’ the arms together (Minnen et al. , 2016; Tran et al. , 2017; Wang et al. , 2018; Wang et al. , 2017). The symmetry of the juxtaposed chromosome arms implies that bSMC should be a two-sided LEF (Brandão et al. , 2019; Wang et al. , 2017). Indeed, previous modeling has shown that pure one-sided loop extrusion produces contact maps that differ from experimental observations (Miermans and Broedersz, 2018). However, it is unknown whether variations of one-sided extrusion can properly juxtapose the arms of a","The different molecules of DNA in a cell are called chromosomes, and they change shape dramatically when cells divide. Ordinarily, chromosomes are packaged by proteins called histones to make thick fibres called chromatin. Chromatin fibres are further folded into a sparse collection of loops. These loops are important not only to make genetic material fit inside a cell, but also to make distant regions of the chromosomes interact with each other, which is important to regulate gene activities. The fibres compact to prepare for cell division: they fold into a much denser series of loops. This is a remarkable physical feat in which tiny protein machines wrangle lengthy strands of DNA. A process called loop extrusion could explain how chromatin folding works. In this process, ring-like protein complexes",380,128,0.3368
dialogsum,"#Person1#: Did you have a good vacation Katie? #Person2#: Yeah, I took a nature adventure tour. For the first part we went hiking. It was so much fun. We hiked all the way up to these beautiful waterfalls. I took lots of pictures. #Person1#: Sounds great, so what else did you do on the tour? #Person2#: Well, the best part was at the end of the trip. I jumped out of an airplane. #Person1#: Wow. #Person2#: Yeah, it was just a fantastic vacation, but anyway, that's enough about my vacation. How did you spend your break, Ryan? #Person1#: Oh, I drove to visit my relatives. Well, it was pretty boring actually, it rained every day, so we had to stay inside. We watched TV a lot. #Person2#: Oh, that's too bad. #Person1#: No, that's ok. I really had a good rest, even though it was a little boring.",Katie tells Ryan about her nature adventure tour during the fantastic vacation. Ryan shares his boring vacation of visiting his relatives.,148,21,0.1419
dialogsum,"#Person1#: Where ' s Sally, Jack? #Person2#: She ' s in the garden, Jane. #Person1#: What ' s she doing? #Person2#: She ' s sitting under the tree. #Person1#: Is Tim in the garden, too? #Person2#: Yes, he is. He ' s climbing the tree. #Person1#: I beg your pardon? Who ' s climbing the tree. #Person2#: Tim is. #Person1#: What about the dog? #Person2#: The dog ' s in the garden, too. It ' s running across the grass. It ' s running after a cat.","Jack tells Jane that Sally, Tim, and the dog are all in the garden.",87,14,0.1609
pubmed-summarization,"recently , the cesarean delivery rate has been reported to be steadily increased in the united states . approximately , one - third of births in the united states are now via cesarean delivery . the increase has been observed to be among women of all ages and race / ethnicities , in every state , and across all gestational ages . many theories have been proffered to explain this trend , including a decrease in vaginal births after cesarean delivery ( vbac ) , decreased vaginal births of breech presentation , and increased prevalence of high risk pregnancies such as advanced maternal age and some subjective indications during labor such as nonreassuring fetal status and arrest of dilation . although cesarean delivery rates that are too low are associated with increased adverse events , cesarean delivery rates higher than the risk - adjusted expected rate for an institution have not been shown to improve maternal or neonatal outcomes , but they do add cost and unnecessary intervention . therefore , the examination of cesarean delivery rate concerning perinatal outcomes is very important for obstetricians . to date , however , there have not been sufficient observations concerning the cesarean delivery rate in japanese populations . in this study , we examined which specific factors contributed to the increase in cesarean delivery rate at our hospital over a 10-year period . the protocol for this study was approved by the ethics committee of the japanese red cross katsushika maternity hospital . our hospital is one of the major perinatal centers in tokyo , japan ( about 1,9002,000 deliveries per year ) . from january 2002 to december 2012 , data on the japanese singleton deliveries at 22-week gestation managed at the japanese red cross katsushika maternity hospital were collected . demographic information and the characteristics of labor were extracted from patient charts to examine the potential factors associated with the increasing cesarean delivery rate . in this study , the factors were selected according to previous studies : nulliparity , advanced maternal age ( 35 years ) , pregnancy - induced hypertension ( pih ) , preterm delivery , low birth weight ( lbw : neonatal birth weight < 2,500 g ) and macrosomia ( neonatal birth weight 4,000 g","objective . we examined which specific factors contributed to the increase in cesarean delivery rate at our hospital over a 10-year period . methods . from january 2002 to december 2012 , data on the japanese singleton deliveries at 22-week gestation managed at japanese red cross katsushika maternity hospital were collected . potential factors associated with the increasing cesarean delivery rate were selected according to previous studies . in this study , the incidences of intrauterine fetal demise , umbilical artery ph < 7.1 , and severe perineal laceration were calculated for each year . results . the cesarean delivery rate at our institution increased significantly during the study period ( 17.3% in 2002 versus 23.4% in 2012 , p < 0.01 ) . during the study period",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Temporal continuity of object identity is a feature of natural visual input and is potentially exploited – in an unsupervised manner – by the ventral visual stream to build the neural representation in inferior temporal (IT) cortex. Here, we investigated whether plasticity of individual IT neurons underlies human core object recognition behavioral changes induced with unsupervised visual experience. We built a single-neuron plasticity model combined with a previously established IT population-to-recognition-behavior-linking model to predict human learning effects. We found that our model, after constrained by neurophysiological data, largely predicted the mean direction, magnitude, and time course of human performance changes. We also found a previously unreported dependency of the observed human performance change on the initial task difficulty. This result adds support to the hypothesis that tolerant core object recognition in human and non-human primates is instructed – at least in part – by naturally occurring unsupervised temporal contiguity experience. Among visual areas, the inferior temporal (IT) cortex is thought to most directly underlie core visual object recognition in human and non-human primates (Ito et al. , 1995; Rajalingham and DiCarlo, 2019). For example, simple weighted sums of IT neuronal population activity can accurately explain and predict human and monkey core object recognition (COR) performance over dozens of such tasks (Majaj et al. , 2015). Moreover, direct suppression of IT activity disrupts COR behavior (Afraz et al. , 2015; Rajalingham and DiCarlo, 2019). These results were found in the face of significant variation in object latent variables including size, position, and pose, and the high performance of the simple IT readout (weighted sum) rests on the fact that many individual IT neurons show high tolerance to those variables (DiCarlo et al. , 2012; Hung et al. , 2005; Li et al. , 2009), reviewed by DiCarlo et al. , 2012. But how does the ventral stream wire itself up to construct these highly tolerant IT neurons? Simulated IT ‘neurons’ in the deep layers of artificial neural networks (ANNs) have such tolerance and provide quite accurate approximations of the adult ventral visual stream processing (Khaligh-Razavi and Kriegeskorte, 2014; Rajalingham et al. , 2018; Yamins et al. , 2014). However, those ANNs are produced by training with millions of supervised (labeled) training images, an experience regime that is almost surely not biologically","A bear is a bear, regardless of how far away it is, or the angle at which we view it. And indeed, the ability to recognize objects in different contexts is an important part of our sense of vision. A brain region called the inferior temporal (IT for short) cortex plays a critical role in this feat. In primates, the activity of groups of IT cortical nerve cells correlates with recognition of different objects – and conversely, suppressing IT cortical activity impairs object recognition behavior. Because these cells remain selective to an item despite changes of size, position or orientation, the IT cortex is thought to underly the ability to recognise an object regardless of variations in its visual properties. How does this tolerance arise? A property called",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The heat shock response is a universal homeostatic cell autonomous reaction of organisms to cope with adverse environmental conditions. In mammalian cells, this response is mediated by the heat shock transcription factor Hsf1, which is monomeric in unstressed cells and upon activation trimerizes, and binds to promoters of heat shock genes. To understand the basic principle of Hsf1 activation we analyzed temperature-induced alterations in the conformational dynamics of Hsf1 by hydrogen exchange mass spectrometry. We found a temperature-dependent unfolding of Hsf1 in the regulatory region happening concomitant to tighter packing in the trimerization region. The transition to the active DNA binding-competent state occurred highly cooperative and was concentration dependent. Surprisingly, Hsp90, known to inhibit Hsf1 activation, lowered the midpoint temperature of trimerization and reduced cooperativity of the process thus widening the response window. Based on our data we propose a kinetic model of Hsf1 trimerization. To cope with changes in physical and chemical properties of the environment as well as with physiological and pathophysiological conditions which cause protein misfolding, organisms mount a homeostatic transcriptional program, the so-called heat shock response (Jolly and Morimoto, 2000). In all eukaryotic cells, heat shock transcription factor (HSF) 1 is the master regulator of this response and alters transcription of a large number of genes, some of which encode chaperones and proteases (Anckar and Sistonen, 2011). Although this response is essentially cell autonomous, systemic modulation of this response has been observed in metazoa (Morimoto, 2008; Prahlad et al. , 2008; Prahlad and Morimoto, 2011). Metazoan Hsf1 consists of a N-terminal winged helix-turn-helix DNA binding domain (Harrison et al. , 1994; Vuister et al. , 1994), a hydrophobic shorter heptad repeat regions (HR-A/B) proposed to function as a leucine zipper coiled-coil trimerization domain (Clos et al. , 1990; Rabindran et al. , 1993), a regulatory domain, a second heptad repeat (HR-C) and a C-terminal transcription activation domain (1A) (Anckar and Sistonen, 2011; Voellmy, 2004). In unstressed cells metazoan Hsf1 is monomeric and supposed to be in complex with molecular chaperones, including Hsp70, Hsp90 and TRiC/CCT (Shi et al. , 1998; Zou et al. , 1998; Neef et al. , 2014). At physiological concentrations monomeric Hsf1 does not bind appreciably to heat shock elements (nGAAn). In the activated state Hsf1 forms trimers or higher order oligomers and","Cells cope with excessive heat, toxic compounds and other adverse environmental conditions by triggering an internal repair process called the heat shock response. In mammalian cells, a protein called Hsf1 is activated by stress and regulates the activity of a large set of target genes. These genes code for proteins that help the cell cope with the effects of stress, for example, by repairing or breaking down damaged proteins. Under normal conditions, Hsf1 exists as a single molecule, but when it is activated, three molecules come together to make a complex called a trimer that is able to bind to DNA and activate the target genes. Proteins are made of long chains that then fold into specific three-dimensional shapes. It is not known how Hsf1 is kept in",380,128,0.3368
dialogsum,"#Person1#: I've been looking for a swimming pool, but I haven't found one yet. #Person2#: We have no pool, sir, but we do have swim stations in our gym. #Person1#: Swim stations? Could you be a little more explicit? #Person2#: You know how you run on a treadmill but don't go anywhere? Well, it's the same thing. #Person1#: Gee, that's a great idea. Now, how much do I have to pay? #Person2#: The stations are absolutely free to guests, sir. #Person1#: Great! Now, when can I go down there and use the stations? #Person2#: The swim stations are open daily from 7 a. m. to 10 p. m. #Person1#: Boy, oh boy! I can't wait to change into my swim trunks. #Person2#: Be warned, sir. At certain hours the swim stations are very crowded.","#Person2# tells #Person1# they have no pool but they have free swim stations for guests, and explains what it is. #Person1# wants to have a try.",134,26,0.194
dialogsum,"#Person1#: I really need to go shopping. #Person2#: What do you need to buy? #Person1#: I need to look for a new bedroom set. #Person2#: Where are you going to go look for one? #Person1#: I have absolutely no idea. #Person2#: You don't know where you want to look for one? #Person1#: No, I'm not sure where they sell nice bedroom sets. #Person2#: Do you want to know where I got mine from? #Person1#: Yes, because I love yours. #Person2#: I purchased mine from IKEA. #Person1#: Is IKEA affordable? #Person2#: Not at all, but you get what you pay for.",#Person1# wants a bedroom set but doesn't know where to buy. #Person2# recommends #Person1# to buy from IKEA.,100,18,0.18
dialogsum,"#Person1#: I think the goverment needs a radical plan to improve things. The government just talks, but in the long run, nothing is done to improve the economy. #Person2#: That's right. They always talk about a need for new, progressive tactics, but they haven't done anything to stimulate new jobs. #Person1#: Well, income taxes were decreased last year in hope to give the economy a boost, but I think it's backfired. The immediate effect of the tax reduction was to cause inflation to rise. #Person2#: The worst part is that the inflation hurts the poor more than the rich. It also leads to more unemployment in the long run. I don't know what a good solution would be to make the economy more vibrant again... #Person1#: I have a good solution... We need some new blood! We should get rid of this president and boat in some new leaders!",#Person1# and #Person2# agree that the government needs a radical plan to improve things. #Person1# thinks they need some new leaders.,149,21,0.1409
dialogsum,"#Person1#: Do you mind helping me? #Person2#: What can I help you with? #Person1#: I'm not sure how to find my next class. #Person2#: Do you know what building that it's in? #Person1#: The C building, I think. #Person2#: Well, that's not far away. #Person1#: Could you point me in that direction? #Person2#: Do you know what the room number is? #Person1#: It's C261. #Person2#: My next class is around there. #Person1#: Can you show it to me? #Person2#: Sure, let's go.",#Person1# is not sure how to find #Person1#'s next class. #Person2# will show #Person1#.,82,14,0.1707
dialogsum,"#Person1#: Hi, I'm home! Can you double that recipe? I ran into an old friend after work and invited him for dinner. #Person2#: No problem. Who is it? Anyone I know? #Person1#: I don't think so. Do you remember Bob Gain from Tulsa? #Person2#: That name doesn't ring a bell. But tell me more. #Person1#: He was on the diving team with me in high school and saved my life one day. #Person2#: Well, I'll have to personally thank him by making him my famous chocolate cake. #Person1#: You're glad he saved me, huh? #Person2#: Absolutely! Bob and his whole family are welcome here any time!","#Person1# asks #Person2# to double the recipe since #Person1# invited Bob, an old friend who saved #Person1#'s life one time, for dinner.",106,22,0.2075
scientific_lay_summarisation-elife-norm,"Xue et al. , 2014). The limitations of CRISPR/Cas9 are that the identity of the generated lesions for the gene of interest may vary in individual cells in the same animal or tissue. Moreover, the mutant cells are not marked and cannot be distinguished from neighboring wild-type cells. Here, we describe a new flippase (FLP) -dependent method ‘Flip-Flop’ that offers several advantages over the current techniques for generating mosaics. (1) The method does not rely on cell division and can, therefore, be broadly used for conditional gene inactivation in post-mitotic cells such as neurons. (2) It allows endogenous tagging of proteins with EGFP, which permits multiple applications, and (3) it simultaneously marks mutant cells with mCherry. We engineered the ‘Flip-Flop’ cassette for conditional gene inactivation. This cassette contains two modules that are placed in opposite orientation: a protein-trap (PT) module and a gene-trap (GT) module (1A). The PT module carries a splice acceptor (SA), followed by an in-frame EGFP coding sequence, and a splice donor (SD) (Venken et al. , 2011). The GT module similarly contains a SA, but is followed by the T2A peptide sequence, an mCherry coding sequence, stop codons in all three reading frames, and an SV40 polyA signal. The PT and GT modules are placed in opposite orientations and are flanked by inverted pairs of canonical FRT and FRT14 sites, forming a flip-excision switch (FLEx) (Schnütgen et al. , 2003; Xue et al. , 2014). The entire cassette is nested between two inverted attB sites that facilitate Recombination-Mediated Cassette Exchange (RMCE) between the Flip-Flop cassette and a target Minos-Mediated Integration Cassette (MiMIC) that resides in a coding intron of the gene of interest. When integrated in the MiMIC in the PT orientation, Flip-Flop should result in expression of the endogenous protein with an internal EGFP tag. The internal EGFP tagging does not or subtly disrupt the protein’s function in 77% of the cases (Nagarkar-Jaiswal et al. , 2015). The cassette can then be converted from a PT to a GT, in vivo, by inverting the cassette’s orientation through the expression of FLP that acts on the FLEx switch (1B). Following the switch from the PT to the GT orientation, transcription is precociously terminated by the polyA sequence. When this truncated transcript is translated, the T2A site","The instructions needed to build and maintain cells in an organism are encoded in their DNA. There are many different cell types, and each type only needs a small portion of the information found in the DNA to do its job. Hence, only some of the instructions, in the form of genes, need to be active or ‘expressed’ in any given cell type. To understand how a gene works, it is necessary to know in which cell the gene is expressed and where in the cell the gene product – normally a protein – is located. Researchers may study a gene by deleting it, which prevents the protein from being made, or by attaching a new instruction into the gene, which generates a fluorescent tag on the protein",380,128,0.3368
dialogsum,"#Person1#: Have the owners come up with a counter-offer to my offer to buy their home yet? #Person2#: The owners have counter-offered three hundred and thirty-five thousand dollars. #Person1#: Should I accept their offer? #Person2#: There are two ways to respond. You can either come back with another offer or go with their counter-offer. #Person1#: What if I make another offer, and they don't accept it? #Person2#: No one else has made an offer, so you could make another offer if you want to do so. #Person1#: I think that I would like to offer three hundred and thirty thousand dollars as a counter-offer. #Person2#: OK, I will present your counter-offer to the owners tonight. #Person1#: How long before I find out what their decision is? #Person2#: By now, the owners probably have a pretty good idea of what they will accept. It will go quickly.",The owners have a counter-offer to #Person1#'s offer to buy their home. #Person2# tells #Person1# that there are two ways to respond. Then #Person1# decides to make a counter-offer.,146,29,0.1986
dialogsum,"#Person1#: And the cover is great! The colors are brilliant! #Person2#: Give me a break. You don't care about the colors. You just like the hot babe on the cover. #Person1#: OK, you got me. So, do you have a subscription? #Person2#: Of course. I'm currently the subscriber of 10 different fashion magazines. #Person1#: So what do you do with all the out-dated issues? #Person2#: I guess I'm lending them to you. . .",#Person1# likes the cover of #Person2#'s fashion magazine. #Person2# plans to lend the out-dated issues magazines to #Person1#.,74,18,0.2432
pubmed-summarization,"the emergency department ( ed ) is known to be one of the most congested units in any hospital that faces greater pressure in terms of patient load and health care resources as compared to other departments of the health care system . studies across various countries reported that quality of care decreases when the ed is overcrowded . overcrowding can result in delayed treatment , long patient waiting time and stay , overburdened working staff , patient elopement , high medical error rate , low productivity and poor patient outcomes . an efficient patient flow system serves critical patient quickly minimizing unnecessary delay in treatment . on the other hand , a patient arriving in the ed encounters repeated waits as he / she progresses in different stages , which may last for hours or even days . waiting time has been often cited as the most important cause of patients dissatisfaction in the ed . cooke cited reduction of waits as the most important area for improvement in ed . delays in the process have been associated with adverse outcome and increased violence in eds . waiting time in turn depends on multiple factors including volume of patients and workload on existing staff . if the outflow of patients from ed ( either by means of transfer out or by discharge ) is obstructed , this upstream bottleneck will also cause delays in the treatment . the present study was conducted to assess the patient flow system by assessing the arrival time pattern and waiting time distribution of patient in the ed of a tertiary health care institute of india . by understanding flow trends , hospital administrators can streamline processes to minimize wait times , improve efficiency , reduce overcrowding in the emergency out patient department ( eopd ) and in turn improve patients satisfaction . it was a short term cross sectional descriptive study conducted in may , 2011 in ed of a tertiary level medical , research and health care institution of north india . the institute caters to medical care needs of around 370 million populations of 7 states of india . in 2010 - 11 , the institute catered to a yearly load of around 16,57,200 out - patients and 64,969 inpatients ,","background : emergency department ( ed ) of tertiary health care institute in india is mostly overcrowded , over utilized and inappropriately staffed . the challenges of overcrowded eds and ill - managed patient flow and admission processes result in excessively long waits for patients.aim:the objective of the present study was to analyze the patient flow system by assessing the arrival and waiting time distribution of patients in an emergency out patient department ( eopd).materials and methods : this short cross - sectional descriptive study was conducted in the eopd of a tertiary level health care institution in north india in the month of may , 2011 . the data was obtained from 591 patients , who were present in the eopd during the month of may ,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"measures means the trend to undertreat pain remains in clinical practice (Carbajal et al. , 2008), despite concerted efforts to improve the management of pain in this population (Anand and International Evidence-Based Group for Neonatal Pain, 2001). For example, it is remarkable that current UK NHS guidelines for ankyloglossia (tongue tie) surgery state that ‘in small babies, being cuddled and fed are more important than painkillers’ (NHS Choices, 2015). Indeed, a recent review of neonatal pain management practice in intensive care highlighted that although infants experience an average of 11 painful procedures per day, 60% of the population did not receive any pharmacological analgesia (Roofthooft et al. , 2014). Recent studies using EEG and near-infrared spectroscopy have been used to provide reliable evidence that nociceptive information is transmitted to the newborn infant brain (Slater et al. , 2006,2010a, 2010b), and have highlighted the limitations of using observational behavioural measures to quantify pain in infants. For example, nociceptive information can be processed in the infant brain without a concomitant behavioural response (Slater et al. , 2008), and interventions thought to alleviate pain (i. e. , oral sucrose) can reduce clinical pain scores without reducing evoked nociceptive brain activity (Slater et al. , 2010a). While these studies confirm that the infant central nervous system can process noxious stimulation, they do not elucidate the nature of the infant experience—in particular, which brain regions are involved, and therefore, whether the sensory, cognitive, and emotional aspects of pain are present in this population. Here, we identify the cortical and subcortical structures activated following acute noxious stimulation in the healthy newborn infant, and compare the activity with that observed in adults. The feasibility of this approach was demonstrated in a foundational pilot study (Williams et al. , 2015). A case study in a single infant demonstrated that noxious stimulation evoked widespread brain activity (Williams et al. 2015), which included brain regions previously reported to be involved in adult pain (Tracey et al. , 2007). Using a reverse inference approach to compare active brain regions in infants with those reported during adult pain, we postulate which aspects of the pain experience are present (Wager et al. , 2013), providing an opportunity to gain insight into the organisation of nociceptive circuitry in the naïve infant brain. In this","Doctors long believed that infants do not feel pain the way that older children and adults do. Instead, they believed that the infants' responses to discomfort were reflexes. Based on these beliefs, it was a routine practice to perform surgery on infants without suitable pain relief up until the late 1980s. Even now, infants may receive less than ideal pain relief. For example, a review found that although newborns in intensive care units undergo 11 painful procedures per day on average, more than half of the babies received no pain medications. Some guidelines continue to emphasize that for infants cuddling and feeding are more important sources of comfort than pain-relieving drugs. There is growing support for better pain control for infants. Doctors and nurses now routinely observe behaviour",380,128,0.3368
dialogsum,"#Person1#: How many credits are you taking this semester? #Person2#: I have to have at least eighteen to keep my scholarships and grant. But so far, I only have fifteen. #Person1#: What's the matter, are the classes you want full? #Person2#: Yes. And now I'm down to either taking a class I'm not going to need or considering a double major. #Person1#: If you were to take on a double major, what would be your first choice? #Person2#: I think with International Business a language would be appropriate. #Person1#: Have you even thought that far ahead? I mean what country would you like to do business with? #Person2#: As a matter of fact, I would like to work in South America. So some Latin language like Spanish or Portuguese would work.","#Person2# tells #Person1# that #Person2# has to take at least 18 credits this semester to keep the scholarship and grant, and is considering taking some Latin languages.",131,27,0.2061
dialogsum,"#Person1#: Hey, where's Cindy? #Person2#: She told me that she's got tennis practice today. #Person1#: You're Mary, right? #Person2#: How did you know? #Person1#: Cindy told me about you in our gym class. #Person2#: I see. Do you live in this neighborhood, too? #Person1#: My house is next door to yours. #Person2#: Oh, Cindy did mention you before. You're Alexander Newman. #Person1#: Just call me Alex. Alex and Alexander are the same thing.",Alex met Mary and they find out Cindy mentioned them to each other.,73,13,0.1781
dialogsum,"#Person1#: Do you know that working overtime in some companies is a regular thing? #Person2#: How regular? #Person1#: An average ten hours or more a day according to a survey, the worst thing is that the employees get no pay for that. #Person2#: You are kidding me? It is against the labor law. They should be aware of their rights. #Person1#: But these people say nothing about that. They are worried about losing their job because there is surplus in labor force these days. #Person2#: That's not right, somebody should do something.",#Person1# tells #Person2# that working overtime in some companies is a regular thing. #Person2# doesn't think it's right.,92,18,0.1957
scientific_lay_summarisation-elife-norm,", 2003). PGBD1 and PGBD2 invaded the common mammalian ancestor, and PGBD3 and PGBD4 are restricted to primates, but are all contained as single coding exons, fused in frame with endogenous host genes, such as the Cockayne syndrome B gene (CSB) -PGBD3 fusion (Sarkar et al. , 2003; Newman et al. , 2008). Thus far, only the function of PGBD3 has been investigated. CSB-PGBD3 is capable of binding DNA, including endogenous piggyBac-like transposons in the human genome, but has no known catalytic activity, though biochemical and genetic evidence indicates that it may participate in DNA damage response (Bailey et al. , 2012; Gray et al. , 2012). PGBD5 is distinct from other human piggyBac-derived genes by having been domesticated much earlier in vertebrate evolution approximately 500 million years (My) ago, in the common ancestor of cephalochordates and vertebrates (Sarkar et al. , 2003; Pavelitz et al. , 2013). PGBD5 is transcribed as a multi-intronic but non-chimeric transcript predicted to encode a full-length transposase (Pavelitz et al. , 2013). Furthermore, PGBD5 expression in both human and mouse appears largely restricted to the early embryo and certain areas of the embryonic and adult brain (Sarkar et al. , 2003; Pavelitz et al. , 2013). These intriguing features prompted us to investigate whether human PGBD5 has retained the enzymatic capability of mobilizing DNA. Human PGBD5 contains a C-terminal RNase H-like domain that has approximately 20% sequence identity and 45% similarity to the active lepidopteran piggyBac, ciliate piggyMac, and mammalian piggyBat transposases () (Sarkar et al. , 2003; Baudry et al. , 2009; Mitra et al. , 2013). In addition, the human genome contains 2358 sequence elements with similarity to the piggyBac transposable elements (Table 1 and 2A). Specifically, MER75 (MER75, MER75A, MER75B) and MER85 elements show considerably similar ITR sequences as compared to lepidopteran piggyBac transposons (Table 2 and 2B). A total of 328 piggyBac-like elements in the human genome have intact ITRs and exhibit duplications of their presumed TTAA target sites (Table 1 and 2C). We reasoned that even though the ancestral transposon substrates of PGBD5 cannot be predicted due to its very ancient evolutionary origin (∼500 My), preservation of its transposase activity should confer residual ability to mobilize distantly related piggyBac-like transposons. To test this hypothesis, we used a synthetic transposon","Transposons are mobile genetic elements that can be cut out of and inserted into DNA. They are present in most living things and make up almost half of the human genome. Transposons help to rearrange and increase the variety of DNA sequences, which can drive evolution and regulate the expression of genes. Enzymes called transposases help to move transposons, but very few genes that encode these enzymes have been studied in humans. PiggyBac transposase—which was first discovered in the cabbage looper moth—helps to move transposons of the piggyBac family. Humans and many other animals have genes that encode similar enzymes. In particular, the gene that encodes the human PGBD5 transposase is expressed in the developing embryo and particular areas of the brain and is highly similar to genes",380,128,0.3368
scientific_lay_summarisation-elife-norm,"There is great interest in understanding human olfactory experience from a principled and quantitative standpoint. The comparison is often made to color vision, where a solid framework with a three-dimensional perceptual space enabled a rigorous search for the underlying neural pathways, and the technological development of lifelike color display devices. A recent, highly publicized report claims that humans can discriminate at least 1 trillion odors, which exceeds by many orders of magnitude the known capabilities of color discrimination. This claim is wrong. I show that the failure lies in the mathematical method used to infer the size of odor space from a limited experimental sample. Further analysis focuses on establishing how many dimensions the perceptual odor space has. I explore the dimensionality of physical, neural, and perceptual spaces, drawing on results from bacteria to humans, and propose some experimental approaches to better estimate the number of discriminable odors. The perceptual space for human color vision has three dimensions. Experimental proof of this dates to the 17th century, when it was found that every color sensation can be matched by mixing together three primary lights, but not if only two lights are available (Mollon, 2003). Therefore every color sensation can be fully characterized by three numbers, namely the intensity of the primaries that match it. We now know that color vision is based on three kinds of cone photoreceptors in the retina that differ in their sensitivity to the wavelength spectrum of light. Any pattern of excitation among cones can be matched by an appropriate mix of three primary lights, and this is the basis for RGB color display devices. Cone signals get processed by several circuits in the retina and beyond. This system ultimately has limited resolution, and in practice human subjects can distinguish about 1–2 million different colors (Masaoka et al. , 2013). Clearly, a quantitative understanding of color perception has both energized the search for the underlying neural circuits and made possible the design of image display technologies that mimic reality. One would like to achieve a similarly satisfying understanding of human smell. Human olfaction begins with the binding of odor molecules to olfactory receptors, of which there exist ∼400 types (Malnic et al. , 2004). It is believed that these receptor types all differ in their relative","Scientists are interested in the number of colors, sounds and smells we can distinguish because this information can shed light onto how our brains process these senses both in health and disease. It is relatively straightforward to determine how many colors we can see or sounds we can hear because these stimuli are well defined by physical properties such as wavelength. We know the range of wavelengths that the eye can see or the ear can hear, and we can also understand how two such stimuli (e. g. , red and blue) are arranged perceptually (think of a color wheel). It is harder, however, to do the same for smell because most ‘olfactory stimuli’ consist of mixtures of different odor molecules. Moreover, we understand much less about how",380,128,0.3368
dialogsum,"#Person1#: Hi, can I help you? #Person2#: No, thanks. I'm just looking. #Person1#: All right. If you need any help, just let me know. My name is Greg. #Person2#: Sure, I'll let you know if I need anything. Hm, this mattress is very firm. Jack will probably like it. #Person1#: Did you find something you like? #Person2#: Yes, this mattress is very good. It's pretty firm. The mattress I'm now sleeping on is saggy. #Person1#: You are right. This is very good brand. It doesn't sag easily and we offer a lifetime warranty, so you don't have to worry about its quality. #Person2#: Does it come with a frame? #Person1#: Unfortunately, it doesn't. However we can give you a 10% discount on the frame. We also offer a very good financing plan. There is no payment no interest until next June. #Person2#: That's an attractive plan. I'll think about it.",#Person2# finds a satisfying mattress at the shop but it doesn't have a frame. Greg says he can offer a discount and a good paying plan. #Person2# will think about it.,150,31,0.2067
scientific_lay_summarisation-elife-norm,"Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns (4,5) P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns (3) P and PtdIns (3,4, 5) P3 co-exist in the phagosomes yet are absent from the surface membrane. Moreover, endo-lysosomal proteins are present only in the phagosomal membrane. Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma. Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly. Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae. Candida albicans is a commensal fungus that colonizes the epithelial surfaces of 30–70% of healthy individuals (Perlroth et al. , 2007). However, in immune-compromised individuals, C. albicans can cause invasive, life-threatening disease. The mortality rate for infected patients is 46–75%, with candidiasis classified as the fourth most common nosocomial bloodstream infection (Brown et al. , 2012). Invasive candidiasis is correlated with a switch of C. albicans from its yeast form to a hyphal form, a shift that can be induced in vitro by nutrient deprivation among other cues (reviewed in Sudbery, 2011). In vivo, C. albicans hyphae are capable of invading epithelium and endothelium; in addition C. albicans is capable of forming recalcitrant biofilms and inducing inflammation (Sudbery, 2011). These conditions activate host defense mechanisms for the control and clearance of C. albicans, mounted predominantly by phagocytic cells of the innate immune system. Phagocytes can effectively sense, internalize and kill invasive C. albicans. Accordingly, impairment of the phagocytic response, e. g. by elimination of macrophages and neutrophils, is associated with disseminated candidiasis (reviewed in Netea et al. , 2015). Phagocytic cells possess receptors that bind the C. albicans cell wall and trigger uptake of the fungus into a phagosome. The C. albicans cell wall is composed mostly (80–90%) of polysaccharides, containing ≈ 60% β- (1,3) and - (1,6) glucans, and ≈ 40% O-","Billions of microorganisms live on, and in, the human body. Known as the human microbiome, most of these microscopic hitchhikers are harmless. But, for people with a compromised immune system, common species can sometimes cause disease. For example, the yeast Candida albicans, which colonises between 30 and 70% of the population, is normally harmless, but can switch to a disease-causing version that makes branching structures called hyphae. These hyphae grow fast, piercing and damaging the tissues around them. Immune cells called macrophages usually engulf invading microbes. These cells recognise sugars on the outside of C. albicans, and respond by wrapping their membranes around the yeast, drawing the microorganism in, and sealing it into closed structures called phagosomes. Then, the macrophages fill the phagosomes with acid, enzymes and destructive",380,128,0.3368
pubmed-summarization,"primary cysts have a lined epithelium and secondary cyst could be secondary to trauma . epidermoid splenic cysts are example of primary congenital cysts that contain an epithelial lining , unlike secondary cysts , which are composed of fibrous tissues , when the cyst is large they have nonspecific abdominal symptoms like pain , nausea , or a palpable mass usually in the left upper quadrant . epidermoid cysts and parasitic cysts are examples of primary cysts and usually have a classic presentation on imaging . despite imaging modalities and the patient s history , it can be difficult to diagnose an epidermoid cyst without a histological examination . the purpose of this paper is to discuss variable and atypical radiological presentation of primary splenic cysts including epidermoid cysts . a 51-year - old female presented to the ed using private transportation with complaints of left upper quadrant abdominal pain , nausea and vomiting for a couple days . she had significant medical history of hypertension , gerd , and hyperlipidemia with a bmi of 37.5 and no previous surgical history . patient had quit smoking cigarettes two years prior , does not drink alcohol or use any illicit drugs . physical exam was significant to being mildly tender to palpation over her left upper quadrant . vitals , complete blood count , basic metabolic panel , liver function tests , and urine analysis were all within normal limits . abdominal ultrasound ( . 1 ) visualized a 7.7 cm complex mass in the medial aspect of the spleen . 2 ) revealed a hypodense cystic mass in the medial aspect of the spleen measuring 10.4 cm 8.2 cm with a hounsfield attenuation of 15 ; containing multiple foci of fat with hounsfield attenuation of 102 . patient was assumed to have a confined cystic tumor of unknown etiology without any acute complications at this point . after long discussion with the patient with this large cystic mass of the spleen of unknown pathology , splenectomy was offered to the patient . she underwent uneventful laparoscopic hand - assisted splenectomy 6 weeks after presentation to the ed . she continued to have an uneventful recovery on follow - up with no recurrence of painful symptoms . 4 ) , it","highlightssplenic tumors are not common , many can have minimal to no symptoms , and they can be found incidentally.splenic tumors can be primary or metastatic . they can be benign or malignant.splenic cysts can be infectious , traumatic or congenital.epidermoid splenic cysts may not always present in a classic fashion on imaging , making diagnosis challenging.many splenic masses and complex cysts would require surgical pathological diagnosis .",380,68,0.1789
dialogsum,"#Person1#: Excuse me, can you show me the cloisonn bracelet in the counter? #Person2#: Sure. Let me get it for you. #Person1#: Can you also show me this one? #Person2#: No problem. This one is made of pure gold. #Person1#: I think the cloisonn bracelet is more beautiful. #Person2#: You're right. This one costs less, but is more beautiful. #Person1#: Will the luster fade out after some time? #Person2#: No, we guarantee the quality. #Person1#: Ok. Can I try it on? #Person2#: Certainly, the mirror is right here.","#Person1# asks #Person2# to show #Person1# the cloisonn bracelet in the counter, and tries it on.",88,16,0.1818
scientific_lay_summarisation-elife-norm,"Photorhabdus is a highly effective insect pathogen and symbiont of insecticidal nematodes. To exert its potent insecticidal effects, it elaborates a myriad of toxins and small molecule effectors. Among these, the Photorhabdus Virulence Cassettes (PVCs) represent an elegant self-contained delivery mechanism for diverse protein toxins. Importantly, these self-contained nanosyringes overcome host cell membrane barriers, and act independently, at a distance from the bacteria itself. In this study, we demonstrate that Pnf, a PVC needle complex associated toxin, is a Rho-GTPase, which acts via deamidation and transglutamination to disrupt the cytoskeleton. TEM and Western blots have shown a physical association between Pnf and its cognate PVC delivery mechanism. We demonstrate that for Pnf to exert its effect, translocation across the cell membrane is absolutely essential. Bacteria belonging to the Enterobacteriaceae genus Photorhabdus exist in a symbiotic partnership with entomopathogenic Heterorhabditis sp. nematodes. This Entomopathogenic Nematode complex (EPN) comprises a highly efficient symbiosis of pathogens that is commonly used as a biological agent to control crop pests (Forst et al. , 1997). The Photorhabdus bacteria are delivered into the hemocoel of the insect, after regurgitation from the worm, where they resist the insect immune response and rapidly kill the host via septicaemic infection. Insect tissues are subsequently bio-converted into a dense soup of Photorhabdus bacteria, which provide a food source to support the replication of the nematode. As food resources are depleted Photorhabdus re-associates with infective juvenile nematodes, and together they emerge from the insect cadaver able to re-infect a new host (Ciche et al. , 2008; Somvanshi et al. , 2012). Three major species have been formally recognized to date within the genus - P. luminescens, P. asymbiotica, and P. temperata. It should be noted however that with increasing numbers of Photorhabdus genome sequences becoming available, the genus structure is under revision (Machado et al. , 2018). In addition to the normal insect life cycle, P. asymbiotica is also the etiological agent of a serious human infection termed Photorhabdosis, which is associated with severe ulcerated skin lesions both at the initial infection foci and later at disseminated distal sites (Gerrard et al. , 2004; Gerrard et al. , 2006; Gerrard et al. , 2003a; Gerrard et al. , 2003b). The Photorhabdus genome encodes a diverse repertoire of virulence genes encoding for","Photorhabdus are the only known group of non-marine bacteria that can produce their own light. These organisms prey on insects, which then glow in the dark once infected. The group also has an unusual weapon system formed of miniscule needle-like structures that can be sent out in the environment. These ‘Photorhabdus virulence cassettes’ are loaded with toxins that are injected inside host cells; the cassettes alone can kill a caterpillar within minutes. However, it is still unclear how exactly these structures work: are they like poison darts, with the toxin on the outside, or like hypodermic needles, with the toxin within? Photorhabdus bacteria make lots of deadly substances, so to look at the needles on their own, Vlisidou et al. had them produced by another species of bacteria",380,128,0.3368
dialogsum,"#Person1#: Oh, hello, I like the holiday that mentioned Whales, was it whale watching? #Person2#: Oh yes, it's very popular. #Person1#: How long does it last? #Person2#: 2 days. We take up to 15 people on this tour, though we usually run it with just 12 or 13. #Person1#: And when is the next tour going? #Person2#: Umm, there is one in 3 weeks time on April the eighteenth and then we don't have another one until June the second. #Person1#: Is there anything else included in the tour? #Person2#: Oh, there are a lot of things. If you don't want to do the whale watching cruise, your guide will take anyone who is interested. In a Bush walk through the National Park near the hotel. There is no extra charge for that or on a fishing trip, which is an extra $12 I think. There is also a reptile park in town, which costs more or less the same. #Person1#: Well, I think I prefer Wales to Snakes. #Person2#: Oh, the hotel has badminton courts, and table tennis tables. But I think you'll be interested in going bowling there. #Person1#: Bowling? That sounds good. That's my favorite, thanks for the information.",#Person2# tells #Person1# the whale watching tour lasts two days and is going in three weeks. #Person2# also introduces the content of the tour and the hotel.,202,27,0.1337
pubmed-summarization,"material within the tract and the uncertainty of tissue in growth into the glue may all explain the possible causes of the poor outcomes . this article aims to review the literature and to identify the new sphincter - preserving techniques , such as the anal fistula plug , the ligation of intersphincteric fistula tract ( lift ) procedure and the cell therapy , used in the management of anal fistulae . the small intestinal submucosa is a natural biomaterial harvested from porcine small intestine and fabricated into a biomedical product of various shapes and thickness . the fact that it has been demonstrably useful as a bioprosthetic material in infected fields makes its application in fistula surgery quite reasonable . 1 ) . the idea is to bridge the defect of the fistula with a biocompatible material that would act as a scaffold for the patient 's own fibroblasts to come in and promote wound healing in the fistula tract . the technique of plug deployment is as follows : the tract is explored , probed , and irrigated gently with hydrogen peroxide . then , the apex of the plug is tied to the probe from the internal opening , and the plug is dragged through to the external opening . it is cut to fit and is secured in the internal opening by using a - of - eight suture , incorporating it with the mucosa of the anorectum to close the internal opening ( . the anal fistula plug has been used in a number of cases with widely varying results ( table 1 ) [ 21 , 24 , 26 - 33 ] . in an early prospective series of 46 patients reported by champagne et al . , after a median follow - up of 12 months ( range , 6 to 24 months ) , 17% of fistulae recurred . johnson et al . published a series comparing two prospective cohort groups of patients undergoing plug closure versus patients undergoing fibrin glue closure . they reported an 87% closure rate for the plug group versus a 40% closure rate for the glue group . others have had less favorable results with fistula recurrence rates as high as 80% [ 21 , 28 -","surgery for an anal fistula may result in recurrence or impairment of continence . the ideal treatment for an anal fistula should be associated with low recurrence rates , minimal incontinence and good quality of life . because of the risk of a change in continence with conventional techniques , sphincter - preserving techniques for the management complex anal fistulae have been evaluated . first , the anal fistula plug is made of lyophilized porcine intestinal submucosa . the anal fistula plug is expected to provide a collagen scaffold to promote tissue in growth and fistula healing . another addition to the sphincter - preserving options is the ligation of intersphincteric fistula tract procedure . this technique is based on the concept of secure closure of the internal",380,128,0.3368
scientific_lay_summarisation-elife-norm,"driven by dynamic changes in gene expression and ultimately protein regulation and activity. To identify candidate circadian regulators for trait improvement in crops, a more detailed time-course resolution of transcript abundance levels is needed to confirm whether the diel and circadian patterns observed in Arabidopsis are maintained in polyploid crops. The crop plant Brassica rapa offers an excellent model system for studies in crops. It is a member of the Brassicaceae and a close relative of Arabidopsis making comparative studies feasible. The morphological diversity in B. rapa with turnip, Chinese cabbage, pak choi, leafy and oil-type varieties provides a wealth of phenotypic traits to study in one species allowing for broad applicability to other crops. Preliminary studies have shown diversity in circadian clock parameters among morphotypes that correlate with various physiology measures suggesting that circadian clock variation has contributed to B. rapa diversification (Yarkhunova et al. , 2016). Examination of the orthologs of known circadian clock genes in Arabidopsis revealed preferential retention of these genes in B. rapa following the triplication and extensive fractionation of the genome after the divergence of Brassica and Arabidopsis from their common ancestor around 24 million years ago (MYA; Lou et al. , 2012). The preferential retention of clock genes is consistent with their involvement in protein complexes and regulation of critical pathways making them sensitive to dosage effects. The gene dosage balance hypothesis proposes that duplication of the entire genome is favored over single or chromosome level duplications because it maintains the appropriate concentration of gene products (Conant et al. , 2014). This is supported by studies in yeast where genes of protein complexes tend to be lost simultaneously with their interacting proteins (Pires and Conant, 2016). The increase in expression of one duplicate could lead to or permit the loss of the other duplicate or neo-functionalization (Pires and Conant, 2016). To assess the functional significance of the retention of circadian clock genes in B. rapa and look for possible examples of neo-functionalization, we performed two high-resolution circadian transcriptome experiments to characterize the circadian network. To compare the expression dynamics of paralogous genes, we developed a novel method for identifying and classifying changes in expression patterns, an R package called DiPALM (Differential Pattern Analysis via Linear Models). DiPALM facilitated a comparison of paralog expression","Like animals, plants have internal biological clocks that allow them to adapt to daily and yearly changes, such as day-night cycles or seasons turning. Unlike animals, however, plants cannot move when their environment becomes different, so they need to be able to weather these changes by adjusting which genes they switch on and off. To do this, plants keep track of how long days are using external cues such as light or temperature. One of the effects of climate change is that these cues become less reliable, making it harder for plants to adapt to their environment and survive. This is a potential problem for crop species, like Brassica rapa. This plant has many edible forms, including Chinese cabbage, oilseed, pak choi, and turnip. It is also a",380,128,0.3368
scientific_lay_summarisation-elife-norm,"our understanding of the molecular mechanisms of these contacts remains incomplete. Many known mechanisms for establishing 3D chromosome conformation may act on both intrachromosomal loops and interchromosomal contacts. The emerging consensus model for such DNA-DNA interactions involves loop extrusion by cohesin and other Structural Maintenance of Chromosomes (SMC) factors, which is thought to primarily mediate intrachromosomal loops (Alipour and Marko, 2012; Rao et al. , 2014; Rowley and Corces, 2018; Sanborn et al. , 2015; Swygert et al. , 2019). However, SMC complexes are also capable of mediating interactions between multiple DNA molecules, such as between sister chromatids (Michaelis et al. , 1997). Interchromosomal contacts (Monahan et al. , 2019) and intrachromosomal contacts (Weintraub et al. , 2017; Deng et al. , 2012) can also be mediated by dimerization of structured proteins. In addition to these well-defined strong molecular interactions, weak interactions such as those underlying phase separation of nuclear factors such as transcription factors (Boija et al. , 2018; Chong et al. , 2018), coactivators (Cho et al. , 2018), RNA polymerase (Boehning et al. , 2018), and heterochromatin proteins (Larson et al. , 2017; Strom et al. , 2017) may play an important role in shaping 3D genome organization. How these and other mechanisms synergize remains an open question. Mitotic (or somatic) homologous chromosome pairing is the preferential association of homologous pairs of loci in mitotically dividing cells. Homolog pairing occurs along the length of the genome in Drosophila (Joyce et al. , 2016), but is more subtle in yeast and other organisms, where the association is often transient and/or genomically localized (Xu et al. , 2006). Fluorescence in situ hybridization screens in flies have nominated various pairing and anti-pairing factors that modulate the strength of homolog pairing (Joyce et al. , 2012), but the precise mechanisms by which these factors regulate pairing are largely unknown. In mammals, X chromosome pairing is mediated by CTCF and Oct4 (Donohoe et al. , 2009), in conjunction with transcription (Xu et al. , 2007). However, cases of highly localized homolog pairing remain rare. Furthermore, the distinctions between homolog pairing and non-allelic interactions between repetitive elements (Gladyshev and Kleckner, 2017; Mirkin et al. , 2014) remain unclear. We recently identified a novel example of an inducible, localized interchromosomal contact between homologous copies","Inside cells, genetic information is stored within molecules of DNA that are folded into three-dimensional structures known as chromosomes. Each fold in a chromosome forms when two points on a single DNA molecule link together to make a loop. DNA in two different chromosomes can also form links with each other (known as “contacts”). Many cells contain two copies of every chromosome and these copies are often able to make contacts with each other. DNA loops and contacts can change in response to the environment and this may help cells switch the right genes on and off at specific times. For example, in budding yeast cells that have used up most of their preferred food source – a sugar called glucose – the two copies of a region",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1: 1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAP–STIL interaction constitutes a conserved key step in centriole biogenesis. Centrioles are small cylindrical organelles whose outer walls contain a ninefold symmetric array of microtubule triplets. These structures form the basal bodies that template the assembly of cilia and flagella, and they also organise a proteinaceous matrix termed the pericentriolar material (PCM) to form centrosomes, the main microtubule organising centres in animal cells. These organelles play an important part in many aspects of cell organisation, and centriolar dysfunction is linked to a plethora of human diseases, including cancer, obesity, macular degeneration and polycystic kidney disease (Nigg and Raff, 2009; Bettencourt-Dias et al. , 2011). Recently, an unexpected genetic link has emerged between centriole/centrosome assembly and human brain size. Autosomal recessive primary microcephaly (MCPH) is a rare condition where patients are born with small brains (Thornton and Woods, 2009). All eight identified MCPH genes encode proteins that localise to centrioles and/or centrosomes/spindle poles (Thornton and Woods, 2009; Hussain et al. , 2012). It is unclear why mutations in these proteins are linked to such a specific neuro-developmental problem in humans, but it seems likely that some aspect of centriole/centrosome function must be particularly important for the proper proliferation of human neural progenitors (Siller and Doe, 2009; Megraw et al. , 2011). In support of this possibility, mutations in the centriolar components CPAP (DSas-4 in Drosophila, here called dCPAP) and STIL (Ana2 in Drosophila, here called dSTIL) in flies lead to","Organisms—and individual tissues—grow and develop by dividing their cells. However, the process of cell division does not have to be symmetric, and the fates of the cells can be very different if cellular contents, including RNAs or proteins, are exclusively retained in the ‘mother’ or passed to her ‘daughter’. Organelles known as centrioles can play an important part in influencing whether cell division is symmetric or asymmetric. Centrioles contain ordered assemblies of various proteins, and mutations in some of these proteins can cause developmental defects in humans. For example, mutations in the centriolar proteins CPAP and STIL cause a syndrome known as microcephaly, in which the brain is smaller than normal. Although CPAP and STIL are known to bind each other, how they interact on a molecular level",380,128,0.3368
dialogsum,"#Person1#: You look happy. #Person2#: I am happy. I just bought a new car. #Person1#: Wow! Is it a good car? #Person2#: It's a great car. It's very comfortable and it goes really fast. #Person1#: Was it expensive? #Person2#: Yes, very expensive. #Person1#: What colour is it? #Person2#: It's red and black.",#Person2# is happy and #Person2# tells #Person1# about #Person2#'s new car.,52,11,0.2115
scientific_lay_summarisation-elife-norm,"The circumventricular organs (CVOs) in the central nervous system (CNS) lack a vascular blood-brain barrier (BBB), creating communication sites for sensory or secretory neurons, involved in body homeostasis. Wnt/β-catenin signaling is essential for BBB development and maintenance in endothelial cells (ECs) in most CNS vessels. Here we show that in mouse development, as well as in adult mouse and zebrafish, CVO ECs rendered Wnt-reporter negative, suggesting low level pathway activity. Characterization of the subfornical organ (SFO) vasculature revealed heterogenous claudin-5 (Cldn5) and Plvap/Meca32 expression indicative for tight and leaky vessels, respectively. Dominant, EC-specific β-catenin transcription in mice, converted phenotypically leaky into BBB-like vessels, by augmenting Cldn5+vessels, stabilizing junctions and by reducing Plvap/Meca32+ and fenestrated vessels, resulting in decreased tracer permeability. Endothelial tightening augmented neuronal activity in the SFO of water restricted mice. Hence, regulating the SFO vessel barrier may influence neuronal function in the context of water homeostasis. In vertebrates, the endothelial blood-brain barrier (BBB) is crucial for providing a permissive microenvironment for neuronal function. During developmental brain vascularization, blood vessels undergo Wnt/β-catenin signaling, driven by Wnt7a/7b that is required for angiogenesis as well as for BBB formation (Daneman et al. , 2009; Stenman et al. , 2008; Liebner et al. , 2008). In the adult, the Wnt pathway remains instrumental to maintain BBB function in endothelial cells (ECs) of the central nervous system (CNS) (Zhou et al. , 2014). Herein activation of β-catenin/TCF signaling can be induced by two flavors of the canonical Wnt pathway mediated by the ligands Wnt7a/7b and the non-Wnt-related norrin disease protein (Ndp), binding to the receptor complexes frizzled-4/Lrp5/6/Gpr124/Reck and frizzled-4/Lrp5/6/Tspan12, respectively (Junge et al. , 2009; Chang et al. , 2017; Cullen et al. , 2011; Posokhova et al. , 2015; Kuhnert et al. , 2010; Wang et al. , 2014; Cho et al. , 2017; Vanhollebeke et al. , 2015; Eubelen et al. , 2018). Although a strict control of the exchange between blood and the CNS tissue by the endothelial BBB is realized in most parts of the CNS, some areas of the brain and the ciliary body of the eye are exceptions to this rule, providing a physiologically highly relevant door to the CNS. The circumventricular organs (CVOs) are a number of small midline structures found in all vertebrate brains, located","Infections and diseases in the brain and spine can be very damaging and debilitating. Indeed, the central nervous system also needs a carefully controlled biochemical environment to survive. As such, all animals with a backbone have barriers and defenses to protect and preserve this key system. One of these is the blood-brain barrier, a physical barrier between the brain and the outside world. Where most blood vessels allow relatively free exchange of chemicals between the blood and surrounding cells, the blood-brain barrier controls what can move between the bloodstream and the brain. Yet, there are gaps in the blood-brain barrier, specifically within structures in the brain called the circumventricular organs. These leaky vessels allow the brain cells in these regions to monitor the blood and respond to changes,",380,128,0.3368
dialogsum,"#Person1#: Have you seen the new Hannibal Lecter movie? #Person2#: Oh, yes. You? #Person1#: Yes. What did you think of it? #Person2#: I thought it was better than the others. I really liked it. What did you think of it? #Person1#: I liked it, too. It was scary, but not disgusting. I always enjoy watching Anthony Hopkins. He's brilliant. #Person2#: Mmm. That's what I thought, too. And I always enjoy watching Anthony Hopkins. #Person1#: Oh, yes, he is brilliant. What's the name of the young actor? #Person2#: Hum, Edward Norton, or something like that. #Person1#: Yes. He was excellent. They worked well together.",Both #Person2# and #Person1# like the new Hannibal Lecter movie and enjoy watching Anthony Hopkins.,103,15,0.1456
dialogsum,"#Person1#: They must have got in through the kitchen window. #Person2#: If only we'd remember to close it. #Person1#: I am afraid your diamond bracelet has gone, darling! #Person2#: I wish I'd put it in the bank. #Person1#: look! they've taken your fur coat too. #Person2#: I know, I am sorry I ever bought it. #Person1#: I noticed they've taken our radio and left the television.","#Person2#'s bracelet, fur coat, and radio were stolen.",66,8,0.1212
dialogsum,"#Person1#: Good morning. I'd like to ask some questions about your insurance policies. #Person2#: Of course. Please sit down. How can I help you? #Person1#: I bought a house recently and would like to insure it and its content. #Person2#: I see. Here's a pamphlet about our home insurance policy. We've named our policy ' umbrella '. May I ask how much you paid for your home and where you live? These are the two main thing that decide how much your premiums are. #Person1#: I understand. I live in the Oakfield area and paid $ 100, 000 for my home. #Person2#: Let me just check that on my computer. Oakfield is a low risk area, so your premiums will probably be around $ 100 a month. The other thing to take into account is deductibles. #Person1#: In this pamphlet it says that the minimum amount for deductibles is $ 2000. what does that mean exactly? #Person2#: It means that the first $ 2000 of any claim you make must be paid by you. The insurance policy covers any amount above that, up to the agreed limit. #Person1#: Oh, I see. That's fine. What is the advantage of having higher deductibles? #Person2#: If you have higher deductibles, your premium are lower, because you will pay more of the claim and we will pay less. #Person1#: It seems that I should do some calculations before deciding. I presume that the insurance period can be for as long as we agree. #Person2#: We initially sign one-year policies with our policyholders. These are renewable after the first year. #Person1#: If I have a claim, how long does it take to make a settlement? I've heard that with some insurance companies, it can take months. #Person2#: That is of great concern to out clients. We aim to satisfy all claims within a month, but we can't guarantee that.","#Person1# consults #Person2# about their insurance policies. #Person1# wants to insure #Person1#'s newly-bought house and its content. #Person2# asks for the price of the house and the address, then #Person2# explains the advantage of having higher deductibles. #Person1#'ll do some calculations before deciding.",314,43,0.1369
dialogsum,"#Person1#: Good evening, ma'am. Table for one? #Person2#: Yes, please. #Person1#: Will this table be all right? #Person2#: Actually, I'd like a booth by the window if that's possible. #Person1#: Certainly. How about this one? #Person2#: This will be fine, thanks. #Person1#: ( Handing her a menu ) Your waiter will be here in a minute to take your order. #Person2#: Thank you.",#Person1# helps #Person2# find a table by the window for dinner.,63,11,0.1746
dialogsum,"#Person1#: Hello, Lucy speaking. #Person2#: Hi, Lucy. This is Jack. Are you still going to the health club? #Person1#: Yes, why? #Person2#: Well, I went to the hospital yesterday, and my doctor suggested I do more exercise. #Person1#: I see. Why not join the club I'm going to. #Person2#: Is it good? #Person1#: Sure. Wonderful equipment, nice people, and it's not far from my home. #Person2#: What do you do there? #Person1#: Well, I often start by running, then swimming. #Person2#: Does the club offer training courses? #Person1#: Yes, basketball, tennis, dancing. You have a lot of choices. #Person2#: Sounds great. How often do you go there? #Person1#: Usually, twice a week. On Mondays and Thursdays. #Person2#: Not bad. I think I can manage. #Person1#: Hey, I'm going again tonight. Why not come along with me? #Person2#: OK. Where shall we meet? #Person1#: I'll wait for you in front of my house at 7:00. #Person2#: See you then.",Jack's doctor suggested he do more exercise. Lucy invites him to join the health club and tells him some information about it. They'll go there together tonight.,158,27,0.1709
scientific_lay_summarisation-elife-norm,"Arthropod-borne rickettsial pathogens cause mild and severe human disease worldwide. The tick-borne pathogen Rickettsia parkeri elicits skin lesions (eschars) and disseminated disease in humans; however, inbred mice are generally resistant to infection. We report that intradermal infection of mice lacking both interferon receptors (Ifnar1-/-; Ifngr1-/-) with as few as 10 R. parkeri elicits eschar formation and disseminated, lethal disease. Similar to human infection, eschars exhibited necrosis and inflammation, with bacteria primarily found in leukocytes. Using this model, we find that the actin-based motility factor Sca2 is required for dissemination from the skin to internal organs, and the outer membrane protein OmpB contributes to eschar formation. Immunizing Ifnar1-/-; Ifngr1-/- mice with sca2 and ompB mutant R. parkeri protects against rechallenge, revealing live-attenuated vaccine candidates. Thus, Ifnar1-/-; Ifngr1-/- mice are a tractable model to investigate rickettsiosis, virulence factors, and immunity. Our results further suggest that discrepancies between mouse and human susceptibility may be due to differences in interferon signaling. Obligate cytosolic bacterial pathogens in the family Rickettsiaceae are a diverse group of arthropod-borne microbes that cause severe human disease worldwide, including spotted fever, scrub typhus, and typhus (Bonell et al. , 2017; Fang et al. , 2017; Sahni et al. , 2019). Human disease caused by the tick-borne spotted fever group (SFG) pathogen Rickettsia parkeri is characterized by a necrotic, dry skin lesion (eschar) at the infection site, as well as generalized rash, headache, fatigue, and fever (Paddock et al. , 2008). There is no approved vaccine for R. parkeri or for the more virulent rickettsial pathogens that can cause fatal or latent disease (Osterloh, 2017). Moreover, many critical aspects of disease caused by obligate cytosolic bacterial pathogens, including the mechanisms of virulence and immunity, remain unknown. R. parkeri can be handled under biosafety level 2 (BSL2) conditions, and characterizing mouse models to recapitulate major features of human disease would enhance research efforts into understanding rickettsial pathogens and disease (Osterloh, 2017; Grasperge et al. , 2012; Sunyakumthorn et al. , 2013). R. parkeri is genetically similar to the more virulent human pathogens R. rickettsii and R. conorii (Roux and Raoult, 2000; Goddard, 2009), and it can be handled under BSL2 conditions. Moreover, mutants can be generated using transposon mutagenesis (Reed et al. , 2014; Lamason et al. , 2018), and small rodents","Tick bites allow disease-causing microbes, including multiple species of Rickettsia bacteria, to pass from arthropods to humans. Being exposed to Rickettsia parkeri, for example, can cause a scab at the bite site, fever, headache and fatigue. To date, no vaccine is available against any of the severe diseases caused by Rickettsia species. Modelling human infections in animals could help to understand and combat these illnesses. R. parkeri is a good candidate for such studies, as it can give insight into more severe Rickettsia infections while being comparatively safer to handle. However, laboratory mice are resistant to this species of bacteria, limiting their use as models. To explore why this is the case, Burke et al. probed whether an immune mechanism known as interferon signalling protects laboratory rodents against",380,128,0.3368
dialogsum,"#Person1#: Mr. Smith, our history professor, announced we would be doing two papers and three exams this semester. I wonder how I'm going to pull through when two other courses have similar requirements. #Person2#: Well, can't you drop one course and pick it up next semester?",#Person1# worries that #Person1# can't pull through all the courses this semester. #Person2# advises #Person1# to drop or postpone one course.,46,21,0.4565
pubmed-summarization,"legends . for hormone - stimulated lipolysis , bt2-camp ( 100 mol / l ) was added to culture medium and cells were incubated for 1 h. total protein was used for certain protein or protein phosphorylation measurements using western blots . for pka rii protein half - life measurement , cycloheximide ( 100 g / ml ) was used to inhibit protein synthesis . for the in vivo lipolysis assays , the selective 3-adrenergic agonist brl37344 was injected i.p . into mice at 5 g / g body blood samples were collected 0 , 10 , and 20 min after the injection . for the lipolysis assay of adipose explants , 20 mg of epididymal adipose tissue explants were cultured in dulbecco s modified eagle s medium with 0.5% fatty acid brl37344 was added to the medium at 50 ng / ml . the culture tubes were shaken at 400 rpm . the medium samples were collected 30 , 60 , 120 , and 180 min after adding brl37344 . the level of free fatty acid ( ffa ) or glycerol was normalized to the weight of adipose explants . for primary adipocyte lipolysis assays , adipocytes were prepared from epididymal fat using collagenase with an optimized procedure ( 11,12 ) . briefly , epididymal fat tissue was minced and digested in a krebs - ringer bicarbonate ( krb ) buffer ( ph 7.4 ) supplemented with 3% fatty acid free bsa fraction v , 0.5 mmol / l adenosine , and 1 mg / ml type i collagenase . after 40-min digestion and three washes , isolated adipocytes were resuspended in krb supplemented with 5 mmol / l glucose and 3% fatty acid . suspended adipocytes ( 6,000 cells ) were used for a lipolysis assay in 400 l krb buffer plus 3% fatty acid free bsa , 1 unit / ml adenosine deaminase , and 100 nmol / l ( -)-n-(2-phenyl - isopropyl)-adenosine ( basal only ) with or without brl37344 ( 50 ng / ml ) . after 1-h incubation at 37c , 200 l of infranatant was removed and stored at 20c . serum free glycerol and glycerol released from fat explants were measured using a free - glycerol kit ( sigma - aldrich co.","objectiveadiponectin is an adipocyte - derived hormone that sensitizes insulin and improves energy metabolism in tissues . this study was designed to investigate the direct regulatory effects of adiponectin on lipid metabolism in adipocytes.research design and methodsbasal and hormone - stimulated lipolysis were comparatively analyzed using white adipose tissues or primary adipocytes from adiponectin gene knockout and control mice . to further study the underlying mechanisms through which adiponectin suppresses lipolysis , cultured 3t3-l1 adipocytes and adenovirus - mediated gene transduction were used.resultssignificantly increased lipolysis was observed in both adiponectin gene knockout mice and primary adipocytes from these mice . hormone - stimulated glycerol release was inhibited in adiponectin - treated adipocytes . adiponectin suppressed hormone - sensitive lipase activation without altering adipose triglyceride lipase and cgi-58 expression",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The cutaneous wound-healing program is a product of a complex interplay among diverse cell types within the skin. One fundamental process that is mediated by these reciprocal interactions is the mobilization of local stem cell pools to promote tissue regeneration and repair. Using the ablation of epidermal caspase-8 as a model of wound healing in Mus musculus, we analyzed the signaling components responsible for epithelial stem cell proliferation. We found that IL-1α and IL-7 secreted from keratinocytes work in tandem to expand the activated population of resident epidermal γδT-cells. A downstream effect of activated γδT-cells is the preferential proliferation of hair follicle stem cells. By contrast, IL-1α-dependent stimulation of dermal fibroblasts optimally stimulates epidermal stem cell proliferation. These findings provide new mechanistic insights into the regulation and function of epidermal cell–immune cell interactions and into how components that are classically associated with inflammation can differentially influence distinct stem cell niches within a tissue. One of the main functions of the skin is to provide the body with a barrier against external assaults while preventing excessive loss of moisture. As a result, the skin is constantly regenerating itself, but once this barrier has been breached through injury, a wound-healing response is rapidly mobilized to restore this barrier. The wound-healing response is a complex process that relies on the careful orchestration of signals coming from various cell types. Following injury, three sequential but overlapping phases are initiated, commencing with inflammation, followed by proliferation of stem cells and concluding with tissue remodeling. Despite their temporal differences, there is significant interdependence among these phases that enables the restoration of tissue function (Gurtner et al. , 2008). One such interdependency is the interaction between the inflammation and proliferation phases, which can be mediated by members of the interleukin-1 (IL-1) family of cytokines (Dinarello, 2009). However, the mechanism (s) by which IL-1 proteins mediate proliferation of different cell types within the repairing organ remain to be elucidated. Epidermal keratinocytes are a rich source of IL-1α, which is released upon tissue damage (Lee et al. , 1997). Unlike IL-1β, which must be proteolytically processed into its active form, IL-1α is active as a zymogen and, upon secretion from epidermal keratinocytes, can play key roles in the early inflammatory phase of the wound-healing response (Bianchi, 2007). In addition,","The skin is a physical barrier that protects the body from the outside world. If the skin is injured, the body mounts a “wound healing” response to rapidly mend and restore this protective barrier. Wound healing is a complex process and relies on the different types of cells in the skin communicating with each other. Stem cells provide tissues, like the skin, with new cells. Normally, stem cells are in a resting or inactive state. Yet, during wound healing, stem cells near the injured area are awakened and start producing more cells to repair the wound. Understanding how stem cells become activated in a wound has proved challenging because only a small number of cells near a damaged site will respond, and it is difficult to distinguish their",380,128,0.3368
pubmed-summarization,"comparar las mediciones de la presin intraocular ( pio ) obtenidas con el tonmetro de rebote ( rt ) , el tonmetro de contorno dinmico ( dct ) y el tonmetro de aplanamiento de goldmann ( gat ) en crneas con queratocono , e investigar los efectos del espesor central de la crnea ( cct ) y los radios de curvatura de la crnea ( cr ) en las mediciones de la pio . este estudio transversal se realiz sobre sesenta y tres ojos de un nmero igual de pacientes con queratocono . se midi la pio de cada sujeto siempre en el mismo orden , icare rt - pascal dct - gat , tras un intervalo mnimo de diez minutos entre mediciones . las mediciones de cct y cr se realizaron utilizando una cmara scheimpflug rotatoria , antes de medir la pio en todos los sujetos . se utilizaron los anlisis de coeficiente de correlacin de pearson y la anova de una va de medidas repetidas para realizar la valoracin estadstica . la pio media para todos los ojos estudiados fue de 11,72 2,59 mm hg para gat , 9,34 3,29 mm hg para rt , y 15,42 3,31 mm hg para dct . se produjeron diferencias estadsticamente significativas entre los tres tonmetros ; gat y rt ( p<0,001 ) , gat y dct ( p<0,001 ) , rt y dct ( p<0,001 ) . gat y rt reflejaron una relacin significativamente positiva con cct ( r=0,288 , p=0,025 y r=0,483 , p<0,001 , respectivamente ) . dct no reflej una correlacin significativa con cct ( r=0,115 , p=0,377 ) ni con cr ( r=0,179 , p=0,168 ) . el tonmetro dct sobreestim las mediciones de la pio , y el rt subestim las mismas , con arreglo a las mediciones de gat en las crneas con queratocono . dct ha demostrado ser el tonmetro ms adecuado para utilizar en las mediciones de la pio en los casos de queratocono , ya que no parece depender de cct y cr . proper measurement of intraocular pressure ( iop ) is fundamental in the diagnosis and follow - up of glaucoma because elevated iop is the basic treatable risk factor in the management of glaucoma . the goldmann applanation tonometer","purposeto compare the intraocular pressure ( iop ) measurements obtained with the rebound tonometry ( rt ) , dynamic contour tonometry ( dct ) and goldmann applanation tonometry ( gat ) in keratoconic corneas and to investigate the effects of central corneal thickness ( cct ) and corneal radius of curvature ( cr ) on iop measurements.methodssixty-three eyes of 63 keratoconus patients were enrolled in this cross - sectional study . iop was measured on each subject always in the same order , icare rt - pascal dct - gat , after a minimum interval of 10 min between measurements . cct and cr were measured using a rotating scheimpflug camera before the iop measurements in all subjects . one way repeated measures anova and pearson correlation coefficient",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Temperate bacteriophages are viruses that can incorporate their genomes into their bacterial hosts, existing there as prophages that refrain from killing the host cell until induced. Prophages are largely quiescent, but they can alter host phenotype through factors encoded in their genomes (often virulence factors) or by disrupting host genes as a result of integration. Here we describe another mechanism by which a prophage can modulate host phenotype. We show that a temperate phage that integrates in Escherichia coli reprograms host regulation of an anaerobic respiratory system, thereby inhibiting a bet hedging strategy. The phage exerts this effect by upregulating a host-encoded signal transduction protein through transcription initiated from a phage-encoded promoter. We further show that this phenomenon occurs not only in a laboratory strain of E. coli, but also in a natural isolate that contains a prophage at this site. Bacteria and the phages that infect them have a generally antagonistic relationship, with evolution arming each side to defeat the other. Sometimes, though, a bacterium and a temperate phage can form an uneasy truce through lysogeny, wherein the integrated prophage confers some beneficial attribute to its host cell that provides a fitness advantage; after all, unless the host cell dies on the phage’s own terms, the phage dies too. Prophage alteration of host phenotype, known as lysogenic conversion (Lederberg, 1955), can benefit the host by conferring abilities to produce toxins, resist antibiotics, increase virulence, and repel further phage infections (for recent reviews, see Argov et al. , 2017; Bondy-Denomy and Davidson, 2014; Davies et al. , 2016; Fortier and Sekulovic, 2013; Harrison and Brockhurst, 2017; Howard-Varona et al. , 2017; Obeng et al. , 2016; and Touchon et al. , 2017). Oftentimes these traits are encoded within prophage genetic elements called morons, which contain genes that are regulated by their own promoters and are not involved in the phage lytic cycle (Hendrix et al. , 2000; Juhala et al. , 2000). Although lysogenic conversion has been under study since its first description nearly 100 years ago (Frobisher and Brown, 1927), there are likely entire classes of phage-encoded proteins that impact host fitness in as-yet-undescribed ways, as most phage genes have unknown function and no homology to any genes with known function. Phages can alter their hosts’ behavior in more","Animals and plants can all fall prey to viruses – and so can bacteria. The viruses that infect bacteria are called bacteriophages (or phages for short), and they are found everywhere bacteria live and probably outnumber bacteria by at least ten to one. While some phages quickly kill every bacterial cell they infect, others enter a dormant state by inserting their DNA into the DNA of their host cell. Here they lie in wait for a signal that reactivates them, triggering the production of more phages and the death of the host cell. While the phage lies dormant its DNA may harm the host by interfering with nearby bacterial genes, or it may actually provide new genes that benefit the host. In most cases the effects of dormant",380,128,0.3368
dialogsum,"#Person1#: Bob, can I talk to you for a minute? There have been some developments for the Stewart case that I really need to talk to you about. #Person2#: Yeah, what's the matter now? We've had so much trouble with this case already. Don't tell me there's more bad news. #Person1#: Well, I'm afraid there is. I have some bad news for you about the results of the forensic tests. . . there won't be any results. #Person2#: What? What does that mean? Why won't there be any results? #Person1#: I hate to tell you this, but it seems that every shred of evidence that would help us to convict were destroyed in a laboratory fire. There's nothing left. I'm so sorry. . . #Person2#: Oh, no, you can't be serious. I never expect anything like this would happened. What are we going to do? #Person1#: There's nothing that can be done. Everything is gone. I wish I could tell you differently, but what has happened has happened. We will just have to out a way to move on.",#Person1# tells Bob that there won't be any results of the forensic tests because it was all destroyed in a laboratory fire. Bob feels shocked and cannot accept it.,179,29,0.162
dialogsum,"#Person1#: Would you like to go sightseeing tomorrow? #Person2#: Not a bad idea! #Person1#: What would you like to see in Beijing? #Person2#: Well, let's see. I'd like to go to the Summer Palace. #Person1#: I'll pick you up here tomorrow.",#Person1# will take #Person2# to the Summer Palace tomorrow.,41,9,0.2195
scientific_lay_summarisation-elife-norm,"this gap by combining publicly available information on country-level mortality, culled and harmonized from various sources. Several teams have already started to collect such data. In April 2020, EuroStat (http: //ec. europa. eu/eurostat) began collecting total weekly deaths across European countries, ‘in order to support the policy and research efforts related to COVID-19’. At the time of writing, this dataset covers 36 European countries and also contains sub-national (NUTS1–3 regions) data as well as data disaggregated by age groups and by sex for some countries. In May 2020, the Human Mortality Database (http: //mortality. org), a joint effort by the University of California, Berkeley, and Max Planck Institute for Demographic Research (Barbieri et al. , 2015), started compiling the Short Term Mortality Fluctuations (STMF) dataset (STMF, 2021; Islam et al. , 2021; Németh et al. , 2021). This dataset consists of weekly data, disaggregated by five age groups and by sex, and currently contains 35 countries with 2020 data. STMF only includes countries with complete high-quality vital registration data in all age groups. Both datasets are regularly updated and have considerable overlap, covering together 44 countries. In parallel, the EuroMOMO project (https: //www. euromomo. eu), existing since 2008, has been displaying weekly excess mortality in 23 European countries, but without giving access to the underlying data. Another source of data is the UNDATA initiative (http: //data. un. org; search for ‘Deaths by month of death’) by the United Nations, collecting monthly mortality data across a large number of countries. However, information there is updated very slowly, with January–June 2020 data currently available for only four countries. Media outlets such as the Financial Times, The Economist, the New York Times, and the Wall Street Journal have been compiling and openly sharing their own datasets in order to report on the all-cause mortality in 2020. However, these datasets are infrequently updated and their future is unclear. For example, the New York Times announced in early 2021 that they would stop tracking excess deaths due to staffing changes. Here, we present the World Mortality Dataset that aims to provide regularly-updated all-cause mortality numbers from all over the world. The dataset is openly available at https: //github. com/akarlinsky/world_mortality and is updated almost daily. Our dataset builds upon the EuroStat and the STMF datasets, adding","Countries around the world reported 4. 2 million deaths from SARS-CoV-2 (the virus that causes COVID-19) from the beginning of pandemic until the end of July 2021, but the actual number of deaths is likely higher. While some countries may have imperfect systems for counting deaths, others may have intentionally underreported them. To get a better estimate of deaths from an event such as a pandemic, scientists often compare the total number of deaths in a country during the event to the expected number of deaths based on data from previous years. This tells them how many excess deaths occurred during the event. To provide a more accurate count of deaths caused by COVID-19, Karlinsky and Kobak built a database called the World Mortality Dataset. It includes information",380,128,0.3368
dialogsum,"#Person1#: Charlotte, have you had your supper? #Person2#: No, I don't want to eat anything. #Person1#: Why? Don't you feel well? #Person2#: I'm down in spirits. #Person1#: What's up? #Person2#: My manager jumped on me for my mistake today. #Person1#: You must not feel depressed about such a trivial thing. #Person2#: I think I'm too clumsy. I can do nothing well. #Person1#: You'd better shape up if you want to get the job done. #Person2#: But I doubt myself. #Person1#: Cheer up! Don't let me down. We all make mistakes, and that is life.",Charlotte is down in spirits because her manager blamed her for her mistake. #Person1# encourages her.,94,16,0.1702
scientific_lay_summarisation-elife-norm,"et al. , 2014). Consistent with this idea, general activation of bulbar inhibitory neurons can accelerate learning (Abraham et al. , 2010), while suppression of inhibitory neuron activity can increase the excitability of MCs and reduce MC pattern separation (Gschwend et al. , 2015). Thus, local inhibitory neurons in the olfactory bulb, including ABNs, likely control olfactory perception by providing inhibition onto MCs. As ABNs integrate into local circuits, they display higher levels of morphological and functional plasticity during the first ~8 weeks after their birth compared to their later mature stage (Kelsch et al. , 2009; Mizrahi, 2007; Nissant et al. , 2009; Sailor et al. , 2016). Furthermore, the spine dynamics, synaptic plasticity, sensory response pattern, as well as survival rate of ABNs are influenced by olfactory experience during this early period (Alonso et al. , 2006; Lemasson et al. , 2005; Lepousez et al. , 2014; Livneh et al. , 2014; Mouret et al. , 2008; Petreanu and Alvarez-Buylla, 2002; Quast et al. , 2017; Rochefort et al. , 2002; Yamaguchi and Mori, 2005). These unique and plastic features of young ABNs make it likely that they play a unique role in the processing of the complex and dynamic olfactory environment. Indeed, some studies have shown that ABNs are essential for certain olfactory behaviors such as odor discrimination and association reversal learning (Alonso et al. , 2012; Bath et al. , 2008; Enwere et al. , 2004; Gheusi et al. , 2000; Moreno et al. , 2009; Sakamoto et al. , 2014). However, other studies have found little effects of ABN manipulation on odor discrimination (Breton-Provencher et al. , 2009; Imayoshi et al. , 2008; Lazarini et al. , 2009). Thus, ABNs are not essential for all olfactory processing. Instead, the inconsistencies between these results raise the possibility that the impact of ABNs may depend on the behavioral context. Consistent with the idea that the functions of ABNs are context-dependent, local inhibitory neurons in the olfactory bulb including ABNs receive abundant glutamatergic centrifugal inputs from higher brain areas such as anterior olfactory nucleus, piriform cortex and entorhinal cortex (Balu et al. , 2007; Boyd et al. , 2015,2012; Chapuis et al. , 2013; Kiselycznyk et al. , 2006; Markopoulos et al. , 2012; Nunez-Parra et al. ,","Most brain cells or neurons form early in life. Yet, in some parts of the brain, new neurons develop throughout adulthood, in a process called adult neurogenesis. These new neurons are incorporated into existing brain circuits and likely help the brain process information. In rodents, adult neurogenesis produces many new cells in the olfactory bulb, a part of the brain that processes smells. This is likely because the sense of smell is important for the survival of these animals. What these adult-born neurons do and how they aid the rodent’s sense of smell is not clear. Previous studies have had conflicting results about whether these cells help animals distinguish smells and under what circumstances. More studies about how these adult-born neurons become incorporated in the brain and how",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Human visual recognition activates a dense network of overlapping feedforward and recurrent neuronal processes, making it hard to disentangle processing in the feedforward from the feedback direction. Here, we used ultra-rapid serial visual presentation to suppress sustained activity that blurs the boundaries of processing steps, enabling us to resolve two distinct stages of processing with MEG multivariate pattern classification. The first processing stage was the rapid activation cascade of the bottom-up sweep, which terminated early as visual stimuli were presented at progressively faster rates. The second stage was the emergence of categorical information with peak latency that shifted later in time with progressively faster stimulus presentations, indexing time-consuming recurrent processing. Using MEG-fMRI fusion with representational similarity, we localized recurrent signals in early visual cortex. Together, our findings segregated an initial bottom-up sweep from subsequent feedback processing, and revealed the neural signature of increased recurrent processing demands for challenging viewing conditions. The human visual system interprets the external world through a cascade of visual processes that overlap in space and time. Visual information is transformed not only feedforward, as it propagates through ascending connections, but also from higher to lower hierarchy areas through descending feedback connections and within the same areas through lateral connections (Ahissar et al. , 2009; Bullier, 2001; Enns and Di Lollo V, 2000; Lamme and Roelfsema, 2000; Lamme et al. , 1998). This concurrent activation of a dense network of anatomical connections poses a critical obstacle to the reliable measurement of recurrent signals and their segregation from feedforward activity. As a result, our knowledge on the role of recurrent processes and how they interact with feedforward processes to solve visual recognition is still incomplete. Here we used an ultra-rapid serial visual presentation (ultra-RSVP) of real-world images to segregate early bottom-up from recurrent signals in the ventral pathway. We postulated that, under such rapid stimulus presentations, visual processes will degrade substantially by suppressing sustained neural signals that typically last hundreds of milliseconds. As a result, neural signals would become transient, reducing the overlap of processes in space and time and enabling us to disentangle distinct processing steps. Recent behavioral evidence exemplified the remarkable robustness of the human visual system to capture conceptual information in stimuli presented at similar rates (Broers et al. , 2018; Evans et al. ,","The human brain can interpret the visual world in less than the blink of an eye. Specialized brain regions process different aspects of visual objects. These regions form a hierarchy. Areas at the base of the hierarchy process simple features such as lines and angles. They then pass this information onto areas above them, which process more complex features, such as shapes. Eventually the area at the top of the hierarchy identifies the object. But information does not only flow from the bottom of the hierarchy to the top. It also flows from top to bottom. The latter is referred to as feedback activity, but its exact role remains unclear. Mohsenzadeh et al. used two types of imaging to map brain activity in space and time in healthy",380,128,0.3368
dialogsum,"#Person1#: Royal Hotel, can I help you? #Person2#: Yes. I urgently need a room for tomorrow night, and do you have any vacancies? #Person1#: Yes, we have. What kind of room would you like? #Person2#: I'd like a suite with an ocean view, please. #Person1#: No problem, sir.",#Person1# helps #Person2# book a suite for tomorrow night.,48,9,0.1875
dialogsum,"#Person1#: What's the matter, dear? #Person2#: Something awful happened. We went to the Portobello Road, and someone stole my handbag. #Person1#: Oh, dear. Did you lose a lot of money? #Person2#: No. Only a few pounds. But my passport was in the bag. That'what I'm really worry about. #Person1#: You must tell the embassy about it. And I think they'll issue you with a new one. #Person2#: I'd better go tomorrow. #Person1#: No. But you mustn't leave it too long. Did you report it the police? #Person2#: No. I couldn't find a policeman. #Person1#: Well. You must report that it's been stolen. And give the police description of your bag. You'd better go to the local police station tomorrow morning. #Person2#: Yes. I'll do it tomorrow. #Person1#: And Lisa. #Person2#: Yes? #Person1#: Don't be too upset. It's not the end of the world.",Lisa tells #Person1# she's upset because her bag with her passport was stolen. #Person1# suggests she report to the police and tell the embassy about it.,143,26,0.1818
dialogsum,"#Person1#: Isn't this lovely weather? Will you help me water the flowers, Jack? #Person2#: Well, do you think I have to? #Person1#: I do. We haven't watered them for quite a few days. #Person2#: Please look at the sky. Don't you see the dark clouds? It's going to rain soon. #Person1#: Good. So we don't have to work. How nice! #Person2#: But I don't think it's so nice. #Person1#: Why? #Person2#: The weather report says it's going to rain for a whole week. #Person1#: Oh, I'm afraid all the flowers will die in the rain.",#Person1# requests Jack to help water the flowers but Jack tells #Person1# it's going to rain for a whole week.,95,20,0.2105
scientific_lay_summarisation-elife-norm,"that the female’s Tdc2 (octopaminergic) neurons make on the musculature of the oviduct above the amount seen in unmated females (Rubinstein and Wolfner, 2013). This is thought to sustain high octopaminergic (OA) signaling on the oviduct musculature of mated female, allowing increased ovulation to persist in mated female, even after ovulin is no longer detectable in the female. Therefore, males mating with previously mated females need transfer less ovulin than males mated to virgin females, presumably because it may be less necessary, as they benefit from the ovulation stimulating effect of ovulin from the prior mating. In another example, prior receipt of Acp36DE can rescue sperm storage of a male that lacks this SFP (Avila and Wolfner, 2009; Chapman et al. , 2000). The benefits to the second male described above are indirect consequences of the first male’s SFPs' effects on female’s physiology. The second male is thus the lucky beneficiary of the first male’s SFPs' actions. However, it is unknown whether a male could directly benefit from a rival’s SFPs, for example, whether the latter could associate with and improve the success of another male’s sperm. There was some suggestion that this might occur from the phenomenon of ‘copulation complementation’ (Xue and Noll, 2000), in which a female Drosophila singly-mated to a male lacking SFPs did not produce progeny unless she remated to a male who provided SFPs. That finding suggested that something from the second mating allowed the first male’s sperm to be used. However, the molecular basis for this phenomenon was unknown. The relevance of such ‘complementation’ to male reproductive fitness was strengthened by several sperm competition studies, that suggested that a male’s reproductive success could benefit from a rival’s SFPs. For example, Avila et al. , 2010 reported that the sperm of SP-null males were better at defensive sperm competition than the sperm of control males. Specifically, females mated to SP-null males and then subsequently remated to a wildtype (wt) competitor produced significantly more progeny from the first male (P1) relative to the P1 of control males who had mated to females before the wt competitor. The higher P1 of SP-null males in this situation likely occurred because at the time of the second mating, the mates of SP-null males contained more of his sperm compared","When fruit flies and other animals reproduce, a compatible male and a female mate, allowing sperm from the male to swim to and fuse with the female’s egg cells. The males also produce proteins known as seminal proteins that travel with the sperm. These proteins increase the likelihood of sperm meeting an egg and induce changes in the female that increase the number, or quality, of offspring produced. Some seminal proteins help a male to compete against its rivals by decreasing their chances to fertilize eggs. However, since many of the changes seminal proteins induce in females are long-lasting, it is possible that a subsequent male may actually benefit indirectly from the effects of a prior male’s seminal proteins. It remains unclear whether the seminal proteins of one",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the impression that the proximal VH gene usage predominates and that there is little N-addition in the B-1a IgH repertoire. Later studies by the Rajewsky group, however, showed that although neonatal (4 day) splenic B-1a cells contain very few N-insertions, N addition is readily detected in substantial numbers of peritoneal B-1a cells from adult animals (Gu et al. , 1990), indicating that B-1a cells are continuously generated after Tdt is expressed. Holmberg lab similarly found the low N-region diversity in the adult peritoneal B-1a repertoire (Tornberg and Holmberg, 1995). Our early studies confirm and extend these findings by showing that roughly two thirds of the IgH sequences from individually sorted peritoneal B-1a cells have N additions (Kantor et al. 1997). Furthermore, recent studies have shown that B-1a progenitors from both fetal liver and adult BM sources generate peritoneal B-1a cells with substantial N-addition (Holodick et al. , 2014). Collectively, these findings demonstrate that the peritoneal B-1a IgH repertoire diversity is greater than previously thought. However, these studies mainly characterized the repertories of B cells in the peritoneal cavity (PerC) and leave the questions open as to whether and how the repertoire changes throughout ontogeny in B cells at various sites of development and function. Studies here address these issues. We show that the B-1a IgH repertoire differs drastically from the repertories expressed by splenic FOB, MZB and peritoneal B-2 cells. In addition, we track the development of B-1a cells from their early appearance in neonatal spleen to their long-term residence in adult peritoneum and spleen, and elucidate the previous unrecognized somatic mechanisms that select and diversify the B-1a IgH repertoire over time. Most importantly, the potent mechanisms that uniquely act in B-1a (not in FOB and MZB cells) operate comparably in germ-free (GF) and conventional mice reared under specific pathogen free (SPF) condition, indicating that these repertoire-defining mechanisms are not driven by microbiota-derived antigens. The dearth of these advanced understandings in the previous studies is largely due to technical difficulties that limited both their scope and depth. Studies analyzing Ig sequences from immortalized cell lines (e. g. , hybridomas) or LPS-stimulated B cells had obvious sampling biases. In addition, earlier studies mainly focused on particular VH families (e. g. , J558,7183), even though the mouse IgH locus contains over 100","Our immune system protects us by recognizing and destroying invading viruses, bacteria and other microbes. B cells are immune cells that produce protective proteins called antibodies to stop infections. These cells are activated by ‘antigens’, which are fragments of molecules from the microbes or from our own cells. When an antigen binds to a B cell, the cell matures, multiplies and produces proteins called antibodies. These antibodies can bind to the antigen, which marks the microbe for attack and removal by other cells in the immune system. Each antibody consists of two ‘heavy chain’ and two ‘light chain’ proteins. B cells are able to produce a large variety of different antibodies due to the rearrangement of the gene segments that encode the heavy and light chains. In mice,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2007). In these cases, CSCs have been characterized by the ability to establish disease in immunocompromised mice, to resist chemotherapeutics, the capability of both self-renewal and differentiation into the full complement of heterogeneous neoplastic cells that comprise the tumor, and the propensity to metastasize. In each case, CSCs are distinguished from other tumor cell types by the expression of various, sometimes divergent cell surface markers. Our lab was the first to identify pancreatic cancer stem cells (PCSCs), which were found to express the markers EPCAM (ESA), CD44, and CD24 (Li et al. , 2007). In addition to these markers, CD133 (Hermann et al. , 2007), CXCR4 (Hermann et al. , 2007), c-MET (Li et al. , 2011), aldehyde dehydrogenase 1 (ALDH1) (Kim et al. , 2011), and autofluorescence (Miranda-Lorenzo et al. , 2014) have all been proposed markers of PCSCs. In all cases, the identified cells are characterized by being able to form spheres of cells (tumorspheres) under non-adherent, serum-free conditions, as well as an increased ability to form tumors in mice compared to bulk tumor cells. While a number of markers have been identified for PCSCs, relatively little is known about the transcriptional platforms that govern their function and set them apart from the majority of bulk PDA cells. Transcriptional regulators such as NOTCH (Wang et al. , 2009; Abel et al. , 2014), BMI1 (Proctor et al. , 2013), and SOX2 (Herreros-Villanueva et al. , 2013) have been demonstrated to play roles in PCSCs, although these proteins are also critical for normal stem cell function in many tissues. In this study, we sought to better understand the biological heterogeneity of PCSCs and their bulk cell counterparts in an effort to identify novel regulators of PCSCs in the context of low-passage, primary patient-derived PDA cells. Using microarray analysis and comparing primary PDA cell subpopulations with different levels tumorigenic potential and stem-cell-like function, we identified hepatocyte nuclear factor 1-alpha (HNF1A), an endoderm-restricted transcription factor, as a key regulator of the PCSC state. Supporting this hypothesis, depletion of HNF1A resulted in a loss of PCSC marker expression and functionality both in vitro and in vivo. Additionally, ectopic expression of HNF1A augmented PCSC properties in PDA cells and enhanced growth and anchorage-independence in normal pancreatic cell lines. Mechanistically, we found that HNF1A","Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer. It is also one of the deadliest types of cancer: fewer than one in ten patients live for five years after being diagnosed with the disease. Several reasons can explain this poor outcome including that the cancer is often diagnosed late, when tumor cells have already spread, and that there are not many effective treatments for it. Pancreatic tumors contain different types of cancer cells with different properties. Among these are the so-called pancreatic cancer stem cells. These aggressive cells produce copies of themselves, contributing to tumor growth and spread. They can also help tumors to resist chemotherapy and radiotherapy. New treatments that specifically target cancer stem cells could therefore prove important for treating pancreatic cancer. It",380,128,0.3368
scientific_lay_summarisation-elife-norm,"severe infectious disease in UK general population settings. Exploiting the shared risk factor relation between susceptibility to severe COVID-19 and pneumonia (Ho et al. , 2020), we used well-powered statistical analyses of biomarkers with severe pneumonia events to develop a multi-biomarker score that condenses the information from the metabolic measures into a single multi-biomarker score. Taking advantage of the time-resolved information on the occurrence of severe pneumonia events in the UK Biobank, we mimicked the influence of the decade lag from blood sampling to the COVID-19 pandemic on the biomarker associations, and used analyses with short-term follow-up to interpolate to a scenario of identifying individuals susceptible to severe COVID-19 in a preventative screening setting. Our primary aim was to improve the molecular understanding on how metabolic risk markers may contribute to increased predisposition to severe COVID-19 and other infections. 2A shows the associations of 37 biomarkers with severe pneumonia events occurring during the follow-up in the entire study population (n = 105 146). The biomarkers highlighted here are those with a regulatory approval for diagnostics use in the Nightingale Health NMR platform. These biomarkers span most of the different metabolic pathways captured with the NMR platform; results for all 249 metabolic measures quantified are shown in —supplements 1–3. Strong associations were observed across several metabolic pathways: increased plasma concentrations of cholesterol measures, omega-3 and omega-6 fatty acid levels, histidine, branched-chain amino acids and albumin were associated with lower susceptibility to contracting severe pneumonia. Increased concentrations of monounsaturated and saturated fatty acids, as well glycoprotein acetyls (GlycA, a marker of low-grade inflammation) were associated with elevated susceptibility to contracting severe pneumonia. Since all the biomarkers are quantified in the same single measurement, we examined if even stronger associations with severe pneumonia could be obtained using a combination of multiple biomarkers. We derived this multi-biomarker combination, denoted ‘infectious disease score’, using logistic regression with LASSO for variable selection, considering the 37 clinically validated biomarkers in a half of the study population as the training set. This resulted in an infectious disease score comprised of the weighted sum of 25 biomarkers, with the weights selected by the machine learning algorithm (Supplementary file 1). Broadly similar results were obtained using all 249 metabolic measures quantified in the Nightingale Health NMR platform to derive the","National policies for mitigating the COVID-19 pandemic include stricter measures for people considered to be at high risk of severe and potentially fatal cases of the disease. Although older age and pre-existing health conditions are strong risk factors, it is poorly understood why susceptibility varies so widely in the population. People with cardiometabolic diseases, such as diabetes and liver diseases, or chronic inflammation are at higher risk of severe COVID-19 and other infections including pneumonia. These conditions alter the molecules circulating in the blood, providing potential ‘biomarkers’ to determine whether a person is more likely to develop a fatal infection. Uncovering these blood biomarkers could help to identify people who are prone to life-threatening infections despite not having ever been diagnosed with a cardiometabolic disease. To find these",380,128,0.3368
pubmed-summarization,"distal anterior cerebral artery aneurysms , also known as pericallosal artery ( pa ) aneurysms , are located on the anterior cerebral artery distal to the anterior communicating artery . these aneurysms represent approximately 6% of all intracranial aneurysms and 4% of those that rupture49 ) . furthermore , they were similarly represented in the international subarachnoid aneurysm trial ( isat ) study population , in which they accounted for 95 of the 2143 patients randomized ( 4.4%)14 ) . pa aneurysms present several problems for direct surgical clipping , that is , difficult exposure via an interhemispheric approach , especially in a swollen brain after subarachnoid hemorrhage ( sah ) , sacrifice of a bridging vein for adequate surgical exposure ( thus increasing the risk of postoperative morbidity ) , difficult controlling the parent artery , and the unfavorable orientation of the aneurysm fundus . as a consequence , surgical morbidity has been reported to be relatively high , with incidences ranging from 0 to 25%141221 ) . advances in endovascular techniques and devices have led to the rapid evolution of coil embolization of ruptured and unruptured intracranial aneurysms , and it has now become an efficient treatment technique that is comparable to surgical clipping . however , because of their distal location and the small diameter of the parent vessel , pa aneurysms pose a technical challenge for endovascular therapy and , as is the case for most bifurcation cerebral aneurysms , have a potential high recurrence rate18 ) . a search of the literature revealed relatively few studies have been performed on the endovascular treatment of ruptured pa aneurysms , and that the studies performed involved relatively small numbers of patient . accordingly , it is evident that the effectiveness and safety of the endovascular treatment of ruptured pa aneurysms have not been well - defined . here , we present 30 patients that were treated endovascularly for a ruptured pa aneurysm and describe their clinical and radiologic outcomes . we retrospectively analyzed the angiographic and clinical records of all patients that underwent endovascular treatment for a ruptured pa aneurysm at our institution from september 2003 to december 2013 . the treatment strategy for ruptured pa aneurysm at our institution was to attempt endovascular treatment as the","objectiveaneurysms arising from the pericallosal artery ( pa ) are uncommon and challenging to treat . the aim of this study was to report our experiences of the endovascular treatment of ruptured pa aneurysms.methodsfrom september 2003 to december 2013 , 30 ruptured pa aneurysms in 30 patients were treated at our institution via an endovascular approach . procedural data , clinical and angiographic results were retrospectively reviewed.resultsregarding immediate angiographic control , complete occlusion was achieved in 21 ( 70.0% ) patients and near - complete occlusion in 9 ( 30.0% ) . eight procedure - related complications occurred , including intraprocedural rupture and early rebleeding in three each , and thromboembolic event in two . at last follow - up , 18 patients were independent with a modified",380,128,0.3368
dialogsum,"#Person1#: Well, Peter. I'm sorry you're ill. What's the matter with you? #Person2#: I don't know, Doctor. I'm ill. I have a headache and a stomachache. #Person1#: Show me your torgue. What did you eat yesterday? #Person2#: Well, Doctor, I. . . #Person1#: Did you eat any cake? #Person2#: Yes, I ate some cake. #Person1#: Did you eat any ice cream? #Person2#: Well, yes, I did. I ate some ice cream. #Person1#: Did you eat any candy? #Person2#: Well, yes, I did. I ate some candy. #Person1#: Young man, tell me everything you ate yesterday evening. #Person2#: weki, Doctor. I went to a birthday party. #Person1#: I see! How many pieces of cake did you eat? #Person2#: Three, Doctor. #Person1#: How many plates of ice ream did you eat, young man? #Person2#: Gosh, Doctor. I had only three plates of ice cream. John had four.","Peter has a headache and a stomachache. Peter tells the doctor he ate some cake, ice cream, and candy yesterday.",145,20,0.1379
scientific_lay_summarisation-elife-norm,"Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective white blood cell differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity, that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics of a conditional knockout mouse, we demonstrate that Kat2a contributes to leukemia propagation through preservation of leukemia stem-like cells. Kat2a loss impacts transcription factor binding and reduces transcriptional burst frequency in a subset of gene promoters, generating enhanced variability of transcript levels. Destabilization of target programs shifts leukemia cell fate out of self-renewal into differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and distinct stages of cancer evolution. Acute Myeloid Leukemia (AML) is the most prevalent leukemia in adults with a dismal prognosis of less than 30% 5 year survival (Döhner et al. , 2017). It is a heterogeneous disease, clinically and pathologically, with common cellular themes of myeloid differentiation block, and recurrent molecular targeting of chromatin and transcriptional regulators. Effects on chromatin and transcription are reflected in the AML mutational spectrum (Ley et al. , 2013), as well as through the implication of general chromatin regulators in AML pathogenesis, in the absence of specific mutation events (Roe and Vakoc, 2013). Specific examples of AML dependence on unmutated chromatin regulators include BRD4 (Dawson et al. , 2011; Zuber et al. , 2011), LSD1 (Harris et al. , 2012) or DOT1L (Bernt et al. , 2011; Daigle et al. , 2011), their importance highlighted by the fact that chemical inhibitors developed to target these regulators have progressed to clinical trials (Gallipoli et al. , 2015). More recently, TAF12, a component of the basal transcription factor complex TFIID, was shown to be critical for AML cell maintenance through regulation of protein stability and activity of the transcription factor MYB (Xu et al. , 2018). In a recent CRISPR drop-out screen of genetic dependencies in AML, we have identified several members of the promoter-bound histone acetyl-transferase SAGA complex, including acetyl-transferase KAT2A, as being required for AML maintenance (Tzelepis et al. ,","Less than 30% of patients with acute myeloid leukaemia – an aggressive cancer of the white blood cells – survive five years post-diagnosis. This disease disrupts the maturation of white blood cells, resulting in the accumulation of immature cells that multiply and survive but are incapable of completing their maturation process. Amongst these, a group of cancer cells known as leukemic stem cells is responsible for continually replenishing the leukaemia, thus perpetuating its growth. Cancers develop when cells in the body acquire changes or mutations to their genetic makeup. The mutations that lead to acute myeloid leukaemia often affect the activity of genes known as epigenetic regulators. These genes regulate which proteins and other molecules cells make by controlling the way in which cells ‘read’ their genetic instructions.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the ventral tegmental area (VTA) are activated by the omission of the aversive unconditioned stimulus (US) during fear extinction. This dopamine signal occurred specifically during the beginning of extinction when the US omission is unexpected, and correlated strongly with extinction learning. Furthermore, temporally-specific optogenetic inhibition or excitation of dopamine neurons at the time of the US omission revealed that this dopamine signal is both necessary for, and sufficient to accelerate, normal fear extinction learning. These results identify a prediction error-like neuronal signal that is necessary to initiate fear extinction and reveal a crucial role of DA neurons in this form of safety learning. The ability to learn which stimuli predict danger is crucial for survival but it is equally important to adapt behavior when those stimuli no longer represent a threat. One classic example of this is fear extinction learning, during which the repeated presentation of a stimulus (conditioned stimulus, CS) that no longer predicts an aversive outcome (unconditioned stimulus, US) leads to a gradual decrease in learned fear responses. Many anxiety disorders, such as post-traumatic stress disorder, are characterized by impaired extinction learning (Craske et al. , 2017; Graham and Milad, 2011; Mahan and Ressler, 2012; Milad and Quirk, 2012; Pitman et al. , 2012) and thus understanding the neural basis of fear extinction has clinical significance. A large body of evidence indicates that fear extinction represents new learning rather than forgetting or the erasure of the original fear memory (Bouton et al. , 2006; Myers and Davis, 2007). In order to initiate extinction learning, the absence of the expected aversive outcome must be detected and signaled to the brain regions mediating fear extinction. Decades of research on fear extinction has revealed that a distributed network of brain structures including the amygdala, medial prefrontal cortex and hippocampus mediates the acquisition, consolidation and retrieval of fear extinction memories (Duvarci and Pare, 2014; Maren et al. , 2013; Pape and Pare, 2010; Sotres-Bayon and Quirk, 2010; Tovote et al. , 2015). However, none","To survive, animals must identify and react to stimuli in their environment that signal danger. But they must also adapt their behavior when those stimuli no longer signal danger – hiding whenever you hear a loud noise might keep you safe, but it also prevents you from searching for food. In the laboratory, we can study this form of learning using procedures called fear conditioning and extinction. During fear conditioning, animals learn that a stimulus, such as a tone, signals that an unpleasant event is about to occur. That event might involve receiving a mild shock to the foot, for example. After experiencing the tone and shock paired together multiple times, animals will initially show signs of fear – such as freezing – when they hear the tone.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"context, the 20S proteasome additionally cooperates with another AAA+ protein, Cdc48 (also known as p97 or VCP) (Baek et al. , 2013; DeLaBarre et al. , 2006; Wolf and Stolz, 2012). Cdc48 has also been implicated in a multitude of other cellular processes like membrane fusion, autophagy and gene expression (Baek et al. , 2013; Yamanaka et al. , 2012). The different Cdc48 functions are largely mediated by various adaptor proteins (>40) binding to the N-terminal domain or C-terminal region of Cdc48 and aiding in recognition of different substrates (Baek et al. , 2013; Buchberger et al. , 2015). Although the exact role played by Cdc48 during ERAD is not fully understood, it is involved in pulling proteins from the membrane or from ribosomes during co-translational degradation, and recent evidence suggests even a direct association with the 20S particle (Barthelme and Sauer, 2013). Such a direct role as 20S proteasome activator has been shown for the Cdc48 homolog from archaea in vitro (Barthelme et al. , 2014). Archaeal Cdc48 forms a complex with the 20S proteasome that is capable of degrading ssrA-tagged model substrates, likely due to the disordered, extended nature of the ssrA-tag at their C-terminus (Barthelme and Sauer, 2013). Eukaryotic Cdc48 on the other hand is not able to recognize ssrA-tagged substrates in vitro, which was proposed to be due to the absence of two hydrophobic residues in the entry pore loop. These residues must be involved in recognition of the ssrA tag, since their introduction into the eukaryotic p97 enabled it to unfold ssrA-tagged model substrates (Barthelme and Sauer, 2013; Rothballer et al. , 2007). Although the ssrA-tag is not a bona fide degradation signal in eukaryots and archaea, the D1 pore-1 loops and the nature of the residues within these loops appear to play a general role in substrate recruitment. A recent study demonstrated that mutating residues in these entry loops in vivo deregulated cellular protein turnover (Esaki et al. , 2017). In the mammalian homolog, the same residues are required for proper function of the ERAD pathway (DeLaBarre et al. , 2006). In this study, we characterize the Cdc48-like protein of actinobacteria (Cpa) by a combination of bioinformatical analysis, genetic modification and biochemical characterization to explore ring formation of Cpa, to probe its ability to","Cells use proteins to carry out the biological processes necessary for life. If a protein becomes damaged or is no longer needed, cells must dispose of it, just as we might take out the trash. The cell’s main ‘garbage disposal unit’ is the proteasome, a barrel-shaped molecular machine that breaks down unwanted proteins. The proteasome binds to other molecules called regulators, which select the proteins to be dismantled. The proteasomes of mycobacteria – a group that includes the bacteria that cause tuberculosis – help them to survive hostile or rapidly changing environments. Mycobacteria contain a molecule called Cpa whose structure is like a regulator that is found in many non-bacterial cells. Ziemski et al. therefore set out to investigate whether Cpa performs a similar role in bacteria. The",380,128,0.3368
dialogsum,"#Person1#: Ouch! I'm hurt. #Person2#: Are you all right? #Person1#: Yes. I'm OK. I just had a tumble. No big deal. #Person2#: Good. You scared me. #Person1#: Sorry. Can you please help me up! I have trouble standing up by myself with the skis on. #Person2#: Sure. Is this your first time skiing? #Person1#: Yes. I tried skiing on grass before. Not very good at it, though.",#Person1# had a tumble and has trouble standing up with the skis on. #Person2# helps #Person1# up.,67,17,0.2537
dialogsum,"#Person1#: Is this Mister Brown's office? #Person2#: Yes, but he's gone out. Did you tell him beforehand about your coming? #Person1#: Yes, I found him yesterday and he told me to come here at 9:00 today, it's almost the time now. How soon will he be back? #Person2#: Well, maybe before 10:30. In fact, I'm waiting to see him too. When I arrived at about 8:00, only his secretary was here. She's gone to the copy shop to have a form copied. #Person1#: Perhaps it's the application form for students to study in Britain? #Person2#: That's right, the secretary said these days, many students have been coming to apply to study in Britain. #Person1#: Perhaps you're one of them? #Person2#: Yes, Mr. Brown told me to fill in a form, so they'll know if I am qualified. Why do you want to see Mr. Brown sir? #Person1#: I want to ask him how much I pay if my 2 daughters study there. #Person2#: So, your daughters have filled in the form already? #Person1#: Yes, that was last Tuesday. Look, Mister Brown is coming, and his secretary is with him.",Both #Person1# and #Person2# are waiting for Mister Brown. #Person2# wants to study in Britain and #Person1# wants to ask about the tuition fees of #Person1#'s two daughters.,189,28,0.1481
dialogsum,"#Person1#: I need to go to the bank. #Person2#: But they're all close today? #Person1#: Closed? Are you kidding? What is it? Some kind of holiday today? #Person2#: Have you already forgotten what's the date today? #Person1#: Oh, it's the first of April. April Fools' Day. #Person2#: You forgot all about it, didn't you? #Person1#: Sort of. But it has reminded me of at least one thing I need to remember. #Person2#: What's that? #Person1#: Tomorrow is my wife's birthday. #Person2#: Better not forget that. It's pretty strange that your wife's birthday changes every year. Why is that? #Person1#: My wife is Chinese. She celebrates her birthday according to the lunar calendar. #Person2#: Ah, I got it. #Person1#: It's so different from our culture. I guess that makes life interesting to have different cultures come together.","#Person2# play a trick on #Person1# as it's April Fools' Day, which reminds #Person1# of his wife's birthday. #Person1# tells #Person2# his wife is Chinese so she celebrates her birthday according to the lunar calendar.",136,35,0.2574
dialogsum,"#Person1#: Here's our sample room. #Person2#: You've got a large collection of sample foodstuffs here. #Person1#: Yes. We are exporting a wide range of foodstuffs to many countries. And the demand is getting greater and greater. By the way, which items are you interested in? #Person2#: I'm particularly interested in shortbreads. Do you have some samples you could show me? #Person1#: Yes. This way, please. Our shortbread is in a variety of flavors, such as almond, walnut, lotus seed, etc. And different packaging has different weights. We can make packages within a reasonable range of any size you require. #Person2#: The small sizes are more marketable than the large ones for us. I wonder if your pastry tastes better... #Person1#: You are welcome to have a try. Here it is. Ours is of prime quality. #Person2#: Oh, it's delicious. . .",#Person1# shows #Person2# their foodstuffs sample room. #Person1# is promoting shortbreads of all tastes and sizes to #Person2#. #Person2# tastes one and thinks it delicious.,141,25,0.1773
dialogsum,"#Person1#: Sarah, you work in the admissions office, don't you? #Person2#: Yes, I've been here for ten years as assistant director. #Person1#: Really? What does that involve? #Person2#: Well, I'm in charge of all the admissions of postgraduate students in the university. #Person1#: Only postgraduates? #Person2#: Yes, postgraduates only. I have nothing at all to do with undergraduates. #Person1#: Do you find that you get particular-sort of...different national groups? I mean, do you get large numbers from Latin America or... #Person2#: Yes. Well, of all the students enrolled last year, nearly half were from overseas. They were from African countries, the Far East, the Middle East, and Latin America. #Person1#: Em. But have you been doing just that for the last 10 years, or, have you done other things? #Person2#: Well, I've been doing the same job. Er, before that, I was secretary of the medical school at Birmingham, and further back, I worked in the local government. #Person1#: Oh, I see. #Person2#: So I've done different types of things. #Person1#: Yes, indeed. How do you imagine your job might develop in the future? Can you imagine shifting into a different kind of responsibility or doing something... #Person2#: Oh, yeah, from October 1, I'll be doing an entirely different job. There's going to be more committee work. I mean, more policy work, and less dealing with students, unfortunately-I'll miss my contact with students.",Sarah has been in charge of all the admissions of postgraduates for ten years. She tells #Person1# some of the students are from overseas. #Person1# also asks her about the work experience. Sarah will do an entirely different job with more policy work.,233,43,0.1845
dialogsum,"#Person1#: Do you have a bf? #Person2#: Yes, I had a bf before. #Person1#: Why you say bf before? #Person2#: We parted from each other last month. #Person1#: Have you got a new one? #Person2#: Mmmm, no. How about you? #Person1#: I am single, I have no real of, only an E-gf, that is you. #Person2#: Haha, so you are my E-bf. #Person1#: I like you. Do you agree to be my of? #Person2#: Mmmm. . . OK, let's try to be. #Person1#: Wow! Blablablabla. . . #Person2#: Hey! What is it? #Person1#: I am flying like a bird. #Person2#: LL #Person1#: I am so happy. I want to drink a cup of champagne. #Person2#: I have no champagne right now. How about this? #Person1#: It's OK, so I send you this. #Person2#: Is it made of chocolate? #Person1#: It's my heart ; it's made of what you like. #Person2#: Oh, I will have a sweet dream. #Person1#: Are you sleepy? #Person2#: A little bit. I have to go to sleep though I don't want to. #Person1#: Yes, I do not want to see ur sleeping in the office. #Person2#: Thx. Bye for now. Kisssssssssss. #Person1#: C U here, honey.",#Person1# and #Person2# are talking about their ex. Then #Person1# shows love to #Person2# and #Person2# agrees to be #Person1#'s girlfriend. They become extraordinarily happy and kiss each other.,200,29,0.145
pubmed-summarization,"expression of il-1 and il-6 in 105 case - samples of human cervical cancer tissues and their paired adjacent tissues . the purpose of this study was to investigate the association of il-1 and il-6 expression with clinicopathological parameters of cervical cancer and evaluate the prognostic value of il-1 and il-6 expression in cervical cancer patients . this study included a total of 105 formalin - fixed , paraffin - embedded cervical cancer tissues and their adjacent non - tumor tissues taken from patients at the time of resection surgery , from january 2002 to november 2013 at east hospital , tongji university . all cancers were confirmed as cervical cancer by the medical examination of hematoxylin and eosin after surgical resection . none of patients had received adjuvant chemotherapy , radiation therapy , or other anti - tumor therapies . important related clinicopathological parameters of the patients , such as age , tumor size , figo stage , lymphatic metastasis , stromal invasion , differentiation , and survival time were obtained from each patient s medical records and are shown in tables 1 and 2 . the survival time was calculated from the date of surgery to the date of death , or the last known follow - up . all cervical cancer tissue samples include in this investigation were obtained with patients written informed consent . a standard immunohistochemistry method was used to inspect il-1 and il-6 expression in cervical cancer tissues and their adjacent tissues . briefly , the tumor tissues and adjacent tissues were fixed in 10% formaldehyde and embedded in paraffin ; then cut into 4-m sections . all 4-m tissue sections are dewaxed and rehydrated with xylene and graded alcohol , respectively . we washed the sections with buffer solution for 5 minutes and then added the primary antibody at 4c overnight . afterwards , we washed the sections with phosphate buffered saline ( pbs ) and stained them with 3 , 3-diaminobenzidine ( dab ) for 5 minutes , then counterstained with hematoxylin . finally , all the sections were assessed under an optical microscope by two independent investigators ; any discrepancy in immunohistochemistry was resolved by consensus . the expression of il-1 and il-6 in cervical cancer and adjacent tissues was compared","backgroundil-1 and il-6 are associated with the prognosis of a wide range of cancers , but their value in cervical cancer remains controversial . the aim of this study was to investigate the expression of il-1 and il-6 in cervical cancer and their significance in clinical prognosis.material/methodsthe expression of il-1 and il-6 in 105 formalin - fixed , paraffin - embedded cervical cancer tissues and adjacent non - tumor tissues was examined by immunohistochemistry . the results were semi - quantitatively scored and analyzed by chi - square test . patient overall survival ( os ) data was collected by follow - up and analyzed by kaplan - meier analysis.resultsthe expression level of both il-1 and il-6 in cervical cancer tissue was higher than in adjacent non -",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The high permeability of TRPV1 to Ca2+ has also been a useful tool in high-throughput screening of regulatory compounds and led to the identification of a family of toxins, first purified from spiders, that act as potent activators of TRPV1 (and have enhanced the survival of the spiders) (Caterina et al. , 1997). In addition, Ca2+ influx through TRPV1 desensitizes sensory neurons (Cholewinski et al. , 1993; Koplas et al. , 1997; Rosenbaum et al. , 2004). Although multiple pathways are likely involved in neuronal desensitization, depletion of the signaling lipid phosphoinositide 4,5-bisphosphate (PI (4,5) P2) via Ca2+-mediated activation of phospholipase C appears to contribute to desensitization of TRPV1 during periods of high channel activity (Stein et al. , 2006; Lukacs et al. , 2007). Optical recording of localized Ca2+ influx through plasma membrane ion channels can be achieved using a combination of Ca2+-sensitive fluorescent dyes and non-fluorescent Ca2+ chelators loaded into cells via a whole-cell patch pipette. When Ca2+-permeable channels open, localized Ca2+ influx produces a fluorescent ‘sparklet’ in the cytosol proximal to the active channel (Wang et al. , 2001). The presence of the nonfluorescent Ca2+ chelator in the cell acts as a sink for the excess Ca2+, enhancing the localization of the source of the influx (Navedo et al. , 2005). Optical approaches have been used to record the activity of L-type Ca2+ channels in urinary bladder smooth muscle (Sidaway and Teramoto, 2014), arterial smooth muscle (Navedo et al. , 2006; Amberg et al. , 2007; Navedo et al. , 2010; Tajada et al. , 2013), ventricular myocytes (Wang et al. , 2001; Zhou et al. , 2009), and mammalian cell lines (Gulia et al. , 2013). More recently, sparklets due to TRPV4 channels have been reported in arterial smooth muscle (Mercado et al. , 2014) and vascular endothelium (Bagher et al. , 2012; Sonkusare et al. , 2012). Two aspects of sparklets reported from L-type Ca2+ channels and TRPV4 channels are remarkable. First, multiple channels were typically clustered at the sparklet sites. Second, the sparklets remained stationary throughout the observation period. Thus, some mechanism (s) for clustering channels must be operating in these cells. Whether the clustering mechanism (s) and the mechanism (s) eliminating diffusion of the clusters are related is unknown. Most importantly, whether any","Cells rely on proteins called receptors to keep them informed about what is going on around them. These receptors, which are embedded in the surface of the cell, detect and respond to specific chemical signals. It is known that receptors move around the cell surface as they search for particular chemical signals, but these movements have not been widely studied in experiments. Senning and Gordon have now investigated the movements of receptors called TRPV1 channels that can detect a chemical called capsaicin. This receptor contains an ion channel that is usually closed. However, when the receptor is activated this channel opens and allows calcium ions to enter the cell. In the experiments the receptors were tagged with a fluorescent marker, and a fluorescent calcium dye was used to",380,128,0.3368
pubmed-summarization,"the incidence of non - hodgkin lymphoma ( nhl ) is 100200-fold higher in hiv - infected individuals than in the general population . nhl is an aids - defining illness and in 35% of cases , the lymphoma is the initial manifestation of aids . the most common hiv - associated lymphomas are diffuse large b cell lymphoma ( dlbcl ; often primary in the central nervous system ) , burkitt lymphoma , primary effusion lymphoma , and plasmablastic lymphoma of the oral cavity . primary mediastinal large b cell lymphoma is a subtype of diffuse large b cell lymphoma arising in the mediastinum with distinctive clinical , morphologic , and genotypic features . most patients are young adult females presenting with localized mediastinal mass and symptoms often related to local effects of the large mediastinal tumor such as superior vena cava syndrome . dlbcl is one of the most common lymphomas in the setting of hiv , but the incidence of pmlbcl in hiv is not well established . only one reported case of hiv - associated pmlbcl has been found in the english literature . a 25-year - old female presented to her physician with 1 week of worsening shortness of breath , cough , and chest pain . she gave birth to her fourth child 5 weeks ago , and her cough and shortness of birth was developed a few days prior to delivery . she was diagnosed with hiv 1 year before ; however , she had no previous manifestation of aids . chest computed tomography ( ct ) revealed a 13.7 9.2-cm superior mediastinal mass , multiple left pleural masses ranging from 2.42.7 cm , a 1.6-cm left upper lobe lung nodule , and bilateral pleural effusions ( . 1 ) . the infiltrating cells were mostly large with irregular and convoluted vesicular nuclei , 13 visible nucleoli , and moderately abundant cytoplasm . the tumor cells were cd45 + , cd20 + , cd23 + , partially cd30 + , weak partial positive for bcl-2 and bcl-6 , and negative for cd3 , cd5 , cd10 , cd15 , cd21 , and alk-1 . eber in situ hybridization was positive in approximately 30% of the tumor cells ( . 2 ) . flow","primary mediastinal large b cell lymphoma ( pmlbcl ) is a subtype of diffuse large b cell lymphoma arising in the mediastinum with distinctive clinical and morphological features . though diffuse large b cell lymphoma is one of the most common non - hodgkin lymphoma associated with aids , there are no data available regarding the association of hiv and pmlbcl . we report here two cases of pmlbcl arising in aids patients . in both cases , pmlbcl presented in a setting of low cd4 t - cell count as rapidly enlarging mediastinal mass . the morphologic and immunophenotypic findings are characteristic of pmlbcl . one of the two patients , a 25-year - old woman who had localized disease and evidence of epstein barr virus in",380,128,0.3368
pubmed-summarization,"desmoplastic fibroma ( df ) , a benign locally aggressive lesion of the bone is recognized as an intra - osseous counterpart of soft tissue fibromatosis and is usually seen affecting the long bones , pelvis and only occasionally presents itself as a jaw lesion . mandible is most commonly affected when compared to the maxilla and the cranium in the head and neck region . a systematic literature search of the pubmed database of national library of medicine using df and mandible as keywords revealed a total of 57 published cases occurring in the mandible alone from the year 19692014 . the cause for df is unknown and is stipulated to have a varied pathogenesis ranging from genetic , endocrine and traumatic factors to an exuberant reactive proliferation . when differentiating it from other neoplasms that behave aggressively , a history of expansion or perforation of the cortical plates along with the histopathological confirmation would be a pointer in the right direction . a 35-year - old female patient visited the department of oral medicine and radiology , with the chief complaint of slowly growing painless swelling in the left lower back tooth region since 3 years [ ] . clinical extra - oral examination revealed expansion of the left inferior border of the mandible and intra - oral examination revealed a solitary bony hard swelling measuring about 4.0 cm 5.0 cm in size with obliteration of the left buccal vestibule in relation to 37 and 38 [ ] . clinical image showing swelling of left side of lower jaw intra - oral photograph showing obliteration of the left buccal vestibule in relation to 37 , 38 a left lateral oblique view of radiograph showed multilocular radiolucencies with fine trabeculations leading to a soap bubble appearance extending from the left angle of the mandible to the mesial root of the mandibular left first molar . no displacement of teeth or resorption of the root was seen [ ] . left lateral oblique view of radiograph showing multilocular radiolucencies a computerized tomography ( ct ) scan demonstrated buccal and lingual cortical plate expansion and a soap bubble appearance [ ] . computed tomography scan showing buccal and lingual cortical plate expansion surgical excision of the lesion the hematoxylin and eosin","desmoplastic fibroma ( df ) is a benign intra - osseous neoplasm , that is , recognized as the intra - osseous counterpart of soft tissue fibromatosis in both gnathic and extra - gnathic sites . it has a propensity for locally aggressive behavior and local recurrence . an occurrence of intra - osseous lesion other than that of odontogenic origin is rare in the jaws . in this case report , we define the clinico - pathological and radiographic features of df of the mandible in a 35-year - old female , who presented to the outpatient department with a 3-year history of a slowly expanding painless mass in the left mandibular posterior region . thus , we present a classic case of df exhibiting characteristic features",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Vaccines induce memory B-cells that provide high affinity secondary antibody responses to identical antigens. Memory B-cells can also re-instigate affinity maturation, but how this happens against antigenic variants is poorly understood despite its potential impact on driving broadly protective immunity against pathogens such as Influenza and Dengue. We immunised mice sequentially with identical or variant Dengue-virus envelope proteins and analysed antibody and germinal-centre (GC) responses. Variant protein boosts induced GCs with a higher proportion of IgM+ B cells. The most variant protein re-stimulated GCs with the highest proportion of IgM+ cells with the most diverse, least mutated V-genes and with a slower but efficient serum antibody response. Recombinant antibodies from GC B-cells showed a higher affinity for the variant antigen than antibodies from a primary response, confirming a memory origin. This reveals a new process of antibody memory, that IgM memory cells with fewer mutations participate in secondary responses to variant antigens, demonstrating how the hierarchical structure of B-cell memory is used and indicating the potential and limits of cross-reactive antibody based immunity. Antibody-based immunity is underpinned by memory B-cells that have undergone antibody somatic hyper-mutation (SHM) and selection for improved antigen binding in germinal centres (GCs) (MacLennan et al. , 1997). Re-challenge with the same antigen stimulates a rapid, higher affinity, secondary antibody response. Protective immunity to highly mutable viruses, like Dengue and Influenza, can be induced by vaccination but the high level of variation often leads to immune escape (Nabel and Fauci, 2010), leading to a focus on generating vaccine responses against conserved antigenic regions (Wu et al. , 2010; Corti et al. , 2011; Wang et al. , 2015). Memory B-cells of IgM and IgG isotypes can also re-instigate GCs after secondary exposure (Dogan et al. , 2009; Pape et al. , 2011; McHeyzer-Williams et al. , 2015), but how this happens against variant antigens is poorly understood despite its potential impact on driving the most broadly protective immunity. Several studies suggest diversity in the memory B-cell population, showing that cells can express IgM or IgG (Dogan et al. , 2009; Pape et al. , 2011), be mutated or non-mutated (Kaji et al. , 2012) and have low affinities (Smith et al. , 1997), but still persist in GCs (Kuraoka et al. , 2016). It has long","Many devastating infectious diseases are caused by viruses that change over time. When a vaccine exists, it usually protects against a particular strain of virus, but often fails to defend against new versions of the microbe. This is why the flu vaccine has to be ‘updated’ every year, for example. Vaccines rely on the memory of our immune system. When a virus enters the body, a group of immune cells known as B cells gets activated. Certain B cells can recognise the invader and produce specific proteins, the antibodies, which can target and kill the invader. During the infection some of these B cells become ‘memory B cells’, having gone through a maturation process that hones their ability to specifically recognize this particular microbe. If the same virus",380,128,0.3368
pubmed-summarization,"the technique of lymphatic mapping and sentinel lymph node biopsy ( slnb ) has emerged in the last two decades as a minimally invasive approach to evaluate regional lymph node basins in patients with intermediate and high - risk primary cutaneous melanoma . in particular , slnb is now recommended as a staging procedure for patients with t2 , t3 or t4 melanomas and clinical uninvolved regional lymph nodes ( clinical stage ib and ii ) and suggested also for patients with t1 melanomas and pathologic features associated with an increased risk of nodal micrometastases ( ulceration , high mitotic rate , ) . also positron emission tomography ( pet ) with 18f - fluorodeoxyglucose ( 18f - fdg ) has been extensively investigated in patients with melanoma and plenty of studies have shown its effective role in detecting distant metastases , further increased after the introduction of co - registered computed tomography ( ct ) scan ( 18f - fdg pet / ct ) . in this article , we introduce a case of pt4b thigh melanoma , in which both procedures were performed , together with ultrasonography . an 82-year - old white male , with a clinically - confirmed cutaneous melanoma of the right thigh , presented to our unit to undergo lymphoscintigraphy , in order to perform slnb at the same time of tumor excision . lymphoscintigraphy with tc - nanocolloids was performed on a hybrid system philips single - photon emission computed tomography / computed tomography ( spect / ct ) precedence 16 slices ( philips healthcare , eindhoven , the netherlands ) after intradermal injection of the radiopharmaceutical around the primary lesion ( four separate injections , 0.1 ml for each aliquot , total activity 100 mbq ) . low dose helical ct scan was performed : 120 kv , 100 ma , d - dom control dose , 3 mm slice thickness , 1.5 mm detector collimation , pitch 0.8 , rotation time 0.75 s. spect scan was acquired with the following parameters : 128 128 matrix size , 120 view angle , 10 s time / angle , 5 mm pixel size . spect / ct images showed uptake of the radiocolloids in a right inguinal lymph node . on ct co","the american society of clinical oncology guidelines recommend sentinel lymph node biopsy ( slnb ) for all patients with melanoma tumors of intermediate thickness ( between 1 and 4 mm ) . in case of patients with thick melanoma tumors ( > 4 mm ) , slnb may be recommended as well , for staging purposes and to facilitate regional disease control . we report a case of an 82-year - old man , undergone excision of a cutaneous melanoma of the right thigh , which shows some limitation of slnb in thick melanoma . lymphoscintigraphy , performed as single - photon emission computed tomography / computed tomography ( spect / ct ) , failed to identify the real sentinel lymph node , as tracer uptake was seen",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2012). On a single cell level in the vertebrate PSM, oscillatory gene expression is believed to be established through negative feedback loops of unstable clock gene products. Previous mathematical models of the somitogenesis clock that invoke the mechanism of delayed negative feedback predict that the clock period can be approximated as a sum of the delays involved in processes such as transcription, splicing, translation and transport and the half-lives of inhibitors of clock gene expression (Lewis, 2003; Monk, 2003; Ay et al. , 2013; Hanisch et al. , 2013). Subsequent studies have confirmed that the period can be altered by genetically modifying genes that encode negative regulators (e. g. , Hes7, Her6, Her7, Nrarp) (Herrgen et al. , 2010; Schröter and Oates, 2010; Kim et al. , 2011; Takashima et al. , 2011; Oates et al. , 2012; Harima, et al. , 2013; Hoyle and Ish-Horowicz, 2013). Moreover, it has been shown that regulation of clock gene mRNA turnover and degradation is gene specific and regulated at the level of the 3′UTR (Hilgers et al. , 2005; Nitanda et al. , 2014). In contrast, there has been relatively little experimental work demonstrating the predicted role of protein stability in regulating the periodicity of clock gene oscillations (Hirata et al. , 2004). It is notable that models that invoke delayed negative feedback as the mechanism underlying the somitogenesis clock were developed primarily from zebrafish data, where the clock period is relatively short and there are significantly fewer oscillating components than other vertebrate species (Krol et al. , 2011). Moreover, in zebrafish there is experimental evidence that Notch plays a key role in the synchronisation of neighbouring oscillators (Delaune et al. , 2012) but that it is not necessary for oscillations themselves (Ozbudak and Lewis, 2008). In contrast, Notch signalling in mouse and chick is thought to be essential for oscillations (Ferjentsik et al. , 2009). One crucial factor in this regard is the Notch1 intracellular domain (NICD) which is cleaved following ligand activation, translocates to the nucleus and activates Notch target gene expression. NICD is unstable and, at least in mouse, its production appears as pulsatile, spatio-temporal waves that traverse the rostro-caudal axis of the PSM in the manner of a clock gene (Huppert et al. , 2005).","During embryo development, animals with backbones (also called vertebrates) repeatedly lay down pairs of segments along the axis that runs from the head to the tail of the embryo. These segments, known as somites, eventually form part of the skeleton, as well as the associated muscle, cartilage, tendons and some skin. Importantly, the segments in some species take longer to form than those in other species, and they also form in proportion to the overall size of the animal. A ‘segmentation clock’ regulates the timing of somite formation via cycles in which genes are repeatedly switched on and then off again. Some aspects of this process are well understood. Firstly, many ‘clock genes’ are known to produce proteins that can inhibit their own production. However, this ‘negative feedback’",380,128,0.3368
scientific_lay_summarisation-elife-norm,"prematurely resulting in the production of a truncated peptide, which typically lacks proper functionality, and may even exert dominant-negative effects (Miller and Pearce, 2014). To guard against the negative consequences of mRNAs harboring PTCs, the conserved nonsense-mediated decay (NMD) machinery, working together with the ribosome, identifies premature stop codons and targets the message for decay (Celik et al. , 2015; Kim and Maquat, 2019). Discrimination of normal and problematic termination contexts must occur independently of the nucleotide sequence of the stop codon since identical stop codons (UAA, UAG, and UGA) signal translation termination at both NTCs and PTCs. In mammals, a strong signal for NMD derives from the position of the stop codon relative to that of a protein complex known as the Exon-Junction-Complex (EJC) deposited upstream of each splice junction during splicing of the mRNA (Le Hir, 2000; Singh et al. , 2012). While NTCs are typically found in the terminal exon of protein coding genes, PTCs often are found in upstream exons, and in these cases are recognized as aberrant when the ribosome encounters a termination codon upstream of a deposited EJC. As nonsense mutations account for approximately 11% of inherited genetic disorders in humans (Mort et al. , 2008), targeted treatments for these particular mutations could substantially alleviate human disease. One class of compound proposed as a treatment for nonsense mutations are collectively known as nonsense-suppression therapeutics (Keeling et al. , 2014; Lee and Dougherty, 2012). Acting at the level of translation, compounds in this class force the ribosome to ‘read through’ a PTC and continue translation thereby restoring synthesis of full-length protein. Typically, such stop codon readthrough (SCR) involves a process in which a near-cognate tRNA (nc-tRNA) base pairs with a termination codon, forcing the ribosome to continue elongation instead of terminating translation (Brody and Yanofsky, 1963; Smith et al. , 1966). Achieving such specificity for PTC readthrough without globally disrupting termination at NTCs remains a critical challenge for nonsense suppression therapies and will require a more complete understanding of translation termination and stop codon readthrough in different sequence contexts. While translation termination is generally the predominant reaction at stop codons, termination efficiencies do vary considerably between different stop codon contexts. Many factors have been reported to influence the probability of termination, readthrough, or frameshifting (where","Many genes provide a set of instructions needed to build a protein, which are read by structures called ribosomes through a process called translation. The genetic information contains a short, coded instruction called a stop codon which marks the end of the protein. When a ribosome finds a stop codon it should stop building and release the protein it has made. Ribosomes do not always stop at stop codons. Certain chemicals can actually prevent ribosomes from detecting stop codons correctly, and aminoglycosides are drugs that have exactly this effect. Aminoglycosides can be used as antibiotics at low doses because they interfere with ribosomes in bacteria, but at higher doses they can also prevent ribosomes from detecting stop codons in human cells. When ribosomes do not stop at a",380,128,0.3368
dialogsum,"#Person1#: Ground Transportation Services,how can I help you? #Person2#: I have 7 guests coming to visit for the holidays. And I want to know how I can get them from the airport to my house. #Person1#: OK, are you familiar with our door to door shuttle service? #Person2#: Yes, I've used it myself. The thing is at $50 a person, that means $350 for 7 people. It's a little expensive. #Person1#: How about hiring our minibus? #Person2#: How much is it? #Person1#: It costs $150 and can drive straight from the airport to your house. #Person2#: Oh, that sounds great. Can I make a reservation now? #Person1#: Sure, but I'll need the flight information for your guests. #Person2#: Sorry, I don't have the information now. I'll call you back. #Person1#: OK, goodbye.","#Person2# phones to find a way to transport 7 guests from the airport to #Person2#'s house. #Person1# introduces several services, and #Person2# will hire the minibus.",132,26,0.197
dialogsum,"#Person1#: What did he say? #Person2#: He said he would tell us the secret of becoming a successful man. #Person1#: It's too good to be true! If I were there, I would ask him if he himself was a successful man. #Person2#: Nobody would drive him up a wall by asking him such a question, you know.",#Person2# tells #Person1# about a man promoting the secret of success.,57,11,0.193
pubmed-summarization,"ablation of the cavotricuspid isthmus ( cti ) for the treatment of atrial flutter ( afl ) has become standard practice . most of the procedures are performed using radiofrequency energy ( rf ) . high chronic success rates are described but the majority of the data comes from a relatively short term follow - up . a recent study by chinitz et al . reported some interesting data regarding the long term follow - up of 80 patients with common type afl who underwent cti ablation using rf . they found a 12.5% ( ten patients ) recurrence rate at an average of 21 months after the procedure with most patients having a recurrence after the first year post ablation . our prior experience using cryothermy in a limited number of patients also showed that afl may recur 1 year after cti cryoablation . the purpose of this study was to evaluate the long term outcome of cti cryoablation in a large patient population with common type afl in a single center . one hundred and eighty patients with sustained symptomatic common type afl referred for cti ablation were enrolled prospectively from july 2001 to july 2006 in our institution . signed written consent , approved by the local ethics committee , was obtained from all participants . before cti cryoablation , anticoagulation with warfarin aiming a therapeutic international normalized ratio of 2 to 3 was kept for at least 3 weeks . we focused our study on the clinical aspects and long term follow - up of patients with afl who were submitted to cti cryoablation . briefly , our methodology was as follows : under local anesthesia and via the femoral route , a decapolar catheter is positioned in the distal coronary sinus ( for evaluation of left atrial activation ) , a duodecapolar catheter ( 2-mm interelectrode spacing , halo catheter , biosense webster , baldwin park , ca ) for mapping the right atrial lateral wall and a quadripolar catheter in the his bundle area . a deflectable , 10.5 f , 6.5 mm tip cryoablation catheter ( cryocor inc . , san diego , ca ) is inserted into the right atrium through a 12f , 65-cm - long sheath ( daig , st","objectiverecent literature has shown that common type atrial flutter ( afl ) can recur late after cavotricuspid isthmus ( cti ) catheter ablation using radiofrequency energy ( rf ) . we report the long term outcome of a large group of patients undergoing cti ablation using cryothermy for afl in a single center.methodspatients with afl referred for cti ablation were recruited prospectively from july 2001 to july 2006 . cryoablation was performed using a deflectable , 10.5 f , 6.5 mm tip catheter . cti block was reassessed 30 min after the last application during isoproterenol infusion . recurrences were evaluated by 12-lead ecg and 24 h holter recording every clinic visit ( 1/3/6/9 and 12 months after the procedure and yearly thereafter ) or if symptoms developed.resultsthe",380,128,0.3368
dialogsum,"#Person1#: Excuse me, I'm sorry to bother you, but would you have time to answer a few questions? #Person2#: What's it about? #Person1#: We're doing some market research for a new television channel starting in two years' time. #Person2#: OK, why not? #Person1#: Lovely, we'll just work through this form. And if we could start with some personal background information. #Person2#: Sure. #Person1#: Right, if I could just have your age... #Person2#: 35. #Person1#: Right, great. And your job? #Person2#: Systems analyst, but for the form I don't know whether it would count as professional or business or what. #Person1#: What do you think? #Person2#: OK, it's more like business. #Person1#: Fine. And would you mind my asking about your salary? Or we can leave it blank. #Person2#: No, I don't mind. It's 40,000 a year. #Person1#: Thank you. Right... about your current watching habits..., what would you say is your main reason for watching TV? #Person2#: Well, at work I tend to read for information and what have you, so I'd say that with TV it probably just helps me relax and unwind. #Person1#: Fine. And how many hours a day on average do you watch TV? #Person2#: Not a lot really... I should say just over an hour. #Person1#: So what are the two main times of the day that you watch TV? #Person2#: Well, a little around breakfast time and then it tends to be really late eleven or even midnight- when I've finished work. #Person1#: And what sort of programmes do you go for? #Person2#: Some news bulletins but I also really like to put my feet up with some of the old comedy shows. #Person1#: Fine. And turning to the new channel..., which type of programmes would you like to see more of? #Person2#: Well, I certainly don't think we need any more factual programmes like news and documentaries. I think we need more about things like local information..., you know, providing a service for the community. And in the same vein, perhaps more for younger viewers..., you know, good quality stuff. #Person1#: Ah ha. And if you had to give the new directors some specific advice when they set up the channel, what advice would you give them? #Person2#: I think I'd advise them","#Person1#'s doing market research for a new television channel, and #Person1# interviews #Person2# about some questions. First, #Person1# learns about #Person2#'s basic personal information, including age, job, and salary. Then #Person1# asks #Person2# the reason for watching TV, frequency of watching TV, and the types of programs #Person2# watches. Finally, #Person2# gives the specific advice of paying attention to the quality of the actual broadcast to the new directors when they set up the channels. #Person2# is willing to attend",380,80,0.2105
dialogsum,"#Person1#: Are you interested in history? #Person2#: Yes, I am. I enjoyed studying it at school, though I had trouble remembering all the dates, so my teacher never gave me good marks. #Person1#: I love history, but I ' Ve always thought that learning the reasons behind events is more important than remembering exactly when they happened. #Person2#: I wish you had been my history teacher! I might have got better marks! #Person1#: Some people say that history repeats itself. #Person2#: What does that mean? The same events never happen twice, do they? #Person1#: The idea is that the people and dates change, but the reason why things happen stay the same. #Person2#: I see. I think I ' d agree with that statement. People often seem to make the same mistakes over and over again.",#Person1# and #Person2# like history but #Person2# can't get good marks for poor memory for the dates. #Person2# thinks learning the reason behind events is more important. #Person2# agrees.,136,29,0.2132
pubmed-summarization,"62.4 million indians were reported to have type 2 diabetes mellitus ( t2 dm ) putting india on the forefront of diabetic epidemic across globe . fear of hypoglycaemia and gain in body weight are barriers for initiation of insulin therapy . modern insulin analogues are a convenient new approach or tool to glycaemic control , associated with low number of hypoglycaemia and favourable weight change . a1chieve , a multinational , 24-week , non - interventional study , assessed the safety and effectiveness of insulin analogues in people with t2 dm ( n = 66,726 ) in routine clinical care . the patient characteristics for the entire cohort divided as insulin - nave and insulin users is shown in table 1 . the majority of patients ( 61.82% ) started on or switched to biphasic insulin aspart . other groups were insulin detemir ( n = 89 ) , insulin aspart ( n = 155 ) , basal insulin plus insulin aspart ( n = 45 ) and other insulin combinations ( n = 21 ) . overall demographic data after 24 weeks of treatment , overall hypoglycaemia reduced from 0.7 events / patient - year to 0.2 events / patient - year in insulin nave group and from 1.8 events / patient - year to 0.3 events / patient - year in insulin user group . the hypoglycaemia incidence in insulin naive group at 24 weeks was lower than that observed in insulin users at baseline . body weight and blood pressure decreased from baseline , while overall lipid profile and quality of life improved at week 24 in the total cohort [ table 2 and 3 ] . mean hba1c and fpg values improved from baseline to study end in the total cohort [ table 4 ] . overall efficacy data of the total cohort , 502 patients started on biphasic insulin aspart ogld , of which 372 ( 74.1% ) were insulin nave and 130 ( 25.9% ) were insulin users . after 24 weeks of treatment , hypoglycaemic events reduced for both insulin naive ( from 0.9 events / patient - year to 0.3 events / patient - year ) and insulin user ( from 1.4 events / patient - year to 0.4 events /","background : the a1chieve , a multicentric ( 28 countries ) , 24-week , non - interventional study evaluated the safety and effectiveness of insulin detemir , biphasic insulin aspart and insulin aspart in people with t2 dm ( n = 66,726 ) in routine clinical care across four continents.materials and methods : data was collected at baseline , at 12 weeks and at 24 weeks . this short communication presents the results for patients enrolled from gujarat , india.results:a total of 812 patients were enrolled in the study . four different insulin analogue regimens were used in the study . patients had started on or were switched to biphasic insulin aspart ( n = 502 ) , insulin detemir ( n = 89 ) , insulin aspart",380,128,0.3368
dialogsum,"#Person1#: Excuse me, do you have the latest issue of Newsworld? #Person2#: Yes, this week's issue just came in. Here it is. #Person1#: How about Music Madness? #Person2#: Let me check. . . yes, we got the October issue a few days ago. It's on that shelf over there. #Person1#: Okay, I'll take these two magazines and a copy of Today's Post.",#Person1# buys two magazines and a copy of Today's post from #Person2#.,62,12,0.1935
pubmed-summarization,"decided to remove the catheter before thoracic cavity was closed . while it was being removed under vision , bleeding was noticed from both puncture sites at the pleural surface . cvcs are routinely inserted in a variety of patients for assessment of intravascular depletion , hemodynamic monitoring , delivery of vasoactive drugs , long - term intravenous access for antibiotic treatment or parenteral nutrition , pulmonary artery catheterization and placement of transvenous cardiac pacemakers . the success of cvc cannulation follows a precise protocol of execution , including methods to verify correct insertion , advancement and final location as well as detecting mechanical and positioning complications . complications of variable magnitude with incidence of ( 5 - 19% ) can accompany the placement of cvc . these complications in decreasing order of frequency include inadvertent arterial puncture or catheterization , puncture of lung apex with or without clinically manifest pneumothorax , thoracic duct injury , venous air embolism , tracheal puncture , hemoptysis , seizures and acute severe asthma . isolated pleural dome puncture in a patient with severe coagulopathy has resulted in life - threatening hemothorax due to continuous bleeding from the puncture site in the pleura . however , this is the first report of transpleural placement of cvc discovered accidentally during thoracotomy in a patient with normal thoracic anatomy . in our patient , it resulted in bleeding from the puncture site when cvc was removed under vision with the chest open . complications unique to the infraclavicular route are direct brachial plexus injury and injury to the clavicle and the periosteum of the first rib . isolated pleural dome puncture is generally detected only if there is pre - existing fluid , blood or air in the pleural dome , none of which was present in our patient . puncture of normal lung apex is unusual by this approach as it lies caudad to the first rib . however , it can occur if positive pressure ventilation and/or large tidal volumes are used or in a patient with grossly disturbed anatomy . lung apex was intact despite pleural injury in our patient possibly because intermittent positive pressure ventilation was withheld during the venous puncture . hemothorax appearing after removal of cvc is well - mentioned","we report an uncommon complication of subclavian central venous catheterization , discovered at thoracotomy . the central venous catheter ( cvc ) was placed by left infraclavicular route after induction of general anesthesia . cvc was secured after aspiration of blood and satisfactory central venous tracing . on thoracotomy , cvc was noticed to traverse the pleural cavity while the tracing was normal . cvc was thus removed consequent to which bleeding from each puncture site was noticed , that were secured surgically .",380,84,0.2211
pubmed-summarization,"2007 and october 2009 with acute coronary syndrome with angiographic evidence of > 50% stenosis in one or more coronary vessels were included in the studyall patients were evaluated for the evidence of ckd . serum creatinine , routine urine analysis , and spot urine for protein to creatinine ratio of all patients were measured using the standard technique in the clinical laboratory . for secondary analysis , creatinine clearance ( ml / min/1.73 m of body surface area ) was estimated by the cockroft gault equation . patients whose creatinine clearance is < 60 ml / min/1.73 m of body surface area for at least 3 months prior to the current admission are diagnosed to have ckd as per k / doqi clinical practice guidelines for ckdaki was defined according to the risk , injury , failure , loss , and end - stage kidney ( rifle ) criteria . we used the change in serum creatinine level to define aki according to rifle criteria . aki was defined as an increase in serum creatinine levels 1.5 baselineserum creatinine levels were measured at the end of 3 months in those patients , who developed aki , to find out how many had complete recovery , partial recovery and no recovery of their renal function . totally , 125 patients admitted to lilavati hospital and research centre , mumbai , between september 2007 and october 2009 with acute coronary syndrome with angiographic evidence of > 50% stenosis in one or more coronary vessels were included in the study all patients were evaluated for the evidence of ckd . serum creatinine , routine urine analysis , and spot urine for protein to creatinine ratio of all patients were measured using the standard technique in the clinical laboratory . for secondary analysis , creatinine clearance ( ml / min/1.73 m of body surface area ) was estimated by the cockroft gault equation . patients whose creatinine clearance is < 60 ml / min/1.73 m of body surface area for at least 3 months prior to the current admission are diagnosed to have ckd as per k / doqi clinical practice guidelines for ckd aki was defined according to the risk , injury , failure , loss , and end - stage kidney","background and objective : to determine the prevalence of chronic kidney disease ( ckd ) and incidence of acute kidney injury ( aki ) in patients with coronary artery disease ( cad ) demonstrated on coronary angiography.materials and methods : totally , 125 patients admitted to lilavati hospital and research centre , mumbai , with cad were included in the study.results:left anterior descending artery was the major vessel involved ( 40% ) , followed by a circumflex artery ( 21.6% ) . 49 out of 125 ( 39.2% ) were found to have underlying ckd . 69% ( 34 ) of these ckd patients developed aki . 21 out of 34 patients who developed aki required hemodialysis . only 47.1% ( 16 out of 34 ) of ckd",380,128,0.3368
dialogsum,"#Person1#: My parents told me my uncles and aunts are planning a big family reunion in Paris this fall. #Person2#: Are you going to the reunion? #Person1#: You bet. All my uncles and aunts will take their children along, too. So I'll meet many cousins there. #Person2#: How nice! But why Paris? #Person1#: Because two of my aunts are French. They met and got married to my uncles in France. Some of their relatives are still living there. #Person2#: Have you ever been to France before? #Person1#: No. Actually I've never traveled abroad. I'm very excited about it. I just can't wait. #Person2#: My parents are going to take me on a trip to Hawaii next month by way of Tokyo, but I've been there three times already.",#Person1# is so excited about going to Paris for a family reunion since it is the first time for #Person1# to travel abroad.,128,23,0.1797
dialogsum,"#Person1#: We have the capital ready. Right now I am looking at three different companies to produce our products. And your company, Mr. Chen, seems to me to be the best for what we want. #Person2#: I appreciate your remarks. And we are always happy to do more business. But, you know, if we take on a contract to produce new products, we want to be confident the product is marketable. Because, to start producing new things requires a lot of preparation. It requires a lot of investment for us. #Person1#: You have some doubts about our products, I understand. #Person2#: I would like to offer you a good price. But I won't be able to do that if I think this is a one-shot deal. So I would like to have some confidence in your idea. #Person1#: Of course. Let me tell you in some detail about our idea. You know the popular Hello Kitty products. #Person2#: Yes, of course. #Person1#: Well, the products in themselves are very simple. It is the logo that is successful. So, Hello Kitty is successful because of the logo, but the products are very simple. #Person2#: And I would say the logo is successful mainly because it comes from Japan. It is the Japanese that have made it a fad. #Person1#: That might be true. But we have a logo concept that is great. It is really great. I think it will catch on in Taiwan at least. Young people will love it. It is because of our logo that our products will sell. We just need someone to produce the products for us. We have the backup and people to do the marketing. #Person2#: So what you are really trying to sell is a fad. #Person1#: Yes, we would like to make things like key chains, plastic pencil sharpeners, plastic rulers, watches, wallets, things like that. Little accessories for young people. But the reason these will sell is the logo. Just like Hello Kitty. #Person2#: I understand. But why won't you show me the logo? #Person1#: Because it hasn't been copyrighted. We want to get some protection for it. But while we wait for copyright, we are investigating companies to produce the products. #Person2#: I see. The problem, however, is that I",#Person1# looks for Mr. Chen's company to produce Hello Kitty-related products. Mr. Chen asks #Person1# about the details of the products and is not confident to give a good price. #Person1# then explains that #Person1# just wants an estimated price.,380,40,0.1053
pubmed-summarization,"deficit . the patient was recovering well when suddenly , 48 hours post - operatively , the patient experienced four generalized tonic - clonic seizures , and was deeply post - ictal following the seizures . a diagnosis of tonic - clonic seizures secondary to low intracranial pressure was made . all routine blood investigations as well as blood amisulpride and olanzapine levels carried out on all post - operative days were found to be within normal limits . a post - operative head / brain computed tomographic ( ct ) scan showed no infarct , haemorrhage or mass lesions . the patient was started on oral phenytoin 3mg / kg daily and had no further episodes of seizures . she never reported any problems during the duration of follow - up and was successfully discharged back to the community . dural tears during spinal surgery are not uncommon , with reported incidence rates of 0.3% to 17% ( 1 , 2 ) . problems arising from this complication are rare , but devastating and require astute recognition of the early signs of neurological impairment . here we are attempting to make an association between the csf hypotension caused by an unintentional durotomy at lumbar surgery and the new onset of epilepsy which might have been propagated by the patients pre - operative anti - psychiatric medication . the phenomenon of intracranial haemorrhage remote from a surgical site has been described in the literature , and several authors have attempted to explain the pathophysiology ( 1 , 2 ) . although intracranial haemorrhage did not occur in this case , the same pathophysiology is thought to have contributed to provoke the new onset epilepsy . the so - called sag model postulates that haemorrhage results from altered cerebrospinal fluid hydrodynamics , causing caudal sagging of the cerebellum with stretching of cerebellar vermian veins ( 1 ) . taking this pathophysiology into account this was satisfactorily repaired intra - operatively , however , the csf leak was substantial and the dura may have been weakened and prone to later leak . we hypothesize that this may have resulted in delayed intracranial hypotension , causing primary tonic - clonic seizures and not an intra - cranial bleed . thus , we believe","we would like to present a rare case report describing a case in which new - onset tonic - clonic seizures occurred following an unintentional durotomy during lumbar discectomy and decompression . unintentional durotomy is a frequent complication of spinal surgical procedures , with a rate as high as 17% . to our knowledge a case of new onset epilepsy has never been reported in the literature . although dural tears during surgery and csf hypovolaemia are thought to be the main contributing factors , one postulates on the effects of anti - psychiatric medication with epileptogenic properties . amisulpride and olanzapine can lower seizure threshold and should be used with caution in patients previously diagnosed with epilepsy . however manufacturers do not state that in cases where",380,128,0.3368
pubmed-summarization,"amyotrophic lateral sclerosis ( als ) is a progressive and fatal neurodegenerative disease characterized by the loss of lower and upper motor neurons , leading to muscle atrophy , paralysis , and death . sleep disorders in patients with als are well - documented , and sleep - related complaints , such as insomnia , disturbed sleep , nightmare , and daytime sleepiness , have been frequently reported . moreover , several clinical studies on sleep disturbances in patients with als have been published , focusing on the frequency , characteristics , and severity of sleep problems . however , there are no animal or mechanistic studies on sleep disturbances in als . animal and mechanistic studies on sleep disturbances in other neurodegenerative diseases , such as alzheimer 's disease ( ad ) and parkinson disease ( pd ) , might give us insights into sleep disturbances in als . sleep problems in ad and pd involve disturbances in the neurotransmitter and hormone signaling , abnormal accumulations of neurotoxic proteins , and damage in the brain regions controlling the sleep / wake cycles , which could exist in als as well . precursor peptide prepro - orexin , which is produced in the hypothalamic neurons , matures into two peptides , orexin a and orexin b. these peptides promote wakefulness by activating wake - active neurons ( wan ) in the hypothalamus and brain stem . the actions of orexins are mediated by two receptors , orexin-1 ( ox1r ) and orexin-2 ( ox2r ) receptors . we hypothesized that there are disturbances of sleep and wakefulness in the als mouse models and that orexin is an important molecule responsible for those disturbances . in the present study with sod1-g93a transgenic mice , which are extensively used as animal model for mechanistic and therapeutic studies on als , we used sleep / wake activity recordings and molecular techniques to test our hypothesis . transgenic sod1-g93a mice used in this study were bred from male hemizygous sod1-g93 a mice ( b6sjl - tg [ sod1-g93a ] 1 gur / j ) to female b6sjl / f1 hybrids . the genotyping of sod1-g93a mice was performed by polymerase chain reaction ( pcr ) , as previously reported . male hemizygous sod1-g93a mice","background : sleep / wake disturbances in patients with amyotrophic lateral sclerosis ( als ) are well - documented , however , no animal or mechanistic studies on these disturbances exist . orexin is a crucial neurotransmitter in promoting wakefulness in sleep / wake regulation , and may play an important role in sleep disturbances in als . in this study , we used sod1-g93a transgenic mice as an als mouse model to investigate the sleep / wake disturbances and their possible mechanisms in als.methods:electroencephalogram/electromyogram recordings were performed in sod1-g93a transgenic mice and their littermate control mice at the ages of 90 and 120 days , and the samples obtained from these groups were subjected to quantitative reverse transcriptase - polymerase chain reaction , western blotting , and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"has been primarily driven by its maternal-fetal (Brasil et al. , 2016a; Yockey et al. , 2016; Driggers et al. , 2016) and sexual modes of transmission (Deckard et al. , 2016; Davidson et al. , 2016; Hills et al. , 2016) as well as its association with congenital abnormalities, especially microcephaly, and Guillain-Barré syndrome in adults (Krauer et al. , 2017; Martines et al. , 2016; Miner et al. , 2016; Brasil et al. , 2016b). These unique aspects set ZIKV apart from other flavivirus infections and have spurred efforts to understand ZIKV host-pathogen interactions. The ZIKV life-cycle starts with virus attachment and receptor-mediated endocytosis (Hamel et al. , 2015; Meertens et al. , 2017). Upon endosome acidification, the viral envelope fuses with the endosomal membrane, releasing the nucleocapsid into the cytoplasm for uncoating and initial viral translation at the cytosolic surface of the endoplasmic reticulum (ER). Translation produces a single polyprotein that is cleaved co- and post-translationally by cellular and viral proteases into 10 mature proteins: three structural proteins forming the virion (capsid, C; pre-membrane, prM; and envelope, E) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) required for viral replication and inhibition of host defense mechanisms (Campos et al. , 2017; Barrows et al. , 2018). Replication of ZIKV RNA and assembly of viral particles occur in close association with rearranged ER membranes (Rossignol et al. , 2017). Assembled virions are transported through the secretory pathway, where the furin protease cleaves prM into and M, resulting in mature virions that are secreted into the extracellular space (Hasan et al. , 2018). The flaviviral genome contains 5′ and 3′ untranslated regions (UTR) that are essential for genome cyclization and initiation of RNA synthesis (Filomatori et al. , 2006; Alvarez et al. , 2005). The ZIKV 3′ UTR is highly structured and consists of four domains: xrRNA1, xrRNA2, the dumbbell (DB) and the 3′ SL (Zhu et al. , 2016). The ZIKV 3′ UTR contains confirmed and predicted pseudoknot interactions located in xrRNA1 and xrRNA2, respectively. These pseudoknots are important for stalling of the cellular 5′ to 3′ exonuclease, XRN1, and accumulation of at least two sfRNA species (sfRNA1 and sfRNA2) (Akiyama et al. , 2016). The sfRNA of a few different flaviviruses has been","Certain mosquitoes can carry pathogens that are able to infect humans, including Zika and dengue viruses. Most people infected with Zika virus only develop mild symptoms, or no symptoms at all. But if the virus infects a pregnant woman, it can lead to miscarriage and other pregnancy complications, or cause severe birth defects in her unborn baby. Viruses must infect the cells of a host to multiply. To do so, they hijack the cellular machinery to make proteins needed to copy their genetic material and assemble new virus particles. The genetic material of Zika virus is made of ribonucleic acid (RNA). When the Zika virus infects cells, pieces of the virus RNA, known as subgenomic flavivirus RNAs (or sfRNAs for short), accumulate in the cell. Cells infected with",380,128,0.3368
dialogsum,#Person1#: Bring an umbrella with you to the baseball game! The weather report on the radio said it was going to rain today. #Person2#: I'm not going to bring an umbrella. It's beautiful outside! There aren't any clouds in the sky. I don't want to carry anything.,"#Person1# asks #Person2# to bring an umbrella, but #Person2# refuses.",47,10,0.2128
dialogsum,"#Person1#: How come you're still up? Shouldn't you be asleep by now? #Person2#: I've been having a hard time sleeping lately. #Person1#: As far as I know, insomnia is usually caused by stress. Are you stressed at all? #Person2#: Well, I'm really worried about my girlfriend. I cannot contact her for a week. #Person1#: You're a good man. I'm sure she is fine. Maybe she is just traveling and lost her phone. What you need to do is to relax. #Person2#: you're probably right. I just wish it were that simple. How can I stop feeling so anxious all the time? #Person1#: Taking a yoga class or learning some relaxation techniques can help you cope with your stress. #Person2#: I don't really have time to learn anything new. I need to know she is fine. #Person1#: You need to take some breaks throughout the day. Just thinking of her all day isn't very helpful. #Person2#: You're right. Maybe I should go to her home and find her. Or should I call her parents? #Person1#: No, calling her parents is not a good idea. Maybe you can go to her house and see what happens. Perhaps she is just sleeping at home. #Person2#: Could you come along with me? I am truly worried and scared that something bad may happen. #Person1#: Sure, I will go with you. #Person2#: What! Who is that guy?! You don't answer my phones because you are with him! You are cheating on me!",#Person2# is having a hard time because #Person2# is worried about his girlfriend who is out of touch. #Person1# recommends #Person2# relaxing and going to her home to out what happens. They find #Person2# is cheating on him.,247,38,0.1538
scientific_lay_summarisation-elife-norm,"All used chemicals were of commercial origin and used without further purification. UHPLC-MS- grade water and methanol were used for chromatography. D. sechellia (14021–0248. 03,14021–0248. 07,14021–0248. 08,14021–0248. 25,14021–0248. 27,14021–0248. 28,14021–0248. 31) were obtained from the Drosophila Species Stock Center (DSSC, https: //stockcenter. ucsd. edu). D. sechellia (14021–0248. 25), D. simulans (14021–0251. 004) and D. mauritiana (14021–0241. 01) were kindly provided by the Division of Chemical Ecology, Swedish University of Agricultural Sciences. D. melanogaster line wild-type Berlin was kindly provided by Silke Sachse. D. melanogaster line Oregon-R was kindly provided by Rafael Cantera. D. melanogaster pforta was captured in the Weingut Kloster Pforta (Naumburg, Germany). D. melanogaster lines Canton-S (BL1), DGRP-357 (BL25184), DGRP-437 (25194), DGRP-304 (BL25177) and Catsup1/CyO (BL5138) were obtained at the Bloomington Stock Center at Indiana University (http: //flystocks. bio. indiana. edu/). The CatsupIn270De/Catsup1 flies were selected as not carrying CyO from the F1 of a corresponding crossing of the parental lines DGRP-357 and Catsup1/CyO. Flies were reared in vials (50 mm diameter × 95 mm high) at 25°C, 70% RH in L: D 12: 12 on standard cornmeal–yeast–agar medium (standard diet), supplemented as specified in the text, or on fresh morinda pulp (morinda diet) collected from fruits of M. citrifolia plants kept in our greenhouse, or on banana. We observed no differences in survival to morinda fruit in our D. sechellia experimental stock along the successive generations (5 days survival in ripe morinda: 70. 7 ± 5. 6% and 83. 2 ± 3. 6% for new and old females [N = 3], p = 0. 147 using Student' s t test to compare stocks, respectively; 83. 3 ± 16. 7 and 64. 7 ± 18. 2 for new and old males, [N = 3], p = 0. 493 using Student' s t test to compare stocks, receptively), discarding an artificial adaptation to morinda acids. On the other hand, morinda toxicity (Legal and Plawecki, 1995) hindered a permanent experimental stock of D. melanogaster in the fruit, for what flies were fed morinda for as long as the experiment lasted. Morinda carboxylic acids were added to the standard diet or agar plates as indicated in the text, using a range of natural concentrations (0. 07% vol/V of 3: 1 octanoic: hexanoic mix) (Legal et al. , 1994). Triplicates of 10–20","Many insect species rely on another animal or plant species for their own reproduction. For example, a fruit fly called Drosophila sechellia—which is found in the Seychelles—will only feed and lay its eggs on the fruit of a species of tree called Morinda citrifolia. This pairing is particularly unusual because these fruits, commonly called morinda, are toxic to all other Drosophila species. Female Drosophila sechellia flies produce fewer eggs than other Drosophila species, which makes it difficult to raise this species in the laboratory. However providing these flies with morinda fruit, or chemicals from this fruit, was known to increase the expression of many genes involved in egg production and stimulate the flies to lay more eggs. Nevertheless, the reasons why this species of fruit fly depends on",380,128,0.3368
pubmed-summarization,"findings , the differential diagnoses were metastatic liver tumor from rectal carcinoma and ihcc . hence , we performed a left hepatectomy with dissection of the lymph nodes in the hepatoduodenal ligament . abdominal contrast - enhanced computed tomography reveals distention of the superior branch of the bile duct of segment iii of the liver ( b3 ; arrow in [ a ] ) and a nodule in the same segment ( arrow in [ b ] ) . a slightly enhancing lesion extends along the inferior branch of b3 ( arrowhead in [ b ] ) . abdominal magnetic resonance imaging shows a tumor ( indicated by the arrow ) along the bile duct in the left lateral segment , with a low - intensity signal on t1-weighted images ( a ) , an isointense signal with background liver parenchyma on t2-weighted images ( b ) , and a high - intensity signal on diffusion weighted images ( c ) . macroscopically , a whitish nodule , measuring 1.5 1.0 cm , was found in the parenchyma of segment iii adjacent to the inferior surface of the liver ( 4figure 4macroscopic findings of the liver tumor . macroscopically , a whitish nodule measuring 1.5 1.0 cm is observed in segment iii adjacent to the inferior surface of the liver ( arrow ) . the shows that the tumor involves the inferior branch of the bile duct in segment iii and predominantly extends along it ( arrowheads ) . the superior branch of b3 and the bile duct in segment ii were preserved . macroscopically , a whitish nodule measuring 1.5 1.0 cm is observed in segment iii adjacent to the inferior surface of the liver ( arrow ) . the shows that the tumor involves the inferior branch of the bile duct in segment iii and predominantly extends along it ( arrowheads ) . histological examination revealed that an adenocarcinoma showed predominantly intraductal papillary growth replacing the bile duct epithelium ( 5a , b , cfigure 5histological findings of the liver tumor . the histological appearance of the area highlighted by the solid box in is shown . on gross appearance ( a ) , the tumor presented with intrabiliary growth . histological examination shows an adenocarcinoma with intrabiliary","liver metastases from colorectal carcinoma commonly form nodular lesions in the liver parenchyma . we report a case of liver metastasis from rectal adenocarcinoma that extended predominantly into the bile duct . a 62-year - old japanese man underwent low anterior resection for rectal adenocarcinoma 9 years ago . approximately 3 years later , he underwent radiofrequency ablation therapy for a metastatic liver tumor . nine years after surgery , a tumor in liver segment iii exhibiting intrabiliary extension was discovered ; it was unclear if this was a metastatic liver tumor or intrahepatic cholangiocarcinoma . accordingly , we performed a left hepatectomy with lymph node dissection . the tumor was negative for cytokeratins 7 and 20 , and was histologically similar to the primary rectal adenocarcinoma ;",380,128,0.3368
pubmed-summarization,"egfp - ha . the y271a mutation has previously been reported to direct the incorporation of n - carbamate - linked lysines , while the l274 m mutation was discovered to facilitate higher amber suppression activities with 2 in vivo , because it allows greater flexibility of the side chain and imposes less steric bulk at the back of the hydrophobic pocket . this synthetase , termed bhckrs , enabled the site - specific incorporation of not only 2 but also 1 and 3 in response to the amber codon tag within sfgfp - y151tag - his6 in e. coli ( ) . this is not surprising , considering the very similar structures of 13 and previous observations of the high promiscuity of pylrs . to further rationalize the ability of bhckrs to incorporate 13 , molecular modeling was employed . the wild - type pylrs structure ( pdb : 2q7h ) was used as a starting template for which the y271a and l274 m mutations were introduced using modeller . the mutant structure was energy minimized in amber molecular dynamics before docking 13 into the active site pocket using autodock4 . as expected , 13 adopt very similar poses , reflecting their similarity in structure ( see supporting information , s1 ) . the mutated synthetase model reveals that the y271a and l274 m mutations greatly enlarge the binding pocket to accommodate the bulky bicyclic caging group , while also orienting it in a favorable -stacking interaction with w382 . this orientation also benefits from a favorable h - bond interaction between the coumarin hydroxyl group and d373 . similar to published crystal structures , the amino group s positioning is maintained by interactions with a structural water and y349 . it has been previously shown that interactions with n311 and r295 play an important role in amino acid recognition by the pylrs system . the docked structure maintains these key interactions with the carbamate carbonyl forming a h - bond with n311 , while the carboxylic acid forms a h - bond with r295 ( 1b , c ) . sds - page analysis reveals coumarin fluorescence of the expressed proteins containing the coumarin lysines 13 . no fluorescence is observed for wild - type sfgfp because its","the site - specific incorporation of three new coumarin lysine analogues into proteins was achieved in bacterial and mammalian cells using an engineered pyrrolysyl - trna synthetase system . the genetically encoded coumarin lysines were successfully applied as fluorescent cellular probes for protein localization and for the optical activation of protein function . as a proof - of - principle , photoregulation of firefly luciferase was achieved in live cells by caging a key lysine residue , and excellent off to on light - switching ratios were observed . furthermore , two - photon and single - photon optochemical control of egfp maturation was demonstrated , enabling the use of different , potentially orthogonal excitation wavelengths ( 365 , 405 , and 760 nm ) for the sequential",380,128,0.3368
pubmed-summarization,"if mitochondrial deficiency causes insulin resistance it must occur before the onset of the insulin resistance . it does not seem possible to answer the question of whether or not mitochondrial deficiency precedes insulin resistance in humans , because t2 dm patients and obese insulin resistant individuals are insulin resistant for many years before they are diagnosed therefore , available evidence comes from studies on laboratory rodents , which develop muscle insulin resistance within a few weeks after being started on a high - fat diet . if the high - fat diet is continued , the rodents become obese and develop the rodent equivalent of the visceral obesity / metabolic syndrome and/or t2 dm ( 17,18 ) . in a number of early studies , high - fat diets were found to induce an increase in the levels of mitochondrial marker enzymes , such as betahydroxybutyrate dehydrogenase and citrate synthase in muscle ( 19,20 ) . more recently , it was found that feeding rats high - fat diets ( 21,22 ) or intermittently increasing plasma fatty acids to high levels ( 23 ) induces an increase in mitochondrial biogenesis in skeletal muscle . this is evidenced by increases in mitochondrial enzyme proteins , in the capacity to oxidize fatty acids , and in mitochondrial dna copy number . the increase in mitochondria appears to be an early , transient event that is lost as the insulin resistance and obesity progress ( 24 ) . the fatty acid - induced increase in muscle mitochondria appears to be mediated by the nuclear receptor peroxisome proliferator activated receptor- ( ppar- ; also referred to as ppar- ) . ppar- is a transcription factor for the genes encoding the enzymes of the mitochondrial fatty acid oxidation pathway . previous studies had shown that overexpression or activation of ppar- in muscle induces an increase in mitochondrial biogenesis ( 25,26 ) . the investigators who performed these studies concluded that the increase in mitochondrial biogenesis was mediated directly by ppar- , because overexpression of ppar- in muscle did not result in an increase in peroxisome proliferator activated receptor coactivator-1 ( pgc-1 ) mrna . however , this did not seem possible , because ppar- regulates expression of only a subset of mitochondrial proteins and","based on evidence that patients with type 2 diabetes ( t2 dm ) , obese insulin - resistant individuals , and lean insulin - resistant offspring of parents with t2 dm have 30% less mitochondria in their muscles than lean control subjects , it appears to be widely accepted that mitochondrial deficiency is responsible for insulin resistance . the proposed mechanism for this effect is an impaired ability to oxidize fat , resulting in lipid accumulation in muscle . the purpose of this counterpoint article is to review the evidence against the mitochondrial deficiency concept . this evidence includes the findings that 1 ) development of insulin resistance in laboratory rodents fed high - fat diets occurs despite a concomitant increase in muscle mitochondria ; 2 ) mitochondrial",380,128,0.3368
dialogsum,"#Person1#: good morning. I understand that you'Ve got a problem with your washing machine. I'm from the repair company. #Person2#: excellent. Come in please. The washing machine is in the bathroom upstairs. It keeps breaking down. #Person1#: when did it first break down? #Person2#: about ten days ago. I'Ve tried to use it since then. Sometimes it works and sometimes it doesn't. it's very frustrating. #Person1#: is it still under warranty. If it is and I can't fix it, it would be quicker and easier to exchange it for a new one. #Person2#: yes, it's still under warranty. Over the last few weeks, it's also been making a high - pitch noise when it's in use. #Person1#: ok. I'll start by looking at the motor. I'll just unplug it and take a look inside the machine. . . oh, yes. There's the problem. It's quite simple. I'll sort it out in a few minutes. #Person2#: what's wrong with it? #Person1#: part of the motor is loose. I can put it back in place quite easily. #Person2#: that's great. Thanks very much. Would you like a cup of tea or coffee?",#Person2#'s washing machine keeps breaking down. It's still under warranty. #Person1# checks it and finds part of the motor is loose. #Person1#'ll fix it.,190,24,0.1263
scientific_lay_summarisation-elife-norm,"in Genetic and Molecular Epidemiology (GP) Mitochondria are semiautonomous organelles present in nearly every human cell that execute fundamental cellular processes including oxidative phosphorylation, calcium storage, and apoptotic signaling. Mitochondrial (MT) dysfunction has been implicated as the underlying cause for many human disorders based on mechanistic in vitro and in vivo studies (Burbulla et al. , 2017; Desdín-Micó et al. , 2020; Sliter et al. , 2018). Complementary evidence comes from recent epidemiological studies that measure mitochondrial DNA copy number (mtDNA-CN), an MT-derived marker that can be conveniently measured from peripheral blood. Since mitochondria contain their own unique set of genomes that are distinct from the nuclear genome, the ratio of mtDNA to nuclear DNA molecules (mtDNA-CN) in a sample serves as an accessible marker of MT DNA abundance per cell (Longchamps et al. , 2020). Indeed, observational studies suggest that individuals with lower mtDNA-CN are at higher risk of age-related complex diseases, such as coronary artery disease, sudden cardiac death, cardiomegaly, stroke, portal hypertension, and chronic kidney disease (Tin et al. , 2016; Ashar et al. , 2017; Zhang et al. , 2017; Hägg et al. , 2021). Conversely, higher mtDNA-CN levels have been associated with increased cancer incidence (Kim et al. , 2015; Hu et al. , 2016). While previous studies demonstrate that mtDNA-CN is associated with various diseases, evidence suggests that it may also play a direct and causative role in human health and disease. For example, in cases of mtDNA depletion syndrome, wherein rare defects in nuclear genes responsible for replicating and/or maintaining mtDNA lead to deficient mtDNA-CN (Gorman et al. , 2016), patients manifest with severe dysfunction of energy-dependent tissues (heart, brain, liver, and cardiac and skeletal muscles). So far, 19 genes have been reported to cause mtDNA depletion (Oyston, 1998). In addition to these rare monogenic syndromes, the importance of common genetic variation in regulating mtDNA-CN is an active area of research with approximately 50 common loci identified so far (Cai et al. , 2015; Guyatt et al. , 2019; Longchamps, 2019; Hägg et al. , 2021). In contrast to marked drops in mtDNA-CN by 60–80% as seen in those with rare mtDNA depletion syndromes, the relevance of subtler perturbations in mtDNA-CN in disease risk remains to be determined (Basel, 2020). Granted, the connection","Our cells are powered by small internal compartments known as mitochondria, which host several copies of their own ‘mitochondrial’ genome. Defects in these semi-autonomous structures are associated with a range of severe, and sometimes fatal conditions: easily checking the health of mitochondria through cheap, quick and non-invasive methods can therefore help to improve human health. Measuring the concentration of mitochondrial DNA molecules in our blood cells can help to estimate the number of mitochondrial genome copies per cell, which in turn act as a proxy for the health of the compartment. In fact, having lower or higher concentration of mitochondrial DNA molecules is associated with diseases such as cancer, stroke, or cardiac conditions. However, current approaches to assess this biomarker are time and resource-intensive; they also do not",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence. Tail-anchored (TA) proteins are integral membrane proteins with a single C-terminal transmembrane segment (TMS). In the budding yeast Saccharomyces cerevisiae, the majority of TA proteins are captured post-translationally by cytosolic factors of the conserved Guided Entry of TA proteins (GET) pathway, which deliver them to the endoplasmic reticulum (ER) membrane for insertion by a dedicated insertase (Denic et al. , 2013; Hegde and Keenan, 2011). TA proteins native to the outer mitochondrial and peroxisomal membranes are directly inserted into these membranes by mechanisms that are not well defined (Chen et al. , 2014a; Papić et al. , 2013, and reviewed in Borgese and Fasana, 2011). Gene deletions of GET pathway components (getΔ) result in reduced cell growth, TA protein mistargeting to mitochondria, and cytosolic TA protein aggregates (Jonikas et al. , 2009; Schuldiner et al. , 2008). Two recent studies identified the ATPase associated with diverse cellular activities (AAA ATPase) Msp1 as an additional factor for supporting cell viability in the absence of GET pathway function (Chen et al. , 2014b; Okreglak and Walter, 2014). Specifically, they observed that msp1Δ cells accumulate mislocalized TA proteins in the mitochondria and that double msp1Δ getΔ cells have synthetic sick genetic interactions. This sick phenotype is associated with disruption of mitochondrial function and is exacerbated by overexpression of TA proteins prone to mislocalization (Chen et al. , 2014b). Msp1 is a cytosolically-facing transmembrane AAA ATPase","The phrase “finding a needle in a haystack” refers to the difficulty of locating a specific target among a large number of very similar objects. Living cells face a comparable challenge whenever they carry out seek and destroy missions aimed at broken or otherwise undesirable molecules. Scientists are still figuring out how these quality control systems can quickly and accurately pick out the few unwanted molecules that occasionally appear in crowds of normal molecules. Msp1 is a quality control protein that resides on the outer surfaces of two compartments within cells: mitochondria and peroxisomes. Previous work showed that when a protein called Pex15, which is normally found in peroxisomes, is mistakenly sent to mitochondria it is rapidly eliminated by Msp1. Weir et al. set out to understand if",380,128,0.3368
dialogsum,"#Person1#: I'm pretty busy these days. I was given a new research project by the professor. He asked me to find research information about countries in Asia. #Person2#: Isn't it interesting? #Person1#: Yes, and there's much information I can get. But I was told to finish it in 3 days. #Person2#: What kind of information do you have to get? #Person1#: Mainly cultural customs, holidays and something like that. #Person2#: I'm pretty good at that kind of thing. #Person1#: Really? Then tell me how many languages are spoken in India. #Person2#: Uh...I think English and maybe a lot? #Person1#: And when was the Great Wall of China built? #Person2#: Sorry, I have no idea. Oh, I guess I can help you look it up on the Internet.","#Person1# is busy working on a new research project. #Person2# thinks #Person2# is good at it but can't answer #Person1#'s questions, so #Person2# turns to help #Person1# look it up on the Internet.",127,33,0.2598
pubmed-summarization,"fluids would be . usually , the value of n of pan / traditional organic solvents solutions is between 0 and 1 . therefore , it could be postulated that there would be some much stronger interaction between pan and the new solvent [ bmim]cl which will be discussed in the following text . the data in shows that the viscosity - shear rate curves for the pan/[bmim]cl solutions of different concentrations . these curves show that solutions of lower concentration remain newtonian in behavior at high shear rates than concentrated solutions . at high concentration , the rheological behavior of pan/[bmim]cl solutions acts like that of liquid crystalline polymers ( lcp ) . the solvent [ bmim]cl reduces the number of entanglements . reducing the number of entanglements at a given shear rate since the orientation of macromolecular is the major cause of non - newtonian behavior , increasing the shear rate would make the non - newtonian behavior more noticeable . besides , it could be found in that when at high shear rate , the viscosity of high concentration solutions is lower than that of low concentration , for example , the viscosity of 22wt% solution is the lowest among all the solutions when the shear rate is close to 1000 1/s . as we known , liquid crystalline polymers usually have rigid chain segment such as aromatic polyamide and aromatic polyester . the flexibility of the c - c bond of the pan main chain is smaller than the c - o bond , c - n bond and decrease because of the strong polarity of the cn , but comparing to the liquid crystalline polymers , the pan chain segment can not be oriented because of lack of strong rigid chain segment . in this case , high concentration means more entanglements , which indicates that only low shear rates would be needed to orient the macromolecules . and the amount of entanglements is so large that there is no enough time and much more difficulties for most of them to slip and disengage . with the increasing of the shear rate the number of the oriented segments increases , so that the viscosity of the high concentration pan/[bmim]cl solution decreases greatly . commonly ,","one of the room temperature ionic liquids ( rtils ) , 1-butyl-3-methylimidazolium chloride ( [ bmim]cl ) was chosen to prepare the concentrated solutions of polyacrylonitrile ( pan ) . the rheological behaviors of the solutions were measured with rotational rheometry under different conditions , including temperatures , concentration , and molecular weight of pan . the solutions exhibited shear - thinning behaviors , similar to that of pan / dmf solutions . the viscosities decreased with the increasing of shear rates . however , the viscosity decreased sharply at high shear rates when the concentration was up to 16wt% . the dependence of the viscosity on temperature was analyzed through the determination of the apparent activation energy . unusually , the viscosity of solutions of higher concentration",380,128,0.3368
dialogsum,"#Person1#: You look upset, is there anything wrong? #Person2#: Yes, to tell you the truth, there is. #Person1#: What is it? #Person2#: Well, I've lost my wallet and my ID card. #Person1#: Oh, that's too bad! I am sorry to hear that! #Person2#: Forget it, there is no use crying over the spilled milk.",#Person2# lost #Person2#'s wallet and ID card. #Person1# feels sorry.,54,10,0.1852
pubmed-summarization,"is the possibility of tumor progression . for this reason , most centers started to use locoregional or neoadjuvant therapies to control tumor growth in patients while waiting . although bridging therapies using ablation , tace , resection , or combination treatments have been used by different transplant centers worldwide , the real impact and indication of any type of neoadjuvant treatments are still in debate . some authors propose that patients with hcc waiting for more than 3 to 6 months should be treated . various studies have suggested that treatment of hcc prior to lt in patients with a waiting time less than 6 months is not associated with an impact in patient survival or tumor recurrence and raises the question of cost effectiveness of treatment . the overall risk of dropout in patients with diagnosis of hcc waiting for liver transplantation has been reported in the range of 15% to 30% at one year . new studies have reported that a lower incidence of dropout in the range of 0% to 25% may be related to the use of neoadjuvant therapies . however , locoregional or neoadjuvant treatments prior to liver transplantation have been used to reduce tumor burden if patients are considered to be outside criteria for transplantation in a strategy called downstaging . the group from paris , france , at l'hopital paul brousse , initially recommended this strategy in 1997 . they observed higher rates of survival in tace responders than in nonresponders in an analysis of patients with more than three nodules or nodules greater than 3 cm . furthermore , several prospective studies have reported good patient survival compared to patients undergoing lt without prior intervention . the use of radiofrequency ablation ( rfa ) for the treatment of liver tumors started in the early 1990s both in europe and in the usa . radiofrequency ablation ( rfa ) is a form of locoregional therapy that utilizes a high - frequency alternating current using a probe inserted into the tumor . the radiofrequency waves are converted into thermal energy within the conducting tissue , destroying the tumor . early experiences reported high risk of seeding , making rfa not an appealing treatment in patients while waiting to be transplanted . however ,","hepatocellular carcinoma ( hcc ) is the most common primary malignancy of the liver accounting for 7% of all cancers worldwide . most cases of hcc develop within an established background of chronic liver disease . for that reason , liver resection is only possible in selected patients . liver transplantation has become the treatment of choice in patients with hcc , end - stage liver disease , and significant portal hypertension . shortage of organ donors has resulted in overall increase of waiting list time with increased risk of dropout due to tumor progression . neoadjuvant therapies have emerged as an alternative to control tumor growth in patients while waiting . the aim of this study is to review the literature on the role of bridging therapy",380,128,0.3368
dialogsum,"#Person1#: What do you do in your spare time? #Person2#: I have many hobbies. I like almost all kinds of sports and I also like to listen to classical music. #Person1#: What kinds of sports do you like? #Person2#: I like playing basketball. Basketball is a very exciting game because it keeps you alert and I also enjoy the team spirit of basketball. #Person1#: Who is your favorite author? #Person2#: I like the novels of Dickens very much. I've read almost all of them in Chinese translation. #Person1#: Are you a music lover? #Person2#: Yes, I like listening to Beethoven's works. #Person1#: What kinds of films do you enjoy? #Person2#: I like all kinds as long as they are exciting.","#Person1# asks about #Person2#'s hobbies, including #Person2#'s favorite sports, favorite author, favorite music, and favorite films.",120,16,0.1333
dialogsum,"#Person1#: Excuse me, can you tell me if there is a gas station around here? #Person2#: Yeah, there are a few. The closest one is only a couple of blocks away. But it's a little expensive. The cheapest one is about 2 miles from here. #Person1#: Well, I think I should just go for the closest one. #Person2#: OK. Just go straight until you see the first traffic lights up there. Take a left turn and go down one block. You'll see the gas station near a post office. #Person1#: OK, I should be able to make it.",#Person1# needs to go a gas station. #Person2# tells #Person1# how to get to the closest one.,98,17,0.1735
dialogsum,"#Person1#: There will be a party at my new house this Saturday. Would you like to come? #Person2#: That sounds good, but I have French class in the morning and dance class in the afternoon. #Person1#: That's OK. The party is to start in the evening, and you can come after the dance class. #Person2#: Great! Should I bring something? #Person1#: Yes, it's a potluck party, so you should prepare something to eat. #Person2#: No problem. A roast turkey, salad, or pudding... I was wondering which to prepare. #Person1#: Anything will be fine. #Person2#: I think I'm good at pudding. I'll make banana-flavored pudding for you. #Person1#: Nice. See you then.",#Person1# invites #Person2# to a party. #Person2# will make a pudding and bring it to the party.,111,17,0.1532
scientific_lay_summarisation-elife-norm,"Posttranslational modifications (PTMs) play a crucial role in a wide range of biological processes. Lysine crotonylation (Kcr) is a newly discovered histone PTM that is enriched at active gene promoters and potential enhancers in mammalian cell genomes. However, the cellular enzymes that regulate the addition and removal of Kcr are unknown, which has hindered further investigation of its cellular functions. Here we used a chemical proteomics approach to comprehensively profile ‘eraser’ enzymes that recognize a lysine-4 crotonylated histone H3 (H3K4Cr) mark. We found that Sirt1, Sirt2, and Sirt3 can catalyze the hydrolysis of lysine crotonylated histone peptides and proteins. More importantly, Sirt3 functions as a decrotonylase to regulate histone Kcr dynamics and gene transcription in living cells. This discovery not only opens opportunities for examining the physiological significance of histone Kcr, but also helps to unravel the unknown cellular mechanisms controlled by Sirt3, that have previously been considered solely as a deacetylase. Histone posttranslational modifications (PTMs) play a crucial role in regulating a wide range of biological processes, such as gene transcription, DNA replication, and chromosome segregation (Kouzarides, 2007). Increasing evidence has indicated that PTMs of histones can serve as a heritable ‘code’ (so-called ‘histone code’), which provides epigenetic information that a mother cell can pass to its daughters (Jenuwein and Allis, 2001). Histone code is ‘written’ or ‘erased’ by enzymes that add or remove the modifications of histones (Goldberg et al. , 2007; Kouzarides, 2007). Meanwhile, ‘readers’ of histone code recognize specific histone modifications and ‘translate’ the code by executing distinct cellular programs necessary to establish diverse cell phenotypes, while the genetic code (DNA) is unaltered (Seet et al. , 2006; Taverna et al. , 2007). Lysine acetylation (Kac) was among the first covalent modification of histones to be described (Allfrey and Mirsky, 1964; Allfrey et al. , 1964). Since its identification, histone Kac has been correlated with gene expression. However, the mechanistic insights into the regulation and functions of histone Kac remained challenging and elusive, until the identification and characterization of the enzymes responsible for the addition and removal of this PTM, which are now known as histone acetyltransferases (Roth et al. , 2001) and deacetylases (Sauve et al. , 2006; Yang and Seto, 2008b; Haberland et al. , 2009), respectively. Extensive studies have now revealed that Kac","Most of the DNA in a cell is wound around histone proteins to form a compacted structure called chromatin. Enzymes can modify the histones by adding small chemical tags on to them, and these histone modifications can cause the chromatin to either become more tightly packed or more open. Opening up the chromatin makes the DNA more accessible to the cellular machinery involved in gene expression. Thus, cells can regulate which genes they express, and by how much, by modifying the histone proteins. Like all other proteins, histones are made of smaller molecules called amino acids. Specific amino acids within histone proteins can be modified in a number of different ways, with different effects. For instance, adding a chemical tag called an acetyl group onto an amino acid",380,128,0.3368
dialogsum,"#Person1#: This is a great jacket, but look at the price! It's too expensive. $ 600! #Person2#: No, wait. It's pretty reasonable. You're thinking in US dollars not Hong Kong dollars. It's only about 100 US dollars. #Person1#: You're right.",#Person1# thinks the jacket is great but too expensive. #Person2# reminds #Person1# that it's reasonable in HK dollars.,40,18,0.45
scientific_lay_summarisation-elife-norm,"It is now clear that microglia and macrophages are present in brain tumors, but whether or how they affect initiation and development of tumors is not known. Exploiting the advantages of the zebrafish (Danio rerio) model, we showed that macrophages and microglia respond immediately upon oncogene activation in the brain. Overexpression of human AKT1 within neural cells of larval zebrafish led to a significant increase in the macrophage and microglia populations. By using a combination of transgenic and mutant zebrafish lines, we showed that this increase was caused by the infiltration of peripheral macrophages into the brain mediated via Sdf1b-Cxcr4b signaling. Intriguingly, confocal live imaging reveals highly dynamic interactions between macrophages/microglia and pre-neoplastic cells, which do not result in phagocytosis of pre-neoplastic cells. Finally, depletion of macrophages and microglia resulted in a significant reduction of oncogenic cell proliferation. Thus, macrophages and microglia show tumor promoting functions already during the earliest stages of the developing tumor microenvironment. Microglia are the resident macrophages of the brain (for review see [Kettenmann et al. , 2011; Casano and Peri, 2015]). Microglia are derived from primitive macrophages that invade the brain during development (Ginhoux et al. , 2010; Schulz et al. , 2012; Herbomel et al. , 2001). Due to the neuronal environment, they finally differentiate to microglia and build up a resident population that is almost evenly dispersed throughout the central nervous system. Microglia fulfil a tremendous repertoire of functions in the brain. In addition to their classical immune functions, numerous studies have described roles for microglia in brain development, vessel patterning, synaptic pruning, the regulation of neuronal activity and even the influence of certain animal behaviors (Casano and Peri, 2015). Despite the variety of beneficial functions in the brain, microglia can also act detrimentally during certain pathologies. Brain tumors represent probably the most severe example of harmful microglial functions. Microglia and infiltrating macrophages have been shown to infiltrate high-grade gliomas and can account for up to 30% of the tumoral mass (Graeber et al. , 2002; Badie and Schartner, 2001; Li and Graeber, 2012; Yang et al. , 2010; Coniglio and Segall, 2013). Instead of anti-tumoural activity, they display pro-tumoural functions and promote tumor growth. Macrophages and microglia have been shown to promote tumor cell proliferation and invasiveness, to modify the extracellular matrix,","Brain tumors can be aggressive, difficult to treat and are often incurable. Removing brain tumors by surgery can be challenging because the tumor cells infiltrate into the healthy tissue. Brain tumors grow in close physical contact with other cells, such as cells of the immune system. This includes cells called macrophages and microglia, which normally defend us against injuries and infections. However, instead of acting against the tumor as one might expect, macrophages and microglia actually support the growth of brain tumors. It is not clear how and when during the development of a brain tumor the macrophages and microglia start helping the tumor cells to grow. Previous studies in this area have focused on these cell types found in advance brain tumors. Chia et al. have now",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKCβ can bypass the Btk and PLC-γ2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCβ-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses. FAK inactivation or deficiency impaired B cell discrimination of substrate stiffness. Conversely, adhesion molecules greatly enhanced this capability of B cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited an altered BCR response to substrate stiffness in comparison with healthy controls. These results provide a molecular explanation of how initiation of B cell activation discriminates substrate stiffness through a PKCβ-mediated FAK activation dependent manner. Cells interact with an intricate mechanical extracellular microenvironment by sensing physical signals and using surface receptors to convert them into chemical signals and, subsequently, cellular responses (Sun et al. , 2012; Liu et al. , 2015). Lymphocytes – the cells of the adaptive immune system – include B and T cells, both of which use surface expressed antigen receptors to sense external antigens. The B cell receptor (BCR) is composed of a membrane-bound entity of immunoglobulin (Ig) and an Igα-Igβ heterodimer in a 1: 1 stoichiometry (Pierce and Liu, 2010). The engagement of the BCR and antigen leads to initiation of B cell activation. It is known that antigens exhibit great diversity and B cell activation is remarkably sensitive to the diversity of antigen properties, including antigen density (Liu et al. , 2010a; Fleire et al. , 2006), antigen affinity (Liu et al. , 2010a; Fleire et al. , 2006), antigen valency (Bachmann et al. , 1993; Liu and Chen, 2005; Liu et al. , 2004), and Brownian mobility of the antigen (Wan and Liu, 2012). Previous studies have suggested the extraordinary capability of B cells to sense the chemical and physical features of the antigen, although the presenting forms of antigen are far more complicated under physiological conditions. Recent studies have also suggested that the antigens encountered by B cells in vivo are presented on substrates with various stiffness (also referred as rigidity or elasticity) features (Bachmann and Jennings, 2010). Stiffness","The human immune system protects the body from harmful bacteria, viruses and other microbes. Immune cells called B cells use proteins called B cell receptors on their surface to identify these invaders. When the B cell receptors detect molecules called antigens on the surface of the microbes, they produce signals that activate the B cell and enable it to combat the infection. Previous research has found that B cells react differently to antigens depending on the stiffness of the surface to which an antigen is attached. Now, Shaheen, Wan, Li et al. have attached antigens to artificial surfaces that were either stiff or soft and examined how B cells responded to them. Some of the B cells were modified to lack particular molecules that are important for B",380,128,0.3368
dialogsum,"#Person1#: Dad, I want to learn how to drive this summer vacation. #Person2#: That's a good idea. You'd better hurry up before they've filled all classes. Many people are learning how to drive now. #Person1#: I will get registered now at once. Do you know any training schools? #Person2#: I am not sure. You can search for them on the Internet. #Person1#: OK. look, I've typed driver schools, and there are so many results coming out. #Person2#: Let me see. teetee Training School, summer program, 3, 000 Yuan, learn how to drive within one month, and get driver's license within three months. #Person1#: 3, 000 Yuan is a little bit steep. #Person2#: I think so. Let's see the next one, 3, 500 Yuan, summer program. Forget it. #Person1#: I've heard that the Ideal Life School is famous. They offer many programs and there are many classes available. The charge is also fair. #Person2#: Search on the Internet then, see if we can find something more about it. #Person1#: Ah, got it. Ideal Life School, programs #Person2#: Don't worry. Let's check out some other schools.","#Person1# tells #Person1#'s dad wants to learn to drive this summer vacation. Then, #Person1# and #Person1#'s dad begin to search for training schools on the internet.",184,26,0.1413
pubmed-summarization,"with the aging of the population worldwide , dementia is a real public health priority . in 2000 , the estimated number of dementia cases was 25.5 million people , representing 0.4% of the worldwide population . nearly two thirds of all people with dementia lived in low- and middle - income countries . the other most important risk factors are low level of education , heredity , low early - life economic conditions , smoking , alcohol , weak social network , hypertension , cardiovascular diseases , stroke , epilepsy , diabetes , anemia , parkinson 's disease , and head trauma . although several population - based studies were conducted in developed countries to better understand the epidemiology of this new epidemic , only a few studies have been done in africa . in senegal , the estimated number of elderly aged 65 years was 421,305 in 2008 and 420,795 in 2009 . considering the economic cost of dementia care , senegal is not able to afford such cost . it is important to have reliable information on the prevalence of dementia to plan for more accurate provision of social and medical services for the elderly population . studies on dementia in the senegalese elderly population are rare . thus , a study was conducted in senegal to determine the epidemiology of dementia in an elderly population utilizing a primary health care service for retirees in dakar , senegal . the aim of the present study was to identify risk factors associated with dementia in this population of retirees utilizing the social and medical center ( smc ) of ipres ( institution de prevoyance retraite du senegal ) , dakar , senegal . this is a health center for the retired senegalese elderly population affiliated to ipres ensuring medical and social services . as a primary care center with diverse health personnel , the study population was composed of senegalese elderly patients aged 65 years who came to the smc of ipres for health problems . those patients who were either < 65 years old or were not able to fulfill the interview ( due to aphasia , delirium , coma , extreme visual and auditory impairment , or cancer at terminal phase ) were excluded . 507","backgroundwith the aging of the population , dementia is increasing worldwide . the objective of this study was to identify risk factors for dementia in an elderly population utilizing a primary health care service in dakar , senegal.methodsthrough a cross - sectional study conducted from march 2004 to december 31 , 2005 , 507 elderly patients aged 65 years who came to the social and medical center of ipres , dakar , senegal , were first screened with the screening interview questionnaire aging in senegal. those who were cognitively impaired underwent a clinical examination to detect dementia . univariate , bivariate , and multivariate logistic regression analyses were done.resultsthe whole population had a mean age of 72.4 years ( 5.2 ) and was mostly male , married ,",380,128,0.3368
pubmed-summarization,"all medical college departments of ophthalmology in a representative state of the country were evaluated by two external assessors . the state was chosen for convenience ; logistical ease ; and the fact that it was one of the beneficiaries of the world bank program , as well as of a second round of funding by a local body . the data were accumulated during two evaluations performed 8 years apart . while the second evaluation was suggested at the end of the first study , it was not part of the plan when the first assessment took place . however , the methodology , as well as the data collected during the second study , was based on the first . eight medical college departments were evaluated during the first visit . during the ensuing years , 3 more departments had developed ; and a total of 11 departments were evaluated during the second phase . a structured questionnaire [ appendix 1 , 2 ] was sent out in advance to the respective heads of department to determine details like the number of students , patients seen , operations done and list of the equipment available . following this , the evaluator scheduled a site visit and spent a day in each of the departments . the preferred characteristics of an ophthalmology training program were specified in advance and were the considered opinion of the first evaluator and agreed to by the second prior to the next evaluation . the criteria considered indicators of suitable outpatient and ward care in a medical college department are shown in table 3 ; those for the operating room are shown in table 4 . undergraduate training was assessed using a questionnaire , observation and personal interview only during the first evaluation . at the time of the first visit , fourteen trainer of trainers who had been trained by the world bank program were interviewed . changes in teaching and practice pattern , including surgery , instrumentation and their use , were documented for the eight departments examined on the two occasions . the number of outpatients seen in the departments varied from 95 ( 70 new and 25 old ) to 1,300 ( 800 new , 500 old ) per month","aim : to evaluate teaching and practice in medical college ophthalmology departments in a representative indian state and changes following provision of modern instrumentation and training.study type : prospective qualitative study.materials and methods : teaching and practice in all medical colleges in the state assessed on two separate occasions by external evaluators . preferred criteria for training and care were pre - specified . methodology included site visits to document functioning and conduct interviews . assessments included resident teaching , use of instrumentation provided specifically for training and standard of eye care . the first evaluation ( 1998 ) was followed by provision of modern instrumentation and training on two separate occasions , estimated at rupees 34 crores . the follow - up evaluation in 2006 used the",380,128,0.3368
dialogsum,"#Person1#: Your office called and said that the owners had made a counter-offer to my offer to purchase their house. #Person2#: To your offer of three hundred and twenty thousand dollars, the owners have counter-offered three hundred and thirty-five thousand dollars. #Person1#: I think that maybe I should accept their offer. #Person2#: You, of course, have two ways of responding. You can say yes or come up with another offer. #Person1#: I want to make another offer, but I am afraid that they will decline and I will lose this house. #Person2#: There is always a chance that someone could outbid you, but you could try one more offer if you like. #Person1#: I would now like to offer three hundred and thirty thousand dollars as a counter-offer. #Person2#: After the owners get home from work tonight, I will approach them with your offer. #Person1#: Can you tell me how long it will take them to get back to me? #Person2#: I don't think that it will take as long as the response to the first offer.",#Person1#'s offer is counter offered by the owner. #Person1# offers once more. #Person2# will get back to #Person1# when the owner responds.,177,22,0.1243
dialogsum,"#Person1#: You only have an hour for lunch. #Person2#: Well, now I have only 45 minutes. #Person1#: That's not much time. Where should we go? How about Tornis Ettling Restaurant? Just across the street. I love the pizza. #Person2#: I love the food too, but they are really slow. Last week, I waited 30 minutes for my food. #Person1#: OK. Let's have a sushi at the David's. We can be in and out in 20 minutes. #Person2#: Today is the Thursday, David's is not open. #Person1#: Alright. Then let's go to the Jungle Cafe. We can be there in 60 seconds. #Person2#: Good idea.",#Person1# and #Person2# talk about where to have lunch and they finally decide to the Jungle Cafe.,104,17,0.1635
dialogsum,"#Person1#: Oh, my goodness, I can't find my book! you must have left the book in the taxi. It's a very good book, you know. #Person2#: But I have to tell you that you are wrong. I didn't take it at all. I remember clearly that you put it in our bedroom. Oh, yes, on your dressing table. #Person1#: Really? Okay, I am sorry.","#Person1# thinks #Person2# left the book in the taxi. Actually, #Person1# put it on the dressing table in their bedroom.",64,20,0.3125
scientific_lay_summarisation-elife-norm,"et al. , 2006) to track movements of single vesicles in voltage-clamped synaptic terminals. We also targeted the exocytosis reporter pHluorin (Sankaranarayanan et al. , 2000) to synaptic vesicles (Granseth et al. , 2006; Voglmaier et al. , 2006) in order to detect vesicle fusion. These approaches then allowed us to analyze the trafficking and fusion of vesicles at the active zone of BPC ribbon synapses during ongoing neurotransmitter release. Previously, studies of synaptic vesicle trafficking and fusion at ribbon synapses of BPCs have been carried out using total internal reflection fluorescence microscopy (TIRFM) to image single vesicles labeled with FM dye (Zenisek et al. , 2000,2002; Holt et al. , 2004; Midorikawa et al. , 2007; Zenisek, 2008; Joselevitch and Zenisek, 2009). Some of the conclusions from this work are: 1) vesicles stably associate with ribbons in the absence of stimulation (‘residents’), 2) these resident vesicles rapidly undergo exocytosis in response to depolarization, and 3) new vesicles (‘newcomers’) appear, move toward the membrane, and fuse during sustained depolarization. Although TIRFM is a powerful approach to study membrane-associated phenomena, it is limited to imaging labeled vesicles within ~100 nm of the plasma membrane (e. g. , Zenisek et al. , 2000), which is insufficient to provide coverage of all the ribbon-associated vesicles. The method also requires tight adherence of the plasma membrane to a planar substrate, which restricts observations to a small part of the terminal and eliminates the natural membrane curvature in that observable region. Furthermore, to our knowledge, only Midorikawa et al. (2007) and Zenisek (2008) have combined vesicle imaging with ribbon labeling, and then only in sequentially acquired images separated by some time, which were intended to test whether observed hotspots of fusion coincided with ribbons. Because of these limitations, we used two-color laser scanning methods that allowed single labeled vesicles to be observed throughout the full extent of the ribbon in voltage-clamped synaptic terminals, while the ribbon and cell border were imaged with a second fluorescent label. Since the positions of the ribbon and a labeled vesicle were known accurately, we were able to detect vesicle movements on the ribbon prior to fusion and determine where vesicles resided on the ribbon when they fused. Therefore, our experiments complement and significantly extend the previous studies based on","Neurons communicate with one another through junctions known as synapses. When a neuron is activated, it triggers the release of chemicals called neurotransmitters at the synapse, which bind to and activate neighbouring neurons. Neurons involved in vision, sound and balance contain “ribbon” synapses, which are able to release neurotransmitters steadily over longer periods of time than other types of synapse. Neurotransmitters inside neurons are packaged into small structures called vesicles, which can then fuse with the cell’s surface membrane to release the neurotransmitters from the cell. Unlike other types of synapse, ribbon synapses are able to release these vesicles in a continuous fashion. How vesicles move around at the synapses remains poorly understood because monitoring the vesicles in living cells is technically difficult and previous studies were limited",380,128,0.3368
scientific_lay_summarisation-elife-norm,"modulated by running direction and spatial location, respectively (Hafting et al. , 2005; Sargolini et al. , 2006). In contrast, cells in the LEC respond to individual objects in the environment rather than to specific locations (Deshmukh and Knierim, 2011; Tsao et al. , 2013; Knierim et al. , 2013). Despite a wealth of data and marked differences in structure and function of the rodent MEC and LEC evidence for their human homologue remains elusive. This hampers translational studies, which is particularly relevant in the case of Alzheimer' s disease (AD) with AD pathology starting in the EC (Braak and Braak, 1992). Within the EC, the vulnerability to AD-related pathology is not homogeneously distributed and differs between medial and lateral strips in humans, which has been related to similar findings in the rodent MEC and LEC, respectively (Khan et al. , 2014). However, the localization of the human homologue of the rodent MEC and LEC remains unclear. A source of considerable confusion is the fact that ‘MEC’ and ‘LEC’ are referring to cytoarchitectonically defined areas and not to anatomical locations. Hence, they do not circumscribe strips of medial and lateral EC. Rather, the MEC is located medially in the septal (posterior) part of the EC and the LEC is located laterally in the temporal (anterior) part of the EC in rodents (Van Strien et al. , 2009). Furthermore, tracing studies on PHC and PRC pathways in non-human primates suggest a dominant anterior-posterior division (Suzuki and Amaral, 1994; Insausti and Amaral, 2008), as do single-unit recordings that show activity consistent with the rodent LEC in the anterior EC in primates (Killian et al. , 2012). In contrast, neuroimaging studies on memory in healthy participants (Schultz et al. , 2012; Reagh and Yassa, 2014) and participants with preclinical AD (Khan et al. , 2014) suggest that the rodent MEC and LEC map on medial and lateral strips of EC in humans. To resolve this discrepancy in the literature, one needs to investigate the relatively small EC (25–30 mm2 in humans) (Krimer et al. , 1997) with high anatomical precision. An earlier study investigated entorhinal connectivity with high-resolution functional magnetic resonance imaging (fMRI), but averaged signal changes over the entire region (Lacy and Stark, 2012). To achieve higher resolution imaging, here we leveraged","In the early 1950s, an American named Henry Molaison underwent an experimental type of brain surgery to treat his severe epilepsy. The surgeon removed a region of the brain known as the temporal lobe from both sides of his brain. After the surgery, Molaison' s epilepsy was greatly improved, but he was also left with a profound amnesia, unable to form new memories of recent events. Subsequent experiments, including many with Molaison himself as a subject, have attempted to identify the roles of the various structures within the temporal lobes. The hippocampus—which is involved in memory and spatial navigation—has received the most attention, but in recent years a region called the entorhinal cortex has also come to the fore. Known as the gateway to the hippocampus, the entorhinal",380,128,0.3368
dialogsum,"#Person1#: Say, have you heard about Jennie? #Person2#: No, what happened? #Person1#: She's had her baby. #Person2#: Oh, that's wonderful! When? #Person1#: A couple of weeks ago. #Person2#: Was it a boy or a girl? #Person1#: A girl. #Person2#: Oh, that's great! That's what she wanted, isn't it? #Person1#: Yeah, she always likes the girls. #Person2#: What are they going to call her? #Person1#: Christine, I think.","#Person1# tells #Person2# Jennie's had a baby girl, and Jennie like girls.",67,12,0.1791
scientific_lay_summarisation-elife-norm,"conditions may still be classified as ‘Hebbian LTP’, because of the requirement for co-incident presynaptic and postsynaptic activation, the existence of LTP under these conditions would imply that Hebbian-like LTP occurs at finer spatial scales than the more cell-wide form that most current models employ. Thus, during behavior, neurons that fire may undergo LTP, but even a neuron that is synaptically activated but axonally silent during a behavioral event can be recruited to participate in the neural engram. Interestingly, hippocampal place cells behave in a manner suggestive of a form of Hebbian LTP that may not require postsynaptic action potential firing: many cells are silent when the animal first goes to a new place, and then they are recruited to participate in the network representation of the spatial map (Frank et al. , 2004). This suggests that if synaptic plasticity contributes to reshaping the network upon initial exposure to a new environment, it need not be conventional Hebbian plasticity, but rather a modified form of Hebbian plasticity that does not require axonal firing, such as the second and third conditions described above. Consistent with this idea, hippocampal neurons receive spatially tuned synaptic inputs even when they are silent (Lee et al. , 2012). Understanding whether and how such inputs can drive synaptic plasticity will be an important step toward understanding how spatial memories are formed in the hippocampus. If axonal action potential firing is required for synaptic plasticity, memories can only be stored in active neurons. On the other hand, if it is not required, memories can also be formed in silent neurons. Furthermore, plasticity that is induced by dSpikes that remain localized to individual dendritic branches has been proposed to enhance the memory-storing capacity of individual neurons (Poirazi and Mel, 2001; Mehta, 2004; Wu and Mel, 2009). Collectively, these considerations underscore the importance of understanding the dendritic events leading to the postsynaptic calcium entry necessary for the induction of LTP. At synapses from the perforant path (PP; which carries predominantly spatial information from the entorhinal cortex) to the distal apical tuft of hippocampal CA1 pyramidal neurons, LTP requires strong synaptic activation, and LTP induction can have a significant impact on the output of CA1 neurons (Colbert and Levy, 1993; Remondes and Schuman, 2002; Ahmed and Siegelbaum, 2009; Takahashi and","When we explore somewhere new, we activate a region of the brain that processes spatial information called the entorhinal cortex. This brain region stimulates the brain' s memory-formation center, known as the hippocampus, which in turn forms a spatial memory of the new place. The process of forming these memories involves strengthening nerve connections, including those between the entorhinal cortex and the hippocampus. Groups of neurons that produce synchronized electrical activity will naturally strengthen the nerve connections between them. This led scientists to predict that synchronized electrical activity between neurons in the entorhinal cortex and the hippocampus may contribute to the formation of spatial memories. Previous research revealed that hippocampal neurons produced short bursts of electrical activity that are localized at specific sites along their branched nerve processes",380,128,0.3368
dialogsum,"#Person1#: We could go to a ball game this evening or would you rather eat in a restaurant and then see a film? #Person2#: To tell you the truth, I can't really go anywhere this evening, because I'm expecting an important phone call.",#Person2# is waiting for an important phone call and refuses #Person1#'s invitation.,43,12,0.2791
scientific_lay_summarisation-elife-norm,"of severe birth defects called ulnar-mammary syndrome (Bamshad et al. , 1997). Efforts to understand the molecular biogenesis of this developmental disorder uncovered additional functions for TBX3 beyond transcriptional repression (Fan et al. , 2009; Frank et al. , 2013; Kumar et al. , 2014) as well as critical roles in adult tissue homeostasis (Frank et al. , 2012). The pleiotropic effects of TBX3 gain and loss of function suggest its molecular activities are context and cofactor dependent. Despite the biologic importance of TBX3, few interacting proteins or target genes have been discovered, and the mechanisms underlying its regulation of cell fate, cell cycle, and carcinogenesis are obscure. We found that TBX3 associates with CAPERα (Coactivator of AP1 and Estrogen Receptor), a protein identified in a liver cirrhosis patient who developed hepatocellular carcinoma (Imai et al. , 1993). CAPERα regulates hormone responsive expression and alternative splicing of minigene reporters in vitro (Jung et al. , 2002; Dowhan et al. , 2005) but its in vivo functions are unknown. We show that a CAPERα/TBX3 repressor complex is required to prevent premature senescence of primary cells and regulates the activity of core senescence pathways in mouse embryos. We discovered co-regulated targets of this complex in vivo and during oncogene-induced senescence (OIS), including a novel tumor suppressor, the lncRNA UCA1. UCA1 is sufficient to induce senescence and does so in part by sequestering hnRNP A1 to specifically stabilize CDKN2A-p16INK mRNA. Our finding that CAPERα/TBX3 regulates p16 levels by dual, reinforcing mechanisms position CAPERα/TBX3 and UCA1 upstream of multiple members of the p16/RB pathway in the regulatory hierarchy that controls cell proliferation, fate and senescence. We recently discovered that TBX3 (human) and Tbx3 (mouse) interact with RNA-binding and splicing factors (Kumar et al. , 2014). Among these, mass spectrometry of anti-TBX3 immunoprecipitated (IP' d) proteins identified CAPERα (1A). Since TBX3 functions in mammary development and may contribute to the pathogenesis of breast and other hormone responsive cancers (Douglas and Papaioannou, 2013), its interaction with an ERα co-activator drove further investigation. 10. 7554/eLife. 02805. 003Figure 1. CAPERα and TBX3 directly interact via the TBX3 repressor domain. (A) Representative spectrum for CAPERα identified in anti-TBX3 co-IP of HEK293 cell lysates. Mass spec analysis identified six specific CAPERα peptides, providing 8. 5% sequence coverage of the protein.","Cell division and growth are essential for survival. But it is equally important that cells can stop dividing, because failing to do so can lead to the uncontrolled tumor growth seen in cancer. One such quality control mechanism is called senescence, which stops the growth and multiplication of cells that are old, damaged or behaving in ways that may harm the organism. All cells eventually stop dividing and undergo senescence, but a number of factors may trigger the process early, such as DNA damage, stress or the appearance of cancer-causing proteins. Senescence can be harmful if it occurs too early in life and interferes with normal growth. Severe birth defects—including fatal heart problems and limb malformations—occur if senescence is inappropriately triggered early in development. Mutations in a gene",380,128,0.3368
dialogsum,"#Person1#: Susan, would you and Frank like to come to our house warming party this weekend? #Person2#: A house warming party? You mean you are moving to a new home? #Person1#: Yeah, Deborah and I are moving to a new home in another city. We bought it 2 months ago. #Person2#: Congratulations! both of you must be very happy. #Person1#: Well, we have always dreamed of owning our own home here, but houses in London are so expensive. #Person2#: I understand. Christopher and I have been living in the house we rent for 13 years. We found it very difficult to buy a house here, although we have been saving Well, when is the party? #Person1#: 7:00 PM this Friday, at Googly Swiss Cottage. I'll send you directions. #Person2#: OK. Christopher and I will be there on time.",#Person1# invites Susan to the house warming party. #Person1#'s moving to a new home in another city because the houses in London are too expensive.,138,25,0.1812
pubmed-summarization,"from 0.5 to 6 cm . cutaneous lesions were violaceous indurated papules and plaques on the anterior aspects of both legs in the previous site of saphenous vein angioplasty from 3 years ago . these lesions clinically resembled ks [ figures 1 and 2 ] . additionally , laboratory findings showed anemia ( hb : 9.6 mg / dl ) , increased esr ( 98 mm / h ) , elevated wbc count ( 11100 mm ) with 12% eosinophilia , and also negative viral markers ( hhv-8 , hiv , hcv , hbv ) . notably , chest ct scan demonstrated extensive bilateral axillary adenopathy , pretracheal and antrosuperior mediastinal adenopathy , subpleural wedge - shaped consolidation on the base of the left lung , and subpleural nodules on the right lung recommended to rule out of lymphoma . abdominopelvic ultrasound revealed mild hepatosplenomegaly with a hyperechoic solid mass in the mid portion of spleen suggesting hemangioma whereas retroperitoneal lymphadenophathy was not detected . also , bone marrow aspiration was normal . brown - bluish papules and nodules of kaposi 's sarcoma violaceous indurated lesions on the legs in the previous location of saphenous angioplasty a skin biopsy of the lesions showed hypercellular neoplasm composed of proliferated spindle - shape cells arranged in a whorled and fascicular pattern with slit - like spaces containing red blood cell with extravasation [ ] . an axillary lymph node biopsy demonstrated follicular hyperplasia with marked vascular proliferation , hyalinization , and few tight concentric layers of lymphocytes , arranged in onion skin appearance [ ] . the patient was treated with granulocyte colony - stimulating factor ( g - csf ) for four sessions , alpha interferon 2b ( ifn-2b ) subcutaneously for 5 months and vinblastin weekly . eventually , patient 's pruritus relieved after 2 months , lymphadenopathy regressed , general condition became good , and also , the patient went into the clinical remission . moreover , radiotherapy within 5 months and ks lesions regressed . the patient received 30 sessions of irradiation on the skin lesions resulting in complete regression . proliferation of spindle cells arranged in a whorled and fascicular pattern with slit - like spaces containing red blood cell extravasation ( hematoxylin and eosin40 ) follicular","castleman 's disease ( cd ) or giant lymph node hyperplasia is a rare disorder that can be unicentric or multicentric . multicentric castleman 's disease ( mcd ) is manifested by generalized lymphadenopathy , hepatosplenomegaly , polyclonal hypergammaglobulinemia , hematological abnormality , and constitutional symptoms . human herpesvirus 8 ( hhv-8 ) infection is present in nearly 100% mcd associated with hiv-1 infection , but in about 50% of cases of hiv negative . herein , we report a 77-year - old man with systemic involvement and skin lesions on the anterior aspect of both legs in the previous site of saphenous vein angioplasty . co - existence of mcd with kaposi 's sarcoma ( ks ) led us to present this rare case .",380,126,0.3316
dialogsum,"#Person1#: Good morning, Mr. Smith. #Person2#: Good morning, Jamie. What time is it now? #Person1#: It is 9 o'clock now. #Person2#: I see. What is today's schedule? #Person1#: You have two meetings today. One is at 10 am, and the other is at 2 pm. After the meeting, you will have dinner with Mr. Brown at the Chinese restaurant in Sister Hotel. #Person2#: OK. Can you prepare things for the meeting in the meeting room? Make enough copies of the handouts. #Person1#: No problem. Do you need the OHP? #Person2#: Yes. I am going to show them some slides in the meeting. Can you call Mr. Brown to remind him of the dinner this evening? #Person1#: OK. Do you want to ask the receptionist to wait for our customers at the receptionist counter before the meeting? #Person2#: That would be great! You are really a good employee.",Jamie tells Mr. Smith about his schedule today. Mr. Smith asks Jamie to prepare things for the meeting and remind Mr. Brown of the dinner.,147,25,0.1701
pubmed-summarization,"phenylketonuria ( pku ; omim 261600 ) is defined as an autosomal recessive genetic inborn error of phenylalanine ( phe ) metabolism ( 1 ) . insufficiency in the hepatic specific enzyme , phenylalanine- 4-hydroxylase ( pah ) ( ec 1.14.16.1 ) leads to hyperphenylalaninemia that is associated with the pku ( 1 ) . deficiency of the pah enzyme results in the elevation of phe concentration in blood and biological fluids that is approximately above 2 mg / dl ( 120 mol / l ) in the pre - treatment condition ( 1 - 4 ) . the prevalence of pku among patients institutionalized for mental retardation varies from 1% to 3% ( 4 - 6 ) . the frequency of pku varies from high incidence in turkey ( about 1 in 2600 births ) to low incidence in japan ( about 1 in 125000 births ) ( 7 ) . overall , the incidence of pku among caucasians is about 1 in 10,000 , giving a carrier frequency of about 1 in 50 to 1 in 70 ( 7 ) . the incidence of pku in iranian population has been expected at 1 in 3627 live births ( 8) . genetic overall diversity in iranian populations is very high and comparable to the other populations from the south caucasus region , anatolia and europe ( 9 ) . it has been shown that iranian azerbaijanis with a population of about 15 to 20 million are more related to the georgians in comparison to other iranian groups ( 9 ) . the finding of derenko et al ( 2013 ) is based on maternal genetic structure on the mitochondrial dna studies ( 9 ) . however , this result may change based on paternal genetic structure and y - chromosome tracing . west azerbaijan province with a population of about 3 million is in north - west of iran and closely related to turks . regarding to a relatively high incidence of pku alleles in iranian population as well as high rate of consanguineous marriages in iran ( 10 ) , this study was carried out for mutation analysis of the pah gene in west azerbaijan province of iran . this study was performed regarding the ethical guideline in","objective(s):phenylketonuria ( pku ) is a genetic inborn error of phenylalanine ( phe ) metabolism resulting from insufficiency in the hepatic enzyme , phenylalanine hydroxylase ( pah ) , which leads to elevated levels of phe in the blood . the present study was carried out for mutation analysis of the pah gene in west azerbaijan province of iran.materials and methods : a total of 218 alleles from 40 pku families were studied using restriction fragment length polymorphism - polymerase chain reaction ( rflp - pcr ) method.results:the frequencies of ivs10 - 11 , s67p , r261q , r252w , ivs11nt-1 g > c , r408q , and q232q mutations were 28(35 ) , 17(21.25 ) , 15(18.75 ) , 3(3.75 ) , 3(3.75 ) , 2(2.5 )",380,128,0.3368
dialogsum,"#Person1#: Honey, do you have a second? #Person2#: Sure! Are you okay? You seem a bit worried. What's on your mind? #Person1#: We need to talk. #Person2#: Okay. . . #Person1#: I'Ve been thinking, and well, I think we need to start seeing other people. #Person2#: What? Why? I mean, we'Ve had our ups and downs, and we have the occasional disagreement, but we're happy together, aren't we? #Person1#: That's just it, I'm not happy anymore, Tim. It's not you, it's me. I know that I can be hard to deal with, and you are a great guy! You are the type of guythat any woman would kill for! #Person2#: So, what are you saying? You're breaking up with me because I'm perfect? #Person1#: Tim, you are too good for me. You deserve someone who can make you smile and make you happy the way that you made me happy. Oh, I could say that I'll be all you need, but that would be a lie. I know I'd only hurt you, I know I'd only make you cry. #Person2#: Baby, come on. Don't do this to me! Whatever it is, we can work it out. Just give me another chance! I know that we can get through this, but we gotta stick together! Don't leave me. #Person1#: I can't, Tim. I hope someday you can find some way to understand I'm only doing this for you. I don't really wanna go but, deep in my heart I know this is the kindest thing to do. #Person2#: Laura. . . #Person1#: Here are your keys. I'll send my sister to pick up the rest of my things next week. I'm sorry, Tim. I wish you all the best, and I hope that one day we can meet again. I'll always love you. Goodbye.",Laura wants to break up with Tim because she thinks she doesn't deserve him. Tim tries to change her mind and wishes her to give him another chance so they can get through this but fails.,303,36,0.1188
scientific_lay_summarisation-elife-norm,"and Joshi, 2000; Schulte-Hostedde and Millar, 2004), but they could also have lower survival during the non-breeding season when resources are scarce (Stockhoff, 1991; Reznick et al. , 2000; Munch et al. , 2003; Monaghan, 2008). In addition, large individuals might take more time to grow and require more resources for maintenance (Munch et al. , 2003), which could negatively impact their survival probability (Kingsolver and Huey, 2008). This association between fitness and body size in seasonal environments could have important consequences for population dynamics, particularly when selection on body size is density-dependent (Mueller, 1997; Sinervo et al. , 2000; Travis et al. , 2013). Differences in the selective advantage of body size across seasons could also shed light on the long-standing question about why population densities of many species fluctuate periodically over time (Elton and Nicholson, 1942; Kendall et al. , 1999; McCauley et al. , 2008; Yan et al. , 2013). For example, when body size is positively related to fecundity, but small individuals survive better in the non-breeding season (Stockhoff, 1991; Munch et al. , 2003; Monaghan, 2008; Betini et al. , 2014), these opposing patterns of selection could cause population cycles if selection is density-dependent. Specifically, if smaller offspring have higher survival when density is high, then the population will be composed of smaller than average individuals with lower average fecundity in the following breeding season. This lower mean fecundity will reduce population growth rates even though larger individuals will be favoured through fecundity selection. As population size declines, the strength of density-dependent viability selection on body size will also decline, which could cause net selection to reverse and favour larger individuals due to the fecundity benefit of being larger. As large individuals increase in frequency, population size should also increase via an improvement of reproductive output, returning populations to high densities. Although changes in the intensity and direction of natural selection caused by environmental variation are widespread (Schluter et al. , 1991; Bell, 2010; Thompson, 2013; Bergland et al. , 2014), we have little information about whether opposing episodes of natural selection could arise from seasonality and indirectly affect population dynamics through the feedback loop between ecological (density dependence) and evolutionary (selection and evolution) processes (Chitty, 1960; Krebs, 1978; Hairston et al. , 2005; Pelletier","Many wild populations go through long cycles in abundance that span several generations. The traditional explanation for such “multigenerational” cycles is that they are driven by predator/prey relationships, the classic example being oscillations between the numbers of lynx and snowshoe hares. Population cycles could also be driven by seasonal changes. For example, traits that help animals to produce large numbers of offspring during the breeding season may reduce the ability of the animal to survive the non-breeding season. Body size is one such trait. Large individuals tend to produce more offspring, but their larger body size means that they find it harder to survive when food is scarce. As a consequence, large individuals should have an advantage and be more common when the population size is low and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins. Glycogen synthase kinase (GSK-3) α and β are serine/threonine kinases that act as key downstream regulators in multiple signaling pathways, including Wnt/β-catenin, receptor tyrosine kinase (RTK) /PI3K, and Sonic hedgehog (Shh) (Kaidanovich-Beilin et al. , 2012). GSK-3s act via mechanisms that include regulation of transcription factors, control of multiple aspects of cellular metabolism, and phosphorylation of cytoskeletal proteins (Hur and Zhou, 2010; Kaidanovich-Beilin and Woodgett, 2011). Most often, although not invariably, GSK-3s function as negatively acting kinases by inhibiting the functions of substrates at baseline. Inhibition is then relieved via signaling pathways that engage GSK-3 (Doble and Woodgett, 2003; Kaidanovich-Beilin and Woodgett, 2011). For most GSK-3 substrates, phosphorylation by another kinase near the GSK-3 site (‘priming’) is required for, or enhances, GSK-3 substrate phosphorylation (Cohen and Frame, 2001; Doble and Woodgett, 2003; Kaidanovich-Beilin and Woodgett, 2011). Priming kinases for GSK-3 substrates include cyclin dependent kinase-5 (cdk5), a kinase that is known to regulate important neurodevelopmental events like radial migration (Tanaka et al. , 2004; Cole et al. , 2006; Li et al. , 2006; Xie et al. , 2006). In the nervous system, GSK-3β has long been thought to be a target of lithium used in treatment of bipolar disorder (Klein and Melton, 1996; O' Brien et al. , 2004). Some of the GSK-3β effects related to lithium actions are due to regulation of signaling downstream of dopamine receptors (Beaulieu et al.","In the brain, one of the most striking features of the cerebral cortex is that its neurons are organized into different layers that are specifically connected to one another and to other regions of the brain. How newly generated neurons find their appropriate layer during the development of the brain is an important question; and, in humans, when this process goes awry, it can often result in seizures and mental retardation. An enzyme called GSK-3 regulates several major signaling pathways important to brain development. The GSK-3 enzyme switches other proteins on or off by adding phosphate groups to them. Morgan-Smith et al. set out to better understand the role of GSK-3 in brain development by deleting the genes for this enzyme specifically in the cerebral cortex of mice.",380,128,0.3368
dialogsum,#Person1#: What do you do? #Person2#: I'm a firefighter. #Person1#: Really? That's so cool. #Person2#: I'm really lucky to do something I really love. #Person1#: What station do you work at? #Person2#: I work downtown at station 24. It can get a little crazy sometimes but that's what makes it challenging.,#Person2# loves to work as a firefighter at station 24.,51,10,0.1961
dialogsum,"#Person1#: Uh, Dad. Are you going to miss me when I leave for college next week? #Person2#: Yahoo! #Person1#: No, Dad ... seriously. I mean you're always talking about how much money you'll save on food, hot water, and gas while I am gone. #Person2#: Of course I will ... no, uh, well, I'll miss you, of course. No, honestly, I'll miss and worry about you, and you've really tried to prepare yourself. You know, I'm proud of you for that. You know, getting a university degree is a real accomplishment. #Person1#: Exactly. #Person2#: But, let's go over the to-do list. Do you have everything ready? I mean, did you pay your tuition and housing fees by the deadline? [Yeap.] Because, you know, if you don't, you'll lose your class schedule, and you have to register all over again. #Person1#: Yeah, I paid for that a few days ago. #Person2#: Okay, did you sign up for the meal plan at the university so you don't have to eat instant noodles everyday? #Person1#: Yeap. But Mom said I could take some food from home to get me started. #Person2#: Uhhh, well, yeah. The oatmeal is in the pantry. #Person1#: Dad! Mom said I could take a bag of rice, some canned food, and ... #Person2#: ... and grandpa's old army rations. #Person1#: Ugh! Not that old stuff. Mom! #Person2#: Okay, okay. And you know you should set up an appointment to meet with your academic advisor to help you select future classes, right? [Yeah.] You know, business administration will be a great major for you. #Person1#: Well, Dad, uh ... #Person2#: And future possibilities ... a great salary, opportunities to make a difference in the community, and [Dad. I changed my major.] supporting ... What? You changed you major ... you switched majors!? #Person1#: Yeah. I really thought about it. After talking it over with Mom, I've decided to major in wildlife science. #Person2#: What? What are you talking about? #Person1#: Yeah. I want to degree in wildlife science. You know, analyzing, maintaining, and conserving national forests and wildlife. #Person2#: What? Uh, uhh ... #Person1#: Dad. You can close your mouth now. I mean, I've ALWAYS been interested in working with nature; [Well.] You know that, and this field will give",#Person1# and #Person1#'s dad talk about the needed preparation before #Person1# heads for college next week. Then #Person1# tells #Person1#'s dad that #Person1# has decided to change the major to wild science and #Person1# is about to get married. #Person1# 's dad is shocked.,380,44,0.1158
dialogsum,"#Person1#: Excuse me, miss. I'm Bob. #Person2#: I'm Amy. How do you do? #Person1#: I'm very glad to meet you. May I have this dance with you? #Person2#: Certainly! I suppose you dance often. #Person1#: No, I don't often dance. Isn't this a wonderful party? #Person2#: Yes, I'm glad I have come. #Person1#: How do you like fox-trot? #Person2#: I like it very much. #Person1#: You dance beautifully. #Person2#: Thank you. It's lucky that I have got a good partner. #Person1#: Thank you.",Bob invites Amy for a dance at the party and praises her beautiful dance.,83,14,0.1687
scientific_lay_summarisation-elife-norm,"of transport in TBDTs is presently poorly understood; however, the large size of most substrates and the absence of any obvious pathway for substrate permeation (Faraldo-Gómez et al. , 2003) have led to proposals that transport is mediated by a significant conformational event that involves a partial rearrangement or full removal of the core domain from the surrounding barrel (Chimento et al. , 2005). Although many high-resolution structures are available for TBDTs, there is no direct evidence for a major structural change within the core of TBDTs that might indicate a transport mechanism. In the Escherichia coli vitamin B12 (cobalamin) transporter, BtuB, EPR spectroscopy shows that substrate binding unfolds the Ton box at the N-terminus and extends it into the periplasm, an allosteric event that may facilitate the binding of TonB to BtuB (Kim et al. , 2007; Xu et al. , 2006); however, no other significant structural changes have been observed in the core. High-resolution crystal structures have been obtained for a C-terminal fragment of TonB in complex with BtuB, the ferrichrome transporter FhuA, and the ferrioxamine B transporter FoxA (Pawelek et al. , 2006; Shultis et al. , 2006; Josts et al. , 2019). When TonB binds, the Ton box extends from the core and interacts with the β-sheets of TonB in an edge-to-edge manner. Except for the Ton box, the remainder of the core remains folded and is essentially unchanged. Because TonB binding does not alter the core of BtuB in the BtuB-TonB structure, it has been proposed that TonB alters the core by exerting a mechanical force on the transporter, and current models for transport favor a mechanism where TonB acts by pulling the Ton box thereby unfolding the core (Gumbart et al. , 2007; Hickman et al. , 2017; Sverzhinsky et al. , 2015). Models involving a rotation of TonB have also been proposed (Klebba, 2016); however, in FhuA there are four to five unstructured residues between the Ton box and core when TonB is bound, making the transfer of torque from TonB to the core unlikely (Sarver et al. , 2018). Pulling models have been explored using steered molecular dynamics (MD) (Gumbart et al. , 2007) as well as single-molecule AFM (atomic force microscopy) pulling experiments (Hickman et al. , 2017), and these studies","Bacteria must obtain nutrients from their surrounding environment in order to survive. In Gram-negative bacteria, proteins in the outer membrane surrounding the cell actively transport carbohydrates and trace nutrients like iron into the cell’s interior. Although the structures of many of these transport proteins have been determined, the mechanism they use to move molecules across the membrane is poorly understood. To better understand this process, Nilaweera, Nyenhuis and Cafiso examined the structure of BtuB, a transport protein found in the outer membrane of Escherichia coli that is responsible for absorbing vitamin B12. Previous experiments analyzing the structure of BtuB, and other similar transporters, have been carried out on purified proteins that were extracted from the outer membrane. However, these isolated proteins fail to replicate the transport activity observed",380,128,0.3368
pubmed-summarization,"sxct ) . sxct has been known since mid-1980 s and resolutions available now are below 1 m , e.g. at esrf / id19 , allowing in - situ experiments due to the short measuring period . spatial resolution of about 180 nm has recently been achieved for relatively large metallic samples on esrf / id22 by using magnifying kb - mirrors . in addition , sxct produces also phase contrast due to the high lateral coherence of the beam , so that even interfaces between phases with very low absorption contrast can be displayed . phase contrast for cone beam sub-xct was also reported but to a much lower extent . the specifications of typical xct systems ( x - ray source and voxel sizes ) are compared in table 1 . there have been several investigations of cone beam xct and sxct applied to various materials . xct and sxct for the 3d - characterization of inhomogeneities in steel are presented in , but no quantitative comparison was carried out . the possible applications of sub-xct are described in , but no comparison with sxct is presented . a quantitative comparison was carried out in , but the resolutions ( voxel sizes ) used are in the range of several micron ( 210 m ) and thus not in the sub-m - xct region . in cone beam xct and sxct are compared quantitatively but no sub-xct cone beam xct measurements were performed . in summary , there are no systematic investigations on metallic samples with up - to - date spatial resolutions down to 1 m ( voxel sizes below 1 m ) published . this paper deals with the application of high resolution cone beam xct in comparison with synchrotron xct applied to fe- and al - based samples containing several phases . the xct - data are analysed with respect to measurement artefacts , detection of details , sharpness , contrast and signal - to - noise ratio . one steel and two al alloys were investigated ; all the samples included various inhomogenities such as inclusions , pores or metallic phases with a higher or lower density than the matrix resulting in distinguishable features in the corresponding ct - data - sets . a","x - ray computed tomography ( xct ) has become a very important method for non - destructive 3d - characterization and evaluation of materials . due to measurement speed and quality , xct systems with cone beam geometry and matrix detectors have gained general acceptance . continuous improvements in the quality and performance of x - ray tubes and xct devices have led to cone beam ct systems that can now achieve spatial resolutions down to 1 m and even below . however , the polychromatic nature of the source , limited photon flux and cone beam artefacts mean that there are limits to the quality of the ct - data achievable ; these limits are particularly pronounced with materials of higher density like metals . synchrotron",380,128,0.3368
dialogsum,"#Person1#: Hello. #Person2#: Susan? #Person1#: Yes, Peter is that you? #Person2#: Yes. #Person1#: Hi. How are you? #Person2#: As a matter of fact, I'm rather weak, that's why I'm calling you. I've had a stomachache and a terrible headache for 2 days. Now I think I need a doctor. #Person1#: Do you have a temperature? #Person2#: No, I don't. But I feel like I'm burning up. I think I need a doctor, but I'm not sure how to get one. #Person1#: Did you take out any medical insurance when you first came to university? #Person2#: Yes, I did. #Person1#: Good our university clinic has excellent doctors. I have a lunch break at noon and I'll drive over and pick you up. #Person2#: Oh, I feel so bad. Couldn't you get a doctor to come here? #Person1#: That's a little difficult. Go back to bed, I'll pick you up just afternoon. #Person2#: Ok, goodbye. #Person1#: Goodbye.",Peter calls Susan because he has a stomachache and a headache. Susan will drive Peter to the university clinic after lunch.,155,21,0.1355
dialogsum,"#Person1#: You know, I'm a pretty laid-back person. I don't like to have lots of arguments or worry about lots of things. For example, I like to keep the apartment clean too, but if it gets a little dirty once in a while, that's not a big deal. #Person2#: I totally agree. I really like my lifestyle to be drama-free, and I don't want to argue about cleaning the apartment. My last roommate was a drama queen. Every time I forgot to take my shoes off, she got really mad and made a big deal out of it. #Person1#: Yeah, I really don't want a lot of drama in the apartment. It's important that we don't get on each other's nerves. #Person2#: That's right. We should try to be laid back and not do lots of things to bother one another.",#Person1# and #Person2# are laid-back people that they don't want to argue about cleaning the apartment and not to do lots of things to bother one another.,141,27,0.1915
scientific_lay_summarisation-elife-norm,"Non-rapid eye movement (NREM) sleep, characterized by slow-wave electrophysiological activity, underlies several critical functions, including learning and memory. However, NREM sleep is heterogeneous, varying in duration, depth, and spatially across the cortex. While these NREM sleep features are thought to be largely independently regulated, there is also evidence that they are mechanistically coupled. To investigate how cortical NREM sleep features are controlled, we examined the astrocytic network, comprising a cortex-wide syncytium that influences population-level neuronal activity. We quantified endogenous astrocyte activity in mice over natural sleep and wake, then manipulated specific astrocytic G-protein-coupled receptor (GPCR) signaling pathways in vivo. We find that astrocytic Gi- and Gq-coupled GPCR signaling separately control NREM sleep depth and duration, respectively, and that astrocytic signaling causes differential changes in local and remote cortex. These data support a model in which the cortical astrocyte network serves as a hub for regulating distinct NREM sleep features. Sleep is characterized by distinct electrophysiological features that reflect the rhythmic activity of large populations of neurons. One phase of sleep—non-rapid eye movement (NREM) sleep—is critical for several important functions including memory consolidation/destabilization and synaptic homeostasis (Klinzing et al. , 2019; Genzel et al. , 2014; Kim et al. , 2019; Tononi and Cirelli, 2014; Diekelmann and Born, 2010; Tononi and Cirelli, 2006; Tononi and Cirelli, 2020; Ji and Wilson, 2007). These functions are thought to require slow-wave activity (SWA), the distinct oscillatory pattern of neural activity in the cortex that occurs during NREM sleep and differentiates it from the relatively desynchronized activity during wakefulness and REM sleep. However, neural activity during NREM sleep is not uniform over the course of sleep, but varies in duration and depth (as measured by SWA intensity). Past work has demonstrated that NREM sleep duration and depth can be independently controlled (Dijk and Beersma, 1989; Patrick and Gilbert, 1896). Indeed, the circuit mechanisms known to underlie sleep depth and duration are largely independent from each other and operate on very different time-scales: sleep duration is mediated by subcortical nuclei that receive direct input from circadian centers and drive sleep/wake transitions through release of neuromodulatory signals (Holst and Landolt, 2018; Saper and Fuller, 2017; Lee and Dan, 2012). On the other hand, SWA intensity is largely regulated by cortical and thalamocortical circuits (Chen et al. ,","Sleep has many roles, from strengthening new memories to regulating mood and appetite. While we might instinctively think of sleep as a uniform state of reduced brain activity, the reality is more complex. First, over the course of the night, we cycle between a number of different sleep stages, which reflect different levels of sleep depth. Second, the amount of sleep depth is not necessarily even across the brain but can vary between regions. These sleep stages consist of either rapid eye movement (REM) sleep or non-REM (NREM) sleep. REM sleep is when most dreaming occurs, whereas NREM sleep is particularly important for learning and memory and can vary in duration and depth. During NREM sleep, large groups of neurons synchronize their firing to create rhythmic waves of",380,128,0.3368
dialogsum,"#Person1#: My mom thinks that we should name the baby after her. What do you think? #Person2#: I think your mom is a little too selfish. Plus, I don't really think Betty Betson sounds like a name I'd want to have. #Person1#: OK, I just had to ask. I didn't like the idea much either. I really love the name Laura, though. #Person2#: That's nice but I think we should give her a really strong name so she stuff. How about Helga or Josephine? #Person1#: Those names make me think of unattractive women. Elga sounds like a lady who could carry me under her arm. #Person2#: That's the idea. I don't want anyone thinking they can mess with my daughter. I want her to be able to stand up to people, especially any boys who might try to look at her. #Person1#: I don't think a name has that much power, dear. #Person2#: OK, I see your point. I'll just have to take care of the boys myself. I know this baby is going to be beautiful. #Person1#: That's right. Let's not give her an ugly name. How about something more elegant like Victoria? #Person2#: I like that.",#Person1#'s mom wants #Person1# to name the baby after her but #Person2# doesn't like the idea. #Person2# wants to give her a strong name but #Person1# doesn't like it. They eventually decide to call her Victoria.,198,36,0.1818
scientific_lay_summarisation-elife-norm,"to both Atm-/- and Atm+/+ cells (Daniel et al. , 2012), and ATM kinase inhibitor, but not loss-of-ATM, reduced homologous recombination (HR) as measured by sister chromatid exchange (SCE) (White et al. , 2010) and the DR-GFP HR reporter (Rass et al. , 2013; Kass et al. , 2013), suggesting a role of ATM auto-phosphorylation in replication associated homology dependent repair. Yet, it is unknown how ATM auto-phosphorylation contributes to DNA replication and HR beyond its previously identified signaling roles. Finally, consistent with the' inter' -molecular autophosphorylation model, Atm+/KD mice are largely normal (Yamamoto et al. , 2012), suggesting that ATMKD mutation carriers could be asymptomatic and somatic loss of the WT allele in the carriers might create the Mut/Del status reported in human cancers and lymphomas. Here we report that 72% of human cancer-associated ATM mutations are missense mutations that are highly enriched in the kinase domain. We further show that conditional expression of Atm-KD protein alone (somatic inactivation of the conditional allele (AtmC) in AtmKD/C mice to generate the AtmKD/- cells) in murine hematopoietic stem cells (HSCs) is more oncogenic than the complete loss of ATM (Atm-/-). AtmKD/- cells are selectively hypersensitive to Topo Isomerase I (Topo1) inhibitors, in part because the Atm-KD protein physically blocks replication-dependent strand cleavage upon Topo1 inhibition. Correspondingly, Topo1 inhibitor selectively eradicates Notch1-driven AtmKD/- leukemia, but not the isogenic parental Atm proficient leukemia, identifying Topo1 inhibitors as a targeted therapy for human cancers carrying missense ATM kinase domain mutations. Among the 5402 cases in The Cancer Genome Atlas (TCGA), we identified 286 unique non-synonymous mutations of ATM. While truncating (nonsense/frameshift) mutations compose 83% (373/447) of A-T associated point mutations (>1000 patients), 72% (206/286) of non-synonymous point mutations of ATM in TCGA are missense mutations (1A, Supplementary file 1A, B). Permutation analyses show that ATM gene is not hyper-mutated, but the kinase-domain is mutated 2. 5 fold more frequently than otherwise expected in TCGA (— 1A, p<0. 01). The mutation density calculated using the Gaussian Kernel model revealed that cancer associated missense ATM mutations in TCGA cluster around the C-terminal kinase domain, while truncating mutations (in A-T or TCGA) span the entire ATM protein (1B and — 1B). Given the severe phenotype of AtmKD/-, but not AtmKD/+ cells, we further analyzed the subset (~105/286)","Cancer is a genetic disease. To remain healthy, therefore, it is essential that cells do not accrue too many dangerous mutations in their DNA that allow cancers to grow and develop. An enzyme called ATM helps to do just that. DNA damage activates ATM, which, in turn, adds phosphate groups to other proteins. These newly tagged proteins then stop cells dividing until the DNA has been repaired. Human cancers often switch off ATM, either by completely deleting the enzyme or mutating it. This renders ATM unable to add phosphate groups to proteins, and so allows the cancer cells to continue proliferating even in the face of DNA damage. Yamamoto et al. wanted to know whether cancers that completely lack ATM behave differently from cancers that contain an inactive",380,128,0.3368
pubmed-summarization,"diagnostic procedure , were not eligible to participate . the three snps ( rs737865 , rs4680 , and rs165599 ) were genotyped using pcr real - time analysis on the lightcycler 480 ( roche ) . lightmix kit ( tib - molbiol ) , which contained specific primers and probes for 96 pcr - rt chain reactions , and lightcycler genotyping 480 dna master of roche diagnostics , which contains tag dna polymerase , reaction buffer , mixture of dntp ( with datp , dctp , dgtp , and dutp ) and 15 mm mgcl2 were used . briefly 20 l of reaction master mix for comt gene was performed with h2o 10.4 l , reagent mix 1.0 l , lightcycler genotyping 480 dna master 2.0 l , mgcl2 1.6 l , dna 5.0 l ( ~50 ng ) . thermal cycling conditions for pcr were as follows : denaturation at 95c for 10 minutes , 1 cycle , followed by 45 cycles of 95c for 10 sec , 60c for 10 sec and 72c for 15 sec , followed by melting at 95c for 30 sec , 40c for 2 min and 75c for 1 sec , 1 cycle and cooling at 40c for 30 sec , 1 cycle . deviations from hardy - weinberg equilibrium ( hwe ) were assessed using the chi - square test at each snp locus separately in cases and controls . to assess the differences in demographic characteristics , we used chi - square for categorical data and t test for continuous data . statistical inference for single , univariate snp associations in the comt gene was derived from fisher 's exact test . the odds ratios for dominant , recessive , and additive genetic models for each individual snp were calculated . the relevant p values derived from wald test for dominant and recessive models and armitage test for trend for additive model . subsequently , all possible combinations of the three snps were constructed , and thus , differences in haplotype frequencies between schizophrenia patients and control individuals were calculated using chi - square test . a logistic regression analysis was performed to estimate the risk for schizophrenia of each one of the eight haplotypes . snp rs737865 carries the alleles","schizophrenia , a severe psychiatric condition , is characterized by disturbances of cognition , emotion , and social functioning . the disease affects almost 1% of world population . recent studies evaluating the role of catechol - o - methyltransferase enzyme ( comt ) polymorphisms in the pathogenesis of schizophrenia have resulted in ambiguous findings . the current study examined the association of schizophrenia with three comt polymorphisms , namely , rs737865 , rs4680 , and rs165599 in a greek population . there was no significant association between schizophrenia and any of the three snps examined . however , haplotype analysis showed that cases have higher frequency of the t - a - a haplotype , and participants with that haplotype were at increased risk for developing schizophrenia",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Efficient transportation is crucial for urban mobility, cell function and the survival of animal groups. From humans driving on the highway, to ants running on a trail, the main challenge faced by all collective systems is how to prevent traffic jams in crowded environments. Here, we show that ants, despite their behavioral simplicity, have managed the tour de force of avoiding the formation of traffic jams at high density. At the macroscopic level, we demonstrated that ant traffic is best described by a two-phase flow function. At low densities there is a clear linear relationship between ant density and the flow, while at large density, the flow remains constant and no congestion occurs. From a microscopic perspective, the individual tracking of ants under varying densities revealed that ants adjust their speed and avoid time consuming interactions at large densities. Our results point to strategies by which ant colonies solve the main challenge of transportation by self-regulating their behavior. Many organisms such as herds of migrating wildebeests, swarms of insects and bacteria, starling flocks, fish shoals or pedestrian crowds take part in flow-like collective movements (Ball, 2004; Berdahl et al. , 2013; Berdahl et al. , 2018; Buhl et al. , 2006; Chowdhury et al. , 2005; Fourcassié et al. , 2010; Giardina, 2008; John et al. , 2009; Moussaïd et al. , 2011; Sumpter, 2010; Vicsek and Zafeiris, 2012; Zhou et al. , 2008). In most cases, all individuals cruise along the same path in a unique direction, which facilitates coordination. The task of maintaining a smooth and efficient movement becomes more challenging when individuals travel in opposite directions and are bound to collide (Fourcassié et al. , 2010). Along with humans (Helbing et al. , 2005; Moussaïd et al. , 2011), ants are one of the rare animals in which collective movements are bidirectional. Ants are central-place foragers, which entails a succession of journeys between their nest and their foraging site. When exploiting large food sources, many species lay chemical trails along which individuals commute back and forth (Czaczkes et al. , 2015; Gordon, 2014). The flow of individuals on these trails can reach several hundred ants per minute (Couzin and Franks, 2003). Yet, ants seem to fare better than us when it comes to traffic management (Burd et","Humans and ants are among the few species that engage in two-way traffic. Maintaining a smooth and efficient traffic flow while avoiding collisions is challenging for humans. Yet ants seem to be masters of traffic management. They can efficiently move back and forth between their nests and food without overtaking or passing each other, forming a steady stream of traffic. Few studies have looked at how ants maintain such a smooth flow even as the number of ants on a path increases. Now, Poissonnier, Motsch et al. have designed an experiment to investigate whether ants can maintain their steady stream of traffic when their path to food gets more crowded. This involved manipulating the density of ants using a combination of different sized colonies (ranging from 400 to",380,128,0.3368
dialogsum,"#Person1#: Alright, tell me what you think about this one. #Person2#: Don't you think it's a bit bright? #Person1#: Yeah, maybe you're right. How about this outfit? #Person2#: That dress looks lovely on you, but it's not very practical, is it? #Person1#: No, I don't have any plans to go to a formal dance any time soon, but I love the way it looks. I just want to try it on! What do you think about this? It's casual, yet sophisticated. #Person2#: I like the jeans, but you need something to go with the top. It's too plain on its own. #Person1#: How about this scarf, these earrings, and an anklet? #Person2#: That might be going overboard a bit. How about just that scarf with a bracelet? #Person1#: That's a good idea. You have a lot of good fashion sense. #Person2#: Thanks. You'd be OK on your own. There are loads of fashion victims out there, and you are not one of them. Have you tried it on yet? #Person1#: Yep. Here it is. What do you think? #Person2#: That looks great. Just one more thing-you need some high heels with those jeans. Do you want a pair with a plain pattern or ones with a leopard print on them? #Person1#: The leopard print sounds fabulous. OK, I'll take it.","#Person2# gives #Person1# some suggestions on clothes selection. #Person1# is satisfied with some jeans, a scarf, and a bracelet, which are matched by #Person2#. #Person2# also suggests some high heels. #Person1# will take the ones with a leopard print on them.",220,41,0.1864
scientific_lay_summarisation-elife-norm,"cavin complex and aid in generating the striated coat. Furthermore, this cavin coat may provide a possible mechanism for spatial and temporal regulation of caveola formation: caveolae form at the plasma membrane as caveolins and cavins associate, rather than earlier in the exocytic pathway (Hill et al. , 2008; Hayer et al. , 2010). In addition, the dissociation of the cavin coat complex could potentially provide a mechanism to disassemble caveolae. This may be crucial for caveolar function in setting membrane tension and in mechanosensing as increased membrane tension causes caveolar flattening and dissociation of cavin1 (Sinha et al. , 2011). However, the mechanisms underlying the formation of the cavin complex (es), their stoichiometry and association with caveolae are all unknown. Here we have developed new methods that allow reconstitution of the cavin complex and performed a quantitative assessment of cavin complex formation. We use single-molecule fluorescence for its proven ability to directly observe multiple populations and quantify interactions in complex mixtures. These techniques are especially well suited for the study of coat proteins and have been used to study the mechanisms of clathrin assembly/disassembly (Böcking et al. , 2011). Those studies required labeling of recombinantly expressed purified proteins, which in the case of the cavin complex is difficult (Hansen et al. , 2009). We have taken an alternative approach to obtain the stoichiometry of the cavin complex and the interactions between the members of the cavin family (cavin1, cavin2, cavin3) directly from cell extracts. We could observe fascinating behaviour of the cavin members, with exquisite segregation of interactors and defined stoichiometries in mixed oligomers. By combining these experiments with novel electron microscopy techniques we show the surprising existence of two distinct cavin complexes, cavin1-2 and cavin1-3. Remarkably, the two complexes co-interact with individual caveolae but associate within distinct striated nanodomains. Formation of higher order structures through oligomerization is a common behaviour of proteins involved in control of membrane dynamics. Here we set out to determine what role oligomerization of cavins plays in the biogenesis of caveolae. To this end we sought a technique that would allow rapid and quantitative analysis of homo- and hetero- interactions of proteins in vivo and in vitro. We chose single-molecule fluorescence spectroscopy as a way of directly assessing interactions between cavin proteins in complex","If you could look closely enough at the surface of some animal cells, especially fat or muscle cells, you would see that they are covered with pocket-like indents called ‘caveolae’. These structures are thought to help the cells communicate with the outside world, but they can also be used by viruses to gain entry into living cells. Examining these caveolae even closer would reveal that these pockets contain proteins called caveolins that bind to each other—and also to cholesterol and fatty acids—to form a scaffold that help to maintain the shape of the caveolae from inside the cell. Each caveolae in a mammalian cell typically contains over 100 caveolin proteins. Caveolar coat proteins, or cavins for short, are also important building blocks for caveolae: however, we know relatively",380,128,0.3368
scientific_lay_summarisation-elife-norm,"cell movement simplifies analysis. A key feature of out-of-plane deformations is that they involve generation of curvature (local rotations out of the plane). Two mechanisms might account for the generation of local rotations for a tissue sheet. The first is that local rotations arise through forces external to the sheet pulling or pushing on particular regions. For example, petals (whorl 2) grow in between sepals (whorl 1) and stamens (whorl 3), and these adjacent organs could apply forces to shape the petal. However, homeotic mutants that change the identity of stamens to petals do not have a major effect on the complexity of whorl 2 petal shape (Bradley et al. , 1993), making it unlikely that such a mechanism plays a major role in this case. The second mechanism is that regions within the tissue sheet are specified to grow at different rates and/or directions. Local rotations can arise because they reduce or resolve potential conflicts brought about by such differential growth (Coen and Rebocho, 2016), as without regions curving or rotating relative to each other, greater levels of stress would be generated. We refer to this second mechanism, in which heterogeneity of specified growth within the tissue leads to local rotations that reduce potential stresses, as tissue conflict resolution (for a more mathematical definition of tissue conflict resolution see Materials and methods). To clarify the notion of tissue conflict resolution we distinguish between two types of growth: specified and resultant (Kennaway et al. , 2011). Specified growth is how a region of tissue would deform if it was free from the mechanical constraints of its neighbouring regions. Resultant growth is how a region deforms in the context of neighbouring mechanical constraints, and includes anisotropies and local rotations that emerge from such constraints. Specified growth therefore refers to the intrinsic or active properties of a region, which may be influenced by local gene expression, while resultant growth also includes the passive changes that arise through connectivity with other regions. It is usually not possible to infer specified growth patterns directly from observed deformations (which reflects resultant growth). Modelling allows the consequences of particular hypotheses for specified growth to be evaluated and compared to the data on resultant growth, such as clones and shape deformations. To illustrate how patterns of specified","Plant and animal organs come in many different shapes, from pitcher-shaped leaves and butterfly wings, to orchid flowers and the convoluted shape of the brain. Unlike pottery or sculpture, no external hand guides the formation of these biological structures; they arise on their own, through sheets of cells developing into particular three-dimensional shapes. But how does this process of self-making operate? We know that patterns of gene activity are important, because mutations that disrupt these patterns change the shape of the organ. But it is not clear how these patterns lead to sheets of cells curving and bending themselves into their characteristic three-dimensional shapes. Plants are particularly useful tools for studying how three-dimensional organs form because, unlike animals, their cells do not slide relative to each other, which",380,128,0.3368
pubmed-summarization,"a pyeloplasty in pediatric patients , we preferred to place an ultrasound - guided antegrade ureteral catheter . before placing the patient in the laparoscopy position , an ultrasound - guided percutaneous access was gained , and two guide wires were placed in the pelvicaliceal system . over one guide wire a nephrostomy was inserted , whereas over another the ureteral catheter was coiled in the renal pelvis . the advantages of this arrangement are that the ureteral catheter apart from being used as a splint can also be used as a conduit for passage of the stent . in addition , as a protocol , we removed the ureteral catheter first , followed by the nephrostomy . the antegrade ureteral catheter and nephrostomy help to avoid the urethral route for stent removal . the salle stent works on a similar principle except that it is inserted intraoperatively and has a flower at its end that is self - retaining . intraoperatively during dissection , the nephrostomy was clamped , which distends the pelvis and facilitated dissection . all pyeloplasties were done with a modified anderson technique , and the pelvis in all cases was extrarenal and required reduction . the pelvis was hitched up by using a suture placed strategically through the abdominal wall . this helped in dissection of the pelviureteral junction and avoided the need to place an extra port . a triport access port was used during the procedure . an ultrasound - guided antegrade ureteral splint along with a percutaneous nephrostomy the stitch was placed by using a taper - cut needle on a 3/8th circle needle ( . the antegrade ureteral catheter that acted as a splint was removed on the third postoperative day , and the nephrostomy was clamped for 24 hours and removed . all procedures were performed with the patient in a position similar to that used for standard laparoscopy . the patient was placed at the edge of the table with the arms padded and secured . it was made certain that no tubes ( suction , irrigation ) were placed on the torso . the patients were secured with the help of tape ; however , the use of a bean bag would also be suitable . the surgeon","purposewe report our experience with laparoendoscopic single - site ( less ) urological procedures in children less than 5 years of age.materials and methodsten patients ( 11 procedures ) underwent less through the umbilicus . seven patients underwent nephrectomy and three patients underwent pyeloplasty ( one simultaneous bilateral ) . r - port port ( advanced surgical concepts , ireland ) was used in nine cases , in one case , the gelpoint access port ( applied medical , rancho santa margarita , ca , usa ) was used . the olympus endoeye camera with coaxial light cable was used . the hilum was secured in all cases with hem - o - lok clips ( teleflex medical , research triangle park , nc , usa ) except",380,128,0.3368
dialogsum,"#Person1#: which countries have you been to? #Person2#: I've been to most of the countries in Europe, several countries in asia, china, Japan, korea, and Thailand, and to the united states and Canada. #Person1#: I thought you had been to Australia too. #Person2#: no, but I'm planning on visiting Australia and New Zealand soon. I've heard that they are beautiful countries. Which is the most beautiful country you've been to? #Person1#: I think I'd say Norway. It has many pictures as fjords, waterfalls, and mountains. #Person2#: isn't it really cold there? #Person1#: well, the north of Norway is almost always cold, but further south it can be fairly warm in summer. It's a wet country, so there's snow almost everywhere in winter. #Person2#: I've been to other Scandinavian countries, but not to Norway. Perhaps I should go and do some winter sports there.",#Person2# tells #Person1# that #Person2# has been to many countries except Australia and plans to visit Australia and New Zealand. #Person1# thinks Norway is the most beautiful country and #Person2# hopes to go there.,143,34,0.2378
dialogsum,"#Person1#: How much for a bus pass? #Person2#: Well, for a monthly pass, it'll cost you $ 65. #Person1#: Is there anything else that doesn't cost as much? #Person2#: If you're a student, you can get a student bus pass. #Person1#: How much does a student pass cost? #Person2#: That actual bus pass is free. #Person1#: It doesn't cost anything? #Person2#: The only thing you'll have to pay for is the monthly sticker. #Person1#: Can you tell me how much that'll cost? #Person2#: It's only $ 24 a month. #Person1#: Sounds good, let me get that. #Person2#: I'll get it for you right now.",#Person1# asks #Person2# some questions about the bus pass and then gets a student bus pass with #Person2#'s help.,104,19,0.1827
pubmed-summarization,"after losses of individual mirnas ( park et al . , 2010 ) . in addition , alterations of mirna regulation are related to many diseases such as neurological disorders ( hebert and de strooper , 2009 ) , various types of cancer ( croce , 2009 ) , and cardiovascular diseases ( olson , 2014 ) . importantly , all of these defects were ultimately caused by a dysregulation in target gene expression . however , the limitation here is our ability to delineate a general principle for identification of specific rna targets upon which mirnas act . the problem stems from the observation that most of mirna target sites have partial complementarity ( ambros , 2004 ) . in contrast to plants , a near - perfect base pairing of mirna to its target is rare in animals , making it a challenge to predict the target sites ( bartel , 2009 ) . however , initial prediction attempts provided evidence that local short stretches ( 6 nt ) of consecutive base - pairing significantly contribute to target recognition ( john et al . , 2004 ; krek et al . , 2005 ; lewis et al . conceptually termed as the nucleus , the short consecutive matches could initiate a mirna - target duplex , followed by the propagation of partial annealing that may further stabilize mirna - target hybridization ( filipowicz , 2005 ; rajewsky , 2006 ) . intriguingly , nuclei were further found to be typically located in the 5 end region of mirnas called the seed , enabling the prediction of mirna target sites ( lewis et al . , functional mirna - target interactions are known to majorly require as few as 6-nt matches within the seed region ( position 2 - 8 , . there are possible 6-mers ( positions 16 , 27 , and 38 ) , 7-mers ( positions 28 and 17 ) , and 8-mer ( position 18 ) matches in the seed . otherwise , offset 6-mer seed because of its position and a marginal effect on repression ( friedman et al . , 2009 ) . such canonical seed sites were initially known by early biological studies ( lee et al . , 1993 ; poy","micrornas ( mirnas ) are small non - coding rnas ( 22 nucleotides ) regulating gene expression at the post - transcriptional level . by directing the rna - induced silencing complex ( risc ) to bind specific target mrnas , mirna can repress target genes and affect various biological phenotypes . functional mirna target recognition is known to majorly attribute specificity to consecutive pairing with seed region ( position 28 ) of mirna . recent advances in a transcriptome - wide method of mapping mirna binding sites ( ago hits - clip ) elucidated that a large portion of mirna - target interactions in vivo are mediated not only through the canonical seed sites but also via non - canonical sites ( 1580% ) , setting the",380,128,0.3368
dialogsum,"#Person1#: I want to say goodbye to everyone. #Person2#: You're leaving so soon. When are you off? #Person1#: I'm catching the nine fifteen train tomorrow morning. #Person2#: how about I come and see you off? #Person1#: You really don't need to. #Person2#: Ok. I'll miss you. I hope we can see each other again soon. #Person1#: I hope so, too. Thank you, Lily. Thank you for everything. #Person2#: You're welcome. #Person1#: Please say goodbye to the rest of the family for me. #Person2#: Ok. Take care. I hope you have a good journey. #Person1#: Thank you. Remember to look me up if you're ever in Washington. #Person2#: Of course. I will. #Person1#: Goodbye, then. Thanks again for everything.",#Person1# is leaving and thanks Lily for everything. They hope to see each other again soon.,118,16,0.1356
scientific_lay_summarisation-elife-norm,"et al. , 2016; Dean et al. , 2018; Heinz et al. , 2014; Tsaousis et al. , 2008). These data suggest that additional transporters must exist to supply Microsporidia with the pyrimidines that they need to grow and replicate. In the present study, we have characterised a family of Microsporidia Major Facilitator Superfamily (MFS) transport proteins which were discovered in Nematocida spp. (Cuomo et al. , 2012) and subsequently shown to be present in all Microsporidia for which genomes are available (Cuomo et al. , 2012; Dean et al. , 2018; Heinz et al. , 2014; Heinz et al. , 2012; Nakjang et al. , 2013; Watson et al. , 2015). Some of the Nematocida proteins share a Pfam domain (PF03825) with the NupG transporter of Escherichia coli (Xie et al. , 2004), suggesting (Cuomo et al. , 2012) that, like NupG, they might be purine and pyrimidine nucleoside transporters, potentially solving the parasite pyrimidine deficit discussed above. To test this hypothesis and to investigate the evolution and role (s) of these MFS transporters in Microsporidia, we characterised the expression, cellular location and functional characteristics of the homologous proteins from Trachipleistophora hominis (Heinz et al. , 2012; Nakjang et al. , 2013; Watson et al. , 2015), a model species that can be maintained in cell culture and was originally isolated from an HIV/AIDS patient (Field et al. , 1996). Our data provide no evidence that the T. hominis proteins can transport the pyrimidine nucleoside uridine, a known substrate for NupG (Xie et al. , 2004), or the pyrimidine nucleotides CTP or UTP, but demonstrate that they do transport the purine nucleotides ATP and GTP. These data reveal that T. hominis, and potentially other Microsporidia, have at least two distinct transport systems for importing the ATP and GTP from infected host cells, that they need to complete their intracellular lifecycles. We used BlastP to search for sequences related to the Microsporidia conserved protein family # c_456 (Nakjang et al. , 2013) which contains the Nematocida spp. putative NupG-like nucleoside/H+ symporter (Cuomo et al. , 2012), in the genomes of Microsporidia and their endoparasitic relatives among the Rozellomycota (Corsaro et al. , 2016), including species of Rozella (James et al. , 2013), Mitosporidium (Haag et al. , 2014) and Amphiamblys,","Microsporidia are a group of microscopic parasites that spend part of their lives inside the cells of a broad range of animal hosts, including humans. These parasites are considered to be related to fungi, some of which also live within the cells of other species and are known as fungal endoparasites. One of the shared characteristics of these parasites is that they cannot make nucleotides, molecules that are both the main source of energy of the cell and also the building blocks of DNA. Instead, they take nucleotides, or the materials needed to make nucleotides, from their host cells. Once Microsporidia have depleted a host cell, they turn into spores that can survive outside the host until they invade a new cell, starting the cycle anew. Microsporidia have",380,128,0.3368
pubmed-summarization,"condition , but the time - frame and the location of these efforts vary with the conditions under which these animals have evolved . some of these considerations may be relevant to a question that was raised at the very beginning of the scientific study of the evolution of behavior ( darwin , 1871 ) : what is the basis for the evolution of the lion 's mane ? is this related to the social systems of lions , which are unique among felids ? there are about 40 species of felids , all stemming from a split from other stem - line carnivores about 1015 million years ago ( mya ) . animals that can be identified with existing species emerged over a period from about 1012 mya ( for ocelots ) to very recently , possibly within historic times . felids range in size from the black - footed cat ( about 3 lbs ) to the siberian tiger , weighing about 200 more , and are world - wide in distribution , excepting only antarctica and most remote islands . felid social systems are relatively similar across species : adult animals tend to be solitary except for females and their young , and amicable adult encounters tend to be connected with reproduction . a great deal is known of the specifics of aggression in felids , due in large part to the work of paul leyhausen , who worked with domesticated cats and with other felid species in captivity , at the max planck institute for behavioral physiology , at wuppertal . large felids , of the genus panthera have also been the subjects of extensive field work , which has generally affirmed leyhausen 's conclusions about conservation of many aggressive behaviors and facial expressions across felid species . briefly , leyhausen ( 1978 ) described intraspecific aggression in these animals as a behavior that is capable of producing great damage , as all felids have weapon systems that have evolved to facilitate their roles as predators but are used also in within - species fighting . leyhausen also indicated that aggression in felids is more regulated by effective defenses than responsive to the submission signals that are quite effective in reducing intra - group fighting in","the function of manes in lions has been a topic of scientific interest since darwin ( 1871 ) suggested that it provides protection in intraspecific fights . recent experimental studies on wild lions have emphasized the role of female selection , but analyses of specific attack behaviors and targets , and the social consequences of manelessness for lions living in very hot climates suggest that male manes may indeed mitigate the outcomes of intraspecific male attack and thus serve a permissive function for multi - male + female groups , facilitating protection of prides against take - overs and infanticide by nomadic males . humans also have unusual structural protections for the head , face and neck , areas that are especially accessible during intraspecies attack , and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"affects cGAMP levels and cGAMP riboswitch transcripts in G. sulfurreducens and is important during bacterial growth on particulate acceptors, such as mineral Fe (III) oxides. In contrast, GacA is not essential for biofilm growth on electrodes, a phenotype associated with cdiG signaling. These results reveal that the general physiological function for cGAMP is to establish a transiently attached lifestyle that is distinct from the permanently attached biofilm lifestyle signaled by cdiG. Furthermore, we sought to understand the molecular mechanism for GacA by obtaining a 1. 4 Å-resolution structure of the Geobacter Hypr GGDEF domain bound to GTP. Combining this structure with kinetic analyses and mathematical modeling afforded insights into how GGDEF enzymatic activity is regulated in general as well as uncovered natural variations that give rise to cGAMP synthesis. Together, these genetic and biochemical analyses provide evidence that this cGAMP signaling pathway emerged from components of cdiG signaling to regulate a distinct surface-associated lifestyle, and gives a full picture of cGAMP signaling from the molecular to the cellular to the environmental level. Geobacter isolates produce energy via contact-dependent electron transfer to extracellular metals, which exist as insoluble precipitates at neutral pH (Navrotsky et al. , 2008). Stimulation of this biological metal reduction activity is useful for bioremediation of metal-rich sites and anaerobic oxidation of petroleum-based groundwater pollutants (Chang et al. , 2005; Lovley et al. , 2011; Rooney-Varga et al. , 1999). Geobacter also can grow via electron transfer to electrode surfaces, where their biofilms produce electricity in bioelectrochemical devices that use wastewater or contaminated groundwater (Bond and Lovley, 2003; Logan and Rabaey, 2012; Lovley, 2012). The ability to transfer electrons to extracellular substrates requires multiple extracellular structures, including pili, polysaccharides, and cytochromes localized to the outer cell surface. cGAMP-responsive riboswitches (GEMM-Ib family) are conserved upstream of many cytochrome, pilus assembly, and polysaccharide biosynthesis genes in most Geobacter species (Kellenberger et al. , 2015; Nelson et al. , 2015), suggesting a possible role for this cyclic dinucleotide in attachment to extracellular surfaces that serve as electron acceptors. The discovery of a GMP-AMP cyclase in Geobacter (GacA) (Hallberg et al. , 2016) presented the hypothesis that GacA synthesizes cGAMP in vivo to alter gene expression via cGAMP-specific riboswitches. However, no Hypr GGDEF enzyme including GacA has been linked yet to intracellular","Microscopic organisms known as bacteria are found in virtually every environment on the planet. One reason bacteria are so successful is that they are able to form communities known as biofilms on surfaces in animals and other living things, as well as on rocks and other features in the environment. These biofilms protect the bacteria from fluctuations in the environment and toxins. For over 30 years, a class of enzymes called the GGDEF enzymes were thought to make a single signal known as cyclic di-GMP that regulates the formation of biofilms. However, in 2016, a team of researchers reported that some GGDEF enzymes, including one from a bacterium called Geobacter sulfurreducens, were also able to produce two other signals known as cGAMP and cyclic di-AMP. The experiments involved",380,128,0.3368
dialogsum,#Person1#: What a nice tie you are wearing! #Person2#: Thank you. But does it really look all right? #Person1#: Certainly. It matches your suit perfectly. #Person2#: Then does it go well with my sweater? #Person1#: Yes. You look very smart today. #Person2#: Thank you very much.,"#Person1# admires the tie #Person2# is wearing, and #Person2# appreciates it.",46,11,0.2391
scientific_lay_summarisation-elife-norm,"Likewise, sodium-glucose transporter two inhibitors (e. g. , Dapagliflozin) have a complementary mechanism of reducing glucose reabsorption in the kidney (Bailey et al. , 2013). Increasing evidence points to additional molecular pathways that can improve metabolic homeostasis independently of insulin, for instance, using leptin therapy (Neumann et al. , 2016) or exercise (Stanford and Goodyear, 2014). Interestingly, currently prescribed drugs were discovered from their historical use in herbal medicine (Ehrenkranz et al. , 2005; Bailey, 2017) or from screens directed against hyperlipidemia (Fujita et al. , 1983). However, so far, an unbiased search for insulin-independent pathways controlling glucose metabolism has remained elusive, primarily due to the lack of a disease-relevant animal model for rapid screening. Due to its high fecundity and amenability to chemical screening, the zebrafish serves as an excellent platform to study diabetes, and it has been successfully used to study β-cell mass and activity, as well as glucose metabolism (Andersson et al. , 2012; Gut et al. , 2013; Tsuji et al. , 2014; Nath et al. , 2015; Li et al. , 2016; White et al. , 2016; Gut et al. , 2017; Matsuda et al. , 2018). Here, using the zebrafish model, we generated an innovative drug discovery strategy, screened chemical libraries and specifically identified insulin-independent effects of androgen signaling on glucose homeostasis. Insulin plays a central role in glucose homeostasis by increasing glucose uptake in peripheral tissues, promoting glycogenesis in the liver and decreasing glucose production by inhibiting glucagon secretion (Aronoff et al. , 2004). We generated zebrafish devoid of insulin signaling and determined the degree to which these mutants recapitulate core features of diabetic metabolism observed in mammals. The zebrafish genome contains two insulin genes – insulin (ins) and insulinb (insb). Using CRISPR/Cas9 mutagenesis, we generated a 16 bp deletion allele of ins (1A) and a 10 bp insertion allele of insb. Although ins and insb mutant embryos appear morphologically unaffected (— 1A), Insulin was entirely absent in pancreatic islets of ins mutants (1B), whereas there was no observable change in insb mutant islets (— 1B and C). ins mutants exhibit a drastic increase in total glucose levels (up to 10-fold), measured from 1 to 6 days post fertilization (dpf) (1C). Additionally, staining for lipid content using Nile Red revealed large unused yolk","Diabetes is a disease that affects the ability of the body to control the level of sugar in the blood. Individuals with diabetes are unable to make a hormone called insulin – which normally stimulates certain cells to absorb sugar from the blood – or their cells are less able to respond to this hormone. Most treatments for diabetes involve replacing the lost insulin or boosting the hormone’s activity in the body. However, these treatments can also cause individuals to gain weight or become more resistant to insulin, making it harder to control blood sugar levels. In addition to insulin, several other factors regulate the levels of sugar in the blood and some of them may operate independently of insulin. However, little is known about such factors because",380,128,0.3368
scientific_lay_summarisation-elife-norm,"instructed attention has commonly been observed to reduce pain (Bantick et al. , 2002). Therefore, it may be that attentional processes that are internally triggered when relief is learnable might provide a key signal that controls reduction of pain. In general, learning involves distinct processes of prediction (‘state learning’) and control (‘action learning’) (Mackintosh, 1983), although relief learning during tonic pain has not been thoroughly investigated. But a quantitative model of relief learning - one that describes the computational processes that are implemented in learning centres in the brain - would allow interrogation of how an attentional process might operate to modulate tonic pain. In the case of phasic pain, learning can be described by reinforcement learning (RL) models - a well-studied computational framework for learning from experience. RL models describe how to predict the occurrence of inherently salient events, and learn actions to exert control over them (maximising rewards, minimising penalties) (Seymour et al. , 2004). RL models aim to provide a mechanistic (beyond a merely descriptive) account of the information processing operations that the brain actually implements (Dayan and Abbott, 2001), and have a solid foundation in classical theories of animal learning (Mackintosh, 1983). In such models, an agent learns state or action value functions through outcomes provided by interacting with the world. These functions can be learned by computing the error between predicted and actual outcomes, and using the error to improve future predictions and actions (Sutton and Barto, 1998). Experimentally, the validity of these models can be tested by comparing how well different model-generated predictors fit the actual behavioural and/or neural data (O' Doherty et al. , 2007). During learning, attention is thought to boost learning of predictive associations and suppress other irrelevant information. Computationally, this can be achieved by estimating the uncertainty as predictive associations are learned, and using this as a metric to control learning rates. Accordingly, high uncertainty corresponds to high attention and leads to more rapid learning (Dayan et al. , 2000; Yu and Dayan, 2005). One well-recognised way of formalising uncertainty in RL is by computing a quantity called the associability, which calculates the running average of the magnitude of recent prediction errors (i. e. frequent large prediction errors implies high uncertainty/associability). The concept of associability is grounded in classical theories","Chronic pain lasting longer than three months is a common problem that affects about 1 in 5 people at some point in their lives. The lack of effective treatments has led to widespread use of a group of drugs called opioids – the best-known example is morphine. Opioids work by activating the brain’s natural painkilling system and are useful to relieve short-term pain, for example in trauma or surgery, or in end-of-life care. Unfortunately, long-term use of opioids can cause many undesirable effects, including drug dependency. Misuse of opioids combined with the widespread availability of prescription drugs have contributed to the current crisis of opioid addiction and overdose. A better understanding of how the brain’s natural painkilling system works could help scientists develop painkillers that offer relief without",380,128,0.3368
pubmed-summarization,"prostate cancer is one of the most common cancers diagnosed in men in the united states : there were 238 590 new cases and 29 720 deaths recorded in 2013 . prostate specific antigen ( psa ) is currently used as a diagnostic biomarker of prostate cancer . psa is an androgen - regulated serine protease and a member of the tissue kallikrein family . the concentration of psa is elevated in the blood serum of prostate cancer patients . this is due to the loss of basal cells , basement membrane , and lumen architecture , thus permitting propsa to have direct access to the peripheral circulation . the simplicity of psa testing , which measures the concentration of psa in blood serum , has prompted its wide use to detect and screen prostate cancer . however , psa testing in the diagnostic gray zone does not clearly distinguish between benign prostate hypertrophy and prostate cancer . to develop new candidate biomarkers for prostate cancer , a deeper understanding of the biochemical properties of psa glycosylation is one of the most common protein post - translational modifications ( ptms ) , and approximately 8% of psa by weight is composed of n - glycans that occupy a single glycosylation site at asn69 . several papers have reported a variable degree of sialylation of psa in sera between healthy subjects and those with prostate cancer . the major isoform , consisting of over 90% of psa , has an isoelectric point ( pi ) of 6.9 , whereas the minor one has a pi of 7.2 . the glycosylation pattern at high pi was observed to have a high level of sialylation . these properties were similarly observed in a study of psa isoenzymes from the serum of patients diagnosed with prostate cancer and the serum of patients diagnosed with benign prostate hyperplasia . psa n - glycans were also reported to be mostly core fucosylated and to have a minor presence of galnac residues with the increasing pi of the psa fraction . these different glycosylation patterns at different pi s could be employed to develop new diagnostic biomarker for detecting different prostate diseases . to effectively characterize the n - glycosylation of psa , a widely used method","prostate specific antigen ( psa ) is currently used as a biomarker to diagnose prostate cancer . psa testing has been widely used to detect and screen prostate cancer . however , in the diagnostic gray zone , the psa test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap . to develop more specific and sensitive candidate biomarkers for prostate cancer , an in - depth understanding of the biochemical characteristics of psa ( such as glycosylation ) is needed . psa has a single glycosylation site at asn69 , with glycans constituting approximately 8% of the protein by weight . here , we report the comprehensive identification and quantitation of n - glycans from two psa isoforms using lc ms",380,128,0.3368
dialogsum,#Person1#: How long have you been washing clothes here? #Person2#: I started washing here about three years ago. #Person1#: How come? #Person2#: I can wash my clothes for less money here. #Person1#: This is my first time washing clothes here. #Person2#: What reason are you washing here today? #Person1#: I can't wash at home because my machine is broken. #Person2#: Go and get it repaired. #Person1#: That'll cost too much. #Person2#: Are you going to continue washing your clothes here for a while? #Person1#: I have no choice. #Person2#: Washing clothes at a Laundromat costs a lot less money.,#Person1# says #Person1# will wash clothes at this Laundromat for a while because #Person1#'s washing machine is broken.,99,18,0.1818
pubmed-summarization,"sensitive molecular method for diagnosing egfr mutation status in nsclc samples . fifty - five cases of formalin - fixed , paraffin - embedded ( ffpe ) nsclc specimens and ten cases of pleural effusion cell blocks from patients with lung adenocarcinoma were collected , which were provided by the central hospital of enshi autonomous prefecture and the hubei cancer hospital from january 2013august 2014 . the cohort consisted of 13 squamous cell carcinomas , 50 adenocarcinomas , and two adenosquamous carcinomas . for each case , the hematoxylin and eosin sections were reviewed by at least two pathologists ( ygq and hlc ) . this study was approved by the institutional ethics committee of the central hospital of enshi autonomous prefecture . nsclc tissue sections ( 4 m thick ) were deparaffinized in xylene and rehydrated in a graded ethanol series . qds - ihc was performed according to the manufacturer s instructions ( wuhan jiayuan quantum dots co. , ltd . , antigen retrieval was performed in ethylene diamine tetraacetic acid ( edta ) ( 10 mm ; ph 9.0 ) at 100c for 3 minutes , followed by cooling at room temperature for 30 minutes . for antibody bindings , sections were first incubated in 2% bovine serum albumin ( bsa ) buffer ( sigma - aldrich co. , st louis , mo , usa ) at 37c for 30 minutes , and then three primary antibodies ( total egfr monoclonal antibody [ d38b1 ] , egfr del e746-a750 mutation - specific monoclonal antibody [ 6b6 ] , and l858r mutation - specific monoclonal antibody [ 43b2 ] ; cell signaling technology , inc . ) were diluted separately at 1:100 and manually applied to the sections . after that , the slides were then washed three times with tris - buffered saline ( tbs ) with tween ( tbs - t ) ( 0.5% tween , 0.1 m tris - base , 0.9% nacl , and ph 7.6 ) for 5 minutes each time , and incubated in biotinylated goat antirabbit immunoglobulin g ( 1:300 dilution ; jackson immunoresearch inc . , finally , qd ( 605 nm)-labeled streptavidin ( 1:400 dilution in 2% bsa ; wuhan jiayuan quantum dots co. , ltd . ) was","backgroundepidermal growth factor receptor ( egfr ) mutation status plays an important role in therapeutic decision making for non - small cell lung cancer ( nsclc ) patients . since egfr mutation - specific antibodies ( e746-a750del and l858r ) have been developed , egfr mutation detection by immunohistochemistry ( ihc ) is a suitable screening test . on this basis , we want to establish a new screening test , quantum dots immunofluorescence histochemistry ( qds - ihc ) , to assess egfr gene mutation in nsclc tissues , and we compared it to traditional ihc and amplification refractory mutation system ( arms).materials and methodsegfr gene mutations were detected by qds - ihc , ihc , and adx - arms in 65 cases of nsclc composed of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"lysine transporter Ypq1 to down-regulate the lysine import activity after lysine withdrawal (Li et al. , 2015b; Sekito et al. , 2014), whereas Zn2+ withdrawal results in the selective ubiquitination of a Zn2+ importer Cot1 by the Dsc E3 ligase complex (Li et al. , 2015a). Interestingly, Rsp5 can work together with the Dsc complex to down-regulate a Zn2+ exporter Zrt3 when excessive Zn2+ is present in the cytoplasm (Li et al. , 2015a). These ubiquitinated membrane proteins will be directly internalized into the vacuole lumen by the ESCRT machinery for degradation (Zhu et al. , 2017). Originally discovered in fission yeast, the S. pombe Dsc complex contains six components, including Tul1, Dsc2, Dsc3, Dsc4, Ubx3, and the AAA+ ATPase Cdc48 (Stewart et al. , 2012,2011). These components, with the exception of Dsc4, also exist in budding yeast (Dobzinski et al. , 2015; Li et al. , 2015a; Tong et al. , 2014). Strikingly, most Dsc components share sequence similarity to the Hrd1 E3 ligase complex, a key player in ER protein quality control. Tul1 is a multi-spanning membrane RING domain E3 ligase that is related to Hrd1. Other components, including Dsc2, Dsc3, Ubx3, are homologous to Der1, Usa1, and Ubx2 of the Hrd1 complex, respectively (Stewart et al. , 2012,2011). Furthermore, both complexes contain the same AAA+ ATPase Cdc48. The striking similarity suggests the Dsc complex might play a role in protein quality control at the downstream organelles of the secretory pathway. Probably the biggest controversy about the Dsc complex is its subcellular localization. In S. pombe, the Dsc complex has been shown to be critical to the proteolytic activation of the sterol regulatory element binding protein (SREBP) transcription factor, which is a Golgi membrane protein. Consistently, fission yeast Dsc complex has been shown to localize to the Golgi (Burr et al. , 2017; Stewart et al. , 2011). In S. cerevisiae, it is also generally accepted that the Dsc complex is a Golgi-specific E3 ligase complex. Tul1 was initially identified as a Golgi protein quality control E3 ligase through its ability to recognize and ubiquitinate an artificial folding mutant of Pep12, which is cycled between Golgi and endosomes (Reggiori and Pelham, 2002). Recently, it has been shown that the Dsc complex is also responsible for the ubiquitination and","Proteins perform many tasks and, to remain healthy, each cell must ensure that its proteins are in good condition and present at the right levels. Plants, animals and fungi all largely deal with damaged, or otherwise unneeded, proteins by tagging them with a small marker called ubiquitin. The tagged proteins are then rapidly destroyed, which prevents them from harming the cells. Enzymes known as E3 ligases attach ubiquitin to proteins. Yet, the number of E3 ligases is dwarfed by the number of proteins modified with ubiquitin. For instance, humans have approximately 20,000 different proteins, about one third of which are found in or on cell membranes. However, there are only around 600 E3 ligases, and only about 50 of them are associated with cell membranes. This is further",380,128,0.3368
dialogsum,"#Person1#: Come in and sit down, Jack. Now, what's the trouble? #Person2#: I've got a terrible pain in my stomach, Doctor. #Person1#: I see. When did it start? #Person2#: It started yesterday. I didn't eat any supper. #Person1#: Have you got a temperature? #Person2#: I think so. I feel very hot. #Person1#: Let's see. Yes. You ' Ve got quite a high temperature. #Person2#: I've got an awful headache, too, and my throat hurts. #Person1#: Hm... I think you ' Ve got the flu. #Person2#: Is it serious? #Person1#: No, not at all, but you must stay in bed for three days and take this medicine. #Person2#: How often must I take it? #Person1#: Three times a day after meals. #Person2#: Thank you, Doctor.Goodbye.",#Person1# asks about #Person2#'s symptoms and thinks #Person2# has got flu. Thus #Person1# suggests #Person2# stay in bed and take flu medicine.,124,22,0.1774
pubmed-summarization,"micrornas ( mirnas ) are single stranded non - coding rna molecules of 22 nucleotides ( nt ) that regulate gene expression via post - transcriptional and/or translational repression ( ambros , 2004 ) . primary mirna ( pri - mirnas ) are transcribed in the nucleus by rna polymerase ii or iii , where 70 nt stem - loop mirna precursors ( pre - mirnas ) are subsequently excised by the microprocessor complex containing the rnase iii enzyme drosha , and exported to the cytoplasm via exportin-5 ( kim et al . , 2009 ) . dicer , another rnase iii enzyme , further processes pre - mirnas to produce mature mirnas , the final product being a 22 base - pair duplex with 2 nt - long 3 overhangs ( he and hannon , 2004 ) . then , one strand of the mature mirna is loaded onto argonaute ( ago , also known as eif2c ) , a core protein of the rna - induced silencing complex ( risc ) . mirna forms base pairs with a target mrna as a guide for ago binding and to direct the specificity of the risc effector , decreasing target mrna levels and/or its translation ( fabian et al . , 2010 ) , where mrna destabilization is the dominant mechanism ( eichhorn et al . , 2014 ; guo et al . , mirnas are abundant in the mammalian genome ( more than 2000 human mirnas are currently reported in mirbase ) ( kozomara and griffiths - jones , 2014 ) and their regulatory role is essential , affecting various biological phenomena ( kim , 2005 ; sim et al . , 2014 ) . supporting evidence derives from the fact that a lethal phenotype during early development was observed in dicer1-null ( bernstein et al . , 2003 ) or ago2-null ( liu et al . , 2004 ) mice , and various biological defects were also reported after losses of individual mirnas ( park et al . , 2010 ) . in addition , alterations of mirna regulation are related to many diseases such as neurological disorders ( hebert and de strooper , 2009 ) , various types of cancer ( croce , 2009 ) , and","micrornas ( mirnas ) are small non - coding rnas ( 22 nucleotides ) regulating gene expression at the post - transcriptional level . by directing the rna - induced silencing complex ( risc ) to bind specific target mrnas , mirna can repress target genes and affect various biological phenotypes . functional mirna target recognition is known to majorly attribute specificity to consecutive pairing with seed region ( position 28 ) of mirna . recent advances in a transcriptome - wide method of mapping mirna binding sites ( ago hits - clip ) elucidated that a large portion of mirna - target interactions in vivo are mediated not only through the canonical seed sites but also via non - canonical sites ( 1580% ) , setting the",380,128,0.3368
pubmed-summarization,"everted uterus following lavage which revealed swollen , hyperaemic and viable tissue clinical assessment revealed normal appetite and demeanour . the vital parameters were within normal limits ( temperature 37.8c , respiratory rate 40 breaths / min , heart rate 140 beats / min ) . the cat received hydromorphone hydrochloride injection ( hydromorphone ; west - ward pharmaceutical ) at 0.1 mg / kg iv q4h for pain management and to facilitate further examination . initial haematological and blood biochemical evaluations revealed a markedly regenerative anaemia ( packed cell volume 24% [ reference interval ( ri ) 2545% ; erythrocytes 4.64 10/l [ ri 510 10/l ] , reticulocytes 375.84 10 /l [ ri 040 10/l ] ) and a neutrophilic leukocytosis with mild toxic changes ( leukocytes 37.72 10/l [ ri 5.519.5 10/l ] ; neutrophils 25.3 10/l [ ri 2.512.5 10/l ] ) . blood biochemistry showed a mild hyperkalaemia ( 6.0 mmol / l [ ri 3.75.8 mmol / l ] ) and mild hypoglycaemia ( 66 mg / dl [ ri 70150 mg / dl ] ) . oestrogen plasma concentrations were retrospectively evaluated at 25.7 pg / ml ( ri 1540 pg / ml ) . intravenous crystalloid fluid solution ( plasmalyte ; travenol laboratories ) was administered to correct an estimated 8% dehydration deficit and maintenance requirement over 12 h. antibiotic therapy consisting of intravenous cefazolin sodium ( cefazolin for injection ; west - ward pharmaceutical ) at a dose rate of 22 mg / kg iv q8h was also administered . attempts at reducing the uterus were again unsuccessful so an internal ovariectomy and external hysterectomy were performed . the ovarian pedicles were transfixed and ligated prior to transection and before manipulating the uterine body further . the everted uterus was circumferentially ligated distal to the cervix ( approximately 5 cm away from the vulva ) and transected . the remaining uterus was returned to the abdominal cavity . from within the abdominal cavity , the serosa of uterine body was noted to be diffusely thickened by multiple - to - coalescing white villous projections ( ) . formalin - fixed perimetrial surface of uterine body revealing diffuse - to - coalescing polypoid lesions there was a small amount of mildly flocculent","case summarythis case describes a young non - pregnant cat that presented with uterine prolapse in association with an unusual diffuse , polypoid , fibrosing perimetritis and parametritis . following ovariohysterectomy the cat recovered fully . no intra - abdominal complications were seen on ultrasound examination 3 months postsurgery . at the time of writing , the cat remains healthy.relevance and novel informationuterine prolapse in the cat is relatively rare and usually associated with the periparturient period . inflammatory polypoid perimetritis and parametritis have not previously been documented in cats , and in dogs have only been reported in association with the administration of oestrogenic compounds . the polypoid inflammation affecting the uterus and parametrium may have contributed to increased laxity of the uterine ligaments and predisposed to",380,128,0.3368
dialogsum,"#Person1#: What kind of account do you prefer? Checking account or savings account? #Person2#: I would like to open a checking account. #Person1#: Ok, please just fill out this form and show us your ID card. #Person2#: Here you are.",#Person1# serves #Person2# to open a checking account.,40,8,0.2
scientific_lay_summarisation-elife-norm,"Perceptual decisions are classically thought to depend mainly on the stimulus characteristics, probability and associated reward. However, in many cases, the motor response is considered to be a neutral output channel that only reflects the upstream decision. Contrary to this view, we show that perceptual decisions can be recursively influenced by the physical resistance applied to the response. When participants reported the direction of the visual motion by left or right manual reaching movement with different resistances, their reports were biased towards the direction associated with less effortful option. Repeated exposure to such resistance on hand during perceptual judgements also biased subsequent judgements using voice, indicating that effector-dependent motor costs not only biases the report at the stage of motor response, but also changed how the sensory inputs are transformed into decisions. This demonstrates that the cost to act can influence our decisions beyond the context of the specific action. In laboratory experiments, participants are often asked to make decisions that are purely based on the features of the sensory input – a process that we refer to here as perceptual decision-making. However, in many of our daily situations, decisions are made in a behavioural context, in which the action that follow our decisions can differ dramatically in terms of required physical effort (or the motor cost). For example, in the orchard, one may aim to pick the reddest-looking apple from the tree. Some of the apples may be hanging high-up on the tree, which will require more effort to pick compared to other fruits hanging on the lower branch. In such situations, does the difference in the motor cost between the options influence the decision of which fruit to pick? If so, is such influence a result of serial integration between the perceptual decision (i. e. decision based on the visual feature) and the motor decision (i. e. decision for action selection to avoid the effortful action) at the output stage, or is the perceptual decision itself is affected by the cost on the downstream action? It has been shown that physical effort is used in motor planning (Huang et al. , 2012; Izawa et al. , 2008), and the physical effort to obtain a reward can influence behavioural decisions (Prévost et al. , 2010; Hosokawa et al. ,","Imagine you are in an orchard, trying to decide which of the many apples to pick. On what do you base your decision? Most research into this type of decision-making has focused on how the brain uses visual information – about features such as colour, size and shape – to make a choice. But what about the effort required to obtain the apple? Does an apple at the top of the tree look more or less tempting than the low-hanging fruit? To answer this kind of question, Hagura et al. asked volunteers to decide whether dots on a screen were moving to the left or to the right. The volunteers indicated their choice by moving one of two levers. If they thought the dots were moving to the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"for details). In order to mimic place cell activity, the simulated virtual space was covered by multiple 2D Gaussian functions uniformly distributed at random (1B), which constituted the input. In order to calculate the principal components, we used a [Neuron x Time] matrix (1C) after subtracting the temporal mean, generated from the trajectory of the agent as it moved through the place fields. Thus, we displayed a one-dimensional mapping of the two-dimensional activity, transforming the 2D activity into a 1D vector per input neuron. This resulted in the [Neuron X Neuron] covariance matrix (1D), on which PCA was performed by evaluating the appropriate eigenvalues and eigenvectors. 10. 7554/eLife. 10094. 003Figure 1. Construction of the correlation matrix from behavior. (A) Diagram of the environment. Black dots indicate places the virtual agent has visited. (B) Centers of place cells uniformly distributed in the environment. (C) The [Neuron X Time] matrix of the input-place cells. (D) Correlation matrix of (C) used for the PCA process. : http: //dx. . org/10. 7554/eLife. 10094. 003 To learn the grid cells, based on the place cell inputs, we implemented a single-layer neural network with a single output (). Input to output weights were governed by a Hebbian-like learning rule. As described in the Introduction (see also analytical treatment in the Methods section), this type of architecture induces the output’s weights to converge to the leading principal component of the input data. 10. 7554/eLife. 10094. 004Figure 2. Neural network architecture with feedforward connectivity. The input layer corresponds to place cells and the output to a single cell. : http: //dx. . org/10. 7554/eLife. 10094. 004 The agent explored the environment for a sufficiently long time allowing the weights to converge to the first principal component of the temporal input data. In order to establish a spatial interpretation of the eigenvectors (from PCA) or the weights (from the converged network) we projected both the PCA eigenvectors and the network weights onto the place cells space, producing corresponding spatial activity maps. The leading eigenvectors of the PCA and the network’s weights converged to square-like periodic spatial solutions (3A–B). 10. 7554/eLife. 10094. 005Figure 3. Results of PCA and of the networks' output (in different simulations). (A) 1st 16 PCA eigenvectors projected on the place cells' input space. (B) Converged weights","Long before the invention of GPS systems, ships used a technique called dead reckoning to navigate at sea. By tracking the ship’s speed and direction of movement away from a starting point, the crew could estimate their position at any given time. Many believe that some animals, including rats and humans, can use a similar process to navigate in the absence of external landmarks. This process is referred to as “path integration”. It is commonly believed that the brain’s navigation system is based on such path integration in two key regions: the entorhinal cortex and the hippocampus. Most models of navigation assume that a network of grid cells in the entorhinal cortex processes information about an animal’s speed and direction of movement. The grid cell network estimates the",380,128,0.3368
dialogsum,"#Person1#: I love your bracelet. When did you get it? #Person2#: I got it a while ago, but I haven't worn it much. You really like it? #Person1#: Yeah. It's beautiful. Is it white gold or silver? #Person2#: It's white gold. #Person1#: Where did you buy it? #Person2#: My boyfriend took me to the Shane Co. and he let me pick it out. #Person1#: That's so sweet. What was the occasion? #Person2#: That's the best part. It wasn't for anything special. He just wanted to buy me something. #Person1#: You're so lucky. If he bought you something for no special day, I wonder what he would buy you for your birthday. #Person2#: My birthday is coming up. We'll find out pretty soon. #Person1#: What do you want? #Person2#: I wouldn't mind a necklace. I was at the jewelry shop looking around, and they have a couple of beautiful necklaces I want. #Person1#: Why not a ring? #Person2#: I don't think I'm ready for a ring from him yet. #Person1#: But you're ready for everything else? #Person2#: Ahha.","#Person1# compliments #Person2#'s bracelet. #Person2# says the bracelet is from #Person2#'s boyfriend, but #Person2# is not ready for a ring yet as #Person2#'s birthday gift.",177,25,0.1412
scientific_lay_summarisation-elife-norm,"Endothelial cells (ECs) in the central nervous system (CNS) acquire their specialized blood–brain barrier (BBB) properties in response to extrinsic signals, with Wnt/β-catenin signaling coordinating multiple aspects of this process. Our knowledge of CNS EC development has been advanced largely by animal models, and human pluripotent stem cells (hPSCs) offer the opportunity to examine BBB development in an in vitro human system. Here, we show that activation of Wnt signaling in hPSC-derived naïve endothelial progenitors, but not in matured ECs, leads to robust acquisition of canonical BBB phenotypes including expression of GLUT-1, increased claudin-5, decreased PLVAP, and decreased permeability. RNA-seq revealed a transcriptome profile resembling ECs with CNS-like characteristics, including Wnt-upregulated expression of LEF1, APCDD1, and ZIC3. Together, our work defines effects of Wnt activation in naïve ECs and establishes an improved hPSC-based model for interrogation of CNS barriergenesis. In the central nervous system (CNS), vascular endothelial cells (ECs) are highly specialized, with complex tight junctions, expression of a spectrum of nutrient and efflux transporters, low rates of vesicle trafficking, no fenestrae, and low expression of immune cell adhesion molecules (Reese and Karnovsky, 1967; Obermeier et al. , 2013). ECs bearing these attributes, often referred to as the blood–brain barrier (BBB), work in concert with the other brain barriers to facilitate the tight regulation of the CNS microenvironment required for proper neuronal function (Daneman and Engelhardt, 2017; Profaci et al. , 2020). During development, the Wnt/β-catenin signaling pathway drives both CNS angiogenesis, during which vascular sprouts originating from the perineural vascular plexus invade the developing neural tube, and the coupled process of barriergenesis by which resulting ECs begin to acquire BBB properties (Liebner et al. , 2008; Stenman et al. , 2008; Daneman et al. , 2009; Engelhardt and Liebner, 2014; Umans et al. , 2017). Specifically, neural progenitor-derived Wnt7a and Wnt7b ligands signal through Frizzled receptors and the obligate co-receptors RECK and GPR124 (ADGRA2) on ECs (Kuhnert et al. , 2010; Cullen et al. , 2011; Vanhollebeke et al. , 2015; Cho et al. , 2017; Eubelen et al. , 2018; Vallon et al. , 2018). Other ligands function analogously in other regions of the CNS, including Norrin in the retina and cerebellum (Ye et al. , 2009; Wang et al. , 2012) and potentially Wnt3a in the dorsal","The cells that line the inside of blood vessels are called endothelial cells. In the blood vessels of the brain, these cells form a structure called the ‘blood-brain barrier’, which allows nutrients to pass from the blood into the brain, while at the same time preventing harmful substances like toxins from crossing. Faults in the blood-brain barrier can contribute to neurological diseases, but the blood-brain barrier can also restrict drugs from accessing the brain, making it difficult to treat certain conditions. Understanding how the endothelial cells that form the blood-brain barrier develop may offer insight into new treatments for neurological diseases. During the development of the embryo, endothelial cells develop from stem cells. They can also be generated in the laboratory from human pluripotent stem cells or ‘hPSCs’,",380,128,0.3368
pubmed-summarization,"patient was in nyha class i. postoperative echocardiography after pseudoaneurysm repair lvp is rare with a prevalence of 0.05% ( 8) , and usually develops in patients having their first mi ( 9 ) . inferior and posterolateral mi are responsible for 82% of the lvp developing after mi . usually , lvp is located inferoposterior due to occlusion of the circumflex artery , but it can be found in the apical region due to anterior mi . mi rarely results in lvp formation because ruptures in the anterior wall generally leads to hemopericardium or tamponade ( 10 , 11 ) . lvp may remain clinically silent and be discovered during routine clinical investigations , or can present with chest pain , congestive heart failure , arrhythmias , or embolism . the development of heart failure is related to an non contracted and dyskinetic region , with dilatation of the pseudoaneurysm sac during systole . cardiac catheterization with left ventriculography has been the gold standard for establishing the diagnosis , and is necessary before surgery to evaluate the need for concomitant bypass grafting ( 13 ) . there is strong indication for surgery in lvp ( 15 ) since untreated pseudoaneurysm have a 30% to 45% risk of rupture ( 16 ) . the general consensus is that surgery is indicated for all patients as soon as the diagnosis is established , unless the surgical risk is prohibitive . if a pseudoaneurysm is diagnosed within 2 to 3 months after mi , emergency surgery should be performed because of the high risk of rupture . if the diagnosis is made years after mi , the necessity and urgency of surgery depends on the symptoms . resection , if necessary , combined with bypass grafting is the treatment of choice in symptomatic patients , but the operative risk is high due ( 7%29% ) to the underlying cardiac pathologies ( 17 ) .","introduction : left ventricular pseudoaneurysm is a rare condition because in most instances ventricular free - wall rupture leads to fatal pericardial tamponade . rupture of the free wall of the left ventricle is a catastrophic complication of myocardial infarction , occurring in approximately 4% of patients with infarcts , resulting in immediate collapse of the patient and electromechanical dissociation . in rare cases the rupture is contained by pericardial and fibrous tissue , and the result is a pseudoaneurysm . the left ventricular pseudoaneurysm contains only pericardial and fibrous elements in its wall - no myocardial tissue . because such aneurysms have a strong tendency to rupture , this disorder may lead to death if it is left surgically untreated.case report : in this case report ,",322,128,0.3975
scientific_lay_summarisation-elife-norm,"rising medical issue (Sen et al. , 2009). Planaria are a classic model system for studying adult wound healing and tissue regeneration (Reddien et al. , 2004). These free living members of the phylum Platyhelminthes contain a persistent pool of adult pluripotent stem cells, termed neoblasts, capable of regenerating all of the tissues and cell types of the organism (Wagner et al. , 2011). Ablation of this population of mitotic cells via irradiation eliminates regenerative capabilities, resulting in regression of anterior structures and eventual tissue lysis (Reddien et al. , 2005). Development of RNAi methodologies has enabled the interrogation of genes involved regeneration (Sanchez Alvarado and Newmark, 1999; Reddien et al. , 2005). These studies have informed our understanding of how wound responses, the recognition of lost tissues, dynamic establishment of positional identity, and activation of appropriate stem cell and differentiation programs all serve to accomplish large-scale complex tissue regeneration (Wenemoser and Reddien, 2010; Petersen and Reddien, 2011; Wenemoser et al. , 2012; Scimone et al. , 2014). While wounding is the stimulus for regeneration across all organisms studied to date, its incidence also presents an additional challenge. Disruption of barrier epithelia and exposure of mucosal surfaces poses an increased risk for bacterial invasion of internal tissues. Yet the role to which, if any, changes in endogenous microbiota or the planarian immune response have in regeneration is entirely unknown. The exemplary regenerative capabilities and conservation of multiple immune signaling genes in planarians make this organism an attractive model for understanding how robust tissue regeneration capabilities can be balanced with an effective immune response (Peiris et al. , 2014). Previous studies in planaria have uncovered components of the immune system conserved in humans, but absent from the well-studied innate immunity models of ecdysozoa (e. g. , flies and nematodes) (Abnave et al. , 2014). This indicates that planaria can serve as a complement to previously established invertebrate models to inform our understanding of the human immune response. While their potent regenerative capabilities and robust capacity for pathogen clearance render them quite resilient, planaria are not invincible. Planaria reared using traditional static culture methods can exhibit features of declining health including decreased appetite, loss of motility, dorsal tissue lesions, tissue degeneration, and lysis. Many of these symptoms can be temporarily alleviated and","Regeneration, the ability to replace missing or damaged tissue, has fascinated biologists for years and has inspired a new direction for the medical field. Figuring out how some animals easily accomplish this while others do not may help us to develop new therapies that enhance regeneration in humans. Previous work has indicated that the immune system, which is normally used to defend the body against bacteria, plays an important but complicated role in regeneration. By studying the relationships between bacteria, the immune system and regeneration in simple systems, it may be possible to see how their interactions either support or prevent the replacement of lost tissues. Flatworms called planaria can regenerate all of their tissues. Arnold et al. have now investigated what bacteria exist in planaria, how the",380,128,0.3368
pubmed-summarization,"rear in laboratory conditions , and new tools such as rna interference have been implemented successfully to study genetics of their immune systems . also , their immune signaling pathways are gradually being revealed by genomic and transcriptomic data . based on these model insect systems a fairly detailed picture of immunity , from pathogen detection to effector function , is emerging , though many gaps remain , particularly with regard to components that are unique to different insect orders . here we review aspects of insect immunity with an emphasis on the similarities and distinctions between d. melanogaster and representative lepidoptera . in insects , the cellular immune response includes phagocytosis , nodulation and encapsulation and the humoral response involves the expression of antimicrobial peptides ( amps ) as well as the pro - phenol oxidase ( propo ) proteolytic cascade that results in formation of melanized nodules and toxic reactive compounds . amps are small cationic peptides that insert into and disrupt microbial membranes , thereby killing and clearing pathogens . they are synthesized by hemocytes and to a greater extent in fat body from which they are released into the insect hemolymph rapidly after microbial infection . amps are also expressed in extra - embryonic tissues of eggs , which may help protect the developing embryo from infection . amps are a conserved component of immunity in plants and animals and while they have diverse structures most can be assigned to larger families such as cecropins , attacins , defensins and diptericins . their diversity and immune effector function as well as their variant representation among insects ( table 1 ) have made them a central focus in the study of invertebrate pathology . in d. melanogaster amp synthesis each of these pathways is activated by detection of microbial components via different pattern recognition receptors ( prrs ) that trigger , through complex regulatory cascades , nuclear factor kappa b ( nf-b ) dependent transcription of the genes encoding amps . after amps are translated in the cytoplasm they are released into the hemolymph where their high concentrations and broad activity are thought to enhance clearance of invading microorganisms from the insect . bioinformatic and experimental data support the existence of the amp - inducing toll and","many lepidopteran insects are agricultural pests that affect stored grains , food and fiber crops . these insects have negative ecological and economic impacts since they lower crop yield , and pesticides are expensive and can have off - target effects on beneficial arthropods . a better understanding of lepidopteran immunity will aid in identifying new targets for the development of specific insect pest management compounds . a fundamental aspect of immunity , and therefore a logical target for control , is the induction of antimicrobial peptide ( amp ) expression . these peptides insert into and disrupt microbial membranes , thereby promoting pathogen clearance and insect survival . pathways leading to amp expression have been extensively studied in the dipteran drosophila melanogaster . however , diptera are",380,128,0.3368
dialogsum,"#Person1#: I'd like to book a ticket to Shanghai. #Person2#: When would you like to fly? #Person1#: As soon as possible. Do you have a flight tomorrow? #Person2#: I will check, please hold on. Sorry to say that flight is all booked up. Can I book you for the 3rd of September? #Person1#: That will be OK. #Person2#: How many people are there in your party? #Person1#: Just me this time. #Person2#: What class will you fly? First class? Business class? Or economy class? #Person1#: Economy class will be fine. #Person2#: Round trip or one way trip? #Person1#: I would like to book a one way trip ticket. #Person2#: How will you pay, cash or charge? #Person1#: I would like to pay by check. #Person2#: I am sorry, we do not accept checks. #Person1#: I'll pay by charge card then. #Person2#: Great. What name shall I put the reservation under? #Person1#: Lucy Green. #Person2#: You are booked, Ms. Green. #Person1#: Thanks a lot. #Person2#: It's a pleasure.",Ms. Green wants to book a ticket to Shanghai and fly economy class. #Person2# helps her book a one-way ticket for September 3rd. Ms. Green will pay by charge card.,167,30,0.1796
dialogsum,"#Person1#: Our current apartment is valued at RMB 700, 000. We can sell it and put that money towards buying the new apartment. #Person2#: Yeah, but we still need RMB 500, 000. Maybe we can use some of our savings to pay part of it. #Person1#: And we can take out a loan to pay the rest. #Person2#: Great, so we can afford the new apartment after all! #Person1#: Uh huh. . . but we're going to have to cut back on our shopping from now on.",#Person1# advises to sell the current apartment and buy a new apartment. Then #Person1# and #Person2# decide to take out a loan.,87,22,0.2529
dialogsum,"#Person1#: I see you have bought the latest copy of beauty and fashion. Are there any interesting articles in it? #Person2#: There's an interesting interview with a top fashion designer about the latest fashions. I enjoyed reading her thought. The which? section is very interesting this month. They tested facial cleaners. T #Person1#: I like to take the tests that they print in this magazine. #Person2#: Which tests do you mean? #Person1#: You know. Tests like how jealous are you? and are you a fashion victim? #Person2#: Oh, I see. I like to do those tests, too, but I don't take them seriously. #Person1#: Of course not, but sometimes the results make you think about yourself and what you do. According to the jealousy test, I'm quite a jealous type of person. Perhaps I need to control my jealousy. #Person2#: You're right. It's sometimes hard to tell which pages are advertisement and which ones are articles.",#Person2# asks about the magazine #Person1# bought. Both #Person1# and #Person2# likes to take the tests in the magazine but #Person2# doesn't take the tests seriously.,156,26,0.1667
dialogsum,"#Person1#: Jack, sit down and listen. This is important. We'll have to tackle the problems of the exporting step by step. And the first move is to get an up-to-date picture of where we stand now. #Person2#: Why don't we just concentrate on expanding here at home? #Person1#: Of course, we should hold on to our position here. But you must admit the market here is limited. #Person2#: Yes, but it's safe. The government keeps out foreigners with import controls. So I must admit I feel sure we could hold our own against foreign bikes, #Person1#: I agree. That's why I am suggesting exporting. Because I feel we canpete with the best of them. #Person2#: What you are really saying is that we'd make more profit by selling bikes abroad, where we have,a cost advantage and can charge high prices. #Person1#: Exactly. #Person2#: But, wait a minute. Packaging, shipping, finaetc. will push up our cost and we could end up no better off, maybe worse off. #Person1#: OK. Now there are extra costs involved. But if we do it right, they can be built into the price of the bike and we can still be competitive. #Person2#: How sure are you about our chances of success in the foreign market? #Person1#: Well, that's the sticky one. It's going to need a lot of research. I'm hoping to get your help. Well, come on, Jack. Is it worth it, or not? #Person2#: There will be a lot of problems. #Person1#: Nothing we can't handle. #Person2#: Um... I'm not that hopeful. But, yes, I think we should go ahead with the feasibility study. #Person1#: Marvelous, Jack. I was hoping you be on my side.",#Person1# is suggesting exporting because the market here is limited and they'll make more profit by selling bikes abroad. Jack is suspicious of their chances of success in the foreign market but agrees to go ahead with the feasibility study.,282,40,0.1418
scientific_lay_summarisation-elife-norm,"Aberrant alternative pre-mRNA splicing (AS) events have been associated with several disorders. However, it is unclear whether deregulated AS directly contributes to disease. Here, we reveal a critical role of the AS regulator epithelial splicing regulator protein 1 (ESRP1) for intestinal homeostasis and pathogenesis. In mice, reduced ESRP1 function leads to impaired intestinal barrier integrity, increased susceptibility to colitis and altered colorectal cancer (CRC) development. Mechanistically, these defects are produced in part by modified expression of ESRP1-specific Gpr137 isoforms differently activating the Wnt pathway. In humans, ESRP1 is downregulated in inflamed biopsies from inflammatory bowel disease patients. ESRP1 loss is an adverse prognostic factor in CRC. Furthermore, generation of ESRP1-dependent GPR137 isoforms is altered in CRC and expression of a specific GPR137 isoform predicts CRC patient survival. These findings indicate a central role of ESRP1-regulated AS for intestinal barrier integrity. Alterations in ESRP1 function or expression contribute to intestinal pathology. The single-layered intestinal epithelium provides an important physical barrier that critically contributes to intestinal homeostasis (Peterson and Artis, 2014). Dysfunction of intestinal epithelial cells (IECs) leading to increased epithelial permeability is associated with intestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC) (Van der Sluis et al. , 2006; Schmitz et al. , 1999; Grivennikov et al. , 2012). IBD is related to polymorphisms in various IBD susceptibility genes (Lees et al. , 2011; Van Limbergen et al. , 2014), and numerous genetic alterations in key cellular pathways that underlie CRC have been identified (Fearon, 2011). However, the role of post-transcriptional modifications in the regulation of IBD and CRC development is still poorly understood. Alternative splicing of pre-mRNAs (AS) is a common posttranscriptional modification that is estimated to occur in 92–94% of human genes (Wang et al. , 2008; Pan et al. , 2008). AS permits generation of protein isoforms with related, distinct or sometimes even opposing functions (Vorlová et al. , 2011). Moreover, certain isoforms influence cancer progression (Brown et al. , 2011) or are associated with autoimmune and inflammatory disorders (Ueda et al. , 2003; Laitinen et al. , 2004). While alterations of mRNA splicing have been reported in human colorectal cancer (CRC) (Freund et al. , 2015; Zhou et al. , 2014) and IBD (Häsler et al. , 2011; Mailer et al. , 2015),","The lining of the intestine is just one cell thick, and yet it can act as an effective barrier between the inside of the body and the contents of the digestive system. This lining is often disturbed during bowel cancer, inflammatory bowel disease and other intestinal diseases, causing the barrier to fail and the gut to become leaky. These diseases often reduce patient life expectancy and quality of life. Intestinal epithelial cells make up the lining of the intestine and the normal activities of these cells are often disturbed during intestinal disease. In the intestine, a protein called ESRP1 is only found in epithelial cells, but its role in maintaining a healthy intestinal lining was not clear. Here, Mager et al. studied the intestines of mice that had",380,128,0.3368
pubmed-summarization,"use and have one 10-mm port channel and two 5-mm channels for instrument access . the port features a plastic sleeve that connects two rings , one abdominal and one peritoneal . the ports were inserted by using the open technique . an umbilical skin crease incision was made and the fascia incised . . the opening should not be too large , because the port tends to slip out ; neither should it be too small , because this may cause difficulty in introduction of both the port and the instruments . once the port was inserted , the plastic sleeve was pulled down so that the plastic rings ( abdominal and peritoneal ) approximated and the port fit snugly on the abdominal wall . in three of our cases , an accessory port was used . the common reasons for introduction of accessory ports included difficulty in upper pole dissection , inadequate exposure of the renal hilum , and difficulty in suturing in reconstructive procedures . the gelpoint mini port accommodates various abdominal wall and incision sizes , provides continuous access , and ensures improved articulation of both 5-mm and 10-mm instruments . the choice of instruments is a matter of surgeon preference ; the surgeon should choose instruments he is familiar with . the nephrectomy followed the typical steps of dissection of the ureterogonadal packets followed by dissection of the hilum ( . the hilum was secured by using hem - o - lok clips ( teleflex medical , research triangle park , nc , usa ) with two clips placed on the patient side . in one case , an endo gia stapler ( covidien surgical , norwalk , ct , usa ) was placed through a 10-mm port inserted through the gelpoint port . the less approach affords the advantage of retrieval of the specimen from the port itself without the need to extend the incision ( figs . 1 , 2 ) . before a pyeloplasty in pediatric patients , we preferred to place an ultrasound - guided antegrade ureteral catheter . before placing the patient in the laparoscopy position , an ultrasound - guided percutaneous access was gained , and two guide wires were placed in the pelvicaliceal system . over one guide","purposewe report our experience with laparoendoscopic single - site ( less ) urological procedures in children less than 5 years of age.materials and methodsten patients ( 11 procedures ) underwent less through the umbilicus . seven patients underwent nephrectomy and three patients underwent pyeloplasty ( one simultaneous bilateral ) . r - port port ( advanced surgical concepts , ireland ) was used in nine cases , in one case , the gelpoint access port ( applied medical , rancho santa margarita , ca , usa ) was used . the olympus endoeye camera with coaxial light cable was used . the hilum was secured in all cases with hem - o - lok clips ( teleflex medical , research triangle park , nc , usa ) except",380,128,0.3368
scientific_lay_summarisation-elife-norm,"decade, several bioactive peptides in the brain were discovered: neuromedin S, TLQP-21, nesfatin-1, and neuroendocrine regulatory peptide (NERP) (Mori et al. , 2005; Bartolomucci et al. , 2006; Oh-I et al. , 2006; Yamaguchi et al. , 2007). These neuropeptides are also involved in energy homeostasis and feeding behavior (Ida et al. , 2005; Bartolomucci et al. , 2006; Oh-I et al. , 2006; Toshinai et al. , 2010). Recently, nonadecaneuropeptide derived from Acyl-CoA binding domain-containing seven was found to be a novel anorexigenic factor in the mouse hypothalamus (Lanfray et al. , 2016). Despite considerable progress in understanding the regulation of energy homeostasis over the last several decades, the neural control of hyperphagia or obesity is not completely understood. To further understand the mechanism regulating energy intake and/or storage, we sought to identify previously unknown bioactive substances in the hypothalamus that regulate energy metabolism. As part of our search for novel neuropeptides and/or peptide hormone precursors in the hypothalamus, we identified a novel cDNA in the chicken hypothalamus and deduced a precursor protein including a secretory protein of 80 amino acids (Ukena et al. , 2014). This small protein has Gly-Leu-NH2 at its C-terminal and was named neurosecretory protein GL (NPGL). In chickens, subcutaneous infusion of NPGL increased body mass gain, suggesting that NPGL may be involved in growth processes, including energy homeostasis (Ukena et al. , 2014). Subsequently, we found homologous Npgl genes in mammals, including human, rat, and mouse; the primary structure of NPGL is highly conserved among mammals and avian species (— 1A). Rat NPGL assumes a circular structure, although the mature structure has not been determined (1A). Given the effects of NPGL administration observed in chickens, along with the highly conserved nature of this gene across species, we hypothesized that NPGL and its precursor serve a prominent, unexplored role in energy homeostasis in mammals. More recently, we found that NPGL could induce food intake in mice (Matsuura et al. , 2017). However, the physiological significance of NPGL in metabolic control in mammals remains to be elucidated. 10. 7554/eLife. 28527. 003Figure 1. Structure of NPGL and expression of NPGL in rats. (A) The amino acid structure of NPGL is shown schematically. The bold line between cysteine residues indicates a disulfide bond. (B) Expression levels of the","Throughout history, our ancestors needed to accumulate fat to survive during times when food sources were scarce. However, for most people in the modern age, food is abundant and eating too much is a major cause of weight gain, obesity and diseases affecting the metabolism. Obesity in particular, can lead to diseases such as diabetes and heart disease. Hunger and appetite are regulated by proteins and other chemicals that act as messengers, for example insulin, and a region of the brain called the hypothalamus. However, the full mechanisms that regulate these sensations remain unclear. Only recently, a protein called NPGL was discovered in a part of the hypothalamus of birds and mammals. However, it was not known if NPGL plays a role in regulating eating habits and weight",380,128,0.3368
dialogsum,"#Person1#: Hi, I'm George. I'll be your waiter this evening. Are you ready to order or do you need a few more minutes? #Person2#: I'm ready now. I'd like the roast chicken and a side order of corn. #Person1#: And would you like an appetizer before your meal? The soup of the day is our delicious tomato soup. #Person2#: I'll pass on the soup, but I'd like a garden salad. #Person1#: Can I get you anything to drink? : #Person2#: Yes, I'd like a glass of iced tea. #Person1#: Okay. I'll be back in a minute with your drink and salad. #Person2#: Thank you.","George helps #Person2# order a garden salad, roast chicken, corn, and a glass of iced tea.",104,16,0.1538
dialogsum,"#Person1#: I watched a very interesting documentary about plants yesterday evening. It was called unusual plants and looked at several species of plants from around the world which have unusual features. #Person2#: Really? Tell me about some of the plants they showed. #Person1#: Well. There was one type of plant that catches insects and eats them. #Person2#: Is that type of plant found in this country? #Person1#: No, it isn't. it's a pity, because I'd like to see it in action. #Person2#: So would i. what other unusual plants did they show? #Person1#: They showed flowers that only provide their nectar to one type of butterfly or bee. The insect has to be the exact size to get the nectar. Other insects cannot get it. Of course, when the insect molle #Person2#: That's very specialized. So, the insects and the flowers rely on each other. If one became extinct, the other would too. #Person1#: That's right. That's one reason why it's so important to protect every species. #Person2#: I see. The plants that fascinate me most are cacti. I find it amazing that they can survive in such dry desert conditions. #Person1#: According to the documentary, they have an incredible ability to find water supplies, however small, and then store them without losing much through evaporation. #Person2#: That's why they often have long roots to find water spines instead of leaves, to reduce water loss.","#Person1# tells #Person2# about some unusual plants in a documentary, including the plant that eats insects and the plant that provides nectar solely for a particular type of bee. #Person2# is most fascinated by cacti's ability to survive in dry conditions.",235,41,0.1745
pubmed-summarization,"fistula - in - ano is an abnormal hollow tract lined by unhealthy granulation tissue connecting a primary opening in the anal canal to a secondary opening in the perianal skin . the fistula tract may be single or multiple and may extend from the same primary opening . it is nearly always caused by a previous anorectal abscess , following either poor surgical or spontaneous drainage in the perianal skin . men are involved in 70% of cases and the majority of cases present initially in the 3 to the 6 decade , which incidentally coincide with the mean age occurrence of fournier 's gangrene . fournier 's gangrene , which was first described by jean alfred fournier in 1883 , is an infective necrotizing fasciitis of the perineal , genital or perianal regions as a result of subcutaneous vascular thrombosis and resulting in gangrene of the overlying scrotal skin . fistula - in - ano and fournier 's gangrene still continue to pose management challenges to surgeons . however , there has been no report on management of this concomitant occurrence of these diseases . this is a retrospective study of all fistulas - in - ano complicated by fournier 's gangrene managed in university of maiduguri teaching hospital and federal medical center yola and gombe within a period of 5 years ( january 2007 to december 2011 ) highlighting the causal relationship . the case files of all patients with the diagnosis of fistula - in - ano complicated by fournier 's gangrene during the study period were retrieved from the central medical records department of these hospitals . information retrieved includes the demographic data , mode of presentation , type of infecting organisms , co - morbidity illnesses , nature and outcome of treatment . data analysis was carried out using the statistical package for the social sciences version 16 ( spss 16 ) to determine the level of significance and correlations with the variables . a total of 10 male patients who developed fistula - in - ano and then complicated by fournier 's gangrene with a mean age of 50.5 ( 50 - 59 ) years were managed within the period of 5 years [ table 1 ] . nearly , 50% of patients","background : fistula - in - ano when complicated by fournier 's gangrene is an unusual finding and always carries high morbidity . this study details our experience in managing 10 cases.methods of study : case files of all patients managed in university of maiduguri teaching hospital and federal medical center of yola and gombe from january , 2007 to december , 2011 were retrieved from medical record departments and other hospital records . these were analyzed for demographic , clinical and pathological variables , the type of treatment and follow-up.results:a total of 10 men with a mean age of 50.5 years ( 35 - 60 ) were managed in the period of study . nearly , 50% of the patients were farmers , 30% businessmen and 20%",380,128,0.3368
dialogsum,"#Person1#: Hi, Mary. We haven't seen each other since we graduated. Where have you been? #Person2#: I have been to Australia. Do you still live there? #Person1#: Oh, no. We have just moved into the new house. #Person2#: Really? Congratulations. #Person1#: Thank you, and we want to buy a new television. #Person2#: What kind of television do you want to buy? #Person1#: A color TV, of course, but I'm not sure about the size. Maybe we should buy a bigger one. If we buy a smaller one, we might have to change it in a few years' time for a bigger one. That would be a waste of money. What is your opinion? #Person2#: In my opinion, I don't think it's necessary to buy a very big one. #Person1#: Any reason? #Person2#: Yes. As I know, your sitting room isn't big enough. If you put in a very big television, that will be bad for your eyes, and a smaller size TV can also pick up good programs. #Person1#: Mmm, that's quite true. I'll think about it. #Person2#: You'd better make a quick decision because the price may go up soon.",#Person1# tells Mary #Person1# wants to buy a new television but #Person1#'s not sure about the size. Mary suggests buying a small one because the space in the new house is limited.,191,32,0.1675
dialogsum,"#Person1#: Hi, I want to see the Terra Cotta Warriors in Xi'an. Could you please remind me when we are arriving at that stop? #Person2#: Oh. You took the wrong bus. You need to take Bus 151 which goes the opposite direction. #Person1#: Oh, no! What should I do now? #Person2#: Don't worry. You can get off at the next stop and walk across the street and take the Bus 151 to the opposite direction. #Person1#: Ok. How many stops do I have to go? #Person2#: About 15 stops. #Person1#: That is a long way to go. It is so kind of you to help me. Thank you very much. #Person2#: My pleasure.",#Person2# tells #Person1# #Person1# took the wrong bus and tells #Person1# how to get to the Terra Cotta Warriors in Xi'an by bus.,113,23,0.2035
dialogsum,"#Person1#: What can I do? #Person2#: The system crashed when I was surfing on the internet. #Person1#: Did you go to any illegal website? #Person2#: No, But does that matter? #Person1#: Yes, your computer can be easily infected by virus if you do that. #Person2#: I see. I'd better never try. #Person1#: That's wise. #Person2#: Do you know what's wrong with my PC? #Person1#: One minute. Oh, yes, it was infected by a virus, and you had no antivirus software. #Person2#: Is anti-virus software necessary for a PC? #Person1#: Of course. You'd better learn something about it. #Person2#: I'm afraid yes. But what about the data I stored in the computer? #Person1#: Don't worry, it should have been protected automatically. And I take an anti-virus software with me. Do you want me to install it now? #Person2#: Yes, please. I'll really appreciate that.",#Person2#'s computer crashed. #Person1# finds it was infected by a virus and #Person1# is going to install anti-virus software for #Person2#.,143,21,0.1469
scientific_lay_summarisation-elife-norm,"SWELL1 (LRRC8A) is the only essential subunit of the Volume Regulated Anion Channel (VRAC), which regulates cellular volume homeostasis and is activated by hypotonic solutions. SWELL1, together with four other LRRC8 family members, potentially forms a vastly heterogeneous cohort of VRAC channels with different properties; however, SWELL1 alone is also functional. Here, we report a high-resolution cryo-electron microscopy structure of full-length human homo-hexameric SWELL1. The structure reveals a trimer of dimers assembly with symmetry mismatch between the pore-forming domain and the cytosolic leucine-rich repeat (LRR) domains. Importantly, mutational analysis demonstrates that a charged residue at the narrowest constriction of the homomeric channel is an important pore determinant of heteromeric VRAC. Additionally, a mutation in the flexible N-terminal portion of SWELL1 affects pore properties, suggesting a putative link between intracellular structures and channel regulation. This structure provides a scaffold for further dissecting the heterogeneity and mechanism of activation of VRAC. VRAC is a ubiquitously expressed mammalian anion channel implicated in diverse physiological processes including volume regulation, cell proliferation, release of excitatory amino acids, and apoptosis (Hyzinski-García et al. , 2014; Nilius et al. , 1997; Pedersen et al. , 2016). It is suggested to play a role in a variety of human diseases including stroke, diabetes, and cancer (Hyzinski-García et al. , 2014; Planells-Cases et al. , 2015; Zhang et al. , 2017). A causative link has been established between a chromosomal translocation in the SWELL1 (LRRC8A) gene and a human B cell deficiency disease, agammaglobulinemia (Sawada et al. , 2003). Previous studies have shown that SWELL1 is required for VRAC activity, and that the presence of other LRRC8 subunits dictates functional characteristics of VRAC, including pore properties (Qiu et al. , 2014; Syeda et al. , 2016; Voss et al. , 2014). While SWELL1 and at least one other LRRC8 subunit are required for canonical whole-cell VRAC currents, purified homomers of SWELL1 reconstituted in lipid bilayers are activated by osmotic stimuli and blocked by VRAC antagonist, DCPIB (Syeda et al. , 2016). Interestingly, CRISPR-engineered HeLa cells lacking all LRRC8 subunits (LRRC8-/- HeLa cells) exhibited very small but significant DCPIB-sensitive hypotonicity-induced currents after SWELL1 overexpression (— 1), supporting previous bilayer results. Since the number and composition of functional native oligomeric assemblies remains unknown, we decided to first elucidate the structure of","Every cell needs to regulate its internal volume or it will burst. Most of a cell’s volume is a watery mixture of salts, proteins and other molecules. A cell can take in more water from its surroundings, diluting this mixture and causing the cell to expand. If a cell starts to take up too much water, it will open channel proteins in its outer membrane called volume regulated anion channels (or VRACs for short). An open VRAC allows negatively charged ions to leave the cell, and in the process causes water to leave the cell too. This relieves the pressure inside the cell, and the cell starts to shrink. The structure of a VRAC is thought to contain six subunits, and most include at least two different kinds",380,128,0.3368
pubmed-summarization,"( 200 ) , ( c ) vimentin ( 100 ) , ( d ) cd 99 ( 200 ) thoracic pnets are the most aggressive form of ppnets arising from chest wall or underlying lung pleura invading bone , lung or mediastinum in children and young adults . they are extremely aggressive with a dismal prognosis as patients may present with an upfront metastatic disease to contralateral lung , bone , bone marrow , lymph nodes , liver , pancreas , adrenals , and ovaries . primary lung pnet can often be misdiagnosed with a metastatic lung lesion , mucinous adenocarcinoma or squamous cell lung carcinoma . since pnets and other small round cell tumors share the same histological picture , ihc plays a vital role in their differentiation . cd 99 , vimentin and s100 are nonspecific while nse , synaptophysin and chromogranin confirm the diagnosis of pnet . ttf-1 is found in pulmonary adenocarcinomas and thyroid malignancies , ck for carcinoma , desmin for rhabdomyosarcoma , sma and ema for soft tissue sarcoma while lca , bcl-2 , cd 20 , cd 45 are for acute lymphoblastic lymphoma and leukemia . however , to confirm the diagnosis , amplification of ewing sarcoma breakpoint region-1 by situ hybridization techniques is required . according to javery et al . and previous other series on extraskeletal ewing sarcoma ( ees ) , lung is the most common site of metastasis followed by bone comprising 80% and 40% cases , respectively . huh et al . reported lymph nodes as the most frequent metastatic site ( 75.9% ) followed by bone , lung , peritoneum , pleura while least being brain ( 3.4% ) . the most prevalent primary sites were extremities , abdomen , pelvis , thorax , paravertebral space followed by head and neck current treatment recommendations for lung pnet and ppnets / ewing 's are same with vac / ie . rt concurrent with chemotherapy is preferred for the limited stage while sequential rt is beneficial for extensive lesions . we have treated two more cases of adult primary lung pnet although with a radiological pr but a significant symptomatic response . both patients are on follow - up for more than a year now without any evidence","primitive neuroectodermal tumors ( pnets ) are highly malignant neoplasms of embryonal origin manifesting in children and adolescents , rarely seen in adults . carcinoma lung with hemorrhagic metastasis to the brain is very common , but primary lung pnet with hemorrhagic brain metastasis is extremely uncommon . we hereby report a 29-year - old female diagnosed as pnet lung was treated with vincristine , adriamycin , and cyclophosphamide alternating with ifosfamide plus etoposide followed by radiotherapy ( rt ) . after 9 months , she developed hemorrhagic brain metastasis from pnet lung confirmed from tissue immunohistology postcraniotomy . received palliative whole brain rt followed by oral pazopanib resulting in significant improvement in performance status . a thorough review of literature reveals that our case may be the",380,128,0.3368
pubmed-summarization,"in terms of phylogeny , aggression is among the oldest of evolved behavior patterns ( blanchard and blanchard , in press ) . exemplars of aggression have been reported in animals without a central nervous system ; in a host of invertebrates ; and in each of the seven classes of vertebrates , including the most primitive ; agnatha , hagfish and lampreys ( malmqvist , 1983 ) . there is an emerging consensus that one major function , i.e. adaptive consequence , of aggression , across animal species , is resource control ( e.g. wilson , 1971 ) , with the further provision that aggression typically occurs in the context of competition from conspecifics over such resources . term enhancement of access to resources that are important for that species ( blanchard and blanchard , 1984 ; moynihan , 1998 ) . resources and their distribution are also major factors in the development of species - typical social systems ( rubenstein , 2009 ) , of which within - species aggressive behaviors are one , important , component . some species such as mice are particularly opportunistic and may show rapid and dramatic changes in social structure in accord with habitat alterations ( bronson , 1979 ; gray and hurst , 1997 ) , a flexibility that may stem in part from their long - term status as human commensals , with its strong requirement of rapid adjustment to host - initiated changes ( blanchard et al . in press ) . however , the ecological conditions under which most mammalian species have evolved are less variable than those associated with human habitations and human geographic movements , and the social systems evolving in most habitats appear also to be more conservative and resistant to change than are those of mice . evaluation of the rate of change in evolved characteristics of animals in response to important alterations in ecological conditions constitutes a difficult field of study , but some estimates may be obtained when a fossil record is available that permits information on relatively specific ecological changes . for example , it has been estimated that reductions in selective behavioral responsivity to rattlesnakes and in resistance to the venom of these snakes by california ground squirrels both decline","the function of manes in lions has been a topic of scientific interest since darwin ( 1871 ) suggested that it provides protection in intraspecific fights . recent experimental studies on wild lions have emphasized the role of female selection , but analyses of specific attack behaviors and targets , and the social consequences of manelessness for lions living in very hot climates suggest that male manes may indeed mitigate the outcomes of intraspecific male attack and thus serve a permissive function for multi - male + female groups , facilitating protection of prides against take - overs and infanticide by nomadic males . humans also have unusual structural protections for the head , face and neck , areas that are especially accessible during intraspecies attack , and",380,128,0.3368
pubmed-summarization,"and carcinoma in situ . however , patients who had preoperative radiation therapy and those who were not able to undergo curative resection were included . routine laboratory measurements , including white blood cell ( wbc ) count , neutrophil count , lymphocyte count , monocyte count , and platelet count , were performed preoperatively , daily until day four postoperatively , and subsequently every two days . we did not consider preoperative infection and inflammatory condition and postoperative infection and inflammatory condition . patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm after surgery ( dsnlc ; group i , 0 - 1 days ; group ii , 2 - 3 days ; group iii , 4 days ) . for a comparative analysis with the results of the other study , grouping of the variables , such as the wbc count , neutrophil count , lymphocyte count , monocyte count , and platelet count , "" right side colon "" was defined as both the right colon and the transverse colon . "" left side colon "" was defined as both the left colon and the recto - sigmoid colon above the peritoneal reflection . staging evaluation was carried out according to the guidelines of american joint committee on cancer , sixth edition . this study was approved by the institutional review board of the college of medicine ( sc11tisi0080 ) . the relationship between the number of days required for the leukocyte count to drop below 10,000/mm after surgery ( group i , 0 - 1 day ; group ii , 2 - 3 days ; group iii , 4 days ) and clinicopathologic factors was assessed using the chi - squared and fisher 's exact tests . the overall duration of survival was calculated from the date of surgery until the date of death . the duration of cancer - free survival was calculated from the date of surgery until the date of detection of disease recurrence , defined using clinical , radiographic or pathological findings . overall and cancer - free survival rates were calculated using the kaplan - meier method , and differences among curves were tested using the log - rank test .","purposecancer - related inflammation affects many aspects of malignancy . we confirm the effects of early postoperative systemic inflammation on cancer prognosis.materials and methodssix hundred consecutive patients underwent surgery for colorectal cancer from 2006 to 2009 . measurements of white blood cells , neutrophils , lymphocytes , monocytes , and platelet counts were performed preoperatively , daily until the fourth postoperative day , and subsequently every two days . patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm3 after surgery.resultspreoperative white blood cell ( wbc ) counts correlated with stage of disease . in univariate survival analyses , tumor , node , metastasis ( tnm ) stage , and monocyte count were associated with cancer - free survival",380,128,0.3368
dialogsum,"#Person1#: I know I'm going to bite the dust going down this hill. I almost got killed on the chair lift! This is going to be so embarrassing. #Person2#: Don't worry. Everyone knows you're getting your feet wet. I'll show you how. I bet you'll be proficient at this in five minutes. #Person1#: This is only your second time skiing. This is definitely a case of the blind leading the blind. #Person2#: Relax. I can hold my own. Now, point your skis toward the bottom of the hill. Easy does it! #Person1#: I don't think I can get up enough nerve to do this. #Person2#: Here. I'll just give you a little push. . . #Person1#: No!!! #Person2#: There. Now, wasn't that fun? As soon as you get a second burst of energy, we'll. . . #Person1#: Don't hold your breath!",#Person1# feels extremely nervous about skiing down the hill. #Person2# who is also a beginner teaches #Person1# how to do it.,141,21,0.1489
dialogsum,"#Person1#: How may I help you today young man? It looks like you have a big package there. #Person2#: Yes, ma'am, I need to mail this present to my grandma, but I don't know how to do it. #Person1#: I can help you. Just go way it over there, it will print out the information on a piece of paper, that tells you the weight of the package, and the price to mail it, and you can bring it back to me. #Person2#: Yes, ma'am, thank you so much.",#Person1# tells #Person2# how to mail a present.,89,8,0.0899
dialogsum,"#Person1#: How was the movie last night? #Person2#: I didn't really like it. #Person1#: Mary said that she was really pleased with the photography. #Person2#: I found it very disappointing. #Person1#: She liked the acting, too, because that's what she wanted to see. #Person2#: I wasn't happy with it. #Person1#: Nothing is to your satisfaction.",#Person2# dislikes the movie while Mary likes the photography and the acting.,55,12,0.2182
pubmed-summarization,"it is essential to find a broadly applicable and cost - effective approach to overcome such problems and to promote bonding . the solvent - assisted bonding is another method for bonding two substrates that has been widely studied and utilized for repairing thermosetting acrylic resins.11016 although polyamide is a particularly chemical - resistant material , the presence of amide groups ( -nhco- ) makes it prone to absorb water or other solvents and form hydrogen bonds.1920 it is well recognized that the plasticization of polyamide matrix occurs in the presence of small amounts of polar molecules capable of hydrogen bonding.2122 the softening enhances the chain mobility and disrupts the hydrogen bond network of polyamides.151923 although acetic acids , propionic acids , and butyric acids with low dissociation constant are non - solvents , they promote the reaction through hydrogen bonding . in addition , they cause hydrolysis that breaks the cross - links and provides swelling generally similar to those of solvents.24 the hydrolytic degradation of polyamide in different environments has been extensively studied.20222526 acidic conditions have been observed to facilitate amide hydrolysis . the chemical effects that acid has on the hydrolysis of polyamide are amine scavenging and acid catalysis . according to previous studies,2027 polyamide hydrolysis reaches an equilibrium molecular status in the absence of oxygen . serpe et al.22 and chaupart et al.28 showed that significant degradation was achieved in strong acids , but the presence of oxygen was uncontrollable . moreover , no equilibrium was observed in the hydrolysis of polyamide chain leading to less swelling . the reports by hocker et al.24 showed that the hydrolysis of polyamide caused by small organic acids was accelerated significantly . the objective of the present study was to evaluate the effect of surface treatment with acetic acid on the bond strength of auto - polymerized resin to polyamides . the null hypothesis was that the application of acetic acid would not affect the bond strength of auto - polymerized resin to polyamide denture base material . a thermoplastic denture base material , a hard chairside reline resin , and an auto - polymerized acrylic resin were selected . 84 polyamide cylinders with the dimensions of 15 mm diameter and 5 mm height were processed , following the","purposepolyamide polymers do not provide sufficient bond strength to auto - polymerized resins for repairing fractured denture or replacing dislodged denture teeth . limited treatment methods have been developed to improve the bond strength between auto - polymerized reline resins and polyamide denture base materials . the objective of the present study was to evaluate the effect of surface modification by acetic acid on surface characteristics and bond strength of reline resin to polyamide denture base.materials and methods84 polyamide specimens were divided into three surface treatment groups ( n=28 ) : control ( n ) , silica - coated ( s ) , and acid - treated ( a ) . two different auto - polymerized reline resins gc and triplex resins were bonded to the samples (",380,128,0.3368
pubmed-summarization,"liver cancer is the second most common cause of cancer - related death worldwide , the fifth most common cancer among men and the ninth most common cancer among women.1 hepatocellular carcinoma ( hcc ) is responsible for ~90% of primary liver cancers.2 in the united states , hcc is the fastest rising cause of cancer - related death , and its incidence has nearly tripled since the 1980s.3,4 despite increased focus and research , the overall prognosis for hcc remains poor . curative modalities , such as liver transplant , resection and radiofrequency ablation , do exist when hcc is diagnosed early ; however , only ~15% of patients are eligible for such treatments ( table 1).3,5,6 the majority of patients are diagnosed with advanced - stage hcc , for which the median survival time is < 50% at 1 year and only 12% at 5 years.7,8 chemotherapy is rarely used for the treatment of hcc due to its minimal success rate of 1020% and high levels of toxicity.2 the only therapy currently approved by the food and drug administration ( fda ) for the treatment of advanced hcc is sorafenib , a tyrosine kinase inhibitor that has been shown to decrease cell proliferation and tumor angiogenesis.9,10 while sorafenib represents a major advancement in the treatment of hcc , its effects are modest , with the sharp trial demonstrating an increase in overall survival from 7.9 months to 10.7 months and an increase from 2.8 months to 5.5 months in the median time to radiological progression.10 it demonstrated even less robust benefits in the asia - pacific trial , with overall survival in the treatment group of 6.5 months and median time to radiological progression of 2.8 months.9 furthermore , after experiencing an initial response to treatment , most hcc patients develop a decrease in efficacy with sorafenib.11 many novel therapies are currently under investigation in clinical trials . in a recently published phase iii trial , regorafenib , an oral multikinase inhibitor , has demonstrated an increase in median overall survival ( 10.6 months vs. 7.8 months ) and an increase in median progression - free survival ( pfs ; 3.1 months vs. 1.5 months ) compared to placebo in patients with advanced hcc who have progressed on","hepatocellular carcinoma ( hcc ) is the fastest rising cause of cancer - related death in the united states and carries a very poor prognosis , with a median survival time of < 50% at 1 year for advanced disease . to date , sorafenib is the only therapy approved by the food and drug administration for the treatment of advanced hcc . tivantinib ( arq-197 ) , a non - atp competitive inhibitor of cellular mesenchymal epithelial transcription factor ( c - met ) , has shown a survival benefit in patients with advanced hcc who have failed or are intolerant to sorafenib in phase i and ii trials . those patients who have tumors with high concentrations of met ( met - high ) appear to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Protective signaling from the leukemia microenvironment leads to leukemia cell persistence, development of resistance, and disease relapse. Here, we demonstrate that fibroblast growth factor 2 (FGF2) from bone marrow stromal cells is secreted in exosomes, which are subsequently endocytosed by leukemia cells, and protect leukemia cells from tyrosine kinase inhibitors (TKIs). Expression of FGF2 and its receptor, FGFR1, are both increased in a subset of stromal cell lines and primary AML stroma; and increased FGF2/FGFR1 signaling is associated with increased exosome secretion. FGFR inhibition (or gene silencing) interrupts stromal autocrine growth and significantly decreases secretion of FGF2-containing exosomes, resulting in less stromal protection of leukemia cells. Likewise, Fgf2 -/- mice transplanted with retroviral BCR-ABL leukemia survive significantly longer than their +/+ counterparts when treated with TKI. Thus, inhibition of FGFR can modulate stromal function, reduce exosome secretion, and may be a therapeutic option to overcome resistance to TKIs. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor' s assessment is that all the issues have been addressed (see decision letter). TKIs have revolutionized the treatment of CML and have shown promise in AML, however development of resistance remains a problem. In CML, resistance develops in a minority of patients, and is most often caused by resistance mutations. However, some patients still develop resistance in the absence of known resistance mutations. In contrast, development of resistance in AML is the norm. Inhibitors of mutated FLT3, which is present in about 30% of AML patients, are initially quite efficacious (Smith et al. , 2012). However, resistance to FLT3 kinase inhibitors in AML typically develops within a few months. In some cases, resistance is cell-intrinsic and due to secondary mutations in the activating loop of FLT3 that prevent drug binding (Weisberg et al. , 2009), however, resistance still develops in the absence of these mutations. Within the marrow microenvironment, leukemia cell survival can be mediated by extrinsic ligands that activate alternative survival pathways (Smith et al. , 2017; Ghiaur and Levis, 2017; Wilson et al. , 2012) and over time can lead to development of intrinsic resistance mutations (Wilson et al. , 2012; Traer et al. , 2012). Bone marrow stromal cells provide a","Leukemias are cancers of white blood cells. The cells grow and divide rapidly, often because of mutations in proteins called kinases. Since the kinase mutations do not occur in healthy cells, they provide a good target for anti-leukemia drugs. Several such kinase inhibitors are effective at treating leukemia patients. However, most leukemia cells develop ways to resist the effects of the kinase inhibitors over time, leading to relapses of the disease. One way that leukemia cells resist kinase inhibitors is by taking advantage of signals coming from supportive cells, known as stromal cells, in the bone marrow. When patients are treated with kinase inhibitors, the bone marrow stromal cells produce more of a signaling protein called FGF2. The leukemia cells then use FGF2 to survive the effects of",380,128,0.3368
pubmed-summarization,"resistance to fluoroquinolones ( flq ) and second - line injectable drugs ( slid ) is becoming more common , especially in eastern european countries , posing a serious threat to effective tuberculosis ( tb ) infection control . according to the most recent world health organization ( who ) report , extensively drug - resistant tb ( xdr - tb ) had been reported by 100 countries by the end of 2013 . on average , an estimated 9.0% ( 95% confidence interval [ ci [ , 6.5% to 11.5% ) of people with multidrug - resistant tb ( mdr - tb ) have xdr - tb ( 1 , 2 ) . to date , only 8 countries among the 36 with a high tb and/or mdr - tb burden have established a national surveillance system for resistance to second - line drugs among patients with mdr - tb ( 1 , 2 ) . efforts should be made to ensure that all patients diagnosed with mdr - tb undergo testing of susceptibility to flq and slid in order to initiate early effective treatment and appropriate measures of infection control . conventional phenotypic methods take weeks to months to fully define the drug resistance profile of mycobacterium tuberculosis isolates due to the low growth rate of the bacterium ( 3 , 4 ) . the development and implementation of rapid molecular assays for the detection of resistance to anti - tb drugs promise more - rapid drug resistance detection , which can be critical in areas with high rates of mdr - tb and xdr - tb and settings with limited conventional dst capacity . in contrast , the choice of molecular assays for second - line drugs is far more limited . to date , genotype mtbdrsl ( hain lifescience , nehren , germany ) is one of the few commercially available molecular tests for detection of resistance to the main second - line anti - tb drugs . it is a qualitative test for the identification of mycobacterium tuberculosis complex ( mtbc ) and its resistance to flq , to aminoglycosides and cyclic peptides ( ag / cp ) , and to ethambutol ( emb ) as either clinical isolates or pulmonary smear - positive clinical","resistance to fluoroquinolones ( flq ) and second - line injectable drugs ( slid ) is steadily increasing , especially in eastern european countries , posing a serious threat to effective tuberculosis ( tb ) infection control and adequate patient management . the availability of rapid molecular tests for the detection of extensively drug - resistant tb ( xdr - tb ) is critical in areas with high rates of multidrug - resistant tb ( mdr - tb ) and xdr - tb and limited conventional drug susceptibility testing ( dst ) capacity . we conducted a multicenter study to evaluate the performance of the new version ( v2.0 ) of the genotype mtbdrsl assay compared to phenotypic dst and sequencing on a panel of 228 mycobacterium tuberculosis",380,128,0.3368
pubmed-summarization,"approximately 3.7%7.5% of the total number of breast cancer patients diagnosed each year in the us and western europe are younger than 40 years . in saudi arabia , the proportion of breast cancer patients 40 years at diagnosis is dramatically larger with 25.1% . multiple retrospective series and subset analyses of larger randomized trials have shown that young patients with breast cancer have a poorer prognosis compared to older age at diagnosis . breast cancer patients 40 years tend to have more triple - negative and fewer luminal a and b breast cancers , tumors of higher grade , more extensive intraductal component , more lymphovascular invasion , more likely estrogen receptor- ( er- ) negative tumors , and more often brca-1 or -2 germline mutations . although young women do appear to have tumors with more aggressive biological characteristics , younger age has been shown in several studies to be an independent predictor of adverse outcome . several current consensus guidelines have included age 35 years as an absolute indication for adjuvant systemic chemotherapy irrespective of other tumor characteristics . more research is needed to optimize the treatment for this patient group . detailed data about prognostic factors and treatment outcome in breast cancer are scarce in saudi arabia and the middle east . the purpose of this study was to characterize the breast cancer patients treated with curative intend of this tertiary care hospital in saudi arabia 40 years of age at diagnosis compared to > 40 years , and to assess their prognosis . medical records were retrospectively reviewed of female breast cancer patients who consulted saad specialist hospital between 2004 and 2011 . eligibility criteria for the analysis were histologically confirmed diagnosis of invasive breast cancer or cancer in situ , surgical treatment with breast conserving surgery or mastectomy with curative intent . patients with distant metastases , synchronous , or metachronous cancer at diagnosis were excluded from the analysis . staging procedures included complete history and physical examination , laboratory assessments , and diagnostic bilateral mammogram . where indicated , ultrasonography of the breast and abdomen , chest radiograph , and radionuclide bone scan were performed . selected patients received magnetic resonance imaging ( mri ) of the breast , computerized tomography ( ct","background . this study was undertaken to evaluate the impact of prognostic factors on the locoregional failure - free survival of early breast cancer patients . methods . in this single - institutional study , 213 breast cancer patients were retrospectively analysed . fifty - five of 213 patients were 40 years of age at diagnosis . the impact of patient- or treatment - related factors on the locoregional failure - free survival was assessed using the kaplan - meier method . the simultaneous impact of factors on the locoregional failure - free survival was assessed using the cox proportional hazards regression analysis . results . the median follow - up time of the censored patients was 22 months ( mean 28 months , range 392 months )",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2004), where ESAGs and BES promoters have not been found, suggesting this part of the archive is simply a store of silent VSGs for recombination. The largest silent store is composed of arrays of VSGs in the subtelomeres of the megabase chromosomes, where the majority of the VSGs are pseudogenes or partial genes (Berriman et al. , 2005). The strategies for VSG recombination in antigenic variation reflect the archive location and gene composition (McCulloch et al. , 2015). A minor route for switching is termed reciprocal VSG recombination, where telomeres are exchanged between two chromosomes, moving the VSG out of the active BES and moving a previously silent VSG into the active BES (Rudenko et al. , 1996). More common is VSG gene conversion, which can involve both intact and impaired VSGs, and involves deletion of the VSG in the BES and replacement by VSG sequence copied from the silent archive. Early in infections gene conversion of intact VSGs predominates (Marcello and Barry, 2007; Morrison et al. , 2005) and, since the VSGs share little sequence homology, the reaction relies on flanking homology. ~90% of VSGs are flanked by 70 bp repeats (Marcello and Barry, 2007), which provide upstream homology to guide recombination of virtually all genes in the archive. In addition, gene conversion of VSGs between BES can use extensive upstream homology: gene conversion can extend to downstream homology within and around the VSG open reading frame (ORF) or, if the silent VSG is telomeric, to the chromosome end. Impaired VSGs are seen as recombination substrates later in infections and here gene conversion differs from intact VSGs, since the reaction involves the production of a functional gene using homology within the ORF; indeed, multiple VSG donors are frequently recombined to generate novel ‘mosaic’ VSGs in a reaction termed segmental gene conversion (Hall et al. , 2013; Mugnier et al. , 2015). All available evidence suggests switching of intact VSGs by recombination is catalyzed by homologous recombination (HR), a universally conserved reaction that directs repair of DNA damage and maintains replication fork progression genome-wide. Mutation of the central catalytic enzyme of HR, RAD51, impairs (but does not abolish) VSG recombination, including gene conversion (McCulloch and Barry, 1999). Consistent with that phenotype, mutation of T. brucei BRCA2 (Hartley and McCulloch, 2008)","The African trypanosome, Trypanosoma brucei, is a parasite that is transmitted between mammals by the tsetse fly, and causes a disease known as sleeping sickness in humans. Like many other parasites, trypanosomes have evolved ways to avoid being killed by their hosts. One such survival strategy involves the parasites constantly changing the molecules that coat their surface, which are the main targets recognized by their hosts’ immune systems. Switching one coat protein for another similar protein, a process called antigenic variation, allows a parasite to evade an attack and establish a persistent infection. Antigenic variation also makes it almost impossible to develop a vaccine that will offer lasting protection against the parasite. Previous research suggested that a trypanosome might deliberately break its own DNA and then exploit a",380,128,0.3368
dialogsum,"#Person1#: Which social problem do you think the government needs to concentrate on most? #Person2#: I think housing is a big problem. There are thousands of homeless people on the streets. #Person1#: How would you solve the problem? #Person2#: I have a good idea to solve it. The government could provide some money for homeless people to build their own homes. #Person1#: It would probably be very expensive. #Person2#: I think the government can afford it. Besides, there are many advantages. Homeless people would find it easier to get jobs if they had an address. They would learn some useful skill for finding jobs i #Person1#: It's not a bad idea. I think education is the biggest problem at the moment. Schools don't seem to have enough money to educate kids properly. #Person2#: If we are to invest more money to education, we will need to raise taxes. That wouldn't be popular with voters. #Person1#: Most voters what everything both ways. They want the government to pay for lots of things, but without increasing taxes. #Person2#: The government should show that it is using money efficiently. Sometimes you hear about how the government has wasted money on a project. #Person1#: Yes. The government has limited funds and must show that it is using the money responsibly",#Person2# thinks housing is a big social problem and the government should offer some money for the homeless. #Person1# thinks education is the biggest problem. They both think the government should use money responsibly.,216,34,0.1574
pubmed-summarization,"received 59.4 gy in 33 fractions . the median time from surgery to the initiation of crt was 26 days ( range of 11 - 77 days ) . tmz concomitant with postoperative rt was administered at 75 mg / m a day . for adjuvant tmz , 150 - 200 mg / m was administered daily for 5 days , every 28 days . in terms of salvage therapy following recurrence , the surgical resection was performed for the patients who had a small progressive lesion involving non - eloquent area , and gamma knife surgery was reserved for the cases with small lesions and medically inoperable condition . bevacizumab with or without cpt-11 was considered as a primary option for salvage therapy in all inoperable cases showing true progression . the patients who had previous episode of intracranial hemorrhage or who were not be able to afford bevacizumab received nimustine ( acnu)/cisplatin ( cddp ) or procarbazine , lomustine , and vincristine ( pcv ) chemotherapy , or metronomic tmz . mri with gadolinium enhancement and t2/flair was performed 1 month after crt and every 3 months thereafter . when a progressive finding was present , mri was performed at 2-month intervals . progression was defined as a more than 25% increase in the sum of the products of perpendicular diameters as in the macdonald criteria , an increase in the non - enhancing lesion in recurrent cancer with bevacizumab15 ) . etpd and ltpd were defined as true progression found at first and second post - treatment mri with the exception of pspd , respectively . psr was scored when progressive enhancement or a non - enhancing t2-weighted lesion was shown right after response to bevacizumab , or after discontinuation of the drug due to toxicity . in some cases , cerebral blood flow ( cbf ) , cerebral blood volume ( cbv ) values using perfusion mri , and apparent diffusion coefficient ( adc ) maps the kaplan - meier method was used for the survival analysis to compare os between etpd and ltpd . all data from patients diagnosed with world health organization ( who ) grade 3 or 4 glioma from march 2005 to february 2011 were retrieved from the archives of the pathologic","objectivewe evaluated pseudoprogression ( pspd ) following radiation therapy combined with concurrent temozolomide ( tmz ) , and we assessed pseudoresponse following anti - angiogenic therapy for patients with recurrent disease using the response assessment of the neuro - oncology working group.methodspatients who were pathologically confirmed as having high - grade glioma received radiotherapy with concurrent tmz followed by adjuvant tmz . bevacizumab ( avastin ) with cpt-11 were used as a salvage option for cases of radiologic progression . magnetic resonance imaging ( mri ) was routinely performed 1 month after concurrent radiochemotherapy ( crt ) and every 3 months thereafter . for cases treated with the bevacizumab - containing regimen for progressive disease , mri was performed every 2 months.resultsof 55 patients , 21 ( 38%",380,128,0.3368
pubmed-summarization,"this work was supported , in whole or in part , by the one hundred person project of sun yat - sen university ( xz ) , national natural science foundation 81302262 ( xz ) , the basser research center for brca ( lz ) , the national institutes of health r01ca142776 , r01ca190415 , p50ca083638 ( lz ) , the ovarian cancer research fund ( lz and xh ) , the breast cancer alliance ( lz ) , department of defense ( lz ) , and the marsha rivkin center for ovarian cancer research ( lz ) .",long non - coding rnas ( lncrnas ) are defined as rna transcripts larger than 200 nucleotides that do not appear to have protein - coding potential . accumulating evidence indicates that lncrnas are involved in tumorigenesis . our work reveals that lncrna fal1 ( focally amplified lncrna on chromosome 1 ) is frequently and focally amplified in human cancers and mediates oncogenic functions .,99,65,0.6566
scientific_lay_summarisation-elife-norm,"review see Kuno and Chang, 2005; Blanc et al. , 2011; Bak et al. , 2012). The most important vectors are found among the arthropods. Those with a piercing-sucking feeding behavior such as mosquitoes (or other blood-feeding dipterans) and ticks are especially significant for vertebrate viruses, and likewise aphids, white flies and other sap-feeding bugs are consequential for plant viruses. These vectors are ideal, as their variety of mouth parts can puncture cells, blood vessels, and plant sap vessels with great precision, thus enabling efficient uptake and injection of pathogens without killing the host. Vector transmission can be classified into two main transmission modes. In circulative transmission, the virus is taken up by the vector together with the nutrients (e. g. , blood, plant sap, cell contents), where it actively crosses from the intestine into the vector interior. Then it cycles through the hemocoel (the internal body cavity awash in hemolymph) to the salivary glands, where the virus can be secreted together with the saliva into a new host. The second transmission mode is alternatively referred to as mechanical transmission (for human and animal viruses) or non-circulative transmission (for plant viruses). In this transmission mode, the arthropod vector only briefly comes into contact with the virus, in which it transiently attaches to the vector mouth parts and is subsequently released; an internalization step does not occur. The viral proteins involved in this seemingly simple process have been well-described in the literature, often down to the molecular level (for review see Ng and Falk, 2006). On the other hand, their precise roles during virus-acquisition by the vector remains largely unexplored (for review see Blanc et al. , 2011). Cauliflower mosaic virus (CaMV), the virus studied here, is a non-circulative virus transmitted by aphids. CaMV binds to a receptor protein located at the tip of the aphid' s needle-like mouth parts, the stylets (Uzest et al. , 2007,2010). The CaMV transmissible complex is composed of the icosahedral viral particle (containing the viral genome enclosed by a shell of capsid protein P4), the virus-associated protein P3, and finally the aphid-transmission factor or helper component, the viral protein P2 (Blanc et al. , 1993a; Leh et al. , 1999; Plisson et al. , 2005). P2 is central to the virus' s transmission, as it","Viruses are infectious agents that can replicate only inside a living host cell. When a virus infects an animal or plant, it introduces its own genetic material and tricks the host cells into producing viral proteins that can be used to assemble new viruses. An essential step in the life cycle of any virus is transmission to a new host: understanding this process can be crucial in the fight against viral epidemics. Many viruses use living organisms, or vectors, to move between hosts. In the case of plant viruses such as cauliflower mosaic virus, the vectors are often aphids. When an aphid sucks sap out of a leaf, virus particles already present in the leaf become attached to its mouth, and these viruses can be transferred to the",380,128,0.3368
dialogsum,"#Person1#: Do you have any questions for me? #Person2#: Yes, I've applied for the post of sales assistant here, but I really care about if there are chances of promotion in the company. #Person1#: Yes, we're growing all the time and if you are prepared to move, there are jobs at other branches. #Person2#: Great. And in the job description, can you tell me something about your working hours? #Person1#: Sure, because we open our book shops in the evenings as well as during the day, we ask staff when they prefer to work. Look at this time table, it says here we have a member whose name is Julia. She works 3 hours in the morning and then 2 hours in the evening.",#Person2# has applied for the post of the sales assistant. #Person1# answers #Person2#'s questions about promotion and working hours.,124,19,0.1532
pubmed-summarization,"g : mra on arrival showed a bilateral occlusion of the internal carotid artery , h : before and after stent placement , i : ct at 24 hours after t - pa showed a hemorrhagic change in the right basal ganglia , j : mra on the 5th hospital day . k : dwi on arrival showed acute cerebral infarction in the left basal ganglia extending to the corona radiata , l : mra on arrival showed an occlusion of the left internal carotid artery , m : before and after stent placement , n : ct at 24 hours after t - pa showed no hemorrhagic change , o : mra on the 14th hospital day . the carotid stent was patent . an 85-year - old man was brought to our hospital with the chief complaints of left hemiplegia and dysarthria . he had a history of hypertension , old cerebral infarction , and nvaf and had been receiving oral administration of aspirin ( 100 mg / day ) . on arrival , head mri revealed acute cerebral infarction in the right frontal temporal lobe and corona radiata ( dwi - aspects : 6 ) ( f ) . mra revealed a bilateral internal carotid artery occlusion ( g ) . at 240 minutes after onset , rt - pa was administered , and cerebral endovascular treatment was additionally administered . because stenosis at the origin of the right internal carotid artery was so severe that a therapeutic catheter could not be crossed over the lesion , clopidogrel was administered at a loading dose of 300 mg , followed by emergency carotid artery stenting ( wallstent ) ( h ) . then , aspiration with the penumbra system was performed for a right middle cerebral artery occlusion ( m1 segment ) , and complete recanalization was achieved at 323 minutes after onset . after treatment , antiplatelet therapy ( clopidogrel 50 mg + aspirin 100 mg ) was continued . sbp was maintained at 100 to 130 mmhg by a continuous intravenous infusion of nicardipine . head computed tomography performed 24 hours later revealed asymptomatic hemorrhagic changes ( i ) . the course of rehabilitation therapy was uneventful , however , aortic dissection occurred on hospital day","we herein report three ischemic stroke patients who underwent emergency carotid artery stenting after receiving intravenous tissue plasminogen activator ( t - pa ) treatment . all patients received antiplatelet medications immediately before stent placement for loading as well as dual antiplatelet therapy after stenting . under high - dose and dual antiplatelet therapy , none of the three patients showed symptomatic intracranial hemorrhaging . however , one case showed reocclusion of the placed stent after acute thrombosis . as a result , new treatment strategies for the use of antiplatelet agents during emergency stent placement must be developed , particularly for patients who have received intravenous t - pa therapy .",380,112,0.2947
dialogsum,"#Person1#: And so, that concludes my outline for our marketing strategy next year. Thank you very much for your time. #Person2#: Hey, that was quite the presentation! Honestly, I was completely blown away by your strategy outline. I've gotta say, Alex, you really wowed me today. #Person1#: Aw, come on ; it was nothing. I'm just doing my job. #Person2#: No, I think you deserve some recognition here ; I mean, if I look back on your previous presentations, this is a huge improvement. #Person1#: Well, Kristin did give me a hand with the slides. She's a real wiz on PowerPoint. #Person2#: And I saw that you took on board my feedback about pricing strategies. I really appreciate you taking the time to think though my suggestions. #Person1#: Yeah, well, that was some good advice. You made some really good points. #Person2#: Well, I just wanted to say well done. Really you did a great job.",#Person2# compliments on Alex's presentation. #Person2# is glad Alex took the advice and has improved a lot.,156,17,0.109
dialogsum,"#Person1#: Good morning. This is Peter Brown of IMA computers. What can I do for you? #Person2#: Hello. I'd like to order some computer monitors. #Person1#: Yes. Which ones? #Person2#: The order number is C106. #Person1#: How many do you need? #Person2#: Three hundred, please. #Person1#: One moment. Yes, we can supply them. #Person2#: Could you send them by July 21st, please? #Person1#: Certainly. #Person2#: Good, thanks. #Person1#: Thank you. Good-bye. #Person2#: Good-bye.",#Person2# orders 300 computer monitors from #Person1# and asks to send by July 21st.,73,14,0.1918
pubmed-summarization,"data management system and web resource constructed to support saliva diagnostics research , and we present below the informatics advances brought about through the skb and through the associated tools and resources . ontologies are controlled structured vocabularies designed to provide consensus - based means to ensure consistent description of data by scientists working in disparate domains . as applied in the biomedical domain , ontology plays a key role in providing consensus - based controlled vocabularies serving the consistent annotation of biological and medical data and information , most conspicuously within the framework of the gene ontology and now of its sister ontologies within the open biomedical ontologies foundry ( ) . the basic formal ontology ( bfo ) is a formal ontological framework developed by barry smith , pierre grenon and others , which serves as the starting point for some 100 ontology projects primarily in the biomedical domain ( ) . the bfo framework can be readily extended to the treatment of families of ontologies of other types , above all to the treatment of relations between ontologies of different levels of granularity , from genes to species and from a single patient to epidemics at a geographical scale ( combining applications of bfo to the medical and to the geographical domain ) . the framework may also be used as a tool for dealing with the relations between distinct perspectives on the biomedical domain , including culturally generated perspectives of the sort which are studied by linguists and anthropologists . two bfo - based ontologies of special significance for our work here are the ontology for biomedical investigations ( obi ) and the ontology for general medical sciences . the obi is an ontology designed to serve the coordinated representation of designs , protocols , instrumentation , materials , processes , data and types of analysis in all areas of biological and biomedical investigation . ontology for general medical science is an ontology of the entities involved in the clinical encounter . thus , it includes very general terms that are used across medical disciplines , including : disease ' , disorder ' , disease course ' , diagnosis ' , patient ' and healthcare provider ' . to advance the consistency of data in the","there is a need recognized by the national institute of dental & craniofacial research and the national cancer institute to advance basic , translational and clinical saliva research . the goal of the salivaomics knowledge base ( skb ) is to create a data management system and web resource constructed to support human salivaomics research . to maximize the utility of the skb for retrieval , integration and analysis of data , we have developed the saliva ontology and sdxmart . this article reviews the informatics advances in saliva diagnostics made possible by the saliva ontology and sdxmart .",380,99,0.2605
dialogsum,"#Person1#: Excuse me, would you like to be our guide? #Person2#: Of course. #Person1#: It's our first time to be here, so would you please arrange a schedule for us? #Person2#: With pleasure. I think we should go to the palace first. #Person1#: When was the palace built?",#Person2# would like to be #Person1#'s guide and arranges a schedule.,48,11,0.2292
dialogsum,"#Person1#: Good evening. I've come to see Miss Morrison #Person2#: Oh! Good evening. I'm sorry, but she is not in. She's gone out to the theatre #Person1#: Oh! I've just come back from Canada and I've brought a parcel from her parents #Person2#: Please come in #Person1#: But you're busy, aren't you? #Person2#: I was preparing my supper but I've finished now. #Person1#: I can leave the parcel with you, can't I? #Person2#: Oh! yes",#Person1# comes to give Miss Morrison the parcel from her parents but she's out. #Person1#'ll leave the parcel with #Person2#.,75,20,0.2667
scientific_lay_summarisation-elife-norm,"cell dendrites (Tolbert et al. , 1980). More recently, it was demonstrated that GlyT2-expressing CN neurons extend axons toward the cerebellar cortex (Uusisaari and Knöpfel, 2010), suggesting that the iNC pathway might be identifiable by its glycinergic phenotype. While the iNC projection is likely to have significant impact on cerebellar computation, its postsynaptic targets and its functional organization remain unknown. To establish the existence and prevalence of an inhibitory connection between the CN and the cerebellar cortex, we employed specific viral targeting of GABAergic and glycinergic neurons in the CN of GAD-cre and GlyT2-cre transgenic mouse lines, respectively (Taniguchi et al. , 2011; Husson et al. , 2014). We found that the GABA-glycinergic CN neurons form an extensive plexus of iNC axons, which contact Golgi cells in the cerebellar granular and molecular layers. Specific optogenetic activation of the iNC axons inhibited spikes in a distinct subpopulation of Golgi cells, characterized by their spontaneous firing, high neurogranin immunoreactivity, and negligible GlyT2 expression. As the functional significance of the iNC pathway is likely to be amplified by the high divergence of Golgi cells, which target thousands of GrCs (Hámori and Somogyi, 1983; Jakab and Hamori, 1988; Andersen et al. , 1992; Korbo et al. , 1993), as well as the remarkable mediolateral extent of the iNC axons, the CN might play a key role in the regulation of the information flow through the GrCL. In order to identify the iNC projection neurons, we specifically labeled the GABAergic and glycinergic CN neurons by injecting floxed adeno-associated virus (AAV) in the CN of GAD-cre and GlyT2-cre transgenic mouse lines, respectively. As shown in 1A1, B1, these procedures resulted in the expression of the fluorophores (mCherry in GAD-cre and YFP in GlyT2-cre mice) in a subset of CN neurons. In the GAD-cre mice, the labeled neurons displayed a wide range of sizes and shapes, including both globular and multipolar morphologies (1A2, arrow and arrowhead, respectively). In contrast, in GlyT2-cre mice, the labeled neurons were predominantly large (1B2, arrowhead) and multipolar, often with a thick principal dendrite (1B2, arrows). To examine the morphological difference between CN cells labeled in GAD-cre and GlyT2-cre mice, we measured and compared their soma sizes. The size distribution in GAD-cre CN was best fitted with a two-component Gaussian model (1D, red","The cerebellum is a region in the brain that plays a central role in controlling posture and movement. The cerebellum is composed of a cortex and several nuclei. The nuclei are thought to ‘compute’ the signals that are sent from the cerebellum to other parts of the brain to control posture and movement. They do this under the supervision of the cortex. The main interaction between the cortex and the nuclei involves cortical neurons called Purkinje cells inhibiting the activity of the nuclei. Ankri, Husson et al. have now used various genetic techniques and mutant mice to identify a new population of neurons in the nuclei of the cerebellum and to express fluorescent markers into these cells. This approach reveals that the axons of these neurons ‘climb’ from",380,128,0.3368
dialogsum,"#Person1#: Excuse me, I am looking for the textbook by a Professor Jordon for the marketing course. #Person2#: I am afraid it's out of stock. You'll have to order it. And it will take the publisher 3 weeks to send it to us.",The textbook that #Person1# wants is out of stock.,43,9,0.2093
pubmed-summarization,"solution containing the internal standards cyclosporin d ( 1234/1217 ) and ascomycin ( 809.6/756.6 ) was prepared before sample preparation . whole blood samples were put into a tube as 100 l volume and 300 l precipitation reagent was added . after vortexing for additional 5 sec , the tubes were centrifuged for 10 minutes at 10000 rpm at 4c . three level quality control serums ( qcs ) were purchased from utak ( valencia , ca ) . the lc - ms / ms was performed using an ionics 3q 120 triple quadrupole mass spectrometer ( bolton , on canada ) with a shimadzu ultra - fast liquid chromatograph ( uflc ) system . 20 l of supernatant was loaded on a porous r1/20 pretreatment column ( 30 2.1 mm ) for on - line washing with water for 0.25 minutes at a liquid flow rate of 3 ml / min and then eluted by an imtakt cadenza cd - c18ht analytical column ( 50 2.0 mm , 3 m ) at flow rate of 0.6 ml / min using solvent a ( water : methanol = 98 : 2 , v / v , with 0.1% formic acid and 10 mm ammonium acetate ) and solvent b ( water : methanol = 2 : 98 , v / v , with 0.1% formic acid and 10 mm ammonium acetate ) . the sensitivity of tac and csa was 0.1 ng / ml and 1.0 ng / ml respectively . repeated measurements made from the same samples kept at different storage conditions were tested using the wilcoxon test . we did not find a significant difference between samples analyzed immediately and those kept at + 4c for 24 hours ( p = 0.241 ) ( percent change 13.78% ) and 48 hours ( p = 0.285 ) ( percent change 10.4% ) , and there was no significant difference between samples analyzed immediately and those stored at 20c for one month ( p = 0.646 ) ( percent change 0.91% ) . however , there was a significant difference between samples analyzed immediately and those kept at room temperature for 24 hours ( p = 0.005 ) ( percent change 32.89% ) ( ) . cyclosporine a. we found","tacrolimus and cyclosporine a are immunosuppressant drugs with narrow therapeutic windows . the aim of this study was to investigate the stability of tacrolimus and cyclosporin a levels in whole blood samples under different storage conditions . whole blood samples were obtained from 15 patients receiving tacrolimus and 15 patients receiving cyclosporine a. samples were immediately analyzed and then stored at different conditions ( room temperature ( 24c26c ) for 24 hours , + 4c for 24 and 48 hours , and 20c for one month ) and then analyzed again . for tacrolimus , there was a significant difference between samples analyzed immediately and those kept 24 hours at room temperature ( p = 0.005 ) ( percent change 32.89% ) . however , there were no",380,128,0.3368
dialogsum,"#Person1#: Dad, can you take me shopping this weekend? I need to find a dress. #Person2#: The big dance is this weekend? Wow, sure, I can do that. When is it? #Person1#: It's at the end of the month. #Person2#: Wow, I cannot believe you were almost done with high school. I still remember your first day of kindergarten. #Person1#: Yeah, I'm not so little anymore. I'm heading off at college at the end of the summer. #Person2#: Don't remind me. I'm really going to miss you. #Person1#: Ah, thanks, dad.",#Person1# wants her dad to take her shopping to buy a dress for the high school big dance. Her dad is nostalgic about her growth.,91,25,0.2747
pubmed-summarization,"routinely . patients with sfu grade 1 hydronephrosis ( equivalent to pyelectasis 1.5 cm in grignon s approach ; table 1 ) had follow - up with b - mode ultrasound . a regular follow - up examination to clarify the pathological obstruction was deemed necessary in patients with sfu grade 2 hydronephrosis ( expanded renal pelvis of > 1.5 cm ) . patients diagnosed with sfu grade 3 hydronephrosis were closely followed due to the possibility of obstructive pathological factors and permanent renal damage . the ect and mru investigations were carried out at one month of age , and ultrasound examinations were undertaken every two to four weeks . surgery was performed at the time of presentation if the initial differential renal function ( drf)was < 35% , with an obstructed curve on renogram and/or parenchymal thickness below 3.5 mm . post - surgery , the patients were closely monitored by ultrasound and followed at one , three , six , and 12 months . the other patients were followed using a standard protocol , with ultrasound and radionuclide studies being performed every three months during the first two years . if renal function and sfu grade remained stable , the patients were followed by ultrasound every six months for another two years . all patients were followed for at least two years after birth . normally distributed continuous variables are presented as mean standard deviation ( sd ) and were analyzed using the student s t test or anova with the tukey s post hoc test , as appropriate . non - normally distributed continuous variables are presented as median ( range ) and were analyzed using the mann - whitney test . the occurrence of surgery during follow - up was analyzed using kaplan - meier curves , which were analyzed by the log - rank test . a multivariate analysis using cox regression analysis was performed to identify the independent factors involved in the occurrence of surgery . the receiver operating characteristic ( roc ) curve approach was used to determine the accuracy of factors associated with the occurrence of surgery . spss 16.0 ( ibm , armonk , ny , usa ) was used for analysis . this was a retrospective study of infants","backgroundhydronephrosis is a common congenital condition . the detection of fetal hydronephrosis by ultrasound presents a treatment dilemma . this study aims to examine postnatal follow - up and treatment for hydronephrosis diagnosed prenatally.material/methodsthis was a retrospective study of 210 infants with hydronephrosis diagnosed at the qilu hospital ( shangdong , china ) between january 2005 and january 2013 . the patient cohort was divided into four groups based on prenatal ultrasound examinations using the society for fetal urology ( sfu ) classification system . data on follow - up investigations and treatment methods were extracted from the charts and analyzed.resultspatients with sfu grade 1 , 2 , and 3 hydronephrosis ( n=125 , n=74 , and n=11 , respectively ) were followed for two years . in",380,128,0.3368
dialogsum,"#Person1#: Why are you in court today? #Person2#: I got a ticket, and I would like to fight it. #Person1#: Is the officer that pulled you over here today? #Person2#: He's here. #Person1#: Tell me what happened. #Person2#: The officer says that I ran a red light, but I didn't. #Person1#: The officer wouldn't lie about that. #Person2#: He must've, because the signal had a camera on top of it. #Person1#: There was no picture taken of your license plate? #Person2#: I don't believe it took my picture. #Person1#: I'm just going to let you go. #Person2#: I appreciate that.",#Person2# is in court to fight a ticket of running a red light. #Person1# lets #Person2# go.,100,17,0.17
dialogsum,"#Person1#: Want to go with me to get some pizza, Sophie? #Person2#: No, Black. I'm waiting for a package to be delivered. #Person1#: This is why I hate shopping online. It would be faster to just get what you want from the store. Now you have to sit here all day. Isn't Mom home? #Person2#: No, Mom went to work. #Person1#: Just download an app to keep track of your package. You can just come back when you get a delivery notice. #Person2#: No, thanks, Mr. Bossy. Even if they leave the package for a short time, someone could steal it. #Person1#: Goodness! You just don't want to be seen with your little brother! #Person2#: It's not that. I really did plan to stay home and wait for this package. Why don't we just have pizza delivered? #Person1#: Great. More waiting.",Black suggests going to get some pizza but Sophie's waiting for a package. They finally decide to have the pizza delivered.,141,21,0.1489
pubmed-summarization,"recent advances in computer hardware and software have greatly extended the time scales that can be covered by biomolecular simulations . these longer time scales ( beyond nanoseconds ) one important characteristic of these force fields is the ability to accurately model the formation of salt bridges , or pairs of amino acids whose oppositely charged side - chains are within hydrogen - bonding distance in proteins . however , it has long been suspected that the forces between oppositely charged amino acids are overly attractive in molecular dynamics ( md ) simulations with current biomolecular force fields , and there have been a number of efforts to reduce this artifact in the improvement of various force fields . previous theoretical studies have analyzed the contribution of salt bridges to protein or protein protein complex stability , using both implicit and explicit modeling of solvation . others have studied salt bridges using amino acid analogues , often employing biasing techniques in the simulations . more recently , a comprehensive comparison of force field / water model combinations was conducted for salt bridge interactions between the amino and carboxyl groups of zwitterionic amino acids , using extensive simulations in explicit solvent on the microsecond time scale . here , we evaluated six biomolecular force fields for their ability to accurately model the strengths of salt bridges between the side - chains of oppositely charged amino acids by unbiased , microsecond - scale md simulations in explicit solvent . in particular , we directly compared current amber , charmm , and opls force fields in simulations of association between the side - chain analogues of three different pairs of amino acids , arg / asp , lys / asp , and his(+)/asp . we further tested one of the pairs , arg / asp , by simulating association of blocked amino acid dipeptides . in addition , we evaluated the influence of the solvent model on the strengths of the salt bridges by simulating the side - chain analogue pairs using a selection of different force field / water model combinations . to our knowledge , our microsecond - scale simulations provide the most extensive sampling of salt bridge formation to date , yielding thousands of association / dissociation events , permitting","recent advances in computer hardware and software have made rigorous evaluation of current biomolecular force fields using microsecond - scale simulations possible . force fields differ in their treatment of electrostatic interactions , including the formation of salt bridges in proteins . here we conducted an extensive evaluation of salt bridge interactions in the latest amber , charmm , and opls force fields , using microsecond - scale molecular dynamics simulations of amino acid analogues in explicit solvent . we focused on salt bridges between three different pairs of oppositely charged amino acids : arg / asp , lys / asp , and his(+)/asp . our results reveal considerable variability in the predicted ka values of the salt bridges for these force fields , as well as differences",380,128,0.3368
pubmed-summarization,") . mass spectrometry grade trypsin gold was obtained from promega ( madison , wi ) . a 20 g aliquot of psa and 5 g aliquot of psah were prepared in 50 mm pbs buffer ( ph 7.5 ) ( phosphate buffered saline containing 50 mm disodium phosphate and 150 mm sodium chloride ) . in both cases , denaturation was performed at 65 c for 1 h. the samples were then reduced by adding by adding a 1.25 l aliquot of 200 mm dtt prior to incubation at 60 c for 45 min . those reduced samples were then alkylated with the addition of a 5 l aliquot of 200 mm iaa and incubated at 37.5 c for 45 min in the dark . excess iaa was consumed through the addition of a second 1.25 l aliquot of 200 mm dtt . the reaction was allowed to proceed at 37.5 c for 30 min in the dark . trypsin was added into the samples using an enzyme / substrate ratio of 1:25 w / w , and the samples were subjected to overnight incubation at 37.5 c for 18 h. to complete the enzymatic digestion , samples were subjected to microwave digestion at 45 c and 50 w for 30 min before adding a 0.5 l aliquot of neat formic acid to the samples . finally , the samples were dried and suspended in 0.1% formic acid prior to lc lc ms / ms was carried out on dionex 3000 ultimate nano - lc system ( dionex , sunnyvale , ca ) interfaced with an ltq orbitrap velos mass spectrometer ( thermo scientific , san jose , ca ) equipped with a nano - esi source . the psa and psah digests were initially online - purified using a pepmap 100 c18 cartridge ( 3 m , 100 , dionex ) . a 2 g aliquot of psa and 0.4 g aliquot of psah digests were injected into the trapping cartridges . the purified peptides were then separated using a pepmap 100 c18 capillary column ( 75 m i.d . the separation was achieved at a 350 nl / min flow rate using the following gradient conditions : 010 min , 5% solvent b ( 98% acn with","prostate specific antigen ( psa ) is currently used as a biomarker to diagnose prostate cancer . psa testing has been widely used to detect and screen prostate cancer . however , in the diagnostic gray zone , the psa test does not clearly distinguish between benign prostate hypertrophy and prostate cancer due to their overlap . to develop more specific and sensitive candidate biomarkers for prostate cancer , an in - depth understanding of the biochemical characteristics of psa ( such as glycosylation ) is needed . psa has a single glycosylation site at asn69 , with glycans constituting approximately 8% of the protein by weight . here , we report the comprehensive identification and quantitation of n - glycans from two psa isoforms using lc ms",380,128,0.3368
dialogsum,"#Person1#: It's a wonderful party, Joan, The food, the drink, the atmosphere. . . Everyone is enjoying himself. #Person2#: Thanks to your help. To our friendship. #Person1#: Bottoms up! By the way what kind of entertainment are we gonna have? #Person2#: Dancing. The boys from the Campus Band have promised to play music for us. #Person1#: Oh, how wonderful! Every girl on the campus has a crush on those handsome guys. #Person2#: I'll surely make introductions for them.","#Person1# and Joan are having fun at the party, and they're going to dance.",78,14,0.1795
scientific_lay_summarisation-elife-norm,"usher organization and detail of its translocation domain. (A) A diagram of the domain organization of PapC usher. NTD (dark-blue) represents the N-terminal domain, CTD1 (light-violet) and CTD2 (dark-violet) represent the C-terminal domains; TD represents the translocation domain, comprising the TP (translocation pore, light-blue) and the PD (plug domain, magenta). (B and C): Ribbon representation of the starting model of the native translocation domain (TD) of PapC with the labels ‘N’ and ‘C’ indicating the N and C termini of the translocation channel. The β-barrel, PD (including the P-linkers), β-hairpin, and α-helix (including the H-linkers) are coloured blue, magenta, orange, and yellow, respectively. The outer membrane position is represented schematically with the labels ‘E’, ’M’, and ‘P’ indicating the extracellular side, the membrane, and the periplasmic side, respectively. Side view of the TD (B) is shown with the α-helix, β-hairpin, H-linker1, H-linker2, P-linker1, P-linker2, and PD, labelled. Extracellular top view of the TD (C) is shown with the barrel β strands labelled β1 through β24 and with the PD strands labelled βA through βF. The figures were created with Chimera (Pettersen et al. , 2004). : http: //dx. . org/10. 7554/eLife. 03532. 00310. 7554/eLife. 03532. 004Figure 1— 1. MD simulations of the native PapC TD and its mutants. (A) Cutaway view across the membrane plane of the native PapC TD starting model in a POPE/POPG lipid bilayer (sim1, t = 0). Molecular surface of PapC TD is coloured as in , the lipids are shown in grey with the lipid head group coloured by element, the water is coloured by element, and the ions (the Na+ in blue and the CL− in yellow) are represented as sphere. The Cα-RMSD values for each system from the starting structure (t = 0) for the native TD (B), the hairpin mutant (C), helix mutant (D), and helix-hairpin mutant (E) are plotted as a function of time. : http: //dx. . org/10. 7554/eLife. 03532. 004 The mutant lacking both the β-hairpin and the α-helix is defective for pilus biogenesis (Mapingire et al. , 2009). It has been observed in other OMP β-barrels that such secondary structure elements (e. g. , an α-helix that protrudes inside the barrel or packs against the transmembrane strands) can use complex allosteric mechanisms to mediate their function (Naveed et","Escherichia coli is a bacterium that commonly lives in the intestines of mammals, including humans, where it is usually harmless and can even be beneficial to its host. However, some types of E. coli produce hair-like filaments called P pili that allow the bacteria to attach to the human urinary tract and cause disease. To pass through the outer membrane of the E. coli cell, the filaments have to travel through a protein in the membrane called PapC usher. The PapC usher protein—which is also involved in the assembly of the P pili filaments—contains a tube-like part called a β-barrel that is usually blocked by another part of the protein called the ‘plug domain’. For the P pili to pass through the β-barrel, the plug domain has to",380,128,0.3368
pubmed-summarization,"alzheimer 's disease ( ad ) is a neurodegenerative disorder that is clinically characterized by progressive mental decline and histopathologically defined by highly abundant amyloid deposits and neurofibrillary tangles in the brain parenchyma . the identification of mutations within the amyloid precursor protein ( app ) and presenilin ( ps ) genes that cause autosomal dominantly inherited ad and that result in increased production of amyloid - prone forms of a established beyond doubt that the processing of app and the production of a peptides are intimately involved in the disease process and led to the proposal and the reinforcement of the alzheimer amyloid cascade hypothesis . the role of amyloid in neuronal dysfunction has recently been extended by the discovery of small , soluble , oligomers of the a peptide , some forms of which have been termed addls ( a-derived diffusible ligands ) , protofibrils , or a*56 . these a oligomers are not only potential intermediates in the formation of amyloid filaments , but they also have been shown to be neurotoxic themselves and to inhibit long - term potentiation ( ltp ) , a cellular model of memory , in hippocampal slices . thus , the amyloid cascade hypothesis now includes the essential role of a oligomers in the neurodegeneration process . despite its strength , the amyloid cascade hypothesis is incomplete without including the essential role of amyloid - associated inflammatory proteins . for example , biochemical and histological studies first showed that , in addition to a , amyloid deposits also contained the inflammation / acute phase protein 1-antichymotrypsin ( act ) and , later , apolipoprotein e ( apoe ) , which were both hypothesized to serve as catalysts or pathological chaperones of amyloid formation . these and other results also indicated that alzheimer 's disease and its manifestation in middle - aged down syndrome may include an inflammatory process , for both act and apoe are inflammatory and/or acute phase proteins in other contexts , and both are overexpressed in affected regions of the ad brain ( for reviews see ) . indeed , alzheimer himself first identified the inflammatory component of alzheimer 's disease when he described reactive astrocytes and microglia in affected brain regions of his first patient . however","the amyloid cascade hypothesis remains a robust model of ad neurodegeneration . however , amyloid deposits contain proteins besides a , such as apolipoprotein e ( apoe ) . inheritance of the apoe4 allele is the strongest genetic risk factor for late - onset ad . however , there is no consensus on how different apoe isotypes contribute to ad pathogenesis . it has been hypothesized that apoe and apoe4 in particular is an amyloid catalyst or pathological chaperone . alternatively it has been posited that apoe regulates a clearance , with apoe4 been worse at this function compared to apoe3 . these views seem fundamentally opposed . the former would indicate that removing apoe will reduce ad pathology , while the latter suggests increasing brain apoe levels",380,128,0.3368
dialogsum,"#Person1#: Please tell me how to file things according to the concerned rules. #Person2#: Well, all right. There are four points you should keep in mind when you file documents, information and other things. #Person1#: What are they? #Person2#: They are, keep the documents in chronological order, remove all the chips and pins, punch the documents evenly and place them in the folder. #Person1#: And what is the most important point? #Person2#: You should always remember that one customer on file is the rule.",#Person2# introduces to #Person1# how to file things according to the concerned rules.,84,13,0.1548
dialogsum,"#Person1#: May I speak to Mr.Huang, please? #Person2#: I'm sorry. Mr.Huang is quite busy right now. Could I pass him the message? #Person1#: Well, you see, I won't be able to keep my patience too long. If the final decision can't be made this week, I will give my offer to other companies. #Person2#: Let me see. He's free from 3:00 to 4:30 tomorrow afternoon. Can you make it then? #Person1#: Yes, of course. Thank you very much. #Person2#: You're quite welcome. Thank you for calling. Bye bye.","#Person1# calls Mr. Huang for the final decision, but he's busy so #Person2# helps #Person1# make an appointment.",88,18,0.2045
dialogsum,"#Person1#: I cannot understand why she always helps and supports her brother. #Person2#: Why do you say so? #Person1#: Because he is often in trouble. #Person2#: She has promised her mother that she would be with him through thick and thin. #Person1#: Oh, I see.",#Person2# tells #Person1# why she always supports her brother.,45,9,0.2
scientific_lay_summarisation-elife-norm,"in other tissues, including the heart, limb, and branchial arches (e. g. Charité et al. , 2000; Fernandez-Teran et al. , 2000; Funato et al. , 2009; Miller et al. , 2003; Srivastava et al. , 1997; Yanagisawa et al. , 2003; Yelon et al. , 2000). Although Hand2 is also expressed in the posterior mesoderm (Angelo et al. , 2000; Fernandez-Teran et al. , 2000; Srivastava et al. , 1997; Thomas et al. , 1998; Yelon et al. , 2000; Yin et al. , 2010), its influence on patterning this tissue has not been extensively explored. Through both loss-of-function and gain-of-function studies, we find that hand2 limits the size of the kidney by repressing IM formation while promoting venous progenitor formation. hand2 is expressed laterally adjacent to the IM, and a set of venous progenitors arise at the interface between the hand2-expressing cells and the IM. Ectopic expression of IM markers within the hand2-expressing territory in hand2 mutants suggests that hand2 establishes the lateral boundary of the IM through direct inhibition of IM fate acquisition. Finally, genetic analysis indicates that hand2 functions in opposition to osr1 to control kidney dimensions. Together, our data demonstrate a novel mechanism for defining territory boundaries within the posterior mesoderm: hand2 represses IM formation to establish its lateral boundary while promoting venous progenitor formation in this region. These important functions of Hand2 help to define the precise dimensions and components of the kidneys and vasculature. Moreover, these findings have implications for understanding the genetic basis of congenital anomalies of the kidney and urinary tract (CAKUT) and for developing new approaches in regenerative medicine. Our interest in the role of hand2 during kidney development began with an observation arising from our previously reported microarray analysis of hand2 mutants (Garavito-Aguilar et al. , 2010). We compared gene expression profiles at 20 hr post fertilization (hpf) in wild-type embryos and hans6 mutant embryos, which contain a deletion that removes the entire coding region of hand2 (Yelon et al. , 2000). Surprisingly, 11 of the 26 transcripts that were increased in hans6 relative to wild-type were expressed in the pronephron, the embryonic kidney. (For a full list of differentially expressed genes, see Garavito-Aguilar et al. , 2010.) We therefore sought to understand the effect of hand2 function on","The human body is made up of many different types of cells, yet they are all descended from one single fertilized egg cell. The process by which cells specialize into different types is complex and has many stages. At each step of the process, the selection of cell types that a cell can eventually become is increasingly restricted. The entire system is controlled by switching different genes on and off in different groups of cells. Balancing the activity of these genes ensures that enough cells of each type are made in order to build a complete and healthy body. Upsetting this balance can result in organs that are too large, too small or even missing altogether. The cells that form the kidneys and bladder originate within a tissue",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Our visual memory percepts of whether we have encountered specific objects or scenes before are hypothesized to manifest as decrements in neural responses in inferotemporal cortex (IT) with stimulus repetition. To evaluate this proposal, we recorded IT neural responses as two monkeys performed a single-exposure visual memory task designed to measure the rates of forgetting with time. We found that a weighted linear read-out of IT was a better predictor of the monkeys’ forgetting rates and reaction time patterns than a strict instantiation of the repetition suppression hypothesis, expressed as a total spike count scheme. Behavioral predictions could be attributed to visual memory signals that were reflected as repetition suppression and were intermingled with visual selectivity, but only when combined across the most sensitive neurons. The everyday act of viewing the things around us leaves us with memories of the things that we have encountered. Under the right conditions, this type of ‘visual recognition memory’ can be quite remarkable. For example, after viewing thousands of images, each only once and only for a few seconds, we can determine with high accuracy the specific images that we have viewed (Brady et al. , 2008; Standing, 1973). Additionally, we can remember not just the objects that we’ve seen, but also the specific configurations and contexts we saw them in (Brady et al. , 2008), suggesting that our brains store these memories with considerable visual detail. Where and how are visual memories stored and where and how is the percept of visual memory signaled? One candidate mechanism for signaling visual memory percepts is the adaptation-like response reduction that occurs in high-level visual brain areas with stimulus repetition, known as ‘repetition suppression’ (Fahy et al. , 1993; Li et al. , 1993; Miller and Desimone, 1994; Riches et al. , 1991; Xiang and Brown, 1998). Consistent with that proposal, individual viewings of a novel image produce response reductions in inferotemporal cortex (IT) that can last tens of minutes to hours (Fahy et al. , 1993; Xiang and Brown, 1998). Signaling visual memories in this way is attractive from a computational perspective, as it could explain how IT supports visual identity and visual memory representations within the same network. That is, insofar as visual representations of different images are reflected as distinct patterns of spikes","As we go about our daily lives, we store visual memories of the objects and scenes that we encounter. This type of memory, known as visual recognition memory, can be remarkably powerful. Imagine viewing thousands of images for only a few seconds each, for example. Several days later, you will still be able to distinguish most of those images from previously unseen ones. How does the brain do this? Visual information travels from the eyes to an area of the brain called visual cortex. Neurons in a region of visual cortex called inferotemporal cortex fire in a particular pattern to reflect what is being seen. These neurons also reflect memories of whether those things have been seen before, by firing more when things are new and less when",380,128,0.3368
pubmed-summarization,"the research reports , accumulated since the fortieth of the last century , regarding the isotope effects in chemical exchange system proved that there are little differences in the chemical properties of the different isotopes of the same element . recently , researches in the isotopes separation field indicated that the isotopes of a given element may show some quantitative differences in chemical reaction equilibria and/or reaction rates ; the former is the equilibrium isotope effects and the later is the kinetic isotope effects . separation of isotopes by ion exchange chromatography is one of the most effective chemical exchange methods , which is based on the chemical equilibrium between isotopic species distributed between the stationary resin phase and the mobile solution phase . it has been applied successfully to the separation of isotopes of various elements in ligand exchange systems , in particular , those using hydroxycarboxylates as ligands , such as ce , gd , zn , eu , cu and nd and in electron exchange systems such as eu and u . the first trial to explore the origin of the isotope effects in chemical exchange reactions was carried out by clewett and schaap , who suggested that the isotope effects in a chemical exchange reaction are due to a slight difference in the affinity of the isotopes for a given molecule or complex due to minor variances in the internal energies , mainly vibrational energy , of the molecule . based on the quantum molecular vibration energy , bigeleisen formulated the method to calculate the isotope exchange equilibrium constant from spectroscopic data . this method was used to calculate the equilibrium constant of the isotopic exchange of many elements ranging from hydrogen to uranium . unfortunately , this method could not explain the anomalous isotope effects of the odd isotopes u and u among the other uranium even isotopes . this anomaly was found to be similar to the odd even staggering of the isotope shift in the atomic spectra . according to the new theory derived by bigeleisen later on , similar odd even isotope effects were found in gd , zn , nd and cd . lanthanides and actinides are known to have deformed nuclei , which cause the charge distribution effects in the","the isotope effects of neodymium in nd - glycolate ligand exchange system were studied by using ion exchange chromatography . the separation coefficients of neodymium isotopes , s , were calculated from the observed isotopic ratios at the front and rear boundaries of the neodymium adsorption band . the values of separation coefficients of neodymium isotopes , s , for the nd - glycolate ligand exchange system were compared with those of nd - malate and nd - citrate , which indicated that the isotope effects of neodymium as studied by the three ligands takes the following direction malate > citrate > glycolate . this order agrees with the number of available sites for complexation of each ligand . the values of the plate height , hetp of",380,128,0.3368
pubmed-summarization,"of the center for neuropsychiatric research of traumatic stress , and the msm0021620849 project at charles university . the measurement of primitive reflexes was done twice by two independent examiners and the results of the two measurements averaged . we measured atnr using the schilder test.15 atnr presents as the tonic reflex response that occurs in newborns ; it normally vanishes at around 3 months of age . in the schilder test , the subject stands with their feet together and the arms held straight out at shoulder level and height but with the hands relaxed at the wrists . in the test when i turn your head , i want you keep your arms straight out in front of you , as they are now . this means your arms remain in the same position , and only your head moves . then the tester slowly rotates the subject s head until the chin is parallel with the shoulder , pauses for 10 seconds , then returns the head to the midline and again pauses for 10 seconds . typical indicators of the atnr include movement of the extended arms in the same direction as the head turn , dropping of the arms , or swaying and loss of balance . it was scored as follows : 0 = no response ( the arms remained straight out in front ) ; 1 = slight movement of the arms up to 20 to the same side as the head is turned or slight dropping of the arms ; 2 = movement of the arms up to 45 as the head is turned or marked dropping of the arms ; 3 = arm movement greater than 45 either to the side or down , swaying or loss of balance may occur . purdue reflex test.16 this reflex emerges at 68 months of life and is inhibited at between 9 and 11 months . in the bender purdue test , the subject is instructed to maintain four point kneeling table position and to slowly move the head to look down as between the thighs . the position is held for up to 5 seconds and then the head is slowly moved upward as if looking at the ceiling . typical indicators of","background and objectivesrecent and historical findings suggest that later - developed functions during brain ontogenesis related to higher levels of cognitive and motor integration tend to replace the older , more primitive , ones , and the persistence of the older functions may be linked to specific neuropsychiatric disorders . currently , there is growing evidence to suggest that persisting primitive reflexes may be related to developmental and neurodegenerative disorders . preliminary data also suggest that persisting primitive reflexes may be specifically linked to attention - deficit and hyperactivity disorder ( adhd).methodsin the study reported here , we tested to what extent the persisting primitive asymmetric tonic neck reflex and symmetric tonic neck reflex are related to adhd symptoms measured by conners parent questionnaire in 35 medication -",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2013; Podtschaske et al. , 2007), cell-cycle entry (Au-Yeung et al. , 2014), and cytokine production (Podtschaske et al. , 2007; Huang et al. , 2013). As a result, differences in the magnitude of responses to ligands of varying affinity would be attributed to greater frequencies of T cells responding at the population level, rather than per-cell variability (Au-Yeung et al. , 2014; Huang et al. , 2013; Zikherman and Au-Yeung, 2015; Butler et al. , 2013). Still, some aspects of the TCR response have been described as analog, or varying in proportion to the strength of signaling: CD3ζ chain phosphorylation (Kersh et al. , 1998a; Sloan-Lancaster et al. , 1994; Daniels et al. , 2006; Kersh et al. , 1999; Kersh et al. , 1998a); Zap70 activation (Daniels et al. , 2006; Prasad et al. , 2009); intracellular calcium concentrations (Irvine et al. , 2002); expression of the transcription factor IRF4 (Man et al. , 2013; Nayar, 2014); and cell division time (Marchingo, 2014). It is unclear how these analog components of the TCR response fit in to a digital model. Both the ability of the TCR to discriminate with high resolution between ligands and the digital nature of TCR signaling have been extensively studied at the level of signaling. Downstream of the TCR, a number of signaling pathways govern the molecular response to engagement, allowing T cells to grow, divide, and acquire immune effector functions consistent with the inciting stimulus (Murphy and Blenis, 2006; O' Sullivan and Immunology, 2015; Proud, 2007; Santamaria and Ortega, 2006; Wang and Green, 2012). AKT and PKCθ interact at the cell membrane and jointly serve to induce nuclear translocation of the pro-inflammatory transcription factor NF-κB, which in turn is able to activate target genes (Huang and Wange, 2004). In particular, AP-1, which comprises homo- or heterodimers assembled from proteins of the Fos, Jun, and ATF transcription factor families (Murphy et al. , 2013), requires both TCR and co-stimulatory signaling (Rincón and Flavell, 1994), and it is usually activated by the Ras/Raf/Mek/Erk pathway (Murphy and Blenis, 2006; Schade and Cutting edge, 2004). At least four feedback loops have been identified in thymocytes and peripheral T cells downstream of the TCR (Coward et al. , 2010; Feinerman et al. , 2008). Collectively, these feedback loops","T helper cells recognize and respond to bacteria, viruses and other invading microbes and thus play a central role in the adaptive immune system. These cells have a receptor on their surface that binds to fragments of proteins – known as oligopeptides – from the microbes that have been digested and presented on the surfaces of other immune cells. Once active, T helper cells multiply, grow and release signals that regulate genes in other cells to promote immune responses. Previous studies suggest that a T helper cell’s response is binary – that is, either on or off. However, this does not explain how the strength of the T cell response to infection can vary. Allison et al. used a technique called high-throughput sequencing to examine the activity of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Millions of naïve T cells with different TCRs may interact with a peptide-MHC ligand, but very few will activate. Remarkably, this fine control is orchestrated using a limited set of intracellular machinery. It remains unclear whether changes in stimulation strength alter the programme of signalling events leading to T cell activation. Using mass cytometry to simultaneously measure multiple signalling pathways during activation of murine CD8+ T cells, we found a programme of distal signalling events that is shared, regardless of the strength of TCR stimulation. Moreover, the relationship between transcription of early response genes Nr4a1 and Irf8 and activation of the ribosomal protein S6 is also conserved across stimuli. Instead, we found that stimulation strength dictates the rate with which cells initiate signalling through this network. These data suggest that TCR-induced signalling results in a coordinated activation program, modulated in rate but not organization by stimulation strength. Effector differentiation of a naïve CD8+ T cell begins when its T cell receptor (TCR) recognizes a peptide-MHCI ligand complex. If the interaction is strong enough, a cascade of signalling events follows that allows the naïve T cell to differentiate and expand into a pool of effector cells. Signal transduction downstream of the TCR involves a highly diverse network of post-translational protein modifications that ultimately drive transcriptional, translational, metabolic and cytoskeletal changes in the cell. It is estimated that fewer than 0. 01% of naïve CD8+ T cells can recognize a particular foreign peptide-MHCI complex (Jenkins and Moon, 2012). Despite the diversity of rearranged TCRs on these naïve cells and the extensive range of antigenic peptides that may be presented, the intracellular machinery within each naïve T cell is able to sense the strength of the receptor-ligand interaction and mount an appropriate response. Previous work has demonstrated that the strength of stimulation a T cell receives upon binding a peptide-MHC ligand complex determines its fate in the thymus and its probability of activating in the periphery. During thymic selection, T cells that weakly recognize self-peptides are retained, while those that strongly recognize self-peptides undergo negative selection and are removed (Daniels et al. , 2006; Hogquist et al. , 1994; Juang et al. , 2010; Prasad et al. , 2009). In the periphery, the population response to stimuli of different strengths can vary in","Amongst the different types of cells the body uses to protect itself, killer T cells have an unique role: they can detect and neutralize cells that have been become dangerous for the organism – for example, cells which are cancerous or hijacked by viruses. In a healthy organism, T cells circulate through the body in an inactivated state. When a disease emerges, receptors at the surface of the cells can detect elements coming from harmful agents; this stimulation then triggers a molecular cascade inside the T cell that leads to activation. This system is relatively simple, pairing a finite number of receptors with a limited set of internal components. At the same time, the activity of T cells is finely regulated, and their activation tightly controlled: they must",380,128,0.3368
dialogsum,"#Person1#: Do you have to leave soon? #Person2#: No. Actually I can stay longer. Dave called to say that there is a beautiful Chinese girl who's going to pick me up at the school gate tonight at ten thirty instead of eight thirty. #Person1#: Oh, that's better. So you don't have to rush. #Person2#: Yeah. You know what Dave just said? #Person1#: What? #Person2#: He said I should put on something very nice, because this girl will be my next target. #Person1#: He knows you very well. #Person2#: He always makes fun of me. He always says things like that. You know the new coming teacher, a Chinese Canadian. He said she would really be my chance. #Person1#: I'm sure you have chances everywhere. You're handsome, talkative, and got a sense of humor. You must be very popular. #Person2#: No, you're kidding. I'm not taking it seriously.",#Person2# can stay longer because a Chinese girl will pick him up later. #Person1# thinks #Person2# can have chances everywhere because he is attractive.,147,24,0.1633
dialogsum,"#Person1#: Hello, Madam. Are you alright? #Person2#: I'm here to pay my telephone bill. I usually go to the post office, but I was told that I could take care of it here. Is that right? #Person1#: Yes, that's correct, Madam. You don't need to go to a counter at all, you can use one of our ATM machines. I'll be more than happy to help you. #Person2#: I don't usually like to use Atms, I like dealing with a real person, you see. #Person1#: I know it does seem a little daunting, but once you get used to it, it will save you a lot of time and trouble.",#Person2# wants to pay her telephone bill. #Person1# tells #Person2# that #Person1# is happy to help #Person2# use the ATM machines.,110,21,0.1909
scientific_lay_summarisation-elife-norm,"groove, which is located on the outer/convex surface of the ring-shaped CRM1 (Dong et al. , 2009; Monecke et al. , 2009; Güttler et al. , 2010). The NESs use almost exclusively their side chains, especially their hydrophobic Φ side chains, to bind CRM1. The NES-binding groove of CRM1, which is wide at one end and narrow at the other end, consists of 5 hydrophobic pockets P0–P4 and is virtually identical in all CRM1-NES structures (1B). NESs from PKI and SNUPN (PKINES and SNUPNNES) share a similar structure when bound to CRM1—an N-terminal 3-turn α-helix followed by a short C-terminal β-strand-like extension (1B) (Dong et al. , 2009; Monecke et al. , 2009; Güttler et al. , 2010; Koyama et al. , 2014). The NES helix binds the wide part of the CRM1 groove, while the β-strand binds the narrow end of the groove. The RevNES peptide binds the CRM1 groove in a different manner by adopting an entirely extended conformation (Güttler et al. , 2010). All three NES peptides bind in the same direction, with their N-termini at the wide part of the groove. The vastly different conformations of the extended RevNES compared to the helix-strand PKINES and SNUPNNES suggest that CRM1 may recognize divergent signal sequences in part by binding different peptide structures. The repertoire of conformations for CRM1-bound NESs remains unclear, but the asymmetric and seemingly structurally invariant NES-bound CRM1 groove presents physical constraints on structures of bound NESs. For example, the class 3 NES consensus of Φ1X (2,3) Φ2X (2,3) Φ3X2Φ4 with two intervening residues between Φ3 and Φ4 suggests a single long NES helix. The substitution of a narrow strand or extended chain at the C-terminus of an NES with a helix presents a steric problem as the thicker helix is unlikely to fit into the tapering CRM1 groove. In current NES databases, class 3 NES sequences are as prevalent as NESs of classes 1b, 1c, 1d, and 2, but information of how they are able to bind CRM1 is missing (Xu et al. , 2015). We have developed a general strategy to crystallize CRM1 bound to NES peptides in order to study how diverse sequences, including the enigmatic class 3 NESs, bind the exportin. Crystal structures of two different class 3 NESs bound to","Many organisms keep their DNA within a structure inside their cells called the nucleus. Two layers of membrane surround the nucleus and keep the DNA separate from the rest of the cell' s contents. Yet, proteins and other molecules can move in and out of the nucleus by passing through small pores in this nuclear membrane. To travel through these pores, larger molecules such as proteins rely on the assistance of transport receptors, including one called CRM1. This transport receptor helps to export hundreds of different proteins from the nucleus by recognizing a part of their structure called the ‘nuclear export signal’. Earlier work has shown that three different nuclear export signals interact with CRM1 in a similar ways by binding to a groove on its outer surface.",380,128,0.3368
pubmed-summarization,"pleuric drain was also applied . at the 7 post - traumatic day , the drain was removed . 9 post - traumatic day , a ct was carried out and a thoracoscopic surgery , with the goal of aspirating the fluidothorax and placement of a right side thoracic drain , indicated . after this , the ventilation improved and the patient was extubated on the 14 post - traumatic day . 1liver herniation intrathoracicaly ( contrast enhanced computed tomography , coronal multi - planar reformatting ) . ( contrast enhanced computed tomography , coronal multi - planar reformatting ) . 2defect in the diaphragma and herniated liver into the thoracic cavity . the edges of the muscle are fuller than the middle area , which is made up from a thin aponeurosis called centrum tendineum . left - sided ruptures of the diaphragm are described in up to 70% of all cases . left - sided ruptures can result in a herniated stomach , small intestine , colon , spleen and omentum . right - sided diaphragm ruptures , occuring in 30% of all cases , result in the herniation of the liver . the reason for this in - equality is that the right side of the diaphragm is , in a way , protected by the liver . however , if a rupture to the right side does occur , it often results in serious or even fatal injury . a right sided diaphragm rupture is often complicated by damage to blood vessels , most commonly vena cava inferion , the hepatic veins can also be damaged . both - sided injury to diaphragm occurs in only 2% of all diaphragm injuries . diaphragm injuries are most commonly accompanied by fractures of the pelvis , damage to the spleen , rib fracture , damage of the liver , contusion or rippage of a lung . our patient , in adition to a ruptured diaphragm , had a brain comotion , right lung contusion , subcapsular liver hematom , dislocated right femur fracture and a right acetabulum fracture , without dislocation . with comparison to adult patients , we find a larger number of isolated diaphragm ruptures amongst children . in larger scales of patients , isolated injury","right - sided traumatic diaphragmatic rupture in childhood is a very rare injury . diaphragmatic rupture often manifests itself later , after an organ progressively herniates into the pleural cavity . when the patient is tubed , the ventilation pressure does not allow herniation of an organ , which occurs when the patient is ex - tubed . we present a patient with a delayed diagnose of right sided diaphragmatic rupture with a complicated post - operation state .",380,79,0.2079
dialogsum,#Person1#: Excuse me. I think I have got lost in the Art Gallery. Can you tell me the way to the exit. #Person2#: Sure. Go back and take the third turning on the left. #Person1#: Thank you very much. I have been wondering here for almost half an hour. #Person2#: It is really like a labyrinth.,#Person2# tells #Person1# where the exit of the art gallery is.,56,11,0.1964
pubmed-summarization,". the study was ethically evaluated by the ethical committee at duhok university ( duhok , iraq ) . a letter was sent by a social worker to the parents for consent before the child was included . the study instruments were administered by a trained social worker . a modified family map ( genogram)1719 was used to obtain the demographic and background information of the children , such as their age , gender , education level , work type , number of working hours , reasons for working ( they were asked whether family need / pressure or peer pressure were among the reasons that drove them to work on the street ) , number of years on the street , socioeconomic status , number of family members ( all members of family living in the same house were counted ) , and history of disabilities and medicosurgical problems . parental information regarding their own education ( never attended school or illiterate , or completed primary school , secondary / high school , or a university degree ) , work type , illness history , parent s death and reason of death , and child s age when the parent died was also collected . a composite score was used to determine the socioeconomic status ; this score was based on : 1 ) whether the father is employed or not ; 2 ) the house is owned , belongs to a relative , or is being rented ; 3 ) monthly income is below or above average , or no income ; 4 ) number of family members working in an income - generating activity ; and 5 ) other sources of income . every item mentioned above had a maximum score of 2 and a minimum score of 0 . a total score between 04 was considered low , 57 was average , and 810 was considered good . trained social workers were involved in the study , and they used the genogram , while also collecting information about each child s background characteristics . the children were given time to recall and answer questions ; if they were not able to answer , one of the parents or siblings was approached . children were not forced","backgrounddue , in part , to family constraints in dealing with the economical burden of raising a family , a wave of street children is sweeping the developing world . such children are prone to both somatic and mental illnesses . this is the first ever study that has been conducted to explore the psychopathology among street children in the duhok governorate.methodsthe study was conducted between march 2004 and may 2005 in duhok city among street children who attended the zewa center the only center for street children in the region at the time of the study . among a total of 107 eligible children , 100 agreed to participate ( 93% response rate ) . a modified family map ( genogram ) was used to obtain demographic",380,128,0.3368
scientific_lay_summarisation-elife-norm,"indicates a specific contribution of terrein in modulating iron homeostasis. In previous studies we showed that terrein is produced on plant-derived media such as PDB, which is in agreement with its phytotoxic biological activity (Zaehle et al. , 2014). To address the question of specific conditions that induce the gene cluster, an A. terreus reporter strain was generated expressing the β-galactosidase gene lacZ from Escherichia coli under control of the terrein synthase promoter PterA (PterA: lacZ). Due to the dependence of PterA expression on TerR, this strain served as a direct indicator of terR expression and terrein production. In agreement with a lack of terrein production, β-galactosidase activity was near the detection limit when the A. terreus PterA: lacZ strain was grown on glucose minimal medium. In contrast, and in agreement with previous observations, a 200–500 fold induction was observed on PDB medium (1A). Similarly, on Sabouraud and yeast extract-peptone-dextrose (YPD) medium, induction levels reached 10–30% compared with PDB. However, potato broth or casamino acids did not induce the cluster without the addition of glucose, indicating that glucose appears to be required for terrein production rather than repressing gene cluster induction as shown for other SM gene clusters (Theilgaard et al. , 1997; Brakhage et al. , 2004; Gressler et al. , 2011). Indeed, when glucose medium was supplemented with 1% casamino acids as the nitrogen source, a 20–30 fold activation was detected. Since terrein can cause lesions on fruit surfaces and inhibits plant seed germination (Kamata et al. , 1983; Zaehle et al. , 2014), we assumed that sugar-rich fruit and root juices might have a strong stimulatory capacity. Therefore, we cultivated the reporter strain on banana, carrot, peach, and apple juice. β-Galactosidase activities from these media exceeded the activity of the already strong inducing PDB medium (1B) by a factor of at least five. Additionally, in subsequent LC analyses of culture extracts, a distinct ultraviolet signal for terrein was detected (— 1A–D). This led us to infect fresh bananas with the A. terreus ΔakuB strain (the parental strain for gene deletions; Gressler et al. , 2011), a ΔterR mutant lacking the transcriptional activator, and a ΔterA deletion mutant that lacks the key polyketide synthase from the cluster. 10. 7554/eLife. 07861. 003Figure 1. Terrein production and expression of terA","Organisms produce a wide variety of small molecules called metabolites through the break down of food and other chemical reactions. Some of these molecules—known as primary metabolites—are required for growth, reproduction and other vital processes. Other molecules called secondary metabolites are not strictly required by the organism, but generally have other roles that may improve the individual’s ability to survive and reproduce. Fungi and other microbes produce a large variety of secondary metabolites, many of which are used as medicines to treat diseases in humans and other animals. For example, a molecule called lovastatin—which is produced by a fungus known as Aspergillus terreus—can reduce a human patient' s risk of heart disease. However, it is not known what role many secondary metabolites play in the microbe that produced",380,128,0.3368
pubmed-summarization,"it s the most common solid tumor and is responsible for 15% of all cancer - related deaths in childhood . this tumor accounts for more than 7% of malignancies in patients fewer than 15 years of age . nb tumors from these patients are often characterized by deregulation of many key signaling pathways regulating growth , proliferation , survival , and apoptosis , with concomitant resistance to chemotherapy . the acquisition of multidrug resistance upon treatment with anti - cancer drugs is a common phenomenon for nbs . this is a major reason for the high frequency of fetal outcome of the disease . recently , there are strong epidemiological evidence and laboratory studies that are naturally occurring terpenes may exert cytotoxic effects against nb cells . guaiazulene ( 1,4-dimethyl-7-isopropylazulene gyz , )is a bicyclic sesquiterpene derived from different plants , guaiac wood oil , callis intratropica blue and matricaria chamomilla l and has attracted much attention due to its beneficial biological activities . moreover , previous reports indicated that gyz has antioxidant , antifungal , antimicrobial , anti - inflammatory , anti - spasmodic , anti - ulcer , antitumoral activities and relaxant properties [ 12 - 18 ] . although it has been demonstrated to have interesting biological effects , gyz has been not proven to be cytotoxic , genotoxic and antioxidant / oxidant effects on neuron and nb cell lines . therefore , the aim of the present study was to firstly evaluate the cytotoxic / antiproliferative ( 3-[4,5 dimetylthiazol -2-yl]-2,5 diphenlytetrazolium bromide [ mtt ] assay ) , cytogenetic ( single cell gel electrophoresis [ scge ] assay)and oxidative effects ( total antioxidant capacity [ tac ] and total oxidative stress [ tos ] analysis)of gyz on neuron and nb cell cultures for its possible use in the complementary and alternative medicine practices . chemical structure of guaiazulene gyz ( cas 489 - 84 - 9 , c15h18 ) , dulbecco modified eagles medium , sodium phosphate ( nah2po4 ) , potassium phosphate monobasic ( kh2po4 ) , ethylenediaminetetraacetic acid ( edta ) , dimethylsulfoxide ( dmso ) , triton - x-100 , tris , low melting point agarose , normal melting point agarose , ethidium bromide were purchased from sigma - aldrich ( steinheim","aim : neuroblastoma ( nb)cells are often used in cancer researches such as glioblastoma cells since they have the potential of high mitotic activity , nuclear pleomorphism , and tumor necrosis . guaiazulene ( gyz 1,4-dimethyl-7-isopropylazulene)is present in several essential oils of medicinal and aromatic plants . many studies have reported the cytotoxic effect of gyz ; however , there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with gyz.materials and methods : in this study , we aimed to describe in vitro antiproliferative and/or cytotoxic properties ( by 3-[4,5 dimetylthiazol -2-yl]-2,5 diphenlytetrazolium bromide [ mtt ] test ) , oxidative effects ( by total antioxidant capacity [ tac ] and total oxidative stress [ tos ] analysis)and genotoxic",380,128,0.3368
pubmed-summarization,"and 3 villages from each town were selected with the probability proportional to the population size , using cluster random sampling . thirdly , 1 residential group including at least 50 households was selected from each village using simple random cluster sampling . random digit function in excel was applied in selection of these households from each residential group . finally , one family member aged 18 years or over was randomly selected from each household using the kish grid method . the subjects who were diagnosed as diabetes according to the american diabetes association criteria the data collected during the face - to - face interview included demographic characteristics , lifestyle factors , and medical history . the investigated smoking history included age at smoking initiation , years of smoking , number of cigarettes smoked per day , and smoking cessation . briefly , an individual who never smoked or smoked less than 100 cigarettes in his lifetime was defined as a never smoker . an individual who smoked at least 100 cigarettes in his lifetime but quit smoking more than 12 months before the interview was considered as a former smoker . current smokers included those currently smoking and those who quit smoking less than 12 months before interview . the pack - year of smoking was calculated according to the number of packs of cigarettes smoked per day and smoking duration ( years ) . an individual who never consumed alcohol or consumed less than or equal to one drink per month was defined as a never drinker , otherwise as an ever drinker . the global physical activity questionnaire was used to evaluate physical activities by calculating the total weekly volume ( metabolic equivalents ( met ) min / wk ) across three separate domains ( work / home , during commuting , and during leisure time ) , by applying met values to the time variables according to the intensity of the activity . height and weight were measured in light underclothes without shoes . in the standing position of participants in light clothing , waist circumference was measured at the midway between the lower edge of the costal arch and the upper edge of the iliac crest . body mass index ( bmi )","the aim of this study was to evaluate the associations between chronic smoking and insulin resistance and -cell function in chinese men without diabetes . a total of 1,568 participants were recruited by multistage sampling . using homeostatic model assessment ( homa ) , geometric means of insulin resistance ( homa - ir ) and -cell function ( homa- ) with 95% confidence interval ( ci ) were calculated by general linear model . odds ratios ( ors ) with 95% ci were estimated to evaluate the associations between smoking status and insulin resistance and -cell deficiency under a logistic regression model . current smokers had higher levels of 2 h glucose ( 6.66 versus 6.48 mmol / l ) for oral glucose tolerance test and lower levels",380,128,0.3368
scientific_lay_summarisation-elife-norm,"a well-studied model of genome conformation, genes targeted to nuclear pores are activated (Taddei et al. , 2006), while those at the nuclear periphery are repressed (Andrulis et al. , 1998). Transcription factors (TFs) are attractive candidates for orchestrating such dynamic changes in chromatin conformation, given their site-specific DNA binding and changes in abundance or activity in response to differentiation and cellular signals (Lambert et al. , 2018). For many conditions, it remains unknown exactly which TFs bind to any given locus. Although binding site motifs are known for many TFs, motif searches poorly predict TF binding (Guertin and Lis, 2010; Jolma et al. , 2015; Le et al. , 2018; Levo et al. , 2015; Liu et al. , 2006; Slattery et al. , 2014). Even if the set of TFs bound to each locus is known, it is unclear which TFs are capable of forming chromosomal contacts. DNA-bound TFs can also recruit other cofactor proteins that can mediate chromosomal contacts (Deng et al. , 2012; Monahan et al. , 2019; Song et al. , 2007), but our understanding of TF-cofactor interactions remains incomplete. Among chromosomal contacts and loops, interchromosomal contacts are less well-understood. This is in part due to the relative paucity of interchromosomal contacts in Hi-C and other 3C (chromosome conformation capture) data, which results from their greater contact distance (Maass et al. , 2018) and chromosomal self-association into territories (Cremer and Cremer, 2010). Nevertheless, many distinct classes of interchromosomal contacts are known, including clustering of transcriptionally active genes (Mitchell and Fraser, 2008; Osborne et al. , 2004; Schoenfelder et al. , 2010), associations with nuclear bodies (Quinodoz et al. , 2018), interactions among developmental enhancers and promoters (Lomvardas et al. , 2006; Monahan et al. , 2019), and mitotic homologous chromosome pairing in organisms ranging from yeast (Burgess et al. , 1999) to flies (Henikoff and Dreesen, 1989; Joyce et al. , 2016; Morris et al. , 1999) and mammals (Xu et al. , 2006). However, our understanding of the molecular mechanisms of these contacts remains incomplete. Many known mechanisms for establishing 3D chromosome conformation may act on both intrachromosomal loops and interchromosomal contacts. The emerging consensus model for such DNA-DNA interactions involves loop extrusion by cohesin and other Structural Maintenance of Chromosomes (SMC) factors, which","Inside cells, genetic information is stored within molecules of DNA that are folded into three-dimensional structures known as chromosomes. Each fold in a chromosome forms when two points on a single DNA molecule link together to make a loop. DNA in two different chromosomes can also form links with each other (known as “contacts”). Many cells contain two copies of every chromosome and these copies are often able to make contacts with each other. DNA loops and contacts can change in response to the environment and this may help cells switch the right genes on and off at specific times. For example, in budding yeast cells that have used up most of their preferred food source – a sugar called glucose – the two copies of a region",380,128,0.3368
dialogsum,"#Person1#: Hello, Golden Time Hotel. #Person2#: Hello. I want to know if there are any rooms available in your hotel? #Person1#: Sure, we have plenty of rooms now. #Person2#: That's good, I want to book 3 single rooms and 2 double rooms. #Person1#: What are your requirements? #Person2#: The single rooms should be on the second or third floor and the double rooms should face the sea and have enough sunshine. #Person1#: Is that all? #Person2#: Oh, it would be better if the rooms were next to each other. #Person1#: No problem. How long do you want to stay? #Person2#: We will stay from next Tuesday until Friday. #Person1#: That will be fine.",#Person1# assists #Person2# in booking 3 single rooms and 2 double rooms next to each other from next Tuesday until Friday.,113,21,0.1858
dialogsum,"#Person1#: Jenny, are you having a good time? #Person2#: Yes, of course. This is a really wonderful party with interesting people and great food. #Person1#: I'm glad you are enjoying yourself. #Person2#: Thank you for the invitation. #Person1#: It's my pleasure. Can I get you another glass of champagne? #Person2#: Yes, I'd love another glass. You're a wonderful host. Thank you for everything. #Person1#: It's my pleasure having you here.",Jenny had a good time at #Person1#'s party and she thanks #Person1#.,70,12,0.1714
dialogsum,"#Person1#: Morning, Mary. I haven't seen you in a long time. What's up? #Person2#: Oh, I took up a new hobby. #Person1#: So you don't travel a lot now? #Person2#: No, Frank. I'm much more interestcd in collecting stamps now. #Person1#: It's certainly a popular hobby. I know a lot of people love stamps. #Person2#: It certainly is. It's so much fun. #Person1#: I believe collecting stamps has something similar to traveling right? #Person2#: Absolutely. Through all kinds of stamps I am able to learn about the world. #Person1#: Well, every stamp has a story to tell. #Person2#: You're right. And I also meet many new friends while collecting stamps. #Person1#: Good. #Person2#: Sometimes we even spend hours discussing our collcctions. #Person1#: There's a lot to share when you have a common interest. #Person2#: Yes, it's really amazing. I got to go now. I'm meeting with some other collectors. #Person1#: Ok, good luck. See you #Person2#: See you, Frank.",Mary tells Frank that she likes collecting stamps instead of traveling. Mary learns about the world by collecting stamps.,159,19,0.1195
pubmed-summarization,"as to what effects these agents have on the progression of oa . herein , based on surgically - induced osteoarthritis model , we performed a study to determine whether celecoxib could inhibit the apoptosis of chondrocytes and ameliorate type ii collagen synthesis to relieve symptoms of oa . one hundred and thirty wistar rats ( 3~4 months old ) were purchased from the laboratory animal center , chongqing medical university . an oa model in wistar rats was induced using the surgical resection of the left achilles tendon , resulting in a decrease in joint stress , performed as previously described . the left knee was used as the experimental side and the right knee as the control side . the experiments were done with reference to the long - term toxicity test methods in the methodology of pharmacological experiments . animals were randomly divided into 4 groups : celecoxib group ( ce ) , ibprofen group ( ibp ) , indomethacin group ( in ) and normal saline group ( ns ) . the daily drug dosages were : ce 24 mg / kg ( american silver pharmaceutical company ) , ibp 72 mg / kg ( chongqing southwest pharmaceutical co.ltd . ) , in 9 mg / kg ( chongqing kerui pharmacy co.ltd . ) , and ns ( sichuan kelun pharmaceutical co. ltd . ) . if there were more than 50 g in the weight difference between rats , the drug would be administered individually . at the end of the 3 , 6 , and 9 months of treatment after the surgically - induced model the knees were dissected from each animal , then fixed in 4% paraformaldehyde and 70% ethanol , and decalcified with 10% edta . after he staining , chondrocytes , cartilage surface , cartilage matrix and tide line were observed with the microscope . type ii collagen antibody , the sabc kit and dab are purchased from boston corp . the ihc stainings of cartilage matrix and chondrocyte were observed and photographed using an olympus microscope . beijing aviation medical image analysis system was adopted to calculate the average density of positive staining in every field . the apoptosis detection kit was purchased from mannheim company ( germany ) ,","summarybackgroundcelecoxib has a positive effect on human osteoarthritic cartilage , but the mechanisms remain unclear . the aim of this study was to test whether celecoxib could inhibit the apoptosis of chondrocyte and ameliorate type ii collagen synthesis to relieve symptoms of oa ( osteoarthritis).material / methods130 wistar rats were randomly divided into 4 groups as celecoxib ( ce ) , ibuprofen ( ibp ) , indomethacin ( in ) and normal saline group ( ns ) . the osteoarthritis was induced by the excision of the left achilles tendon . at the 3th , 6th , 9th month of treatment , the histological structure of articular cartilage was observed using he staining . type ii collagen was examined using immunohistochemistry . chondrocyte apoptosis was detected by tunel",380,128,0.3368
dialogsum,"#Person1#: You want to argue your ticket today? #Person2#: Yes. That is why I'm here. #Person1#: Tell me your argument. #Person2#: I was pulled over for allegedly speeding. #Person1#: Are you sure you weren't speeding? #Person2#: To be honest, I really wasn't. #Person1#: What speed were you going? #Person2#: I was under the speed limit. I was going 35, when the speed limit was 40. #Person1#: I'm just going to let you go, since the arresting officer isn't here. #Person2#: What about my ticket? Do I still need to pay? #Person1#: Don't worry about it. #Person2#: I'm so glad for your help.",#Person2# argues the ticket for allegedly speeding and claims #Person2# wasn't speeding. #Person1# revokes #Person2#'s ticket.,102,16,0.1569
dialogsum,"#Person1#: Oh no, not again! This happens every day. #Person2#: What's wrong? #Person1#: Look at the mess, Jim. You have your supper and never do the washing up afterwards. #Person2#: I don't do the washing up. But I wash the car every week. #Person1#: I don't care about that. You never help me with the housework. #Person2#: That's not true, darling. I prepare your meals, right? #Person1#: Oh, so what? The kitchen's always a mess afterwards. You cook meals, and I do the rest everyday. #Person2#: Calm down. OK. I will do everything in our house from next weekend.",#Person1# complains that Jim doesn't do the housework except for preparing the meal. Jim promises to do everything next week.,99,20,0.202
scientific_lay_summarisation-elife-norm,"distinct conditioning boxes (1B). To examine the cells’ selectivity for stimulus relationship, in the remaining three blocks (CS-alone block) the CS was presented by itself in the box. The CS presentations were separated with pseudorandom inter-trial intervals (ITI) ranging from 20 to 40 s. Each rat daily received six trial blocks in a fixed temporal sequence (an example pattern, 1C; patterns used for each rat, Table 1), enabling the rats to acquire the temporal context predictive of what would happen in the present trial block. Consistent with our previous findings (Morrissey et al. , 2017; Takehara-Nishiuchi and McNaughton, 2008), the rats gradually increased the expression of CRs in the CS-US paired trials but not CS-alone trials (1D; Two-way repeated measures ANOVA, Session × Block, F75,450 = 2. 99, p<0. 001). The asymptotic level of CR expression during the three CS-US blocks was significantly different from that during the three CS-alone blocks (follow-up one-way repeated measures ANOVA on CR% during the last session, F5,30 = 21. 9, p<0. 001, planned pairwise comparisons, ps < 0. 05/6), but it was comparable between all three CS-US blocks (all ps > 0. 7). In addition, the increased frequency of eyeblink responses was not observed during the ITIs of any of six trial blocks (— 1A; Session × Block interaction, F70,420 = 8. 48, p=0. 717), suggesting that the eyeblink responses were conditioned to the CS, but not to the conditioning environment (see also, Morrissey et al. , 2017). In the last session, the frequency of CR expression changed upon the transition from the CS-alone to the CS-US block within the first ten trials (1E), suggesting that blocks of CS-alone trials did not simply extinguish associations acquired on previous days, rather they formed a distinct temporal context between earlier and later trials. On a trial-by-trial basis, all except one rat responded correctly on the first trial of two blocks in which the change in stimulus contingency was signaled by the change in the conditioning environment (1F, the performance of Rat 2, 1G, the performance of four rats that underwent the trial blocks in the same temporal order). In contrast, when the stimulus contingency was changed in the same environment, the rats gradually adjusted the frequency of CR expression over ten CS-US paired trials, suggesting that","The context in which an event occurs plays a large role in how the brain understands and responds to the event. While a key part of context is where we are, contexts can also change within the same space: different meetings are held at different times and with different people in the same room, and a grassy field can be a place of intense competition or a place to relax and gaze at clouds. However, we have little understanding of how the brain sets up and maintains a sense of context. A region of the brain called the lateral entorhinal cortex (LEC) responds to events as they happen, but may also maintain a record of past experiences, and helps us to learn new associations between events. To find",380,128,0.3368
dialogsum,"#Person1#: So, you friend's getting married on Saturday. What have you bought her as a wedding gift. I find is so hard to choose the right gift. #Person2#: My friend and her fiance had a really good idea. They have cut out pictures from catalogues and pasted them in a notebook. The picture are of things they want. People sign their name by the item they will buy. #Person1#: That's clever! Then everyone knows that they are buying something the couple really want and there's no chance of two people buying the same gift. What things were in the notebook? #Person2#: Most of the things were household appliance. You know, everything from an iron through a vacuum cleaner to a cooker. I think it's an excellent way for everyone who knows the couple to help them set up home. #Person1#: So, what did you get them? #Person2#: I bought a sewing machine. I know that my friend likes making her own clothes, but her current sewing machine is quite old and has some problems. #Person1#: What's wrong with it? #Person2#: She says that after several years of use, it's not working properly. When she uses it, it makes a funny noise. #Person1#: Household appliance don't seem to last for a long time nowadays. #Person2#: I think it's because the manufactures are constantly bringing out new models. Because they know that we will buy the new models, the appliances don't need to last more than five or ten years at most.",#Person2# tells #Person1# #Person2#'s friend and her fiance thought of a good idea to prevent people from buying the same gift. #Person2# says that most of the things that the couple wants are household appliance and #Person2# bought a sewing machine for them.,250,43,0.172
dialogsum,"#Person1#: Did you go out yesterday evening? #Person2#: Yes, we went to the Tianjin sports center to watch a women volleyball game between Tianjin and US. The US team was led by Lang Ping, the former coach of the Chinese national team. #Person1#: How was the game? #Person2#: It's very exciting, we enjoyed it very much, but we missed the first 30 minutes. #Person1#: Why? #Person2#: We took a wrong bus, so we were late for the game. We got there at 7:30. #Person1#: That's too bad.",#Person1# asks about yesterday evening. #Person2# watched a volleyball game but missed the first 30 minutes.,87,16,0.1839
dialogsum,"#Person1#: (sniffing) Is that a French cigarette? #Person2#: Pardon? #Person1#: Is that a French cigarette you're smoking? #Person2#: Yes, that's right. Why? What's the matter? #Person1#: I don't understand why yousmoke French cigarettes. They make a terrible smell. #Person2#: I like them very much. I prefer them to English cigarettes. #Person1#: Have you got a lot of them? #Person2#: Yes, about 200, why? #Person1#: Well... er... could I buy some from you? #Person2#: Buy some from me? But... you don't like French cigarettes! #Person1#: No, I don't. But my wife does.","#Person1# asks #Person2# if #Person2# is smoking French cigarettes. #Person1# doesn't like French cigarettes, but he wants to buy some from #Person2# for his wife.",91,25,0.2747
dialogsum,"#Person1#: Waitress, can I have the bill, please? #Person2#: Yes, sir. How would you like to pay the bill, sir? #Person1#: Do you accept credit cards? #Person2#: Yes, sir. But we only accept American Express, Master card and Visa. What kind do you have? #Person1#: Master card. Here you go. #Person2#: Wait a moment, please.",#Person1# wants to pay the bill and is served by #Person2#.,55,11,0.2
scientific_lay_summarisation-elife-norm,"Tactile information available to the rat vibrissal system begins as external forces that cause whisker deformations, which in turn excite mechanoreceptors in the follicle. Despite the fundamental mechanical origin of tactile information, primary sensory neurons in the trigeminal ganglion (Vg) have often been described as encoding the kinematics (geometry) of object contact. Here we aimed to determine the extent to which Vg neurons encode the kinematics vs. mechanics of contact. We used models of whisker bending to quantify mechanical signals (forces and moments) at the whisker base while simultaneously monitoring whisker kinematics and recording single Vg units in both anesthetized rats and awake, body restrained rats. We employed a novel manual stimulation technique to deflect whiskers in a way that decouples kinematics from mechanics, and used Generalized Linear Models (GLMs) to show that Vg neurons more directly encode mechanical signals when the whisker is deflected in this decoupled stimulus space. Rats, like many rodents, rely heavily on tactile information from their vibrissae (whiskers) to explore their world. Tactile signals are generated both during active whisker movement – when the rat brushes and taps its whiskers against objects – and during passive contact. Deformations of the vibrissae are transduced by mechanoreceptors in the follicle (Ebara et al. , 2002), and the resulting electrical signals are integrated by primary sensory neurons in the trigeminal ganglion (Vg). From the Vg, signals are relayed to the brainstem trigeminal nuclei, thalamus, and primary somatosensory cortex. Neurons in the Vg are thus the' gatekeepers' of tactile information for the vibrissal trigeminal system (Jones et al. , 2004a; Leiser and Moxon, 2006,2007). Several studies have demonstrated that rodents can use their vibrissae to localize objects with high precision (Kleinfeld and Deschênes, 2011; Knutsen and Ahissar, 2009; Knutsen et al. , 2006; Krupa et al. , 2001; Mehta et al. , 2007; O' Connor et al. , 2010; Pammer et al. , 2013). Accordingly, previous work has focused on quantifying the response of Vg neurons in terms of kinematic (geometric) variables of contact, including radial distance to an object, angular position, and angular velocity (Gibson and Welker, 1983a, 1983b; Jones et al. , 2004a, 2004b; Leiser and Moxon, 2007; Lichtenstein et al. , 1990; Lottem and Azouz, 2009,2011; Lottem et al. , 2015; Shoykhet et al. , 2000,2003;","Animals must gather sensory information from the world around them and act on that information. Specialized sensory cells convert physical information from the environment into electrical signals that the brain can interpret. In the case of hearing, this physical information consists of changes in air pressure, and for vision, it is patterns of light bouncing off of objects. Rodents rely heavily on touch information from their whiskers to explore their world. When a whisker touches an object, it deforms and bends. The first neurons to respond to whisker touch – so called primary sensory neurons – represent contact between the whisker and the object in the form of electrical signals, but exactly how they do this is unclear. One possibility is that primary sensory neurons encode the movement",380,128,0.3368
dialogsum,"#Person1#: I have made up my mind. I am getting a tattoo. #Person2#: Really? Are you sure? #Person1#: Yeah! Why not? They are trendy and look great! I want to get a dragon on my arm or maybe a tiger on my back. #Person2#: Yeah but, it is something that you will have forever! They use indelible ink that can only be removed with laser treatment. On top of all that, I have heard it hurts a lot! #Person1#: Really? #Person2#: Of course! They use this machine with a needle that pokes your skin and inserts the ink. #Person1#: Oh, I didn't know that! I thought they just paint it on your skin or something. #Person2#: I think you should reconsider and do some more research about tattoos. Also, find out where the nearest tattoo parlor is and make sure they used sterilized needles, and that the place is hygienic. #Person1#: Maybe I should just get a tongue piercing!","#Person1# wants a tattoo because it's trendy. #Person2# tells #Person1# that either getting a tattoo or removing it hurts a lot, which changes #Person1# 's mind.",159,26,0.1635
dialogsum,"#Person1#: Good afternoon. Can I help you? #Person2#: Yes. We'd like some information, please. #Person1#: Ok, where do you plan to go? #Person2#: Yes, we've agreed on Italy. How much is the air fare to Italy? #Person1#: When are you going there? #Person2#: We don't really know. June, or maybe July. #Person1#: I see. Well, in May and June, the fare is $480. But it's much less in March and April. #Person2#: Much less? How much is it then? #Person1#: It's only $410. #Person2#: That's really a good price. But my husband hates the cold weather there. So let me talk with him first. #Person1#: No problem.",#Person1# tells #Person2# about the airfare to Italy. #Person2#'ll discuss it with her husband first.,107,15,0.1402
scientific_lay_summarisation-elife-norm,"Exploration of developmental mechanisms classically relies on analysis of pattern regularities. Whether disorders induced by biological noise may carry information on building principles of developmental systems is an important debated question. Here, we addressed theoretically this question using phyllotaxis, the geometric arrangement of plant aerial organs, as a model system. Phyllotaxis arises from reiterative organogenesis driven by lateral inhibitions at the shoot apex. Motivated by recurrent observations of disorders in phyllotaxis patterns, we revisited in depth the classical deterministic view of phyllotaxis. We developed a stochastic model of primordia initiation at the shoot apex, integrating locality and stochasticity in the patterning system. This stochastic model recapitulates phyllotactic patterns, both regular and irregular, and makes quantitative predictions on the nature of disorders arising from noise. We further show that disorders in phyllotaxis instruct us on the parameters governing phyllotaxis dynamics, thus that disorders can reveal biological watermarks of developmental systems. Developmental systems strikingly produce regular patterns and analysis of eukaryote development has classically been focused on regularities as the main source of information to understand these complex systems. However, it is becoming increasingly evident that intrinsic molecular noise is an inherent property of biological systems (Elowitz et al. , 2002; Kupiec, 1997; Lander, 2011). This noise can be buffered, e. g. (Okabe-Oho et al. , 2009), but can also theoretically propagate through scales and generate patterning disorders e. g. (Itoh et al. , 2000). In this case, disorders observed during development could be informative not only on the origin of noise but also on the underlying developmental mechanisms that propagate the noise. Here we address this question theoretically using phyllotaxis, the remarkably regular geometric organization of plant aerial organs (such as leaves and flowers) along the stem, as a model system (Appendix section 1). Phyllotaxis primarily arises at the shoot apical meristem, a specialized tissue containing a stem cell niche and located at the tip of growing shoots. Rooted in early works of pioneers such as (Bonnet, 1754; Braun, 1831; Bravais and Bravais, 1837) and after decades of research, the idea that phyllotactic patterns emerge from simple physical or bio-chemical lateral inhibitions between successive organs produced at the meristem has become largely prevalent, (Adler et al. , 1997; Jean, 1995; Kuhlemeier, 2007; Pennybacker et al. , 2015; Reinhardt, 2005). Microscopic observations","Plants grow throughout their lifetime, forming new flowers and leaves at the tips of their stems through a patterning process called phyllotaxis, which occurs in spirals for a vast number of plant species. The classical view suggests that the positioning of each new leaf or flower bud at the tip of a growing stem is based on a small set of principles. This includes the idea that buds produce inhibitory signals that prevent other buds from forming too close to each other. When computational models of phyllotaxis follow these ‘deterministic’ principles, they are able to recreate the spiral pattern the buds form on a growing stem. In real plants, however, the spiral pattern is not always perfect. The observed disturbances in the pattern are believed to reflect the",380,128,0.3368
pubmed-summarization,"haemophilus spp . generally colonize the upper respiratory tract and can cause infections such as bronchitis , sinusitis , epiglottitis , pneumonia and meningitis . h. influenzae has been reported as a rare cause of genitourinary tract infection such as urinary tract infection , , , , , pyelonephritis , , prostatitis , epididymitis , salpingitis and endometritis . we report here an immunocompetent japanese man with bacteremic pyelonephritis caused by nontypable h. influenzae associated with a left ureteral calculus . a 44-year - old japanese man with a history of left ureteral renal calculus presented to our hospital with a one - day history of left flank pain , fever and malaise without any respiratory symptoms . he had left flank pain caused by a left ureteral calculus over the past two decades . otherwise , his past history and family history were unremarkable . on physical examination , his blood pressure was 153/91 mm hg , pulse rate 112 beats / min , respiratory rate 20 breaths / min , oxygen saturation on ambient air 98% and body temperature 38.9 c . laboratory tests showed an elevated white blood cell ( wbc ) count 12.2 10/l and creatinine level of 1.25 mg / dl . microscopic examination of the urine sediment showed an elevated wbc and red blood cell ( rbc ) count of 50 and 99 per high power field , respectively . two sets of blood cultures were obtained using bactec plus aerobic / f and anaerobic / f culture bottles ( becton , dickinson and company , sparks , md ) . urine culture was performed using sheep blood agar and drygalski improved medium ( eiken chemical co , ltd , tokyo , japan ) . abdominal ultrasound and computerized tomography ( ct ) scan of the abdomen and pelvis without contrast showed a left ureteral calculus ( 17 10 19 mm ) , left hydronephrosis and a normal - sized prostate gland . after admission , treatment with intravenous ceftriaxone 2 g every 24 h was initiated and the ureteral stent was inserted into his left ureter . after 32 h of incubation , gram - negative bacilli were isolated from an aerobic blood bottle . both blood and urine cultures using sheep blood","haemophilus species are known to colonize the upper respiratory tract and can cause infections . however haemophilus influenzae has been rarely described as a cause of genitourinary tract infection . we report a 44-year - old nonimmunocompromised japanese man with bacteremic pyelonephritis caused by a nontypable h. influenzae associated with a left ureteral calculus . the organism was isolated from both blood and urine cultures . treatment consisted of 14 days of intravenous ceftriaxone and oral amoxicillin one after than other and insertion of a left ureteral stent . after discharge , he underwent extracorporeal shock wave lithotrity for the left ureteral calculus . he had no recrudescence of the symptoms . h. influenzae should be considered as a genitourinary pathogen among patients with certain risk factors such",380,128,0.3368
pubmed-summarization,"z selectivity for cyclometalated ruthenium catalysts involves approach of the olefin from a side - bound position ( i.e. , cis to the nhc ligand and trans to the chelating adamantyl ) and is favored through a combination of steric and electronic effects imposed by the nhc ligand . although catalysts 1 and 2 demonstrate excellent selectivity in olefin metathesis , their activity on complex substrates , including peptides , remained unexplored . to this end , we sought to initiate a comprehensive evaluation of z - selective metathesis on peptides using newly developed cyclometalated ruthenium catalysts . through the combined efforts of homodimerization , cross metathesis and ring - closing metathesis , we have developed guidelines for assessing the influence of amino acids and peptides on catalyst activity and selectivity . these principles were applied for carrying out z - selective metathesis on challenging substrates including peptides that comprise parallel -sheets and on stapling of -helical peptides . our goal for expanding the utility of z - selective ruthenium catalysts was to examine the influence of amino acids on the selectivity and activity of catalysts 1 and 2 . catalysts bearing n - adamantyl substituents and bidentate nitrato ligands were found to be critical for achieving high z selectivity , and we set out to determine whether such catalysts could be applied to substrates bearing multiple functionalities and with varying steric profiles . to benchmark the reactivities of catalysts 1 and 2 , we chose to investigate the homodimerization of protected amino acids modified with homoallyl functionality ( table 1 ) . our initial studies focused on the use of alanine 3 , as we anticipated that amino acids bearing unhindered and aliphatic side chains would provide an ideal platform for comparative studies . we began with a catalyst loading of 2.5 mol % in tetrahydrofuran ( thf ) at 40 c , and this afforded the homodimerization product 4 in 53% yield after 4 h using catalyst 1 and 58% yield in the presence of catalyst 2 ( entry 1 ) . gratifyingly , the z selectivity remained high ( 90% ) throughout the course of the reaction . catalyst loadings of 5 mol % afforded product 4 in 65% yield with 92% z selectivity in the presence","olefin metathesis has emerged as a promising strategy for modulating the stability and activity of biologically relevant compounds ; however , the ability to control olefin geometry in the product remains a challenge . recent advances in the design of cyclometalated ruthenium catalysts has led to new strategies for achieving such control with high fidelity and z selectivity , but the scope and limitations of these catalysts on substrates bearing multiple functionalities , including peptides , remained unexplored . herein , we report an assessment of various factors that contribute to both productive and nonproductive z - selective metathesis on peptides . the influence of sterics , side - chain identity , and preorganization through peptide secondary structure are explored by homodimerization , cross metathesis , and ring",380,128,0.3368
dialogsum,"#Person1#: Jane, Professor Keller asked about you today and how you were coming along with the project on pollution. By the way, I handed mine in the day before yesterday. #Person2#: Whoops. I was supposed to give it to her yesterday.",#Person1# tells Jane that Professor Keller asked about her project today.,41,11,0.2683
scientific_lay_summarisation-elife-norm,"Ultraviolet-protective compounds, such as mycosporine-like amino acids (MAAs) and related gadusols produced by some bacteria, fungi, algae, and marine invertebrates, are critical for the survival of reef-building corals and other marine organisms exposed to high-solar irradiance. These compounds have also been found in marine fish, where their accumulation is thought to be of dietary or symbiont origin. In this study, we report the unexpected discovery that fish can synthesize gadusol de novo and that the analogous pathways are also present in amphibians, reptiles, and birds. Furthermore, we demonstrate that engineered yeast containing the fish genes can produce and secrete gadusol. The discovery of the gadusol pathway in vertebrates provides a platform for understanding its role in these animals, and the possibility of engineering yeast to efficiently produce a natural sunscreen and antioxidant presents an avenue for its large-scale production for possible use in pharmaceuticals and cosmetics. The sunscreen compounds, mycosporine-like amino acids (MAAs) and related gadusols, commonly found in bacteria, fungi, algae, and marine invertebrates (Shick and Dunlap, 2002; Miyamoto et al. , 2014), have been proposed to fulfill a variety of functions, such as sunscreen, antioxidant, stress response, intracellular nitrogen reservoir, and/or optical filter (Gao and Garcia-Pichel, 2011; Bok et al. , 2014). Although their formation had long been proposed to originate from the shikimate pathway, more recent bioinformatic and biochemical studies revealed that in cyanobacteria, MAAs are synthesized by desmethyl-4-deoxygadusol synthase (DDGS), a dehydroquinate synthase (DHQS) homolog (Wu et al. , 2007; Balskus and Walsh, 2010; Singh et al. , 2010; Asamizu et al. , 2012). Interestingly, inactivation of the DDGS gene in Anabaena variabilis ATCC 29413 did not abolish the production of MAAs, suggesting that additional pathways exist for the biosynthesis of MAAs (Spence et al. , 2012). DDGS converts sedoheptulose 7-phosphate (SH7P) to desmethyl-4-deoxygadusol via a unique sequence of dephosphorylation, aldol condensation, enolization, dehydration, reduction, and tautomerization reactions (— 1) (Balskus and Walsh, 2010; Asamizu et al. , 2012). The product is subsequently converted by a methyltransferase to 4-deoxygadusol, the building block of MAAs. 4-Deoxygadusol has also been proposed to be the precursor of gadusol (Starcevic et al. , 2010; Rosic and Dove, 2011), a related compound initially isolated from cod roe (Gadus morhua L.) (Plack et al. , 1981), but also found in roes of","Sunlight is the Earth' s primary energy source and is exploited by an array of natural and man-made processes. Photosynthetic plants harness solar energy to convert carbon dioxide and water into biomass, and solar panels capture light and convert it to electricity. Sunlight is critical to life on Earth, and yet excessive exposure to sunlight can cause serious harm as it contains ultraviolet (UV) radiation, which damages the DNA of cells. In humans, this damage can lead to conditions such as cataracts and skin cancer. The marine organisms and animals that live in the upper ocean and on reefs are subject to intense and unrelenting sunlight. In their effort to protect against potentially deadly UV radiation, many small and particularly vulnerable marine organisms, such as bacteria and algae,",380,128,0.3368
dialogsum,"#Person1#: You must be Kelly. Thanks for coming. It's hard to find a good babysitter on a Friday night. #Person2#: I like watching kids, and I need the extra money. I'd like to talk to you about my new rate increases.",#Person1# thanks Kelly for coming as a babysitter. Kelly wants a raise.,41,12,0.2927
scientific_lay_summarisation-elife-norm,"The hippocampus is linked with both sleep and memory, but there is debate about whether a salient aspect of sleep – dreaming – requires its input. To address this question, we investigated if human patients with focal bilateral hippocampal damage and amnesia engaged in dreaming. We employed a provoked awakening protocol where participants were woken up at various points throughout the night, including during non-rapid eye movement and rapid eye movement sleep, to report their thoughts in that moment. Despite being roused a similar number of times, dream frequency was reduced in the patients compared to control participants, and the few dreams they reported were less episodic-like in nature and lacked content. These results suggest that hippocampal integrity may be necessary for typical dreaming to occur, and aligns dreaming with other hippocampal-dependent processes such as episodic memory that are central to supporting our mental life. Dreaming has intrigued humans for thousands of years, being variously interpreted as having premonitory, religious, psychoanalytic, or mnemonic significance. Defined as an internally-generated subjective mental experience during the sleep state (Cipolli et al. , 2017), dreaming can be present at initial sleep onset (hypnagogic sleep; Horikawa et al. , 2013; Stickgold et al. , 2000), during non-rapid eye movement (NREM) sleep (Antrobus et al. , 1995; Foulkes, 1962; Nielsen, 2000; Siclari et al. , 2017; Wamsley, 2013; Wamsley et al. , 2007), and rapid eye movement (REM) sleep (Hobson et al. , 2000; Maquet et al. , 2000; Maquet et al. , 2005). Although dreams are not a precise replay of our memories (Fosse et al. , 2003; Stickgold et al. , 2001a), it has been proposed that dreaming may be associated with memory consolidation processes (Payne, 2010; Wamsley, 2014; Wamsley et al. , 2010; Wamsley and Stickgold, 2019). Indeed, in rodents and humans, patterns of brain activity exhibited during a learning experience were found to be subsequently expressed during sleep (Peigneux et al. , 2004; Wilson and McNaughton, 1994). Bilateral damage to a brain structure called the hippocampus is known to adversely affect memory processing (Miller et al. , 2017; Miller et al. , 2020; Scoville and Milner, 1957; Spiers et al. , 2001) and daydreaming (McCormick et al. , 2018). While sleep dreaming has been examined previously in patients with hippocampal lesions, results","Dreaming has intrigued humans for thousands of years, but why we dream still remains somewhat of a mystery. Although dreams are not a precise replay of our memories, one idea is that dreaming helps people process past experiences as they sleep. If this is true, then part of the brain called the hippocampus that is important for memory should also be necessary for dreaming. Damage to the hippocampus can cause a condition called amnesia that prevents people from forming new memories and remembering past experiences. However, studies examining dreaming in people with amnesia have produced mixed results: some found that damage to the hippocampus had no effect on dreams, while others found it caused people to have repetitive dreams that lacked detail. One reason for these inconsistencies is",380,128,0.3368
scientific_lay_summarisation-elife-norm,"function, and in neuronal migration (Huang et al. , 2005; Jensen et al. , 2000; Ruggiu et al. , 2009; Yano et al. , 2010). We show here that Nova1/2 loss of function reduces the migration of the spinal cord interneurons and their progenitors, and disturbs the axon outgrowth and guidance of the commissural interneurons. Interestingly, these defects resemble those seen in Dcc knockouts. Consistently, Dcc alternative splicing is perturbed by Nova deficiency in vivo. Through rescue experiments, we show that restoring Dcclong, the diminished isoform in Nova knockouts, is able to reverse the defects. Furthermore, NOVA1/2 regulate Dcc pre-mRNA splicing in in vitro assays. Together, our results demonstrate that Dcc alternative splicing is important for the gene function and is controlled by the NOVA splicing factors. Using the whole mouse embryo culture technique (Chen et al. , 2008), we transiently knocked down candidate RBPs with small interference RNAs (siRNAs) in the spinal cord and examined the resulting phenotype in commissural axon guidance. We selected RBPs that have neural-specific expression and have been implicated in alternative splicing (Table 1). The list of candidates is not exhaustive, and the screening against additional RBPs is ongoing. Some of the RBPs, including NOVA, FOX, and PTBP2/nPTB, directly regulate splicing by recognizing specific sequences in pre-mRNAs and controlling spliceosome assembly (Agnès and Perron, 2004; Li et al. , 2007). Some, such as CELF, UPF, and IGF2BP1, play an indirect role, often by regulating the stability of selective pre-mRNAs and thus influencing their splicing (Agnès and Perron, 2004; Ladd, 2013; Li et al. , 2007; Yap and Makeyev, 2013). Others, such as ELAVL/HU, can have both direct and indirect effects on alternative splicing (Agnès and Perron, 2004; Li et al. , 2007; Scheckel et al. , 2016; Ince-Dunn et al. , 2012). 10. 7554/eLife. 14264. 003Table 1. RNA-binding proteins targeted in the RNAi screenDOI: http: //dx. . org/10. 7554/eLife. 14264. 003GeneProtein familyPhenotypeNoteNova1/2 Neuro-oncological ventral antigen Neuronal migration, axon outgrowth, and axon guidance defects Ptbp2 Polypyrimidinetract-binding protein - Sfpq Splicing factor proline/glutamine rich (polypyrimidine tract-binding protein associated) - Fmr1 Fragile X mental retardation protein - Nufip1/2 Nuclear FMRP interacting protein - Elavl1/2/3/4 ELAV (embryonically lethal abnormal vision) homolog; Hu syndrome protein Partial midline crossing defect caused by Elavl2 single RNAi Rbfox1/2/3 RNA-binding protein, Fox (feminizing locus","The first step of producing a protein involves the DNA of a gene being copied to form a molecule of RNA. This RNA molecule can often be processed to create several different “messenger” RNAs (mRNAs), each of which are used to produce a different protein by a process known as alternative splicing. A class of proteins that bind to RNA molecules controls alternative splicing. These “splicing factors” ensure that the right protein variant is produced at the right time and in the right place to carry out the appropriate activity. Many genes that play important roles in the nervous system have been reported to undergo alternative splicing to generate different protein variants. However, it is unclear whether alternative splicing is important for controlling how the nervous system develops,",380,128,0.3368
dialogsum,"#Person1#: Hi, my name is Violet. Come with me, and I'll help you wash your hair. #Person2#: My hair is kind of dry and brittle. . . #Person1#: I'll pick a shampoo that's just right for your hair type. Sit right here, and rest your neck on the side of the sink. Is the water too hot? #Person2#: No, it's just perfect. #Person1#: Let me know if I'm using too much force. #Person2#: No, really, it feels great. #Person1#: OK! You're all set! Come back with me to your seat, and Eva will be right with you.",Violet helps #Person2# wash #Person2#'s hair. Violet picks the right shampoo and the proper water temperature. #Person2# feels great.,97,19,0.1959
dialogsum,"#Person1#: What did you say when Alice told you the news? #Person2#: I calmed up and hesitated indeed. And finally, I asked her to chew the cud for such an important decision. I could not have the heart to disappoint her with a blunt refusal. But I put my foot down and insisted on her forgetting that. #Person1#: How could you have the heart to do that? She needs warmth and help.","#Person2# asked Alice to forget the news, but #Person1# thinks she needs comforts.",72,13,0.1806
pubmed-summarization,"in 70% ethanol during 2 min , the eyes were washed in clean dmem supplemented with 10% antibiotic - antimycotic at room temperature . briefly , the eyes were dissected at the ora serrata to exclude the iris and lens . the vitreous was then removed from the posterior eyecup with cotton swabs , and then the neuroretina was detached and discarded . the remaining eye cup was covered with 0.05% trypsin - tetrasodium ethylene diamine tetra - acetate ( trypsin - edta , gibco ) for 30 min at 37 c . rpe cells were removed by filling the eye cup with dmem supplemented with 10% fetal bovine serum ( fbs ; gibco ) plus 1% antibiotic - antimycotic mixture ( complete dmem ) and swabbing gently . after resuspension in complete dmem , the cells were plated in 25 cm flasks ( nunc , roskilde , denmark ) . the rpe cells were maintained in complete dmem under standard culture conditions of 37 c in an atmosphere of 5% co2 with 95% humidity . rpe cell morphology was evaluated with a nikon eclipse ts100 inverted - phase contrast microscope ( nikon instruments inc . , louis , mo ) was used to determine viability and cell numbers . after reaching > 90% confluence , the cells were trypsinized with 0.05% trypsin - edta , washed , and resuspended in pbs ( gibco ) . passage 2 rpe cells were seeded ( 30,000 cells / cm ) on the bottom of transwell culture plates ( corning inc . , corning , ny ) and grown for 24 h in complete dmem to allow cellular adhesion before coculturing with neuroretina explants . the porcine cone - enriched visual streak was identified , as described by hendrickson and hicks , and two 55 mm adjacent explants from each eye were obtained with castroviejo corneal scissors ( john weiss & son ltd . , milton keynes , uk ) from the temporal area 1 mm superior to the optic disc ( ) . the neuroretina explants were laid over the transwell membranes ( 24-mm diameter with 0.4-m pore polycarbonate membrane insert ; product # 3412 , corning inc . ) with the photoreceptor layer facing the membrane . nine neuroretina explants were","purposeto develop and standardize a novel organ culture model using porcine central neuroretina explants and rpe cells separated by a cell culture membrane.methodsrpe cells were isolated from porcine eyes , expanded , and seeded on the bottom of cell culture inserts . neuroretina explants were obtained from the area centralis and cultured alone ( controls ) on cell culture membranes or supplemented with rpe cells in the same wells but physically separated by the culture membrane . finally , cellular and tissue specimens were processed for phase contrast , cyto-/histological , and immunochemical evaluation . neuroretina thickness was also determined.resultscompared to the neuroretinas cultured alone , the neuroretinas cocultured with rpe cells maintained better tissue structure and cellular organization , displayed better preservation of photoreceptors containing rhodopsin ,",380,128,0.3368
pubmed-summarization,"in the table 2. medicine as a target for counterfeiting drivers of counterfeiting counterfeit medicines globally authentication is of utmost importance because the use of counterfeit medicines can be harmful to the health and wellbeing of the patients . overt features are expected to assist the users to confirm the genuineness of a pack . the process can be untidy and does not always provide the print quality necessary for creating small codes , which must stay clear for weeks or months . barcodes are high - density linear or two - dimensional codes incorporated onto the product package , which are scanned and sent to the central database as shown in . users must make sure that there is a sufficient print contrast between light and dark bars to produce a legible representation . package showing two - dimensional barcodes , scanned and sent to the central database holography is well known for its capacity to produce striking three - dimensional images , which are difficult to get through with the conventional photography . a major benefit of this process is that they can be reformed under white light . holograms are generated from the interference patterns obtained through the contact of laser beams by either angular image or laser technology . such high - definition holograms are used as a security feature on the product bottle as shown in . the complexity of the hologram varies from the traditional three - dimensional images to computer - generated two - dimensional diffraction patterns . holograms are now widely available in variety of formats such as holographic shrink sleeves , blister packaging aluminum foil , holographic induction cap seals , polyester - based tamper evident labels , and holographic hot stamping foil . but still it is reported that more than half the sales of the artesunate drug in south east asia is forged , despite the presence of the hologram. the overall advantages and disadvantages of overt technologies are described in table 3 . bottle with a hologram as a security feature advantages and disadvantages of overt and covert technologies the rationale of a covert feature is to aid the brand owner to recognize a counterfeited product . the general public will not be aware of its presence nor","packaging is the coordinated system that encloses and protects the dosage form . counterfeit drugs are the major cause of morbidity , mortality , and failure of public interest in the healthcare system . high price and well - known brands make the pharma market most vulnerable , which accounts for top priority cardiovascular , obesity , and antihyperlipidemic drugs and drugs like sildenafil . packaging includes overt and covert technologies like barcodes , holograms , sealing tapes , and radio frequency identification devices to preserve the integrity of the pharmaceutical product . but till date all the available techniques are synthetic and although provide considerable protection against counterfeiting , have certain limitations which can be overcome by the application of natural approaches and utilization of the principles",380,128,0.3368
pubmed-summarization,"electrocardiogram were within the normal range . she was prescribed aripiprazole 10 mg orally in two divided dosages per day , eszopiclone 2 mg orally at nighttime dosage and was advised follow - up after 2 weeks . during her first follow - up visit , she showed improvement in sleep . for improvement in psychotic symptoms , aripiprazole was increased to 20 mg orally in two divided dosages and was advised follow - up after 2 weeks . after 5 days of dose increment , she was brought with complaints of upward rolling of eye balls suddenly , unexpected , occurring five to seven times a day , which were difficult to bring back to original position by the patient . after evaluation for conversion disorder , tardive dystonia , epileptic encephalopathy , anti epileptic drug intake , she was diagnosed of having oculogyric crisis ( acute dystonia ) . the patient was admitted in psychiatry ward . aripiprazole was withdrawn and immediately injection promethazine 50 mg intramuscularly was given , which was repeated after half an hour . her symptoms improved in next 1 hour and the patient was prescribed 25 mg promethazine orally in night time dosage . within 3 days of admission , she was put on aripiprazole 10 mg orally in two divided dosages for her psychotic symptoms , while continuing eszopiclone with promethazine 25 mg nocte . the patient was advised to follow up after a week . the repeat challenge with aripiprazole 20 mg orally in two divided dosages resulted into oculogyric crisis within 4 days . the patient was advised cap ziprasidone 20 mg orally in two divided doses per day ( i.e. , 40 mg per day ) with food and was asked to follow up 2 weeks later with electrocardiogram done . later uptitration of cap ziprasidone to 20 mg orally in three divided doses per day ( i.e. , 60 mg per day ) with food was done . she improved in her psychotic symptoms over 2 months with no extrapyramidal symptoms , normal electrocardiogram , and other baseline investigations . various case reports of aripiprazole - induced acute dystonia report symptoms of neck extension , torticollis , rigidity , and tongue movements. in addition , various studies describe","aripiprazole is the third generation atypical antipsychotic and a dopamine serotonin system stabilizer ( dss ) effective against positive and negative symptoms of schizophrenia . it has a low propensity for extrapyramidal side effects , causes minimal weight gain or sedation , produces no elevation in serum prolactin levels , and does not cause prolongation of qtc interval . this case report is of a patient suffering from schizophrenia ( paranoid ) . the patient developed oculogyric crisis ( acute dystonia ) with aripiprazole dose uptitration . dystonic reaction resolved with promethazine administration . naranjo 's causality assessment reveals probable association of aripiprazole with oculogyric crisis . a thorough workup and vigilance is required prior to initiation of aripiprazole in the case of schizophrenia .",380,125,0.3289
dialogsum,"#Person1#: Welcome! Welcome to Little Italy. We're the most Italian family here! #Person2#: So I've heard. That's why I'm having such a great time. #Person1#: If I hadn't married an Italian man, I probably wouldn't be pregnant so often. And maybe I could raise pigs instead of bambinos! #Person2#: Huh? Um. . . well, it's nice to see that some people still have big families. #Person1#: It is nice, but it would be nicer if my macho husband would get off his tush and help me. Ha-ha. . . Have this. It's from Italy!","#Person2# has fun in the Little Italy. #Person1#, the hostess, complains about having too many children.",94,16,0.1702
dialogsum,"#Person1#: There's so much to do and so little time. #Person2#: I know. Did your mom double check on the church reservations? #Person1#: Yes. We're going to be married in my hometown church, the first minute of the new millennium! #Person2#: OK. . . and what about the buffet and the cake? Did your mom call the caterer? #Person1#: All set. And we're having a red bean cake and dim sum for the Taiwanese guests, just like your mom wanted. #Person2#: Great. She'll be so happy.",#Person2# asks #Person1# if their wedding preparation is all set up as each other's mother expects.,86,16,0.186
pubmed-summarization,"teneligliptin group vs 20.93% in the placebo group ; p < 0.001 ; s2 , file s1 ) . approximately 34.69% of all subjects in the teneligliptin group achieved an hba1c level < 6.5% at week 24 , whereas only 4.65% achieved this level in the placebo group ( p = 0.0016 ; s2 , file s1 ) . in subgroup analysis of subjects with high or low hba1c level ( 8.0 or < 8.0% ) at baseline , the effect of teneligliptin was greater in the hba1c 8.0% group ( 1.15 0.99% , n = 25 ) than in the hba1c < 8.0% group ( 0.69 0.70% , n = 73 ; p = 0.0019 ) . effects of teneligliptin and placebo on glucose metabolism between baseline and week 24 . ci , confidence interval ; fpg , fasting plasma glucose ; hba1c , glycated haemoglobin ; homa , homeostatic model assessment of cell function ; homair , homeostatic model assessment of insulin resistance ; s.d . , standard deviation ; s.e . , * according to threeway analysis of variance ( anova ) . * * p < 0.0001 versus placebo according to threeway anova . teneligliptin decreased the fpg level from baseline to week 24 , while the fpg level did not change in the placebo group . at week 24 , the difference in change in fpg between the two groups was 1.21 mmol / l [ 95% confidence interval ( ci ) 1.72 , 0.70 ; p < 0.0001 ( table 1 ) ] . cell function , as assessed by homa , was improved in the teneligliptin group at week 24 but not in the placebo group . at week 24 , the difference in homa change between the groups was 12.23% [ 95% ci 5.78 , 18.67 ; p = 0.0003 ( table 1 ) ] . the teneligliptin group exhibited an improved homa score compared with the placebo group at week 8 and throughout the randomized treatment period ( s3 , file s1 ) . no significant difference in homair was observed between the two treatment groups . during this study , 81 adverse events ( aes ) occurred in 49 ( 34.5% ) of the 142 randomized subjects . among the","we assessed the 24week efficacy and safety of teneligliptin , a novel dipeptidyl peptidase4 inhibitor , in korean patients with type 2 diabetes mellitus ( t2 dm ) that was inadequately controlled with diet and exercise . the present study was designed as a multicentre , randomized , doubleblind , placebocontrolled , parallelgroup , phase iii study . patients ( n = 142 ) were randomized 2 : 1 into two different treatment groups as follows : 99 received teneligliptin ( 20 mg ) and 43 received placebo . the primary endpoint was change in glycated haemoglobin ( hba1c ) level from baseline to week 24 . teneligliptin significantly reduced the hba1c level from baseline compared with placebo after 24 weeks . at week 24 , the differences",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Rotavirus genome replication and assembly take place in cytoplasmic electron dense inclusions termed viroplasms (VPs). Previous conventional optical microscopy studies observing the intracellular distribution of rotavirus proteins and their organization in VPs have lacked molecular-scale spatial resolution, due to inherent spatial resolution constraints. In this work we employed super-resolution microscopy to reveal the nanometric-scale organization of VPs formed during rotavirus infection, and quantitatively describe the structural organization of seven viral proteins within and around the VPs. The observed viral components are spatially organized as five concentric layers, in which NSP5 localizes at the center of the VPs, surrounded by a layer of NSP2 and NSP4 proteins, followed by an intermediate zone comprised of the VP1, VP2, VP6. In the outermost zone, we observed a ring of VP4 and finally a layer of VP7. These findings show that rotavirus VPs are highly organized organelles. Rotavirus is a non-enveloped virus composed of three concentric layers of proteins that enclose a genome constituted by eleven segments of double stranded RNA (dsRNA) that encode six structural proteins (VP1 to VP4, VP6 and VP7) and six non-structural proteins (NSP1 to NSP6). The inner layer is formed by dimers of VP2 that enclose the viral genome and small numbers of molecules of the viral RNA-dependent RNA polymerase (RdRp), VP1, and the capping enzyme, VP3. This nucleoprotein complex constitutes the core of the virus, which is surrounded by an intermediate protein layer of trimers of VP6, to form double-layered particles (DLPs). The surface of the virion is occupied by two polypeptides, VP7, a glycoprotein, and VP4, which forms spikes that protrude from the VP7 shell (Estes and Greenberg, 2013). Replication of the rotavirus genome and assembly of DLPs take place in cytoplasmic electron dense inclusions termed viroplasms (VPs) (Estes and Greenberg, 2013). Once the double-shelled particles are assembled, they bud from the cytoplasmic VPs into the adjacent endoplasmic reticulum (ER). During this process, which is mediated by the interaction of DLPs with the ER transmembrane viral protein NSP4, the particles acquire a temporary lipid bilayer, modified by VP7 and NSP4, which after being removed in the lumen of the ER by an unknown mechanism, yields the mature triple-layered virions (Estes and Greenberg, 2013). It has been reported that VP4 is located between the VP and the ER","Rotaviruses are small viruses that can infect cells in the intestine. They are responsible for most cases of severe infectious diarrhea, the most common cause of death among young children in developing countries. Controlling the spread of rotavirus infections is difficult, even with high levels of hygiene, so effective treatments are essential to curtail the virus’ infections. Understanding how new rotaviral particles are made in infected cells is one of the first steps toward developing new therapies. Once rotaviruses enter the cells, proteins from the virus and the cell aggregate into compact spheres called viroplasms to make new viral particles. Studying these viroplasms used to be difficult because they are too small to see with the resolution of standard microscopes. In recent years, advances in microscopy and mathematical",380,128,0.3368
scientific_lay_summarisation-elife-norm,"long-term memory (LTM) whether a protein synthesis inhibitor is applied either immediately prior to, or immediately after, training (e. g. , Agranoff et al. , 1966; Barondes and Cohen, 1968; Flexner and Flexner, 1968). Consequently, both early and late protein synthesis are commonly regarded as participating in a more-or-less unitary consolidative process. In particular, protein synthesis is believed to mediate critical late events in memory consolidation, including late gene transcription via the synthesis of transcription factors, such as the CCAAT/enhancer-binding protein (C/EBP), and the consequent synthesis of proteins involved in the construction of new synaptic connections (Bailey et al. , 2015; Kandel et al. , 2014). One mechanism increasingly implicated in the consolidation of LTM is the epigenetic process of DNA methylation (Levenson et al. , 2006; Maddox et al. , 2014; Miller et al. , 2008; Monsey et al. , 2011; Oliveira, 2016; Rajasethupathy et al. , 2012). However, the relationship between protein synthesis and DNA methylation in memory consolidation is unclear. Mechanistically, is protein synthesis upstream or downstream of DNA methylation during consolidation? DNA methylation is usually associated with gene silencing. If DNA methylation is required for the synthesis of necessary consolidative proteins, this would imply that a prerequisite for this synthesis is the silencing of one or more repressor genes. On the other hand, it is possible that activation of DNA methyltransferase (DNMT), the family of enzymes that catalyze the transfer of a methyl group to DNA, during memory consolidation itself depends on protein synthesis. Of course, these two possibilities are not mutually exclusive. Here, we have examined the potentially distinctive roles of early and late protein synthesis in the consolidation of the LTM for behavioral sensitization in Aplysia. In addition, we have tested the effect on memory consolidation of both early and late inhibition of DNA methylation. We find that LTM can be induced by partial training, which is insufficient to induce LTM in naïve (untrained) animals, after the disruption of LTM by late, but not early, administration of a protein synthesis inhibitor. By contrast, both early and late inhibition of DNMT block LTM consolidation as indicated by the preclusion of subsequent memory induction by partial training. These results point to a functional distinction between early and late protein synthesis in memory consolidation, and suggest a","The formation of long-term memory depends on new proteins being made in the brain. These new proteins are used partly to build the new connections among neurons that essentially store the memory, and must be made within a critical period of time. Experiments on animals have found that new proteins must be made during or shortly after training to form a stable memory; if protein synthesis is blocked during this period, the memory will not be stabilized (a process also known as memory consolidation). Changes that alter the activity of genes in neurons also play essential roles in memory consolidation. One such change involves the attachment of a methyl group – a molecule that contains one carbon atom surrounded by three hydrogen atoms – to the DNA of",380,128,0.3368
dialogsum,"#Person1#: Good morning. I'm thinking about buying some new furniture for my living room. Could you help me? #Person2#: Certainly. As you can see, we have several three-piece suites on sale. Feel free to sit down and test how comfortable they are. #Person1#: I came to your store yesterday and have come back today to make a final decision. I think I like the black leather suite. It's on sale, isn't it? #Person2#: Yes. The price has been reduced by 50 %. It's a real bargain. #Person1#: I'll take it. I also need to improve the lighting in my living room. Do you have any suggestions? #Person2#: Those floor lamps are very nice and you can vary the brightness according to whether you're reading or watching tv. How big is your living room? #Person1#: It's quite large. It's about 40 square metres. #Person2#: I'd suggest you buy two. That allows you to change the brightness of the room better. #Person1#: Ok. I like the design of this lamps. I also need some cushion covers. I'll just browse through those ones over there.","#Person1# will take a black leather suite which is on sale, two lamps to change the brightness of the room suggested by #Person2#, and some cushion covers.",182,27,0.1484
pubmed-summarization,"nucleic acids are highly attractive class of therapeutics due to their potential to regulate any selected gene of interest . given their capacity to modulate conventionally undruggable targets , oligonucleotides ( ons ) have been extensively investigated as potential therapeutics to treat cancer , viral infections , genetic diseases , and immunological disorders . despite the clear therapeutic potential of ons , their poor permeability across cellular membranes ( due to their intrinsic polyanionic nature and high molecular weight ) and susceptibility to degradation by ubiquitous nucleases hamper their clinical translation . recent advances in the development of various delivery vehicles ( e.g. , polymer- , lipid- , peptide- , nano / microparticles- , or viral - based ) have helped overcoming some of the on delivery problems ; however , issues such as systemic toxicity , low concentration at target sites and pharmaceutical complexity of the delivery systems still represent obstacles to the clinical translation of on therapeutics . the conception of stable ons with enhanced affinity via various chemical modifications is one of the most remarkable achievements in this field . for example , the combination of phosphorothioate ( ps ) backbone modification with 2-o - methyl ( ome ) and 2-o-(2-methoxyethyl ) ( moe ) moieties in the sugar units or bicyclic ribonucleosides are the most widely used chemical strategies under clinical investigation . another approach is modification with 2-deoxy-2-fluoro - arabinonucleic acid ( fana ) , which upon binding to the target mrna induces its rnase h - mediated degradation . several chemically stabilized ons are already marketed ( e.g. , mipomersen for homozygous familial hypercholesterolemia ) or in late - phase clinical trials . nucleic acid therapy could be especially beneficial for several disorders of the gastrointestinal ( gi ) system that currently lack appropriate treatments such as inflammatory bowel diseases , colon cancer , and familial adenomatous polyposis . the delivery of nucleic acids directly to the gi mucosa is ideal to achieve high local concentrations while minimizing systemic exposure and subsequent side - effects . indeed , a group of carrier - free ons targeting gi mucosa for inflammatory bowel disease therapy is progressing through clinical trials , although high doses of ons are required to obtain the positive therapeutic effects . therefore","nucleic acid therapy can be beneficial for the local treatment of gastrointestinal diseases that currently lack appropriate treatments . indeed , several oligonucleotides ( ons ) are currently progressing through clinical trials as potential treatments for inflammatory bowel diseases . however , due to low uptake of carrier - free ons by mucosal cells , strategies aimed at increasing the potency of orally administered ons would be highly desirable . in this work , we explored the silencing properties of chemically modified and highly resistant ons derivatized with hydrophobic alkyl chain on intestinal epithelial cells . we screened a set of lipid - on conjugates for the silencing of model bcl-2 mrna and selected 2-deoxy-2-fluoro - arabinonucleic acid modified on bearing docosanoyl moiety ( l - fana )",380,128,0.3368
dialogsum,"#Person1#: Hello, Anna. Come in and sit down. #Person2#: Hello, doctor. #Person1#: What's the matter? #Person2#: I've got a backache. #Person1#: Do you often suffer from backache? #Person2#: No, I don't. I've never had a bad one before. #Person1#: When did it start? #Person2#: About four days ago. #Person1#: Well, go home and rest in bed for two days, then you'll feel better. #Person2#: Can you give me some medicine? It's very painful. #Person1#: Yes, I'll give you some pills. Take one a time and three times a day, and come back in three days. If you don't feel. . .","Anna sees the doctor because of the painful backache, and the doctor gives her some pills.",101,16,0.1584
pubmed-summarization,"making processes , will not only improve the average long - term outcome of published series focusing on any severe underlying comorbidity but also reduce the burden for individual patients and their relatives at the bedside . health - care workers will also benefit , since real or perceived disproportional care in the icu leads to acute or , much worse , more subtle chronic conflicts within the team , resulting in poor quality of care . the latter is particularly deleterious since it will affect the patient s short- and long - term outcome in general , regardless of whether the admission is justified or not . a good admission policy is necessary in order to safeguard the quality of icu care provided to patients with good long - term expectations on the one hand and to reduce the burden for patients and relatives with poor long - term expectations on the other . this can be achieved only by creating working environments enhancing close collaboration and communication between intensivists and hematologists and where the patient and relatives are closely involved in the decision - making process upon icu referral and during icu stay . it is important to note that this holds not only for patients with hematological malignancies such as in the study by bernal and colleagues but also for patients with any other severe underlying comorbidity that are increasingly referred to the icu . a good admission policy is necessary in order to safeguard the quality of icu care provided to patients with good long - term expectations on the one hand and to reduce the burden for patients and relatives with poor long - term expectations on the other . this can be achieved only by creating working environments enhancing close collaboration and communication between intensivists and hematologists and where the patient and relatives are closely involved in the decision - making process upon icu referral and during icu stay . it is important to note that this holds not only for patients with hematological malignancies such as in the study by bernal and colleagues but also for patients with any other severe underlying comorbidity that are increasingly referred to the icu .","the spectacular improvement in long - term prognosis of patients with hematological malignancies since the 1980s , coupled with the subsequent improvement over the past decade in short- and mid - term survival in cases of critical illness , resulted in an increasing referral of such patients to the icu . a remaining question , however , is how these patients perform in the long term with regard to survival and quality of life . here we discuss the present multicenter study on survival beyond 1 year in critically ill patients with hematological malignancies . we conclude with suggestions on how we can further improve the long - term outcome of these patients .",368,114,0.3098
pubmed-summarization,"human metapneumovirus ( hmpv ) is an rna virus in the pneumovirinae subfamily of the paramyxoviridae family that was first isolated in the netherlands in 2001 and has subsequently been identified worldwide . it has been implicated as a significant cause of hospitalization for young children , second only to respiratory syncytial virus ( rsv ) in infants hospitalized with acute respiratory infections ( aris ) . hmpv has been detected in 1.543.0% of patients with aris . while it circulates predominantly in the winter , seroprevalence studies have shown that almost all children over five years of age have evidence of past infection . clinical syndromes associated with hmpv infection are similar to those of rsv infection , ranging from mild upper respiratory tract infections to wheezing and severe lower respiratory tract infections requiring mechanical ventilation . rare cases of fatalities have been associated with hmpv and it has been implicated in a handful of cases of encephalitis . although hmpv infections have been diagnosed in adults , their greatest impact occurs in children . a significant association with hmpv and wheezing is seen in young children , and hmpv has been linked to apparent life - threatening events in infants . hmpv has been associated with aris with super - infections as a result of staphylococcus aureus and streptococcus pneumoniae . to begin to understand the impact of hmpv on our institution , we analyzed children admitted to our tertiary care center in southeast michigan with respiratory symptoms during the respiratory season of 20062007 through an observational , retrospective study . the primary purposes of our study were to establish the utility of testing for hmpv in children who were admitted to our hospital during the respiratory virus season and to compare the impact of hmpv and rsv on the healthcare system . we identified a convenience sample of 256 nasopharyngeal ( np ) specimens from children younger than 18 years of age admitted with respiratory symptoms between november 1 , 2006 and may 31 , 2007 . the specimens were obtained by a np wash or swab based on the admitting physician s discretion . after routine testing by direct fluorescent antibody ( dfa ) and/or culture for rsv , parainfluenza viruses 13 , influenza viruses a","human metapneumovirus ( hmpv ) is a recently discovered virus that causes respiratory illness in children that can lead to hospitalization . our study was undertaken to further understand hmpv - associated illness , compare clinical characteristics of hmpv and respiratory syncytial virus ( rsv ) , and establish the utility of routine screening for hmpv . we retrospectively identified hmpv - associated illnesses described among children with respiratory symptoms admitted to a tertiary care center in southeast michigan during the 20062007 respiratory viral season . a convenience sample of 256 nasopharyngeal specimens was subjected to nucleic acid extraction and amplification to identify those specimens positive for hmpv . a medical record review was undertaken to retrieve demographic and clinical data of patients with hmpv , comparing them",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The ability to isolate rare live cells within a heterogeneous population based solely on visual criteria remains technically challenging, due largely to limitations imposed by existing sorting technologies. Here, we present a new method that permits labeling cells of interest by attaching streptavidin-coated magnetic beads to their membranes using the lasers of a confocal microscope. A simple magnet allows highly specific isolation of the labeled cells, which then remain viable and proliferate normally. As proof of principle, we tagged, isolated, and expanded individual cells based on three biologically relevant visual characteristics: i) presence of multiple nuclei, ii) accumulation of lipid vesicles, and iii) ability to resolve ionizing radiation-induced DNA damage foci. Our method constitutes a rapid, efficient, and cost-effective approach for isolation and subsequent characterization of rare cells based on observable traits such as movement, shape, or location, which in turn can generate novel mechanistic insights into important biological processes. Characterization of biological samples relies heavily on microscopy where, in response to various stimuli, molecular probes and a myriad of contrast reagents are routinely used to identify and label individual live cells of interest. These methods often require prior knowledge of cellular markers or use of elaborate reporter constructs. On the other hand, based solely on visual inspection or using image processing algorithms, it is possible to distinguish rare cells which exhibit distinct biological properties from among thousands of counterparts within a microscopy field. Such visually discernable traits include movement, shape, intracellular protein distribution, and location within the sample, and in turn can reflect important physiological features of individual cells. For example, cell migration (movement) is an essential determinant in normal embryonic development, wound healing, immune responses, tumor progression, and vascular disease (Kurosaka and Kashina, 2008). Moreover, changes in cellular morphology (shape) constitute biomarkers of cellular growth, division, death, and differentiation, as well as of tissue morphogenesis and disease (Prasad and Alizadeh, 2019). Cell-to-cell contacts (location) or distance to sources of chemical cues such as senescent cells, inflammation or necrotic tissue are critical factors in chemokinesis, differentiation, neural function, and immune responses (Garcia et al. , 2018). Finally, expression and visualization of fluorescent fusion proteins permits the identification of cells presenting molecular behaviors of interest, such as differential relocalization of proteins to subcellular compartments or structures upon various stimuli. Unfortunately,","When scientists use microscopes to look at cells, they often want to then isolate certain cells based on how these look like. For example, researchers may want to select cells with specific shapes, movements or division rates, because these visual clues give important information about how the cells may be behaving in the body. However, it remains difficult to precisely pick a few live cells within a bigger sample. To address this problem, Binan et al. created a new approach, called single cell magneto-optical capture (scMOCa), to set aside specific cells within a larger population. The technique uses the lasers present on confocal microscopes to attach tiny metallic beads to the surface of chosen cell. Then, a magnetic field is applied to gently pull the cell to a",380,128,0.3368
pubmed-summarization,"and the mortality analysis of all npcss adopting the same analytical approach and adjusting for deprivation , there are several limitations that should be noted , such as its ecological design and the use of mortality data at municipal level for a short period of time . with the aim of overcoming the above limitations , this paper presents an epidemiological profile of taranto npcs residents analyzing different health indicators available at municipality level , that is , cause - specific mortality ( 20032009 ) , mortality time trend ( 19802008 ) , and cancer incidence ( 2006 - 2007 ) . a cohort study of the resident population examined mortality ( 19982008 ) and morbidity ( 19982010 ) in the districts close to the steel plant . details on the codes used during the study period for the 9th and 10th revisions of the international classification of diseases ( icd-9 and icd-10 ) and on the demographic data of the two municipalities included in taranto npcs are presented in appendix a. mortality in taranto npcs residents was initially studied for the period 19952002 and then updated for the years 20032009 ( note that the period 2004 - 2005 was not available from istat ) . the analysis considered 63 single or grouped causes ( all ages , both genders ) ; 0 - 1 and 014 age classes were also analyzed for a selection of causes ( both genders combined ) . standardized mortality ratios both crude ( smrs ) and adjusted for deprivation together with 90% confidence intervals ( 90% cis ) were computed using regional rates for comparison . in sentieri project the deprivation index ( di ) was constructed using the 2001 national census variables representing the following socioeconomic domains : education , unemployment , dwelling ownership , and overcrowding . the strengths and weaknesses of sentieri i d , its correlation with 2001 national deprivation index , its efficacy in representing deprivation in different categories of demographic dimensions , together with suggestions about the use of socioeconomic indices in small area studies of environment and health are discussed in pasetto et al . the analysis was performed for the population 099 years separately for men and women ; directly standardized death rates ( sdrs )","the national environmental remediation programme in italy includes sites with documented contamination and associated potential health impacts ( national priority contaminated sites npcss ) . sentieri project , an extensive investigation of mortality in 44 npcss , considered the area of taranto , a npcs where a number of polluting sources are present . health indicators available at municipality level were analyzed , that is , mortality ( 20032009 ) , mortality time trend ( 19802008 ) , and cancer incidence ( 2006 - 2007 ) . in addition , the cohort of individuals living in the area was followed up to evaluate mortality ( 19982008 ) and morbidity ( 19982010 ) by district of residence . the results of the study consistently showed excess risks for a",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. , 1991). Mathematical models can be used to translate entomological endpoint trial data into predictions of public health impact. Currently this has only been done for a small number of sites (Briët et al. , 2013) making it difficult for malaria control programmes to understand the problems caused by insecticide resistance in their epidemiological setting. There are no easy to use genetic markers that can reliably predict the susceptibility of mosquitoes to pyrethroid insecticide (Weetman and Donnelly, 2015). The current most practical phenotypic method for assessing resistance is the use of bioassays which take wild mosquitoes and measures their mortality after exposure to a fixed dose of insecticide (WHO, 2013a). However the discriminating doses used in the assay are unrelated to the field exposure and so the predictive value of these bioassays for assessing the problems of pyrethroid resistance is unknown. A meta-analysis has shown that insecticide treated bednets still outperform untreated nets in experimental hut trials even against pyrethroid resistant populations (Strode et al. , 2014) though the community impact (herd effects) of the LLIN was not assessed (Killeen et al. , 2007). The population prevalence of pyrethroid resistance is known to be changing at a fast rate (Toé et al. , 2014) making it important to regularly re-evaluate the efficacy of LLINs in order to guide current vector control and resistance management strategies (WHO, 2012). There are limited tools available for tackling pyrethroid resistance and protecting the advances made in malaria control. Until new LLINs containing alternative insecticide are available the only alternative bednet are those containing pyrethroids plus the insecticide synergist piperonyl butoxide (PBO). Studies have shown that PBO LLINs are substantially better at killing insecticide resistant mosquitoes in some locations but not others (Ngufor et al. , 2014a, 2014b; Kitau et al. , 2014; Asale et al. , 2014; Ngufor et al. , 2014c; Koudou et al. , 2011; Corbel et al. , 2010; Tungu et al. , 2010; Malima et al. , 2008; Adeogun et al. , 2012a; Agossa et al. , 2014; Malima et al. , 2013). PBO LLINs are more expensive than standard LLINs, with one manufacturer’s 2012 price for PBO LLIN being US$4. 90 compared to a comparable standard LLIN price of US$3. 25 (Briët et al. , 2013). This makes","In recent years, widespread use of insecticide-treated bednets has prevented hundreds of thousands cases of malaria in Africa. Insecticide-treated bednets protect people in two ways: they provide a physical barrier that prevents the insects from biting and the insecticide kills mosquitos that come into contact with the net while trying to bite. Unfortunately, some mosquitoes in Africa are evolving so that they can survive contact with the insecticide currently used on bednets. How this emerging insecticide resistance is changing the number of malaria infections in Africa is not yet clear and it is difficult for scientists to study. To help mitigate the effects of insecticide resistance, scientists are testing new strategies to boost the effects of bednets, such as adding a second chemical that makes the insecticide on",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Tendons are extracellular matrix (ECM) -rich structures that mediate muscle attachments with the skeleton, but surprisingly little is known about molecular mechanisms of attachment. Individual myofibers and tenocytes in Drosophila interact through integrin (Itg) ligands such as Thrombospondin (Tsp), while vertebrate muscles attach to complex ECM fibrils embedded with tenocytes. We show for the first time that a vertebrate thrombospondin, Tsp4b, is essential for muscle attachment and ECM assembly at myotendinous junctions (MTJs). Tsp4b depletion in zebrafish causes muscle detachment upon contraction due to defects in laminin localization and reduced Itg signaling at MTJs. Mutation of its oligomerization domain renders Tsp4b unable to rescue these defects, demonstrating that pentamerization is required for ECM assembly. Furthermore, injected human TSP4 localizes to zebrafish MTJs and rescues muscle detachment and ECM assembly in Tsp4b-deficient embryos. Thus Tsp4 functions as an ECM scaffold at MTJs, with potential therapeutic uses in tendon strengthening and repair. Cellular structure and function depend on dynamic interactions with extracellular matrix (ECM) proteins, defects in which cause many diseases such as muscular dystrophies and osteoarthritis (Emery, 2002; Mayer, 2003; Kanagawa and Toda, 2006; Carmignac and Durbeej, 2012; Maldonado and Nam, 2013). Tendons and ligaments are especially rich in ECM proteins, predominantly laminins (Lams) and collagens (Cols) (Hauser et al. , 1995; Kannus, 2000; Kjaer, 2004; Södersten et al. , 2007; Snow and Henry, 2009; Schweitzer et al. , 2010; Aparecida de Aro et al. , 2012; Charvet et al. , 2011). These multimeric proteins assemble into extremely strong fibrillar structures capable of resisting the contractile forces of muscles and enabling movement (Banos et al. , 2008; Thorsteinsdóttir et al. , 2011; Thorpe et al. , 2013). Muscles interact with these tendon ECM proteins through integrin (Itg) heterodimers as well as the dystrophin-associated glycoprotein complex to form attachments at myotendinous junctions (MTJs) (Kannus et al. , 1998; Kardon, 1998; Blake et al. , 2002; Bassett et al. , 2003; Henry et al. , 2005; Carmignac and Durbeej, 2012). While the organization of the ECM at MTJs has been described (Kardon, 1998; Aparecida de Aro et al. , 2012), the developmental processes underlying its establishment and maintenance are poorly studied. In zebrafish embryos, early MTJs form as epithelial attachments between muscle fibers and ECM at somite boundaries (Henry et al. , 2005;","Tendons, the tough connective tissues that link muscles to bones, are essential for lifting, running and other movements in animals. A matrix of proteins, called the extracellular matrix, connects the cells in a tendon, giving it the strength it needs to prevent muscles from detaching from bones during strenuous activities. To achieve this strength, extracellular matrix proteins bind to one another and to receptors on the muscle cell surface that are linked to its internal scaffolding, thereby organizing other proteins into a structure called a myotendinous junction. However, despite the essential roles of tendons, scientists do not fully understand how this organization occurs, or how it can go awry. Subramanian and Schilling screened zebrafish for genes that are essential for proper muscle attachment, and zeroed in on a",380,128,0.3368
pubmed-summarization,"level of 3.5 mmol / l . an acute abdominal series was obtained demonstrating free air below the right hemidiaphragm ( . 1 ) . the patient was subsequently boarded for an exploratory laparotomy with repair of perforated viscus , as that is the usual cause of pneumoperitoneum , especially under the right hemidiaphragm . because the patient 's vital signs stabilized after being resuscitated , the decision was made to obtain a ct scan to better assess the location of the perforated viscus . much to our surprise , the patient did not have a perforated viscus , but a splenic abscess that had ruptured causing the pneumoperitoneum ( . 2 ) . :ct scan demonstrating gas - forming splenic abscess and free air in the peritoneal cavity . ct scan demonstrating gas - forming splenic abscess and free air in the peritoneal cavity . the patient then became increasingly confused and her vital signs again deteriorated demonstrating worsening sepsis . the patient was taken to the operating room where a laparoscopic splenectomy was attempted but was quickly converted to laparotomy with splenectomy due to the gross contamination of the abdomen . the patient was continued on antibiotics and taken to the intensive care unit for post - operative care . the splenic abscess grew prevotella intermedia , a bacterium commonly found in the oral flora . the patient underwent a full work - up looking for the source of the splenic abscess . a transesophageal echocardiogram was performed but was negative for any masses , thrombus or vegetation . furthermore , a panorex was performed and was negative as the patient had reported tooth pain 1 week prior to her admission . she returned to the clinic on post - operative day 14 to receive her splenectomy vaccinations . although a rare disease , splenic abscess should be included on the differential diagnosis of a patient presenting to the hospital with peritonitis or pneumoperitoneum . this is especially true for patients who are immunocompromised or have underlying comorbidities including neoplasia , diabetes , trauma or history of splenic infarct or embolization . in our case , ct scan provided important information about the cause of our patient 's pneumoperitoneum , as we had assumed it was due to","we encountered a case of ruptured splenic abscess presenting as peritonitis and pneumoperitoneum . our patient did not have an underlying neoplasm nor was she immunosuppressed . in our case , splenectomy was the treatment of choice in combination with antibiotics , which proved to be a good outcome for the patient . work - up for the cause of the abscess was negative , although bacteria predominately found in the oral flora were isolated from the abscess . we strongly encourage that splenic abscess be considered on the differential diagnosis of patients presenting with pneumoperitoneum and peritonitis , although a clinical rarity .",380,104,0.2737
dialogsum,"#Person1#: Hello. #Person2#: Hello. Is Steve there? #Person1#: I'm sorry. He's not here right now. #Person2#: What time will he be back? #Person1#: Around five thirty. #Person2#: This afternoon? #Person1#: Yes. May I ask who's calling? #Person2#: This is his friend, Greg. #Person1#: Okay. I'll tell him you called. #Person2#: Thanks.",Greg calls Steve but he's not here. #Person1# will tell Steve Greg called.,51,13,0.2549
scientific_lay_summarisation-elife-norm,"BMP and Chordin protein stability (Inomata et al. , 2013). In this model, BMP and ADMP induce the secreted, highly diffusible and stable Chordin protease inhibitor Sizzled. This protects Chordin from proteolysis and promotes its expansion towards the ventral side. Over time the resulting inhibition of BMP signaling leads to decreased Sizzled production, destabilizing Chordin and relieving inhibition of BMP. In this way, an appropriate balance between ventral BMP and dorsal Chordin levels can be established even in differently sized embryos. In the ‘Self-regulating reaction-diffusion model’ (Model 4, — 1, Table 1), BMP and Chordin both have low diffusivities and equivalent protein stabilities. Interactions with highly mobile ADMP and Sizzled in two coupled reaction-diffusion networks eventually result in the restriction of BMP signaling activity on the ventral side, assuming an initial dorsal Chordin or ventral BMP bias (Francois et al. , 2009). Such a system self-regulates even with noisy initial conditions and could provide robustness during embryogenesis – e. g. , the ability of developing organisms to withstand noise in gene expression or fluctuating environmental conditions – that can be difficult to explain with other models. Finally, the prominent ‘Shuttling model’ (Model 5, — 1, Table 1) postulates that Chordin not only acts as an inhibitor of BMP, but also modulates the mobility and distribution of BMP protein (Ben-Zvi et al. , 2008; Barkai and Ben-Zvi, 2009; Ben-Zvi et al. , 2011b; Ben-Zvi et al. , 2014). In this model, BMP is poorly diffusive, Chordin is highly diffusive, and BMP mobility increases when bound to Chordin. Cleavage of the BMP/Chordin complex by the uniformly distributed protease Tolloid/Xlr combined with a flux of Chordin from the dorsal side is thought to ‘shuttle’ BMP towards the ventral side by facilitated diffusion over time. In this way, Chordin is responsible for the accumulation of BMP protein on the ventral side, and actively helps establish the subsequent ventral BMP signaling peak. These five conflicting models postulate different diffusion (no diffusion, equal diffusion, differential diffusion, facilitated diffusion) and stability properties of BMP and Chordin proteins (Table 1, — 1). However, these biophysical properties have not been fully measured experimentally, in part due to the lack of reagents and techniques to detect active BMP and Chordin in living vertebrate embryos. To test the biophysical tenets of","Animals start life as clumps of cells that ultimately give rise to complex structures and organs. Over a century of research has revealed a small number of proteins that are crucial for complex structures to form from these clumps, including one protein called BMP. Different levels of BMP instruct cells to give rise to different tissues. In zebrafish, BMP is more abundant on one side of the embryo than the other. This gradient in BMP levels causes different tissues to form at distinct positions and helps coordinate embryo development. Several theories have been proposed to explain how the BMP gradient is established. They all suggest that a second protein – Chordin – plays an important role in influencing how cells sense the BMP gradient by blocking BMP’s activity.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"In addition, mesenchymal stem cell proliferation is stimulated by adrenaline (Wu et al. , 2014). However, the when, how, and why these humoral factors are produced, circulated, and received during stem cell regulation remain to be elucidated. The ovaries of the fruit fly Drosophila melanogaster are an excellent model system on how stem cell lineages are shaped by both local niche signals and tissue-extrinsic signals (Drummond-Barbosa, 2019). D. melanogaster ovary is composed of 16–20 chains of developing egg chambers called ovarioles. The anterior-most region of which, known as the germarium, contains germline stem cells (GSCs) that give rise to the eggs (1A and B). GSCs are adjacent to the somatic niche cells, which comprises cap cells, escort cells, and terminal filament cells (1A). After GSC divides, one daughter cell that remains attached to the niche cells retains its GSC identity, whereas the remaining daughter cells are displaced away from the niche cells and differentiate into cystoblast (CB). Each CB then undergoes differentiation into 15 nurse cells and one oocyte in each egg chamber, which is surrounded by somatic follicle cells. GSC niche produces and secretes several local niche signals that regulate the balance between GSC self-renewal and differentiation (Hayashi et al. , 2020; Kirilly and Xie, 2007; Spradling et al. , 2011). For example, bone morphogenetic protein (BMP) ligands Decapentaplegic (Dpp) and Glass bottom boat (Gbb) are produced from the niche cells and directly activate BMP receptors in GSCs, leading to the repression of the differentiation inducer, bag-of-marbles (bam) (Morrison and Spradling, 2008; Zhang and Cai, 2020). Recent D. melanogaster GSC studies have also contributed to understanding of the systemic regulation of stem cell proliferation and maintenance in response to external environmental cues (Ables and Drummond-Barbosa, 2017; Drummond-Barbosa, 2019; Lin and Hsu, 2020; Yoshinari et al. , 2019). For example, protein restriction results in a reduction in GSC division, which is mediated by Drosophila insulin-like peptides (DILPs) (LaFever, 2005). In addition, nutrients influence GSC maintenance via the adipocyte metabolic pathway (Armstrong and Drummond-Barbosa, 2018; Matsuoka et al. , 2017). Besides nutrients, we have recently found out that mating is another external cue that significantly affects D. melanogaster GSC increase. Mated females show a dramatic increase in egg production, as well as GSC, which is induced by a male-derived peptide from","Stem cells have the unique ability to mature into the various, specialized groups of cells required for organisms to work properly. Local signals released by the tissues immediately surrounding stem cells usually trigger this specialization process. However, recent studies have revealed that external signals, such as hormones or neurotransmitters (the chemicals used by nerve cells to communicate), can also control the fate of stem cells. This is particularly the case during development, or in response to events such as injury. In the right conditions, germline stem cells can specialize into the egg or sperm required for many animals to reproduce. In fruit flies for example, the semen contains proteins that activate a cascade of molecular events in the female nervous system, ultimately resulting in female germline stem cells",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Mitochondrial fusion and fission affect the distribution and quality control of mitochondria. We show that Marf (Mitochondrial associated regulatory factor), is required for mitochondrial fusion and transport in long axons. Moreover, loss of Marf leads to a severe depletion of mitochondria in neuromuscular junctions (NMJs). Marf mutants also fail to maintain proper synaptic transmission at NMJs upon repetitive stimulation, similar to Drp1 fission mutants. However, unlike Drp1, loss of Marf leads to NMJ morphology defects and extended larval lifespan. Marf is required to form contacts between the endoplasmic reticulum and/or lipid droplets (LDs) and for proper storage of cholesterol and ecdysone synthesis in ring glands. Interestingly, human Mitofusin-2 rescues the loss of LD but both Mitofusin-1 and Mitofusin-2 are required for steroid-hormone synthesis. Our data show that Marf and Mitofusins share an evolutionarily conserved role in mitochondrial transport, cholesterol ester storage and steroid-hormone synthesis. Mitochondrial dynamics plays a critical role in the control of organelle shape, size, number, function and quality control of mitochondria from yeast to mammals (Westermann, 2009; Chan, 2012). It consists of fusion and fission of mitochondria, which are regulated by several GTPases (van der Bliek et al. , 2013). Mitochondrial fusion requires the fusion of the outer membrane followed by inner membrane fusion (Chan, 2012; Mishra et al. , 2014). In mammals, Mitofusin 1 (Mfn1) and Mitofusin 2 (Mfn2) regulate outer mitochondrial fusion whereas inner membrane fusion is controlled by Optic atrophy protein 1 (Opa1). Mitochondrial fission is regulated by Dynamin related protein 1 (Drp1) (van der Bliek et al. , 2013). Decreased fusion results in fragmented round mitochondria, while defective fission leads to fused and enlarged mitochondria (van der Bliek et al. , 2013). Loss of these mitochondrial GTPases results in lethality in worms, flies and mice (Chen et al. , 2003; Westermann, 2009; Debattisti and Scorrano, 2012). Mutations in the human DRP1 gene causes a dominant fatal infantile encephalopathy associated with defective mitochondrial and peroxisomal fission (Waterham et al. , 2007). On the other hand, missense mutations in OPA1 lead to a dominant optic atrophy (Alexander et al. , 2000; Delettre et al. , 2000). Depending on the severity of the mutation, patients may also suffer from ataxia and neuropathy (Yu-Wai-Man et al. , 2010). Also, missense mutations in MFN2 cause Charcot-Marie-Tooth type 2A,","Mitochondria are the main source of energy for cells. These vital and highly dynamic organelles continually change shape by fusing with each other and splitting apart to create new mitochondria, repairing and replacing those damaged by cell stress. For nerve impulses to be transmitted across the gaps (called synapses) between nerve cells, mitochondria need to supply the very ends of the nerve fibers with energy. To do this, the mitochondria must be transported from the main body of the nerve cell to the tips of the nerve fibers. This may not happen if mitochondria are the wrong shape, size or damaged. While searching for genetic mutations that disrupt nerve function in the fruit fly Drosophila, Sandoval et al. spotted mutations in a gene called Marf. Further investigations revealed",380,128,0.3368
dialogsum,"#Person1#: Very glad to know something about you, then what are you going to do when you finish. #Person2#: Oh, I'll go to shanghai to practice there. #Person1#: That's a good idea. It must be easy to find a job in shanghai. #Person2#: I think so, you know there is a great deal of opportunity for business there. #Person1#: And English is very useful in your job. #Person2#: I think it will be very useful in many ways. Beside, shanghai is an important trade center, not only in China, but also in the world, English is useful in almost all walks of life. #Person1#: You will be a very promising one. #Person2#: That's my wish.",#Person2# will go to shanghai to practice there and #Person1# thinks it's great. They think there are many opportunities for business in Shanghai and English is useful.,115,27,0.2348
dialogsum,"#Person1#: Hello. Is that Mr. Nelson? This is Linda speaking. #Person2#: Hello, Miss Linda. What can I do for you? #Person1#: I'm on my way to visit you now, but I've lost my way. #Person2#: That's too bad. Where are you now, Miss Linda? #Person1#: I don't know exactly. I think I'm somewhere on New Hampshire Street. I'm calling you from a bookstore. #Person2#: A bookstore on New Hampshire Street. It's at a corner, isn't it? #Person1#: Yes, it is. And I can see a restaurant at the other corner. #Person2#: Now I'm almost sure where you are. You turned at the second corner. You should have turned at the first corner from the railway station. #Person1#: Is that so? Then I'll go back to the first corner. #Person2#: It'll be better that way. You'll find a one-way traffic sign. That's where you have to turn to the left. Come up the slope to reach a six-storied apartment house. My room is on the third floor. #Person1#: I'm sure I won't have any trouble this time. Thanks. #Person2#: I'll be waiting for you. Bye.",Linda lost her way to visit Nelson so she calls to tell him she is in a bookstore. Nelson knows where Linda is and directs Linda to reach a six-storied apartment house.,184,32,0.1739
pubmed-summarization,"in postmortem studies , dementia with lewy bodies ( dlb ) accounts for 1020% of all cases of dementia and can therefore be regarded as the second most common cause of dementia after alzheimer 's disease ( ad ) . for a definite diagnosis , autopsy is required . however , confirmation of the diagnosis during the patient 's lifetime is both reasonable and important , since patients with dlb respond to acetylcholine esterase inhibitors and furthermore demonstrate a hypersensitivity to antipsychotic treatment . clinical consensus criteria from 1996 possess a fairly high specificity with 8090% , but only a low sensitivity , decreasing to 30% according to some studies . an improvement in clinical accuracy particularly when ad is part of the differential diagnosis seems to be worthwhile . in postmortem studies , a 5790% loss of presynaptic dopamine transporters could be demonstrated in dlb but not in ad . the presence a dopaminergic abnormality in dlb including striatal dopaminergic transporter loss was outlined in vivo with positron ( pet ) and single - photon emission computed tomography ( spect ) . on the grounds of these observations , a positive , i.e. abnormal , fp - cit - spect was included as a feature suggestive of dlb in the revised clinical consensus criteria from 2005 . sensitivity could thereby be increased up to 81.3% . moreover , in a follow - up study over a period of 1 year , it was shown that in case of clinical suspicion , an fp - cit scan may be helpful . of 19 patients initially diagnosed as having possible and after 1 year as having probable dlb , 12 patients ( 63.2% ) had pathological fp - cit - spect , while the remaining 7 cases that were assessed as non - dlb at the 1-year follow - up had normal datscan ( 100% specificity ) . another challenge in differential diagnosis resides in the distinction between parkinson 's disease and dementia ( pdd ) . it is still an open question whether the underlying neurobiological changes result from one and the same mechanism in both entities . fp - cit - spect is abnormal in both dlb and pdd , possibly with a lower dopamine transporter uptake in pdd","clinically , alzheimer 's disease ( ad ) is by far the most common cause of dementia . criteria for the diagnosis of dementia with lewy bodies ( dlb ) are highly specific but not at all sensitive , which is reflected by the higher number of dlb cases detected histopathologically at autopsy . imaging of dopamine transporter with fp - cit spect is one possibility to increase sensitivity . pathological confirmation was also included in the revised consensus criteria for the diagnosis of dlb . however , in the absence of parkinsonism , one of the core features , a clinical diagnosis of ad is more likely . the role of fp - cit spect in dlb diagnosis remains to be clarified . based on our 3",380,128,0.3368
dialogsum,"#Person1#: Hello? Beechgrove School? This is Mr. Holloway speaking. Brad Holloway. I'm ringing about my son Michael. He came home yesterday and said he'd been in trouble at school with his P. E. teacher, Miss Sanderson. She said he didn't have the right kit for P. E. Everyone else thought it was all highly amusing, of course, and Michael was very embarrassed about it. Perhaps I could speak to the Headmistress. #Person2#: She's engaged at the moment, I'm afraid. This is her secretary. #Person1#: I can hold on for a while if she's going to be free soon... #Person2#: I have a feeling she's going to be busy all morning, Mr. Holloway. She's at a Governors' meeting. It could go on for a very long time... #Person1#: Oh. Well, in that case, perhaps you could help me. #Person2#: Of course. What form is Michael in? #Person1#: He's a first year. He's in 1B. His form teacher's Mr. Hopkins. #Person2#: And what kit should Michael have brought with him? #Person1#: Well that's the point. In the school information booklet it says black shorts and blue singlet, with black or blue plimsolls. So that's what we bought him. We went to the sports shop the school actually recommends. You know, Atlas Sports, West Street. #Person2#: I'm just looking at the information booklet, Mr. Holloway. There seems to have been some mistake. #Person1#: I thought so. Maybe you could point it out to Miss Sanderson. #Person2#: What Michael came to school with was the senior girls' basketball kit. #Person1#: What? How on earth could that have happened? It says quite clearly in the booklet, black shorts and blue vest. I've got it in front of me. #Person2#: You're looking at the top of Page 11, aren't you? #Person1#: That's right. #Person2#: Well, unfortunately the layout of the booklet is a bit misleading. If you look at the bottom of the previous page you'll see it says Boys' Kit in the left-hand column and Girls' Kit in the right-hand one, but when you turn over the page it's not difficult to forget which column was which because the headings aren't repeated. #Person1#: So it looks as though were going to have to write another cheque... #Person2#: I'm afraid so. #Person1#: Oh well. Anything for","Mr. Holloway phones the Headmistress to talk about his son Michael's trouble at school. His P. E. teacher, Miss Sanderson said Michael's kit wasn't right for P.E. class, which everyone in the class found amusing and Michael was embarrassed. The secretary answers the phone and helps Mr. Holloway out what Michael was wearing was the senior girls' basketball kit because of the booklet's misleading.",380,64,0.1684
pubmed-summarization,"the operation . we present the case of an 85-year - old white female who was diagnosed with a cholecystocutaneous fistula that developed as a complication following removal of a percutaneous drain that was used to treat her acute cholecystitis . re - occurrence of her cholecystitis after drain removal and the presence of gallstones promoted the production of a fistula along the pre - existing tract of the drain . her concurrent treatment with anticoagulants for a pulmonary embolism delayed the definitive management of her cholecystitis and fistula . fortunately , the patient remained in reasonably good health throughout the waiting period from time of fistula diagnosis to surgery . more conservative approaches such as percutaneous cholecystotomy have been used in high - risk patients , leading to spontaneous closure of the fistula . however , in this case the fistula developed through the old drain tract , so surgical intervention was employed . as with uncomplicated cholecystitis , laparoscopic techniques are favorable compared to open surgery and thus a laparoscopic cholecystectomy was undertaken in this case . the gallstones removed during cholecystectomy were of orange - brown color consistent with cholesterol stones . although fistula formation is now a rare complication of cholecystitis , it remains a possibility and should be considered in the differential diagnosis of any fistulous tract in the right abdominal wall . we have demonstrated that previous percutaneous drainage of an acute gallbladder infection can promote the formation of such a fistula if the infection is not properly dealt with or re - occurs . physicians should be prepared to recognize this complication in patients after drain removal and prior to definitive surgery .","cases of cholecystocutaneous fistulas are now a rare occurrence as a result of rapid diagnosis and treatment . we present a case of cholecystocutaneous fistula developing after the removal of a percutaneous drain for the treatment of acute cholecystitis . re - occurring infection and presence of gallstones led to fistulization of the gallbladder fundus and the development of a tract along the path created by the drain . the patient presented with re - occurring right upper quadrant abdominal pain , purulent discharge from the fistulous opening and expulsion of multiple gallstones . she underwent laparoscopic cholecystectomy and fistula excision .",280,102,0.3643
pubmed-summarization,"ct of thorax , abdomen and pelvis . although surveillance studies proved negative initially for disease recurrence , a routine ct thorax , abdomen and pelvis at twenty three months post initial presentation revealed left sided para aortic lymphadenopathy and two suspicious splenic lesions measuring 2.7 2.5 cm and 2.4 2.2 cm respectively which were not present on imaging , performed twelve months previously ( . 2 a and b ) . the splenic lesions were biopsied under ultrasound guidance using an 18 gauge tru cut needle without complication ( . subsequent histology of the biopsied lesions revealed normal splenic parenchyma infiltrated by poorly differentiated adenocarcinoma with abundant signet ring cells , morphologically identical to the initial presentation with an obstructing caecal tumour ( . the disease although of low burden and primarily localised to the spleen was associated with the presence of suspicious para aortic lymphadenopathy prompting chemotherapy rather than operative intervention . the oncology team advised further systemic chemotherapy comprising 5 fluorouracil , oxaliplatin and avastin . the patient remains well on chemotherapy and further imaging studies are planned in 4 months time to assess response to treatment . metastases to the spleen from any primary tumour are rare despite the highly vascular nature of the organ and it 's proximity to many potential primary sites including the pancreas , stomach , lung , breast and the colon . a number of theories have been put forward to explain the hostile nature of the spleen preventing tumour implantation and proliferation of neoplastic cells . anatomical features thought to play a role include the sharp angle at the origin of the splenic artery with the coeliac axis , the rhythmic contraction of splenic sinusoids and the scarcity of lymphatic vessels extending to the intrasplenic parenchyma . immunological factors considered to negatively impact on the rate of malignant cell implantation include the presence of abundant kupffer cells , immunoglobin synthesis and opsonin production . in most of the reported cases of colorectal metastases to the spleen , the primary tumour is located on the left side of the colon or in the rectum . this distribution of colorectal metastases favours the theory that neoplastic cells reach the spleen via retrograde dissemination through the inferior mesenteric vein . to the best","introductionthe spleen is a highly vascular organ and is in close proximity to many potential primary sites such as the stomach , breast , pancreas and colon . it is however an unusual site for metastatic disease . the reasons for this are not fully understood at the present time . a number of hypotheses have been postulated . definitive diagnosis and subsequent treatment of metastatic disease to the spleen presents a number of challenges for the surgeon and the wider multi disciplinary team.presentation of casea 60 year old male presented with a three week history of lower abdominal pain , distension , nausea and a palpable mass in the right iliac fossa . imaging revealed a large circumferential caecal mass consistent with malignancy with secondary small bowel",380,128,0.3368
dialogsum,"#Person1#: How's your new car? #Person2#: Perfect! Couldn't be better. #Person1#: You made a good choice, then? #Person2#: It's just what I want. #Person1#: No regrets? #Person2#: I am really pleased with it. #Person1#: I am glad you are happy. #Person2#: It's super.",#Person1# is glad #Person2# is pleased with the new car.,43,10,0.2326
dialogsum,"#Person1#: You're a big fan of Andy Lau, aren't you? #Person2#: Yes, I've been got all his albums and most of his films on dvd. I adore him. He's my idol. #Person1#: How come you don't have all of his films on dvd? #Person2#: Some of his early films are hard to find nowadays, especially the ones where he only played a bit part. #Person1#: I see. I'm sure you'll find them one day. I see you also have several poster of him. #Person2#: Yes. These posters are new. I bought them last week and put them up on my bedroom walls yesterday. #Person1#: Are you a member of his fan club? #Person2#: I was, but then I discovered you can find out everything for free on the internet, so I'm not a member now. #Person1#: Did you see the interview with Andy Lau in cosmopolitan magazine last month? #Person2#: Of course! I bought two copies. #Person1#: Two copies? One to keep and one to cut the pictures out of, right?",#Person2# is a big fan of Andy Lau and shares with #Person1# how much #Person2# likes Andy Lau.,171,18,0.1053
dialogsum,"#Person1#: Good afternoon. madam. How can I help you? #Person2#: Someone has stolen my cell phone. #Person1#: I am sorry to hear that. Would you mind coming with me to my office and tell me what exactly happened there? #Person2#: OK. I left my cell phone in my room this morning before I want out. When I come back it was gone. I have looked every where in my room and I can't find it. #Person1#: Well, in that case. I will call the manger, you can talk directly with him.",#Person2#'s cell phone was stolen and #Person2# reports the details to #Person1#.,91,12,0.1319
dialogsum,"#Person1#: Today we are going to discuss how to write better. #Person2#: Excuse me. #Person1#: Ah, Tom, you're late again. #Person2#: I'm sorry, Mrs. Green. #Person1#: What's the excuse this time? #Person2#: I must have turned off my alarm clock and gone back to sleep again. #Person1#: If you had gone to bed earlier, you wouldn't be late for school now. #Person2#: Last night I did my homework until midnight. #Person1#: So, where is it? #Person2#: Oh, I just don't know what to say. I can't tell you how sorry I am. #Person1#: This is the third time you've been late for my class and the sixth time you forgotten to bring your homework this month. #Person2#: I'm really sorry. I promise it won't happen again. Please forgive me. #Person1#: OK. I hope this is the last time. Go to your seat. #Person2#: Thank you, ma'am.",Tom is late for school and forgets to bring his homework again. He explains that he must have turned off his alarm clock. Mrs. Green forgives him.,146,27,0.1849
scientific_lay_summarisation-elife-norm,"1991; Kobayashi, 2010; Fages et al. , 2017; Katz and Springer, 2016; Katz et al. , 2018). But single-celled organisms operate in a severely hardware-limited regime rarely probed by neuroscience. Streamlined by evolution, bacterial genomes quickly shed any unused complexity. Whether we could expect learning-like behaviors from bacteria depends on whether useful networks could be simple enough to plausibly be beneficial. Known examples of phenotypic memory, for example, when the response is mediated by a long-lived protein, can be interpreted as a simple form of learning (Lambert et al. , 2014; Hoffer et al. , 2001); circuits capable of adapting to the current mean of a fluctuating signal, as in bacterial chemotaxis (Barkai and Leibler, 1997), also belong in this category. Prior theory work has also proposed that simple genetic circuits could learn more subtle binary features, such as a (transient) presence or absence of a correlation between two signals (Sorek et al. , 2013). Here, we show that a simple generalization of a ubiquitous regulatory motif, the end-product inhibition, can learn, store, and ‘act upon’ the information on continuous-valued features such as timescales and correlations of environmental fluctuations, and moreover, can do so near-optimally. We identify the key ingredients giving rise to this behavior, and argue that their applicability is likely more general than the simple metabolically inspired example used here. For a simple model capturing some of the challenges of surviving in a fluctuating environment, consider a situation where some internal physiological quantities P→= (P1, …, PN) must track fluctuating external variables D→= (D1, …, DN). For example, the expression of a costly metabolic pathway would ideally track the availability of the relevant nutrient, or the solute concentration in the cytoplasm might track the osmolarity of the environment. In abstract terms, we describe these environmental pressures by the time-dependent D→⁢ (t), and postulate that the organism fitness is determined by the average mismatch -⟨∑i=1N (Pi-Di) 2⟩, a quantity we will henceforth call ‘performance’. Here and below, angular brackets denote averaging over time. In this simple model, a given static D→ clearly defines a unique optimal state P→; the regulatory challenge is entirely due to D→ being a fluctuating quantity. The challenges faced by real organisms are certainly vastly more rich: even in the static case, the optimal behavior","Associations inferred from previous experience can help an organism predict what might happen the next time it faces a similar situation. For example, it could anticipate the presence of certain resources based on a correlated environmental cue. The complex neural circuitry of the brain allows such associations to be learned and unlearned quickly, certainly within the lifetime of an animal. In contrast, the sub-cellular regulatory circuits of bacteria are only capable of very simple information processing. Thus, in bacteria, the ‘learning’ of environmental patterns is believed to mostly occur by evolutionary mechanisms, over many generations. Landmann et al. used computer simulations and a simple theoretical model to show that bacteria need not be limited by the slow speed of evolutionary trial and error. A basic regulatory circuit could,",380,128,0.3368
pubmed-summarization,"therefore , developed to support coverage 24 hours a day , 7 days a week . initially , this employed static images run in a store - and - forward mode . communication was limited to a private network using a thick client - server architecture between the host ( e.g. , italy ) and upmc consulting pathologists . analysis of early ( 14-month period ) accrued data for 102 transmitted cases showed full agreement with the original diagnosis in 86% of cases . for cases with disagreement ( 14% ) , 8 resulted in minor and 3 clinically significant differences in opinion . subsequently , during the 12-year partnership between upmc and ismett , approximately 3000 cases have been reviewed by telepathology . teleconsultation using static images improved with respect to workflow with only infrequent discrepancies being noted . this first generation home - grown static telepathology system has since been replaced by second generation dynamic robotic microscopy ( nikon coolscope streaming ) , third generation hybrid rapid virtual microscopy ( trestle live viewing ) , and most recently , in 2009 , with fourth generation wsi ultra - rapid virtual microscopy ( mirax midi ) [ ] . with better technology allowing pathologists to view entire slides at high resolution , the performance of telepathology has improved . however , we did not change to these newer technologies until these approaches were proven to be technically feasible . although static images were quicker to read than robotic microscopy , being limited to specific field of views forced evolution . the evolution from static imaging to a wsi scanning system was necessitated due to the lag time required for robotic objective magnification changes and positional adjustments of the slide . with wsi scanning , these magnifications are digitally incorporated into the resultant image , as such the time required for biopsy interpretation was greatly reduced . secondly , configuring the wsi system with a high numerical aperture ( na ) objective ( e.g. , 40x , 95na ) enabled an image resolution that maximized image clarity ( detail ) , therefore , reducing eye fatigue of the reviewing pathologist , enabling longer review sessions . lower resolution imagery ( e.g. , 25 micron ) forces the human eye to","several modes of telepathology exist including static ( store - and - forward ) , dynamic ( live video streaming or robotic microscopy ) , and hybrid technology involving whole slide imaging ( wsi ) . telepathology has been employed at the university of pittsburgh medical center ( upmc ) for over a decade at local , national , and international sites . all modes of telepathology have been successfully utilized to exploit our institutions subspecialty expertise and to compete for pathology services . this article discusses the experience garnered at upmc with each of these teleconsultation methods . static and wsi telepathology systems have been utilized for many years in transplant pathology using a private network and client - server architecture . only minor clinically significant differences",380,128,0.3368
pubmed-summarization,"was that soluble ctla-4 might block proliferation by gumming up b7 's interaction with cd28 . and the ctla-4 antibody might enhance proliferation not because it stimulates clta-4 's proliferative power , but because it blocks ctla-4 's negative signal . this alternative role for ctla-4 was supported by the work of james allison and his team at the university of california ( berkeley , ca ) , which was also published in the jem ( 7 ) . this group studied cross - talk among tcr , cd28 , and ctla-4 by cross - linking these receptors . t cells proliferated when the tcr was linked to cd28 , but not with ctla-4 . t cell proliferation was greatly reduced when all three receptors were cross - linked simultaneously , suggesting that ctla-4 inhibits cd28 costimulation . the generation of ctla-4 knock - out mice finally put the conflict to rest . these animals develop a fatal t cell proliferative disorder , as their t cells lack the brakes to hold them in check ( 8) . one benefit of enhancing t cell responses via ctla-4 blockade is the strengthening of antitumor immunity . allison 's team found that tumor - transplanted mice injected with antibodies that block ctla-4 activity rejected several different types of tumors and had long - lasting antitumor immunity ( 9 ) . human anti - ctla-4 mabs are now in phase iii clinical trials against melanoma and renal carcinomas . the t cell inhibiting soluble ctla-4 originally defined by linsley and ledbetter is now used to treat autoimmune diseases such as rheumatoid arthritis .","ctla-4 was first identified in 1991 as a second receptor for the t cell costimulation ligand b7 . uncertainties about its biological function plagued the early years after its discovery until 1995 , when it was confirmed to be an inhibitor of t cell responses . ctla-4 has since scored in the clinic as a target for antitumor therapy and as a soluble inhibitor of autoimmunity .",270,67,0.2481
pubmed-summarization,"maintaining the microsurgical field , free from flooding with irrigation fluid , is important to get good vessel approximation in microsurgery . the commonly followed practice is to keep dry gauze at the periphery of the field so as to siphon off the excessive fluid . a certain amount of the irrigation fluid still remains in the field and causes adhesion of the suture material with the anastomotic clamp or the background material or to the vessel wall and thereby frustrating the surgeon while applying the microknots . we present our technique that avoids the aforementioned , and in addition provides a good platform to perform microvascular anastomosis . this is folded over a dry gauze and then fenestrations are made in the surface and on the two margins [ ] of the glove component so as to provide for continuous drainage of the irrigation fluid to the gauze . the tip of the infant feeding tube ( size 4 ) is then passed in to the gauze [ ] and the whole assembly is then placed in the microsurgical field deep to the vessels to be anastomosed and thus provides a platform for the microanastomosis . the vessels to be anastomosed are laid over a background on the platform and then the proximal part of the feeding tube is connected to a suction system so as to provide continuous suctioning of the irrigation fluid that keeps the microsurgical field clean and dry and also by keeping away the tip of the feeding tube from the surgical field [ ] . the wrist part of the glove with open ends and fenestrations on the surface to facilitate siphoning off of the irrigation fluid the tip of a size 4 infant feeding tube is passed between the layers of gauze the entire assembly is shifted to the neck for anastomosis forming a good platform for anastomosis . the proximal end of the infant feeding tube is connected to the suction tube the wrist part of the glove component has been described in the past to transfer the pedicle of the flap from the oral cavity to the neck for microanastomosis and in this report we present a technique in which the component can be used to keep the operative field clean","during microvascular anastomosis , it is important to maintain the microsurgical field irrigated yet dry so as to achieve a good view of the vessels for approximation . in this method , an infant feeding tube ( size 4 ) , with its tip sandwiched between layers of dry gauze and a surgical glove component placed in the anastomotic field and the other end connected to a suction apparatus , is used to maintain the microsurgical field free from flooding . it also has the additional advantage of providing a stable platform for microvascular anastomosis .",380,96,0.2526
dialogsum,"#Person1#: Is it really all you can eat for only $12.50? That price is not bad. #Person2#: That's what the sign says, but take your time. Otherwise, you might become ill. #Person1#: Ill from the food here? #Person2#: Yes, if you eat too much food too fast, you might start to feel sick. #Person1#: Wow, I never thought about that. Any other advice? #Person2#: Yes, try the cherry pie. It's delicious. #Person1#: I don't like sweets. I will stick to the meat and vegetables.","#Person2# warns #Person1# not to eat too fast and recommends the cherry pie, but #Person1# don't like sweets.",84,18,0.2143
scientific_lay_summarisation-elife-norm,"Behavioral plasticity is widespread in swarming animals, but little is known about its underlying neural and molecular mechanisms. Here, we report that a neuropeptide F (NPF) /nitric oxide (NO) pathway plays a critical role in the locomotor plasticity of swarming migratory locusts. The transcripts encoding two related neuropeptides, NPF1a and NPF2, show reduced levels during crowding, and the transcript levels of NPF1a and NPF2 receptors significantly increase during locust isolation. Both NPF1a and NPF2 have suppressive effects on phase-related locomotor activity. A key downstream mediator for both NPFs is nitric oxide synthase (NOS), which regulates phase-related locomotor activity by controlling NO synthesis in the locust brain. Mechanistically, NPF1a and NPF2 modify NOS activity by separately suppressing its phosphorylation and by lowering its transcript level, effects that are mediated by their respective receptors. Our results uncover a hierarchical neurochemical mechanism underlying behavioral plasticity in the swarming locust and provide insights into the NPF/NO axis. Swarming occurs in a wide variety of animal taxa, including insects, fish, birds, and mammals. Individuals benefit from swarming in many aspects, including food searching, territory selection, and defense (Okubo, 1986; Weaver et al. , 1989). Typically, to maintain the required fission–fusion dynamics, swarming animals exhibit striking behavioral plasticity of different types (Snell-Rood, 2006; Szyf, 2010). Biochemical changes in the levels of neuromodulators, such as monoamines, neuropeptides, and neurohormones, are able to induce behavioral variation thus mediate behavioral plasticity (Freudenberg et al. , 2015; Godwin et al. , 2015; Zupanc and Lamprecht, 2000). Nevertheless, the molecular basis by which neural factors orchestrate behavioral plasticity in swarming animals is poorly understood in detail. Neuropeptides, a group of chemically diverse neural modulators, affect a broad range of physiological and behavioral activities (Lieberwirth and Wang, 2014; Nässel, 2002). Accumulating evidence shows that neuropeptides serve as conserved neuronal signals that modulate animal behaviors in social contexts (Lieberwirth and Wang, 2014; Nilsen et al. , 2011). These peptides exert their actions by binding to specific membrane receptors, most of which are G-protein-coupled receptors (Quartara and Maggi, 1997). The binding initiates a second-message cascade unique for each receptor and results in a distinct molecular response (Hökfelt et al. , 2003). It has been revealed that neuropeptides can induce plasticity in a series of behavioral processes, including sensory detection (Shankar et al. , 2015),","Migratory locusts are widespread throughout the Eastern Hemisphere, especially in Asia, Australia and Africa. Although usually solitary insects, locusts can also form swarms made up of millions of individuals, which can devastate crops. Swarming can be studied on a smaller scale in the laboratory by forcing locusts to crowd together. This causes the locusts to enter a so-called gregarious state in which they are more active and sociable, which in turn promotes swarming. Isolating individual locusts has the opposite effect, causing the insects to enter a solitary state in which they are less active. Chemicals in the locust brain called neuropeptides control phase transitions between solitary and gregarious behavior. Neuropeptides bind to specific proteins called receptors in the outer membranes of neurons and initiate unique signaling cascades inside",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Neonatal inflammation is common and has lasting consequences for adult health. We investigated the lasting effects of a single bout of neonatal inflammation on adult respiratory control in the form of respiratory motor plasticity induced by acute intermittent hypoxia, which likely compensates and stabilizes breathing during injury or disease and has significant therapeutic potential. Lipopolysaccharide-induced inflammation at postnatal day four induced lasting impairments in two distinct pathways to adult respiratory plasticity in male and female rats. Despite a lack of adult pro-inflammatory gene expression or alterations in glial morphology, one mechanistic pathway to plasticity was restored by acute, adult anti-inflammatory treatment, suggesting ongoing inflammatory signaling after neonatal inflammation. An alternative pathway to plasticity was not restored by anti-inflammatory treatment, but was evoked by exogenous adenosine receptor agonism, suggesting upstream impairment, likely astrocytic-dependent. Thus, the respiratory control network is vulnerable to early-life inflammation, limiting respiratory compensation to adult disease or injury. At birth, neonates transition from a sterile maternal environment into an environment filled with pathogens, microbes, and toxins and must simultaneously begin robust, rhythmic breathing. Respiratory problems represent a significant clinical problem for neonatologists (Martin et al. , 2012), especially in preterm infants where breathing is unstable (Poets and Southall, 1994; Poets et al. , 1994) and infections are common (Stoll et al. , 2002; Stoll et al. , 2004). Further, inflammation appears to augment respiratory dysfunction in neonates, whereby inflammation depresses hypoxic responses (Olsson et al. , 2003; Rourke et al. , 2016) and induces recurrent apneas (Hofstetter et al. , 2007). Despite the prevalence of early life inflammation, little is known about the long-lasting consequences of neonatal inflammation on adult neurorespiratory control. We are beginning to understand the potential for long-term consequences of early life inflammation in other physiological systems. Neonatal inflammation blunts adult immune function (Bilbo et al. , 2010; Mouihate et al. , 2010; Spencer et al. , 2011), increases adult stress reactivity (Shanks et al. , 2000; Wang et al. , 2013; Grace et al. , 2014), impairs adult learning and hippocampal plasticity (Bilbo, 2005a; Bilbo et al. , 2006), increases the risk of neuropsychiatric disorders (Rantakallio et al. , 1997; Hornig et al. , 1999), and worsens age-related cognitive decline (Bilbo, 2010). Yet, we know very little about the long-term effects of neonatal inflammation","Breathing is essential to life. At birth, the brain quickly adapts and learns to control breathing in different situations. This adaptability is called neuroplasticity. Most breathing-related adjustments in the brain are short-term, like breathing faster during exercise. The brain can also learn from prior experience to prepare for future situations. For example, intermittent exposure to low oxygen causes long-term changes in signals from the brain to muscles controlling breathing, which may help them prepare for future low oxygen situations. This is called long-term facilitation (LTF). This neuroplasticity may also help the brain to compensate or stabilize breathing during an illness or injury. Illnesses shortly after birth can affect how the brain controls breathing and may contribute to respiratory diseases later in life. They may also have lasting effects",380,128,0.3368
dialogsum,#Person1#: I heard that James was fired because he got a keep back of 20 thousands dollars from a vender. #Person2#: That's open secret. #Person1#: But mine could be a lie for his job. #Person2#: How did you know that? #Person1#: A little bird whispered to me. Keep that to yourself.,#Person1# tells #Person2# James was fired because he got a keep back of money.,51,14,0.2745
scientific_lay_summarisation-elife-norm,"channels plays a key role in regulating the magnitude of Ca2+ influx. The general consensus is that CDF and CDI involve Ca2+ binding to calmodulin (CaM) in the IQ domain in the C-terminal tail of these channels. During excitation-contraction (EC) coupling, membrane depolarization opens CaV1. 2 channels in the sarcolemma of ventricular myocytes. This allows a small amount of Ca2+ to enter ventricular myocytes that can be detected optically in the form of a ‘CaV1. 2 sparklet’, raising local [Ca2+]i beyond the threshold for activation of ryanodine receptors (RyRs) in the sarcoplasmic reticulum (Wang et al. , 2001). Synchronous activation of multiple RyRs by CaV1. 2 channels produces a global rise in [Ca2+]i that initiates myocardial contraction (Cheng et al. , 1993). EC coupling in ventricular myocytes is remarkably reproducible, with each action potential (AP) invariably evoking a whole-cell [Ca2+]i transient that results in contraction. At the membrane potentials reached during the plateau of the ventricular AP (approximately +50 mV), the driving force for Ca2+ entry at physiological Ca2+ levels (∼2 mM) is so low that opening of a single CaV1. 2 channel is not sufficient to raise local [Ca2+]i beyond the RyR activation threshold. However, the probability of RyR activation during this phase of the AP is very high (>0. 9). This degree of reliability would presumably require 5–10 CaV1. 2 channels to open simultaneously (Inoue and Bridge, 2003; Sobie and Ramay, 2009). However, because the maximum open probability (Po) of CaV1. 2 channels at physiological [Ca2+]o is ∼0. 3 (Josephson et al. , 2010), the probability of 5–10 independently gating channels opening simultaneously is extremely low (i. e. , 0. 35 to 0. 310). This raises a fundamental question: if the probability of coincident openings of the requisite number of CaV1. 2 channels is so low, why is the probability of RyR activation during the cardiac AP so high? Answering this question is critical for understanding the mechanistic basis of reliable cardiac performance. A potential answer to this conundrum lies in the recently proposed concept that clusters of Cav1. 2 channels can be functionally coupled to one another through physical interactions between their C-terminal tails (Dixon et al. , 2012). This interaction enables physically linked channels to coordinate their gating, leading to amplification of Ca2+ influx, Ca2+ current","To pump blood around the body, the muscle cells within the heart must contract and relax together with a regular rhythm. A contraction begins when proteins called CaV1. 2 channels embedded in the cell membranes of heart cells open to allow calcium ions to enter the cells. The calcium ions that enter through these CaV1. 2 channels trigger the release of calcium ions from storage compartments within the cells, which leads to the heart contracting. However, to trigger this release of calcium ions, many CaV1. 2 channels have to open at the same time and we do not yet know how this is co-ordinated. Dixon et al. studied CaV1. 2 channels in heart muscle cells from mice. The experiments show that these proteins are arranged in clusters of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Immunogold electron microscopy revealed that ACh and glutamate vesicular transporters colocalize in a significant fraction of SVs in the central IPN (IPC). Patch clamp recordings showed that glutamatergic miniature excitatory postsynaptic currents (mEPSCs) were smaller in IPC neurons of ChAT-cKO, but unchanged in neurons of the lateral IPN (IPL) which receives non-cholinergic input, indicating that glutamate release is reduced in the absence of ACh. Upon ACh or nicotine superfusion, wild-type (wt) IPC neurons displayed an increased frequency of mEPSC. In ChAT-cKO slices this response was not observed, indicating that presynaptic facilitation of glutamate release is impaired. Direct measurements of glutamate reuptake into IPN SVs in the presence and absence of ACh demonstrated vesicular synergy. Behaviorally, ChAT-cKO mice were insensitive to the rewarding properties of nicotine and displayed no withdrawal signs after cessation of chronic nicotine treatment. Our results, therefore, establish an essential role for ACh corelease with glutamate in habenular neuron function and reveal an additional mechanism that may play an important role in nicotine dependence. CHAT is the only enzyme that synthesizes ACh, and it is expressed at the neuromuscular junction and in several brain areas including the MHb, basal forebrain (BF), laterodorsal tegmental nucleus (LDTg), third cranial nerve (3N) and nucleus of the solitary tract (NTS) (1A). Null mutant mice for Chat obtained by crossing a floxed allele of the Chat gene (Chatflox/flox) to β-actin-Cre transgenic mice die at birth (Misgeld et al. , 2002). Therefore to elucidate the contribution of cholinergic transmission to the function of the MHb-IPN pathway, we sought to conditionally delete Chat in habenular neurons. To drive Cre-recombinase activity specifically to MHb cholinergic neurons we analyzed their translational profile (Gorlich et al. , 2013) and selected the Kiaa1107-Cre mouse BAC transgenic line for its specific pattern of expression in the MHb (GENSAT, www. gensat. org; 1A). Kiaa1107-Cre mice were crossed to reporter Gt (ROSA) 26Sortm1 (EYFP) Cos mice (1B) to verify that EYFP expression resulting from Cre-recombinase activity was achieved in MHb neuron somata and habenular axonal projections in the IPN (1C). Double immunostaining with CHAT and EYFP antibodies in Kiaa1107-Cre mice crossed to reporter Gt (ROSA) 26Sortm1 (EYFP) Cos mice (1D) demonstrated that 99% (1912 of 1933) of CHAT positive neurons in the MHb are positive for the EYFP reporter. In contrast, CHAT","Neuroscientists are making progress in understanding the brain regions and neural circuits that are involved in reward and addiction. One such region, called the habenula, is found near the center of the brain and sends nerves to another brain region called the interpeduncular nucleus (or IPN for short); this creates a neural circuit that is important for the brain’s responses to nicotine. The habenular-IPN circuit is rich in receptors for a neurotransmitter called acetylcholine. These receptors are also activated by nicotine, the addictive component of tobacco. Neurotransmitters are chemicals that transmit a signal from one nerve to another. These chemicals are packaged into small structures called vesicles, which are found at nerve endings. When a nerve impulse reaches the end of a nerve, it triggers the release of",380,128,0.3368
dialogsum,"#Person1#: Mrs. Miller, you are an old friend of ours. In order to encourage future business and as a gesture of friendship, we are prepared to cut our price by 5 %. Will that satisfy you? #Person2#: That's great. Thank you for making this concession. I accept. #Person1#: Now I repeat, 5, 000 transistor sets, specifications as shown in our catalogue at $ 20 each C. I. F. Los Angeles. #Person2#: Good. Now that the price is decided on, we can discuss the packaging. #Person1#: As to packaging, we'll pack them two dozens to one carton, gross weight about 25 kilos a carton. #Person2#: Carton? #Person1#: Yes, corrugated cardboard boxes. #Person2#: Could you use wooden cases instead? #Person1#: Why use wooden cases? #Person2#: I'm afraid the cardboard boxes are not strong enough for ocean transportation. #Person1#: Cartons are comparatively light, and there fore easy to handle. They'll not be stowed away with the heavy cargo. Besides, we'll reinforce the cartons with metal straps. #Person2#: All right. Carton or no carton, the packaging must be waterproof as well as strong enough to stand shock and rough handling. #Person1#: You needn't worry about that. Cartons are extensively used in our shipments to foreign countries and there have never been complaints from our clients. Now, as regards payment, we have agreed to use dollars, am I right? #Person2#: That's right. As soon as I get home, I'll see about the opening of the letter of credit. #Person1#: Please open the letter of credit 15 to 30 days before the date of delivery so that we'll have enough time to make all the necessary arrangements. Another thing, the L / C should be valid until the 15th day after shipment. #Person2#: No problem. That can be done. I understand you'll ship the goods before the end of May? #Person1#: Right. We'll ship the goods according to the agreed time schedule. Last, but not least, the inspection is to be carried out by Houston Commodities Inspection Bureau, which is final and binding on both parties. #Person2#: Yes, we agreed to that. We have great confidence in your inspection institution. Through years of dealing with you, we've convinced of your commercial integrity. #Person1#: Thank you. You can rest assured that we'll do everything possible to prevent",#Person1# offers to cut the price by 5% and Mrs. Miller is satisfied with this. They discuss the way of packaging and the opening time of the letter of credit. #Person1# will ship the goods according to the agreed schedule and Mrs. Miller has confidence in #Person1#'s inspection institution. Mrs. Miller requests #Person1# to let her have the contract today since she's leaving tomorrow. #Person1# will send the contract to Mrs. Miller by airmail if it's not ready by then.,380,80,0.2105
scientific_lay_summarisation-elife-norm,"The large number of individuals placed into quarantine because of possible severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) exposure has high societal and economic costs. There is ongoing debate about the appropriate duration of quarantine, particularly since the fraction of individuals who eventually test positive is perceived as being low. We use empirically determined distributions of incubation period, infectivity, and generation time to quantify how the duration of quarantine affects onward transmission from traced contacts of confirmed SARS-CoV-2 cases and from returning travellers. We also consider the roles of testing followed by release if negative (test-and-release), reinforced hygiene, adherence, and symptoms in calculating quarantine efficacy. We show that there are quarantine strategies based on a test-and-release protocol that, from an epidemiological viewpoint, perform almost as well as a 10-day quarantine, but with fewer person-days spent in quarantine. The findings apply to both travellers and contacts, but the specifics depend on the context. Quarantining individuals with high risk of recent infection is one of the pillars of the non-pharmaceutical interventions to control the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (Kucharski et al. , 2020). Owing to the large fraction of transmission of SARS-CoV-2 that is pre-symptomatic or asymptomatic (Ashcroft et al. , 2020; Buitrago-Garcia et al. , 2020; Ferretti et al. , 2020b; He et al. , 2020), quarantine can prevent a substantial fraction of onward transmission that would not be detected otherwise. In mathematical modelling studies, it was estimated that thermal screening at airports would allow more than 50% of infected travellers to enter the general population (Quilty et al. , 2020; Gostic et al. , 2020), which could have been prevented by mandatory quarantine. Quarantine is also a fundamental part of the test–trace–isolate–quarantine (TTIQ) intervention strategy to break chains of transmission within a community (Salathé et al. , 2020). With the high or increasing case numbers that are observed in many places around the globe, however, more and more people are being placed into quarantine. There is ongoing public debate about the appropriateness of quarantine and its duration. Quarantine lowers onward transmission in two ways: first, preventing transmission prior to symptom onset (with the assumption that symptomatic individuals will isolate) and decreasing overall transmission from persistently asymptomatic individuals. The appropriate length of quarantine thus depends","The COVID-19 pandemic has led many countries to impose quarantines, ensuring that people who may have been exposed to the SARS-CoV-2 virus or who return from abroad are isolated for a specific period to prevent the spread of the disease. These measures have crippled travel, taken a large economic toll, and affected the wellbeing of those needing to self-isolate. However, there is no consensus on how long COVID-19 quarantines should be. Reducing the duration of quarantines could significantly decrease the costs of COVID-19 to the overall economy and to individuals, so Ashcroft et al. decided to examine how shorter isolation periods and test-and-release schemes affected transmission. Existing data on how SARS-CoV-2 behaves in a population were used to generate a model that would predict how changing quarantine length",380,128,0.3368
dialogsum,"#Person1#: I want to buy a wallet. #Person2#: Here are all the wallets with various designs. How about this one ? It is quite fashionable. #Person1#: May I pick it up? #Person2#: Of course. #Person1#: Do you have one of better quality? #Person2#: This one is much better, but it is also much more expensive. #Person1#: There is no problem about the price. How much is it? #Person2#: Two hundred and thirty-five yuan. #Person1#: OK, I'll take it.",#Person2# recommends wallets to #Person1# and #Person1# buys the one with better quality and higher price.,78,16,0.2051
scientific_lay_summarisation-elife-norm,"emits feedback GABAergic projections to the STN (Carpenter et al. , 1981) and the striatum (Hegeman et al. , 2016; Mallet et al. , 2012) as well as massive feedforward GABAergic projections to the GPi/SNr (Parent and Hazrati, 1995b). Thus, aside from the action of the BG neuromodulators and lateral connectivity, the increase-decrease balance of spiking activity (I/D balance) of pallidal and nigral neurons is fined-tuned by the inhibitory and excitatory drives exerted by the striatum and STN, respectively. However, how these antagonistic drives operate to convey relevant information from the state-encoding thalamo-cortical areas through the central (GPe) and output (GPi and SNr) BG structures to brain motor centers is still unknown. Many human disorders are caused by malfunctions of the BG neuromodulators which impact neuronal activity along the BG main axis. Traditionally, in Parkinson' s disease (PD), it is assumed that degeneration of midbrain dopaminergic neurons leads to striatal dopamine depletion which provokes a cascade of physiological disturbances in the BG main axis, notably the emergence of synchronized oscillatory activity in the BG and cortical networks (Levy et al. , 2002; Nini et al. , 1995; Oswal et al. , 2013). These abnormal oscillations likely compromise information flow through the BG main axis and result in the release of abnormal commands by BG output structures. Despite evidence of subthalamic dopamine depletion in PD and its role in the pathophysiology of the disease (Francois et al. , 2000; Galvan et al. , 2014; Rommelfanger and Wichmann, 2010), the striatum remains the main site of dopamine depletion in human patients and animal models of PD. In addition, the striatum is much larger than the STN (107 vs. 105 neurons in non-human primates, respectively, Hardman et al. , 2002). Nevertheless, the STN, not the striatum, is the prime target for deep brain stimulation (DBS) of human patients with advanced PD (Limousin et al. , 1998; Odekerken et al. , 2016). Moreover, it has been shown that STN-DBS abolishes abnormal synchronized oscillations in the BG network of animal models of PD (Meissner et al. , 2005) and human PD patients (Kühn et al. , 2008; Wingeier et al. , 2006). These findings suggest that STN plays a pivotal role in the release of commands by BG output structures, but the respective influence of","The symptoms of Parkinson’s disease include tremor and slow movement, as well as loss of balance, depression and problems with sleep and memory. The death of neurons in a region of the brain called the substantia nigra pars compacta is one of the major hallmarks of Parkinson’s disease. These neurons produce a chemical called dopamine, and their death reduces dopamine levels in another area of the brain called the striatum. This structure is one of five brain regions known collectively as the basal ganglia, which form a circuit that helps to control movement. The most effective treatment currently available for advanced Parkinson’s disease entails lowering electrodes deep into the brain in order to shut down the activity of part of the basal ganglia. However, the target is not",380,128,0.3368
pubmed-summarization,"lead level , higher than 40 g / dl for occupational and 30 g / dl for nonoccupational exposure . primary and secondary preventions should be the first steps in the management of lead poisoning as public health problem . if a patient is found with high blood lead level , the test must be repeated before considering any therapy . chelating agents are recommended only if the level is above 45 g / dl , and the type will be chosen according to the blood level and symptoms . the available agents nowadays include : 2,3 dimercaptosuccinic acid ( dmsa ) , dimercaprol , ethylene diamine tetra - acetic acid ( cana2edta ) , d - penicillamine . in certain cases , the management can also include supportive therapy , like airway protection in acute encephalopathy or antiepileptic drugs in case of seizures . we present a case report of lead poisoning in a 16-year - old girl with the aim of highlighting the difficulty in diagnosing this condition , and the fact that even though occupational exposure is the main cause of lead poisoning in adults by inhalation , it can also be present in children in certain circumstances , as in our case . the informed consent was given by the patient 's father ( legal guardian ) for publication of this case report . we present the case of a 16-year - old girl , admitted to our clinic with severe abdominal pain , loss of appetite , nausea , and vomiting . the anamnesis revealed that the girl comes from a family of potters , and that she also participated in the process of pottery , her father being diagnosed with lead poisoning 2 years before . the patient 's personal history underlined that approximately 1 year ago she presented with severe abdominal pain , being diagnosed with acute appendicitis and she underwent appendectomy , but the pain persisted , thus due to family history of lead poisoning , the suspicion of saturnine colic rose , and she was diagnosed with lead poisoning ( urinary lead : 219 g / l ) , but she received only symptomatic treatment . approximately 3 weeks before admission to our clinic , she was admitted to the regional","abstractbackground : lead is a toxic element of the environment which leads to major complications once it enters the blood stream , affecting multiple organs and systems of the body.methods:we present the case of a 16-year - old girl , diagnosed with lead poisoning after occupational exposure due to the fact that the girl was actively involved in the family 's pottery business.history revealed that the girl participated in the process of pottery , her father was also diagnosed with lead poisoning 2 years before . the patient 's personal history underlined that approximately 1 year ago she presented with severe abdominal pain , being diagnosed with acute appendicitis and she underwent appendectomy , but the pain persisted , thus due to family history of lead poisoning ,",380,128,0.3368
pubmed-summarization,", 16 iu / l ; alanine aminotransferase , 21 iu / l ; total bilirubin , 0.6 mg / dl ; alkaline phosphatase , 129 iu / l ; total protein , 6.5 g / dl ; albumin , 4.4 g / dl ; blood urea nitrogen , 12.2 mg / dl ; creatinine , 0.9 , mg / dl ; na , 139 meq / l ; k , 3.4 meq / l ; and cl , 98 meq / l . the serum carcinoembryonic antigen level was 2.69 ng / ml , which was within the reference range . colonoscopy revealed a semipedunculated polyp , approximately 2 cm in size , in the sigmoid colon . in private clinics , the tumor was diagnosed as a tubular adenoma ; however , a diagnosis of submucosal tumor was not completely ruled out . we performed emr by en bloc resection of the polyp with a flex knife and a snare after injecting a glycerin solution into the submucosa ( . resected specimens histologically showed lymphoepithelial lesions with diffuse proliferation of atypical lymphocytes , which immunohistochemically stained positively for cd20 , cd5 , and bcl-6 , but negatively for cd3 , bcl-2 , and cyclin d1 . these findings were compatible with low - grade b - cell malt lymphoma ( . 2 ) . there was no evidence of lymph node metastasis or involvement of any other organ , except for a gallstone , in the thoracic and abdominal computed tomography performed for staging . according to the ann arbor staging system , the resected lesion was replaced with normal mucosa on sigmoidoscopy 2 months after the emr ( . malt lymphoma , a subtype of non - hodgkin lymphoma , is classified as an extranodal marginal zone b - cell lymphoma and is a lymphoepithelial lesion characterized by epithelial infiltration by lymphoplasma cells.1,2 malt lymphoma of the stomach is known to be associated with helicobacter pylori infection,11 whereas nongastric malt lymphomas have been associated with borrelia burgdorferi , chlamydia psittaci , hepatitis c virus , campylobacter jejuni , and autoimmune disease.12 colonic malt lymphoma occurs at an average age of 59.8 years and shows no sex preference . clinically , it is usually asymptomatic or present with","mucosa - associated lymphoid tissue ( malt ) lymphomas are characterized by lymphoepithelial lesions pathologically . colonic malt lymphomas are relatively rarer than lymphomas of the stomach or small intestine . endoscopically , colonic malt lymphoma frequently appears as a nonpedunculated protruding polypoid mass and/or an ulceration in the cecum and/or rectum . we report a unique case of a colonic malt lymphoma presenting as a semipedunculated polyp . a 54-year - old man was found to have a 2-cm semipedunculated polyp in the sigmoid colon during screening colonoscopy . the polyp was removed by endoscopic mucosal resection . histologic examination of the resected polyp revealed diffuse epithelial infiltration by discrete aggregates of lymphoma cells . we diagnosed the tumor as low - grade b - cell malt",380,128,0.3368
dialogsum,"#Person1#: What's that book you just picked up? #Person2#: The sociology text professor Smith uses in his course. #Person1#: You had better read it if you want to pass the course. #Person2#: But it is too expensive. I simply can't afford it. #Person1#: How much does it cost? #Person2#: It costs 40 dollars. #Person1#: Did you check the used book section here? Maybe they have one. #Person2#: No, they don't. I have asked. #Person1#: Why don't you get it from the library? #Person2#: Are you joking? I've been trying for months and the book is always out. There are more than 45 students in the course and every single one wants the book. #Person1#: Listen, you know my roommate, Henry, don't you? He took the same course last year and I believe he owns the book. I'll ask him if he'll lend it to you. #Person2#: Oh, Tom, that would settle everything. That's very kind of you. #Person1#: My pleasure.",#Person2# needs a book but can't afford it. Tom tells #Person2# that his roommate has the book and will ask him if he'll lend it to #Person2#.,160,27,0.1688
pubmed-summarization,"cell culture performed as previously described . briefly , k562 cells ( atcc ) were cultured in rpmi 1640 ( gibco ) media and supplemented with 10% fbs ( hyclone ) , penicillin ( 10,000 i.u./ml ) , streptomycin ( 10,000 ug / ml ) , and l - glutamine ( 2 mm ) . cells were grown in log phase during all biological assays by returning the population to 500,000 cells / ml each day . k562 cells were maintained in a controlled humidified incubator at 37 c , with 5% co2 . briefly , to generate sufficient lentivirus to infect the genome - wide shrna library into k562 cells , we plated 293 t cells on 15 cm tissue culture plates . 293 t cells were transfected with third generation packaging plasmids and shrna encoding vectors . after 48 hrs and 72 hrs of incubation we filtered the pooled lentivirus through a 0.45 m pvdf filter ( millipore ) to remove any cellular debris . approximately 560 million k562 cells were infected with our next - generation genome - wide lentiviral shrna library to maintain roughly 1,000-fold coverage of the shrna library after selection . infected cells grew for 3 days before selecting the cells with puromycin ( 0.7 g / ml , sigma ) . after three days of selection , infection efficiency was monitored using flow cytometry ( bd accuri c6 ) . once the cells reached 90100% mcherry positive cells , they were spun out of selection and allowed to recover in normal rpmi 1640 media . at t0 , 500 million cells were pelleted by centrifugation ( 300 g for 5 min ) . cells were then split into two populations and maintained at logarithmic growth ( 500,000 cells / ml ) each day for 14 days . after 14 days of growth genomic dna was extracted for all 3 time points separately following qiagen s blood maxi kit protocol . a previously designed 4 sgrna / gene crispr - cas9 library was used targeting 5 ends of conserved exons with sgrnas varying in length between 19 and 25 base - pairs . the library was generated first by infecting k562 cells with a sffv - cas9-bfp vector to create a stably expressed cas9","we compare the ability of shrna and crispr / cas9 screens to identify essential genes in the human chronic myelogenous leukemia cell line k562 . we find that the precision of the two libraries in detecting essential genes is similar and that combining data from both screens improves performance . notably , results from the two screens show little correlation , which can be partially explained by identification of distinct essential biological processes with each technology .",380,77,0.2026
dialogsum,"#Person1#: Guess who I saw yesterday? #Person2#: I don't know. Who? #Person1#: Avril Lavigen! #Person2#: The Canadian rock singer? But I heard you had a part-time job yesterday. How did you see her? #Person1#: Yeah, I worked as temporary staff in her concert. Look, her poster, a CD. . . #Person2#: So you're a big fan, eh? #Person1#: Not really. But I like some of her songs. She's actually very talented. She's a song writer and fashion designer, too. #Person2#: And she was in a movie once again, right? #Person1#: Yeah, though I don't think her acting skills are that great. #Person2#: What was your impression of her when you saw her in person? #Person1#: She looked sweeter than her pictures. #Person2#: Did you take a photo with her? #Person1#: No, there were too many people. When she got out of the car, her fans were all screaming, trying to give her flowers and to get her autographs. #Person2#: Crazy!",#Person1# tells #Person2# the experience of seeing Avril Lavigne when working as a temporary staff in her concert. #Person1# thinks she looked sweeter but didn't take photos with her.,160,29,0.1812
pubmed-summarization,"and rates of inadequate treatment around 20%36% of those reporting depression . in a cross - sectional community study of patients with ms by cetin et al . , 59% of the patients who had significant symptoms of depression were not taking medication , possibly due to missed diagnosis , denial of symptoms , or false reporting , whereas the rest 41% received inadequate treatment . in the whole sample ( n = 542 ) , 28% of the patients were adequately treated for depression and therefore had achieved remission . in another study by mohr et al . , 65.6% of depressed patients did not receive medication , 4,7% received subthreshold treatment , 26,6% received threshold , and only 3.1% received overthreshold , indicating that in most cases , therapy is not in accordance with treatment guidelines for depression . given the fact that depression is a treatable condition , correct diagnosis and adequate treatment are issues of immense importance for the management of multiple sclerosis patients . the present paper is focused on current knowledge on diagnosis , assessment , and therapeutic interventions for depression in the context of multiple sclerosis . although the symptom of depressive mood is almost always experienced by patients suffering from disabling diseases , the syndrome of major depression , as defined by the classification systems of icd-10 and dsm - iv - tr , corresponds to a constellation of symptoms comprising depressive mood , anhedonia , fatigue , psychomotor retardation or restlessness , suicidal ideation or suicide attempt , feelings of guilt and worthlessness , and difficulty in concentrating , as well as vegetative symptoms , including altered sleep , appetite , and sexual arousal . a common challenge for correctly diagnosing depression in the context of multiple sclerosis is distinguishing whether a certain symptom emanates from a depressive disorder or can be attributed to the demyelinating disease . potential confounders are fatigue , insomnia , altered appetite , and impaired memory and concentration , and misjudgments will lead to false positives or false negatives . varied presentations of depression , for example , unexplained somatic complaints , anxiety , or hopelessness instead of sadness , could also complicate diagnosis , especially in older persons . patients with ms might exhibit pathological","multiple sclerosis is a chronic demyelinating disease affecting one million people worldwide , with a significant burden of psychiatric comorbidity . depression is the commonest psychiatric manifestation but still remains largely underdiagnosed and undertreated . the present work reviews current knowledge on diagnosis , assessment , and somatic and psychotherapeutic treatment interventions for depression in adult and pediatric populations of patients with multiple sclerosis .",380,65,0.1711
scientific_lay_summarisation-elife-norm,"voice disorders in human birth defect patients is not the only factor motivating a deeper study of laryngeal developmental biology. Indeed, vocal communication is ubiquitous in tetrapod animals, impacting a wide array of behaviors. For example, the Panamanian Tungara frog creates a complex, multi-tonal call that critically influences female mate choice, and this call requires a sexually dimporphic elaboration of the male larynx, the developmental basis of which is entirely unknown (Griddi-Papp et al. , 2006; Ryan and Drewes, 1990). So too is the morphology of the songbird syrinx central to sound production, yet almost nothing is known of the developmental biology of this functional cognate of the larynx, despite the key role of bird song as a model for the study of acoustic communication. Likewise, the larynx of mice is central to their production of ultrasonic vocalizations throughout life. Despite the widespread use of mice for studies of developmental biology, the molecular genetics of mouse laryngeal development remain only cursorily poorly defined (e. g. [Böse et al. , 2002; Lungova et al. , 2015]). Clearly, a deeper understanding of the molecular genetic basis of laryngeal patterning and morphogenesis will inform our understanding of vertebrate animal behaviors involving acoustic communication. In mammals, the larynx and vocal folds are comprised of an elaborate mixture of cartilages, muscles, nerves, and connective tissue (Harrison, 1995; Henick, 1993; Lungova et al. , 2015). The flanged circle of the cricoid cartilage, along with the C-shaped thyroid cartilage and intervening paired arytenoid cartilages provide the core of the laryngeal skeleton (, blue, yellow, purple). Anchored to these are the vocal folds, which are in turn comprised of paired cricoarytenoid, thyroarytenoid, cricothyroid and vocalis muscles (, pink, magenta, grey), as well as paired vocal ligaments (, dark blue) and associated loose mesenchyme which we designate as the thyroglottal connective tissue (, green). The general laryngeal structure is similar across the mammals (Harrison, 1995; Kaufman, 1992; Roberts, 1975a; Thomas et al. , 2009), though rodents communicate most commonly in the ultrasonic range, using a mechanism for sound production that is distinct from that generating audible sound (Mahrt et al. , 2016; Roberts, 1975b). Importantly however, diverse aspects of rodent ultrasound production parallel those of audible vocalizations in other mammals, including tight control of laryngeal muscle activity and mechanical","Nearly all animals communicate using sound. In many cases these sounds are in the form of a voice, which in mammals is generated by a specialized organ in the throat called the larynx. Millions of people throughout the world have voice defects that make it difficult for them to communicate. Such defects are distinct from speech defects such as stuttering, and instead result from an inability to control the pitch or volume of the voice. This has a huge impact because our voice is so central to our quality of life. A wide range of human birth defects that are caused by genetic mutations are known to result in voice problems. These include disorders in which the Hedgehog signaling pathway, which allows cells to exchange information, is defective.",380,128,0.3368
dialogsum,"#Person1#: Wasn't that a great flick? I was on the edge of my seat through the whole movie. #Person2#: I would say it was a typical run-of-the-mill Hollywood thriller. #Person1#: Well, I'm no movie expert, but those special effects were impressive by any standards. #Person2#: Special effects? Baloney! That movie was made on a shoestring budget. They've been using trick photography like that for years #Person1#: Okay. But you have to admit that it was an exciting story, especially with that surprise ending. #Person2#: You should read the book. The original story is much better and has a different twist at the end. #Person1#: Oh, really? How does the book end? #Person2#: Read it yourself and find out!",#Person1# thinks it's a great flick and was impressed by the special effects of the movie. #Person2# disagrees and recommends the original story.,118,23,0.1949
dialogsum,"#Person1#: Doctor, may I ask my mother's condition? #Person2#: Well, you'd better sit down for this. It has been terminal lung cancer. #Person1#: Oh my god. Please save her life. #Person2#: We'll try our best, but you'd better prepare for the worst. #Person1#: I see, D. But I plead you to help her. #Person2#: I have said that we will try our best. You can trust us. But you know her situation. #Person1#: How long do you expect her to live? #Person2#: About half a year.",#Person2# tells #Person1# about #Person1#'s mother's lung cancer and suggests #Person1# should better prepare for the worst.,86,17,0.1977
dialogsum,"#Person1#: You're from New York, aren't you? #Person2#: Yes, that's right. #Person1#: What do you suggest I should see in New York? #Person2#: Well, how about the Museum of Modern Art? #Person1#: No, I don't like museums. They're boring. #Person2#: Why don't you go to see the Empire State Building? #Person1#: Ah! That sounds interesting.",#Person2# is from New York and recommends the Empire State Building to #Person1#.,55,13,0.2364
pubmed-summarization,"current techniques in acl surgery have been associated with satisfactory long - term results in the majority of patients . however , there remains a considerable subset , up to 30% of patients , with unsatisfactory outcomes . specifically , patients report problems relating to rotational instability and return to previous level of activity . it has been suggested that a more anatomical approach to restore the original acl anatomy may benefit these patients . some authors have advocated placing a single graft in a position closer to the oblique femoral attachment of the acl . however , it is not possible to fully restore normal knee kinematics with a single graft , regardless of the position . the double bundle reconstruction technique ( dbt ) for acl reconstruction aims at restoring the acl anatomy with its two bundles and is gaining popularity . anatomic studies have demonstrated the presence of two functional bundles within the acl , the anteromedial ( am ) and the posterolateral ( pl ) bundle . although it is somewhat of a simplification , the double bundle description of the acl is generally accepted as an anatomic model for understanding the complex structure and function of the ligament . the am bundle often obscures the pl bundle , and it may appear that only one bundle is present without careful inspection . the goal of this study was to describe the presence of the double bundle structure from an arthroscopic point of view , and to evaluate the value of different portals in knee arthroscopy . we prospectively examined 60 knees during standard arthroscopy . in each knee , the double bundle acl structure was evaluated , along with the usefulnes of different portals for visualization . all knees that were included in the study had a previous x - ray and mri in order to rule out any significant changes to the bone , and to ensure that the acl was intact . all patients were less than 60 years and had no history of acl injury . surgical indications for the 60 total subjects examined included 31 cases treated for meniscal findings alone , 21 treated for articular cartilage findings alone , and 8 cases of a combined repair of meniscus and cartilage","in order to describe the arthroscopic presence of the double bundle structure and to evaluate the value of different portals in knee arthroscopy , we assessed the am and pl bundle anatomy . we prospectively examined the knees of 60 patients undergoing arthroscopic surgery for pathology unrelated to the acl . arthroscopy was performed in a two portal technique using an anterolateral ( alp ) and an anteromedial ( amp ) portal . with the arthroscope in the alp , we could distinguish an am and pl bundle in 28% . switching the arthroscope to the amp , differentiation of the bundles was possible in 67% . in all remaining cases visualization of the pl bundle was possible after retraction of the am bundle . use of amp",380,128,0.3368
scientific_lay_summarisation-elife-norm,"at a 45° angle. A single high-speed camera captures side and bottom views at 400 fps. Infrared (IR) sensors trigger data collection. (B) Machine learning algorithms identify paws, nose and tail segments and track their movements in 3D. Example ‘paw’ and ‘not paw’ training images for SVM (Support Vector Machine) feature detectors are shown for side and bottom views. (C) Continuous tracks are obtained by post-processing the feature detections with a Multi-Target Tracking algorithm. (D) Continuous forward trajectories (x position vs time) for paws, nose, and tail. The inset illustrates the color code used throughout the paper to identify individual features. (E) Continuous vertical (z) trajectories of the two front paws. (F) Side-to-side (y) position of proximal (green) to distal (yellow) tail segments vs time. (G) Individual strides were divided into swing and stance phases for further analysis. Further validation of tracking algorithm is presented in — 1. : http: //dx. . org/10. 7554/eLife. 07892. 00310. 7554/eLife. 07892. 004Figure 1— 1. LocoMouse tracking validation. (A) Comparison of manual (gray) and automated tracking (blue) for front left paw across 3 dimensions. From left to right, plots show normalized x, y, and z paw position aligned to stance onset (n = 43 strides from 9 movies of 3 mice). (B) Scatterplots of manual vs automated tracking positions (x, y, and z) for all frames (n = 4194) of the same 9 movies. Values where the difference between manual and automated tracking are larger than average paw size are color-coded in green. Correlation coefficients are Pearson' s r. (C) Example tracking traces demonstrate that stride lengths can differ at similar walking speeds due to pauses in walking. : http: //dx. . org/10. 7554/eLife. 07892. 004 Mice walked across a glass corridor, 66. 5 cm long and 4. 5 cm wide (1A). A mirror was placed at 45 deg under the mouse, so that a single high-speed camera (AVT Bonito, 1440x250 pixels @400 frames per second) recorded both bottom and side views. Individual trials consisted of single crossings of the corridor. Mice freely initiated trials by walking back and forth between two dark ‘home’ boxes on each end of the corridor. Data collection was performed in LABVIEW and was automatically triggered by infrared sensors that detected when the mouse entered and exited the corridor.","Though it seems simple, walking is a complex activity. The arms, legs, body, and head all need to work together. A part of the brain called the cerebellum helps to coordinate the movements of different body parts allowing both simple and complex tasks to be carried out smoothly. But it is not known exactly how the cerebellum coordinates body movements. Studies of mice have helped shed some light on the coordination of movement. Several mutations that naturally occur in mice can cause them to walk abnormally. These mutations often cause changes in the cerebellum. Neuroscientists studying these mutant mice often use balance beams or other challenging tasks to compare their coordination with typical mice. But studies attempting to measure specific changes in walking movements under natural conditions have",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The coordination of activity across neocortical areas is essential for mammalian brain function. Understanding this process requires simultaneous functional measurements across the cortex. In order to dissociate direct cortico-cortical interactions from other sources of neuronal correlations, it is furthermore desirable to target cross-areal recordings to neuronal subpopulations that anatomically project between areas. Here, we combined anatomical tracers with a novel multi-area two-photon microscope to perform simultaneous calcium imaging across mouse primary (S1) and secondary (S2) somatosensory whisker cortex during texture discrimination behavior, specifically identifying feedforward and feedback neurons. We find that coordination of S1-S2 activity increases during motor behaviors such as goal-directed whisking and licking. This effect was not specific to identified feedforward and feedback neurons. However, these mutually projecting neurons especially participated in inter-areal coordination when motor behavior was paired with whisker-texture touches, suggesting that direct S1-S2 interactions are sensory-dependent. Our results demonstrate specific functional coordination of anatomically-identified projection neurons across sensory cortices. Sensory perception, fine voluntary motor control, and higher cognitive functions depend on neural dynamics in the mammalian neocortex, which itself relies on the exchange of information between cortical areas through both bottom-up (feedforward) and top-down (feedback) neuronal pathways across the cortical hierarchy (Bressler and Menon, 2010; Buschman and Miller, 2007). Cortico-cortical connections are formed between columnar microcircuits via long-range axons of pyramidal neurons in superficial layer 2/3 (L2/3) and deeper layer 5. A given cortical area typically establishes connectivity patterns not only with one particular area but with multiple target areas in a distributed and often reciprocal fashion (Markov et al. , 2013; Oh et al. , 2014; Zingg et al. , 2014). Thus, in order to fully understand the cortical interactions underlying behavior, it is necessary to disentangle how neuronal subpopulations defined by both their functional properties and their specific anatomical projections contribute to local computation and long-range communication. Such an understanding has been limited by the difficulty in measuring population activity across areas with sufficient spatial and temporal resolution. Present methods to study large-scale cortical dynamics either lack cellular resolution and sensitivity to low numbers of action potentials (e. g. , human fMRI; Hutchison et al. , 2013; or wide-field functional imaging in mice, Ferezou et al. , 2007; Lim et al. , 2013; Minderer et al. , 2012) or they are restricted to","Behavior and cognition – the process of thought – emerge from computations that occur within vast networks of neurons in the brain. Within these networks, neurons may communicate with their neighbours in the same brain region as well as with distant counterparts in remote brain regions. Neuroscientists have studied these networks by measuring the activity of neurons within a single region or across the brain as a whole. However, it has not been possible to study long-distance communication between pairs of neurons in different brain regions. This has made it difficult to work out exactly what information brain regions exchange. Chen, Voigt et al. now overcome these challenges by developing a new microscope system that allows researchers to measure the activity of individual neurons in different brain regions",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the tone conditioned stimulus (CS) (1b). These animals were then divided into two groups – one was subjected to 10 days of chronic immobilization stress (Days 1–10, 1a) while the other served as unstressed control. 24 hr after the end of chronic stress there was no difference in CS-induced freezing behavior between the two groups (Day 11, Block1, 1b). Thus, the recall of fear memory formed earlier was not affected by subsequent stress. This ensured that both stressed and unstressed animals were at the same levels of freezing when the extinction protocol was initiated after stress. Next, repeated tone presentations reduced freezing levels significantly such that both groups eventually underwent comparable extinction of fear, though the stressed rats were slower in achieving the same reduction in freezing (Day 11, 1b). Notably, a day later stressed animals showed no difference in recall of extinction memory compared to unstressed animals (Day 12, 1b). Thus, freezing levels during both fear and extinction recall were unaffected in stressed animals. This result differs from past reports of stress-induced deficits in fear extinction. However, as mentioned earlier, those earlier studies subjected animals to fear conditioning and extinction after exposure to stress (Izquierdo et al. , 2006; Maren and Holmes, 2016; Miracle et al. , 2006). Taken together, this suggests that the timing of stress may be a critical determinant of whether extinction recall is impaired. Thus, to examine this possibility we repeated the experimental design adopted in earlier studies by administering the same 10 day chronic immobilization stress protocol before (1c, e) the same fear conditioning paradigm depicted in 1a. Consistent with earlier findings, prior exposure to chronic stress caused a significant impairment in the recall of fear extinction (1e). However, these animals, unlike those used in 1b (i. e. conditioning before stress) were not implanted with electrodes for simultaneous in vivo recordings. Hence, we repeated the behavioral experiments described in 1b without surgical interventions related to in vivo recordings. This too yielded the same results as seen in the implanted animals – extinction recall was intact in stressed animals (1d, f) when they were subjected to conditioning before chronic stress. Next, we examined the neural basis of this result by recording local field potentials (LFPs) in these freely behaving rats (Karalis et al. , 2016;","Patients with stress-related psychiatric disorders experience debilitating emotional symptoms, including excessive fear that they are unable to control. Decades of research have shown that such disorders have opposite effects on two key structures in the brain. Normally, a region called the amygdala helps to form fear-related memories, while the prefrontal cortex helps control these memories and eliminate them through a process called extinction. But brain imaging on patients with stress-related psychiatric disorders reveals a smaller prefrontal cortex, and an overactive amygdala. Animal studies confirm that chronic stress shrinks brain cells in the prefrontal cortex, but grows them bigger in the amygdala. These and other studies have led scientists to believe that stress causes people to both form stronger fear memories and then have difficulties getting rid of such",380,128,0.3368
pubmed-summarization,"( except for uncomplicated cataract surgery or glaucoma surgery ) , coexisting retinal pathologies , nonglaucomatous optic neuropathy , uveitis , or ocular trauma were excluded from the study . participants were also excluded if there was a diagnosis of parkinson 's disease , alzheimer 's disease , dementia , or a history of stroke . participants with systemic hypertension and diabetes mellitus were included unless they were diagnosed with diabetic or hypertensive retinopathy . participants having unreliable visual field , poor quality oct - a , or optic nerve head sd - oct scans were also excluded from our study . systemic measurements included two blood pressure ( bp ) measurements obtained using an omron automatic ( model bp791it ; omron healthcare , inc . mean arterial pressure was calculated as one - third systolic bp + two - thirds diastolic bp . mean ocular perfusion pressure ( mopp ) was defined as the difference between two - thirds of mean arterial pressure and iop . optical coherence tomography angiography and sd - oct images were obtained by the same operator and at the same visit using the angiovue , which is a dual modality oct system . the angiovue is an angiographic platform implemented on an existing commercially available sd - oct platform . informed consent was obtained from all participants , and all methods adhered to the tenets of the declaration of helsinki and the health insurance portability and accountability act and were approved by the institutional review boards at the university of california san diego . standard automated perimetry visual field tests were completed using swedish interactive threshold algorithm standard 24 - 2 ( humphrey field analyzer ; carl zeiss meditec , dublin , ca , usa ) strategies . the quality of the visual fields was reviewed by the visual field assessment center ( visfact ) staff . only reliable tests ( 33% fixation losses and false - negative errors and 15% false - positive errors ) and visual fields without rim and eyelid artifacts , evidence of inattention or fatigue effects , and no evidence that the abnormal results of the visual field were caused by a disease other than glaucoma , were included . visual field result was considered to be abnormal if","purposethe purpose of this study was to compare retinal nerve fiber layer ( rnfl ) thickness and optical coherence tomography angiography ( oct - a ) retinal vasculature measurements in healthy , glaucoma suspect , and glaucoma patients.methodstwo hundred sixty - one eyes of 164 healthy , glaucoma suspect , and open - angle glaucoma ( oag ) participants from the diagnostic innovations in glaucoma study with good quality oct - a images were included . retinal vasculature information was summarized as a vessel density map and as vessel density ( % ) , which is the proportion of flowing vessel area over the total area evaluated . two vessel density measurements extracted from the rnfl were analyzed : ( 1 ) circumpapillary vessel density ( cpvd )",380,128,0.3368
pubmed-summarization,"obtained by using a tanita scale sc240 . early morning spot urine sample were recollected in polyethylene containers and stored at 20c until analysis . urine fluoride ( uf ) concentrations were determined using an electronic meter ( orion 720a ) and a fluoride - specific ion electrode , which was calibrated with fresh , serially diluted standard solutions . during the measurement , written informed consent was obtained from all the participants or by their legal guardians in case they were minors . this study was approved by the committee of ethics the national autonomous university of mexico , enes len . descriptive analysis of the data ( arithmetic mean , standard deviation and percentages ) were obtained , bivariate analyses were performed to compare variables , and then a logistic regression model was created . population was divided into two groups according to the presence or absence of severe fluorosis ( tfi < 6 vs tfi > 6 ) . data was processed using spss version 21 for windows ( statistical package for the social sciences , spss inc . a total of 307 participants were included ; 59.9% ( n = 184 ) were females and 40.1% ( n = 123 ) were males . fluoride content in urine ranged between 0.5 and 6.65 mg / l , with a mean of 1.27 1.2 mg / l [ table 1 ] . descriptive data about age and urine fluoride concentration by sex most of the population ( 62.5% ) showed normal weight ; 21.5% were underweight , 11.1% were overweight , and 4.9% were obese . df was present in 91.9% of the participants , of which 61.6% were ( tfi > 4 ) moderate or severe cases , as observed in table 2 . teeth more frequently affected were premolars and those less affected were central inferior incisors . nutritional status and dental fluorosis severity by sex bivariate tests were performed to compare uf concentration according to different variables such as sex , bmi , and tfi . according to the kolmogorov smirnov test , the distribution of data was not normal and hence nonparametric tests were used . no differences in uf concentrations among girls and boys were observed ( mann whitney u test =","objective : the aim of this study was to assess urine fluoride concentration , nutritional status , and dental fluorosis in adolescent students living in the rural areas of guanajuato , mexico.materials and methods : a cross - sectional study was conducted including participants aged 1120 years . the presence and severity of dental fluorosis was registered according to the thylstrup and fejerskov index ( tfi ) criteria . anthropometric measures were also recorded . urine sample of the first morning spot was recollected to assess urine fluoride concentration by using the potentiometric method with an ion - selective electrode . water samples were also recollected and analyzed . bivariate tests were performed to compare urine fluoride concentration according to different variables such as sex , body mass",380,128,0.3368
dialogsum,"#Person1#: Well, what is your trouble? #Person2#: I'm not feeling well, doctor. I have a sore throat. #Person1#: Have you any aches and pains? #Person2#: Yes, my back aches. #Person1#: I'll take your temperature. How long have you been feeling ill? #Person2#: It began the night before last. #Person1#: You have a temperature, but it's nothing serious. It's probably just the flu. I'll give you a prescription. Take this to the chemist's. Take one tablet every four hours. You should stay in bed tom #Person2#: Lots of people are ill at the moment. #Person1#: It's this cold weather we're having.",#Person1# doesn't feel well. The doctor thinks it's probably the flu and gives #Person1# a prescription.,100,16,0.16
dialogsum,"#Person1#: Can I help you, Sir? #Person2#: Yes, I'd like to withdraw some money. #Person1#: Fill in the slip, stating the exact amount you wish to withdraw, please. #Person2#: OK. Here's my bank book, is that all right? #Person1#: OK, do you want large notes or small ones? #Person2#: In 50 Yuan or 100 Yuan would be fine. #Person1#: Here's the cash for you. #Person2#: Thanks.",#Person1# helps #Person2# withdraw some money in 50 yuan or 100 yuan.,66,12,0.1818
dialogsum,"#Person1#: Our company's wei-ya is tomorrow night! It's your first Chinese New Year in Taiwan--you must be excited! #Person2#: Excited? What's there to be excited about? It's just another company dinner, right? #Person1#: You have no idea! There's a banquet with prizes, performances. . . you name it! #Person2#: Really? What kind of prizes? #Person1#: Well, I heard that last year Vivian from accounting won a new car! #Person2#: A new car! You're kidding! #Person1#: No, really! And she told me the secret to winning, wear red underwear! #Person2#: Wear red underwear? ! Does that really work? Are you going to try it? #Person1#: Of course! I'm not only going to wear red underwear, but I'm going to wear red socks and a red shirt, too! #Person2#: Gee, I don't think I own any red underwear, but I can buy some!",#Person1# tells #Person2# in the company's wei-ya they can win prizes. Vivian won a car last year and she tells #Person1# the secret is to wear red underwear.,141,28,0.1986
dialogsum,"#Person1#: Welcome to the company. We are conducting a survey of new employees to find out what influenced them to choose our company. #Person2#: That's easy. It was your office ergonomics that decided me. #Person1#: You're kidding! Something as simple as that? #Person2#: Yes. It is very important to me. My mother worked in offices for twenty years, and she finally had carpal tunnel syndrome. I have been reading about repetitive stress injuries, and I know that so I have determined that I need to work in a company that can protect my body. #Person1#: Yes, there has been a lot of research into RSI's. Something so simple as proper chair height can prevent injuries. Tell me, did anything else influence your decision? #Person2#: Yes, I noticed that you have professional training and team-building days. I like the idea of working for a company that invests in its staff. #Person1#: Well, welcome to the team.",#Person2# tells #Person1# that it was the office ergonomics that decided #Person2# to choose the company and #Person2# likes working for a company that invests in its staff.,155,28,0.1806
scientific_lay_summarisation-elife-norm,"As of November 2015, the Ebola virus disease (EVD) epidemic that began in West Africa in late 2013 is waning. The human toll includes more than 28,000 EVD cases and 11,000 deaths in Guinea, Liberia, and Sierra Leone, the most heavily-affected countries. We reviewed 66 mathematical modeling studies of the EVD epidemic published in the peer-reviewed literature to assess the key uncertainties models addressed, data used for modeling, public sharing of data and results, and model performance. Based on the review, we suggest steps to improve the use of modeling in future public health emergencies. On March 23,2014, the Ministry of Health Guinea notified the World Health Organization (WHO) of a rapidly evolving outbreak of Ebola virus disease (EVD), now believed to have begun in December 2013. The epidemic spread through West Africa and reached Europe and the United States. As of November 4,2015, WHO reported more than 28,000 cumulative cases and 11,000 deaths in Guinea, Liberia, and Sierra Leone, where transmission had been most intense (World Health Organization, 2016). As the emergency progressed, researchers developed mathematical models of the epidemiological dynamics. Modelers have assessed ongoing epidemics previously, but the prominence of recent EVD work, enabled by existing research programs for infectious disease modeling (National Institutes of Health, 2016a; National Institutes of Health, 2016b) and online availability of EVD data via WHO (World Health Organization, 2016), Ministries of Health of affected countries, or modelers who transcribed and organized public WHO or Ministry of Health data (Rivers C) may be unprecedented. The efforts for this outbreak have been numerous and diverse, with major media incorporating modeling results in many pieces throughout the outbreak. U. S. Government decision making has benefited from modeling results at key moments during the response (Robinson R). We draw on this vigorous response of the epidemiological modeling community to the EVD epidemic to review (Moher et al. , 2009) the application of modeling to public health emergencies, and identify lessons to guide the modeling response to future emergencies. We identified 66 publications meeting inclusion criteria (). 10. 7554/eLife. 09186. 003Figure 1. Literature search flow. : http: //dx. . org/10. 7554/eLife. 09186. 003 Models addressed 6 key uncertainties about the EVD epidemic: transmissibility, typically represented by the reproduction number (R, the average number of people each infected person","The outbreak of Ebola that started in West Africa in late 2013 has caused at least 28,000 illnesses and 11,000 deaths. As the outbreak progressed, global and local public health authorities scrambled to contain the spread of the disease by isolating those who were ill, putting in place infection control processes in health care settings, and encouraging the public to take steps to prevent the spread of the illness in the community. It took a massive investment of resources and personnel from many countries to eventually bring the outbreak under control. To determine where to allocate people and resources during the outbreak, public health authorities often turned to mathematical models created by scientists to predict the course of the outbreak and identify interventions that could be effective. Many",380,128,0.3368
dialogsum,"#Person1#: Well hi there. What are you looking for today? #Person2#: Uh, I'm just looking. #Person1#: Well, how about a ring for someone special? #Person2#: There IS no one special. #Person1#: Well, take a look at this CD player. A great bargain today only. #Person2#: Nah. I already have one, plus the handle is cracked. #Person1#: Okay. Well what about this genuine leather jacket? It would look great on you. #Person2#: Hum. Let me take a look at it. #Person1#: Sure. #Person2#: Umm. There are stains on the sleeves. I'll pass. #Person1#: Well okay. Well, wouldn't you like to walk home with some of these great records? Some of the best hits from the 1960's. #Person2#: Yeah, let's see. [Yeah] Now here's something I'd ... Ah, these records are scratched. #Person1#: [Laughter] Just in a couple places. Listen. I'll sell you these ten records for fifty dollars. A steal! #Person2#: Whoa! They're way too expensive. I'll give you twenty-five bucks for them. #Person1#: Ah, come on. I can't charge you less than thirty dollars and break even. #Person2#: Well, that guy over there is selling similar records for a much better price [Ah!], so thanks anyway. #Person1#: Wait, wait, wait, wait. You drive a hard bargain. Twenty-eight dollars, and that's my final offer. #Person2#: Huh ... I'll think about it. #Person1#: Wait, wait, wait, wait. Listen. I'll even throw in this vase. #Person2#: Now what am I going to do with a vase? #Person1#: Well, you can give it to that someone special when you find her... and this ring would look great with it. #Person2#: Oh, I'll stick with the records.","#Person2# is looking around in the store and #Person1# recommends #Person2# with several items, including a ring, a CD player and a genuine leather jacket. #Person2# drives a hard bargain and finally buys the records.",272,35,0.1287
dialogsum,"#Person1#: Are you ready to go to the bank? #Person2#: Sure, what do you need to do there? #Person1#: There's problem with my bank statement. There's a mistake on it. I also need to withdraw some money some the ATM. #Person2#: I have to exchange some money. #Person1#: that's right. You're going away next week. #Person2#: I also want to see if my salary has been paid into my bank account. There was a problem last week. #Person1#: I have to pay my credit bill too. If I don't pay it soon, the credit card company will charge me interest. #Person2#: Their interest rates are usually quite high. It's a good idea to pay off your credit card debts before they attract interest.","#Person1# is going to the bank to check the bank statement, withdraw some money, and pay the credit bill. #Person2# is going to exchange some money and check the salary.",123,30,0.2439
scientific_lay_summarisation-elife-norm,"depending on the underlying mutation, ciliopathies present a broad spectrum of phenotypes comprising cystic kidneys, polydactyly, obesity or heart malformation. Truncated SALL1 likely interferes with multiple factors to give rise to TBS phenotypes. Here we focus on LUZP1, a leucine-zipper motif containing protein that was identified by proximity proteomics as an interactor of truncated SALL1 (Bozal-Basterra et al. , 2018). LUZP1 has been previously identified as an interactor of ACTR2 (ARP2 actin related protein two homologue) and filamin A (FLNA) and, recently, as an actin cross-linking protein (Hein et al. , 2015; Wang and Nakamura, 2019). Furthermore, LUZP1 shows homology to FILIP1, a protein interactor of FLNA and actin (Gad et al. , 2012; Nagano et al. , 2004). Interestingly, mutations in Luzp1 resulted in cardiovascular defects and cranial NTD in mice (Hsu et al. , 2008), phenotypes within the spectrum of those seen in TBS individuals and mouse models of dysfunctional cilia (Botzenhart et al. , 2007; Botzenhart et al. , 2005; Klena et al. , 2016; Kohlhase et al. , 1998; Surka et al. , 2001; Toomer et al. , 2019). Both the non-canonical Wnt/PCP (Wingless-Integrated/planar cell polarity) and the Shh pathways are influenced by the presence of functional cilia and regulate neural tube closure and patterning (Campbell, 2003; Copp, 2005; Fuccillo et al. , 2006). Remarkably, ectopic Shh was observed in the dorsal lateral neuroepithelium of the Luzp1-/- mice (Hsu et al. , 2008). However, in spite of the phenotypic overlaps, a link between LUZP1 and ciliogenesis has not been explored. Here we demonstrate that LUZP1 is associated with centrosomal and actin cytoskeleton-related proteins. We show that LUZP1 localizes to the PCM, actin cytoskeleton and the midbody, and also provide evidence towards its regulatory role on actin dynamics and its subsequent impact on ciliogenesis. Notably, we demonstrate that Luzp1-/- cells exhibit reduced filamentous actin (F-actin), longer primary cilia, higher rates of ciliogenesis and increased Shh signaling. Furthermore, TBS-derived primary fibroblasts show a reduction in LUZP1 and actin filaments, possibly through SALL1-regulated LUZP1 degradation via the ubiquitin (Ub) -proteasome system (UPS). As a novel regulator of ciliogenesis and the actin cytoskeleton, LUZP1 might contribute to the aberrant cilia phenotype in TBS. Using proximity proteomics, we have previously shown that a truncated and mislocalized form of SALL1 present in","Primary cilia are the ‘antennae’ of animal cells: these small, flexible protrusions emerge from the surface of cells, where they help to sense and relay external signals. Cilia are assembled with the help of the cytoskeleton, a dynamic network of mesh-like filaments that spans the interior of the cell and controls many different biological processes. If cilia do not work properly, human diseases called ciliopathies can emerge. Townes-Brocks Syndrome (TBS) is an incurable disease that presents a range of symptoms such as malformations of the toes or fingers, hearing impairment, and kidney or heart problems. It is caused by a change in the gene that codes for a protein called SALL1, and recent work has also showed that the cells of TBS patients have defective cilia. In addition,",380,128,0.3368
dialogsum,"#Person1#: I need some new clothes for the coming season. Where shall I go to pick up some? #Person2#: I'm thinking of buying some stuff, too. Let's go to the speciality stores. There will be some new models for sale now. #Person1#: Will the new models be very expensive? #Person2#: Depends on the brands. But there will be some out-of-season clothes on discount, too. So maybe we can also get some stuff, good and cheap. #Person1#: Great. Let's go. #Person2#: Do you like this one? I think it will be great on you. #Person1#: I like the style. Especially the Porsche logo. Let me try it on in the fitting room. Wait a minute! #Person3#: Hmm, not bad, but I'm afraid it's a bit too big for you. #Person2#: Yeah, that's the only problem. Well, do you think they've got a smaller one? #Person1#: Probably not. Most of the clothes here have only one average size. #Person2#: Never mind. What about going to check out the discount section? #Person1#: That's what I'm thinking about. Oh, this one. #Person2#: What's up? #Person1#: This dress was a new model this time last year. I loved it but it was a bit too expensive. So I gave it up. #Person2#: Good for you. It's 50 percent off now. Take it! #Person1#: Sure. I won't miss this chance. It's my lucky day.",#Person1# and #Person2# are looking for new clothes in specialty stores. #Person1# likes the one with a Porsche logo but it is too big. Then #Person1# is attracted by another one and takes it with 50% off.,228,37,0.1623
scientific_lay_summarisation-elife-norm,"(Dunn et al. , 2002; Dunn et al. , 2004). Escape from immune control is a critical step toward progressive malignant growth in many cancers, and tumors achieve this in a number of ways, amongst them the dampening of antitumor T cell responses (Dunn et al. , 2002; Dunn et al. , 2004; Beatty and Gladney, 2015; Zappasodi et al. , 2018). The activity of immune cells is tightly linked with their metabolism (O' Neill et al. , 2016; Pearce and Pearce, 2013). Many aspects of immune cell energetics are likely sensitive to the metabolic changes induced by exercise (Henderson et al. , 2004). Exercise is known to affect immune cell function, and an altered immune response has been suggested as a mechanism underlying effects of exercise on cancer risk and progression (Christensen et al. , 2018). In this study, we investigate the association between exercise, tumor growth, and CD8+ T-cell function. To address this, we undertook studies of exercise-induced changes in tumor progression, and asked what metabolites are released in response to exercise; as well as whether metabolites produced by exercise can alter cytotoxic T-cell function. We found that exercise itself can modify cytotoxic T-cell metabolism, and that exercise-induced effects on tumor growth are dependent on cytotoxic T-cell activity. To address the role of immunity on the effects of exercise in neoplasia, we first assessed how repeated voluntary exertion influenced tumor progression in mice, using a genetic model of mammary cancer induced by the MMTV-PyMT transgene on the FVB inbred strain background (— 1A). FVB inbred mice are enthusiastic runners relative to most other inbred strains (Avila et al. , 2017), and the MMTV-PyMT model in many regard mimics the gradual progression of human breast cancer (Lin et al. , 2003). PyMT+ mice ran on average 6 km/day (— 1B). Contrary to what was previously shown (Goh et al. , 2013), the running mice in our experiments showed no statistically significant differences in tumor growth between the groups (— 1C- G). However, the infiltration of Granzyme B (GZMB) -positive cells was significantly higher in primary tumors of running mice, even though voluntary running had no effect on the frequency of CD3, F4/80, PCNA, or podocalyxin-expressing cells (— 1H). This indicates that exercise in this tumor model modulates the infiltration","Exercise affects almost all tissues in the body, and scientists have found that being physically active can reduce the risk of several types of cancer as well as improving outcomes for cancer patients. However, it is still unknown how exercise exerts its protective effects. One of the hallmarks of cancer is the ability of cancer cells to evade detection by the immune system, which can in some cases stop the body from eliminating tumor cells. Rundqvist et al. used mice to investigate how exercise helps the immune system act against tumor progression. They found that when mice exercised, tumor growth was reduced, and this decrease in growth depended on the levels of a specific type of immune cell, the CD8+ T cell, circulating in the blood. Additionally, Rundqvist",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2014; Hendry, 2016; Weber et al. , 2017). Thus, we have a link from interactions to eco-evolutionary dynamics, suggesting that we do not need to follow all evolutionary changes at the genetic or phenotypic level if we are interested in macro-eco-evolutionary dynamics, but only those changes that affect interactions. In this picture, evolution can be considered as an exploration of interaction space, and modeling at this level can help us to study how complex competitive interaction networks evolve and shape diversity. This neglect of genetic and phenotypic details in interaction-based models (Ginzburg et al. , 1988; Solé, 2002; Tokita and Yasutomi, 2003; Shtilerman et al. , 2015) equals a coarse-graining of the eco-evolutionary system (). This coarse-graining not only reduces complexity but it should also make the approach applicable to a broader class of biological systems. Interaction-based evolutionary models have received some attention in the past (Ginzburg et al. , 1988; Solé, 2002) but then were almost forgotten, despite remarkable results. We think that these works have pointed to a possible solution of a hard problem: The complexity of evolving ecosystems is immense, and it is therefore difficult to find a representation suitable for the development of a statistical mechanics that enables qualitative and quantitative analysis (Weber et al. , 2017). Modeling at the level of interaction traits, rather than modeling of detailed descriptions of genotypes or phenotypes, coarse-grains these complex systems in a natural way so that this approach may be helpful for developing a biologically meaningful statistical mechanics. The first eco-evolutionary interaction-based model was introduced by Ginzburg et al. (1988) based on Lotka–Volterra dynamics for competitive communities. Instead of adding species characterized by random coefficients, taken out of some arbitrary species pool, they made the assumption that a new mutant should be ecologically similar to its parent, which means that phenotypic variations that are not ecologically neutral generate mutants that interact with other species similar to their parents (). Thus, speciation events were simulated as ecologically continuous mutations in the strength of competitive interactions. This model, although conceptually progressive, was not able to produce a large stable diversity, possibly because diversity requires components not included in this model. Therefore subsequent interaction-based models supplemented it with ad hoc features to specifically increase diversity, such as special types of","A patch of rain forest, a coral reef, a pond, and the microbes in our guts are all examples of biological communities. More generally, a community is a group of organisms that live together at the same place and time. Many communities are composed of a large number of different species, and this diversity is maintained for long times. Although diversity is a key feature of biological communities, the mechanisms that generate and maintain diversity are not well understood. Research had hinted at links between diversity and the trade-offs that species are subject to. For instance, there is a trade-off between competitiveness and reproduction: if there are limited resources in the environment a species may either produce many offspring that are not very competitive, or fewer, more competitive",380,128,0.3368
pubmed-summarization,"use of lithotripsy clearly decreases with increase in the stone diameter . despite notable technological progress , 510 % of patients with sialolithiasis can not be successfully treated using minimally invasive techniques . the main cause appears to be the large size of the stones and long - standing history of recurrent inflammations , which lead to the impaction of the sialolith to the wall of the efferent duct . in these cases , the aim of the study was to analyze the trends in the treatment methods in submandibular sialolithiasis in the past decade , the effectiveness of particular methods and to present treatment schedule proposed by the authors . 112 patients with submandibular gland sialadenitis were treated in tertiary university centre ( otolaryngology , head and neck surgery department pozna medical university ) in the years 20042012 . data were analyzed retrospectively on the basis of medical documentation ( outpatient charts , operating protocols ) . the epidemiological data ( gender , age ) , duration of complaints , the treatment method and its effectiveness were analyzed and compared in both groups . in preoperative diagnosis , additionally , in the recent 3 years , ct was performed in 11 cases . during first period , patients were treated in outpatient department by incision of mucosa of floor of the mouth in local anesthesia . following the introduction of sialendoscopy , patients were admitted to the hospital for 1 day . during interventional sialendoscopy , 1.3 and 1.6 mm diameter endoscope ( karl storz tutlingen , germany ) was used . stones were removed with the help of the basket and forceps , introduced through the working canal . the se procedure was carried out under local anesthesia after premedication with ( midazolam , 7.5 mg ) . once the size of the stone localized in submandibular hilum was determined to be larger than 67 mm and endoscopic removal was deemed impossible , the decision of combined approach was made . the combined approach ( incision of the floor of the mouth at the level of submandibular hilum and sialendoscopy ) was performed also under local anesthesia . in case of failure of this treatment and when stone was primarily localized in gland parenchyma , the decision of","our research was conducted to determine the algorithm changes during the treatment of submandibular sialolithiasis . two time periods were compared between 20042008 and 20092012 . the turning point was december 2008 , when sialendoscopy procedure was introduced . in the first period , 48 patients were treated : 31 outpatient duct incisions with stone evacuation and 17 surgical excision of submandibular gland . in the second period , 207 sialendoscopy procedures were performed on 197 patients . out of this particular group , 158 patients were diagnosed with pathological obstruction of salivary glands and 64 of them were confirmed to have sialolithiasis of submandibular gland . deposits of calcifications in 40 individuals ( 62.5 % ) affected by sialolithiasis were removed endoscopically ; however , in 21",380,128,0.3368
dialogsum,"#Person1#: You won't believe who's been elected to do overtime on the Baker account! Me! I've already logged in 20 hours of overtime! #Person2#: Wow! Why so much? I thought they were getting you an assistant. #Person1#: They were supposed to, but so far nobody's turned up, and I'm left on my own to do the work. This is the first break I've had all day. #Person2#: They're really running you into the ground. Why don't you ask for some time off? You could take a long weekend and go away somewhere.",#Person1#'s been elected to do overtime without an assistant. #Person2# suggests #Person1# ask for some time off.,92,17,0.1848
scientific_lay_summarisation-elife-norm,"Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll-like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation. Polarised cell rearrangements drive the simultaneous elongation and narrowing of cell sheets (convergence and extension) during development. These collective cell behaviours have been mostly studied in the context of axis elongation that accompanies gastrulation in bilaterian animals, but are also found in organogenesis, for example underlying kidney tubule elongation (Keller, 2002; Tada and Heisenberg, 2012). Understanding convergence and extension movements is important as their failure is associated with congenital diseases, including neural tube defects (Wallingford et al. , 2013). The first molecular mechanism for convergence and extension was found in Drosophila, where planar polarisation of actomyosin was shown to underlie the polarised cell rearrangements of germband extension (GBE) (Zallen and Wieschaus, 2004; Bertet et al. , 2004). This discovery paved the way for in-depth studies of how the planar polarisation of actomyosin and other components such as Bazooka (Par-3) and E-Cadherin drives the selective shortening of cell-cell junctions during active intercalation of epithelial cells (Zallen and Wieschaus, 2004;  Rauzi et al. , 2008; 2010; Levayer et al. , 2011; Levayer and Lecuit, 2013; Blankenship et al. , 2006; Fernandez-Gonzalez et al. , 2009; Simões et al. , 2010; 2014; Tamada et al. , 2012). Recently, actomyosin planar polarisation was also found to be required during convergence and extension in vertebrate tissues","Early in development, a growing embryo elongates to form its main body (head–tail) axis. This elongation is driven by a process called cell intercalation – when cells insert between each other. The mechanism that controls this coordinated cell movement is well understood on a small scale. However, it is not known how hundreds of cells rapidly intercalate across a whole tissue without deforming a tissue or inappropriately mixing. During fruit fly development, an embryo divides into repeated segments of tissue while elongating. While this happens, cells redistribute an essential structure called the actomyosin cytoskeleton so that it is found more commonly along certain sides of the cell. This structure, which can be thought of as the cell’s “muscle”, is a contractile web made of proteins called actin and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Vocal development is the adaptive coordination of the vocal apparatus, muscles, the nervous system, and social interaction. Here, we use a quantitative framework based on optimal control theory and Waddington’s landscape metaphor to provide an integrated view of this process. With a biomechanical model of the marmoset monkey vocal apparatus and behavioral developmental data, we show that only the combination of the developing vocal tract, vocal apparatus muscles and nervous system can fully account for the patterns of vocal development. Together, these elements influence the shape of the monkeys’ vocal developmental landscape, tilting, rotating or shifting it in different ways. We can thus use this framework to make quantitative predictions regarding how interfering factors or experimental perturbations can change the landscape within a species, or to explain comparative differences in vocal development across species : http: //dx. . org/10. 7554/eLife. 20782. 001 In our study, the specific vocal behavior under investigation is the production of mature contact (‘phee’) calls. Adult marmoset monkeys produce these vocalizations when alone and out of sight of others (undirected context) (Borjon et al. , 2016). If another marmoset is within earshot, then the pair will begin taking turns exchanging these calls (directed context) (Takahashi et al. , 2013). Very young infants are only gradually able to produce mature sounding contact calls (Takahashi et al. , 2015; Zhang and Ghazanfar, 2016), and contingent vocal interactions with parents appears to accelerate this process (Takahashi et al. , 2015,2016). Here, we use optimal control theory to construct a Waddington-like developmental landscape to model this process. Optimal control approaches have long been used in studies of motor behaviors and their application requires four specifications: (1) well-defined behaviors, (2) a biomechanical model of the system, (3) a cost function, and (4) an optimization criterion that describes the probabilities of those behaviors (Wolpert and Landy, 2012). The theory posits that the probability of producing a specific motor action can be calculated by knowing the cost that a given behavior demands (Wolpert and Landy, 2012). If the cost to produce an action is high, that action should be less probable than another whose cost is lower. In the current study, the four specifications are the following: (1) Immature and mature contact calls are the behaviors; (2) The biomechanical model is one established","As infants develop they learn new behaviors and refine existing ones. For example, human infants progress from crying to babbling to producing speech-like sounds. A complex sequence of changes in muscles, the nervous system and in patterns of interactions with other individuals all contribute to these emerging behaviors. Despite this complexity, most studies of vocal development have only considered single factors in isolation. A study of speech development, for example, might examine how changes in the brain enable infants to imitate sounds. However, that same study will probably ignore how changes in the structure of the vocal cords, or in the behavior of the parents, also promote imitation. Young marmoset monkeys, like human infants, gradually develop from producing immature cries to adult-like calls. Teramoto, Takahashi et al. built",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Regulatory T (Treg) cells, which suppress autoimmunity and other inflammatory states, are characterized by a distinct set of genetic elements controlling their gene expression. However, the extent of genetic and associated epigenetic variation in the Treg cell lineage and its possible relation to disease states in humans remain unknown. We explored evolutionary conservation of regulatory elements and natural human inter-individual epigenetic variation in Treg cells to identify the core transcriptional control program of lineage specification. Analysis of single nucleotide polymorphisms in core lineage-specific enhancers revealed disease associations, which were further corroborated by high-resolution genotyping to fine map causal polymorphisms in lineage-specific enhancers. Our findings suggest that a small set of regulatory elements specify the Treg lineage and that genetic variation in Treg cell-specific enhancers may alter Treg cell function contributing to polygenic disease. Lineage specification factors promote cellular differentiation by binding DNA regulatory elements to stably alter the local chromatin state and affect gene transcriptional outputs (Visel et al. , 2009; Thurman et al. , 2012; Nord et al. , 2013; Ostuni et al. , 2013). Since the majority of protein-coding genome sequence is under constraint, due to the cost of deleterious mutational perturbations in protein function, changes in non-coding regulatory portions of the genome are thought to serve as a major source of evolutionary innovation and substrates for selection (King and Wilson, 1975; Schmidt et al. , 2010; Goncalves et al. , 2012; Ward and Kellis, 2012). Histone modifications and chromatin accessibility, which serve as proxies for epigenetic transcriptional control, can exhibit conservation shared with the underlying genetic elements in a given cell lineage across species and within the genetically diverse human population (Kasowski et al. , 2013a; Kilpinen et al. , 2013a; Long et al. , 2013; McVicker et al. , 2013a; Stergachis et al. , 2014; Vierstra et al. , 2014). However, it remains unknown if changes in the chromatin state of regulatory elements associated with cell lineage specification are conserved in their lineage-specificity (Odom et al. , 2007). That is, it is unknown to what extent regulatory elements are cell lineage-specific across multiple organisms and individuals. Strong conservation would imply that the differentiation process of a specialized cell population is highly constrained at a genomic level, whereas extensive variation would suggest that lineage specification is dependent","The immune system protects the body from infection. Key to this protection is the ability to mount an immune response that is sufficient to deal with the threat, but is not so large that the damage it causes to the body exceeds its immediate benefit. Immune cells called regulatory T cells (or Treg cells for short) help to shut down the immune response after a threat has been successfully destroyed. They also prevent the immune system from attacking the body' s own cells, a phenomenon known as autoimmunity. All cells in the body carry the same set of genes, but the activity of these genes varies between cell types to enable the cells to perform their different jobs. This is possible because our DNA contains regions called regulatory",380,128,0.3368
scientific_lay_summarisation-elife-norm,"hand, missense mutations in OPA1 lead to a dominant optic atrophy (Alexander et al. , 2000; Delettre et al. , 2000). Depending on the severity of the mutation, patients may also suffer from ataxia and neuropathy (Yu-Wai-Man et al. , 2010). Also, missense mutations in MFN2 cause Charcot-Marie-Tooth type 2A, a common autosomal dominant peripheral neuropathy associated with axon degeneration (Zuchner et al. , 2004). Finally, aberrant levels of mitochondrial GTPases have been associated with Parkinson' s, Huntington' s and Alzheimers' diseases (Itoh et al. , 2012). These observations in model organisms and human patients suggest that mitochondrial dynamics affects neuronal maintenance in many different contexts. A significant imbalance of mitochondrial fission and fusion may affect the subcellular distribution of mitochondria, especially in neurons since they need to efficiently traffic from the soma to the synapses (Sheng, 2014). Loss of Drosophila Drp1 impairs the delivery of mitochondria to neuromuscular junctions (NMJs), likely because they are large and interconnected. This defect is also associated with a severe depletion of mitochondria in NMJs, which affects local ATP production. This in turn affects the trafficking of synaptic vesicles upon endocytosis during prolonged stimulation (Verstreken et al. , 2005). Similarly, in vertebrates, loss of Drp1 leads to an accumulation of mitochondria in the soma and reduced mitochondrial density in dendrites of hippocampal neurons (Li et al. , 2004). The Drp1 data in flies and vertebrates indicate that the expanded size of mitochondria affects their mobility (Sheng, 2014). Mitochondrial trafficking may also be affected by the physical interaction between the mitochondria and the transport machinery. Recent studies have documented a direct interaction between Mfn2 and a motor adaptor complex for mitochondrial transport, Miro2 (Misko et al. , 2010). Moreover, loss of MFN2 in Purkinje cells displayed reduced mitochondrial motility in cerebellar dendrites (Chen et al. , 2007) and reduced mitochondrial transport in axons in cultured dorsal root ganglion neurons (Misko et al. , 2010). These data suggest that an interaction of Mfn2 with Miro2 may be important for its role in trafficking (Misko et al. , 2010). Although loss of both Drp1 and MFN2 impair mitochondrial trafficking, a careful comparison of the phenotypes associated with loss of Drosophila Drp1, Mitofusin or Marf, would be useful as the suggested mechanisms by which they impair transport seem","Mitochondria are the main source of energy for cells. These vital and highly dynamic organelles continually change shape by fusing with each other and splitting apart to create new mitochondria, repairing and replacing those damaged by cell stress. For nerve impulses to be transmitted across the gaps (called synapses) between nerve cells, mitochondria need to supply the very ends of the nerve fibers with energy. To do this, the mitochondria must be transported from the main body of the nerve cell to the tips of the nerve fibers. This may not happen if mitochondria are the wrong shape, size or damaged. While searching for genetic mutations that disrupt nerve function in the fruit fly Drosophila, Sandoval et al. spotted mutations in a gene called Marf. Further investigations revealed",380,128,0.3368
pubmed-summarization,"mmp-9 and 13 ) in human chondrocytes . on the other hand , leptin has also been reported to increase proliferation and to enhance proteoglycan and collagen synthesis in human chondrocytes . in vivo , leptin injection into rat knee was reported to increase synthesis of insulin - like growth factor 1 ( igf - i ) and transforming growth factor ( tgf ) both contributing to increased proteoglycan synthesis . these effects are linked to increased cartilage matrix production , and also to osteophyte formation . inducible nitric oxide synthase ( inos ) is expressed in oa cartilage , and there are markers of enhanced no production in oa joints . prostaglandins ( pgs ) , especially pge2 , mediate inflammation , tissue destruction , and pain in oa and in oa joints they are formed by cyclooxygenase ( cox ) enzymes ( particularly cox-2 ) and prostaglandin synthases . interleukin-6 ( il-6 ) and interleukin-8 ( il-8 ) are produced by oa cartilage and have a proinflammatory and modulatory role in the pathogenesis of oa . the presence of bioactive leptin in oa joint and the effects of leptin on cartilage metabolism point to a pathophysiological role for leptin in oa . the aim of the present study was to investigate the effects of leptin on mediators of cartilage metabolism by measuring its effects on the production of no , pge2 , il-6 , and il-8 in oa cartilage and by evaluating the signaling mechanisms involved in these effects by pharmacological means . the study was approved by the ethics committee of tampere university hospital , and the patients gave their written approval . the donor patients , age ranging from 53 to 87 years and body mass index ranging from 20 to 32 , were all diagnosed to have osteoarthritis . cartilage samples were washed with phosphate buffered saline ( pbs ) and processed for the experiments within two hours after the operation . full thickness pieces of articular cartilage from femoral condyles , tibial plateaus , and patellar surfaces showing macroscopical features of early oa were removed aseptically from subchondral bone with a scalpel and cut into small pieces ( about 2 2 2 mm ) . cartilage cubes randomly selected from 3 different areas of","obesity is an important risk factor for osteoarthritis ( oa ) in weight - bearing joints , but also in hand joints , pointing to an obesity - related metabolic factor that influences on the pathogenesis of oa . leptin is an adipokine regulating energy balance , and it has recently been related also to arthritis and inflammation as a proinflammatory factor . in the present paper , the effects of leptin on human oa cartilage were studied . leptin alone or in combination with il-1 enhanced the expression of inos and cox-2 , and production of no , pge2 , il-6 , and il-8 . the results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor b ( nf-b ) and",380,128,0.3368
pubmed-summarization,"simulated annealing algorithm ; however , robust software that implements the algorithm into effective practice is not available . here we describe nmrmix , a freely available , open - source software solution that utilizes a simulated annealing algorithm to generate mixtures with minimal peak overlap . nmrmix was written in python 2.7 ( ) and utilizes the qt 5 framework ( ) with pyqt5 bindings ( ) to build a graphical user interface ( gui ) . the input to nmrmix consists of a list of peaks from 1d h nmr spectra for each compound , a target value for the number of compounds in each mixture , and a user - defined parameter that specifies overlap ranges for the peaks . in optimizing mixtures nmrmix utilizes a scoring function that considers the proportion of peaks in a compound that are overlapped as well as the intensity of the peaks . the graphical interface supports access to customizable parameters , downloads of peak list data , interactive views of simulated spectra for each mixture , and graphs of statistics . nmrmix outputs regions of interest ( rois ) in a simple , text - based tabular format that can be used to automate the analysis of nmr ligand affinity screening data . nmrmix can be built on most operating systems ( linux , mac osx , and windows ) , and it is available preinstalled in the nmrfam virtual machine ( ) . generating optimized nmr mixtures in nmrmix requires information on the compounds to be mixed as well as a peak list containing the h chemical shifts for each compound . the compound information can be added manually within the nmrmix interface , or it can be imported from a csv ( comma - separated values ) file that contains the information for all of the compounds in the library . the only required compound information for optimization is the name of the compound , a unique identifier , and the source of the peak list . additional characteristics , such as smiles strings or stock solution solvent , can also be included to provide enhancements within nmrmix . the h nmr peak lists can be imported from either local or online sources . nmrmix can input peak","nmr ligand affinity screening is a powerful technique that is routinely used in drug discovery or functional genomics to directly detect protein ligand binding events . binding events can be identified by monitoring differences in the 1d 1h nmr spectrum of a compound with and without protein . although a single nmr spectrum can be collected within a short period ( 210 min per sample ) , one - by - one screening of a protein against a library of hundreds or thousands of compounds requires a large amount of spectrometer time and a large quantity of protein . therefore , compounds are usually evaluated in mixtures ranging in size from 3 to 20 compounds to improve the efficiency of these screens in both time and material .",380,128,0.3368
pubmed-summarization,"infused into brain regions where neurodegenerative processes associated with brain ischemia or ad normally take place . moreover , dkk1 is also associated with neuronal death in cellular and animal models of excitotoxic / ischemic neuronal death , and the treatment of ischemic animals with dkk1 antisense oligonucleotides protects hippocampal neurons against ischemic damage and cultured cortical neurons against nmda toxicity . for these reasons , the dkk1-lrp6 interaction can be considered as a potentially interesting therapeutic intervention point and dkk1 a potential drug target for the treatment of bone and neurodegenerative disorders . a small molecule ( nci8642 ) has been described as an inhibitor of the interaction between dkk1 and one of its receptors ( lrp5 ) , as well as an inhibitor of dkk1 activity in reducing wnt/-catenin signaling activation . in this study , we sought to further characterise nci8642 activity , using biochemical and biophysical approaches , and to extend its characterization in relation to lrp6 , given the prominent expression in brain of lrp6 and its relevance to the neurodegenerative diseases field . human embryonic kidney cells ( hek293 ) were obtained from the german collection of microorganisms and cell cultures . wnt3a all cell lines were cultured in dmem supplemented with fbs and glutamax ( gibco ) . the monoclonal antibody against -catenin was obtained from bd biosciences , the polyclonal goat anti - dkk1 antibody from r&d , while the fluorescently conjugated secondary antibodies were all from invitrogen . the dna encoding the full - length human lrp6 sequence was cloned into the pcdna3.1/zeo(+ ) expression vector ( invitrogen ) . the dna encoding the human dkk1 sequence was cloned into pcdna6.2/clumio - dest ( invitrogen ) . the sequence encoding the secreted alkaline phosphatase from clontech was amplified by pcr and inserted at the c - terminus of dkk1 sequence into the pcdna6.2/clumio - dest - dkk1 plasmid . the luciferase reporter plasmid p4tcf - luc comprises four copies of a tcf - responsive element upstream of a tata element luciferase coding sequence transcriptional unit . all cell lines were cultured in dmem supplied with 10% fbs , 2 mm glutamax , 100 units / ml penicillin , 100 g / ml streptomycin , and the appropriate selection antibiotic ( 50","background . dkk1 antagonizes canonical wnt signalling through high - affinity binding to lrp5/6 , an essential component of the wnt receptor complex responsible for mediating downstream canonical wnt signalling . dkk1 overexpression is known for its pathological implications in osteoporosis , cancer , and neurodegeneration , suggesting the interaction with lrp5/6 as a potential therapeutic target . results . we show that the small - molecule nci8642 can efficiently displace dkk1 from lrp6 and block dkk1 inhibitory activity on canonical wnt signalling , as shown in binding and cellular assays , respectively . we further characterize nci8642 binding activity on lrp6 by surface plasmon resonance ( spr ) technology . conclusions . this study demonstrates that the dkk1-lrp6 interaction can be the target of small molecules and",380,128,0.3368
dialogsum,"#Person1#: Hey. Have you been watching any of the World Cup soccer matches? #Person2#: Well, I was watching until my favorite team was bounced out of the first round of play. I mean, they should have made all the way to the second round, but a whole series of events cost the team the opportunity to prove themselves on the world stage. #Person1#: What do you mean? #Person2#: Well, in the first match, two of their star players were out with nagging injuries, so the rest of the players, unfortunately, just couldn't keep up with the opposing team. #Person1#: Well, that just life. I mean every team is going to have players out with injuries. #Person2#: Yea, but that's beside the point. And, and then, in the second game, the refs made some terrible calls, allowing the opposing team to slip by with a victory. I mean, we were robbed on that one. The refs must have been walking in their sleep! #Person1#: But, didn't one of your own players accidentally kick the ball twice into his own goal? I mean that doesn't sound like a bad call to me. #Person2#: That's just beside the POINT! #Person1#: Really? #Person2#: And finally, our team was ahead in the final watch---I mean they were way out ahead until the other team rallied in the final three minutes of play to squeak out a victory. It was a total embarrassment for our team. Our team was booed. All I can say is that the sun must have been in our players' eyes ... #Person1#: Uh, wasn't it a night game? #Person2#: That's beside the point, too. You just not understanding anything I'm saying. #Person1#: So, who are you rooting for now, seeing that your team has been eliminated? #Person2#: Ah, I can't watch any more soccer, so I've been following an online chess tournament. #Person1#: What?! Now, that has to be the most ridiculous reaction I have ever heard of. So, you're going to completely boycott the rest of the play just because your team got bounced out of the tournament? #Person2#: Ah, forget it. You just don't understand.","#Person2# finds excuses for the soccer team's loss in the World Cup. #Person1# asks which team will #Person2# root for next, but #Person2# is instead following an online chess tournament.",356,30,0.0843
scientific_lay_summarisation-elife-norm,"Complex biological systems rely on cell surface cues that govern cellular self-recognition and selective interactions with appropriate partners. Molecular diversification of cell surface recognition molecules through DNA recombination and complex alternative splicing has emerged as an important principle for encoding such interactions. However, the lack of tools to specifically detect and quantify receptor protein isoforms is a major impediment to functional studies. We here developed a workflow for targeted mass spectrometry by selected reaction monitoring that permits quantitative assessment of highly diversified protein families. We apply this workflow to dissecting the molecular diversity of the neuronal neurexin receptors and uncover an alternative splicing-dependent recognition code for synaptic ligands. The remarkable anatomical and functional complexity of nervous systems relies on molecular programs for cell intrinsic properties and selective cellular interactions. Major advances in transcriptomics have enabled the identification of gene regulatory programs and mRNA targets that underlie specification of neuronal cell types and their plasticity (Hobert, 2011; Ebert and Greenberg, 2013; Molyneaux et al. , 2015). For example, specific transcriptional programs direct the neurotransmitter phenotypes of neuronal populations, the targeting of axonal projections, or the modification of synapse numbers in response to neuronal activity. In addition, transcript-based studies have uncovered gene families with substantial molecular complexity that may encode neuronal recognition events (Zipursky and Sanes, 2010; Schreiner et al. , 2014a). What remains a major challenge is the exploration of such molecular programs and their function at the protein level. mRNA and protein turnover rates as well as mRNA translation rates exhibit a significant dynamic range. Thus, transcript abundance cannot easily be extrapolated to provide quantitative assessments of the proteome or insights into the stoichiometry of protein complexes (Helbig et al. , 2011; Schwanhausser et al. , 2011; Vogel and Marcotte, 2012). Notably, such post-transcriptional forms of gene regulation are particularly prevalent in the central nervous system highlighting the need for quantitative approaches that enable targeted dissection of the neuronal proteome. Additionally, many neurons possess long-distance projections. The localization of presynaptic proteins in many cases differs from the anatomical place of their mRNA expression. Thus, the possibility to detect and quantify isoforms at the protein level provides an important advantage in order to understand the functional role of these proteins. New developments in proteomics have driven major advances in understanding the","To create a protein, a gene is first copied to form an RNA molecule that contains regions known as introns and exons. Splicing removes the introns and joins the exons together to form a molecule of ‘messenger RNA’, which is translated into a protein. Over the course of evolution, many groups—or families—of proteins have expanded and diversified their roles. One way in which this can occur is through a process known as alternative splicing, in which different exons can be included or excluded to generate the final messenger RNA. In this way, a single gene can produce a number of different proteins. These closely related proteins are known as isoforms. The brain contains billions of neurons that communicate with one another across connections known as synapses. A family",380,128,0.3368
dialogsum,"#Person1#: Would you like to order now? #Person2#: This all looks good! I think we know what we want. #Person1#: Please let me point out the chef's special, which is blackened catfish. #Person2#: I am dieting, so could the chef prepare the food with no extra sauce? #Person1#: We are always happy to adjust our cooking to meet your needs. #Person2#: Could you tell me if there are any entrees that are vegetarian? #Person1#: The cashew broccoli noodles or the cheese and veggie enchiladas would be an excellent choice. #Person2#: I am going to go with the grilled shrimp with garlic sauce. I would like the garlic sauce on the side. #Person1#: Would you like your salad brought to you with your entree, or would you like it served now? #Person2#: You can serve our salads with our dinner.",#Person2# is dieting and wants vegetarian entrees. #Person1# gives some recommendations and will serve #Person2#'s salad with #Person2#'s dinner.,139,19,0.1367
scientific_lay_summarisation-elife-norm,"spleen and expressing the NK1. 1 antigen on CD3ε-negative cells, NK cells are also present in solid organs, such as the thymus, uterus, and liver (Yokoyama, 2013). Like the conventional NK (cNK) cells in the spleen, thymic NK cells are cytotoxic and require IL-15 but they differ from cNK cells by their characteristic expression of CD127 (IL-7 receptor α) and requirement for a thymus where they can arise from early thymocyte precursors (Vosshenrich et al. , 2006; Ribeiro et al. , 2010; Vargas et al. , 2011). Furthermore, thymic NK cells uniquely require the transcription factor GATA-3 for development (Vosshenrich et al. , 2006). NK cells are normally present in the non-pregnant uterus (Parr et al. , 1991; Yadi et al. , 2008; Mallidi et al. , 2009) but have been mostly studied after they expand at the site of embryo implantation during pregnancy (Moffett and Loke, 2006; Hatta et al. , 2012). Like cNK cells, uterine NK (uNK) cells require IL-15 for development (Ashkar et al. , 2003). In addition, they are cytotoxic as they express perforin and granzymes, and they produce IFNγ (Parr et al. , 1990; Ashkar et al. , 2000). Interestingly, however, uNK cells appear relatively normal in Tbet-deficient mice (Tayade et al. , 2005) and recent studies suggest that a subset of uNK cells can be distinguished from cNK cells (Yadi et al. , 2008). Thus, NK cell subsets can be identified in different tissues that appear to be distinguishable from cNK cells. In the liver, we recently showed that there are two populations of NK cells, distinguished by mutually exclusive expression of CD49a and DX5 (Peng et al. , 2013). Phenotypically, CD49a−DX5+ are very similar to splenic cNK cells whereas CD49a+ DX5– are unlike splenic cNK cells. In parabiotic mice, the host liver contains CD49a+ DX5− NK cells of host origin and circulating CD49a−DX5+ NK cells derived from both host and the other parabiont, indicating that the CD49a+ DX5− cells are tissue-resident NK (trNK) cells whereas the CD49a−DX5+ cells are cNK cells. The trNK cells appear similar to immature cNK cells because they express similar markers (NK1. 1, NKp46) but low levels of CD11b, are DX5−, and display high levels of TNF-related apoptosis-inducing ligand (TRAIL) (Kim et al. , 2002; Di Santo, 2006; Peng","Our immune system has white blood cells that migrate throughout the body in search of invading microbes or diseased and damaged cells. When these events are encountered, the white blood cells move into the affected tissue and launch an immune response to eliminate the threat. Natural killer cells are white blood cells that kill cells that are infected with viruses or are cancerous. Most of what is known about conventional natural killer cells is derived from studying the spleen, which filters the blood and contains many immune cells. Natural killer cells also circulate around the body or are found within other tissues, and it was thought that both types of cells were either the same, or that one type could develop into the other. However, the thymus—an organ",380,128,0.3368
dialogsum,"#Person1#: Do you think I could borrow your car to go grocery shopping? The supermarkets outside the city are so much cheaper. I'd also be happy to pick up anything you need. #Person2#: Well, I don't like to let anyone else drive my car. Tell you what, why don't we go together?",#Person1# wants to borrow #Person2#'s car. #Person2# suggests going together.,52,10,0.1923
scientific_lay_summarisation-elife-norm,"The SNAREs SNAP25 and SNAP23 are proteins that are initially cytosolic after translation, but then become stably attached to the cell membrane through palmitoylation of cysteine residues. For palmitoylation to occur, membrane association is a prerequisite, but it is unclear which motif may increase the affinities of the proteins for the target membrane. In experiments with rat neuroendocrine cells, we find that a few basic amino acids in the cysteine-rich region of SNAP25 and SNAP23 are essential for plasma membrane targeting. Reconstitution of membrane-protein binding in a liposome assay shows that the mechanism involves protein electrostatics between basic amino acid residues and acidic lipids such as phosphoinositides that play a primary role in these interactions. Hence, we identify an electrostatic anchoring mechanism underlying initial plasma membrane contact by SNARE proteins, which subsequently become palmitoylated at the plasma membrane. Palmitoylation is a post-translational modification of a protein which causes its stable attachment to a cellular membrane. Examples of proteins that follow this paradigm are the homologous SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) proteins SNAP25 and SNAP23, which after translation are initially cytosolic proteins. In order to function in vesicle fusion, they relocate to the plasma membrane. SNAP23 is ubiquitously expressed, whereas the neuronal SNAP25 is highly abundant in the synapse and in the plasma membrane of neuroendocrine cells (Jahn and Fasshauer, 2012; Wilhelm et al. , 2014; Knowles et al. , 2010). Stable attachment to membranes is achieved after palmitoylation of a cysteine cluster, which is most probably catalyzed by the plasma membrane resident palmitoyl acyltransferase DHHC2. DHHC2 is characterized by the presence of a conserved DH (H/Y) C motif and can palmitoylate SNAP25 and SNAP23 (Greaves et al. , 2010). The majority of SNAP25 molecules reside in the plasma membrane, while 20% are located in a perinuclear recycling endosome-trans-Golgi network (Aikawa et al. , 2006). A two-compartment model for SNAP25 trafficking has been proposed which speculates that the endocytic recycling of SNAP25 might be coupled to its depalmitoylation, followed by its repalmitoylation and recycling back to the plasma membrane (Aikawa et al. , 2006). In any case, in steady-state, the large majority of SNAP25 molecules are stably attached to the cell membrane. The minimal domain necessary for SNAP25 plasma membrane targeting has been mapped to amino acids 85–120 (Gonzalo et","Cells often communicate with each other by releasing chemicals that normally are stored in small membrane-bound compartments called vesicles. For example, when a neuron is stimulated, vesicles merge with its cell membrane and release their content into a gap between itself and other neurons. This complicated process involves many steps and molecules, including proteins called SNAREs. Some SNARE proteins reside at the inner side of the cell membrane and help vesicles to fuse with this membrane. Two SNARE proteins called SNAP25 and SNAP23 are produced in the liquid inside the cell and initially float freely. Eventually, these proteins become directly anchored to the cell membrane, however, not much is known about what happens to these proteins in between these stages, or how they first attach to the membrane",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of bacterial species (with the exception of some proteobacteria such as Escherichia coli), all archaea, some mitochondria and other organelles (Sheppard and Söll, 2008). Bacteria lacking specific glutamine and/or asparagine tRNA synthetases instead utilize a non-discriminatory glutamyl- (asparaginyl) synthetase that forms misacylated Glu-tRNAGln and Asp-tRNAAsn aminoacyl complexes, respectively (Curnow et al. , 1997; Rathnayake et al. , 2017). These misacylated complexes are specifically recognized by GatCAB and amidated to the cognate Gln-tRNAGln and Asn-tRNAAsn aminoacyl tRNAs, thereby preserving the fidelity of the genetic code. We recently identified that in mycobacteria, strains with mutations in gatA causing partial loss of function are not only viable, but can be isolated from patient samples (Su et al. , 2016). These strains have much higher rates of specific mistranslation – of glutamine to glutamate, and asparagine to aspartate – since a proportion of misacylated Glu-tRNAGln and Asp-tRNAAsn complexes are not fully converted to the cognate aminoacyl forms before taking part in translation at the ribosome. Importantly, wild-type GatCAB could also be limiting. Wild-type mycobacteria flow-sorted for lower GatCAB expression had both higher mistranslation rates and rifampicin tolerance (Su et al. , 2016), suggesting that targeting the indirect tRNA aminoacylation pathway may present a novel and attractive means for increasing mycobacterial rifampicin susceptibility. Here, we identify the natural product kasugamycin as a small molecule that can specifically decrease mistranslation due to the indirect tRNA aminoacylation pathway. At sub-inhibitory concentrations, kasugamycin, but not another aminoglycoside streptomycin can increase mycobacterial rifampicin susceptibility both in vitro and in animal infection. We hypothesized that a small molecule that could specifically decrease mycobacterial mistranslation would result in increased susceptibility to rifampicin. GatCAB-mediated mistranslation is not due to ribosomal decoding errors – but rather due to misacylated Glu-tRNAGln and Asp-tRNAAsn complexes taking part in translation (Su et al. , 2016). In addition to other reported activities in E. coli (Lange et al. , 2017; Müller et al. , 2016; Kaberdina et al. , 2009; Moll and Bläsi, 2002), the aminoglycoside kasugamycin decreased ribosomal misreading of mRNA (van Buul et al. , 1984), but it was not known if it could also decrease errors due to translation of misacylated tRNAs, as the indirect tRNA aminoacylation pathway is not present in E. coli. We tested whether kasugamycin could increase fidelity of misacylated tRNA-mediated","A bacterium called Mycobacterium tuberculosis is responsible for nearly 98% of cases of tuberculosis, which kills more people worldwide than any other infectious disease. This is due, in part, to the time it takes to cure individuals of the disease: patients have to take antibiotics continuously for at least six months to eradicate M. tuberculosis in the body. Bacteria, like all cells, make proteins using instructions contained within their genetic code. Cell components called ribosomes are responsible for translating these instructions and assembling the new proteins. Sometimes the ribosomes produce proteins that are slightly different to what the cell’s genetic code specified. These ‘incorrect proteins’ may not work properly so it is generally thought that cells try to prevent the mistakes from happening. However, scientists have recently found",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the cofactor’s redox potential. Since non-flavinylated FMN-binding domains have low flavin-binding affinity, the ApbE-catalyzed reaction may simply function to secure the cofactor to the protein (Borshchevskiy et al. , 2015). Once the flavin is linked to the FMN-binding domain, interactions with the folded protein stabilize the flavin’s semiquinone state in a fashion that presumably enhances electron transfer (Barquera, 2014; Backiel et al. , 2008). ApbE-flavinylated FMN-binding domains have been found to be critical for five characterized extracytosolic electron transfer systems. These systems include the cation-pumping NADH: quinone oxidoreductase (NQR) and Rhodobacter nitrogen fixation (RNF) complexes (1B and C), nitrous oxide and organohalide respiratory complexes (1D and E), and a Gram-positive extracellular electron transfer system (1F; Backiel et al. , 2008; Buttet et al. , 2018; Light et al. , 2018; Zhang et al. , 2017; Zhou et al. , 1999). In addition, ApbE-flavinylated [S/T]GA[S/T]-like sequence motifs in homologous extracytosolic fumarate and urocanate reductases facilitate transfer from respiratory electron transport chains (Bogachev et al. , 2012; Kees et al. , 2019; Light et al. , 2019). Notably, each of these characterized activities links AbpE flavinylation to a different aspect of microbial cellular respiration, with the NQR and RNF complexes being particularly noteworthy. These systems are widely distributed throughout microbial life and catalyze key intermediate steps in the energy metabolism of numerous microbes (Barquera, 2014; Buckel and Thauer, 2018; Reyes-Prieto et al. , 2014). In recent years, large-scale comparative genomic analyses have emerged as a powerful tool for discovering functionally and/or mechanistically related features of prokaryotic biology (Burstein et al. , 2017; Crits-Christoph et al. , 2018; Doron et al. , 2018). Here, we develop a ‘guilt by association’ approach (Aravind, 2000) (summarized in — 1) that exploits genomic diversity to contextualize the significance of extracytosolic flavinylation. Our analysis of flavinylation-associated gene clusters provides evidence of widespread flavinylation throughout bacteria and uncovers new connections to respiration and iron assimilation. We further identify uncharacterized aspects of extracytosolic flavinylation, including novel ApbE substrates and a class of multi-flavinylated proteins. These findings place ApbE-flavinylated proteins alongside cytochromes and thioredoxin-like proteins as central mediators of bacterial extracytosolic electron transfer. As all previously characterized flavinylation systems contain genes that encode for an ApbE enzyme and a substrate that contains an FMN-binding domain, we reasoned that these features","In bacteria, certain chemical reactions required for life do not take place directly inside the cells. For instance, ‘redox’ reactions essential to gather minerals, repair proteins and obtain energy are localised in the membranes and space that surround a bacterium. These chemical reactions involve electrons being transferred from one molecule to another in a cascade that connects the exterior of a cell to its internal space. The enzyme ApbE allows proteins to perform electron transfer by equipping them with ring-like compounds called flavins, through a process known as flavinylation. Yet, the prevelance of flavinylation in bacteria and the scope of redox reactions it facilitates has remained unclear. To investigate this question, Méheust, Huang et al. analysed over 30,000 bacterial genomes, finding genes essential for ApbE flavinylation in about",380,128,0.3368
dialogsum,"#Person1#: My God! Where is my suitcase? #Person2#: Oh! I think that they've unloaded all the luggage. Well, it's not here. #Person1#: I suppose that suitcase is lost, doesn't it? #Person2#: Which suitcase was it? #Person1#: The one with all the souvenirs, the one that you told me not to pack. #Person2#: Are you sure you checked it? #Person1#: Sure. #Person2#: It might be, loaded on another flight. #Person1#: Do you think that it could be left behind? #Person2#: That's always a possibility. Sooner or later, it'll be traced and rerouted. #Person1#: I hope you are right. #Person2#: Well... What do we do now? #Person1#: I should report it to the airline, look, why don't you wait for me in the coffee shop? I'll meet you there as soon as I'm through. #Person2#: Ok! Good luck!",#Person1# cannot find #Person1#'s suitcase and thinks it might be lost. #Person2# thinks there are many possibilities. #Person1# will report it to the airline.,136,24,0.1765
dialogsum,"#Person1#: Can I help you? #Person2#: Yes. When is the next train to New York City? #Person1#: Let me see. . . the train to New York City. . . here it is. . . daily except Sunday at 10, 30, 12, 20 and 15, 10. #Person2#: Aren't there any trains before 10:30? #Person1#: Sorry, not before 10:30. #Person2#: Then one to New York at 10:30. #Person1#: One way or round trip? #Person2#: One way. #Person1#: A soft seat or hard one? #Person2#: How much is a soft? #Person1#: $ 15. And for a hard one, only $ 6. #Person2#: Then one hard seat, please. #Person1#: OK. Here is your change. The train leaves on platform 8.",#Person2# buys a one-way hard-seat train ticket to New York City at 10:30 with #Person1#'s assistance.,117,16,0.1368
pubmed-summarization,"their mothers make an informed decision about whether to undergo cervical cerclage procedure from neonatologist s perspective . the study was approved by research ethics committee in beijing obstetrics and gynecology hospital , capital medical university ( beijing , china ) . written informed consent we performed a retrospective cohort study reviewing all preterm neonates with birth weight less than 2000 g that were admitted to the neonatal intensive care unit or neonatal department of beijing obstetrics and gynecology hospital , capital medical university , beijing , china between january 1 , 2009 and december 31 , 2013 . the preterm births eligible for this study were divided into two groups : neonates born to mothers with cervical incompetence and those born to mothers without cervical incompetence . twins , multiple births , neonates with chromosome abnormalities and/or congenital malformations , and those who died in the delivery room despite adequate resuscitation , were excluded . cervical incompetence was defined as painless dilatation and effacement of the cervix in the second trimester of pregnancy , resulting in situations of a miscarriage or a preterm birth in the absence of labor , or had sonographic evidence of cervical shortening ( cervical length < 2.5 cm measured by transvaginal ultrasound ) or funneling . cervical cerclage either elective ( when the clinical history suggests risk of mid - trimester loss ) or emergency ( when there is evidence of a short cervix < 25 mm or cervical shortening on ultrasound ) was performed based on the attending obstetrician s judgment . gestational age was based on mother s last menstrual period ( lmp ) or verified by early ultrasound examination if the mother s menstrual period was irregular or lmp was unknown . as co - morbidities , rds , eos , bpd , rop , pvl , ivh ( above grade 3 ) , nec , severe asphyxia small for gestational age ( sga ) , and mortality of premature neonates were analyzed in the experimental and control groups . nec was defined as bell 's stage ii or greater and bpd was defined as oxygen dependence at 36 weeks postmenstrual age . we categorized infants as sga if their birth weights were less than the 10th percentile for their gestational","objective : this study aimed to determine the impact of maternal cervical incompetence ( with or without mcdonald cerclage ) on mortality and morbidity of preterm infant with birth weight < 2000g.methods:581 neonates were eligible for this study , 79 with cervical incompetence and 502 without it ( control ) . incidences of neonatal respiratory distress syndrome ( rds ) , bronchopulmonary dysplasia ( bpd ) , intraventricular hemorrhage ( ivh ) , neonatal necrotizing enterocolitis ( nec ) , retinopathy of prematurity ( rop ) , periventricular leukomalacia ( pvl ) , severe asphyxia , small for gestational age ( sga ) , early - onset sepsis ( eos ) , and mortality were compared between the two groups.findings:mean gestational age was earlier in cervical incompetence group",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Electrophysiological methods, that is M/EEG, provide unique views into brain health. Yet, when building predictive models from brain data, it is often unclear how electrophysiology should be combined with other neuroimaging methods. Information can be redundant, useful common representations of multimodal data may not be obvious and multimodal data collection can be medically contraindicated, which reduces applicability. Here, we propose a multimodal model to robustly combine MEG, MRI and fMRI for prediction. We focus on age prediction as a surrogate biomarker in 674 subjects from the Cam-CAN dataset. Strikingly, MEG, fMRI and MRI showed additive effects supporting distinct brain-behavior associations. Moreover, the contribution of MEG was best explained by cortical power spectra between 8 and 30 Hz. Finally, we demonstrate that the model preserves benefits of stacking when some data is missing. The proposed framework, hence, enables multimodal learning for a wide range of biomarkers from diverse types of brain signals. Non-invasive electrophysiology assumes a unique role in clinical neuroscience. Magneto- and electophencephalography (M/EEG) have an unparalleled capacity for capturing brain rhythms without penetrating the skull. EEG is operated in a wide array of peculiar situations, such as surgery (Baker et al. , 1975), flying an aircraft (Skov and Simons, 1965) or sleeping (Agnew et al. , 1966). Unlike EEG, MEG captures a more selective set of brain sources with greater spectral and spatial definition (Ahlfors et al. , 2010; Hari et al. , 2000). Yet, neither of them is optimal for isolating anatomical detail. Clinical practice in neurology and psychiatry, therefore, relies on additional neuroimaging modalities with enhanced spatial resolution such as magnetic resonance imaging (MRI), functional MRI (fMRI), or positron emission tomography (PET). Recently, machine learning has received significant interest in clinical neuroscience for its potential to predict from such heterogeneous multimodal brain data (Woo et al. , 2017). Unfortunately, the effectiveness of machine learning in psychiatry and neurology is constrained by the lack of large high-quality datasets (Woo et al. , 2017; Varoquaux, 2017; Bzdok and Yeo, 2017; Engemann et al. , 2018) and comparably limited understanding about the data generating mechanisms (Jonas and Kording, 2017). This, potentially, limits the advantage of complex learning strategies proven successful in purely somatic problems (Esteva et al. , 2017; Yoo et al. , 2019; Ran et al. , 2019). In","How old are you? What about your body, and your brain? People are used to answering this question by counting the years since birth. However, biological age could also be measured by looking at the integrity of the DNA in cells or by measuring the levels of proteins in the blood. Whether one goes by chronological age or biological age, each is simply an indicator of general health – but people with the same chronological age may have different biological ages, and vice versa. There are different imaging techniques that can be used to study the brain. A method called MRI reveals the brain’s structure and the different types of tissue present, like white and grey matter. Functional MRIs (fMRIs for short) measure activity across different brain regions,",380,128,0.3368
dialogsum,"#Person1#: Mister Jones, I just got off the phone with Mister Dawson. He wants to schedule a meeting with you for later today or tomorrow. #Person2#: What does he want to talk about? #Person1#: One of the factories that makes his products. He said it was pretty urgent. #Person2#: Well, I don't want to stay too late like last night, my wife was not happy with me. #Person1#: How about tomorrow at 11:00 am? I checked your schedule and the only thing you have that day is a phone call at 2:00 PM. #Person2#: 11:00 tomorrow sounds fine, can you set everything up and then email me all the information, please? #Person1#: Of course, I was just about to go to lunch actually. Do you want to join me? #Person2#: I'd love to, but I have to look at some samples from a new customer. I'll join you next time.",Dawson wants to have a meeting with Jones. Jones refuses to stay late today so #Person1# arranges the meeting tomorrow. #Person1# invites Jones for lunch but Jones is busy.,150,29,0.1933
scientific_lay_summarisation-elife-norm,"In this study, we report a new protein involved in the homeostatic regulation of sleep in Drosophila. We conducted a forward genetic screen of chemically mutagenized flies to identify short-sleeping mutants and found one, redeye (rye) that shows a severe reduction of sleep length. Cloning of rye reveals that it encodes a nicotinic acetylcholine receptor α subunit required for Drosophila sleep. Levels of RYE oscillate in light–dark cycles and peak at times of daily sleep. Cycling of RYE is independent of a functional circadian clock, but rather depends upon the sleep homeostat, as protein levels are up-regulated in short-sleeping mutants and also in wild type animals following sleep deprivation. We propose that the homeostatic drive to sleep increases levels of RYE, which responds to this drive by promoting sleep. Sleep is a common and prominent behavior in almost all vertebrate animals and also in most invertebrates (Cirelli, 2009; Sehgal and Mignot, 2011). The function of sleep is a mystery, but it is surely of great importance to animals, as prolonged sleep deprivation can lead to death. Anatomical studies in mammals and birds have revealed brain structures and neurotransmitters that regulate sleep and wakefulness (Saper et al. , 2010). However, our understanding of the molecular mechanisms that drive the need to sleep is still in its infancy, partially due to the challenge of performing genetic experiments with mammalian models. In the past decade, several premier genetic organisms have been introduced into the sleep field, including fruit flies, worms and zebra fish. Mammalian counterparts of some sleep components identified in these model animals also regulate sleep (Joho et al. , 2006), which argues that (i) behavioral genetics in lower organisms provides an efficient tool to identify sleep components, (ii) at least some of the mechanisms underlying sleep are conserved through evolution. A two-process model for sleep regulation has been widely accepted by the sleep field. Process C (the circadian clock) controls the timing, in other words the onset and offset of sleep, whereas process S (the sleep homeostat) regulates sleep duration based on the sleep pressure built up during prior wakefulness (Borbely, 1982). This simple model explains sleep related phenomena, including sleep rebound after sleep deprivation. Molecular mechanisms of circadian control have been well characterized (Zheng and Sehgal, 2012), but, as noted","Almost all animals need to sleep, including most insects. In experiments in the 1980s, a group of rats that were completely deprived of sleep died within only a few weeks. Sleep has been implicated in processes including tissue repair, memory consolidation and, more recently, the removal of waste materials from the brain. However, a full understanding of why we sleep is still lacking. As anyone who has experienced jetlag can testify, the timing of the sleep/wake cycle is governed by the circadian clock, which leads us to feel sleepy at certain points of the day–night cycle and alert at others. The duration of sleep is regulated by a second process called sleep/wake homeostasis. The longer we remain awake, the more the body’s need for sleep—or ‘sleep drive’—increases, until",380,128,0.3368
pubmed-summarization,"adult onset still s disease ( aosd ) is a chronic systemic inflammatory disorder in which high spiking fever , typical skin rash , and polyarthritis occur . the main biological features are neutrophilic leukocytosis , hyperferritinemia , and negative rheumatoid factor ( rf ) or antinuclear antibodies ( ana ) . others may include splenomegaly , pleuritis , pericarditis , and hepatic abnormalities . even though functional prognosis essentially depends on articular involvement , life - threatening prognosis depends on serious complications , such as hepatic failure , disseminated intravascular coagulopathy , hemophagocytosis , infections , amyloidosis , and cardiomyopathy . in this article we suggest a successful combined therapy of prednisolone ( pd ) , colchicine ( col ) , and cyclophosphamide ( ctx ) and review the literature . a 25-year - old korean woman was diagnosed with aosd four years ago after experiencing a high spiking fever , maculopapular rash , and polyarthritis in her hands , elbows and knees . in laboratory findings , the leukocyte count was 19,900/ l , the serum ferritin level was 719.3 ng / ml ( 10240 ) , and rf and ana were negative . during a follow - up , typical skin rash had disappeared after administration of pd , sulfasalazine or hydroxychloroquine and methotraxate ( mtx ) , but either high fever or polyarthitis was wax and wane , and occasionally , intra - articular injections of corticosteroid were administered . in july 1998 , she was admitted to our hospital because of slowly increasing proteinuria over a 7 month period without pitting edema or hypertension . she was single and had no family history of any rheumatic disease or drug history , such as gold or d - penicilliamine . the results of laboratory data showed that the white - cell count ( wbc ) was 12,800 / l , hemoglobin ( hb ) was 10.6 g / dl , platelet was 610,000 / l , esr was 61 mm / hr , and c - reactive protein ( crp ) was 9.50 mg / dl ( < 0.8 ) . the serum protein and albumin had decreased to 4.5 g / dl ( 6.48.5 ) and 2.1 g / dl ( 3.25.5 ) , respectively","we report a 25-year - old korean woman with adult onset still s disease ( aosd ) presented with renal amyloidosis , which had developed four years after disease onset . we successfully treated her with prednisolone , colchicine and cyclophosphamide . a review of the literature uncovered about 10 cases , most of which were treated by various regimens that resulted in poor outcomes . renal amyloidosis should be suspected in patients with aosd who have unexplained proteinuria . although the mechanism of renal amyloid deposition is not well known , earlier histopathologic diagnosis and choice of regimen may affect prognosis .",380,103,0.2711
pubmed-summarization,"diabetic retinopathy is the name given to the changes in the retina , which develop over a period of time in diabetics . it remains one of the major causes of new - onset visual loss in developed countries . if the central part of the retina ( i.e. , the macula ) is involved , it is referred to as diabetic maculopathy . the traditional approach to diagnosis of diabetic maculopathy includes fundus ophthalmoscopy and fluorescein angiography ( fa ) . the early treatment diabetic retinopathy study ( etdrs ) identified stereoscopic slit - lamp biomicroscopy and stereo colour fundus photography as standard methods of macular thickness assessment utilized in order to determine whether the treatment should be commenced as they defined the clinically significant macular oedema ( etdrs report number 10 , 1991 ) . however , these methods are subjective and relatively insensitive to small changes in retinal thickness and , therefore , may be unable to identify mild or localized macular thickening . they also do not provide any data on retinal morphology and blood flow . on the other hand , fa is a highly effective test of evaluating retinal blood vessels , macular perfusion , and pattern of leakage causing the oedema . although very useful clinically , it also does not contribute much to the evaluation of retinal morphology and its thickness profile . in 1991 the researchers from massachusetts institute of technology and harvard university patented the technique of optical coherence tomography ( oct ) , which was a major breakthrough in ophthalmic diagnostics ( us5321501 a , swanson ea , huang d , fujimoto jg , puliafito ca , lin cp , schuman js . method and apparatus for optical imaging with means for controlling the longitudinal range of the sample ) . the first paper to present the potential of the new diagnostic method four years later the first paper was published which described the use of oct in diagnosis of macular diseases . the purpose of this paper is to provide an overview of clinical utility of oct in retinal assessment of diabetic patients . oct enables obtaining the high resolution ( few micrometres ) cross - sectional images ( tomograms ) of the human retina in a noninvasive","diabetic maculopathy ( dm ) is one of the major causes of vision impairment in individuals with diabetes . the traditional approach to diagnosis of dm includes fundus ophthalmoscopy and fluorescein angiography . although very useful clinically , these methods do not contribute much to the evaluation of retinal morphology and its thickness profile . that is why a new technique called optical coherence tomography ( oct ) was utilized to perform cross - sectional imaging of the retina . it facilitates measuring the macular thickening , quantification of diabetic macular oedema , and detecting vitreoretinal traction . thus , oct may assist in patient selection with dm who can benefit from treatment , identify what treatment is indicated , guide its implementing , and allow precise monitoring",380,128,0.3368
dialogsum,"#Person1#: Hey, Paul, why the long face? #Person2#: It's difficult to explain. #Person1#: Try me. #Person2#: Well, I had a terrible day of work, I'm thinking of quiting my job. #Person1#: Take it easy, maybe tomorrow will be different. #Person2#: I don't know, I can't stand my job these days. #Person1#: Cheer up, I hope you'll feel better soon.",Paul is thinking of quitting his job. #Person1# tries to cheer him up.,59,13,0.2203
dialogsum,"#Person1#: Which pair of jeans do you like best? #Person2#: I really like the straight legs. #Person1#: But they aren't very fashionable. What about these? #Person2#: I don't like the way they sag down. I feel like I have plumber butt in them. #Person1#: That's the style! You just wear boxers. #Person2#: What if someone got it in their head to give them a tug? What then? #Person1#: You're so old fashioned! Nobody is going to pull down your pants! #Person2#: If you ask me, it's a walking invitation!",#Person2# likes jeans of straight legs. #Person1# thinks #Person2# is old fashioned.,89,12,0.1348
scientific_lay_summarisation-elife-norm,"PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signaling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42 -dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here, we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis. Effects of PTEN deficiency were phenocopied by β-Arrestin1 KD or inhibition of β-Arrestin1-ARHGAP21 interactions. Conversely, silencing of ARHGAP21 enhanced Cdc42 activation and rescued aberrant morphogenic processes of PTEN-deficient cultures. Expression of the PTEN C2 domain mimicked effects of full-length PTEN but a membrane-binding defective mutant of the C2 domain abrogated these properties. Our results show that PTEN controls multicellular assembly through a membrane-associated regulatory protein complex composed of β-Arrestin1, ARHGAP21 and Cdc42. PTEN (phosphatase and tensin homolog) is the second most commonly mutated tumor suppressor gene in human cancer (Cantley and Neel, 1999) and has a central role in multicellular morphogenesis (Martin-Belmonte et al. , 2007; Jagan et al. , 2013a; Deevi et al. , 2016). While PTEN antagonizes the phosphoinositol 3-kinase (PI3K) /AKT pathway via its N-terminal phosphatase domain (Cantley and Neel, 1999), three-dimensional (3D) multicellular assembly was unaffected by forced variation of PI3K activity in colorectal organotypic model systems (Jagan et al. , 2013a; Magudia et al. , 2012). The PTEN domain structure includes an N-terminal phosphatase domain, a C2 domain, a C-terminal tail and a PDZ-binding domain. The C2 domain binds to membrane phospholipids by inserting a hydrophobic (CBR3) loop into the membrane bilayer and thereby provides a scaffold for juxtamembrane signaling (Lee et al. , 1999). Furthermore, the PTEN C2 domain regulates polarized migration (Raftopoulou and Hall, 2004), multicellular morphology (Leslie et al. , 2007; Jagan et al. , 2013b) and has an important but poorly understood tumor suppressor function (Caserta et al. , 2015). Within complex systems, protein scaffolding enhances signaling efficiency by assembly of spatially distinct subcellular complexes for different cellular tasks (Weng et al. , 1999; Pertz, 2010). The PTEN C2 domain binds the plasma membrane and interacts with the scaffold protein β-Arrestin1 (Lima-Fernandes et al. , 2011) that in turn binds and suppresses ARHGAP21 (Anthony et","The protein PTEN helps to organize cells in the body to form complex structures. In particular, it collects signals from a cells’ surroundings and changes where cells divide so new cells are produced in the right places. The control of cell division by PTEN is also thought to help limit the progression and spread of cancer. PTEN can interact with another protein called β-Arrestin1, which behaves as a so-called scaffolding protein – in other words, one that helps groups of proteins to interact with each other. β-Arrestin1 has been found to control cell division via a series of other proteins, including ARHGAP21 and Cdc42. The relationship between PTEN and these other proteins in dividing cells is still not fully understood. Javadi, Deevi et al. studied PTEN in human",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect. There is renewed interest in the medical application of psychedelic drugs, such as lysergic acid diethylamide (LSD) and psilocybin. Contemporary research is predominantly focusing on ‘psychedelics assisted psychotherapy’, where a few (one to three) large doses of psychedelics are used as adjunct to psychotherapy. Using this paradigm, psychedelics have shown promise in the treatment of conditions such as depression, end-of-life-anxiety, addiction, and obsessive-compulsive behaviors (Carhart-Harris and Goodwin, 2017; Nutt et al. , 2020). Recently, ‘microdosing’ has emerged as an alternative paradigm of psychedelic use. Due to its underground origin, microdosing does not have a universally agreed upon definition, and inconsistencies exist in substance, dose, frequency, and duration of use (Kuypers et al. , 2019). However, microdosing can be broadly defined as the frequent use (one to three times per week) of low doses of psychedelics (10–20% of a typical ‘full’ dose, e. g. 10–15 μg LSD or 0. 1–0. 3 g of dried psilocybin containing mushrooms). Anecdotal evidence suggests that microdosing may improve well-being, creativity, and cognition (Fadiman and Krob, 2017), and recent uncontrolled, observational studies have provided some empirical support for these claims (Anderson et al. , 2019; Polito and Stevenson, 2019; Prochazkova et al. , 2018). While encouraging, these studies are vulnerable to experimental biases, including confirmation-bias and placebo effects, in particular, because microdosers are a self-selected sample with optimistic expectations about psychedelics and microdosing (Polito","Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of ‘magic mushrooms’), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, ‘microdosing’ – a way of administering psychedelics that involves taking about 10% of a recreational dose two or three times per week – has gained popularity. Unlike taking large doses of psychedelics, microdosing does not induce hallucinations, but anecdotal reports suggest that it yields similar benefits as psychedelic therapy. A key feature of modern medicine are ‘placebo control’ studies that compare two groups of patients: one that takes a drug and another that takes inactive pills, known as placebos. Crucially, neither group knows whether",380,128,0.3368
scientific_lay_summarisation-elife-norm,"to the membrane associated with completion of the Ca2+ coordination sphere. Moreover, a conserved polybasic lysine patch located on the C2B domain also binds to anionic lipid in the absence of Ca2+, being particularly attracted to multivalent phosphoinositides (PtdIns) (Jahn and Fasshauer, 2012; Südhof, 2013; Chapman, 2008; Brose et al. , 1992; Corbalan-Garcia and Gómez-Fernández, 2014; Südhof, 2012). Membrane binding of syt-1 has been widely studied (Kuo et al. , 2009; Wang et al. , 2003; van den Bogaart et al. , 2012; Vrljic et al. , 2011; Kuo et al. , 2011; Radhakrishnan et al. , 2009; Li et al. , 2006; Bai et al. , 2004,2002; Schiavo et al. , 1996), mostly using a cytoplasmic fragment including both C2 domains (termed the syt-1 C2AB fragment). However, the mechanism of syt-1 binding to the membrane remains a matter of controversy. For example, recent studies have reported that a double Lys-to-Ala mutation in the polybasic lysine patch (termed the KAKA mutant) does not alter the binding of the syt-1 C2AB fragment to vesicles containing phosphatidylserine (PtdSer) and/or phosphatidylinositol-4,5-bisphosphate (PtdIns (4,5) P2) (Radhakrishnan et al. , 2009). By contrast, the same mutant was reported in other studies to decrease the binding of the C2AB fragment to vesicles (Vrljic et al. , 2011), even in the absence of PtdIns (Li et al. , 2006), or to almost completely abolish the binding to soluble PtdIns (4,5) P2, in either the absence or the presence of Ca2+ (van den Bogaart et al. , 2012). On the other hand, several studies suggest that not only the tandem C2AB fragment (Vrljic et al. , 2011) but also the individual C2B (van den Bogaart et al. , 2012) and C2A domains (Guillen et al. , 2013; Zhang et al. , 1998) might bind to PtdIns predominantly through the Ca2+-binding loops in the presence of Ca2+, and as a consequence, might compete with PtdSer to complete the coordination sphere of bound Ca2+ (Honigmann et al. , 2013). To resolve these discrepancies, and to shed light on the binding mechanism of syt-1 to its main lipid effectors, PtdSer and PtdIns, we examined the kinetics of syt-1 binding to vesicles containing different amounts of PtdSer and PtdIns (4,5) P2. We also used isothermal titration calorimetry (ITC) to measure the affinities","The human nervous system contains billions of neurons that communicate with each other across junctions called synapses. When a neuron is activated, the levels of calcium ions inside the cell rise. This causes molecules called neurotransmitters to be released from the neuron at a synapse to make contact with the second neuron. The neurotransmitters are stored inside cells within compartments known as synaptic vesicles and are released when these vesicles fuse with the membrane surrounding the cell. Proteins called SNAREs regulate the membrane fusion process. These proteins assemble into bundles that help to drive vesicle and cell membranes together. Another protein called synaptotagmin-1 sticks out from the vesicle membrane and senses the levels of calcium ions in the cell to trigger membrane fusion at the right time. Synaptotagmin-1",380,128,0.3368
dialogsum,"#Person1#: Fred, is it a good time to talk with you? #Person2#: Sure, what's the matter? #Person1#: As you know, I have accepted three new programs in our company this year, but I am not sure I can do my work well. And right now my dilemma is that I can not find a person whom I can trust for these three programs. #Person2#: What do you think we can do about this? #Person1#: We are not willing to miss the chance ; however, our staff is not big enough now. So, to be honest, I want you to help me to finish all these programs. #Person2#: Well, sir, I am busy in market development. So I am worried whether I can do this. #Person1#: I am aware you have been working so hard. Before hiring more employees, you are still needed to do this. #Person2#: OK! I will try this.","#Person2# accepts three new programs and wants Fred to help finish these programs. Fred is worried whether he can do it because he is busy in market development, and #Person2# persuades him.",151,32,0.2119
dialogsum,"#Person1#: Hey Mark, have you been able to sell your old piano yet? #Person2#: Oh, you were right, just posting notices on bulletin boards at a couple of supermarkets wasn't enough. I think I have to place an advertisement in the local newspaper.",Mark tells #Person1# he'll place an advertisement in the newspaper to sell his old piano set.,43,16,0.3721
scientific_lay_summarisation-elife-norm,"in breast cancer and its importance to cancer cell proliferation and tumor survival make targeting this pathway an attractive therapeutic approach. However, inhibition of the PI3K pathway often leads to proliferative arrest rather than cell death (Elkabets et al. , 2013; Klempner et al. , 2013; Serra et al. , 2008) and to date has shown limited clinical benefit. Specifically, PI3K/AKT/mTOR inhibitor therapy induced a partial response in 18–30% of patients whose tumors harbor PIK3CA and/or PTEN mutations (Janku et al. , 2014,2013,2012). Although this rate of partial responses was significantly higher than that achieved following treatment with therapies other than PI3K/AKT/mTOR inhibitors, this response was not associated with an improvement in either progression-free or overall survival of treated patients. Combination therapy consisting of Trastuzumab and Buparlisib, a PI3K inhibitor, resulted in a 17% partial response (Saura et al. , 2014), and mTOR inhibition combined with aromatase inhibitors in patients with hormone-receptor positive advanced breast cancer showed extended progression-free survival (Baselga et al. , 2012). Together, these studies suggest that targeting the PI3K pathway alone is only partially effective clinically. We hypothesized that identifying targets whose inhibition in the context of PI3K inhibition leads to cell death would provide a foundation to develop combination therapies. Here using a genome-scale loss of function screen, we identified genes whose suppression induces cell death only in the presence of PI3K inhibition both in vitro and in vivo. To identify genes whose suppression converts the cytostatic response to PI3K inhibition into a cytotoxic response, we performed a positive-selection genome scale shRNA screen (1A) using MDA-MB-453 breast cancer cells, which harbor a PIK3CA H1047R mutation and ERBB2 amplification. Treatment with the PI3K inhibitor GDC0941 leads to a complete proliferation arrest (— 1A) and suppression of AKT activity (— 1B) with minimal basal- and PI3Ki-induced cell death (— 1C–D). 10. 7554/eLife. 24523. 003Figure 1. Genome scale shRNA screen identifies genes whose suppression facilitates PI3Ki-induced cell death. (A) A schematic representation of the pooled shRNA screen design. (B) Z-scores for fold-change of proliferation of MDA-MB-453-eGFP cells infected with multiple shRNAs targeting the indicated genes and treated for 9 days with GDC0941 (0. 625 μM; red), or vehicle (DMSO; blue). Cells infected with five different control shRNAs (shCTRLs) were used to calculate Z-scores. Bars indicate standard deviation between","When cells become cancerous, they accumulate mutations in their DNA that switch on some genes at the wrong time and to higher levels than normal. These over-active genes help cancer cells to survive, grow and evade death. One of the genes that is often mutated and over-active in breast cancer encodes an enzyme called PIK3CA. There are several drugs that bind to and inhibit the mutant version of PIK3CA. Recent experiments show that inhibiting over-active forms of this enzyme can stop cancer cells from growing, but it does not cause them to die. This means that the cells have the opportunity to become resistant to the drug, which can subsequently lead to tumor relapse. Therefore, researchers have been looking for other drugs that, when combined with the PIK3CA-inhibiting",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and the importance of APC mutation, we investigated the mechanistic relationship between the mutational status of apc and mpc1. Herein, we report that apc regulates pyruvate metabolism by controlling the levels of mpc1 via RA. Further, mpc1 is required and sufficient for initiating normal intestinal differentiation downstream of apc. Our findings strongly suggest that changes in metabolic profile can drive cell fate and differentiation decisions. To investigate the relationship between apc and mpc, we utilized the apcmcr zebrafish, which is homozygous for a truncating mutation in the Mutation Cluster Region (MCR) of apc and similar to what is found in human colon tumors (Hurlstone et al. , 2003; Miyoshi et al. , 1992a, 1992b). In parallel, we also knocked down the expression of apc in wild type (WT) embryos using antisense morpholino (apc mo) (— 1). Evaluating gene expression of mpc1 and mpc2 by qRT-PCR, we found that both genes were significantly downregulated in apcmcr and apc mo embryos compared to WT/het siblings and control mo, respectively (1A, B). This was confirmed by whole mount in situ hybridization for mpc1 and mpc2 (1C, D). Additional in situ analyses for mpc1 and mpc2 in WT embryos revealed staining in the head, eyes, vasculature and somites at 24–48 hr post-fertilization (hpf) (1E). At later time points, expression in the pectoral fin buds, liver and gut emerged (1E). Cross sections of 72 hpf WT embryos previously probed with mpc1 and mpc2 confirmed gut expression for both genes (black arrows) (1F). 10. 7554/eLife. 22706. 003Figure 1. mpc1 and mpc2 are downregulated in apcmcr and apc morphant embryos. (A, B) Quantitative RT-PCR analysis of mpc1 and mpc2 gene expression in apcmcr (A) and apc mo (B) embryos. Values represent mean ± SD. Graph shown above is representative of at least three independent experiments. Statistical significance was analyzed using unpaired t-test. (C, D) Whole mount in situ hybridization for mpc1 and mpc2 in 72 hpf apcmcr (C) and apc mo (D) embryos. (E) Whole mount in situ hybridization for mpc1 and mpc2 in wild type (WT) embryos. head (h), eyes (e), somite (som), vasculature (vas), gut (g), liver (l). (F) Cross sections from 96 hpf WT embryos probed with either mpc1 or mpc2 confirmed gut-specific expression of both genes. See also — 1. : http: //dx.","Colon cancer remains an important problem in healthcare. Cancer researchers are looking for new ways to detect the disease earlier and treat it more effectively. This is challenging because many of the genetic and molecular causes of colon cancer are still poorly understood. Mutations in the gene that encodes a protein called APC are one of the major causes of the disease. The APC protein normally keeps cells from growing and dividing too fast or in an uncontrolled way and is hence referred to as a tumor suppressor. For example, APC induces stem cells in the intestine to develop into specialized cells that keep the gut working normally. Mutations in tumor suppressor genes are common in many cancers. Other research has shown that cancer cells must reprogram their",380,128,0.3368
dialogsum,"#Person1#: I would love to be famous and have thousands of adoring fans. #Person2#: Really? I'm not sure that I would like all the attention. There have been numerous cases of paparazzi interfering with star's private live in recent years. #Person1#: I love being photographed! If I were famous, I'd do interviews for all the top magazines, like cosmo and elle. #Person2#: I wouldn't mind having my photo taken a few times or being interviewed once or twice, but it would get tedious after a while. Imagzine the things the gossip columnists would write about you. #Person1#: no-one really believes gossip columnists. #Person2#: I think you'll find that many people believe what they read in gossip columns. You'd also have to be very careful about every word you said. If you appeared on a chat show and said something silly, it would be reported in all the newspapers and magazines. #Person1#: I think you're right about that. I'd need a good manager to be my spokesperson. I could do a lot of charity work, which would help a lot of people. #Person2#: That's a great idea. Which charities would you support? #Person1#: I love children, as you know, so probably a children's charity. #Person2#: You'd have to remember that anything you said or did might reflect on the charity, so you'd really need to be very careful. Anyway, I'd be the first to buy your posters and I'd attend your first book-singing when you wrote your autobiography. #Person1#: Thanks, but actually I was hoping I could ask you to write my biography.","#Person1# would love to be famous because #Person1# loves being photographed and doing interviews and could do children's charity work then. But #Person2# isn't sure whether to do that because a famous person has to pay attention to gossip and words. #Person2# will support #Person1#, but #Person1# wants #Person2# to write a biography for #Person1#.",262,55,0.2099
scientific_lay_summarisation-elife-norm,"to hydrocarbons catalysed by P450 enzymes (Qiu et al. , 2012). Only this latter step has been delineated in Anopheles mosquitoes with two P450 decarbonylases identified, Cyp4G16 and Cyp4G17 (Balabanidou et al. , 2016; Kefi et al. , 2019). Only a subset of the large number of lipid metabolic enzymes encoded in the genome are likely to be significant players in CHC synthesis, but we hypothesised that transcripts from these genes will be specifically enriched in oenocytes to enable this function. Here we report the isolation of oenocytes from adult An. gambiae mosquitoes using a transgenic line with fluorescently tagged oenocytes (Lynd et al. , 2019). RNAseq of the isolated oenocytes identified the key biological processes enriched in these cells and revealed candidate genes for each step of the CHC biosynthetic pathway. A member of the putative pathway was validated by perturbing expression of the AGAP001899 fatty acid synthase (hereafter called FAS1899). The elucidation of this pathway is a major milestone in delineating the role of variable hydrocarbon composition on key traits that impact vectorial capacity of these important vectors of human disease. To tag adult An. gambiae oenocytes, we expressed the red fluorescent marker m-cherry specifically in these cells using the GAL4/UAS system (Lynd and Lycett, 2012). Two transgenic lines were crossed: 1) a homozygous UAS-mCD8: mCherry responder line (Adolfi et al. , 2018) with 2) a homozygous oenocyte enhancer-GAL4 driver line (Oeno-Gal4) (Lynd et al. , 2019). Progeny of this cross had the expected m-cherry fluorescent oenocytes throughout their development (Lynd et al. , 2019). To purify adult oenocytes, mosquitoes were dissected to expose the oenocytes that are dispersed throughout tissues attached to the ventral abdominal integument. Their release was facilitated using trypsin and mechanical homogenisation of the tissue (1A) and subsequent isolation with Fluorescent Activated Cell Sorting (FACS) (1B). Tagged cells corresponded to 1–5% of the total events counted during the FACS sorting and their morphology was consistent with oenocytes by microscopic inspection of sorted cells (— 1). Triplicate RNAseq libraries were generated using mRNA from isolated tagged cells and total cell populations (cell preparation before FACS, referred herein as carcass cells) from female and male mosquitoes, barcoded and run on the same lane of an Illumina HiSeq sequencer (CGR University of Liverpool). Paired end reads were","The bodies of insects are encased in an exoskeleton or cuticle that is key for their survival. The cuticle helps protect insects against damage, prevents water loss and can defend against pesticides. A better understanding of the role of the cuticle for survival in mosquitoes and other insects could lead to new ways to prevent the spread of diseases such as malaria. The cuticle is coated with various molecules from a group of chemicals called hydrocarbons. This coating is made by specialized cells called oenocytes and helps to protect insects. Hydrocarbons can also influence communications between certain insects by acting as recognition signals. In mosquitoes, oenocytes make several hydrocarbons using a set of processes that are not well understood, and the types of hydrocarbons they make can vary",380,128,0.3368
pubmed-summarization,"this study was approved by the university of wisconsin - madison health sciences institutional review board . the methods used in this study were adapted from methods described previously ( 6 ) . in brief , patients included were 20 years of age on 1 january 2005 and had at least one family practice or internal medicine visit to the physician group in each of the 3 study years , 2005 , 2006 , and 2007 , in addition to a yearly visit in each of the 2 preceding years , 2003 and 2004 . a 3-year period from 2005 to 2007 was chosen based on ada recommendations to screen every 3 years ( 5 ) . data from years 2003 and 2004 were used to determine prior diagnosis of diabetes , prediabetes , preexisting comorbidities , and pregnancy and to determine visit eligibility . patients with any visit for pregnancy in the years 2003 to 2007 were excluded , as were patients who died during the 3-year study period . patients with two or more outpatient encounters with a diagnosis of diabetes in the years 2003 to 2004 were excluded , as were patients without health care insurance . patients clinical , laboratory , encounter , and demographic information were obtained from the electronic health record of a large , midwestern , academic physician group as described previously ( 6 ) . for all patients , data were extracted on age , sex , ethnicity , bmi , evaluation and management ( e / m ) outpatient encounter data , provider specialty , and laboratory data . in addition , we abstracted fasting plasma glucose ( fpg ) , random glucose ( rg ) , 2-h glucose tolerance test ( gtt ) , and hemoglobin a1c ( hba1c ) . glucose laboratory tests were classified as fpg if they were labeled as fasting or were drawn at the same time as a fasting ldl or triglyceride level per institution protocol . these fasting tests , in addition to gtts and hba1c , were considered the screening tests for this analysis . although hba1c was not an accepted test for diabetes screening during the study years , it was included in our screening profile and used in the sensitivity test","objectiveethnicity has been identified as a risk factor not only for having type 2 diabetes but for increased morbidity and mortality with the disease . current american diabetes association ( ada ) guidelines advocate screening high - risk minorities for diabetes . this study investigates the effect of minority status on diabetes screening practices in an ambulatory , insured population presenting for yearly health care.research design and methodsthis is a retrospective population based study of patients in a large , midwestern , academic group practice . included patients were insured , had 1 primary care visit yearly from 2003 to 2007 , and did not have diabetes but met ada criteria for screening . odds ratios ( ors ) , 95% confidence intervals ( ci ) , and",380,128,0.3368
dialogsum,"#Person1#: Hello . this is Susan. #Person2#: Hello, I'm Mark. I'm just wondering if you are free this weekend. #Person1#: Yes, I think So. #Person2#: Good. I was thinking that I'd like to invite you to watch a movie. I can meet you at the cinema gate. #Person1#: What's the time? #Person2#: Six thirty, tonight. #Person1#: Oh, I'm sorry I can't. because I have to do some housework. You can ask Jenny to go with you. #Person2#: All right. Maybe next time I can go with you. Bye! #Person1#: Good bye!","Mark invites Susan to a movie tonight, but Suan has to do some housework.",91,14,0.1538
dialogsum,"#Person1#: I'm so sorry to call you on such short notice, but something's come up. #Person2#: You mean for this afternoon's meeting? #Person1#: That's right I'm afraid I have to postpone it. Mr. Scott got sick and I have to attend the Speechmaker's Symposium in his place. I'm leaving today, and I won't be back until a week from Friday. #Person2#: That's quite a while. Let's make it the week after you get back, then. #Person1#: That will be great. So it's two weeks from tomorrow, same time and place. I'm really sorry to do this to you. #Person2#: No problem at all. To tell you the truth, I could use the extra time in my schedule to catch up on some paperwork.",#Person1# calls #Person2# to postpone the meeting for two weeks because #Person1# has to attend a symposium. #Person2# is OK with that.,123,22,0.1789
scientific_lay_summarisation-elife-norm,"tissue (1A, B). Interestingly, the loss of Gravin was accompanied by a decrease in two essential cell cycle regulator kinases, Aurora A and Plk1 (1A, mid panels, and 1B). Similar trends were observed in four additional clinical samples from seminoma patients (— 1A). 10. 7554/eLife. 09384. 003Figure 1. Loss of Gravin correlates with perturbed mitosis in human seminomas and mouse seminiferous tubules. (A) Immunoblot analysis of tissue lysates from resected seminomas (lanes 2,4, and 6) and normal adjacent tissue (lanes 1,3, and 5). Proteins were identified using antibodies against (top) Gravin, (upper-mid) Aurora A, (lower-mid) Plk1, and (bottom) GAPDH loading control. (B) Quantification of immunoblot data (A) by densitometry (n = 3 ± SEM). (C, D) Representative testis sections from (C) a 30-year-old individual and (D) a 26-year-old seminoma patient. Immunofluorescent staining shows Gravin (green), p-H3B (red), and DNA (DAPI, blue). Scale bar, 40 μm. (E, F) Magnified insets from C and D are included. Scale bar, 40 μm. (G) Gravin signal intensity per mitotic cell was quantified from normal and seminoma sections of testis (p-H3B positive, n-values are indicated, ***p < 0. 001). The number of cells used in each analysis is indicated. (H) The mitotic index was calculated for (normal; n = 4) and (seminoma; n = 6) tissue sections by determining the percentage of pH3B-positive cells. (*p < 0. 05). (I, J) Related experiments were conducted on testis sections from 7-week-old wild-type (I), and Gravin knockout (J) mice. Immunostaining with antibodies against Par3 (green), p-H3B (red), and DAPI (blue) is presented. Scale bar, 40 μm. (K) Calculation of the mitotic index in testis sections from wild-type (gray) and Gravin knockout (orange) mice. The number of tissue sections measured is indicated below each column (*p < 0. 05). (L) TUNEL staining was used to monitor apoptosis in seminiferous tubule sections from wild-type (gray) and Gravin knockout (orange) mice. Data are presented as TUNEL-positive cells per seminiferous tubule. The number of sections is depicted below each column. (**p = 0. 01). : http: //dx. . org/10. 7554/eLife. 09384. 00310. 7554/eLife. 09384. 004Figure 1— 1. Loss of Gravin in human summons and mouse tissues, and correlation with altered mitosis. (A) Immunoblot analysis of human testis lysates from normal (lane 1) and seminoma samples (lanes 2,3, 4, and 5). Antibodies were","The genetic material inside our cells is contained within structures called chromosomes. When a cell divides, these chromosomes are copied and then must be correctly divided between the two daughter cells so that each cell has a complete set of genetic material. The correct separation of the chromosomes depends on a structure called the mitotic spindle whose location in the cell also determines where the point of division will be. Two structures called centrioles are associated with the mitotic spindle and help to organize and direct cell division. The cell carefully controls how these structures are inherited by the daughter cells. For example, when a stem cell divides to produce one stem cell and one cell of a different type, the older centriole can be inherited by the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"layer located between the luminal cells and the surrounding stroma. Despite being mostly quiescent under homeostatic conditions, the prostate gland encompasses incredible plasticity. In mice, surgical castration-induced prostate involution has proven an invaluable tool to identify progenitor castration-resistant cell populations, characterized by their ability to survive in the absence of androgens, and to fully regenerate an intact adult prostate after re-administration of testosterone (Barros-Silva et al. , 2018; Kwon et al. , 2016; McAuley et al. , 2019; Tsujimura et al. , 2002; Wang et al. , 2015; Wang et al. , 2009; Yoo et al. , 2016). Such plasticity has also been shown in defined experimental conditions to stimulate regenerative properties of epithelial subpopulations, including transplantations (Barros-Silva et al. , 2018; Burger et al. , 2005; Lawson et al. , 2007; Lukacs et al. , 2010; Richardson et al. , 2004; Wang et al. , 2009; Xin et al. , 2005; Yoo et al. , 2016), injury repair (Centonze et al. , 2020; Horton et al. , 2019; Kwon et al. , 2014; Toivanen et al. , 2016), and organoid assays (Chua et al. , 2014; Höfner et al. , 2015; Karthaus et al. , 2014). In addition, several studies have proposed that progenitor populations with distinct physiological roles and regenerative capacity reside at different locations within the prostate (Burger et al. , 2005; Crowell et al. , 2019; Goldstein et al. , 2008; Goto et al. , 2006; Kwon et al. , 2016; Leong et al. , 2008; McNeal, 1981; Tsujimura et al. , 2002). However, the precise cellular hierarchy and how it is established during development remains controversial. RUNX transcription factors (TF) are master regulators of lineage commitment and cell fate (Mevel et al. , 2019). In particular, RUNX1 is essential for the ontogeny of the hematopoietic system and alterations of RUNX1 have been associated with a broad spectrum of hematological malignancies. Interestingly, increasing evidence implicates RUNX1 in the biology and pathology of hormone-associated epithelia (Lie-A-Ling et al. , 2020; Riggio and Blyth, 2017; Scheitz and Tumbar, 2013), including breast (Browne et al. , 2015; Chimge et al. , 2016; Ferrari et al. , 2014; van Bragt et al. , 2014), uterine (Planagumà et al. , 2004; Planagumà et al. , 2006), ovarian (Keita et al. ,","The prostate is part of the reproductive organs in male mammals. Many of the cells lining the inside of the prostate – known as ‘luminal cells’ – need hormones to survive. Certain treatments for prostate cancer, including surgical and chemical castration, lead to fewer hormones reaching the prostate, which shrinks as luminal cells die. But some of these luminal cells are able to survive the damaging effects of castration, rebuilding the prostate upon treatment with hormones, which can lead to the cancer reappearing. It is unclear which type of luminal cells survive during periods without hormones and are responsible for regenerating the prostate. RUNX1 is a protein responsible for switching genes on and off, and is usually found in blood cells, which it helps to mature and perform",380,128,0.3368
dialogsum,"#Person1#: More and more people are using reusable grocery bags now. #Person2#: They're much stronger than plastic bags. And I can fit more in them, too. #Person1#: Grocery stores like them, too. Because they can make money by selling them. #Person2#: What's more, you can use them for more than one purpose. I heard that only 3% of plastic bags. Imagine all that waste. #Person1#: And my local grocery store, regular plastic bags aren't free anymore. In addition, they take $0.10 off your bill for every reusable bag you bring yourself. #Person2#: It's great to see we're taking steps to create a healthier environment.",More people use reusable grocery bags now. #Person1# and #Person2# think it's a step to create a healthier environment.,104,19,0.1827
scientific_lay_summarisation-elife-norm,"Adult neural stem cells, located in discrete brain regions, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions do not generate neurons under physiological conditions. After stroke, however, striatal astrocytes undergo neurogenesis in mice, triggered by decreased Notch signaling. We used single-cell RNA sequencing to characterize neurogenesis by Notch-depleted striatal astrocytes in vivo. Striatal astrocytes were located upstream of neural stem cells in the neuronal lineage. As astrocytes initiated neurogenesis, they became transcriptionally very similar to subventricular zone stem cells, progressing through a near-identical neurogenic program. Surprisingly, in the non-neurogenic cortex, Notch-depleted astrocytes also initiated neurogenesis. Yet, these cortical astrocytes, and many striatal ones, stalled before entering transit-amplifying divisions. Infusion of epidermal growth factor enabled stalled striatal astrocytes to resume neurogenesis. We conclude that parenchymal astrocytes are latent neural stem cells and that targeted interventions can guide them through their neuronal differentiation. Neurogenesis is extremely limited in the adult brain. In most mammals, specialized astrocytes in the subventricular zone (SVZ) and hippocampal dentate gyrus (DG) are stem cells and generate new neurons continuously, but apart from that, the brain’s ability to replace lost neurons is very limited. However, in response to an experimental stroke or excitotoxic lesion, some astrocytes in the mouse striatum can generate neurons (Magnusson et al. , 2014; Nato et al. , 2015). This neurogenic response is regulated by Notch signaling and can be activated even in the uninjured mouse striatum by deleting the Notch-mediating transcription factor Rbpj (Magnusson et al. , 2014). Striatal astrocytes undergo neurogenesis by passing through a transit-amplifying cell stage. But it is not known whether these astrocytes become bona fide neural stem cells. If they do, this could have far-reaching implications for regenerative medicine. Astrocytes make up a large fraction of all brain cells (10–20% in mice) (Sun et al. , 2017) and are distributed throughout the central nervous system. They would thus represent a very abundant source of potential neural stem cells that might be recruited for therapeutic purposes. Although certain injuries and Rbpj deletion can both trigger neurogenesis by astrocytes, it almost exclusively does so in the striatum. And even within the striatum, primarily the astrocytes in the medial striatum readily activate neurogenic properties (1a). This suggests that neurogenic parenchymal astrocytes either","Regenerative medicine aims to help the body replace damaged or worn-out tissues, often by kick-starting its own intrinsic repair mechanisms. However, the brain cannot easily repair itself, and therefore poses a much greater challenge. This is because nerve cells or neurons, which underpin learning, memory, and many other abilities, are also the brain’s greatest weakness when it comes to tissue repair. In most parts of the adult brain, neurons are never replaced after they die. This means that damage to brain tissue – for example, after a stroke – can have severe and long-lasting consequences. Neural stem cells are one type of brain cell that can turn into new neurons if needed, but they are only found in a few parts of the brain and cannot fix damage",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Continuous adaptation allows survival in an ever-changing world. Adjustments in the synaptic coupling strength between neurons are essential for this capability, setting us apart from simpler, hard-wired organisms. How these changes can be mathematically described at the phenomenological level, as so-called ‘plasticity rules’, is essential both for understanding biological information processing and for developing cognitively performant artificial systems. We suggest an automated approach for discovering biophysically plausible plasticity rules based on the definition of task families, associated performance measures and biophysical constraints. By evolving compact symbolic expressions, we ensure the discovered plasticity rules are amenable to intuitive understanding, fundamental for successful communication and human-guided generalization. We successfully apply our approach to typical learning scenarios and discover previously unknown mechanisms for learning efficiently from rewards, recover efficient gradient-descent methods for learning from target signals, and uncover various functionally equivalent STDP-like rules with tuned homeostatic mechanisms. How do we learn? Whether we are memorizing the way to the lecture hall at a conference or mastering a new sport, somehow our central nervous system is able to retain the relevant information over extended periods of time, sometimes with ease, other times only after intense practice. This acquisition of new memories and skills manifests at various levels of the system, with changes of the interaction strength between neurons being a key ingredient. Uncovering the mechanisms behind this synaptic plasticity is a key challenge in understanding brain function. Most studies approach this monumental task by searching for phenomenological models described by symbolic expressions that map local biophysical quantities to changes of the connection strength between cells (1A, B). Approaches to deciphering synaptic plasticity can be broadly categorized into bottom-up and top-down. Bottom-up approaches typically rely on experimental data (e. g. , Artola et al. , 1990; Dudek and Bear, 1993; Bi and Poo, 1998; Ngezahayo et al. , 2000) to derive dynamic equations for synaptic parameters that lead to functional emergent macroscopic behavior if appropriately embedded in networks (e. g. , Gütig et al. , 2003; Izhikevich, 2007; Clopath et al. , 2010). Top-down approaches proceed in the opposite direction: from a high-level description of network function, for example, in terms of an objective function (e. g. , Toyoizumi et al. , 2005; Deneve, 2008; Kappel et al. , 2015; Kutschireiter et al. , 2017;","Our brains are incredibly adaptive. Every day we form memories, acquire new knowledge or refine existing skills. This stands in contrast to our current computers, which typically can only perform pre-programmed actions. Our own ability to adapt is the result of a process called synaptic plasticity, in which the strength of the connections between neurons can change. To better understand brain function and build adaptive machines, researchers in neuroscience and artificial intelligence (AI) are modeling the underlying mechanisms. So far, most work towards this goal was guided by human intuition – that is, by the strategies scientists think are most likely to succeed. Despite the tremendous progress, this approach has two drawbacks. First, human time is limited and expensive. And second, researchers have a natural – and reasonable",380,128,0.3368
pubmed-summarization,"were encouraged to increase activity gradually . a 20-year - old man presented with a right knee injury resulting from a motor vehicle accident . clinical examination revealed a swollen knee , limited range of motion and posterior tibial sag at 90 on knee flexion . the knee range of motion was 135 with a flexion 135 and flexion contracture 0 after 2 weeks postoperatively . the patient was able to return to his usual daily activities after postoperative 6 months ( . a 13-year - old boy presented with left knee injury resulting from a fall . clinical examination revealed hemarthrosis of the knee , limited range of motion , and posterior tibial sag . the knee range of motion was 140 with flexion 140 and flexion contracture 0 after 4 weeks postoperative . currently , open reduction or arthroscopic fixation is more commonly used in treatment of displaced pcl tibial bony avulsion.3456 ) the latter has both advantages and disadvantages . since the site of attachment of the pcl to the tibia is located deep within the posterior tibial plateau , multiple arthroscopic sutures and tunnels are required , making the procedure more challenging and difficult . furthermore , some authors reported that arthroscopic fixation using suspensory device needs a sizeable drill hole that may break thinner bone fragments.9 ) open reduction can be performed with a traditional s - shaped approach , but this incision is associated with injury to adjacent neurovascular structures . in contrast , we used a less invasive posteromedial approach , which had several advantages , including exposure of the posterior capsule through the gap between the medial head of the gastrocnemius and the semitendinosus muscle . with the approach in this study , it is possible to minimize risks of damage to vessels and nerves , as well as providing satisfactory exposure of the fracture site . similar methods using posteromedial approach with suture anchors are previously reported.6 ) these studies used 2 suture anchors and fixed bony fragment by knotting with the sutures of 2 suture anchors . the most important advantage of the present suture bridge fixation technique with posteromedial incision , is its indication for use regardless of the thickness , size , and comminution of bony fragment .","we presented a surgical technique including a suture bridge technique with relatively small incision for the reduction and fixation of posterior ligament avulsion fractures . a suture anchor was used to hold the avulsed fragment and a knotless anchor was used to continuously compress the bony fragment into the fracture site , thereby maintaining reduction during healing .",380,58,0.1526
dialogsum,"#Person1#: Lisa, why do you keep a night light on in your room? #Person2#: I thought you knew that I'm scared of the dark. #Person1#: I had no idea. Why are you afraid? #Person2#: When I was very little, around 4 years old, a man broke into our home. I heard a noise later at night and then I saw my father walk by my room quietly. He was carrying a baseball bat. A few minutes later, I heard a crash. I was so scared. #Person1#: What happened then? #Person2#: I don't know, but my father wasn't hurt. I've kept a light on at night ever since though.",Lisa tells #Person1# she keeps a night light on because a man once broke into her house when she was young.,108,21,0.1944
pubmed-summarization,"organizations and different professions , even when those professions want to co - operate to help individuals to satisfy their needs . health and social services today face groups of patients who have composite problems and are often unstable . they include , very obviously , elderly persons with multiple problems , chronically ill children , and persons suffering mental ill - health . they have continuing need of care and in search of care they move between primary care , hospital care and municipality care , such as that provided for elderly persons . their situation demands some form of integration between health and social services , the benefits of which have been identified as including reduced hospital use , a strong focus on prevention and keeping patients healthy , and the provision of care closer to home . from the perspective of the person seeking care , medical and social needs are connected . individuals do not see themselves as multi - ill , but as needing support for their needs as they know them . it must be said that from the 1970s onwards a number of integrative approaches have been tried out , not least in education . although there are exceptions to learn from , generally speaking european health and social services are fragmented and poorly equipped to take care of patients with composite needs . so far , and to a great extent , the task of integrating different delivery systems , of managing the transitions from one provider to another , has fallen on the shoulders of patients themselves or their relatives . much of the evidence indicates that the problem we face is a result of the prevailing mindset . how can we increase our understanding of health and social services that are located in different organizations ? lindberg observed examples of meaningful co - operation at the local level , with colleagues from different organizations meeting and pooling their knowledge of local conditions with the patient or user as the focal point . the phenomenon has been variously called the chain of care , integrated care , seamless care or shared care . this co - operation aims at creating a continuing relationship with the patient / user regardless of who","introductionorganizations can be regarded as systems . the traditional model of systems views them as machines . this seems to be insufficient when it comes to understanding and organizing complex tasks . to better understand integrated care we should approach organizations as constantly changing living organisms , where many agents are interconnected in so - called complex adaptive systems ( cas).theory and discussionthe term complex emphasizes that the necessary competence to perform a task is not owned by any one part , but comes as a result of co - operation within the system . adaptive means that system change occurs through successive adaptations . a cas consists of several subsystems called agents , which act in dependence of one another . examples would be the ant -",380,128,0.3368
scientific_lay_summarisation-elife-norm,"which plays an important role in shaping the adaptive immune responses (Jenkins and Moon, 2012). Employing a newly validated approach for the study of low-frequency (< 10–5) antigen-specific T cells (Alanio et al. , 2010), we evaluated this prediction in patients with chronic viral infection of the liver. The α/β T cell preimmune repertoire is defined as the set of mature but antigen inexperienced lymphocytes that circulate in blood and secondary lymphoid organs, ready to be activated by cognate high-affinity peptide-class I MHC (pMHC) complexes (Jenkins et al. , 2010). They are maintained in the periphery by survival factors such as IL-7, as well as transient contacts with low affinity non-cognate pMHC complexes (Sprent and Surh, 2011). Over the last decade, studies using newly-developed tetramer-enrichment assays - sensitive enough to detect and track antigen-specific populations prior to immunization - have provided new insights into the impact of preimmune repertoire heterogeneity (Jenkins et al. , 2010). First, the number of antigen-specific T cells (i. e. precursor frequency) is not equivalent across inexperienced populations, with the absolute number positively correlating with the magnitude of responses that are induced upon priming (Obar et al. , 2008; Moon et al. , 2007; Kwok et al. , 2012; Schmidt et al. , 2011; Kotturi et al. , 2008; Tan et al. , 2011). Second, antigen-inexperienced CD4+ and CD8+ T cell populations contain variable proportions of memory-phenotype (MP) cells (Legoux et al. , 2010; Su et al. , 2013). These cells have been explained in the literature as a result of cross-reactivity or homeostatic proliferation (Sprent and Surh, 2011). Cross-reactivity is now recognized as an essential feature of the T-cell receptor (TCR) / MHC interaction (Mason et al. , 1998), and a major determinant of virus-specific MP cells in the CD4+ T cell repertoire of unexposed healthy donors (Su et al. , 2013). Alternatively, homeostatic proliferation may occur in settings of lymphopenia (Jones et al. , 2013). Finally, differential CD5 expression by antigen-specific T cell populations has been shown to dictate clonal recruitment and expansion (Fulton et al. , 2015; Tabbekh et al. , 2013). To date, the impact of non-heritable influences such as human chronic viral infection on the quantitative and qualitative aspects of the preimmune repertoire remains unknown. In our study, we focused on","Long-lasting or “chronic” infections massively perturb the immune system as a way to favor their own growth. In particular, they can stop T cells – a subtype of immune cells that help to destroy viruses – from working well. For example, HIV and hepatitis C viruses can overwork T cells and cause them to die. This can make individuals vulnerable to other infections. In healthy people, T cells that have participated in the fight against particular infections continue to live to provide a memory of those past infections. Groups of “naïve” T cells that have not yet encountered an infected cell also patrol the body, ready to respond to infections by a new virus. There are relatively few virus-specific naïve T cells in the body, so until recently",380,128,0.3368
dialogsum,"#Person1#: Hi, Nally, are you hungry? #Person2#: I'm starving. Let's go grab a bite. #Person1#: Where to? #Person2#: How about Karlis? #Person1#: Are you kidding? That place is too ritzy for lunch. #Person2#: True. ok. Let's go to Grumose? #Person1#: Same thing, meals there all coarsen arm and leg. #Person2#: I guess it is a little pricy. #Person1#: Let's stop it at Multicolor for a quick lunch.. #Person2#: That will be Ok. Come on, I can't wait to chow down. #Person1#: That was a great lunch, the food was good, but the service was lousy. #Person2#: Is that why you stiffed the waiter? #Person1#: You got it. All right, Let's go back to school.",#Person1# and Nally discuss where to eat. They finally go to Multicolor where the food was good but the service was lousy.,114,22,0.193
scientific_lay_summarisation-elife-norm,"Anthracycline-induced cardiotoxicity (ACT) is a key limiting factor in setting optimal chemotherapy regimes, with almost half of patients expected to develop congestive heart failure given high doses. However, the genetic basis of sensitivity to anthracyclines remains unclear. We created a panel of iPSC-derived cardiomyocytes from 45 individuals and performed RNA-seq after 24 hr exposure to varying doxorubicin dosages. The transcriptomic response is substantial: the majority of genes are differentially expressed and over 6000 genes show evidence of differential splicing, the later driven by reduced splicing fidelity in the presence of doxorubicin. We show that inter-individual variation in transcriptional response is predictive of in vitro cell damage, which in turn is associated with in vivo ACT risk. We detect 447 response-expression quantitative trait loci (QTLs) and 42 response-splicing QTLs, which are enriched in lower ACT GWAS p-values, supporting the in vivo relevance of our map of genetic regulation of cellular response to anthracyclines. Anthracyclines, including the prototypical doxorubicin, continue to be used as chemotherapeutic agents treating a wide range of cancers, particularly leukemia, lymphoma, multiple myeloma, breast cancer, and sarcoma. A well-known side-effect of doxorubicin treatment is anthracycline-induced cardiotoxicity (ACT). For some patients ACT manifests as an asymptomatic reduction in cardiac function, as measured by left ventricular ejection fraction (LVEF), but in more extreme cases ACT can lead to congestive heart failure (CHF). The risk of CHF is dosage-dependent: an early study (Von Hoff et al. , 1979) estimated 3% of patients at 400 mg/m2,7% of patients at 550 mg/m2, and 18% of patients at 700 mg/m2 develop CHF, where a more recent study puts these numbers at 5%, 26% and 48% respectively (Swain et al. , 2003). Reduced LVEF shows a similar dosage-dependent pattern, but is not fully predictive of CHF. Perhaps most daunting for patients is that CHF can occur years after treatment: out of 1807 cancer survivors followed for 7 years in a recent survey a third died of heart diseases compared to 51% of cancer recurrence (Vejpongsa and Yeh, 2014). Various candidate gene studies have attempted to find genetic determinants of ACT, but are plagued by small sample sizes and unclear endpoint definitions, resulting in limited replication between studies. Two ACT genome-wide association studies (GWAS) have been published (Aminkeng et al. , 2015; Schneider et al. ,","Many cancers, including leukaemia, lymphoma and breast cancer, are treated with potent chemotherapy drugs such as anthracyclines. However, anthracyclines have strong side effects known as anthracycline cardiotoxicity, which affect the health of the heart. Almost half of the patients given high doses of anthracyclines develop chronic heart failure. While anthracycline cardiotoxicity is very common, people’s genes may contribute to how sensitive they are to these drugs but it is not understood which genes can cause this effect. Previous studies using only a small number of participants have not been able to pin down the genetic factors that make some patients respond well to anthracyclines, and others prone to developing heart failure when taking these drugs. To find out which genes affect anthracycline cardiotoxicity, Knowles, Burrows et al. transformed",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and Glickstein, 2007). In particular, avian song learning has been used as a paradigm to study the neural mechanisms of vocal learning, as it shares striking similarities with human speech learning (reviewed in Doupe and Kuhl, 1999). The basal ganglia-thalamo-cortical network is involved in sensorimotor learning in several species, from lamprey to primates (Hikosaka et al. , 2002; Stephenson-Jones et al. , 2013; Wickens et al. , 2007). The basal ganglia are thought to rely on reward prediction error signals conveyed by dopaminergic neurons (Gadagkar et al. , 2016; Schultz et al. , 1997; Wickens et al. , 2003) to drive reinforcement learning strategies (Doya, 2000; Sutton and Barto, 1981). In songbirds, a specialized circuit homologous to the motor loop of the mammalian basal ganglia (McCasland, 1987; Doupe et al. , 2005) is critical for song learning in juveniles and plasticity in adults (Brainard and Doupe, 2002). This circuit is thought to correct vocal errors through reinforcement learning driven by an internal song evaluation signal conveyed by dopaminergic neurons (Fee and Goldberg, 2011; Gadagkar et al. , 2016; Hoffmann et al. , 2016). The cerebello-thalamo-cortical circuit also participates in sensorimotor learning in vertebrates, from fishes to primates (Brooks et al. , 2015; Gómez et al. , 2010; Lewis and Maler, 2004). It is believed to implement error-based supervised learning (Albus, 1971; Ito, 1984; Knudsen, 1994; Marr, 1969; Raymond et al. , 1996) based on an error prediction denoting a mismatch between sensory prediction and actual sensory feedback (Doya, 2000; Dreher and Grafman, 2002). The cerebellum also drives on-line correction during movements building on the same sensory error prediction (Tseng et al. , 2007) and controls the duration of movements and its prediction during sensorimotor learning (Day et al. , 1998; Flament and Hore, 1988; Izawa et al. , 2012). The existence of a pathway from the cerebellum to the song-related basal ganglia has been suggested by previous anatomical studies in songbirds (Person et al. , 2008; Vates et al. , 1997; Nicholson et al. , 2018), but whether cerebellar circuits are involved in avian song learning and production remains unknown. Beyond the indirect interaction via their respective loop with thalamo-cortical and brainstem networks, the basal ganglia and the cerebellum interact via a subcortical disynaptic pathway through the dentate nucleus, the","Human infants learn to speak by imitating the speech of adults around them. Over time, they learn to coordinate movements of their vocal cords and breathing muscles to produce specific sounds. Juvenile songbirds go through a similar process while learning to sing. Fledglings mimic adult birds and each other as they learn to produce their own songs. Songbirds are therefore often used as a model for how the brain drives vocal learning – whether of speech or song. Circuits made up of similar brain regions support vocal learning in infants and in songbirds. These regions include areas of cortex, the outermost layer of the mammalian brain, as well as structures deep below the cortex. The latter include the basal ganglia, a set of structures that help mammals learn",380,128,0.3368
dialogsum,"#Person1#: Well, what did you think about Candy, the last candidate? Do you think we should hire her? #Person2#: She had a very impressive resume, but she seemed to lack the confidence that I think a good manager needs. Did you notice the way that she avoided making eye contact with us while she talked? #Person1#: She was a bit nervous, I guess. What else? #Person2#: When she first walked into the room to greet us, she didn't shake hands with us or introduce herself at all. I thought that was a bit unprofessional. #Person1#: You're right. If she walked into a meeting with our clients like that, it would make our company look bad. That made me worried most. #Person2#: It sure would.",#Person1# and #Person2# are discussing the performance of the last candidate. They think she lacks confidence and her manners are unprofessional.,124,21,0.1694
pubmed-summarization,"risk behavior web - based survey ( kyrbs ) . the kyrbs has been conducted annually since 2005 by the korean centers for disease control and prevention ( kcdc ) , the korea ministry of education , science and technology , and the korea health and human services . the data were collected via an ongoing , anonymous web - based survey in a self - reporting format that was conducted on a nationally representative sample of middle- and high - school students . it aimed to plan and assess the korean adolescent health promotion policies by investigating health - related behaviors and status . in the 2014 survey , 799 middle and high schools were selected , including 72,060 students in grades 7 to 12 ( stratified ) on a national scale . however , we excluded 2,334 individuals due to missing data for variables used in this study ; therefore , our cohort ultimately comprised 69,726 adolescents ( 35,224 boys and 34,361 girls ) . suicide ideation and attempt were measured via responses to the following questions : "" have you seriously considered suicide during the past 12 months ? "" and "" have you tried suicide during the past 12 months ? "" the possible responses to both questions were "" yes "" or "" no . "" we characterized wcb via responses to the following multi - part question : "" have you experienced the following weight control methods during the past 30 days , with the following activities listed : 1 ) did regular exercise , 2 ) fasted at least 24 hours , 3 ) ate less , 4 ) took prescription diet pills , 5 ) took nonprescription diet pills , 6 ) took laxatives or diuretics , 7 ) vomited , 8) ate only one food , 9 ) took oriental medicine , and 10 ) ate diet food . "" the possible responses to all questions were "" yes "" or "" no . "" if participants responded ' yes ' to at least one of 2 ) , 5 ) , 6 ) , 7 ) , and 8) , we classified them into the "" inappropriate wcb "" group ( 16 ) . if participants responded ' no '","suicide is a leading cause of death among adolescents globally , and body weight is also a recognized reason for adolescent suicide . therefore , we investigated the association between weight control behaviors ( wcb ) and suicide ideation and attempt , focusing on inappropriate weight control measures . we used data from the 2014 korea youth risk behavior web - based survey , representing a total of 35,224 boys and 34,361 girls aged 12 to 18 years . adolescents were classified into groups based on wcb : appropriate wcb , inappropriate wcb , and no wcb . we performed logistic regression models to examine associations between wcb and suicide ideation and attempt , controlling for covariates . both boys and girls with inappropriate wcb were more likely",380,128,0.3368
pubmed-summarization,"the data from the articles by goldstein et al . suggest that both cardiologists and their patients tend to think that once a device such as an icd is in place , one ought not stop it . as a general rule , philosophers have suggested that the conditions under which one could justify withholding a treatment are those under which one could justify withdrawing a treatment . for example , if the patient were irreversibly and imminently dying of a painful cancer and had recurrent ventricular tachycardia , one would be perfectly justified in not placing an icd . rationally , if the patient had an icd implanted 2 years ago and now develops a painful cancer and death is imminent , deactivating the icd seems just as justifiable as withholding it . tell us , however , is that what seems equivalent according to the logic of ethics continues to feel psychologically different to both patients and practitioners . does the fact that the icd is required intermittently rather than continuously mark a moral difference ? the discontinuation of an intermittent treatment such as hemodialysis , should it become burdensome , has been judged morally acceptable by persons holding a wide variety of ethical viewpoints . reports , the very fact that it functions only intermittently might make it psychologically easier to deactivate an icd than to deactivate the pacemaker of a patient with complete heart block . some might consider the duration of therapy morally important . but is this true ? if the icd in the case of the patient with cancer that i discussed above had been in place for 20 years instead of 2 , with no changes except for batteries , would the duration alone make us think that it would be immoral to deactivate it if the patient were imminently dying , in great pain , and the device might only prolong that state ? consider a patient who has been ventilator - dependent for 30 years after contracting polio , is not depressed , and comes to the conclusion , might we not be more willing to accept his request to discontinue the ventilator as a well thought out and morally acceptable choice than if the same request were made by","as implantable cardioverter defibrillators ( icds ) have become more common , ethical issues have arisen regarding the deactivation of these devices . goldstein et al . , have shown that both patients and cardiologists consider icd deactivation to be different from the discontinuation of other life - sustaining treatments . it can not be argued ethically that icds raise new questions about the distinction between withholding and withdrawing treatment , and neither the fact that they are used intermittently , nor the duration of therapy , nor the mere fact that they are located inside the body can be considered unique to these devices and morally decisive . however , frequent allusions to the fact that they are located inside the body might provide a clue about",380,128,0.3368
pubmed-summarization,"and he was discharged from hospital 3 months later . at the time of discharge , he still had significant cardiac functional disorder with an ejection fraction ( ef ) rate of less than 20% . in april 2014 , he developed ulceration of the right toes , diagnosed as arteriosclerosis obliterans of the lower limb at the cardiovascular medicine department and underwent percutaneous transluminal angioplasty ( pta ) . in september 2014 , delayed healing of the ulceration of the skin was noted ; thus , he was referred to the plastic surgery department . upon the first consultation at the plastic surgery department , ischaemic ulcer of the left third toe biological data on the left limb were examined between the revascularization procedure and surgical management , and blood test and wound culture were examined at the time of surgical management . ajb : ankle joint nerve block ; crp : c - reactive protein ; mrsa : methicillin - resistant staphylococcus aureus ; pta : percutaneous transluminal angioplasty ; snb : sciatic nerve block ; s. maltophilia : stenotrophomonas maltophilia . endovascular surgery was not conducted after october 2016 . in september 2014 , after performing pta for the left lower limb , amputation of the left third toe was conducted . in december 2014 , re - stenosis of the bilateral below - knee arteries and necrosis of the left first toe were noted , thus re - pta was conducted for the bilateral limbs . subsequently , amputation of the left first toe was performed . in september 2015 , arterial re - stenosis of the lower extremity developed along with necrosis of all the left toes , plantar and dorsum , and so pta was performed again ; transmetatarsal amputation ( tma ) was also performed in the same month . however , delayed wound healing , infection and necrosis progressed in the transected surface of the left limb . therefore , in january 2016 , the first and second toes were amputated at lisfranc s joint , and the other three toes were further amputated at the base of the transmetatarsal bone , and the amputated surface was left as an open wound for wbp and post - operative infection management . at",abstractischaemic skin ulcer occurred on the foot of a 73-year - old man who had a history of fulminant myocarditis with severe cardiac dysfunction . we attempted wound bed preparation by maggot debridement therapy and salvaged his limb . it can be one of the adjuvant treatment strategies for critical limb ischaemia .,380,53,0.1395
scientific_lay_summarisation-elife-norm,"is assembled at the AUG start site of an mRNA, whose 3′ end had been previously annealed to a complementary DNA handle harboring a 5′ digoxigenin. The complex is then tethered between a pair of 2. 1 µm diameter polystyrene beads: a streptavidin-coated bead, which binds to the ribosome and is held by suction on the end of a micropipette, and an anti-digoxigenin antibody-coated bead, which binds to the DNA handle and is held in an optical trap. Next, a mixture containing elongation factors, aminoacyl-tRNAs and GTP is introduced into the experimental chamber. The tension in the tether, stabilized by an automated feedback routine, produces a constant opposing force as translocation proceeds. Translation is followed in real time as a decrease in the tether length between the beads (1B–C, — 1). No translation signals were detected in the absence of GTP and EF-G. (1E, F). 10. 7554/eLife. 03406. 003Figure 1. Following translation by a single ribosome on a single mRNA. (A) Geometry for single-molecule translation experiments. A biotinylated ribosome is loaded onto a single-stranded mRNA and attached to a streptavidin-coated polystyrene bead fixed to a micropipette. The 3′ of the message is anchored to a second bead through a 1460 bp DNA/RNA hybrid handle. Calibrated forces can be applied to the ribosome by manipulating the second bead with an optical trap, while the translation progress of the ribosome is determined by the change in extension of the tether. (B–D) Typical translation events recorded under 4,6 and 8 pN of constant tension. The upper panels show the codons translated as a function of time, and indicate that translation proceeds not in a continuous manner, but in a series of translational bursts separated by long pauses. The gray line shows the raw (1 kHz) data, while green (translocation) and red (pause) are filtered down to 1 Hz. The lower panels show the instantaneous velocities calculated from the traces above. (E and F) Control experiments, under 8 pN of tension, showing that in the absence of GTP or EF-G, no translation signals were detected. : http: //dx. . org/10. 7554/eLife. 03406. 00310. 7554/eLife. 03406. 004Figure 1— 1. A partial translation trace showing an unusually low noise level, and a sequence of presumptive single-codon translocation steps. The data was sampled at 2 kHz and","Producing a protein first requires its gene to be transcribed into a long molecule called a messenger RNA (mRNA). A complex molecular machine called the ribosome then translates the mRNA code by reading it three letters at a time. Each triplet of letters—known as a codon—tells the ribosome which amino acid to add next into the protein. After adding an amino acid, the ribosome moves along the mRNA molecule to read the next codon and add another amino acid into the protein chain. While researchers understand how protein chains are formed, how the ribosome shifts along the mRNA strand—a process called translocation—is still unclear. It is known that this process involves many force-generating movements and changes to the shape of the ribosome. However, it is only recently that",380,128,0.3368
dialogsum,"#Person1#: Excuse me. I bought this just now and here's a receipt. I'm afraid I was short-changed. Could you look into it? #Person2#: Oh, really? Just a moment. . . You paid with a ten-dollar note and I gave you. . . Oh, sorry, here's a five left. I'm terribly sorry.",#Person1# is short-changed five dollars by #Person2#.,51,7,0.1373
scientific_lay_summarisation-elife-norm,"express bag of marbles (bam), which is necessary and sufficient for their differentiation (Sheng et al. , 2009; Gönczy et al. , 1997). The testis niche also supports a somatic stem cell population called cyst stem cells (CySCs) that produces somatic support cells, which exit the cell cycle and ensheath differentiating GSC daughter cells. During aging, the population of GSCs declines such that at 50 days of adulthood ~35% of GSCs are lost from the niche and the remaining GSCs have reduced proliferation (Boyle et al. , 2007; Wallenfang et al. , 2006). The 35% reduction in the GSC pool in aged males is much smaller than predicted. The average half-life of a GSC is 14 days, and for a testis with 10 GSCs at day 0 of adulthood, there should be <1 GSC at 50 days (Boyle et al. , 2007; Wallenfang et al. , 2006). In other words, the reduction in the total GSC pool should be more than 90% at 50 days. This discrepancy in predicted vs observed size of the GSC pool raised the possibility that a mechanism such as spermatogonial dedifferentiation could be responsible for the apparent resistance of the GSC pool to the deleterious effects of aging (Wang and Jones, 2011; Wallenfang et al. , 2006; Cheng et al. , 2008). However, to date no study has tested this hypothesis by specifically inhibiting dedifferentiation in spermatogonia. Certain genetic manipulations (transient removal of responses to niche signals or transient mis-expression of the key differentiation factor bam) cause all GSCs to differentiate. However, upon silencing of these triggers, spermatogonia break apart, migrate back to the niche, outcompete the resident CySCs and become functional GSCs by transducing JAK/STAT signals and repressing bam expression (Brawley and Matunis, 2004; Sheng et al. , 2009; Sheng and Matunis, 2011). Interestingly, these studies revealed that the 8-cell spermatogonial cyst is the oldest stage still competent to dedifferentiate. bam-lineage labeling analysis of 4- and 8-cell spermatogonial cysts revealed that the proportion of dedifferentiated cells in the GSC pool increases with aging; in 50 day old males, ~40% of the GSCs are derived from bam-lineage spermatogonia that dedifferentiated (Cheng et al. , 2008). Here, we have developed a methodology that enabled us to inhibit specifically dedifferentiation of bam-expressing, 4- and 8-cell spermatogonial cysts","From the heart to the brain, our bodies are made of a collection of cells that are specialized to perform precise roles. Yet, certain organs host ‘stem cells’, which can become any kind of tissue. For example, the testicles of the fruit fly contain germline stem cells; when one of these cells divides, a daughter remains unspecialized, while the other specializes – or differentiates – to become sperm. Despite previous beliefs, a cell that is undergoing specialization can dedifferentiate to become a stem cell again. As the organism gets older, stem cells become ‘exhausted’: they divide less, and lose their ability to remain unspecialized. Scientists therefore proposed that dedifferentiation could be a way to replenish a dwindling pool of stem cells, and ward off the effects of age.",380,128,0.3368
pubmed-summarization,"perioral and buccal muscles would strengthen . the baby was checked at intervals of six weeks for a period of six months ( ) . when the baby was eight months , an operation was done to correct anomalies in the skull . a silicon - based impression material was preferred to make the maxillary impression easier . during the impression the baby s head is tilted backwards by holding the left knee forward.9 it is postulated that mutation in the frfr2 gene has an effect on the mesenchymal development , which has an effect on tooth morphogenesis.10 many oral manifestations can be attributed to the presence of this mutation . failure in the anteroposterior and downward growth of the maxilla causes the maxillary hypoplasia and a resultant contraction of nasopharyngeal airway.11 therefore , one should pay attention to obstructive sleep apne syndrome and premature death.1 in patients with apert syndrome , severe skeletal class iii open bite malocclusion can be observed due to the maxillary deficiency and the inclination of the upper jaw . the infant is likely to suffer from oral hygiene problems during treatment . for the patient with apert syndrome , the new generation of electric tooth brushes and fluoride mouth rinses may make the task easier . professional care -including frequent dental examinations , oral hygiene prophylaxis , fluoride treatments , and dental sealants- are very important.4 tosun and sener s study showed that apert syndrome was in parallel with g6pd deficiency.4 g6pd deficiency is an enzymatic hereditary disorder leading to hemolytic anemia as a result of red blood cell destruction . the main problem in g6pd deficiency is that hemolysis can be precipitated by a number of factors , such as oxidant drugs , eating fava beans , or intercurrent infection . drugs that may induce hemolysis include sulphonamides , chloramphenicol , aspirin , acetaminophen , penicillin , and streptomycin . therefore , the dentist must avoid drugs that may potentially induce hemolysis as result of g6pd deficiency.4 a significant proportion of patients with apert syndrome has mental retardation . in these patients , significant social problems , speech difficulties , and attention deficit are noted.1 in apert syndrome , definite diagnosis can be made by dna analysis . crouzon syndrome -another craniosynostosis disorder-","the purpose of this report is to present apert syndrome patient by highlighting craniofacial characteristics and orthodontic approach to treatment.the patient , a 16-day - old female and the second child of healthy parents , was admitted to our department with primary complaint of cleft palate . she had a cone - shaped calvarium , midface hypoplasia , syndactyly of the hands and feet , hypertelorism , proptosis and cleft palate . after taking maxillary impression , an acrylic appliance was applied to orientate the growing and enable the feeding.a case with apert syndrome undergoes the orthodontic treatment for a long time and also a multidisciplinary approach is essential to determine the best collaborative corrective plan for the deficiencies of the patient .",380,123,0.3237
dialogsum,"#Person1#: Peter? This is Steven from China. I've got the document you want. #Person2#: Great. Send it to me by FedEx tomorrow morning. Or better, call Federal Express for a pick-up. That way I'll get it even earlier. #Person1#: That'll cost me a fortune. #Person2#: Don't worry about that. I'll reimburse you as soon as I receive the package. #Person1#: OK. I'll try. But I'm not sure Federal Express picks up mail in this city. If that's the case, I'll send the package through Chinese express mail service. #Person2#: OK.",Steven from China phones Peter to tell him the availability of the document. Peter requests Steven to send it to him and he will reimburse Steven.,90,26,0.2889
dialogsum,"#Person1#: Bang? ! Bang! Bang! What are the Kings doing at seven o'clock on Sunday morning? #Person2#: Well, Mr. King is singing. #Person1#: Yes, but what's the banging noise? #Person2#: He's standing on a ladder and banging some nails into the wall with a hammer. Now he's hanging some strong strings on the nails. #Person1#: And what's Mrs. King doing? #Person2#: She's bringing something pink for Mr. King to drink. Now she's putting it. . . OK. #Person1#: What's happening? #Person2#: The ladder's falling? #Person1#: What's Mr. King doing? #Person2#: He's hanging from the string. He's holding onto the string with his fingers and shouting to Mrs. King. #Person1#: And is she helping him? #Person2#: No, she's running toward our house. That's her ringing the bell. #Person1#: Well, I'm not going to answer it. I'm sleeping.","#Person1# is annoyed by Mr. King's banging noise. Mr. King's hanging from the string as the ladder falls. Mrs. King's running toward #Person1#'s house, but #Person1#'s not going to answer.",136,30,0.2206
dialogsum,"#Person1#: Hey, do you want to go for a picnic in the park tomorrow afternoon? #Person2#: I can't. I just started coaching a boys' football team. We have a game tomorrow. #Person1#: Oh, that sounds fun. Maybe I can come see it. #Person2#: Sure! The game starts at two, but we'll be there at 1:00 to prepare. It'll be at the football field beside the high school, across from the post office. #Person1#: OK, great. I'll be there at 1:30, then. But why did you decide to coach a football team? #Person2#: Well, I thought it might be a bad idea at first, because I was so busy at work. But then I thought, why not?","#Person1# invites #Person2# to go for a picnic, but #Person2# refuses because #Person2# needs to coach a football team. #Person1# wants to see it and #Person2# agrees.",116,27,0.2328
scientific_lay_summarisation-elife-norm,"unwound DNA forming a ‘transcription bubble’. Within this bubble a position or positions will be identified to serve as transcription start sites (TSSs). Initial promoter melting appears to occur stereotypically ~20–25 nt downstream of promoter elements such as the TATA box across eukaryotes, though most promoters lack a TATA box or other strong sequence signature. During initiation, the process of TSS selection determines the identity and distribution of transcript isoforms that differ by their 5’ ends. Differences in 5’ UTR can alter transcript properties such as translation efficiency or transcript stability through differences in sequence or RNA secondary structure (Arribere and Gilbert, 2013; Rojas-Duran and Gilbert, 2012; Malabat et al. , 2015; Sample et al. , 2019; Cuperus et al. , 2017; Akirtava and McManus, 2021; Lin et al. , 2019). Furthermore, in conjunction with activators and coactivators, the efficiency of the initiation process will also establish mRNA synthesis rates. How TSS selection is governed by these factors is not well understood for the majority of eukaryotic promoters that utilize multiple TSSs. Transcription initiation by Saccharomyces cerevisiae Pol II has been the subject of extensive analysis both in vivo and in vitro, and thus provides a powerful model for system for mechanistic studies of TSS selection. TSS selection by S. cerevisiae Pol II occurs over a range of positions located ~40–120 bp downstream of the core promoter region. Numerous lines of evidence suggest that TSS selection by S. cerevisiae Pol II involves a unidirectional scanning mechanism in which the preinitiation complex (PIC) assembles at an upstream core promoter and interrogates consecutive downstream positions for usable TSSs (Giardina and Lis, 1993; Kuehner and Brow, 2006; Hampsey, 2006; Fishburn et al. , 2016; Qiu et al. , 2020). TFIIH is proposed to drive Pol II scanning through ATP-dependent DNA translocase activity (Fishburn et al. , 2016; Tomko et al. , 2021; Tomko et al. , 2017; Fishburn et al. , 2015; Fazal et al. , 2015). An optical-tweezer-based single molecule analysis of reconstituted S. cerevisiae PICs indicated that an ATP/dATP-induced activity within the PIC causes shortening of the distance between upstream and downstream DNA (Fazal et al. , 2015). This shortened distance approximates the distance downstream from TATA elements where TSSs are positioned in yeast (40–120 nt) (Struhl, 1987) and suggests downstream","In eukaryotic organisms such as yeast, the process of converting genes into proteins begins with the transcription of DNA sequences into mRNA molecules. An enzyme called RNA Polymerase II (Pol II) is responsible for creating new strands of mRNA, but a variety of other so called transcription factors is also needed to kickstart the transcription process. These transcription factors are delivered to genes, where they attach to specific sequences, or promoters, which sit at the beginning of each gene. Once these transcription factors are in place, the double stranded DNA is unzipped to provide access to the DNA that will serve as the template for transcription. In budding yeast, Pol II and another specific transcription factor, known as TFIIH, work together to scan these promoter sequences to find",380,128,0.3368
pubmed-summarization,"hcc and curative resection of tumor without preoperative or postoperative adjuvant therapy . we defined curative resection as complete resection of all tumor nodules with clear microscopic resection margins and no residual tumors as indicated by a computed tomography scan one month after surgery . microvascular invasion was considered present when at least one or more endothelial cells or the tunica media of the vessel surrounded a neoplastic cell group . tumor stage was determined by both the american joint committee on cancer ( ajcc ) staging system and barcelona clinic liver cancer ( bclc ) staging classification . using 2 years as the cut off , all hcc patients were followed by monitoring serum -fetoprotein levels and three phase dynamic computed tomography scans or magnetic resonance imaging every three months after surgery . the follow - up period for recurrence was at least 18 months , and the median follow - up period was 120.0 months ( range , 14.0 to 151.4 months ) for survivors . recurrence - free survival ( rfs ) was defined as from the date of resection until the detection of tumor recurrence . we chose disease - specific death ( hcc - related death ) as the clinical endpoint for survival analysis , defined as : ( 1 ) tumor occupying more than 80% of the liver , ( 2 ) portal venous tumor thrombus proximal to the second bifurcation , ( 3 ) obstructive jaundice due to the tumor , ( 4 ) distant metastases , or ( 5 ) variceal hemorrhage with portal venous tumor thrombus proximal to the first bifurcation . disease - specific survival ( dss ) was defined from the date of resection to the date of hcc - related death . histologic sections were examined by two pathologists and representative tumor regions were marked in the formalin - fixed paraffin - embedded blocks . two tissue cores measuring 2.0 mm in diameter were punched from the marked areas of each block and arranged into new paraffin blocks . as controls , two cores of normal liver tissue from 12 patients with metastatic colon carcinoma of the liver were included in each array block . antigen retrieval was performed with 0.01 mol / l citrate buffer at ph","purposecancer cells frequently express genes that are specifically or preferentially expressed in male germ cells under normal conditions . the atpase family aaa domain - containing 2 ( atad2 ) is one such and works as an important cofactor for myc - dependent transcription . in hepatocellular carcinoma ( hcc ) , atad2 has been identified as a candidate driver gene located within the amplified 8q24 locus . however , the prognostic significance of atad2 protein expression in hcc remains uncertain.materials and methodswe investigated atad2 protein expression by immunohistochemistry in tumor tissue from 182 hcc patients who underwent curative resection . associations of atad2 expression with clinicopathologic variables or prognosis of hcc patients were analyzed.resultsatad2 expression was observed in 119 ( 65.4% ) of the 182 hccs and",380,128,0.3368
dialogsum,"#Person1#: Hah! For three hours while you threw up. And Femi dumped me for that. I really loved her. #Person2#: I'm so sorry, Taylor. Go talk to her. I'm sure she'd be happy to see you. #Person1#: She probably wouldn't even recognize me. She's probably married. #Person2#: Yi-jun said Femi was talking about you. So get out there, Tiger! #Person1#: Was she really? So you're telling me there's a chance? #Person2#: Can't hurt to try. Carpe diem. Who can say if we'll be here tomorrow or not?","Taylor was dumped by Femi, and #Person2# encourages Taylor to talk to her and seize the day.",87,17,0.1954
scientific_lay_summarisation-elife-norm,"domain one protein, also known as HAVCR1) was identified as a receptor for HAV twenty years ago (Feigelstock et al. , 1998; Kaplan et al. , 1996), prior to the discovery of quasi-enveloped virions. TIM1 has since been shown to facilitate the binding of eHAV but not naked HAV virions to the cell surface (Das et al. , 2017), presumably through binding PtdSer displayed on the surface of the eHAV membrane (Feng et al. , 2015). However, TIM1 is not essential for attachment or entry of either HAV or eHAV, nor is it required for infection of permissive strains of mice (Das et al. , 2017). Thus far, an essential receptor has yet to be identified for either HAV or eHAV. Little is known about how these two virion types enter cells, although prior studies point to the existence of distinct entry pathways for naked versus quasi-enveloped virions as might be expected from the presence of the limiting lipid membrane in eHAV. eHAV is selectively sensitive to the lysosomal poison chloroquine (Feng et al. , 2013), and slower to enter cells and begin replication than naked HAV capsids (Das et al. , 2017; Feng et al. , 2013). eHAV is resistant to anti-capsid neutralizing antibodies in quantal, plaque reduction-like assays, but neutralizing antibodies restrict its replication when added to cells 4–6 hr after adsorption of the virus, suggesting a delay in uncoating within an endocytic compartment (Feng et al. , 2013). Here, we report detailed roadmaps for the entry of these different types of infectious hepatitis A virions in hepatocytes, identify a key role for integrin β1 in endocytosis of both, and demonstrate distinct trafficking of these virion types through the endocytic system. We demonstrate critical temporal and spatial differences in the uncoating of HAV and eHAV capsids, and show that eHAV entry is uniquely dependent on the ESCRT accessory protein ALIX as well as lysosomal proteins involved in lipid metabolism. To identify the endocytic pathways responsible for internalization of HAV and eHAV virions in Huh-7. 5 human hepatoma cells, we used pharmacological and genetic approaches to disrupt the function of regulators of several canonical endocytic routes. Inhibition of clathrin- and dynamin-mediated endocytosis by the drugs chlorpromazine and dynasore, respectively, strongly inhibited the uptake of both gradient-purified HAV and eHAV","The Hepatitis A virus is a common cause of liver disease in humans. It is unable to multiply on its own so it needs to enter the cells of its host and hijack them to make new virus particles. Infected human cells produce two different types of Hepatitis A particles. The first, known as ‘naked’ virus particles, consist of molecules of ribonucleic acid (or RNA for short) that are surrounded by a protein shell. Naked virus particles are shed in the feces of infected individuals and are very stable, allowing the virus to spread in the environment to find new hosts. At the same time, a second type of particle, known as the ‘quasi-enveloped’ virus, circulates in the blood of the infected individual. In a quasi-enveloped particle, the",380,128,0.3368
dialogsum,"#Person1#: Good morning, Miss Monica. Nice to meet you again! #Person2#: Good morning, Mr. Thomas, it is nice to see you too. #Person1#: After the internal discussion, we have all agreed that you are the most suitable person for this position among all the candidates. So, today let ' s talk about your expected salary and social benefits. What is your expected salary? #Person2#: I ' Ve worked in the field for more than 4 years. Depend on my work qualifications and experience, I would like to have 5000 Yuan to start. #Person1#: The basic salary for your position in our company would be 4800 Yuan to start with increases giving according to your performance. #Person2#: It is a bit lower than I expected. But I can accept that. What are the working hours? #Person1#: 40 hours a week, Monday to Friday, 9 AM to 5 PM with one hour lunch break every day.. #Person2#: Do I have to work on weekend? If so, how do you pay for the overtime? #Person1#: We do expect overtime work when it is necessary, but we pay twice of the work hour for working on weekends and three times for working on national holidays like Spring Festival and the Mid-Autumn Day. #Person2#: Is there probation? #Person1#: No probation is involved. If you feel good, you can start next week.",Mr. Thomas talks with Monica about her expected salary and social benefits. They finally reach a consensus on 4800 Yuan to start with. Monica also asks the payment for the overtime and the existence of probation.,226,36,0.1593
scientific_lay_summarisation-elife-norm,"a repressive Rpd3 deacetylase complex to sites of active elongation (Carrozza et al. , 2005; Keogh et al. , 2005). It is also implicated in suppressing active incorporation of acetylated histones via histone exchange (Venkatesh et al. , 2012). In cultured cells, ablation of human SETD2, which catalyzes H3K36 trimethylation, is suggested to alter a number of exon inclusion events by recruiting RNA binding proteins (Luco et al. , 2010; Pradeepa et al. , 2012). Conversely, H3K36me3 distribution across gene bodies is itself sensitive to perturbations in splicing (de Almeida et al. , 2011; Kim et al. , 2011). In addition to its role in transcription and RNA processing, a range of other activities have been attributed to H3K36me, including X-chromosome dosage compensation (Larschan et al. , 2007), DNA damage response (Jha and Strahl, 2014; Li et al. , 2013; Pai et al. , 2014; Pfister et al. , 2014), and three dimensional chromosome organization (Evans et al. , 2016; Smith et al. , 2013; Ulianov et al. , 2016). However, to date, none of these putative roles for H3K36me have been evaluated directly in an H3K36 mutant animal. Here, we report a comprehensive analysis of H3K36 function, focused on differential gene expression, transcription initiation, and chromatin accessibility phenotypes in transgenic Drosophila whose entire complement of replication-dependent H3 genes has been mutated to arginine at lysine 36 (H3K36R). Arginine approximates the charge and steric conformation of lysine, but cannot be targeted by lysine methyltransferases, and therefore represents an appropriate mutation with which to study the PTM-specific functions of H3K36. Although arginine is a conservative amino acid change, it also enables hydrogen bonding modalities that are distinct from those of lysine. In principle, in addition to phenotypes resulting from loss of H3K36 methylation, such a change could also result in other hypomorphic (partial loss of function) or neomorphic (gain of function) phenotypes. In H3K36R mutants, we observed a decrease in the steady-state levels of highly expressed RNAs concomitant with increased transcription and productive expression from a variety of low-usage promoters. Though mutants exhibited bulk increases in histone acetylation, chromatin accessibility did not appreciably change at promoters. Surprisingly, we found that previously reported roles for H3K36 methylation, including suppression of transcription initiation in coding regions and regulation of alternative splicing, are not","In a single human cell there is enough DNA to stretch over a meter if laid end to end. To fit this DNA inside the cell – which is less than 20 micrometers in diameter – the DNA is tightly wrapped around millions of proteins known as histones, which look like “beads” along a “string” of DNA. These histones can prevent other proteins from binding to DNA and activating specific genes. Therefore, cells use enzymes to chemically modify histones to allow particular stretches of DNA to be unwrapped at specific times. Proteins are made up of building blocks called amino acids. A specific amino acid on histones known as H3K36 is modified in certain sections of DNA that suggest it affects the activities of many genes. However, the",380,128,0.3368
pubmed-summarization,"reported 28 cases ( 5.3% ) of iatrogenic type a aortic dissection ( itaad ) as a complication of cardiac surgery or cardiac catheterization , nine of which ( 32% ) died . the german registry for acute aortic dissection type a ( geraada ) reported a comparable incidence of 100 cases ( 4.7% ) of itaad out of a total of 2,137 cases of type a aortic dissection , but with a lower 30-day mortality of 16% . leontyev et al reported 48 cases over a 15-year follow - up , undergoing surgery for itaad , with a frequency of 0.06% ( 36 cases ) of open heart surgeries , and 0.01% ( 12 cases ) of cardiac catheterizations ; early surgical mortality was 50% for itaads associated with coronary angiography . dunning et al reported nine cases ( 0.02% ) of coronary artery - aortic dissections out of over 40,000 cardiac catheterizations performed over a 6-year period ; these were significantly more prevalent in the setting of ami ( 0.19% ) , compared with non - ami ( 0.01% ) . while outcomes were favorable for the less severe dissections treated conservatively , two of the reported cases had dissection extending into the arch , and both died following surgery . they proposed a classification scheme based on the extent of aortic dissection beyond the involved coronary cusp ( . 3 ) , and concluded that the best treatment in class 1 and 2 dissections is stenting of the intra - coronary entry point when possible and close clinical follow - up , while class 3 dissections usually require surgical intervention . gomez - moreno et al reported 17 cases ( 0.04% incidence ) of itaad associated with cardiac catheterizations over a 10-year follow - up period , with a significantly higher incidence after interventional procedures ( 0.12% ) than after diagnostic procedures ( 0.01% ) . patients were treated conservatively with either stenting to seal the entry door or expectant management ; no patients died during hospitalization or follow - up . nunez - gil et al reported 14 cases ( 0.02% incidence ) of iatrogenic dissection of the descending aorta / arch without coronary involvement over a 15-year follow - up treated conservatively , with only","we report a 63-year - old female with hypertension , hyperlipidemia , and prior pacemaker insertion for atrial fibrillation with symptomatic bradycardia , who was admitted with substernal chest pressure and diaphoresis . her electrocardiogram revealed atrial fibrillation with demand ventricular pacing and her cardiac biomarkers were negative for acute coronary syndrome . echocardiogram revealed normal left ventricular systolic function and normal aortic root diameter . coronary angiography revealed 60 - 70% obtuse marginal lesion , otherwise mild disease . she was treated medically and discharged in stable condition . she was readmitted 1 month later with recurring chest pain , and shortness of breath which started shortly after her most recent discharge . blood pressure was 152/93 mm hg , and heart rate was 105 bpm .",380,128,0.3368
dialogsum,"#Person1#: Here's the schedule we've prepared. #Person2#: Oh, thank you. #Person1#: Do you mind if we talk about your schedule tomorrow? #Person2#: That will be best. I'd like to have a good rest first. #Person1#: And this is the schedule for Mrs. Watson. Eileen from our department will take care of her. #Person2#: Ok. Shall we discuss the schedule in the lobby? #Person1#: All right. I'll see you in the lobby tomorrow morning.",#Person1# takes out Mrs. Watson's schedule and will talk about the schedule prepared for #Person2# tomorrow.,73,16,0.2192
scientific_lay_summarisation-elife-norm,"a result, ratiometric Vmem sensors cannot be used to optically quantify slow signals in the resting Vmem, which may be on the order of tens of millivolts. Indeed, ratiometric Vmem probes are most commonly applied to detect - rather than quantify - fast changes in Vmem (Zhang et al. , 1998), much like their single wavelength counterparts. An alternative approach to improved quantification in optical measurements is fluorescence lifetime (τfl) imaging (FLIM), which measures the excited state lifetime of a population of fluorophores. Because fluorescence lifetime is an intrinsic property, FLIM can avoid many of the artifacts that confound extrinsic fluorescence intensity measurements, such as uneven dye loading, fluorophore bleaching, variations in illumination intensity, and detector sensitivity (Berezin and Achilefu, 2010; Yellen and Mongeon, 2015). If a fluorescent probe responds to the analyte of interest via changes in the lifetime of its excited state, there is the opportunity to use fluorescence lifetime to provide a more quantitative estimate of analyte parameters than can be achieved with fluorescence intensity alone. Although FLIM measurements can be affected by environmental factors such as temperature, ionic strength and local environment (Berezin and Achilefu, 2010), FLIM has been widely employed to record a number of biochemical and biophysical parameters, including intracellular Ca2+ concentration (Zheng et al. , 2015), viscosity (Levitt et al. , 2009), GTPase activity (Harvey et al. , 2008), kinase activity (Lee et al. , 2009), and redox state (NADH/NAD+ ratio) (Blacker and Duchen, 2016), among others (Yellen and Mongeon, 2015). Attempts to record absolute voltage with FLIM, however, have been limited in success (Dumas and Stoltz, 2005; Hou et al. , 2014; Brinks et al. , 2015). Previous work focused on genetically encoded voltage indicators (GEVIs), which either possess complex relationships between τfl and voltage (Hou et al. , 2014) or show low sensitivity to voltage in lifetime (Brinks et al. , 2015) and require complex and technically challenging measurements of fast photochemical kinetics to estimate voltage (Hou et al. , 2014). Because of this poor voltage resolution, the fluorescence lifetimes of GEVIs cannot be used to detect most biologically relevant voltage changes, which are on the order of tens of millivolts. Fluorescent voltage indicators that use photoinduced electron transfer (PeT) as a voltage-sensing mechanism are promising candidates for a FLIM-based approach","All living cells are like tiny batteries. As long as a cell is alive, it actively maintains a difference in electrical charge between its interior and exterior. This charge difference, or voltage, is called the membrane potential, and it is vital for our bodies to work properly. For example, fast changes in membrane potential control our heartbeat and underpin the electrical signals that brain cells use to communicate. Slower changes in membrane potential – ranging from minutes to days – may also play important roles in other organs. To understand how and why membrane potential is important in these contexts, we need methods to measure it accurately in individual cells. One way is to puncture cells with microscopic electrodes: this yields accurate results but damages the cells and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"reported to be associated with some, but not all cases of SCD (Thiel et al. , 1977; Brownstein et al. , 1991; Crispin, 2002). In 2007, two groups independently identified SCD-associated mutations in the gene encoding UBIAD1 (UbiA prenyltransferase domain-containing protein-1) (Orr et al. , 2007; Weiss et al. , 2007). UBIAD1 (also known as TERE1) was first described as being absent or markedly diminished in bladder and prostate tumors (McGarvey et al. , 2001,2003) and belongs to the UbiA superfamily of prenyltransferases (Heide, 2009). These enzymes, which are found in a wide variety of species, contain 8–10 transmembrane helices and catalyze transfer of isoprenyl groups to aromatic acceptors, producing a diverse range of molecules including ubiquinone, chlorophylls, hemes, vitamin E, and vitamin K (Forsgren et al. , 2004; Nakagawa et al. , 2010; Bonitz et al. , 2011). Indeed, UBIAD1 catalyzes transfer of the 20-carbon geranylgeranyl group from geranylgeranyl pyrophosphate to menadione (vitamin K3) derived from plant-derived phylloquinone (vitamin K1), generating MK-4 (menaquinone-4, vitamin K2) () (Nakagawa et al. , 2010; Hirota et al. , 2013). It has also been proposed that UBIAD1 mediates polyprenylation of 4-hydroxybenzoate to produce 3-polyprenyl-4-hydroxybenzoate (PPHB), an intermediate in the synthesis of CoQ10 (coenzyme Q10 or ubiquinone-10) (Mugoni et al. , 2013). 10. 7554/eLife. 05560. 003Figure 1. Biosynthesis of cholesterol and menaquinone-4 (MK-4, vitamin K2) in mammalian cells. : http: //dx. . org/10. 7554/eLife. 05560. 003 To date, 24 UBIAD1 mutations have been identified in ∼50 SCD families (Nickerson et al. , 2013; Nowinska et al. , 2014). Several of these mutations alter amino acid residues that localize to the active site of the UBIAD1 prenyltransferase domain as determined by molecular modeling using structural models of bacterial and archaeal UbiA prenyltransferases (Bräuer et al. , 2004,2008; Nickerson et al. , 2010; Cheng and Li, 2014; Huang et al. , 2014). Cells from patients harboring four SCD-associated mutations (N102S, D112N, and G177E/R) exhibited reduced MK-4 biosynthetic activity (Nickerson et al. , 2013). A possible link between UBIAD1 and cholesterol metabolism was provided by co-immunoprecipitation studies that showed an association of UBIAD1 with the cholesterol biosynthetic enzyme HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase (Nickerson et al. , 2013). However, the relevance of this association to regulation of cholesterol metabolism and pathogenesis of SCD is not clear.","People with a rare genetic disorder called ‘Schnyder corneal dystrophy’ gradually lose their vision, because their corneas become increasingly cloudy. This cloudiness is caused by a build-up of excessive amounts of cholesterol, and the disorder itself is caused by mutations in a gene that encodes a protein called UBIAD1. Researchers have previously discovered that the UBIAD1 protein is involved in making vitamin K2, but it is not clear how this protein also helps to control cholesterol levels in the cornea. An enzyme called HMG CoA reductase makes a molecule that is used to make cholesterol and many other similar sterol molecules. A ‘feedback loop’ operates in cells to control the amount of the reductase and prevent cholesterol from becoming too high or too low. Sterol molecules, together with",380,128,0.3368
dialogsum,"#Person1#: Are you ready, honey? #Person2#: Sorry, not yet! can you help me to select the dress? i don, t what i should wear to fit thinner party. #Person1#: Just dress formal. #Person2#: How about transom? #Person1#: It is too loud, we'll handle some official business first before the dinner. #Person2#: Oh, i nearly forget it. #Person1#: You can put on your white shoes, it fits every occasion.","#Person2# asks #Person1# to help select the dress, and #Person1# advises to dress formally.",68,14,0.2059
pubmed-summarization,"and privacy of individual , protected health information ( phi ) in an era of open science . however , there are also substantial prevailing interests arguing against open sharing that do not necessarily represent the public s interest . these include the potential value of intellectual property to investigators who withhold data sets in order to preserve the ability to conduct new analyses over time , and even concerns that more reproducible research enables competing researchers to identify flaws in the original work if the original data is reanalyzed . these issues can be heightened in the clinical health domain given its close relationship with a trillion dollar marketplace for health services that is increasingly dependent on data and analytic tools . both examples highlight incentives not to share and not to collaborate that , if not entirely wholesome , are nonetheless entirely human . there are many reasons to believe oa and open science are crucial to enabling a national learning health system . as demonstrated by arxiv in the physics , mathematics , engineering , and astrophysics communities,12 a key value proposition for open science is the ability to spread promising scientific approaches rapidly in a more open and transparent environment both to accelerate innovation and to reduce redundancy . note , however , that as we move beyond the current period in which unprecedented support has been provided for health it infrastructure and research , it is imperative that we consider ways to provide open source tools that can reduce disparities between wealthier systems and regions on the one hand and those that may be more resource constrained , including safety net and public health systems , on the other . open science offers tools to minimize the digital and analytic divide between disparate systems while promoting continuous learning and improvement . the result of these debates over oa can be extremely polarizing because open science is , at its core , a philosophy . while formal requirements to instantiate open science principles as part of the scientific workflow may be on their way , for now we re relying on the goodwill of data liberators13 and individual actors to demonstrate the benefits of openness . those in health care who more freely share data and","open science includes a variety of approaches to facilitate greater access to data and the information produced by processes of scientific inquiry . recently , the health sciences community has been grappling with the issue of potential pathways and models to achieve the goals of open science namely , to create and rapidly share reproducible health research . egems continued dedication to and milestones regarding the publication of innovative , useful , and timely research to help contribute to the push towards open science is discussed , as well as the edm forum s new data sharing platform , cielo . although strides have been made , there is still more work to be done to help health sciences community truly embrace open science .",380,125,0.3289
scientific_lay_summarisation-elife-norm,"Anatomical and physiological studies have led to the assumption that the dorsal striatum receives exclusively excitatory afferents from the cortex. Here we test the hypothesis that the dorsal striatum receives also GABAergic projections from the cortex. We addressed this fundamental question by taking advantage of optogenetics and directly examining the functional effects of cortical GABAergic inputs to spiny projection neurons (SPNs) of the mouse auditory and motor cortex. We found that the cortex, via corticostriatal somatostatin neurons (CS-SOM), has a direct inhibitory influence on the output of the striatum SPNs. Our results describe a corticostriatal long-range inhibitory circuit (CS-SOM inhibitory projections → striatal SPNs) underlying the control of spike timing/generation in SPNs and attributes a specific function to a genetically defined type of cortical interneuron in corticostriatal communication. It is very well established that cortical neurons regulate the activity of spiny projection neurons (SPNs) in the striatum through long-range glutamatergic/excitatory projections (Landry et al. , 1984; Wilson, 1987; 2004; Graybiel et al. , 1994; Lovinger and Tyler, 1996; Reiner et al. , 2003; Kress et al. , 2013), while inhibition is mediated by local feed-forward and feed-back circuits (for review [Tepper et al. , 2008]). The feed-forward circuit is characterized by GABAergic striatal interneurons that receive excitatory inputs from the cortex and monosynaptically inhibit SPNs. The feed-back circuit is characterized by SPNs and their interconnections via local axon collaterals (Calabresi et al. , 1991; Kawaguchi, 1993; Kita, 1993; 1996; Kawaguchi et al. , 1995; Mallet et al. , 2005; Planert et al. , 2010; Ibanez-Sandoval et al. , 2011). Because striatal neuronal activity has been shown to be involved in movement, learning, and goal-directed behavior (Graybiel, 1995; Schultz et al. , 2003; Barnes et al. , 2005; Kreitzer and Malenka, 2008), it is crucial to understand the cortical connectivity pattern and dynamics that shape the flow of information in the striatum. Anatomical studies using retrograde tracers and immunohistochemistry have proposed that between 1–10% of the GABAergic' interneurons' in rodents, cats, and monkeys also give rise to long-range corticocortical projections (McDonald and Burkhalter, 1993; Tomioka et al. , 2005; Higo et al. , 2007; Tomioka and Rockland, 2007; Higo et al. , 2009). A growing body of evidence suggests that many of these projections arise from somatostatin-expressing neurons (Tomioka et al.","The striatum is located beneath the cerebral cortex, where it contributes to processes including learning and movement. The Spanish anatomist Ramon y Cajal, working in the early 20th century, was the first to observe individual neurons extending from the cortex to the striatum. Cajal published drawings of these neurons in his now celebrated anatomical papers, but knew little about their properties. In the 1980s, advances in techniques for labeling individual cells made it possible to study these neurons in detail. The results suggested that the pathways are exclusively excitatory: that is, the cortical neurons always increase the activity of their partners in the striatum. However, this result made it difficult to explain why electrically stimulating the cortex can sometimes reduce or inhibit the activity of the striatum. To",380,128,0.3368
dialogsum,"#Person1#: Do you know how happy I am? The Ant Kingdom is a perfect world with colorful fairy tales. It seems like the air is fresh here. #Person2#: Just kids like that. #Person1#: Come on baby, stop trying to pretend like a man. If you go there, you are sure to like them. #Person2#: Hurry up! Hurry up! What lovely caterpillars are over there! #Person1#: I said you are sure to like them. There is the Grand Parade Of Ants Carnival in a few minutes in the square. You will experience a dream of fantasy. #Person2#: What's that? #Person1#: All kinds of insects dress themselves up. They drive straight their own Flower Cars along the Parade Avenue of Ants Kingdom. #Person2#: That's splendid. Can you take three pictures of me with them? #Person1#: I thought you had grown out of such child practices. #Person2#: Cut it out. Look at my smile, and it seems like the flowers in the spring. Right? #Person1#: Gross! #Person2#: Hurry up! The smile is frozen on my face.",#Person1# is crazy about the Ant Kingdom. #Person2# thinks it's childish at first but then loves the place and even asks #Person1# to take pictures for #Person2#.,173,27,0.1561
scientific_lay_summarisation-elife-norm,"Nanoparticles are used extensively as biomedical imaging probes and potential therapeutic agents. As new particles are developed and tested in vivo, it is critical to characterize their biodistribution profiles. We demonstrate a new method that uses adaptive algorithms for the analysis of hyperspectral dark-field images to study the interactions between tissues and administered nanoparticles. This non-destructive technique quantitatively identifies particles in ex vivo tissue sections and enables detailed observations of accumulation patterns arising from organ-specific clearance mechanisms, particle size, and the molecular specificity of nanoparticle surface coatings. Unlike nanoparticle uptake studies with electron microscopy, this method is tractable for imaging large fields of view. Adaptive hyperspectral image analysis achieves excellent detection sensitivity and specificity and is capable of identifying single nanoparticles. Using this method, we collected the first data on the sub-organ distribution of several types of gold nanoparticles in mice and observed localization patterns in tumors. Nanoparticles (NPs) can be fashioned in precise shapes and sizes from a wide variety of materials. This synthetic versatility makes NPs excellent tools for wide-ranging biomedical applications including in vivo imaging (Jokerst et al. , 2012; Durr et al. , 2007), drug delivery (Hauck et al. , 2008), photothermal therapy (Huang et al. , 2006; von Maltzahn et al. , 2009), and gene transfection (Huang et al. , 2009). In particular, metal and metal oxide NPs made from gold, silver, iron, and titanium are commonly used in biomedicine owing to their unique electromagnetic properties (Giustini et al. , 2011; Husain et al. , 2015; Lee and El-Sayed, 2006). Once administered to a living subject, these NPs may exhibit vastly different pharmacokinetics and uptake profiles that are contingent on NP shape, size, surface coating, and other factors (Owens III and Peppas, 2006; Chen et al. , 2009; Zhang et al. , 2009; He et al. , 2010; Decuzzi et al. , 2010). These differences manifest not only at the scale of whole organs but also at the cellular level (Giustini et al. , 2011; Yang et al. , 2014; Sadauskas et al. , 2009). Ideally, biodistribution studies should address various scales – from whole animal to tissue and cellular interactions – in order to understand a given NP’s in vivo behavior. Current studies commonly employ inductively-coupled plasma (ICP) techniques (Niidome et al. , 2006)","Metallic elements like gold and silver can be made into particles that are one thousand times smaller than the width of a human hair. Researchers can create these “nanoparticles” in different sizes and shapes that exhibit unique properties. For example, gold can be made into rod-shaped particles that interact with infrared light. Other nanoparticles can be loaded with drug molecules and designed to bind to cancer cells. As a result, nanoparticles have been explored for use in a variety of biomedical imaging and therapy applications. However, we must fully understand how the nanoparticles bind to the cancer cells and how the body tolerates these nanoparticles before they can be used in humans. Experiments that explore where nanoparticles accumulate in the body are typically called biodistribution studies. However, current",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Mutations in Park8, encoding for the multidomain Leucine-rich repeat kinase 2 (LRRK2) protein, comprise the predominant genetic cause of Parkinson' s disease (PD). G2019S, the most common amino acid substitution activates the kinase two- to threefold. This has motivated the development of LRRK2 kinase inhibitors; however, poor consensus on physiological LRRK2 substrates has hampered clinical development of such therapeutics. We employ a combination of phosphoproteomics, genetics, and pharmacology to unambiguously identify a subset of Rab GTPases as key LRRK2 substrates. LRRK2 directly phosphorylates these both in vivo and in vitro on an evolutionary conserved residue in the switch II domain. Pathogenic LRRK2 variants mapping to different functional domains increase phosphorylation of Rabs and this strongly decreases their affinity to regulatory proteins including Rab GDP dissociation inhibitors (GDIs). Our findings uncover a key class of bona-fide LRRK2 substrates and a novel regulatory mechanism of Rabs that connects them to PD. Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting 1–2% of the elderly population (Lees et al. , 2009). Environmental and genetic factors contribute to the development of the disease, but its precise etiology still remains elusive (Burbulla and Krüger, 2011). Genome-wide association studies (GWAS) have related 28 genetic risk variants at 24 loci with nonfamilial PD (Nalls et al. , 2014). Among those, mutations in LRRK2 (Park8) are also found in hereditary forms, pinpointing a shared molecular pathway driving pathogenesis in both familial and non-familial PD and comprising the most common cause of the disease (Simón-Sánchez et al. , 2009; Satake et al. , 2009). LRRK2 encodes a large protein composed of central kinase and GTPase (ROC-COR) domains that are surrounded by multiple protein-protein interaction regions. PD pathogenic LRRK2 mutations map predominantly to the kinase (G2019S, I2020T) and the ROC-COR domains (R1441C/G/H, Y1699C), implying that these enzymatic activities are crucial for pathogenesis (Rudenko and Cookson, 2014). Presently, it is unclear how LRRK2 mutations occurring in different functional domains all predispose to PD. The most common PD-associated LRRK2 mutation is the G2019S amino acid substitution, which activates the kinase two- to threefold (West et al. , 2005; Khan, 2005; Jaleel et al. , 2007). Since protein kinases are attractive pharmacological targets, this finding has raised hopes that selective LRRK2 inhibition can prevent or delay the onset of PD (Yao","Parkinson’s disease is a degenerative disorder of the nervous system that affects approximately 1% of the elderly population. Mutations in the gene that encodes an enzyme known as LRRK2 are the most common causes of the inherited form of the disease. Such mutations generally increase the activity of LRRK2 and so drug companies have developed drugs that inhibit LRRK2 to prevent or delay the progression of Parkinson’s disease. However, it was not known what role LRRK2 plays in cells, and why its over-activation is harmful. Steger et al. used a' proteomics' approach to find other proteins that are regulated by LRRK2. The experiments tested a set of newly developed LRRK2 inhibitors in cells and brain tissue from mice. The mice had mutations in the gene encoding LRRK2 that",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 1996; Packschies et al. , 1997; Gisler et al. , 1998; Russell et al. , 1998; Laufen et al. , 1999; Mayer et al. , 2000). Intriguingly, several experimental evidences suggested that the effective affinity of Hsp70 for substrates when the chaperone was running through its ATP-hydrolysis driven cycle was significantly higher than both the ones of Hsp70⋅ATP and Hsp70⋅ADP (Laufen et al. , 1999; Wittung-Stafshede et al. , 2003). Because this remarkable result would not be possible within the boundaries of thermodynamic equilibrium, it is therefore necessary to clarify how ATP hydrolysis, and thus energy consumption, can affect the binding strength of Hsp70s to their substrates. According to the consensus Hsp70 cycle () substrate binding/unbinding takes place with rates that depend on the state of the bound nucleotide (kATPon, kATPoff, kADPon, kADPoff) (Schmid et al. , 1994; Gisler et al. , 1998; Mayer et al. , 2000), with Hsp70⋅ATP exchanging the substrate two to three orders of magnitude faster than Hsp70⋅ADP. The conversion from Hsp70⋅ADP to Hsp70⋅ATP occurs through a nucleotide exchange process which is described here at an effective level as a simple first-order reaction with rate kDT, or kDTS in the presence of a bound substrate (, and ‘Materials and methods’ for a full derivation). The conversion from Hsp70⋅ATP to Hsp70⋅ADP can occur by means of two different processes: nucleotide exchange (dashed arrows in , with rate kTDex, and kTDex, S in the presence of the substrate) and ATP hydrolysis (red arrows in ), whose rate depends on the absence or presence of a bound substrate (kh and khS respectively). The total conversion rate from Hsp70⋅ATP to Hsp70⋅ADP is thus kTD=kTDex+kh (and analogous expressions in the presence of a substrate). In the cell, several cochaperones tune the exchange and hydrolysis rates: J-domain proteins (JDPs) enhance the rate of ATP hydrolysis, and nucleotide exchange factors (NEFs) catalyze nucleotide release (Youker and Brodsky, 2007; Kampinga and Craig, 2010). Within the present description, cochaperones are not taken into account explicitely. Rather, their action is captured as a modulation of the cycle timescales. In particular, JDPs are known to bind the substrate and subsequently interact with Hsp70, enhancing ATP hydrolysis. Consequently here only the hydrolysis rate in the presence of the substrate, khS, is affected by the action","Proteins perform numerous essential tasks in cells. Most of these tasks require the protein to have a very specific structure, which is maintained by a balance of chemical and physical interactions. However, this delicate balance is vulnerable to excessive heat, changes in the pH of the cell, and certain chemicals. As a consequence, proteins could lose their specific structure and stop working. Cells employ a group of specialized proteins—called chaperones—to check that other proteins have the correct structure, and to ‘refold’ those that do not. The Hsp70 chaperone family needs energy to do its job, and it gets this energy from a molecule called ATP. However, the exact way that Hsp70s work and use this energy is not fully understood. One major puzzle is how Hsp70 binds to",380,128,0.3368
pubmed-summarization,"it can be developmental or acquired and rarely may be associated with temporomandibular joint ( tmj ) ankylosis . it has been only occasionally reported since then , probably due to its usually asymptomatic nature . in 1941 , hrdlicka reported the first cases of bmc in 21 specimens from an unspecified number of dried skulls , and in 1948 , sicher first reported this anomaly in a living person . honee and bloem described a case of bifid condyle in the cadaver of a 71-year - old patient . although this type of morphologic change is generally associated with trauma , conditions such as teratogenic drug use , genetic inheritance , infection and exposure to radiation can also cause the development of this anomaly . the first patient was a 14-year - old female with a history of extraction of lower decayed and painful left first molar done about 3 months earlier . the patient continued to have pain and recurrent swelling on and off after extraction and was managed by her treating dentist with medications . the patient presented to the department with dull pain and facial swelling in relation to lower left molar region extending to the angle of mandible . axial and coronal computed tomography ( ct ) images of bilateral tmj and mandible with multiplanar reformatting ( mpr ) were done for evaluating any pathologic fracture and tmj pathosis . these findings are best seen on the axial and sagittal images [ ] . coronal and axial ct images demonstrate left bmc oriented anteroposteriorly with articular surface irregularity the second patient was a 12-year - old female patient , referred for ct examination for evaluation of mild facial asymmetry and suspected tmj ankylosis . she had a reduced degree of jaw opening since childhood , and subsequently developed midline deviation to the left along with difficulty in mastication . these images demonstrated sagittal splitting of the left mandibular condyle into medial and lateral condylar head . the first patient was a 14-year - old female with a history of extraction of lower decayed and painful left first molar done about 3 months earlier . the patient continued to have pain and recurrent swelling on and off after extraction and was managed by her treating dentist","bifid condyle is a rare anatomic variation of mandibular condyle . it can be symptomatic or diagnosed incidentally on routine radiographic examination . no definite etiologic factor has been identified . it is suggested that bifid condyle could be a developmental anomaly or secondary to trauma . we are reporting two cases of bifid mandibular condyle . both were diagnosed using computed tomography scan , which additionally revealed the associated pathosis in the angle of the mandible in first patient and the ankylosis of temporomandibular joint in the second patient .",380,91,0.2395
dialogsum,"#Person1#: Oh, hi. What was your name again. I can't keep straight all the students' names this being the second day of school. #Person2#: It's okay. I have a hard time remembering names myself. #Person1#: How, uh, Karen, right? #Person2#: No, it's Nancy. My mom's name is Karen. #Person1#: Nancy. Okay. I think I heard you were from England. #Person2#: Well, I was born there, but my parents are American. I grew up in France. #Person1#: Oh, a world traveller! #Person2#: But then we moved here when I was nine. #Person1#: So, what does your father do now? #Person2#: Well, he's a college professor, and he is in Scotland at the moment. #Person1#: How interesting. What does he teach? #Person2#: Oh, I haven't a clue. Nah, just joking. He teaches chemistry. #Person1#: Oh, chemistry, and uh, what about your mother? #Person2#: She works full time at home. #Person1#: Oh, and what, does she have her own business or something? #Person2#: Nah, she takes care of me. #Person1#: Well, being a homemaker can be a real hard, but rewarding job. #Person2#: I think so too.","Nancy tells #Person1# her name and she was born in England and grew up in France. Nancy's father's a college professor who teaches chemistry, and her mother works full time at home.",184,32,0.1739
dialogsum,"#Person1#: Mark is the best candidate for chairman of the student union, isn't he? #Person2#: Well, that guy won't be able to win the election unless he gets some majority vote from women students. And I'm not sure about that.","#Person1# thinks Mark is the best candidate for chairman of the student union, but #Person2# isn't sure he'll win.",40,19,0.475
dialogsum,"#Person1#: Tom, what are we going to do this weekend? #Person2#: I am planning to work in the yard. Why? #Person1#: Maybe we should take a look at the new Winfield Mall. The Grand Opening's this week. #Person2#: Already? Amazing! That place went up fast. Well, I'd rather finish the yard work, but if you really want to...Anything special is going on? #Person1#: You might be interested in the car show. The ad says it's the biggest and the best in Winfield history. #Person2#: Come on. You know ads always exaggerate. #Person1#: I know, but there's a fashion show I'd like to see, too. I might get some good ideas. #Person2#: OK. That sounds good to me. Let's see if the kids want to go. But let's try not to spend too much money.",Tom's planning to do the yard work this weekend. #Person2# persuades Tom into going to the Grand Opening of the new Winfield Mall.,134,23,0.1716
scientific_lay_summarisation-elife-norm,"Neural computations underlying cognitive functions require calibration of the strength of excitatory and inhibitory synaptic connections and are associated with modulation of gamma frequency oscillations in network activity. However, principles relating gamma oscillations, synaptic strength and circuit computations are unclear. We address this in attractor network models that account for grid firing and theta-nested gamma oscillations in the medial entorhinal cortex. We show that moderate intrinsic noise massively increases the range of synaptic strengths supporting gamma oscillations and grid computation. With moderate noise, variation in excitatory or inhibitory synaptic strength tunes the amplitude and frequency of gamma activity without disrupting grid firing. This beneficial role for noise results from disruption of epileptic-like network states. Thus, moderate noise promotes independent control of multiplexed firing rate- and gamma-based computational mechanisms. Our results have implications for tuning of normal circuit function and for disorders associated with changes in gamma oscillations and synaptic strength. Cognitive processes are mediated by computations in neural circuits and are often associated with gamma frequency oscillations in circuit activity. Gamma activity and cognitive performance often co-vary within tasks and between individuals, while cognitive deficits in psychiatric disorders such as autism and schizophrenia are linked to altered gamma frequency network dynamics (Uhlhaas and Singer, 2012; Spellman and Gordon, 2014). Such disorders are also linked to changes in the efficacy of excitatory glutamatergic and inhibitory GABAergic synapses (Rubenstein and Merzenich, 2003; Lewis et al. , 2012). A critical and unresolved issue is the mechanistic relationship between gamma oscillations, the strength of excitation and inhibition, and circuit computations. On the one hand, neural codes based on firing rates may be sufficient for circuit computations (Shadlen and Newsome, 1994; Histed and Maunsell, 2014). In this scenario gamma oscillations might index circuit activation, but would not be required for computation. Evidence that rate coded computations and gamma oscillations arise from shared circuit mechanisms could be interpreted to support this view (Lundqvist et al. , 2010; Pastoll et al. , 2013), which predicts that when synaptic properties of a circuit are altered then gamma activity and the output of the rate-coded computation will co-vary. Alternatively, gamma oscillations, while sharing cellular substrates with rate-coded computations, may nevertheless support independent or multiplexed computational modes. For example, according to the communication through coherence hypothesis, tuning of gamma frequency","When electrodes are placed on the scalp, or lowered into the brain itself, rhythmic waves of electrical activity are seen that reflect the coordinated firing of large numbers of neurons. The pattern of the waves varies between different brain regions, and according to what the animal or person is doing. During sleep and quiet wakefulness, slower brain waves predominate, whereas faster waves called gamma oscillations emerge during cognition—the act of processing knowledge. Gamma waves can be readily detected in a region of the brain called the medial entorhinal cortex (MEC). This brain region is also known for its role in forming the spatial memories that allow an individual to remember how to navigate around an area they have previously visited. Individual MEC cells increase their firing rates whenever",380,128,0.3368
scientific_lay_summarisation-elife-norm,"from cheese has revealed several instances of HGT in this environment. Lactic acid bacteria (LAB) such as Lactobacillus and Lactococcus, which are used in the initial fermentation of milk, are known to harbor antibiotic resistance genes and may be reservoirs for transfer to pathogenic enterococci (Wang et al. , 2006; Mathur and Singh, 2005) and other pathogenic microbes. Other food-associated bacteria may also contribute to antibiotic resistance gene transfer (Cocconcelli et al. , 2003; Delorme, 2008; Flórez et al. , 2005). In yogurt, another dairy ferment using LAB, HGT of metabolic genes has been observed between protocooperative species L. bulgaricus and S. thermophilus (Li et al. , 2013; Liu et al. , 2009). Sequencing of Penicillium species isolated from the cheesemaking environment identified HGT of large genomic islands between these key fungal inhabitants of cheese (Cheeseman et al. , 2014; Ropars et al. , 2015; Gibbons and Rinker, 2015). During the aging of traditional styles of cheese in caves or aging rooms, bacteria and fungi form a multi-species biofilm called the rind (Button and Dutton, 2012). We have previously shown that these communities can be used to examine community-based processes, such as succession and interspecies interactions, within an experimentally tractable system (Wolfe et al. , 2014; Kastman et al. , 2016). Given that biofilms such as these are densely populated, and microbes in cheese rinds are under strong selection to obtain limited nutrients (e. g. free amino acids, iron) as well as tolerate cell stress (Monnet et al. , 2015), we predicted that HGT might be widespread in cheese rind microbiomes and therefore might provide a useful experimental model for HGT within microbial communities. We sought to determine the diversity, distribution, and functional content of HGT in bacterial species isolated from cheese rinds. Specifically, we predicted that (1) HGT would be widespread, (2) HGT genes would be enriched for functions related to survival in cheese environment, and (3) there would be uneven distribution of HGT events across taxa. We analyzed the genomes of newly isolated and sequenced cheese-associated bacterial species (31 genomes) and those available in public databases (134 additional genomes). We present data which suggest that there is extensive HGT in cheese-associated bacteria. The regions of DNA identified appear to encode a number of functions which would be expected","From the depths of the ocean to the lining of the human gut, almost every environment on Earth is home to a unique community of microorganisms referred to as a microbiome. Within these communities, unrelated microorganisms can exchange genetic information through a process known as horizontal gene transfer. For example, genes linked to antibiotic resistance are often transferred between different microorganisms, which can create increasingly drug resistant microbes and has important implications for human health. Horizontal gene transfer has been studied for almost 100 years, but examining it directly is challenging because, almost by definition, it requires studying a community of microbes rather than one microbe in isolation. As such, researchers are looking for simple models of microbial communities that can be easily manipulated in experiments. Bonham et",380,128,0.3368
dialogsum,"#Person1#: Are you looking for an apartment? #Person2#: Yes, I am interested in finding a one-bedroom apartment near Washington Square. #Person1#: I think I have just a right apartment for you. #Person2#: Oh, good. Can you describe it? #Person1#: Yes. It has one bedroom, a large living space and 4 kitchens. #Person2#: So is there a refrigerator? #Person1#: Yes, it's brand-new. #Person2#: It sounds great. How much is the rent? #Person1#: It's $ 8. 50 a month. #Person2#: When can I see it? #Person1#: We can take a see by there now if you like. The landlord left me a set of keys with me. #Person2#: Ok, that would be great.",#Person2#'s looking for an apartment. #Person1# knows one that meets all #Person2#'s requirements. They will go to see it now.,111,20,0.1802
dialogsum,"#Person1#: Room Service. May I help you? #Person2#: This is Room 603. I'm afraid that the heating system doesn't work. It's very cold here. #Person1#: Have you switched on the radiator? #Person2#: Yes. I have switched it on for a long time. The room is still very cold. #Person1#: We're terribly sorry for that. We'll send our staff io fix it now. Or do you want to change your room? #Person2#: I prefer not to move first. #Person1#: OK. Is it convenient for us to come now? #Person2#: Yes, please.",#Person2# phones Room Service because the heating system in #Person2#'s room doesn't work. #Person1#'ll send their staff to fix it now.,90,21,0.2333
scientific_lay_summarisation-elife-norm,"signals that would create a functional difference between the normal and the readthrough-extended form. To achieve this aim, we concentrated on proteins deriving from BTR. Based on experimental data, we assigned regression coefficients to all possible nucleotides in the stop codon context (SCC) and, using those regression coefficients, estimated the readthrough propensity (RTP) of all stop codons in the human genome or transcriptome. We were able to formally derive a new nucleotide consensus for high RTP from the regression coefficients of our model. Then we screened all predicted C-terminal extensions for peroxisomal targeting signals because peroxisomes import most of their matrix proteins through a short targeting signal (PTS1) at the very C-terminus (Smith and Aitchison, 2013). We here show that lactate dehydrogenase B (LDHB) combines a very high translational readthrough with a hidden, yet functional and evolutionarily conserved, PTS1. This peroxisomal isoform of LDH, containing the readthrough-extended LDHBx subunit, is likely to be involved in the regeneration of redox equivalents for peroxisomal β-oxidation. In order to develop a computational method to assess the RTP of all human SCCs that would allow the identification of genes with high BTR, we focused on SCCs comprising 15 nucleotides including and surrounding the stop codon (nucleotides −6 to +9, stop codon at positions 1 to 3). In order to calculate linear regression between the SCCs and their experimental BTR values, we formalized SCCs using a binary vector that represented the stop context in a multi-dimensional vector space (1A and — 1). The three stop codons were condensed into one position, so that the binary vector required 51 dimensions, for the four possible nucleotides in the six positions before and after the stop codon, and for the three stop codons (12 × 4 + 3). The vector was combined with experimentally accessible BTR frequencies. For the first approximation model (LIN), we used 66 sequences derived from human nonsense mutations (Floquet et al. , 2012). The nucleotide sequences of these stop contexts show no bias with respect to RTP, because the contexts and the stop codons evolved independently, and therefore the context nucleotides are random in relation to the stop codon. We calculated a linear regression model for these SCCs and used only the experimental BTR values that had been measured in the absence of aminoglycosides.","Amino acids are the building blocks of proteins, and the order of the amino acids in a protein is determined by the order in which ‘codons’ appear in a messenger RNA molecule. Most codons represent a specific amino acid, but there are also three stop codons that are used to mark the end of a protein. When the cellular machinery that ‘translates’ the messenger RNA molecule into a protein encounters a stop codon, it stops and releases the completed protein. Sometimes, however, the stop codon is not interpreted as a stop signal, and the translation of the messenger RNA molecule continues until another stop codon is encountered. This process is known as readthrough. Some organisms, in particular viruses and fungi, use readthrough to produce a wider range of",380,128,0.3368
pubmed-summarization,"clinical spectrum varying from spontaneous regression to rapid progression , recurrence and long - lasting sequelae.11 lch encompasses three main clinical subtypes ; unifocal lch ( eosinophilic granuloma ) , multifocal lch ( hand - schuller - christian disease ) and systemic lch ( abt - letterer - siwe disease).1 younger patients with lch , have a predisposition for multifocal involvement.12 the etiology of lch remains unclear but immune dysregulation with different cytokines has been postulated.1 the orbit is the most common site of involvement in the eye which often includes the orbital diploe . mononuclear histiocytes and multinucleated giant cells are intermixed with eosinophils , lymphocytes , plasma cells and neutrophil polymorphs.10 langerhans cells are immune reactive for s-100 protein and cd1a.1 electron microscopy demonstrates tennis racket shaped cytoplasmic inclusions named birbeck granules in histiocytes which are the gold standard for a diagnosis of lch.1,12 treatment options for unifocal lesions include observation , partial or complete resection , combined resection and low dose radiation , and intralesional corticosteroids . systemic chemotherapy may be indicated for extensive multifocal and systemic lesions.1,9 to the best of our knowledge , after the report by saxena et al2 , our patient is the second case of unifocal limbal lch presenting as a recurrent solitary vascularized nodule . despite the presence of mono- and multi - nucleated histiocytes amongst the intrastromal inflammatory cell infiltrates on histopathological examination of the primary lesion , lch was not diagnosed initially which might be due to the very rare presentation of this condition in the limbocorneal area . differential diagnoses for limbocorneal lch include dermoid , amyloidosis , fibrous histiocytoma and juvenile xanthogranuloma.2 in our case , a limbal papilloma was the initial clinical diagnosis which should be added to this list . there is only a single case report of limbal lch in which the patient remained asymptomatic for a while after complete excision of the primary lesion , but the tumor recurred 15 months afterwards.2,7 based on clinical and histopathological evaluations , the recurrent tumor partially responded to combination chemotherapy and the patient was clinically stable for 5.5 years.7 in our case , recurrence developed 10 months after resection of the primary lesion for which repeat resection together with corneoscleral patch grafting were performed and the","purposeto report a rare presentation of unifocal langerhans cell histiocytosis ( lch ) simulating a limbal papilloma.case reporta 24-year - old man presented with a limbal mass in his left eye which had initially been suspected to be a papilloma based on clinical findings . the mass was excised and a histopathological diagnosis of acute bullous inflammation with granulation tissue was made . the lesion relapsed 10 months later which necessitated repeat resection along with corneoscleral patch grafting . histopathological studies of the excised lesion led to a final diagnosis of lch.conclusionto the best of our knowledge , this is the second report of a rare presentation of lch in the limbus which recurred after excision of the primary mass . the recurrent lesion was diagnosed based on",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the membrane, it is possible that the regulation of phospholipid arachidonate has effects on membrane shape change. When triglycerides (TGs) are synthesized by diacylglycerol acyltransferases, they accumulate between the two leaflets of the lipid bilayer and deform the membrane (Yen et al. , 2008; Thiam et al. , 2013). Molecular dynamics simulation showed that TGs between leaflets generate a ‘blister-like’ shape, where the membrane on its surface is highly curved (Khandelia et al. , 2010). Therefore, the ability of the membrane to form curved structures might affect the properties of the TG pool between the leaflets. This pool serves as a precursor for cytosolic lipid droplets in most cells (Thiam et al. , 2013). In hepatocytes and enterocytes, this pool is also used for transport by microsomal triglyceride transfer protein (MTP) into the endoplasmic reticulum (ER) lumen to generate lipoproteins and luminal lipid droplets (Sturley and Hussain, 2012). MTP transfers TGs to nascent apolipoprotein B (apoB) to form primordial lipoproteins (Abumrad and Davidson, 2012). MTP also transfers TGs to generate apoB-free lipid droplets in the ER lumen (Kulinski et al. , 2002), which are required for TG enrichment in nascent lipoproteins. MTP deficiency in humans leads to an impaired absorption of dietary lipids, which is called abetalipoproteinemia (Wetterau et al. , 1992). Therefore, the normal luminal transfer of TG is critical in vivo, but factor (s) and environment enabling an efficient transport by MTP remain poorly understood (Yao et al. , 2013). Here, using LPCAT3-deficient cells and mice, we report that LPCAT3 is critical and relatively specific for the regulation of arachidonate levels in membrane phospholipids in vivo. In addition, we show that LPCAT3 regulates the directionality of TG transfer into lipoproteins, preventing the over-accumulation of cytosolic lipid droplets in hepatocytes and enterocytes. Additional analyses suggest that membrane PUFAs facilitate TG local clustering, which enables efficient transport by MTP. This study identifies LPCAT3 as a major regulator of membrane phospholipid arachidonate, which is a critical factor affecting luminal TG transport. To investigate whether the remodeling pathway contributes to arachidonate incorporation into phospholipids, we analyzed the enzymatic properties of LPCAT3. We first examined whether LPCAT3 regulates the acyl-chain composition of the major phospholipid PC. We established rat hepatoma RH 7777 cells that stably overexpress FLAG-tagged murine LPCAT3 (— 1A). Control cells","Membranes made of molecules called lipids surround every living cell and also form compartments inside the cell. There are hundreds of different lipid molecules that can be found in membranes. The amount of each type within the membrane can vary, which affects the flexibility and other physical properties of the membrane. One type of lipid found in membranes is called arachidonic acid. It is involved in cell communication and other processes, and is required for young animals to grow and develop properly. An enzyme called LPCAT3 is thought to incorporate arachidonic acid into membranes, but this has not yet been proven to occur in living animals. Here, Hashidate-Yoshida, Harayama et al. studied the role of LPCAT3 in newborn mice. The experiments show that this enzyme is found at",380,128,0.3368
pubmed-summarization,"the sample size of 850 wives was estimated considering hiv prevalence of 3.41% among the wives and taking design effect of 1.5 . villages were selected by probability proportional to the population size and were mapped by the field investigators . we randomly selected 30 houses and recruited the first 25 wives who consented for both the interviews and blood draw . we used a pre - tested structured questionnaire in hindi to collect information about the socio - demographic characteristics of wives and their husbands , awareness about hiv / aids , and sexual behaviors with the husband . the data was collected using face - to - face paper - pencil based personal interviews by trained female investigators from local ngos for the non - sensitive items and color - coded audio - assisted self - interviews for the sensitive questions . the interviews were held either in the participants houses or a private place in the neighborhood as per the convenience of the participants . after completing the questionnaire and obtaining separate written consent , the participants were pre - counseled before drawing a 3-ml venous blood sample . the serum samples were tested for hiv using three commercially available rapid antibody tests ( sd bioline hiv 3.0 , standard diagnostic inc . , gyeonggi - do , south corea ; combaids rs - advantage , span diagnostics , gujrat , india ; hiv tridot , j. mitra and co. pvt . ltd . , new delhi , india ) as per the guidelines of india s national aids control organization ( naco ) . the participants were assigned unique study identification number , which they could also use to get their test results after post - test counseling at the nearest integrated counseling and testing centre ( ictc ) . we calculated a living standard index ( lsi ) , as a surrogate indicator for wealth , on the basis of house type , availability of electricity , fuel used for cooking , presence of a lavatory facility , and possession of household consumer items including car , scooter / motorcycle , television , radio , sewing machine , electric fan , and bicycle . a ranked score was assigned for each factor and the sum","background : migration has been linked to the spread of hiv epidemic from the urban areas of western india to the rural areas of north india.objectives:this is the first population - based study among the wives of migrant workers of muzaffarpur district in bihar with objectives to describe their sexual behavior within marriage , estimate the prevalence of hiv , and to know their awareness regarding hiv / aids.methods : a two - stage cluster survey was conducted by randomly selecting 25 eligible wives from each of the 34 selected villages . a total of 850 wives were interviewed and the blood samples were collected for hiv testing . to determine the factors associated with hiv / aids - awareness , we calculated adjusted odds ratios and 95%",380,128,0.3368
dialogsum,"#Person1#: Jonas, have you finished the report yet? #Person2#: I'm afraid I'm still reading through all these papers. Do you need it right now? #Person1#: I don't, but Mr. Steadman will be asking about it soon. You know, he always starts to get anxious about the weekly report about this time of the day. #Person2#: But it's only Thursday morning. We have a day and a half left before he needs it. And what if something big happens today? #Person1#: I know. The report should include everything from the week, but he just likes to know that we're not finishing it off at the last minute. #Person2#: When have I ever done that? #Person1#: Of course, you never would. But last month, we had a lot of trouble getting the reports in on time. #Person2#: Well, good thing he hired me.",Jonas hasn't finished the weekly report and #Person1# reminds her that Mr. Steadman will be asking about it soon. Jonas is confident to finish it on time.,141,27,0.1915
dialogsum,"#Person1#: ABC company. Can I help you? #Person2#: Can you put me through to Mr. Brown in the Sales Department? #Person1#: I'm afraid Mr. Brown is at a meeting at the moment. #Person2#: Can I leave a message? #Person1#: Certainly. #Person2#: Can you ask Mr. Brown to call me at 1300-621-7865? #Person1#: Who is calling, please? #Person2#: Alan Peterson. #Person1#: OK. Mr. Peterson. Can you repeat the phone number? #Person2#: That's 1300-621-7865. #Person1#: OK. I'll ask Mr. Brown to call you as soon as the meeting is over. #Person2#: Thanks. Bye.",Alan Peterson calls ABC company and leaves a message for Mr. Brown.,91,12,0.1319
dialogsum,"#Person1#: Can I help you, Miss? #Person2#: I would like to order 2 office-style cabinets and desk calendars. We want office-style cabinets in white. The catalogue number is 90 - f - 2356. #Person1#: How soon do you want it? #Person2#: Could you deliver it tomorrow? #Person1#: No problem. #Person2#: Please handle the items carefully. #Person1#: Certainly. #Person2#: We will pay by collect on delivery.",#Person2# orders 2 office-style cabinets and desk calendars. #Person1# will deliver them tomorrow.,65,13,0.2
pubmed-summarization,"lepidoptera include agricultural pests that , through feeding and other activities , negatively affect stored grains , food and fiber crops . since a single lepidoptera adult can produce hundreds of eggs , and their primary food source is typically plant material , they can cause significant damage to agricultural crops . although biological agents can help manage these insect pests , insecticides currently are essential for large - scale effective and economical pest control . these insecticides can also affect non - target organisms , including pollinators , and their application not only disrupts natural ecosystems but also reduces yields of crops that rely on pollination . the non - target effect of some pesticides is in part due to their effects on insect immunity , which is necessary for insect survival in natural environments . for example , currently used pesticides have been shown to affect cellular and humoral immune responses and interfere with grooming behavior . these effects on immunity are likely non - specific and negatively impact the health of both the target pest and beneficial arthropods . therefore , there is a need for novel target - specific approaches to control insect pests without affecting beneficial arthropods . although immune pathways can be generally and non - specifically inhibited by pesticides , they also are a likely source of candidate molecules that could be inhibited for target - specific insect control since multiple classes of insect immunity genes , including signaling pathways , can be under strong selection for diversification . fundamental mechanisms of innate immunity comprising cellular and humoral pathways are conserved throughout the animal kingdom and are controlled by signaling pathways activated by various stimuli , including pathogen recognition by immune surveillance systems . despite this overall conservation , aspects of immune systems are subject to strong selection to evolve in response to varying pathogen exposure and to pathogen evolution of virulence determinants that modulate immunity . such co - evolutionary dynamics can promote diversification of conserved elements of immunity as well as the recruitment of novel effectors . as such , the investigation of insect immune pathways and mechanisms of pathogen modulation can yield insights into components that may be susceptible to inhibition . for example , the insect pathogen xenorhabdus nematophila","many lepidopteran insects are agricultural pests that affect stored grains , food and fiber crops . these insects have negative ecological and economic impacts since they lower crop yield , and pesticides are expensive and can have off - target effects on beneficial arthropods . a better understanding of lepidopteran immunity will aid in identifying new targets for the development of specific insect pest management compounds . a fundamental aspect of immunity , and therefore a logical target for control , is the induction of antimicrobial peptide ( amp ) expression . these peptides insert into and disrupt microbial membranes , thereby promoting pathogen clearance and insect survival . pathways leading to amp expression have been extensively studied in the dipteran drosophila melanogaster . however , diptera are",380,128,0.3368
dialogsum,"#Person1#: Hi, I'm Benjamin. Nice to meet you here. You look great. #Person2#: Thank you. Nice to meet you too. I'm John. Is this your first time to take a long-distance trip on plane? #Person1#: No, this is the second time. But I also feel bad because of the lower pressure and the jet lag. #Person2#: Oh, I am sorry to hear that. Take it easy. It will be OK soon. You see, I take this long-hour plane frequently, but the jet lag still makes me uneasy. #Person1#: Oh, that's too bad. Do you get a good knowledge of China? #Person2#: Yes, whenever I think about China, I'd see the Tian'an Men Square. China is a very beautiful country. And I've seen many landmarks in China but I like the Great Wall most. #Person1#: All of the Chinese are proud of the Great Wall. And it was built before the In dynasty near Shan Haiguan-the First Pass in the World. #Person2#: Was it built before the In dynasty? I thought it was in the Ming dynasty. #Person1#: No, before the In dynasty. #Person2#: Oh, yeah. Thought I am an American, I know quite a lot about China and I like Chinese tea very well. #Person1#: Both the green tea and the black tea are good for our health. And I usually refresh myself with a cup of tea. #Person2#: Yeah, many of my friends like Chinese tea and whenever I go back to China, I'll take some Dragon-well green tea for them. #Person1#: Do you like the Chinese traditional silk? #Person2#: I heard about it, but I don't have any clothes made from silk. #Person1#: Go and pick some stuff up. The price can always surprise foreign friends. #Person2#: Oh, I'm eager to have a try.","Benjamin meets John on the plane. Benjamin tells John he feels sick because of the lower pressure and the jet lag and John asks him to take it easy. Then they start to talk about the landmarks in China, Chinese tea, and Chinese traditional silk.",296,45,0.152
scientific_lay_summarisation-elife-norm,"cells in a network may contain unique information both about current tuning of this network, and the mechanisms behind this tuning that may act through local recalibration of properties in individual cells (O' Leary et al. , 2013). Yet relatively few studies have attempted this kind of analysis on a large scale so far. Here we perform a large-scale electrophysiological census of retinorecipient neurons in the developing Xenopus laevis tectum to better understand the electrophysiological variability of tectal neurons in development, and in response to a need for homeostatic change. Using a comprehensive suite of tests we describe relationships between 33 electrophysiological variables, and show that both the variability and the predictability of multivariate cell tuning increases over development, and undergo changes in response to sensory stimulation. By analyzing groups of neurons that produce similar spike trains, we also show that similar spiking behaviors may be supported by different combinations of underlying electrophysiological properties. We recorded from 155 deep-layer, retinorecipient tectal cells across developmental stages 43 to 49 (Nieuwkoop and Faber, 1994) from 42 animals, measuring from 9 to 33 different electrophysiological variables in each cell (median of 26 variables per cell; see and Supplementary file 1 for a graphical description and a concise table of variables, and the Materials and methods for a detailed description of each variable). Of 155 cells, 35 cells contributed to all 33 variables, 62 contributed to 30 variables, 124 to 20 variables, and 154 to 10 variables. Across different variables, the least covered variable had measurements from 64 cells, while the most covered one had measurements from 154 cells (median of 134 cells per variable); in total, 18% of all possible observations were missing. The dataset containing analysis parameters is available online as Supplementary file 2. The entire dataset including raw electrophysiology files has also been made available and can be accessed with the following : 10. 5061/dryad. 18kk6. 10. 7554/eLife. 11351. 003Figure 1. A review of cell properties characterized in this study (See methods for a detailed description of every measurement). (A) Response to voltage clamp steps after passive current subtraction; full currents on the left, a zoom-in look at early active currents on the right. Red vertical lines show how voltage-gated sodium (INa), stable potassium (IKS), and transient potassium currents (IKT) were","Brains consist of many cells called neurons: billions of them in a human brain, and hundreds of thousands in the brain of a small fish or a frog tadpole. Many of these neurons are very much alike, and work together to process information in the brain. Yet while they are similar, they are not exactly identical. One of the reasons for these differences seems to be to allow each neuron to contribute something unique to the overall working of the brain. By looking at how individual neurons within a specific type differ from each other, it is possible to understand more about how they work together. Ciarleglio, Khakhalin et al. have now compared the properties of the neurons in a part of the brain of a developing frog",380,128,0.3368
dialogsum,"#Person1#: How are you paying for your college education? #Person2#: My expense for every semester is almost $15,000. At the start of each semester my parents pay the $10,000 in tuition. I also get $2,000 in financial aid. I have to earn the rest myself. #Person1#: How do you do that? #Person2#: I have a part-time job at a hotel. I work about twenty hours a week, and earn $400. Mter taxes, I make about $320. #Person1#: How do you spend the money? #Person2#: It helps to pay for my room and board on campus. It also pays for things like my cell phone, book, transportation, and clothes. #Person1#: You don't have much money for fun, do you? #Person2#: That's time! I stick to my budget carefully so I don't have to borrow. I don't like to owe people money. I hardly ever go to movies. My roommates and I usually rent videos, and split the cost, so it's cheaper. #Person1#: How else do you save money? #Person2#: I don't go to restaurants. I make meals with my roommates so it's cheaper to eat. I try to walk or ride my bicycle to college. Oh, and I buy a lot of my clothes at second-hand stores. You can find some very cheap, decent clothes in those stores.","#Person2# tells #Person1# #Person2# has to do part-time job to earn the rest expense for #Person2#'s college education. #Person2# sticks to #Person2#'s budget and tries to save money in watching movies, eating, transportation and clothes.",217,35,0.1613
dialogsum,"#Person1#: Excuse me, sir. Could you spare a minute? #Person2#: Uh, yes. #Person1#: Do you go to work by train every day? #Person2#: Yes. I commute five days a week by train. #Person1#: And would you mind telling us what you think of the rail service? #Person2#: It's really very good. #Person1#: Why do you say that? #Person2#: Well, trains are frequent and come on time. #Person1#: Which train do you catch in the evening? #Person2#: I usually take the 5 thirty home. #Person1#: And can you get a seat? #Person2#: No, I usually have to stand. #Person1#: Would you agree that the service is fast? #Person2#: Yes, it's reasonably fast but it certainly isn't cheap. Fares have gone up25%.","#Person1# asks #Person2#'s attitude towards the rail service. #Person2# thinks the service is good but isn't cheap, and usually has to stand.",120,22,0.1833
scientific_lay_summarisation-elife-norm,"executor activity) into a single protein—to functionally specialized interconnected receptor pairs and networks (Adachi et al. , 2019a). However, our knowledge of the functional connections and biochemical mechanisms underpinning plant NLR networks remains limited. In addition, although dozens of NLR proteins have been subject to functional studies since their discovery in the 1990 s, this body of knowledge has not been interpreted through an evolutionary biology framework that combines molecular mechanisms with phylogenetics. NLRs are multidomain proteins of the ancient group of Signal Transduction ATPases (STAND) proteins that share a nucleotide-binding (NB) domain. In addition to the NB and LRR domains, most plant NLRs have characteristic N-terminal domains that define three subgroups: coiled-coil (CC), CCR or RPW8-like (RPW8) and toll and interleukin-1 receptor (TIR) (Shao et al. , 2016). In metazoans, NLRs confer immunity to diverse pathogens through a wheel-like oligomerization process resulting in multiprotein platforms that recruit downstream elements, such as caspases (Qi et al. , 2010; Zhou et al. , 2015; Hu et al. , 2015; Zhang et al. , 2015; Tenthorey et al. , 2017). Plant NLRs have long been thought to oligomerize through their N-terminal domains when they’re activated (Bentham et al. , 2018). However, the precise molecular mechanisms that underpin NLR activation and subsequent execution of HR cell death have remained largely unknown until very recently. In two remarkable papers, Wang et al. (2019a) and Wang et al. (2019b) have significantly advanced our understanding of both the structural and biochemical basis of CC-NLR activation in plants. They reconstituted the inactive and active complexes of the Arabidopsis CC-NLR ZAR1 (HOPZ-ACTIVATED RESISTANCE1) with its partner receptor-like cytoplasmic kinases (RLCKs) (Wang et al. , 2019a; Wang et al. , 2019b). Cryo-electron microscopy (cryo-EM) structures revealed that activated ZAR1 forms a resistosome—a wheel-like pentamer that undergoes a conformational switch to expose a funnel-shaped structure formed by the N-terminal α helices (α1) of the CC domains (Wang et al. , 2019a; Wang et al. , 2019b). They propose an engaging model in which the exposed α1 helices of the ZAR1 resistosome mediate cell death by translocating into the plasma membrane and perturbing membrane integrity similar to pore-forming toxins (Wang et al. , 2019b). However, whether the ZAR1 model extends to other CC-NLRs is unknown. One important unanswered question is the","Just like humans, plants get sick. They can be infected by parasites as diverse as fungi, bacteria, viruses, nematode worms and insects. But, also like humans, plants have an immune system that helps them defend against disease. Their first line of defence are disease resistance genes. Many of these genes encode so-called immune receptors, which are proteins that detect parasites and kick-off the immune response. Plant genomes may encode anywhere between 50 and 1000 immune receptors; some of which work solo as singletons, while others operate in pairs or as complex networks. Understanding how immune receptor genes have evolved would give fundamental knowledge about how they work, which in turn would set the stage for researchers to be able to use them to protect agricultural crops from disease.",380,128,0.3368
pubmed-summarization,"and to prevent later fat necrosis . dissection proceeded through the platysma until the midline raphe between the strap muscles was identified ( 3b ) . the sternocleidomastoid muscle was thus separated , retracted laterally , and preserved . by tracing , the right recurrent laryngeal nerve was assessed to be intact and half of the trachea ( 5.5 2.3 cm ) was dissected including 5 cartilaginous rings together with the left recurrent laryngeal nerve . the tumor was removed together with the invaded paratracheal tissue bilaterally ( 3c ) . the medial edges of the sternocleidomastoid muscle were sutured to a rectangular tracheal opening . to avoid tracheal stenosis , the anterior side of the defect was open , and a stent tube was kept in place . for muscle - flap prefabrication , the prepared ktnme , as described by muhamedov et al . the cut edges of the tracheal opening were circumferentially overedged to the skin with a few absorbable sutures to facilitate cannulation . after the airway was confirmed intact based on co2 return and bilateral breath sounds , the tracheostomy tube was secured to the skin with 40 sutures ( 3e ) . to avoid the risk of subcutaneous emphysema and subsequent pneumomediastinum , the skin was not tightly closed . a sponge soaked with iodine between the skin and the flange was placed for 24 h to deflect infection and anxiety about minor oozing of the skin edge . the patient was extubated after 7 days , and there was no granulation tissue or stenosis of the tracheal lumen 3 weeks thereafter ( ) . the reconstructive stage was performed on may 19 , 2014 . the o - shaped incision around the formed tracheotomy having the gap 1.5 cm from the right edge was made . a cellulocutaneous flap was separated and overturned so that the epidermis overlapped the tracheostomy lumen ( 5a ) . the harvested ktnme after prefabrication was separated with the pedicle flap of the medial edge of the sternocleidomastoid muscle ( 5b ) , placed over the trachea , and sutured to the trachea ( 5c ) . the remaining defect in the anterior part of trachea was closed without any special procedure . the sliding skin flap was","published reports on salvage treatment for trachea reconstruction after total thyroidectomy or partial tracheotomy are available , some of them using structures of the trachea itself , auricular cartilage , a musculocutaneous flap , or other methods . in our report , we emphasize the importance of a search for a new material and approach for sparing surgery . the purpose of this article is to describe a case of a successful sparing surgery in a patient with advanced thyroid papillary carcinoma invading the trachea . after total thyroidectomy in 2012 , partial resection of the trachea was performed in 2014 . the lesion defect was 5.5 2.3 cm in size , located between 4 ( 2nd6th ) tracheal cartilaginous rings and involving about a semicircumference . it",380,128,0.3368
dialogsum,"#Person1#: I was anxious to find out what the sellers had to say about my counter-offer. #Person2#: I was able to contact them so, if you'll step into my office, we'll talk. #Person1#: Did they go with the proposed counter-offer? #Person2#: They want you to pick up the cost of the home inspection, but they accepted your offer. #Person1#: Is a home inspection very expensive? #Person2#: It can cost between five hundred and one thousand dollars. #Person1#: Do I get to choose who inspects the home? #Person2#: Yes, you get to choose. I would spend a little more to get a really thorough inspection. #Person1#: Can you call the owners with my acceptance right away? #Person2#: I am going to contact the sellers immediately. They were looking forward to your acceptance.",#Person1# agrees to pick up the cost of the home inspection and #Person2# will contact the sellers immediately.,131,18,0.1374
pubmed-summarization,"the vertebral fractures is the most common complications of osteoporosis.13 ) these fractures result in significant mortality and morbidity including prolonged and intractable pain.4,13 ) percutaneous vertebroplasty , a therapeutic procedure for filling the collapsed vertebral body with polymethylmethacrylate , provides pain relief.2,4 ) in general , percutaneous vertebroplasty is simple and safe if performed under continuing fluoroscopic control and technical precautions . vertebroplasty has the potential risk of serious complications such as leakages of bone cement , cardiopulmonary complications , infection and the new fractures of the adjacent vertebrae.6,7 ) we present a case of extraspinal leakage after vertebroplasty at our hospital . a 73-year - old male was admitted to our hospital for low back pain after slip down at one day earlier . the patient had experienced l1 vertebroplasty and t12-l2 screw fixation for l1 compression fracture at another hospital before 2 years ago . after incision of the skin , an 11-guage vertebroplasty needle was placed percutaneously on the posterior part of the vertebral body via bilateral transpedicular approach . the needle was pushed through the cortex , situated the center of the pedicle as possible , and then directed into the vertebral body . the contrast medium ( iohexol ) was injected to estimate bone cement distribution and minimize bone cement leakage and intraoperative complication such as pulmonary thromboembolism . when a thin toothpaste consistency was achieved , the bone cement was injected into the vertebral body under continuous fluoroscopic control . the filling process was stopped immediately when leakage of bone cement was observed into lateral space of body . lumbar simple x - rays after procedure showed leakage of bone cement to right lateral side of the l4 vertebral body ( ) . lumbar computed tomography ( ct ) scanning revealed extraforaminal leakage of bone cement to outside of right l4 pedicle and it caused significant compression of l4 nerve root ( ) . the leaked bone cement along the l4 nerve root was removed carefully via paraspinal muscle - splitting approach . during surgery , two pieces of bone cements were removed carefully . two whitish bone cements were located in the right lateral space of l4 - 5 body and the intervertebral foramen ( ) . postoperative lumbar spine plain images","we experienced a 73-year - old male with lumbar nerve root compression due to leakage of bone cement after vertebroplasty . he was underwent vertebroplasty for acute osteoporotic l4 compression fracture at our hospital . after vertebroplasty , his back pain was improved but right leg pain was newly developed . lumbar computed tomography scanning showed that bone cements were leaked along the l4 nerve root . the leaked cements around l4 nerve root were removed carefully via paraspinal muscle - splitting approach . after operation , severe right leg radiating pain was improved . we recommend proper entry point , high viscosity of polymethylmethacrylate and constant monitoring can reduce complication .",380,112,0.2947
pubmed-summarization,"the utriculo - endolymphatic valve at the anteromedial wall of the utricle , was discovered by bast in 1928 in human fetuses . the utricular duct connects the utricle with the saccular space , close to the entrance of the endolymphatic duct . bast suggested that the function of the valve was closing of the utricular end of the utricular duct . bast himself proposed rotation of the valve lip at its base , where it is made - up of loose periotic tissue , as the functional mechanism . with rising intra - utricular fluid pressure a second theory proposes the opposing utricular wall as the functional part of the valve : bending of the single cell layer of the highly compliant utricular wall opposite the lip is responsible for the opening or closure of the valve . in the early decades of the twentieth century bast reported two cases of ruptured saccules in human ears , resulting in a closed valve and an expanded utricle . bast and eyster withdrew endolymph from the cochlear duct of the guinea pig , causing a collapsed saccule and cochlear duct , while the utricle was distended and the valve closed . konishi found open valves in the guinea pig at various stages of endolymphatic hydrops , after operatively obstructing the endolymphatic duct . although there is no conclusive evidence up to now , bast s valve seems to be capable of protecting the utricle and the semicircular canal system when the evolutionary younger , cochlear part of the system ruptures . in the evolutionary chain of land living vertebrates , amphibians and reptiles have hearing organs that are small specialized regions of their vestibular systems . in birds , with a cochlear duct , a clear distinction can be made between an inferior and a superior part of the labyrinth . if the function of bast s valve in mammals is a protective one , it is expected to find a similar structure in birds between the two parts of the labyrinth . retzius made highly detailed drawings of the labyrinth of the pigeon and depicted the connection between the utricle and the saccule as a simple hole in a membrane . no utricular duct , nor a valve - like","the first description of the presence of a utriculo - endolymphatic valve in human fetuses was given by bast in 1928 . since then this valve - like structure is called bast s valve . its exact function has not yet been established . the general opinion is that it has a protective function by having the possibility to separate the superior endolymphatic compartments of the labyrinth from the inferior compartment . phylogenetically seen birds are the first vertebrates with a cochlear duct and a distinct inferior and superior part of the labyrinth . a structure in the pigeon inner ear , resembling bast s valve in mammals , is described .",380,112,0.2947
scientific_lay_summarisation-elife-norm,"are determined by the backward stepping rate constants kbn and forward stepping rate constants kfn. The inset shows cartoon configurations of the TEC in a pre-translocated and a post-translocated state. : http: //dx. . org/10. 7554/eLife. 00971. 00310. 7554/eLife. 00971. 004Figure 1— 1. A branched Brownian ratchet model for the nucleotide addition cycle. This kinetic model, proposed by Larson et al. (Larson et al. , 2012), allows NTP to bind to the TEC both before and after translocation, postulating a secondary nucleotide binding site for NTP binding to the pre-translocated TEC (TECn, 0). Additionally, the model assumes rapid forward and reverse translocation of the polymerase and hence describes the translocation step simply with an equilibrium constant Kδ. : http: //dx. . org/10. 7554/eLife. 00971. 004 Pausing is an off-pathway process that plays crucial roles in the regulation of transcription elongation (Landick, 2006; Nudler, 2012). In one view of the mechanisms of transcriptional pausing, RNAP first enters an elemental pause state (Herbert et al. , 2006; Toulokhonov et al. , 2007; Sydow et al. , 2009), whose structural evidence was recently presented in bacterial RNAP (Weixlbaumer et al. , 2013). However, similar evidence is lacking for eukaryotic polymerases. These elemental pauses can be subsequently stabilized into longer-lived pauses by the formation of a hairpin structure in the nascent RNA transcript or by RNAP backtracking (Artsimovitch and Landick, 2000; Herbert et al. , 2008). The backtracking process is caused by upstream movements of the polymerase, displacing the 3′-end of the nascent RNA away from the active site into the secondary channel of the enzyme (Nudler et al. , 1997; Komissarova and Kashlev, 1997b). An alternative view poses that most pauses are attributed to backtracking, which can be described as a one-dimensional random walk of the enzyme along the DNA template (Galburt et al. , 2007; Mejia et al. , 2008; Depken et al. , 2009; Hodges et al. , 2009). RNA synthesis resumes when the polymerase diffusively realigns its active site with the 3′-end of the transcript. Both the nucleotide addition phase and the pausing phase are closely regulated by conserved structural motifs near the active center of the polymerase, namely the bridge helix and the trigger loop (TL) (Bar-Nahum et al. , 2005; Wang et al. , 2006; Vassylyev et al.","The production of a protein inside a cell starts with a region of the DNA inside the cell nucleus being transcribed to form a molecule of messenger RNA. This process involves an enzyme called RNA polymerase that moves along the DNA, reading the bases and making a complementary strand of messenger RNA from molecules called nucleoside triphosphates (NTPs). Just as there are four different bases in DNA, there are four different natural NTPs. In addition to supplying the correct bases for the messenger RNA molecule, these NTPs also provide the energy needed to drive the transcription process. In many species the RNA polymerase oscillates between two neighbouring positions on the DNA, with this back-and-forth motion–which is powered by thermal energy–being converted into forward movement of the enzyme along",380,128,0.3368
dialogsum,"#Person1#: The Smiths are arriving at our city tomorrow. Can you draw up a schedule for them? If they want to make any changes, minor changes can then be made. #Person2#: Is there anything special they would like to do? #Person1#: They would like to visit our factory and have a look at the new type computer products. Besides, they will introduce their technique in computer manufacturing. #Person2#: That can easily be arranged. I will arrange a comfortable meeting room for them. Anything else? #Person1#: They would also like to have a meeting with our designers. And this time, their visit to our company will lay the basement for our cooperation, so you need to pay more attention. #Person2#: I will set it up. #Person1#: They will stay for two days. Try to work out an efficient schedule.",#Person1# asks #Person2# to arrange a schedule of the Smiths' visit to their factory based on the Smiths' expectations and emphasizes the visit's importance.,138,24,0.1739
dialogsum,"#Person1#: Sam, we are hard up for the everyday expenses. When can you find a job. #Person2#: I'm looking for it, but you see, the market is hard up for jobs, too. #Person1#: You liar, I saw you again in the inn. I bet you don't want to work at all.",Sam says he's looking for a job. #Person1# thinks he's lying.,51,11,0.2157
pubmed-summarization,"- nitro - l - arginine methyl ester ( l - name , 10 m ) to prevent release of endogenous nitric oxide from any residual endothelium before the addition of local anesthetics to the organ bath . acetylcholine , phenylephrine , and l - name were obtained from sigma chemical co. ( st . louis , mo , usa ) . ropivacaine and levobupivacaine were kind gifts of astrazeneca korea ( seoul , korea ) and abbott korea ( seoul , korea ) , respectively . contractile responses to local anesthetics are expressed as a percentage of the respective maximum contraction elicited by isotonic 60 mm kcl . the logarithm of the drug concentration ( ed50 ) eliciting 50% of the maximum contractile response was calculated using nonlinear regression analysis by fitting the concentration - response relation to a sigmoidal curve using commercially available software ( prism version 5.0 ; graphpad software , san diego , ca , usa ) . responses to each concentration of local anesthetic were compared using repeated measures analysis of variance followed by bonferroni posttest ( prism version 5.0 ; graphpad software ) . statistical analyses for comparisons of ed50 of local anesthetics were performed using a one - way analysis of variance followed by a bonferroni multiple comparison test . as the independent variables were highly correlated with each other ( a situation called multicollinearity ) , a traditional regression analysis is not suitable . as an alternative , a ridge regression analysis for solving multicollinearity was performed to determine the relationship between the ed50 of local anesthetic - induced vasoconstriction in endothelium - denuded aorta and the reported physicochemical properties of local anesthetics ( table 1 ) using sas statistical software for windows , version 9.1 ( sas institute inc . , cary , nc , usa ) . standardized coefficients are estimates resulting from an analysis carried out on variables that have been standardized so that their variances are 1 . standardized regression coefficients ( srcs ) were used to determine which independent variables among octanol / buffer partition coefficient , molecular weight , pka , and potency have a greater effect on dependent variables like ed50 in the multiple regression analysis when the variables are measured in different units of","aminoamide local anesthetics induce vasoconstriction in vivo and in vitro . the goals of this in vitro study were to investigate the potency of local anesthetic - induced vasoconstriction and to identify the physicochemical property ( octanol / buffer partition coefficient , pka , molecular weight , or potency ) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction . cumulative concentration - response curves to local anesthetics ( levobupivacaine , ropivacaine , lidocaine , and mepivacaine ) were obtained from isolated rat aorta . regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% ( ed50 ) of the local anesthetic - induced maximum vasoconstriction . we determined",380,128,0.3368
dialogsum,"#Person1#: Oh, we still haven't decided what to get him. #Person2#: I know. It's hard. What does he need? #Person1#: Well, darling, the other day he said that he needed a car. #Person2#: Yeah, right. Well, I think that's a little beyond us. #Person1#: Yeah, it'd be fun, but it's just a little too expensive. #Person2#: There's the usual kind of thing, like a wallet or tie. #Person1#: Oh, please, not for his sixtieth. I think we should get him something more expensive than that, don't you? I mean, we want to get something good, something... #Person2#: Something unusual? #Person1#: Yeah. #Person2#: Well, how about a computer? We could get him a computer. That way we could keep in touch on email. #Person1#: No, no, no. You know him. He says he's too old to learn how to use a computer. He isn't, of course, but I don't think he'd ever use it.","#Person1# and #Person2# want to get something special but affordable for an old man's sixtieth. They deny a car, a tie, and a computer and make no-decision.",153,27,0.1765
pubmed-summarization,"stem were isolated from the brain tissue for real - time reverse transcriptase ( rt)-pcr , western blotting , and enzyme - linked immunosorbent assay ( elisa ) . surgeries and eeg / emg recordings were performed as previously described . briefly , after anesthesia , 28 mice were implanted with eeg and emg electrodes . the eeg electrodes were placed epidurally on the cortex , and the emg electrodes were placed in the dorsal neck muscles . ten days after surgery , the electrodes were connected to recording cables attached to the mp150 system ( biopac , goleta , ca , usa ) . eeg and emg recordings were performed in this manner from the freely behaving mice for 24 hours . data were analyzed using sleep sign 2.0 software ( biopac , goleta , ca , usa ) . total rna from the hypothalamus and brainstem tissues was extracted using trizol reagent ( takara , dalian , china ) according to the manufacturer 's instructions . first - strand cdna was synthesized at 42c with fastquant rt kit ( tiangen , beijing , china ) using 1 g of total rna . the amplification was performed using a superreal premix plus kit ( tiangen ) and an abi 7500 rt - pcr system ( applied biosystems , foster city , usa ) . the cdna was amplified with an initial denaturation step ( 95c , 15 minutes ) , and then with 40 pcr cycles consisting of a denaturation step ( 95c , 10 seconds ) and an annealing / extension step ( 58c , 32 seconds ) . -actin was used as internal control to calculate the relative abundance of each mrna ( n = 46/group ) . the specific sets of primers were as follows : prepro - orexin : f : tgaactttccttctacaaaggttc , r : caacagttcgtagagacggca ; orexin1 receptor : f : cgccaaccctatcatctacaa , r : gctctgcaaggacaaggactt ; orexin2 receptor : f : gctcaccagcataagcacact , r : tatctctttgagcagacatggg ; -actin : f : cctagcaccatgaagatcaagat , r : actcatcgtactcctgcttgct . total protein was extracted from the hypothalamus samples using the total protein extraction kit ( applygen , beijing , china ) , consisting of radioimmunoprecipitation assay lysis buffer , phenylmethylsulfonyl fluoride , protease inhibitors , and","background : sleep / wake disturbances in patients with amyotrophic lateral sclerosis ( als ) are well - documented , however , no animal or mechanistic studies on these disturbances exist . orexin is a crucial neurotransmitter in promoting wakefulness in sleep / wake regulation , and may play an important role in sleep disturbances in als . in this study , we used sod1-g93a transgenic mice as an als mouse model to investigate the sleep / wake disturbances and their possible mechanisms in als.methods:electroencephalogram/electromyogram recordings were performed in sod1-g93a transgenic mice and their littermate control mice at the ages of 90 and 120 days , and the samples obtained from these groups were subjected to quantitative reverse transcriptase - polymerase chain reaction , western blotting , and",380,128,0.3368
dialogsum,"#Person1#: Red House Restaurant. May I help you? #Person2#: I'd like to book a table. #Person1#: For how many? #Person2#: Just two. #Person1#: For what time? #Person2#: 8:00. #Person1#: I'm sorry, there aren't any tables left for 8: 00, but we can give you one for 7:00 or 9:00. #Person2#: All right. 9:00 then. #Person1#: May I have your name, please? #Person2#: Miller. #Person1#: A table for two at 9:00 for Mr. Miller. Thank you. #Person2#: Thank you.",A table at 8:00 is unavailable and #Person1# helps Miller book one at 9:00.,78,14,0.1795
dialogsum,"#Person1#: What a pity you are leaving so soon. I wish you could stay a few more days. Sir, can you deliver a speech for us? #Person2#: Dear friends. Here, I wish to say a word of thanks for holding this send-off party for me. Actually I didn't expect at all for this. I owe a lot to all of you here. It's been 5 days since I came to visit here. Time really flies. I feel grateful for your welcome and help in the five days. I will miss you while I am leaving. Let's keep in touch in any way. What's more, to the success of our face-to-face meeting, to the upcoming cooperation of our two companies, bottom up! #Person1#: Cheers! And we are honored to have such an honored guest today. Mr. James, I hope we will meet somewhere in the near future. #Person2#: Madam, we also welcome you to visit our company. I hope you can also bring your family there to have a look of our company. In this way, we will know each other better. #Person1#: Definitely! Thank you!",#Person1# asks Mr. James to deliver a speech at his send-off party. They would like to meet each other in the near future.,185,23,0.1243
dialogsum,"#Person1#: Excuse me, can you tell me where central Park Street is? #Person2#: Turn right at the third light and then go straight for two blocks. #Person1#: Is it far? #Person2#: No. It's only a ten-minute walk. #Person1#: I see. Thanks a lot. #Person2#: You're welcome.",#Person1# asks #Person2# the way to central Park Street,46,9,0.1957
dialogsum,"#Person1#: So what brings you to my office today? #Person2#: My tooth is killing me! #Person1#: How long has your tooth been bothering you? #Person2#: It just started hurting me last night. #Person1#: Have you injured your tooth in any way? #Person2#: I think one of my fillings might be coming loose. #Person1#: Do you have a special kind of toothbrush that you like to use? #Person2#: I have an electric toothbrush. #Person1#: Does it bother you when you eat something really sweet? #Person2#: Oh yeah, when I do that, it hurts a lot more!",#Person2# comes to #Person1#'s office because #Person2# has a toothache. #Person2# says it started last night and one of #Person2#'s fillings might be loose.,95,24,0.2526
scientific_lay_summarisation-elife-norm,"the intracellular transport of TMPs and membranes within the cell. Following endocytosis from the plasma membrane, TMPs enter the endosomal system where they undergo cargo specific sorting. This process provides separation of proteins destined for degradation from those that exit the endosomal system to be recycled. Two evolutionary conserved endosomal sorting machineries, the endosomal sorting complex required for transport (ESCRT) and the retromer complex, mediate cargo sorting into the degradative and recycling pathway, respectively (Cullen and Steinberg, 2018). To coordinate these opposing transport activities, the endosomal system comprises a highly dynamic membrane network governing retromer-dependent tubulation for recycling and ESCRT-mediated generation of intraluminal vesicles (ILV) for degradation. Endocytosed proteins can evade ESCRT-dependent packaging into ILVs by exiting the maturing endosome (ME) through tubular retrieval domains induced by specialized recycling machineries such as retromer. Initially characterized as a regulator of endosome-to-Golgi cargo retrieval in yeast, this endosomal agent comprises two subcomplexes that cooperatively drive cargo sorting into tubular recycling carriers (Carlton et al. , 2004; Horazdovsky et al. , 1997; Seaman et al. , 1997). Similar to the ESCRT machinery, cargo clustering and membrane deformation is performed by distinct functional units within the retromer pathway. Motif-based cargo recognition and aggregation is mediated by the endosomally localized Vps26: Vps29: Vps35 complex, which has been termed cargo-selective complex (CSC) (Lucas et al. , 2016; Nothwehr et al. , 2000; Seaman et al. , 1997). Since the ancient CSC does not possess membrane bending activity, cooperation with tubulating factors such as proteins of the SNX-BAR (Sorting Nexin-Bin/Amphiphysin/Rvs) family is required for recycling carrier generation (Cullen, 2008). Proteins containing the curved BAR-domain can assemble into regular helical coats on endosomes, thereby inducing cytoplasm faced tubulation (Frost et al. , 2009). Concerted action of CSC stably complexed with SNX-BAR proteins to retrieve endosomal cargo was initially characterized as the classical retromer pathway in yeast (Horazdovsky et al. , 1997; Seaman et al. , 1998). In metazoans however, retromer function is not restricted to SNX-BAR-dependent pathways. Specifically, cooperations of CSC with SNX3 or SNX27 (both lacking BAR-domains) emerged as alternative routes for endosomal retrieval (Harterink et al. , 2011; Lauffer et al. , 2010; Steinberg et al. , 2013). Proteomic data from mammalian cells suggest that surface levels of well over 100 TMPs depend on retromer and","Proteins are large molecules responsible for a variety of activities that cells needs to perform to survive; from respiration to copying DNA before cells divide. To perform these roles proteins need to be transported to the correct cell compartment, or to the cell membrane. This protein trafficking depends on the endosomal system, a set of membrane compartments that can travel within the cell and act as a protein sorting hub. This system needs its own proteins to work properly. In particular, there are two sets of proteins that are crucial for the endosomal systems activity: a group of proteins known as the ESCRT (endosomal sorting complex required for transport) machinery and a complex called retromer. The retromer complex regulates recycling of receptor proteins so they can be reused,",380,128,0.3368
pubmed-summarization,"the world health organization ( who ) , in 2012 , indicated there were an estimated 8.6 million new cases of active tb and 1.3 million tb deaths . the world health organization reported saudi arabia as having a moderate tb incidence rate , with 15 for every 100,000 . tb remains an important public health problem in saudi arabia , affecting all age groups and regions , and is associated with higher mortalities among saudis . since pulmonary tb this has become even more important with the development of drug - resistant tb , making effective treatment even more difficult . tuberculosis was accepted as a diagnosis if the sputum culture was positive for mycobacterium tuberculosis ( mtb ) . the interferon alpha release assay ( qft - g ) is a new diagnostic test for latent tuberculosis infection ( ltbi ) . qft - g is similar to the tuberculin skin test ( tst ) , but can not differentiate between ltbi and active tb . however , despite the limitation of qft - g in the diagnosis of active disease , it has been recommended by some investigators and it has been used in the diagnosis of active tuberculosis in the private sector . , using qft - g , was performed for the diagnosis of active tuberculosis in 13 studies , and there were 13 studies on cases with known active tuberculosis . the overall sensitivity of qft - g in the diagnosis of active tuberculosis was 6983% . another meta - analysis by dai y et al . revealed the overall sensitivity and specificity of qft - g in the diagnosis of active tuberculosis to be 85 and 84% . few other studies recommended the use of qft - g for ruling out active tuberculosis , especially in high - income countries where the prevalence of tuberculosis was low . legesse m et al . documented in their study that the sensitivity and specificity of qft - g , using the manufacturer 's cut - off value , was very low in the diagnosis of active tuberculosis in tuberculosis - endemic regions . the qft - g - tb gold kit ( cellestis limited , melbourne , australia ) was approved in 2009 for use","background : the utility of quantiferon - tb gold in - tube ( qft - g ) test in the diagnosis of tuberculosis disease has been validated in high and low tuberculosis - prevalent ( tb ) countries . aim : the aim of this study is to assess the performance of the qft - g test in the diagnosis of tuberculosis disease among tuberculosis patients in an intermediate prevalent country.setting and design : a retrospective study at the king abdulaziz medical city - riyadh ( kamc - r)materials and methods : we retrospectively reviewed all the patients with a diagnosis of pneumonia , including tuberculosis , admitted to kamc - r between 1 january 2009 and 31 december 2013 . we included only patients with an available",380,128,0.3368
dialogsum,"#Person1#: Hello Michael. #Person2#: Hello Todd. #Person1#: We're going to talk about Australia. Or your going to talk about Australia. So first of all how any people live in Australia? #Person2#: Australia? Oh, there's about twenty million people in Australia right now. A little bit under, but close to twenty. #Person1#: OK. What are the biggest cities? #Person2#: The biggest city? The biggest city is Sydney, then it's followed by Melbourne and then Brisbane and then I think it's Perth. But most of the big cities are on the East Coast of Australia. And Perth is on the west coast, but sort of of out there by itself. #Person1#: OK. Um, if you had to live in one place where would you live? #Person2#: I like Brisbane. I had my teenage years in Brisbane, growing up in Brisbane, um or maybe Sidney because it is a big city, but Brisbane has got the gold coast and the sunshine. #Person1#: Oh, nice. Actually, what is the capital city of Australia? #Person2#: Ah, Canberra is the capital city. But is not the biggest city. Sydney is the biggest city. Canberra was made sort of by the politicians so Sydney wouldn't get to crowded. It's a separate territory.","Todd asks Michael to talk about Australia. Michael tells him the population, the biggest cities, the city he prefers to live in and the capital.",205,25,0.122
pubmed-summarization,"involved in the development of human obesity . in addition , some studies in transgenic mice indicate that gas6/axl signaling might recruit macrophages and other immune cells into the adipose tissue resulting in the production and secretion of proinflammatory mediators . this suggests that the gas6/axl signaling might play a role in the pathogenesis of obesity - associated systemic inflammation . recent studies have indicated that systemic inflammation , a hallmark of childhood and adult obesity , is a pivotal mechanism linking obesity to insulin resistance and type 2 diabetes . although gas6 gene polymorphisms are reported to be associated with stroke , acute coronary syndrome , and type 2 diabetes , to our knowledge , both gas6 and axl gene polymorphisms associated with childhood obesity have not yet been identified . in order to address this issue , we conducted a community - based study to determine whether common variations in the gas6 and axl genes correlate with adiposity , systemic inflammation , insulin resistance among adolescents . the taipei children heart study - iii was an epidemiological survey that investigated obesity and cardiovascular disease risk factors among adolescents in taipei city during 2006 . the sampling method and results briefly , the survey included junior high school students in taipei city to collect a representative distribution of demographic , lifestyle , and biochemical characteristics to measure their risk for cardiovascular disease . those with autoimmune diseases , cancers , or active infection and those taking medications known to interfere with insulin or glucose metabolism were excluded . excluding any missing data , 727 adolescents ( 358 boys and 369 girls ) the institutional review board of the tri - service general hospital approved these studies and obtained informed consent from both parents and adolescents . all the participants completed a structured questionnaire detailing their gender , age , puberty development , and lifestyle characteristics ( including cigarette smoking , alcohol consumption , and physical activity ) . based on their responses , the subjects were divided into young adolescents with history of smoking , those without , and those who currently smoke . physical activity was divided into 5 levels based on amount of exercise per week : less than 1 h , 13 h , 35 h","the present study was designed to explore the effects of gas6 and axl gene polymorphisms on adiposity , systemic inflammation , and insulin resistance in adolescents . after multistage sampling from the data of the taipei children heart study - iii , we collected 358 boys and 369 girls with an average age of 13.3 years . we genotyped the adolescents ' gas6 rs8191973 , gas6 rs8191974 , axl rs4802113 , and axl rs2304232 polymorphisms . significantly higher body mass index ( bmi ) , waist circumference ( wc ) , and hscrp levels were found in boys with the gg genotype of gas6 rs8191974 than a allele carriers ; higher il-6 and insulin levels and increased homa - ir were found in boys with the gg genotype",380,128,0.3368
pubmed-summarization,"- ceramic to tooth structure and the influence of textures on the ceramic material . ceramic laminate veneers have high survival rates when bonded to enamel and provide a safe and predictable treatment option that preserves tooth structure . in a retrospective study evaluating porcelain laminate veneers up to 12 years , survival rates of 99% for veneers with preparations confined to enamel and 94% for veneers with enamel - only margins were observed . despite these high success rates , the authors also reported that laminate veneers bonded to dentin and teeth with preparation margins in dentin were approximately 10 times more likely to fail than when the veneers were bonded to enamel . hence , it is important to evaluate the effects of surface roughness on enamel and dentin surfaces created with different types and granulations of diamond burs and tips on bond strength using new glass - ceramic systems used for indirect laminate veneers . the objectives of the present study were to evaluate the influence of enamel and dentin surface finishing with medium and fine - grit diamond burs and tips mounted on a high - speed turbine handpiece and ultrasonic device on the surface roughness and influence of surface roughness on the microshear bond strength of a lithium silicate glass - ceramic to enamel and dentin . two null hypotheses were tested : ( 1 ) there are no differences in the surface roughness parameters evaluated on enamel and dentin surfaces finished with medium and fine - grit diamond burs and tips mounted on a high - speed turbine handpiece and ultrasonic device , and ( 2 ) there are no differences in the microshear bond strength of a glass - ceramic luted to enamel and dentin surfaces finished with medium and fine - grit diamond burs and tips mounted on a high - speed turbine handpiece and ultrasonic device . thirty - five bovine incisors were selected and stored in chloramine t 0.5% at 4c until use . the crowns were separated from the roots at the enamel - cemental junction and each crown was sectioned at the incisal third using a slow - speed diamond saw ( isomet 1000 , buehler , lake bluff , il , usa ) so enamel and dentin","objectives . this study evaluated the influence of cavity surface finishing with diamond burs of different grit mounted on high - speed turbine and ultrasound on the roughness and microshear bond strength ( mbs ) of a lithium silicate glass - ceramic to enamel and dentin . methods . enamel and dentin specimens were divided into seven groups , according to the type of surface finishing : 1200-grit sandpaper ( control ) , two different brands of medium - grit and fine - grit diamond burs in a high - speed turbine ; medium - grit and fine - grit cvd ( chemical vapor deposition ) tips in an ultrasonic device . roughness parameters ( n = 5 ) and msbs to a glass - ceramic ( n",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 1974; Pardee, 1974; Spencer et al. , 2013), when cells make this decision in living organisms while integrating intrinsic and the extrinsic cues of their local microenvironment during development remains poorly understood. A cell-cycle sensor that is amenable to such in vivo studies can shed new light on this four-decade-old biological phenomenon. In 2008, Sakaue-Sawano and colleagues engineered a multicolor fluorescent ubiquitination-based cell-cycle indicator (FUCCI) for mammalian cell culture (Sakaue-Sawano et al. , 2008). FUCCI has since been adapted for many research organisms (Özpolat et al. , 2017; Zielke and Edgar, 2015). However, FUCCI on its own cannot distinguish between a cell residing in G1 that will cycle again upon completing mitosis and a cell that is poised to enter G0 (Oki et al. , 2015). Separating G1 from G0 is an essential first step to understanding mechanisms controlling cell cycle exit during quiescence or terminal differentiation. To distinguish G1 from G0 in mammalian cell culture, Hanh, Spencer and colleagues developed and implemented a single-color ratiometric sensor of cell-cycle state composed of a fragment of human DNA helicase B (DHB) fused to a fluorescent protein that is phosphorylated by CDKs (Hahn et al. , 2009; Schwarz et al. , 2018; Spencer et al. , 2013). Notably, through quantitative measurements of CDK activity, this sensor provided new insights into the proliferation-quiescence decision in cultured mammalian cells by identifying cycling cells that exit mitosis in a CDK-increasing (CDKinc) state and quiescent cells that exit mitosis in a CDK-low (CDKlow) state (Spencer et al. , 2013). Nonetheless, a DHB-based CDK sensor has not been utilized to evaluate the proliferation-quiescence decision in vivo. In this study, we investigate the proliferation-quiescence decision in Caenorhabditis elegans and zebrafish, two powerful in vivo systems with radically different modes of development. We generate transgenic CDK sensor lines in each organism to examine this decision live at mitotic exit. By quantifying CDK activity, or DHB ratios, at mitotic exit, we are able to predict future cell behavior across several embryonic and post-embryonic lineages. Despite cells generally exiting mitosis with decreased CDK-activity levels, we reliably distinguish cycling cells that exit mitosis into G1, in a CDKinc state, from quiescent cells that exit mitosis into G0, in a CDKlow state. To gain insights into cell-cycle progression commitment, we","All living things are made up of cells that form the different tissues, organs and structures of an organism. The human body, for example, is thought to consist of some 37 trillion cells and harbor over 200 cell types. To maintain a working organism, cells divide to create new cells and replace the ones that have died. Cell division is a tightly controlled process consisting of several steps, and cells continuously face a Shakespearean dilemma of deciding whether to continue dividing (also known as cell proliferation) or to halt the process (known as quiescence). This difficult balancing act is critical during all stages of life, from embryonic development to tissue growth in an adult. Problems in the underlying pathways can result in diseases such as cancer. Cell division",380,128,0.3368
dialogsum,"#Person1#: What sort of experience do you have? #Person2#: I used to work as a mechanic and I was responsible for the maintenance of all the company vehicles. #Person1#: Where was your last job? #Person2#: I worked in Hanson Paper Company. #Person1#: Why did you quit your last job? #Person2#: Because the company is far away from home, and I have to study after work so I can't afford to waste time on the road everyday.",#Person1# interviews #Person2# on work experience and the reason #Person2# quited #Person2#'s last job.,76,14,0.1842
scientific_lay_summarisation-elife-norm,"hatching to sexual maturity within 2–3 months (— 1A). Unlike embryonic morphogenesis, during post-embryonic growth all organs must scale with the increasing body size while fully functioning. In the eye, continuous growth must be additionally balanced with continuous shape-keeping: Proper optics, and thus vision, requires a precise 3D shape. Highly visual shallow water fish such as medaka have near-perfect hemispherical eyes (Fernald, 1990; Nishiwaki et al. , 1997; Beck et al. , 2004). The growth rates of all eye tissues must perfectly match, otherwise the organ would deform, akin to a bimetallic strip. Thus, the eye of fish provides an excellent system to explore how anatomically and functionally distinct tissues coordinate to grow and maintain the shape of an organ in functional homeostasis (Johns and Easter, 1977; Centanin et al. , 2014). The vertebrate eye consists of multiple concentric tissues, including the neural retina (NR) and the retinal pigmented epithelium (RPE) (1A; Table 1). In fish and amphibians, these tissues grow from a ring-shaped stem cell niche in the retinal periphery: the ciliary marginal zone (CMZ) (Johns, 1977; Harris and Perron, 1998; Amato et al. , 2004). The CMZ can be subdivided into a peripheral stem- and a central progenitor cell domain; stem cells are believed to have the potential for indefinitely many cell divisions while progenitor cells divide only a handful of times (Raymond et al. , 2006; Centanin et al. , 2014; Wan et al. , 2016; Shi et al. , 2017). At the very periphery of the CMZ, about 5 rows of cells express the stem cell marker retina-specific homeobox gene 2 (Rx2) (Reinhardt et al. , 2015; Wan et al. , 2016; Tang et al. , 2017). The CMZ is a bi-partite niche, with tissue-specific stem cells for NR and RPE (Shi et al. , 2017). In medaka, stem cells for NR and RPE are strictly separate, as demonstrated by transplantations at blastula stage and genetic recombination after hatching (Centanin et al. , 2011; Centanin et al. , 2014). Thus, medaka NR and RPE are independently growing tissues with identical topology. As a population, CMZ cells appositionally add new cells in concentric rings as shown by label incorporation with thymidine analogues (Johns, 1977; Centanin et al. , 2011). Individual stem cells labelled by genetic markers form","By the time babies reach adulthood, they have grown many times larger than they were at birth. This development is driven by an increase in the number and size of cells in the body. In particular, special types of cells, called stem cells, act as a reservoir for tissues: they divide to create new cells that will mature into various specialized structures. The retina is the light-sensitive part of the eye. It consists of the neural retina, a tissue that contains light-detecting cells, which is supported by the retinal pigment epithelium or RPE. In fish, the RPE and neural retina are replenished by distinct groups of stem cells that do not mix, despite the tissues being close together. Unlike humans, fish grow throughout adulthood, and their eyes must",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The Hippo signaling pathway regulates tissue growth in Drosophila through the transcriptional coactivator Yorkie (Yki). How Yki activates target gene transcription is poorly understood. Here, we identify Nuclear receptor coactivator 6 (Ncoa6), a subunit of the Trithorax-related (Trr) histone H3 lysine 4 (H3K4) methyltransferase complex, as a Yki-binding protein. Like Yki, Ncoa6 and Trr are functionally required for Hippo-mediated growth control and target gene expression. Strikingly, artificial tethering of Ncoa6 to Sd is sufficient to promote tissue growth and Yki target expression even in the absence of Yki, underscoring the importance of Yki-mediated recruitment of Ncoa6 in transcriptional activation. Consistent with the established role for the Trr complex in histone methylation, we show that Yki, Ncoa6, and Trr are required for normal H3K4 methylation at Hippo target genes. These findings shed light on Yki-mediated transcriptional regulation and uncover a potential link between chromatin modification and tissue growth. The Hippo signaling pathway has recently emerged as a central mechanism in organ size control, tissue regeneration, and stem cell biology (Harvey and Tapon, 2007; Badouel et al. , 2009; Pan, 2010; Zhao et al. , 2010; Halder and Johnson, 2011; Barry and Camargo, 2013). Initially discovered in Drosophila for its critical role in restricting imaginal disc growth, the Hippo pathway comprises several tumor suppressor proteins acting through a core kinase cascade that ultimately phosphorylates and inactivates the transcriptional coactivator Yorkie (Yki) (Huang et al. , 2005). Consistent with its essential role in normal development and tissue homeostasis, YAP, the mammalian counterpart of Yki, encodes a bona fide oncogene and is overexpressed and/or activated in a wide spectrum of human cancers. Elucidating the molecular mechanism by which Yki functions as a transcriptional coactivator is not only relevant for understanding the fundamental mechanisms of growth control but also has important implications for the development of therapeutic strategies targeting the Hippo pathway in cancer and regenerative medicine. Posttranslational modifications of histones are important features of transcriptional regulation in all eukaryotes. A particularly prevalent modification involved in transcriptional activation is histone H3 methylation. Drosophila contains three COMPASS (complex of proteins associated with Set1) -like histone H3 lysine 4 (H3K4) methyltransferase complexes, each defined by a distinct methyltransferase subunit, namely, Trithorax (Trx), Trithorax-related (Trr), and dSet1 (Mohan et al. , 2011). Previous genetic analysis has implicated Trx","Cells need to work together for a multi-celled organism, such as a plant or an animal, to thrive. Many complicated signaling pathways therefore exist that allow cells to communicate with one another and to control their own activity in response to the signals that they receive. One such pathway, called the Hippo signaling pathway, regulates when cells grow and divide, which allows organs and tissues to develop correctly and helps to prevent cancerous tumors from forming. Signaling pathways often control the activity of cells by affecting how particular genes are expressed from DNA. One way of doing this is to activate or inactivate proteins called transcription factors, which bind to sections of DNA to alter the expression of nearby genes. In fruit flies, the Hippo signaling pathway stops",380,128,0.3368
scientific_lay_summarisation-elife-norm,"chromatin-targeted Aurora B sensor after INbox recruitment to centromeres. (A) Schematic of the experiment in which the Aurora B-INbox complex labeled with mCherry (mCH) is recruited to centromeres by addition of rapamycin; see Materials and methods for details. (B) Cells were treated as in 1B, but arrested with nocodozole instead of STLC; scale bar is 5 µm. Graph on the right shows FRET emission ratio averaged over chromatin in n≥11 cells, N = 3 independent experiments. FRET ratio = 1. 24 (horizontal dotted line) represents maximal Aurora B activity in cells with no INCENP depletion. : http: //dx. . org/10. 7554/eLife. 10644. 004 One model to explain such well-controlled long-range spatial activity is by a specialized pool of Aurora B localized in close proximity to its targets (Krenn and Musacchio, 2015). At the outer kinetochore, for example, the observed gradient of substrate phosphorylation could correspond to the outermost region of the localization gradient of chromatin-bound kinase (Liu et al. , 2009), or reflect the ability of Aurora B to reach these substrates by an elongated INCENP tether, the CPC component that directly binds Aurora B and is important for its mitotic functions (Samejima et al. , 2015). In this view, the less abundant but proximally located Aurora B pool plays a more physiologically important role than the distant centromeric pool. Support for the kinetochore pool model comes from experiments in budding yeast, which show that the centromere localized pool of Aurora B (Ipl1) can be removed without major consequences for mitotic progression (Campbell and Desai, 2013). In several other systems, however, disrupting CPC targeting to centromeres leads to strong mitotic defects (Vader et al. , 2006; Tsukahara et al. , 2010; Wang et al. , 2010; 2012; Yamagishi et al. , 2010), suggesting that the centromere-localized pool is essential for normal cell division. An alternative model to explain how Aurora B activity is controlled at distances away from its most abundant localization sites is that this pattern depends on a biochemical crosstalk between the bound Aurora B and its cytosolic pool, which recent quantitative measurements estimate as ~25% of total Aurora B (Mahen et al. , 2014). Cytosolic gradients of another mitotic regulator, RanGTP, play important roles in regulating spindle assembly (O’Connell and Khodjakov, 2007; Kalab and Heald, 2008), and","Cell division is a highly organized process that involves a series of major changes. First, the cell’s chromosomes are copied and arranged at the middle of the cell. Then, the pairs of copied chromosomes are separated and pulled towards opposite ends of the cell and, finally, the cell splits in two. These steps are mainly regulated by modifications to proteins, and enzymes called protein kinases play an important role because they add phosphate groups to, or phosphorylate, so-called' substrate' proteins to change their activities. Other enzymes called phosphatases are also important because they remove the phosphate groups from the substrates to reverse the effects. The kinase Aurora B is required for several steps during cell division and has been widely studied. This kinase is enriched in specific locations",380,128,0.3368
dialogsum,"#Person1#: Hi. I ' m here for flight 514 returning to Beijing but the board shows there is a delay.How long of a delay is expected? #Person2#: So far it looks like we will be leaving two hours late, but keep checking the departing flights status board just in case. #Person1#: Do you think it ' s safe to leave to get a quick bite? #Person2#: I think you should stay in the airport. Even though the delay is expected to be two hours, the flight departure could be announced any minute. Who knows? #Person1#: What seems to be the problem? #Person2#: It seems there are some loose bolts on one of the wings. It happens all the time. No need to worry. #Person1#: Umm... You know... Actually I was thinking of trying another airline. No need to hold my seat.","#Person1# goes to ask #Person2# something about delay of #Person1#'s flight , such as how long the delay will be and decides to try another airline.",141,26,0.1844
scientific_lay_summarisation-elife-norm,"The sulfhydration of cysteine residues in proteins is an important mechanism involved in diverse biological processes. We have developed a proteomics approach to quantitatively profile the changes of sulfhydrated cysteines in biological systems. Bioinformatics analysis revealed that sulfhydrated cysteines are part of a wide range of biological functions. In pancreatic β cells exposed to endoplasmic reticulum (ER) stress, elevated H2S promotes the sulfhydration of enzymes in energy metabolism and stimulates glycolytic flux. We propose that transcriptional and translational reprogramming by the integrated stress response (ISR) in pancreatic β cells is coupled to metabolic alternations triggered by sulfhydration of key enzymes in intermediary metabolism. Posttranslational modification is a fundamental mechanism in the regulation of structure and function of proteins. The covalent modification of specific amino acid residues influences diverse biological processes and cell physiology across species. Reactive cysteine residues in proteins have high nucleophilicity and low pKa values and serve as a major target for oxidative modifications, which can vary depending on the subcellular environment, including the type and intensity of intracellular or environmental cues. Oxidative environments cause different post-translational cysteine modifications, including disulfide bond formation (-S-S-), sulfenylation (-S-OH), nitrosylation (-S-NO), glutathionylation (-S-SG), and sulfhydration (-S-SH) (also called persulfidation) (Finkel, 2012; Mishanina et al. , 2015). In the latter, an oxidized cysteine residue included glutathionylated, sulfenylated, and nitrosylated on a protein reacts with the sulfide anion to form a cysteine persulfide. The reversible nature of this modification provides a mechanism to fine tune biological processes in different cellular redox states. Sulfhydration coordinates with other post-translational protein modifications such as phosphorylation and nitrosylation to regulate cellular functions (Altaany et al. , 2014; Sen et al. , 2012). Despite great progress in bioinformatics and advanced mass spectroscopic (MS) techniques, identification of different cysteine-based protein modifications has been slow compared to other post-translational modifications. In the case of sulfhydration, a small number of proteins have been identified, among them the glycolytic enzyme glyceraldehyde phosphate dehydrogenase, GAPDH (Mustafa et al. , 2009). Sulfhydrated GAPDH at Cys150 exhibits an increase in its catalytic activity, in contrast to the inhibitory effects of nitrosylation or glutathionylation of the same cysteine residue (Mustafa et al. , 2009; Paul and Snyder, 2012). The biological significance of the Cys150 modification by H2S is not well-studied, but H2S could serve as a","Proteins play essential roles in almost every aspect of a cell’s life, and also contribute to the structure and function of body tissues and organs. Cells and tissues adapt to their continuously changing environments by regulating the activity of their proteins. For example, proteins that are not fully active immediately after they are built instead require further ‘posttranslational’ modifications to become active. Amino acids are the building blocks of proteins, and cysteine amino acids are frequent sites of posttranslational modifications because they are particularly chemically reactive. Under certain conditions inside the cell, the sulfur atom in a cysteine can bond with chemical group containing a second sulfur atom plus a hydrogen atom. This process, which is known as sulfhydration, can be triggered by the presence of the gas",380,128,0.3368
dialogsum,"#Person1#: I have never bought a house before and don't know how to make an offer. #Person2#: The process of actually making the offer is something that I will take care of for you. What price were you considering offering? #Person1#: I love this house and would be willing to pay the full asking price of three hundred and fifty thousand dollars. #Person2#: Let's leave some room on this offer. I think that three hundred and twenty thousand dollars is a fair offer in this housing market. #Person1#: We could try that, but I really want this house! #Person2#: It is common practice to offer and then have a counter-offer. #Person1#: How long will it take to find out if they are going to accept the offer? #Person2#: The sellers are usually fairly quick to respond. They want to get things moving. #Person1#: Should I tell my bank that I have made an offer? #Person2#: There really isn't anything else to do right now except wait. You are already pre-qualified for your loan.","#Person1# loves the house and is willing to pay $350,000. #Person2# suggests make it $320,000. #Person2# tells #Person1# the seller usually responds quickly and now #Person1# just needs to wait.",173,30,0.1734
scientific_lay_summarisation-elife-norm,"aging and in myelin-related disorders. However, the molecular mechanisms that might prevent myelin outfoldings have remained unknown. A striking variety of myelin-related genes causes – when mutated in human disorders and in animal models - common pathological features including axonopathy, neuroinflammation, hypomyelination, and structural impairments affecting myelin. For example, abundant constituents of CNS myelin such as proteolipid protein (PLP), cyclic nucleotide phosphodiesterase (CNP), and myelin associated glycoprotein (MAG), are not essential for the biogenesis of myelin per se but their deficiency in mice causes complex CNS pathology (Edgar et al. , 2009; Griffiths et al. , 1998; Li et al. , 1994; Montag et al. , 1994). The neuropathological profiles observed in these and other myelin mutants are highly overlapping, which has made it difficult to explain distinct aspects of neuropathology by the loss of individual structural myelin proteins. Here, we followed the hypothesis that mutations of single genes can have secondary consequences for the entire protein composition of myelin, which allow elucidating the molecular cause of distinct neuropathological features. We report the discovery of a previously unrecognized filamentous scaffold in the innermost layer of CNS myelin that extends longitudinally along myelinated axons. This filament is composed of distinct septin monomers (SEPT2/SEPT4/SEPT7/SEPT8) and associated with the adaptor protein anillin (ANLN). The formation of myelin septin filaments is a late stage of myelin maturation, thereby avoiding that the property of septins to rigidify the membranes they are associated with (Gilden and Krummel, 2010; Tooley et al. , 2009) could hinder the normal developmental ensheathment of axons. Importantly, this sub-membranous septin/anillin-scaffold (SAS) is required for the normal structure of the axon/myelin unit in vivo as its deficiency causes a specific structural impairment of the myelin sheath, myelin outfoldings, and reduced nerve conduction velocity. These findings were possible by systematic label-free myelin proteome analysis in several models of complex neuropathology. By quantitative evaluation of electron micrographs (1A; — 1A–E), hypomyelination was a significant feature in Plp1null and Magnull mice, swellings of the inner tongue of myelin in Magnull and Cnpnull mice, axonal spheroids in Plp1null mice, and degenerated axons in Cnpnull mice. Split myelin lamellae (not quantified) were observed in Plp1null mice. Together, these mouse mutants display distinct but overlapping profiles of neuropathology. Notably, myelin outfoldings (1B; — 1A) were common to all","Normal communication within the brain or between the brain and other parts of the body requires information to flow quickly around the nervous system. This information travels along nerve cells in the form of electrical signals. To speed up the signals, a part of the nerve cell called the axon is frequently wrapped in an electrically insulating sheath made up of a membrane structure called myelin. The myelin sheath becomes impaired as a result of disease or ageing. In order to understand what might produce these changes, Patzig et al. have used biochemical and microscopy techniques to study mice that had similar defects in their myelin sheaths. The study reveals that forming a normal myelin sheath around an axon requires a newly identified ‘scaffold’ made of a group",380,128,0.3368
dialogsum,"#Person1#: Have you seen the new girl in school? #Person2#: No, I haven't. #Person1#: She's really pretty. #Person2#: Describe her to me. #Person1#: She's not too tall. #Person2#: Well, how tall is she? #Person1#: She's about 5 feet even. #Person2#: What does she look like, though? #Person1#: She has pretty light brown eyes. #Person2#: I may know which girl you're talking about. #Person1#: So you have seen her around? #Person2#: Yes, I have.",#Person1# is describing to #Person2# about a new girl in school who is pretty.,73,14,0.1918
scientific_lay_summarisation-elife-norm,"arguing for the predominance of cone-based (Allen et al. , 2011; Butler and Silver, 2011; Dkhissi-Benyahya et al. , 2007; Lall et al. , 2010) or rod-based (Altimus et al. , 2010; McDougal and Gamlin, 2010) synaptic input to ipRGCs and their behavioral responses. Additionally, it has been suggested that melanopsin mediates persistent light detection in ipRGCs (Altimus et al. , 2008; Gooley et al. , 2012; Lupi et al. , 2008; Mrosovsky and Hattar, 2003; Zhu et al. , 2007) because melanopsin phototransduction is relatively slow to initiate but stable for minutes to hours (Berson et al. , 2002; Gooley et al. , 2012; Wong, 2012). However, animals lacking melanopsin still retain sustained light responses in ipRGCs and their central targets (Schmidt et al. , 2014; van Diepen et al. , 2013; Wong, 2012) and relatively normal circadian photoentrainment (Panda et al. , 2002; Ruby et al. , 2002) and PLR (Lucas et al. , 2003; Xue et al. , 2011). In total, it remains unclear how ipRGCs utilize each distinct photoreceptive input, especially across the environmental range of light intensities and durations. ipRGCs must faithfully relay information about the light environment to the brain. Many neurons, including ipRGCs, release multiple neurotransmitters, a classical neurotransmitter and one or more neuropeptides (Vaaga et al. , 2014). However, methods to evaluate mammalian cotransmitter systems in vivo in real time are lacking. ipRGCs contain the principal excitatory neurotransmitter glutamate and the neuropeptide PACAP (pituitary adenylyl cyclase-activating polypeptide) (Engelund et al. , 2010; Hannibal et al. , 2002). Recent studies have suggested that glutamate is the predominant regulator of ipRGC-dependent behaviors, including circadian photoentrainment and the PLR (Delwig et al. , 2013; Gompf et al. , 2015; Purrier et al. , 2014). By comparison, animals lacking PACAP or its receptors show at best minor deficits in circadian photoentrainment and the PLR (Beaulé et al. , 2009; Colwell et al. , 2004; Engelund et al. , 2012; Kawaguchi et al. , 2010,2003). This difference in outcomes between glutamate and PACAP has led to the conclusion that PACAP is dispensable and serves primarily as a modulator of glutamatergic signaling (Chen et al. , 1999). It remains puzzling why ipRGCs, like many other neuronal cell types, would possess two distinct neurotransmitters. To date, the precise behavioral","The retina is the part of our eye that detects light and sends visual information to the brain. There are several different types of light-sensitive cell in the retina that perform different roles. For example, retinal cells called intrinsically photosensitive retinal ganglion cells (or ipRGCs for short) rapidly respond to the intensity of background light and regulate the size of the pupils to control how much light enters the eyes. These cells receive information from other light-sensitive cells in the retina called rods and cones. There are at least two mechanisms that ipRGCs may use to relay information to the brain: one uses a protein called PACAP, while the other involves a molecule called glutamate. However, it is still not clear which mechanisms are actually used by ipRGCs,",380,128,0.3368
dialogsum,"#Person1#: Good morning, sir! Can I help you? #Person2#: Good morning! I'd like to buy twelve tickets to Beijing for October 14th. #Person1#: Yes, sir. We have many trains going to Beijing, fast train, through train, express train and tourist train. Which train do you prefer? #Person2#: Well, the express one, with air-conditioning. #Person1#: Then you'll have two choices. Train No. 14 leaves at 6:00 p. m, and train No. 22 leaves at 8: 00 p. m. #Person2#: When do they arrive in Beijing? #Person1#: They will arrive the next morning, at 8: 00 a. m. and 10:00 a m. respectively. #Person2#: In that case I think Train No. 14 will be better. We can do more sightseeing in Beijing. #Person1#: Right. Trains No. 13 and No. 14 are the best trains on the line between Beijing and Shanghai. Which seats do you prefer, cushioned seats, ordinary seats, cushioned berth, or ordinary berth? #Person2#: In a cushioned sleeper, please.","#Person1# helps #Person2# buy twelve express train tickets of Train no.14 to Beijing in a cushioned sleeper, the train will leave at 8 pm and arrived at 10 am next morning.",159,31,0.195
dialogsum,"#Person1#: So, Lauren, I just wanted to talk to you quickly about our new customer support representative, Jason Huntley. #Person2#: Sure, what's up? #Person1#: Basically, I'Ve got a few concerns about him, and the bottom line is, I don't think he's a good fit for our company. #Person2#: Okay. . . what makes you say that? I thought you were pleased with his overall performance. Didn't you just tell me last week how impressed you were with his attitude? #Person1#: Yeah, his attitude is great, but he's really unreliable. Sometimes he's really productive, but then other times. . . take last Tuesday for instance, he was forty-five minutes late for our morning meeting! #Person2#: Well, I'm sure he had a perfectly good reason. . . #Person1#: But that's not the only thing. . . you know, he really doesn't have the best work ethic, I'm constantly catching him on MSN and Facebook when he should be talking to clients. #Person2#: Yeah, but come on, Geoff, as if you don't check Facebook at work. Look, you hired this guy, we'Ve invested a lot of time and money in his training, so now it's up to you to coach him. Make it work, Geoff!",Geoff tells Lauren Geoff thinks their new customer support representative Jason is unreliable and doesn't have the best work ethic. Lauren suggests Geoff coach Jason because they've invested a lot in Jason.,202,32,0.1584
pubmed-summarization,"malaria , which is caused by a protozoan parasite of the plasmodium genus , represents a serious global health concern given that nearly half of the world population is at risk of infection ( who , 2014 ) . although several anti - malarial drugs for treating the symptomatic stage ( or blood stage ) of malarial infection are commercially available ( antony and parija , 2016 ) , their efficacy has declined appreciably in the last few decades owing to widespread drug resistance developed by the parasite ( breman et al . , chloroquine was the first - line malaria treatment for many decades until drug - resistant p. falciparum strains became common . the drug causes a dose - dependent decrease in hemozoin formation ( chou and fitch , 1992 , slater and cerami , 1992 ) and an associated increase in toxic free heme in the food vacuole of the parasite ( combrinck et al . , 2013 , loria et al . , 1999 ) . over the past few decades , researchers have proposed many different mechanisms for chloroquine action , including 1 ) dna intercalation ( meshnick , 1990 ) , 2 ) alteration of digestive food vacuole ph ( yayon et al . , 1985 ) , 3 ) inhibition of heme polymerase ( yayon et al . , 1985 ) , and 4 ) formation of a toxic chloroquine - ferriprotoporphyrin ix complex ( sugioka et al . , yet , there is no consensus on the exact mechanisms by which chloroquine kills the parasite and under what circumstances they operate . shedding light on the possible actions of chloroquine is critical for developing more potent drugs or combination drug treatments against the parasite and for understanding how the parasite can develop resistance against them . here we used systems biology model and transcriptional profiles of p. falciparum to obtain information about metabolic and biological precursors that determine the physiological or pathophysiological state of the parasite . specifically , we used the p. falciparum transcriptomic data obtained by hu and colleagues during the intraerythrocytic development cycle ( idc ) at different concentrations of chloroquine ( hu et al . , 2010 ) . our primary goal was to use these data to","chloroquine , long the default first - line treatment against malaria , is now abandoned in large parts of the world because of widespread drug - resistance in plasmodium falciparum . in spite of its importance as a cost - effective and efficient drug , a coherent understanding of the cellular mechanisms affected by chloroquine and how they influence the fitness and survival of the parasite remains elusive . here , we used a systems biology approach to integrate genome - scale transcriptomics to map out the effects of chloroquine , identify targeted metabolic pathways , and translate these findings into mechanistic insights . specifically , we first developed a method that integrates transcriptomic and metabolomic data , which we independently validated against a recently published set of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"mCherry fluorescence ratio showing active state Ca2+ transients in HSNs (B), VCs (C), and vulval muscles during twitching (D) and egg-laying behaviors (E). Arrowheads, HSN and VC presynaptic termini; asterisks, cell bodies; scale bar, 10 µm. (F) 30 min recordings of HSN, VC, and vulval muscle activity (left panel), showing distinct active (yellow) and inactive (grey) egg-laying behavior states, with expanded timescale of one active state at right. Arrowheads show egg-laying events. (G) Scatter plots and median HSN, VC, and vulval muscle (vm) inter-transient intervals during egg-laying inactive (–, filled circles) and active (+, open circles) states. Asterisks indicate significant differences (p<0. 0001). (H) Relationship between Ca2+ transient amplitude and egg release. Scatter plots and medians of normalized amplitude with (+; open circles) and without (–; closed circles) egg release. Also shown is the percent of total transients that accompanied egg release. (I) Timing of HSN, VC, and vulval muscle Ca2+ transients and egg release. Shown at top is a curve of the median of Ca2+ from HSN (green), VC (blue), and vulval muscles (orange) from normalized ∆R/R traces (with the peak Ca2+ set to 100%) synchronized to the moment of egg release (0 s, arrowhead and dotted line). Bars indicate 20% change in median GCaMP5/mCherry ratio. The timing of the HSN Ca2+ peak is significantly different from that of the VCs and vulval muscles (p<0. 0001). Shown at bottom is a trace of median vulval muscle size. Bar shows a 5% change in median object size based on mCherry fluorescence. : http: //dx. . org/10. 7554/eLife. 21126. 003 C. elegans egg-laying behavior is controlled by a small circuit that offers many experimental advantages for study (Schafer, 2006). This circuit, diagrammed in 1A, consists of two serotonergic Hermaphrodite Specific Neurons (HSNs) and six cholinergic Ventral C neurons (VCs), each of which synapse onto a set of vulval muscles whose contraction expels eggs. Four neuroendocrine uv1 cells also regulate egg laying (Jose et al. , 2007). Despite its anatomical simplicity, the egg-laying circuit produces a regulated, rhythmic behavior that alternates between quiescent periods of about 20 min during which no egg laying occurs, and active states lasting a few minutes during which ~5 eggs are laid (Waggoner et al. , 1998). Active states appear to result when the HSNs release serotonin","It has been said that if the human brain were so simple that we could understand it, we would be so simple that we couldn’t. This quote neatly captures the challenge of working out how 80 billion neurons collectively generate our thoughts and behavior. Fortunately, the nervous system is also organized into simpler units called circuits. Each consists of a relatively small number of neurons, which communicate with one another to control as little as a single behavior. These circuits should in principle be simple enough for us to understand, particularly if we study them in nervous systems less complex than our own. Despite this, there is currently not a single circuit in any organism in which we can explain how communication between individual neurons generates behavior. Collins",380,128,0.3368
pubmed-summarization,"four of the activated tfs were upregulated in l1 overexpressing cells ( stat1 , stat2 , irf7 and atf4 ) , while one of the inhibited tfs was downregulated ( foxm1 ) . we then performed the mechanistic networks analysis to further explore the contribution of the tfs in regulating gene networks . we found that stat1 , stat2 , irf7 , atf4 and stat3 ( that was among the 18 tfs predicted to be activated ) interact with each other ( . 2 ) , thus exerting a coordinated control on a directional network of 105 genes regulated by l1 ( i.e. 11% of all the l1-regulated genes ) . most of these genes were consistently up- or downregulated with the expression change of their upstream tfs . these findings were supported by functional studies which implicated the jak / stat signaling pathway in the biological response of luecs to l1 overexpression . mouse luecs were immortalized with polyoma middle t antigen and cultured in mcdb131 medium ( gibco ; life technologies ) supplemented with 20% fbs ( invitrogen ) , 2 mm l - glutamine ( lonza ) , 1 mm na - pyruvate ( gibco ; life technologies ) , 100 g / ml heparin ( sigma - aldrich ) , and 50 g / ml ec growth ( ecgs ) obtained from calf brain . ecs were seeded on plates coated with glutaraldehyde - crosslinked gelatin and cultured in complete medium for 4 days to reach confluence . total rna was extracted from ~ 5 10 cells using the rneasy mini kit ( qiagen ) following manufacturer 's instruction . quality control of the rna samples was performed using an agilent bioanalyzer 2100 ( agilent technologies ) . the rna from three independent extractions was processed for each of the cell line under analysis . a total of 150 ng of rna from each sample was used for rna quality check , labeling and hybridization on a mouse gene 1.0 st genechip array according to the manufacturer 's instructions ( affymetrix ) . three independent biological replicates were performed for each condition ( l1-transfected vs. mock - transfected luecs ) . we used the robust multi - array average ( rma ) to normalized data .","we recently identified a novel role for the l1 transmembrane glycoprotein ( also known as l1cam or cd171 ) in the regulation of tumor angiogenesis and vessels stabilization . l1 overexpression in cultured endothelial cells of the lung ( luecs ) exerted a pleiotropic effect in that it regulated proliferation , migration , tubulogenesis , vascular permeability , and endothelial - to - mesenchymal transition ( endmt ) . in addition , we provided strong evidence that antibody - mediated targeting of l1 may be an effective strategy for vessel normalization with the potential to increase efficacy of chemotherapeutic agents.high-throughput microarray expression profile revealed that l1 modulates the expression of hundreds of genes mainly involved in cell cycle regulation , dna replication , cellular assembly , migration ,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"to sample (DMS) task (1a). In this task, water-restricted mice were presented a 200 ms auditory stimulus (3 kHz or 12 kHz tone) as the sample, followed by a delay period (1. 5 s) and then a testing auditory stimulus, either matched or nonmatched to the sample. Licking within a response time window (1 s) in the match trial was rewarded with water (1b). Thus, mice had to remember the briefly presented auditory sample stimulus during the delay period. The behavioral performance declined with increasing duration of the delay period, indicating that the task required short-term memory processes (1d). To examine the neural correlate of auditory WM in AC, we recorded the single-unit activity of AC by using tetrodes while mice were performing the auditory DMS task (n = 13 mice, 1e). A total of 915 neurons were recorded, of which 287 (31. 4%) exhibited activity related to the task (compared with baseline activity, evaluated with a paired t test, at the p<0. 05 level) and were selected for further analysis. Responses from one typical AC neuron are shown in 2a left. The neuron exhibited a phasic response during the auditory sample stimulus presentation. After the offset of the sample stimulus, the neuron continued to exhibit activity for 800 ms into the delay period. This response pattern was representative of our population (2b). 2c shows that more than 60% of AC neurons exhibited increased firing rate during the first 500 ms of the delay. The incidence decreased to ~30% during 500–800 ms of the delay. For the majority of these units (~90%), the elevated firing rate appeared in the first 800 ms of the delay period and did not persist any further. As shown in the example (2a left) and population (2e), the firing rate of AC neurons showed selectivity of the preceding sample stimulus during both the auditory stimuli and early delay. To quantify the ability to discriminate between the two stimuli, we performed a receiver operating characteristic (ROC) analysis. The mean ROC values for the population of AC neurons increased rapidly after the onset of the auditory stimulus and retained above the value of 0. 5 during the early delay (<800 ms) (2g). The permutation test also showed that about 50% of neurons showed significant sample selectivity during","Working memory is the ability to hold information in your head for a few seconds while making decisions, planning or applying logical reasoning to problem solving. It is a fundamental component of cognition, and yet it remains unclear where working memory is stored in the brain. The prefrontal cortex – the front lobe of the brain – is likely the main hub of working memory, since it is responsible for executive functions, such as decision making and planning. This idea is supported by experiments showing sustained brain activity in the prefrontal cortex during working memory tasks. Lesions in that part of the brain also lead to profound deficits in working memory. However, there is increasing evidence that other parts of the brain which process sensory information also participate",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Motor proteins of the conserved kinesin-14 family have important roles in mitotic spindle organization and chromosome segregation. Previous studies have indicated that kinesin-14 motors are non-processive enzymes, working in the context of multi-motor ensembles that collectively organize microtubule networks. In this study, we show that the yeast kinesin-14 Kar3 generates processive movement as a heterodimer with the non-motor proteins Cik1 or Vik1. By analyzing the single-molecule properties of engineered motors, we demonstrate that the non-catalytic domain has a key role in the motility mechanism by acting as a ‘foothold’ that allows Kar3 to bias translocation towards the minus end. This mechanism rivals the speed and run length of conventional motors, can support transport of the Ndc80 complex in vitro and is critical for Kar3 function in vivo. Our findings provide an example for a non-conventional translocation mechanism and can explain how Kar3 substitutes for key functions of Dynein in the yeast nucleus. Motors of the kinesin family are ubiquitous enzymes essential for intracellular transport along microtubules in eukaryotes. The mechanism by which kinesin motor proteins convert the chemical energy of ATP hydrolysis into coordinated, long-range directional movement has fascinated cell biologists, biochemists, and engineers for many decades. Biophysical studies of kinesins have focused on conventional Kinesin-1 and established the ‘hand-over-hand’ model for the processive walking behavior of this type of motor (Asbury et al. , 2003; Yildiz et al. , 2004; Kaseda et al. , 2003). In analogy to other enzymes, the term ‘processivity’ describes the ability of individual motor molecules to undergo multiple catalytic cycles—and therefore translocate—before releasing from the microtubule. Kinesin-14 family members, exemplified by the Drosophila Ncd motor, are common examples for nonprocessive kinesins (Case et al. , 1997; Foster and Gilbert, 2000). They generate motility through the minus-end-directed rotational movement of a coiled-coil mechanical element that occurs upon ATP binding (Endres et al. , 2006). After each catalytic cycle, Ncd motors release from the microtubule lattice, meaning that to support microtubule sliding and crosslinking in the spindle, many Ncd motors must work together cooperatively in an ensemble (Braun et al. , 2009; Fink et al. , 2009). Budding yeast kinesin-14 Kar3 is distinct from other family members in its heterodimeric composition with either Cik1 or Vik1 (Manning et al. , 1999) (1A). High-resolution structural analysis has","Molecules can be transported around a cell by so-called motor proteins that move along a network of filaments called microtubules. Many motor proteins—including the kinesin family of these proteins—can only move in one direction along a microtubule. In most cells, kinesins tend to transport other molecules away from the center and towards the cell edge. Kinesins can have different structures, but most are made up of two subunits that are joined and work together to create a walking-like movement. Each subunit has a region called a motor domain (also known as its ‘head’) that can bind to the microtubule and to a molecule called ATP, which provides the energy required for the motor to step forward. Kinesins can be classed either as processive or non-processive motors. Processive motors",380,128,0.3368
dialogsum,"#Person1#: What is my ideal weight? #Person2#: It depends on your height and body type. #Person1#: How can I avoid injuring myself during exercise? #Person2#: By warming up before and cooling down after your workout. #Person1#: Sir, tell us about your experience with Super Bulk-up. #Person2#: Well, it's completely changed my life. #Person1#: Tell us how. #Person2#: Well, before, I was the skinniest guy on the beach. #Person1#: And now? #Person2#: Just look! In six short weeks I've put on 30 pounds of pure muscle. #Person1#: Wow! All because of Super Bulk-Up.",#Person2# instructs #Person1# how to exercise and shares his experience with Super Bulk-up.,92,13,0.1413
dialogsum,"#Person1#: Good afternoon, Mr. Yang. I'm Jill, Mr. Smith's secretary. Would you like to look around the factory first? #Person2#: Yes, I would. #Person1#: Now this is our office block. We have all the administrative departments Sales, Accounting, Personnel, Market Research and so on. #Person2#: What's that building opposite us? #Person1#: That's the warehouse where the larger items of medical instruments are stored. We keep a stock of the fast-moving items so that urgent orders can be met quickly from stock. ( in the workshop ) This is one of our three workshops. This is the delivery bay here. #Person2#: Oh, I see. #Person1#: The steel sheets and bars come in, as you see, in different sizes and are unloaded onto the delivery bay here. We buy them in from a steel works in Wales. This is the new conveyor belt we installed last year. We doubled our output in this department as a result. #Person2#: Oh, really? #Person1#: I'll take you to the assembly shop. . .","Jill shows Mr. Yang around their factory and introduces the office block, the warehouse, the workshop, etc.",168,17,0.1012
dialogsum,"#Person1#: Can I help you, madam? #Person2#: Yes. Did you have this room checked before we moved in? The toilet doesn't seem to have enough power and the water doesn't flow away in the shower. What do you have to say to that? #Person1#: I'm extremely sorry to hear that. I'll attend to it right away. We usually check every room before new guests move in. We've been busy with a large conference. #Person2#: That's not what you should do after all. One doesn't expect this sort of thing here. #Person1#: No, madam. I do apologize. It's most unusual. We do try to check the room as thoroughly as possible. Anything else? #Person2#: Well, your air conditioning doesn't seem to be working too well. It's so hot up here. #Person1#: I'll just try to make it work better and you'll find it a little cooler in a short time. Also, I'll send someone along right away to look at the toilet and shower.","#Person2# complains about the air conditioning, the toilet and the shower of the room. #Person1# apologizes and will check all the problems.",163,22,0.135
scientific_lay_summarisation-elife-norm,"is utilized to achieve the dual functions. We previously reported that dimeric KIF19A-379 has dual activities: MT-based motility toward the plus-end and MT-depolymerizing activity mainly from the plus-end (Niwa et al. , 2012). To clarify which region is responsible for these dual functions, we made the monomeric construct KIF19A-353 (353WT) and assessed its motility and MT-depolymerizing activities. 353WT includes the motor domain followed by the neck-linker, but does not include the neck coiled coil, which is required for the dimerization of KIF19A (1A). We first performed the in vitro MT gliding assay, in which tetramethylrhodamine (TMR) -labeled and polarity-marked MTs were used to show the tracking direction. The strongly-labeled MT minus-ends lead the MT gliding, suggesting that the monomeric 353WT moves toward the plus-end (Video 1). MT gliding velocity was 5. 3 ± 1. 2 nm/s (n = 105 MTs from three independent preparations, mean ± SD, 1B and C), which was slower than that of dimeric KIF19A-379 (21 ± 3 nm/s) (Niwa et al. , 2012). An in vitro MT depolymerizing assay was also performed for KIF19A-353 (Desai et al. , 1999). GMPCPP-MTs were dose-dependently depolymerized by 353WT (1D). The half-maximal effective concentration for MT depolymerization (EC50) was 142 ± 2 nM, which was approximately half that of KIF19A-379 (253 nM) (1E). Considering that one of two motor domains will reach the plus-end of the MT, EC50 values of one catalytic unit for depolymerizing MTs might be similar between monomeric 353WT and dimeric KIF19A-379. Either way, these in vitro experiments collectively indicate that the KIF19A monomer construct, 353WT, is a dual function motor that moves along and depolymerizes MTs. 10. 7554/eLife. 18101. 003Figure 1. Characteristics of the dual function mouse KIF19A motor domain. (A) Schematic of mouse KIF19A motor domain constructs. The KIF19A monomer KIF19A-353 (referred to as 353WT) was used in this study. NL, neck-linker. (B) MT gliding assays of 353WT on taxol-stabilized MTs. Data are presented as the mean ± SEM, n = 105 MTs. (C) Kymograph showing movement of 353WT along MTs as imaged by TIRF microscopy. Scale bars, 2 μM (horizontal) and 3 min (vertical). The average MT length is 8. 39 ± 2. 71 μM. (D) 1. 5 μM GMPCPP-stabilized MTs were incubated with 250 nM 353WT in the presence of 5 mM ATP","The cells that line the airways and other passages in the body have hair-like structures called cilia on their surface. Maintaining the cilia at an appropriate length is key to allowing fluid to flow efficiently in these passages. A protein called tubulin forms scaffolds known as microtubules that give each cilium its shape and allow it to change length. Motor proteins are also found in cilia, and travel along the microtubules to transport substances. One of these microtubule-based motors, referred to as KIF19A, accumulates at the tip of cilia and controls their length. It does so by combining two actions: it moves along the microtubule to the tip of the cilium, and then removes tubulin molecules from the end. Microtubules are straight along their length and curved at",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and γ-subunits (Behrens et al. , 2000; Brenner et al. , 2000; Uebele et al. , 2000; Yan and Aldrich, 2010,2012; Yang et al. , 2011), which interact with the S0 segment of the α subunit. Several studies demonstrate that the association with different subunits impacts channel pharmacological and gating properties. In addition, splice variants of the Slo1 mRNA contribute to the functional diversity of BK channels (Fodor and Aldrich, 2009; Johnson et al. , 2011). Apart from responding to different stimuli, Slo1 and Slo3 channels are distributed discretely within the body as shown in numerous animal studies. Slo1 is detectable in excitable tissues, such as in hippocampus (Hicks and Marrion, 1998), smooth muscle cells (Knaus et al. , 1994a, 1994b) and adrenal chromaffin cells (Solaro and Lingle, 1992), whereas Slo3 transcripts are exclusively expressed in male germ cells (Schreiber et al. , 1998). Male Slo1−/− animals are able to produce offspring when paired with Slo+/+ females. However, the litter size was normal only in 10% of the matings (Meredith et al. , 2004). Abolishing the Slo3 gene results in more dramatic changes in testicular spermatozoa, such as morphological abnormalities after capacitation, reduced progressive motility, impaired acrosome reaction, and membrane depolarization during capacitation (Schreiber et al. , 1998; Santi et al. , 2010; Zeng et al. , 2011). These data indicate that Slo channels are essential for male fertility in mice, which makes them possible candidates for being the major K+ channel of human sperm. The goal of our work was to resolve the identity of the major K+ channel in human ejaculated spermatozoa. By applying the patch-clamp technique to ejaculated and epididymal human sperm cells, we found that human K+ currents are insensitive to intracellular alkalinization but are dependent on intracellular [Ca2+]. We furthermore demonstrate that the human sperm potassium (hKSper) current is inhibited by three known Slo1 channel inhibitors: charybdotoxin (Anderson et al. , 1988; MacKinnon and Miller, 1988), iberiotoxin (Galvez et al. , 1990; Candia et al. , 1992; Giangiacomo et al. , 1992) and paxilline (Knaus et al. , 1994c; Sanchez and McManus, 1996; Zhou et al. , 2010), as well as by the micromolar concentrations of progesterone. Taking together our electrophysiological, biochemical, and immunocytochemistry data, we conclude that the Slo1 protein constitutes a major potassium","The sperm cells that are released into the female reproductive tract when a mammal ejaculates, are not capable of fertilizing an egg right away, so they must go through a process called maturation. The early stages of this process involve interactions with the seminal fluid that increase the motility of the sperm cells, and the latter stages involve interactions with the walls of the reproductive tract and vaginal secretions to ensure that the sperm cells move toward the egg. Many of these interactions involve positive ions entering and leaving the sperm cells via ion channels. The properties of the ion channels that allow protons and calcium ions to move into and out of human sperm cells are well understood, but little is known about the channels that control",380,128,0.3368
scientific_lay_summarisation-elife-norm,"responses (DeLong et al. , 1984; Turner and Anderson, 1997; Spraker et al. , 2007; Vaillancourt et al. , 2007). Direct recordings from basal ganglia targets in patients suggest that changes in frequency specific activities in the local field potential (LFP) contribute to the selection of effort or force levels for voluntary movements. For example, the power over the gamma band (60–80 Hz) in the LFP in the globus pallidus correlates with the movement amplitude and velocity of the contralateral hand of patients with cranial dystonia (Brücke et al. , 2012). Similar correlations have been noted in patients with Parkinson’s disease between movement speed and the power in the gamma band in the LFP picked up from the STN (Joundi et al. , 2012). Our previous studies also showed that suppression in the beta band (13–30 Hz) and power increase in the gamma band of the STN LFP may correlate with forces or efforts made over the lower and higher effort ranges, respectively, in a manner independent from the effector that was activated (Tan et al. , 2013,2015). These results suggest that the signals from basal ganglia may serve as a central signal indexing motor effort, which in turn modulates force in manual grips. However, most previous studies are based on static linear correlations and averaged data; the dynamic relationship between activities of different frequencies in the basal ganglia LFP and generated force, and whether this relationship can be used to decode gripping force based on basal ganglia LFP signals has not been investigated on a trial by trial basis. The aim of the current study was to decode gripping force profiles from LFPs recorded in the STN. We hypothesized that beta and gamma band activities will be the most informative features in predicting the force profile generated by the contralateral hand, and that a simple first order linear dynamic model is sufficient to capture the relationship between STN LFP features and generated force. Our results suggest that reciprocal changes in synchronised oscillatory population activity in different frequency ranges provide potential control signals for the motor plant, the action of which can be modelled as a first order linear dynamical system. At the same time our results raise the possibility of using the LFP signal recorded from deep brain structures","The basal ganglia are a group of structures deep within the brain. Alongside its many other roles, it is thought to be able to control the vigour of movements, including how quickly we move and how much force we use to grip objects. Some of the best evidence for this comes from patients with Parkinson’s disease, who show abnormal activity of the basal ganglia. These patients move more slowly than healthy individuals and often struggle to grip objects with desired force, making it difficult to perform everyday tasks. Inserting electrodes into the brain and using them to electrically stimulate the basal ganglia is one of the most effective treatments for severe Parkinson’s disease. To examine the relationship between activity in the basal ganglia and grip strength, Tan et",380,128,0.3368
dialogsum,"#Person1#: Hello, this is South Airlines. May I help you? #Person2#: Yes, please. Mrs. Dick booked a ticket for Fight No. 112 to New York at 9:00 tonight. I'm afraid it's difficult for her to take it at that time. Is there a later fight tonight? #Person1#: Hold on, please. I'll check it. ...Yes, Mrs. Dick booked a ticket for Fight No. 112 to New York at 9:00 pm. #Person2#: That's right. Please help me to call it off. #Person1#: OK. And here's another flight, No. 211, at twenty to twelve. Is it OK? #Person2#: That's fine. Please book a ticket for this one. #Person1#: All right. Call off the ticket for Fight No. 112 and book one seat on Fight No. 211 to New York. #Person2#: Flight No. 211 to New York at twenty to twelve. That's perfect. Mrs. Dick will pick up the ticket at the airport herself. #Person1#: Good. But please remember it must not be collected later than 11:10, and I need to check the ID card. #Person2#: I'm sure she will do it by the time. I'll remind her. Thanks. #Person1#: You are welcome.",#Person2# wants to call off a flight and books a later one for Mrs. Dick. #Person1# deals with it for #Person2# and asks #Person2# to remind Mrs. Dick to collect the ticket on time with her ID.,189,37,0.1958
pubmed-summarization,"of two or more risk factors ) for their potential impact on the prevalence of prediabetes and ir within and across the ses gradient . within and across each level of ses , to examine the associations between known behavioral risk factors for diabetes ( low diet quality , poor sleep , low physical activity , and high waist circumference ) and both prediabetes and ir ; to examine these modifiable factors collectively ( presence of two or more risk factors ) for their potential impact on the prevalence of prediabetes and ir within and across the ses gradient . the boston area community health ( bach ) survey is a longitudinal cohort study of residents of boston , ma , aged 3079 years at baseline ( march 2002june 2005 ) . briefly , a stratified two - stage cluster sample was used to recruit an approximately equal number of participants by gender , race / ethnicity ( black , hispanic , white ) , and age group ( 3039 , 4049 , 5059 , 6079 ) . 5,502 adults participated in baseline bach i ( 1767 black , 1876 hispanic , 1859 white ; 2301 men , 3201 women ) . follow - up surveys were collected at two time points approximately 5 ( bach ii 20062010 ) and 7 ( bach iii 20102012 ) years later . for bach iii , completed interviews were obtained for 3155 individuals ( 1184 men ; 1971 women ) . in all surveys , data were collected during a two - hour interview in english or spanish , after obtaining written informed consent . analyses for this paper use data from the most recent interview , bach iii ( 20102012 ) . education , based on years of education completed , is composed of four categories : < high school , high school or ged , some college , or college or advanced degree . income was collected as total annual income and categorized into three categories : < $ 20,000 , $ 20,000$49,999 , or $ 50,000 + . physical activity was measured using the physical activity for the elderly ( pase ) scale and categorized into low , moderate , or high . anthropometric measures - trained field interviewers directly","to examine whether behavioral risk factors associated with diabetes ( diet , bmi , waist circumference , physical activity , and sleep duration ) are also related to both prediabetes and insulin resistance ( ir ) , we used data from boston area community health ( bach ) survey ( 20102012 , n = 3155 ) . logistic and linear regression models were used to test the association of lifestyle factors with prediabetes status , insulin resistance , and prediabetes or insulin resistance . all regression models were stratified by education and income levels ( to examine whether risk factors had differential effects across socioeconomic factors ) and adjusted for age , gender , race / ethnicity , family history of diabetes , and smoking status . we",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the outer plasmalemma monolayer with bacterial sphingomyelinase C (Lariccia et al. , 2011). It has been suggested that this form of MEND becomes activated during cell wound responses when native sphingomyelinases are translocated to the cell surface via exocytosis (Tam et al. , 2010; Corrotte et al. , 2013). We describe here experiments that suggest an entirely different pathway by which MEND occurs in BHK fibroblasts subsequent to large Ca transients. These ATP-dependent endocytic responses are functionally similar to ‘excessive’ endocytosis that occurs after large Ca transients in secretory cells (Smith and Neher, 1997). Up to 70% of the cell surface of fibroblasts can be internalized, followed by replenishment of the plasmalemma from internal membrane pools over 20 to 40 min (Lariccia et al. , 2011). To elucidate the cellular pathway by which MEND occurs, we attempted first to resolve how Ca promotes MEND, and second, to understand why more ordered membrane domains would be selectively internalized. As described here, our data support the hypothesis that Ca transients act initially to prime mitochondria to open PTPs (permeability transition pore) (Giorgio et al. , 2013), releasing metabolites to the cytoplasm (Azzolin et al. , 2010). At the distal end of the pathway, our data suggest that palmitoylation of surface membrane proteins promotes the coalescence of ordered membrane domains by promoting protein clustering, as described biochemically (Levental et al. , 2010) and as occurs in anoxia-related metabolic stress (Frank et al. , 1980). That mitochondria might regulate surface membrane palmitoylation and thereby endocytosis is a novel hypothesis. Nevertheless, studies that suggest how this might occur have been available for decades. First, it is known that coenzyme A (CoA), which is synthesized on the outer mitochondrial surface, is accumulated into the matrix space by voltage-sensitive transporters (Tahiliani, 1991; Leonardi et al. , 2005), generating CoA gradients to the cytoplasm of at least 50: 1 (Tahiliani and Neely, 1987). Therefore, transient openings of nonselective mitochondrial pores, PTPs, can potentially release CoA and generate cytoplasmic CoA transients in the range of tens of micromolar without serious consequences for other mitochondrial metabolites. Second, the low micromolar concentration of free CoA in the cytoplasm has long been suggested to limit cytoplasmic acyl CoA synthetase activities (Idell-Wenger et al. , 1978), whereas free CoA is less likely to","Cells use a process called endocytosis to absorb proteins and other molecules. There are many forms of endocytosis, but they usually involve the molecule of interest becoming tucked into a bud that forms in the cell membrane. This bud is then pinched off to leave the molecule inside a vesicle that is inside the cell. In general endocytosis is triggered by ‘caging’ proteins such as clathrin, but other forms are also possible. These “non-classical” forms of endocytosis are involved in processes as diverse as the internalization of pathogens and the response of cells to wounding, and sometimes they involve large fractions of the cell membrane being pinched off. Several different forms of “massive endocytosis” have been observed, but they have remained enigmatic in comparison to the classical forms",380,128,0.3368
dialogsum,"#Person1#: Is there anything I can do for you? #Person2#: Yes, I'd like to buy a color TV. #Person1#: We carry products from three large manufacturers and some imported ones, too. Do you have a specific model in mind? #Person2#: No. Which one do you recommend? #Person1#: This one from Sony gives a very sharp picture. #Person2#: Thank you, but I'd prefer to buy a China-made set. #Person1#: Which brand do you prefer? #Person2#: Sky worth. #Person1#: OK. Come with me, please.",#Person1#'s assisting #Person2# in choosing a color TV.,82,8,0.0976
dialogsum,"#Person1#: Ma'ma, come in, please. #Person2#: Excuse me, are you a manager? #Person1#: Yes, what can I do for you? #Person2#: Well, I have received such poor service from your employees this morning. I felt I had to let you know. #Person1#: I'm sorry, ma'am, please tell me what happened. #Person2#: I was asking that woman over there in the black dress where the men section was, and she completely ignored me while continuing to talk on her cellphone. #Person1#: That's not ok. #Person2#: There's more, I waited outside the changing room for 10 minutes, only to find the person inside was another staff member. #Person1#: That should never happen, I... #Person2#: I'm not finished yet. When I came out of the changing room, there were 3 employees outside. The lady in red said I looked fat, I was so embarrassed. #Person1#: Ma'am I promise you I will speak with them immediately about this. In the mean time. I'll give you 50% off whatever you decide to purchas. #Person2#: Well, that's the least you can do.",#Person2# complains to #Person1# about the poor service of employees in their store. #Person1# apologizes and offers a 50% discount.,176,20,0.1136
pubmed-summarization,"but seeding into surrounding muscle , fascia , and skin may only be apparent months , or even years , after surgery . as was seen with this case , the biopsy needle traversed skin , subcutaneous tissue , multiple muscle and fascia layers , and perinephric fat before reaching the renal lesion ( . thus , the tumor could theoretically seed into one or more of these tissues ; seeding as superficial as the subcutaneous tissue has been reported ( table 1 ) . this delayed presentation may increase the risk of adverse outcomes such as further metastasis and poorer prognosis . time to presentation or diagnosis of tumor seeding after renal mass biopsy has ranged from 24 days to 84 months in previously reported cases where tumor seeding was not found on the initial histopathological analysis ( table 1 ) . in conclusion , a common feature in all reported cases of needle tract seeding from a renal mass biopsy is that a coaxial needle was not used . however , because of the paucity of cases , there is currently no satisfactory association between the risk of needle tract seeding and needle size or the number of needle passes . it is important to consider that histopathological evidence of needle tract seeding may not be apparent in all cases , especially if seeding occurred beyond the excised tissues .","a 66-year - old man underwent computed tomography - guided needle biopsy of a suspicious renal mass . two months later he underwent partial nephrectomy . histology revealed a 30-mm clear cell renal cell carcinoma , up to fuhrman grade 3 . an area of the capsule was interrupted , which corresponded to a hemorrhagic area on the cortical surface . under microscopy , this area showed a tongue of tumor tissue protruding through the renal capsule . a tumor deposit was found in the perinephric fat . these features suggest that tumor seeding may have occurred during the needle biopsy .",232,102,0.4397
pubmed-summarization,"activity was within the fluid density space of the pericardial effusion and not limited to solely the pericardium itself [ ] . additionally , there were moderate bilateral pleural effusions and abdominal ascites , which demonstrated similar persistent and uniform radiotracer uptake [ figures 2 and 3 ] [ table 1 ] . these findings are compatible with malignant involvement , particularly given this patient 's history of prior pathology - proven malignant pericardial effusion . axial pet / ct images demonstrate 18-f fdg radiotracer uptake in moderate pericardial effusion ( arrows ) . pet = positron emission tomography , ct = computed tomography , 18-f fdg = 18-flourodeoxyglucose whole body mip . coronal whole body mip image obtained 1 h after the intravenous injection of 19.6 mci 18-f fdg . mip = maximum intensity projection , 18-f fdg = 18-flourodeoxyglucose ( a and b ) the 18f - fdg accumulation over time . metabolically active bilateral pleural effusions ( crosshairs ) at ( a ) 1-h and ( b ) 2-h postinjection . 18-f fdg = 18-flourodeoxyglucose standardized uptake value maximum over time of note , the pet / ct also demonstrated no significant hypermetabolic cervical , thoracic , abdominal , or pelvic lymphadenopathy despite the above - described fdg - avid fluid collections [ ] . axial pet / ct images demonstrate 18-f fdg radiotracer uptake ( crosshairs ) in ( a ) abdominal and ( b ) pelvic ascites . pet = positron emission tomography , ct = computed tomography , 18-f fdg = 18-flourodeoxyglucose the patient received chemotherapy and follow - up restaging pet / ct demonstrated interval resolution of the hypermetabolic pericardial , pleural , and peritoneal effusions [ ] . pel is a rare subtype of non - hodgkin 's lymphoma characterized by malignant effusions in the body cavities such as the pericardial , pleural , and peritoneal cavities in the absence of lymphadenopathy or organomegaly . pel was first described in 1989 in a patient with hhv8 and human immunodeficiency virus ( hiv ) infection . when pel occurs in the absence of hhv8 , the term hhv8-unrelated pel - like lymphoma has been used in the literature . the described pet / ct findings in our case of hhv8-unrelated pel - like","we present a 71-year - old female with human herpes virus 8 ( hhv8)-unrelated primary effusion lymphoma ( pel)-like lymphoma . dyspnea and pericardial effusion led to pericardiocentesis , diagnosing diffuse large b - cell lymphoma . she underwent positron emission tomography / computed tomography ( pet / ct ) , which demonstrated hypermetabolic pericardial , pleural , and ascites fluid without lymphadenopathy elsewhere . malignant fluid in the absence of lymphadenopathy is a hallmark of pel . pel is associated with immunodeficiency states such as acquired immunodeficiency syndrome ( aids ) and infectious agents such as hhv8 . our patient had no such history and had not received immunosuppressive chemotherapy . we present the pet / ct findings of this rare case of hhv8-unrelated pel - like",380,128,0.3368
pubmed-summarization,"hcv - containing blood resulted in a transient increase the frequency of activated nk cells in the blood and their effector functions ( both cytotoxicity and ifn production ) . the magnitude of the nk cell response correlated with that of the subsequent hcv - specific t - cell response . this likely represents an early innate response to an abortive or rapidly contained and cleared infection , because neither viremia nor hcv - specific antibodies are detected . collectively , these studies demonstrate that nk cells are sensitive biomarkers of subclinical hcv exposure . while it is possible that nk cells along with other components of the innate immune system contribute to viral containment in this setting , it is obvious that innate immune responses on their own can not clear the infection once high - level hcv viremia is established . data from prospectively studied humans and experimentally infected chimpanzees demonstrate that high - level hcv viremia persists for weeks despite induction of a large set of intrahepatic interferon - stimulated genes ( isgs ) . this immune response is initiated in the cytoplasm and in endosomes of infected cells by the pattern recognition receptors protein kinase , retinoic acid inducible gene - i , and toll - like receptor 3 ( tlr3 ) . downstream signals , mediated by interferon regulatory factor 3 ( irf3 ) and nuclear factor - kb , result in the transcription of the ifn gene . ifn is released from infected cells , binds to the ifn/ receptor ( ifnar1 and ifnar2 ) on neighboring cells , and induces a diverse isg set that includes many antiviral and proinflammatory genes . however , owing to hcv s elaborate strategies to escape from ifn responses , there is no decrease in viremia , just a plateau . the onset of clinically symptomatic acute hepatitis with increased alanine aminotransferase levels occurs 8 to 10 weeks after infection . without treatment , two - thirds of the infected patients develop chronic hepatitis c , which is associated with a 23 log10 reduction in viral titer . because liver biopsies are clinically not indicated in the acute phase of hepatitis c , the intrahepatic effector responses responsible for the decrease in viremia have not been studied","natural killer ( nk ) cells are traditionally regarded as first - line effectors of the innate immune response , but they also have a distinct role in chronic infection . here , we review the role of nk cells against hepatitis c virus ( hcv ) and hepatitis b virus ( hbv ) , two agents that cause acute and chronic hepatitis in humans . interest in nk cells was initially sparked by genetic studies that demonstrated an association between nk cell related genes and the outcome of hcv infection . viral hepatitis also provides a model to study the nk cell response to both endogenous and exogenous type i interferon ( ifn ) . levels of ifn - stimulated genes increase in both acute and chronic",380,128,0.3368
dialogsum,"#Person1#: May I help you, sir? #Person2#: Yes, please. I'm looking for a cotton polo shirt. #Person1#: Any particular colour? #Person2#: Not really. #Person1#: How about this one? #Person2#: I like the design, but don't particularly care for the colour. Do you have that in other colours, too? #Person1#: Well, they come in white, pale yellow, aqua, red and green. Will a white one do? #Person2#: Yes. I prefer white - and may I see a pale yellow one, too? #Person1#: Why, of course. Let's see... White... Pale yellow. Here you are, sir.","#Person2# is looking for a cotton polo shirt. #Person1# recommends a white one. #Person2# likes it and wants to see a pale yellow one, too.",93,25,0.2688
dialogsum,"#Person1#: Have you find any job that you are interested in? #Person2#: I'Ve only find a few openings in my field. #Person1#: There's not a very high demand for that kind of job, isn't there? #Person2#: Unfortunately not. If I can't find anything in that field, then I could also work in the marketing field. #Person1#: That's a good idea. You have plenty of experience in marketing, don't you? #Person2#: Yes. #Person1#: By the way, I saw a job in the paper this morning that you might be interested in. #Person2#: Really? What is it? #Person1#: It is a job at an advertisement company. #Person2#: Do you think they'd hire me? #Person1#: Anyway, it is worth trying.",#Person2# can't find a job in #Person2#'s field. #Person1# saw a job in an advertisement company and recommends it to #Person2#.,117,21,0.1795
dialogsum,"#Person1#: Have you bought a bus pass yet? #Person2#: I'm not getting one. #Person1#: Why is that? #Person2#: It's cheaper if I don't buy one. #Person1#: Buying a bus pass will save you money. #Person2#: How do you that? #Person1#: There's no limit to how often you can use your bus pass. #Person2#: Really? #Person1#: Plus, you don't have to use change for the bus anymore. #Person2#: I like that. #Person1#: You want to buy one now? #Person2#: I'm going to.",#Person2# isn't getting a bus pass. #Person1# explains it will save #Person2# money. #Person2# will buy one.,81,17,0.2099
dialogsum,"#Person1#: Tell me, what do you enjoy doing in your spare time? #Person2#: I enjoy drawing and painting. #Person1#: You know how to draw and paint? #Person2#: Yes, I do. #Person1#: When did you learn how to do that? #Person2#: I learned back in high school. #Person1#: Oh, so you took an art class? #Person2#: Yeah, I loved that art class. #Person1#: I see that you're pretty talented. #Person2#: Thank you very much. #Person1#: I wish I had a talent like that. #Person2#: I'm sure you have a talent. It's just hidden.",#Person2# enjoys drawing and painting in the spare time. #Person1# wishes #Person1# has a talent like #Person2#.,92,17,0.1848
dialogsum,"#Person1#: Has your son started school yet, Tom? #Person2#: Next week, it's going to be quite a shock for him! #Person1#: He'll get used to it. They always do. I still remember when my daughter started. Are you going with him on his first day? #Person2#: You bet. I wouldn't miss it!",Tom tells #Person1# he will go with his son on the first day of school.,52,15,0.2885
scientific_lay_summarisation-elife-norm,"(Li et al. , 2015), and germ cells in the testes (Li et al. , 2016). HMMR is expressed in the developing nervous system (Casini et al. , 2010) and proliferative regions of the adult mouse brain (Lindwall et al. , 2013), Recently, HMMR has been shown to be required for anterior neural tube closure and morphogenesis in Xenopus, where HMMR reduction leads to the absences of ventricular lamina and increased intraocular distance, olfactory bulb size, and forebrain width (Prager et al. , 2017). The N-terminal microtubule binding region in HMMR is needed for neural tube morphogenesis in Xenopus (Prager et al. , 2017) and the very terminal region is similar to that of Miranda (Chang et al. , 2011), a regulator of asymmetric NP cell division in Drosophila (Ikeshima-Kataoka et al. , 1997; Shen et al. , 1997). Hmmr mutant mice models are viable, including when central exons are targeted in Hmmr−/− mice (Tolg et al. , 2003) and Hmmrm/m mice (Li et al. , 2015), which result in the expression of truncated Hmmr transcript and protein (exons 1–7 or exons 1–10, respectively). Here, we studied the requirement of HMMR during oriented NP cell division and nervous system development through the creation of Hmmr-deficient mice with targeted disruption of Hmmr following exon 2. We find that HMMR is needed for neonatal survival and proper brain development. Our studies using cultured primary fibroblasts, directed differentiation of embryonic stem cells, and immortalized cancer cell lines, including neuroblastoma-like cells, uncovered a role for HMMR in the PLK1-dependent positioning pathway at mitotic spindle poles. We generated mice encoding a targeting construct following Hmmr exon 2, termed Hmmrtm1a (EUCOMM) Hmgu (hereafter Hmmrtm1a/tm1a, 1A, — 1A–B). Western blot analysis of lysates from tissues known to have elevated levels of HMMR expression (spleen and testes) (Line et al. , 2002) using antibodies targeting the N-terminal peptide in HMMR revealed that HMMR expression was completely lost in Hmmrtm1a/tm1a mice (1B). Adult Hmmrtm1a/tm1a mice were rare, and those Hmmrtm1a/tm1a mice that did survive were smaller than their wild-type (WT) littermates (1C). Similar to the phenotypes seen in Hmmrm/m mice attributed to misoriented germ cell divisions (Li et al. , 2016), we observed atrophic seminiferous tubules and an increase in apoptosis in the testes as indicated by TUNEL staining","As an embryo develops, its cells divide, grow and change into many different types of cells that eventually build our body. When cells divide, they first need to duplicate their genetic material. A structure called the spindle then distributes the two copies of the genetic information between the new cells. Cells must position their spindle precisely, and the way the spindle is oriented helps to determine what type of cell will develop. If the spindle fails to align properly, it can disrupt the development of specific tissues and organs and even lead to diseases such as cancer. Numerous proteins help to position the spindle. For example, a protein called Ran-GTP ensures that motor proteins are anchored on opposite sides of the dividing cell, which tug on the spindle",380,128,0.3368
pubmed-summarization,"nurses with expertise should be used in various stages of the crisis , including disaster response . in studies on the experiences of nurses working in emergency departments , most of the participants emphasized on the key role of skilled and trained nurses in crisis interventions and expressed that nurses should have the knowledge and competencies for professional services in critical situations . despite the important role of nurses in response to the crisis , little information on specialized skills or competencies needed to participate effectively in these situations are available . few nurses have the experience of providing care in critical situations and in providing care in response to a crisis . studies conducted on the nurses experiences in the presence of these situations suggest that most of them , after participating in the crises response team , declared that they did not have the adequate ability to meet the crisis . this can be attributed to the lack of relevant content and appropriate education in the field of their formal education . hsu believes that the available information about the competencies needed in response to the crisis are not strongly evidence - based , and most of the nurses do not earn these capabilities and only after attending a critical situation they discover that these skills are also required . therefore , determining the competencies required by nurses to effectively participate in response to disaster team is necessary . magnaye suggested that in this area , during response to crisis , nurses require specialized skills and competencies in order to care for the victims . furthermore , technical skills are the most important among other skills . however , the details of these competencies are not clearly explained . in iran , at the current moment , nursing in a crisis is not well - defined and the competencies required of nurses to provide services in a crisis have not been well - established . therefore , integrated educational programs based on the needs in this area are not available . nurses only receive a limited amount of training during their undergraduate courses on emergency and nursing care in these situations . moreover , their training is not based on their needs for successful participation during critical times","background : today disasters are a part of many people 's lives . iran has a long history of disaster events and nurses are one of the most significant groups within the iranian disaster relief operations , providing immediate and long - term care for those affected by the disaster . however , the technical competence of iranian nurses and their training for this work has received little attention . this article presents the results of a study that aims to explore this context.materials and methods : a qualitative study was conducted using in - depth interviews to collect data from 30 nurses , who were deliberately selected from the health centers affiliated to the isfahan university of medical sciences . themes were identified using the conventional qualitative",380,128,0.3368
dialogsum,"#Person1#: Hey neighbor, I'm going out of town this weekend and I was wondering if you could take care of my dog while I'm gone. You know, my dog Jaws, don't you? #Person2#: Yeah. #Person1#: Just feed him a can of dog food a day and make sure he has plenty of water in his dish. Oh, and he needs someone to take him for a walk around the block every afternoon. #Person2#: Well, how about if I just throw a ball over the fence to give him some exercise. #Person1#: No, he really needs a walk. Ah, and he likes to watch the 3:00 o'clock soap opera on Channel 4 and then you'll need to brush his teeth after you give him doggie treats at 4:00 o'clock. #Person2#: You must be out of your mind if you think I'm going to watch your dog. I wouldn't watch that dog even if you paid me.",#Person1# asks the neighbor #Person2# to take care of dog Jaws. #Person1# lists many things that #Person2# needs to do. #Person2# wouldn't watch that dog even if #Person1# paid #Person2#.,155,30,0.1935
scientific_lay_summarisation-elife-norm,", 2005; Ceresa, 2006; Vanlandingham and Ceresa, 2009; Levkowitz et al. , 1999). Although EGFR vesicular trafficking was extensively studied after ligand stimulation, little is known about the role of vesicular trafficking in suppressing spontaneous EGFR activation as well as regulating its signaling response. To assess how vesicular membrane dynamics modulates spontaneous and ligand-induced phosphorylation of EGFR, we studied three phosphorylation sites on EGFR with distinct functionality: 1) Y845—a regulatory autocatalytic tyrosine whose phosphorylation increases EGFR activity (Shan et al. , 2012), 2) Y1045—a site that upon phosphorylation affects vesicular trafficking of EGFR by binding the E3 ligase c-Cbl that ubiquitinates the receptor (Levkowitz et al. , 1998), and 3) Y1068—a site that upon phosphorylation binds the adapter Grb2 via its SH2 domain to propagate signals in the cell (Okutani et al. , 1994). We show that spontaneously and ligand-induced EGFR activation gives rise to distinct molecular states that are recognized and processed differently by the endocytic machinery. While unliganded monomeric receptors continuously recycle to the PM to suppress autocatalytic activation, ligand-bound dimeric receptors are ubiquitinated by the E3-ligase c-Cbl that commits them to unidirectional vesicular trafficking toward lysosomes. This route through perinuclear endosomes enables their efficient dephosphorylation by high local PTP activity to produce a finite signaling response to growth factors. We demonstrate by a compartmental model that ligand-responsive EGFR signaling can only occur in conjunction with suppression of spontaneous autocatalytic EGFR activation if a ligand-induced switch in EGFR trafficking changes its cyclic interaction with spatially partitioned PTPs to a sustained one. To investigate how EGFR auto-phosphorylation depends on its cell surface density, we quantified the relative phosphorylation (pY/EGFR) of three tyrosine residues with distinct regulatory functionality of autocatalysis, signaling, and trafficking in single COS-7 cells as a function of EGFR-mCitrine expression level. The variance in ectopic expression of EGFR-mCitrine was thereby exploited to sample a broad range of receptor expression levels. The EGFR-mCitrine expression level in single cells was determined relative to endogenous EGFR by an independent immunofluorescence experiment where the level of endogenously expressed EGFR was quantified from the abscissa-intercept of a linear fit to an EGFR-mCitrine intensity versus anti-EGFR antibody intensity plot (— 1A, B). This analysis showed that most COS-7 cells expressed EGFR-mCitrine at similar level as endogenous EGFR, whereas the expression varied by a","In living tissue, the ability of individual cells to grow is influenced by signal molecules in the environment around each cell. For example, after an injury, a molecule called epidermal growth factor can stimulate cells to grow to repair the wound. Epidermal growth factor binds to and activates a receptor protein called EGFR, which faces outwards from the cell surface. However, this signal needs to be switched off again afterwards to prevent the cells from growing too much. Epidermal growth factor activates EGFR by triggering a process called “autophosphorylation”, in which EGFR attaches molecules called phosphates to itself. To quench the signal, EGFRs that are bound to growth factors are removed from the cell surface and taken into the cell in small membrane bubbles called vesicles. Enzymes called",380,128,0.3368
dialogsum,"#Person1#: What can I get for you today? #Person2#: Could I get a hamburger, please? #Person1#: Would you like cheese on that? #Person2#: No, thank you. #Person1#: Would you like a drink? #Person2#: Let me have a soda. #Person1#: What kind of soda would you like? #Person2#: May I have a Sprite, please? #Person1#: Sure, no problem. #Person2#: I would also like a bag of chips. #Person1#: Will that be all? #Person2#: That's everything.","#Person2# orders a hamburger, a Sprite and chips from #Person1#.",74,10,0.1351
dialogsum,"#Person1#: We've overspent dreadfully this month. #Person2#: By how much? #Person1#: It looks to me as if it's getting on for almost 400 pounds. #Person2#: Oh, does that mean we won't be able to get our holiday? #Person1#: I honestly don't think that we could afford to go really. #Person2#: But we haven't had a holiday for three years! Just because we can't afford it. #Person1#: That's true. #Person2#: I was really looking forward to this holiday... three weeks in Barbados at Christmas-warmth, sea, sunshine. #Person1#: I know. So was I. #Person2#: Can't we ask your mother for the money? Can't we borrow the money from somewhere for the holiday? #Person1#: Well, You know we're still in debt over the car. And we've always said we wouldn't borrow money for things that weren't absolutely essential. A holiday isn't essential. #Person2#: I really feel it is this time. #Person1#: Well, let's look at cheaper holidays then. Let's look at somewhere closer to home, right. Let's look at Europe. #Person2#: Well, there's no point in going to Europe at Christmas, is there? #Person1#: Well, you said you wanted to get away from the cold here. Well, you only want to go where it's hot and sunny? #Person2#: Yes, I want some warmth. #Person1#: Oh, I think we ought to borrow the money from your mother. #Person2#: I don't want to talk about it anymore. Let's discuss it some other time.","#Person1# and #Person2# overspent, so they cannot afford the holiday as they have planned. Both of them are disappointed but don't want to borrow money from their mothers.",238,28,0.1176
scientific_lay_summarisation-elife-norm,"Individuals with neurofibromatosis type 1 (NF1) frequently exhibit cognitive and motor impairments and characteristics of autism. The cerebellum plays a critical role in motor control, cognition, and social interaction, suggesting that cerebellar defects likely contribute to NF1-associated neurodevelopmental disorders. Here we show that Nf1 inactivation during early, but not late stages of cerebellar development, disrupts neuronal lamination, which is partially caused by overproduction of glia and subsequent disruption of the Bergmann glia (BG) scaffold. Specific Nf1 inactivation in glutamatergic neuronal precursors causes premature differentiation of granule cell (GC) precursors and ectopic production of unipolar brush cells (UBCs), indirectly disrupting neuronal migration. Transient MEK inhibition during a neonatal window prevents cerebellar developmental defects and improves long-term motor performance of Nf1-deficient mice. This study reveals essential roles of Nf1 in GC/UBC migration by generating correct numbers of glia and controlling GC/UBC fate-specification/differentiation, identifying a therapeutic prevention strategy for multiple NF1-associcated developmental abnormalities. Neurofibromatosis type 1 (NF1) is a genetically inherited disorder that afflicts 1 in 2700 newborns (Evans et al. , 2010). NF1 is caused by loss-of-function mutations in the NF1 tumor suppressor gene, which encodes neurofibromin, a negative regulator of proto-oncogene RAS (Cichowski and Jacks, 2001; Upadhyaya and Cooper, 2012). RAS mediates multiple signaling pathways including extracellular signal-regulated kinase (ERK) subfamily of mitogen-activated protein kinases (MAPK), phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin complex 1 (mTORC1) (Schubbert et al. , 2007; Mendoza et al. , 2011). In addition to the development of tumors in the peripheral and central nervous system (CNS), neurodevelopmental deficits are highly prevalent among children with NF1, negatively impacting cognition, motor function, and social interaction (Hyman et al. , 2005,2006; Johnson et al. , 2010; Krab et al. , 2011; Lorenzo et al. , 2011; Lehtonen et al. , 2013; Walsh et al. , 2013; Garg et al. , 2013a, 2013b; Adviento et al. , 2014; Champion et al. , 2014; Plasschaert et al. , 2014). While cognitive impairments associated with NF1 have been well documented, motor dysfunction, social and behavioral deficits including autism spectrum disorders (ASD) have only recently been established as common features of NF1 in childhood (Johnson et al. , 2010; Krab et al. , 2011; Lorenzo et al. , 2011; Walsh et al. , 2013; Garg et al. , 2013a, 2013b; Champion et","Neurofibromatosis type 1 is a condition characterized by the growth of tumors along the nerves of the body. It is caused by mutations in a gene called NF1, which codes for a protein that normally works to inhibit the activity of another protein called Ras. In healthy cells, Ras is needed to stimulate the cells to grow and divide. However, if the Ras protein is not turned off at the right time or if it is activated at the wrong time, it can force cells to keep growing and dividing; this leads to the growth of tumors. Along with being prone to developing cancer, individuals with neurofibromatosis type 1 also develop a range of neurodevelopmental disorders that alter their learning, motor skills and social interactions. Some also exhibit",380,128,0.3368
pubmed-summarization,"steroid hormones have been traditionally associated with regulation of peripheral organs , associated with stress ( corticosterone ) or with gonadal function ( estrogen and androgens ) . over the years , it became evident that these hormones also act within the hypothalamus , in a feedback regulatory loop , to affect the release of the neural factors that modulate production of the steroid hormones . more recently , several observations have elucidated new roles of steroid hormones in modulating higher cns functions . specifically , both stress and steroid hormones have been shown to affect synaptic receptors and ion channels and therefore regulate in several different ways synaptic transmission and neuronal plasticity . consequently , stress hormones have been implicated in processes ranging from homeostatic to cognitive functions . furthermore , in some disorders of the nervous system , hormones have been shown to play critical roles : favoring or halting the disease process . thus , the interaction between peripheral hormones and central networks seem to be more intense than ever imagined before . in the present study we review current knowledge on the effects of steroid hormones on synaptic plasticity and define their influence on hippocampal cognitive and emotional functions . following the exposure to stressful stimuli , the steroid hormone corticosterone ( cortisol in humans ) is released from the adrenal glands in order to set up the best response to the challenge by acting on steroid receptors ( de kloet et al . , 2005 ) . these are distributed throughout the body and have a particularly dense distribution in the cns ( de kloet et al . , 2005 ) . in the brain , the cellular and molecular targets for the action of corticosterone include , in addition to basic metabolic processes , an effect on excitatory ( karst and joels , 2005 ) and inhibitory ( maggio and segal , 2009a ) synaptic transmission , as well as an effect on voltage - gated calcium channels ( vgcc ; karst et al . , 2000 ; these effects are mediated by the activation of mineralocorticoid receptors ( mrs ) and glucocorticoid receptors ( grs ; joels , 1999 , 2008 ; de kloet et al . , 2005 ) . initially ,","several new observations have shifted the view of the hippocampus from a structure in charge of cognitive processes to a brain area that participates in the formation of emotional memories , in addition to its role in cognition . specifically , while the dorsal hippocampus is involved in the processing of cognitive memories ; the ventral sector is mainly associated with the control of behavioral inhibition , stress , and emotional memory . stress is likely to cause this switch in control of hippocampal functions by modulating synaptic plasticity in the dorsal and ventral sectors of the hippocampus through the differential activation of mineralocorticosteroid or glucocorticosteroid receptors . herein , we will review the effects of stress hormones on synaptic plasticity in the hippocampus and outline the outcomes",380,128,0.3368
dialogsum,#Person1#: I can't believe how hot it is. #Person2#: It's not even noon yet. #Person1#: That means it will get hotter. #Person2#: I am dying from the heat. #Person1#: Turn on the air conditioner. #Person2#: It doesn't work. #Person1#: What happened? #Person2#: I don't know. #Person1#: Did you call the repairman? #Person2#: Of course. #Person1#: When is he coming? #Person2#: He's busy. He said next week.,#Person1# wants to turn on the air conditioner. #Person2# says it doesn't work and the repairman will come next week.,66,20,0.303
pubmed-summarization,"colchicine is a widely used drug for treatment of familial mediterranean fever ( fmf ) . clinical manifestations of colchicine intoxication include abdominal cramps , diarrhea , myotoxicity , hemolytic anemia and ( pan)cytopenia . a 9-years - old female patient , receiving colchicine for four months with a dose of 1 mg / day for fmf , was admitted to a hospital with gastrointestinal disturbance four days ago . she was referred to our hospital with liver and kidney dysfunction . at the initial physical examination her laboratory results revealed : hemoglobin 13.6 g / dl ; leukocyte , 9.610/l ; thrombocyte 5710/l ; fibrinogen 157 mg / dl ( 230 - 500 ) ; pt 26.1 sec ; inr 2.3 ; aptt 43.8 sec ; ldh 5329 iu / l ; ferritin 2320 g / l ( 10 - 55 ) ; triglyceride 7.1 mmol / l ( 0.32 - 1.46 ) . the patient was taken to intensive care unit ; vitamin k and fresh frozen plasma were administered . on the second day of her hospitalization hemoglobin was 9.6 g / dl ; leukocyte was 2.310/l ; neutrophil was 0.7210/l and thrombocyte was 2410/l . on peripheral blood smear , loss of lobulation in neutrophils was detected ( pelger - hut anomaly ) . laboratory tests revealed ferritin 54,632 g / l , triglyceride 7.4 mmol / l , and fibrinogen 63 mg / dl , serum creatinine 3.2 mg / dl ( 0.4 - 1.4 ) , serum blood urea nitrogen 43 mg / dl ( 6 - 21 ) , serum sodium 131 meq / l ( 134 - 148 ) , potassium 5.2 meq / l ( 3 - 4.8 ) , calcium 8.1 mg / dl ( 7.9 - 9.9 ) , and inorganic phosphate 2.1 mg / dl ( 2.4 - 4.7 ) . at the bone marrow aspiration , many pelger - hut cells were observed . soluble cd25 level was 2840 u / ml ( 220 - 710 ) , and creatine kinase level was 18,959 when the history of colchicine intoxication was detailed , during fmf attack - free period of five days prior to admission to the hospital , it is learned that the patient was upset","colchicine is frequently used in the treatment of familial mediterranean fever ( fmf ) . first symptoms of colchicine intoxication are gastrointestinal disturbances , such as abdominal cramps , diarrhea , pancytopenia and so on . herein , we report a female fmf patient with pancytopenia and hemophagocytic lymphohitiocytosis ( hlh ) , following colchicine intoxication for committing suicide . to our knowledge , this is the first reported case of a patient with hlh associated with colchicine intoxication .",380,80,0.2105
dialogsum,"#Person1#: Well, it's illegal to bring food and drinks into the theater. #Person2#: Too bad. I did anyway. #Person1#: No wonder you brought such a big bag today. #Person2#: I brought Strawberry Sticks. See? #Person1#: Those are the ones that are pre-dipped in sweet coating! #Person2#: Yep. And there's real strawberry chunks in the coating.","Although it's illegal, #Person2# brought Strawberry Sticks into the theater.",55,10,0.1818
dialogsum,"#Person1#: Good morning. #Person2#: Good morning. #Person1#: What's the problem? #Person2#: I'm running a high fever and feeling terribly bad. #Person1#: How long have you had that problem? #Person2#: Since last night. #Person1#: Then, you'd better go to the Medical Department. But first, you should fill in the registration card and the registration fee is one Yuan. #Person2#: Fine. But can you tell me how to get to the Medical Department, please? #Person1#: Take the lift to the third floor and then go along until you see the sign on your right. #Person2#: Thanks a lot. #Person1#: You're welcome.",#Person2# is running a high fever so #Person1# asks #Person2# to go to the Medical Department after registration.,99,18,0.1818
scientific_lay_summarisation-elife-norm,"al. , 2006; Shambharkar et al. , 2007; Yeh, 2009), which are believed to contribute significantly to signal specificity by directing downstream cues. NEMO, a key player of the IKK signalsome, is a scaffold protein that lacks enzymatic activity; yet, it is essential for NF-κB signaling evident by convergence of upstream signals directed by TRAFs prior to assembly of downstream IKK signals (Li et al. , 2001; May et al. , 2002; Prajapati and Gaynor, 2002; Yamamoto et al. , 2001). Recent studies have shown that specific NEMO domains and numerous lysine residues throughout the different domains of NEMO, especially the ubiquitin and zinc finger domains, undergo extensive ubiquitination, SUMOylation, and other post-translational modifications (PTMs) in response to various stimuli (Cordier et al. , 2009; Hay, 2004; May et al. , 2002; Rushe et al. , 2008; Schröfelbauer et al. , 2012; Sebban et al. , 2006; Wu et al. , 2006). Specifically, these domains and lysine residues serve as specific docking sites utilizing PTM moieties to enable recruitment of unique signaling complexes and pathway substrates in one hand, and proteasome-mediated degradation, in the other hand. Indeed, the critical role of a number of lysines and other residues such as K270, K302, K312, K392, C417 in cellular signaling have been described (Alhawagri et al. , 2012; Bloor et al. , 2008; Ni et al. , 2008; Yang et al. , 2004). In this regard, series of NEMO mutants at specific lysine residues located at the coil zipper domain revealed dominant negative and constitutive activation properties of NEMO (Bloor et al. , 2008). In the current study, we tested the functional significance of key lysine residues individually in the ubiquitin and zinc finger domains of NEMO in response to RANKL. This approach was designed to test our hypothesis that certain NEMO lysine residues serve as signal-specific docking sites that facilitate the assembly of unique signal activating- or suppressing-protein complexes in cell and stimulus specific manner. To address our aforementioned hypothesis, we conducted broad lysine (K) screen of NEMO and substituted strategic K and D residues in tandem with alanines and asparagine, as indicated, (1A), to disrupt post-translational modifications of specific NEMO lysines, and hence, impede assembly of protein complexes and alter subsequent signaling. Wild type (WT) NEMO (NEMOWT) and various NEMO","The human skeleton contains over 200 bones that together act as an internal framework for the body. Over our lifetime, the body constantly removes older bone tissue from the skeleton and replaces it with new bone tissue. This “bone remodeling” also controls how bones are repaired after being damaged by injuries, disease or normal wear and tear. Cells known as osteoclasts are responsible for breaking down old bone tissue and participate in repairing damaged bone. A cellular pathway known as NF-kB signaling stimulates other cells called “bone marrow macrophages” to become osteoclasts. A certain level of NF-kB signaling is required to maintain a healthy skeleton. However, under certain inflammatory conditions, the level of NF-kB signaling becomes too high causing hyperactive osteoclasts to accumulate and inflict severe bone breakdown.",380,128,0.3368
dialogsum,"#Person1#: Hello, Jim. Where are you going? #Person2#: To the cinema. What about coming with me? #Person1#: No, thanks. I'm going home. My friend's expecting me. #Person2#: What a pity! I believe it's a very good film. #Person1#: Do you go to the cinema a lot? #Person2#: Once a week. Most nights I sit at home and watch TV. #Person1#: Oh, I see. By the way, where are you going for your holidays this year? #Person2#: I don't know yet. My wife's going to her mother's for a couple of weeks. She lives by the sea, you know. #Person1#: Oh, does she? That's convenient. #Person2#: Yes, but I want to go to the country. #Person1#: Don't you like the sea? #Person2#: Yes, very much. But I need peace and quiet when I'm on holiday.",Jim is going to the cinema and invites #Person1# to join him but #Person1# is going home. They then talk about where to go for the holidays.,134,27,0.2015
dialogsum,"#Person1#: What's the matter with you? You don't look well. #Person2#: Nothing. Maybe it is just the weather. Rainy days often make me feel a little sad. #Person1#: Really? I like rainy days. The moisture in the air is good for my skin. #Person2#: Sure. But it is too cold today. I have to put on warm clothes and look stupid. #Person1#: Me, too. At this time of the year, I often miss my home in the warm south.","Rainy days make #Person2# sad, but #Person1# likes the moisture in the air.",79,13,0.1646
scientific_lay_summarisation-elife-norm,"Serine recombinases are often tightly controlled by elaborate, topologically-defined, nucleoprotein complexes. Hin is a member of the DNA invertase subclass of serine recombinases that are regulated by a remote recombinational enhancer element containing two binding sites for the protein Fis. Two Hin dimers bound to specific recombination sites associate with the Fis-bound enhancer by DNA looping where they are remodeled into a synaptic tetramer competent for DNA chemistry and exchange. Here we show that the flexible beta-hairpin arms of the Fis dimers contact the DNA binding domain of one subunit of each Hin dimer. These contacts sandwich the Hin dimers to promote remodeling into the tetramer. A basic region on the Hin catalytic domain then contacts enhancer DNA to complete assembly of the active Hin tetramer. Our results reveal how the enhancer generates the recombination complex that specifies DNA inversion and regulates DNA exchange by the subunit rotation mechanism. Site-specific recombination reactions have evolved as a relatively simple solution to a myriad of biological problems including gene regulation, viral integration, DNA transposition, chromosome segregation, and the programmed creation of genetic diversity (Craig, 2002). Most site-specific recombinases can be classified into two structurally and mechanistically unrelated groups that are named for the use of either a serine or tyrosine as the active site residue (Grindley et al. , 2006). Some reactions, such as those mediated by the tyrosine recombinases Cre and FLP, only require the recombinase and its cognate DNA binding sites, whereas others involve additional accessory proteins and assemble elaborate synaptic complexes that provide tight control over chemical and mechanical steps of the reaction. The synaptic complexes formed by serine recombinases contain the two recombining DNA segments on the outside of a tetrameric protein core (Dhar et al. , 2004; Nollmann et al. , 2004; Li et al. , 2005). All four DNA strands are cleaved by near simultaneous attack on the DNA backbone by the catalytic serines to form 5′-phosphoserine linkages, thereby generating double-strand breaks at both recombination sites. DNA strands are then exchanged by a subunit rotation mechanism where one pair of synapsed subunits, together with their covalently-bound DNA strands, rotates 180° relative to the other pair (Stark et al. , 1989; Dhar et al. , 2004,2009a, 2009b; Li et al. , 2005; Bai et al. , 2011).","Many processes in biology rely on enzymes that break both the strands in a DNA molecule, then rearrange the strands, and finally join them back together in a new configuration. These recombination reactions can, for example, change the positions of genetic elements such as enhancers and promoters within the DNA molecule and, therefore, influence how a given gene is expressed as a protein. Cells need to be able to control recombination reactions because they can lead to leukemia and lymphomas if they go wrong. The enzymes that catalyze these recombination reactions are called recombinases. One type of recombinase binds to specific sequences of DNA bases and uses an amino acid in the enzyme–usually serine or tyrosine–to break and rejoin the DNA strands. Recombination reactions require the assembly of",380,128,0.3368
dialogsum,"#Person1#: I hear there will be a football competition between all senior schools next month. Is that so? #Person2#: That's true. #Person1#: Would you please go into some more details? #Person2#: Well, the competition will be held in our school and it will begin on August 11. The competition will last a whole week. #Person1#: Anything else? #Person2#: Yes, both the girls and boys competition will be held at the same time. The girls competition will be held in the morning and the boys competition will be held in the afternoon. #Person1#: Yes? Sounds exciting. #Person2#: We are both members of our school football team. We should be ready for it. #Person1#: Of course. It's a long time since we had the last football competition last time. I'm really looking forward to another competition. #Person2#: Me, too.",#Person2# tells #Person1# the details of a football competition between all senior schools next month. They both look forward to it.,137,21,0.1533
dialogsum,"#Person1#: Tired again, Samantha. #Person2#: Oh, sorry, James. I've had such a busy week and this morning was just. Uh...I woke up really early at 5:30 AM and then I couldn't get back to sleep. So I got up. #Person1#: What? At 5:30 AM on a Saturday morning? #Person2#: Yes, then I had a shower and went out to catch a bus into town. Instead of 8 o'clock AM, it didn't come until 8:15 AM and it was raining hard. #Person1#: Oh, dear. What happened next? #Person2#: When I got to town, it was 9:15 AM. So first of all, I went to the library, but it was closed. So I waited until 10:00 AM for it to open. #Person1#: Why did you go to the library? #Person2#: I needed some information for my school project, but I spent 2 hours looking for something about the Kings and Queens of England. But all the books I needed were out of the library. #Person1#: Why didn't you go to the book shop in Stanley Street? #Person2#: I've didn't have enough money on me, so I caught the bus home at 12:30. #Person1#: What time did you get home? #Person2#: Not until 2:00 PM. The bus broke down and I had to walk the rest of the way home. #Person1#: Oh, dear.",Samantha tells James about her terrible morning. Samantha woke up at 5:30. The bus was late and it was raining. She waited until 10:00 outside the library and spent 2 hours but found nothing valuable. Then the returned bus broke down so she walked home until 2:00.,220,47,0.2136
scientific_lay_summarisation-elife-norm,"family transcription factor daf-19 is the central regulator of ciliogenesis, and dozens of target genes are known to effect its action (Efimenko et al. , 2005; Phirke et al. , 2011; Burghoorn et al. , 2012). The one Rfx factor in Drosophila is likewise well characterized (Laurencon et al. , 2007; Newton et al. , 2012). By contrast, multiple RFX family members are essential for ciliogenesis in vertebrates, but as yet, there has been no comprehensive genome-wide survey of Rfx-dependent gene expression as it relates to ciliogenesis (Bonnafe et al. , 2004; Ashique et al. , 2009; El Zein et al. , 2009). This gap in our knowledge of the genomics of RFX factors is made the more important because these proteins also possess cilia-independent functions about which very little is yet known, including control neuronal and pancreatic development (e. g. , Senti and Swoboda, 2008; Ait-Lounis et al. , 2010; Pearl et al. , 2011; Benadiba et al. , 2012). One vertebrate cell type in which Rfx factors are known to play particularly important roles is the multi-ciliated epithelial cell (MCC). These cells project dozens or hundreds of motile cilia from their apical surfaces, and the polarized beating of these cilia generates fluid flow that is essential for development and homeostasis in many organ systems (). Such cells are central to the normal homeostasis of airway, brain and reproductive tracts (Worthington and Cathcart, 1963; Yeung et al. , 1991; Lyons et al. , 2006; Fahy and Dickey, 2010), and defective functioning of these cells is associated with pathologies ranging from chronic infection to hydrocephalus (Afzelius, 1976). Despite these cells’ importance and long history of study (Sharpey, 1830), the transcription factors that control MCC development and function are only now being elucidated (You et al. , 2004; Stubbs et al. , 2008; Marcet et al. , 2011; Stubbs et al. , 2012; Tan et al. , 2013), and among these factors is Rfx2 (Chung et al. , 2012). 10. 7554/eLife. 01439. 003Figure 1. Conserved cell behaviors during multi-ciliated cell development in mammalian airways and Xenopus epidermis. : http: //dx. . org/10. 7554/eLife. 01439. 003 In this study, we sought to combine systems biology approaches with in vivo cell biological studies in order to better define the genomic control of MCC","Cells that have hundreds of tiny hair-like structures called cilia on their surface have important roles in our airways and also in the brain and reproductive system. By beating in a coordinated manner, the cilia cause fluid to flow in a particular direction. The development of these multiciliated cells is a complex process in which genes are expressed as proteins, with this gene expression being regulated by other proteins called transcription factors. In invertebrates the development of the cilia is controlled by transcription factors from the RFX family, which also appear to be important for development of cilia in vertebrates. However, the details of this process—in particular, the identities of the genes that are involved and how their functions are related—are not well understood in vertebrates. Chung et",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The status signalling hypothesis aims to explain within-species variation in ornamentation by suggesting that some ornaments signal dominance status. Here, we use multilevel meta-analytic models to challenge the textbook example of this hypothesis, the black bib of male house sparrows (Passer domesticus). We conducted a systematic review, and obtained primary data from published and unpublished studies to test whether dominance rank is positively associated with bib size across studies. Contrary to previous studies, the overall effect size (i. e. meta-analytic mean) was small and uncertain. Furthermore, we found several biases in the literature that further question the support available for the status signalling hypothesis. We discuss several explanations including pleiotropic, population- and context-dependent effects. Our findings call for reconsidering this established textbook example in evolutionary and behavioural ecology, and should stimulate renewed interest in understanding within-species variation in ornamental traits. Plumage ornamentation is a striking example of colour and pattern diversity in the animal kingdom and has attracted considerable research (Hill, 2002). Most studies have focused on sexual selection as the key mechanism to explain this diversity in ornamentation (Andersson, 1994; Dale et al. , 2015). The status signalling hypothesis explains within-species variation in ornaments by suggesting that these ornaments signal individual dominance status or fighting ability (Rohwer, 1975). Aggressive contests are costly in terms of energy use, and risk of injuries and predation (Jakobsson et al. , 1995; Kelly and Godin, 2001; Neat et al. , 1998; Prenter et al. , 2006; Sneddon et al. , 1998). These costs could be reduced if individuals can predict the outcome of such contests beforehand using so-called ‘badges of status’ – that is, two potential competitors could decide whether to avoid or engage in aggressive interactions based on the message provided by their opponent’s signals (Rohwer, 1975). Patches of ornamentation have been suggested to function as badges of status in a wide range of taxa, including insects (Tibbetts and Dale, 2004), reptiles (Whiting et al. , 2003) and birds (Senar, 2006). The status signalling hypothesis was originally proposed to explain variation in the size of mountain sheep horns (Beninde, 1937; Geist, 1966), but the hypothesis has become increasingly important in the study of variability in plumage ornamentation in birds (Rohwer, 1975; Senar, 2006). Among the many bird species studied (Santos et al.","Many bird species have colourful, intricately patterned plumage. This ornamentation is generally believed to exist to attract partners. In the 1970s, however, scientists proposed an alternative idea, called the ‘status signalling hypothesis’. This suggests that some birds have plumage ornaments that indicate the fighting abilities or dominance status of their bearers, much like the military badges worn by humans. These badges of status might evolve because fights, which commonly determine who gets valuable resources such as food, are a risky business. Individuals would greatly benefit from being able to predict the fighting abilities of any potential competitor and so avoid fights that they will probably lose. Male house sparrows have a black patch on their throat, known as the bib, that has been considered to be a textbook",380,128,0.3368
pubmed-summarization,"autozygome . this resulted in the identified of a novel splicing variant in rnf216 that is likely to abolish the canonical splice site at the junction of exon / intron 13 ( nm_207111.3:c.2061g > a ) . this variant was absent in ~600 ethnically matched exomes , in the 1000 genomes and exac browser . the shared autozygome of the two individuals was checked against known disease genes but no good candidate was identified ( rnf216 had not been identified ) . therefore , we proceeded with whole - exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome . this resulted in the identified of a novel splicing variant in rnf216 that is likely to abolish the canonical splice site at the junction of exon / intron 13 ( nm_207111.3:c.2061g > a ) . this variant was absent in ~600 ethnically matched exomes , in the 1000 genomes and exac browser . rnf216 ( ring finger protein 216 ) is an e3 ubiquitin ligase involved in regulation of autophagy witch is a cellular process concerned with cellular homeostasis via the degradation of the cell own cytosolic components or protein aggregates . margolin et al . identified digenic homozygous mutations in rnf216 and otud4 in three affected siblings of a consanguineous family originally from the middle east , as well as a compound heterozygous truncating and missense mutations in rnf216 and single mutations in another family . homozygous stub1 mutation have recently been reported in a consanguineous family with ghs thus expanding the genetic heterogeneity of this condition . the phenotype of rnf216-mediated neurodegeneration have been expanded recently to include huntington - like disorder after identifying of rnf216 mutation in belgian families presented initially with prominent chorea , behavioral problems , severe dementia and low gonadotropin serum levels . the novel mutation we identified in this report further expands the allelic heterogeneity of this neurodegenerative disease . our patients presented in their early adulthood with idiopathic hypogonadotropic hypogonadism and no other pituitary abnormalities . we observed in patient 1 , normal cognitive functions and only mild cerebellar ataxia consistent with the radiological evidence of mild cerebellar atrophy , although the white matter involvement was significant . in contrast , patient 2 suffered from a more","gordon holmes syndrome ( ghs ) is a distinct phenotype of autosomal recessive cerebellar ataxia , characterized by ataxia , dementia , reproductive defects and hypogonadism ; it has been recently found to be associated with rnf216 mutation . we performed whole - exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome . we identified a novel splicing variant in rnf216 that is likely to abolish the canonical splice site at the junction of exon / intron 13 ( nm_207111.3:c.2061g > a ) . we herein report two patients with ghs caused by a novel rnf216 mutation as the first follow up report on rnf216-related ghs , and show interfamilial variability of phenotype supporting the previously reported rnf216-related cases .",380,126,0.3316
scientific_lay_summarisation-elife-norm,"Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. These in silico insights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis. Tumor suppressor and oncogenic pathways function in part by subverting existing cellular programs to promote cancer ‘hallmark’ properties that engender malignant growth (Hanahan and Weinberg, 2011). This corruption of normal cellular physiology is mediated by aberrant activities of these tumorigenic pathways, which are predominantly driven by genetic mutation. Importantly, genetic mutation is not the sole source of this dysregulation, as changes in gene expression via promoter methylation or protein turnover can phenotypically resemble driver mutations and contribute to tumorigenesis (Esteller et al. , 1999; Hegi et al. , 2004; Pineda et al. , 2015; Reinstein and Ciechanover, 2006; Semenza, 2003; Shen et al. , 2005; Zöchbauer-Müller et al. , 2001). While these broad regulatory processes have been linked to cancer, the underlying molecular mechanisms that regulate expression of key components of tumorigenic pathways are very poorly characterized. VHL is a key tumor suppressor that is mutated in Von Hippel-Landau disease, a hereditary cancer predisposition syndrome that often manifests as clear-cell renal carcinoma (ccRCC) (Chen et al. , 1995; Gossage et al. , 2015; Kim and Kaelin, 2004; Maher et al. , 1990). VHL functions by binding to HIF1α and hydroxylated Akt and modulating their degradation and activity, respectively. Mutant forms of VHL associated with ccRCC are incapable of binding HIF1α or pAkt, resulting in stabilized expression and activation of these proteins, which ultimately facilitates tumorigenesis (Guo et al. , 2016; Ivan et al. , 2001; Jaakkola et al. , 2001; Maxwell et al. ,","Glioblastoma is the deadliest form of brain cancer, and the rate of patient survival has not significantly improved over the past 70 years. This cancer arises when glial cells, which provide support and insulation to nerve cells, develop mutations that alter the activity of certain genes or alter the role they play in cells. However, there are also several key genes linked to glioblastomas that don’t exhibit mutations, such as the gene that encodes the Von Hippel Landau protein (or VHL for short). This protein normally helps to protect us from developing cancer, but it is not clear how this protein is prevented from performing this role in glioblastomas. One possibility is that proteins that regulate how cells grow and develop may control VHL. For example, a protein",380,128,0.3368
dialogsum,"#Person1#: well, I finished my last final today. #Person2#: the end of all the hard work for my master's. what a nice feeling to get my degree! #Person1#: do you want to attend the convocation? #Person2#: certainly. After years of hard work, I wouldn't miss it. By the way, where can I find cap and gown? #Person1#: do you want to have them made or do you want to rent them? #Person2#: oh, I think they're provided by the school for that special day. #Person1#: no. those you have to provide for yourself. #Person2#: what do most of the students do? #Person1#: well, most of them only need a cap and gown for that particular convocation service, but some of the education majors have had them made, because they will be faculty members, and they'll need them for student commencement each year. #Person2#: then, I might as well have them made. #Person1#: Mary, don't move. Stand right there. It's a good shot. The background is very pretty. #Person2#: hold it a second. I want to fix my hairpin. #Person1#: it doesn't matter. Say'cheese'. #Person2#: here's Lisa. May I take a picture with her? #Person1#: Certainly. Ok, got you.",Mary feels very nice to get her degree and will attend the convocation and have the cap and gown made. #Person1# takes some photos for her.,198,26,0.1313
dialogsum,"#Person1#: I think this spring is a good time for us to start looking. #Person2#: We should plan to move out of here before July. I'm tired of living in apartments. #Person1#: I know, dear. I am too. But we've just been too busy to look for a house. #Person2#: We need to find a good realtor. #Person1#: Not necessarily. If we use a realtor to find a house, it will be more expensive. #Person2#: What do you mean? #Person1#: Realtors always get a commission.If the realtor helps us find something, we have to pay him. #Person2#: But doesn't a realtor help with the contract? I thought they take care of all the legal troubles. #Person1#: Yes, that's often true. But you have to pay them. #Person2#: I still think we should have a realtor.We ' re new in this country. We don't know all the laws of buying a house.And also, the realtor will inspect the house.He can tell us if the house has #Person1#: Of course we need a home inspector.But we can hire an inspector on our own.And as for the legal problems, I have friends. They can help us. #Person2#: So how can we find a house if we don't have a realtor? #Person1#: It takes a little more time. We have to check the ads in the paper.Probably also there are special real estate magazines with ads.Then we have to drive to the homes and look at them. #Person2#: And doesn't the person selling the house have a realtor? #Person1#: Sometimes they do, sometimes they don't. It's best to find someone who is selling by themselves. #Person2#: Why? #Person1#: Because if the seller has a realtor, their price will be higher.He will have to pay a commission to the realtor. #Person2#: Hmm. It all sounds very complicated. #Person1#: It is. But buying a house is very important. So it takes time.That ' s why we haven't done it yet. It's very troublesome. #Person2#: I want to look in the papers today. Maybe we can see something we like. #Person1#: Alright. I'll buy a newspaper when I go to the drug store.",#Person1# and #Person2# are too busy to look for a house. #Person2# advises to find a good realtor but #Person1# thinks they just need a home inspector because #Person2#'s friends can help with the legal problems. #Person2# prefers finding someone who's selling the house by themselves which saves some money.,356,50,0.1404
dialogsum,"#Person1#: I'm looking forward to relaxing this coming weekend. #Person2#: I hope that I can finally find free time too. I'Ve been so busy at work recently. #Person1#: How might you spend the weekend. #Person2#: I hope to do a little gardening. I find it very relaxing. #Person1#: I might do that too. I hope the weather is nice. I could go and play some golf. #Person2#: I heard that the weather should be good. There's a possibility of a shower, but it's not very likely. #Person1#: Hopefully, we'll both have relaxing weekends. #Person2#: Of course, something could come up and stop that wish coming true. #Person1#: Unfortunately, there's always the possibility of some urgent work requiring our attention.",#Person1# and #Person2# are planning a relaxing weekend if they both have time.,119,13,0.1092
pubmed-summarization,"epinephrine intended to be delivered intramuscularly in cases of severe anaphylaxis . for stability purposes , approximately 1.7 mls remains in the auto - injector after activation and can not be used . since preliminary work by zucker in the 1950s into adrenaline analogue reversal ( 3 ) and later a case report by jordan in 1969 whereby a dental assistant had self administered epinephrine to a cut finger to reduce bleeding ( 10 ) , phentolamine reversal of epinephrine has been suggested in the literature repeatedly as the most suitable method of reversal for accidental digital epinephrine injection . phentolamine is a competitive -receptor antagonist that has similar affinities for -1 and -2 receptors . it can be used in large doses for the short term control of hypertension in patients with phaeochromocytoma or in the treatment of hypertensive crisis following the abrupt withdrawal of clonidine . warm water immersions , the administration of systemic or topical nitroglycerin preparations and even topical terbutaline infiltration have been used to treat the accompanying vasospasm that occurs in the digit with limited success ( 4,5 ) . despite this , using phentolamine in this manner remains poorly publicised and lacks a license for use in the uk for the reversal of end artery vasospasm caused by epipen administration . in fact it is only available as rogitine ( ciba ) , containing 10 mg of phentolamine in 1 ml of clear solution . since administration of around 2 - 5 mls of 0.1% phentolamine appears in most reported cases to be completely effective in reversing the effects of 0.3mgs of epinephrine , the greatest danger in administering phentolamine surely comes from drug errors in calculating the correct dilution . many case reports in fact report the reversal of epinephrine after 12 hours with no harmful sequelae at all ( 6,7 ) . this raises the possibility that the ischaemia induced is not complete or that the digital arteries are augmented by another blood supply . indeed , the dalhousie project clinical phase trial recorded 1340 fingers electively injected with low dose adrenaline ( 1:100,000 ) without a single case of digital skin , or fat loss , let alone digital infarction ( 1,2,6 - 8 ) . treatment with phentolamine is nevertheless","after the accidental injection of epinephrine into a digit , various techniques to try and reverse the ensuing ischaemia were unsuccessful . to identify a further treatment strategy and as members of the admitting team were unfamiliar with digital injection of epinephrine a google search was performed . previous cases were described and separate sources indicated appropriate management protocols utilising phentolamine . after administration , an almost immediate reversal of ischaemic symptoms occurred . this highlights the role of the internet as an adjunct in managing unfamiliar situations and practising evidence based medicine .",380,94,0.2474
dialogsum,"#Person1#: Whew! It's pretty cold today. #Person2#: Yeah. My fingers are numb. #Person1#: So, do you often ski here? #Person2#: No, this is my first time. Actually, this is my first time skiing ... ever. #Person1#: So, how do you like it so far? #Person2#: The snow is great [ Yeah ...], but it's too crowded. You know, two people crashed into me on my first run, and some stupid skier was going way too fast ... drove me into some trees. [ Wow! ] I crashed and lost one of my gloves. [ Oh, man. ] Fortunately, I had an extra pair with me. #Person1#: Wow. Well, did the woman stop and apologize? #Person2#: No, it was a man. I'm certain of it. He just ... he just laughed at me. Why do you think it was a woman, anyway? #Person1#: Uh, well, no reason. I mean, well, you know. #Person2#: What? You know what? #Person1#: Uh, uh, nothing. #Person2#: Yeah. You just wait until I find that guy. #Person1#: Uh, well, what are you going to do to him, I mean, if you find him? #Person2#: First, I'm going to break his skis. [ Oh, well ... ] And then, I'm going to take his picture and post it on Facebook. #Person1#: Uh, don't you think that's a little drastic? Perhaps, it was a simple mistake. And how are you going to identify him anyway? #Person2#: Oh, that's easy. He was wearing bright red boots and a purple hat ... um, just like yours. Heh, heh, heh ... #Person1#: Now, now, now. Wait, wait! Yeah. What do you mean? [ Yeah ... ] Wait! Why are you looking at me? You don't think it was me, do you? ... Do you like jazz music?","#Person2# was skiing in a crowded place and was crashed by a man. #Person2# tells #Person1# that he will break his skis and post his picture on Facebook, who wears the same clothes as #Person1#'s.",296,35,0.1182
dialogsum,#Person1#: You look really wiped out? #Person2#: I had meetings back to back all morning. And phone rang off the hook from the minute I walked into the office. #Person1#: Not a good day. I hate to tell you that Mr. Thomas wants to see the profit's statement for new project tomorrow morning. #Person2#: I can't believe it. I guess I'll be here until 10 again tonight.,#Person2# thinks #Person2# has to work overtime when #Person1# tells the bad news.,67,13,0.194
scientific_lay_summarisation-elife-norm,"of sound localization in humans. One prominent neural model for sound localization, originally proposed by Jeffress (1948), consists of a labelled line of coincidence detector neurons that are sensitive to the binaural synchronicity of neural inputs from each ear, with each neuron maximally sensitive to a specific magnitude of ITD (1A). This labelled-line model is computationally equivalent to a neural place-code based on bandlimited cross-correlations of the sounds reaching both ears (Domnitz and Colburn, 1977). Several studies support the existence of labelled-line neural place-code mechanisms in the avian brain (Carr and Konishi, 1988; Overholt et al. , 1992), and versions of it have successfully been applied in many engineering applications predicting human localization performance (e. g. Durlach, 1963; Hafter, 1971; Stern and Trahiotis, 1995; Breebaart et al. , 2001; Hartmann et al. , 2005). A growing literature proposes an alternative to the labelled-line model to explain mammalian sensitivity to ITD (Lee and Groh, 2014). One reason for an alternative is that two excitatory inputs should suffice to implement the labelled-line model, but evidence from experiments on Mongolian gerbils shows that in addition to bilateral excitatory inputs, sharply tuned bilateral inhibitory inputs to the MSO play a crucial role in processing ITDs (Brand et al. , 2002). Moreover, to date no labelled-line type neurons encoding auditory space have been discovered in a mammalian species. Indeed, using a population rate-code, several studies proposed that mammalian sound localization can be modeled based on differences in firing rates across the two populations of neurons that are tuned to opposing hemispheres (1B; van Bergeijk, 1962; McAlpine and Grothe, 2003; Devore et al. , 2009). Rate-based models generally predict that neuronal responses carry most information at the steepest slopes of neural-discharge-rate versus ITD curves, where neural discharge changes most strongly (Stecker et al. , 2005), consistent with the observation that the peak ITDs of rate-ITD curves often fall outside the physiologically plausible range (McAlpine and Grothe, 2003; Grothe et al. , 2010; but see also Joris et al. , 2006). In addition, some authors have suggested that how mammalian sound localization adapts to stimulus history further supports a rate-based neural population code, as assessed behaviorally or via magnetoencephalography (Phillips and Hall, 2005; Stange et al. , 2013; Salminen et al. , 2010). It is unknown which","Being able to localize sounds helps us make sense of the world around us. The brain works out sound direction by comparing the times of when sound reaches the left versus the right ear. This cue is known as interaural time difference, or ITD for short. But how exactly the brain decodes this information is still unknown. The brain contains nerve cells that each show maximum activity in response to one particular ITD. One idea is that these nerve cells are arranged in the brain like a map from left to right, and that the brain then uses this map to estimate sound direction. This is known as the Jeffress model, after the scientist who first proposed it. There is some evidence that birds and alligators actually use",380,128,0.3368
scientific_lay_summarisation-elife-norm,"endosomal vesicles, autophagosomes, and AP-3 vesicles to the vacuolar target membrane (Bröcker et al. , 2010; Nickerson et al. , 2009), including the Rab7-like Ypt7, its guanine nucleotide exchange factor (GEF) Mon1-Ccz1 and the homotypic fusion and vacuole protein sorting (HOPS) complex (Brett et al. , 2008; Nordmann et al. , 2010; Ostrowicz et al. , 2010). In animal cells, HOPS is responsible for autophagy, the infectivity of Ebola virus, and linked to multiple diseases (van der Beek et al. , 2019). Based on ensemble and single-molecule GIET, we quantitatively unraveled the axial organization and dynamics of Ypt7 and its interacting HOPS complex. Our data reveal that HOPS adopts an upright orientation on membranes with characteristic axial dynamics. We thus introduce GIET as a powerful novel technique to uncover the nanoscale spatiotemporal architecture of extended multi-protein complexes at membranes. To apply GIET to explore the structural and functional organization of protein complexes at membranes, we established lipid monolayer coating of graphene. Solid-supported graphene monolayers were prepared by transferring commercially available graphene sheets onto glass substrates. Coating of lipid on graphene was carried out by either liposome fusion or solution-assisted lipid deposition as reported previously (Blaschke et al. , 2018; Lima et al. , 2016; Tabaei et al. , 2016). For site-specific capturing of His-tagged proteins, tris-nitrilotriacetic acid (trisNTA) moieties were incorporated into the lipid monolayer. For this purpose, vesicles made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) containing 5% trisNTA conjugated with dioctadecyl amine (trisNTA-DODA) (Beutel et al. , 2014; Lata et al. , 2005) were fused on freshly prepared graphene slides (1A). Lipid monolayer formation, protein immobilization, and interactions were monitored in real-time using simultaneous total internal reflection fluorescence spectroscopy and reflectance interference (TIRFS-RIF) detection (Gavutis et al. , 2005). A mass signal of lipid deposition on graphene of 2. 5 ng/mm² was observed after washing out excess vesicles (1B). For trisNTA-functionalized lipid bilayer formation by vesicle fusion on a silica surface, which has been previously established for protein interaction analysis at membranes (Beutel et al. , 2014; Gavutis et al. , 2005; Lata et al. , 2006), a lipid deposition of 5 ng/mm² was observed (— 1). These results confirmed formation of a lipid monolayer on the hydrophobic graphene surface. Stable, Ni (II) ion specific immobilization of an anti-GFP nanobody fused to","Proteins are part of the building blocks of life and are essential for structure, function and regulation of every cell, tissue and organ of the body. Proteins adopt different conformations to work efficiently within the various environments of a cell. They can also switch between shapes. One way to monitor how proteins change their shapes involves energy transfer. This approach can measure how close two proteins, or two parts of the same protein, are, by using dye labels that respond to each other when they are close together. For example, in a method called FRET, one dye label absorbs light and transfers the energy to the other label, which emits it as a different color of light. However, FRET only works over short distances (less than 10nm apart",380,128,0.3368
dialogsum,"#Person1#: The environment varies greatly because of difference in language, customs and traditions. #Person2#: Yes. This gap can be filled by export market research before exporting. #Person1#: But the importance of the export research is often neglected by the managers. #Person2#: That's right. They do not appreciate its value and consider it to be a luxury. #Person1#: Therefore, when enterprises are spending a lot of money in trying to penetrate a new market, they should research whether their products can be sold at high enough a price and in a satisfactory amount. #Person2#: Exactly!",#Person1# and #Person2# are talking about the importance of export market research.,94,12,0.1277
dialogsum,"#Person1#: Can I help you? #Person2#: Yes, I would like to buy a Walkman. Can you tell me about the models you have? #Person1#: Well, we have a lot of models here. Did you want to listen to CD's or cassettes or the radio? #Person2#: Mostly cassette tapes. #Person1#: Alright. There are several models you may want to look at. This Kreng portable cassette player is very good. #Person2#: Kreng? I've never heard of that company. #Person1#: It's a German company. This unit has auto-reverse, recording capability, and an AM / FM radio band. It also has a built-in microphone. #Person2#: I suppose I don't want that one then. I don't like auto-reverse. It breaks too easily. #Person1#: Really? Have you had an auto-reverse break before? #Person2#: Yes, twice now. I think it's too high-tech, and so it's the first part that breaks. #Person1#: Hmm. You know, the problem might be dust. Did you clean the unit often? #Person2#: Well. No, I didn't clean it. But still, I only had the last one two months, and it broke. I don't trust auto-reverse. #Person1#: Alright. Well. We have many units without auto-reverse. Here is a good unit. Very reliable. It has an AM / FM band, built-in microphone, recording capability, and no auto-reverse. #Person2#: How much is it? #Person1#: This one sells for $ 39. 99. #Person2#: Can I test it out? #Person1#: Of course. #Person2#: It sounds great. I'll take it. #Person1#: Fine. I think you'll be happy with it. It's a very good unit. Very reliable. I'll go get you a new one in a box. I will be back in just a moment. #Person2#: Thanks.",#Person2# wants to buy a walkman. #Person1# recommends one with auto-reverse but #Person2# doesn't want it because #Person2# has broken two walkmans with auto-reverse. #Person1# tells #Person2# that might be caused by dust but #Person2# still doesn't trust auto-reverse and buys one without it.,277,44,0.1588
dialogsum,"#Person1#: So click here, then up to the top. #Person2#: Er. . . Hum. . . Got it. #Person1#: Then open that window. Yeah, that one. #Person2#: Right! #Person1#: And that's it. You're done. #Person2#: I see what you mean. That was pretty easy after all.",#Person1# gives #Person2# instructions on a computer task.,46,8,0.1739
dialogsum,"#Person1#: Hello, Anna. Are you free this Friday evening? #Person2#: Yes, why? #Person1#: There is a get-together at my home. Would you like to join us? #Person2#: Who else will be there? #Person1#: Oh, there all our friends. Peter, Paul, Daniela and some other classmates. #Person2#: Is Jack coming? #Person1#: No. I didn't invite him. I know you 2 are on bad terms. #Person2#: Thank you. Shall I bring something to the get-together? #Person1#: That will be wonderful if you can. #Person2#: By the way, can Bob come with me? #Person1#: Sure, he's welcome since he is your deskmate. You know my place, don't you? #Person2#: It has been so long since I went there last time, but I think I can find the way. #Person1#: Great! Be there at about 5:00 PM, OK?",#Person1# invites Anna to come to a get-together. Anna agrees after she knows Jack won't come because they are on bad terms.,134,22,0.1642
pubmed-summarization,"all protocols and experiments were approved by the washington university animals studies committee ( protocol 20150285 ) and followed national institutes of health animal care guidelines . male c57bl/6 mice , tsc1 and raptor mice , were purchased from the jackson laboratory ( bar harbor , me ) . villin cre mice were obtained via a generous donation from sylvie robine ( curie institute , paris , france ) . intestinal epithelial - specific tsc1 and raptor knockout mice were generated by crossing villin cre mice with tsc1 or raptor , respectively . wild - type littermates villin cre ( ) ; tsc1 or villin cre(- ) ; raptor were used as control mice . louis , mo ) was dissolved in sunflower oil at 10 mg / ml and injected intraperitoneally at 50 g per gram of body weight for 3 consecutive days to induce deletion of gene expression . mice were kept in the animal holding area with a 12-hour light - dark cycle and given rodent chow ad libitum after weaning . the intestinal resections were performed by transecting the bowel 1- to 2-cm distal from the ligament of treitz and at 12-cm proximal to the ileocecal junction , followed by removal of the intervening segment . intestinal continuity was re - established by an end - to - end primary anastomosis using interrupted 9 - 0 monofilament sutures . mice then were fed with a standard liquid diet ( pmi micro - stabilized rodent liquid diet ld 101 ; testdiet , richmond , in ) until death . at the time of death , a midline laparotomy was performed and the entire small intestine was flushed with ice - cold phosphate - buffered saline containing protease inhibitors ( 0.2 nmol / l phenylmethylsulfonyl fluoride , 5 g / ml aprotinin , 1 mol / l benzamidine , 1 mmol / l sodium orthovanadate , and 2 mol / l cantharidin ) . a 2-cm segment of bowel distal to the anastomosis was fixed in 10% neutral - buffered formalin for histology . the remainder of the distal segment was used to isolate crypt and villus . protein extracted from isolated crypt or villus was used for western blot assay , and rna was used for real","background & aimsintestinal adaptation is a compensatory response to the massive loss of small intestine after surgical resection . we investigated the role of intestinal epithelial cell specific mammalian target of rapamycin complex 1 ( i - mtorc1 ) in intestinal adaptation after massive small bowel resection ( sbr).methodswe performed 50% proximal sbr on mice to study adaptation . to manipulate i - mtorc1 activity , villin - creer transgenic mice were crossed with tuberous sclerosis complex ( tsc)1flox / flox or raptorflox / flox mice to inducibly activate or inactivate i - mtorc1 activity with tamoxifen . western blot was used to confirm the activity of mtorc1 . crypt depth and villus height were measured to score adaptation . immunohistochemistry was used to investigate differentiation and rates",380,128,0.3368
pubmed-summarization,"cases for each nevus and primary melanoma subtype was determined to reflect the lesion 's relative representation in cases obtained at the pdl during the above period . atypical nevi were diagnosed using criteria originally proposed by clark and lesion architecture as reviewed by roth et al . . primary antibodies used in the study are as follows : ( i ) anti--catenin ( is702 ) was purchased from dako ( glostrup , denmark ) and used in an undiluted form ; and ( ii ) anti - rad6 ( ab31917 ) was purchased from abcam ( cambridge , ma ) and used at a 1 : 500 dilution . in humans , the yeast homologous rad6 gene is duplicated and the proteins encoded by the two genes hhr6a ( or rad6a ) and hhr6b ( rad6b ) from chromosomes xq24-q25 and 5q23-q31 , respectively , share 95% identical amino acid residues . neither ab31917 , our own rad6 antibody , nor any other commercially available anti - rad6 antibody is currently able to distinguish between rad6a and rad6b proteins . therefore , rather than referring as rad6a or rad6b , we refer to the protein detected by the antibody as rad6 . briefly , five - micrometer sections were deparaffinized in xylene and rehydrated in graded ethanol . for antigen retrieval , sections were microwaved in citrate buffer ph 6.0 ( biogenex , san ramon , ca , usa ) for 12 min at 95c and cooled for 30 min prior to immunostaining . sections were incubated with 3% hydrogen peroxide for 15 min , followed by incubation with primary antibody for 60 min . an automated immunostainer ( i6000 ; biogenex ) was utilized for subsequent incubation steps : sections were incubated in multilink biotinylated anti - igg for 20 min , horseradish peroxidase conjugated secondary antibody for 20 min , followed by development with 3-amino-9-ethyl - carbazole for 10 min ( biogenex ) . all incubation steps were performed at room temperature , and sections were washed with tris - buffered saline between incubations . lung and colon cancer tissues were included as positive controls for immunostaining with anti--catenin antibody , and breast cancer tissues were included as positive controls for staining with anti - rad6 antibody","we have previously demonstrated that rad6 and -catenin enhance each other 's expression through a positive feedback loop to promote breast cancer development / progression . while -catenin has been implicated in melanoma pathogenesis , rad6 function has not been investigated . here , we examined the relationship between rad6 and -catenin in melanoma development and progression . eighty - eight cutaneous tumors , 30 nevi , 29 primary melanoma , and 29 metastatic melanomas , were immunostained with anti--catenin and anti - rad6 antibodies . strong expression of rad6 was observed in only 27% of nevi as compared to 100% of primary and 96% of metastatic melanomas . -catenin was strongly expressed in 97% of primary and 93% of metastatic melanomas , and unlike rad6 , in",380,128,0.3368
pubmed-summarization,"treatment with a tki can be challenging when encountering asymptomatic patients with slowly progressive radioiodine - refractory thyroid carcinomas , a relatively common finding in this disease . this article aims to critically review the data on antitumor activity , toxicity , and potential patient selection tools for the newly approved multikinase inhibitor lenvatinib.9 a better understanding of the molecular biology of malignancies and the advent of targeted therapies represented an unprecedented development in the therapy of several solid tumors in recent years , including non - small - cell lung cancer , breast cancer , melanoma , and gastrointestinal stromal tumors.1013 a comprehensive genetic analysis of 496 samples of ptc as part of the cancer genome atlas ( tcga ) project showed that driver genomic alterations were found i97% of cases.14 the vascular endothelial growth factor receptor ( vegfr ) was one of the first signaling pathways to be associated with the aggressiveness of thyroid cancer.1517 despite its key role in the pathophysiology of thyroid malignancies , other signaling pathways drive the thyroid cancer cell behavior . fibroblast growth factor receptor ( fgfr ) , platelet - derived growth factor receptor ( pdgfr ) , v - ras oncogene homologue ( ras ) , b - raf proto - oncogene , serine / threonine kinase ( braf ) , and ret / ptc rearrangement receptor , among others , have been recognized as important signaling pathways that are implicated in the pathophysiology of thyroid tumors.1824 until recently , sorafenib was the only kinase inhibitor approved by the us fda for the treatment of metastatic iodine - refractory dtc . sorafenib is an oral tki that abrogates signaling from numerous molecules including braf , ret / ptc , vegfr13 , pdgfr , and c - kit.25,26 the antineoplastic activity of sorafenib for the treatment of thyroid cancer was demonstrated in many trials including the decision trial , which was a phase iii placebo - controlled randomized study of 417 patients with progressive radioactive iodine - refractory , locally advanced , or metastatic thyroid cancer assigned to sorafenib 400 mg twice daily or placebo.27,28 the histological subtypes , confirmed by a central review , primarily consisted of ptc and ftc . the primary end point of the study was met with","thyroid cancer is the most common endocrine malignancy , with over 60,000 cases reported per year in the us alone . the incidence of thyroid cancer has increased in the last several years . patients with metastatic differentiated thyroid cancer ( dtc ) generally have a good prognosis . metastatic dtc can often be treated in a targeted manner with radioactive iodine , but the ability to accumulate iodine is lost with decreasing differentiation . until recently , chemotherapy was the only treatment in patients with advanced thyroid cancer , which is no longer amenable to therapy with radioactive iodine . the modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field . new insights in thyroid cancer biology propelled the",380,128,0.3368
dialogsum,"#Person1#: Hello. Is that doctor Brown's office, please? #Person2#: Yes, but doctor Brown is busy now. Is there anything I can do for you? #Person1#: Yes, my name is Jim Anderson and I'm hoping I can come this afternoon to see the doctor. #Person2#: So what seems to be the problem? #Person1#: Well, I've got a pain in my left eye and I don't know the cause of it. #Person2#: Is it serious? #Person1#: It's not that serious, but I'm worried. So can I come this afternoon? #Person2#: I'm sorry, but doctor Brown will be busy the whole afternoon. What about tomorrow morning? #Person1#: Does doctor Brown work in the evening? I'm really worried, you know. #Person2#: sorry, but tomorrow morning at 10:00 is OK for you to come.",Jim Anderson wants to make an appointment with Dr. Brown because Jim has pain in the left eye. #Person2# says Brown's only available tomorrow morning.,129,25,0.1938
dialogsum,"#Person1#: Good afternoon. Is this the Roley Hotel? #Person2#: Yes, madam. May I help you? #Person1#: Yes. I ' m calling from Westwood and Westwood Attorneys. I need to make a reservation for Mr. Alex Brent. #Person2#: Fine, madam. When will Mr. Brent be arriving, and how many nights will he be staying?",#Person1# phones to make a reservation for Mr. Brent. #Person2# helps her.,53,12,0.2264
pubmed-summarization,"horseradish peroxidase ( jackson immunoresearch laboratories , inc , west grove , pa ) , diaminobenzidine ( sigma - aldrich , st . p - histone h3 antibody ( 9701 , 1:400 ; cell signaling technology , danvers , ma ) for cell proliferation ; mucin-2 ( 15334 , 1:1000 ; santa cruz , dallas , tx ) for goblet cell differentiation ; chromogranin a ( 20085 , 1:800 ; immunostar , hudson , wi ) for enteroendocrine cell differentiation ; matrix metalloproteinase ( mmp)-7 ( 3801 , 1:100 ; cell signaling technology , danvers , ma ) ; and lysozyme ( rp 028 - 05 , 1:100 ; diagnostic biosystems , pleasanton , ca ) for paneth cell differentiation . isolated crypt and villus samples were lysed with sodium dodecyl sulfate sample buffer ( 50 mmol / l tris - hcl , ph 6.8 , 2% sodium dodecyl sulfate , 10% glycerol , and 5% mercaptoethanol ) . the lysate then was heated for 5 minutes at 100c , and the protein concentration was determined using the rc - dc kit ( bio - rad , hercules , ca ) . antibodies used in this study were as follows : tsc1 ( # 6935 ) , tsc2 ( # 4308 ) , raptor ( # 2280 ) , ps6k ( # 9234 ) , s6k ( # 2708 ) , ps6 ( s235/236 ; # 4858 ) , ps6 ( s240/244 ; # 5364 ) , s6 ( # 2217 ) , glyceraldehyde-3-phosphate dehydrogenase ( # 5174 ) , and mmp-7 ( # 3801 ) ( all from cell signaling technology ) . the proteins were detected using the bio - rad chemidoc xrs+ system with image lab software ( bio - rad ) . isolated crypts and villi were homogenized in lysis buffer and rna was extracted according to the manufacturer s protocol ( rnaqueous kit ; ambion , austin tx ) . the total rna concentration was determined using a nanodrop spectrophotometer ( nd-1000 ; nanodrop technologies , wilmington , de ) . tsc1 , tsc2 , mmp-7 , and lysozyme primers were obtained from life technologies ( carlsbad , ca ) . -actin was used as the endogenous control ( applied biosystems , foster city ,","background & aimsintestinal adaptation is a compensatory response to the massive loss of small intestine after surgical resection . we investigated the role of intestinal epithelial cell specific mammalian target of rapamycin complex 1 ( i - mtorc1 ) in intestinal adaptation after massive small bowel resection ( sbr).methodswe performed 50% proximal sbr on mice to study adaptation . to manipulate i - mtorc1 activity , villin - creer transgenic mice were crossed with tuberous sclerosis complex ( tsc)1flox / flox or raptorflox / flox mice to inducibly activate or inactivate i - mtorc1 activity with tamoxifen . western blot was used to confirm the activity of mtorc1 . crypt depth and villus height were measured to score adaptation . immunohistochemistry was used to investigate differentiation and rates",380,128,0.3368
dialogsum,"#Person1#: Hi. My name's Carl. Nice to meet you. #Person2#: Nice to meet you, too. My name is Francisco. #Person1#: What? #Person2#: Francisco, but all my friends and family back in Peru call me Pancho. #Person1#: Okay, Pancho. So, tell me about your family? #Person2#: Well, I have seven brothers and six sisters. #Person1#: Wow. That is a big family. So are you the oldest, Pancho? #Person2#: No. I'm the second oldest in my family. #Person1#: So, what do your parents do? #Person2#: My father is a taxi driver in Lima, Peru. It's a hard job, but he works hard to support the family. #Person1#: How about your mother? #Person2#: She helps run a small family store with some of my older brothers and sisters. #Person1#: What kind of store? #Person2#: We mainly sell food, like bread, eggs, soft drinks, rice, sugar, and cookies. Things that people buy every day.",Francisco and Carl meet each other for the first time. Francisco tells Carl he's the second oldest. His father is a driver and his mother runs a store.,150,28,0.1867
dialogsum,"#Person1#: I heard you were teaching English over there. Tell me about it. Did you like it? #Person2#: Oh, yes, it was very interesting. #Person1#: What were the schools like? #Person2#: Oh, I didn't actually teach in the schools. I taught after school. I taught in English institutes. #Person1#: But you taught children, yes? #Person2#: Yes. That's right. But children in Taiwan are very different from children in America. At least as far as studying is concerned. Many children in Taiwan go to special institutes after school. #Person1#: They actually study after school? #Person2#: That's right. After their school day is over, they go to a special institute to study math or English. They are very serious about learning over there. #Person1#: Hmm. That sounds pretty oppressive for the kids. Don't they ever relax? #Person2#: Of course they do. You know, Eliza, before I went over there I thought the same thing. I thought that maybe kids in Taiwan study too much. But now that I've worked there, and taught them, I feel it is a good thing. Their parents are very concerned about their education. More than American parents are. And that is good. American kids don't study enough. #Person1#: Asian cultures value learning very much. I know that. #Person2#: So it was interesting for me to see parents very concerned about education. They would come to me after the class and ask how their son or daughter was doing. I don't think that's a bad thing. I think it's a good thing. In America, too many parents don't pay attention. #Person1#: But aren't the kids tired out? I mean, they go to school all day, and then they go to school in the evening too. #Person2#: As an English teacher, I tried to make the lessons as fun as possible. I tried to have a good time with my classes. The students often enjoyed it. And if the students enjoyed it, they learned more. So it was a good experience. #Person1#: Are the kids in Taiwan very obedient? #Person2#: That's a stereotype we Americans have. We think that Asian kids are very obedient and quiet. But it's not true. There are plenty of naughty kids too. #Person1#: Hmm. I know you taught in Costa Rica also. Which did","#Person2# describes the experience of teaching English in Taiwan to Eliza. #Person2# taught children in English institutes and says kids in Taiwan study after school. #Person2# thinks it's good for parents in Taiwan to be concerned about children's education, and in contrast, American kids don't study enough. As an English teacher, #Person2# tried to make the lesson as fun as possible.",380,61,0.1605
scientific_lay_summarisation-elife-norm,"et al. , 2010). Most ApoE receptors, which are all members of the low-density lipoprotein (LDL) receptor gene family, are expressed in the brain and several are intrinsic components of excitatory synapses where they are present in the presynaptic and postsynaptic compartments (reviewed in Lane-Donovan et al. , 2014; Pohlkamp et al. , 2017). Of these, ApoE receptor-2 (Apoer2, a. k. a. LRP8) is the best characterized. It is present both pre- as well as postsynaptically where it primarily functions as a receptor for Reelin (Bal et al. , 2013; Beffert et al. , 2005; Lane-Donovan and Herz, 2017). Reelin is a large secreted protein that is essential for the formation of cortical layers during embryonic brain development where it serves as a guidance molecule in the regulation of neuronal migration (D' Arcangelo et al. , 1995; Del Río et al. , 1997). As the brain continues to develop and mature postnatally, its expression pattern changes and Reelin is now produced by a subset of GABAergic interneurons that are interspersed throughout the neocortex and the hippocampus (Alcántara et al. , 1998; Pesold et al. , 1998; Pohlkamp et al. , 2014). In the adult brain, this secreted Reelin now functions as a neuromodulator by signaling through Apoer2 and its closely related family member Vldlr to activate Src-family tyrosine kinases directly in the synapse, which results in increased Ca2+ influx through NMDA receptors and thus the robust elevation and maintenance of synaptic potentiation (Chen et al. , 2005; Hiesberger et al. , 1999; Wasser and Herz, 2017). This is the key event in the maintenance of synaptic homeostasis that is impaired by ApoE4 and which occurs independent of Aβ accumulation (Chen et al. , 2005). Indeed, ApoE4-specific alterations in brain structure have been found in <2 year old children (Dean et al. , 2014; Shaw et al. , 2007). The molecular basis by which ApoE4 causes the disruption of normal endosomal vesicle transport and recycling is most likely the result of its propensity to unfold and assume a ‘molten-globule’ conformation upon entering an acidic environment (Morrow et al. , 2002). ApoE4 differs from ApoE3 by a single amino acid, which alters its isoelectric point to coincide with the pH of ~6. 5 that is present in the early endosome (Casey et","Alzheimer’s disease is a degenerative condition that destroys connections between brain cells leading to memory loss, confusion and difficulties in thinking. Apolipoprotein E is a protein that carries fatty substances called lipids and cholesterol around the brain, and plays an important role in repair mechanisms. There are three major forms of Apolipoprotein E, and individuals who carry a version known as ApoE4 are up to 10 times more likely to develop Alzheimer’s disease than those who carry other variations. In nerve cells, or neurons, Apolipoprotein E binds to a specific family of receptors. One of these receptors, called Apoer2, is found in the synaptic gap between neurons, where it regulates their activities. Both Apolipoprotein E and Apoer2 are taken into the cell within compartments known as endosomal vesicles.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"between-host dynamics. This model is based on experimental viro-immunological data and allows an accurate estimation of the exogenous boosting characteristics and explicit insertion or validation of experimental data. Using a step-wise algorithm we initially found eight unique parameter sets leading to a reasonable fit of Belgian HZ incidence data (see Table 1 and ). All best-fitting parameter sets were based on boosting scenario 3 (predefined exponential loss of boosted VZV-CMI). Seven of these models include exogenous boosting (defined as an exponential decay) with a peak value of 1. 3, a boosting duration ranging between 2 and 15 years, no endogenous boosting, a weekly VZV reactivation probability and an annual VZV-CMI loss (= waning) estimated to be 1–1. 5% and 1–2%, respectively. We note that although the fits are excellent for the most relevant age groups, 25 years and older, they are less suited to predict HZ incidence for younger ages. One model predicted a peak boosting value of 2. 5, a boosting duration of only 1 year and no endogenous boosting. Although this model was less suited to fit to HZ data for older age groups, it fitted much better to HZ data for younger age groups. In additional analyses relaxing on some parameter constraints, we obtained final parameter sets that led to excellent predictions across all age groups (see Table 1 and ). The two best fitting parameter sets predicted peak boosting values between 2. 8 and 4 (maximum allowable value), a duration of boosting limited to 1 or 2 years and, as before, no endogenous boosting. Averaged VZV-specific CMI levels are shown in . 10. 7554/eLife. 07116. 003Table 1. Best fitting parameter setsDOI: http: //dx. . org/10. 7554/eLife. 07116. 003Parameter setDeviance*Annual waning rate (%) Boosting scenarioDuration of boosting (years) Peak fold increase following exogenous boostingVZV weekly reactivation probability (%) Distribution threshold VZV-CMI for HZPeak fold increase following endogenous boostingOriginal Search (obtained after Step 2 in Table 1) 19262. 03101. 31. 541 29391. 5331. 31. 541 39492. 0371. 31. 541 49512. 03121. 31. 541 59682. 0371. 31. 041 69701. 0321. 31. 041 79692. 03151. 31. 541 89341. 0312. 55. 041Border search 97511. 0312. 85. 041 107991. 0313. 15. 041 119651. 5323. 45. 041 128041. 5323. 75. 041 137221. 5324. 05. 041*Results shown are averaged results per parameter set. VZV,","The itchy-scratchy misery of a chickenpox was until recently a rite of passage for children around the world. The varicella-zoster virus causes chickenpox infections. This virus persists in small numbers in nerve cells for many years after infection, and can reactivate from these cells. Often this reactivation causes no symptoms, but sometimes it results in a painful skin condition called shingles (or herpes zoster), especially in older adults. Some countries—including the United States, Australia, Taiwan and Greece—have virtually wiped out childhood cases of chickenpox by requiring that children be vaccinated against the varicella-zoster virus. But some countries have hesitated. One reason for this hesitation is that exposure to individuals with a chickenpox infection helps boost the immunity of individuals who have previously been infected. This may help reduce",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and protects cardiac LDH exposed to HPS produced by the contracting heart. Male, Sprague-Dawley and Spontaneously-Hypertensive-Heart-Failure (SHHF) rats were treated orally with either water (control) or TMAO. In vitro, LDH with or without TMAO was exposed to HPS and was evaluated using fluorescence correlation spectroscopy. TMAO-treated rats showed higher diuresis and natriuresis, lower arterial pressure and plasma NT-proBNP. Survival in SHHF-control was 66% vs 100% in SHHF-TMAO. In vitro, exposure of LDH to HPS with or without TMAO did not affect protein structure. In conclusion, TMAO reduced mortality in SHHF, which was associated with diuretic, natriuretic and hypotensive effects. HPS and TMAO did not affect LDH protein structure. Some clinical studies have shown that increased levels of trimethylamine-oxide (TMAO) in the plasma are associated with an increased risk of adverse cardiovascular events (Tang et al. , 2015; Trøseid et al. , 2015; Tang et al. , 2013). However, other studies have not confirmed this relationship (Meyer et al. , 2016; Yin et al. , 2015; Stubbs et al. , 2019). Furthermore, basic research data regarding the effect of TMAO on the circulatory system are contradictory (Huc et al. , 2018; Aldana-Hernández et al. , 2019; Collins et al. , 2016; Organ et al. , 2016; Savi et al. , 2018). In the plasma, TMAO originates from the liver oxidation of trimethylamine (TMA), a product of gut bacteria metabolism of l-carnitine and choline (Zeisel and Warrier, 2017; Ufnal et al. , 2015). However, another direct source of TMAO in humans is TMAO-rich seafood (Cheung et al. , 2017; Yancey and Siebenaller, 2015). Therefore, populations whose diet are rich in seafood, such as the Japanese, have higher urine TMAO concentrations than those that do not, for example, Americans (Dumas et al. , 2006; Holmes et al. , 2008). Interestingly, prevalence and mortality rates of heart failure (HF) are lower in Japan compared to the US or Europe, despite the fact that Japan has the highest proportion of elderly people in the world (Nagai et al. , 2018; Ogawa et al.","Heart failure is a common cause of death in industrialized countries with aging populations. Japan, however, has lower rates of heart failure and fewer deaths linked to this disease than the United States or Europe, despite having the highest proportion of elderly people in the world. Dietary differences between these regions may explain the lower rate of heart failure in Japan. The Japanese diet is rich in seafood, which contains nutrients that promote heart health, such as omega-3 fatty acids. Seafood also contains other compounds, including trimethylamine oxide (TMAO). Fish that live in deep waters undergo high pressures, which can damage their proteins, but TMAO seems to protect the proteins from harm. In humans, eating seafood increases TMAO levels in the blood and urine, but it is unclear",380,128,0.3368
dialogsum,"#Person1#: I'm worried about Monday's exam. #Person2#: Take it easy. I'm sure you will do well. If you take it easy, and remain calm. #Person1#: Is it alright if I use dictionaries? #Person2#: You are not allowed to use them, I think. #Person1#: Do you think I could discuss the questions with others during the exam? #Person2#: I'm afraid that's impossible, teachers would not allow that to happen. #Person1#: May I bring some paper to write drafts? #Person2#: Yes, that's alright, I suppose. #Person1#: Thank you very much for the information.",#Person1#'s worried about Monday's exam. #Person2# tells #Person1# some rules about the exam.,91,13,0.1429
dialogsum,"#Person1#: Oh hello nice to see you again. Did you have a good holiday? I was thinking of ringing you to ask you about it? #Person2#: Yes, it was lovely. We had to set off really early because the plane took off at 6:00 AM. But then we were on the beach in the sun by lunchtime. #Person1#: Great and what did you do most days? #Person2#: Well, we usually slept in. It was very nice not having to get up early and then we stayed up late at night. Going out to discos and nightclubs. During the day we usually lay on the beach or looked round the town. #Person1#: And what about the food? #Person2#: Well, we didn't usually have any breakfast. By the time we got downstairs at the hotel. They had cleared away all the breakfast things. We tried out different restaurants for lunch and most of them were very good. The fish was particularly nice. And we usually stayed in for dinner at the hotel. #Person1#: So what did you like best? #Person2#: I liked everything, the beaches, the weather, the food and the nightlife, the people. I'd like to go back again next year. So I'm saving up for it already. People book very early for that area, so I must fix it up right after the new year. If I carry on saving for a few months I'll have enough money.","#Person2# tells #Person1# about #Person2#'s holiday. #Person2# enjoyed the leisure schedule and restaurants at the hotel. #Person2# likes everything there, and would like to go back next year.",238,28,0.1176
scientific_lay_summarisation-elife-norm,"The Atlantic herring is one of the most abundant vertebrates on earth but its nucleotide diversity is moderate (π = 0. 3%), only three-fold higher than in human. Here, we present a pedigree-based estimation of the mutation rate in this species. Based on whole-genome sequencing of four parents and 12 offspring, the estimated mutation rate is 2. 0 × 10-9 per base per generation. We observed a high degree of parental mosaicism indicating that a large fraction of these de novo mutations occurred during early germ cell development. The estimated mutation rate – the lowest among vertebrates analyzed to date – partially explains the discrepancy between the rather low nucleotide diversity in herring and its huge census population size. But a species like the herring will never reach its expected nucleotide diversity because of fluctuations in population size over the millions of years it takes to build up high nucleotide diversity. Empirical observations of nucleotide diversity in different species show that the variation is often much smaller than would be expected from simple population genetic models (Leffler et al. , 2012). The Atlantic herring (Clupea harengus) is a good example of the paradox, since, in spite of an enormous census population size about 1012 (Supplementary file 1), its nucleotide diversity (π = 0. 3%) (Martinez Barrio et al. , 2016) is middle-of-the-road when compared to terrestrial mammals, e. g. 0. 1% for humans (Hernandez et al. , 2011) and 0. 9% for European rabbits (Carneiro et al. , 2014) with much smaller census populations. A large census population does not necessarily mean that the long term effective population size (Ne) is large but the extremely low genetic differentiation at selectively neutral loci between geographically distant populations strongly suggests that current Ne must be high and genetic drift very low in the Atlantic herring (Martinez Barrio et al. , 2016). Before the NextGenerationSequencing-era, mutation rates were estimated by comparative genomics, by relating sequence differences to fossil record-dated estimates of species divergence times, or by tracking changes at specific loci in experimental studies. However, since species divergence is hard to date and the use of a small subset of loci can introduce bias, these methods have limited accuracy (Drake et al. , 1998). More recently, affordable whole genome sequencing has facilitated two","Evolution by natural selection favours the survival of individuals that are well suited to their environment. This process depends on genetic differences between individuals that make some more able to survive than others. These genetic differences are the result of mutations in DNA of germ-line cells, that is, the cells that produce egg cells and sperm. These mutations mean that new offspring always have a few small differences in some of the genes they inherited from each of their parents. DNA contains strings of molecules known as bases. These act as individual “letters” in the genetic code of an individual. Rapid sequencing of DNA to find out the order of these bases makes it possible to study the rate of mutations within a species. This provides a way",380,128,0.3368
dialogsum,"#Person1#: Hello, Madam. What can I do for you today? #Person2#: Hello. Yes, I'm here to redeem a Treasury Note. It's not at the maturity date yet, but it is an emergency. #Person1#: OK, can I see the note and some ID, please? #Person2#: There you are. As you can see, the maturity isn't up yet. #Person1#: You do realise that you must pay a 0. 2 % charge for premature cancellation, right? #Person2#: Oh, really? No, I wasn't aware of that. #Person1#: Unfortunately, yes. You see, this is a three-year note ; it was issued over a year ago, but not over two years. So, you will have to pay. I'm sorry about that.",#Person2# wants to redeem a Treasury Note before maturity. #Person1# reminds her she'll have to pay a charge which she wasn't aware of.,115,23,0.2
pubmed-summarization,"natriuretic peptide ( ntpbnp ) levels of 5201 pg / ml and slightly increased transaminases ( alt 40 u / l , ast 60 u / l ) , without changes in tnt , hscrp , or leukocyte numbers . over the following 7 days , based on these findings , we discussed at least four possible differential diagnosis : ( 1 ) tachycardiainduced cardiomyopathy ( cm ) , ( 2 ) progression of hcm including ( micro)angiopathyinduced changes , ( 3 ) development of a severe primary mitral valve regurgitation , and ( 4 ) another undetected acquired form of cm . in an invasive electrophysiological evaluation , no malignant heart rhythm disturbances were inducible . we found a sufficient working atrioventricular node without any signs of accessory bundles excluding a wpwsyndrome induced tachycardiomyopathy . for further evaluation of the myocardial structure , we performed cardiac magnetic resonance imaging ( mri ) . the mri showed a significant hypertrophic and dilated lv ( lv diastolic volume of 286 ml ) with a further reduced lvef ( 17% ) . there was a pronounced signal of late gadolinium enhancement ( lge ) sequences of myocardial necrosis ( scar ) and/or fibrosis to detect , especially in the septum , apical and lateral part of the lv ( reticular delayed enhancement ) ( ) . further on , there were no signals of myocardial inflammatory processes in the t1weighted and t2weighted images detected . to investigate whether or not a primarily hcmdependent progression of the disease or other etiologies were responsible for these findings , we evaluated right ventricular endomyocardial biopsies ( embs ) after exclusion of coronary abnormalities . histological characterization of the embs demonstrated perivascular and interstitial fibrosis and significant hypertrophy of myocytes indicated by diameters up to 31 m . a hcmtypical disarray was not detected . similar , no signs of cardiac storage diseases were found using different staining techniques . however , immunohistochemical staining showed an extensive active inflammation response of the myocardium ( ) : highly increased 2leukocyteintegrins / infiltrates ( lfa1/cd11a+ and mac1/cd11b+ ) and mixed cellular infiltrates of both lymphocytes and macrophages ( cd45ropositive and hlapositive cells ) ( table 1).2 molecular biological analyses by nested polymerase chain reaction excluded the presence of","abstractwe report the case of a 17yearold female patient with known hypertrophic cardiomyopathy and a wolffparkinsonwhite syndrome . she came to our department for further evaluation of a new diagnosed dilated cardiomyopathy characterized by an enlargement of the left ventricle and a fall in ejection fraction . clinically , she complained about atypical chest pain , arrhythmic episodes with presyncopal events , and dyspnea ( nyha iii ) during the last 6 months . noninvasive and invasive examinations including magnetic resonance imaging , electrophysiological examinations , and angiography did not lead to a conclusive diagnosis . therefore , endomyocardial biopsies ( embs ) were taken to investigate whether a specific myocardial disease caused the impairment of the left ventricular function . emb analysis resulted in the diagnosis of",380,128,0.3368
pubmed-summarization,"cardiovascular disease is the leading cause of death in patients with chronic kidney disease ( ckd ) . cardiovascular mortality in patients with end - stage renal disease ( esrd ) is 10 to 20 times higher than in the general population . classic risk factors ( diabetes mellitus , smoking , dyslipidemia , high blood pressure , sedentary lifestyle , and obesity ) do not entirely explain the high incidence of cv disease in these patients ; other , non - traditional risk factors must play a role and amongst them oxidative stress ( os ) and inflammation should be emphasized . os and inflammation are inseparably linked , as they induce and amplify one another and may cause cardiovascular damage . in addition , os may be involved in the pathogenesis of other cardiovascular risk factors in ckd , such as anemia , amyloidosis and malnutrition . hd patients are subjected to enhanced oxidative stress , as a result of increased pro - oxidant activity and reduced anti - oxidant systems related both to end stage renal disease ( esrd ) and hemodialysis techniques . diabetes mellitus , advanced age , inflammation , uremia , bio - incompatibility of dialysis membranes and solutions ( use of ultrapure dialysate results in less os than standard dialysate ) , intravenous iron therapy are the main causes of increased pro - oxidant activity in hd patients . excessive reactive oxygen species ( ros ) levels can produce cellular damage by interacting with biomolecules ( proteins , lipids , and nucleic acids ) and thus have negative effects on tissue function and structure . malondialdehyde ( mda ) is the breakdown product of the major chain reactions leading to definite oxidation of polyunsaturated fatty acids such as linolenic acid and thus is a useful indicator for assessing oxidative damage . mda can interact with dna and proteins and has been shown to have mutagenic and cytotoxic effects and possibly to be involved in the pathogenesis of several human diseases , including atherosclerosis . mda levels increase with the progression of kidney dysfunction and in hd patients with dialysis vintage . in biological systems , mda exists both free ( fmda ) and bound ( bmda ) to sh and/or nh2 groups of","background and aimscardiovascular ( cv ) disease is the leading cause of morbidity and mortality in hemodialysis ( hd ) patients . kidney disease is associated with increased oxidative stress ( os ) , a nontraditional cv risk factor . few studies evaluate the effect of os markers on cv events ( cve ) and survival in hd patients . the aim of this study is to examine potential determinants of os markers and their predictive role on survival and cv morbidity and mortality in hd patients during a long - term follow - up ( 108 months).methodswe conducted an analytical cross - sectional prospective observational study , carried on a cohort of randomly selected hd patients . we registered in 44 hd patients baseline characteristics , os",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The extensive use of mollusc shell as a versatile raw material is testament to its importance in prehistoric times. The consistent choice of certain species for different purposes, including the making of ornaments, is a direct representation of how humans viewed and exploited their environment. The necessary taxonomic information, however, is often impossible to obtain from objects that are small, heavily worked or degraded. Here we propose a novel biogeochemical approach to track the biological origin of prehistoric mollusc shell. We conducted an in-depth study of archaeological ornaments using microstructural, geochemical and biomolecular analyses, including ‘palaeoshellomics’, the first application of palaeoproteomics to mollusc shells (and indeed to any invertebrate calcified tissue). We reveal the consistent use of locally-sourced freshwater mother-of-pearl for the standardized manufacture of ‘double-buttons’. This craft is found throughout Europe between 4200–3800 BCE, highlighting the ornament-makers’ profound knowledge of the biogeosphere and the existence of cross-cultural traditions. Two modern marine mollusc shells, O. edulis and M. modiolus, were collected in northern Jutland (Denmark) by Søren H. Andersen and were selected for the following reasons: O. edulis shells had been suggested as the potential raw material for the Hornstaad-Hörnle IA assemblage (Heumüller, 2010) and are very abundant at the shell midden site of Havnø; M. modiolus is a thick-shelled mussel with a nacreous layer, therefore a suitable raw material for the Havnø ornaments (Appendix 1, section 2). Furthermore, close relatives of both species are present in public sequence databases, which is important for palaeoproteomics: O. edulis belongs to family Ostreidae (genomes available for Crassostrea gigas and C. virginica) and M. modiolus to family Mytilidae (genome available for Mytilus galloprovincialis). With regard to the freshwater species (order Unionoida), U. pictorum and U. crassus belong to family Unionidae, P. auricularius and M. margaritifera to family Margaritiferidae. Modern U. pictorum shells were collected in a stream close to Izeure (Burgundy) by Frédéric Marin and modern M. margaritifera was collected in northern Jutland by Søren H. Andersen. The morphological determination of both taxa was carried out by Frédéric Marin. U. crassus and P. auricularius are archaeological shell specimens from the sites of Peştera Ungurească and Isorella (Neolithic, Po Plain, Italy [Starnini et al. , 2018]). The determination of U. cf. crassus had been carried out by Alberto Girod on the basis of morphological","Just like people do today, prehistoric humans liked to adorn themselves with beautiful objects. Shells, from creatures like clams and snails, were used to decorate clothing or worn as jewelry at least as far back as 100,000 years ago. Later people used shells as the raw materials to make beads or bracelets. Learning where the shells came from may help scientists understand why prehistoric people chose certain shells and not others. It may also offer clues about how they used natural resources and the cultural significance of these objects. But identifying the shells is difficult because they lose many of their original distinctive features when worked into ornaments. New tools that use DNA or proteins to identify the raw materials used to craft ancient artifacts have emerged that",380,128,0.3368
dialogsum,"#Person1#: Hello. Thank you for calling Spend Mart. #Person2#: Is this the Customer Service Desk? #Person1#: Yes. How can I help you? #Person2#: I bought a sweater from your store a week ago. It says size 12. But actually, it is a size 10. Can I exchange it? #Person1#: Do you have the receipt with you? #Person2#: Yes, I do. #Person1#: I like to apologize for the problem. Please come down with your receipt and sweater to exchange it for the size you want. #Person2#: Thank you very much. #Person1#: You're welcome.",#Person2# calls to exchange the sweater in the wrong size. #Person1# asks #Person2# to come down with the receipt and the sweater.,92,22,0.2391
dialogsum,"#Person1#: Could you tell me if you have ever taken a class from Dr. Miller? #Person2#: Yes. Are you going to be taking a class from him? #Person1#: Yes, but I have never taken his class before. #Person2#: He is very interesting and challenging. Is that what you are looking for? #Person1#: Yes, that's what I need. #Person2#: He is really clear on what you need to learn to get a good grade. Are you willing to study hard? #Person1#: Yes, I guess so. #Person2#: What I really liked about him is that he was an understanding and friendly teacher. Do you enjoy that in a teacher? #Person1#: Yes, I had a teacher like that before. #Person2#: Did you know that he has 20 years teaching experience? #Person1#: No, I didn't, but that could be a good thing. #Person2#: Well, take a look at everything and out what is best for you. Good luck!","#Person1# asks #Person2# about Dr. Miller. #Person2# thinks he's interesting, challenging, understanding, friendly, and experienced.",154,15,0.0974
dialogsum,"#Person1#: You'v been work here for nearly a month, how do you feel about the job? #Person2#: Not bad. Thank you for your help. I am alawys busy with this job, I feel a bit tired. #Person1#: I had the same feeling when I first came to work here. but after a period of time, I feel better, I am sure you 'll get used to this busy job. #Person2#: I also feel that work efficiency here is very high. and you have strong working ability and professional skill, it seems that you know all, that's really wonderful! #Person1#: You know the phrase, the survival the fittest. We have no choices. #Person2#: That's right, I have to work hard.",#Person2# thanks #Person1# for #Person1#'s help at work. #Person2# thinks the work is busy and #Person2# has to work hard.,119,20,0.1681
pubmed-summarization,"full body skin examination , using their total body photographs as a reference point , were diagnosed as melanoma . in comparison , in the cohort of patients 50 years and older , 30% of new lesions discovered using the same method were diagnosed as melanoma . several other studies have demonstrated the usefulness of total body photography in the detection of melanoma in high - risk populations . despite these documented benefits in detecting melanoma using total body photography , there is still a lack of data to support whether this modality leads to decreased morbidity and/or mortality [ 11 - 13 ] . total body photography , while effective for tracking clinical change in lesions or the development of new lesions , is time - consuming and laborious . in addition , in the us , health insurance often does not cover the cost of taking the professional photos , which ranges from $ 400-$500 . traditional digital total body photography relies on physical photographs , which the patient brings to each appointment , or which the physician stores as part of the paper medical record . molemax ( derma medical systems , vienna , austria ) , fotofinder ( fotofinder systems inc , columbia , md , usa ) , molemap cd ( digitalderm inc , columbia , sc , usa ) , smartscope ( midcon distribution inc , overland park , ks , usa ) , dermspectra ( dermspectra , tuscon , az , usa ) , dermatrak skin imaging centers ( canfield scientific , fairfield , nj , usa ) , and melanoscan ( melanoscan inc , stamford , ct , usa ) all offer alternatives to traditional full body photography . all of these devices allow for comparison of high - resolution digital images , and some have software that calculates the likelihood of malignancy based on clinical features . while these devices are promising , many lack large - scale clinical trials supporting their efficacy . of published studies in peer - reviewed journals that examined these devices , all of these devices need to be coupled with clinical judgment when examining any patient for melanoma . confocal scanning laser microscopy ( cslm ) uses the inherent reflective properties of the tissue to","melanoma is a malignancy of melanocytes or pigment - producing cells located predominantly in the skin . it is less common than other skin cancers but causes the greatest number of skin cancer - related deaths worldwide . the incidence of melanoma continues to increase and early detection is the most promising means of decreasing morbidity and mortality . currently , physicians perform routine skin cancer screenings for melanoma without the benefit of imaging devices more advanced than handheld magnifiers or dermatoscopes . however , it is possible that the diagnosis of melanoma may be improved with technology that provides diagnostic discrimination beyond what is possible on routine inspection . this article reviews current and emerging technologies to aid in the diagnosis of melanoma . ultimately , these",380,128,0.3368
dialogsum,"#Person1#: Mark, did you once study abroad? #Person2#: Yes, I went to Australia as an exchange student about 8 years ago. I was only 16 years old then. I studied there for 2 years. #Person1#: What was the biggest surprise about your study abroad experience? #Person2#: Well, before I went to Australia, I was afraid I wouldn't make any friends there. But it turned out it was quite easy for me to make friends there, and there was another big surprise for me too! #Person1#: What was it? #Person2#: I didn't expect to have so many great experiences in the country. But in Australia, I often traveled with my new friends. I was even able to travel up and down the East Coast with some great new friends. #Person1#: Now I can say you really enjoyed your life there.",Mark tells #Person1# his study-abroad experience in Australia. He's surprised that he made many friends and had so many great experiences there.,139,22,0.1583
pubmed-summarization,"neobladder was performed by using the studer method and ureteral stents were used and brought out anteriorly through separate stab wounds . urethro - enteric anastomosis was then performed intracorporeally after redocking the robotic system ( . a jackson - pratt drain was placed in the pelvic cavity and around the uretero - enteric anastomosis site , respectively . the nasogastric tube was removed 4 days after surgery and oral liquids were started as tolerated . patients were reviewed at 4 weeks and checked by a renal ultrasound at 2 weeks after stent removal , by computed tomography scans at 3 and 6 months postoperatively , and then at 6-month intervals . at these visits , they had a clinical examination , assessment of hemoglobin , electrolytes , creatinine , chloride , bicarbonate , and urethral washing cytology . the mean total operative time was 379.1 minutes ( range , 330 - 460 minutes ) , including 32.6 minutes for pelvic lymph node dissection , 185.2 minutes for rlrc , and 159.4 minutes for urinary diversion . all patients underwent extracorporeal urinary diversions ( 13 ileal conduits and 4 orthotopic neobladders by the studer method ) , and there were no patients who underwent urethrectomy . the mean operative time for the ileal conduit ( ic ) group was significantly shorter than that for the orthotopic neobladder ( on ) group ( 371.0 minutes vs. 442.5 minutes , p=0.010 ) . the mean estimated blood loss was 215.3 ml ( range , 120 - 400 ml ) for the ic group and 195.0 ml ( range , 180 - 200 ml ) for the on group ( p=0.871 ) . the time to oral intake and time to ambulation were 5.0 days ( range , 4 - 8 days ) and 1.3 days ( range , 1 - 3 days ) , respectively . mean hospital stay was 20.7 days ( range , 11 - 41 days ) , including 18.2 days ( range , 11 - 41 days ) for the ic group and 27.5 days ( range , 17 - 40 days ) for the on group ( p=0.245 ) . the time to oral intake ( 5.1 vs. 4.5 days ) and time to ambulation ( 1.4","purposerobot - assisted laparoscopic radical cystectomy ( rlrc ) is a new option for the treatment of muscle - invasive bladder cancer , and case series for rlrc have been increasing recently . we report our operative technique and initial experiences with rlrc with extracorporeal urinary diversion.materials and methodsbetween october 2008 and november 2009 , 17 consecutive patients with muscle - invasive bladder cancer underwent rlrc , pelvic lymph node dissection , and extracorporeal urinary diversion . urinary diversion included 13 ileal conduits and 4 orthotopic neobladders ( studer method ) . data were collected prospectively on patient demographics , intraoperative parameters , pathologic staging , and postoperative outcomes.resultsthe mean patient age was 63.7 years . the mean body mass index was 22.6 kg / m2 . no",380,128,0.3368
dialogsum,"#Person1#: Are you a blogger? #Person2#: Sure I am. I've been writing a blog for almost three years. #Person1#: Oh, it seems that I'm the only one who never blogs. When did you get started? #Person2#: I began blogging when I first went to the US for my graduate strides. #Person1#: What do you usually write about? #Person2#: At first, I'll write about my life there. Like interesting things on the campus, travel stories, special English words that I come across. Sometimes, I'll post my pictures on my blog so my friends and family can get to know how everything's going. #Person1#: That's interesting. How often do you write a blog? #Person2#: It's random. If there happen to be a lot of things going on, I may add several new entries in a week, and if I've got nothing to share, I may leave my blog untouched for weeks. #Person1#: Got it. Are you still updating your blog? #Person2#: Sure, since I came back from the US, I've been keeping the habit of blogging, simply to share my personal insights on any topic I like. #Person1#: Good for you. I know many people just leave their blogs alone after the first few months.",#Person2# has been writing blogs for three years. #Person2# writes about #Person2#'s life and #Person2# is still updating blogs.,203,19,0.0936
scientific_lay_summarisation-elife-norm,"The host–pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections. Enteric fever is a serious bacterial infection caused by Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A) (Parry et al. , 2002). S. Typhi is more prevalent than S. Paratyphi A globally, with the best estimates predicting approximately 21 and 5 million new infections with each serovar per year, respectively (Ochiai et al. , 2008; Buckle et al. , 2012). Both S. Typhi and S. Paratyphi A are systemic pathogens that induce clinically indistinguishable syndromes (Maskey et al. , 2006). However, they exhibit contrary epidemiologies, different geographical distributions, and different propensities to develop resistance to antimicrobials (Vollaard et al. , 2004; Karkey et al. , 2013). Additionally, they are genetically and phenotypically distinct, having gone through a lengthy process of convergent evolution to cause an identical disease (Didelot et al. , 2007; Holt et al. , 2009). The agents of enteric fever induce their effect on the human body by invading the gastrointestinal tract and spreading in the bloodstream (Everest et al. , 2001). It is this systemic phase of the disease that induces the characteristic symptoms of enteric fever (Glynn et al. , 1995). However, the host’s reaction to this systemic spread, outside the adaptive immune response, is not well described. There is a knowledge gap related to the scope and the","Enteric fever is estimated to affect over 37 million people every year. Although treatable with antimicrobial drugs, a slow and/or incorrect diagnosis can result in serious and often life-threatening complications. Enteric fever is the combined name for typhoid fever and paratyphoid fever. While the symptoms of these diseases are indistinguishable, the strains of Salmonella bacteria that cause them are genetically distinct. Moreover, the two organisms that cause the disease exhibit different propensities to develop resistance to antimicrobials. It is important, therefore, to be able to distinguish between typhoid fever and paratyphoid fever so that the correct treatment can be prescribed. However, the diagnostic tools available today struggle to discriminate between Salmonella Typhi (which causes typhoid fever) and Salmonella Paratyphi A (which causes paratyphoid fever). Now, Näsström et al.",380,128,0.3368
dialogsum,"#Person1#: Oh! You're engaged! What a beautiful engagement ring! Who to? #Person2#: Of course Mike. Who else? We fell in love at first sight. #Person1#: When's the wedding going to be? #Person2#: We haven't decided yet. There are a lot of things to sort out, you know. #Person1#: Are you having a big wedding? #Person2#: Yes, I've always dream of having a big wedding. #Person1#: But what do you say about that? #Person2#: I don't really enjoy big occasions, but I think I'll come round to the idea in the end, It only happens once in a lifetime. #Person1#: Perhaps I'll agree with Mike. I couldn't stand a big wedding with many relatives and friends of my parents or my wife whom I'd never met before.",#Person1# sees #Person2#'s engagement ring and asks about her wedding. #Person2# will agree with Mike that not have a big wedding.,126,21,0.1667
pubmed-summarization,", nevi at traumatic regions , racial pigmentation , etc . some literatures explain that during embryologic development , melanocytes migrate from the neural crest to epithelial lining , which later show reactive changes by cytotoxic stimulant in the basal epithelial layer . though dendritic cells , derived from neural crest , produces the melanocytes but the exact mechanism of proliferation of these cells in melanoma particularly , mucosal melanomas are asymptomatic in their initial phase , resulting in late diagnosis , thus allowing them to invade the deeper regions . the clinical characteristics include , dark brown / black in color , asymmetrical margins , and irregular surface , etc . , hence , the pigmented lesions of oral cavity ; which does not possess clinical specificity need to be carefully evaluated for possibility of omm . differential diagnosis include : smoke related melanosis , drug pigments , physiologic or racial pigmentation , melanotic macule , kaposi 's sarcoma , nevus or melanoacanthoma , chronic leukemic , etc . pigmentation is not the only criteria , as around 15% of the melanomas are nonpigmented . the omm has distinct gender variation with majority of them showing male predominance . among the oral melanomas ; hard palate and maxillary gingiva , we report a case of omm , in a 45-year - old female patient , who is conscious about the discoloration and growing bulk over mandibular anterior mucosa . a 42-year - old indian female with average height and moderate built reported to the dental office , complaining of blackish discoloration on the lower jaw since 6 months and difficulty while eating ; especially with the lower front teeth . intraoral examination revealed nontender and painless bluish - black growth with rough and irregular surface extending over the gingiva of 3544 regions , which revealed no findings of ulceration and bleeding [ ] . there was major involvement over the labial aspect of mandibular gingiva followed by anteroposterior extension into the vestibule and oral aspect of lip mucosa ; but with minimal extension of the lesion on lingual aspect . the patient noticed a small blackish patch approximately 1 cm 1 cm which gradually increased to present size with associated mobility of teeth . the overall general examination of","according to the world health organization , oral malignant melanoma ( omm ) is a rare disease , accounting for only 0.8% of all melanomas , 8% of head and neck melanomas , and up to 0.5% of all oral malignancies . omm presents as a pigmented lesion with asymmetrical borders , irregular surface characteristics , and a distinct color . melanoma - associated pigmented lesion of the oral cavity does not possess clinical specificity and frequently divert the clinical diagnosis ; hence , differential diagnosis becomes mandatory . furthermore , the unpredictable pathophysiological behavior and delayed detection , contributes for poor prognosis of the disease . as a result , the 5 years survival rate is only 1025% . commonly omm is seen in maxillary gingiva of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"As the activity of individual full-length Kar3 motors had not been observed directly, we developed assays to investigate motors at the single molecule level and analyze the contribution of the non-catalytic domain. 10. 7554/eLife. 04489. 003Figure 1. Purification and characterization of Cik1–Kar3 kinesin motors. (A) Schematic representation of conventional Kinesin-1 in comparison to the kinesin-14 Cik1–Kar3. (B) Purification of recombinant Cik1–Kar3 from yeast extracts. Motors are covalently labeled with Tetramethylrhodamine (TMR) via a HaloTag on the amino-terminus of Kar3. Coomassie-stained SDS-PAGE shows purity of the motor preparation and fluorescent labeling of the Kar3 subunit. (C) Size-exclusion chromatography of Cik1–Kar3-Halo motors on a Superose 6 column. The void volume of the column (V0) and the elution position of standard proteins with their respective stokes radii is indicated. (D) SDS-PAGE analysis of Superose 6 fractions from (C). (E) Sucrose gradient centrifugation of Cik1–Kar3 motors. Consecutive fractions from top to bottom of a 5–25 (wt/vol) % sucrose gradient were analyzed by SDS-PAGE and Coomassie staining. The gradient positions of standard proteins are indicated together with their sedimentation coefficients. (F) Low angle Pt/C rotary shadowing electron microscopy of Cik1–Kar3 motors obtained after size exclusion chromatography. Overview of Cik1–Kar3 motors, scale bar 100 nm. (G) Gallery view of selected Cik1–Kar3 motors, scale bar 50 nm. : http: //dx. . org/10. 7554/eLife. 04489. 003 To study Kar3 motors at the single molecule level, we developed a protocol to express and purify full-length kinesin-14 heterodimers from Saccharomyces cerevisiae using affinity tagged Cik1 and Kar3 fused COOH-terminally to a HaloTag that served as covalent attachment site for the fluorescent dye tetramethylrhodamine (TMR). Purification and labeling yielded a homogenous preparation containing a heterodimer of Cik1 and TMR-labeled Kar3 (1B). During size exclusion chromatography, Cik1–Kar3 motors eluted as a single major peak with a Stokes radius of ∼9. 1 nm, well separated from the void volume of the column (1C, D). Sucrose-gradient centrifugation revealed the presence of a single major species with an apparent sedimentation coefficient of ∼5. 6S (1E). Combining these hydrodynamic values yielded a native molecular weight of 214 kDa, close to the calculated molecular weight of a Halo-tagged Cik1–Kar3 heterodimer of 190 kDa. We further characterized the oligomeric state of full-length Cik1–Kar3 motors by performing low-angle Pt/C rotary shadowing electron microscopy on peak fractions from the gel","Molecules can be transported around a cell by so-called motor proteins that move along a network of filaments called microtubules. Many motor proteins—including the kinesin family of these proteins—can only move in one direction along a microtubule. In most cells, kinesins tend to transport other molecules away from the center and towards the cell edge. Kinesins can have different structures, but most are made up of two subunits that are joined and work together to create a walking-like movement. Each subunit has a region called a motor domain (also known as its ‘head’) that can bind to the microtubule and to a molecule called ATP, which provides the energy required for the motor to step forward. Kinesins can be classed either as processive or non-processive motors. Processive motors",380,128,0.3368
dialogsum,"#Person1#: Excuse me, is anyone sitting here? #Person2#: Erm..no, I'll just move my bag. #Person1#: Thanks, how long have you been waiting? #Person2#: Oh, about half an hour. I'm waiting for my friend to meet me. How about you? #Person1#: Oh, I've just got here about 3:30. I'm picking up my younger sister, she'll be arriving on a 4:00 o'clock bus. #Person2#: Where is she from? #Person1#: London. She's studying there. #Person2#: Me too. I'm studying business at the London School of Economics. #Person1#: She studies photography at the London College of Fashion. #Person2#: Yes, I know it. It's a very famous college. She must be good. #Person1#: Maybe, all I know is that she is always asking our dad for money to buy new cameras or something. What do you plan to do after University? #Person2#: Well, I might work in a cafe called the blue. But if possible, I'd really like to travel for a year, maybe to... Oh, I'm sorry. I've got to say goodbye, my friend just arrived. Well, it was nice chatting with you.",#Person2# is waiting for a friend. #Person1# tells #Person2# that #Person1# is waiting for #Person1#'s younger sister. Then they talk about #Person1#'s sister and #Person2#'s plan after University.,179,28,0.1564
pubmed-summarization,"paroxysmal nocturnal hemoglobinuria ( pnh ) is an acquired clonal hematopoietic stem cell disorder characterized by a variety of clinical manifestations , including the classic triad of chronic intravascular hemolysis , thrombotic events , and bone - marrow ( bm ) failure . somatic mutation of x - linked gene pig - a in hematopoietic stem cells , which encodes the first essential enzyme of the glycosylphosphatidylinositol ( gpi)-anchor biosynthetic pathway , results in absent or decreased cell membrane expression of all surface proteins normally anchored by it including cd55 and cd59 in all circulating cells . the incidence of pnh - like defect has been also demonstrated in many hematological diseases and on peripheral blood cells ( pbcs ) of normal individuals . complement system ( cs ) represents a fundamental part , not only of the host s innate immunity against pathogen invasion , but also of adaptive and humoral immunity . nevertheless , when not properly regulated , cs is recognized as having the potential to provoke severe impairment to host tissues through a process mainly mediated by autoantibodies ( aab ) against specific tissue antigens or non - specific immune complexes ( ic ) deposited in organs , like renal glomerulus known as damage to the innocent bystander . this has been demonstrated in autoimmune diseases , but the mechanisms have not been thoroughly explained . however , autoimmunity is also characterized by the loss of immunological tolerance , the over - activation of t - cell populations against specific antigenic epitopes and , generally , an enhanced and extensive overall immune response . multiple regulatory and inhibitory enzymes , either membrane - bound or soluble in plasma , known as complement regulatory proteins ( cregs ) , regulate the progression of complement cascade ( cc ) at all levels , protecting the autologous cells . cd55 or daf ( decay- accelerating factor ) , cd59 or mirl ( membrane inhibitor of reactive lysis ) , cd46 or mcp ( membrane cofactor protein ) , and cd35 or cr1 ( complement receptor 1 ) are the 4 major membrane - bound cregs . both cd55 and cd59 are globular gpi - anchored membrane glycoproteins widely expressed in all circulating cells and most human tissues . cd55","backgroundcomplement has the potential to provoke severe impairment to host tissues , as shown in autoimmune diseases where complement activation has been associated with diminished cd55 and/or cd59 expression on peripheral blood cell membranes . the aim of this study was to evaluate the presence of cd55- and/or cd59-deficient erythrocytic populations in patients with different rheumatic diseases and to investigate possible correlations with clinical or laboratory parameters.material/methodscd55 and cd59 expression was evaluated in erythrocytes of 113 patients with rheumatic diseases , 121 normal individuals , and 10 patients with paroxysmal nocturnal hemoglobinuria ( pnh ) using the sephacryl gel microtyping system . ham and sucrose tests were also performed.resultsinterestingly , the majority of patients ( 104/113 , 92% ) demonstrated cd55- and/or cd59-deficient erythrocytes : 47 ( 41.6%",380,128,0.3368
pubmed-summarization,"patient was noted to have a normal body temperature , but remained on paralytics in a medically induced coma . one additional blood culture was obtained , and ebv and cmv serologies were performed ; all returned negative . cultures of an endotracheal tube aspirate ( eta ) that were obtained on admission were notable for growth of a fluffy , sterile white mold with yellow center on standard blood agar media . on hospital day four , endoscopic bronchoscopy was performed . bal fluid was collected from the left and right lower lobes ( lll & rll ) of the lung and submitted for gram and gomori methenamine silver ( gms ) staining , which were negative . histoplasma and legionella antigen testing on the bal fluid was negative , but an aspergillus galactomannan antigen was positive ( > 3.75 ng / ml ) . pcr for influenza ( cepheid genxpert ) as well as multiplex pcr for respiratory pathogens ( film array , biofire , inc . ) were both negative . again , within 48 h , a similar appearing fluffy , white mold grew in cultures of both lll and rll bal fluid samples on all media ( blood agar , sabouraud agar , and mycosel agar ( becton dickinson ) ; a selective medium containing cycloheximide and chloramphenicol to inhibit bacterial growth ) . potato dextrose agar ( pda ) was inoculated with a sample of mold , but serial lactophenol cotton blue prep exams of the non - sporulating cultures were non - diagnostic , although clearly not consistent with mucormycosis . empiric treatment with lipid formulation of intravenous amphotericin b was initiated on hospital day 5 due to failure to improve on broad spectrum empiric antibiotic treatment . over the next 48 h respiratory status was unchanged and oxygenation parameters and radiographic imaging showed no improvement . on hospital day 7 , following two iv doses of liposomal amphotericin b , repeat bronchoscopy was performed . gram and gms stains , and histoplasma antigen testing were repeated , and returned negative for yeast , pneumocystis or fungal elements . methylprednisolone 125 mg iv every 8 h was added to the empiric iv amphotericin b for treatment of possible allergic bronchopulmonary aspergillosis ( apba","we describe the first reported case of acute respiratory distress syndrome ( ards ) attributed to neosartorya udagawae infection . this mold grew rapidly in cultures of multiple respiratory specimens from a previously healthy 43-year - old woman . neosartorya spp . are a recently recognized cause of invasive disease in immunocompromised patients that can be mistaken for their sexual teleomorph , aspergillus fumigatus . because the cultures were sterile , phenotypic identification was not possible . dna sequencing of its , calmodulin and -tubulin genes supported identification of neosartorya udagawae . our case is the first report of ards associated with neosartorya sp . infection and defines a new clinical entity .",380,113,0.2974
scientific_lay_summarisation-elife-norm,"identified through genetic quantitative trait loci mapping between progeny of crosses between virulent and avirulent strains. These proteins were shown to be protein kinases that are injected from the rhoptries into host cells during invasion (Saeij et al. , 2006; 2007; Taylor et al. , 2006; Peixoto et al. , 2010). Two canonical effector rhoptry proteins, ROP16 and ROP18, are only known to be injected into the host cell at the onset of invasion, where ROP16 levels peak within the host cell nucleus between 10 min and 4 hr post infection. ROP16 phosphorylates signal transducers and activators of transcription 1/3/5/6 (Rosowski et al. , 2012; Yamamoto et al. , 2009; Jensen et al. , 2013; Ong et al. , 2010), thus skewing the immediate-early immune response to limit parasite clearance (Saeij et al. , 2007). While ROP16 and ROP18 were shown to be required for virulence differences between the three canonical Toxoplasma strains, they did not explain many other known phenotypic changes that occur during Toxoplasma infection of host cells. Recently, an additional class of Toxoplasma effector proteins was identified as coming from the dense granules. These include dense granule protein 16 (GRA16), which is exported to the host cell nucleus post invasion via the dense granules, where it contributes to cell cycle arrest, potentially as a mechanism to prevent apoptosis (Bougdour et al. , 2013). Other parasite processes and host pathways now known to be impacted by the GRA proteins include: a skewing of the immune response through the effector GRA24 (Braun et al. , 2013), influencing nuclear factor kappa-light-chain-enhancer of activated B cells nuclear translocation in some strains via GRA15 (Rosowski et al. , 2011), transport of small molecules across the PVM via GRA17 and GRA23 (Gold et al. , 2015), generation of the nanotubular network (NTN, thought to aid nutrient acquisition [Mercier, 2002]) via GRA2 (and others) as well as recruitment of the host mitochondria to the PVM through the dense granule protein mitochondrial association factor 1 (MAF1) (Pernas et al. , 2014). The recent and rapid discovery of these effectors suggests that there may be many more proteins that are exported via the dense granules and that they may use a conserved export pathway to mediate changes in the infected host cell. While some exported proteins","Toxoplasma gondii is a parasite that is thought to infect over two billion people worldwide. Often these infections cause no noticeable symptoms, but can cause serious illness in people with weakened immune systems. Toxoplasma parasites must enter human cells in order to survive. To dramatically increase their chances of survival, the parasites then deliver specialized proteins into the host cell that disarm the host’s immune defenses. Understanding how these specialized proteins are transported from inside the parasite into the host cell, and how this process can be blocked, may lead to new treatments for these and related parasitic infections. By genetically modifying Toxoplasma parasites to lack a parasite enzyme, Coffey et al. have now discovered that this molecule is required for correctly transporting parasite proteins. This enzyme is",380,128,0.3368
dialogsum,"#Person1#: I've been at this for two weeks now and nothing's turned up. #Person2#: You're right. I think it's time to seek professional help. #Person1#: What do you mean? #Person2#: I know you don't want to pay for a job, but I think it's time we consulted a headhunter. #Person1#: You're right, I don't want to pay, but I don't want to live without pay, either. #Person2#: Ha, ha, ha! I agree. That's not much fun. #Person1#: Do you have anyone in mind? #Person2#: Actually I do. #Person1#: Who? #Person2#: Cooke & Co. does a lot of placements in your field. #Person1#: Ya, they do. Anyone else come to mind? #Person2#: Not at the moment, but I'll let you know.",#Person1# can't find a job. #Person2# suggests #Person1# consult a headhunter and recommends Cooke & Co. #Person1# asks if there is anyone else.,120,23,0.1917
dialogsum,"#Person1#: Hi, Mary, I have decided to look for a job as a salesman. #Person2#: Good! Have you got the recruitment information on marketing? #Person1#: Yes. I have found some through different channels. #Person2#: Really? That's great! Tell me. #Person1#: OK. The first piece of job information I got was from the Internet, and it is about selling medicines. #Person2#: What do you think of this job? #Person1#: I am not familiar with the medicine industry, and I don't think it fits me well. #Person2#: Then how about the others? #Person1#: Another is about electronic commerce, and its products are mainly large machinery equipments. #Person2#: I have heard about electronic commerce, and many people say it has good prospects for development. #Person1#: I also feel it's nice. I want to give it a try. #Person2#: Come on! I believe you will succeed. #Person1#: Thanks. You can also seek job information on the Internet. #Person2#: Good idea. I will think it over.","#Person1# is looking for a job as a salesman. After gathering the recruitment information from different channels, #Person1# wants to try the one about electronic commerce.",161,26,0.1615
dialogsum,"#Person1#: I ' m glad you could find time to meet with me, Mr. Johnson. I can ' t think of a nicer environment for our meeting today, the ambiance here is lovely! #Person2#: No problem, if possible I always combine business with pleasure. Now, let ' s hear more about these chocolates you ' re offering. #Person1#: Well, as you know, I have recently become the sole distributor for Grangers Gourmet Bon-bons here in the United States. They ' re a new manufacturer and are looking to break into the luxury market. Naturally, your restaurant sprang into my mind immediately. I think your brand exemplifies many of the same traits as Grangers and serving these chocolates would really add to your reputation for providing elegant, luxurious, first class dining. #Person2#: Mmmm, sounds interesting... gourmet chocolates, where are they produced? Belgium? #Person1#: Actually, the factory is located in Scotland. #Person2#: Really? I didn ' t think they were known for their luxury chocolate production #Person1#: That ' s what makes this such a fantastic opportunity! The government is one hundred percent supportive of creating new export markets and has guaranteed a low tariff for all wholesale orders of over one thousand units. They ' Ve also reduced the red tape involved at customs as well. Here, I brought these especially for you, try one! #Person2#: Oh, thanks. Mmm, hmm, creamy texture, very smooth... #Person1#: Unique, aren ' t they? I bet you ' Ve never tasted anything like it! Quality is assured as I personally visit the factory to make sure no one ' s cutting corners with the ingredients. Only the creme make it through inspection. #Person2#: Yes, very interesting flavors... Slightly spicy, very unique, that ' s for sure. Exactly what ARE the ingredients? #Person1#: I have it on highest authority that this traditional secret recipe has been handed down in the Granger family for generations. I ' m sure you can keep a secret. Buttermilk, cacao beans, sugar and Haggis. #Person2#: Haggis? What ' s Haggis? #Person1#: It ' s a traditional Scottish delicacy, you take sheep ' s liver, heart and lung and stuff it inside of the sheep ' s stomach. #Person2#: Ah, get back to you. #Person1#: Mr. Johnson? Mr. Johnson?","#Person1# thinks Mr. Johnson's brand exemplifies similar traits as Grangers, and serving these chocolates would add to the reputation for providing first-class dining to his restaurant. #Person1# tells that the factory is located in Scotland and invites Mr. Johnson to taste the chocolate. Mr. Johnson is satisfied with its taste and asks #Person1# the ingredients. However, Mr. Johnson gets it back to #Person1# when hearing what the Haggis is.",377,69,0.183
dialogsum,#Person1#: Can I help you with something? #Person2#: I need to cancel one of my accounts. #Person1#: Is there a problem with it? #Person2#: I don't need it anymore. #Person1#: What would you like to do with all the money in this account? #Person2#: Just transfer it over to my remaining account. #Person1#: I can do that. #Person2#: That would be great. #Person1#: Do you want to take any money out? #Person2#: Not today. #Person1#: It's going to take a moment for me to cancel your account. #Person2#: That's fine. Take your time.,#Person2# asks #Person1# to cancel one of #Person2#'s account and transfer the money to #Person2#'s remaining account.,93,17,0.1828
dialogsum,"#Person1#: Why don't we get you some shirts, darling? #Person2#: I want to leave, we've already been here 2 hours. #Person1#: But we should get you some shirts. You need summer shirts. #Person2#: I would rather buy them somewhere else. #Person1#: Why? They have everything here. #Person2#: I don't like shopping in the malls. I like shopping on the street, there was more variety. #Person1#: Let's just look and see what they have. #Person2#: Alright. #Person1#: What about these shirts? #Person2#: The styles here are too boring for me. #Person1#: Oh come on, don't be so sour. These are beautiful shirts, look at this red shirt, try it on. #Person2#: Do they have it in large? #Person1#: Let me look on the rack. Here is one, large, try it on. #Person2#: OK. #Person1#: It looks good on you. #Person2#: Well. I don't think it's the best style for me. #Person1#: You should be happy. I want you to look good. If I let you shop for yourself, you would never buy anything. #Person2#: Yes. Maybe.","#Person1# wants to get some shirts for #Person2#, who would like shopping on the street instead of in the malls. #Person1# believes that #Person2# would never buy anything without #Person1#.",175,30,0.1714
dialogsum,"#Person1#: Excuse me, but do you have this T-shirt in size L? #Person2#: Sorry. We're out of size L's. #Person1#: Too bad. I really like it. #Person2#: Why don't you try this other T-shirt? I think it would look nice on you. #Person1#: Do you have it in size L? #Person2#: Yes, we do. #Person1#: Where is the fitting room? #Person2#: It's on your right hand side at the end of this hallway. #Person1#: Thanks.",#Person2# tells #Person1# the T-shirt #Person1# wants is sold out and recommends another T-shirt.,75,14,0.1867
dialogsum,"#Person1#: Where were you today? I searched for you everywhere. I thought we could study together for tomorrow's quiz. #Person2#: I went to the countryside. I forgot we would have the history quiz tomorrow. In fact, my trips to the countryside are few and far between.",#Person2# forgot tomorrow's history quiz and went to the countryside.,46,10,0.2174
scientific_lay_summarisation-elife-norm,"separation is necessary because the crossover-mediated linkages between homologs require sister-chromatid cohesion distal to the crossover site. Thus, only crossovers formed after DNA replication serve to hold homologous chromosomes together in metaphase I. Moreover, replication forks are unable to cross a DSB (Doksani et al. , 2009), so the presence of >100 DSBs in the genome would severely interfere with the completion of DNA replication. The mechanisms that coordinate pre-meiotic DNA replication and DSB formation are not well understood. DNA replication and DSB formation are coordinated at the local level, because delayed replication of a single chromosome arm delays DSB formation on that arm (Borde et al. , 2000). However, DSB formation does not require DNA replication; pre-meiotic replication initiation mutants introduce full levels of DSBs on chromosomes that are not replicated in both budding and fission yeasts (Murakami and Nurse, 2001; Hochwagen et al. , 2005; Blitzblau et al. , 2012). In addition, the initiation of meiotic recombination is prevented globally when DNA replication is delayed by nucleotide depletion (Schild and Byers, 1978; Tonami et al. , 2005; Ogino and Masai, 2006). In fission yeast, a replication checkpoint blocks DSB formation in this situation (Tonami et al. , 2005; Ogino and Masai, 2006). Although a related checkpoint was found to delay the meiotic divisions upon nucleotide depletion in budding yeast (Stuart and Wittenberg, 1998), a subsequent study came to the conclusion that it did not regulate DSB formation (Borde et al. , 2000). Thus, it remains unclear how budding yeast prevent DSB formation on unreplicated DNA. The replication checkpoint couples DNA replication and cell cycle progression by sensing and coordinating the response to delayed replication forks (reviewed in (Labib and De Piccoli, 2011). In vegetatively growing yeast cells, stalled replication forks activate a conserved kinase cascade including Mec1/ATR and Rad53/CHK2. Mec1 and Rad53 inhibit cell cycle progression by preventing chromosome segregation and mitotic entry, respectively (Clarke et al. , 2001; Clarke et al. , 2003). Additionally, their activation stabilizes replication forks, preventing catastrophic fork collapse. Finally, activated Rad53 also phosphorylates and directly interacts with the Dbf4 subunit of DDK (Weinreich and Stillman, 1999; Duncker et al. , 2002; Chen et al. , 2013), which delays further initiation of DNA replication. The replication checkpoint has not been characterized in budding","Most cells in an organism contain two sets of chromosomes, one inherited from the mother and the other from the father. However, sexual reproduction relies on the production of gametes—eggs and sperm—which contain only one set of chromosomes. These are produced through a specialized form of cell division called meiosis. Meiosis begins with a cell replicating its entire genome. Maternal and paternal versions of each chromosome then pair up and swap sections of their DNA through a process known as homologous recombination. This gives rise to chromosomes with new combinations of maternal and paternal genes. Finally, the cell undergoes two successive rounds of division—the first to produce a cell with two nuclei containing two sets of chromosomes each, and the second to produce four gametes, each containing a",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. , 2004; del Camino and Yellen, 2001; Jiang et al. , 2002). Critical to voltage-dependent gating are the interactions between the VSDs and the pore, which couple the activation of the VSD to the opening of the pore, resulting in a voltage-gated conductance (Chen et al. , 2001; Lu et al. , 2001,2002; Long et al. , 2005; Lee et al. , 2009; Zaydman et al. , 2013). In their pioneering work on the action potential of the squid giant axon, Hodgkin and Huxley empirically derived a model for the K+ conductance in which a transmembrane pathway is gated by four voltage-dependent particles (Hodgkin and Huxley, 1952). The legacy of the Hogdkin and Huxley model can still be found in the current Kv channel models, which assume that (1) VSD activation and pore opening are two-state (i. e. , all or none) processes and (2) gating and permeation are independent so that the VSD conformation changes the probability of pore opening, but does not affect the properties of the open pore. Several recent studies call into question the assumption that VSD activation and pore opening are two-state processes. Computational and experimental studies have demonstrated that VSD activation actually occurs in a series of stepwise transitions due to salt bridge interactions between the basic residues on S4 and acidic residues on S1 and S2, which define resting, intermediate, and activated states (Papazian et al. , 1995; Tiwari-Woodruff et al. , 1997; Wu et al. , 2010a; Delemotte et al. , 2011; Jensen et al. , 2012; Lacroix et al. , 2012). With regards to pore opening, recordings of single channel currents from Kv channels revealed multiple open states discernable by their different conductance levels (Chapman et al. , 1997), although the identities of these subconductance states remain unclear. In our present study of KCNQ1 (Kv7. 1, KvLQT1) channels, we found that both the intermediate and fully-activated states of the VSD yielded robust pore-opening. Remarkably, the intermediate-open and activated-open states had different permeation and pharmacological properties revealing that VSD-pore interactions determine both open probability and open conformation, demonstrating that gating and permeation are not independent. KCNQ1 channels generate currents with very different properties as a result of tissue specific expression of KCNE family accessory subunits (Abbott, 2014). In the heart, channels","Cells are surrounded by a membrane that prevents charged molecules from flowing directly into or out of the cell. Instead ions move through channel proteins within the cell membrane. Most ion channel proteins are selective and only allow one or a few types of ion to cross. Ion channels can also be ‘gated’, and have a central pore that can open or close to allow or stop the flow of selected ions. This gating can be affected by the channel sensing changes in conditions, such as changes in the voltage across the cell membrane. Research conducted more than half a century ago—before the discovery of channel proteins—led to a mathematical model of the flow of potassium ions across a membrane in response to changes in voltage. This model",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Humans and other animals base important decisions on estimates of number, and intraparietal cortex is thought to provide a crucial substrate of this ability. However, it remains debated whether an independent neuronal processing mechanism underlies this ‘number sense’, or whether number is instead judged indirectly on the basis of other quantitative features. We performed high-resolution 7 Tesla fMRI while adult human volunteers attended either to the numerosity or an orthogonal dimension (average item size) of visual dot arrays. Along the dorsal visual stream, numerosity explained a significant amount of variance in activation patterns, above and beyond non-numerical dimensions. Its representation was selectively amplified and progressively enhanced across the hierarchy when task relevant. Our results reveal a sensory extraction mechanism yielding information on numerosity separable from other dimensions already at early visual stages and suggest that later regions along the dorsal stream are most important for explicit manipulation of numerical quantity. One largely debated theme in cognitive neuroscience is how the human brain developed the ability to perform mathematics. While mathematical skills certainly rely on the interplay of a wide range of cognitive functions (De Smedt et al. , 2013; Fias, 2016; Iuculano and Menon, 2018), an influential theory in the field proposes that a necessary prerequisite to develop such a sophisticated uniquely human ability resides in the ‘number sense’ (Dehaene, 1997). This is a phylogenetically ancient competence that enables humans and other animals to assess and mentally manipulate the approximate number of objects in sets. In humans the precision of the number sense (or ‘numerical acuity’, typically measured by visual number discrimination) sharpens with age and with the acquisition of formal mathematical education (Piazza et al. , 2013), and correlates with arithmetical skills throughout the life-span (Halberda et al. , 2008; Libertus et al. , 2011; Libertus et al. , 2013; Chen and Li, 2014; Anobile et al. , 2016a; Anobile et al. , 2018). Deviations from the typical developmental trend of numerical acuity can be a symptom of developmental dyscalculia (Piazza et al. , 2010), a neurodevelopmental disorder that causes specific mathematical learning difficulties. The neural substrate subtending this sense of numerical quantity is thought to be shared across species and has been linked to a network of areas in the frontal and parietal cortices sensitive to changes in","Numbers and the ability to count and calculate are an essential part of human culture. They are part of everyday life, featuring in calendars, computers or the weekly shop, but also in some of humanity’s biggest achievements: without them the pyramids or space travel would not exist. A precursor of sophisticated mathematical skill could reside in a simpler mental ability: the capacity to assess numerical quantities at a glance. This ‘number sense’ appears in humans in early childhood and it is also present in other animals, but it is still poorly understood. Brain imaging techniques have identified the parts of the brain that are active when perceiving numbers or making calculations. As techniques have advanced, it has become possible to resolve fine differences in brain activity that occur",380,128,0.3368
dialogsum,"#Person1#: Have you received any degrees? #Person2#: Yes. In 1996 I received my Bachelor of Science degree from Hebes University, and in 2001 I received my MBA degree from Peking University. #Person1#: How about your academic records at college? #Person2#: In fact my records were excellent. My overall GPA was 9 on a 10 scale, which was the highest in my class. #Person1#: That's very impressive. Which course did you like best? #Person2#: English. It was both interesting and useful, so I showed a great interest in it. #Person1#: Can you tell me why you changed your major when you were a graduate student? #Person2#: Because I am very interested in administration and I did take some courses in it. I also performed well in the subjects. Hence I believe that I can do a good job in this position. #Person1#: Did you get any honors and awards at college? #Person2#: Yes. I was awarded a scholarship from the university every year. In 1995 I participated in the National Contest of Maths Models and I won the prize.","#Person1# interviews #Person2# and asks #Person2# some questions, including #Person2#'s degrees, academic records, the favorite course, and awards in college. #Person2# also tells #Person1# why #Person2# changed the major into administration.",178,31,0.1742
dialogsum,"#Person1#: So it looks like we start selling in the U. S. next year. #Person2#: Did Mr. Lin put you in charge of marketing? #Person1#: He's still not sure whether he wants to put me in charge, or whether he wants to hire an American. But even if he hires an American, I'll probably be transferred to our American office. #Person2#: Where will it be? #Person1#: We aren't sure yet. Maybe L. A. I think L. A. would be the best idea. #Person2#: Is it because of trade negotiations that we can start selling in the U. S. ? #Person1#: Yes, the recent agreements between the two governments have changed everything. Now we have the right to sell in America at a much lower tariff. It's going to be good. We can compete more directly with them. #Person2#: Great. #Person1#: Our computers have a high level of quality now. We can demonstrate it. And our prices will be good. So I think it will really be worthwhile. #Person2#: You seem excited about it. #Person1#: Well, you know I studied marketing in America. So maybe the thought of going back there to promote our brand is kind of exciting to me. I'd love to be part of the team. #Person2#: Do you honestly think we can compete though? All the computer giants are there. #Person1#: Yes, I do. I think we can compete. I think we can make a name for ourselves. It will be hard at first. But if we develop a good advertising campaign, I think we can break into the market. #Person2#: The company will have to choose a good advertising firm. And then there's the problem of quality. How do we convince American buyers that our quality is good? #Person1#: It takes some time. Because even if the quality is high, people won't accept a high tech product unless they recognize the name. Name recognition is crucial. #Person2#: Well, I hope it all works out, John. I think if you're part of the team, things will go well. But you know we'd all miss you here. So I won't say I'm happy to think that you're leaving. #Person1#: That's very nice of you to say. But if we set up an office there in the States, maybe",John will probably be transferred to the American office to start selling there because the recent agreements between governments enable them to sell at a much lower tariff. John thinks they can compete and break into the market if they develop a good advertising campaign. John invites #Person2# to join their office in the States in the future. #Person2# rejects because #Person2# doesn't want to leave Taiwan.,380,67,0.1763
scientific_lay_summarisation-elife-norm,"evolutionary analysis using ancestral protein reconstruction – phylogenetic inference of ancestral sequences followed by gene synthesis, genetic manipulation, and experimental characterization – has proven to be an effective strategy for elucidating these questions (Harms and Thornton, 2010; Harms and Thornton, 2013). Here, we apply ancestral protein reconstruction to investigate the historical trajectory, timing, and mechanisms of evolution of a new protein function important to organized multicellularity in diverse animal phyla. For dividing animal cells to generate and maintain organized tissues, the mitotic spindle must be oriented relative to the position of surrounding cells (Morin and Bellaïche, 2011; Gillies and Cabernard, 2011; Lu and Johnston, 2013; Cabernard and Doe, 2009; Williams et al. , 2011). Cells that orient the spindle parallel to the epithelial plane, for example, expand the tissue; those that rotate it orthogonally to the plane escape the epithelium, as in epithelial-mesenchymal transitions during development (Morin and Bellaïche, 2011; Gillies and Cabernard, 2011; Nakajima et al. , 2013). Experiments have identified a protein complex that mediates robust positioning of the mitotic spindle by using a scaffolding protein to link the spindle’s astral microtubules to a molecular marker that is localized on the cell’s cortex by external signals (1A) (Lu and Johnston, 2013; Johnston et al. , 2009; Siegrist and Doe, 2005; Siegrist, 2006). The complex and its functions have been most extensively studied in Drosophila melanogaster neuroblasts, but it plays a similar role in birds and mammals (Saadaoui et al. , 2014) and in other cell types, such as several kinds of epithelium (Nakajima et al. , 2013; Saadaoui et al. , 2014; Bergstralh et al. , 2013; Bell et al. , 2015). In this complex, the scaffold is the GK protein interaction domain (GKPID) of the protein Discs large (Dlg), which binds microtubule-associated motor proteins, such as the kinesin-3 family member KHC-73, and the Partner of Inscuteable protein (Pins in insects, LGN in vertebrates). In neuroblasts, the complex is localized relative to the position of adjacent cells by the interaction of a transmembrane receptor – which receives local extracellular signals – with Pins, which in turn recruits GKPID, KHC-73, and the spindle microtubules (Yoshiura et al. , 2012). In epithelia, in contrast, localization of the complex relative to surrounding cells appears to be mediated by Dlg itself; Pins","For billions of years, life on Earth was made up of single cells. In the lineage that led to animals – and independently in those that led to plants and to fungi – multicellular organisms evolved as cells began to specialize and arrange themselves into tissues and organs. Although the evolution of multicellularity is one of the most important events in the history of animal life, very little is known about the molecular mechanisms by which it took place. To form and maintain organized tissues, cells must coordinate how they divide relative to the position of their neighbours. One important aspect of this process is orientation of the mitotic spindle, a structure inside the dividing cell that distributes the chromosomes —and the genetic material they carry — between",380,128,0.3368
scientific_lay_summarisation-elife-norm,"e. , journey type and subtask) experienced in the maze could be decoded from the ensemble activity of place cells. Since the rats ran along similar spatial paths while performing different subtasks throughout this task, differences between subtasks can be interpreted as non-spatial “what” information. Provided that the mechanisms are preserved in temporally compressed replays that occur during brief periods of immobility, the subtask as “what” information occurring along the path in the maze might be examined in the replay. Building on this previous study (Takahashi, 2013), I accordingly investigated whether “what” information is contained in the replay of place cell activity sequences during the brief immobility periods that occur while the animal is engaging in the task. I tested whether the methods used for the subsequent replay analyses could predict running path and trial type from the place cell activity sequences recorded during running. A total of 1084 principal cells in the dorsal hippocampal CA1 were recorded using an array of 10 extracellular dodecatrodes (Takahashi and Sakurai, 2005) in four well-trained rats (individuals that had achieved an overall task performance of >90% for a week), while they were performing the task (Table 1). Because running speed, head direction, and physical position can influence place cell firing (McNaughton et al. , 1983; Wiener et al. , 1989), only 556 place cells were examined in the following analyses. These cells, which had spatial information >0. 3 bits/spike, fired at significantly different rates during different trial types (i. e. , journey type and subtask), even when running speed, head direction, and x and y coordinates were taken into account (Analysis of covariance (ANCOVA) with these covariates, p < 0. 05) (Wood et al. , 2000). The rats were exposed to each of the subtasks intermittently at least twice throughout the entire session, but my previous study suggested that place fields are not remapped between trials of the same type, regardless of differences in levels of exposure to the trials (Takahashi, 2013). I therefore combined place cell activity from all trials of the same type, irrespective of the level of exposure. 10. 7554/eLife. 08105. 005Table 1. Behavioral and electrophysiological measurements and estimation accuracy of position and trial-type during runningDOI: http: //dx. . org/10. 7554/eLife. 08105. 005RAT numberIIIIIIIVTotalNumber of erroneous laps091415Number of correct laps142142139139562Task","Place cells are neurons that respond to a particular location in the physical world. For example, as a rat runs around a maze, some place cells will become active when the rat reaches one corner. When the rat moves on towards a different corner, other place cells activate instead. The real-time activity of these place cells helps the rat to work out where it is in the maze. This activity also contains information about what the rat is doing. In addition to their real-time activity, place cells also help previous events to be ‘replayed’ mentally, which is important for making decisions. Previous studies have shown that when a rat pauses during a task, place cell replays allow it to mentally map out the route it needs to take.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"1979; Alspaugh et al. , 1981; Hazelton et al. , 1987). Further, RA patients have increased EBV-specific CD8+ T cells (Lünemann et al. , 2008), yet these cells have a reduced ability to kill EBV-infected B cells when compared to the same subset of EBV-specific CD8+ T cells from healthy controls (Takei et al. , 2001). However, the precise role of EBV in RA pathogenesis remains unknown. Evidence from in vivo models is scarce and previous studies have focused primarily on the direct relationship between EBV infection and damage to the joint capsule, with little attention given to systemic effects of EBV infection on immune modulation preceding and continuing throughout disease (Kuwana et al. , 2011; LeBel et al. , 2018). Mice with humanized immune systems, namely NOD/Shi-scid/IL-2Rγnull mice reconstituted with CD34+ hematopoietic stem cells, that were infected with EBV went on to spontaneously develop erosive arthritis, suggesting a causative role of EBV in arthritis development (Kuwana et al. , 2011). Related, a serum transfer‐induced arthritis model was used to demonstrate that Ly6Chigh monocytes play a role in transporting murine gammaherpesvirus 68 (γHV68), an EBV homolog, to the synovium (LeBel et al. , 2018). Our group has previously shown that latent γHV68 infection exacerbates experimental autoimmune encephalomyelitis (EAE) and leads to a disease that more closely resembles MS, with increased demyelination and infiltration of CD8 to cells of the central nervous system in γHV68-infected mice (Casiraghi et al. , 2012). Critically, this enhancement was specific to γHV68; other viruses, including lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV), did not lead to enhancement of EAE. Additionally, enhancement took place without changes to autoantibody levels. An in vivo model that recapitulates the temporal and systemic immunological aspects of the relationship between EBV and RA is critical. To examine the relationship between EBV and RA, we have adapted in vivo models of both. γHV68 is a natural pathogen that is a well-established and widely-used murine model of EBV infection that shares an array of characteristics with human EBV infection, including latent persistence in B cells, viral reactivation from latency, a potent CD8 T cell response, and immune evasion tactics (Olivadoti et al. , 2007; Wirtz et al. , 2016). Type II collagen-induced arthritis (CIA) is a commonly used model of RA wherein","Rheumatoid arthritis is one of the most common autoimmune diseases, leaving patients in pain as their immune system mistakenly attacks the lining of their joints. The precise cause is unknown, but research suggests a link to the Epstein-Barr virus, the agent responsible for mononucleosis (also known as glandular fever). After infection and recovery, the virus remains in the body, lying dormant inside immune ‘B cells’ which are often responsible for autoimmune diseases. Of particular interest are a sub-group known as ‘age-associated B-cells’, which are mostly cells left over from fighting past infections such as mononucleosis. Yet, the link between Epstein-Barr virus and rheumatoid arthritis remains hard to investigate because of the long gap between the two diseases: the virus mostly affects children and young people, while rheumatoid arthritis",380,128,0.3368
dialogsum,"#Person1#: Are you ready to go shopping? #Person2#: Not yet. I'm not finished with my research yet. #Person1#: What research? #Person2#: Reading my fashion magazines! How do you think I know so much about all the latest trends? #Person1#: But they're just ads. . . #Person2#: Duh. . . That's the point. The people in the ads are wearing what's in. Plus, there are articles on new trends. . .",#Person1# wants to go shopping with #Person2# but #Person2# hasn't finished reading fashion magazines.,70,14,0.2
dialogsum,"#Person1#: The winter in Ottawa is freezing. #Person2#: From mid-November, snow started to pile up in Ottawa. #Person1#: I think I will be adapted to it. #Person2#: Although the weather here is very cold, the people are warm. #Person1#: Yes, that's the reason why I remain here.",#Person1# thinks winter in Ottawa is freezing while #Person2# says people in Ottawa are warm.,47,15,0.3191
dialogsum,"#Person1#: I'd like to send this parcel to Spain, please. #Person2#: Do you want to send it by airmail or by surface mail? #Person1#: Well, how long will it take if I send it by surface mail? #Person2#: About five weeks. #Person1#: Oh, dear. It won't get there for New Year's Day if I send it by surface mail. How much will it cost if I send it by air? #Person2#: Just a moment. I'll weigh it.",#Person2# serves #Person1# to send a parcel by air so that it'll get to Spain for New Year's Day.,77,19,0.2468
pubmed-summarization,"a 17-year - old healthy male was seen with complaints of painless swelling over the left eye for the past four weeks . the rest of the systemic and ocular history was not significant . on examination his vision was 20/20 both eyes . on slit - lamp examination there was erythematous , subconjunctival nodular mass in the left eye [ ] . the lesion had a smooth surface with normal surrounding sclera and was not tender . hemoglobin , red blood cell count , total and differential white blood cell count , platelet count , erythrocyte sedimentation rate ( esr ) and blood smear were normal . hematoxylin and eosin stained sections showed a mixed cellular infiltrate , predominantly composed of histiocytes mixed with lymphocytes , including plasma cells and polymorphous nuclear leucocytes . histiocytes were filled with pink cytoplasm and contained lymphocytes , a pathognomic finding also known as lymphophagocytosis [ ] . stains for bacteria , fungus and acid - fast bacilli were negative . the patient was started on systemic prednisolone ( 1mg / kg body weight ) on a tapering dose for a period of four weeks . at six weeks follow - up there were no new lesions and the subconjunctival mass showed no increase in size . rosai and dorfman first described sinus histiocytosis with massive lymphadenopathy in 1969.1 this disease mainly presents as a massive painless cervical adenopathy in children or young adults of african ancestry . extranodal disease has been found to occur in 43% cases which may be widespread and most frequently involves the respiratory tract , paranasal sinuses , visceral organs , skin , bone , central nervous system , genitourinary tract , and orbit.2 other features include low- grade fever , leukocytosis with neutrophilia , elevated esr , and hypergammaglobulinemia.5 ocular involvement is relatively uncommon ( 8.5% ) , and most cases have presented as lymphoproliferation in the soft tissues of the orbit and eyelids.6 epibulbar mass as isolated finding of extranodal rdd is very rare with only four cases reported in the literature so far.7 - 9 the underlying cause of rdd is unclear . epstein - barr virus2 and human herpes virus 6,10 have been isolated in a few patients , but no clear association has","rosai - dorfman disease is a rare idiopathic disorder characterized by painless lymphadenopathy with cervical involvement in more than 80% cases . we report a case of rosai - dorfman disease presenting as an isolated epibulbar mass in a healthy young adult male . epibulbar involvement in rosai - dorfman disease is a rare presentation as can be seen from a review of all literature . the presentation , differential diagnosis and treatment are discussed .",380,76,0.2
pubmed-summarization,"hospital located in the midwest . patients admitted to this picu include children ranging from one day to over 18 years of age , with a wide range of disease processes including trauma , cardiothoracic surgery , respiratory failure , metabolic disease , and sepsis . orders for iv medication infusions and ivf may be entered into the cpoe system by attending physicians , trainees ( fellows and resident physicians ) , and nurse practitioners and physician assistants . data were gathered over a period of seventeen weekdays . between study periods , the picu also underwent relocation and expansion from 30 beds to 72 beds . the cpoe system , sunrise clinical manager version 4.5 by eclipsys technologies corporation , was implemented in september of 2000 a closed - loop system consisting of a bidirectional interface between cpoe and pharmacy systems was established in september of 2008 . intravenous medication infusions were defined as medications requiring the use of an infusion pump . only medications given as continuous iv infusion were included . medications given via infusion pump were excluded if dosing was intermittent , a change from methodology of the previous study . intravenous fluids were defined as total parenteral nutrition ( tpn ) , lipids , and crystalloid infusions given continuously via infusion pump . data were simultaneously collected from the medication orders in the cpoe system and the bedside infusion pumps by trained observers once a day over a period of seventeen days in august of 2010 . one observer recorded date , time , bed number , each infused medication or fluid , and corresponding dose or rate . a second observer simultaneously recorded existing orders by bed space , capturing the date and time of observation , and each ordered medication or fluid with its respective dose or rate . a line - by - line comparison of order observation data with the pump observation data was performed , matched by time and bed number . observations occurring more than fifteen minutes apart were excluded to minimize the effect of any interim changes to order or pump . for each observed medication infusion or ivf , analysis began with verifying the presence of a corresponding order . for those that had a corresponding order","background . the ability of safety technologies to decrease errors , harm , and risk to patients has yet to be demonstrated consistently . objective . to compare discrepancies between medication and intravenous fluid ( ivf ) orders and bedside infusion pump settings within a pediatric intensive care unit ( picu ) before and after implementation of an interface between computerized physician order entry ( cpoe ) and pharmacy systems . methods . within a 72-bed picu , medication and ivf orders in the cpoe system and bedside infusion pump settings were collected . rates of discrepancy were calculated and categorized by type . results were compared to a study conducted prior to interface implementation . expansion of picu also occurred between study periods . results . of",380,128,0.3368
pubmed-summarization,"since stroke onset was 10.3 1.4 months . meansd , eg : experimental group , cg : control group the experimental group conducted pnf lower extremity patterns using the rhythmic initiation ( ri ) method 110 cm below the water surface ; the water temperature was 3133 c . exercises were performed in a supine posture after simple stretching ; subjects wore a body ring between l5 and s1 and a neck collar . the control group conducted pnf lower extremity patterns on the ground in a supine posture after simple stretching . the ri method starts from passive exercise , proceeds to active resistance exercise , and helps increase coordination , motor sensation , and balance . the pnf lower extremity patterns consisted of patterns d1 and d2 . the d1 pattern ends at either flexion - adduction - external rotation knee flexion or extension - adduction external rotation knee extension . the d2 pattern ends at either flexion - adduction external rotation knee flexion or extension - adduction - external rotation knee extension . pnf lower extremity patterns were conducted 30 minutes / day , 5 days / week for 6 weeks . balance was measured with the berg balance scale ( bbs ) , timed up and go test ( tugt ) , functional reach test ( frt ) , and one leg stand test ( olst ) . the bbs consists of 14 items and can be categorized into sitting , standing , and postural changes . scores in each category range from 04 , with 56 possible total points ; higher scores indicate better balance . the tugt measures the time required to stand up from a chair and shuttle back and forth between the chair and a spot in front of the subject three times . the frt measures the distance one can reach with an arm from a standing posture . the olst measures how long one can stand on one foot with the eyes open without placing the other foot on the ground . adl were measured with the functional independence measure ( fim ) , which consists of 13 items related to mobility and 5 related to recognition . the items were scored on a scale of 17 with 126 possible","[ purpose ] this study investigated the effect of aquatic proprioceptive neuromuscular facilitation ( pnf ) patterns in the lower extremity on balance and activities of daily living ( adl ) in stroke patients . [ subjects ] twenty poststroke participants were randomly assigned to an experimental group ( n = 10 ) or a control group ( n = 10 ) . the experimental group performed lower extremity patterns in an aquatic environment , and the control group performed lower extremity patterns on the ground . both exercises were conducted for 30 minutes / day , 5 days / week for 6 weeks . balance was measured with the berg balance scale ( bbs ) , timed up and go test ( tugt ) , functional reach",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Flexibility in the bilateral coordination of muscle contraction underpins variable locomotor movements or gaits. While the locomotor rhythm is generated by ipsilateral excitatory interneurons, less is known about the commissural excitatory interneurons. Here we examined how the activity of the V0v interneurons – an important commissural neuronal class – varies with the locomotor speed in adult zebrafish. Although V0v interneurons are molecularly homogenous, their activity pattern during locomotion is not uniform. They consist of two distinct types dependent on whether they display rhythmicity or not during locomotion. The rhythmic V0v interneurons were further subdivided into three sub-classes engaged sequentially, first at slow then intermediate and finally fast locomotor speeds. Their order of recruitment is defined by scaling their synaptic current with their input resistance. Thus we uncover, in an adult vertebrate, a novel organizational principle for a key class of commissural interneurons and their recruitment pattern as a function of locomotor speed. The precise coordination of movements on the two sides of the body is an essential feature of locomotion in animals with bilateral symmetry (Grillner and Jessell, 2009; Arber, 2012; Moult et al. , 2013; Kiehn, 2016). The left-right coordination during locomotion can vary in a context-dependent manner to produce alternating, e. g. walking in limbed animals or swimming in fish, or synchronous, e. g. hopping movements in limbed animals. This is largely achieved by regulating the activity of populations of commissural interneurons connecting local interacting circuits on the two sides of the spinal cord (Soffe et al. , 1984; Dale, 1985; Buchanan, 1999a, 1999b; Butt and Kiehn, 2003). The V0 interneurons, which originate from the p0 progenitor domain, represent a major commissural neuronal population controlling the left-right alternation of locomotor movements. The molecular mechanisms of differentiation of the V0 interneurons display striking similarities between zebrafish and mice. This interneuron population can be subdivided into two broad classes; one is excitatory and located ventrally early during development (V0v), and the other is inhibitory and occupies a dorsal position (V0d) (Moran-Rivard et al. , 2001; Pierani et al. , 2001; Lanuza et al. , 2004). In addition, a detailed birth-date analysis in zebrafish has revealed three different subclasses of excitatory V0v interneurons arising in an order that correlates with their morphology and axonal projections, arguing for a further subdivision of","During movements such as swimming and walking, the left and right sides of the body are kept coordinated by specific neurons in the spinal cord. Some of these neurons – called V0 neurons – can either excite or inhibit neurons on the opposite side of the spinal cord. In mice, the inhibitory V0 neurons are responsible for left-right coordination when the mice are moving slowly, while the excitatory neurons operate when the animals are moving more quickly. However, in zebrafish larvae a group of excitatory V0 neurons are only active when the larvae are swimming slowly. Björnfors and El Manira investigated whether excitatory V0 neurons in adult zebrafish behave like those in the larvae, or whether they act more like those in mice. The experiments show that the",380,128,0.3368
dialogsum,"#Person1#: Office software like Windows might be one of the best inventions in this information age. It saves us from so much work and makes the communication even around the world much easier. #Person2#: Fully agree. I do enjoy the convenience though I am still a beginner in using Excel. The latest office equipment is more type-functional. It combines fax machine, copy machine and printer in one. It saves a lot of place one machine instead of three. #Person1#: Yes, this machine is even smaller than those before. #Person2#: When will we get one of those? #Person1#: You know our boss always trying to save the last penny. We have to use up the equipment first.",#Person2# and #Person1# admires the latest office equipment. #Person1# thinks they won't get the new machines as their boss is a saver.,116,22,0.1897
scientific_lay_summarisation-elife-norm,"of insecticide resistance in vivo and in cultured cells. We combined Pacific Biosciences long reads and Illumina short reads (1A, Table 1, and Materials and methods) to sequence genomic DNA from Hi5 cells and T. ni male and female pupae. The initial genome assembly from long reads (46. 4 × coverage with reads >5 kb) was polished using paired-end (172. 7 × coverage) and mate-pair reads (172. 0 × coverage) to generate 1976 contigs spanning 368. 2 megabases (Mb). Half of genomic bases reside in contigs > 621. 9 kb (N50). Hi-C long-range scaffolding (186. 5 × coverage) produced 1031 scaffolds (N50 = 14. 2 Mb), with >90% of the sequences assembled into 28 major scaffolds. Karyotyping of metaphase Hi5 cells revealed that these cells have 112 ± 5 chromosomes (1B, — 1). Because lepidopteran cell lines are typically tetraploid (Hink, 1972), we conclude that the ~368. 2 Mb T. ni genome comprises 28 chromosomes: 26 autosomes plus W and Z sex chromosomes (see below). To evaluate the completeness of the assembled T. ni genome, we compared it to the Arthropoda data set of the Benchmark of Universal Single-Copy Orthologs (Simão et al. , 2015) (BUSCO v3). The T. ni genome assembly captures 97. 5% of these gene orthologs, more than either the silkworm (95. 5%) or monarch butterfly (D. plexippus; 97. 0%) genomes (Supplementary file 1A). All 79 ribosomal proteins conserved between mammals and D. melanogaster (Yoshihama et al. , 2002; Marygold et al. , 2007) have orthologs in T. ni, further evidence of the completeness of the genome assembly (Supplementary file 1B). Finally, a search for genes in the highly conserved nuclear oxidative phosphorylation (OXPHOS) pathway (Porcelli et al. , 2007) uncovered T. ni orthologs for all known D. melanogaster OXPHOS genes (Supplementary file 1C). The genomes of wild insect populations are typically highly heterogeneous, which poses a significant impediment to assembly (Keeling et al. , 2013; You et al. , 2013). We were unable to generate an isogenic T. ni strain by inbreeding. Therefore, our T. ni sequence reflects the genome of Hi5 cells, not cabbage looper itself. Hi5 cells presumably derive from a single immortalized, germline founder cell, which should reduce genomic variation among the cell line’s four sets of chromosomes. To test this supposition, we","A common moth called the cabbage looper is becoming increasingly relevant to the scientific community. Its caterpillars are a serious threat to cabbage, broccoli and cauliflower crops, and they have started to resist the pesticides normally used to control them. Moreover, the insect’s germline cells – the ones that will produce sperm and eggs – are used in laboratories as ‘factories’ to artificially produce proteins of interest. The germline cells also host a group of genetic mechanisms called RNA silencing. One of these processes is known as piRNA, and it protects the genome against ‘jumping genes’. These genetic elements can cause mutations by moving from place to place in the DNA: in germline cells, piRNA suppresses them before the genetic information is transmitted to the next generation. Not",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 1994; Mombaerts et al. , 1996; Sakano, 2010). Odorants activate complex spatio-temporal patterns of glomeruli, which can be monitored with various imaging techniques (Rubin and Katz, 1999; Uchida et al. , 2000; Wachowiak and Cohen, 2001; Spors and Grinvald, 2002; Bozza et al. , 2004; Bathellier et al. , 2007; Vincis et al. , 2012; Patterson et al. , 2013). The sensory information received in the glomeruli by OB output neurons is then transferred to cortical areas. Several plasticity mechanisms have been reported in olfactory cortical regions (Quinlan et al. , 2004; Franks and Isaacson, 2005; Stripling and Galupo, 2008) as well as OB circuitry (Saghatelyan et al. , 2005; Marks et al. , 2006; Gao and Strowbridge, 2009; Livneh and Mizrahi, 2012). At the input level, both sensory deprivation (Cummings et al. , 1997) and developmental reorganization (Zou et al. , 2004; Kerr and Belluscio, 2006) have been reported to induce structural plasticity in the glomerular layer. Despite these facts, little is known about learning-mediated functional plasticity of sensory inputs in the adult OB of awake mice. Here, we investigate plasticity at the periphery induced by learning or passive exposure by combining olfactory behavior and functional imaging in awake mice. Olfactory training caused an enhanced sensitivity and potentiation of sensory inputs, which helped the animals to achieve fast and accurate odor discrimination. Most strikingly, this functional plasticity was induced specifically by the learning process but not by a passive exposure to the same odorants, and lasted up to several weeks. To investigate the potential functional plasticity at the level of sensory neurons induced by olfactory learning, mice were trained to discriminate two odorants (rewarded vs unrewarded) on a go/no-go operant conditioning paradigm (Abraham et al. , 2004,2010). As perception can vary with the odorant dilution, we used a wide spectrum of dilutions covering several orders of magnitude ranging from 100 to 10−10 (percentile dilution in mineral oil) for two different odor pairs (cineol [Cin] vs eugenol [Eu] and isoamyl acetate [IAA] vs ethyl butyrate [EB]) (1A). After training, odorant-evoked input patterns were measured in the olfactory bulb by intrinsic optical signal (IOS) imaging (1B, C). To control for the effect of odorant exposure during olfactory discriminative learning, two other groups of mice were also imaged (naïve and passively","The mammalian brain is not static, but instead retains a significant degree of plasticity throughout an animal’s life. It is this plasticity that enables adults to learn new things, adjust to new environments and, to some degree, regain functions they have lost as a result of brain damage. However, information about the environment must first be detected and encoded by the senses. Odors, for example, activate specific receptors in the nose, and these in turn project to structures called glomeruli in a region of the brain known as the olfactory bulb. Each odor activates a unique combination of glomeruli, and the information contained within this ‘odor fingerprint’ is relayed via olfactory bulb neurons to the olfactory cortex. Now, Abraham et al. have revealed that the earliest stages of",380,128,0.3368
dialogsum,"#Person1#: Let's got out tomorrow night. We can go to a bar and try to find you a girlfriend. #Person2#: I don't think that's a good idea. I am just not good with approaching someone and starting up a conversation. #Person1#: Maybe you just need a few pick-up lines, you know, break the ice. #Person2#: Pick-up lines don't work! #Person1#: Come on! You can just walk up to a girl and say ' If you were a booger I 'd pick you first. ' #Person2#: What? Come on! That's just lame! No girl would fall for that! #Person1#: Fine, then you can say, ' So there you are! I'Ve been looking all over for YOU, the woman of my dreams! ' #Person2#: That's a good one! I think that's pretty funny. #Person1#: Yeah, so you make her laugh, you make a fool of yourself a little bit and then you buy her a drink. #Person2#: Ok, how does this sound, ' I was so enchanted by your beauty that I ran into that wall over there. So I am going to need your name and number for insurance purposes. ' #Person1#: Nice! Let's go!",#Person2#'s not good with approaching someone. #Person1# offers some pick-up lines to break the ice with girls. #Person2# finally comes up with a nice pick-up line and they are going to put it into practice.,194,35,0.1804
scientific_lay_summarisation-elife-norm,"(chamber A) and US (foot shocks) on Day 1. On Day 2, they received a prolonged CS presentation without any US (extinction training), then their freezing time gradually decreased. On Day 3, they were re-exposed to CS to confirm retention of extinction (test 1). To reinstate the conditioned fear, they immediately received a weak US (reminder shock) in chamber B on Day 4, and they were exposed to CS again on Day 5 (test 2). The mice showed higher freezing time in test 2 than they did in test 1, suggesting successful reinstatement. Freezing time was comparable between tests 1 and 2 if mice were exposed to chamber B without a reminder shock on Day 4 (39. 5 ± 4. 2% in test 1 and 32. 6 ± 5. 3% in test 2, n = 4). When we gave the reminder shock to naive mice, the reminder shock alone did not induce high fear responses (6. 0 ± 2. 1%, n = 5), indicating that the reminder shock-induced increase in freezing was derived from the original conditioned fear, not from new learning. 10. 7554/eLife. 08274. 003Figure 1. Reinstatement is associated with low IL activity. (A) A reminder shock reinstated extinguished fear (n = 10 mice; paired t-test, t (9) = 3. 6, p = 0. 0059). (B) Representative images of the infralimbic cortex (IL), the ventral intercalated amygdala neurons (ITCv), and the central nucleus of the amygdala (CeM) in the Fear, Extinction, and Reinstatement groups. (C) c-Fos+ cell density decreased in the IL and the ITCv and increased in the CeM with reinstatement (n = 8–11 mice; F (2,27) = 4. 3, p = 0. 023 [IL]; F (2,26) = 4. 8, p = 0. 0016 [ITCv]; F (2,26) = 6. 3, p = 0. 0058 [CeM]; Tukey' s test, PExtinction vs Reinstatement = 0. 029 [IL], 0. 035 [ITCv], 0. 013 [CeM]). (D) IL muscimol infusions resulted in high freezing (n = 10 mice; t (18) = 2. 4, p = 0. 030). **p < 0. 01, *p < 0. 05. Data represent mean ± standard error. : http: //dx. . org/10. 7554/eLife. 08274. 00310. 7554/eLife. 08274. 004Figure 1— 1. Freezing behaviour of the mice subjected to c-Fos activity mapping. Mice of the Reinstatement group showed greater freezing behaviour","Anxiety disorders affect millions of people worldwide. While many people with anxiety disorders can recover with appropriate treatment, about 40% of these individuals will encounter a relapse of their condition. Researchers can investigate the causes of relapses by creating animal models of the processes involved. For example, if a mouse receives a small shock every time it enters a particular cage, it will learn to associate that cage with the shock. Once this association has been created, it can be ‘undone’ using a procedure called extinction. In the cage example, this may be performed by placing the mouse in the cage for a long time, but without giving it any shocks. Over time, the animal learns that the cage is no longer linked to an unpleasant outcome. However,",380,128,0.3368
dialogsum,"#Person1#: Good morning, Golden Bridge Hotel at your service. #Person2#: Good morning, I'd like to make a reservation, please. Do you have any rooms available for next week? #Person1#: Alright, single room or double room? #Person2#: Double room, please. It's for an American couple. #Person1#: Hold on, please. Let me check the bookings. Yes, we have double rooms available, what kind of room would you like, Sir? #Person2#: I'd like a room with a nice view, please? #Person1#: We have a nice garden view room. #Person2#: Good, I'll take that one. Is there a bar in your hotel? #Person1#: Yes, Sir. And there is also a party on each Saturday night in the bar till the next morning. #Person2#: Party all night? No kidding. Anyway, what's the room charge? #Person1#: $188. 00 per night, with breakfast, North Pole star buffet. What is their arrival time? #Person2#: They should turn up around 5:00 PM next Tuesday and then check out next Sunday. #Person1#: I see, may I have your name and phone number? #Person2#: Yes, 66301321, Martin.",#Person1# helps Martin make a reservation for a double room with a nice garden view and tells Martin about the price and the bar in the hotel.,176,27,0.1534
dialogsum,"#Person1#: Hello? #Person2#: Hey Tina. What are you doing? #Person1#: I was just watching TV. What's going on with you? #Person2#: I just watched a movie and I'm scared. #Person1#: What did you watch? #Person2#: I saw the Sixth Sense. I didn't know it was going to be so scary. #Person1#: I remember that. It was a great movie. But it was definitely scary. #Person2#: If you're not busy, do you want to come over? I'm afraid to be alone. #Person1#: Sure. I can come over. What should we do? #Person2#: How about if we watch a comedy. I need something to get my mind off the frightening images I have from the Sixth Sense. #Person1#: Ok. I'll get ready and leave. I'll see you in about 20 minutes. #Person2#: Hurry, ok. It's dark out. #Person1#: Don't worry, nothings going to happen. I'll be there real soon. #Person2#: Ok. See you soon.","#Person2# watches the Sixth Sense and is scared. So #Person2# calls Tina to come over and watch a comedy together, and Tina will arrive soon.",152,25,0.1645
dialogsum,"#Person1#: I think your speech was excellent. #Person2#: Was it? #Person1#: Sure it was. #Person2#: Thank you. It was really a challenge to speak before such a large audience, you know. #Person1#: But you did it and did it well!",#Person1# praises #Person2# for #Person2#'s speech.,40,6,0.15
scientific_lay_summarisation-elife-norm,"Pignatelli and Belluzzi, 2017; Roland et al. , 2016; Vaaga et al. , 2017). The complexity and sometimes mutually exclusive nature of such functions – especially in relation to spatial connectivity – make it unlikely that a single class of interneuron could perform them all. Indeed, morphological variability has been demonstrated among OB DA neurons and has been linked to their time of birth (Halász et al. , 1981; Kiyokage et al. , 2010; Kosaka and Kosaka, 2007; Kosaka et al. , 2008; Kosaka and Kosaka, 2009; Kosaka and Kosaka, 2011; Kosaka and Kosaka, 2016; McLean and Shipley, 1988; Pignatelli and Belluzzi, 2017; Pignatelli et al. , 2005). However, no discrete features demarcating distinct OB DA subpopulations have yet been identified. More importantly, nothing is currently known regarding the functional properties of putative OB DA subtypes. Are there physiological differences between embryonically generated and adult-born DA cells? And might such differences start to account for the various functional roles ascribed to this cell type in sensory processing? Here, we build on previous work in vitro (Chand et al. , 2015), to show that different classes of OB DA neuron in vivo can be clearly distinguished based on the presence or absence of an axon and its key subcellular specialisation, the axon initial segment (AIS). AIS-positive DA cells are larger, with broader dendritic arborisations, and are exclusively born in early embryonic development. Postnatally generated DA cells, in contrast, are all small and anaxonic. Crucially, these morphological and ontological distinctions also map onto clear functional differences in both cellular excitability and odorant response properties in vivo, strongly constraining the potential role of adult-born DA cells in sensory processing. To investigate the presence of an axon initial segment (AIS) in DA cells we performed immunohistochemistry on fixed slices of the olfactory bulb of juvenile (P28) wild-type C57/Bl6 mice. We identified DA cells by labelling them with an antibody against tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of dopamine. For AIS identification we stained for ankyrin-G, the master AIS organising molecule (AnkG, 1A) (Hedstrom et al. , 2008; Jenkins et al. , 2015; Zhou et al. , 1998). While for most TH-positive cells we could not detect AnkG label on any of their processes, we identified a subset of large DA neurons","Most of your brain cells were born before you were. But in mammals, including humans, some of these brain cells, also known as nerve cells or neurons, are created after birth. These later-generated neurons are often extremely similar to their counterparts produced in the womb, and also seem to perform a similar role once they are fully mature. However, it has not been entirely clear if the later-produced neurons may also have a specific purpose. Neurons are made of a cell body with a cable-like structure called axon that transmits information to more distant neurons, and dendrites, which are branches that receive information from other neurons. Neurons use different signalling molecules to communicate, one of which is called dopamine, and the neurons that use this specific signal are",380,128,0.3368
dialogsum,"#Person1#: Hey, Jenny, what's the matter? #Person2#: I was just online in a chat room with three Germans. They used a lot of idioms on purpose and I didn't understand, so I asked them what they meant. Then they started to ignore me and after a while I started to feel stupid. #Person1#: Oh, you shouldn't. Your German is really good. #Person2#: But it seems they were using their German ability to have fun with each other. They didn't really want to include me. #Person1#: Well, some people are like that. That's all. You can't let them bother you. One nice thing about chat room is that you can leave and go to another one.",Jenny complains to #Person1# that three Germans used lots of idioms in a chat room and ignored her. #Person1# suggests leaving that room and going to another one.,115,28,0.2435
dialogsum,"#Person1#: Do you want any meat today, Mrs. Bird? #Person2#: Yes, please. #Person1#: Do you want beef or lamb? #Person2#: Beef, please. #Person1#: This lamb's very good. #Person2#: I like lamb, but my husband doesn't. #Person1#: What about some steak? This is a nice piece. #Person2#: Give me that piece please, and a pond of meet, too. #Person1#: Do you want a chicken, Mrs. Bird? They're very nice. #Person2#: No, thank you. My husband likes steak, but he doesn't like chicken. #Person1#: To tell you the truth Mrs. Bird, I don't like chicken, either!",Mrs. Bird buys beef and steak from #Person1# because her husband likes steak.,94,13,0.1383
dialogsum,"#Person1#: I am fed up with Jack. He is so weak in dealing with other people and always eats dirt. #Person2#: So he is. But, why not try to help him to become stronger? #Person1#: How do you know that I didn't try? I just couldn't manage it.",#Person1# complains to #Person2# about Jack because Jack is so weak.,48,11,0.2292
scientific_lay_summarisation-elife-norm,"18 families with neither children nor dogs. Each family consisted of at least two cohabiting adults (which we define as ‘partners’ or ‘couples’) between the ages of 26 and 87 years, and all children included in this study were biologically related to and cohabited with the focal couple. Sampling was performed as described in Costello et al. (2009). For humans, fecal, oral (dorsal tongue), forehead, and right and left palm communities were sampled (n = 5 samples per individual all taken at a single time point). Dogs were sampled similarly (n = 36), except that all four paws were swabbed (n = 7 samples per dog taken at the same time that humans were sampled). The age and gender of humans surveyed in each family plus the number and breed of dogs in families with pets are summarized in Table 1. All samples were initially frozen at −20°C before they were transferred to the laboratory where they were stored at −80°C until they were subjected to DNA extraction, PCR of the variable region 2 (V2) of bacterial 16S rRNA genes and subsequent multiplex sequencing with an Illumina GAIIx instrument (Illumina, Inc. , San Diego, CA; n = 969 samples used for the analyses reported, 74,855,127 total reads; average read length, 105 ± 19 nt). The resulting 16S rRNA dataset was analyzed using UniFrac (Lozupone and Knight, 2005), a phylogeny-based measure of the degree of similarity between microbial communities, to assess patterns of similarity within and between families across body sites. 10. 7554/eLife. 00458. 003Table 1. Summary of the number, age classification, and gender of humans surveyed in each family and the number and types of animals in families with petsDOI: http: //dx. . org/10. 7554/eLife. 00458. 003Adults (Sex) Infants (Sex) Adolescents (Sex) Seniors (Sex) Dogs (breed) Other pets2 (M, F) 1 (F) 1 (F) Cat2 (M, F) 1 (Unknown) 2 (M, F) Cats2 (M, F) 1 (F) 2 (M, F) 2 (Unknown) 2 (M, F) 1 (F) 2 (Unknown) 2 (M, F) 1 (F) 1 (M) 2 (M, F) Cats, guinea pigs2 (M, F) 2 (M, F) 2 (Unknown) 2 (M, F) 3 (Unknown) 2 (M, F) 1 (Unknown) 2 (M, F) 2 (M, F) 1 (F) Cat, fish2 (M, F) 1 (M) Cat2 (M, F) 2 (M, F) 2","The human body is home to many different microorganisms, with a range of bacteria, fungi and archaea living on the skin, in the intestine and at various other sites in the body. While many of these microorganisms are beneficial to their human hosts, we know very little about most of them. Early research focused primarily on comparing the microorganisms found in healthy individuals with those found in individuals suffering from a particular illness. More recently researchers have become interested in more general issues, such as understanding how these collections of microorganisms, which are also known as the human microbiota or the human microbiome, become established, and exploring the causes of similarities and differences between the microbiota of individuals. We now know that the communities of microorganisms found in",380,128,0.3368
dialogsum,"#Person1#: Good morning, Plaza Hotel. Can I help you? #Person2#: Hello, I'm just checking the room rates. How much are the single rooms, please? #Person1#: Well, sir, the singles are now from 180 to 240 dollars. #Person2#: And the doubles? #Person1#: The double rooms are now 270 to 330 dollars. #Person2#: That includes tax, I suppose. #Person1#: No. But the price does include breakfast and service charge is extra. #Person2#: Thank you very much. I think I got that. That's singles from 180 to 240 dollars, doubles to 270 dollars. #Person1#: No. The price of doubles is from 270 to 330 dollars. #Person2#: Oh, I see. And can I get an extra bed if we need one? #Person1#: Yes, of course. An extra bed is 45 dollars. #Person2#: Okay, that's fine. Thank you very much. #Person1#: You're welcome.",#Person2# is checking the room rates and #Person1# tells #Person2# the prices. The price doesn't include tax and service charge but includes breakfast.,138,23,0.1667
dialogsum,"#Person1#: Honey, the house is such a mess! I need you to help me tidy up a bit. My boss and her husband are coming over for dinner and the house needs to be spotless! #Person2#: I ' m in the middle of something right now. I ' ll be there in a second. #Person1#: This can ' t wait! I need your help now! #Person2#: Alright, alright. I ' m coming. #Person1#: Ok, here ' s a list of chores we need to get done. I'll do the dishes and get all the groceries for tonight. You can sweep and mop the floors. Oh, and the furniture needs to be dusted. #Person2#: You know what, I have to pick something up at the mall, so why don ' t you clean the floors and I'll go to the supermarket and get all the groceries. #Person1#: Sure that ' s fine. Here is the list of all the things you need to get. Don't forget anything! And can you pick up a bottle of wine on your way home? #Person2#: Hey, honey I ' m back. Wow, the house looks really good! #Person1#: Great! Can you set the table? #Person2#: Just a sec I ' m just gonna vacuum this rug real fast #Person1#: Wait! Don ' t turn it on...",#Person1#'s boss and her husband will come for dinner. #Person1# asks #Person2# to help and they are getting prepared for their coming by cleaning the room and buying groceries.,221,29,0.1312
dialogsum,"#Person1#: We agree to give you a break on the price, all together a discount of 6 %. Good news is, I talked to my boss, he confirmed that if you take care of the shipping costs, we'll throw in insurance. #Person2#: Great! I'd love to get a little better discount than 6 %, but if your company provides the insurance, that will save us a few bucks. . . #Person1#: Now, all this is available to you, as far as you make payment within a 30 day grace period. That shouldn't be a problem, right? #Person2#: No. . . We shouldn't have any problem with that. I know we talked about a possibility for 90 days, but we won't be needing that after your discounted price. #Person1#: So, if all this is agreeable to you, I'll put it all down on paper and fax a contract to you this afternoon. If you can get a signed version of the contract we've agreed upon back to me by tomorrow morning, we can go ahead and make arrangements to ship the product on Tuesday. #Person2#: Great!","#Person1# agrees to give #Person2# a discount of 6% and cover the insurance, given that #Person2# will pay the shipping costs. They are both satisfied with the agreement and #Person1# will fax a contract to #Person2#.",185,36,0.1946
pubmed-summarization,"sum of possible pd manifestations would be tremors at rest , rigidity , bradykinesia , and loss of postural reflexes which represents the cardinal manifestations besides possibility of the following . the basal ganglia include the neostriatum ( caudate nucleus and putamen ) the external and internal pallidal segments ( gpe , gpi ) , the subthalamic nucleus ( stn ) , and the substantia nigra with its pars reticulata ( snr ) and pars compacta ( snc ) . they participate in anatomically and functionally segregated loops that involve specific thalamic and cortical areas . striatum and stn receive glutamatergic afferents from specific areas of the cerebral cortex or thalamus , and transfer the information to the basal ganglia output nuclei , gpi and snr . the nigrostriatal projection terminates predominately at the necks of dendritic spines of the striatal medium spiny output neurons ( msns ) . this anatomic arrangement places the dopaminergic inputs in a position to regulate or gate the corticostriatal transmission . in parkinson 's disease , the degeneration of dopaminergic snc neurons and their projections to the striatum is a slowly evolving process that may take decades to develop . snc projections to the putamen degenerate earlier than projections to associative or limbic portions of the striatum . corresponding to this time course of degeneration , the motor symptoms and signs of parkinson 's disease develop before the nonmotor signs . recognizable motor or nonmotor signs appear only after substantial degeneration of the nigrostriatal neurons ( affecting at least 70% ) , this is due to the remarkable compensatory capacity within the dopaminergic system , or in the circuits it modulates . there may be mild frontal atrophy is some cases , but this is variable . histologically , there is neuronal loss in the substantia nigra pars compacta along with compensatory astrocytic and microglial proliferation . although biochemically there is loss of dopaminergic termini in the striatum , the striatum is histologically unremarkable . hyaline cytoplasmic inclusions or lewy bodies and less well - defined pale bodies are found in some of the residual neurons in the substantia nigra . lewy bodies are proteinaceous neuronal cytoplasmic inclusions . in some regions of the brain , such as the dorsal motor nucleus of the","parkinson 's disease ( pd ) is one of the neurodegenerative diseases which we can by certainty identify its pathology , however , this confidence disappeares when talking about the cause . a long history of trials , suggestions , and theories tried linking pd to a specific causation . in this paper , a new suggestion is trying to find its way , could it be toxicology ? can we in the future look to pd as an occupational disease , in fact , many clues point to the possible toxic responsibility either total or partial in causing this disease . searching for possible toxic causes for pd would help in designing perfect toxic models in animals .",380,119,0.3132
dialogsum,"#Person1#: What are you doing there with your mobile phone? #Person2#: I'm moblogging! #Person1#: Moblogging? what does that mean? #Person2#: Oh, moblogging is a combination of the word 'mobile' and 'blogging'. It's another form of blogging. Users can publish blog entries to the web from a mobile phone or other mobile devices. #Person1#: Sounds interesting! That must be very convenient. #Person2#: Yes, you're right. I can blog wherever and whenever I'm on the move. It's especially good when I'm on a business trip and my laptop happens to be away from me. #Person1#: How can you do that? #Person2#: Well, if I simply want to write a few words, I'll send it by email or edit it all from the cell phone browser. #Person1#: What if you want to publish some photos? #Person2#: Then I'll shoot some pictures, re-size the images and upload them with text descriptions to my blog. #Person1#: I see. Moblogging must have done a great favor for habitual bloggers like you. #Person2#: You bet it!",#Person2# introduces moblogging to #Person1#. Moblogging combines 'mobile' and 'blogging' so that it's convenient for #Person2# to publish blogs anytime anywhere.,169,21,0.1243
dialogsum,"#Person1#: Hello. Good evening. #Person2#: Hello, may I please speak to George Hatton? #Person1#: To whom, did you say? #Person2#: George Hatton. #Person1#: I'm sorry but no one of that name lives here. What number are you calling? #Person2#: 123-4567. #Person1#: That's our number all right but no Mr. Hatton lives here. This is the Smith residence. #Person2#: Oh, I must have the wrong number. I'm terribly sorry. #Person1#: That's all right. I hope you find Mr. Hatton. Good-bye. #Person2#: Good-bye and thank you.",#Person2# tries to phone George Hatton but finds the number is wrong.,84,12,0.1429
pubmed-summarization,"simpar s multidisciplinary collaboration has included several professionals of different disciplines and has produced a number of publications on the personalization of pain therapy through a multidisciplinary approach , including traditional medical , genetic , epigenetic , and table s1 lists each of the 18 papers published by at least two simpar members in collaboration between 2010 and 2015 . as described herein , we have been able to obtain statistically significant results regarding the force of the group as a whole in both the research and public communities . for each of the 12 researchers of which our team is comprised , we created an orcid ( open researcher and contributor i d ) account ( www.orcid.org ) , in addition to an impact story ( ) account that imported our data and synchronized it with the unique orcid identifiers . collected items were assigned to specific categories , such as cited ( or highly cited ) , saved ( or highly saved ) , or discussed . in doing so , our impact story provided us with data regarding the number of times an article was saved by scholars , cited by other researchers , publicly discussed ( facebook , etc ) , and cited by the general public ( blog posts , wikipedia ) . these metrics were classified along two dimensions : audience ( scholars or the public ) and type of engagement with the online research products ( viewed , discussed , saved , cited).7 from impact story , we were able to retrieve all altmetrics data for the 12 researcher accounts ( paper citations , discussions , views by the research community or public ) . through the personal profiles of altmetrics , for each member of the simpar group , we were able to count the number of citations , times a paper was saved , and discussions from the public community for each paper published . then , we compared the simpar group percentages of articles cited ( or highly cited ) , saved ( or highly saved ) , or discussed relative to those published by single authors ( either written alone or in collaboration with coauthors who were not members of the simpar group ) by means of fisher s","in this study , we investigated the impact of scientific publications of the italian simpar ( study in multidisciplinary pain research ) group by using altmetrics , defined as nontraditional metrics constituting an alternative to more traditional citation - impact metrics , such as impact factor and h - index . by correlating traditional and alternative metrics , we attempted to verify whether publications by the simpar group collectively had more impact than those performed by its individual members , either in solo publications or in publications coauthored by non - simpar group investigators ( which for the purpose of this study we will refer to as individual publications ) . for all the 12 members of the group analyzed ( pain therapists , biologists , and pharmacologists",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the initial cell contact to the final maturation of functional synapses. Not only the cells themselves but also the connections between newly recruited members and their old counterparts are survivors of a selection process depending upon neuronal activity patterns. The vast majority of excitatory inputs are received by small bulbous protrusions residing on the dendrites of glutamatergic neurons, called dendritic spines. In newborn GCs, dendritic spines first appear around 16 days after neuronal birth. The spine density increases sharply before cells reach 4 weeks of age and continues to increase at a slower pace until reaching a plateau at 8 weeks (Zhao et al. , 2006). Notably, the NMDAR-dependent survival/death of adult-born GCs is restricted to the time window of 2–3 weeks after neuronal birth, shortly after formation of the first dendritic spines (Tashiro et al. , 2006a). This temporal overlap suggests that the survival of newborn GCs may be related to the state of spinogenesis or synaptogenesis. Indeed, cell death can be induced by non-innervation at the peak of synaptogenesis during embryonic and postnatal development (Naruse and Keino, 1995). Since activation of NMDARs has been shown to support new spine formation (Maletic-Savatic et al. , 1999; Kwon and Sabatini, 2011), we hypothesize that NMDAR is required for initial spine gain on dendrites of newborn GCs and that insufficient spine growth may be the underlying cause of the cell death associated with the genetic deletion of the NMDAR subunit NR1 in newborn GCs. There is a positive correlation between spine volume and the number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) or, more generally, the synaptic strength (Matsuzaki et al. , 2001), supporting the model that spine outgrowth and enlargement are tightly coupled to the formation and maturation of glutamatergic synapses (Zito et al. , 2009). Subject to activity-dependent modifications, spines are highly dynamic in their number, shape and size. Long-term potentiation (LTP) and long-term depression (LTD) at mature synapses, expressed by synaptic insertion and removal of AMPARs, respectively, are associated with NMDAR-dependent enlargement and shrinkage of dendritic spines (Yuste and Bonhoeffer, 2001; Matsuzaki et al. , 2004; Zhou et al. , 2004). Stimuli that induce LTP or LTD may also result in rapid outgrowth or loss of spines, and these changes can be prevented by NMDAR blockers (Engert and","The brain contains billions of cells called neurons. Although most neurons have already formed by the time we are born, part of the brain called the hippocampus produces new neurons throughout our life. These new neurons are thought to be important for learning and forming new memories. Neurons send signals to each other across connections called synapses. Small protrusions called spines stick out of the neuron and each tends to have one synapse that receives a signal from another neuron. Via these connections, the neurons are organized into networks and circuits that control how different parts of the brain work. Therefore, once new neurons are made, they also need to be connected to the correct neurons. The NMDA receptor is found in the surface of neurons, and mutated",380,128,0.3368
pubmed-summarization,"a gallbladder strangulation through an abdominal wall defect on the site of a previous colostomy was described ( 4 ) . in this case , the most remarkable thing is that herniation does not occur through a natural orifice or an acquired defect , such as respectively for the winslow foramen or for an incisional hernia , but directly into the abdominal wall . to our knowledge , there are only 3 published cases of spontaneous herniation of the gallbladder through the abdominal wall ( 5,6,7 ) . another interesting aspect of this case is the presence of a chronically distended gallbladder ( gallbladder hydrops ) , associated with extrinsic compression of the common hepatic duct by an impacted stone in the infundibulum ( mirizzi syndrome type i ) ( 8) . it is probably the gallbladder dilatation that plays an important role in the development of the hernia pressing constantly the gallbladder against the abdominal wall . usually the clinical picture is represented by a right upper quadrant pain , associated with variable degrees of a compromised general condition . in our experience the preoperative study based on computed tomography is essential for the diagnosis of the gallbladder hernia , and it provides also additional information on the abdominal wall defect . the management of this type of hernia consists in reducing the content and repairing the abdominal wall defect . in this case we suggest the laparoscopy as surgical approach of first choice because it allows to solve three problems at the same time : first , the reduction of the gallbladder s incarcerated hernia ; second , it enables to perform a cholecystectomy that was indicated for the presence of gallstones and hydrops ; third , it allows to repair the hernia defect preferably with a mesh , if the local conditions are favorable . in our experience , preoperative imaging has been proved to detect the gallbladder disease and the morphology of the fascial defect . mesh repair is the gold standard for hernias ; however , acute cholecystitis still remains a contraindication for mesh repair due to the high risk of infection .","a gallbladder incarcerated hernia associated with mirizzi syndrome is a very rare entity and to our knowledge this is the first case ever described in literature . an 85-year - old man presented at the emergency department with a tender right upper quadrant mass . computed tomography ( ct ) revealed the presence of a gallbladder lithiasis with signs of acute cholecystitis , herniated through the abdominal wall with an associated mirizzi syndrome . laparoscopic cholecystectomy and repair of the abdominal wall defect were performed . the patient recovered very well and the postoperative period was uneventful .",358,98,0.2737
pubmed-summarization,"conventional nontargeted chemotherapeutics , such as antimetabolites , microtubule inhibitors , and dna intercalating / alkylating agents , are effective at killing cancer cells , but due to their indiscriminate penetration into nearly all cells , they can also damage healthy cells , causing such toxicities as myelosuppression , alopecia , mucositis , peripheral neuropathy , and cardiotoxicity . to minimize such collateral damage to healthy tissues , physicians must often either reduce the dosage or decrease the frequency of drug administration , leading to incomplete elimination of diseased tissue . on the basis of these considerations , recent approaches to cancer therapy have focused on developing methods that specifically target chemotherapeutic agents to cancer cells , allowing for improved tumor suppression with fewer adverse events . the most common approach to drug targeting has relied on the specificity of a monoclonal antibody for its tumor - specific antigen . through the conjugation of a highly cytotoxic drug to a tumor - specific antibody , tumor - selective drug delivery examples of such tumor - targeted antibody drug conjugates ( adcs ) include trastuzumab emtansine and brentuximab vedotin . although several adcs have shown significant success in preclinical and clinical settings , some questions as to their ability to penetrate solid tumors have been raised . a related strategy to achieve tumor - selective drug delivery involves the use of low molecular weight targeting ligands that can similarly deliver attached drugs specifically to cancer cells . drug conjugates ( 1a ) also target receptors that are overexpressed on malignant cells , and their much smaller sizes may permit more thorough tumor penetration . ( a ) general representation of ligand conjugated to cytotoxic payload via a peptide linker . the circle represents the cholecystokinin 2 receptor ( cck2r ) binding ligand , whereas the linker is represented by an oval . the cytotoxic drug , or payload , the solid black line represents a covalent bond between the ligand and the linker , and the dotted line symbolizes a cleavable self - immolative bond . ( b ) chemical structures of the cck2r ligand crl conjugated to the cytotoxic antimicrotubule agents desacetyl vinblastine hydrazide and tubulysin b hydrazide via a hydrophilic peptide linker . in this paper , z-360 ,","as the delivery of selectively targeted cytotoxic agents via antibodies or small molecule ligands to malignancies has begun to show promise in the clinic , the need to identify and validate additional cellular targets for specific therapeutic delivery is critical . although a multitude of cancers have been targeted using the folate receptor , psma , bombesin receptor , somatostatin receptor , lhrh , and v3 , there is a notable lack of specific small molecule ligand / receptor pairs to cellular targets found within cancers of the gi tract . because of the selective gi tract expression of the cholecystokinin 2 receptor ( cck2r ) , we undertook the creation of conjugates that would deliver microtubule - disrupting drugs to malignancies through the specific targeting of cck2r",380,128,0.3368
pubmed-summarization,"and the effort reward imbalance questionnaire.14,15 these instruments are considered complementary sources since they are based on different concepts of the work - related stress . they are mainly focused on measuring the job climate , the facets of job organization , or the balance between effort and reward , but an in - depth examination of individual resources and capabilities is lacking . newman and beehr16 underlined that job stress is a situation wherein job - related factors interact with the worker to change his / her psychological and/or physiological condition , forcing a person to deviate from normal functioning . from this viewpoint , the focus is not the stressful situation or the subjective perception , but the interaction between these two components . in agreement with this rationale , we developed a new multidimensional instrument called the maugeri stress index ( masi ) designed to investigate individual resources for coping with stressful situations on the job . the instrument was developed for an in - depth examination , but it is also usable in the preliminary phase and for monitoring homogeneous groups of workers when individual resources play a critical role in coping with the demands arising from organizational changes . this group of workers represents a category particularly at risk for the development of job stress , and for this reason they can be considered a representative sample of the target population . the first version was tested on a restricted sample ( n=329 ) and has already been published with some clinical qualities and some limitations.17 the aims of this study were to develop a shorter form of the questionnaire using an item reduction procedure and to assess the psychometric properties of the resulting instrument using the rasch measurement model . the masi ( s1 ) requires participants to express their level of agreement with 51 items on a five - point likert scale ( never , little , enough , much , very much ) . the questionnaire is composed of four main scales including 47 items : wellness ( eleven items ) , resilience ( 20 items ) , perception of social support ( nine items ) , and negative coping styles ( seven items ) . further , a lie scale (","introduction and objectivesa multidimensional self - report questionnaire to evaluate job - related stress factors is presented . the questionnaire , called maugeri stress index reduced form ( masi - r ) , aims to assess the impact of job strain on a team or on a single worker by considering four domains : wellness , resilience , perception of social support , and reactions to stressful situations.material and methodsthe reliability of a first longer version ( 47 items ) of the questionnaire was evaluated by an internal consistency analysis and a confirmatory factor analysis . an item reduction procedure was implemented to obtain a short form of the instrument , and the psychometric properties of the resulting instrument were evaluated using the rasch measurement model.resultsa total of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and CV categories. : http: //dx. . org/10. 7554/eLife. 08351. 00410. 7554/eLife. 08351. 005Figure 1— 1. Descriptive analysis of (A) internal, construct, and (B) external validity design elements for all experiments (n = 332) extracted for validity data parameters. : http: //dx. . org/10. 7554/eLife. 08351. 00510. 7554/eLife. 08351. 006Table 1. Demographics of included studiesDOI: http: //dx. . org/10. 7554/eLife. 08351. 00610. 7554/eLife. 08351. 007Table 1—source data 1. (C) Search Strategies. (D) PRISMA Flow Diagram. (E) Demographics of included studies at qualitative level. : http: //dx. . org/10. 7554/eLife. 08351. 007Study level demographicsIncluded studies (n = 74) Conflict of interest Declared19 (26%) Funding statement* Private, for-profit44 (59%) Private, not-for-profit35 (47%) Public37 (50%) Other2 (3%) Recommended clinical testing Yes37 (50%) Publication date 2003–200613 (18%) 2007–200917 (23%) 2010–201344 (59%) *Does not sum to 100% as many studies declared more than one funding source. 10. 7554/eLife. 08351. 008Figure 2. Summary of pooled SMDs for each malignancy type. Shaded region denotes the pooled standardized mean difference (SMD) and 95% confidence interval (CI) (−1. 8 [−2. 1, −1. 6]) for all experiments combined at the last common time point (LCT). : http: //dx. . org/10. 7554/eLife. 08351. 00810. 7554/eLife. 08351. 009Figure 2—source data 1. (B) Heterogeneity statistics (I2) for each malignancy sub-group. : http: //dx. . org/10. 7554/eLife. 08351. 00910. 7554/eLife. 08351. 010Figure 2— 1. Effect sizes for all included experiments (n = 158). : http: //dx. . org/10. 7554/eLife. 08351. 01010. 7554/eLife. 08351. 011Figure 3. Relationship between study design elements and effect sizes. The shaded region denotes the pooled SMD and 95% CI (−1. 8 [−2. 1, −1. 6]) for all experiments combined at the LCT. : http: //dx. . org/10. 7554/eLife. 08351. 01110. 7554/eLife. 08351. 012Figure 4. Funnel plot to detect publication bias. Trim and fill analysis was performed on pooled malignancies, as well as the three malignancies with the greatest study volume. (A) All experiments for all malignancies (n = 182), (B) all experiments within renal cell carcinoma (RCC) (n = 35), (C) breast cancer (n = 32), and (D) colorectal cancer (n = 29). Time point was the LCT. Open circles denote original data points whereas black circles denote ‘filled’ experiments. Trim and fill did not produce an estimate in RCC; therefore, no overestimation of effect size could be found. :","Developing a new drug can take years, partly because preclinical research on non-human animals is required before any clinical trials with humans can take place. Nevertheless, only a fraction of cancer drugs that are put into clinical trials after showing promising results in preclinical animal studies end up proving safe and effective in human beings. Many researchers and commentators have suggested that this high failure rate reflects flaws in the way preclinical studies in cancer are designed and reported. Now, Henderson et al. have looked at all the published animal studies of a cancer drug called sunitinib and asked how well the design of these studies attempted to limit bias and match the clinical scenarios they were intended to represent. This systematic review and meta-analysis revealed that many",380,128,0.3368
pubmed-summarization,"the potential relevance of endothelial activation biomarkers to sepsis has been raised in both this journal and others [ 1 - 3 ] . biomarkers for sepsis associated with the endothelial glycocalyx remain relatively unknown , however , and this commentary attempts to reverse this omission . the term glycocalyx ( sweet husk ) was introduced 50 years ago to describe an extracellular polysaccharide coating of cells . whilst electron microscopy revealed that the luminal surface of the endothelium expressed this structure , it was thought to be of little consequence or functional significance . what has become increasingly evident , however , is that the glycocalyx - now estimated to extend up to 1 m from the endothelial cell membrane - represents a substantial intravascular compartment contributing significantly to vascular wall homeostasis . specifically , roles of the glycocalyx include maintenance of the vascular permeability barrier , mediation of shear - stress - dependent nitric oxide production , and housing vascular protective enzymes ( for example , superoxide dismutase ) and a wide array of coagulation inhibition factors such as antithrombin , the protein c system and tissue factor pathway inhibitor . the glycocalyx also modulates the inflammatory response by preventing leukocyte adhesion and binding numerous ligands , including chemokines , cytokines and growth factors [ 4 - 6 ] . negatively charged and with a mesh - like structure , the endothelial glycocalyx is comprised of glycoproteins , proteoglycans , glycosaminoglycans ( gags ) and associated plasma proteins including albumin . proteoglycans consisting of a core membrane - bound protein of the syndecan or glypican families with attached heparan or chondroitin sulphate gag side chains are a prominent feature . hyaluronan - a nonsulphated , uncharged gag with water - retaining properties - is attached or adsorbed onto other cell - surface anchored proteins ( for example , cd44 ) and helps to stabilise the glycocalyx structure . alteration in the composition of the glycocalyx following exposure to an inflammatory insult is one of the earliest features of endothelial activation . it is now accepted that tnf , oxidised lipoproteins , lipopolysaccharide , thrombin , ischaemia / reperfusion , hyperglycaemia and growth factors all cause glycocalyx disruption via the action of proteases - leading either to partial degradation","sepsis is the third largest cause of death in industrialised countries , but treatment remains largely supportive and effective therapeutic interventions are urgently needed . disruption and dysfunction of the microvascular endothelium leading directly or indirectly to multiple organ failure are now recognised to underpin the pathophysiology of sepsis . biomarkers of endothelial activation may therefore assume an important role in guiding future research efforts . we suggest that integral to this approach is the investigation and evaluation of endothelial glycocalyx biomarkers , not only as indicators of the pathogenic process but also to inform the development of pharmacological and other therapies .",380,103,0.2711
dialogsum,"#Person1#: Do you have any direct flight to New Zealand? #Person2#: Sorry, we don't. But I think you can fly on Northwest 212 to Tokyo and then have a connecting flight on Japan Airline 123 to Auckland, New Zealand's gateway city. And it is the most economical flight, just 580. #Person1#: When does the Flight 212 leave? #Person2#: At 11:30 am, by the way, it also makes a stop at Chicago. #Person1#: How long will it stay at Chicago? #Person2#: Less than one hour. #Person1#: And how long do I have to stay in Tokyo for the connecting flight? #Person2#: Not so long, just one hour. #Person1#: So the time for the whole journey is about... #Person2#: About eleven hours. #Person1#: Let me count...OK, it works out for my time schedule. Thanks a lot. #Person2#: You are welcome.","#Person2# recommends #Person1# to fly to Auckland, New Zealand's gateway city, with a connecting flight stop by Tokyo. #Person1# thinks it works out for #Person1#'s time schedule.",138,27,0.1957
dialogsum,"#Person1#: Good morning. My name is Mr. Brown. I ' m from Australia. Here is my card. #Person2#: Thank you. I ' m pleased to meet you, Mr. Brown. My name is Kathy Pewless, the representative of Green Textile Import and Export Corporation. #Person1#: Pleased to meet you too, Ms. Pewless. I travel a lot every year on business, but this is my first visit to your country. I must say I have been much impressed by your friendly people. #Person2#: Thank you for saying so. Have you seen the exhibition halls? On display are most of our products, such as silk, woolen knitwear, cotton piece goods, and garments. #Person1#: Oh, yes. I had a look yesterday. I found some of the exhibits to be fine in quality and beautiful in design. The exhibition has successfully displayed to me what your corporation handles. I have gone over the catalogue and the pamphlets enclosed in your last letter. I've got some idea of your exports. I ' m interested in your silk blouses. #Person2#: Our silk is known for its good quality. It is one of our trade - trional exports. Silk blouses are brightly colored and beau - fully designed. They have met with great favor overseas and are always in great demand.",Ms. Pewless meets with Mr. Brown and introduces her corporation's exhibition and products to him. Mr. Brown gets interested in their silk blouses,213,23,0.108
dialogsum,"#Person1#: Are you ready to order, madam? #Person2#: I'm on a diet. So I have to avoid food containing too much fat. Do you have vegetarian dishes? #Person1#: Yes, We do have some choices for ladies like you. What about some green salad? #Person2#: Does it taste good ? #Person1#: Sure. It's a popular dish among young ladies. #Person2#: I think I'll try it. #Person1#: We have three kinds of dressings for salad. Italian, French and Thousand Island. Which one would you like? #Person2#: French, please. #Person1#: OK. Do you want to order something else? #Person2#: Milan Style Macaroni. Don't put sugar or salt on it, please.",#Person2# wants vegetarian dishes. #Person2# offers her some choices and she chooses green salad with French dressings and Macaroni.,107,19,0.1776
dialogsum,#Person1#: What are you going to do tonight? How about going to the movies? There's one that starts at 7:00 p. m. #Person2#: Good. I'm going to play tennis this afternoon but I'll be home by 4:00 p. m. Then we can go out for a big dinner before seeing the movie.,#Person1# and #Person2# will have a dinner and go to the movies tonight.,52,13,0.25
dialogsum,"#Person1#: Dad. Can I go outside to play? #Person2#: Well, did you get you Saturday's work done? #Person1#: Ah, Dad. Do I have to? #Person2#: Well, you know the rules. No playing until the work is done. #Person1#: So, what is my work? #Person2#: Well, first you have to clean the bathroom including the toilet. And don't forget to scrub the bathtub. #Person1#: No, I want to do the family room. #Person2#: Well, okay, but you have to vacuum the family room and the hall, and be sure to dust everything. Oh, and don't forget to wipe the walls and clean the baseboards. [Okay.] And after that. [Oh, no.] Next, sweep and mop the kitchen floor and be sure to polish the table in the living room. #Person1#: Okay. Okay. #Person2#: And make your bed and pick up all your toys and put them away. And ... #Person1#: More? #Person2#: Yeah. And then, how about going out for lunch and getting a big milk shake, but you probably don't want to do that. #Person1#: No, No. I want to. #Person2#: Okay. While you're doing your work, I'll be out in the yard raking leaves and pulling weeds.","#Person1# wants to go outside to play. #Person2#, #Person1#'s dad, asks #Person1# to get the Saturday's housework done and then he'll take #Person1# out for lunch and get a big milkshake.",197,31,0.1574
scientific_lay_summarisation-elife-norm,"and Prives, 2009). In humans, naturally occurring single nucleotide polymorphisms (SNPs) in the p53 pathway, which modulate the activity or levels of p53, have been found to significantly impact cancer risk (Bond et al. , 2004; Whibley et al. , 2009; Lin et al. , 2008; Basu and Murphy, 2016). p53 codon 72 SNP is a common coding SNP in the TP53 gene, which results in either an arginine (R72) or a proline (P72) residue at codon 72. We and others have reported that compared with the R72 allele, the P72 allele displays a weaker p53 transcriptional activity towards a group of its target genes, many of which are involved in apoptosis and suppressing cell transformation (Dumont et al. , 2003; Jeong et al. , 2010). Studies in human populations indicate that p53 codon 72 SNP may modify cancer risk, but currently the consensus has not been reached on this in the literature (van Heemst et al. , 2005; Whibley et al. , 2009). Several studies of aged or general human populations indicate that the P72 carriers have an increased lifespan despite an increased mortality from cancer (van Heemst et al. , 2005; Bojesen and Nordestgaard, 2008; Smetannikova et al. , 2004). These epidemiological results support the dual functions of p53 in longevity, and suggest that codon 72 SNP may have an impact upon aging and longevity. Considering the genetic background variations of human populations and environmental factors in epidemiological studies, the precise role of p53 codon 72 SNP in aging and longevity remains elusive. In this study, we employed a mouse model with knock-in of human TP53 gene (Hupki) carrying codon 72 SNP to directly investigate the impact of p53 codon 72 SNP upon longevity and its underlying mechanism. The Hupki mice carrying codon 72 SNP recapture the impacts of codon 72 SNP upon p53 transcriptional activity and function in tumor suppression, which is widely used for studies on p53 and codon 72 SNP (Feng et al. , 2011; Kung et al. , 2016; Azzam et al. , 2011; Reinbold et al. , 2008; Frank et al. , 2011; Leu et al. , 2013). We found that despite the increased cancer risk, P72 mice that have escaped tumor development have a longer lifespan than R72 mice and display a","How long most animals live depends on the balance between the biological processes that allow them to regenerate their tissues when damaged and those that prevent them from developing cancer. Regeneration relies mostly on cells, in particular stem cells, dividing to make new cells, while cancer occurs when cell division becomes uncontrolled. Tumor suppressor genes protect against cancer. One such gene encodes a protein called p53 that eliminates damaged cells before they can become cancerous. The p53 protein is also believed to be involved in regulating how quickly an animal ages and how long it lives, but this second role has not yet been clearly established. Previous studies using different strategies to change the activity of p53 in several mouse models have led to inconsistent results. However, the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Value-based decisions could rely either on the selection of desired economic goods or on the selection of the actions that will obtain the goods. We investigated this question by recording from the supplementary eye field (SEF) of monkeys during a gambling task that allowed us to distinguish chosen good from chosen action signals. Analysis of the individual neuron activity, as well as of the population state-space dynamic, showed that SEF encodes first the chosen gamble option (the desired economic good) and only ~100 ms later the saccade that will obtain it (the chosen action). The action selection is likely driven by inhibitory interactions between different SEF neurons. Our results suggest that during value-based decisions, the selection of economic goods precedes and guides the selection of actions. The two selection steps serve different functions and can therefore not compensate for each other, even when information guiding both processes is given simultaneously. Value-based decision-making requires the ability to select the reward option with the highest available value, as well as the appropriate action necessary to obtain the desired option. Currently it is still unclear how the brain compares value signals and uses them to select an action (Gold and Shadlen, 2007; Cisek, 2012). The goods-based model of decision-making (Padoa-Schioppa, 2011) suggests that the brain computes the subjective value of each offer, selects one of these option value signals, and then prepares the appropriate action plan (1A). Support for this model comes from recording studies in orbitofrontal cortex (OFC) during an economic choice task (Padoa-Schioppa and Assad, 2006; Cai and Padoa-Schioppa, 2012). In contrast, the action-based model of decision making (Tosoni et al. , 2008; Cisek and Kalaska, 2010; Christopoulos et al. , 2015a) suggests that all potential actions are represented in the brain in parallel and compete with each other (1B). This competition is influenced by a variety of factors including the value of each actions’ outcome. According to this model, option value signals should not predict the chosen option, since these signals only serve as input into the decision process, which is determined by the competition among the potential actions. Support for this model comes primarily from recording studies in parietal and premotor cortex (Platt and Glimcher, 1999; Sugrue et al. , 2004; Shadlen et al. , 2008; Cisek and Kalaska,","Much of our decision making seems to involve selecting the best option from among those currently available, and then working out how to attain that particular outcome. However, while this might sound straightforward in principle, exactly how this process is organized within the brain is not entirely clear. One possibility is that the brain compares all the possible outcomes of a decision with each other before constructing a plan of action to achieve the most desirable of these. This is known as the' goods-based' model of decision making. However, an alternative possibility is that the brain instead considers all the possible actions that could be performed at any given time. One specific action is then chosen based on a range of factors, including the potential outcomes that might",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Using a novel, fMRI-based inter-subject functional correlation (ISFC) approach, which isolates stimulus-locked inter-regional correlation patterns, we compared the cortical topology of the neural circuit for face processing in participants with an impairment in face recognition, congenital prosopagnosia (CP), and matched controls. Whereas the anterior temporal lobe served as the major network hub for face processing in controls, this was not the case for the CPs. Instead, this group evinced hyper-connectivity in posterior regions of the visual cortex, mostly associated with the lateral occipital and the inferior temporal cortices. Moreover, the extent of this hyper-connectivity was correlated with the face recognition deficit. These results offer new insights into the perturbed cortical topology in CP, which may serve as the underlying neural basis of the behavioral deficits typical of this disorder. The approach adopted here has the potential to uncover altered topologies in other neurodevelopmental disorders, as well. Understanding the neural basis of developmental disorders such as congenital prosopagnosia (CP) remains a challenge from both a basic science and a translational perspective as there are no obvious identifiable deficits on conventional anatomical MR brain scans. Furthermore, many studies show that CP individuals evince normal fMRI activation in the' core' face-related posterior patches of the brain (Hasson et al. , 2003; Avidan et al. , 2005,2014; Avidan and Behrmann, 2009) (but see von Kriegstein et al. , 2008; Dinkelacker et al. , 2011; Furl et al. , 2011). In contrast, more sensitive methods that have been used to map structural changes in CP relative to controls, such as diffusion tensor imaging (DTI) have revealed a reduction in long-range white matter tracts connecting the ‘core’ face-related posterior patches and the anterior temporal lobe face patch (ATL) in CP (Thomas et al. , 2009; for related papers, see Grossi et al. , 2014; Scherf et al. , 2014). Other studies have also reported local structural and functional atypicalities in the vicinity of face-selective regions (Gomez et al. , 2015; Song et al. , 2015; Lohse et al. , 2016). Using standard functional connectivity (FC) analysis, which measures the temporal correlations across different brain areas within an individual, we have previously documented abnormal deviations from the control pattern in the connectivity patterns between the' core' and' extended' nodes of the face system (Avidan and Behrmann, 2014).","Human babies prefer to look at faces and pictures of faces over any other object or pattern. A recent study found that even fetuses in the womb will turn their heads towards dots of light shone through the mother’s skin if the dots broadly resemble a face. Brain imaging studies show that face recognition depends on the coordinated activity of multiple brain regions. A core set of areas towards the back of the brain processes the visual features of faces, while regions elsewhere process more variable features such as emotional expressions. Around 2% of people are born with difficulties in recognizing faces, a condition known as congenital prosopagnosia. These individuals have no obvious anatomical abnormalities in the brain, and brain scans reveal normal activity in core regions of",380,128,0.3368
dialogsum,"#Person1#: The time has come to say goodbye. #Person2#: So soon. It seems as if you've just got here. #Person1#: I feel that way, too, but they say all good things must come to an end. #Person2#: It certainly has been a pleasure seeing you again and renewing old memories. #Person1#: I've had a nice time and I really want to thank you for spending so much time showing me the sights. #Person2#: Oh. It was fun for me, too. It gave me the chance to get away from my everyday work and do something a little bit different. #Person1#: You'll be out to see us next year, then, as you promised? #Person2#: Oh, yes. That's our present plan unless something bad comes up. We should be there sometime in early September. #Person1#: We'll be expecting you.",#Person1#'s leaving and thanks #Person2# for showing #Person1# the sights. #Person2# promises to visit #Person1# next year.,137,17,0.1241
dialogsum,"#Person1#: How do you eat sushi, Mister Nakamura? #Person2#: I usually use chopsticks but some people prefer just using hands. #Person1#: You can eat with your hands at the restaurant? #Person2#: Yeah, it's totally acceptable in the traditional sushi restaurant. #Person1#: Hmm, interesting. So do I just eat it straight? #Person2#: Well, I like to eat it straight and enjoy the natural flavor of the fish, but you can always go with wasabi. #Person1#: Wasabi? What's wasabi? #Person2#: Wasabi is a sauce, which gives sushi a spicy flavor. #Person1#: Oh, you mean the green stuff, which always makes my tears come out? #Person2#: Correct. Some restaurants actually give you wasabi along with your sushi dish so that you can control the hotness. #Person1#: That's considerate. You've really taught me so much about Japanese culture. Thank you, Mister Nakamura. #Person2#: Don't mention it. We should help each other since we work in the same company now.",Mr. Nakamura helps #Person1# learn about the way to eat sushi and the use of wasabi because they work in the same company.,155,23,0.1484
dialogsum,"#Person1#: Tell me, Peter, what makes Harrods so famous? #Person2#: Well, it's the biggest department store in the UK. And its food hall and the Egyptian hall are very famous. People come to Harrods just to see them. #Person1#: What is special about the food hall? #Person2#: It sells many different kinds of food. For example, it has 250 kinds of cheese from all over the world and more than 180 kinds of bread. Customers also love all the different kinds of chocolate. They buy a hundred tons every year. #Person1#: That's amazing! And why is the Egyptian hall so famous? #Person2#: Well, when people see it, they feel they are in another world. It looks like in Egyptian building from 4,000 years ago. And it sells beautiful objects. They are not 4,000 years old, of course. #Person1#: Is it true that Harrods produces its own electricity? #Person2#: Yes, it does 70%, enough for a small town. To light the outside of the building, we use 11,500 light bulbs. #Person1#: Really? Tell me, how many customers do you have on an average day? And how much do they spend? #Person2#: About 30,000 people come on an average day. But during the sales, the number increases to 300,000 customers a day. How much do they spent? Well, on average, customers spend about 1.5 million pounds a day. The record for one day is nine million pounds. #Person1#: Nine million pounds in one day? #Person2#: Yes, on the first day of the January sales. #Person1#: Harrods says it sells everything to everybody, everywhere. Is that really true? #Person2#: Oh, yes. of course! Absolutely everything!","Peter explains to #Person1# the reasons why the food hall and the Egyptian hall are famous. #Person1# also asks Peter about Harrods' electricity, customer flow and sales daily.",272,28,0.1029
scientific_lay_summarisation-elife-norm,"Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters. Transient responses utilize input from rod photoreceptors and output by the classical neurotransmitter glutamate, but adapt within minutes. In contrast, sustained responses are dominated by non-conventional signaling mechanisms: melanopsin phototransduction in ipRGCs and output by the neuropeptide PACAP, which provide stable pupil maintenance across the day. These results highlight a temporal switch in the coding mechanisms of a neural circuit to support proper behavioral dynamics. Environmental light influences a variety of subconscious physiological functions, including circadian photoentrainment, light modulation of sleep/mood, and the pupillary light response (PLR). These diverse effects of light are all mediated by a small subpopulation of retinal output neurons called intrinsically photosensitive retinal ganglion cells (ipRGCs) (Altimus et al. , 2008; Göz et al. , 2008; Güler et al. , 2008; Hatori et al. , 2008; LeGates et al. , 2012; Lupi et al. , 2008; Tsai et al. , 2009). Even in the vast array of environmental light conditions, subconscious visual behaviors are remarkable for their rapid induction and stable maintenance throughout the day. However, how the ipRGC circuit achieves rapid and stable control of visual behaviors remains uncertain. Multiple photoreceptive systems participate in the ipRGC circuit, including their endogenous melanopsin-based phototransduction and indirect synaptic input from the classical rod and cone photoreceptors (Hattar et al. , 2003; Panda et al. , 2003). Each photoreceptive system presumably encodes a unique aspect of the light environment, but to date no consensus exists on the photoreceptive mechanisms supporting ipRGC-dependent behaviors. Several studies using a variety of methods have proposed competing models arguing for the predominance of cone-based (Allen et al. , 2011; Butler and Silver, 2011; Dkhissi-Benyahya et al. , 2007; Lall et al. , 2010) or rod-based (Altimus et al. , 2010; McDougal and Gamlin, 2010) synaptic input to ipRGCs and their behavioral responses. Additionally, it has been suggested that","The retina is the part of our eye that detects light and sends visual information to the brain. There are several different types of light-sensitive cell in the retina that perform different roles. For example, retinal cells called intrinsically photosensitive retinal ganglion cells (or ipRGCs for short) rapidly respond to the intensity of background light and regulate the size of the pupils to control how much light enters the eyes. These cells receive information from other light-sensitive cells in the retina called rods and cones. There are at least two mechanisms that ipRGCs may use to relay information to the brain: one uses a protein called PACAP, while the other involves a molecule called glutamate. However, it is still not clear which mechanisms are actually used by ipRGCs,",380,128,0.3368
dialogsum,"#Person1#: Did you pack this bag yourself? Has it been out of your possession at any time before checking-in? #Person2#: Yes, I packed it myself, and it hasn ' t been out of my possession. #Person1#: Are you bringing in any plants or animal products? #Person2#: No. #Person1#: Our sniffer dog seems to disagree. Do you mind if we look in your suitcase? #Person2#: Not at all. Go right ahead. #Person1#: What ' s this sir? #Person2#: It ' s traditional Chinese Medicine. I mix it with hot water like tea. Sorry. I forgot about it. #Person1#: What are these red things sir? #Person2#: Oh no! I forgot about those too! Those are Chinese sausages for my Aunt Lily. #Person1#: I ' m sorry sir, but you can ' t take any of this into the country. We will also have to check your carry-on. Please step this way. Don ' t ' be nervous ; we ' ll just look through it briefly and then",#Person1# finds Chinese Medicine and sausages that are not allowed into the country in #Person2#'s suitcase. #Person1# also needs to check #Person2#'s carry-on.,166,23,0.1386
scientific_lay_summarisation-elife-norm,"UNC93B1, a multipass transmembrane protein required for TLR3, TLR7, TLR9, TLR11, TLR12, and TLR13 function, controls trafficking of TLRs from the endoplasmic reticulum (ER) to endolysosomes. The mechanisms by which UNC93B1 mediates these regulatory effects remain unclear. Here, we demonstrate that UNC93B1 enters the secretory pathway and directly controls the packaging of TLRs into COPII vesicles that bud from the ER. Unlike other COPII loading factors, UNC93B1 remains associated with the TLRs through post-Golgi sorting steps. Unexpectedly, these steps are different among endosomal TLRs. TLR9 requires UNC93B1-mediated recruitment of adaptor protein complex 2 (AP-2) for delivery to endolysosomes while TLR7, TLR11, TLR12, and TLR13 utilize alternative trafficking pathways. Thus, our study describes a mechanism for differential sorting of endosomal TLRs by UNC93B1, which may explain the distinct roles played by these receptors in certain autoimmune diseases. Toll-like receptors (TLRs) recognize conserved microbial features and initiate signals critical for induction of immune responses to infection. A subset of TLRs (TLR3, TLR7, TLR8, and TLR9) recognizes forms of nucleic acids, including double-stranded RNA, single-stranded RNA, and DNA (Barbalat et al. , 2011). This specificity facilitates recognition of a broad array of microbes but introduces the potential for recognition of self-nucleic acids. TLR7 and TLR9 recognition of self-RNA and self-DNA, respectively, contributes to autoimmune diseases such as systemic lupus erythematosus (SLE) (Marshak-Rothstein, 2006; Christensen and Shlomchik, 2007). Discrimination between self and microbial nucleic acids cannot be achieved solely through recognition of distinct features but instead relies on differential delivery of these potential ligands to TLRs (Barton and Kagan, 2009). All of the TLRs capable of nucleic acid recognition localize within endosomal compartments which sequesters these receptors away from self nucleic acids in the extracellular space (Barton and Kagan, 2009). Our previous studies as well as work from other groups indicate that a requirement for ectodomain cleavage of intracellular TLRs further restricts receptor activation to protease-rich acidic compartments (Ewald et al. , 2008,2011; Park et al. , 2008; Garcia-Cattaneo et al. , 2012). Bypassing this requirement enables responses to extracellular self nucleic acid and leads to fatal inflammatory disease in mice (Mouchess et al. , 2011). Moreover, the system appears carefully balanced as simply overexpressing TLR7 in mice causes responses to self-RNA and development of an SLE-like disease (Pisitkun et al. , 2006; Subramanian","Toll-like receptors (TLRs) are proteins that are responsible for recognizing specific molecules associated with invading pathogens, known as pathogen-associated molecular patterns. Upon detecting these signals, TLRs activate the body' s immune response, which fights the infection. A subset of TLRs recognizes nucleic acids, including DNA and RNA, enabling the immune system to respond to foreign material from a diverse range of bacteria and viruses. However, some of the body' s own DNA and RNA is also found outside cells (e. g. , in the bloodstream) and TLRs must be able to discriminate between these nucleic acids and those belonging to pathogens, because failure to tell the difference between the two could result in autoimmune disease. To reduce this risk, TLRs are sequestered inside the cell within membrane-bound compartments",380,128,0.3368
dialogsum,"#Person1#: I am rejoiced to tell you that you are employed. #Person2#: Thank you for hiring me. I'm very proud to be employed by your firm. #Person1#: You are expected to report for on-job training on the 15th of May. Will you be there? #Person2#: Yes, I will. I hope I'll enjoy working with you.",#Person2# is employed and will report for on-job training soon.,55,10,0.1818
pubmed-summarization,"migraine is the leading neurological cause for seeking medical care , and is associated with significant disability in the sufferer . the greatest impact is on migraineurs with headaches on more days than not , a condition defined as chronic migraine ( cm ) . cm is defined as at least 15 days of headache per month in which at least eight of the days fulfill migraine criteria and/or are treated with specific migraine medications , in the absence of a diagnosis of medication overuse headache . patients with cm often had a history of episodic migraine that began in adolescence or early adulthood , reporting a process of transformation marked by headaches that become more frequent over years . among migraineurs , defining risk factors for cm , or for the progression of episodic migraine to cm , identified risk factors include medication overuse , obesity , sleep problems , and psychiatric comorbidity . studies in both community and tertiary settings have demonstrated an association between migraine and several psychiatric conditions . however , the frequency of psychiatric disorders in both setting has not been compared before in a single study . furthermore , differences in methods of studies based in community or tertiary centers prevent appropriate comparison . population studies fail to conduct face - to - face assessments , while clinic - based studies carry the potential for selection bias . studies focusing on best methods to address this gap are of interest , and one strategy is to compare data obtained from the community with those from specialty care , where methods of collection have been virtually identical , and that was the scope of this study . we compared demographic data and psychiatric comorbidity in a sample of individuals with cm from the community with another from a tertiary care clinic . in light of the fact that patients suffering from migraine and comorbid psychiatric disorders are greater health - care service users , we hypothesized that the frequency of psychiatric disorders , notably depression , is higher in patients followed in tertiary care . community data were gathered in capela nova , a city from the state of minas gerais , brazil . according to the 2000 brazilian census , its population was 2,066","although the association between episodic migraine and psychiatric comorbidities is well documented , few studies have focused on the comorbidity with chronic migraine ( cm ) and discrepancies exist between population - based and clinic - based data . the objective of this study is to compare demographic and psychiatric comorbidity correlates between cm samples drawn from the community and tertiary care . all inhabitants from a city borough were interviewed for the presence of headaches occurring 15 or more days per month . cm was diagnosed after subjects had been interviewed and examined by a headache doctor . participants were also assessed with a structured interview by a psychiatrist , who assigned diagnoses based on the dsm - iv . the same investigators assessed all patients consecutively",380,128,0.3368
dialogsum,"#Person1#: Excuse me. Do you study Chinese at the university here? #Person2#: Yes, I do. But my characters are very bad. #Person1#: It takes a long time to learn Chinese writing. #Person2#: Are you Chinese? #Person1#: Yes, I am. I am from Taiwan. I came here to study political science. #Person2#: How do you like it? #Person1#: I like it so far. But my English still needs work. #Person2#: I want to study Mandarin and international relations. #Person1#: Does the Chinese department here teach regular characters or simplified characters? #Person2#: They teach regular characters. #Person1#: I see. I'm from Taiwan, so I know regular characters better than simplified. #Person2#: You just said your English needs work, yes? #Person1#: Yes, that's true. Especially my writing. I think my papers aren't good enough. I make too many grammatical mistakes. #Person2#: Well, I am very serious about learning Chinese. But for me the hard part now is pronunciation. You have the four tones in Chinese. It is very hard. Maybe, if you have time, maybe we could do a language exchange. #Person1#: You mean you and I? #Person2#: Yes, why not? I mean, if you come to this cafe often, maybe we could meet here and practice Chinese and English. #Person1#: That sounds like a good idea. How often would you like to do it? #Person2#: Let's see. . . My schedule right now is quite busy. But I think I could spend 90 minutes a week in language exchange. #Person1#: How would we manage it though? How would we spend the 90 minutes? #Person2#: First, we could spend 45 minutes working on your English writing. If you want, I could help you edit your papers. Or we could do English conversation. Whatever you want. And then the next 45 minutes you would help me with my Chinese. #Person1#: Would I help you with writing? #Person2#: No. For me right now, the important thing is spoken Chinese. I need practice. So you could tutor me in speaking. We could use my textbook, and you could ask me questions. Then you could correct my mistakes. #Person1#: I think it sounds like a good system. But when is it convenient to meet? #Person2#: Well, today is Monday. Actually, for me Monday at this time would","#Person2# is learning Chinese, and #Person2# thinks the hard part is pronunciation. #Person1# thinks #Person1#'s English still needs work. #Person2# advises that they can do a language exchange, and #Person1# agrees. They plan to spend 90 minutes a week in language exchange. They spend the first 45 minutes working on #Person1#'s English writing, and the next 45 minutes #Person1# will help #Person2# with spoken Chinese.",380,65,0.1711
dialogsum,"#Person1#: Is there a lot of snow in this region at this time of the year? #Person2#: Yes, the snow is often falling thick and fast here. #Person1#: Well, I think I like it. I appreciate the snow very much. #Person2#: Yes, It's really so beautiful with all the things covered by snow. #Person1#: By the way, where can I go ski? #Person2#: There are so many places around. Take a look at the advertisement.",#Person2# tells #Person1# it snows a lot here and #Person1# can find places to go ski at the advertisement.,75,19,0.2533
dialogsum,"#Person1#: I'm sorry to make you wait. What did you decide? #Person2#: Well, I wasn't planning on spending that much money today, so. . . #Person1#: Trust me, it's worth it. With the ' Love, Amy Card ', you'll get a 20 percent discount on everything in the store, every time you shop! #Person2#: Even if an item is on sale? #Person1#: Yes! And there are more bargains. See these pajamas? If you buy a pair now, you get this teddy bear as a gift! #Person2#: Oh! It's so cute!","#Person1# persuades #Person2# to buy the 'Love, Amy card' for getting a 20 percent discount.",90,15,0.1667
dialogsum,"#Person1#: What's the matter here? #Person2#: Somebody broke into my house in the morning. #Person1#: When did you find out? #Person2#: About 12 o'clock, when I came home from work. #Person1#: Apparently forced entry. The lock is battered to pieces. #Person2#: I wonder how the burglar did it. #Person1#: He is so unskillful. I have never seen such an awkward burglar. #Person2#: That's because we have a strong lock. #Person1#: Probably. Let's check the inside then. #Person2#: Did you find anything? #Person1#: Yes, the house was in a terrible mess. It was almost turned upside down by the burglar. #Person2#: Oh, er. . . sorry that's because we didn't have time to clean it. #Person1#: You mean it is not created by the burglar? #Person2#: Definitely not, sir.","#Person2#'s house was broken into. #Person1# comes to check and thinks the burglar caused the mess. But actually, that's because #Person2# didn't clean it.",128,24,0.1875
dialogsum,"#Person1#: Steven, have you any friend in London? #Person2#: Yes, my old friend Hanson lives there #Person1#: Are you close? #Person2#: Yes. He's one of my best friends. Our friendship formed at college. Why did you ask that? #Person1#: I'm going to London on business next week. But I know nothing about it. #Person2#: I get it. You want to find a guide, don't you? #Person1#: Yes, Steven. You always know what I want. #Person2#: Don't worry. I will call Hanson, and ask him to help you. #Person1#: Thank you!",#Person1# is going to London on business and wants to find a guide. #Person2# will call Hanson to help #Person1#.,90,20,0.2222
dialogsum,"#Person1#: This is the fifth Club. May I help you? #Person2#: Yes, I believe you have a luncheon meeting this coming Saturday. Could you give me some more information about that? #Person1#: Yes, of course. The guest speaker is Professor Wong Lan from Beijing Foreign Language University. She'll speak about modern English. #Person2#: I'm a student of English. That sounds interesting. And when does the meeting begin? #Person1#: Lunch will be served at 12:00 o'clock and Professor Wong will speak at 2:00 o'clock. #Person2#: Is there an emission fee? #Person1#: Yes, the luncheon lecture are 30 yuan per person. #Person2#: And do you have any idea when it will end? #Person1#: Oh, sorry. I'm not so sure. Maybe at about 3:00 o'clock. #Person2#: Very well. Thank you. #Person1#: You are quite welcome.",A student consults the fifth Club assistant about the luncheon meeting on Saturday and its emission fee.,132,17,0.1288
dialogsum,"#Person1#: Were you always interested in starting a food business? #Person2#: Actually, I was interested in sales at first, because that's what both my parents do. But I used to work part time in a cafe when I was a kid and that's what got me interested. #Person1#: What was the first place you opened? #Person2#: I rented a cheap place near the university and I started selling lunches to the students. The place was always crowded at lunchtime, so one day I sold it. With that money, I opened a much bigger place downtown.","#Person2# tells #Person1# how #Person2# started a food business, and the first place #Person2# opened.",95,15,0.1579
scientific_lay_summarisation-elife-norm,"To better understand smoking cessation, we examined the actions of varenicline (Chantix) during long-term nicotine exposure. Varenicline reduced nicotine upregulation of α4β2-type nicotinic receptors (α4β2Rs) in live cells and neurons, but not for membrane preparations. Effects on upregulation depended on intracellular pH homeostasis and were not observed if acidic pH in intracellular compartments was neutralized. Varenicline was trapped as a weak base in acidic compartments and slowly released, blocking 125I-epibatidine binding and desensitizing α4β2Rs. Epibatidine itself was trapped; 125I-epibatidine slow release from acidic vesicles was directly measured and required the presence of α4β2Rs. Nicotine exposure increased epibatidine trapping by increasing the numbers of acidic vesicles containing α4β2Rs. We conclude that varenicline as a smoking cessation agent differs from nicotine through trapping in α4β2R-containing acidic vesicles that is selective and nicotine-regulated. Our results provide a new paradigm for how smoking cessation occurs and suggest how more effective smoking cessation reagents can be designed. Tobacco continues to be widely used world-wide, primarily via cigarette smoking, and is the leading cause of preventable deaths in the United States (National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health, 2014). The currently approved treatments for smoking cessation are nicotine replacement therapy, bupropion, and varenicline (Chantix). While varenicline is the most effective, successful quit rates only reach ~50% of smokers (Agboola et al. , 2015). Other therapies or novel approaches are clearly needed to increase rates of smoking cessation, and the design of smoking cessation reagents would be greatly aided with a mechanistic understanding of how the reagents act. Nicotine binds to high-affinity nicotinic acetylcholine receptors (nAChRs) in the brain, and binding initiates its addictive effects. nAChRs are members of the Cys-loop family of ligand-gated ion channels, all of which are pentameric neurotransmitter receptors (Karlin, 2002; Albuquerque et al. , 2009). In the mammalian CNS, these critical binding sites are nAChRs composed of α2 - α6 and β2 - β4 subunits; the most predominant contains α4 and β2 subunits (Lindstrom, 1996; McGehee and Role, 1995). The α4β2 nAChR subtype (α4β2R) is closely linked to nicotine addiction (Govind et al. , 2009; Vezina et al. , 2007; Lewis and Picciotto, 2013). Loss of either subunit in α4 or β2 subunit knockout mice reduces the pharmacological and behavioral effects of nicotine (Picciotto","Tobacco continues to be widely used worldwide, primarily via cigarette smoking, and is a leading cause of preventable deaths. Stopping smoking is difficult because the nicotine in tobacco is highly addictive, and so several drugs have been developed to help people break their addiction. Varenicline (also known by the trade name Chantix) is a commonly prescribed anti-smoking drug, but it is not fully understood how it works. Nicotine affects the brain by binding to proteins called nicotinic acetylcholine receptors (nAChRs) that sit on the surface of neurons. This binding releases a number of chemical signals, including some that produce feelings of pleasure. Over time, the receptors become less sensitive to nicotine and produce more “high-affinity” binding sites for nicotine to bind to. This adaptation is one reason why",380,128,0.3368
scientific_lay_summarisation-elife-norm,"In budding yeast, a single cenH3 (Cse4) nucleosome occupies the ∼120-bp functional centromere, however conflicting structural models for the particle have been proposed. To resolve this controversy, we have applied H4S47C-anchored cleavage mapping, which reveals the precise position of histone H4 in every nucleosome in the genome. We find that cleavage patterns at centromeres are unique within the genome and are incompatible with symmetrical structures, including octameric nucleosomes and (Cse4/H4) 2 tetrasomes. Centromere cleavage patterns are compatible with a precisely positioned core structure, one in which each of the 16 yeast centromeres is occupied by oppositely oriented Cse4/H4/H2A/H2B hemisomes in two rotational phases within the population. Centromere-specific hemisomes are also inferred from distances observed between closely-spaced H4 cleavages, as predicted from structural modeling. Our results indicate that the orientation and rotational position of the stable hemisome at each yeast centromere is not specified by the functional centromere sequence. Centromeres are the genetic loci that organize the proteinaceous kinetochore, which attaches to spindle microtubules to pull the chromosomes to the poles in both mitosis and meiosis. There is general agreement in the centromere field that the central determinant of centromere identity and propagation is the special centromeric nucleosome containing the cenH3 (CENP-A in mammals and Cse4 in budding yeast) histone variant (Quenet and Dalal, 2012). CenH3 nucleosomes have been shown to occupy the centromeres of nearly all eukaryotes studied, and to be necessary for kinetochore formation. Despite the central importance of this nucleosome, its composition and structure have been the subject of controversy. In vitro and in vivo studies have led to proposals for several mutually exclusive models, including conventional octameric (cenH3/H4/H2B/H2A) 2 nucleosomes (‘octasomes’) (Camahort et al. , 2009), cenH3/H4/H2B/H2A half-nucleosomes (‘hemisomes’) (Dalal et al. , 2007), (cenH3/H4) 2 tetrasomes (Aravamudhan et al. , 2013), mixed (cenH3/H3/H42/H2B2/H2A2) octasomes (Lochmann and Ivanov, 2012) and (cenH3/H4/Scm3) 2 hexasomes (Mizuguchi et al. , 2007), where Scm3 is a cenH3-specific histone chaperone. Evidence for each of these conflicting models has been presented for budding yeast, where the centromere is genetically defined by an ∼120-bp functional sequence on each of the 16 chromosomes. The functional centromere has a tripartite organization: the 8 bp CDEI sequence is a binding site for the Cbf1 protein, the Cse4 nucleosome maps to the 78–86 bp CDEII sequence, and the","DNA is tightly packaged in cells for a variety of reasons—to allow it to fit inside the nucleus, to protect it from damage, and to help control the production of proteins from genes. The basic unit of packaged DNA is called a nucleosome, which consists of DNA wrapped around a structure formed by two pairs of four different proteins. These proteins, which are called histones, have a role that extends beyond providing structural support for DNA. When cells divide, for example, pairs of ‘sister chromosomes’ are pulled apart to ensure that the two daughter cells both have the same chromosomes as the original cell. The sister chromosomes are pulled apart from a single position called a centromere, and the nucleosomes at this position contain a histone that is",380,128,0.3368
scientific_lay_summarisation-elife-norm,"(Emonet and Kullmer, 2014). Neanderthal molars show elongated root trunks and apically positioned root furcations (Kupczik and Hublin, 2010; Macchiarelli et al. , 2006). Therefore, investigating root development offers unique insights into organogenesis and human evolution. Epithelial-mesenchymal interactions are required for root development and integration with the jawbone. The tooth root begins to develop with the guidance of a bilayered structure called Hertwig’s epithelial root sheath (HERS). The cranial neural crest cell (CNCC) -derived mesenchyme forms the dental papilla and dental follicle. The mesenchyme of the apical papilla interacts with the inner layer of HERS and differentiates into odontoblasts that form dentin. The dental follicle also interacts with HERS and eventually produces the cementum, PDL, and adjacent alveolar bone (Li et al. , 2017). Disruption of the interaction between HERS and the dental papilla or dental follicle leads to root development defects. For instance, if there is a disturbance to the developing HERS, differentiation of root odontoblasts will be compromised (Kim et al. , 2013). HERS has been considered critical for determination of the tooth root number. It develops tongue-shaped epithelial protrusions (known as the epithelial diaphragm) that join horizontally to form a bridge, called the furcation, which constitutes the base of the pulp cavity and divides the roots. After the furcation forms, the apical growth of HERS drives root development in multi-rooted teeth, just as it does in single-rooted teeth. The different orientations of HERS in different types of teeth contribute to the formation of two-rooted lower molars, three-rooted upper molars, and single-rooted incisors (Li et al. , 2017). However, the mechanisms involved in HERS regulation of furcation development remain unknown. Although previous studies have shown that changes in cell proliferation activity in the dental mesenchyme can lead to furcation defects (Fons Romero et al. , 2017; Sohn et al. , 2014), it is not clear whether the instructions that ultimately determine root furcation development and number reside in the dental mesenchyme or epithelium. Recently, multiple signaling pathways have been implicated in the processes of root initiation and elongation (Alfaqeeh et al. , 2015; Kim et al. , 2015; Li et al. , 2015; Ono et al. , 2016), but how the number of tooth roots is determined remains unknown. Ezh2 is the enzymatic subunit of Polycomb repressive complex","Different teeth have different numbers of roots. Incisors and canines each have one, and molars have two or three. Roots anchor the teeth to the jawbone, and provide a route for blood and nerves to reach the tooth. Getting the shape and number of the roots right during development is important to make sure that each tooth has proper support and function. A protein called Ezh2 helps the bones of the face to develop, but it was not known how it affects how the roots of teeth grow. Teeth form from two layers of tissue; epithelium on the outside and mesenchyme on the inside. Jing et al. have now looked at what happens when Ezh2 is not present in these tissues in the molar teeth of developing mice.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo (a) pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13’s critical role in PAH-induced lung carcinogenesis. Air pollution is a diverse mixture of pollutants that originated from anthropogenic and natural sources, is comprised of particulate matter (PM), gases (e. g. , sulfur oxides, carbon monoxide, ozone), organic compounds (e. g. , polycyclic aromatic hydrocarbons, PAHs), metals (e. g. , lead, vanadium, and nickel), and others, such as microbes (Akimoto, 2003; Huang et al. , 2014). Air pollution is a global environmental health risk that affects the populations in developed and developing countries alike, and satellite observations suggest that 80% of the global population resides in locations where the ambient pollutant concentrations exceed the World Health Organization (WHO) Air Quality Guideline (van Donkelaar et al. , 2010). Outdoor air pollution in cities and rural areas was estimated to cause 3. 7 million premature deaths annually worldwide in 2012, including 220,000 deaths due to lung cancer (WHO, 2014). Recently, outdoor (Loomis et al. , 2013) and indoor (WHO, 2010) air pollution has been classified as a Group 1 carcinogen in humans by the International Agency for Research on Cancer (IARC) of WHO. Indeed, the risk of lung cancer rises by 18% for every increase of 5 μg/m3 of PM smaller than 2. 5 μm in diameter (PM2. 5) in the environment; the risk increases by 22% for every increase of 10 μg/m3 in PM smaller than 10 μm (PM10) (Raaschou-Nielsen et al. , 2013). There","Lung cancer causes the most cancer deaths worldwide. For decades, people have known that lung cancer is associated with environmental factors, and both cigarette smoke and air pollution are known to cause cancers in humans. Smoke and air pollution both contain chemicals called polycyclic aromatic hydrocarbons (or PAHs). These chemicals cause chronic inflammation of the lung, which in turn is a major risk factor for developing lung cancer. However, it is unclear exactly how PAHs trigger inflammation and cancer. Xuanwei City in China is suited to the study of this question because until the 1970s its inhabitants used' smoky coal' for cooking in unventilated indoor spaces; this produced high levels of small particles that contain high concentrations of PAHs. Women from this region, who traditionally do most of",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2016). Moreover, spatially organized numerosity maps were recently claimed to extend to the occipital cortex (Harvey and Dumoulin, 2017a) and early ERP components compatible with generators in early visual areas responded to variations in the numerosity of visual arrays (Park et al. , 2015; Fornaciai et al. , 2017; Fornaciai and Park, 2017). Several properties characterizing numerosity perception, such as being ratio-dependent (Weber’s law) and being susceptible to adaptation, led some authors to suggest that number is a ‘primary’ visual property of the image that is directly perceived through specialized and dedicated mechanisms (Burr and Ross, 2008; Ross, 2010; Anobile et al. , 2016b). However, in spite of dedicated efforts on modeling the extraction of numerosity from the visual image (Dehaene and Changeux, 1993; Verguts and Fias, 2004; Dakin et al. , 2011; Stoianov and Zorzi, 2012; Morgan et al. , 2014), the detailed neural processing mechanisms used by the brain to arrive at a representation of numerosity from the visual input remain little understood, and much less understood than the ones for other basic visual features such as orientation, colour, motion, etc. Numerosity is a notoriously difficult feature to study since changes in numerosity tend to be associated with changes in other quantitative features of the sets during natural viewing conditions (e. g. , more items tend to occupy a larger area, or be spaced more densely), and it appears impossible to control for all of these associated quantities at the same time. For this reason, in spite of a large body of behavioral and neuroscientific work on this topic, it still remains debated whether the available evidence supports a sensory extraction mechanism directly sensitive to numerosity. Some have argued instead that numerosity might be judged indirectly by weighing a combination of other, non-numerical, quantitative features of the stimuli (Gebuis and Reynvoet, 2012; Gebuis et al. , 2014; Leibovich et al. , 2016a). For example, numerosity can be mathematically defined as the product of density (number of items per unit of area) by field area; or by the total surface area divided by mean item size. Thus, decisions on numerical quantity could be taken merely indirectly, on the basis of representations of these non-numerical properties, without numerosity being encoded directly by perceptual systems. While this possibility is interesting,","Numbers and the ability to count and calculate are an essential part of human culture. They are part of everyday life, featuring in calendars, computers or the weekly shop, but also in some of humanity’s biggest achievements: without them the pyramids or space travel would not exist. A precursor of sophisticated mathematical skill could reside in a simpler mental ability: the capacity to assess numerical quantities at a glance. This ‘number sense’ appears in humans in early childhood and it is also present in other animals, but it is still poorly understood. Brain imaging techniques have identified the parts of the brain that are active when perceiving numbers or making calculations. As techniques have advanced, it has become possible to resolve fine differences in brain activity that occur",380,128,0.3368
dialogsum,"#Person1#: What will you be having this evening? #Person2#: I think I'll start with some soup, and then I'll have the steak. #Person1#: And how would you like your steak cooked, sir? #Person2#: Medium rare, please. Also I'd like the vegetables instead of the salad. #Person1#: Sure. And what will you be having to drink? #Person2#: I think I'll have a glass of your red wine with some ice water as well. #Person1#: Coming right up, sir.","#Person1# helps #Person2# order some soup, the medium-rare steak, vegetables, wine, and ice water.",77,14,0.1818
dialogsum,"#Person1#: The new baby must be keeping you up at all hours of the night. #Person2#: She's been pretty good since my mother moved in, and she's sleeping for a longer time at night. It's my thoughts as a mother that keep me awake at night.","#Person2# says since her mother moved in, her baby's been pretty good.",46,12,0.2609
pubmed-summarization,"the nuclear receptors comprise a family of transcriptional regulators involved in a wide variety of biological processes such as embryonic development , differentiation and homeostasis . the family includes ligand - dependent zinc - finger transcription factors for steroid hormones , estrogens , thyroid hormones , retinoids , vitamin d and other hydrophobic molecules . in addition , several family members are ' orphan receptors ' for which ligands have yet to be identified . nuclear receptors have been assigned to six subfamilies on the basis of evolutionary studies . as the first member of the sixth subfamily , gcnf is also known by its systematic name nr6a1 . on the basis of homology and expression profile , the receptor has been given the alternative name of retinoic acid receptor - related testis - associated receptor ( rtr ) . transfection experiments reveal that gcnf can act as a constitutive repressor when binding as a homodimer to promoters containing a direct repeat dna element 5'-aggtcaaggtca-3 ' ( dro ) . the mouse receptor ( mgcnf ) is highly expressed in the developing embryonic nervous system and the labyrinthine layer of the placenta . in the adult , high transcript levels are restricted to the developing germ cells . northern analysis reveals a transcript of 7.5 kilobases ( kb ) in somatic cells and an additional message of approximately 2.4 kb in male germ cells . this size difference is at least partially due to different polyadenylation sites , and it is therefore assumed that both transcripts code for identical proteins of 495 amino acids . the protein sequence is encoded by 11 exons . when differentiation of p19 embryonal carcinoma cells is triggered by retinoic acid , the transcript and the protein are temporarily upregulated and then downregulated . isolation of a human cdna coding for a protein ( hgcnf ) with an identity to the mouse protein of 98.7% , similar regulation in mouse p19 cells and in the human embryonal carcinoma cell line nt2/d1 , together with the presence of two mrnas of approximately 7.5 and 2.2 kb in human testis , suggested similar functions for mouse and human gcnf . the cloning of human cdnas that give rise to different hgcnf isoforms , however , suggests a","background : germ - cell nuclear factor ( gcnf , nr6ai ) is an orphan nuclear receptor . its expression pattern suggests it functions during embryogenesis , in the placenta and in germ - cell development . mouse gcnf cdna codes for a protein of 495 amino acids , whereas the four reported human cdna variants code for proteins of 454 to 480 amino acids . apart from this size difference , there is sequence conservation of up to 98.7% . to elucidate the genomic structure that gives rise to the different human gcnf mrnas , the sequence information of the human gcnf locus is compared to the previously reported structure of the mouse locus.results:the genomic structures of the mouse and human gcnf genes are highly conserved .",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The zebrafish was used to assess the impact of social isolation on behaviour and brain function. As in humans and other social species, early social deprivation reduced social preference in juvenile zebrafish. Whole-brain functional maps of anti-social isolated (lonely) fish were distinct from anti-social (loner) fish found in the normal population. These isolation-induced activity changes revealed profound disruption of neural activity in brain areas linked to social behaviour, social cue processing, and anxiety/stress. Several of the affected regions are modulated by serotonin, and we found that social preference in isolated fish could be rescued by acutely reducing serotonin levels. Social preference behaviour, the drive for individuals to identify and approach members of their own species (Rogers-Carter et al. , 2018; Winslow, 2003), is a fundamental component of all social behaviour. We previously found that most zebrafish develop a strong social preference by 2–3 weeks of age (Dreosti et al. , 2015), yet we also found a small number (~10%) of ‘loner’ fish that were averse to social cues. A similar diversity of individual social preferences has been found in many species, including humans (Sloan Wilson et al. , 1994). Loneliness, undesired isolation from social interaction, has been linked to a reduction in social preference (Engeszer et al. , 2004; Shams et al. , 2018). We therefore asked whether the socially-averse loner fish found in the normal population would show a similar behavioural phenotype and neuronal activity to socially-averse lonely fish raised in isolation. To answer this question, we compared the behavioural and functional responses of isolated fish to controls during viewing of conspecifics. This comparison found that isolation induces patterns of brain activity that are not present in the normal population. We then asked if we could rescue the aversive behaviour of isolated fish. Since some of the highly activated areas in isolated fish are serotoninergic, we used Buspirone, a 5HT1A receptor agonist. These findings will have important implications for how we understand and treat the impact of social isolation. Prolonged periods of social isolation are particularly detrimental to humans during early development. However, even brief periods of social isolation have been shown to impact mental and physical health. We therefore tested two models of social isolation, Full (fish raised completely without social interaction) and Partial (fish isolated for 48","Socialising is good for people’s mental health and wellbeing. The connections and relationships that we form can make us more resilient and healthier. Researchers also know that prolonged periods of social isolation, and feeling lonely, can be detrimental to our health, especially in early childhood. The paradox is that loneliness often results in an even lower desire for social contact, leading to further isolation. But not everyone craves social contact. Some people prefer to be alone and feel more comfortable avoiding social interaction. Zebrafish display the same social preferences. This, along with their transparent brains, makes them a useful model to study the links between social behaviour and brain activity. Like humans, zebrafish are social animals, with most fish taking a strong liking to social interactions by the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"evolutionary conserved protein complexes, including the cytoplasmic dynein motor, its binding partner dynactin, and the cortically-anchored NuMA-LGN-Gαi complex (1A) (Kiyomitsu and Cheeseman, 2012). Prior work has conceptualized that the cortical complex is distributed along the cell cortex and individually pulls on astral microtubules using dynein-based motility and/or by controlling microtubule dynamics (Kiyomitsu and Cheeseman, 2012; Kotak and Gönczy, 2013; Laan et al. , 2012). However, compared to the focal kinetochore structure, how this diffusion-prone membrane-associated complex efficiently captures and pulls on dynamic plus-ends of astral microtubules remains poorly understood. Here, we sought to understand the mechanisms of cortical pulling-force generation by reconstituting a minimal functional unit of the cortical force-generating complex in human cells using a light-induced membrane tethering. We found that cortical targeting of NuMA is sufficient to control spindle position, and that NuMA makes multiple, distinct contributions for spindle pulling through its N-terminal dynein recruitment domain, central long coiled-coil, and C-terminal microtubule-binding domains. In addition, we demonstrate that NuMA assembles focal clusters at the mitotic cell cortex that coordinate multiple dynein-based forces with NuMA’s microtubule binding activities. We propose that the cortical Dynein-Dynactin-NuMA clusters (hereafter referred to as the cortical DDN clusters) act as the core spindle-pulling machinery that efficiently captures astral microtubules and generates cooperative pulling forces to position the mitotic spindle. To understand the molecular mechanisms that underlie cortical force generation, we sought to reconstitute a minimal functional unit of the cortical force-generating machinery in human cells using a light-induced hetero-dimerization system (iLID) (Guntas et al. , 2015). In this system, cytoplasmic RFP-Nano fusion proteins can be targeted to a locally illuminated region of the mitotic cell cortex by interacting with membrane-bound iLID (1A; — 1A–B; and Video 1). Because the N-terminal fragment of NuMA is sufficient to recruit dynein-dynactin to the cell cortex (Kotak et al. , 2012), we first sought to manipulate endogenous NuMA. We established triple knock-in cell lines that stably express membrane-targeted BFP-iLID (Mem-BFP-iLID), a NuMA-RFP-Nano fusion (1A; — 1C–E), and SNAP-tagged dynein heavy chain (DHC) or the dynactin subunit p150 (— 1F–G). To prevent cortical recruitment of NuMA by the endogenous LGN-Gαi complex, we depleted LGN by RNAi (1A middle, 1B t = 0: 00; — 1H). We then continuously illuminated the cortical region next to one of spindle poles (indicated","Almost every time a cell divides, it must share copies of its genetic material between two new daughter cells. A large molecular machine called the mitotic spindle makes this happen. The spindle is made of protein filaments known as microtubules that radiate out from two points at opposite ends of the cell. Some of these filaments attach to the genetic material in the center of the cell; some extend in the other direction and anchor the spindle to the cell membrane. The anchoring filaments – also known as astral microtubules – can position the mitotic spindle, which controls whether the cell splits straight down the middle (to give two identically sized cells) or off-center (which gives cells of different sizes). The force required to move the spindle comes",380,128,0.3368
scientific_lay_summarisation-elife-norm,"highlighted the neural mechanisms that allow this to happen (Gazzaley and Nobre, 2012; Hopfinger et al. , 2000). However, in daily life, it is exceedingly rare to receive explicit instructions on how we should direct our attention. Instead, our attentional states are often guided by past experiences in similar situations (Awh et al. , 2012). Such memory-guided attention is effective in guiding goal-directed behavior (Aly and Turk-Browne, 2017; Chen and Hutchinson, 2018; Nobre and Stokes, 2019) but is relatively under-explored. Here, we examine the mechanisms underlying memory-guided attention with the aim of determining the nature of neural representations that enable past experiences to be used to prepare for upcoming attentional states. We define ‘attentional state’ as the prioritized processing of particular environmental features in order to perform a given task. This entails focusing on task-relevant features, often at the expense of task-irrelevant features. Attentional states can be considered an instance of a task representation or a task set (Mayr and Kliegl, 2000; Sakai, 2008), with the task defining what should be attended to. What brain regions may establish memory-guided attentional states? We focus on two candidate regions, the hippocampus and medial prefrontal cortex (mPFC). Interactions between these regions have been linked to a variety of goal-directed behaviors that are guided by long-term memory (Euston et al. , 2012; Kaplan et al. , 2017; Shin and Jadhav, 2016). Furthermore, both the hippocampus (Aly and Turk-Browne, 2016a; Aly and Turk-Browne, 2016b; Aly and Turk-Browne, 2018; Córdova et al. , 2019; Fenton et al. , 2010; Mack et al. , 2016; Muzzio et al. , 2009; Ruiz et al. , 2020) and mPFC (Mack et al. , 2016; Small et al. , 2003) contribute to attentional processing. These findings suggest that the hippocampus and mPFC may work together to guide attentional behaviors on the basis of memory. Below, we explore their potential roles in more detail. Previous work from our lab has demonstrated that the hippocampus represents online attentional states (Aly and Turk-Browne, 2016a; Aly and Turk-Browne, 2016b; Córdova et al. , 2019). Moreover, decades of work have highlighted the critical role of the hippocampus in encoding and retrieving long-term memories (Lepage et al. , 1998; Shapiro and Eichenbaum, 1999). These findings therefore suggest that the hippocampus might play an important role in","At any given moment, humans are bombarded with a constant stream of new information. But the brain can take in only a fraction of that information at once. So how does the brain decide what to pay attention to and what to ignore? Many laboratory studies of attention avoid this issue by simply telling participants what to attend to. But in daily life, people rarely receive instructions like that. Instead people must often rely on past experiences to guide their attention. When cycling close to home, for example, a person knows to watch out for the blind junction at the top of the hill and for the large pothole just around the corner. Günseli and Aly set out to bridge the gap between laboratory studies of attention and",380,128,0.3368
pubmed-summarization,"reduction by 20% ( definition one ) or an iop < 18 mmhg to baseline measures ( definition two ) with ( qualified success ) and without ( complete success ) iop - lowering medication . prior to surgical treatment , neodymium : yttrium - aluminium - garnet ( nd : yag ) laser iridotomy was performed in all patients of the nontrab group to rule out a pupillary block . of these , three patients required additional surgical iridectomy for inconsistent iridotomy . as intensive medical treatment ( including cycloplegic agents and topical and systemic iop - lowering medication ) remained unsuccessful and iop was persistently elevated , pars plana vitrectomy became a prerequisite . a 20-gauge port was used in six patients of the trab group and in all six patients of the nontrab group and a 23-gauge port in three patients of the trab group . anterior vitrectomy via pars plana was performed using a three - port technique to disrupt the anterior hyaloid membrane ensuring aqueous outflow from the vitreous cavity into the anterior chamber in order to interrupt the ciliolenticular block mechanism . existing adhesions and remnants of the vitreous body around the peripheral iridectomy were removed to allow patency for anterior aqueous flow . vitrectomy was continued until the anterior chamber deepened . in phakic eyes with significant cataract , combined vitrectomy and cataract extraction spss version 19.0 for windows ( ibm corporation , armonk , ny , usa ) was used for statistical analyses and to create figures . categorical variables were evaluated with pearson s chi - squared test or fisher s exact test . differences between groups in single discrete variables of nonnormal distribution were tested for significance using the mann . a maximum two - tailed p - value of < 0.05 was considered an indication of statistical significance . clinical records of 15 patients were reviewed retrospectively undergoing pars plana vitrectomy for treatment of malignant glaucoma at the university eye hospital of wuerzburg , germany between 1995 and 2010 . the following parameters were recorded : age , sex , lens status , primary ophthalmic diagnosis , past medical history , glaucoma medication , and the event preceding malignant glaucoma . preoperatively , all patients received a standard ophthalmic","purposeto assess the outcomes of pars plana vitrectomy for the treatment of malignant glaucoma in patients with and without previous filtration surgery.patients and methodsdata of 15 patients developing malignant glaucoma after trabeculectomy ( 60% ) or following ophthalmic interventions other than filtration surgery ( 40% ) were recorded retrospectively . pars plana vitrectomy was performed in case of failed medical or laser treatment recreating the normal pathway of aqueous humor . the main outcome measures were the postoperative intraocular pressure ( iop ) , the frequency of complications , and success rate based on the following criteria : iop reduction by 20% and to 21 mmhg ( definition one ) or an iop < 18 mmhg ( definition two ) with ( qualified success ) and without (",380,128,0.3368
pubmed-summarization,"vibrissae provide input to specific thalamic nuclei and these nuclei have well - defined connections with the somatosensory cortical region where sensory information is processed ( woolsey and van der loos , 1970 ) . these connections have a somatotopic organization , and sensory information from each vibrissa reaches a specific barreloid in the thalamic ventrobasal ( vb ) complex and is relayed to a specific cortical barrel field in the primary somatosensory cortex . during their developmental outgrowth , thalamocortical axons are guided by a variety of cues ( molnr et al . , 2012 ) . after crossing the subpallial - pallial border , thalamocortical axons advance within the intermediate zone ( iz ) and , approaching the cortex , they accumulate below the cortical plate ( cp ) at the subplate ( ghosh et al . , the interaction of thalamocortical axons with the subplate is one of the most enigmatic processes in the development of thalamocortical fibers . even in reeler or p35 knockout ( ko ) mice , where the subplate is aberrantly located , thalamocortical axons cross the cp toward the misplaced subplate before connecting to their final targets ( hoerder - suabedissen and molnr , 2015 ) . however , the molecular mechanisms that control thalamocortical axon - subplate interaction and ultimately the correct targeting of thalamic projections are largely unknown . in the developing brain , bioactive phospholipids like lysophosphatidic acid ( lpa ) play important roles in cortical migration ( fukushima et al . , 2000 ) and neuronal apoptosis ( kingsbury et al . , 2003 ) . these effects are mediated by lpa receptors , namely lpa1-r and lpa2-r , which are expressed in the developing brain ( kingsbury et al . , 2003 ) . lpa is a well - described repellent factor for axons , eventually leading to growth cone ( gc ) collapse ( campbell and holt , 2003 ) . however , while in vitro experiments suggested an involvement of lpa1-r in lpa - mediated axonal retraction , deletion of specific lpa receptors did not lead to significant alterations of fiber tracts in the brain ( contos et al . , 2002 ) and did not affect inhibitory lpa effects on retinal gcs ( birgbauer","summaryprecise connection of thalamic barreloids with their corresponding cortical barrels is critical for processing of vibrissal sensory information . here , we show that prg-2 , a phospholipid - interacting molecule , is important for thalamocortical axon guidance . developing thalamocortical fibers both in prg-2 full knockout ( ko ) and in thalamus - specific ko mice prematurely entered the cortical plate , eventually innervating non - corresponding barrels . this misrouting relied on lost axonal sensitivity toward lysophosphatidic acid ( lpa ) , which failed to repel prg-2-deficient thalamocortical fibers . prg-2 electroporation in the prg-2/ thalamus restored the aberrant cortical innervation . we identified radixin as a prg-2 interaction partner and showed that radixin accumulation in growth cones and its lpa - dependent phosphorylation depend on",380,128,0.3368
pubmed-summarization,"to be safe . based on the experiences described by those involved in the process , it can be argued that it is important to learn more about how to enhance and organize icu transitional care . therefore , the aim of this study was to describe , as experienced by intensive care and general ward staff , what strategies could be used when organizing patient 's care before , during , and after transfer from intensive care . before , during , and after transfer from the icu to a general ward , patients experience a transition process . the patients are transferred from the context of high technology to the culture of the general ward . the specific process of transition from the icu to the general ward has become a topic of interest because difficulties that arise during the process have been increasingly frequent . transitions can be initiated by such events as acute illness or injury , which also explains why the concept is a nursing concern . the process requires a beginning , middle , and end and how the person feels and perceives the situation is critical as the process continues . transition could result in a feeling of displacement and lack of control over their lives . the situation and time span vary and may consist of short periods or months and years ; an example of transition is hospitalization for an acute injury or illness . the study has been approved by the northern ethical committee in sweden ( d - number 07 - 159 ) . the first author informed and asked the nurses about participation in the study in accordance with verbal and written criteria . they were informed about confidentiality and their rights to withdraw their participation without giving reason . as the aim of the study was to describe and illuminate the transition process between icu and general ward , qualitative content analyses were considered . the data were also used in a larger study that aimed to generate theories about main concerns in icu transitional care . data were collected between 2008 and 2010 in two hospitals located in sweden with different sizes . the participants were recruited in three icus and five general wards specializing in","background . organizing and performing patient transfers in the continuum of care is part of the work of nurses and other staff of a multiprofessional healthcare team . an understanding of discharge practices is needed in order to ultimate patients ' transfers from high technological intensive care units ( icu ) to general wards . aim . to describe , as experienced by intensive care and general ward staff , what strategies could be used when organizing patient 's care before , during , and after transfer from intensive care . method . interviews of 15 participants were conducted , audio - taped , transcribed verbatim , and analyzed using qualitative content analysis . results . the results showed that the categories secure , encourage , and collaborate",380,128,0.3368
pubmed-summarization,". it is a 4- bedded closed , multidisciplinary , medical - surgical unit with about 350 admissions per year . trends of mortality were categorized into 4 groups : ( 1 ) failed cardiopulmonary resuscitation ( cpr ) , ( 2 ) dnr , ( 3 ) brain death , and ( 4 ) wlst . the decision of dnr was made by the attending physician after detail discussion and informed consent from parents / guardians . the wlst was done with the involvement of a hospital ethical committee and the attending consultant after obtaining informed consent from parents / guardians . we have hospital ethical committee , having members , who are trained with accredited ethical fellowship program . other data collected from the medial records included patient demographics ( i.e. age , sex , admission source such as the emergency room [ er ] or operating theatre , ) along with the admitting diagnosis . a total of 1919 children were admitted to the picu over the 6 years period , of which 248 children died with mortality rate of 12.9% . most of the children who died were male 60.5% ( n = 150 ) with a median age of 2.8 years ( interquartile range 0.48 years ) , and 65% of children who died were under 5 years old . overall , the incidence of admission was highest from the er ( 57.7% , n = 143 ) [ table 1 ] . characteristics of children who died in pediatric icu most of the children died with a sepsis or sepsis - related diagnosis ( 17.3% , n = 43 ) followed by central nervous system ( cns ) involvement . in 63.7% ( n = 158 ) children , death was followed by some kind of limitation of lst , which involved dnr and wlst with dnr being more prevalent while in 28.2% of children ( n = 70 ) full resuscitative procedures were carried out . we also found an increasing trend of limitation of lst ( dnr ) over the period of 6 years [ ] . modes of death among critically ill pediatric patients in pediatric intensive care unit pattern of modes of death over 6 years study period among critically","background and aim : advances in biomedical technology have made medical treatment to be continued beyond a point , at which it does not confer an advantage but may increase the suffering of patients . in such cases , continuation of care may not always be useful , and this has given rise to the concept of limitation of life - sustaining treatment . our aim was to study mortality patterns over a 6-year period in a pediatric intensive care unit ( picu ) in a developing country and to compare the results with published data from other countries.materials and methods : retrospective cohort study was conducted in a picu of a tertiary care hospital in pakistan . data were drawn from the medical records of children aged",380,128,0.3368
dialogsum,"#Person1#: Could you give us a detailed description of the properties of your product? #Person2#: OK. The X2500 has the unique feature of providing better data flow with less input time. It will reduce your work load at the office. #Person1#: Could you tell me more about it? #Person2#: Of course. One of the real pluses of this product is that it is of very high quality, and of compact size. No one can match us so far as quality is concerned. #Person1#: Can you introduce its price level to me? #Person2#: We have this item in three price level. #Person1#: We need the best possible quality. #Person2#: That means this one. #Person1#: I see, that's what I will order.","#Person1# asks #Person2# to describe the properties of the product in detail. #Person2# tells #Person1# the features, the size and the price.",120,22,0.1833
dialogsum,"#Person1#: Albert and I need a lot of things to furnish our house. But I don't know where the best place to shop is. Can you give me some advice? #Person2#: Sure, Carolyn. I'm happy to help you. What kinds of things do you need right now? #Person1#: Well, we have most of the furniture already. We mostly need kitchen utensils, bathroom accessories, cleaning and laundry accessories--things like that. And Albert wants to set up a little offi #Person2#: Well, as for Albert, he should go to an office supply store. There's a very good one called Office Depot. They have everything he will need. And their prices are good too. It's very conven #Person1#: Can I write that down? #Person2#: Sure, it's spelled Office and then D - E - P - O - T. It's in the Yellow Pages. #Person1#: Thanks. #Person2#: And as for the kitchen things, do you want very high quality? #Person1#: What do you mean? #Person2#: I mean, do you want the best quality, or do you want good prices? #Person1#: Probably good prices. You know we will only be in America for about a year. #Person2#: Then I suggest you go to K-Mart or Wal-Mart. #Person1#: What are those stores? #Person2#: They are very large, discount department stores. That means their prices are very good. And you can find everything you need for the kitchen or bathroom. #Person1#: Even silverware? #Person2#: Yes, everything. They don't have the most expensive brands, but their quality is usually decent. The main thing is, they have good prices, and they are very convenient. #Person1#: I have a friend that said something about a place called Price Club. Do you know about that? #Person2#: I have never shopped there, but I think Price Club is a kind of membership store. #Person1#: What does that mean? #Person2#: That means you have to pay a membership fee to shop there. I have heard they have very good prices on electronics. #Person1#: Electronics? #Person2#: Yes. Like stereos and televisions. #Person1#: How much is the membership fee? #Person2#: I'm not sure. But if you are only going to stay a year, I don't think Price Club is good to join. They have great deals occasionally. They are very good for people who",Carolyn wants some advice from #Person2# for the place to buy furniture. #Person2# recommends some stores where she can find everything her need for the kitchen or bathroom with good prices. #Person2# doesn't think Price Club is good to join because they are only going to stay a year.,380,49,0.1289
pubmed-summarization,"rufinamide ( ruf ) is a triazole derivative that is structurally unrelated to other antiepileptic drugs ( aed).1 it was approved by the united states , food and drug administration ( fda ) in 2004 for the treatment of lennox - gastaut syndrome ( lgs ) in patients aged 4 years and older.2 ruf was authorized for the same indication in europe in january 2007.2,3 the mechanism of action involves limiting the firing of excessive sodium - dependent action potentials.1 ruf has been reported to reduce the number of drop attacks and major motor seizure in about 60% of patients with lgs and has subsequently been regarded as an effective adjunctive therapeutic agent.2 in recent years , studies have been reported that ruf is also efficacious and well tolerated in the treatment of various epilepsy syndromes other than lgs , including cases of refractory epilepsy in pediatric patients.3 however , there are still limited data regarding the long term treatment results of ruf for pediatric refractory epilepsy . the aim of this study was to delineate the long term efficacy and tolerability of ruf in children and infants with intractable epilepsies . we performed a retrospective study for the patients who met the following inclusion criteria ; ( 1 ) who were followed up for more than one year at samsung medical center since the beginning of the ruf use , at the time of 31 aug 2011 , ( 2 ) who were less than 19 years of age at the time of the start of ruf treatment , ( 3 ) who were classified as intractable epilepsy , meaning presence of persistent seizures despite the use of more than three antiepileptic drugs , and ( 4 ) whose data on the clinical characteristics and seizure outcome were available . the data concerning demography , clinical characteristics , seizure - related characteristics , laboratory works including electroencephalography ( eeg ) and brain magnetic resonance imaging ( mri ) , and treatment outcome were collected . we conformed to the classification of the international league against epilepsy ( ilae ) in 1981 and 1989 in classifying the seizure and epilepsy of the patients.4,5 the efficacy of ruf was evaluated by the response rate , by comparing the seizure frequencies at","background and purpose : rufinamide ( ruf ) is a novel antiepileptic drug ( aed ) and its efficacy has been proven in lennox - gastaut syndrome ( lgs ) . however , there is a lack of data regarding the efficacy in pediatric intractable epilepsies other than lgs . the purpose of the study was to explore the efficacy and tolerability of ruf in pediatric patients with intractable epilepsies as well as lgs.methods:this retrospective observation study was conducted in samsung medical center from august 2010 to september 2011 . thirty seven patients ( 27 males , 10 females , aged between 1.8 and 18.4 years ) , with refractory epilepsies or lgs were treated with ruf as an adjunctive drug . efficacy was represented by the response",380,128,0.3368
dialogsum,"#Person1#: I would like to open a checking account at this branch. #Person2#: Do you have any other accounts with this bank? #Person1#: I do, at a different location, I have a savings account and a CD. #Person2#: In that case, we will need to fill out this paperwork. Do you have identification with you? #Person1#: Here is my driver's license. Will that work? #Person2#: Yes. Do you know what type of checking account you would like to open, business or personal? #Person1#: Business please. And I want the most simple one you have. #Person2#: Then you would like the'no frills'business account.","#Person1# wants to open a checking account at the bank branch, and #Person1# helps choose the 'no frills' business account.",102,20,0.1961
dialogsum,"#Person1#: Good morning, Mister Black. #Person2#: Good morning. Could you help me please? I'm looking for some books for my mother. #Person1#: OK. What kind of books is she interested in? #Person2#: She's very fond of romantic love stories. #Person1#: I see. What about this one? Has she read it before? #Person2#: I'm not sure. But she probably won't remember the story even if she has. She's very forgetful. #Person1#: How old is she? #Person2#: She'll be 90 next year. #Person1#: No wonder! Remember to renew it if she can't finish reading it within half a month. #Person2#: Yes, I will. Thank you very much. #Person1#: You are welcome.","Mister Black asks for #Person1#'s help to find some books for Black's mother, and #Person1# recommends one about romantic stories.",109,20,0.1835
dialogsum,"#Person1#: I want to settle my account. #Person2#: Wait for a moment. Mr. Bush. this is your bill, please sign your name here #Person1#: Well, I think something must be wrong with my bill. I didn't have any laundry. #Person2#: I am sorry, we will connect with the room service. Please Warta moment.",#Person2# shows Mr. Bush the bill but he didn't have any laundry. #Person2# will check again.,53,16,0.3019
dialogsum,"#Person1#: Today, we've invited a former student at our school to speak with us, so pay attention children. Mister Lee is a successful inventor of a popular smartphone app. #Person2#: Thanks for having me, Miss Smith. #Person1#: We're glad you could take the time. Now, how does it feel to be so successful at such a young age? #Person2#: Well, I sometimes feel a little worried and it's hard running a new company. #Person1#: You have your own company? Great, then surely you must feel proud to have done so well so quickly. #Person2#: Well, I'm probably the only 19-year-old in the millionaires club, and thank you for this opportunity to speak here, Miss Smith. I didn't really know I could speak to so many people without getting nervous.","Smith invites Mister Lee, a successful inventor of a popular smartphone app, to speak with the children.",129,17,0.1318
scientific_lay_summarisation-elife-norm,"well as nucleotides, and glutamine can contribute carbon to the TCA cycle to replace cycle intermediates that are removed for the production of biomass, a process termed anaplerosis (Altman et al. , 2016; Daye and Wellen, 2012; DeBerardinis and Cheng, 2010; Hensley et al. , 2013). Analysis of the fate of glutamine nitrogen in proliferating cancer cells in vitro suggests that most glutamine nitrogen is excreted as ammonia and alanine, suggesting that the high rate of glutamine consumption is not due to nitrogen demand (DeBerardinis et al. , 2007). Instead, glutamine metabolism is important for TCA cycle anaplerosis in multiple contexts (Altman et al. , 2016; DeBerardinis et al. , 2007; Yuneva et al. , 2007). Across cancer cell lines, the majority of aspartate, glutamate and TCA cycle metabolites are glutamine-derived (Altman et al. , 2016; Wise and Thompson, 2010), with production of amino acids being a major fate of anaplerotic glutamine carbon (Hosios et al. , 2016). In line with these results, proliferation of many cell types following glutamine starvation is rescued by providing an alternative source of the TCA cycle intermediates α-ketoglutarate (αKG) (van den Heuvel et al. , 2012; Wise et al. , 2008; Wise et al. , 2011) or oxaloacetate (Patel et al. , 2016). Collectively, these results suggest that anaplerosis contributes to the large cellular consumption of glutamine in culture, and to dependence on this amino acid for cell proliferation and survival. Glutamine can enter the TCA cycle through multiple metabolic routes. First, several transporters are capable of transporting glutamine into cells (Hediger et al. , 2013; Hyde et al. , 2003). Relevant to cancer, the neutral amino acid transporters ASCT2/SLC1A5 and LAT1/SLC7A5 are known to have higher expression in certain tumors, and can mediate glutamine uptake in cell lines derived from these tumors (Bhutia et al. , 2015; Pochini et al. , 2014). Intracellularly, glutamine is converted to glutamate either by donating the amide nitrogen for the production of nucleotides or asparagine, or by glutaminase activity (encoded by GLS1 or GLS2), which produces glutamate and ammonia from glutamine (Curthoys and Watford, 1995; Krebs, 1935). In proliferating cells, glutaminase activity can be the primary driver of glutamate production from glutamine, as amide nitrogen incorporation into mass is low compared to release of glutamine nitrogen as","Cancer cells need to consume certain nutrients in order to grow, and some cancer drugs work by affecting the ability of the cells to use these nutrients. For decades researchers have grown cancer cells in petri dishes with standard nutrient formulations (also known as tissue culture), but the nutrients available to cancer cells in tissue culture are not the same as those found in the body. Cancer cells growing in tissue culture consume large amounts of a nutrient called glutamine. These cells die when exposed to a class of drugs called glutaminase inhibitors that prevent them from processing glutamine. However, when these same cancer cells grow as tumors in animals, they process less glutamine and are not affected by glutaminase inhibitors. So what differences are there between growing",380,128,0.3368
dialogsum,"#Person1#: Hello, I'm calling about the apartment you have advertised in today's the daily mail. #Person2#: Yes, I will have a trip, so the house will be empty for 2 weeks. #Person1#: Great. I'd like to hire a short period of time. 2 weeks is just enough. Could you introduce your apartment to me? #Person2#: Sure. It's a one bedroom apartment with a big balcony, but it has a small kitchen. #Person1#: That's just my cup of tea. What's the price? #Person2#: $400 per month. You need only to pay for electricity, for gas and water are included. And you can use the parking lot free of charge. #Person1#: Sounds good. Then I can save some money. May I come over tomorrow to take a look? #Person2#: Today is Wednesday. How about the day after tomorrow? I've got an appointment tomorrow. #Person1#: OK.",#Person1# wants to rent for a short period of time and #Person1# likes the apartment #Person1# is renting out. #Person1# will go over and have a look on Friday.,143,29,0.2028
scientific_lay_summarisation-elife-norm,"lineage tracing in fixed tissues has established that cells derived from secretory progenitors intermix with cells derived from absorptive progenitors along the crypt and villus length (Yang et al. , 2001). At the crypt base, stem cells are interspersed with Paneth cells (Farin et al. , 2016). Interspersion of cell lineages plays important roles in determining local signaling environments required for intestinal homeostasis. For example, intestinal stem cells receive signals critical to their identity from neighboring Paneth cells (Sato et al. , 2011). Indeed, direct contact between stem and Paneth cells supports stem cell maintenance (Farin et al. , 2016). However, the molecular mechanisms that underlie the intermixing of lineages are poorly understood. Here, we use light sheet and confocal imaging of live murine small intestinal organoids to define the mechanisms of cell interspersion. We find that rearrangements of the actin cytoskeleton displace mitotic cells along the apical-basal axis, such that cell division occurs at the apical surface. Interspersion arises when elongated interphase neighboring cells wedge between apically dividing daughters during cytokinesis. We find that the propensity to intersperse during division requires an elongated shape of cells in the epithelium; reducing the cellular aspect ratio (height: width) in organoids disrupts interspersion, resulting in outgrowth of lineage patches. Consistent with our data indicating that the physical parameters of the tissue are a critical determinant of interspersion during division, we demonstrate that the elongated epiblast/primitive ectoderm of post-implantation (E7. 5) mouse embryos, but not the short visceral endoderm, also undergoes division-coupled cell interspersion. Thus, tissues of distinct developmental context from the adult small intestine exhibit similar mechanisms for patterning cellular progeny according to cellular dimensions. Together, our data indicate that cell shape differences between interphase and mitotic cells in elongated mammalian epithelia can allow a neighboring cell to insert between nascent daughter cells during cytokinesis and drive interspersion of cellular progeny. To identify the basis for cell interspersion, we performed time-lapse imaging of adult murine small intestinal organoids (Kretzschmar and Clevers, 2016; Sato et al. , 2009) by confocal and light sheet microscopy (single plane illumination microscopy - SPIM) (Wu et al. , 2013) (1A). To visualize cell lineages, we first used organoids in which the cytoplasm of cells of the secretory lineage was labeled with RFP (Atoh1CreER; R26RFP). Strikingly, we observed","The body has an impressive ability to renew itself by replacing old and damaged cells with new ones. This can happen rapidly; for example, the lining of the intestine renews itself approximately every five days. The lining contains many different cell types, which exchange important signals with their neighbors. This means that the new cells need to occupy similar positions to the ones they are replacing to keep the intestine working. New cells form when existing cells double their contents and divide. In many tissues the resulting cells sit side-by-side. But when cells in the intestine divide, the new cells often separate, ending up on either side of a cell that did not divide. To investigate how this happens, McKinley et al. used live microscopy techniques to watch",380,128,0.3368
dialogsum,"#Person1#: Hello, Mr. Jan Erick Freedman. You're a frequent traveler. And we also know that you eat out twice a day. How come you're so fond of eating out? #Person2#: When I got my first job back in 1982 and started travelling, I had no other choice but eat out. I found that I felt different due to what I was eating, so I tried to find places that served food that made me feel good. The secret was the quality of the food and how well the food was prepared. I made an effort to find good restaurants as well as nice dishes. #Person1#: How did you manage to make a list of 218 favorite restaurants? #Person2#: I've lived in many cities and when I moved back to Sweden from the United States, people asked me where to go and eat when they went to cities I knew. I got a lot of ideas. Then I wrote about restaurants for the Swedish club magazine and someone suggested I gather the information about the restaurants together since I had all the facts about the restaurants I've been to. I started to do that. #Person1#: How do you find restaurants? #Person2#: The best way is to ask the people there. I may talk to the people at the street market or take a walk and look for a place for myself. I never asked a hotel clerk or a taxi driver. I don't go empty restaurants or places with menus too difficult to understand.",Mr. Freedman tells #Person1# he became fond of eating when he started traveling and he tried to find places that served food that made him feel good. He tells #Person1# how he managed to make a list of 218 favorite restaurants. He asks the people there to find restaurants.,253,49,0.1937
dialogsum,"#Person1#: I'm going to have to do some shopping today. #Person2#: Oh yeah? What do you need to go shopping for? #Person1#: I want to find a new bedroom set. #Person2#: Do you know where you're going to find your bedroom set? #Person1#: I have no clue. #Person2#: There's no particular place that you want to look at? #Person1#: I don't know where to go to find a nice bedroom set. #Person2#: I can tell you where I got mine, if you'd like. #Person1#: Please do. #Person2#: I bought mine from IKEA. #Person1#: Are the bedroom sets at IKEA affordable? #Person2#: Not really, but you're paying for quality.",#Person1# wants to find a new bedroom set. #Person2# suggests #Person1# look at IKEA.,108,14,0.1296
dialogsum,"#Person1#: Where are you going for your holidays, Charles? #Person2#: To Australia. I'm going to visit my uncle in Brisbane for three weeks. #Person1#: Good gracious! You certainly are lucky. How are you going there? #Person2#: By air, of course. It takes over two weeks to go by sea. #Person1#: I once went to Singapore by air. It was very exciting-but never again. #Person2#: Why? Did you feel frightened? #Person1#: For a short time. One of the engines caught fire. #Person2#: What did the pilot do? #Person1#: He put it out and flew back to the airport. Then he asked the people at the airport where the emergency runway was. #Person2#: Did you land safely? #Person1#: Yes, we did. But I shall never fly again.","Charles tells #Person1# he will visit his uncle by air. Then #Person1# talks about an accident #Person1# once had during a flight, which made #Person1# afraid of flying.",125,28,0.224
dialogsum,"#Person1#: It seldom rains this summer. #Person2#: Yeah, some places are very short of water. #Person1#: Because of pollution and other things, our environment has become worse and worse. #Person2#: You see, This time I traveled to the West. When I looked out of the windows of the rain, all the lands that I could see are as dry as a bone. #Person1#: It is serious.",#Person1# and #Person2# are talking about the serious drought this summer.,66,11,0.1667
pubmed-summarization,"out in order to eliminate the amorphous shape of the maxillary central incisors . the impressions of the prepared teeth were obtained utilizing polyether based elastomeric impression material ( impregum penta h , duosoft grant l , duosoft , 3 m espe , germany ) after casting the model , all ceramic cores manufactured utilizing heat - press ceramic technique ( ips empress 2 , ivoclar , schaan , liechtenstein ) with # 100 lithium disilicate ceramic ingots . after the heat - press procedure completed ceramic cores were ready for try in procedures ( ) . final restoration conducted by layering technique ( empress 2 dentine ivoclar , schaan , liechtenstein ) . all ceramic crowns were bonded to the prepared abutments using dual cure composite resin luting cement ( rely - x arc , 3m - espe , germany ) . these fixed restoration treatment resulted in marked improvement in the esthetics of the anterior region and also enhanced periodontal health ( ) . the patient was encouraged to practice strict oral hygiene . after a 3-month period , the patient returned for evaluation . at the 1-year recall appointment , the terminology dental fusion and gemination are used to define two different morphological dental anomalies , characterized by the formation of a clinically wide tooth . despite the considerable number of cases reported in the literature , case history and clinical and radiographic examinations can provide the information required for the diagnosis of such abnormalities.1,36,12 after a judicious evaluation of all information we can report that this case represents bilateral gemination of maxillary incisors . while the literature on the occurrence of double teeth is extensive , there is still much discussion concerning the nomenclature . some authors have tried to differentiate them by counting the teeth or by observing the root morphology : others use fusion and gemination as synonyms . finally , some authors simply call the phenomenon double teeth or connoted teeth to avoid confusion over terminology.9,10 the use of levitas classification to distinguish between cases of fusion and gemination is very practical.9 the differential diagnosis between fusion and gemination , based on the number of teeth present on the dental arch , is not , however , always possible.5 this is because nothing","geminated teeth are the consequences of developmental anomalies leading to the eruption of joined elements . according to current definitions , gemination occurs when one tooth bud tries to divide , while fusion occurs if two buds unite . clinical experience shows , however that diagnosis can be complicated due to superimposed anomalies . this report describes a unique case of bilateral gemination of permanent maxillary central incisors . the esthetic rehabilitation of the geminated incisors accomplished utilizing all ceramic crowns . it is important that in these types of cases , reaching to the available esthetics and avoiding the complication of caries and periodontal problems with prosthetic application is satisfactory .",380,112,0.2947
dialogsum,"#Person1#: I am trying to decide what school to apply to? #Person2#: Are you thinking about a public school or a private one? #Person1#: I am not sure. What's the difference between them? #Person2#: Public schools are usually state funded, whereas private schools usually get their funding elsewhere. #Person1#: Which is better? #Person2#: One isn't necessarily better than the other. It depends a lot on the school administration and the teachers. #Person1#: I hear you have to wear uniforms at private school. #Person2#: Yes, sometimes.",#Person2# tells #Person1# the differences between a public school and a private school to help #Person1# choosing a school.,85,19,0.2235
dialogsum,"#Person1#: Hello there. I'm Paul Daddy Lee. And there is fun time. I'm very happy to welcome actress Gemma Louis today. #Person2#: Thank you. #Person1#: Actually, shouldn't I call you a film star rather than an actress? After all, you've been world famous since making the film Starshine 2 years ago, haven't you? #Person2#: Well. Yes, I suppose. I enjoyed making that film, but I really want to be a stage actress. #Person1#: It was quite a surprise to get the lead in Starshine, wasn't it? #Person2#: Yes. I got the part in spite of having no film experience. #Person1#: How was that? #Person2#: I was at a theater school. The director chose me to play the part after visiting several schools. I had a long talk with my parents before I accepted it. In the end, I went for it. #Person1#: But you didn't make anymore films after finishing Starshine. Why is that? You must have had plenty of offers. #Person2#: Yes, I did. But working far from home, I sometimes felt very lonely. So I came back to England. #Person1#: So no more films? #Person2#: Oh, I don't know. I'd be happy to do another film, but I'm booked up for the next few months. #Person1#: Now, what about the play you're appearing in at the moment? #Person2#: It's great. It's actually a comedy called Dark Days. #Person1#: And it's at the arts theater. Well, Gemma, thank you for coming to talk to our listeners.","Gemma Louis tells Paul Daddy Lee She enjoyed making the film, Starshine, but she wants to be a stage actress. Gemma talks about how she got the part as the lead with no film experience and her future work plans.",247,40,0.1619
scientific_lay_summarisation-elife-norm,"meiocytes cultured for a maximum of 9 hr in liquid medium (Nannas et al. , 2016; Yu et al. , 1997). The method of Nannas et al. combined the DNA dye Syto12 with the expression of β-tubulin fused to CFP, thereby allowing the concomitant observation of chromosomes and MTs. This revealed a spatially asymmetric positioning of the spindle at anaphase I and II, and chromosome-dependent phragmoplast deposition (Nannas et al. , 2016). The second approach involved imaging entire anthers of maize by exploiting the high depth of field of two-photon microscopy, as earlier proposed by Feijó et al. (Feijó and Cox, 2001; Feijó and Moreno, 2004; Sheehan and Pawlowski, 2012; Sheehan and Pawlowski, 2009). This method, which allowed imaging for periods of 24 hr, led to the characterization of three different movements and trajectories followed by the chromosomes during pairing in prophase I (Sheehan and Pawlowski, 2009). The studies in maize relied on visualizing DNA by chemical stains such as Syto12 and DAPI and the power of Arabidopsis as a molecular model, which enables the relatively fast generation of fluorescent reporter lines for different meiotic proteins, has largely not been exploited in combination with live cell imaging of meiosis. A first approach was made by Ingouff et al. who observed methylation changes during Arabidopsis sporogenesis and gametogenesis, albeit without resolving specific meiotic stages (Ingouff et al. , 2017). Here, we set out to develop a live cell imaging system for meiosis in Arabidopsis. To this end, we have generated an easy applicable microscopic set up, a combination of meiotic reporter lines covering central aspects of meiosis, and an evaluation system based on morphological characteristics that allowed the quantification of meiotic phases with high temporal resolution. This work gives insights into the robustness of meiocyte differentiation steps and provides important criteria to judge and/or re-evaluate mutants affecting meiosis. As a test case, we have re-analyzed tam mutants and find new phenotypic aspects that suggest that TAM is a central factor coordinating the cytoskeleton with nuclear events. Live cell imaging can be performed at three general levels and all three have been applied to the analysis of meiosis in multicellular organisms. First, imaging can be performed on isolated cells as for instance seen in the case of mammalian oocytes where confocal microscopy","In plant cells, as in other cells, genetic information is stored within structures known as chromosomes. Most of the cells in a plant contain a duplicated set of chromosomes that the plant needs to survive. However, plants also produce some cells known as sex cells that only have a single set of chromosomes. This ensures that, when plants sexually reproduce, a male and female sex cell will fuse together and eventually grow into a new plant that carries a doubled set of chromosomes. Cells known as meiocytes make sex cells by dividing through a process known as meiosis. Previous studies have identified several genes that regulate meiosis in plants. For example, a gene known as TAM is required to make sex cells in a small weed known as",380,128,0.3368
dialogsum,"#Person1#: I'd love to continue this conversation, but I really need to go now. I have to get back to the office. #Person2#: Well, let's get together soon. #Person1#: Okay. Would you like to have lunch some day next week? #Person2#: Sure. How about Monday? #Person1#: Hmm. I'm afraid I can't make it on Monday. I've got to fly to Chicago on business. #Person2#: Well unfortunately, I'm tied up on Tuesday. I'm supposed to have lunch with an important visitor from out of town, and I don't think there's any way I can get out of it. Are you free on Wednesday? #Person1#: Wednesday? Let me see. Hmm. Somehow I think I've already got something scheduled for Wednesday. Oh, yes! I've got an appointment with my dentist to have my teeth cleaned, and it's essential that I keep it. #Person2#: Well, I'm afraid Thursday is out for me. I'm expected to attend a meeting of our personnel committee, and it's very important for me to be there. #Person1#: So that leaves Friday. I don't have any obligations or commitments on Friday. How about you? #Person2#: Friday sounds good. Where should we meet? #Person1#: You know, I really must be going now or I'll be very late. Can you give me a call tomorrow an we'll decide?",#Person1# and #Person2# are discussing when to continue their conversation. #Person1# can't make it on Monday or Wednesday and #Person2# is busy on Tuesday and Thursday. #Person1# asks #Person2# to give #Person1# a call tomorrow so that they can make a decision.,216,42,0.1944
dialogsum,"#Person1#: Now you've seen this table of figures about the pocket money children in Britain get? #Person2#: Yes. I thought it was quite interesting, but I don't quite understand the column entitled change. Can you explain what it means? #Person1#: Well, I think it means the change from the year before. I am not a mathematician, but I assume the rise from 70p to 90p is a rise of 25 percent. #Person2#: Oh yes, I see. And the inflation rate is there for comparison. #Person1#: Yes. Why do you think the rise in pocket money is often higher than inflation? #Person2#: I am sorry I've no idea. Perhaps parents in Britain are too generous. #Person1#: Perhaps they are. But it looks as if children were not better off in 2001 than they were in 2002. That's strange, isn't it? And they seem to have been better off in 2003 than they are now. I wonder why that is. #Person2#: Yes, I don't understand that at all. #Person1#: Anyway, if you had children, how much pocket money would you give them? #Person2#: I don't know. I think I'll probably give them 2 pounds a week. #Person1#: Would you? And what would you expect them to do with it? #Person2#: Well, out of that, they have to buy some small personal things, but I wouldn't expect them to save to buy their own socks, for example. #Person1#: Yes. By the way, do most children in your country get pocket money? #Person2#: Yeah, they do.",#Person1# explains to #Person2# that the column entitled change means the change from the year before. #Person1# and #Person2# don't understand why children were better off in the past. #Person2# might give #Person2#'s children 2 pounds a week if #Person2# has kids.,252,42,0.1667
dialogsum,"#Person1#: How did you meet Bill? #Person2#: I met him through a computer bulletin board on the network. #Person1#: Oh, really? Which bulletin board? #Person2#: It was the one I used down at the local coffee house called the San Francisco Net. It has been around since 2016. #Person1#: I've heard about that, but I've never tried it. #Person2#: You ought to. Fifty cents buys you an hour of computer time. A 'Chat Session' links you with people in other cafs. We can make new friends by that means. #Person1#: But I don't like to talk on the network with strangers. #Person2#: You can do that. A private room lets you talk alone. #Person1#: OK. I'll try it.",#Person2# tells #Person1# #Person2# met Bill through a computer bulletin board on the network. Then #Person2# teaches #Person1# how to chat in that way.,118,24,0.2034
scientific_lay_summarisation-elife-norm,"a recent longitudinal study from the European Prospective Investigation of Nutrition and Cancer (Zhu et al. , 2011; Terry et al. , 2016). In a separate strategy to improve EOC outcome, several panels (which have CA125 as part of them) have received FDA approval to be used in the differential diagnosis of EOC to encourage referral of EOC cases to centers with greater expertise in cancer surgery and chemotherapeutic treatment (Karst and Drapkin, 2010). However, these have not been effective for early diagnosis. Among the alternatives to serum proteins for the diagnosis or early detection of EOC, circulating microRNAs (miRNAs) have shown great potential (Nakamura et al. , 2016). miRNAs are short (18–24 nucleotide) non-coding RNAs that regulate gene expression through post-transcriptional modification of mRNA transcripts. miRNAs have several advantages over protein measures: (1) PCR amplifies detection of rare transcripts in blood; (2) all miRNAs use the same units of measure, easing incorporation into multiplexed panels; and (3) miRNAs play a critical role in ovarian cancer biology, whereas the function of CA125 is unknown (Deb et al. , 2017; Katz et al. , 2015). Moreover, non-invasive sampling of circulating miRNAs has a clear advantage over analytes obtained through biopsy (Wang et al. , 2016). Preliminary studies have suggested that circulating miRNAs profiles are altered in women with ovarian cancer (Nakamura et al. , 2016; Chung et al. , 2013; Langhe et al. , 2015; Resnick et al. , 2009; Zuberi et al. , 2015; Samuel and Carter, 2016). In addition, miRNAs have prognostic significance for EOC survival (Merritt et al. , 2008; Bagnoli et al. , 2016; Cramer and Elias, 2016). However, efforts to develop a diagnostic signature based on circulating miRNAs have been hampered by issues regarding the best statistical approach to develop a model, reproducibility of miRNA measurement across technology platforms (e. g. qPCR, next generation sequencing, microarray), and the biologic heterogeneity of EOC (Nakamura et al. , 2016). In this study, our objective was to develop a serum-based miRNA model for the diagnosis of ovarian cancer that could address these concerns and demonstrate the biologic and clinical relevance of this diagnostic tool. To produce our diagnostic circulating miRNA signature from human sera, we constructed a study population of pre-treatment (prior to either surgery or chemotherapy) subjects comprising","Ovarian cancer is a major cause of cancer death among women. A woman’s survival often hinges on doctors detecting the tumor before it has spread beyond the ovary. Unfortunately, most women with ovarian cancer are not diagnosed until they have symptoms – such as pelvic pain, bloating, swelling of the abdomen or appetite loss. By then, the disease has usually spread and is difficult to treat. There is currently no reliable test to diagnose ovarian cancer before symptoms emerge. Some tests measure proteins in the blood or use ultrasound images to identify ovary tumors. These tests usually still identify the disease too late. Sometimes they produce “false positive” results, which may cause women without cancer to undergo unnecessary surgery. Many ovarian cancers have defects in small pieces of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"in our understanding of this process. Three primary reasons combine to account for the absence of such data. First, until relatively recently, the only feasible approach for measuring genome-wide gene expression levels on a population scale was microarray technology. This constraint limited the diversity of systems that could be assessed because cost-effective, commercially available arrays have only been developed for a handful of taxa. Second, genomic resources, especially detailed catalogs of known genetic variants (e. g. , 1000 Genomes Project Consortium et al. , 2010, International HapMap Consortium, 2005), are also limited to a small set of species. The lack of such resources creates major barriers to genome-scale studies of the genetics of gene expression in other organisms, which rely on complementary gene expression and genotype data. Finally, for many taxa, samples suitable for gene expression profiling can be challenging to collect. In nonhuman primates, for example, RNA samples are rarely available even for the most intensively studied natural populations. Recently, sequencing-based methods for measuring gene expression levels (e. g. , RNA-seq) have eliminated the need for species-specific arrays. Comparative genomic studies using RNA-seq have thus vastly expanded the set of taxa for which genome-wide expression data are available (including primates: Brawand et al. , 2011; Perry et al. , 2012). Importantly, because fragments of expressed genes are resequenced many times in RNA-seq studies, data on genetic variation are also generated in the process. Although these data can be affected by technical biases, several studies have demonstrated the generally high reliability of genotypes inferred from RNA-seq reads (Perry et al. , 2012; Piskol et al. , 2013). Such data can provide important insight into genetic diversity in species for which little other information exists (Perry et al. , 2012). Additionally, they provide the two ingredients necessary for mapping gene expression traits to genotype, at moderate cost and without the requirement for previously ascertained genetic variants. Here, we evaluate the potential for such work in an intensively studied wild primate population, the baboons (Papio cynocephalus) of the Amboseli basin in Kenya. 43 years of prior research on this population have established it as an important model for human social behavior, health, and aging (Alberts and Altmann, 2012), and have facilitated the development of protocols for collecting samples appropriate for gene expression","Our genes contain the instructions needed to make all aspects of the body. These instructions can be changed by altering the sequence of the DNA that makes up the genes, which can account for many of the different characteristics found in humans and other animals. However, our characteristics can also be altered by changing how often the genes issue their instructions, which is known as gene expression. For example, it is thought that changes in the expression of some genes in primates may account for the expansion of brain sizes over evolutionary time, particularly in the ancestors of modern humans. Most studies into gene expression in primates have compared different species or focused on humans. It is less clear how many, and what type of, genes vary in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"significant body of research into cues that affect the severity of perceived blur (Ciuffreda et al. , 2006; Crete et al. , 2007; Ferzli and Karam, 2006; Pentland, 1987; Tadmor and Tolhurst, 1994; Webster et al. , 2002) and the role of depth of field defocus as a cue to depth (Held et al. , 2010; Marshall et al. , 1996; Mather, 1996; Mather, 1997; Mather and Smith, 2000; Mather and Smith, 2002; O' Shea et al. , 1997; Watt et al. , 2005), it is still unknown how the visual system distinguishes blur from environmental sources of low spatial frequency image structure. The computational problem of discriminating optical defocus from environmental sources of low frequency structure does not appear to have been explicitly addressed previously. This may be due to the absence of empirical evidence that the visual system can misattribute image gradients produced by environmental sources to defocus or misattribute gradients produced by defocus to environmental sources. Here, we provide evidence of both. We show that defocus can be experienced in fully focused images and that optical defocus can be misperceived as distortions in the perceived 3D shape of smoothly shaded surfaces. Consider the surface depicted in , which was created by illuminating a smooth (i. e. , differentiable) Lambertian (‘matte’) surface with a collimated light source. The surface has shallow surface relief to avoid the formation of sharp attached shadows and is viewed along the axis of relief to avoid the formation of self-occluding contours. Although rendered as a fully focused surface, this image elicits a strong perception of blur; while some 3D shape from shading may be perceived, the surface appears ‘contaminated’ by optical defocus. The perceptual conflation of low frequency shading gradients and optical focus does not appear to have been previously reported. Most research into the perception of shading has attempted to understand how shading provides information about 3D shape using images where it was assumed or somehow ‘known’ that the intensity gradients were caused by focused patterns of shading. The potential conflation of shading and blur may have been overlooked because of the particular surface geometries and viewing conditions that were used in these studies. Most previous work on shape from shading has studied images that contained sharp contours generated by either smooth","We perceive the visual world as made of objects of different shapes, sizes and colors. Some may be smooth, shiny and reflective, whereas others are rough and uneven; some may be in shadow, while others are brightly lit. The brain must identify and distinguish all of these different features to build an accurate, three-dimensional model of the environment. Information about any visual feature originates as light bouncing off an object and entering the eye, which then captures the reflected light and focuses it onto the retina. There, cells generate electrical signals for the brain to process. However, different types of visual features can result in the same pattern of activity. The brain must rely on prior knowledge and educated guesses to disentangle the contributions made by different features,",380,128,0.3368
pubmed-summarization,"their association with p53 gene . the present study was a prospective conducted in the department of general surgery and department of immunology and molecular medicine , sher - i - kashmir institute of medical sciences , srinagar , from january 2005 to december 2009 . young patients were defined as less than 40 years of age . a detailed history , every patient underwent abdominal ultrasonography and contrast enhanced computerized tomogram ( cect ) for proper preoperative staging . fine needle aspiration cytology ( fnac ) of any extra abdominal enlarged lymph node was carried out to rule out metastasis . all the patients who after clinical and radiological assessment had an operable tumor were subjected to laparotomy for any possible resective or bypass procedure . histological examination of resected specimen was conducted to know the type , grade , and stage of tumor . specimens from 7 young and 16 old patients were taken from normal tissue , tumor tissue , and blood and lymph nodes and were sent to the department of immunology and molecular medicine for the study of p53 . pcr amplification technique was standardized to amplify 2nd para exon 5 , 6 , 7 , and 8 of p53 gene from genomic dna . mutation in the amplified exons of p53 was asserted by a single stranded conformational polymorphism ( sscp ) and restriction fragment length polymorphism . all the cases were discharged after stabilization , followed , and regularly monitored for any complication . data was described in percentages and chi - square , and odds ratio analysis was used for valid inferences . software , microsoft excel , minitab , and spss ( 11.5 versions ) were used for statistical analysis . analysis of 502 patients of stomach cancer admitted in the study period was done . out of these studied patients 50 patients belonged to less than or equivalent to 40 years of age group ( ) . around 10% of patients were younger than 40 years . male female ratio was 1 : 1.08 in young and 2.5 : 1 in older patients . a positive family history of stomach cancer in the first degree relatives was present in 10% of young and 3% of old patients which was statistically","aim . the aim of this study was to see the clinical , pathological , and demographic profile of young patients with stomach carcinoma besides association with p53 . patients and methods . prospective study of young patients with stomach carcinoma from january 2005 to december 2009 . a total of 50 patients with age less than 40 years were studied . results . male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients . a positive family history of stomach cancer in the first degree relatives was present in 10% of young patients . resection was possible only in 50% young patients . 26% young patients underwent only palliative gastrojejunostomy . the most common operation was lower partial gastrectomy in",380,128,0.3368
dialogsum,"#Person1#: Oh, it's a fine day, isn't it? And the food smells nice. It's a perfect day for a picnic. #Person2#: Yes, it is. I'm glad it doesn't rain. My name's Mike Gates, by the way. #Person1#: Oh, hi! I'm Alice. Nice to meet you. #Person2#: Nice to meet you too. So Alice...what do you do? #Person1#: I'm studying medicine. #Person2#: Really? Where? #Person1#: At Harvard. What about you? #Person2#: I'm working for IBM. #Person1#: Oh, are you? That sounds interesting. #Person2#: Yeah. I like it. Hey, it looks like the food is ready.",Mike Gates meets Alice. Alice studys medicine at Harvard. Mike Gates works for IBM.,94,14,0.1489
dialogsum,"#Person1#: You are not looking very cheerful. What's the matter with you? #Person2#: Oh, nothing special. I'm just thinking a lot. #Person1#: About the job? #Person2#: About everything. About catching the same train every morning, sitting in the same office all day and watching the same television program. #Person1#: You need a holiday. #Person2#: It wasn't always like this, you know. #Person1#: What do you mean? #Person2#: Well, our great great grandfathers had more fun, didn't they? I mean, they haunted for their food and grow their own vegetables and dip things for themselves. We do the same sort of job for years and years. There's no variety in our lives. #Person1#: You need a holiday. That's what the matter is with you.",#Person1# suggests #Person2# take a holiday to rest as #Person2# thinks too much about everything around #Person2#.,123,17,0.1382
dialogsum,"#Person1#: What do you think of the former champ? #Person2#: There were some bad misses in his defence, so he lost it. #Person1#: No champion can remain at the top for ever. #Person2#: I suppose he's not in top form.",#Person1# and #Person2# talk about the former champ.,40,8,0.2
dialogsum,"#Person1#: What are you reading, Bill? #Person2#: It's this week New Scientist. Why? #Person1#: I was just wondering. It looks interesting. But I've never actually read myself. It's for real scientists, or can ordinary people like me understand it? #Person2#: Always for anyone, really. It usually has articles or stories about current affairs about science, as well as papers about new development in research. I'm reading about new telephone that allows you to see the person you are speaking to as well as see him. #Person1#: Oh, I heard about it. Is it on the market yet? Can I buy one? #Person2#: No. Not this one. But the company has made other models to try on business. This one is special because its color and image is moving. #Person1#: Oh, that's interesting. #Person2#: You see the first video phones. That's what they are called. They made in Japan. But they can only show still black and white image. So this video phone is much better than that. Mind you, I'm not sure I want one, would you? #Person1#: Well, no, I don't think a word. I bet it costs a lot of money. Did it say how much it costs? #Person2#: Yes. The yearly black and white one costs several hundreds pounds. But one in the story is about to cost several thousands pounds. #Person1#: Hmm, what does anybody want one, do you think? #Person2#: Business organizations that need frequent contact overseas want it. It's like a face-to-face conversation, so maybe a lot of overseas travels can be avoided. #Person1#: Yes, I suppose so.",Bill is reading New Scientist and introduces it to #Person1# that everyone can understand it. Bill tells that this one is special because its color and image are moving so #Person1# cannot buy it on market. Then they discuss the first video phones about the price and who wants it.,264,50,0.1894
dialogsum,"#Person1#: Good morning. Is this where I can get a library card issued to me? #Person2#: No problem, we have a short form right here ; just hand it to me when you are done. #Person1#: I'm done. #Person2#: That looks great, but I will also need your driver's license or other form of I. D. #Person1#: Sure, here it is. #Person2#: Well, this looks nice. Do you know how to use it? #Person1#: I am pretty sure how to use it, but can you remind me? #Person2#: Of course, just remember that all of the needed information is on the card. #Person1#: I see. #Person2#: Well, I hope you have a wonderful time on your library visits!",#Person2# helps #Person1# to get a library card and reminds #Person1# how to use it.,118,15,0.1271
scientific_lay_summarisation-elife-norm,"same individuals. We identified differentially expressed genes in both organisms attributed to the intracellular association. The algal endosymbiont undergoes drastic changes in metabolism, displaying signs of cellular stress, fermentation, and decreased nutrient transport, while the host salamander cell displays a limited innate immune response and changes to nutrient sensing, but does not appear to invoke cell stress responses such as apoptosis or autophagy. Ectosymbiotic, intra-capsular algal cells were isolated from egg capsules with a syringe (1a). Individual A. maculatum cells were manually separated into groups of 50 cells with or without intracellular algal symbionts (1a, b). Total RNA was extracted from A. maculatum cells or from intra-capsular algal samples, and converted to cDNA (1c). A test for contaminating mRNA from A. maculatum lysed during dissociation was shown to be negative (— 1) A total evidence assembly contained all reads from all samples (n = 3 intra-capsular algal samples from three different eggs; salamander cells with and without algae from n = 4 individual salamander embryos). This was followed by homology and abundance filtering (—supplements 2,3 and 4), producing 46,549 A. maculatum and 6,726 O. amblystomatis genes that were used in differential expression analysis. 10. 7554/eLife. 22054. 003Figure 1. Three populations of cells from A. maculatum egg capsules containing stage 39 embryos were collected and prepared for mRNA extraction, cDNA sequencing, and differential expression analysis revealing several hundred significantly differentially expressed genes detected for the salamander and alga. (a) Intracapsular algae (Population 1) were removed from intact eggs using a syringe and hypodermic needle (photo credit: Roger Hangarter). Embryos were decapsulated and washed, and the liver diverticulum region (dashed line), containing high concentrations of algae (red dots), was isolated and dissociated into a single cell suspension (illustration adapted from Harrison, 1969). The dissociated cells were screened for A. maculatum endoderm cells without alga (black arrowheads) and endoderm cells with intracellular alga (green arrowhead). Scale bars on microscope images are 20 µm. (b) Isolated endoderm cell, and isolated endoderm cell with intracellular alga. Scale bars on microscope images are 20 µm. (c) Representative cDNA distribution (bioanalyzer trace) from a population of 50 manually isolated A. maculatum endoderm cells. Peaks at 35 bp and 10380 bp are markers. Due to evidence of lysed A. maculatum cells observed in the cell suspension fluid after","Throughout the natural world, when different species form a close association, it is known as a symbiosis. One species can depend on another for food, defense against predators or even for reproduction. Corals, for example, incorporate single-celled algae into their own cells. The algae photosynthesize, harnessing energy from sunlight to make sugars and other molecules that also feed the coral cells. In return, corals protect the algae from the environment and provide them with the materials they need for photosynthesis. This type of relationship where one organism lives inside another species is called an endosymbiosis. In animals with a backbone, endosymbioses with a photosynthetic organism are rare. There is only one known example so far, which is between a green alga called Oophila amblystomatis and the spotted salamander,",380,128,0.3368
dialogsum,"#Person1#: To start with, may I ask why you chose to work at our company? #Person2#: First, you have had an impressive growth record, ever since the company had been founded for half a century. Second, I can improve myself by working here. #Person1#: Well, please look at the employment contract. I'd like to go over the main details again before signing. First, you will be getting a monthly salary, and no probation is involved. #Person2#: Yes, I get it. Will the medical plan cover me while on duty? #Person1#: Of course. A reasonable number of sick days will be covered by the company. Any extended illness will be covered by insurance. Have you read the other terms of the contract? #Person2#: Yes, I have read. In the contract, I am expected to be available up to two hours past normal working hours. Is that right? #Person1#: Yes, any approved overtime of more than two hours will be paid twice of the salary or take time-off. #Person2#: That's exactly my understanding. #Person1#: Good. Now, you sign here, you can start work the beginning of next month.",#Person2# tells #Person1# that #Person2# chose the job because of the company's impressive growth record and chances of improvement. Then they go over some details of the contract. #Person1# tells #Person2# about the medical plan and overtime payment.,186,38,0.2043
dialogsum,"#Person1#: You know that this job requires frequent business travel. Can you accept it? #Person2#: Yes, I can. #Person1#: Mostly short business trips, but sometimes long ones are also needed. #Person2#: Then how about the expenses during the trips? #Person1#: The company will pay all the expenses. #Person2#: Would you tell me where we often travel? #Person1#: Usually Shanghai, Qingdao, Hong Kong and so on. #Person2#: It's great! I like these places. #Person1#: And you need to go abroad once in a while. Can you? #Person2#: Yes, I can. #Person1#: After the business trip, you could apply for reimbursement of all the expenses, such as passage money and accommodation charges and so on. #Person2#: I see. #Person1#: You can take a break for one or two weeks after you have a business trip every time, which depends on the circumstances. #Person2#: OK. Thank you very much for telling me all these things.",#Person2# tells #Person1# #Person2# can accept frequent business travels. #Person1# says #Person2# can apply for reimbursement of all the expenses and take breaks after each trip depending on the circumstances.,152,30,0.1974
dialogsum,"#Person1#: Could you project what you would like to be doing five years from now? #Person2#: As I have some administrative experience from my last job, I may use my organizational and planning skills in the future. #Person1#: How do you plan to accomplish this? #Person2#: By doing everything necessary and for further study. #Person1#: How long would you like to stay with this company? #Person2#: How long I will stay with the company depends on whether the company and I are satisfied with each other. #Person1#: What do you think of this industry's outlook in five years? #Person2#: I do believe this industry will be developed rapidly in 5 years time.",#Person1# asks #Person2# about #Person2#'s career plan five years from now and #Person2#'s opinion on this industry's outlook in five years.,112,21,0.1875
pubmed-summarization,"epilepsy is associated with a two- to three - fold increase in mortality among patients compared with the general population . sudden unexpected death in epilepsy ( sudep ) is one of the most frequent causes of death among patients with epilepsy . there is strong evidence suggesting that sudden unexpected death in epilepsy ( sudep ) is a seizure - related phenomenon , , , . the first description of this phenomenon was introduced by russell in 1906 . since then , several cases have been reported in the literature presenting with a drop in heart rate or asystole during the seizure . bradycardia and asystole resulted from increased parasympathetic flow through the vagus nerve , which originates in the nucleus ambiguous and dorsal nucleus of the vagus in the medulla . on the basis of one study , the incidence of sudep ranges from 1:1000 and 1:2000 person - years to 1:200 person - years , . according to a recent revised definition , sudep consists of sudden , unexpected , witnessed or unwitnessed , nontraumatic and nondrowning death in patients with epilepsy , with or without evidence of a seizure , excluding documented status epilepticus ( seizure duration > 30 min or seizures without recovery in between ) and asphyxia ; if postmortem examination does not reveal a cause of death , the diagnosis is definite sudep , and if there is a preexisting condition before or after autopsy , which could have contributed to the death , it is classified as sudep plus . strong risk factors for sudep include young age , early onset of seizures , the presence of generalized tonic clonic seizures , male sex , and bedtime occurrence . less significant risk factors for sudep include the prone position , one or more subtherapeutic blood levels , sleep occurrence , and a structural brain lesion . the underlying pathophysiologic mechanisms for sudep are not completely understood , but autonomic dysfunction ; ictal arrhythmias , ictal bradyarrhythmia , and asystole , ; neurogenic pulmonary edema ; and ictal central or obstructive apnea , , were introduced in the literature . in this report , we describe two patients with seizure - associated asystole monitored by simultaneous video electroencephalography electrocardiography . a thirteen -","ictal asystole is a rare , probably underestimated manifestation of epileptic seizures whose pathophysiology is still debated . this report describes two patients who had cardiac asystole at the end of their seizure . the first patient was a 13-year - old boy with complex partial seizures .. his mri showed symmetrical signal abnormality in the bilateral parietooccipital lobe accompanied by mild gliosis and volume loss . during a 3-day long - term video - eeg monitoring , he had cardiac arrest at the end of one of his seizures that was secondarily generalized . the second one was a 42-year - old veteran with penetrating head trauma in the left frontal lobe due to shell injury . during long - term video - eeg monitoring , he",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and external fluctuations and whether these demands are compatible. We find that free running clocks, based on limit cycle attractors, are a double-edged sword when subject to such internally and externally fluctuating conditions. The flat direction along such continuous limit cycle attractors can selectively project out external amplitude fluctuations while retaining phase information. However, the flat direction along the attractor makes these continuous attractor-based clocks susceptible to internal fluctuations (e. g. low protein copy number [Potoyan and Wolynes, 2014]). In contrast, point attractor-based damped clocks are relatively resistant to internal fluctuations because they have no flat directions. Hence such ‘hourglass’ clocks out-perform free running clocks at sufficiently high internal noise. We first demonstrate our results in diverse biochemical oscillators, drawn from the literature (Leloup et al. , 1999; Schmal et al. , 2014; Locke et al. , 2005; Leloup and Goldbeter, 2003; Goldbeter, 1991; Goodwin, 1965; Gonze and Abou-Jaoudé, 2013; Kondepudi and Prigogine, 2014; Elowitz and Leibler, 2000; Buşe et al. , 2009; Potvin-Trottier et al. , 2016) on clocks in cyanobacteria, plants and mammals to cell cycle and synthetic oscillators. We complement this detailed network-based study with dynamical systems theory that explains the same trade-off in terms of the broad features common to the diverse models studied here. In all cases, our approach involves systematically deforming the dynamics to interpolate between free running and ‘hourglass’ clocks and using information theoretic measures to quantify clock performance in the presence of fluctuations. By continuously interpolating between these clock architectures, our work predicts that a survey of clock systems in different environmental niches will reveal that clock architecture vary systematically with the relative strength of external and internal fluctuations (Laughlin, 1981). Further, our work suggests intriguing forward evolution experiments in the lab where the same structured external environment can nevertheless result in distinct regulatory systems, depending on the size of internal fluctuations. Finally, the existence of ‘hourglass’ clocks are easier to overlook experimentally than free running oscillations. Hence our theoretical demonstration that ‘hourglass’ clocks have functional benefits in specific conditions highlights the importance of experiments that specifically look for such damped clocks. More broadly, our work highlights the need to experimentally probe regulatory strategies by varying different kinds of noise independently when possible, since the strategies to deal with different kinds of","The daily rising and setting of the sun is perhaps the most predictable pattern on Earth. Many organisms, from ancient bacteria to animals and plants, have evolved internal biological clocks to anticipate specific events such as dusk and dawn. However, biological clocks also need to continue working when faced with irregularities – both arising from within the organism and from external factors, such as a passing cloud that darkens the sky. Some organisms, including humans, have a so-called ‘free-running’ clock that generates a 24-hour rhythm, and keeps ticking even in the absence of any time triggers. Others, such as certain cyanobacteria, have an ‘hourglass’ clock that is not self-sustained – rather, these clocks show a simple response to the sunrise (or sunset) that would gradually perish without another",380,128,0.3368
pubmed-summarization,"the retromolar area almost to the tip of the coronoid process . medial subperiosteal dissection proceeded posteriorly , exposing the lingula and inferior alveolar neurovascular bundle up to the condyle neck . 3 ) the tooth was easily removed from the area between the lingula and the sigmoid notch . 4 ) sharp areas were smoothened , with the site curetted and cleaned with sterile saline solution . a small follicular space enveloping the crown of the tooth was also identified , suggesting inflamed granulation tissue.( . 5 ) a connection to the periodontal space of the mandibular second molar was detected . in view of the sclerotic change of the underlying mandible ( . 3b ) , we assume that there had been prolonged communication with the oral cavity . several studies have reported ectopic mandibular third molar in the mandibular ramus3,4 , mandibular condyle5 - 7 , and coronoid process8 . an aberrant eruption pattern has been suggested to occur when the tooth has been displaced by a lesion , usually an odontogenic cyst3,10,11 . dentigerous cyst is the most common benign lesion related to impacted mandibular third molar12 . over time , the pressure exerted by the intracystic fluid on the occlusal aspect of the third molar may cause its displacement , sometimes from its original location3,4,13 . in the present case , the mandibular third molar was not displaced by a cystic lesion but by an uncertain cause . the development of the tooth germ in an aberrant position or aberrant tooth germ eruption pattern may be the most likely etiology . otherwise , primary and total dislocation of tooth base may be the cause8 . in the process of mandibular skeletal growth , bone is typically added along the posterior ramus border and resorbed along the anterior border ; mandibular condyle develops as a result of bone apposition in the posterior ramus14 . in this case , the presence of dental caries implies that tooth dislocation occurred after its exposure to the oral cavity . keros and susi8 reported the ectopic mandibular third molar in the coronoid process and assumed that the bone forming the mandibular base in childhood may shift to the region beneath the coronoid process in adulthood , with the ectopic mandibular","impacted mandibular third molars are located between the second mandibular molar and mandibular ramus . however , ectopic mandibular third molars with heterotopic positions are reported in the subcondylar or pterygomandibular space . the usual cause of malposition is a cyst or tumor , and malposition without a pathology is rare . this case report described an impacted mandibular third molar in the pterygomandibular space without any associated pathology .",380,70,0.1842
scientific_lay_summarisation-elife-norm,"-to-3' exonucleolytic decay (Jonas and Izaurralde, 2015). For highly complementary targets, RISC activity generally results in 5’ and 3’ cleavage fragments (Bartel, 2009). Both 5’ and 3 cleavage products undergo various decay processes. In mammals, the 3’ cleavage fragments are canonically degraded in the 5’ to 3’ direction by an exonuclease 1 (XRN1). In Arabidopsis, the 3’ fragment is accumulated at a higher level in loss-of-function mutant of XRN4 compared with the amount in wild type (Souret et al. , 2004). Since Arabidopsis XRN4 is an ortholog of mammalian XRN1, the 5’-to-3’ decay of RISC 3’ cleavage fragments appears to be implemented through an evolutionarily conserved mechanism. RISC 5’ cleavage fragments turn over rapidly reflected by the relative inability to detect them when compared with 3’ cleavage fragments. However, the RNA decay mechanism for 5’ cleavage fragments has remained unclear. Previous studies showed that 5’ cleavage fragments from miRNA-RISC activity are typically uridylated at their 3’ ends throughout eukaryotes; and that this nontemplated modification is a signature license for immediate decay (Ren et al. , 2014; Shen and Goodman, 2004). In human cells, the uridylation of the RISC 5’ cleavage products is fulfilled through the terminal uridylyl transferases (TUTs) (Lim et al. , 2014). The uridylation promotes decapping of RISC 5’ products, and subsequently 5’-to-3’ exonucleolytic decay by XRN1 (Song and Kiledjian, 2007). In Arabidopsis, HEN1 suppressor 1 (HESO1) uridylates the 5’ fragments and stimulates their degradation, since a few 5’-cleavage fragments display modest overaccumulation in heso1 mutants (Ren et al. , 2014). Notably, HESO1 was initially recovered as a miRNA nucleotidyl transferase. HESO1 functions together with UTP: RNA uridylyl transferase one to promote miRNA degradation in absence of canonical miRNA methylation (Ren et al. , 2012; Tu et al. , 2015; Wang et al. , 2015). In Arabidopsis, different pathways might account for RNA decay of RISC 5’ cleavage fragments. It has been shown that 5’ cleavage fragments accumulate in xrn4 mutant in Arabidopsis; and obviously XRN4 catalyzes 5’-to-3’ degradation of the fragments in a way similar to clearing RISC 3’ fragments. The RNA exosome also appears to contribute to degrade the 5’ cleavage fragments because their abundance is increased in the loss-of-function mutant of SKI2/3/8, Arabidopsis orthologs of RNA exosome subunits in yeast (Branscheid et al. , 2015).","DNA contains all the information needed to build a body, yet molecules of RNA carry these instructions to the sites in the cell where they can be used. Cells must control how much RNA they produce in order to ensure that they develop properly and can respond well to their environment. RNA silencing refers to a collection of mechanisms that use smaller RNA molecules called microRNAs to incapacitate certain RNA molecules and selectively switch off the genes that encode them to stop more from being made. One key player in RNA silencing is the multi-protein complex called RISC, which contains microRNA and a group of proteins called AGOs. Once the microRNA has identified its RNA target, the AGOs cut the RNA into two pieces, known as the 5’",380,128,0.3368
pubmed-summarization,"1 ) . the action of different mechanisms of kidney development in human beings . genes in kidney development with inducing effects in 10% of patients with syndromic cakut will carry dna various tissues , such mesenchyme , ureteric bud and cloaca , micro imbalances , and four chromosomal regions acting in different ontogenic stages is necessary for normal presumably associated with the cakut phenotype were morphogenesis of kidney and urinary tract . a single identified : 1q21.1 , 2q37 , 1-q37.3 , 3q23-q25.1 and 7q36.2- gene mutation might affect kidney development at multiple q36.3 . pax2 , a paired - box transcription factor , has been identified as the responsible gene whose mutation is associated with the subgroup of cakut seen in the renal - coloboma syndrome . pax2 is required for the growth and elongation of nefric duct ( nd ) prior to ureteral budding . bor 's patients presents abnormalities of all parts of the ear associated with conductive , sensorineural , or mixed hearing impairment , branchial fistulae and cysts , and different cakut manifestations . bor is linked to haploinsufficiency for eya1 , a homolog of drosophila melanogaster gene eyes absent ( eya ) [ 28 - 30 ] . molecular genning testing for eya1 detects mutations in approximately 40% of individuals with the clinical diagnosis of bor . the genetic cause for the most common forms of non - syndromic cakut are unknown . in non - syndromic form of cakut the structural anomalies are confined only to the kidney and urinary tract . the causes for the non - syndromic cakut types are considered multifactorial , resulting from the combination of epigenetic and environmental factors that affect genetically susceptible individuals . only few genes has been implicated as responsible for nonsyndromic causes of human cakut ( table 1 ) . renal abnormalities are also observed in close relatives of up to 10% of cakut patients , although these are frequently asymptomatic . there are related cases of familial ureterocele , renal agenesis , hypodysplasia , renal tubular dysgenesis , multicystic dysplastic kidney ( mcdk ) , or vur [ 34 - 38 ] . the phenotype often does not follow the classic mendelian inheritance : family members with the same genetic defect may","congenital anomalies of the kidney and urinary tract ( cakut ) form a group of heterogeneous disorders that affect the kidneys , ureters and bladder , with frequent asynchronous presentations and multiple cakut associations in the same individual . urinary tract formation is a complex process , dependent of the interaction of multiple genes and their sub - product . the same genic alterations can lead to different molecular expressions and different morphological anomalies . the ureterocele is a cystic dilation of the distal intramural ureter , resulting in obstruction of urine flow , dilation of the ureter and renal pelvis and loss of renal function . two key steps in the urinary tract ontogenesis may be related to ureterocele development : formation and migration of the ureteric",380,128,0.3368
scientific_lay_summarisation-elife-norm,"showing the axoneme with A-tubules in pink, B-tubules in dark blue and central pair in green. Flagellar membrane is shown in transparent pink. : http: //dx. . org/10. 7554/eLife. 01479. 00310. 7554/eLife. 01479. 004Figure 1— 1. Gallery of long growing T. brucei tips, all showing disordered axonemes (20 nm thick tomography slices). : http: //dx. . org/10. 7554/eLife. 01479. 004 In most multicellular organisms, the cilium is produced after the cell has exited the cell cycle, but in many protozoan flagellates, new flagella must be built to maintain motility in daughter cells (Ginger et al. , 2008; Dawson and House, 2010). Flagellar elongation occurs by addition of protein subunits at the axoneme’s distal end (Rosenbaum and Child, 1967; Marshall, 2001). Large protein complexes containing the precursor axoneme building blocks are delivered to this site via an evolutionary conserved process called intraflagellar transport (IFT; [Kozminski et al. , 1993]). The roles of IFT in ciliary function are well studied (Pedersen and Rosenbaum, 2008), and the molecular mechanisms that mediate IFT of axonemal proteins are beginning to be characterized (Bhogaraju et al. , 2013). The structure of the flagellar tip has been characterized; the B-tubule ends before the A-tubule creating a distal ‘singlet region’ in the flagellum tip of most species (Ringo, 1967; Satir, 1968; Sale and Satir, 1976; Woolley and Nickels, 1985); the CPs extend further into the distal tip than the dMTs (Ringo, 1967); the dMTs and CPs are linked to the membrane through capping structures (Dentler, 1980; Woolley et al. , 2006). Yet, we know very little about how the flagellar components, once delivered to the distal tip, are assembled to form the beating flagellum (Ishikawa and Marshall, 2011; Fisch and Dupuis-Williams, 2012). For example, does the CP extend beyond the dMTs during tip growth, like in the mature flagellum, or is the growth of all MTs synchronized? Alternatively do the dMTs extend beyond the CP during flagellar extension? When do other structural modules such as radial spokes, dynein arms, and central pair projections get incorporated? Clearly, there are multiple possibilities for how a flagellum might extend. We have examined two evolutionary distant organisms, the green algae Chlamydomonas reinhardtii and the parasitic protozoa Trypanosoma brucei, to determine if a consistent pattern of flagellar extension exists. By studying the tips","Some cells have a whip-like appendage called a flagellum. This is most often used to propel the cell, notably in sperm cells, but it can also be involved in sensing cues in the surrounding environment. Flagella are found in all three domains of life—the eukaryotes (which include the animals), bacteria and ancient, single-celled organisms called Archaea—and they perform similar functions in each domain. However, they also differ significantly in their protein composition, overall structure, and mechanism of propulsion. The core of the flagellum in eukaryotes is made up of 20 hollow filaments called ‘microtubules’ arranged so that nine pairs of microtubules form a ring around two central microtubules. The core also contains many other proteins, but it is not clear how all these components come together to make",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2013; Leone et al. , 2008; Molyneaux et al. , 2007; Srinivasan et al. , 2012) act by both promoting the identity of a given neuronal class and repressing alternative ones (Fame et al. , 2011; Greig et al. , 2013; Kiritani et al. , 2012; Molnar and Cheung, 2006; Molyneaux et al. , 2007; Reiner et al. , 2010; Sohur et al. , 2014). For example, Satb2, a chromatin remodeling protein, drives CPN specification and axonal pathfinding, and represses the expression of the transcription factor Ctip2 (gene name Bcl11b), which controls the connectivity of SCPN (Alcamo et al. , 2008; Arlotta et al. , 2005; Baranek et al. , 2012; Britanova et al. , 2008; Srivatsa et al. , 2014). However, Satb2 was shown to control also subcerebral connectivity (Leone et al. , 2014), indicating that the final acquisition of a given cell type is not based on the function of a unique transcriptional regulator but most probably on the combination of more determinants expressed at different levels. This is in agreement with observations performed on early embryonic stages, where neuronal types are not yet fully specified and factors with mutually exclusive functions largely overlap. Notably, expression of transcriptional determinants tends to segregate after birth in a cell- or time-specific manner when neurons differentiate and the major neocortical classes become more distinct from each other (reviewed in Greig et al. , 2013). Nevertheless, it is still not clear whether the transcriptional regulators acting during early stages of neuronal specification play any additional roles during postnatal maturation when PNs acquire their final properties. Even if antithetic factors promoting callosal or subcerebral PNs can co-localize in a small subset of neurons after birth (Azim et al. , 2009; Baranek et al. , 2012; Leone et al. , 2008; Tomassy et al. , 2010), it is not known whether their co-expression has a functional meaning, nor whether this hybrid molecular population corresponds to a permanent subgroup of cortical PNs. In particular, the persistence of few double Ctip2/Satb2-positive neurons at early postnatal stages of corticogenesis represents a conundrum, since Satb2 is a strong repressor of Ctip2 (Alcamo et al. , 2008; Baranek et al. , 2012; Britanova et al. , 2008; Leone et al. , 2014). Moreover, Satb2 and Ctip2 regulate the expression","The cerebral cortex is part of the outer layer of the mammalian brain, and it is important for a range of processes, including sensing, movement and conscious thought. The cerebral cortex is subdivided into several areas that are deputed to different functions. Each area is composed of an astounding variety of cells called projection neurons, which send information from the cerebral cortex to distant parts of the brain. There are three main types of projection neurons, which each connect to a different brain region. However, when projection neurons first form in the embryo, they are all broadly similar. They then activate a combination of genes that determine their identity and behaviour through the activity of a vast range of transcription factors (proteins that control gene expression). At first,",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2012). However, systematic approaches to repurpose drugs based on mining EHRs alone will likely lack power due to multiple testing. Similar to the approach followed to increase the power of genome-wide association studies (GWAS) (Stephens and Balding, 2009; Sawcer, 2008), integration of biological knowledge to prioritize drug repurposing will help overcome limited EHR sample size and data quality. In addition to repurposing, several other paradigm shifts in drug development have been proposed to improve efficiency. Since small molecules tend to bind to many targets, polypharmacology aims to find synergy in the multiple effects of a drug (Roth et al. , 2004). Network pharmacology assumes diseases consist of a multitude of molecular alterations resulting in a robust disease state. Network pharmacology seeks to uncover multiple points of intervention into a specific pathophysiological state that together rehabilitate an otherwise resilient disease process (Hopkins, 2008; Hopkins, 2007). Although target-centric drug discovery has dominated the field for decades, phenotypic screens have more recently resulted in a comparatively higher number of first-in-class small molecules (Swinney and Anthony, 2011). Recent technological advances have enabled a new paradigm in which mid- to high-throughput assessment of intermediate phenotypes, such as the molecular response to drugs, is replacing the classic target discovery approach (Iskar et al. , 2012; Lamb, 2007; Qu and Rajpal, 2012). Furthermore, integration of multiple channels of evidence, particularly diverse types of data, can overcome the limitations and weak performance inherent to data of a single domain (Hodos et al. , 2016). Modern computational approaches offer a convenient platform to tie these developments together as the reduced cost and increased velocity of in silico experimentation massively lowers the barriers to entry and price of failure (Hurle et al. , 2013; Liu et al. , 2013). Hetnets (short for heterogeneous networks) are networks with multiple types of nodes and relationships. They offer an intuitive, versatile, and powerful structure for data integration by aggregating graphs for each relationship type onto common nodes. In this study, we developed a hetnet (Hetionet v1. 0) by integrating knowledge and experimental findings from decades of biomedical research spanning millions of publications. We adapted an algorithm originally developed for social network analysis and applied it to Hetionet v1. 0 to identify patterns of efficacy and predict new uses for drugs. The algorithm","Of all the data in the world today, 90% was created in the last two years. However, taking advantage of this data in order to advance our knowledge is restricted by how quickly we can access it and analyze it in a proper context. In biomedical research, data is largely fragmented and stored in databases that typically do not “talk” to each other, thus hampering progress. One particular problem in medicine today is that the process of making a new therapeutic drug from scratch is incredibly expensive and inefficient, making it a risky business. Given the low success rate in drug discovery, there is an economic incentive in trying to repurpose an existing drug that has already been shown to be safe and effective towards a new disease",380,128,0.3368
dialogsum,"#Person1#: Hello, this is Bob. Is that Mary? #Person2#: Yes. #Person1#: How are you feeling today? #Person2#: A little better. Thank you, Bob. #Person1#: You're welcome. I hope you can come back soon. #Person2#: I hope so, too, but the doctor said I had to stay in bed for at least a week. #Person1#: Oh, dear! That's too long! Is there anything I can do for you? #Person2#: Well, now I'm worried about my lessons. #Person1#: Oh, I see. You needn't worry about them. Just get lots of rest. I'll go to help you with your lessons after school from tomorrow on. #Person2#: That's very kind of you. Thanks a lot. #Person1#: By the way, Mrs. Smith will go to see you tomorrow evening after work. #Person2#: Oh. She's so busy. She needn't do that. Please tell her that I am all right, OK? #Person1#: OK. See you tomorrow. #Person2#: Bye-bye.",Mary has to stay in bed for at least a week. Bob'll help her with her lessons. Bob says Mrs. Smith'll visit Mary but Mary thinks she needn't do that.,151,30,0.1987
scientific_lay_summarisation-elife-norm,"Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinase Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A. Using a combination of biophysical techniques, we propose a universal drug-binding mechanism, that rationalizes selectivity, affinity and long on-target residence time for kinase inhibitors. These new concepts, where protein dynamics in the drug-bound state plays the crucial role, can be applied to inhibitor design of targets outside the kinome. Protein kinases have become the number one drug target of the 21th century (Cohen, 2002; Hopkins and Groom, 2002), due to their central role in cellular processes and involvement in various types of cancer (Carvajal et al. , 2006; Gautschi et al. , 2008; Katayama and Sen, 2010). Despite their therapeutic significance, the development of specific kinase inhibitors proves to be extremely challenging because they must discriminate between the very similar active sites of a large number of kinases in human cells. One of the biggest success stories is Gleevec: a highly selective drug that specifically targets Abl kinase, providing an efficient treatment of chronic myelogenous leukemia (CML) and minimizing side effects (Iqbal and Iqbal, 2014). Despite being a multi-billion-dollar cancer drug, the mechanism responsible for its impressive selectivity has been elusive until recently. Seminal work by the Kuriyan lab demonstrated that Gleevec can only bind to an inactive DFG (for Asp-Phe-Gly) loop conformation in the ‘out-conformation’ due to steric clash of the active, DFG-in conformation (Nagar et al. , 2002; Schindler et al. , 2000; Seeliger et al. , 2007). Since then it has long been proposed that the conformational state of the fully-conserved DFG loop (Taylor et al. , 2012) dictates the selectivity for Gleevec and other kinase inhibitors (Lovera et al. , 2012; Nagar et al. , 2002; Schindler et al. , 2000; Treiber and Shah, 2013;","Protein kinases are a family of enzymes found in all living organisms. These enzymes help to control many biological processes, including cell division. When particular protein kinases do not work correctly, cells may start to divide uncontrollably, which can lead to cancer. One example is the kinase Aurora A, which is over-active in many common human cancers. As a result, researchers are currently trying to design drugs that reduce the activity of Aurora A in the hope that these could form new anticancer treatments. In general, drugs are designed to be as specific in their action as possible to reduce the risk of harmful side effects to the patient. Designing a drug that affects a single protein kinase, however, is difficult because there are hundreds of different kinases",380,128,0.3368
dialogsum,"#Person1#: Now, this is Westminster Abbey. It's one of the oldest buildings in London and in its architecture, you will recognize different styles. #Person2#: Wow, it's really splendid. #Person1#: There, to the left, you will see a small Street called Downing Street No.10, the last of its 10 houses has always been the living place of the British Prime Minister. #Person2#: Oh, is that the Tower Bridge? #Person1#: Yeah, look, the bridges parting in the middle and the two halves are moving upwards, a big ship is passing underneath.","#Person1# shows #Person2# around Westminster Abbey, Downing Street No.10, and Tower Bridge.",89,12,0.1348
dialogsum,"#Person1#: I think you're being a little naive. #Person2#: If I want, I can protect myself by paying through an escrow account, which holds the money until I receive the item. #Person1#: That proves my point! Protect yourself or you'll get burned. #Person2#: eBay also offers free insurance. You can get a refund of up to $ 200 if you're not satisfied with your purchase. #Person1#: $ 200? If they get a hold of your credit card number, you're going to be out a lot more than $ 200! I had a friend who...","#Person2# regrets not protecting #Person2# by paying through an escrow account, but eBay offers free insurance.",94,16,0.1702
dialogsum,"#Person1#: I have difficulty with this form. Will you please explain it to me? #Person2#: Actually there is a sample over there. But if you still have a problem, let me know. #Person1#: Oh, that's great. Thank you very much.",#Person2# tells #Person1# there is a sample for the form.,40,10,0.25
scientific_lay_summarisation-elife-norm,"Facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy caused by inefficient epigenetic repression of the D4Z4 macrosatellite array and somatic expression of the DUX4 retrogene. DUX4 is a double homeobox transcription factor that is normally expressed in the testis and causes apoptosis and FSHD when misexpressed in skeletal muscle. The mechanism (s) of DUX4 toxicity in muscle is incompletely understood. We report that DUX4-triggered proteolytic degradation of UPF1, a central component of the nonsense-mediated decay (NMD) machinery, is associated with profound NMD inhibition, resulting in global accumulation of RNAs normally degraded as NMD substrates. DUX4 mRNA is itself degraded by NMD, such that inhibition of NMD by DUX4 protein stabilizes DUX4 mRNA through a double-negative feedback loop in FSHD muscle cells. This feedback loop illustrates an unexpected mode of autoregulatory behavior of a transcription factor, is consistent with ‘bursts’ of DUX4 expression in FSHD muscle, and has implications for FSHD pathogenesis. Facioscapulohumeral muscular dystrophy (FSHD) is typically an adult-onset muscular dystrophy characterized by muscle weakness initially affecting the face (facio), shoulders (scapulo), and upper arms (humeral). FSHD is caused by decreased epigenetic repression of the D4Z4 macrosatellite array in the subtelomeric region of chromosome 4q, due to either D4Z4 repeat contractions (Lemmers et al. , 2010) or mutations affecting trans-acting epigenetic regulators of the D4Z4 repeat such as SMCHD1 (Lemmers et al. , 2012), which results in the misexpression of DUX4 mRNA in skeletal muscle and possibly other somatic tissues. DUX4 encodes a double homeobox transcription factor that activates germline genes and repetitive elements (Geng et al. , 2012) and causes apoptosis and atrophic myotube formation when misexpressed in skeletal muscle (Kowaljow et al. , 2007; Vanderplanck et al. , 2011; Wallace et al. , 2011; Mitsuhashi et al. , 2012). DUX4 is expressed in only a small fraction of nuclei (Snider et al. , 2010), likely due to occasional ‘bursts’ of DUX4 expression. However, the mechanism (s) regulating DUX4 expression and toxicity remain incompletely understood. We previously ectopically expressed DUX4 in immortalized (54-1) and primary (MB135) myoblasts and used RNA-seq to identify coding genes, repetitive elements, and non-coding RNAs induced by DUX4 (Young et al. , 2013). Further analysis of this data showed that DUX4 expression also resulted in the increased abundance of many coding RNA isoforms containing premature","Genes are sequences of DNA that contain instructions for the cell that must be carefully controlled because it is not always appropriate or safe for these instructions to be followed. When genes are active, copies of the DNA are made using molecules of ribonucleic acid (RNA) and these can then be used as templates to make proteins. One way genes can be controlled is by adding small chemical tags that mark them out to be activated or deactivated, known as epigenetic control. The muscle disease facioscapulohumeral muscular dystrophy (FSHD) is caused by the loss of the chemical tags that normally keep certain genes switched off in many cell types. One of these genes is DUX4, which in healthy males is normally only active in the testes, but in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"interactions stabilize a microbial community (Coyte et al. , 2015). Phyllosphere network analysis of A. thaliana identified a small number of microbes as ‘hub’ organisms, i. e. influential microbes that have severe effects on the community structure. The major hub microbe in the A. thaliana phyllosphere is the oomycete Albugo laibachii, which is a pathogenic symbiont biotrophic of Arabidopsis (Agler et al. , 2016). This pathogen has been shown to significantly reduce the bacterial diversity of epiphytic and endophytic leaf habitats. Since bacteria generally comprise a large proportion of the phyllosphere microbiome (Vorholt, 2012), phylogenetic profiling of A. thaliana was also directed toward identifying a small group of bacteria that frequently colonize A. thaliana leaves. The analysis helped to develop a synthetic community of bacteria for experiments in gnotobiotic plants. Besides bacteria and oomycetes, the microbiota of the A. thaliana leaf also comprises a broad range of fungi. Among those fungi, basidiomycete yeasts are frequently found and the most frequent ones are the epiphytic basidiomycete genus Dioszegia (Agler et al. , 2016), as well as an anamorphic yeast associated with A. laibachii infection belonging to the Ustilaginales. This order includes many pathogens of important crop plants, for example corn smut and loose smut of oats, barley, and wheat are caused by Ustilago maydis, U. avenae, U. nuda, and U. tritici, respectively. Generally, the pathogenic development of smut fungi is linked with sexual recombination and plant infection is only initiated upon mating, when two haploid sporidia form a dikaryotic filament (Brefort et al. , 2009). Ustilaginales Pseudozyma sp. yeasts, however, are found mostly in their anamorphic stage in nature. They tend to epiphytically colonize a wide range of habitats, where an infrequent sexual recombination might occur when they meet on a susceptible host (Kruse et al. , 2017). Phylogenetic reconstruction (Kruse et al. , 2017; Wang et al. , 2015) showed that the smut pathogen of millet, Moesziomyces bullatus and four species of Pseudozyma, namely P. antarctica, P. aphidis, P. parantarctica, and P. rugulosa form a monophyletic group. The latter do represent anamorphic and culturable stages of M. bullatus and, hence, can be grouped to this genus. Moesziomyces strains have been reported in a number of cases to act as microbial antagonists. A strain formerly classified as Pseudozyma aphidis (now M.","Much like the ‘good bacteria’ that live in our guts, many microscopic organisms can co-exist with and even benefit the plants they live on. For instance, the yeast Moesziomyces bullatus ex Albugo (MbA for short) can shield the leaves of its plant host against white rust, a disease caused by the organism Albugo laibachii. Studies have started to unveil how the various microbes at the surface of leaves interact and regulate their own community, yet the genetic mechanisms at play are less well-known. To investigate these processes, Eitzen et al. examined the genes that were switched on when MbA cells were in contact with A. laibachii on a leaf. This experiment revealed a few gene candidates that were then deleted, one by one, in MbA cells. As a",380,128,0.3368
dialogsum,"#Person1#: We can go to see the movie, saving the planet at the rock. What time does it start? #Person2#: 8:00 o'clock. #Person1#: So we can be back about 10:30, right? #Person2#: No, it doesn't end until 11. #Person1#: I can't sit in the cinema so long. #Person2#: Well then, what do you want to see? #Person1#: Shakespeare in love is at the regal and twister at the royal. Shakespeare in love starts at 7:45 and it ends at 9:00. #Person2#: Ok, let's go to see Shakespeare in love. I can see saving the planet with my friend Barbara later. #Person1#: What are we going to do after the movie? #Person2#: We can go hiking and have a picnic.","#Person2# tells #Person1# the movie, saving the planet at the rock, takes a long time. #Person1# can't stand sitting in the cinema for long, so they decide to see Shakespeare in love.",119,32,0.2689
pubmed-summarization,"symptom burden using the afss instrument and freedom from af ( based on clinical data , 12-lead ekg and 7-day holter monitor at yearly follow - ups ) . secondary outcomes of left atrial volume and left ventricular thickness were assessed by echocardiography , and metabolic/ inflammatory markers were assessed by measuring high sensitivity c reactive protein ( hs - crp ) , lipid profile and fasting insulin at baseline and final follow up . changes in primary and secondary outcomes from baseline to follow - up ( 5-years ) were assessed for statistical significance . additionally , survival analyses for freedom from af were also estimated . baseline demographics , risk factor characteristics , cardiac structure and medication use appeared to be balanced among the 3 wl categories . one important baseline difference was in the degree of wl clinic attendance84% of patients in group 1 ( 10% wl ) , 57% of patients in group 2 and 30% of patients in group 3 attended the wl clinic ( p < 0.001 ) . among primary outcomes , af symptom burden improved across all 3 groups , but were more pronounced in group 1 as compared to the other groups . there were improvements across every component of the afss instrument- af frequency , duration , severity and global well - being scores . at final follow - up , arrhythmia - free survival rates were 86.2% in group 1 vs. 65.5% in group 2 vs. 39.6% in group 3 ( p < 0.001 ) ; this was despite decreased aad use in group 1 as compared to groups 2 & 3 ( p < 0.001 ) . however , there were no differences in mean ablation procedures across groups . in order to show that the superior rhythm control in group 1 was independent of differential ablation or aad use among the groups , the authors also presented data regarding ablation and drug - free rhythm control . over 5 years , it was estimated that 45.5% of group 1 as compared to 13.4% of group 3 ( p < 0.001 ) maintained af freedom without ablation or aad use . further , there were dose - dependent improvements in all risk factors and secondary outcomes patients in","as the global burden of atrial fibrillation ( af ) and its attendant economic impact on the healthcare system surges , there is increasing interest in the secondary prevention of af with various therapies . of the several identified risk factors for af , obesity is an important contributor that may be managed with intensive lifestyle modification . prior studies have demonstrated the short - term and long - term benefits of weight loss in reduction of af symptoms . in the legacy study [ long - term effect of goal - directed weight management in an atrial fibrillation cohort : a long - term follow - up study ] , the investigators evaluated the long - term effects of a weight management program on af symptoms .",380,128,0.3368
dialogsum,"#Person1#: My name is Mary, and I will be your waitress tonight. #Person2#: Thank you, Mary. We have been looking forward to trying out this restaurant. #Person1#: Before your main course, would you like to order an appetizer? #Person2#: Sure, that sounds great. Where are your appetizers listed? #Person1#: There is a special appetizer menu right here in the center of the table. #Person2#: The chicken and cheese quesadilla looks good. Is that pretty good? #Person1#: You know, that is one of my favorites! #Person2#: OK, I'll take one order of that. #Person1#: You could choose another appetizer for half price to share. #Person2#: Perfect! Please add on an order of onion rings.",#Person2# comes to a restaurant for the first time. #Person2# orders the chicken and cheese quesadilla and onion rings with Mary's assistance.,113,22,0.1947
dialogsum,"#Person1#: Can I take your drink order? #Person2#: Where is your wine list? #Person1#: The wine choices are posted on the little menu in the middle of the table. #Person2#: Do you have any mixed drinks available here? #Person1#: We can make a number of mixed drinks at our bar. #Person2#: I heard that you are famous for your drinks. What are your specials? #Person1#: Our house special is our Cuervo Gold margarita. #Person2#: I would love a margarita right now! That is what I am going to order. #Person1#: Can I prepare your drink on the rocks, or would you prefer it blended? #Person2#: I prefer my margarita on the rocks, please. #Person1#: Do you like your margarita with salt or no salt? #Person2#: No salt, please.",#Person2# wants mixed drinks and #Person1# recommends Cuervo Gold margarita. #Person2# wants it on the rocks without salt.,128,18,0.1406
scientific_lay_summarisation-elife-norm,"analogue, in combination with structure-guided biophysical and cell-based studies, defines the basis for ligand recognition. Structural comparison with the Xenopus Wnt8 in complex with mouse Fz8CRD (Janda et al. , 2012) shows that Norrin uses its β-strands to mimic a finger-like loop in Wnt for binding to the Fz receptor CRD. Finally, we note that engineered Norrin mutants resulting from our analyses may be of use as agents for blocking Wnt receptor activation. To address the challenge of producing Norrin in large quantities, we screened conditions and constructs for Norrin expression (1A). We found that fusion of Norrin to the C-terminus of small ubiquitin-like modifier (SUMO) (Peroutka et al. , 2008), in combination with addition of valproic acid (Backliwal et al. , 2008), a putative histone deacetylase inhibitor, substantially boosted expression of the secreted protein in human embryonic kidney (HEK) 293T cells (1B, C). After removal of the SUMO fusion tag, the recombinant Norrin shows a monodispersed state in size-exclusion chromatography (SEC; 1D) and is biologically active in a cell-based luciferase reporter assay (1E). 10. 7554/eLife. 06554. 003Figure 1. Expression and purification of biologically active recombinant Norrin. (A) Schematic diagrams of the expression constructs including Norrin (a signal peptide, SP, followed by Norrin and Rho-1D4 tag at C-terminus) and SUMO-Norrin (a SP followed by a Strep-tag II, an octahistidine, SUMO, HRV 3C protease cleavage site, Norrin, and Rho-1D4 tag at C-terminus). (B and C) Conditioned media from transfected HEK293T cells were immunoblotted (IB) with the anti-Rho-1D4 antibody. (B) SUMO fusion improves Norrin secreted expression. (C) The expression level of SUMO tagged Norrin was further boosted for HEK-293T cells treated with valproic acid. (D) SEC elution profile and SDS-PAGE under reducing conditions with fractions analysed marked by red lines. (E) Purified recombinant untagged Norrin actives the canonical Wnt/β-catenin pathway in the luciferase reporter assay. RLU: relative light unit. Error bars indicate standard deviations (n = 3). : http: //dx. . org/10. 7554/eLife. 06554. 003 We determined three crystal structures of Norrin (2A and Table 1), using selenomethionine-labeled protein for phasing (— 1). The Norrin protein fold is identical to that of the previously reported MBP-Norrin crystal structure (Ke et al. , 2013). Each Norrin monomer comprises three β-hairpins (β1-β2, β3-β4 and β5-β6), a β7 strand at the C-terminus, and four intramolecular","The cells within an animal need to be able to communicate with each other to coordinate many complex processes in the body, such as the formation of tissues and organs. One way in which the cells can communicate is through a pathway called Wnt signalling. Generally, one cell releases a protein called Wnt, which binds to a receptor protein called Frizzled that sits on the surface of the same or another cell. This activates a series of events in the cells that can change the activity of particular genes. Wnt signalling has many roles in animals, and defects in it can contribute to cancer and other devastating diseases. Another protein called Norrin can also activate Wnt signalling by binding to Frizzled and another receptor protein called Lrp5/6. This",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Inc proteins act to bind and manipulate host cell proteins. Reported examples include the binding of the small GTPase Rab4A by CT229 (Rzomp et al. , 2006), Rab11A by Cpn0585 (Cortes et al. , 2007), SNARE proteins by IncA (Delevoye et al. , 2008), centrosomal and cytoskeletal proteins by Inc850 and inclusion protein acting on microtubules (IPAM) (Dumoux et al. , 2015; Mital et al. , 2015,2010), myosin phosphatase by CT228 (Lutter et al. , 2013), 14-3-3 and Arf family proteins by IncG and InaC (Kokes et al. , 2015; Scidmore and Hackstadt, 2001), and the lipid transfer protein CERT by IncD (Derré et al. , 2011; Elwell et al. , 2011). Despite these reports, there are no known structures of Inc family members either alone or in complex with host effectors. 10. 7554/eLife. 22311. 003Figure 1. SNX5, SNX6 and SNX32 tare recruited to C. trachomatis inclusions. (A) HeLa cells stably expressing the mCherry-Rab25 inclusion membrane marker (red) were infected with C. trachomatis serovar L2 (24 hr) and transfected with myc-tagged SNX expression constructs. The samples were fixed and immunolabeled with anti-myc (green) and anti-chlamydial HtrA antibodies (white) and counterstained with DAPI (blue). Similar experiments using GFP-tagged proteins are shown in — 1A. : http: //dx. . org/10. 7554/eLife. 22311. 00310. 7554/eLife. 22311. 004Figure 1— 1. SNX5, SNX32 and SNX1 are recruited to C. trachomatis inclusions and membrane tubules. (A) Hela cells were transiently transfected with GFP-tagged SNX and mCherry-Rab25 proteins as indicated, and infected with C. trachomatis serovar L2. Cells were imaged by confocal fluorescence microscopy for GFP-tagged proteins (green), endogenous SNX1 (blue), mCherry-Rab25 (red) and DAPI-stained nuclear material (white). Both GFP-SNX5 and GFP-SNX32 are recruited to inclusion membranes, but the distantly related SNX-BAR protein SNX8 is not. The images are maximum projections. (B) An example of SNX1-decorated tubules (green) often observed emanating from inclusion membranes (mCherry-Rab25 in red; DAPI staining in blue). The image is a maximum projection. : http: //dx. . org/10. 7554/eLife. 22311. 00410. 7554/eLife. 22311. 005Figure 1— 2. Recruitment of SNX1, SNX2 and SNX5 to inclusions is not dependent on 3-phosphoinositides. HeLa cells stably expressing mCherry-Rab25 were infected with C. trachomatis serovar L2 (MOI ~0. 5) for 24 hr and imaged by immunofluorescence microscopy using antibodies to SNX1, SNX2 and SNX5. mCherry-Rab25 provides marker for","The bacterium Chlamydia trachomatis, commonly known as chlamydia, is a frequent cause of sexually transmitted infections, and a leading cause of blindness due to infection. The bacteria must directly enter the cells of its human host to grow and multiply. Inside a human cell, the bacteria form and then develop within specialized compartments called inclusions that are surrounded by membrane. The outside of the inclusion membrane becomes coated with dozens of unique bacterial proteins. The major role of these bacterial proteins is to hijack other proteins in the human cell to generate and maintain the membrane of the inclusion compartments. One bacterial protein in particular, called IncE, is able to bind to specific host proteins called sorting nexins. These host proteins normally control the formation of tube-like membrane",380,128,0.3368
pubmed-summarization,"in pursuit of large - scale evolutionary questions , biologists are increasingly using massive phylogenetic datasets to reconstruct evergrowing portions of the tree of life . these large phylogenetic trees are commonly inferred using a supermatrix approach , in which multiple datasets are combined and analyzed simultaneously.1 however , assembling and utilizing supermatrices is challenging due to difficulties such as determining homology of molecular sequences , assembling chimeric operational taxonomic units , and managing the amount of missing data . despite these challenges , the phylota browser2 provides a web interface to view all genbank sequences within taxonomic groups clustered into homologs . a different approach is implemented in the programs , such as phlawd3 and ncbiminer,4 which mine genbank for sequence clusters homologous to guide sequences provided by the user . the method implemented in supermatrix constructor ( sumac ) combines elements of both approaches ; the user can perform an exploratory clustering of all genbank sequences within a taxonomic group or provide guide sequences to build homologous sequence clusters in a more targeted manner . furthermore , by calculating supermatrix assessment metrics derived from the concept of phylogenetic decisiveness,5 sumac provides a unique toolkit with which genbank can be repeatedly mined using different settings and the resulting data matrices can be compared . in this article , my objectives are to ( 1 ) introduce the sumac software , ( 2 ) describe a novel metric that assesses the effect of missing data in phylogenetic supermatrices , and ( 3 ) illustrate the use of sumac with a case study . sumac is a python package designed to run as a stand - alone command - line program , though the modules can also be imported and used in other python scripts . when run from the command line first , sumac creates a local sqlite36 database of the specified genbank division ( eg , pln or mam ) , automatically downloading sequences from ncbi if necessary . using ncbi taxonomy , sumac searches the local database for all sequences in the user - specified ingroup and outgroup . found sequences are then clustered as putative homologs in one of the two ways : ( 1 ) performing exhaustive all - by - all blastn7 comparisons of each","the amount of phylogenetically informative sequence data in genbank is growing at an exponential rate , and large phylogenetic trees are increasingly used in research . tools are needed to construct phylogenetic sequence matrices from genbank data and evaluate the effect of missing data . supermatrix constructor ( sumac ) is a tool to data - mine genbank , construct phylogenetic supermatrices , and assess the phylogenetic decisiveness of a matrix given the pattern of missing sequence data . sumac calculates a novel metric , missing sequence decisiveness scores ( msds ) , which measures how much each individual missing sequence contributes to the decisiveness of the matrix . msds can be used to compare supermatrices and prioritize the acquisition of new sequence data . sumac constructs supermatrices",380,128,0.3368
dialogsum,"#Person1#: I usually bowl with an eight ball. I like the control of a light ball. I can spin it more, so that the ball hooks. #Person2#: Well. I like them a little heavier. I don't have as much control, usually bowling straight, but the extra momentum compensates for that. #Person1#: Well, let's see which technique is better. I think I'll go up first. . . Yes! I hit a strike. I knocked them all down on my first bowl. #Person2#: Well done. You got them all. You get 10 points and your next two bowls are added to this frame's score. I'II dry my ball off and try to knock them all down as well. #Person1#: Good start. You knocked eight pins down. But you are left with a 7, 10 split. Unless you can bowl a UFO-ball on this bowl, it is going to be impossible. #Person2#: I certainly can try. . . No! It went straight through the wickets.",#Person1# and #Person2# share their different techniques about bowling and decide to try which is better. #Person1# knocks all the ball down but #Person2#'s ball goes straight through the wickets.,162,30,0.1852
dialogsum,"#Person1#: Where will we go during this break? #Person2#: I was thinking of a place in Mexico. Do you remember when we went to that really hot place several years ago, where the water was almost as warm as the air, and we had a hard time sleeping at night? #Person1#: Yeah. #Person2#: I'd like to go back there. #Person1#: But... #Person2#: Don't worry though. We went during the summer last time, August I think. This time it'll be winter. It's perfect weather there in January. And we'll be able to watch the whales that live there from December to February.",#Person2# convinces #Person1# to travel to a place in Mexico again because the weather there in January is perfect.,101,19,0.1881
pubmed-summarization,"whether supernormal resuscitation truly reduced mortality in critically ill patients . the results of these studies were varied and suggested that there are subgroups of patients who do benefit from this strategy . benefits of hemodynamic optimization were most readily observed in acutely ill patients who had not succumbed to end - organ failure . in the late 1990s at the university of texas houston medical school , a team of surgical intensivists collaborated with bioengineers and health information experts to further refine the logic for traumatic shock resuscitation and implemented it with a computerized clinical decision support application . patients meeting specific criteria ( evidence of major torso trauma , evidence of shock as documented by base deficit > 6 meq , and anticipated blood transfusions > 6 units in 12 hours ) had pa and peripheral artery catheters inserted upon icu arrival . they were resuscitated to a do2 goal of 600 ml / min / mwith a series of escalating interventions to achieve this goal in nonresponders . this became the standard of care in the shock trauma icu at the memorial hermann hospital in houston , texas . the protocol provided a unique opportunity to prospectively collect data on how patients responded to interventions and to further refine the existing protocol to optimize resuscitation . abg , arterial blood gas ; art , arterial ; bd , base deficit ; ci , cardiac index ; do2 , oxygen delivery ; hb , hemoglobin ; icu , intensive care unit ; lr , lactated ringer 's solution ; ng , nasogastric ; pa , pulmonary artery ; pcwp , pulmonary wedge pressure ; prbc , packed red blood cells ; prco2 , regional carbon dioxide tension measured by gastric tonometry . reproduced with permission from . this protocol also provided the opportunity to test the utility of various monitors in this process of care . to evaluate skeletal and subcutaneous sto2 changes as surrogates for do2 i changes and to compare these variables with other commonly used indices of shock resuscitation , we conducted a prospective study using sto2 monitors in shock resuscitation . 2a , b represents the variables tracked over the first 24 hours of icu admission . these included at 6 mm ( subcutaneous","introductionthe purpose of the present review is to review our experience with near - infrared spectroscopy ( nirs ) monitoring in shock resuscitation and predicting clinical outcomes.methodsthe management of critically ill patients with goal - oriented intensive care unit ( icu ) resuscitation continues to evolve as our understanding of the appropriate physiologic targets improves . it is now recognized that resuscitation to achieve supranormal indices is not beneficial in all patients and may precipitate abdominal compartment syndrome.resultsover the years , icu technology has provided physicians with specific physiologic parameters to guide shock resuscitation . throughout this time , the tissue hemoglobin oxygen saturation ( sto2 ) monitor has emerged as a non - invasive means to obtain reliable physiologic parameters to guide clinicians ' resuscitative efforts .",380,128,0.3368
scientific_lay_summarisation-elife-norm,"that vmPFC DBS-enhanced memory function by modulating the hippocampal neurogenic activity in the middle-aged rat model with aging-related memory impairment. The use of this animal model was supported by previous data that showed aged-related deficits in both the memory and the hippocampal functioning (Rex et al. , 2005; Kaczorowski and Disterhoft, 2009). In acute DBS, animals were tested with either high- or low-frequency stimulation (HFS or LFS) at various amplitudes using the conventional novel-object recognition (NOR) test. Subsequently, another set of animals was used to assess the chronic stimulation effects on memory enhancement using the NOR and the MWM tests. For investigation of the underlying mechanism, we analyzed the effects of chronic stimulation on the molecular and cellular levels of hippocampal neurogenesis-related functions. Progressive age-related memory decline has been previously described for human (Davis et al. , 2003) and animal studies (Sloane et al. , 1997; Ward et al. , 1999; Kaczorowski and Disterhoft, 2009). We compared the short- and long-term memory functions in young (n = 20) and middle-aged (n = 15) rats using the NOR test (1A). Three-way ANOVA (group age × retention interval × object) with repeated-measures showed significant effects for object (F (1,82) = 18. 043, p < 0. 001), retention interval (F (2,82) = 13. 956, p < 0. 001), and the interaction group age × retention interval × object (F (1,82) = 4. 160, p = 0. 019) (1C, D). No differences were observed for group (F (1,82) = 0. 009, p = n. s.). With regard to the duration of object exploration, there was no significant difference between the young and middle-aged rats in the acquisition phase (t (28) = −0. 742, p = n. s.), see Supplementary file 1A. However, a decrease in the duration of novel object exploration was observed for the middle-aged group when compared to the young in the long-term (t (26) = 4. 129, p < 0. 001), but not the short-term (t (29) = 0. 014, p = n. s.) memory. Interestingly, the young animals spent relatively more time with the novel object as compared to the familiar object in both the short- (t (18) = −5. 23, p < 0. 001) and long-term (t (14) = −8. 722, p < 0. 001) phase (1C, D). In","Memory loss in older people is a serious and widespread problem that affects up to 50% of those over the age of 85. It is a key symptom of dementia, but despite the growing impact of this disease on society, there are no treatments currently available that can effectively stop or delay the progression of the symptoms. One therapy that may reduce memory loss is called deep brain stimulation. Electrodes are implanted into the brain and used to stimulate brain cells in particular areas of the brain to alter mental and emotional processes. Deep brain stimulation is already used to treat Parkinson' s disease, depression and other conditions that affect how the brain works. Liu et al. studied the effect of deep brain stimulation on memory in rats.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two ‘PPXY’ motifs, that direct it to degradation in lysosomes. These signals are recognized by two HECT-domain ubiquitin E3 ligases, Smurf1 and Smurf2, which are induced by Shh and become enriched in Caveolin-1 lipid rafts in association with Ptch1. Smurf-mediated endocytic turnover of Ptch1 is essential for its clearance from the primary cilium and pathway activation. Removal of both Smurfs completely abolishes the ability of Shh to sustain the proliferation of postnatal granule cell precursors in the cerebellum. These findings reveal a novel step in the Shh pathway activation as part of the Ptch1 negative feedback loop that precisely controls the signaling output in response to Shh gradient signal. The secreted Sonic hedgehog (Shh) protein specifies spatial tissue patterns during development by providing positional cues embedded in its concentration gradient (Jiang and Hui, 2008; Robbins et al. , 2012; Ryan and Chiang, 2012). During embryogenesis, neighboring progenitor cells in a developing field are able to discern incremental changes in the Shh signal strength and adopt their respective fate accordingly (Ribes and Briscoe, 2009; Balaskas et al. , 2012). This ability requires a cell surface reception system that can transform the graded Shh signal into different levels of signaling output, but how this is accomplished is poorly understood. In the adult, Shh plays a crucial role in guiding the differentiation of tissue-specific stem cells (Jaks et al. , 2008; Shin et al. , 2011; Arwert et al. , 2012), and inappropriate activation of Shh signaling could be the culprit that underlines neoplastic growth in the gut epithelium (Nielsen et al. , 2004) or lead to outright cancers (Scales and de Sauvage, 2009; Stecca and Ruiz, 2010; Northcott et al. , 2012). At the cell surface, whereas a network of membrane proteins, including Hip1 (Chuang et al. , 2003), Gas1 (Lee et al. , 2001), Boc/iHog, and Cdo/Boi (Okada et al. , 2006; Tenzen et al. , 2006; Yao et al. , 2006; Beachy et al. , 2010), bind Shh and control the range and competence of its receiving cells, the core of Shh","Sonic hedgehog protein fulfils many vital roles in establishing the body plan of multicellular organisms during development. And in adult organisms it regulates the stem cells that maintain organs and tissues. In the embryo, Sonic hedgehog is secreted by certain cells to create a concentration gradient; cells then measure this concentration to work out where they are, which allows them to develop into the right sort of cells. However, many details of this process are not completely understood. At the core of this process are the interactions between the Sonic hedgehog protein, a receptor called Patched1 that is found on plasma membranes, and another membrane protein called Smoothened. The job of Smoothened is to activate proteins that enter the cell nucleus and ‘switch on’ the pathway' s target",380,128,0.3368
scientific_lay_summarisation-elife-norm,"recently for sensitive short-term cell tracking over a period of a few cell divisions (Comenge et al. , 2016; Dixon et al. , 2016). Using luciferase reporter genes, bioluminescence constitutes the most sensitive optical modality due to its excellent signal-to-noise ratio, as light emission only occurs in the presence of a functional enzyme and its required co-factors. Firefly, luciferase has become the most widely used reporter as its substrates, D-luciferin or CycLuc1 (Evans et al. , 2014), are very well tolerated by animals and, compared to other luciferases, its peak light emission at around 562 nm is closest to the infrared window for in vivo imaging (de Almeida et al. , 2011). Although highly sensitive in vivo cell tracking via bioluminescence imaging of firefly luciferase is well established (de Almeida et al. , 2011; Mezzanotte et al. , 2013), this modality provides poor information about the spatial localisation of cells. Fluorescence has recently gained importance for animal imaging, since novel near-infrared fluorescent proteins (iRFPs) were developed from bacterial phytochrome photoreceptors (Shcherbakova et al. , 2015; Shcherbakova and Verkhusha, 2013). Similar to bioluminescence imaging, fluorescence only allows limited spatial resolution due to the high scattering coefficient of photons in tissues. On the other hand, photoacoustic imaging is based on the generation of ultrasound waves after absorption of light emitted by a pulsed laser. The sound waves are well transmitted in fluid media and less prone to scattering through tissues than emitted light. In fact, acoustic scattering is three orders of magnitude less than photon scattering (Wang and Hu, 2012), which overcomes deep tissue spatial resolution drawbacks of other optical-based imaging technologies. Interestingly, some iRFPs, such as iRFP720, have an absorption profile in the NIR window, thus enabling their use as reporter genes for photoacoustic imaging, and allowing deep tissue imaging and tumour monitoring in mice (Deliolanis et al. , 2014; Jiguet-Jiglaire et al. , 2014). For example, new iRFPs have been proven to be useful genetic photoacoustic reporters in mammary gland and brain tumour monitoring, which establishes them as dual-modality imaging probes (Deliolanis et al. , 2014; Filonov et al. , 2012; Krumholz et al. , 2014). In addition, in multispectral optoacoustic tomography (MSOT), a rapid multiwavelength excitation allows the distinction between different absorbers simultaneously after applying multispectral unmixing algorithms (Tzoumas","Many scientists are studying the possibility of using human cells to treat diseases. For example, using stem cells to regenerate damaged body parts or genetically engineered immune cells to destroy cancer. Scientists need new tools to track what happens to these cells once they have been injected into a laboratory animal. This will help them understand how they work and make sure these potential treatments are safe. One concern with using cells as a treatment is that they might form cancerous tumors. To track these cells in a laboratory animal, scientists need two things: a way to distinguish the treatment cells from the animal’s normal cells and an imaging tool that allows them to see where the cells are in a living animal. One way to differentiate treatment",380,128,0.3368
dialogsum,#Person1#: The plants next to the window always look brown. You wouldn't know by looking at them that I water them every week. #Person2#: Maybe they don't like direct sunlight. I had the same problem with some of my plants. And a little shade helps them immensely.,#Person2# suggests #Person1# keep the plants from direct sunlight.,47,9,0.1915
dialogsum,"#Person1#: Good afternoon, Ma'am, My name is Mike and I am selling subscriptions to all sorts of periodicals. #Person2#: No, thank you, I am not interested. #Person1#: Please ma'am, if you could spare five minutes of your time, I am sure we could find something that interests you! #Person2#: I wish I could, but I have to walk the dog and finish cooking so if you would excuse me. #Person1#: We have a great variety of magazines all about cooking! This one for example, is a bi-monthly publication with recipes from all over the world! #Person2#: Wow, that would be kind of useful, do you have any other cooking magazines? #Person1#: Sure do! This one is a quarterly publication, but each issue has over 200 color pages of recipes and also many home decorating ideas! #Person2#: Wow, this is nice! Ok, sign me up for both publications. #Person1#: You mentioned you have a dog, most pet owners sign up for this weekly newsletter that has information on dog care, pet shops and even pet sitters! #Person2#: That is exactly what I needed! What else do you have? #Person1#: Well, I also have. . .","#Person2# at first is not interested in subscribing periodicals, but she changes her mind after hearing Mike's introduction.",194,18,0.0928
scientific_lay_summarisation-elife-norm,"with various cells have been unveiled (Boissonnas et al. , 2007; Deguine et al. , 2010). Recent studies indicate that lymphocytes can recruit each other indirectly into tumours; natural killer (NK) lymphocytes produce chemokines that attract dendritic cells (Böttcher et al. , 2018), which in turn can recruit CTLs (Spranger et al. , 2017). Although intravital microscopy enables imaging of cellular interactions in the TME in situ, it is typically restricted to relatively short imaging periods and sub-millimetre fields of view (Gabriel et al. , 2018). Furthermore, the inherent complexities of the TME, its constituent cell populations and its biochemical landscape have limited our ability to uncover the contribution of an individual immune subset or signalling mechanism to progressive, large-scale phenomena. Here, we developed a 3D tumouroid model and in silico simulations to reveal independent collective behaviour in CTL populations attacking tumour masses. We show that CTLs coordinate their migration in a process reminiscent of the swarming observed in insects (Avitabile et al. , 1975) and neutrophils (Lämmermann et al. , 2013). CTLs engaging tumour targets induce rapid chemotaxis in distant T cells through homotypic chemokine signalling. Newly arriving CTLs augment the chemotactic signal, further accelerating mass recruitment in a positive feedback loop. Furthermore, we show that local chemokine delivery triggers directed CTL movement through dense tumour tissue in vivo, and sustained secretion of CCL3 and CCL4 from tumours promotes CTL recruitment. Human effector and chimeric antigen receptor (CAR) T cells similarly employ intra-population signalling to drive rapid convergence. Our findings provide insights into how CTL populations amplify directed recruitment to an effector site independently of other leukocytes. We sought to investigate the population-wide movements and signals mediating interactions between CTLs during tumour clearance. To this end, we developed an ex vivo model enabling us to study the large-scale movements of primary CTLs around solid tumouroids embedded in three-dimensional (3D) collagen matrices (1A). We used primary murine CTLs isolated from OT1 (Hogquist et al. , 1994) and gBT1 (Coles et al. , 2003) T cell receptor transgenic mice that recognise ovalbumin (SIINFEKL) or herpes simplex virus glycoprotein B (SSIEFARL) residues, respectively, both in the context of the H-2Kb class I major histocompatibility complex. CTLs engaging a cognate tumouroid were rapidly recruited to its edge, where they accumulated over time (1B","Immune cells known as cytotoxic T lymphocytes, or CTLs for short, move around the body searching for infected or damaged cells that may cause harm. Once these specialised killer cells identify a target, they launch an attack, removing the harmful cell from the body. CTLs can also recognise and eliminate cancer cells, and can be infused into cancer patients as a form of treatment called adoptive cell transfer immunotherapy. Unfortunately, this kind of treatment does not yet work well on solid tumours because the immune cells often do not infiltrate them sufficiently. It is thought that CTLs arrive at their targets either by randomly searching or by following chemicals secreted by other immune cells. However, the methods used to map the movement of these killer cells have made",380,128,0.3368
dialogsum,"#Person1#: Hi dear, I'm tired and don't want to cook. Shall we have dinner in a restaurant? #Person2#: Oh, I forgot to tell you. Jane and Bill invited us to dinner this evening. I promised we'd go. #Person1#: Good. You know, I love Jane's cooking. What's the time? #Person2#: 6:30 PM. Bill said we could go to the bar together after dinner. That's nice. Shall we take them anything? No Jane said she'd like to do all the food preparation herself. #Person1#: That's nice. Shall we take them anything? #Person2#: No Jane said she'd like to do all the food preparation herself. What about taking a bottle of wine? Bill loves wine. #Person1#: I'd rather take some Flowers. I know Jane loves roses. #Person2#: Good, I'll buy some on my way home.",#Person2# tells #Person1# Jane and Bill invited them to have dinner together. #Person1# and #Person2# will buy some roses for Jane.,132,21,0.1591
scientific_lay_summarisation-elife-norm,"Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized AcnS437D. Expression of aggregation-prone polyQ-containing proteins or the Amyloid-β42 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges. Cdk5 shares strong homology with other members of the family of cyclin-dependent kinases (Cdks), but it is distinct in its modes of regulation and function (Dhavan and Tsai, 2001; Pozo and Bibb, 2016). Unlike other Cdks, Cdk5 is best known for its function in post-mitotic cells rather than cell cycle regulation (Dhariwala and Rajadhyaksha, 2008). In post-mitotic cells, Cdk5 is regulated by binding to its obligatory membrane-associated p35 or p39 co-activators (Tsai et al. , 1994; Tang et al. , 1995). These co-activators are highly expressed in the brain and loss of Cdk5 activity in mice or flies has been associated with defects in neurite outgrowth (Su and Tsai, 2011; Trunova et al. , 2011), neuronal migration (Nishimura et al. , 2014), pre- and post-synaptic functions (Bibb et al. , 1999; Li et al. , 2001), the maintenance of synaptic plasticity (Hawasli et al. , 2007), retinal degeneration (Kang et al. , 2012), and neurodegeneration in aging brains (Trunova and Giniger, 2012; Shah and Lahiri, 2017). Accordingly, dysregulation of Cdk5 has been observed in numerous brain diseases, including schizophrenia and epilepsy (Patel et al. , 2004; Engmann et al. , 2011) and neurodegenerative disorders, including Huntington’s disease, Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS) (Cheung and Ip, 2012). Cdk5 substrates regulating microtubule-based transport (Klinman and Holzbaur, 2015) and synaptic function (Tan et al. , 2003; Lai and Ip, 2015),","Cells have a problem that we recognize from our own homes: if nobody cleans up, garbage accumulates. Unwanted material in cells can include proteins that clump together and can no longer carry out their normal tasks. If left to build up, these protein aggregates can damage the cell and even kill it. Many neurodegenerative disorders, including Huntington’s disease and Alzheimer' s disease, arise when such faulty proteins accumulate inside brain cells. Autophagy is a process that can destroy protein aggregates and other defective material to keep cells healthy. Understanding how cells regulate autophagy is thus of great interest to scientists. A protein called Acinus promotes autophagy and is found in many organisms including fruit flies and humans. All Acinus proteins share a common feature; they contain a site",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the storage drives (). 10. 7554/eLife. 06664. 003Figure 1. Workflow for analyzing cryo-EM data on Amazon' s cloud computing infrastructure. After collecting cryo-EM data (Step 1), particles are extracted from the micrographs and prepared for further analysis (Step 2). After logging into an ‘instance’ (Step 3), data are uploaded to a storage server (elastic block storage) (Step 4). At this point, STARcluster can be configured to launch a cluster of 2–30 instances that is mounted with the data from the storage volume (Step 5). A detailed protocol can be found at an accompanying Google site: http: //goo. gl/AIwZJz. : http: //dx. . org/10. 7554/eLife. 06664. 003 While users can utilize a single instance for calculations, the maximum number of CPU cores per instance is 18. Therefore, creating a computing cluster with a larger number of CPUs on AWS requires additional steps. The Software Tools for Academics and Researchers (STAR) group at the Massachusetts Institute of Technology developed a straightforward package that allows users to group individual AWS instances into a cluster. The STARcluster program is a python-based, open source package that automatically creates a cluster preconfigured with the necessary software to manage a computer cluster (Ivica et al. , 2009). This package allows users to specify the number of instances to be included in the clusters as well as the instance type. By taking advantage of this tool, private clusters can be built with sizes ranging from 16 to 480 CPUs (). While Amazon provides dedicated access to instances through ‘on-demand’ reservations, there are ‘spot instances’ that are 80–90% cheaper than the on-demand price. Spot instances are unused instances within Amazon EC2 that are open for competitive bidding, where users gain access to them by making offers above the current minimum bid. This means that while the on-demand rate for high-memory, 16-CPU instances (called ‘r3. 8xlarge’) is $2. 80/hr, spot instance prices can be as low as $0. 25–$0. 35/hr. In order to determine if spot instances offer a consistent reduction in price, we analyzed the global availability of r3. 8xlarge spot instances. Currently, Amazon has 9 regions worldwide within 7 countries: US-East-1 (United States), US-West-1 (United States), US-West-2 (United States), SA-East-1 (Brazil), EU-Central-1 (Germany), EU-West-1 (Ireland), AP-Northeast-1 (Japan), AP-Southeast-1 (Singapore), and AP-Southeast-2 (Australia). For each region, we retrieved spot","Microscopes can be used to view objects or structural details that are not visible with the naked eye. A type of microscope called an electron microscope—which uses beams of particles called electrons—is particularly useful for examining tiny objects or structures because it can produce images with a higher level of detail than microscopes that use light. There are several ways to prepare biological samples for electron microscopy. One technique is called cryo-electron microscopy, or cryo-EM for short, where the sample is rapidly frozen and then viewed under the electron microscope. Using this technique it is possible to produce highly detailed images of viruses, individual compartments within cells and even single proteins. To convert the images of proteins into three-dimensional models, high-performing clusters of computers are required. It can",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2009). Pitx2, for example, specifies mandibular arch mesoderm but not hyoid arch mesoderm in the mouse (Shih et al. , 2007a). In contrast to cranial muscle, formation of trunk muscle is Pax3-dependent (Tajbakhsh et al. , 1997). The domain of the vertebrate neck contains two muscle groups: the hypobranchial muscles ventrally and the cucullaris dorsally. Hypobranchial muscles are derived from occipital somites, which form the hypoglossal cord and migrate towards the tongue (Noden, 1983; O' Rahilly and Müller, 1984). The number of occipital somites contributing to cranial structures varies among species, however. For example, somites 2 and 3 form both hypobranchial musculature and the occipital arch in the axolotl (Piekarski and Olsson, 2007; 2014), whereas in chicken somites 2–5 form both the occipital region of the skull and tongue musculature (Couly et al. , 1993; Huang et al. , 1999; 2000). The cucullaris muscle, a feature of gnathostomes, connects the head to the pectoral girdle, thus spanning the transition zone between cranial and trunk myogenic signaling regimes (Kuratani, 1997). It is the putative homologue of the trapezius and sternocleidomastoid in amniotes (Lubosch et al. , 1938). In sharks and the Queensland lungfish, the cucullaris elevates the gill arches and protracts the pectoral girdle. It originates near the skull and continues caudally and ventrally to insert on the scapular region of the pectoral girdle; a ventral fascicle extends to the posteriormost branchial bar (Edgeworth, 1926; 1935; Allis, 1917; Vetter, 1874; Greenwood and Lauder, 1981). The cucullaris is a thin muscle, and it can be difficult to visualize its three-dimensional position vis-à-vis adjacent skeleton and musculature. Hence, it is poorly described in many taxa with regard to both its shape and its relation to other cranial and trunk musculature. It is innervated by the accessory ramus of the vagus (X) nerve in anamniotes, but primarily by the accessory (XI) nerve in amniotes (Edgeworth, 1935). While in chicken the connective-tissue component of hypobranchial muscles and the ventrolateral neck region is derived from neural crest (Le Lièvre and Le Douarin, 1975), the cucullaris is reported to have somite-derived connective tissue (Noden, 1983). The derivation of connective-tissue components of the mouse trapezius is not fully resolved; both lateral plate mesoderm (Durland et al. , 2008) and neural crest (Matsuoka et al. , 2005) are reported","Muscles in the head and trunk (main body) form from different parts of the embryo, and their development uses different genes. Trunk muscles are derived from somites – paired blocks of cells arranged in segments on either side of the midline (which divides the body into left and right halves). By contrast, cells that give rise to head muscles are arranged in a continuous mass. But what about neck muscles? Some studies claim they develop like head muscles; others suggest they are trunk muscles. These studies commonly examine mice or chickens. By examining species that have a more primitive complement of head and neck muscles, Sefton et al. now show that a neck muscle should be considered a kind of head muscle. Gill muscles are definitive head muscles.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2016). In maize, THICK TASSEL DWARF1 (TD1) and FEA2 are CLV1 and CLV2 orthologs, and function similarly to restrict inflorescence shoot meristem proliferation (Taguchi-Shiobara et al. , 2001; Bommert et al. , 2005). Two maize WUS orthologs, ZmWUS1 and ZmWUS2, have been predicted by phylogenetic analysis, and a ZmWUS1 reporter is expressed in the presumptive organizing center of the inflorescence shoot meristem (Je et al. , 2016), but these genes have not been functionally characterized (Nardmann and Werr, 2006). In rice, FLORAL ORGAN NUMBER 1 (FON1), the CLV1 ortholog, and FON2, the CLV3 ortholog, similarly function in floral development in a common pathway, as expected (Suzaki et al. , 2004; Chu et al. , 2006; Suzaki et al. , 2006; Suzaki et al. , 2008; Suzaki et al. , 2009), whereas a second rice CLE peptide gene, FON2-LIKE CLE PROTEIN1 (FCP1) controls stem cell proliferation independent of FON1 (Suzaki et al. , 2008). The rice WUS homolog, TILLERS ABSENT1/MONOCULM3 functions in axillary shoot meristem formation (Tanaka et al. , 2015; Lu et al. , 2015), and WUS function in the shoot apical meristems appears to have been taken over by the WUSCHEL RELATED HOMEOBOX4 (WOX4) gene (Ohmori et al. , 2013). How specificity is achieved is a common question in signal transduction pathways. Recently, we identified a distinct CLV receptor, FASCIATED EAR3 (FEA3) in maize and Arabidopsis, and found that FEA3 controls responses to the maize FCP1 (ZmFCP1) CLE peptide (Je et al. , 2016). Here, we show that the maize CLV2 ortholog FEA2 also participates in ZmFCP1 signaling, in addition to controlling responses to the maize CLV3 ortholog, ZmCLE7 (Je et al. , 2016). To ask how specificity from these different CLE peptide inputs is achieved, we first isolated mutant alleles of the maize CRN gene. Consistent with results in Arabidopsis (Miwa et al. , 2008; Müller et al. , 2008; Bleckmann et al. , 2010; Zhu et al. , 2010; Nimchuk et al. , 2011a), we found that fea2 was epistatic to Zmcrn in control of meristem size, but Zmcrn; ct2 double mutants showed an additive enhanced phenotype, suggesting they act in parallel pathways, despite the fact that FEA2 binds both ZmCRN and CT2 in co-immunoprecipitation (co-IP) experiments. Strikingly, ct2 and Zmcrn mutants were resistant","Like animals, plants are made up of many different types of cells, which descend from undifferentiated cells called stem cells. Thanks to these cells, plants are able to grow and develop throughout their lives. Stem cells live at the tips of the plant’s shoots and roots. They constantly divide to produce new cells to self-renew or replace specific plant cells in need of repair. Over time, they change – or differentiate – to go on to become part of tissues like leaves, roots, stems, shoots, flowers or fruits. To maintain a continuous pool of undifferentiated stem cells and to make sure that stem cells divide at the correct pace, neighbouring cells emit signals that control the activity of stem cells. The new stem cells that remain close to",380,128,0.3368
dialogsum,"#Person1#: Good morning, Madam. This is room service, may I help you? #Person2#: Good morning. I'd like to reserve some rooms for a tourist party. #Person1#: All right. What kind of room would you like? #Person2#: You see, we are tourists whose requests are different, so please tell me more about it, will you? #Person1#: It's my pleasure. We have single rooms, double rooms, suites and luxury suites, ect. Well, here is an introduction to our hotel. #Person2#: That's great. I'd like to book four single rooms, five double rooms and three suites. #Person1#: All right, madam. For which dates do you want to book the rooms? #Person2#: From tomorrow till January 8th. That's five days in all. #Person1#: I see. Now please fill out the form. #Person2#: Here you are. Is everything OK? #Person1#: Just a minute, madam. You should pay a deposit of 500 yuan beforehand. #Person2#: OK. Here you are. #Person1#: Thank you. Please keep this receipt. #Person2#: Thank you. By the way, is there any preferential rate for the party? #Person1#: Yes, there is a 15 percent discount. #Person2#: That's wonderful. Thank you. #Person1#: You're welcome. I hope all of you will have a good time here.","#Person1# helps #Person2# book four single rooms, five double rooms, and three suites for a tourist party from tomorrow till January 8th with a deposit of 500 yuan and gives #Person2# a 15% discount.",201,34,0.1692
dialogsum,"#Person1#: Eddie, you've got to come over and see my parrot. It's learning so many words now. #Person2#: Really? Last time I saw him all he could say was something that sounded like hello. #Person1#: Well, now, he can a sing a song too. #Person2#: Which song did you teach him? #Person1#: Calorie. You know that popular song by a group of girls right? Actually I didn't teach Goby the words. I was dancing to the song on the radio and he just picked it up. #Person2#: That's a pretty smart bird. I'll come over after school today. Let's take a video of him and put it on line.",#Person1# tells Eddie about #Person1#'s smart parrot. Eddie's interested and wants to film it.,109,14,0.1284
pubmed-summarization,"- dimensional plane and entered into the game for coordination . 1a shows the cop capture device which consists of two plates ( 30 245 10 mm , 304 stainless steel ) , one for each foot . the bottom displays an equilateral triangle ( width 165 mm ) consisting of three load cells acting as a unit ( . the center of this equilateral triangle is the geometric center of the stepping zone . the user needs to step on the center of the stepping zone to align the geometric center of the plantar area and the center of the load cell as closely as possible . 1c and 1d show how movements are captured when the cop capture device has been set up . the load cell retrieves signals from the right and left feet of the user , and the movements of foot pressure center are post - processed to construct the center distribution . if the region d is located in the two - dimensional coordinate system , which is the density function (x , y ) , region d is further divided into left and right sides , sub - regions dl and dr . the overall weight of the system is the subject s weight on both feet , which is calculated using the formula : the center of gravity of the system is calculated using the formula : the three vertices of a subject s plantar force on the region dl(dr ) , have force and moment arm values li ( ri ) and xli , yli ( xri , yri ) ; for i = 13 , respectively . 2fig . 2.the relationship between the force and the moment arm shows the relationship between the force and the moment arm diagram , and the center of gravity is be derived as follows : the relationship between the force and the moment arm 3fig . a signal transmitter is used to provide the operational voltage to the load cell and amplify the signal for transmission to the analog / digital converter . converted data is saved in a buffer zone and transmitted when the software requests it . after acquisition by the analysis software , data is processed by a finite impulse response","[ purpose ] stroke and other cerebrovascular diseases are major causes of adult mobility problems . because stroke immobilizes the affected body part , balance training uses the healthy body part to complete the target movement . the muscle utilization rate on the stroke affected side is often reduced which further hinders affected side functional recovery in rehabilitation . [ subjects and methods ] this study tested a newly - developed interactive device with two force plates to measuring right and left side centers of pressure , to establish its efficacy in the improvement of the static standing ability of patients with hemiplegia . an interactive virtual reality game with different side reaction ratios was used to improve patient balance . the feasibility of the proposed approach was",380,128,0.3368
pubmed-summarization,"with or without brl37344 ( 50 ng / ml ) . after 1-h incubation at 37c , 200 l of infranatant was removed and stored at 20c . serum free glycerol and glycerol released from fat explants were measured using a free - glycerol kit ( sigma - aldrich co. , st . glycerol in the assay media of primary and 3t3-l1 adipocytes was measured using bioluminescence , which is very sensitive and especially well adapted when only small amounts of adipose tissue or cells are available ( 13,14 ) . statistical analysis was performed using the student t test or anova , followed by contrast test . adipoq mice were created as previously described ( 5 ) on the 129/svev genetic background and had been back - crossed to c57bl/6 for five generations . the experiments using mouse models were carried out under the association for assessment and accreditation of laboratory animal care guidelines with approval of the animal care and use committee . for some animal studies , 1 10 pfu of purified adenovirus vectors was injected into the mouse tail vein ( 6 ) . 3t3-l1 and 3t3-l1car1 cells and induction of adipocyte differentiation were described in a previous publication ( 7 ) . op9 adipocyte differentiation was induced using knockout sr ( 8) . although both 3t3-l1 and op9 adipocytes secrete adiponectin into the medium , adiponectin in overnight cultured medium accumulated only to 0.1% of mouse serum adiponectin . therefore , co - culture or conditioned medium was used to increase adiponectin protein levels . for co - culture , adipocytes were cultured in the outside well of the bd biosciences ( franklin lakes , nj ) transwell co - culture system , and fao cells were grown on the protein and cytokine - permeable membrane of the insert well . fao cells were transduced with adenovirus encoding mouse adiponectin ( ad - acrp30 ) or green fluorescent protein ( gfp ) for 12 h in a regular 6-well plate , and then the inserts with transduced fao cells were washed and transferred to the co - culture plates with differentiated adipocytes in the bottom wells . this system allows increase of medium adiponectin levels ( 40% of mouse serum adiponectin ) without physical interaction","objectiveadiponectin is an adipocyte - derived hormone that sensitizes insulin and improves energy metabolism in tissues . this study was designed to investigate the direct regulatory effects of adiponectin on lipid metabolism in adipocytes.research design and methodsbasal and hormone - stimulated lipolysis were comparatively analyzed using white adipose tissues or primary adipocytes from adiponectin gene knockout and control mice . to further study the underlying mechanisms through which adiponectin suppresses lipolysis , cultured 3t3-l1 adipocytes and adenovirus - mediated gene transduction were used.resultssignificantly increased lipolysis was observed in both adiponectin gene knockout mice and primary adipocytes from these mice . hormone - stimulated glycerol release was inhibited in adiponectin - treated adipocytes . adiponectin suppressed hormone - sensitive lipase activation without altering adipose triglyceride lipase and cgi-58 expression",380,128,0.3368
scientific_lay_summarisation-elife-norm,"provides a specific example of the power of global RNA modulatory events in the selection of pro-metastatic phenotypic traits. We combined gene expression data from triple negative metastatic breast cancer models (Minn et al. , 2005; Bos et al. , 2009) and a cohort of 368 untreated clinical breast cancer cases (Minn et al. , 2005; Wang et al. , 2005) with mutational data from a brain metastasis that originated from a basal breast cancer (Ding et al. , 2010; 1A). Specifically, we looked for genes that had reduced mRNA expression in functionally metastatic cancer cells, evidence for low mRNA expression associated with poor patient outcome in clinical samples, and an enriched mutation in the brain metastasis sequenced by Ding et al. (2010). RBM47, a gene encoding a previously uncharacterized putative RNA-binding protein was the only one that fulfilled all these criteria (Baltz et al. , 2012; Castello et al. , 2012; Ray et al. , 2013). We confirmed the lower expression of RBM47 mRNA in the highly metastatic cells (1B). This translated into a comparable difference at the protein level (1C). In the clinical data sets, low RBM47 mRNA expression was significantly associated with relapse to brain and lung (1D, E) but not to bone (1F). In multivariate analysis combining RBM47 expression with estrogen, progesterone and HER2 receptor status (ER, PR and HER2), the association with brain metastasis remained statistically significant (— 1A). We further characterized the expression patterns of RBM47 in the TCGA cohort of 748 breast cancer samples studied by RNA-seq (Cerami et al. , 2012; Cancer Genome Atlas Network, 2012). We found that low RBM47 expression was significantly associated with claudin-low and basal breast cancers (1G), two subtypes of poor prognosis (Smid et al. , 2008; Lu et al. , 2013). 10. 7554/eLife. 02734. 003Figure 1. RBM47 expression associated with breast cancer progression. (A) A schematic of the analytical approach. Genes identified as mutated in a breast cancer brain metastasis by Ding et al. (2010) where compared to metastasis-associated gene expression traits in both clinical data sets and experimental model systems. This identified RBM47 as a putative breast cancer suppressor gene. (B) RBM47 mRNA expression measured by quantitative real-time RT-PCR in two cell line systems of breast cancer metastasis. In both panels, the data are normalized","Tumors form when mistakes in the genes of a single cell allow it to multiply uncontrollably. Sometimes further mutations in genes allow the cancerous cells to escape from the tumor, enter the bloodstream and start a second cancer elsewhere in the body. However, many of the genetic changes behind this process, which is called metastasis, are poorly understood—especially those changes in genes that occur rarely, but can still help the cancer to spread. Vanharanta, Marney et al. have looked at data on which genes are switched ‘on’ or ‘off’ in metastatic breast cancer cells. A gene called RBM47 was often switched off in these cells, and patients with a low level of RBM47 tended to have a poor clinical outcome. To test the function of the gene, Vanharanta,",380,128,0.3368
dialogsum,"#Person1#: Your garden is looking very beautiful this summer. The flowers are really colorful. #Person2#: Thank you. I have roses, tulips, and daffodils. Do you like the rockery with the smaller flowers? #Person1#: Yes, I do. Those are violets, aren't they? #Person2#: Yes, they are. This afternoon, I'm going to prune the hedge. #Person1#: The lower branches on that tree are hanging very low. Would you like me to cut them off for you? #Person2#: Thank you! That would be very kind of you. I have a saw in the garden shed. #Person1#: When the lower branches are removed, you'll be able to sit under the tree. #Person2#: Tomorrow, I'll cut the grass. Then the garden will look perfect. #Person1#: Just make sure children don't play in the flower beds and destroy the flowers.",#Person1# thinks #Person2#'s garden is very beautiful. #Person2# will prune the hedge and cut the grass. #Person1# will help #Person2# cut off the lower tree branches.,134,26,0.194
pubmed-summarization,"an anal fistula is a chronic phase of anorectal sepsis and is characterized by chronic purulent drainage or cyclical pain associated with abscess formation , followed by intermittent spontaneous decompression . the goals in the treatment of an anal fistula are to eliminate the primary fistula opening , any associated tracts , and any secondary openings without a change in continence . most anal fistulae are simple and can be treated using a fistulotomy , which has a low recurrence rate and an acceptable rate of morbidity [ 3 - 6 ] . however , the treatment of a complex anal fistula , which is defined as a fistula whose treatment poses an increased risk for a change in continence , still represent a challenge [ 7 - 9 ] . the recurrence rate for a complex anal fistula managed with a cutting seton is reported to be 0 to 8% , with minor and major incontinence being reported in 34 to 63% and 2 to 26% of patients , respectively [ 10 - 14 ] . advancement flap is still considered to be the gold standard of treatment for a complex anal fistula . successful healing of the fistula has been demonstrated in 55 to 98% of patients [ 8 , 10 , 15 - 17 ] . however , this procedure is technically demanding , and although the sphincter mechanism is not divided during advancement flap repair of the fistula , minor incontinence has been found in up to 31% patients and major incontinence in up to 12% of patients . because of the risk of a change in continence with these conventional techniques , sphincter - preserving techniques for the management of complex anal fistulae have been evaluated . glue was easy to apply , but probably not ideal for fistula treatment because of its liquid consistency . a failure of the formed glue clot in a properly sealed tract , the inability to securely fix the material within the tract and the uncertainty of tissue in growth into the glue may all explain the possible causes of the poor outcomes . this article aims to review the literature and to identify the new sphincter - preserving techniques , such as the anal fistula plug , the","surgery for an anal fistula may result in recurrence or impairment of continence . the ideal treatment for an anal fistula should be associated with low recurrence rates , minimal incontinence and good quality of life . because of the risk of a change in continence with conventional techniques , sphincter - preserving techniques for the management complex anal fistulae have been evaluated . first , the anal fistula plug is made of lyophilized porcine intestinal submucosa . the anal fistula plug is expected to provide a collagen scaffold to promote tissue in growth and fistula healing . another addition to the sphincter - preserving options is the ligation of intersphincteric fistula tract procedure . this technique is based on the concept of secure closure of the internal",380,128,0.3368
scientific_lay_summarisation-elife-norm,"is halted and the SAC is inactivated. Timely SAC inactivation requires two factors, TRIP13 (Wang et al. , 2014) and the HORMA domain protein p31 (comet) (Habu et al. , 2002; Xia et al. , 2004; Hagan et al. , 2011; Varetti et al. , 2011; Westhorpe et al. , 2011; Ma et al. , 2012), which recent evidence suggests may act together to directly disassemble the MCC. p31 (comet) specifically recognizes and binds C-MAD2, and the p31 (comet) -MAD2 interface overlaps MAD2' s interface with BUBR1 in the intact MCC (Xia et al. , 2004; Yang et al. , 2007; Tipton et al. , 2011b; Chao et al. , 2012), suggesting that p31 (comet) may compete with BUBR1 for MAD2 binding. Further, the combined activities of p31 (comet) and TRIP13 can cause the dissociation of MAD2 from immunoprecipitated CDC20 or BUBR1 complexes in vitro (Teichner et al. , 2011; Eytan et al. , 2014). Intriguingly, human TRIP13 has also been identified as an oncogene: TRIP13 is overexpressed in a number of human cancers (Larkin et al. , 2012; van Kester et al. , 2012; Banerjee et al. , 2014; Wang et al. , 2014), and can promote proliferation and invasion when overexpressed in human cell lines (Banerjee et al. , 2014). The source of TRIP13' s oncogenic activity is unknown, but may stem from effects on chromosome structure and DNA repair pathways (as its meiotic functions would suggest), or may instead arise from aberrant regulation of the SAC. Pch2/TRIP13 is thus directly implicated in the regulation of HORMA domain-mediated signaling in two separate pathways, meiotic recombination and the SAC. The mechanistic basis for this regulation, however, remains unknown. Here, we show that Pch2/TRIP13 comprises a new family of AAA+ ATPase protein remodelers, with a substrate-recognition domain similar to the NSF/p97/PEX1 remodeler family and a physical mechanism closely related to the bacterial ClpX unfoldase. We show that TRIP13 converts closed, active MAD2 to its inactive open conformer, and that p31 (comet) functions as an adapter to recognize closed MAD2 and deliver it to TRIP13. Thus, TRIP13 regulates the SAC through MAD2 conformational conversion and safety belt disengagement, and a similar mechanism for HORMAD complex disassembly likely underlies the enzyme' s regulatory functions in meiosis. Pch2/TRIP13 proteins are members of the","The genetic material inside human and other animal cells is made of DNA and is packaged in structures called chromosomes. Before a cell divides, the entire set of chromosomes is copied so that each chromosome is now made of two identical sister ‘chromatids’. Next, the chromosomes line up on a structure called the spindle, which is made of filaments called microtubules. Cells have a surveillance system known as the spindle assembly checkpoint that halts cell division until every chromosome is correctly aligned on the spindle. Once the chromosomes are in place, the checkpoint is turned off and the spindle pulls the chromatids apart so that each daughter cell receives a complete set of chromosomes. A protein called MAD2 plays an important role in the spindle assembly checkpoint. It",380,128,0.3368
dialogsum,"#Person1#: May I help you? #Person2#: Yes, please. Can I exchange money here? #Person1#: Here we can exchange HAD, USD and Euros. Which do you require? #Person2#: To be honest, I really wanted to exchange my GBP, but I suppose USD will be fine. I have some and I just need a little local currency for expenses. Could you tell me what the rate is like today? #Person1#: At the moment it's 830. 43 RMB for 100 USD, which is a pretty good rate. #Person2#: OK, that sounds fine. I think 200 USD worth of RMB should be plenty, thanks.",#Person2# wanted to exchange some GBP for local expenses. #Person1# tells #Person2# what currencies they do. #Person2# gets 200 USD worth of RMB.,100,23,0.23
dialogsum,"#Person1#: Hello, Mary. Why are you standing here? #Person2#: I'm waiting for a bus. The buses are so full at this time of the day. #Person1#: Sure. Where are you going? I don't think this is your way home. #Person2#: You are right. I'm going for a walk in the park. #Person1#: Going for a walk even after along day's work? #Person2#: Yes. I always enjoy walking alone in the park after work. #Person1#: I see. Then why not go there on foot? It's not so far from here. #Person2#: Oh, no. I hate walking through the streets.",Mary tells #Person1# she is waiting for a bus to the park because she enjoys walking alone in the park.,98,20,0.2041
dialogsum,"#Person1#: Grandpa, this seat is for you, for you are the eldest person here and also it's your birthday today. #Person2#: Oh, you are such a good child today. Come here. Sit next to me. #Person1#: I'm afraid I can't do that. It's Dad's seat, according to the book about table manners. #Person2#: Oh, you read? Very good. Then, I think we should do something different today. I'll give you some privilege. #Person1#: Great. That's my favorite seat which will be the nearest to the birthday cake. #Person2#: Now I see what you read the book for. But it's fine. I'll give you the lion's share. #Person1#: Why do they serve up the noodles first? I don't like it. Where is the cake? #Person2#: This is not common noodles. They're ' long-lived ' noodles. it's an old Chinese tradition to eat. long - lived noodle on birthday. #Person1#: I see. Then I'll try it.",#Person1# saves the seat for Grandpa according to table manners. Grandpa asks #Person1# to have 'long-lived' noodles first.,154,18,0.1169
dialogsum,"#Person1#: What do you say to eating out, Maggie? #Person2#: Yeah, why not? We haven't been out for dinner for quite a long time. A new French restaurant has just opened in our neighborhood. We can go there. #Person1#: Do we need to book a table in advance? #Person2#: No need for that. It's not usually busy on weekdays. #Person1#: What time shall we go? #Person2#: Why not now? I'm hungry.",#Person1# and #Person2# plan to eat out. #Person2# thinks they should go now.,71,13,0.1831
scientific_lay_summarisation-elife-norm,"to the hijacking of host ribosomes to produce viral proteins (Jackson et al. , 2010; Hertz and Thompson, 2011). A common strategy used by different types of viruses relies on structured RNA sequences at the ends of their mRNAs (Filbin and Kieft, 2009). These sequences are called Internal Ribosomal Entry Sites (IRES) and form specific three-dimensional structures able to manipulate and co-opt the host translational machinery (Yamamoto et al. , 2017). IRES sequences are classified according to the subset of factors they require for initiation (Filbin and Kieft, 2009). Type IV IRES sequences, including the Cricket Paralysis Virus IRES (CrPV-IRES) and the Taura Syndrome Virus IRES (TSV-IRES) do not require initiation factors and are the best studied IRESs. Biochemical and structural studies have provided a detailed view on how these approximately 200-nucleotide-long sequences interact with and manipulate the ribosome (Wilson et al. , 2000; Spahn et al. , 2004; Petrov et al. , 2016). A modular architecture of three pseudoknots (PKI, PKII and PKIII, 1A) is crucial for these IRESs to establish a balance between structural flexibility and rigidity, essential for interaction with the ribosome and with two elongation factors (eEF2 and eEF1A) required for IRES translocation through the ribosome (Jan et al. , 2003). PKI mimics an anti-codon stem loop (ASL) of a tRNA interacting with its cognate mRNA codon, and plays an essential role in setting up the correct reading frame in the aminoacyl site (A site) of the ribosome (Costantino et al. , 2008). A ribosome primed with a type IV IRES alternates between rotated and non-rotated configurations of the small ribosomal subunit (Fernández et al. , 2014; Koh et al. , 2014). Similarly, after peptidyl-transfer in canonical translocation, the ribosome alternates between rotated and non-rotated configurations of the small ribosomal subunit with respect to the large ribosomal subunit (Voorhees and Ramakrishnan, 2013). This pre-translocation stage of the ribosome is recognized by a protein translocation factor (EF-G in Bacteria, eEF2 in Eukarya), which in GTP-bound form induces an additional rotation of the small subunit and blocks the A site of the ribosome (Tourigny et al. , 2013). Translocation proceeds forward by a back rotation of the small subunit to recover a canonical configuration of the ribosome. This is accomplished by a swiveling movement of the head of","Viruses cannot replicate themselves, but instead depend on components of the host cell for their own survival. Once a virus successfully enters a cell, it must use part of the cell’s machinery – specifically the ribosomes – to produce its own proteins. Ribosomes normally make the cell’s proteins by reading instructions written in molecules known as messenger RNAs (or mRNAs for short). Viruses hijack ribosomes using structured RNA segments in its mRNAs that can mimic natural components of the cell’s protein-producing machinery. These RNA sequences, known as IRESs, feature a refined balance between rigidity and flexibility. Their flexible nature has made them difficult to study in the past, though the latest advances in electron cryo-microscopy mean that IRESs can now be directly observed in complex with ribosomes. Pisareva",380,128,0.3368
dialogsum,"#Person1#: Sam, you look unhappy, what's going on? #Person2#: It's about my business. #Person1#: Why? What's wrong with it? #Person2#: I don't have enough customers. I don't know what to do with it. #Person1#: Are you advertising? #Person2#: Yes, I've advertised with newspapers, magazines and billboards, but failed to see any obvious effect. #Person1#: Then, have you posted anything on line? #Person2#: No, I don't think people will see my business on the Internet. #Person1#: Come on! people are surfing the Internet all the time these days. Definitely they would see it. #Person2#: But people are just chatting, watching movies or playing games on line. I mean, mostly for entertainment. #Person1#: Oh no, the Internet has become a very big market for business, don't you know that? #Person2#: Alright I'll have a try.",#Person1# finds Sam look unhappy. Sam tells #Person1# he doesn't have enough customers. #Person1# suggests putting some advertisements online and Sam'll have a try.,133,24,0.1805
pubmed-summarization,"phosphate ( -ca3(po4)2 ) , calcium hydrogen phosphate ( cahpo4 ) , calcium carbonate ( caco3 ) , and hydroxyapatite ( ca10(po4)6(oh)2 ) , and was supplied by innotere gmbh ( radebeul , germany ) . srcpc powder was obtained by substitution of caco3 by srco3 ( alfa aesar ) in the cpc cement precursor powder . a mouldable paste was obtained by mixing the cement powder with na2hpo4 solution using a liquid - to - powder ratio of 500 and 350 l / g for cpc and srcpc , respectively , immediately prior to implantation . srcpc was previously shown to release significant amounts of sr upon immersion in aqueous media ( e.g. , cell culture medium ) and to positively influence both in vitro osteoblast proliferation and differentiation and in vivo bone formation ( 15 ) . composites of silica and fibrillar bovine collagen were used for implantation as monolithic xerogels ( b30 , 70 wt% silica , 30 wt% collagen ) or as porous scaffold ( sc - b30 , xerogel particles b30 , size < 250 m , embedded in a collagen matrix with xerogel / matrix weight ratio of 1.0 ) . for preparation of compact silica / collagen xerogels , bovine tropocollagen type i ( gfn , germany ) was dialysed ( nominal molecular weight cut - off 1214 kda , roth , germany ) against deionized water followed by fibrillation in 30-mm neutral sodium phosphate buffer solution , lyophilisation ( christ alpha 14 laboratory freeze - dryer , osterode , germany ) , and resuspension in 0.1 m trishcl ph 7.4 ( roth ) to obtain homogeneous 30 mg / ml suspensions . the silica component was prepared by hydrolysing tetraethoxysilane ( teos , 99% , sigma , germany ; molar ratio teos / water=1/4 ) under acidic conditions ( 0.01 m hcl ) to obtain silicic acid . vigorous stirring of calculated volumes of silicic acid and collagen suspension to obtain a final composition of 70% silica and 30% collagen ( b30 ) resulted in the formation of 800-l hydrogels . a modification of the scaffolds was prepared by using xerogel particles consisting of 50 wt% silica , 30 wt% fibrillar bovine collagen , and 20 wt% strontium carbonate ( sc -","backgroundthe aim of the current study was to measure and compare the effect of various biomaterials for the healing of osteoporotic bone defects in the rat femur using 18f - sodium fluoride dpet-ct.material/methodsosteoporosis was induced by ovariectomy and a calcium - restricted diet . after 3 months , rats were operated on to create a 4-mm wedge - shaped defect in the distal metaphyseal femur . bone substitution materials of calcium phosphate cement ( cpc ) , composites of collagen and silica , and iron foams with interconnecting pores were inserted . strontium or bisphosphonate , which are well known for having positive effects in osteoporosis treatment , were added into the materials . eighteen weeks after osteoporosis induction and 6 weeks following femoral surgery , dpet -",380,128,0.3368
scientific_lay_summarisation-elife-norm,"are provisioned maternally. C. elegans L1 arrest provides a powerful organismal model to investigate gene regulatory and metabolic mechanisms that enable animals to cope with acute starvation. Insulin-like signaling is a critical regulator of starvation survival during L1 arrest (Baugh and Sternberg, 2006; Muñoz and Riddle, 2003). Feeding promotes insulin-like signaling through the receptor daf-2/InsR (Chen and Baugh, 2014), which antagonizes the transcription factor daf-16/FoxO (Lin et al. , 1997; Ogg et al. , 1997). In the absence of insulin-like signaling, daf-16 is active and promotes developmental arrest and starvation survival (Baugh and Sternberg, 2006). daf-16 promotes developmental arrest by inhibiting the dbl-1/TGF-β and daf-12 steroid hormone receptor pathways, but these pathways do not affect starvation survival (Kaplan et al. , 2015; Lee and Ashrafi, 2008). That is, the effects of daf-16 on developmental arrest and starvation resistance are distinct, and how daf-16 promotes starvation resistance is unknown. daf-16 also promotes longevity in fed adults (Kenyon et al. , 1993), and understanding how it does so has received considerable attention. A variety of studies have identified daf-16 target genes in the context of aging (Dong et al. , 2007; Kaletsky et al. , 2016; Lee et al. , 2003; Murphy et al. , 2003), resulting in identification of over 3000 genes affected directly or indirectly by daf-16 (Tepper et al. , 2013). However, these experiments typically examined the effect of constitutive daf-16 activation in fed daf-2/InsR mutant adults rather than conditional effects of daf-16 in response to nutrient availability. We examined the effect of daf-16 on gene expression in L1 larvae starved for ~12 hr (Kaplan et al. , 2015), but this is well after the starvation response is mounted (Baugh et al. , 2009), and this experiment did not include nutrient availability as a factor. Consequently, the immediate-early targets of daf-16 involved in the conditional response to starvation have not been identified. Metabolic adaptations in dauer larvae represent a ‘microaerobic’ metabolism, with reduced reliance on respiration and oxidative phosphorylation, instead oxidizing fatty acids as fuel for cellular maintenance (Braeckman, 2009; Burnell et al. , 2005; O' Riordan and Burnell, 1989; 1990; Wadsworth and Riddle, 1989). Expression analysis suggests that dauer larvae are metabolically similar to long-lived daf-2/InsR mutant adults, with expression of enzymes involved in the glyoxylate shunt (a","Most animals rarely have access to a constant supply of food, and so have evolved ways to cope with times of plenty and times of shortage. Insulin is a hormone that travels throughout the body to signal when an animal is well fed. Insulin signaling inhibits the activity of a protein called FoxO, which otherwise switches on and off hundreds of genes to control the starvation response. The roundworm, Caenorhabditis elegans, has been well studied in the laboratory, and often has to cope with starvation in the wild. These worms can pause their development if no food is available, or divert to a different developmental path if they anticipate that food will be short in future. As with more complex animals, the worm responds to starvation by reducing",380,128,0.3368
pubmed-summarization,"hr , 1 , 3 , 5 and 7 days of last drug application , in broilers . matrices were cleaned of blood and stored at 20c until the day of analysis by hplc . chromatographic conditions : the sulfa drug under investigation is separated on a sep column by isocratic elution using a mobile phase that consisted of acetonitrile - kh2po4 ( 13:87 ; v / v ) at a constant flow rate of 1.7 ml / min . the kh2po4 was of ph 7.4 , 0.01 m. the standards of sulphachloropyrazine and the tissue extracts were monitored at a wavelength of 270 nm . all analyses were performed at ambient temperature . the retention time of sulphachloropyrazine and dvd was about 10 min , similar to those in other studies . extraction procedure : frozen tissue samples were thawed to room temperature prior to extraction . 2.00 g of test minced tissue ( muscle , liver , kidney and skin with fat ) was transferred into a test - tube and mixed with 15 ml of acetonitrile . after homogenization and centrifugation for 2 min at 15,000 rpm , the samples were sonicated for 5 min and centrifuged at 5,000 rpm for 10 min . the upper supernatant layer was transferred into a clean tube , for mixed 30 sec in vortex with 15 ml of acetone and sonicated for 5 min . after third centrifugation for 3 min , the upper layer was combined and mixed with 5 ml of n - propanol . four ml of acetonitrile and 0.017 mol / l kh2po4 ( 32/68 ) were added and next shaken for 5 min . the same amount of n - hexane was added to wash the liquid by vortexing for 2 min and centrifuging for 10 min at 4,000 rpm . the lower liquid layer of 2 ml was added onto the mcx solid phase extraction column , which was balanced with 5 ml of methanol and 5 ml of hydrochloric acid in advance . after the liquid flow off , the column was washed with 2 ml of 0.1 mol / l hydrochloric acid , 2 ml of methanol and 10 ml of 10% ammoniation acetonitrile . the residue was dissolved with 1 ml","diaveridine ( dvd ) is used in combination with sulphachloropyrazine ( spz ) as an effective antibacterial agent and antiprotozoal agent , respectively , in humans and animals . to gain a better understanding of the metabolism of spz and dvd in the food - producing animals , a high performance liquid chromatography ( hplc ) method to determine and quantify sulphachloropyrazine ( spz ) and diaveridine ( dvd ) suspension residues from broilers is reported . thirty healthy chickens were orally administered with sulphachloropyrazine - diaveridine ( spz - dvd ) suspension in water of 300 mg / l ( spz ) per day for seven successive days . six chickens per day were slaughtered at 0 , 1 , 3 , 5 and 7 days after",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and sequesters the H4 tail under certain conditions (Hwang et al. , 2014). ISWI recognizes amino acids R17H18R19 within the H4 tail, which are part of a stretch of amino acids called basic patch (Fazzio et al. , 2005; Hamiche et al. , 2001; Clapier et al. , 2002). Notably, ISWI contains an identical motif, here called AutoN. Mutation of AutoN’s two arginines to alanines (referred to as 2RA) increased the DNA-stimulated ATPase activity and nucleosome sliding, and suppressed the dependence of ISWI’s ATPase and sliding activities on the H4 tail. According to the current model, AutoN directly binds to and blocks the H4-tail binding site, acting as a gatekeeper for the H4 tail. This model necessitates a conformational change of the NTR to allow binding of H4 (Hwang et al. , 2014; Clapier and Cairns, 2012). Indeed, a conformational change could be traced to AutoN upon nucleic acid binding (Mueller-Planitz et al. , 2013). Of note, the 2RA mutation diminished but did not abolish the H4-tail dependency, implicating also other regions in the H4 recognition process (Clapier and Cairns, 2012). The AutoN motif is embedded in a structurally and functionally poorly characterized domain referred to as the N-terminal region (NTR). Besides AutoN, the NTR contains additional motifs: an acidic region that we termed AcidicN, the ‘post-post-helicase-SANT-associated' (ppHSA) motif, so named because it follows the post-HSA motif in remodelers of the Snf2 family (Mueller-Planitz et al. , 2013; Szerlong et al. , 2008), and a weakly conserved AT-hook (Mueller-Planitz et al. , 2013; Aravind and Landsman, 1998). Their functions remain unknown. Here, we systematically interrogated the functions of all conserved motifs within the NTR by mutagenesis and a series of quantitative biochemical assays in vitro and in vivo. We paid particular attention to probe for possible crosstalk between these motifs and the H4 tail to understand its recognition process. Using protein crosslinking followed by mass spectrometry and protein structural modeling we obtained information about the general structural architecture of the NTR-ATPase module. With similar approaches, we mapped the H4-tail binding site. We interpret our results within a unified structural and functional framework for the combined inhibition of ISWI by the NTR and recognition of the histone H4 tail. Contrary to current models, we propose that AutoN does not occlude the","In the cells of animals, plants and other eukaryotes, DNA wraps tightly around proteins called histones to form structures known as nucleosomes that resemble beads on a string. When nucleosomes are sufficiently close to each other they interact and clump together, which compacts the DNA and prevents the genes in that stretch of DNA being activated. But how do cells mobilize their nucleosomes? A nucleosome remodeling enzyme called ISWI can slide nucleosomes along DNA. ISWI becomes active when it interacts with a ‘tail’ region of a histone protein called H4. However, the H4 tail prefers to interact with neighboring nucleosomes instead of with ISWI. Therefore when ISWI slides a nucleosome close to another one, the H4 tail of the nucleosome binds instead to its new neighbor so that",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Although seasonality is widespread and can cause fluctuations in the intensity and direction of natural selection, we have little information about the consequences of seasonal fitness trade-offs for population dynamics. Here we exposed populations of Drosophila melanogaster to repeated seasonal changes in resources across 58 generations and used experimental and mathematical approaches to investigate how viability selection on body size in the non-breeding season could affect demography. We show that opposing seasonal episodes of natural selection on body size interacted with both direct and delayed density dependence to cause populations to undergo predictable multigenerational density cycles. Our results provide evidence that seasonality can set the conditions for life-history trade-offs and density dependence, which can, in turn, interact to cause multigenerational population cycles. In many organisms, reproduction is confined to seasonal fluctuation in periods of high resource, in which both fecundity (reproduction) and viability (survival) selection can occur, and periods of low resources, when reproduction stops and natural selection occurs only through viability selection. Consequently, sequential episodes of reproduction and survival caused by seasonality could be a major source of fluctuations in the strength and direction of natural selection (Darwin, 1859; Lack, 1954; Fretwell, 1972; Schluter et al. , 1991; Bell, 2010; Bergland et al. , 2014), giving rise to classic life-history trade-offs (Lack, 1947; Roff, 1992; Stearns, 1992; Garland, 2014). More specifically, traits that confer a fecundity advantage, but which are associated with a survival cost, will experience natural selection in one season that is opposed by selection in the subsequent season (Levins, 1968; Michod, 2006; Bell, 2010; Bergland et al. , 2014). The sequential rather than simultaneous nature of trade-offs driven by seasonality could have important consequence for the trait distribution within and across generations (Levins, 1968; Grafen, 1988; Michod, 2006) and population dynamics (Ozgul et al. , 2010). One way by which life history trade-offs might arise from seasonal variation in resources is via body size (Ozgul et al. , 2010,2014). Large individuals usually have higher fecundity (Mueller and Joshi, 2000; Schulte-Hostedde and Millar, 2004), but they could also have lower survival during the non-breeding season when resources are scarce (Stockhoff, 1991; Reznick et al. , 2000; Munch et al. , 2003; Monaghan, 2008). In addition, large individuals might take more time to grow and require more resources","Many wild populations go through long cycles in abundance that span several generations. The traditional explanation for such “multigenerational” cycles is that they are driven by predator/prey relationships, the classic example being oscillations between the numbers of lynx and snowshoe hares. Population cycles could also be driven by seasonal changes. For example, traits that help animals to produce large numbers of offspring during the breeding season may reduce the ability of the animal to survive the non-breeding season. Body size is one such trait. Large individuals tend to produce more offspring, but their larger body size means that they find it harder to survive when food is scarce. As a consequence, large individuals should have an advantage and be more common when the population size is low and",380,128,0.3368
dialogsum,"#Person1#: Okay, here are the graphs and figures for this month's sales. Let's review them all together. #Person2#: This first one, I have a question. . . This graph is marking the sales performance for our line of hair products, right? Can this line be right? It looks like our sales plummeted. I can't believe we did that poorly. . . If I remember correctly, sales went down slightly, but not as dramatically as the graph shows. #Person1#: I think you are looking at the wrong line. The rapid drop in sales wasn't our hair products. You are correct, the hair product sales decreased slightly, but not dramatically. The one that didn't do so hot this month was the cleaning products. I think there was a problem in the marketing plan. Some people were offended by our advertisements for the cleaning products, but it was already too late to mitigate the damage, so our mistake shows up in the sales. #Person2#: Well, the good news is the new industrial cleaning products really took off. Look how the sales have shot up over the last two weeks. #Person1#: That is our one major success. If you look at the other graphs, you can see that most of the other product lines remained steady with little increase. #Person2#: At lease they stayed the same. That's better than dropping.",#Person1# and #Person2# are reviewing the graphs and figures for this month's sales and analyzing aspects of success and failure.,226,20,0.0885
scientific_lay_summarisation-elife-norm,"Frogs in the secondarily aquatic genus Xenopus (Evans et al. , 2015) present an informative system for addressing these questions. In Xenopus, social communication is dominated by vocal signaling (Kelley et al. , 2017). Males in each species produce distinctive advertisement calls underwater whose acoustic features inform species identity (Evans et al. , 2015). These calls consist of a series of sound pulses that form species-typical temporal patterns and characteristically include two dominant frequencies (DFs) (Hall et al. , 2013; Tobias et al. , 2011). The sound pulses that comprise Xenopus calls are produced in the larynx, (Tobias and Kelley, 1987) a vocal organ interposed between the nasal and buccal cavities and the lungs (1A). Vocal folds are absent (Ridewood, 1897) and a separate glottis gates air flow to and from the lungs (Brett and Shelton, 1979). The larynx consists of a cricoid frame or ‘box’ of hyaline cartilage flanked bilaterally by bipennate muscles. These insert anteriorly, via a tendon, onto paired, closely apposed arytenoid cartilage discs (1B; — 1) whose medial faces are coated by mucopolysaccharide secreted by adjacent cells (Yager, 1992). The discs are suspended in elastic tissue composed of elastic cartilage and elastin fibrils (— 1) (Yager, 1992). Electrical stimulation of laryngeal muscles or nerves results in species-specific sound pulses, both in situ and ex vivo (Yager, 1992; Tobias and Kelley, 1987). Sound is thus produced without air flow or vocal folds. In X. borealis, separations of the paired arytenoid discs accompany sound pulses, (Yager, 1992) but how disc motion results in sound production has not been resolved. An unusual mechanism – implosion of air bubbles or cavitation (Yager, 1992) - is the currently accepted (Irisarri et al. , 2011; Ladich and Winkler, 2017) hypothesis for underwater laryngeal sound production in Xenopus. In this scenario, the high velocity separation of the arytenoid discs causes formation of bubbles that then implode and produce sounds. Cavitation bubbles are known to produce hydrodynamic propeller noise (Carlton, 2012) and the ‘snaps’ of some species of shrimp (Versluis et al. , 2000). However, a priori cavitation - creating"" a bubble between the discs at a pressure below ambient … that … implodes as air rushes into the cleft at high speeds, producing a click"" (Yager, 1992) - seems an unlikely cause of","The voice is a unique characteristic that we use to identify one another – including someone' s sex, age and mood. We speak by using air flow to vibrate our vocal folds, commonly known as vocal cords. The land-living ancestors of the African clawed frog Xenopus also used breath and vocal cords to communicate, but they returned to aquatic life 180 million years ago and had to evolve a different way to create sounds. Today’s Xenopus live in water and use a new mechanism that lets them sing for hours underwater without coming up to breathe. Males from each major group of Xenopus species produce courtship songs with harmonic intervals corresponding to an octave, a perfect fourth, or a major or minor third. Today' s Xenopus species do",380,128,0.3368
pubmed-summarization,"this study combines four coordinated protocols sharing the same dias artificial pancreas technology conducted at the universities of padova ( italy ) and montpellier ( france ) , the university of virginia ( uva ) , and the sansum diabetes research institute , santa barbara , california . to test whether a smart phone is capable of running outpatient closed - loop control , we have configured a system comprising available components , which were linked as follows : cgm idex dias ( running all closed - loop computations , user interface , and communications to peripheral devices ) idex pump . the idex is an experimental device manufactured by insulet ( bedford , ma ) , which combines a dexcom seven plus receiver and omnipod insulin pump . in addition , dias transferred data in real time to a central location allowing remote monitoring of patient state and system functions . the primary engineering end point was the percent time with all system communications working properly ; the protocol criterion for success in this early feasibility study was this time reaching > 80% of the total time of investigation . secondary end points included the estimation of the failure rates of system components , frequency analysis of lost or inaccurate cgm records , and control algorithm performance . the clinical goal was to assess patients and clinicians subjective impressions of the system , i.e. , the feasibility of its ambulatory use , including patient usability and wearability . a total of 20 adults ( age 2165 years ) with type 1 diabetes were studied ( 5 subjects at each site ) . before the tests , a pilot subject was performed in italy , france , and in the united states . all participants were experienced insulin pump users and were required to have the following : prestudy hba1c of 69% ; predefined insulin pump parameters for basal rates , carbohydrate ratios , and insulin sensitivity factors ; and proper mental status / cognition . the exclusion criteria were directed toward safety and included recent history of diabetic ketoacidosis or severe hypoglycemia , pregnancy , breastfeeding , or intention of becoming pregnant ( females ) , uncontrolled arterial hypertension , and conditions that may increase the risk of hypoglycemia","objectiveto evaluate the feasibility of a wearable artificial pancreas system , the diabetes assistant ( dias ) , which uses a smart phone as a closed - loop control platform.research design and methodstwenty patients with type 1 diabetes were enrolled at the universities of padova , montpellier , and virginia and at sansum diabetes research institute . each trial continued for 42 h. the united states studies were conducted entirely in outpatient setting ( e.g. , hotel or guest house ) ; studies in italy and france were hybrid hospital hotel admissions . a continuous glucose monitoring / pump system ( dexcom seven plus / omnipod ) was placed on the subject and was connected to dias . the patient operated the system via the dias user interface",380,128,0.3368
dialogsum,"#Person1#: The trouble is not that. It is that he may suddenly remember something I promised him a couple of weeks ago, out of a clear blue sky. Then he complains that I have gone back on my words. #Person2#: Does he do that with his Dad? I mean, does he complain things to his father? #Person1#: He never does, and in fact, he seldom communicates with him. #Person2#: But didn't you say that his Dad takes him under his wings? #Person1#: Yes, I did. He only takes side with him. He seldom asks what Dick is doing.",#Person1# complains to #Person2# that the man will accuse #Person1# of breaking promises and takes side with the man's dad.,98,20,0.2041
dialogsum,"#Person1#: Could you please help me to check out the book? #Person2#: Sure, what's the author's name, please. #Person1#: I can't remember that clearly. It probably be Charles... #Person2#: Charles Dickens? #Person1#: No, no, no. I'm not interested in literature. #Person2#: OK, do you know the title of the book? #Person1#: Oh, sorry. I'm always absent-minded. I remember that I've put a note in my pocket. #Person2#: So, show me the note please. #Person1#: I can't find it now. #Person2#: Oh, such bad luck, sir. Can you please name the category of the book? #Person1#: Let me see. It's not fiction. It's biography. #Person2#: OK, I'll search it for you. A moment, please. #Person1#: Thanks.",#Person2#'s helping #Person1# check out a biography which #Person1# cannot remember the title and the author.,115,16,0.1391
dialogsum,"#Person1#: Hello, Pam. #Person2#: I'm glad that you can make it. #Person1#: It looks like there are a lot of people inside. #Person2#: Yeah. I've invited a lot of friends besides you. #Person1#: Should I take my shoes off? #Person2#: We all keep our shoes on indoors. #Person1#: Where are your parents? #Person2#: They've gone out so that we could have the house to ourselves. #Person1#: That's great!",Pam has invited lots of friends including #Person1#. Pam's parents are out so they could have the whole house.,68,19,0.2794
dialogsum,"#Person1#: Hello. I need to disconnect my phone, please. #Person2#: All right. Where do you live, sir? #Person1#: At 345 Lincoln Avenue. Oklahoma City. #Person2#: Very well. Why do you want to disconnect your phone, sir? #Person1#: I'm moving to a new home. #Person2#: O. K. May I have your name please? #Person1#: John Smith. #Person2#: Thank you. Mr. Smith. What's your telephone number? #Person1#: 555-7658 #Person2#: Thank you. Where should I send your final phone bill? #Person1#: 623 West Side Drive. New York, New York. #Person2#: Thank you, Mr. Smith. Your phone will be disconnected after this phone call. Have a nice day. #Person1#: Thank you, you too.",Mr. Smith wants to disconnect his phone because he is moving to a new home. #Person2# helps and asks for some information.,109,22,0.2018
scientific_lay_summarisation-elife-norm,"(E) Activation of basal ATPase activity by EMD 57033. The observed turnover of ATP is 1. 4-fold (Dd myosin-2) and 1. 5-fold (β-cardiac myosin) higher than expected for preparations of 100% active protein (dashed line). (F) EMD 57033-mediated activation of motor activity. The histograms and Gaussian fits show the distribution and average sliding velocity of actin filaments on lawns of β-cardiac myosin in the absence (blue histograms) and presence of EMD 57033 (orange histograms). Errors indicate SD (G) EMD 57033-mediated increase in force production. A constant frictional load of 8 µg/ml α-actinin was applied to stall β-cardiac myosin-based motility in the absence of EMD 57033. Filament movement is restarted after the addition of EMD 57033. Errors indicate SD. : http: //dx. . org/10. 7554/eLife. 01603. 00310. 7554/eLife. 01603. 004Figure 1— 1. EMD 57033-mediated activation of motor activity for a recombinant Dd myosin-2 motor domain construct. The histograms and Gaussian fits show the distribution and average sliding velocity of actin filaments on lawns of Dd myosin-2 motor (blue histograms). In the presence of EMD 57033 (100 µM, orange histograms) the sliding velocity is increased from 0. 86 ± 0. 15 µm s−1 to 1. 35 ± 0. 2 µm s−1. Errors indicate SD. : http: //dx. . org/10. 7554/eLife. 01603. 00410. 7554/eLife. 01603. 005Figure 1— 2. Frictional loading experiments. Faster filament movment is observed in the presence of EMD 57033 and higher concentrations of α-actinin are required to stall filament movement on surfaces decorated with β-cardiac myosin. Errors indicate SD. : http: //dx. . org/10. 7554/eLife. 01603. 00510. 7554/eLife. 01603. 006Table 1. Interaction of EMD 57033 with myosin isoformsDOI: http: //dx. . org/10. 7554/eLife. 01603. 006Myosin constructAC50 ATPaseNormalized maximal ATPase activation (basal) Normalized maximal ATPase activation (with 30 µM actin) Binding affinity (MST) β-Cardiac myosin-2 (S1, full-length) 7. 0 µM1. 52. 57. 3 µMSkeletal muscle myosin-2 (HMM) 15. 1 µM1. 62. 2–Dd myosin-2 motor domain25. 8 µM1. 42. 823. 0 µMDd myosin-5b motor domain35. 4 µM1. 41. 6–Dd myosin-1B, -1C, -1D, -1E motor domainsn. a. no effectno binding (myosin-1C/-1D/-1E) Dd myosin-2 ΔSH3 22 (lacks residues 33–79) n. a. no effectn. a. The number of experimentally accessible active sites is always smaller in preparations of purified enzymes than the number of active sites calculated based on protein concentration. The observed deviation results","Our muscles contain large numbers of ‘motor proteins’ called myosins. To contract a muscle, many myosin molecules expend energy to ‘walk’ along a filament made from another molecule, called actin, and generate a pulling force. Like other proteins, myosins must fold into the correct shape to work, but high temperatures or other types of stress can disrupt their ability to adopt or maintain the correct shape. Misfolding of myosins, for example, can result in muscular diseases, including those that affect the heart; so there is an ongoing effort to find compounds that can stabilize protein folding and treat these diseases. The small molecule EMD 57033 was discovered over 20 years ago, and its ability to increase the strength of muscle contractions suggested that it could be used to",380,128,0.3368
pubmed-summarization,"large number of human diseases including cancers , cardiovascular diseases , diabetes and complications , as well as bipolar disorder , pkc is widely studied as a model for conventional pkcs ( cpkcs : , i , ii , and isoforms ) for understanding how c1 domains regulate signaling proteins . similar to other cpkcs , pkc possesses two tandem c1 domains , namely , c1a and c1b , in addition to a c2 targeting domain and a c - terminal kinase domain . the evidence shows that a mature pkc in its compact inactive state is activated via sequential binding of individual domains to the plasma membrane surface . at first , calcium triggers c2 domain binding to anionic lipids and the entire pkc protein is directed to the membrane . dissociating from the kinase domain , the inhibitory c1a and c1b domains are then recruited to the membrane to bind lipid coactivators ( such as ps ) and activators ( such as dag and pma ) . this process results in an activated pkc , which catalyzes the phosphorylation of substrate proteins . significant recent progress highlights the importance of the two c1 domains in the activation mechanism , and the need for further computational and experimental efforts are required to better understand the membrane interactions of these domains . a growing body of experimental evidence suggests that the two c1 domains in cpkcs are not equivalent , but the molecular basis for this nonequivalence is only partly understood . for example , although both c1 domains are thought to interact with membranes , some evidence suggests that only one of the two cpkc c1 domains can bind to a lipid activator . other results suggest that , in the case of pkc , both domains bind to activators yet with opposite affinities . it is generally believed that the pkc c1a domain has a higher affinity for dag than the c1b domain , while the latter has a higher affinity for pma . regarding mutations of equivalent or ionic residues , more pronounced impacts appeared in the c1a domain than in the c1b domain on pkc membrane binding and activation . lastly , in the cpkc activation mechanism , recent work indicate that c1a stabilizes the predominant","protein kinase c- ( pkc ) has been studied widely as a paradigm for conventional pkcs , with two c1 domains ( c1a and c1b ) being important for the regulation and function of the kinase . however , it is challenging to explore these domains in membrane - bound environments with either simulations or experiments alone . in this work , we have combined modeling , simulations , and experiments to understand the molecular basis of the pkc c1a and c1b domain interactions with membranes . our atomistic simulations of the pkc c1 domains reveal the dynamic interactions of the proteins with anionic lipids , as well as the conserved hydrogen bonds and the distinct nonpolar contacts formed with lipid activators . corroborating evidence is obtained from",380,128,0.3368
pubmed-summarization,"malignant glaucoma is a rare but serious condition of secondary angle closure mostly seen after filtration surgery , but it may also occur spontaneously.1 it has also been described after laser iridotomy,2 laser capsulotomy,3 cataract surgery,4 topical miotic therapy,5 and blunt trauma.6 some basic mechanisms of ciliolenticular block glaucoma are poorly understood . lens disproportion and lens ciliary body apposition in small eyes and anterior hyaloid changes with increased hydraulic resistance are supposed to be major pathophysiological factors.7 besides these factors , poor vitreous flow and a tendency towards expansion of the choroidal volume in small eyes with angle closure refractory to iridotomy are further possible mechanisms of malignant glaucoma as proposed by quigley et al.8 these features lead to aqueous misdirection into the vitreous cavity restricted by the anterior hyaloid membrane and additional forward movement of the lens iris diaphragm.9,10 it is clinically characterized by an axial shallowing of the anterior chamber in the absence of a pupillary block mechanism , choroidal effusion , or hemorrhage , despite the presence of a patent iridectomy.11 intraocular pressure ( iop ) is usually dramatically increased , but may also be within the normal range.12 treatment of malignant glaucoma should be done stepwise . medical treatment includes topical antiglaucomatous medication , cycloplegic agents , aqueous suppressants , systemic carbonic anhydrase inhibitors , and hyperosmotic drugs inducing a posterior movement of the lens iris diaphragm , reducing production of aqueous humor , and dehydrating the vitreous volume.13 the performance of laser capsulotomy,14 or laser anterior hyaloidectomy,15 and argon laser of ciliary processes through a peripheral iridectomy16 to relieve the ciliolenticular block are recommended for unsuccessful medical treatment . when medical and laser treatment failed , surgery should be performed to interrupt the ciliolenticular block . pars plana vitrectomy in pseudophakic eyes or combined vitrectomy and cataract surgery in phakic eyes are effective methods to allow aqueous outflow into the anterior chamber.17,18 apart from anterior vitrectomy alone or in combination with phacoemulsification1719 or trabeculectomy20 via a posterior approach ( pars plana ) , a procedure called zonulo - hyaloido - vitrectomy through a peripheral iridectomy or iridotomy via the anterior chamber was described by lois et al in 2001.21 due to the difficulty in visualization of the anterior hyaloid membrane in phakic eyes and","purposeto assess the outcomes of pars plana vitrectomy for the treatment of malignant glaucoma in patients with and without previous filtration surgery.patients and methodsdata of 15 patients developing malignant glaucoma after trabeculectomy ( 60% ) or following ophthalmic interventions other than filtration surgery ( 40% ) were recorded retrospectively . pars plana vitrectomy was performed in case of failed medical or laser treatment recreating the normal pathway of aqueous humor . the main outcome measures were the postoperative intraocular pressure ( iop ) , the frequency of complications , and success rate based on the following criteria : iop reduction by 20% and to 21 mmhg ( definition one ) or an iop < 18 mmhg ( definition two ) with ( qualified success ) and without (",380,128,0.3368
dialogsum,"#Person1#: Jane, pleases come with us. #Person2#: I cannot dance, you know. I have't such a talent. #Person1#: Just for fun, not for showing. What do you worry about? #Person2#: Nothing. I have told you before that I won't go to the party and that's flat. #Person1#: But. . . OK.",Jane refuses #Person1#'s invitation to dance because she won't go to the party.,51,13,0.2549
scientific_lay_summarisation-elife-norm,"animal to choose one of two targets while still unsure about the correct choice (Coallier et al. , 2015; Thura and Cisek, 2014), which results in decisions that are made despite a lingering uncertainty. Studies of reach-related brain areas during target selection tasks have suggested that the dorsal premotor cortex (PMd) plays a significant role in sensorimotor decision-making. Historically, PMd has been viewed as a movement planning area, displaying activity consistent with a representation of upcoming movements to visual targets (Cisek et al. , 2003; Shen and Alexander, 1997; Weinrich and Wise, 1982). Later studies showed that these pre-movement representations can include multiple simultaneous potential targets (Cisek and Kalaska, 2005) and reflect motor plans even in the absence of visual targets (Klaes et al. , 2011). Furthermore, the representations during multiple-target tasks are modulated by decision-related variables (Coallier et al. , 2015; Pastor-Bernier and Cisek, 2011). These more recent results are consistent with an interpretation that activity in PMd modulates with the complexity (or uncertainty) of a motor decision. In general, sensorimotor decision-making should take into account the uncertainty present in all task-relevant information sources – namely the current sensation and prior experience. When sensation provides a highly reliable action cue (e. g. , when reaching toward a well-lit, foveated object), it can be used exclusively to plan and execute the appropriate motor output. However, as uncertainty in sensation increases, it becomes more beneficial to combine sensory information with information learned through prior experience. The optimal method for integrating sensory and prior information was formulated centuries ago as Bayes’ theorem (Bayes and Price, 1763). A direct application of Bayes’ theorem states that cues should be weighted in inverse proportion to their variance (Knill and Saunders, 2003; Körding and Wolpert, 2006). The Bayes optimal decision will lead to better results than either cue alone, but will still contain a degree of uncertainty. Bayesian models have been used to describe human behavior in a wide array of psychophysical studies, including visual (Knill and Saunders, 2003; Mamassian and Landy, 2001; Weiss et al. , 2002), auditory (Battaglia et al. , 2003), somatosensory (Goldreich, 2007), cross-modal (Alais and Burr, 2004; Ernst and Banks, 2002; Gu et al. , 2008; Rowland et al. , 2007), and sensorimotor (Greenwald and Knill, 2009; Körding and Wolpert, 2004;","Whether it is trying to find the light switch in a dimly lit room or reaching for your glasses when you wake in the morning, we often need to reach toward objects that we cannot see clearly. In these situations, we plan our movements based both on the limited sensory information that is available, as well as what we have learned from similar situations in the past. The brain areas involved in using information to decide on the best movement plan appear to be different from those involved in actually executing that plan. One area in particular, called the dorsal premotor cortex (or PMd), is thought to help a person decide where to reach when they are presented with two or more alternative targets. However, it was not",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel ‘ratio’ model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1616 children (median age 4. 3 years at ART initiation) and 14,542 adults (median age 36 years at ART initiation). We found that the scaled carrying capacity, maximum CD4+ count relative to an HIV-negative individual of similar age, and baseline scaled CD4+ counts were closer to healthy values in children than in adults. Post-ART initiation, CD4+ growth rate was inversely correlated with baseline CD4+ T-cell counts, and consequently higher in adults than children. Our results highlight the impacts of age on dynamics of the immune system of healthy and HIV-infected individuals. The key outcome variable is scaled CD4+ T-cell count. In both infected adults and children, the cell counts post-ART initiation were scaled by reference values from healthy populations, to obtain the outcome variable. For HIV-infected children these reference values were calculated from the cross-sectional data (see description in Appendix 1) of healthy children at specific ages, due to the large variability in CD4+ T-cell counts in the early years of life. For the reference values by age, a single exponential model was fitted to the healthy children’s cross-sectional data and continuous population estimates were simulated (see Appendix 1—table 1 and Appendix 1—). These were within the normal CD4+ T-cell counts ranges published in South Africa (Lawrie et al. , 2009; Lawrie et al. , 2015) and elsewhere (Idigbe et al. , 2010; Pediatric AIDS Clinical Trials Group et al. , 2003). We then scaled all HIV-infected children’s CD4+ T-cell counts as follows: (8) zi, ja=xi, jay (a), 1≤i ≤N, 0 ≤j ≤ ni, 0 ≤a ≤ 203, where zi, j is the scaled CD4+ T-cell counts of patient i of age a (in months) at time j (measured as time since ART initiation); xi, j is the CD4+ T-cell counts of an HIV-infected child i of age a and y (a) is the CD4+ T-cell counts of a healthy child of similar age a as patient i. Scaling CD4+","The human immunodeficiency virus (HIV) remains an ongoing global pandemic. There is currently no cure for HIV, but antiretroviral therapies can keep the virus in check and allow individuals with HIV to live longer, healthier lives. These drugs work in two ways. They block the ability of the virus to multiply and they allow numbers of an important type of infection-fighting cell called CD4+ T cells to rebound. As more patients with HIV survive and transition from one life stage to the next, it is critical to understand how long-term antiretroviral therapies will affect normal age-related changes in their immune systems. The health of an immune system can be evaluated by looking at the number of CD4+ T cells an individual has, though this will vary by age",380,128,0.3368
dialogsum,"#Person1#: Can I help you, sir? #Person2#: Yes, I want to book a plane ticket from Beijing to Shanghai. #Person1#: OK. Which day do you want to book? #Person2#: The day after tomorrow. #Person1#: Which flight do you want? #Person2#: I'd prefer a morning flight. #Person1#: What about Flight 516? #Person2#: Book it for me, please. How much should I pay? #Person1#: 1 500 yuan. How will you pay for this, sir? #Person2#: Credit card. #Person1#: OK. Here's your ticket. #Person2#: Thank you.",#Person1# helps #Person2# to book a flight from Beijing to Shanghai. #Person2# pays by card.,83,15,0.1807
dialogsum,"#Person1#: I'm searching for an old music box. #Person2#: You came to the right place. Any particular decade? #Person1#: If you had a box made in the 20's, that would be nice. #Person2#: We just got one in yesterday, so now we have six. #Person1#: Would any of them have dancing figures? #Person2#: Yes, we still have two boxes left that have dancing figures. #Person1#: Oh, they're both so beautiful. Let me have this one, I think. #Person2#: That one truly is a beautiful piece of work, isn't it? #Person1#: One last question #Person2#: Oh, no. Everything we sell here is ' as is. ' #Person1#: I guess I was asking for too much. #Person2#: If it breaks down, maybe you can find a repairman on the Internet.",#Person1# comes to #Person2#'s store to buy a 20's music box with dancing figures. #Person2# tells #Person2# where to fix it if it breaks down.,128,25,0.1953
dialogsum,"#Person1#: How are your French lessons going? #Person2#: Well, I'm no longer taking French lessons. #Person1#: Are you kidding? You told me you made up your mind to study French well this summer. Didn't you sign up for the four-week course? #Person2#: I did. But the teacher told me not to come back any more after only one week and he returned my money for the remaining three weeks. #Person1#: How come? I've never heard of a case like that before. Did you have a quarrel with your teacher? #Person2#: Of course not. At first everything went well and he was satisfied with me. But he got angry after I broke the class rules several times. #Person1#: It was your fault, I think. You'd gone too far. #Person2#: Perhaps. But I don't understand why he told me to stop coming. He was very kind, you know. #Person1#: Just forget it.",#Person2# is no longer taking French lessons because #Person2# has been kicked out for broking the class rules several times. #Person1# comforts #Person2#.,150,23,0.1533
scientific_lay_summarisation-elife-norm,"Negative-strand RNA viruses condense their genome into helical nucleocapsids that constitute essential templates for viral replication and transcription. The intrinsic flexibility of nucleocapsids usually prevents their full-length structural characterisation at high resolution. Here, we describe purification of full-length recombinant metastable helical nucleocapsid of Hantaan virus (Hantaviridae family, Bunyavirales order) and determine its structure at 3. 3 Å resolution by cryo-electron microscopy. The structure reveals the mechanisms of helical multimerisation via sub-domain exchanges between protomers and highlights nucleotide positions in a continuous positively charged groove compatible with viral genome binding. It uncovers key sites for future structure-based design of antivirals that are currently lacking to counteract life-threatening hantavirus infections. The structure also suggests a model of nucleoprotein-polymerase interaction that would enable replication and transcription solely upon local disruption of the nucleocapsid. The Bunyavirales order is one of the largest groups of segmented negative-strand RNA viruses (sNSV) that include many pathogenic strains (Sun et al. , 2018). In particular, the Hantaviridae family comprises the virus Hantaan (HTNV) that gives rise to haemorrhagic fevers with renal syndrome and the virus Sin Nombre that is linked to severe pulmonary illnesses with fatality rates up to 40%. Neither treatment nor vaccine is currently available to counteract them. The Bunyavirales genome is usually divided into three RNA segments enwrapped by the viral nucleoproteins (NP). The resulting nucleocapsids (NCs) protect the genome and serve as a replication/transcription template for the viral polymerase (Reuter and Krüger, 2018). They coat the genomic and anti-genomic RNA during replication but not the mRNA produced by transcription. As they are specific and essential to the viral cycle, NCs constitute an attractive potential target for antiviral drugs. Nucleoproteins of segmented NSV (sNSV) present a large diversity of folds (Sun et al. , 2018). Most of the available structures have been determined as rings and monomers that present the advantage of being rigid enough for crystallisation. However, the relevant conformations of assembled NPs in the viral context correspond to flexible helices or pearl-necklaces that encapsulate long RNA segments. Helical crystal structures of La Crosse virus NP (Peribunyaviridae, LACV) (Reguera et al. , 2013) and Crimean Congo Fever Virus NP (Nairoviridae, CCFHV) (Wang et al. , 2012) have been determined but they correspond to local organisations of pearl-necklace-like native NCs. Influenza double-helical NCs 3D structures","Rats and mice sometimes transmit hantaviruses, a family of microbes that can cause deadly human diseases. For example, the Hantaan virus leads to haemorrhagic fevers that are potentially fatal. There are no vaccine or even drugs against these infections. To multiply, viruses must insert their genetic material inside a cell. While the body often detects and destroys foreign genetic information, hantaviruses can still evade our defences. Molecules called nucleoproteins bind to the viral genome, hiding it away in long helices called nucleocapsids. When the virus needs to replicate, an enzyme opens up the nucleocapsid, reads and copies the genetic code, and then closes the helix. Yet, researchers know little about the details of this process, or even the structure of the nucleocapsid. Here, Arragain et al. use a",380,128,0.3368
pubmed-summarization,"k score above 2411 , could maintain an independent sitting posture without support . two of the cp children were subsequently excluded because they refused to participate in this experiment . all parents of the enrolled participants provided their written informed consent to their children s participation prior to this experiment , in accordance with the ethical principles established in the declaration of helsinki . as a result of the exclusion , this study used two school chairs mounted on a force platform to assess the quiet - sitting pressure distribution of the subjects . fsa seating assessment ( canada ) the acquisition frequency was set at 5 hz . the stated working range of the device is 0200 mmhg , with a resolution of 1 mmhg . the system was also calibrated to assign absolute pressure values to the digital output from an a / d converter connected to the sensing pad . this was done by applying a pressure distribution as similar to actual conditions as possible . then thus subjects sat on one of two school chairs according to their height . the chairs were those generally used in school . for research purposes , this study used two basic school chair because students spend a long time of day - to - day sitting on them . one chair had a 40 cm floor to seat height , a 35 cm seat depth , and a 32 cm seat width and is designed for 122.4133.5 cm height of subjects . the another had a 35 cm floor to seat height , a 38 cm seat depth , and a 35 cm seat width , and is designed for 133.6152.7 cm height of subjects . it has been used for the posture symmetry in other study13 statistical analyses were performed using pasw 18.0 . descriptive statistics were calculated ( frequency , mean , standard deviation , range ) . the mann - whitney u - tests and wilcoxon s signed rank tests were used to analyze differences between the groups and differences in lesion side , respectively . the si of the age matched td group was employed as the normal criteria . table 1table 1.general characteristics of the subjectscerebral palsygroup ( n=10)typicaldevelopmentalgroup ( n=10)age ( years)8.040.827.840.94gender",[ purpose ] the purpose of this study was to investigate the differences in symmetry of sitting posture between typical developmental ( td ) children and hemi - cerebral palsy ( cp ) children . [ subjects and methods ] a school chair mounted on a force platform was used to assess the quiet - sitting pressure distribution of 10 td and 10 cp children . [ results ] the symmetry index of the td children was significantly closer to zero than that of the cp children irrespective of the latter group s hemiparetic side . [ conclusions ] sitting posture on school chairs of cp children was more asymmetrical than that of td children .,380,116,0.3053
scientific_lay_summarisation-elife-norm,"Mycobacterium tuberculosis (Mtb) expresses a broad-spectrum β-lactamase (BlaC) that mediates resistance to one of the highly effective antibacterials, β-lactams. Nonetheless, β-lactams showed mycobactericidal activity in combination with β-lactamase inhibitor, clavulanate (Clav). However, the mechanistic aspects of how Mtb responds to β-lactams such as Amoxicillin in combination with Clav (referred as Augmentin [AG]) are not clear. Here, we identified cytoplasmic redox potential and intracellular redox sensor, WhiB4, as key determinants of mycobacterial resistance against AG. Using computer-based, biochemical, redox-biosensor, and genetic strategies, we uncovered a functional linkage between specific determinants of β-lactam resistance (e. g. β-lactamase) and redox potential in Mtb. We also describe the role of WhiB4 in coordinating the activity of β-lactamase in a redox-dependent manner to tolerate AG. Disruption of WhiB4 enhances AG tolerance, whereas overexpression potentiates AG activity against drug-resistant Mtb. Our findings suggest that AG can be exploited to diminish drug-resistance in Mtb through redox-based interventions. Mycobacterium tuberculosis (Mtb) displays tolerance to several clinically important antibacterials such as aminoglycosides and β-lactams (Flores et al. , 2005a; Morris et al. , 2005). Innate resistance of Mtb toward β-lactams is likely to be due to the presence of a broad-spectrum Ambler class A β-lactamase (BlaC) (Flores et al. , 2005b). Other physiological mechanisms such as cell envelope permeability, induction of drug efflux pumps, and variations in peptidoglycan (PG) biosynthetic enzymes may also play a role in the β-lactam-resistance of Mtb (Gupta et al. , 2010; Lun et al. , 2014). The Ambler class A β-lactamases are mostly susceptible to inhibition by clavulanate (Clav), sulbactam (Sub), and tazobactam (Taz) (Kurz et al. , 2013). Indeed, intrinsic resistance of Mtb toward β-lactams can be overcome by combining β-lactams with Clav (Chambers et al. , 1998; Hugonnet et al. , 2009). The combined amoxicillin (Amox) and Clav preparation, referred to as Augmentin (AG), was not only active against Mtb in vitro, but also had significant early bactericidal activity in patients with drug-resistant TB (Chambers et al. , 1998; Cynamon and Palmer, 1983). Furthermore, a combination of meropenem and Clav showed significant bactericidal activity against drug-resistant strains of Mtb (Hugonnet et al. , 2009). In view of this, there is an imminent need to investigate the mechanisms of action of β-lactams in combination with Clav against Mtb, and the potential development of","A bacterium called Mycobacterium tuberculosis causes tuberculosis in humans. Multiple antibiotics are available to treat this infection, yet around one million people still die from tuberculosis each year. One of the reasons that the number of deaths is so high is because many M. tuberculosis cells have become resistant to these drugs. Therefore, new drug treatments are urgently needed to tackle the disease. When cells are under stress – for example, when a bacterial cell is exposed to an antibiotic – they can increase the production of chemicals known as reactive oxygen species. These chemicals are vital to many processes in cells, but if their levels get too high they can kill cells by damaging DNA and other molecules. To prevent this damage, bacterial cells produce molecules, such",380,128,0.3368
dialogsum,"#Person1#: Hello. What can I do for you today? #Person2#: I've got some documents here that go with the L / C our company opened 10 days ago. I think there is something wrong. #Person1#: Really? Have you checked everything carefully? #Person2#: Very carefully, that's when I found the problem. #Person1#: Ah, I see. The goods description is totally different from what you are expecting, right? #Person2#: Yep, you've got it! What should we do? #Person1#: Usually, if the problem is insignificant I advise the customer to go ahead ; it's normally a translation problem or something like that. But this does seem a little more serious. I suggest you get back on to them right now and ask them about it. Hopefully you can sort it out over the phone. #Person2#: That's a great idea ; thanks for your help.","Something's wrong with #Person2#'s company's L/C, and the goods description is different from what #Person2#'s expecting. #Person1# suggests going back to them and asking about it.",141,26,0.1844
scientific_lay_summarisation-elife-norm,"The embryonic mouse lung is a widely used substitute for human lung development. For example, attempts to differentiate human pluripotent stem cells to lung epithelium rely on passing through progenitor states that have only been described in mouse. The tip epithelium of the branching mouse lung is a multipotent progenitor pool that self-renews and produces differentiating descendants. We hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining morphology, gene expression and in vitro self-renewal and differentiation capacity of human tips. These experiments confirm that human and mouse tips are analogous and identify signalling pathways that are sufficient for long-term self-renewal of human tips as differentiation-competent organoids. Moreover, we identify mouse-human differences, including markers that define progenitor states and signalling requirements for long-term self-renewal. Our organoid system provides a genetically-tractable tool that will allow these human-specific features of lung development to be investigated. During mouse lung development the distal tip epithelial cells are SOX9+, ID2+ and function as multipotent progenitors producing first bronchiolar, and then alveolar, descendants (Alanis et al. , 2014; Rawlins et al. , 2009). Between ~E10–15 cells that exit the distal tip turn off SOX9, upregulate SOX2 and differentiate along bronchiolar lineages. Whereas, ~E16–18 cells exiting the tip turn off SOX9 and co-express markers of alveolar type 1 (AT1) and alveolar type 2 (AT2) fate. As morphogenesis proceeds these bipotent cells line developing alveolar sacs and differentiate as mature AT1 or AT2 cells (Desai et al. , 2014; Treutlein et al. , 2014). Many factors controlling self-renewal and differentiation in the developing mouse lung epithelium have been identified. By contrast, relatively little is known about human lung development. This is largely due to practical considerations about tissue availability and culture system limitations (Benlhabib et al. , 2015; Haitchi et al. , 2009; Rajatapiti et al. , 2010). A small number of human studies show the detailed expression of specific genes (Al Alam et al. , 2015; Gonzalez et al. , 1996; Khoor et al. , 1993, Khoor et al. , 1994; Laresgoiti et al. , 2016; Stahlman et al. , 2007; Zhang et al. , 2012). Whereas, transcriptomics has provided a genome-wide view of human lung developmental transitions, but currently lacks cellular resolution (Feng et al. , 2014; Kho et","Degenerative lung disease occurs when the structure of the lungs breaks down, which makes it harder to get enough oxygen into the bloodstream. Most, but not all, cases occur in smokers and ex-smokers or people who have been exposed to a lot of air pollution. Currently, there is no way to reverse the damage, and even slowing the progress of the disease is extremely difficult. Some researchers are looking for ways to treat patients with degenerative lung diseases by regenerating the surface of their lungs. However, it is still not clear what the most effective route towards this long-term goal will be. One approach to lung regeneration is to use findings from developmental biology to understand how embryos normally build the gas exchange surfaces in the lungs. This",380,128,0.3368
dialogsum,"#Person1#: That looks like a bad accident. #Person2#: Yeah, should we get out and help? #Person1#: No, there's a police car behind us. He'll stop. #Person2#: Looks like the one guy lost control in all this rain, and the other one hit him. #Person1#: Yeah. It's pretty bad, that car looks like a coke can. #Person2#: These accidents always cause traffic jams on rainy days. #Person1#: Yeah, it looks like we're in for a long drive. #Person2#: Ah, well. Put on the news. I got up late and missed it. #Person1#: All right.",#Person1# and #Person2# come across a car accident and #Person2# asks #Person1# to put on the news.,93,17,0.1828
pubmed-summarization,"factors associated with care seeking in these groups , over all , and factors associated with not seeking care for psychological symptoms . this study aims to describe the prevalence of care seeking among persons with depression and anxiety disorders using data from a population - based study in sweden . first , we aim to study whether affected persons seek care and if care seeking is associated with socioeconomic factors and health status . further , we aim to study if those who seek care for psychological symptoms at the general practitioners differ compared to those who seek care from other health care facilities or do not seek at all . this study is based on the part study ( an acronym in swedish for mental ill - health , work , and relationships ) . part is a longitudinal population - based study of mental health conducted in the stockholm county , sweden . in 1998 - 1999 , 19742 randomly selected swedish citizens aged 2064 years , residing in the stockholm county , were invited to participate and 10441 persons ( response rate 53% ) responded to the self - administrated questionnaire ( baseline ) that included questions on demographic and socioeconomic characteristics , somatic and psychiatric health , and use of drugs . three years after they had answered the first questionnaire ( baseline ) those who answered were reassessed with another similar questionnaire including questions on health care seeking ; 8700 persons participated ( retention rate 83% ) . psychiatrists performed interviews using schedules for clinical assessment in neuropsychiatry ( scan ) , in order to validate the answers of the questionnaires . a comparison between depressions according to the major depression inventory ( mdi ) used in the questionnaire and scan showed good compliance . nonparticipation analysis , using national registers , performed after the first two waves , revealed that the association between gender , age , income , education , country of birth , and psychiatric diagnoses in the national registers was similar among participants and nonparticipants . for detailed information about the part study see the technical report . for the purpose of this study we restricted our analyses to the 8387 subjects that participated in both baseline and the first","background . in primary care , a vast majority of patients affected with depression and anxiety present with somatic symptoms . detection rate of psychiatric symptoms is low , and knowledge of factors influencing care seeking in persons affected by depressive and anxiety disorders on a population level is limited . objective . this study aims to describe if persons , affected by depression and anxiety disorders , seek care and which type of care they seek as well as factors associated with care seeking . method . data derives from a longitudinal population - based study of mental health conducted in the stockholm county in 19982010 and the present study includes 8387 subjects . definitions of anxiety and depressive disorders were made according to dsm - iv",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and Nicolas, 1997; Blitzblau et al. , 2007; Buhler et al. , 2007; Fowler et al. , 2013; Gerton et al. , 2000; Hellsten et al. , 2013; Pratto et al. , 2014; Singhal et al. , 2015; Smagulova et al. , 2011; Wijnker et al. , 2013). In budding yeast, this non-uniform distribution of Spo11-DSBs is influenced by meiosis-specific proteins, Red1 and Hop1, which are components of the meiotic chromosome axis. The meiotic chromosome axis coordinates sister chromatids and forms the axial element of the synaptonemal complex, which holds homologs in tight juxtaposition (Hollingsworth et al. , 1990; Page and Hawley, 2004; Smith and Roeder, 1997). Spo11-DSBs form frequently in large (ca 50–200 kb)' hot' domains that are also enriched for Red1 and Hop1, and these' hot' domains are interspersed with similarly-sized' cold' regions where Spo11-DSBs are infrequent and Red1/Hop1 occupancy levels are low (Baudat and Nicolas, 1997; Blat et al. , 2002; Blitzblau et al. , 2007; Buhler et al. , 2007; Panizza et al. , 2011). Normal Spo11-DSB formation requires recruitment of Spo11 and accessory proteins to the meiotic axis (Panizza et al. , 2011; Prieler et al. , 2005), and Red1/Hop1 are also central to mechanisms that direct Spo11-DSB repair towards use of the homolog as a recombination partner (Carballo et al. , 2008; Niu et al. , 2005; Schwacha and Kleckner, 1997). Other eukaryotes contain Hop1 analogs that share a domain, called the HORMA domain (Rosenberg and Corbett, 2015), and correlations between these meiotic axis proteins and DSB formation are observed in fission yeast, nematodes and in mammals (Fowler et al. , 2013; Goodyer et al. , 2008; Wojtasz et al. , 2009). Thus, most meiotic interhomolog recombination occurs in the context of a specialized chromosome structure and requires components of that structure. Meiotic recombination pathways diverge after DSB formation and homolog-directed strand invasion. In budding yeast, about half of meiotic events form NCOs via synthesis-dependent strand annealing, a mechanism that does not involve stable recombination intermediates (Allers and Lichten, 2001a; McMahill et al. , 2007) and is suggested to be the predominant HR pathway in mitotic cells (Bzymek et al. , 2010; McGill et al. , 1989). Most of the remaining events are repaired by a meiosis-specific CO pathway, in which an ensemble of","Inside the cells of many species, double-stranded DNA is packaged together with specialized proteins to form structures called chromosomes. Breaks that span across both strands of the DNA can cause cell death because if the break is incorrectly repaired, a segment of the DNA may be lost. Cells use a process known as homologous recombination to repair such breaks correctly. This uses an undamaged DNA molecule as a template that can be copied to replace missing segments of the DNA sequence. During the repair of double-strand breaks, connections called crossovers may form. This results in the damaged and undamaged DNA molecules swapping a portion of their sequences. In meiosis, a type of cell division that produces sperm and eggs, cells deliberately break their chromosomes and then repair them",380,128,0.3368
dialogsum,"#Person1#: Hi, Bob. I heard that you had passed your driving test. Is it true? #Person2#: Yes. A few days ago I have no right to get a driving licence. But now I get it. #Person1#: Is the driving test difficult? #Person2#: Yes, it can be quite tough. Many people fail to pass the test at the first time. #Person1#: What does the driving test require? #Person2#: You should enroll in driving school and then take a road test and a written test. After you pass both tests, you'll get your licence. #Person1#: Oh, I see. I need more practice before I take the driving test. #Person2#: Don't worry about your driving test. I think you will pass the test and get the driver's licence very soon. #Person1#: Hopeful! Thank you.",Bob passed his driving test. He tells #Person1# the requirements of the test and encourages #Person1# that #Person1#'ll soon pass the test.,131,22,0.1679
dialogsum,"#Person1#: What should I get Uncle Teddy? #Person2#: You could get him a tie. #Person1#: Are you kidding? That's the stupidest gift one can buy. I don't want to get a tie. #Person2#: Why not? #Person1#: Everybody gets men ties for Christmas. It's too boring. Everybody buys either ties or sweaters. I want a more unique gift. #Person2#: Well, you can buy him a pet iguana then. #Person1#: That's a cool idea. At least it would be a surprise. But I'm afraid he wouldn't take care of it. #Person2#: He would think you were crazy, Caroline. #Person1#: Yes. An iguana is too strange for a gift, and a tie is too normal. So I have to find something halfway between. #Person2#: How much do you want to spend? #Person1#: Well, he was very good to me. He helped me edit my essay for the scholarship contest. So I want to spend at least 75 dollars. #Person2#: Alright, I have an idea. You know he carries that conservative-looking briefcase every day. #Person1#: Yes. #Person2#: Well, he isn't a lawyer, so I don't think he needs to have a briefcase like that. #Person1#: What should he have then? #Person2#: I think he would appreciate having a very fine leather bag. But more like a workbag or shoulder bag. You know, not so hard and square like a briefcase. #Person1#: I think that's a great idea. Men look great with that kind of bag. Where can we buy one? #Person2#: I don't think this mall has a leather goods store. So we have to go to State Street. #Person1#: Alright. We can go later then. #Person2#: We can buy something for Mom and Dad here, and then go buy Uncle Teddy's gift on State Street. #Person1#: Good plan. What should we get for Mom though? #Person2#: She said she wants one of those automatic foot massagers. I think they sell them at Sears. #Person1#: Alright. We can go check at Sears and see if they have them. And what about Dad? #Person2#: How about the iguana? #Person1#: I think it would be a great joke. But I know we'd have to take the iguana back. And the pet store might not let us. So why don't we get him something else? Some clothes","Caroline is discussing with #Person2# about picking gifts for Uncle Teddy and Mom and Dad. Caroline wants a unique gift and spends at least 75 dollars for Uncle. #Person2# makes a few suggestions and finally, they agree on a leather bag. Also, they will buy an automatic foot massager for mom and they continue discussing what they should buy for dad.",380,61,0.1605
scientific_lay_summarisation-elife-norm,"Pollinating insects utilise various sensory cues to identify and learn rewarding flower species. One such cue is floral temperature, created by captured sunlight or plant thermogenesis. Bumblebees, honeybees and stingless bees can distinguish flowers based on differences in overall temperature between flowers. We report here that floral temperature often differs between different parts of the flower creating a temperature structure or pattern. Temperature patterns are common, with 55% of 118 plant species thermographed, showing within-flower temperature differences greater than the 2°C difference that bees are known to be able to detect. Using differential conditioning techniques, we show that bumblebees can distinguish artificial flowers differing in temperature patterns comparable to those seen in real flowers. Thus, bumblebees are able to perceive the shape of these within-flower temperature patterns. Floral temperature patterns may therefore represent a new floral cue that could assist pollinators in the recognition and learning of rewarding flowers. Many flowering plants require pollen transport by animals to ensure reproductive success (Ollerton et al. , 2011). These pollinating animals are often insects (Kevan and Baker, 1983), such as bees. To encourage pollinator visits flowering plants create floral displays (Raguso, 2004; Leonard et al. , 2012) which produce diverse floral cues in different sensory modalities (Kevan and Lane, 1985; Bhagavan and Smith, 1997; Whitney et al. , 2009; Hempel de Ibarra and Vorobyev, 2009; von Arx et al. , 2012; Lawson et al. , 2017b). These signals allow pollinators to find and locate flowers (Spaethe et al. , 2001; Chittka and Spaethe, 2007), and also allow pollinators to learn and recognise them (Heinrich, 1979; Raine and Chittka, 2008). Bees and other pollinators adjust their foraging behaviour to favour visits to more rewarding species found in their environment (Heinrich, 1979), avoiding ‘mistake visits’ to less rewarding flowers in order to enhance their foraging success (Raine and Chittka, 2008). Similarly, a floral display that is easily learnt and distinguished from others in its environment ensures greater visitation to the flower (Galen and Newport, 1988; Lynn et al. , 2005) and thus greater reproductive success (Ashman et al. , 2004; Bell et al. , 2005; Schiestl and Johnson, 2013). Identifiable floral cues are therefore critical to both plant and pollinator. One flower cue bees can use to recognise flowers is floral temperature (Whitney et","Bees experience the world in a different way to humans. The plants that they visit exploit the bee’s senses to make sure that a searching bee can easily find, handle and pollinate flowers. For example, bumblebees can learn to choose between flowers that are different temperatures, using heat as a way of identifying the best flowers. Some wild flowers are warmer than others when they grow in their natural environment. Recent advances in technology mean that scientists are now able to take a more detailed look at flower temperature than ever before. Harrap et al. used this technology to look at 118 species of plant, including daisies, rockroses and poppies. Over half of the plants examined had flowers with complex patterns of heat across their petals, echoing the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"stimulates RAF/MEK/ERK activity. These cell signaling pathways have been found to regulate the levels of BIM (also called BCL2L11) and BMF, two pro-apoptotic members of the BCL2 family of apoptosis regulators previously shown to contribute to anoikis (Reginato et al. , 2003; Schmelzle et al. , 2007). However, depletion of BIM or BMF diminishes but does not completely prevent anoikis (Reginato et al. , 2003; Schmelzle et al. , 2007), suggesting the existence of other factors and regulatory pathways that can promote anoikis. Moreover, the basis of anoikis resistance remains to be determined and to date has not been linked to alterations in expression or activity of BIM or BMF. To investigate the possibility that there are additional factors and regulatory pathways that promote anoikis, we performed a large-scale RNA interference (RNAi) screen for genes whose loss of expression confer anoikis resistance. The screen was performed in MCF10A cells, an immortalized but non-transformed human breast epithelial cell line that has been frequently used to study anoikis (see, for example, Huang et al. , 2010; Reginato et al. , 2003; Schmelzle et al. , 2007; Taube et al. , 2006). A genome-wide human small hairpin RNA (shRNA) library comprising ~62,400 shRNAs directed against ~28,000 genes (Silva et al. , 2003; Silva et al. , 2005) was divided into 10 pools, which were packaged into retroviral particles and used to stably transduce MCF10A cells. Following selection, the cells were divided into two populations, one of which was plated on poly-2-hydroxyethylmethacrylate (HEMA) -coated plates for 10 days to inhibit cell attachment to matrix, and another that was cultured attached to matrix for 10 days as a control (1A). Surviving cells were selected and shRNAs identified by deep sequencing. Bioinformatic analysis of the two populations identified 26 shRNAs whose abundance was significantly enriched >500-fold following detachment (—source data 1); such shRNAs presumably confer upon MCF10A cells a selective advantage by protecting them from undergoing anoikis. 10. 7554/eLife. 16844. 003Figure 1. Identification of KDM3A as an anoikis effector in breast cancer epithelial cells. (A) Schematic of the design of the large-scale RNAi screen to identify anoikis effectors. (B) Cell death, monitored by annexin V staining, in MCF10A cells expressing a non-silencing (NS) shRNA and cultured attached to the matrix, or in detached cells (cultured in","Epithelial cells line the inside of blood vessels, intestines and other organs throughout the body. Any epithelial cells that become detached from their natural surroundings die by a process called anoikis (a Greek word meaning “being without a home”). This process has an important role in preventing cancer from spreading around the body because it eliminates cells that are not in their proper environment. However, some cancers that start from epithelial cells, such as breast cancer, develop resistance to anoikis. Gaining a better understanding of the cellular factors that regulate anoikis, and how resistance develops, may reveal new drug targets for the treatment of breast cancer. Previous studies found proteins called BIM and BMF promote anoikis by inducing cell suicide. However, it is possible that other factors can",380,128,0.3368
pubmed-summarization,"three - dimensional ( 3d ) computer reconstruction of a target volume or of a surface is an important activity in modern biomedical imaging . the accurate anatomical reconstruction in trauma or for use in image - guided intervention relies on mathematical imaging technology ; and this paper develops the mathematical technique of stochastic function recovery and illustrates its use for noisy boundary reconstruction . this is an alternative approach to the standard polynomial - based methods that we see as an add - on or complement to other techniques in use or being developed to improve upon the reconstruction of noisy boundary data to provide enhanced biomedical visualization . the ability to distinguish features related to boundaries is intrinsic to technology of visualization . for example , in mri imaging , a range of specialized methods have been developed for extracting information from signals so as to reconstruct images representing internal body structures . boundary recovery techniques apply to complex surgical procedures as with electroanatomical mapping that tracks the position of catheters inside the body with sparse signals recorded from electrodes at the tip of the catheter . resulting surface maps must integrate real - time measurements with preoperative mr or ct images , and account for mapping data errors in registration and error due to patient movement . in general , when signals are affected by noise , it must be effectively removed in order to improve the visualization and compared with other medical imaging modalities , ultrasound images suffer from speckle noise that often makes for weak or incomplete boundaries . our approach is to use stochastic convolution - deconvolution operators , which have useful statistical properties , to smooth noisy surface data in a manner that does not obliterate detail , and which effectively removes gaussian noise . the motivation for the approach is that , intrinsically , stochastic interpolation using probabilistic kernels for the generating function of the row space of the linear operator performs well at removing noise when used to approximate data . however , the difficulty in applying these methods directly is that they bias the data to a mean of zero . in approximating one - dimensional data , however , in approximating multidimensional data , this can cause an apparent","determining the outline or boundary contour of a two - dimensional object , or the surface of a three - dimensional object poses difficulties particularly when there is substantial measurement noise or uncertainty . by adapting the mathematical approach of stochastic function recovery to this task , it is possible to obtain usable estimates for these boundaries , even in the presence of large amounts of noise . the technique is applied to parametric boundary data and has potential applications in biomedical imaging . it should be considered as one of several techniques to improve the visualization of images .",380,100,0.2632
scientific_lay_summarisation-elife-norm,"populations, including minor and rare populations (Hwang et al. , 2018), assigning precursor–product relationships is difficult based on gene expression alone. In the current manuscript, we reasoned that combining scRNA-seq with in vivo tools would better resolve our understanding of the developmental relationships between mTECs. First, we used a bioinformatic approach on scRNA-seq of control thymus to characterize mTEC lineage relationships. Second, we combined scRNA-seq with a lineage tracing approach (Kretzschmar and Watt, 2012) in which the developmental relationships of Aire-expressing mTECs and their progeny are readily discernible (Metzger et al. , 2013). Third, we combined scRNA-Seq with a transient ablation model in which differentiation of mTEC-hi cells is selectively blocked after treatment with anti-RANK-ligand (RANKL) antibody. Inhibition of RANK signaling depletes the Aire-expressing mTEC population, which then recovers over 10 weeks (Khan et al. , 2014; Metzger et al. , 2013). Using these approaches, we created a molecular roadmap of Aire-expressing mTEC development that details the kinetics of TSA expression in relation to Aire and identified a transit-amplifying population of mTECs that we propose is the immediate precursor of the Aire-expressing and Ccl21a-expressing populations. First, we utilized a bioinformatic approach to identify TEC populations and lineage relationships at the single-cell level that could be subsequently validated using lineage tracing and transient in vivo ablation (1a). We performed single-cell transcriptome analysis of total TECs purified by flow cytometry (EpCAM+ CD45-) and subjected to scRNA-seq on the 10x Genomics platform (Zheng et al. , 2017; 1a and — 1a). A total of 2434 cells were included in the downstream analysis. Single cells were projected into a reduced-dimensional space using UMAP and were clustered based on the top 13 principle components, yielding six total clusters (Adey, 2019; Becht et al. , 2018; Butler et al. , 2018; 1b and — 1b). To identify clusters, we performed differential gene-expression analysis and searched for gene signatures previously associated with thymic epithelial subsets. As described in previous TEC single-cell studies, the ‘cTEC’ cluster was marked by high expression of Ackr4 and Prss16 (Bornstein et al. , 2018; Kernfeld et al. , 2018; Miragaia et al. , 2018; 1c and d, — 1c). The ‘Ccl21a-high’ cluster was marked by high expression of Ccl21a (Lkhagvasuren et al. , 2013) and Krt5 (1c and d, — 1c). The","Specialized cells in the immune system known as T cells protect the body from infection by destroying disease-causing microbes, such as bacteria or viruses. T cells use proteins on their surface called receptors to stick to infectious microbes and remove them from the body. Some newly developed T-cells, however, contain receptors that recognize and bind to cells that belong in the body. If these faulty T cells are released, they can attack healthy tissues and cause an autoimmune disease. After a new T cell is developed, it gets carried to a gland in the chest known as the thymus. Cells in the thymus called mTECs screen T cells for receptors that may bind to the body’s tissues. mTECs do this by presenting T cells with proteins that are",380,128,0.3368
dialogsum,"#Person1#: Can I help you? #Person2#: I'd like to buy a tie to match this suit. #Person1#: We have various colors. How about this one? #Person2#: Well, the color is all right. But it looks outdated. Can you show me that one? #Person1#: You have a very good taste. It's our best seller. #Person2#: Really? #Person1#: Sure! Look, it suits you well.",#Person1# serves #Person2# to buy a tie that is the best seller.,62,12,0.1935
pubmed-summarization,"be performed to allow a trainee to perform unsupervised meniscectomies . simulator a was evaluated by 22 participants in april 2009 and simulator b by 22 participants in october 2009 ( . subgroups were made on arthroscopic experience at three levels based on the number of arthroscopies performed : novices ( 0 ) , intermediates ( 159 ) , and experts ( > 60 ) . the age in years and the number of attended arthroscopies ( observation ) are expressed as median with range in parentheses . the number of participants who previously had used a simulator ( simulator ) or had experience in playing computer games ( games ) is shown . subgroups were made on arthroscopic experience at three levels based on the number of arthroscopies performed : novices ( 0 ) , intermediates ( 159 ) , and experts ( > 60 ) . the age in years and the number of attended arthroscopies ( observation ) are expressed as median with range in parentheses . the number of participants who previously had used a simulator ( simulator ) or had experience in playing computer games ( games ) is shown . the researcher showed the selection of exercises and performance of the calibration protocol and tasks for the test . the assessment of construct validity ( time to perform a task ) was based on one basic navigation task . as the simulators were unlikely to offer a navigation task that was the same , one navigation task was prescribed that can and could be performed on all simulators for comparison . with the arthroscope placed in the anterolateral portal and the probe in the anteromedial portal , nine anatomic landmarks had to be probed sequentially : medial femoral condyle , medial tibial plateau , posterior horn of the medial meniscus , midsection of the medial meniscus , acl , lateral femoral condyle , lateral tibial plateau , posterior horn of the lateral meniscus , and midsection of the lateral meniscus . the participants were asked to repeat this navigation task up to five times in a limit of 10 minutes . the navigation task time was defined as described previously and determined with a separate video recording of the simulator monitor in which the","backgroundsome commercial simulators are available for training basic arthroscopic skills . however , it is unclear if these simulators allow training for their intended purposes and whether the perception of usefulness relates to level of experience.questions/purposeswe addressed the following questions : ( 1 ) do commercial simulators have construct ( times to perform tasks ) and face validity ( realism ) , and ( 2 ) is the perception of usefulness ( educational value and user - friendliness ) related to level of experience?methodswe evaluated two commercially available virtual reality simulators ( simulators a and b ) and recruited 11 and nine novices ( no arthroscopies ) , four and four intermediates ( one to 59 arthroscopies ) , and seven and nine experts ( > 60 arthroscopies",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2011). In neural plate stage embryos, the PPE is located as a horseshoe-shaped domain around the anterior neural plate (and abutting the cranial neural crest laterally) which subsequently breaks up into individual placodes (Schlosser, 2010; Grocott et al. , 2012; Saint-Jeannet and Moody, 2014). Molecularly, the PPE is characterised by the expression of Six1 and Eya1, which also continues in most placodes derived from the PPE (Schlosser and Ahrens, 2004). Whereas Six1 encodes a transcription factor, Eya1 encodes a transcriptional co-activator that also has phosphatase activity (Kumar, 2009; Tadjuidje and Hegde, 2013), and Six1 and Eya1 have been shown to form a protein complex and synergistically activate transcription (Ohto et al. , 1999; Li et al. , 2013). However, both Six1 and Eya1 also interact with other protein interaction partners; Six1, for example, has been shown to act as a transcriptional repressor after binding to the co-repressor Groucho (Brugmann et al. , 2004) whereas Eya1 is known to form protein complexes with other binding partners including the transcription factor Sox2 (Ahmed et al. , 2012a; Tadjuidje and Hegde, 2013). Loss of Six1 or Eya1 function in mouse, zebrafish, chick or Xenopus embryos leads to a similar spectrum of PPE and placodal defects, with altered expression of other PPE genes, decreased proliferation and increased apoptosis in many placodes, compromised morphogenetic movements (invagination or cell delamination) and a decreased production of sensory cells and neurons (Xu et al. , 1999; Laclef et al. , 2003; Zheng et al. , 2003; Brugmann et al. , 2004; Zou et al. , 2004; Kozlowski et al. , 2005; Schlosser et al. , 2008; Christophorou et al. , 2009; Ahmed et al. , 2012a, 2012b). In human patients, mutations in both Six1 and Eya1 lead to branchio-oto-renal (BOR) and branchio-otic (BO) syndromes with congenital hearing loss (Kochhar et al. , 2007). These findings suggest that these proteins are core regulators of placode development and promote multiple aspects of placode development synergistically, although Eya1-independent roles of Six1 have also been reported (Brugmann et al. , 2004; Bricaud and Collazo, 2011). Specifically, Six1 and Eya1 have been shown to play central roles, during multiple steps, in the development of sensory cells (e. g. hair cells in the inner ear) as well as sensory neurons, and promote both the","Animals that possess a backbone – also known as vertebrates – have several paired sense organs in their heads, such as the eyes and the olfactory system. These organs are thought to have arisen as vertebrates evolved from their filter-feeding ancestors and adopted an increasingly active and predatory lifestyle. The cranial placodes are tissues in the vertebrate embryo that give rise to many of these sense organs early in development. The sensory neurons that transmit information from the organs to the brain – including those that process hearing and smell – also develop from these tissues. While much is known about how the sense organs work, relatively little is known about the early processes involved in their development. Two genes have been established as crucial for the formation",380,128,0.3368
dialogsum,"#Person1#: Do you like this house? #Person2#: Yes, it's beautiful. #Person1#: It's perfect for us and the kids. #Person2#: 3 bedrooms, 3 bathrooms and a big backyard. #Person1#: And we can afford it! #Person2#: So are we going to buy it? #Person1#: I'm afraid not. #Person2#: It's too far from your job, isn't it? #Person1#: Yes, I can't spend 4 hours on the road every day. #Person2#: By the time you get home you'll be too tired to even eat. #Person1#: I won't be able to play with the kids! #Person2#: No. We have to find someplace closer to your job.",#Person1# and #Person2# like this house but they decide to find someplace closer to #Person1#'s job.,101,16,0.1584
dialogsum,"#Person1#: Welcome to our factory. #Person2#: I've been looking forward to visiting your factory. #Person1#: Actually, you'll know our products better after the visit. I'll show you around and explain the operations as we go along. #Person2#: That'll be most helpful. #Person1#: Maybe we could start with the Design Department. And then we could look at the production line. #Person2#: How much do you spend on design development every year. #Person1#: About 10 % of the gross sales. #Person2#: That's fine.",#Person1# is showing around and explaining the operation of #Person1#'s factory to #Person1#. They start from the design department.,81,19,0.2346
dialogsum,"#Person1#: Hello, Frank. Your roommate told me that I could find you here in the TV studio. Sure enough! #Person2#: I was just taking a break. What's up? #Person1#: We'll have a math test next Monday, so I thought you'd be studying for it and maybe I can study with you. #Person2#: But I can't believe you are coming to me. I mean you do know what I got on the last test, don't you? #Person1#: Yeah, I know. You told me, but I thought two heads might be better than one. #Person2#: Well, that's a nice idea. But I wish I knew the person in our class who got a hundred on the last test. She even didn't miss any question, you know! Umm, was it Elizabeth? #Person1#: Oh yeah, Elizabeth! She is a good friend of mine. I think she'd be a big help to us right now. Why don't we give her a call? #Person2#: What? At this hour? It's already ten thirty. It's too late. #Person1#: But you know she owes me a big favor. Let's at least give her a call and see what she says. Maybe going over some of the problems with us would also help her review the material. #Person2#: You're right. Anyway, it's worth a try.","#Person1# comes to the TV studio to find Frank and asks Frank whether #Person1# can study math with him together. Franks suggests they ask Elizabeth and #Person1# is going to call her, although it's quite late.",215,36,0.1674
dialogsum,"#Person1#: Good afternoon, Chloe, I'm Doctor Evans. What seems to be the problem? #Person2#: Hi, Dr. Evans. Thanks for seeing me on such short notice. When I woke up this morning I had a really sore throat and a really bad cough. I think I am coming down with the flu. #Person1#: Ah I see, yes you do sound rather croaky. Well let's have a look, shall we? Could you please open your mouth and say ah. #Person2#: Ahhhhhhhh #Person1#: Good, yes, your tonsils are a little swollen and red. How are your ears, blocked at all? #Person2#: A little actually. My sinuses are a little blocked up as well-I really feel terrible. #Person1#: Ok Chloe, can you please breathe in and out slowly for me while I listen to your chest? You really are all bunged up, you don't sound too good at all. Ok, I'm going to set you up with a bunch o #Person2#: Whoa! So many drugs. . . I hate swallowing pills. Am I able to go to work? #Person1#: Absolutely not! You are highly contagious! You don't want to infect the rest of your co-workers do you? I recommend staying in bed for at least three days and drinking plenty of fluids so yo #Person2#: Ok! Would you mind writing me a doctor's note for work, otherwise they may think I am faking it! #Person1#: Ha-ha, sure not a problem! Here you are. Now off you go and away to bed. If you have any questions just give me a call! Feel better soon and take care. #Person2#: Thanks doc, bye!","Chole thinks she has a flu. Dr. Evans has a look at her throat, asks about her ears, checks her breath, gives her drugs, and recommends her to stay in bed. Chole asks the doctor to write her a note to ask for a leave from work.",267,47,0.176
dialogsum,"#Person1#: Hello, I'm looking for a shop that sells inexpensive cashmere sweaters. #Person2#: Have you tried an outlet? #Person1#: Why didn't I think of that? #Person2#: Many of my friends shop at outlets. #Person1#: Thanks. That is a good suggestion. #Person2#: I'm only too happy to help.",#Person2# suggests #Person1# try an outlet instead of cashmere sweaters.,47,10,0.2128
dialogsum,"#Person1#: Excuse me. Do you mind if I try this shirt on? #Person2#: Not at all. The changing rooms are just this way. #Person1#: Thanks. It's a little tight. Do you have any in a larger size? #Person2#: Sure. I'll give you the next size up. That one is small, right? #Person1#: Yes. Also, I'm not so sure about the color. #Person2#: Well. It doesn't go with your skirt. I think the color itself is fine though.","#Person1# tries on a shirt at #Person2#'s shop, but #Person1# thinks its color and size are not suitable.",77,18,0.2338
dialogsum,"#Person1#: Richard? Do you have the number for that Chinese restaurant on the corner? #Person2#: Yeah, hold on a second. I'Ve got it in my office. Here it is. 553-2213. #Person1#: 553-2213. Great, thanks. #Person2#: No problem. Pick me up something to eat too, please.",#Person1# asks Richard for the number of a Chinese restaurant. Richard asks #Person1# to pick up something to eat for him.,45,21,0.4667
dialogsum,"#Person1#: Hey, Jake. Are you ready for your trip? #Person2#: Well, not really. I still have to buy some clothes. #Person1#: Well, what's the weather like where you're going? #Person2#: Well, uh, it's really hot in the summer, so I'm going to buy some shorts, sandals, and a few t-shirts. #Person1#: What about the rest of the year? #Person2#: People say that the fall can still be warm until November, so I'm going to buy some jeans and a few casual shirts. #Person1#: Will you need any warm clothes for the winter? #Person2#: Well, the weather doesn't get too cold, but it often snows in the mountains, so I'm going to buy a couple of warm sweaters, a jacket, and a hat. I don't have room in my suitcase to pack a coat, so I'm going to wait until I get there and buy it when I really need it. #Person1#: Are you going to take anything else? #Person2#: They say it rains cats and dogs in the spring, but again, I'll probably just wait and pick up a raincoat or an umbrella later on. But, I'm going to take a good pair of shoes because I plan on walking to and from school everyday. #Person1#: Do you need any clothing for formal occasions? #Person2#: Well, you never know when you might need something on the spur of the moment for a wedding or maybe someone's graduation, or a nice date, so I'll probably take some nice slacks, a dress shirt, and a couple of crazy ties or two. #Person1#: Um, that makes sense. #Person2#: And I'll just rent a suit or tuxedo if I need anything more formal. Hey, maybe I'll get married. #Person1#: You? Married? Hah! #Person2#: Wait. What are you trying to say? #Person1#: I just can't imagine you decked out in a tuxedo for any formal occasion. #Person2#: What?! #Person1#: I mean, for high school graduation, you wore an old pair of jeans and tennis shoes. #Person2#: Hey, there was a reason for that, so let me explain. #Person1#: Yeah, ha, ha. #Person2#: No, really. You see, it goes like this ...","Jake tells #Person1# about the weather of his destination and they talk about what clothes Jake needs. Jake's going to buy some shorts, sandals, and a few t-shirts for the summer, some jeans and a few casual shirts for the fall, a couple of warm sweaters, a jacket, and a hat for the winter. He'll also take some nice slacks, a dress shirt, and a couple of crazy ties or two for formal occasions.",356,74,0.2079
scientific_lay_summarisation-elife-norm,"we made 3D structured-light scans to quantify roughness (Supplementary file 1A) and reconstruct surface profiles (see Materials and methods). The profiles show the variation in surface roughness, from smoothest, Teflon, to roughest, sandpaper (1A). To evaluate the effect of these properties on foot-surface interactions, we conducted toe and claw drag tests to measure friction forces on each surface. We also performed claw indentation tests to measure surface deformation (see Materials and methods; 1B). Finally, we made high-speed recordings of parrotlets landing on the nine different perches. The perches were split in half and instrumented on a pair of force/torque sensors for measuring net and squeeze forces exerted by their feet (see Materials and methods; 1C). The parrotlets exhibit a stereotyped set of landing behaviors across all perch variations (2A, Video 2). Landing is initiated by braking with the wings (‘aerial’), and then the legs absorb the remaining momentum upon impact with the perch (‘absorption’). Both feet would make contact with the perch within a few milliseconds of each other, but initial contact tended to be led by one preferred foot (bird 1 = 100% right foot, bird 2 = 83% left, bird 3 = 85% left). The parrotlets then wrap their toes and claws more securely around the perch to establish a static grasp (‘anchoring’). After this stage, they often take additional steps (2. 0 ± 0. 7, n = 78 landings) to adjust their footing (‘adjustments’). The birds would occasionally overshoot or undershoot the perch, leading to more variance in the foot angle at which they establish a static grasp (2B). However, while the net leg force magnitudes (2B) and directions (2C) also exhibit some variance, the average landing force trends remain remarkably similar across the different perches. The variation seen during landing may be explained by the parrotlets’ landing strategy. According to Tau theory (Lee et al. , 1993), birds control their landings by visually estimating their time to contact, τ (t). To land, they adjust their approach speed to maintain a constant τ˙ (t), the time rate of change of tau. More specifically, tau is defined as the distance to the perch s divided by the speed of approach v, and is therefore a first-order approximation for the time to contact. If a bird brakes with constant","Most of the flying vehicles designed by humans need to land on smooth, standardized surfaces such as runways. A bird, on the other hand, can use structures that vary widely in diameter and texture, from phone lines to branches to statues. Yet, few studies have focused on how these animals transition from the air to a perch, and especially on how they adapt to different surfaces. To fill this gap, Roderick, Chin et al. recorded how Pacific parrotlets landed on nine natural and man-made perches that varied in diameter and texture, ranging from smooth Teflon to rough sandpaper. High-speed cameras tracked each of the landings while sensors measured how hard the birds landed on and squeezed the perches. The experiments revealed that the first landing phase was the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"genes in modulating lifespan (Ren et al. , 1996; Alcedo and Kenyon, 2004; Bishop and Guarente, 2007). tph-1 is expressed in the NSM foregut neurons, the ADF sensory neurons, and the HSN motorneurons involved in egg-laying (Sze et al. , 2000). Both serotonin signaling mutants and NSM ablation affect food-modulated locomotion, consistent with the idea that serotonin from NSM acts in this food-related response (Sawin et al. , 2000). In the food-responsive ADF neurons (Zaslaver et al. , 2015), tph-1 expression is responsive to pathogenic bacteria and starvation, to respectively mediate aversive olfactory plasticity and stress responses (Zhang et al. , 2005; Liang et al. , 2006). daf-7 and tph-1 are therefore strong candidates for mediating the link between environmental cues and longevity. Nonetheless, how these genes cooperate to quantitatively encode a broad range of food levels to modulate lifespan is unknown. Gene-expression responses to food cues have largely been studied as ON/OFF switches to the presence or absence of food (Zinke et al. , 2002; Baugh et al. , 2009). Because food abundance is a continuous variable, we sought to understand how expression of tph-1 and daf-7 could allow animals to distinguish multiple food levels. Furthermore, gene expression is inherently variable (Eldar and Elowitz, 2010), but this property is rarely studied in vivo in multicellular animals; thus we also sought to determine how gene-expression variability affects the ability of the worm to encode its environment. Here we show that daf-7 and tph-1 expression in three pairs of neurons forms a distributed circuit that quantitatively encodes food abundance and mediates dietary effects on lifespan in C. elegans. Specific disruptions to this circuit resulted in corresponding attenuation in the ability to discriminate between food levels in both the gene-expression code and lifespan output. We found that this circuit tunes its own accuracy, largely via the regulation of the dynamic range and variability of food-responsive gene expression by tph-1 and daf-7 signalling, respectively. Our work suggests that neural regulation of gene expression in conserved pathways can couple environmental sensation to physiological output, and highlights a novel mechanism for information processing by the nervous system to impact physiology. During DR, lifespan increases as food levels are decreased from ad libitum conditions until reaching a maximum, beyond which further food reduction lowers lifespan (Bishop","To maximize their chances of survival, animals need to be able to sense changes in the abundance of food in their environment and respond in an appropriate manner. The nervous system is able to sense cues from the environment and coordinate responses in the whole organism, but it is not clear how this leads to long-term changes in the organism' s biology. In nematode worms, two genes called daf-7 and tph-1 appear to be involved in connecting the sensing of food availability with changes in the biology of the organism. The daf-7 gene encodes a hormone, while tph-1 encodes an enzyme that makes a neurochemical called serotonin. Here, Entchev, Patel, Zhan et al. found that daf-7 and tph-1 genes are active in three pairs of neurons in nematode",380,128,0.3368
pubmed-summarization,": palm oil ( + 640% ) , soybean oil ( + 635% ) , and vegetable oils ( + 259% ) . on the positive side , the intake of fruits and vegetables also increased by 600 and 367% , respectively ( 16 ) . between 1980 and 2003 , there has been an increase in meat as well as greasy food consumption in china , as well as increased use of tropical oils ( which is associated with high cholesterol and not healthy for heart ) in preparing food . similarly , in india , mexico , south africa and other nations the elevated kcal intake of palm oil in the diets was reported ( 16 ) . the causes of the decline in cvds in developed countries offer potential lessons for achieving similar results in developing countries . the major risk factors for cvds have been reported for childhood and adolescence ( 1720 ) . these include use of tobacco , diets and physical activities , overweight and obesity , and adverse childhood experiences . poor social life circumstances in childhood have also been linked to cvds later in life in different cohort studies conducted in the usa and europe ( 21,22 ) . a cohort study of 20,040 individuals four measures of health were examined : smoking , low physical activity , low plasma vitamin c levels ( used as a proxy for fruit and vegetable intake ) , and not drinking alcohol in moderation ( abstaining from alcohol or consuming more than 14 drinks per week ) and the results indicated that one or more of the abovementioned risk factors alone or in combination with other risk factors constituted a > 2-fold increase in stroke incidence ( 23 ) . this is consistent with prior findings in large cohort studies on men and women in the usa whereby a healthy diet and lifestyle of not smoking , regular exercise , moderate alcohol consumption , and not being overweight was associated with an almost 80% lower risk of ihd compared to having none of the abovementioned healthy lifestyle components ( 24 ) . the major risk factors for cvd in young individuals or adults include fats , abnormal blood lipids , tobacco smoking , alcohol ,","cardiovascular diseases ( cvds ) are the leading cause of mortality worldwide . coronary heart disease ( chd ) is the main cause of mortality in heart patients following stroke , rheumatic heart disease and myocardial infarctions . approximately 80% of individuals succumb to cvds , due to poor living conditions in low and middle income families and malnutrition . infectious diseases , human immunodeficiency , tuberculosis , malaria , high blood pressure or hypertension , obesity and overweight , and nutritional disorders including smoking , excessive alcohol consumption , high salt and sugar intake , as well as other factors are responsible for cvds and chds in young as well as elderly individuals . the focus of the present review are recent epidemiological aspects of cvd and",380,128,0.3368
dialogsum,"#Person1#: Shall I pick you up then? #Person2#: I don't know. The traffic will be really bad at that time. You know what it's like after a concert. I was thinking of catching the train. #Person1#: Hmm...It will be late. Won't that be a bit dangerous? I'm not busy you know. #Person2#: That's really kind of you. I've also thought of getting a taxi, but then there's still the traffic to worry about. I think my original idea is the best.","#Person1# offers to pick up #Person2# after the concert, but #Person2# prefers catching the train considering the traffic.",81,18,0.2222
scientific_lay_summarisation-elife-norm,"A loss of the checkpoint kinase ataxia telangiectasia mutated (ATM) leads to impairments in the DNA damage response, and in humans causes cerebellar neurodegeneration, and an increased risk of cancer. A loss of ATM is also associated with increased protein aggregation. The relevance and characteristics of this aggregation are still incompletely understood. Moreover, it is unclear to what extent other genotoxic conditions can trigger protein aggregation as well. Here, we show that targeting ATM, but also ATR or DNA topoisomerases, results in the widespread aggregation of a metastable, disease-associated subfraction of the proteome. Aggregation-prone model substrates, including Huntingtin exon 1 containing an expanded polyglutamine repeat, aggregate faster under these conditions. This increased aggregation results from an overload of chaperone systems, which lowers the cell-intrinsic threshold for proteins to aggregate. In line with this, we find that inhibition of the HSP70 chaperone system further exacerbates the increased protein aggregation. Moreover, we identify the molecular chaperone HSPB5 as a cell-specific suppressor of it. Our findings reveal that various genotoxic conditions trigger widespread protein aggregation in a manner that is highly reminiscent of the aggregation occurring in situations of proteotoxic stress and in proteinopathies. The PI3K-like serine/threonine checkpoint kinase ataxia telangiectasia mutated (ATM) functions as a central regulator of the DNA damage response (DDR) and is recruited early to DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex (Shiloh and Ziv, 2013). Defects in ATM give rise to ataxia-telangiectasia (A-T), a multisystem disorder that is characterized by a predisposition to cancer and progressive neurodegeneration (McKinnon, 2012). Impaired function of ATM has also been linked to a disruption of protein homeostasis and increased protein aggregation (Corcoles-Saez et al. , 2018; Lee et al. , 2018; Liu et al. , 2005). Protein homeostasis is normally maintained by protein quality control systems, including chaperones and proteolytic pathways (Hipp et al. , 2019; Labbadia and Morimoto, 2015). Together, these systems guard the balance of the proteome by facilitating correct protein folding, providing conformational maintenance, and ensuring timely degradation. When the capacity of protein quality control systems becomes overwhelmed during (chronic) proteotoxic stress, the stability of the proteome can no longer be sufficiently guarded, causing proteins to succumb to aggregation more readily. Proteins that are expressed at a relatively high level compared to their intrinsic aggregation propensity, a","Cells are constantly perceiving and responding to changes in their surroundings, and challenging conditions such as extreme heat or toxic chemicals can put cells under stress. When this happens, protein production can be affected. Proteins are long chains of chemical building blocks called amino acids, and they can only perform their roles if they fold into the right shape. Some proteins fold easily and remain folded, but others can be unstable and often become misfolded. Unfolded proteins can become a problem because they stick to each other, forming large clumps called aggregates that can interfere with the normal activity of cells, causing damage. The causes of stress that have a direct effect on protein folding are called proteotoxic stresses, and include, for example, high temperatures, which make proteins",380,128,0.3368
scientific_lay_summarisation-elife-norm,"collagen concentration is a key determinant of abnormal ECM structure-function, and that targeting pathways which dysregulate collagen architecture may restore ECM homeostasis and so prevent persistent mechanosensitive cellular activation and fibrosis progression. We performed an integrated biochemical and biomechanical characterisation comparing human IPF lung tissue with age-matched control lung tissue. We first used atomic force microscopy (AFM) cantilever-based microindentation to assess lung tissue stiffness at the micrometre-scale. IPF tissue was significantly stiffer than control tissue (1A), with spatially heterogeneous changes in stiffness in IPF tissue including highly localised areas of increased stiffness which were not present in control lung tissue (1B and C), consistent with the known histopathological heterogeneity of IPF tissue (Raghu et al. , 2011). We then explored the relative contribution of collagen amount and/or post-translational modifications to these differences in stiffness. Whilst an increase in fibrillar collagen was suggested by second harmonic generation imaging of IPF lung tissue (1D), quantitation of total collagen concentration by hydroxyproline assay showed no difference in mean total collagen in IPF tissue relative to control tissue following normalisation to either dry weight or to total protein (1E and — 1); in addition, no dependence of lung tissue stiffness on collagen concentration was found (1F). In contrast, differences in the expression of collagen cross-linking enzymes were identified in IPF tissue. Whilst mRNA expression levels of LOX and LOXL1 were unchanged (2A and B), there were significant increases in the relative expression of LOXL2, LOXL3, and LOXL4 (2C–E). This was associated with detection of increased amine oxidase activity in IPF lung tissue sections (2F). Consistent with previous reports of increased LH2 expression in fibrotic tissue (Brinckmann et al. , 1999; van der Slot et al. , 2003), we identified increased expression of LH2 in IPF tissue (3A and B) suggesting the potential for altered collagen cross-linking involving hydroxylysine residues. Therefore, we quantified immature (dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL) ) and mature trivalent (deoxypyridinoline (DPD) and pyridinoline (PYD) ) hydroxyallysine-derived collagen cross-links. This revealed a significant increase in the density of immature divalent (3C) and mature trivalent (3D) cross-links in IPF tissue, with an increase in the relative ratio of immature to mature cross-links in IPF tissue (3E) consistent with increased collagen metabolism in IPF tissue and an increase in the DHLNL to HLNL ratio","Idiopathic pulmonary fibrosis (IPF) is a devastating disease of the lung, which scars the tissue and gradually destroys the organ, ultimately leading to death. It is still unclear what exactly causes this scarring, but it is thought that increasing amounts of proteins in the space surrounding the cells of the lungs, the extracellular matrix, could play a role. These proteins, including collagen, normally form a ‘scaffold’ to stabilize cells, but if they accumulate uncontrollably, they can render tissues rigid. It has been assumed that these changes are a consequence of the disease. However, recent evidence suggests that the increased stiffness itself could stimulate cells to produce even more extracellular matrix, driving the progression of the disease. A better understanding of what exactly causes the tissue to become gradually",380,128,0.3368
pubmed-summarization,"exception of the renal and splenic arteries.7 some reports in the literature have described mnckeberg arteriosclerosis . in 1977 , lachman et al.7 described the involvement of coronary , peripheral , and visceral arteries with mnckeberg calcification . a case of mnckeberg arteriosclerosis involving the aorta , pelvic , and lower limb arteries was reported by lanzer in 1998.16 the nonvascular involvement of soft tissue ( pharynx and larynx ) with mnckeberg sclerosis was reported by couri et al.6 in this report , we described a diabetic patient with end - stage renal disease on dialysis , who had advanced and previously undiagnosed mnckeberg medial calcinosis of the facial and lingual arteries . knowledge of the radiographic appearance of this calcification is clinically useful in developing a differential diagnosis . the proper interpretation of radiographic images presupposes a thorough knowledge of the anatomy , distribution , number , size , and shape of the calcifications . the calcified vessel appears as a parallel pair of thin , radiopaque lines that may have a straight course or a tortuous path , showing a pattern of blood vessels that looks like railroad tracks.511 carotid artery calcifications and phleboliths are calcifications that can be seen in the same location on a panoramic radiograph . carotid artery calcifications radiographically appear as curvilinear irregular parallel radiopacities in the soft tissues of the neck at or below the third and fourth cervical vertebrae , and inferior and lateral to the hyoid bone.1718 phleboliths can be seen on a panoramic radiograph as round or oval in shape with a homogeneously radiopaque center , giving phleboliths a "" target "" appearance.19 mnckeberg sclerosis is listed among the primary diseases of vessels that can be visualized on panoramic radiographs . to the best of our knowledge , our report describes the first known case of medial calcification in the facial artery on the panoramic radiograph of a diabetic patient with end - stage renal disease . soft tissue calcifications in the maxillofacial area are relatively common and can occur as the result of physiologic or pathologic mineralization , and generally correspond to radiographic findings in routine examinations , such as panoramic radiographs . a comprehensive review and thorough interpretation of all conventional and routine dental radiographs , especially beyond","mnckeberg sclerosis is a disease of unknown etiology , characterized by dystrophic calcification within the arterial tunica media of the lower extremities leading to reduced arterial compliance . medial calcinosis does not obstruct the lumina of the arteries , and therefore does not lead to symptoms or signs of limb or organ ischemia . mnckeberg sclerosis most commonly occurs in aged and diabetic individuals and in patients on dialysis . mnckeberg arteriosclerosis is frequently observed in the visceral arteries , and it can occur in the head and neck region as well . this report describes a remarkable case of mnckeberg arteriosclerosis in the head and neck region as detected on dental imaging studies . to the best of our knowledge , this is the first case that",380,128,0.3368
pubmed-summarization,"to concerns regarding hyperkalemia and renal impairment in high - risk patients . finerenone is a novel non - steroidal mra with greater receptor selectivity than spironolactone and better receptor affinity than eplerenone in vitro , which may have the potential to reduce side effects of hyperkalemia and renal impairment . the arts - hf ( mineralocorticoid receptor antagonist tolerability study - heart failure ) double - blind controlled phase 2b trial ( clinicaltrials.gov # nct01807221 ) randomized 1060 patients with heart failure ( hf ) , type 2 diabetes mellitus ( t2 dm ) chronic kidney disease ( ckd ) to finerenone ( titrated from one of five doses from 2.5 to 20 mg ) or eplerenone ( titrating from 25 to 50 mg ) . although the proportion of patients with a relative decrease of 30% in 90-day nt - probnp ( primary endpoint ) was similar in all groups , the measurement of nt - probnp to predict clinical outcome is not well established , and the subgroup of patients receiving finerenone 1020 mg showed a 44% reduction the secondary clinical composite endpoint of 90-day all - cause death , cv death , hospitalization , or emergency presentation for worsening chronic hf . finerenone 1020 mg appeared better tolerated than eplerenone with a smaller increase in potassium ( 0.119 vs. 0.262 mmol / l ; p = 0.016 ) and lower incidence of estimated glomerular filtration rate ( egfr ) decrease > 40% ( 4.2% vs. 9.4% ) . hyperkalemia is a common concern in hf patients using renin - angiotensin - aldosterone ( raas ) inhibitors . in a previous trial , opal - hk ( clinicaltrials.gov # nct01810939 ) , investigators showed a short - term sustained decrease in potassium in patients with hf taking the potassium binder patiromer with raas inhibitors . the phase 2 amethyst dn trial ( clinicaltrials.gov # nct01371747 ) assigned 304 patients with ckd , hypertension ( htn ) , t2 dm , serum potassium above 5 meq / l and who were taking raas inhibitors to patiromer ( starting dose stratified by baseline potassium ) . meq / l in patients with hf ( n = 105 ) or without hf ( n = 199 ) for up to","introductionmultiple significant , potentially practice changing clinical trials in cardiology have been conducted and subsequently presented throughout the past year.methodsin this paper , the authors have reviewed and contextualized significant cardiovascular clinical trials presented at major international conferences of 2015 including american college of cardiology , european association for percutaneous cardiovascular interventions , american diabetes association , european society of cardiology , transcatheter cardiovascular therapeutics , heart rhythm congress , and the american heart association scientific sessions.resultsthe authors describe new trial data for heart failure ( including eplerenone , finerenone , patiromer , sacubitril / valsartan , the beta 3 agonist mirabegron , sitagliptin , empagliflozin , alginate - hydrogel lv epicardial implant ) , anticoagulation ( idarucizumab and andexanet alfa reversal agents , adherence programmes , practice",380,128,0.3368
dialogsum,"#Person1#: Excuse me, could you tell me which line I'm supposed to stand in to buy bubble wrap and to post a package? #Person2#: You can buy the bubble wrap here, but you'll have to stand in line over here to post your package. #Person1#: That's a really long line. How long do you think it'll take to get through all those people? #Person2#: It takes about 3 minutes per person, so it'll probably be about an hour's wait. #Person1#: Can I buy stamps here? #Person2#: Sure. How many would you like? #Person1#: I need 30 for my Christmas cards. #Person2#: Are you sending them abroad? #Person1#: Twenty of them are going abroad to China and America. #Person2#: Do you have any going anywhere in the EU? If you do, those are less expensive. #Person1#: No. #Person2#: Ok, here you go. That will be 18 pounds and seventy two pence. #Person1#: And the bubble wrap? #Person2#: That's another quid. #Person1#: Thanks a lot. You'Ve been very helpful.",#Person2# tells #Person1# which line #Person1# should stand in to buy bubble wrap and to post a package. #Person2# also helps #Person1# buy stamps and the bubble wrap.,167,28,0.1677
scientific_lay_summarisation-elife-norm,"Insect neuroscience generates vast amounts of highly diverse data, of which only a small fraction are findable, accessible and reusable. To promote an open data culture, we have therefore developed the InsectBrainDatabase (IBdb), a free online platform for insect neuroanatomical and functional data. The IBdb facilitates biological insight by enabling effective cross-species comparisons, by linking neural structure with function, and by serving as general information hub for insect neuroscience. The IBdb allows users to not only effectively locate and visualize data, but to make them widely available for easy, automated reuse via an application programming interface. A unique private mode of the database expands the IBdb functionality beyond public data deposition, additionally providing the means for managing, visualizing, and sharing of unpublished data. This dual function creates an incentive for data contribution early in data management workflows and eliminates the additional effort normally associated with publicly depositing research data. Data are the essence of what science delivers - to society, to researchers, to engineers, to entrepreneurs. These data enable progress, as they provide the basis on which new experiments are designed, new machines are developed, and from which new ideas emerge. Independent of the research field, many terabytes of data are produced every year, yet only a small fraction of these data become openly available to other researchers, with even less penetrating the invisible wall between the scientific community and the public (Mayernik, 2017). While research papers report conclusions that are based on data and present summaries and analyses, the underlying data most often remain unavailable, despite their value beyond the original context. Whereas this is changing in many fields and the use of open data repositories becomes increasingly mandatory upon publication of a research paper, this is not ubiquitous and older data remain inaccessible in most instances. Additionally, merely meeting the data deposition requirement by' dumping' poorly annotated raw files on an internet platform does not aid transparency or reuse of the data. To ensure common standards for data repositories and the datasets to be stored in them, the FAIR principles for data deposition (Findability, Accessibility, Interoperability, and Reusability) were developed (Wilkinson et al. , 2016). It is clear from these principles that annotation and rich metadata are essential, if a dataset is supposed to be beneficial to others.","Insect neuroscience, like any field in the natural sciences, generates vast amounts of data. Currently, only a fraction are publicly available, and even less are reusable. This is because insect neuroscience data come in many formats and from many species. Some experiments focus on what insect brains look like (morphology), while others focus on how insect brains work (function). Some data come in the form of high-speed video, while other data contain voltage traces from individual neurons. Sharing is not as simple as uploading the raw files to the internet. To get a clear picture of how insect brains work, researchers need a way to cross-reference and connect different experiments. But, as it stands, there is no dedicated place for insect neuroscientists to share and explore such a",380,128,0.3368
dialogsum,"#Person1#: I think it's very important to relax because if you don't. You can get too stressed. What do you think? #Person2#: Yes, I think so, once I even got ill because I was too stressed out studying for exams. But what do you do to relax? #Person1#: Well, sometimes I go to my room and lie down and listen to my favorite music or read a book. What about you? #Person2#: I want to relax, I often play computer games. #Person1#: I don't think computer games are relaxing. Yhey can be so exciting and then it's difficult to stop playing. #Person2#: It's not a problem for me, it's good fun. I sometimes play until midnight. #Person1#: Really? That's too bad for your health, you'd better not stay up for it again. Going out is a better way. I sometimes like to take my dog for a long walk in the country or a park. That makes me feel healthy and relaxed. #Person2#: I agree with you.","Both #Person1# and #Person2# think it's important to relax. #Person1# likes listening to music or reading books to relax. #Person2# likes playing computer games, but #Person1# thinks it's not good for health.",167,32,0.1916
dialogsum,"#Person1#: Hi, are you being helped? #Person2#: No, I'm not. I'm interested in some gloves. #Person1#: All our gloves are here. What do you think of this pair here? It's made of silk. #Person2#: Hm, it looks nice, but I'd like to have something warm for the winter. #Person1#: Maybe you would like heavy wool gloves. How about this pair? #Person2#: I think that's what I want. How much is it? #Person1#: It's... forty dollars. #Person2#: It's a little expensive. Do you think it's possible to get a discount? #Person1#: Hm, since you like it so much, how about a 10 percent discount. That's the best I can offer. #Person2#: That's good. #Person1#: Is there anything else I can get for you, a pair of socks? #Person2#: No, that should be it. Thank you.",#Person1# assists #Person2# in buying gloves. #Person2# wants something warm for winter so #Person2# buys a pair of wool gloves with a 10% discount.,134,24,0.1791
scientific_lay_summarisation-elife-norm,"and endocytosis in hippocampal neurons. Taken together our data suggest that CB1R polarity is determined, at least in part, by a novel determinant in the C-terminus of CB1R that contributes to targeted delivery to the axonal compartment and the rapid removal of CB1Rs that reach the somatodendritic membrane. To investigate how CB1R surface polarity is established we used the retention using selective hooks (RUSH) system (Boncompain et al. , 2012) and antibody feeding techniques to examine its secretory pathway trafficking and surface expression (). We used CB1R tagged at the N-terminus with streptavidin binding peptide (SBP) and EGFP (SBP-EGFP-CB1R). When co-expressed with a Streptavidin-KDEL ‘hook’ that localises to the lumen of the Endoplasmic Reticulum (ER), SBP-EGFP-CB1R is anchored at the ER membrane. The retained SBP-EGFP-CB1R can then be synchronously released by addition of biotin and its trafficking through the secretory pathway and surface expression in both axons and dendrites can be monitored (Evans et al. , 2017). The intracellular ctCB1R is implicated in desensitization and internalization (reviewed in Mackie, 2008; Stadel et al. , 2011) and structural motifs and potential interaction partners have been identified (3A; Stadel et al. , 2011). However, the role of this region in determining axonal polarity has not been investigated and the function of the H9 structural motif is unknown. We therefore wondered whether ctCB1R, and H9 in particular, contribute to CB1R surface polarisation. To test the role of the C-terminal domain we initially used CD4, a single-pass membrane protein that has no intrinsic localisation signals and is normally surface expressed in a non-polarised manner (Garrido, 2001; Fache et al. , 2004). We expressed chimeras of CD4 alone or CD4 fused to either ctCB1RWT or a ctCB1R lacking the H9 domain (ctCB1RΔH9; 3B) in hippocampal neurons and examined surface expression by immunostaining (3C). Analysis of the axon to dendrite ratio of surface expression (the surface polarity index) revealed that CD4-ctCB1RWT was markedly more axonally polarised than CD4 alone, indicating that ctCB1R may play a role in polarisation despite its lack of defined canonical localisation signals. Moreover, although still significantly axonally polarised, the degree of polarisation was significantly lower for CD4-ctCB1RΔH9, suggesting that H9 may also contribute to this process (3D). We next analysed constitutive endocytosis of CD4-ctCB1RWT and CD4-ctCB1RΔH9 (4A, B). H9 does not determine","The brain contains around 100 billion neurons that are in constant communication with one another. Each consists of a cell body, plus two components specialized for exchanging information. These are the axon, which delivers information, and the dendrites, which receive it. This exchange takes place at contact points between neurons called synapses. To send a message, a neuron releases chemicals called neurotransmitters from its axon terminals into the synapse. The neurotransmitters cross the synapse and bind to receptor proteins on the dendrites of another neuron. In doing so, they pass on the message. Cannabinoid type 1 receptors (CB1Rs) help control the flow of information at synapses. They do this by binding neurotransmitters called endocannabinoids, which are unusual among neurotransmitters. Rather than sending messages from axons to dendrites, endocannabinoids",380,128,0.3368
dialogsum,"#Person1#: I found out when Jim's birthday is. It's this Friday. #Person2#: Let's plan a surprise party for him! #Person1#: Can you spread the word and ask everyone to bring some kind of snack food? #Person2#: That's easy. Anything else? #Person1#: Will you call his wife and let her know so that if she is available, she can come too? #Person2#: Won't he be surprised! #Person1#: I don't know how old he is though. #Person2#: That's O. K. Maybe his wife will spill the beans!",#Person1# and #Person2# are planning a surprise party for Jim. They want to call Jim's wife for it.,85,18,0.2118
dialogsum,"#Person1#: Hello. This is Mike. Who is it, please? #Person2#: Oh, Mike. This is Amy. My goodness! I've got hold of you, at last. #Person1#: Nice to hear from you again after all these years. What have you been doing? #Person2#: Well, I've tried many things since school. I'm now working for a food processing company in charge of sales. So I travel a lot. #Person1#: Oh, that's great. You must really enjoy it. #Person2#: Oh, I do. Yeah, it's interesting, but it's quite tiring. But, What about you, Mike? #Person1#: I work in a law firm, practicing in business law. #Person2#: Oh, that's challenging. #Person1#: Yeah, but I like my job.",Amy and Mike are talking on the phone. They haven't met for years and they talk about their current jobs.,112,20,0.1786
dialogsum,"#Person1#: I want to ask you for a favor. I want to rent an apartment here in Beijing, but as a foreigner, I don't know the normal practice. Can you give me some advice? #Person2#: First, why don't you tell me what you need, such as how big a room, where you want to live, whether you want to live downtown, and what you like to do. Then I can out which apartment is most suitable for you. #Person1#: I am a student and want to live in Haitian, so that I can live close to my school. I like to play soccer and I like a quiet apartment so I can study. #Person2#: I think that an apartment with two rooms and a kitchen would suit your needs. I can introduce you to a place for rent near your school. The apartment is on the 7th floor, so it is very quiet and suitable for studying. #Person1#: That sounds great! #Person2#: You can also go to the school's sports field to play soccer, and if you're lucky you might make some Chinese friends there. It is right near the market and has comfortable facilities. #Person1#: Thank you so much. That's very kind of you.",#Person1# wants to rent a quiet apartment in Haitian. #Person2# suggests an apartment near #Person2#'s school where #Person2# can play soccer in the school's sports field and make some Chinese friends.,205,31,0.1512
pubmed-summarization,"played by mirna in colon cancer initiation and progression , especially in the context of the synergism existing among hypoxic condition , expression of il-6 pro - inflammatory cytokine and up - regulation of vegfa165 . we report that this cooperation could act on the neoplastic cell , also by the dysregulation of mirnas involved in colon cancer progression relevant pathways . both the over - expression and the silencing of specific mirnas recent studies have identified specific mirnas present in colorectal cancer tissues and blood that may aid the diagnosis of cancer and help to predict disease recurrence . such a role in oncogenesis suggested that mirnas could represent important targets for gene therapies . although little is known about the exogenous factors that interfere with the regulation of mirna expression , the microenvironment seems to play an essential role , affecting the epigenetic mechanisms that modulate mirna gene expression , including methylation , histone deacetylation , or influencing the function of proteins involved in the maturation processing of micrornas . the present review will focus on the peculiar relationship between colon cancer cells and microenvironment , that could influence mirnas dysregulation , the apoptosis escaping and the metabolic shift , leading to invasion and metastasis . micrornas ( mirnas ) are ~22-nt small noncoding rnas that are processed from larger ( 80-nt ) precursor hairpins by the rnase iii enzyme dicer into mirna : mirna duplexes . one strand of these duplexes associates with the rnainduced silencing complex ( risc ) , whereas the other is generally degraded . the mirna risc complex targets messenger rnas triggering either translational repression or mrna degradation . the total number of mirnas that are encoded in the human genome remains to be clarified . initial estimates suggested there were up to 255 human mirnas , but cloning and bioinformatic analyses have demonstrated that there are numerous nonconserved human mirnas and suggest this number may be significantly larger . thousands of mammalian messenger rnas are under selective pressure to maintain nucleotide sites matching micrornas . usually conserved targets are often highly expressed at developmental stages , before mirnas expression and their levels tend to fall as the mirna that targets them begins to accumulate . the phenomenon of the selective avoidance extended","the influence of the microenvironment through the various steps of cancer progression is signed by different cytokines and growth factors , that could directly affect cell proliferation and survival , either in cancer and stromal cells . in colon cancer progression , the cooperation between hypoxia , il-6 and vegf - a165 could regulate the dna repair capacity of the cell , whose impairment is the first step of colon cancer development . this cooperation redirects the activity of proteins involved in the metabolic shift and cell death , affecting the cell fate . the pathways triggered by micro environmental factors could modulate cancer - related gene transcription , affecting also small non coding mrna , micrornas . micrornas have emerged as key post - transcriptional regulators of",380,128,0.3368
dialogsum,"#Person1#: Have you heard about Anlesen David? #Person2#: No, have they have another fight? #Person1#: No, they got engageed. #Person2#: You must be joking. Those two. #Person1#: Well, my dear. I didn't believe either. But got it straight form the horse's mouth. Davi called me this morning. #Person2#: So when did this happen? #Person1#: Last weekend , while they were on the sik trip. #Person2#: Well, I believe it now, and when are they are getting marry? #Person1#: Next june. #Person2#: I can hardly believe it.",#Person1# says David got engaged and will get married next June. #Person2# is really surprised.,86,15,0.1744
scientific_lay_summarisation-elife-norm,"Follicle rupture, the final step in ovulation, utilizes conserved molecular mechanisms including matrix metalloproteinases (Mmps), steroid signaling, and adrenergic signaling. It is still unknown how follicles become competent for follicle rupture/ovulation. Here, we identify a zinc-finger transcription factor Hindsight (Hnt) as the first transcription factor regulating follicle’s competency for ovulation in Drosophila. Hnt is not expressed in immature stage-13 follicle cells but is upregulated in mature stage-14 follicle cells, which is essential for follicle rupture/ovulation. Hnt upregulates Mmp2 expression in posterior follicle cells (essential for the breakdown of the follicle wall) and Oamb expression in all follicle cells (the receptor for receiving adrenergic signaling and inducing Mmp2 activation). Hnt’s role in regulating Mmp2 and Oamb can be replaced by its human homolog Ras-responsive element-binding protein 1 (RREB-1). Our data suggest that Hnt/RREB-1 plays conserved role in regulating follicle maturation and competency for ovulation. Ovulation is a complex process of releasing fertilizable oocytes from mature follicles and is essential for animal reproduction (Espey and Richards, 2006). To ensure successful ovulation, a follicle must be developed to full maturity to be competent to receive an ovulatory stimulus and to activate proteolytic systems for follicle rupture. Several proteolytic systems have been found to regulate follicle rupture in vertebrates, including matrix metalloproteinase (Mmp), plasminogen activator/plasmin, and ADAMS-TS (Curry and Smith, 2006; Takahashi et al. , 2013). In addition, a surge of luteinizing hormone (LH) serves as a master regulator to initiate the ovulation event and activates the EGF/EGFR-Ras-MAPK signaling pathway to propagate the ovulatory signal from outer granulosa cells to inner cumulus cells in the preovulatory follicles (Conti et al. , 2012; Fan et al. , 2009,2011,2012; Hsieh et al. , 2007). However, molecular mechanisms coupling the Ras-MAPK pathway to the activation of proteolytic systems for follicle rupture are largely unknown. Ovulation in Drosophila utilizes conserved molecular mechanisms and involves a follicle rupture process to release mature oocytes from the ovary. Drosophila have two ovaries, connected at their posterior ends by bilateral oviducts (). Each ovary contains ~16 ovarioles, where egg chambers are assembled in the germarium at the anterior and develop through 14 characteristic stages toward the posterior end (Spradling, 1993). Each egg chamber contains one oocyte and 15 nurse cells surrounded by a layer of somatic follicle cells. In stage-14 egg chambers","The release of an egg from the ovary of a female animal is a process known as ovulation. Animals as different as humans and fruit flies ovulate in largely similar ways. Yet the systems involved in controlling ovulation are still not well understood. An egg cell develops within a collection of cells that help the egg to form properly. Together, this unit is called a follicle. During ovulation, connections between the egg and the rest of the follicle break down and the egg is eventually ejected. Ovulation happens in response to a hormone signal from the brain. In humans, this hormone is called luteinizing hormone, whereas in flies it is called octopamine. Specialized protein molecules on the surface of the follicle cells receive these hormone signals, but can",380,128,0.3368
dialogsum,"#Person1#: Oh, my! It's really hot. I've never seen such scorching weather in my life. #Person2#: Tell me about it! It's like the whole world is broiling. #Person1#: Oh, look at the thermometer! The temperature has hit 98. #Person2#: I hope it's not gonna break into three digits #Person1#: But it's already awfully close. #Person2#: Well, I just hope it'll level off. #Person1#: I guess you can't do anything until after dark then. #Person2#: I guess so. What else can we do? You can't stay in the heat for long.",#Person1# and #Person2# complain about the hot weather and consider what they can do during the daytime.,90,17,0.1889
pubmed-summarization,"the use of nanoparticles for cellular imaging is among the most important clinical breakthrough of the past decade . in particular , superparamagnetic iron oxide ( spio ) nanoparticles enhance contrast in magnetic resonance imaging ( mri ) , which allows clinicians to monitor anatomical , physiological , and molecular changes during the evolution of a disease or treatment . following intravenous injection , these nanoparticles accumulate in macrophages residing in the liver , bone marrow , and spleen , as well as tumors and sites of inflammation . accordingly , applications include the detection of inflammatory diseases , in vivo stem cell tracking,1 hyperthermia therapy,2 lymph node detection,3 and anticancer drug delivery.4 the current applications for spio nanoparticles are limited because these relatively large particles , with an average diameter of 80 nm , are rapidly internalized by the mononuclear phagocytic system of the liver and the spleen . this problem is currently addressed by the development of ultrasmall superparamagnetic iron oxide ( uspio ) nanoparticles ( < 50 nm).5 in vivo studies recently showed that uspio nanoparticles of 35 nm in diameter have a longer half - life in the circulation system , allowing the labeling of macrophages migrating to remote areas.6,7 these studies opened the door to a number of new applications for molecular imaging because macrophages migrate and accumulate at sites of inflammation,8 autoimmune neuritis,9 renal ischemia,10 and solid organ transplant rejection.11 the use of uspio agents has allowed for the direct visualization of macrophage infiltration of carotid atheroma in clinical study.12,13 the surface coating of uspio nanoparticles also influences their stability and cellular uptake by macrophages.6 dextran - based coatings are preferred because of their low toxicity and they are biodegradable.14 for instance , dextran - coated spio nanoparticles and ferucarbotran are approved for liver mri . moreover , carboxydextran - coated spio nanoparticles have undergone clinical trials for mri evaluation of lymph node metastasis;15,16 however , the impact of uspio nanoparticles size and dextran coating composition on the uptake by macrophages has not been determined . the aim of the present study is to determine the impact of particle size and surface coating on the cellular uptake and relaxing time of spio nanoparticles in mouse macrophages by mri and microscopy . the uspio (","purposemagnetic resonance imaging ( mri ) using contrast agents like superparamagnetic iron oxide ( spio ) is an extremely versatile technique to diagnose diseases and to monitor treatment . this study tested the relative importance of particle size and surface coating for the optimization of mri contrast and labeling efficiency of macrophages migrating to remote inflammation sites.materials and methodswe tested four spio and ultrasmall superparamagnetic iron oxide ( uspio ) , alkali - treated dextran magnetite ( atdm ) with particle sizes of 28 and 74 nm , and carboxymethyl dextran magnetite ( cmdm ) with particle sizes of 28 and 72 nm . mouse macrophage raw264 cells were incubated with spios and uspios , and the labeling efficiency of the cells was determined by the percentage of",380,128,0.3368
dialogsum,"#Person1#: I'd like to start by talking about prices. #Person2#: I'd be glad to answer any questions you may have. #Person1#: Your products are very good, but the price you ask is much too high. #Person2#: If you consider our high research costs and excellent quality, the price we are asking is only reasonable. #Person1#: I know, but we want 1000 pieces. This is a very large order. So, can you give us a 25 percent discount?",#Person2# makes #Person1# believe that the price is reasonable but #Person1# still wants a discount because of the large order.,77,20,0.2597
pubmed-summarization,"wilms tumor ( wt ) , also known as nephroblastoma , is the most frequent renal tumor occurring in children aged 0 to 15 years , especially among those younger than 6 years . wt accounts for roughly 6% of all childhood cancers ; 5% of whom had bilateral involvement , and 1% of whom had a family history . thanks to the prospective clinical trials performed by the international society of pediatric oncology renal tumor study group ( siop - rtsg , europe ) and the children s oncology group ( cog , formerly nwtsg , north america ) , most patients ( 85% ) affected by wt can be successfully cured . however , some studies released surveys reporting that there are still a few children who may have a poor prognosis or relapse with current therapies , 50% of whom will die despite intensive re - treatment . it has been proven that genetic variants are strongly associated with the development of wt . mutations in wt1 or epigenetic defects on chromosome 11p15 contribute to the major genetic susceptibility locus . previous studies have reported several non - wt1 loci with smaller effects on the genetic predisposition for wt , including p53 gene , insulin - like growth factor - ii gene , ctnnb1 gene , and h19 . however , less than half of wt cases are attributable to known genes that are associated with wt risk ; therefore , the exact pathogenesis of most wt cases remains unknown and identification of novel genetic loci is urgently needed . the reversion - inducing cysteine - rich protein with kazal motifs ( reck ) gene , known as a transformation suppressor gene , can restrain tumor invasion and metastasis through suppression of matrix metalloproteinases ( mmps ) , including mmp-4 and mmp-9 . mmps proteolytically degrade extracellular matrix proteins , which is critical for tumor metastasis and invasion . reck is expressed in a number of normal tissues , but it appears to be down - regulated in several types of cancers , including esophageal cancer , breast cancer , lung cancer , colorectal cancer , osteosarcoma , gastric carcinoma , prostatic cancer , oral cancer , pancreatic cancer , and cholangiocarcinoma . moreover , clinical investigations","backgroundwilms tumor ( wt ) is the most common malignant renal tumor in children . previous studies suggested the reversion - inducing , cysteine - rich protein with kazal motifs ( reck ) down - regulation might have a role in numerous human cancers . the current study was done to investigate the associations of reck single - nucleotide polymorphisms ( snps ) with the wt susceptibility in chinese children.material/methodswe analyzed 2 snps ( rs10972727and rs11788747 ) in a total of 97 wt children and 194 healthy matched controls ( 1:2 ratio ) by real - time pcr and pcr - rflp genotyping analysis.resultswe found that the g allele of rs11788747 in the reck gene was significantly associated with wt in chinese children ( or=0.7 , 95% ci",380,128,0.3368
scientific_lay_summarisation-elife-norm,"amino acid balance by ISR activation. In animal cells, eIF2a phosphorylation is reversed by cellular phosphatase complexes consisting of a protein phosphatase 1 catalytic subunit (PP1) and a substrate-specific regulatory subunit. Two such regulatory subunits have been identified in mammals: PPP1R15A (known as GADD34) is encoded by an ISR-inducible gene (Novoa et al. , 2001; Ma and Hendershot, 2003), whereas PPP1R15B (known as CReP) is constitutively present (Jousse et al. , 2003). Cells lacking PPP1R15A are impaired in recovery of protein synthesis during resolution of the stress response (Novoa et al. , 2003; Marciniak et al. , 2004), whereas elimination of PPP1R15B results in developmental impairment and perinatal lethality of mice. Importantly, inactivation of both PPP1R15 isoforms is lethal to cells (Tsaytler et al. , 2011), but can be rescued by converting serine 51 of eIF2a to the non-phosphorylatable alanine, providing genetic proof for the narrow in vivo substrate specificity of the PPP1R15 family of regulatory subunits (Harding et al. , 2009). In mammals, PPP1R15 genes encode proteins of over 600 amino acids, but conspicuous conservation of sequence between the A and B isoform is confined to a stretch of ∼70 residues at their C-termini. This is also the only sequence in eIF2a-specific regulatory subunits that is conserved broadly across phyla and is encoded by a separate exon; a conserved feature of the genomic organization of the two isoforms of PPP1R15. Viruses have co-opted PPP1R15; presumably to neutralize the effects of host PKR (He et al. , 1996,1997) and conservation amongst these viral proteins is also confined to the same stretch of 70 residues. The preeminence of the PPP1R15 C-terminus is also supported by functional experiments, as over-expression of this portion was the basis of their identification as ISR inhibitors in the first place (Novoa et al. , 2001; Jousse et al. , 2003), whereas the extended N-terminal region of PPP1R15 participates in membrane binding, regulating subcellular localization and turnover (Brush et al. , 2003; Brush and Shenolikar, 2008; Zhou et al. , 2011). Binding to the PP1 catalytic subunit has been mapped to the C-terminal functional core of the PPP1R15 family (Connor et al. , 2001; Novoa et al. , 2001) and is shared by the pared-down viral proteins (He et al. , 1998). An RVxF motif, common to","For a cell to build a protein, it must first copy the instructions contained within a gene. A complex molecular machine called a ribosome then reads these instructions and translates them into a protein. This translation process involves a number of steps. Proteins called eukaryotic translation initiation factors (or eIFs for short) coordinate the first step in the process, which is known as ‘initiation’. The eIFs also provide the cell with ways to control how quickly it makes proteins. For example, when a cell is stressed, either by starvation or toxins, it adds a phosphate group onto part of an eIF protein, called eIF2α. This modification makes this eIF protein less able to initiate translation, and so the cell builds fewer proteins and conserves more of its resources",380,128,0.3368
scientific_lay_summarisation-elife-norm,"In mammalian cells three closely related cavin proteins cooperate with the scaffolding protein caveolin to form membrane invaginations known as caveolae. Here we have developed a novel single-molecule fluorescence approach to directly observe interactions and stoichiometries in protein complexes from cell extracts and from in vitro synthesized components. We show that up to 50 cavins associate on a caveola. However, rather than forming a single coat complex containing the three cavin family members, single-molecule analysis reveals an exquisite specificity of interactions between cavin1, cavin2 and cavin3. Changes in membrane tension can flatten the caveolae, causing the release of the cavin coat and its disassembly into separate cavin1-cavin2 and cavin1-cavin3 subcomplexes. Each of these subcomplexes contain 9 ± 2 cavin molecules and appear to be the building blocks of the caveolar coat. High resolution immunoelectron microscopy suggests a remarkable nanoscale organization of these separate subcomplexes, forming individual striations on the surface of caveolae. Caveolae are an abundant feature of the plasma membrane of many vertebrate cells. The surface of adipocytes, endothelial cells, smooth muscle, skeletal muscle and many other cell types is characterized by a dense covering of these small invaginations with a characteristic striated coat, as viewed by electron microscopy, and by the presence of membrane proteins termed caveolins (Peters et al. , 1985; Kurzchalia et al. , 1992; Rothberg et al. , 1992; Way and Parton, 1995; Scherer et al. , 1996; Parton and Del Pozo, 2013). Three caveolins are present in mammalian cells with caveolin-1 (CAV1) and caveolin-3 (CAV3) essential for caveolar formation in nonmuscle and muscle cells respectively. Caveolins bind cholesterol and fatty acids and form homo-oligomers required for caveolar formation. Approximately 140 CAV1 molecules associate with a single caveola in mammalian cells (Pelkmans and Zerial, 2005) and in a model prokaryotic system upon caveolin expression (Walser et al. , 2012). Genetic ablation of caveolins in mice has diverse cellular consequences with impact upon numerous signal transduction pathways and lipid dysregulation. Human patients lacking CAV1 show a severe lipodystrophy while CAV3 mutations, many of which disrupt caveola formation in muscle, are associated with a number of muscle diseases. Recent years have seen a dramatic increase in our understanding of caveolae with the characterization of a family of caveolar coat proteins (Hill et al. , 2008; Bastiani et","If you could look closely enough at the surface of some animal cells, especially fat or muscle cells, you would see that they are covered with pocket-like indents called ‘caveolae’. These structures are thought to help the cells communicate with the outside world, but they can also be used by viruses to gain entry into living cells. Examining these caveolae even closer would reveal that these pockets contain proteins called caveolins that bind to each other—and also to cholesterol and fatty acids—to form a scaffold that help to maintain the shape of the caveolae from inside the cell. Each caveolae in a mammalian cell typically contains over 100 caveolin proteins. Caveolar coat proteins, or cavins for short, are also important building blocks for caveolae: however, we know relatively",380,128,0.3368
scientific_lay_summarisation-elife-norm,"hydrophobic interactions with amino acids in the antigen binding cleft (Kjer-Nielsen et al. , 2012; Patel et al. , 2013), whereas binding of unstable 5-RAU-derivatives requires covalent trapping within the MR1 pocket via formation of a Schiff base with Lysine 43 (Corbett et al. , 2014; Patel et al. , 2013). While three additional molecules have also been demonstrated to bind MR1 via the same mechanism, including 6-formyl-pterin (6-FP), acetyl-6-formyl-pterin (Ac-6-FP), and acetylamino-4-hydoxy-6-formylpteridine dimethyl acetal (Kjer-Nielsen et al. , 2012; Patel et al. , 2013; Soudais et al. , 2015), these compounds lack the ribityl moiety necessary for MAIT cell activation and instead inhibit stimulation by microbial ligands (Corbett et al. , 2014; Kjer-Nielsen et al. , 2012; Soudais et al. , 2015). A recent study reported that 6-FP and Ac-6-FP can also stimulate a second population of ‘atypical’ MR1-restricted T cells of unknown function in the blood of healthy human donors (Gherardin et al. , 2016), but this population, did not express the canonical TRAV1-2 gene which defines MAIT cells. Together, these findings indicate a degree of MR1 plasticity in accommodating diverse chemical structures and suggest that other MR1-restricted T cell populations may exist in vivo. Here we report a novel population of MR1-restricted T cells (hereafter termed MR1T cells) that is readily detectable in blood from healthy individuals. MR1T cells express diverse TCRα and β genes and were not able to recognize previously identified microbial or folate-derived ligands of MR1. Instead, MR1T cells recognized self-antigens presented by MR1 and expressed a broad selection of cytokines and chemokine receptors. Functionally, MR1T cells were capable of inducing dendritic cell (DC) maturation and promoted innate defense in intestinal epithelial cells. These findings demonstrate that MR1 can present non-microbial antigens to a novel population of functionally diverse human T cells with potentially wide-ranging roles in human immunity. During our previous study on the repertoire of human MAIT cells (Lepore et al. , 2014), we detected an atypical MR1-restricted T cell clone that did not react to microbial ligands. This T cell clone (DGB129) recognized cell lines constitutively displaying surface MR1 (CCRF-SB lymphoblastic leukemia cells, or THP-1 monocytic leukemia cells; 1A) or A375 melanoma cells (A375-MR1) transfected with an MR1-β2m fusion gene construct (Lepore et al. , 2014) (1A) in the absence of","White blood cells called T cells recognize germs and infected cells, and get rid of other cells in the body that look different to healthy cells – for example, tumor cells. These activities all depend on a molecule called the T cell receptor (or TCR for short), which is found on the surface of the T cells. Each TCR interacts with a specific complex on the surface of the target cell. One of the molecules recognized by the TCR is known as MHC class I-related (shortened to MR1). This molecule attracts TCRs to infected cells, but it was not know if the MR1 molecule could attract TCRs to cancer cells too. Lepore et al. now show that there are indeed T cells in humans that recognize cancer cells",380,128,0.3368
dialogsum,"#Person1#: If that man gives me any more letters to type, I'll scream. He's given me ten already today, and there'll be more when I get back from coffee break. I'll be here till midnight. #Person2#: Calm down, Franny. He can't make you stay after five. Finish what you can, and leave the rest for Mary. #Person1#: But they're important letters, Joe. They should go out tonight. #Person2#: That's not your worry. If they're important, he should have given them to you earlier.",Franny is anxious about the large amount of letters to type but Joe thinks he can leave it to Mary.,83,20,0.241
dialogsum,"#Person1#: I've really given it some thought, and I'm going to go back to school. I'm going to... #Person2#: Well, When... #Person1#: I'm going to take some night courses and maybe, within a couple of years. I'll have a ...uh... Associate Degree in Business. #Person2#: Well, when are you going to get started? #Person1#: I'm going to start this fall. #Person2#: Now are you sure you can get enough money? #Person1#: I've talked to my parents and it's uh...It's green light from them. #Person2#: Well, that's great. I hope you follow through with it. I've heard about this kind of thing before...you've been talking about it for years. #Person1#: Well, it took me a while to put it together, but I've finally made up my mind where I'm going to go and this fall, it's 'go' time. #Person2#: Well, I just hope you follow through with it this time. #Person1#: I will.",#Person1# decides to go back to school and takes some courses. #Person1# will start this fall and has received his parents' financial support.,152,23,0.1513
scientific_lay_summarisation-elife-norm,"T. b. gambiense, a unique point polymorphism is found in HpHbR (Symula et al. , 2012) that reduces the monovalent affinity for ligand by 20-fold (Higgins et al. , 2013). This contributes to resistance to TLF1, illustrating the importance of HpHbR. Haptoglobin-haemoglobin is an elongated ‘dumbell-shaped’ complex consisting of a dimer of haptoglobin molecules, each joined to an αβ haemoglobin dimer (Andersen et al. , 2012). Trypanosomes take up this HpHb complex but not the individual components (Vanhollebeke et al. , 2008). The structure of the T. congolense HpHbR is an elongated three-helical bundle with a small membrane distal head (Higgins et al. , 2013). Residues involved in HpHb binding are part of a small conserved patch ∼25 Å below the tip of the receptor, but details of ligand binding and uptake were not characterized. Here, we present the structure of T. brucei HpHbR. We show that the receptor adopts a similar architecture to its T. congolense homologue, but with a ∼50° kink a third of the way along from the membrane proximal end. We also present the structure of TbHpHbR in complex with HpHb, revealing the molecular basis for ligand binding and selectivity. Finally, we show that the kink allows two independent membrane attached receptors to interact with a single dimeric HpHb molecule and confirm using cell uptake experiments that this causes dimeric ligand to be taken up with greater efficiency than monomeric ligand. This reveals the molecular basis for the uptake of HpHb and trypanolytic factor-1 and identifies adaptations in the trypanosome receptor that allow efficient ligand uptake in the context of the tightly packed VSG coat. To provide detailed molecular knowledge of the mechanism of uptake of haptoglobin-haemoglobin and trypanolytic factor-1 (TLF1), we aimed to determine the structure of T. brucei HpHbR (TbHpHbR) alone and bound to a human haptoglobin-haemoglobin complex. TbHpHbR is longer than its homologue from T. congolense due to the presence of an additional C-terminal membrane-proximal domain. We therefore used the previously determined structure of T. congolense HpHbR (Higgins et al. , 2013) to design a construct containing the corresponding region of TbHpHbR (residues 36–299). This region of the protein is identical in the human infective T. b. rhodesiense. Haptoglobin-haemoglobin consists of a dimer of haptoglobin chains, each interacting with an αβ dimer of","African Trypanosomes are a group of single-celled parasites that are a major concern for livestock farmers in sub-Saharan Africa. They are carried by the tsetse fly and can cause disease in domestic livestock that diminishes productivity through reduced growth, and may ultimately lead to death. The parasites are coated in a dense layer of protein that help them evade the host’s immune system by preventing immune cells from identifying them. Humans have evolved immunity to many trypanosome species by exploiting a weakness in their lifestyle. Trypanosomes need to get haem—a molecule found in the protein haemoglobin—from their host to survive. In blood plasma, haemoglobin is found associated with a carrier protein called haptoglobin. To acquire haem, the parasites have a protein called HpHbR that binds to these haptoglobin-haemoglobin",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Plants rely on transcriptional dynamics to respond to multiple climatic fluctuations and contexts in nature. We analyzed the genome-wide gene expression patterns of rice (Oryza sativa) growing in rainfed and irrigated fields during two distinct tropical seasons and determined simple linear models that relate transcriptomic variation to climatic fluctuations. These models combine multiple environmental parameters to account for patterns of expression in the field of co-expressed gene clusters. We examined the similarities of our environmental models between tropical and temperate field conditions, using previously published data. We found that field type and macroclimate had broad impacts on transcriptional responses to environmental fluctuations, especially for genes involved in photosynthesis and development. Nevertheless, variation in solar radiation and temperature at the timescale of hours had reproducible effects across environmental contexts. These results provide a basis for broad-based predictive modeling of plant gene expression in the field. Plants have evolved responses to complex environmental fluctuations that take place at time scales that vary from seconds to years and shape plant developmental and physiological responses. Variations in environmental signals, including temperature, water levels, solar radiation, biotic interactions and resource availability, are often unpredictable and need to be integrated and transduced to changes in gene expression, which may then be associated with physiological and/or morphological adaptations (Ahuja et al. , 2010; Weston et al. , 2008). Predicting the adaptive responses occurring in natural environments is a key challenge in plant biology. This is an undertaking that will not be achieved without understanding how genes and functional genetic networks are regulated in response to fluctuating stimuli out in nature (Richards et al. , 2009). Studies of plant transcriptional responses to environmental perturbations are nearly exclusively undertaken in controlled, static laboratory conditions that are divergent from what is seen in the natural world. While these laboratory experiments have enriched our knowledge of the molecular pathways involved in abiotic stimulus responses, it is clear that organismal phenotypes and the genetic architecture of various traits differ between controlled laboratory and field conditions (Malmberg et al. , 2005; Mishra et al. , 2012; Weinig et al. , 2002). This so-called “laboratory/field (lab-field) gap” is often referred to when trying to explain why the improvement of crops for resistance to abiotic stresses, for example, has not met the expectations arising from","Plants need to be able to sense and respond to changes in temperature, light levels and other aspects of their environment. One way in which plants can rapidly respond to these changes is to modify how genes involved in growth and other processes are expressed. Therefore, understanding how this happens may help us to improve the ability of crops to grow when exposed to drought or other extreme environmental conditions. Most previous studies into the effect of the environment on plant gene expression have been carried out under controlled conditions in a laboratory. These findings cannot reflect the full range of gene expression patterns that occur in the natural environment, where multiple factors (e. g. sunlight, water, nutrients) may vary at the same time. Therefore, it is important",380,128,0.3368
dialogsum,"#Person1#: Guess what? Paul and Susan are engaged. #Person2#: Really? When did that happen? #Person1#: A week ago? They met last summer and now just sink. They will be married soon. #Person2#: Have they set a date for the wedding? #Person1#: No, not yet. But Susan says they'd like to get married in November or December. Then they'll go to Hawaii for their honeymoon.",#Person1# tells #Person2# the news that Paul and Susan are engaged. #Person2#'s surprised.,64,13,0.2031
dialogsum,"#Person1#: Hey, dad, I have just been given this project at school. Do you think you can help me out? #Person2#: Sure, what's this project about? #Person1#: Well, I should interview someone that I admire about their jobs. #Person2#: Well, I am an expert when it comes to my job. Accounting is a respectable job and one that I am always happy to talk about. #Person1#: Dad, I know how much you love your job. It isn't that I don't admire you. But what I was hoping actually was that you could speak to Mr. Chung, your diving friend, and see if he would agree to an interview. Diving for a living sounds cool. #Person2#: I see. That's a great idea. You know how I really dislike talking about myself again and again for too long. Let me give David Chung a call right now and find out. #Person1#: Thanks, dad. I know this will be a wonderful project.","#Person1# has a project about interviewing someone that #Person1# admires about their jobs. #Person1# wants #Person1#'s dad to talk to his diving friend, Mr. Chung.",159,25,0.1572
scientific_lay_summarisation-elife-norm,"birds, and mammals offered mixed empirical support (Smith and Blumstein, 2008). This meta-analysis showed that bolder animals put themselves at greater risk and die at younger ages, but enjoy greater reproductive success than their shyer counterparts, which do not enjoy as many opportunities for copulation, but live longer, and so are able to invest more in their offspring (Smith and Blumstein, 2008). Boldness therefore is associated with a ‘faster’ (r-selected) life-history strategy. The findings of the meta-analysis for exploration and aggression were less clear: more aggressive individuals had greater reproductive success than less aggressive individuals, but this was not offset by reduced lifespan; individuals more prone to exploring their environment lived longer than neophobic individuals, but did not experience reduced reproductive success (Smith and Blumstein, 2008). Two concurrent reviews showed that, across a range of species, greater boldness, activity, and aggressiveness, and lower sociability and exploration, were associated with a faster life history strategy (Réale et al. , 2010; Biro and Stamps, 2008). Recent research found evidence that variation in the personality traits of humans and nonhuman primates are also associated with variables related to life history strategies. Studies of humans predominate this literature and, although there are exceptions (e. g. , Alvergne et al. , 2010; Gurven et al. , 2014), this human literature grew out of personality psychology, health psychology, and epidemiology. Consequently, these studies did not set out to deliberately test whether personality variation reflected individual differences in life history. The studies of human personality described above tended to focus on one or more of five traits - extraversion, agreeableness, openness, neuroticism, and conscientiousness - known collectively as the ‘Big Five’ or ‘Five-Factor Model’ (Digman, 1990). These five traits are operationalized as dimensions onto which several related lower-order traits cluster (Digman, 1990). Four of the five human traits correspond to personality traits studied by behavioral ecologists. Extraversion and agreeableness characterize how often and how well humans navigate their social world (Digman, 1990). Among other characteristics, extraversion features sociability and activity (Costa and McCrae, 1995), which are comparable to the same-named traits studied in behavioral ecology; agreeableness is the opposite of aggressiveness (Réale et al. , 2007). Openness captures curiosity, originality, and a tendency to find novel ideas and situations appealing (Digman, 1990), and corresponds to exploration (Réale","Like humans, animals have distinct personalities. Our close evolutionary cousins chimpanzees even display the same five major personality traits that we do – extraversion, neuroticism, conscientiousness, openness, and agreeableness – as well as a distinct trait, for dominance. How did these distinct personality traits evolve and persist across different species? Ultimately, each trait must provide some fitness benefits that help the animal to reproduce and pass on the trait to its offspring. Longevity is an important factor in promoting fitness; an animal that lives for longer will have more opportunities to reproduce. Previous work in humans and other animals suggested that some personality traits are associated with a longer life. However, few studies have been large enough to test all major personality traits in both sexes of an",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Insects have evolved diverse and remarkable strategies for navigating in various ecologies all over the world. Regardless of species, insects share the presence of a group of morphologically conserved neuropils known collectively as the central complex (CX). The CX is a navigational center, involved in sensory integration and coordinated motor activity. Despite the fact that our understanding of navigational behavior comes predominantly from ants and bees, most of what we know about the underlying neural circuitry of such behavior comes from work in fruit flies. Here, we aim to close this gap, by providing the first comprehensive map of all major columnar neurons and their projection patterns in the CX of a bee. We find numerous components of the circuit that appear to be highly conserved between the fly and the bee, but also highlight several key differences which are likely to have important functional ramifications. Honeybees and desert ants are iconic navigators (Reviewed in Collett, 2019). Honeybees can forage tens of kilometers away from their nest and can also communicate the distance and direction of foraging locations to fellow workers (Frisch, 1967). Desert ants forage hundreds of meters away from their nest in landscapes sometimes entirely bereft of visual landmarks (Wehner, 2020). Both insects preferentially make use of the most reliable visual cues, such as polarized skylight, but can also make use of an arsenal of backups to ensure a robust compass signal, including windflow (Müller and Wehner, 2007) and magnetoreception (Collett and Baron, 1994; Fleischmann et al. , 2020). Although their navigational behavior is less well characterized than that of honeybees and desert ants, bumblebees are also impressive foragers, as well as generally charismatic insects that play vital ecological roles (Goulson, 2003). Bumblebees forage hundreds to thousands of meters away from their nest and have been shown to be capable of homing from novel locations at distances up to 9. 8 km (Goulson and Stout, 2001; Prŷs-Jones and Corbet, 2011). Like honeybees, bumblebees rely on celestial cues such as polarized light for homing (Wellington, 1974) and have been shown to compensate for wind drift (Riley et al. , 1999). Bumblebees also show a remarkable capacity to learn novel tasks (Loukola et al. , 2017; Chittka, 2017). While behaviorally, navigation and orientation are best understood in ants and bees,","Bumblebees forage widely for pollen and nectar from flowers, sometimes travelling kilometers away from their nest, but they can somehow always find their way home in a nearly straight line. These insects have been known to return to their nest from new locations almost 10 kilometers away. This homing ability is a complex neurological feat and requires the brain to combine several processes, including observing the external world, controlling bodily movements and drawing on memory. While the navigational behavior of bees has been well-studied, the neuronal circuitry behind it has not. Unfortunately, most of what is known about insects’ brain activity comes from studies in species such as locusts or fruit flies. In these species, a region of the brain known as the central complex has been shown",380,128,0.3368
dialogsum,"#Person1#: Have you ever been to Xi'an? #Person2#: Yes, I'Ve been there several times on business trips. But I have never really seen the terra-cotta warriors as it is outside the city. #Person1#: I'Ve heard many people saying that it is a place worth touring. I really want to see the old walls and terra-cotta warriors one day. Of course I won't miss the local food either. You know, the sites interests a food in scenery, food is a key factor when visiting a place. #Person2#: I agree. As long as the food is not too bizarre once I saw some people eating insects. That is frightening. #Person1#: Sure it is. Is it convenient to get there by plane? #Person2#: Well, the airport is quite far from the downtown area, but it is still more convenient than taking the train.","#Person1# thinks Xi'an is worth visiting and #Person2# agrees, but #Person2# thinks the food is bizarre. #Person2# also tells #Person1# it's convenient to get there by plane.",140,27,0.1929
dialogsum,"#Person1#: Have you heard of the Love Bug? #Person2#: Do you mean the'I love you'virus that attacks computers through e-mail? #Person1#: Yes. It is one of the most harmful computer viruses in the world. People say it will break out again om Valentines'Day this year. #Person2#: This is terrible. Why do hackers play such a dirty trick? #Person1#: Hackers are smart, and they want people to know about it. #Person2#: So they create viruses to tell people they are smart? That's really sick.","#Person1# and #Person2# are discussing the Love Bug, and #Person1# explains why hackers play the trick.",83,16,0.1928
dialogsum,#Person1#: During the last thunder storm I noticed several leaks in my bedroom ceiling and they really caused a mess. #Person2#: Maybe you have some broken tiles. I have the phone number of a good roofing company that could do a good repair job for you at a reasonable price.,#Person2# tells #Person1# a good company to fix the leaks.,50,10,0.2
dialogsum,#Person1#: What will I earn per year in this job? #Person2#: You can expect to earn sixty-five thousand dollars per year. #Person1#: Are we covered by a good benefits plan? #Person2#: The job has a menu plan where you are given a fixed amount of money and you choose what you most need in terms of benefits. #Person1#: Can we take personal days off? #Person2#: You get 2 weeks paid vacation and an additional 10 days of sick leave. #Person1#: What do you offer in terms of a retirement plan? #Person2#: We do not currently offer any retirement plan. #Person1#: Do you reimburse for education that relates to my job? #Person2#: We allow several weeks release time each year for our employees to attend job-related seminars and conferences. #Person1#: Do you have a benefits brochure? #Person2#: Whoa! Who said you got the job?,"#Person2# answers #Person1#'s questions about annual salary, the benefits plan, vacations, retirement plan, etc. #Person2# gets impatient at the end because #Person1# hasn't got the job.",143,26,0.1818
scientific_lay_summarisation-elife-norm,"and MINS are generally tailored to specific applications (Luengo et al. , 2017; Stegmaier et al. , 2016; Lou et al. , 2014; Cabernard and Doe, 2013; Homem et al. , 2013; Arganda-Carreras et al. , 2017; Logan et al. , 2016; Gertych et al. , 2016). Recently, efforts to make deep learning approaches easily accessible have made great strides (Falk et al. , 2019); such implementations have the potential to increase access to these powerful supervised segmentation methods, but at present hardware and installation requirements are likely to be too complex for the typical biologist. In general, we find that existing tools can be powerful in specific examples, but lack the flexibility, speed and/or ease of use to make them effective solutions for most biologists in the analysis of large time-lapse movies of 3D developing tissues. In developing CytoCensus, we sought to design a widely applicable, supervised machine leaning-based image analysis tool, addressing the needs of biologists to efficiently characterise and quantitate dense complex 3D tissues at the single-cell level with practical imaging conditions. This level of analysis of developing tissues, organoids or organs is frequently difficult due to the complexity and density of the tissue arrangement or labelling, as well as limitations of signal to noise. We therefore aimed to make CytoCensus robust to these issues but also to make it as user friendly as possible. In contrast to other image analysis approaches that require the user to define the cell boundaries, CytoCensus simply requires the user to point-and-click on the approximate centres of cells. This single click training need only be carried out on a few representative 2D planes from a large 3D volume, and tolerates relatively poor image quality compatible with extended live cell imaging. To make the task very user friendly, we preconfigured most algorithm settings leaving a few, largely intuitive, parameters for the user to set. To improve performance, we enabled users to define regions of interest (ROIs) which exclude parts of a tissue that are not of interest or interfere with the analysis. We also separated the training phase from the analysis phase, allowing efficient batch processing of data. For the machine learning, we choose a variation of Random Forests with pre-calculated image features, which allows for much faster training compared to neural","There are around 200 billion cells in the human brain that are generated by a small pool of rapidly dividing stem cells. For the brain to develop correctly, these stem cells must produce an appropriate number of each type of cell in the right place, at the right time. However, it remains unclear how individual stem cells in the brain know when and where to divide. To answer this question, Hailstone et al. studied the larvae of fruit flies, which use similar genes and mechanisms as humans to control brain development. This involved devising a new method for extracting the brains of developing fruit flies and keeping the intact tissue alive for up to 24 hours while continuously imaging individual cells in three dimensions. Manually tracking the division",380,128,0.3368
dialogsum,"#Person1#: Hello, what can I do for you? #Person2#: Um. . . Hello, I would like to open an account. #Person1#: OK! What kind of account do you want to open? #Person2#: I want to open a current account. #Person1#: I will open it for you right now. #Person2#: What's the minimum deposit for opening a current account? #Person1#: It's 10 yuan. How much money do you want to deposit? #Person2#: Well, here's 3, 000 yuan. #Person1#: Please write down your name, address and the amount of your deposit here. And please choose a passcode of six numbers and confirm it. #Person2#: OK, here you are. #Person1#: Thank you. Please confirm your information and sign your name in the blank. #Person2#: Done! What else should I do? #Person1#: That's all. Here's your bank card, and here's the certificate of deposit. Bring your bank card with you every time you come to deposit or withdraw money. #Person2#: OK. Thanks. Goodbye! #Person1#: Bye!","#Person1# helps #Person2# open a current account, deposit 3,000 yuan, set the passcode and confirm all the information.",161,18,0.1118
scientific_lay_summarisation-elife-norm,"in natural settings (Madsen et al. , 2012; Molin and Tolker-Nielsen, 2003). Undomesticated strains of B. subtilis form complex biofilms on agar plates and at the air-liquid interface in standing cultures (Vlamakis et al. , 2013). There is also extensive spore formation in B. subtilis biofilms (Branda et al. , 2001; Vlamakis et al. , 2008). In addition, during growth in a biofilm, ICEBs1 is naturally activated and transfers efficiently, generating on the order of 10 new ICEBs1-containing host cells (transconjugants) per donor cell under appropriate conditions (Lécuyer et al. , 2018). B. subtilis biofilms are held together by a matrix composed of secreted exopolysaccharides, protein fibers, and DNA (Vlamakis et al. , 2013). This matrix reinforces cell-cell contacts, likely promoting rapid spread of ICEBs1 by conjugation. Additionally, the conditions that promote biofilm formation (high cell density) also promote activation and transfer of ICEBs1 and sporulation (Auchtung et al. , 2005; Grossman and Losick, 1988). Although biofilm growth is clearly beneficial to conjugation, it is unknown how ICEBs1 impacts its host cells under these conditions. In this study, we describe a selective advantage provided by ICEBs1 to its host cells during growth in biofilms. This fitness benefit was due to inhibition of host biofilm and spore development. We identified the ICEBs1 gene devI (formerly ydcO) as necessary and sufficient to inhibit host development and provide a selective advantage to ICEBs1-containing cells. We also provide evidence indicating that devI likely inhibits the key developmental transcription factor Spo0A, reducing its ability to stimulate biofilm and sporulation gene expression. devI (ydcO) is conserved in other ICEBs1-like elements, indicating that manipulation of host development may be a conserved strategy among this family of mobile genetic elements. We postulate that manipulation of host pathways may be a common function of many of the as yet uncharacterized cargo genes in ICEs. Biofilm formation is characteristic of many bacteria growing in natural settings, including B. subtilis. We used biofilm growth to determine if ICEBs1 affected the fitness of its host cells under conditions that naturally promote its spread. We performed competition experiments in biofilms using strains of undomesticated B. subtilis (NCIB3610 plasmid-free) with or without ICEBs1. We observed highly efficient spread of ICEBs1 at low donor to recipient ratios (Table 1) during growth in biofilms, similar to","Many bacteria can ‘have sex’ – that is, they can share their genetic information and trade off segments of DNA. While these mobile genetic elements can be parasites that use the resources of their host to make more of themselves, some carry useful genes which, for example, help bacteria to fight off antibiotics. Integrative and conjugative elements (or ICEs) are a type of mobile segments that normally stay inside the genetic information of their bacterial host but can sometimes replicate and be pumped out to another cell. ICEBs1 for instance, is an element found in the common soil bacterium Bacillus subtilis. Scientists know that ICEBs1 can rapidly spread in biofilms – the slimly, crowded communities where bacteria live tightly connected – but it is still unclear whether it",380,128,0.3368
dialogsum,"#Person1#: Hi, Janice. Our first weekend after being employed is coming. Show me your plan. #Person2#: My mom phoned me this morning, and asked me to go back home to have housework chores. #Person1#: What are you assigned to do? #Person2#: God knows. Speaking of chores, I would rather do some washing than cooking. #Person1#: For me, I think I will iron my shirt and trousers. Actually, weekends tend to be the most hectic day in the whole week. #Person2#: I really hope that I could sleep like a log all through two nights. But. . . Some one said that weekends are a bit like rainbows ; they look good from a distance but disappear before we get up close to them. #Person1#: I couldn't agree more.",Janice'll go back home and do chores this weekend. #Person1#'ll iron #Person1#'s shirt and trousers. They think weekends are less attractive than expected.,128,23,0.1797
pubmed-summarization,"in plastic film and transported in ice - cooled isothermal boxes to the laboratory of seafood and environmental microbiology of the marine sciences institute ( federal university of cear ) for immediate bacteriological analysis . the e. coli investigation followed the guidelines of the fourth edition of the compendium of methods for the microbiological examination of foods released by the american public health association . presumptive tests were performed separately for gills , muscle , and body surface . to sample the body surface , an area measuring 10 10 cm was stroked with a sterile cotton swab previously soaked in difco brain heart infusion ( bhi ) broth and subsequently immersed in 9 ml 0.85% nacl solution ( vetec ) diluted serially to 10 . to sample the gills , a 25 g aliquot was homogenized in 225 ml 0.85% nacl solution , shaken in a magnetic stirrer for 30 min , and diluted serially to 10 . to sample the muscle , a 25 g aliquot was ground and homogenized in 225 ml 0.85% nacl solution and diluted serially to 10 . a 1 ml aliquot was retrieved from each saline dilution and seeded with three repetitions in a test tube containing 10 ml lauryl sulfate tryptose ( lst , difco ) . aliquots from positive lst tubes were seeded in 4 ml tubes containing ec broth and incubated in a water bath at 45c for 48 hours . e. coli was isolated using eosin - methylene blue agar plates ( difco ) , from which 35 colonies suspected of e. coli were selectedand submitted to imvic testing . colonies were considered to be e. coli when positive in the indole and methyl - red test , negative in the voges - proskauer and citrate test , and gram - negative with short rods in the gram staining test . the antibiogram was done with the disk diffusion method using mueller - hinton agar ( difco ) . initially , an emulsion of sample in saline solution was prepared by adjustment to the 0.5 mcfarland turbidity standard , equivalent to 1 10 cfuml ( clsi 2010 ) . the susceptibility of the e. coli strains was tested in relation to several families of antibiotics , including the aminoglycoside","the contamination of seafood by bacteria of fecal origin , especially escherichia coli , is a widely documented sanitary problem . the objective of the present study was to isolate e. coli strains from the gills , muscle , and body surface of farmed nile tilapias ( oreochromis niloticus ) fresh - marketed in supermarkets in fortaleza ( cear , brazil ) , to determine their susceptibility to antibiotics of different families ( amikacin , gentamicin , imipenem , cephalothin , cefotaxime , ciprofloxacin , aztreonam , ampicillin , nalidixic acid , tetracycline , and sulfametoxazol - trimetoprim ) , and to determine the nature of resistance by plasmid curing . forty - four strains ( body surface = 25 , gills = 15 , muscle = 4",380,128,0.3368
scientific_lay_summarisation-elife-norm,"g. , Yervoy and Keytruda), the non-Hodgkin’s lymphoma drug Rituxan, and the breast cancer drug Herceptin. However, the biochemical properties of many CSSP interactions prevent them from being detected by commonly used techniques employed in high-throughput PPI screens, and CSSPs are underrepresented in global interactomes (Guruharsha et al. , 2011; Braun et al. , 2009; Miller et al. , 2005). There are several reasons for this. First, these proteins are usually glycosylated and have disulfide bonds, so they need to be expressed in the extracellular compartment (Wright et al. , 2010). CSSP interactions between monomers are also often weak, with KDs in the μM range (van der Merwe et al. , 1994), making them difficult to capture due to their short half-lives. Lastly, insoluble transmembrane domains on cell surface proteins preclude their purification with standard biochemical techniques, which makes them difficult to study using methods such as AP-MS (Wright, 2009). Despite these difficulties, recent advances have been made in the study of global CSSP interaction patterns. Interactions among cell-surface proteins (CSPs) often occur between clusters of proteins on cell surfaces, and avidity effects (stronger binding due to clustering) can make these cell-cell interactions stable even when monomers bind only weakly. To facilitate detection of interactions among CSSP extracellular domains (ECDs) in vitro, several groups have taken advantage of avidity effects by attaching ECDs to protein multimerization domains and expressing ECD fusions as soluble secreted proteins (Bushell et al. , 2008; Wojtowicz et al. , 2007; Söllner and Wright, 2009; Ramani et al. , 2012). These methods have been shown to be effective, allowing detection of interactions that otherwise would not have been observable. Özkan et al. scaled up the avidity-based approach, developing a high-throughput ELISA-like screening method, the Extracellular Interactome Assay (ECIA). The ECIA was used to define interactions among 202 Drosophila CSSPs, comprising all CSSPs within three ECD families. These were the immunoglobulin superfamily (IgSF), fibronectin type III (FNIII) and leucine-rich repeat (LRR) families. The ECIA utilized dimers as ‘bait’ and pentamers as ‘prey’. It detected 106 interactions, 83 of which were previously unknown (Özkan et al. , 2013). The most striking finding from the ECIA interactome was that a subfamily of 21 2-IgSF domain CSPs, the Dprs, selectively interacts with a subfamily of 9 3-IgSF domain CSPs, the","Within every organ of the body, cells must be able to recognise and communicate with one another in order to work together to perform a particular role. Each cell has a specific protein on its surface that acts like a molecular identity card, and which can form weak bonds with a complementary protein on another cell. There are thousands of different cell surface proteins, and the interactions between them – known collectively as the interactome – dictate the how cells interact with one another. Many cell surface proteins are similar across species. Humans and fruit flies, for example, both possess a family of cell surface proteins that contain a region called the Immunoglobulin Superfamily domain. This family can be further divided into subfamilies, two of which are known",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of wild type levels (1A, B). Interestingly, unc-75 (md1344), a small deletion affecting the last exon encoding part of RRM3 and a nuclear localization signal (— 1A), displayed impairment in regrowth equivalent to the null mutants (1A, B). Transgenic animals expressing Pmec-4-GFP: : UNC-75ΔNLS (aa 1–472) showed diffuse fluorescence throughout the cell, as compared to full-length GFP: : UNC-75, which localizes to neuronal nuclei (— 1B) (Loria et al. , 2003), suggesting that nuclear localization may be critical for UNC-75 function in axon regeneration. We further tested whether unc-75 affected regeneration of GABAergic motor neurons. In wild type, around 35% of DD2 commissures and 50% of VD4 commissures regrow to the dorsal cord by 24 hr after axotomy, whereas in unc-75 mutants fewer than 10% of commissures regrew to the dorsal cord (1E). Thus UNC-75 is critical for regenerative regrowth of multiple neuron types. 10. 7554/eLife. 16072. 003Figure 1. UNC-75 is required cell autonomously for axon regeneration. (A) Images of regenerating PLM axons at 24 hr post axotomy; anterior is to the left and dorsal up. Red asterisk: PLM cell body; red arrow: injury site. (B) Quantitation of PLM axon regrowth 24 hr post laser axotomy, normalized to wild type. The unc-75 alleles md1309 and md1344 display defects in axon regrowth similar to e950. The unc-75 (e950) PLM regrowth defect is rescued by multicopy and single copy unc-75 (+) transgenes. Statistics: One-way ANOVA with Bonferroni post test. (C) unc-75 (e950) animals showed reduced axon regrowth at all time points examined, and reduced growth rate 0–24 hr post axotomy. (D) Representative image series from time-lapse movies of the tip of a regenerating PLM axon from wild-type and unc-75 (e950) animals starting at 14 hr post axotomy; see Video 1 and 2. Red and orange arrows point to the ends of regenerating axons at 14 and 15h post axotomy respectively. (E) unc-75 (e950) is defective in regeneration of GABAergic motor neurons [marked by Punc-25-GFP (juIs76) ]; this was rescued by Prgef-1-UNC-75 (juSi76). Images of GABAergic motor neuron commissures at 24 hr post axotomy. DD2 and VD4 were axotomized, and VD3 was uncut. Red arrowheads indicate the ends of regenerating or non-regenerating axons. Scale: 10 μm. Bar charts showing reduced regrowth of DD2 and VD4 neurons; N = 30–52. : http: //dx. .","Nerve cells or neurons carry information around the body along projections known as axons. An injury or trauma, such as a stroke, can damage the axons and lead to permanent disability because the damaged axons fail to regenerate over long distances. Axon damage triggers large changes in the activity of many genes that promote regeneration. When a gene is active, its DNA is copied to make molecules of messenger RNA (mRNA), which are then used as templates to make proteins. Many mRNAs undergo a process called alternative splicing, in which different combinations of mRNA sections may be removed from the final molecule. This enables a single gene to produce more than one type of protein. Recent studies point to an important role for so-called RNA binding proteins in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"dimer to walk toward the MT plus-end using one ATP per step (1B) (Svoboda et al. , 1993; Block, 2007). It unbinds from the MT in the ADP state, and after making a step, it releases ADP and enters the nucleotide-free APO state with high MT-affinity (Cross, 2016; Hancock, 2016). Binding of an ATP triggers forward force generation (the ‘power stroke’; 1A) by driving the cover strand (CS) and the neck linker (NL), which are located respectively on the N- and C-terminal ends of the motor head, to fold into a β-sheet named the cover-neck bundle (CNB; 1C) (Rice et al. , 1999; Hwang et al. , 2008; Khalil et al. , 2008). ATP hydrolysis completes a step (Milic et al. , 2014; Andreasson et al. , 2015). The pre- and post-stroke states differ in the motor head orientation relative to the MT. In the pre-stroke state, the head tilts rightward relative to the MT plus-end direction, and rotates clockwise when viewed from above (wide arrows in 1D). The head rotates in the opposite direction in the post-stroke state (Sindelar and Downing, 2010). The nucleotide pocket on the rear-left side of the motor consists of the phosphate loop (P-loop), switch-I (sw-I), and switch-II (sw-II) (1E). These elements are conserved among different proteins including myosin and G-protein (Vale and Milligan, 2000). Compared to an isolated kinesin, a MT-bound kinesin has an at least 10-fold higher ATP hydrolysis rate (Vale, 1996; Ma and Taylor, 1997), which suggests that the nucleotide pocket is allosterically controlled by the interface with the MT. Among kinesin’s MT-facing domains (1C), L11 and α⁢4 undergo large conformational changes upon binding to the MT. L11 is located after sw-II (1E), followed by α⁢4 that N-terminally extends by a few turns when the motor head binds to the MT (Supplementary file 1) (Sindelar and Downing, 2010; Atherton et al. , 2014; Shang et al. , 2014). However, substantial conformational variations are present in these conserved domains, notably in sw-I and L11 (see Supplementary file 1). Also, the extent of the kinesin-MT interface varies depending on experimental conditions (Morikawa et al. , 2015). Thus, it is necessary to identify core features of the motor head that are essential for nucleotide processing. Such information about a single head is a prerequisite for","Motor proteins called kinesins perform a number of different roles inside cells, including transporting cargo and organizing filaments called microtubules to generate the force needed for a cell to divide. Kinesins move along the microtubules, with different kinesins moving in different ways: some ‘walk’, some jump, and some destroy the microtubule as they travel along it. All kinesins power their movements using the same molecule as fuel – adenosine triphosphate, known as ATP for short. Energy stored in ATP is released by a chemical reaction known as hydrolysis, which uses water to break off specific parts of the ATP molecule. The site to which ATP binds in a kinesin has a similar structure to the ATP binding site of many other proteins that use ATP. However, little was",380,128,0.3368
dialogsum,"#Person1#: Hi, John Phillips? I'm Rose Green. I'Ve been asked to handle your training and introduce a little bit of the company to you. It's nice to meet you. #Person2#: It's nice to meet you, too, Ms. Green. This company seems so big right now ; I don't know how I'll ever get used to it. #Person1#: After a week, you'll be running around here like a pro. Let me give you this list of departments first, next to each department is its location and the name of the manager. #Person2#: Great, That'll be big help, Ms. Green.",Rose Green tells John Phillips she will handle his training and introduces the company to him.,98,16,0.1633
scientific_lay_summarisation-elife-norm,"This conclusion is substantiated by the observation that an increase in the internal Na+ concentration does not stimulate citrate uptake (— 2C), which argues against a previously proposed citrate/proton symport (or citrate/hydroxide antiport) in exchange for internal sodium (Pos and Dimroth, 1996). 10. 7554/eLife. 09375. 003Figure 1. Sequence alignment. Sequence alignment of 2-hydroxycarboxylate transporters. The secondary structure of SeCitS is shown above the alignment. R402 and R428 of the citrate-binding site are outlined in red. Symbols above the sequence indicate residues involved in sodium binding. A hashtag (#) marks the residues that form the Na1 site. Residues with sidechains coordinating Na2 are marked with a diamond (♦), and those that coordinate Na2 with backbone carbonyls with an open circle (○). Most of the conserved residues (*) are found in the two helix hairpins H6 and H12, and in transmembrane helix H13. SeCitS: Citrate/sodium symporter from Salmonella Enterica (WP_024797394. 1) KpCitS: Citrate/sodium symporter from Klebsiella pneumoniae (WP_025860623. 1) VcCitS: Citrate/sodium symporter from Vibrio_cholerae (WP_001003397. 1) BsCimH: Citrate/malate transporter from Bacillus_subtillis, (P94363. 1) KpCitW: Citrate/acetate transporter from Klebsiella_pneumoniae, (AF411142. 1) LmCitP: Citrate transporter from Leuconostoc_mesenteroides (AAA60396. 1) LlMleP: Malate transporter from Lactococcus lactis, (CAA53590. 1) BsMaeN: Malate/sodium symporter from Bacillus_subtilis, (AFQ59004. 1) : http: //dx. . org/10. 7554/eLife. 09375. 00310. 7554/eLife. 09375. 004Figure 2. Substrate specificity of SeCitS. (A) The substrate specificity of SeCitS was established by a proteoliposome uptake inhibition assay. Potential substrates or competitors were added in thousandfold excess of 14C-citrate (5 µM) and transport was measured. The 2-hydroxycarboxylates malate and iso-citrate inhibit 14C-citrate uptake completely. α-Ketoglutarate, which has a carbonyl instead of the citrate hydroxyl group, inhibits less strongly. Succinate and glutarate inhibit transport only slightly. Tricarballate has no effect. (B) While malate inhibits citrate uptake, it is not a substrate for SeCitS, as uptake of 14C-malate (43 µM) is not detectable. (C, D) SeCitS is highly specific for Na+. Neither Li+ nor K+ drive (C) or inhibit (D) citrate uptake. Choline was used as a negative control in both assays. Initial uptake rates were plotted relative to (A) absence of competitor, (B) citrate transport or (C, D) sodium-driven transport. : http: //dx. . org/10. 7554/eLife. 09375. 00410. 7554/eLife. 09375. 005Figure 3. Citrate and sodium transport kinetics. (A) Citrate uptake by SeCitS containing proteoliposomes in presence of 25 mM","Cells have specialized proteins known as transporters in their surface membranes that move molecules into or out of the cell. Transporters pass their cargo through the membrane by changing shape. This process requires energy and is sometimes driven by simultaneously transporting a charged ion such as sodium. There are different classes of transporters and researchers have described a range of structural changes, and therefore transport mechanisms, that different transporters use. Citrate transporters are found in a wide range of organisms. In bacteria, they bring the citrate substrate molecule into the cell to be used as a nutrient. In humans, citrate transporters are important in metabolism, and are of interest as targets for drugs that could potentially treat obesity and diabetes. This requires an understanding of the atomic structure",380,128,0.3368
scientific_lay_summarisation-elife-norm,"machinery. In addition to forming a complex with Rec114-Mei4, Mer2 interacts directly with the PHD domain-containing protein Spp1 (Acquaviva et al. , 2013; Sommermeyer et al. , 2013). Spp1 binds to nucleosomes that are tri- (or di-) methylated on H3K4 (i. e. H3K4me3 nucleosomes) (He et al. , 2019; Miller et al. , 2001), and this association is important for the association of Spo11-dependent DSB formation with gene promoter regions. Spp1 is canonically part of the COMPASS (aka Set1 complex), but during meiosis, Spp1 forms an independent, and mutually exclusive, interaction with Mer2. The reciprocal interaction domains between Spp1 and Mer2 have been previously identified (Acquaviva et al. , 2013; Sommermeyer et al. , 2013). The C-terminal region of Spp1 interacts with a central, predicted coiled-coil, region of Mer2 (Acquaviva et al. , 2013; Sommermeyer et al. , 2013; 1B). A single amino acid substitution in Mer2 (V195D) is sufficient to disrupt the interaction with Spp1 (as judged by yeast-2-hybrid [Y2H] analysis) (Adam et al. , 2018). Through its interaction with Spp1, a key role for Mer2 appears to link the Spo11 machinery directly to Spp1-mediated nucleosome interactions. Interestingly, Spp1 associated with Mer2 has a longer residence time on nucleosomes when compared with Spp1 when part of COMPASS (Karányi et al. , 2018), suggesting additional functions for Mer2 in mediating nucleosome tethering. In line with the central position for Mer2 in DSB machinery assembly is the observation that – in contrast to deletion of Set1 or Spp1 which severely reduces, but not eliminates DSB formation – mer2Δ cells completely fail to form meiotic DSBs (Rockmill et al. , 1995). Mer2 likely establishes additional biochemical interactions that enable a functional Spo11 assembly. For example, homologs of Mer2 in fission yeast (Kariyazono et al. , 2019) and mouse (Stanzione et al. , 2016) interact with meiotic chromosome axis-associated HORMA proteins, suggesting that Mer2 can mediate a link between the chromosome axis (via HORMA protein interaction) and chromatin loops (through Spp1 association). Despite hints to the central position of Mer2 in assembly of DSB machinery, a more comprehensive biochemical understanding of these interactions is critically needed. Here, we use a combination of in vitro biochemical reconstitution with yeast genetics to investigate several distinct protein-protein interactions of Mer2. We examine the interaction of Mer2","Organisms are said to be diploid when they carry two copies of each chromosome in their cells, one from each of their biological parents. But in order for each parent to only pass on one copy of their own chromosomes, they need to make haploid cells, which only carry one copy of each chromosome. These cells form by a special kind of cell division called meiosis, in which the two chromosomes from each pair in the parent cells are first linked, and then pulled apart into the daughter cells. Accurate meiosis requires a type of DNA damage called double-stranded DNA breaks. These breaks cut through the chromosomes and can be dangerous to the cell if they are not repaired correctly. During meiosis, a set of proteins gather around",380,128,0.3368
scientific_lay_summarisation-elife-norm,"translesion polymerase (Hogg et al. , 2011; Seki et al. , 2004). However, in contrast to Y-family polymerases, Polθ is capable of replicating past the most lethal type of lesion, the double-strand break (DSB) (Chan et al. , 2010; Kent et al. , 2015; Koole et al. , 2014; Mateos-Gomez et al. , 2015; Yousefzadeh et al. , 2014). For example, in recent studies we demonstrated the ability of the polymerase domain of POLQ, herein referred to as Polθ, to perform microhomology-mediated end-joining (MMEJ) —also referred to as alternative end-joining (alt-EJ) —in the absence of any co-factors (Kent et al. , 2015). MMEJ requires the ability of the polymerase to perform DNA synthesis across a synapse formed between two opposing single-strand DNA (ssDNA) overhangs containing sequence microhomology (1A) (Kent et al. , 2015). ssDNA overhangs are formed by partial resection of DSBs via Mre11-Rad50-Nbs1 (MRN complex) and CtIP, and potentially other factors (Lee-Theilen et al. , 2011; Truong et al. , 2013; Zhang and Jasin, 2011). Specifically, Polθ was shown to generate MMEJ products by promoting DNA synapse formation of 3’ ssDNA overhangs containing a minimal amount (≥2 base pairs (bp) ) of sequence microhomology, then using the opposing ssDNA overhang as a template in trans to extend the DNA, resulting in stabilization of the end-joining intermediate (1A) (Kent et al. , 2015). The polymerase then likely extends the second overhang resulting in gap filling (1A). Ligase III (Lig3) is required to seal the DNA junction formed during alt-EJ/MMEJ (Audebert et al. , 2004; Simsek et al. , 2011), presumably after other enzymes such as endonucleases further process the end-joining intermediate (1A). This end-joining activity appears to be dependent on a unique insertion motif, called insertion loop 2, that also enables Polθ to bypass of other types of DNA lesions (Hogg et al. , 2011; Kent et al. , 2015). Thus, although Polθ is an A-family polymerase, which normally exhibit high-fidelity DNA synthesis and lack translesion synthesis activity, its unique sequence composition confers end-joining, translesion synthesis, and low-fidelity DNA synthesis activities (Arana et al. , 2008; Hogg et al. , 2011; Kent et al. , 2015; Seki et al. , 2003; 2004). 10. 7554/eLife. 13740. 003Figure 1. Polθ exhibits robust template-independent terminal transferase activity in the presence of manganese. (A-C)","DNA polymerases are enzymes that replicate DNA by using single-stranded DNA as a template. DNA replication is needed to duplicate an organism’s genome, and repair it if it is damaged. For example, when DNA double-strand breaks occur in the genome, DNA polymerases help repair these potentially lethal DNA breaks. If not repaired accurately, double-strand breaks in DNA can lead to genetic mutations and cancer. Cells have evolved many different pathways to repair damaged DNA. DNA polymerase θ (called Polθ for short) is a key player in a repair mechanism called ‘alternative end-joining’ in mammals. In this pathway, certain enzymes trim back DNA strands on both sides of the double-stranded break to expose overhanging single strands of DNA. Polθ binds to the ends of both overhanging strands and helps",380,128,0.3368
dialogsum,"#Person1#: How do you like Hong Kong, Mr. Green? #Person2#: Very much. #Person1#: Are you staying at a hotel? #Person2#: Yes, at the Star Hotel, next door to this building. #Person1#: Oh, yes. #Person2#: It's nearly one o'clock! I'm hungry. Is there a good restaurant nearby? #Person1#: Yes, there are several. Would you like to eat Chinese food or European? #Person2#: Er, European, I think. But would you like to have lunch with me? #Person1#: Well, thank you. I'd like to. #Person2#: Good, would you like to choose a better restaurant? #Person1#: Well, there's Brown's. The food's very good, but I'm afraid it's rather expensive. #Person2#: That's all right, Miss Jiang. Shall we go, then?",Mr. Green likes Hong Kong and stays at the Star Hotel. He invites Miss Jiang to have lunch and she recommends Brown's.,115,22,0.1913
pubmed-summarization,"increased number of lattice defects . we postulate that the free area available for diffusive transport in a two - dimensional analog of the classic cohen and turnbull free volume model of viscosity is inversely proportional to the number of molecules in a coherence area . using this relationship , the surface viscosity data for all surface pressures and cholesterol fractions collapses to a simple logarithmic relation with no adjustable parameters . this suggests that the decreased molecular ordering caused by the incompatibility of cholesterol with the alkane chain lattice is the origin of the orders of magnitude decrease in surface viscosity . 1,2-dipalmitoyl - sn - glycero-3-phosphocholine ( dppc , r - enantiomer ) and dihydrocholesterol ( avanti , alabaster , al ) with 0.1 wt % texas - red dhpe ( n-(texas red sulfonyl)-1,2-dihexadecanoyl - sn - glycero-3-phosphoethanolamine , invitrogen , grand island , ny ) were mixed in the appropriate ratios and diluted to 0.2 mg / ml in hplc - grade chloroform ( fisher scientific , st . dihydrocholesterol ( chol ) was used instead of cholesterol to minimize oxidation but has little impact on phase behavior . surface pressure area isotherms were recorded at 25 c using a teflon trough ( nima , coventry , england ) with custom designed stainless steel ribbons which reduce film leakage at high surface pressures . a filter paper wilhelmy plate ( riegler and kirstein , gmbh ; potsdam , germany ) was used to measure surface pressure . the open area of the trough used was 125 cm and each complete compression / expansion cycle took about 8 min ( 0.42 cm / s ) . for fluorescence imaging , the langmuir trough was mounted on a nikon optiphot optical microscope with a custom designed stage equipped with long working distance objectives designed for fluorescent light . a dichroic mirror / barrier filter assembly directed the excitation light onto the monolayer films at a normal angle of incidence and filtered the emitted light and the images were detected by a silicon intensified ccd camera . videos of the monolayer film were recorded during the compression - expansion cycle directly onto the computer using the pinnacle studio capture software . the continuous , fluid lipid phase appears bright due","adding small fractions of cholesterol decreases the interfacial viscosity of dipalmitoylphosphatidylcholine ( dppc ) monolayers by an order of magnitude per wt % . grazing incidence x - ray diffraction shows that cholesterol at these small fractions does not mix ideally with dppc but rather induces nanophase separated structures of an ordered , primarily dppc phase bordered by a line - active , disordered , mixed dppc - cholesterol phase . we propose that the free area in the classic cohen and turnbull model of viscosity is inversely proportional to the number of molecules in the coherence area , or product of the two coherence lengths . cholesterol significantly reduces the coherence area of the crystals as well as the interfacial viscosity . using this free area collapses",380,128,0.3368
dialogsum,"#Person1#: Will you give your friends a buzz and put out a feeler to see if they like to offer me a loan? #Person2#: Give them a buzz? What can I say to them? Say that you want a loan? #Person1#: I just want to make sure that there is possibility of giving us a loan. #Person2#: And they, too, want to make sure their loan is worthwhile.",#Person1# wants #Person2# to call to ask #Person2#'s friends for loans but #Person2# doubts whether it works.,68,17,0.25
dialogsum,"#Person1#: Have we met? #Person2#: I don't think so. Michael. #Person1#: Hello, Michael. My name's Shirley. Pleased to meet you. #Person2#: Pleased to meet you, too, Shirley. So, what do you do? #Person1#: I work in marketing. I'm a regional marketing manager for an IT company. Normally, I work out of Beijing, but I'm here on business. My friend Judy over there, she lives here and she invited me to this party. And you? How about you? #Person2#: I live here. I was invited by George-he's the tall guy over there. He looks a bit drunk, actually. . .",Shirley and Michael introduce themselves. Shirley was invited to the party by Judy while Michael was invited by George.,99,19,0.1919
dialogsum,"#Person1#: What do you do in summer? #Person2#: I love going out into the countryside for walks or bike ride. I love being out in the fresh summer air. How about you? #Person1#: I don't often go for walks, but I either play sports outside-you know, tennis or badminton-or just sit in the sunshine and read a good book. #Person2#: What do you do in winter? #Person1#: Well, I play sports indoors quite often. If I'm feeling lazy, I just watch a film at home. I prefer summer to winter. #Person2#: I think most people do. I like wearing nice, colorful clothes in summer-you know, a nice dress or skirt. It's too cold for those kinds of clothes in winter. #Person1#: Yes. I like wearing shorts in summer. My legs would freeze! #Person2#: Do you think we'll have a nice summer this year? #Person1#: Thanks to global warming, it could be hotter than ever!",#Person1# and #Person2# talk about what they do in summer and winter. They prefer summer to winter because it's too cold to wear the clothes they like in winter.,154,29,0.1883
pubmed-summarization,"as well as along the major retinal blood vessels . the vitreomacular junction has an annular shape , with a diameter of 3 - 4 mm . the set of events that occur as the eye ages are associated with a series of physiological changes in the vitreous gel , with progressive liquefaction ( at the age of 80 , around 50% of the vitreous gel has been liquefied ) and gradual destruction of the collagen - hyaluronic acid network . this occurs as a result of the development of fluid - filled pockets beginning in front of the macula , which over the time coalesce and enlarge , resulting in a weakened adhesion between the vitreous and the retina . this gradually predisposes to pvd , defined as separation of the posterior cortex from the ilm of the retina , which represents the final step of the normal vitreous aging process . pvd is an insidious process that occurs over the course of months or years , being asymptomatic in many cases until complete separation of the vitreous from the macula and optic nerve , which is the final stage . however , the anterior attachment to the vitreous base is very strong and remains for a long time . acute symptoms of complete pvd include photopsia ( by vitreous traction on the peripheral retina ) and floaters by condensation of the vitreous collagen , glial tissue , or blood around the optic nerve . studies in healthy adults have shown that focal perifoveal pvd occurs in 50% of subjects aged between 30 and 39 , whereas complete pvd is found in 50% of subjects aged 70 years or older . in addition to advanced age , pvd is more frequent in postmenopausal women by the effects of decreased estrogens on the connective tissue ( within the vitreous gel ) , as well as in the presence of myopia . the normal process of pvd due to vitreous aging may be complicated by the presence of vitreomacular adhesions between the cortex and the macular area , resulting from vitreous syneresis . these adherences may be focal or extensive , affecting the foveola only or a wide region of the macular area and the optic disc . simple vitreomacular adhesion","the paper presents a review of the sequence of events of posterior vitreous detachment ( pvd ) , vitreomacular adhesion ( vma ) , vitreomacular traction ( vmt ) , and macular hole ( mh ) from their pathophysiological aspects , clinical features , diagnostic implications , and current management strategies . a treatment algorithm to be used in clinical practice in patients with vma , vmt , and mh based on the presence of symptoms , visual acuity , associated epiretinal membrane , and width of the vitreous attachment is presented . observation , pharmacologic vitreolysis with ocriplasmin , and surgical treatment are positioned as treatment options in the different steps of the therapeutic algorithm , with clear indications of the paths to be followed according to",380,128,0.3368
dialogsum,"#Person1#: Polly, Ms. Kelly has agreed to come and give a talk about international relations next week. When do you think we can fit her lecture in? #Person2#: That's Great, Nick. What about Friday afternoon then? #Person1#: I'm afraid some students are planning to go on a trip. Maybe we can have it on Wednesday afternoon. #Person2#: No, that's not possible, either. Most students are having group activities for their research projects. Well, I have an idea. I have a class on Tuesday afternoon and probably Ms. Kelly can use my time. #Person1#: That's possible, but I have to speak to Dr. Lee about that. And you should also talk to the students about the change. #Person2#: Oh, yes, I'll certainly do that.",Nick asks Polly to arrange Ms. Kelly's lecture. Polly suggests using her class on Tuesday. Nick'll speak to Dr. Lee about that and asks Polly to talk to the students.,123,30,0.2439
pubmed-summarization,"was generated by reverse transcription ( rt ) and used for hybridization . in the rt reaction , 4 l of first strand buffer , 1 l random hexmer ( 8 g/l ; boehringer mannheim ) , 2 l 10 low t - dntp ( 5 mm a , c and gtp , 2 mm dttp ) , 2 l 1 mm cy - dutp ( cy3 for reference sample or cy5 for test sample unless otherwise specified ) , 2 l 0.1 m dtt , 1 l rnasin and 1.2 g amplified rna in 8 l depc h2o were mixed and heated for five minutes at 65c . this was followed by addition of 1 l superscript ii ( life technology , ) , 40 minutes of incubation at 42c , another 1 ul of superscript ii and 50 more minutes continued incubation at 42c . reactions were stopped by addition of 2.5 l 500 mm edta , 5 l 1 m naoh and heated to 65c for 15 minute to hydrolyze the rna . tris buffer ( 12.5 l of 1 m ) was added immediately to neutralize the ph , and the volume risen to 70 l by adding 35 l of 1 te . the flow through mixed with 200 l 1 te was concentrated to 2040 l using microcon ym-30 column ( millipore ) and further concentrated to 8 ul using speed - vacuum . cy3- and cy5-labeled probes were combined ( 1:1 ratio ) and 5 l 20 ssc , 0.5 l 10% sds and 0.5 l of 4 mg / ml salmon sperm dna were added to the probe for hybridization . prepared probe mixture was applied to an array slide with cover slid and hybridized at 47c for different amounts of time as described in the text . slides were washed with 4 ssc , 2 ssc with 0.1 % sds , 1 ssc , 0.2 ssc and 0.05 ssc sequentially for one minute each step and dried by centrifugation at 800 rpm for 3 minutes . the slides were then scanned for fluorescent signal using a genepix 4000b scanner and the results analyzed using genepix pro3 software ( axon instruments , inc . ) . the hla - a locus exon","detection of unknown single nucleotide polymorphism ( snp ) relies on large scale sequencing expeditions of genomic fragments or complex high - throughput chip technology . we describe a simplified strategy for fluorimetric detection of known and unknown snp by proportional hybridization to oligonucleotide arrays based on optimization of the established principle of signal loss or gain that requires a drastically reduced number of matched or mismatched probes . the array consists of two sets of 18-mer oligonucleotide probes . one set includes overlapping oligos with 4-nucleotide tiling representing an arbitrarily selected "" consensus "" sequence ( consensus - oligos ) , the other includes oligos specific for known snp within the same genomic region ( variant - oligos ) . fluorescence - labeled dna amplified from a",380,128,0.3368
pubmed-summarization,"cyclosporine a has improved allograft survival and the quality of life for solid - organ transplant recipients . its effectiveness in transplantation by suppression of the immune system has led to its use in treating autoimmune diseases . csa inhibits the immune system by binding to cyclophilin , this complex then inhibits calcineurin , which in turn inhibits the translocation of the nuclear factor of activated t cells ( nfat ) and subsequent gene transcription . calcineurin inhibitors ( cni ) can cause nephrotoxicity involving acute renal vasoconstriction progressing on to glomerulosclerosis , tubulointerstitial fibrosis , and renal failure . due to cni - induced nephrotoxicity , the use of the immunosuppressive agent sirolimus ( srl ) in transplantations is becoming more widespread . srl has a different mechanism of immunosuppression compared to cnis , and a lesser degree of nephrotoxicity is observed with srl compared to that observed with the calcineurin inhibitors . when administered with a cni , srl has been suggested to have a protective role when administered in conjunction with csa . the rapamune us study group conducted a large multicentre clinical trial in which the efficacy of srl compared to azathioprine for reducing acute renal allograft rejection was investigated . the use of srl reduced occurrence and the severity of biopsy - proven acute rejection episodes . however , there have also been studies indicating enhanced nephrotoxicity when srl and csa are used in combination . in another study , the authors showed that a combination of srl and csa significantly potentiated the nephrotoxic actions of csa by augmenting transforming growth factor ( tgf- ) . tgf- has been implicated as a major factor in the development of chronic cni toxicity . increased tgf- levels have been observed in renal cells exposed to csa , in animal models of csa toxicity and in patients with cni nephropathy ; however , the nephrotoxicity caused by csa remains to be fully elucidated . in this study , our hypothesis was to determine whether csa or srl had direct detrimental effects on the glomerulus and identify the possible mechanisms involved , using glomerular mesangial cells . human mesangial cells ( hmcs ) are key cells of the glomerulus and have an important role in regulating glomerular structure and","end stage renal disease ( esrd ) is an ever increasing problem worldwide . however the mechanisms underlying disease progression are not fully elucidated . this work addressed nephrotoxicity induced by the immunosuppressive agents ' cyclosporine a ( csa ) and sirolimus ( srl ) . nephrotoxicity is the major limiting factor in long term use of csa . srl causes less nephrotoxicity than csa . therefore investigations into the differential effects of these agents may identify potential mechanisms of nephrotoxicity and means to prevent esrd induced by therapeutic drugs . using elisa , western blotting , quantitative pcr and a reporter gene assay we detailed the differential effects of csa and srl in human renal mesangial cells . csa treatment increased profibrotic tgf-1 secretion in human mesangial",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable. For proper neuronal functioning, brain tissue oxygen levels are normally maintained through exquisite regulation of blood supply (Erecińska and Silver, 2001). However, during neurological events when brain tissue oxygen levels fall below the severe hypoxic threshold (pO2 < 10 mmHg), neuronal dysfunction and behavioural disturbances are observed (Farrar, 1991; van den Brink et al. , 2000; Maloney-Wilensky et al. , 2009). Following termination of a seizure, behavioral impairments related to the specific brain structures that participated in the seizure are expressed (Leung et al. , 2000; Gallmetzer et al. , 2004). Todd’s Paresis, for example, specifically refers to moderate to severe motor weakness following seizures and typically subsides within a few hours (Todd, 1849). The symptoms are so similar to ischemic stroke that Todd’s paresis is often misdiagnosed (Mathews et al. , 2008; Masterson et al. , 2009). The occurrence of these behavioral impairments have been attributed to the affected cortex being ‘exhausted’ (Franck and Pitres, 1878) or silenced due to increased inhibition (Gowers, 1901), but these conjectures are not supported. Despite being first described over 160 years ago, the cause of postictal behavioral disturbances has not been determined. A few case studies of persons experiencing Todd’s paresis demonstrated that the affected cortex was inadequately perfused during this period (Mathews et al. , 2008; Yarnell and Paralysis, 1975; Rupprecht et al. , 2010). Thus, we hypothesized","It has long been known that after an epileptic seizure, individuals often experience an extended period of impairments that affect how the brain works. Because the brain is organized so that specific tasks happen in particular areas, seizures that affect areas of the brain that control movement are often followed by muscle weakness. Likewise, amnesia may follow a seizure that affects brain areas involved in memory. While these events reduce quality of life in people with epilepsy, they have gone untreated because we did not understand what occurs in the brain after seizures. It has been observed that the impairments that follow seizures are similar to those that follow strokes, where for a period of time blood flow to certain areas of the brain is restricted and these",380,128,0.3368
scientific_lay_summarisation-elife-norm,"involving physiological tissue remodelling, including during embryo development, placenta formation, and wound healing (Muñoz-Espín and Serrano, 2014; Van, 2014). By contrast, persisting senescent cells cause chronic inflammation or ‘inflammaging’ (Birch and Gil, 2020), a pathological state that underpins ageing and age-related disorders. We demonstrated that inflammatory reprogramming of EnSC burdened by replication stress leads to the emergence of acute senescent cells during the implantation window (Brighton et al. , 2017; Lucas et al. , 2020; Kong et al. , 2021). Upon successful implantation and continuous progesterone signalling, decidual cells co-opt uNK cells to eliminate their senescent counterparts through granule exocytosis (Brighton et al. , 2017; Lucas et al. , 2020; Kong et al. , 2021). Clearance of senescent decidual cells likely necessitates recruitment of bone marrow-derived decidual precursor cells, which confer tissue plasticity for rapid decidual expansion in early pregnancy (Diniz-da-Costa et al. , 2021). Importantly, lack of clonogenic decidual precursor cells and a pro-senescent decidual response are linked to recurrent pregnancy loss (Lucas et al. , 2016; Lucas et al. , 2020; Tewary et al. , 2020). Based on these insights, we hypothesized that acute senescence is integral to successful implantation by creating conditions for anchorage of the conceptus in an otherwise tightly adherent decidual matrix. To test this hypothesis, we developed an ‘assembloid’ model, consisting of endometrial gland-like organoids and primary EnSC, which recapitulates the complexity in cell states and gene expression of the midluteal implantation window, improving resemblance to endometrial tissue in comparison with existing co-culture models (Cheung et al. , 2021; Rawlings, 2021). We used this model to establish co-cultures with human blastocysts and demonstrate that aspects of different pathological states associated with implantation failure and miscarriage can be recapitulated in endometrial assembloids by modulating decidual senescence. Organoids consisting of gland-like structures are established by culturing endometrial EpCs seeded in Matrigel in a chemically defined medium containing growth factors and signal transduction pathway modulators (Supplementary file 1: Table 1; Turco et al. , 2017; Boretto et al. , 2017). Gland-like organoids grown in this medium, termed expansion medium, are genetically stable, easily passaged, and can be maintained in long-term cultures (Boretto et al. , 2017; Turco et al. , 2017). Oestradiol (E2) promotes proliferation of gland-like organoids and cooperates with NOTCH signalling to activate ciliogenesis in","At the beginning of a human pregnancy, the embryo implants into the uterus lining, known as the endometrium. At this point, the endometrium transforms into a new tissue that helps the placenta to form. Problems in this transformation process are linked to pregnancy disorders, many of which can lead to implantation failure (the embryo fails to invade the endometrium altogether) or recurrent miscarriages (the embryo implants successfully, but the interface between the placenta and the endometrium subsequently breaks down). Studying the implantation of human embryos directly is difficult due to ethical and technical barriers, and animals do not perfectly mimic the human process, making it challenging to determine the causes of pregnancy disorders. However, it is likely that a form of cellular arrest called senescence, in which cells",380,128,0.3368
dialogsum,"#Person1#: I am in hot water now, all the things seem to be blown up. #Person2#: Don't be scared. Bite the bullet and everything will be right again. #Person1#: Thanks for encouraging me. There are problems cropping up here and there. But I will overcome them one by one.",#Person2# encourages #Person1# and cheers #Person1# up.,49,7,0.1429
scientific_lay_summarisation-elife-norm,"that order) precedes delivery of an aversive unconditioned stimulus (US, footshock). Following repeated SCS-US presentations, mice exhibit distinct defensive behaviors to each SCS component: tones elicit freezing whereas white noise elicits flight. The paradigm thus appears to model natural behavioral shifts that occur as the perceived probability of directly encountering threat increases. As posited by ‘predatory imminence theory’, prey animals initially freeze (to avoid detection) when predators are present at a distance, but then switch to flight (escape) to avoid entrapment if a predator becomes close enough that avoiding detection is no longer possible (Blanchard and Blanchard, 1989; Blanchard et al. , 1995; Bouton and Bolles, 1980; Fanselow, 1994; Fanselow and Lester, 1988; Perusini and Fanselow, 2015). Given the presence of a specific, repeating sequence of auditory stimuli preceding shock during conditioning, defensive behaviors elicited by individual components of the SCS could in principle be driven by learned CS-US temporal relationships. However, the form of both appetitive and aversive conditioned responses is known to vary substantially according to the particular properties of a given conditioned stimulus, even when the same underlying construct has been learned (Holland, 1977; Holland, 1979; Holland, 1980). Therefore, differences in the intrinsic properties of tone and white noise stimuli themselves, rather than their temporal relationship to the US, could underlie the distinct behaviors these stimuli evoke during SCS conditioning. To define the key factors responsible for the topography of behavioral responding in this paradigm, we systematically varied CS-US temporal relationships and properties of SCS component stimuli during or following conditioning. We found that when presented at equal sound pressure levels (SPL), white noise elicits greater active defensive behavior than tones, irrespective of stimulus order during conditioning. Following standard tone-white noise SCS conditioning, each stimulus was also capable on its own of evoking either conditioned freezing or flight, according to SPL. Furthermore, when presented at equivalent SPL, white noise promoted greater arousal and simple locomotor responding than pure tone stimuli, even in the absence of any prior conditioning. Together, these data argue that stimulus salience is the major factor determining the form of conditioned responses during SCS conditioning. We first tested whether reversing the order of 7. 5 kHz tone (TN) and white noise (WN) presentation during SCS conditioning reverses the behaviors these stimuli elicit. To distinguish","If you notice the skies above you becoming darker, your first thought might be to seek shelter. Experience will have taught you that darkening skies are often a sign of an approaching storm. Learning to recognise changes that occur prior to an unpleasant event can help us avoid danger. But this is not the only strategy people can use to predict when something bad is about to happen. Another option is to use the intensity, or salience, of sensory information. Soldiers fighting on the front line, for example, might rely on the loudness of enemy voices or vehicles to judge how close an advancing enemy is. This information will help them decide when to retreat. Different brain processes are active when individuals use each of these two strategies",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2012). miR-150 is upregulated in adult T-cell leukemia cells (Bellon et al. , 2009), gastric cancers (Wu et al. , 2010), and lung cancers (Zhang et al. , 2013). The canonical Wnt pathway signal is transduced by β-catenin and plays a critical role in many adult stem cells, including those of the breast and intestine (Reya and Clevers, 2005; Zeng and Nusse, 2010). The fact that some cancer cells share the extended self-renewal ability with normal stem cells, and that the canonical Wnt signaling pathway is implicated in both stem cell self-renewal and cancer suggests that normal physiological regulators of stem cell functions might be ‘hijacked’ in cancer (Reya and Clevers, 2005). A variety of putative transcriptional targets of the canonical Wnt signaling pathway, such as c-Myc and cyclin D1, are identified (He et al. , 1998; Shtutman et al. , 1999). Adenomatous polyposis coli (APC) is a component of the destruction complex that destabilizes β-catenin and suppresses the activity of the canonical WNT signaling pathway. In human colon cancers, mutations in the APC gene are the most commonly known acquired genetic change for the aberrant activation of the canonical WNT signaling pathway during the tumor development and progression (Kinzler et al. , 1991; Nishisho et al. , 1991; Cottrell et al. , 1992). In a model for the stepwise progression of the colon tumorigenesis, APC gene mutations play an important role in the initiation step followed by successive mutations in other genes, including K-Ras and p53 (Fearon and Vogelstein, 1990). During clonal progression, dysregulation of downstream β-catenin targets, such as c-Myc, can relieve colon cancer cells of their dependence on β-catenin signaling (van de Wetering et al. , 2002). The expression of APC is not limited to the intestine but is widely observed in many other tissues, including lung, liver, kidney, and mammary tissue. However, the role of the suppression of APC and the activation of the canonical WNT signaling in the tumor initiation process of the tissues other than the colon largely remains unknown, because APC mutations are less frequent in tumors originating from these tissues. For example, recent data from the TCGA reveals an ∼2% incidence of APC mutations in breast cancer (the TCGA Research Network: http: //cancergenome. nih. gov/). Dampening of APC inhibition","Messenger RNA molecules take the information encoded in a gene' s DNA sequence and turn it into instructions for building a protein. However, if certain smaller molecules of RNA—called microRNAs—bind to a messenger RNA molecule, they ‘silence’ it, which prevents the information in the messenger RNA from being translated to make a protein. Despite their small size, microRNAs are very powerful. These molecules are able to simultaneously inhibit the translation of hundreds of messenger RNAs and perform many roles, including controlling cell growth and maintaining populations of stem cells. Furthermore, microRNAs have been linked to different aspects of the growth of cancerous cells. Certain microRNAs appear to suppress tumors by regulating the growth of the stem cells found there, while others appear to be ‘hyperactive’ in cancers—including breast",380,128,0.3368
scientific_lay_summarisation-elife-norm,"(LC), are rapidly recruited, in a time-locked fashion, during elementary decisions (Aston-Jones and Cohen, 2005; Bouret and Sara, 2005; Dayan and Yu, 2006; Parikh et al. , 2007). Pupil diameter, a reliable peripheral marker of central (cortical) arousal state (McGinley et al. , 2015b), also increases during decisions (Beatty, 1982; de Gee et al. , 2014; Gilzenrat et al. , 2010; Lempert et al. , 2015; Nassar et al. , 2012). These observations point to an important role of phasic (i. e. , fast) pupil-linked arousal signals in decision-making (Aston-Jones and Cohen, 2005; Dayan and Yu, 2006). Yet, the precise nature of this role has remained unknown. Here, we investigated how phasic, task-related arousal interacts with decision computations in the human brain. We combined pupillometry, fMRI, and computational modeling to probe into the interplay between task-related arousal and decision computations underlying elementary sensory-motor choice tasks. Sensory-motor decisions entail the gradual accumulation of noisy ‘sensory evidence’ about the state of the world towards categorical decision states governing behavioral choice (Bogacz et al. , 2006; Brody and Hanks, 2016; Gold and Shadlen, 2007; Ratcliff and McKoon, 2008). A large-scale network of regions in frontal and parietal cortex seems to accumulate stimulus responses provided by sensory cortices towards choices of motor movements (Gold and Shadlen, 2007; Siegel et al. , 2011) (but see [Brody and Hanks, 2016; Katz et al. , 2016]). We here aimed to elucidate the interaction between pupil-linked arousal responses, evidence accumulation, and decision processing across several (cortical and subcortical) brain regions. Large task-evoked pupil responses were consistently accompanied by a reduction in perceptual decision bias in different sensory modalities (visual and auditory) and task protocols (detection and discrimination). Decision bias reflects the degree to which an observer’s choice deviates from the objective sensory evidence. Using fMRI for one of these tasks revealed that the bias reduction was accompanied by a modulation of choice-encoding pattern signals in prefrontal and parietal cortex. Further, the bias reduction was predicted by task-evoked, pupil-linked responses in a network of neuromodulatory brainstem nuclei controlling cortical arousal state. We conclude that phasic neuromodulatory signals reduce biases in the brain’s decision-making machinery. As a consequence, phasic arousal accounts for a significant component of the variability of choice behavior, over and above the objective evidence gathered from the","When asked to make repeated decisions we will often choose differently each time even when we are given the same information to inform our choice. A stock trader, for example, will typically be more inclined to buy on some days and sell on others even if the financial markets remain unchanged. Fluctuations in the brain’s level of alertness or excitability, otherwise known as its arousal, are thought to contribute to this variability in decision-making. An area at the base of the brain called the brainstem – and in particular one of its subregions, the locus coeruleus – helps shape arousal levels by releasing chemicals called neuromodulators. For reasons that remain unknown, activation of the locus coeruleus also causes the pupil of the eye to suddenly increase in size.",380,128,0.3368
dialogsum,"#Person1#: Welcome, how may I help you today? #Person2#: I'd like a pizza, please. #Person1#: Then you'll be happy to hear that today. All our pizzas are on sale 2 for one. #Person2#: You're right, that is great! #Person1#: What size would you like? #Person2#: A medium one would be perfect. Thank you. #Person1#: Which kind you want? #Person2#: I like seafood on my pizza. #Person1#: We have 2 seafood pizzas, fish and crab. #Person2#: Crab sounds good, today. #Person1#: Will that be for here, or take away? #Person2#: That will be to go. #Person1#: That should only be about 10 minutes. Please sit over there and I will call you over as soon as it's ready. #Person2#: No problem.",#Person1# serves #Person2# to order a medium-size crab pizza. #Person2# wants to take the pizza away and has to wait for about ten minutes.,120,24,0.2
dialogsum,"#Person1#: Good morning. I'm thinking about buying some new furniture for my living room. Could you help me? #Person2#: Certainly. As you can see, we have several three-piece suites on sale. Feel free to sit down and test how comfortable they are. #Person1#: I came to your store yesterday and have come back today to make a final decision. I think I like the black leather suite. It's on sale, isn't it? #Person2#: Yes. The price has been reduced by 50 %. It's a real bargain. #Person1#: I'll take it. I also need to improve the lighting in my living room. Do you have any suggestions? #Person2#: Those floor lamps are very nice and you can vary the brightness according to whether you're reading or watching tv. How big is your living room? #Person1#: It's quite large. It's about 40 square meters. #Person2#: I'd suggest you buy two. That allows you to change the brightness of the room better. #Person1#: OK. I like the design of this lamps. I also need some cushion covers. I'll just browse through those ones over there.",#Person1# decides to buy a black leather suite from #Person2#. #Person2# recommends two floor lamps to #Person1# for changing the brightness of the room. #Person1# also will browse through some cushion covers.,182,32,0.1758
scientific_lay_summarisation-elife-norm,"includes life-style changes and interventions or therapies in the absence of detectable invasive carcinoma (e. g. , Etzioni et al. , 2003; Lippman and Lee, 2006; William et al. , 2009; Hochberg et al. , 2013), for example, reduced cigarette consumption (Doll and Peto, 1976) or chemoprevention (Steward and Brown, 2013). In depth consideration of preventive measures and their likely impact on individual risk and epidemiological trends is important given the likelihood that all individuals harbour pre-cancerous lesions, some of which may transform into invasive carcinoma (Bissell and Hines, 2011; Greaves, 2014), and concerns as to whether technological advances will continue to make significant headway in treating clinically detected cancers (Gillies et al. , 2012; Vogelstein et al. , 2013). Here, we model how continuous, constant measures affect tumour progression and the emergence of resistant lineages. We assume that an individual can contract at most a single cancer, originating from a single lesion. Importantly, we consider cases where the measure may select for the evolution of resistant phenotypes and cases where no resistance is possible. Our approach is to quantify the daily extent to which a growing neoplasm must be arrested in order to either eradicate it or to delay a potentially lethal cancer. Several authors have previously argued how constant or intermittent low toxicity therapies either before or after tumour discovery could be an alternative to MTD chemotherapies (Wu and Lippman, 2011; Hochberg et al. , 2013), but to our knowledge, no study has actually quantified based on empirical parameter estimates, the extent to which cancer cell population growth needs to be arrested for such approaches to succeed (see related discussion in Bozic et al. , 2010; Gerstung et al. , 2011; Bozic et al. , 2013). Below we employ the terms ‘treatment’, ‘measure’, and ‘therapy’ interchangeably, all indicating intentional measures to arrest cancer cell population growth. We first derive analytical expressions for the expected total number of cells within a tumour at any given time. We explore dynamics of tumour sizes at given times, and times to detection for given tumour sizes. Specifically, we show that the expected mean tumour size in a population of subjects can be substantially different from the median, since the former is highly influenced by outliers due to tumours of very large size.","About one person in every two will get cancer during their lives. Surgery and chemotherapy have long been mainstays of cancer treatment. Both, however, have substantial downsides. Surgery may leave behind undetected cancer cells that can grow into new tumours. Furthermore, in response to chemotherapy drugs, some cancer cells may emerge that resist further treatment. There is therefore interest in whether preventive strategies—including lifestyle changes and medications—could reduce the likelihood of confronting a life-threatening cancer. Now, Akhmetzhanov and Hochberg have developed a mathematical model to help compare the effectiveness of preventive strategies and traditional cancer treatments. The model—which assumes that a person can only develop a single cancer from a single region of pre-cancerous cells—suggests that long-term cancer prevention strategies reduce the risk of a life-threatening cancer by",380,128,0.3368
pubmed-summarization,", receiving chronic pain treatment , diabetes , and acid peptic disease were excluded from the study . on preoperative rounds , patients were explained regarding the procedure and were also taught to interpret the visual analogue scale ( vas ) ( graded from 0 = no pain to 10 = maximum pain ) . ranitidine was repeated on the day of surgery 2 h before induction with sips of water . on the operation table , routine monitoring ( electrocardiography , pulse oximetry , noninvasive blood pressure ) was started and baseline vital parameters like heart rate ( hr ) , blood pressure ( systolic , diastolic , and mean ) , and arterial oxygen saturation ( spo2 ) were recorded . after preoxygenation for 3 min , induction of anesthesia was done by fentanyl 2 g / kg and propofol 2 mg / kg intravenously ( i.v . ) . trachea was intubated with appropriate size endotracheal tube after muscle relaxation with vecuronium bromide in a dose of 0.08 mg / kg i.v . anesthesia was maintained with 33% oxygen in nitrous oxide and isoflurane was adjusted to maintain a minimum alveolar concentration ( mac ) of 0.7 . hr and mean arterial pressure were maintained within 20% of baseline value by giving additional bolus doss of fentanyl 25 g and propofol 10 mg i.v . patients were randomly allocated using a computer - generated randomization list into two groups ( n = 25 ) . prefilled syringes were prepared with either levobupivacaine and saline or levobupivacaine and dexamethasone and kept in number coded sealed envelopes , made sterile by sterrad sterilization machine . the anesthesiologist and surgeon were unaware of the nature of the drug in each syringe . at the end of the surgical procedure , intraarticular solutions were injected into the knee joint through the cannular sheath after withdrawal of camera by the orthopedic surgeon before the arthroscope was removed . in group l , 18 ml of 0.25% levobupivacaine and 2ml isotonic saline [ total volume 20 ml ] was administered into the knee joint . similarly group d patients received 8 mg dexamethasone ( 2 ml ) added to 18 ml 0.25% levobupivacaine ( again making a volume of 20 ml ) .","background and aims : in an attempt to improve the recovery and early rehabilitation after arthroscopic knee surgery , various medications have been administered via intra - articular route to prolong the duration and improve the quality of postoperative analgesia . among the potentially effective substances , steroids like dexamethasone could be of particular interest.materials and methods : fifty patients undergoing elective knee arthroscopy were randomly assigned to one of the following groups containing 25 patients each . group d patients received 8 mg ( 2 ml ) of dexamethasone added to 18 ml of 0.25% levobupivacaine intra - articularly , ( total volume 20 ml ) . group l patients received 18 ml of 0.25% levobupivacaine and 2 ml of isotonic saline ( 20 ml in total",380,128,0.3368
dialogsum,"#Person1#: Do you have a boyfriend? #Person2#: Yes. Why? #Person1#: Well, I came to know a girl 3 weeks ago and we have so much in common. #Person2#: So? #Person1#: So I think I may fall in love with her. #Person2#: You are attracted to her. That sounds great, but how do you know that it is a crush or it's real love? #Person1#: Then what's the difference between having a crush and falling in love? #Person2#: That's a big question. Well, if you are in love, maybe you'll take every opportunity to talk to her or telephone her for no reason at all. #Person1#: That's what I did. #Person2#: And you think about her all the time? #Person1#: Yes. #Person2#: And maybe you suddenly have new interests. I mean you suddenly begin to do things you used to avoid, ie. You used to sleep in every morning, but because she jogs every morning, then you begin to like jogging. #Person1#: That's it. She likes dogs so much now, and I begin to love dogs. #Person2#: Oh, congratulations! Sounds like you'Ve found your soul mate. #Person1#: Thanks. But I know falling in love is one thing, while staying in love is another. #Person2#: Yeah, that's right. If you find this person is more and more important to you and you can totally trust her, then you can stay in love. #Person1#: Yeah. Falling in love is so good! #Person2#: While staying in love is even better.","#Person1# tells #Person2# that #Person1# may fall in love with a girl. #Person2# asks #Person1# about #Person1#'s feelings to the girl and thinks #Person1# is in love instead of a crush. #Person1# thinks that falling in love is great, and #Person2# thinks that staying in love in better.",246,48,0.1951
pubmed-summarization,"detailed examination performed to classify cp children according to topography and physiological classification and also for associated comorbidities . in this study , most of children ( 35.56% ) were in 34 years age group followed by 56 years age group ( 22.78% ) . of the 180 children , males were 56.11% while females were 43.33% of total children [ table 1 ] . in other prenatal risk factors , antepartum hemorrhage , pregnancy - induced hypertension ( pih ) and infections contributed to 5.5% , 4.4% , and 3.3% , cases respectively [ table 2 ] . among natal factors , small for gestational age ( sga ) ( 25.5% ) and prematurity ( 17.7% ) were also common risk factors for cp [ table 3 ] . seizure in postnatal life was the second most common risk factor for cp after asphyxia . pathological jaundice and infections are responsible for 15.5% and 25% cases , respectively [ table 4 ] . distribution of patients according to age and sex antenatal risk factors , n ( % ) natal risk factors , n ( % ) postnatal risk factors , n ( % ) spastic cp ( 84.4% ) was the most common physiological type and quadriplegia ( 56.6% ) was the most common topographical type observed in this study . hypotonic and dyskinetic types contributed for equal cases ( 5.5% each case ) [ table 5 ] . distribution of cerebral palsy children according to physiological and topographical classification , n ( % ) one or more comorbidities were present in cp children in this study . intellectual disability ( 47.7% ) followed by epilepsy ( 41.6% ) was the most common comorbidity . speech delay , hearing defects , and visual impairment were present in 27.7% , 10% , and 10% cases , respectively [ table 6 ] . in the present study , we described the clinical spectrum , risk factor profile , and comorbidities associated with cp children . as cp is the most common and costly form of chronic motor disability in children , understanding of probable risk factors that can cause cp is utmost important . a european study by johnson also showed similar result with male : female ratio of 1.33:1","aim and objective : cerebral palsy ( cp ) is the most common motor disability in childhood . this study aimed to describe clinical spectrum , comorbidities , and risk factors associated with cp children.materials and methods : this hospital - based observational study was conducted in tertiary level hospital in jaipur including 180 cp children aged 112 years , attending the paediatric neurology outdoor and child development centre . a detailed history of antenatal , natal , and postnatal events taken and thorough examination was performed to stratify children in proper topographical and physiological classification.results:mothers of 47.7% cp children were primigravida and 17.7% mothers had anemia during pregnancy . among natal factors , asphyxia contributed to maximum cases ( 52.2% ) . seizure in postnatal life was",380,128,0.3368
scientific_lay_summarisation-elife-norm,"with actin cables that is still mechanistically unexplained (Huckaba et al. , 2004; Toshima et al. , 2006). Yeast actin cables, which are bundles of actin filaments that align along the long axis of budding yeast, are crucial for the establishment of cell polarity (Yang and Pon, 2002). Actin cables are also used as tracks for polarized transport during the secretion of exocytic vesicles and the segregation of organelles from mother to daughter cells (Bretscher, 2003). Many of these types of transport along actin cables are known to depend on the type V myosins, Myo2/4p, which mediate the movement of cargo from the minus to plus ends of actin filaments (Bretscher, 2003). However, transport of endocytic vesicles along actin cables is not likely to depend on these myosins, because a temperature sensitive mutant of MYO2 (myo2-66) or a deletion of MYO4 gene did not exhibit any defect in endocytosis (Govindan et al. , 1995; Haarer et al. , 1994). Other myosins, such as type II myosin (Myo1p) and type I myosin (Myo3/5p) also do not seem to mediate this transport. Myo1p has an important role in controlling actin cable dynamics at the bud sites or neck, but it is not localized to endocytic vesicles (Huckaba et al. , 2006). Myo3/5p are necessary for promoting actin assembly and endocytosis at cortical patches, but they stay at the cell cortex when endocytic vesicles are internalized along actin cables (Sun et al. , 2006). Interestingly, a previous study demonstrated that endocytic vesicle movement occurs at the same velocity and in the same direction as the movement of actin cables (Huckaba et al. , 2004). They also reported that an endocytic vesicle stays at the same position on the cable and moves together with the actin cable, suggesting that endocytic vesicles are fixed on the actin cables and move as a result of actin cable flow (Huckaba et al. , 2004). In addition to endocytic vesicles, early endosomes also associate with the actin cytoskeleton, and the motility of endosomes is significantly inhibited by treatment of latrunculin A (LatA), a drug that sequesters actin monomers (Chang et al. , 2003; Fernandez-Borja et al. , 2005; Toshima et al. , 2006; Voigt et al. , 2005). Similarly to endocytic vesicles, early endosome motility also does not","The cells of all eukaryotes – including plants, animals and fungi – absorb many substances that they need from their surroundings by forming pockets around them, and then pinching off these pockets to create structures called vesicles. Clathrin is a protein that acts as a scaffold for these vesicles. Inside a eukaryotic cell, clathrin-coated vesicles first go to a structure known as an endosome, possibly by following a track made from filaments of a protein called actin. Researchers have shown previously that a yeast protein called Pan1 binds to actin filaments and helps the cells to create clathrin-coated vesicles. However it was unclear if the Pan1 protein is also important for transporting clathrin-coated vesicles to endosomes. Previous studies have also shown that adding phosphate groups on to the",380,128,0.3368
pubmed-summarization,"alzheimer s disease ( ad ) is the most frequent neurodegenerative disease ( ferri et al . , 2005 ) and is characterized by a progressive dementia that occurs in middle or late life . the neuropathological hallmark of ad is the presence of cortical intracellular neurofibrillary tangles ( nft ) and extracellular -amyloid ( a ) plaques ( braak and braak , 1991 ) , which leads to synapse dysfunction , neuronal cell loss and subsequent brain atrophy ( ballard et al . , 2011 ) . in the past few decades the knowledge of the key pathogenic mechanisms of the disease has improved , but they are still not completely understood ( querfurth and laferla , 2010 ) . the natural history of ad could be divided in three different phases : the pre - clinical phase , where the pathogenic mechanisms of the disease have started but no symptoms can be identified ; the prodromal phase , where mild cognitive symptoms appear , but there are not severe enough to meet dementia criteria ; and the dementia phase ( dubois et al . , 2007 ) . on the other hand , mild cognitive impairment ( mci ) is a clinical construct created to capture patients with subtle cognitive symptoms at risk for ad ( petersen et al . , 2009 ) . however , some subjects develop other types of dementias , do not progress , or even revert to normal cognition ( ganguli et al . , 2004 ; brooks and loewenstein , 2010 ) . therefore , it is difficult to label mci patients as having prodromal ad . currently , the most frequently used clinical diagnostic criteria for ad are the diagnostic and statistical manual of mental disorders ( dsm - iv - tr ; apa , 2000 ) and the national institute of neurological disorders and stroke - alzheimer disease and related disorders ( nincds adrda ; mckhann et al . , 1984 ) working group . first , the dementia syndrome is established and then , criteria based on the clinical features of the ad type dementia are applied . the dsm - iv - tr criteria require the presence of impairment in multiple cognitive domains of sufficient severity to interfere","alzheimer s disease ( ad ) is the most common form of dementia in the elderly , and it is characterized by progressive impairment in multiple cognitive domains of sufficient severity to interfere with individuals daily living activities . historically , the diagnosis of ad has been based on the identification of a clinical syndrome , and accuracy studies of the current clinical criteria conducted in referral clinics have shown high sensitivity for ad . however , the identification of the disease is still not perfect , and there is growing evidence that the use of biomarkers will increase our ability to better indentify the underlying biology of ad , especially in its early stages . these biomarkers will improve the detection of the patients suitable for research",380,128,0.3368
pubmed-summarization,"in past years , numerous studies have described the role of microalbuminuria ( mau ) as a predictor of cardiovascular disease ( cvd ) and death among subjects with type 2 diabetes ( t2d).13 mau is one of the earliest clinical signs for diabetic nephropathy and a significant risk factor for progression to proteinuria.1 additionally , hypertensive t2d individuals with mau have an increased risk of developing end - stage renal disease ( esrd).4 risk factors known to be associated with cvd and diabetic nephropathy are high blood pressure ( bp ) and elevated glycosylated hemoglobin ( a1c).5,6 achieving adequate bp and glycemic control ( gc ) plays an essential role in preventing renal and cvd events in individuals with t2d . a current secondary analysis from the hispanic health and nutritional examination survey ( hhanes)7 indicated that cuban americans have higher serum cholesterol and systolic bp than puerto ricans and mexican americans . furthermore , compared with other hispanic subgroups , cuban americans have the highest proportion of hypertension ( htn ) and mean serum creatinine levels.8 smith and barnett9 examined the national center for health statistics ( nchs ) from 1996 to 1997 and concluded that cuban americans 35 years of age and older have the highest percentage of diabetes - related deaths compared with other hispanics . although previous studies have shown significant differences and diversity within hispanics , further studies conducted in the cuban american population are scarce . over the past decade , the prevalence of t2d has increased , especially among cuban americans who have a higher incidence of diabetes ( 8.2% ) compared with 6.6% of non - hispanic whites.10 the high incidence of t2d combined with an increased risk for developing diabetes complications warrants further examination of the cuban american population . screening for mau can detect individuals at risk for renal dysfunction and cvd events and possibly reduce the burden associated with diabetes complications . therefore , the purpose of this study was to investigate to what degree the coexistence of htn and poor gc influences the likelihood of having mau among cuban americans with t2d . it was hypothesized that individuals with t2d , htn , and poor gc will have an increased likelihood to test positive for mau .","purpose : to investigate to what degree the presence of hypertension ( htn ) and poor glycemic control ( gc ) influences the likelihood of having microalbuminuria ( mau ) among cuban americans with type 2 diabetes ( t2d).methods : a cross - sectional study conducted in cuban americans ( n = 179 ) with t2d . participants were recruited from a randomly generated mailing list purchased from knowledge - base marketing , inc . blood pressure ( bp ) was measured twice and averaged using an adult size cuff . glycosylated hemoglobin ( a1c ) levels were measured from whole blood samples with the roche tina - quant method . first morning urine samples were collected from each participant to determine mau by a semiquantitative assay (",380,128,0.3368
pubmed-summarization,"safer anticoagulants may lead to lowering of the threshold for anticoagulation.14 the selection of antithrombotic agent ( warfarin vs. noacs ) should be individualized on the basis of risk factors , cost , tolerability , patient preference , potential for drug interactions , and other clinical characteristics such as renal function and ttr.15 it would be unnecessary to switch from warfarin to noacs in patients who already achieve stable and good inr control with warfarin . good anticoagulation control ( ttr>70% ) is associated with the best efficacy and safety of warfarin,2 and the recent meta - analysis of the four phase iii noacs trials showed that there was a greater relative reduction in major bleeding with noacs when the ttr was less than 66% than when it was greater.16 first of all , it appears that asians more often have cerebral small vessel disease , which is prone to bleeding . it has been shown that hemorrhagic stroke ( intracerebral or subarachnoid hemorrhage ) , which accounts for 15% to 20% of strokes in whites,17 is more frequent among asians.18 death from hemorrhagic stroke is also much more common in asians.19 the prevalence of cerebral microbleeds , which increase the risk of intracerebral hemorrhage on anticoagulation , also appears to be higher in asian than in white population.20 the ethnic differences in bleeding - prone small artery disease are in part related with the high prevalence of uncontrolled hypertension or hypocholesterolemia in this region.21 ethnic differences in the salt sensitivity of intracranial hemorrhage ( ich ) have also been addressed.22 whatever the reason , these small artery diseases predispose patients to cerebral bleeding when they are given antithrombotics ; the presence of cerebral small artery diseases , such as lacunar infarcts , white matter ischemia or microbleeds , increases the risk of ich in patients receiving antiplatelet agents23 or anticoagulants.24,25 a recent study showed a high prevalence of warfarin - associated ich in asians , even if the inr levels were comparable ; the hazard ratio for ich was 4.06 for asians , and 2 for hispanics and blacks compared to whites.26 considering that noacs have a lower bleeding risk than warfarin , the benefit of noacs may be greater in asian patients . second , asians generally favor","atrial fibrillation ( af ) is an emerging epidemic in both high - income and low - income countries , mainly because of global population aging . stroke is a major complication of af , and af - related ischemic stroke is more disabling and more fatal than other types of ischemic stroke . however , because of concerns about bleeding complications , particularly intracranial hemorrhage , and the limitations of a narrow therapeutic window , warfarin is underused . four large phase iii randomized controlled trials in patients with non - valvular af ( re - ly , rocket - af , aristotle , and engage - af - timi 48 ) demonstrated that new oral anticoagulants ( noacs ) are superior or non - inferior to",380,128,0.3368
pubmed-summarization,"candidemia and invasive candidiasis ( c / ic ) show an increasing incidence in the nosocomial setting . the crude mortality of those infections ranges between 36%63% depending on patient population.14 comorbidities , aging and age - associated physiological changes , higher rates of oropharyngeal colonization with candida species , and concomitant drug use make elderly patients ( > 65years old ) more vulnerable to infections . for this reason fungal infections have become a major problem in older adults , since age is a well - documented predisposing factor with increased impact on mortality.57 the cutoff age for the elderly population can not be clearly defined because aging is a continuous process . it is also clear that aging is a multifactorial process influenced by both genetic and environmental parameters . many studies dealing with candida infection in the elderly have used several different arbitrary cutoff points such as over 60 , 65 , or 70 years old . however , most prospective epidemiological studies define elderly population as the age group > 65 years.59 the elderly population is large and is growing in proportion to the general hospitalized population , but available data on epidemiology , clinical impact , and outcome of nosocomial fungal infections are limited.710 the indications for antifungal therapy are the same for older as well as younger individuals , and the initial antifungal therapy should be selected on the basis of the infecting organism and the local epidemiology.9,11 fluconazole is generally effective against c / ic but its use may be limited by the increasing prevalence of candida species ( spp . ) with acquired or intrinsic resistance . echinocandins are recommended as first - line treatment for c / ic in all patients , and more specifically in hemodynamically unstable patients or in those with prior azole exposure , or for invasive infections caused by c. krusei or c. glabrata because of their activity against azole - resistant strains , while amphotericin b remains the cornerstone of antifungal treatment.1,9,1115 in this review , we aim to discuss the management and treatment options of fungal infections in the elderly population , considering additionally the specific conditions and the impact of potential comorbidities and drug interactions . invasive candidiasis ( ic ) ( also called","fungi are major causes of infections among immunocompromised or hospitalized patients with serious underlying diseases and comorbidities . candida species remain the most important cause of opportunistic infections worldwide , affecting predominantly patients over 65 years old , while they are considered to be the fourth most common cause of nosocomial bloodstream infections . the rapidly growing elderly population has specific physiological characteristics , which makes it susceptible to colonization and subsequent infection due to candida species . comorbidities and multidrug use should be taken into account any time the therapeutic regimen is under consideration . different classes of antifungal drugs are available for the treatment of invasive fungal infections but echinocandins , apart from their activity against resistant strains ( candida glabrata and candida krusei ) ,",380,128,0.3368
dialogsum,"#Person1#: Can you help me find a pan? #Person2#: Are you looking for a small, medium, or large pan? #Person1#: I want a big pan. #Person2#: Does this one look big enough? #Person1#: Yes, it's the right size, but it weighs too much. #Person2#: Well, what do you think of the aluminum pan? #Person1#: It's light enough, but the handle will get too hot after cooking. #Person2#: Here's the same pan, but it has a space-age, heat-resistant plastic handle. #Person1#: Oh, my family's going to love this one. I'll take it. #Person2#: I'm so happy that you found what you wanted. Do you want to use a credit card? #Person1#: Sure. Wait, wait. Does a lid come with this pan? #Person2#: Oh, I'm sorry. Here's the lid. Yes, it comes with the pan.",#Person2# helps #Person1# find an aluminum pan with a plastic handle. #Person1# reminds #Person2# to give #Person1# the lid.,133,19,0.1429
pubmed-summarization,". therefore , we investigated the relationship between ag , which is diagnosed based on serum pg levels , and cad in general japanese individuals . the human dry dock , is one of the most popular medical services in japan , for the purpose of the medical health checkup promoting public health through early detection of chronic diseases and their risk factors . a standard human dry dock features anamnesis and a survey of lifestyle , a physical examination , serum and urine examination , a chest x - ray , abdominal ultrasonography , and other tests . the fee is paid by participants or supported ( fully or partially ) by their employers or medical insurers . this study was designed to cross - sectionally evaluate the relationship between ag and cad in japanese population . the study included 1,758 male and 875 female subjects , aged 2190 years , who attended the human dry dock of oike clinic in kyoto , japan in 2009 . medical history and lifestyle factors were obtained from a self - administered questionnaire completed by all the subjects , which included medication use , family history of diseases , and habits of smoking and drinking . in addition , all participants underwent physical examinations , routine biochemical screening tests obtained by venipuncture after an overnight fast . all participants gave their informed consent , and the study was approved by the ethics committee of oike clinic . body mass index ( bmi ) was calculated as body weight in kilogram divided by the square of the participant s height in meters . systolic blood pressure and diastolic blood pressure were measured in the right upper arm of participants in a sedentary position using an automatic oscillometric blood pressure recorder . hypertension was defined as systolic blood pressure / diastolic blood pressure 140/90 mmhg or pharmacological treatment for hypertension . dyslipidemia was defined as total cholesterol 5.7 mmol / l , triglyceride 1.7 mmol / l , or pharmacological treatment for hyperlipidemia . hyperuricemia was defined as serum uric acid 416.3 mol / l , or pharmacological treatment for hyperuricemia . atrophic gastritis was defined as pg i 70 ng / ml and pg i / ii ratio 3.0 . coronary artery disease","atrophic gastritis is characterized by chronic inflammation of gastric mucosa by helicobacter pylori infection and other factors . helicobacter pylori infection has been linked to coronary artery disease . to our knowledge , however , no reports are available on the relationship between atrophic gastritis and coronary artery disease . in this study , we investigated the relationship between atrophic gastritis , which is diagnosed based on serum pepsinogen levels ( pepsinogen i 70 ng / ml and pepsinogen i / ii ratio 3.0 ) , and the prevalence of coronary artery disease in general japanese population . among 2,633 study subjects , 531 subjects ( 20.2% ) were diagnosed as atrophic gastritis . the prevalence of coronary artery disease was higher in the atrophic gastritis - positive",380,128,0.3368
dialogsum,"#Person1#: How was your date recently? #Person2#: Not too bad. It is seemingly too hard for me to find a place for our date. #Person1#: I guess so. Going to watch a movie and having dinner at a restaurant are usual. #Person2#: She said she wanted to go Dutch in dating. #Person1#: Yes, now many girls want to be independent, so it is a little popular, especially among white collars. #Person2#: But I am still traditional, so I felt weird when she paid for herself. #Person1#: Forget about it! #Person2#: Are you satisfied with your girlfriend? #Person1#: It will be a long story. We have many differences, for example, she usually puts all her clothes into washing machine. That is the sort of thing I can not bear.",#Person2# tells #Person1# he feels weird when his girlfriend goes Dutch in dating. #Person1# also tells #Person2# the difference between #Person1# and his girlfriend.,128,24,0.1875
scientific_lay_summarisation-elife-norm,"ramp protocol (1A, upper panel). A common way to characterize temperature sensitivity is the Q10 value (defined as the folds increase in current amplitude upon a 10°C increase in temperature). For TRPV1, the Q10 value is above 20 over a more than 200 mV voltage range (1A, lower panel) (Benham et al. , 2003), reflecting outstanding sensitivity of channel activation to heat. Having high temperature sensitivity at a wide voltage range is crucial for the channel' s physiological role as a temperature sensor—it allows TRPV1-expressing sensory neurons to detect heat no matter the neurons are in the resting state or excited state. 10. 7554/eLife. 03255. 003Figure 1. Heat sensitivity of TRPV1 and Shaker channel exhibits distinct voltage dependence. (A) TRPV1 current was elicited by a voltage ramp at varying temperatures (upper panel). Q10, quantified between 36. 6°C and 46. 0°C, remains high across the entire voltage range from −100 mV to +150 mV (lower panel). (B) Shaker channels exhibit a low heat sensitivity at most voltages as quantified by Q10 between 22. 4°C and 27. 7°C. However, Q10 transiently peaks (red arrow) around the voltage (−70 mV) where the channel just starts to open. Simplified gating schemes involving two transitions are shown on the bottom. The C→C′ transition is weakly voltage-dependent for TRPV1 but highly voltage-dependent for Shaker. (C) TRPV1 and Shaker channels show distinct voltage-dependent activation behaviors. TRPV1 conductance (open circle) has a shallow voltage dependence (with an apparent gating charge of 0. 76 ± 0. 06 e0, n = 4) that occurs in a highly depolarized range (V1/2 = 114. 9 ± 10. 9 mV, n = 4). Shaker activation has a steep voltage dependence (with an apparent gating charge 5. 1 ± 1. 3 e0, n = 5) that occurs at hyperpolarized voltages (V1/2 = −54. 2 ± 4. 7 mV, n = 5). The Q-V curve for Shaker (dotted curve) is reproduced from a published study (Schoppa and Sigworth, 1998). : http: //dx. . org/10. 7554/eLife. 03255. 003 Activity of Shaker potassium channel, in contrast, exhibited much lower temperature sensitivity (1B, upper panel). As a voltage-gated channel, Shaker activates upon depolarization to about −60 mV (1C). The threshold voltage for activation was only slightly shifted by raising temperature. The average Q10 value remained low, at below","If you touch something too hot, it can cause you pain and damage your skin. Sensing the heat given off by an object or the temperature of the environment is possible, at least in part, because of proteins called temperature-sensitive TRP ion channels. These proteins are found in the cell membranes of nerve endings that are underneath the skin; and they open in response to heat, allowing ions to flow into the nerve cell. This in turn triggers a nerve impulse that is sent to our central nervous system and is perceived as heat and/or pain. The ability to sense heat was thought to be unique to these TRP ion channels, and it was believed that these ion channels contained an as-yet unidentified temperature-sensing domain. However, Yang and",380,128,0.3368
dialogsum,#Person1#: Could you tell me how to use the washer and dryer? #Person2#: What do you need help with? #Person1#: Do you know how to turn them on? #Person2#: Do you have any change? #Person1#: I need change for the machines? #Person2#: You need to put 50 cents into the washer machine and a dollar into the dryer. #Person1#: So what do I need to do? #Person2#: The machines will turn on once you put the quarters into the slot. #Person1#: That's really all I have to do? #Person2#: That's everything. #Person1#: Thanks for all your help. #Person2#: I'm here if you need any more help.,#Person2# tells #Person1# to put quarters into the washer machine and the dryer. Then the machines will turn on.,106,19,0.1792
dialogsum,"#Person1#: Still feeling ill? #Person2#: Yes. And that medicine hasn't helped. Not a good start to our vacation, I'm afraid. #Person1#: Do you have any idea what caused it? #Person2#: Well, I thought it might be last night's dinner. #Person1#: But I am fine. Could it be the heat? It's enough to make anyone ill. #Person2#: I know. But we've been here a week now. Anyway, I've been careful in the sun and I've been drinking bottled water. #Person1#: Then we'd better stay in the hotel today.",#Person1# and #Person2# are having a vacation but #Person2# feels ill.,87,11,0.1264
dialogsum,"#Person1#: Isaac, something's wrong with the shower. It can't be turned off completely. It keeps dripping. #Person2#: Yeah, maybe the shower head needs replacing. #Person1#: Oh, it's probably just a washer or something that needs to be replaced. Can you take a look at it? #Person2#: Me? I'm not a repairman. I don't even know what's wrong with it. #Person1#: I know, but you're always so good when the TV needs to be fixed. You know, when the screen needs adjusting. #Person2#: Yeah, well, that's an emergency.",#Person1# asks Isaac to check the dripping shower but Isaac doesn't think he can handle it.,87,16,0.1839
scientific_lay_summarisation-elife-norm,"The rate of protein synthesis in the adult heart is one of the lowest in mammalian tissues, but it increases substantially in response to stress and hypertrophic stimuli through largely obscure mechanisms. Here, we demonstrate that regulated expression of cytosolic poly (A) -binding protein 1 (PABPC1) modulates protein synthetic capacity of the mammalian heart. We uncover a poly (A) tail-based regulatory mechanism that dynamically controls PABPC1 protein synthesis in cardiomyocytes and thereby titrates cellular translation in response to developmental and hypertrophic cues. Our findings identify PABPC1 as a direct regulator of cardiac hypertrophy and define a new paradigm of gene regulation in the heart, where controlled changes in poly (A) tail length influence mRNA translation. Cellular growth and function depend heavily on protein synthesis, which is often considered a constitutive activity for a cell. However, it is becoming clear that global protein synthesis rates are not always static, that they vary widely among cell types, and that these differences are necessary for normal tissue development and homeostasis (Buszczak et al. , 2014). Particularly, the rate of protein synthesis in adult heart is one of the lowest amongst different tissues but increases markedly in response to stress and hypertrophic stimuli (Garlick et al. , 1980; Lewis et al. , 1984). The molecular basis for these historical observations, however, is still poorly understood. Translation initiation is the rate-limiting step in protein synthesis (Aitken and Lorsch, 2012; Hinnebusch et al. , 2016; Sonenberg and Hinnebusch, 2009). Interactions between the 5’ m7GpppN cap structure, the pre-initiation factors (including eIF4A, eIF4E, and eIF4G), and poly (A) -binding protein C1 (PABPC1) form a stable, looped mRNP complex (Amrani et al. , 2008; Gallie, 1991; Park et al. , 2011; Safaee et al. , 2012; Tarun and Sachs, 1996; Wells et al. , 1998) that stimulates translation while safeguarding the mRNA from exonucleases (Coller et al. , 1998; Gray et al. , 2000; Kahvejian et al. , 2005; Lewis et al. , 2017; Zekri et al. , 2013). Based on these central roles, PABPC1 is thought to be ubiquitously expressed and serve ‘house-keeping’ roles in protein synthesis. Here, we report that PABPC1 protein expression is post-transcriptionally silenced in adult human and mouse hearts through shortening of its mRNA poly (A) tail, which results in reduced polysome association","Hundreds of thousands of different proteins are needed to build and maintain the cells in the human body. All proteins are produced when copies of genetic information in the form of molecules of messenger RNA (mRNAs) are translated by the ribosome. The rate at which proteins are made varies widely between different tissues and at different times. In particular, the adult heart has one of the lowest rates of protein production, though this rate can increase markedly during exercise and heart disease. The mechanisms that drive this kind of dynamic change in protein production remain unclear. A better understanding of this process would tell scientists more about how and why cells regulate the translation of mRNAs in general, and might uncover new ways for treating heart disease. Molecules",380,128,0.3368
dialogsum,"#Person1#: Whoa, whoa, what's going on? Watch out! #Person2#: Hey, watch where you're going! #Person1#: Oh, no! I'm so sorry! Are you all right? #Person2#: Oh. . . I don't know. #Person1#: I feel terrible, I really didn't mean to knock you over. My tire, just exploded, and I lost control of my bike. Really, it was an accident. Please accept my apologies. #Person2#: Oh, wait a second, you seem really familiar, I think I know you from somewhere. #Person1#: Yeah, I think we have met somewhere before. That's right! We met at Aaron's place last weekend! What a coincidence! But anyway, I'm glad to see that you're not too badly hurt, and I should probably get going. I have a nine o'clock meeting. #Person2#: Ouch! My ankle! I think it's broken! You can't just leave me like this! Are you calling an ambulance? #Person1#: Nope, I'm canceling my appointment so that I can stay here with you.",#Person1#'s tire exploded and #Person1# knocked #Person2# over. #Person2#'s ankle was therefore hurt. They find they have met before. #Person1# cancels #Person1#'s appointment so that #Person1# can stay with #Person2#.,158,30,0.1899
dialogsum,"#Person1#: Good afternoon. Welcome to China. May I see your passport, customs and health declaration form? #Person2#: Yes, here you are. #Person1#: Thank you. W hat's your occupation, Mr. Smith? #Person2#: I'm the general manager of the Far-East Industry Corporation. #Person1#: You are here on business, aren't you? #Person2#: Yes, I have been invited by the East Import #Person1#: I see. Do you have anything to declare? #Person2#: Yes, I have some foreign currency to declare. #Person1#: Would you please fill out this currency declaration form? It's a record of the foreign currency you have brought in. #Person2#: All right.","Mr. Smith's entering China. He tells #Person1# his occupation, the reason why he comes here and things to declare.",100,19,0.19
scientific_lay_summarisation-elife-norm,"flight muscle (Canavoso et al. , 2003; Van der Horst and Rodenburg, 2010). Compared to short-term flight, which exclusively employs carbohydrates as energy substrates, many physiological activities subsequently occur in the flight muscle during long-term flight, including carbohydrate/lipid metabolism transition, fatty acid transport, lipid oxidation, and lipid mobilization in the fat body. Clearly, complex and precise spatial and temporal regulation of energy metabolism is essential for long-term fight performance. However, the mechanisms underlying the highly efficient energy utilization associated with long-term flight have not been elucidated to date. A number of reports have emphasized the central roles played by neuropeptides in coordinating systematic energy metabolism during insect flight (Gade, 1992; Lorenz and Gäde, 2009). Most neuropeptides are produced by the central nervous system and perform distinct tasks through binding with their cognate G-protein-coupled receptors (GPCRs) (Nässel, 2002). By affecting energy metabolism either directly or indirectly, neuropeptides participate in a variety of biological events, such as flight, reproduction, diapause, and immune response (Gäde and Marco, 2009; Sim and Denlinger, 2013; Ling et al. , 2017; Urbanski and Rosinski, 2018). Furthermore, a single behavior or physiological process is usually controlled by multiple neuropeptides that play distinct roles in energy metabolism (Waterson and Horvath, 2015; Toprak, 2020). For example, adipokinetic hormone (AKH) has been demonstrated to be a conserved regulator of flight-related energy metabolism by promoting glycolysis and lipid mobilization in the fat body in different insect species (Gäde et al. , 2006; Kaufmann and Brown, 2008). Downstream signal transduction of AKH involved in lipid mobilization has been elucidated in insects (Gäde and Auerswald, 2003). In addition, other neuropeptides are also involved in either lipogenesis or lipolysis and play distinct roles in insect flight (Toprak, 2020). The migratory locust, Locusta migratoria, which possesses a notable long-term flight capacity, is one of the most destructive agricultural pests (Wang and Kang, 2014) and has been employed as a useful study model for the neurohormonal regulation of flight-related energy metabolism (Jutsum and Goldsworthy, 1976; Van der Horst and Rodenburg, 2010; Bullard et al. , 2017). The locust displays strong adaption to long-distance flight at both the physiological and morphological levels, exhibiting clear expansion of the energy gene family and high plasticity of muscle metabolism (Wang et al. , 2014). In the locust, the patterns of energy","Flight allows insects to find food or seek a better environment. Some insects have developed the ability of ‘long-term flight’, which allows them to make continuous journeys over large distances. For example, one locust species regularly crosses the Red Sea which is up to 300 km wide – a spectacular feat for insects only a few inches long. However, flight is an energy-intensive activity, and insects’ muscles need the right sort of chemical fuel to work properly. Previous work has shown that this ‘fuel consumption’ is highly dynamic and happens in two stages. First, immediately after take-off, the muscles rapidly consume carbohydrates (sugars); then, during the prolonged phase of the flight, muscles switch to exclusively consume lipids (fats). How the flight muscles ‘know’ when to start using fats",380,128,0.3368
pubmed-summarization,"congenital anomalies of the kidney and urinary tract ( cakut ) form a group of heterogeneous disorders that affect the kidneys , ureters and bladder . in this group are included common problems such as vesicoureteral reflux to severe life - threatening malformations as bilateral renal agenesis [ 1 - 4 ] . in young children , cakut are the main cause of end - stage kidney disease , leading to the need for kidney transplantation or dialysis , causing major impact on growth , maturation , and disturbed cognitive development and leading to a poor life expectancy . the survival rate of this group is 30 times lower than that of healthy children . it may be also associated with kidney problems in latter life , such as hypertension and proteinuria . cakut has also a significant economic impact on health care systems because of the patients lifelong costly therapeutic needs and impact of the employment potential of affected individuals and their families . they are present in 0.5 to 0.6% of gestations , accounting for 20 to 30% of all congenital anomalies detected in the neonatal period . this is a group diseases with an inherited polygenic trait , in addition to variable and incomplete penetrance , of multifactorial order , and can be related to de novo mutations , exposure to teratogenic substances , and maternal diet . the development of the urinary tract depends on a series of complex events derived from several genic products ( transcription factors , growthfactors , receptors ) necessary to the distinct stages of organogenesis . recent progresses in the understanding of the origins of urinary tract development in mice and other animals suggest a new picture to the interpretation of these defects in humans . genetic manipulations in mice identified a number of genes and genes network that direct the normal development of kidney and urinary tract , providing a new insight into the pathogenesis of cakut [ 1 , 3 , 15 - 17 ] . a list of these can be found in a database available online ( www.gudmap.org , www.omin.org ) . the mechanistic basis for cakut associated with altered intra - uterine environment remains to be elucidated further . maternal history of use of alcohol and","congenital anomalies of the kidney and urinary tract ( cakut ) form a group of heterogeneous disorders that affect the kidneys , ureters and bladder , with frequent asynchronous presentations and multiple cakut associations in the same individual . urinary tract formation is a complex process , dependent of the interaction of multiple genes and their sub - product . the same genic alterations can lead to different molecular expressions and different morphological anomalies . the ureterocele is a cystic dilation of the distal intramural ureter , resulting in obstruction of urine flow , dilation of the ureter and renal pelvis and loss of renal function . two key steps in the urinary tract ontogenesis may be related to ureterocele development : formation and migration of the ureteric",380,128,0.3368
pubmed-summarization,"a total of 10 male patients who developed fistula - in - ano and then complicated by fournier 's gangrene with a mean age of 50.5 ( 50 - 59 ) years were managed within the period of 5 years [ table 1 ] . nearly , 50% of patients were peasant farmers , 30% businessmen and 20% were civil servant . all patients presented with initial perianal pain , external opening and discharge and then followed by scrotal swelling and high grade fever [ table 2 ] . nearly , 70% of these patients presented with fournier 's gangrene within 1 - 4 weeks of development of fistula - in - ano , which were preceded by perianal abscess and the rest within 8 weeks [ table 3 ] . fistula - in - ano was submuscular ( intersphincteric ) , 30% subcutaneous with straight anterior external opening and 10% were complex or recurrent running curved course from internal posterior to anterior external opening [ ] . age distribution of 10 patients with fistula - in - ano and fournier 's gangrene major clinical features of 10 patients with fistula - in - ano and fournier 's gangrene duration of symptoms prior to presentation of 10 patients with fistula - in - ano and fournier 's gangrene types of fistula - in - ano with fournier 's gangrene at presentation of the 10 patients nearly , 40% of these patients had initial nick for drainage of their perianal abscess and 20% incision and drainage ( i and d ) , but 40% came with spontaneously ruptured perianal abscess , which developed fistula - in - ano and then fournier 's gangrene with no initial treatment [ table 4 ] . types of treatment prior to presentation of 10 patients with fistula - in - ano and fournier 's gangrene all patients were given adequate intravenous fluid and parenteral antibiotics before definitive treatment . 20% of patients had fistulotomy and seton ( rubber band ) application for adequate drainage . in 50% of patients mucosal advancement flap was done to close the internal opening of the fistula , but 30% had fistulotomy and sitz bath [ table 5 ] . types of procedure and surgery for 10 patients with fistula","background : fistula - in - ano when complicated by fournier 's gangrene is an unusual finding and always carries high morbidity . this study details our experience in managing 10 cases.methods of study : case files of all patients managed in university of maiduguri teaching hospital and federal medical center of yola and gombe from january , 2007 to december , 2011 were retrieved from medical record departments and other hospital records . these were analyzed for demographic , clinical and pathological variables , the type of treatment and follow-up.results:a total of 10 men with a mean age of 50.5 years ( 35 - 60 ) were managed in the period of study . nearly , 50% of the patients were farmers , 30% businessmen and 20%",380,128,0.3368
pubmed-summarization,"catalyzed by vitamin k epoxide reductase , which can use certain dithiols as the reductants ( ii ) . vitamin k quinone can be reduced to vitamin k hydroquinone in the reactions catalyzed by either a dithiol - dependent ( iii ) or an nad(h)p - dependent ( iv ) entzyme . ( uotila l. recent findings on the functions and requirements of vitamin k in humans . klinlab 1998 ; 3 : 97101 ) the enzyme reactions involved in the metabolic function of vitamin k. vitamin k - dependent carboxylase catalyzes the transformation of peptide- ( factors ii , vii , ix , and x ) bound glutamate residues ( glu ) to -carboxyglutamate ( gla ) residues in the presence of vitamin k hydroquinone , carbon dioxide , and molecular oxygen ( i ) . vitamin k hydroquinone is oxidized in the reaction to vitamin k 2,3 epoxide . the reduction of the latter to vitamin k quinone is catalyzed by vitamin k epoxide reductase , which can use certain dithiols as the reductants ( ii ) . vitamin k quinone can be reduced to vitamin k hydroquinone in the reactions catalyzed by either a dithiol - dependent ( iii ) or an nad(h)p - dependent ( iv ) entzyme . ( uotila l. recent findings on the functions and requirements of vitamin k in humans . klinlab 1998 ; 3 : 97101 ) warfarin treatment reduces the number of gla residues ( normal , 9 to 13 ) per clotting factor molecule , with a concomitant fall in coagulant activity . when the number of residues decreases from 13 to 9 , only 70% of the activity of the clotting factor remains ; when one molecule contains six carboxylated residues , only 2% activity is present . the liver excretes both active and inactive coagulation factors to the plasma and both affect international normalized ratio ( inr ) measurement , which possibly has escaped notice in the world health organization ( who ) recommendation for the prothrombin time methodology . the calculation formula is for : inr = ( samplesec / normalsec ) , where isi is the international sensitivity index . when the isi is near 1.0 , the reagent is sensitive and isi has little","warfarin is the most widely used medicine for oral anticoagulant therapy ( oat ) . it inhibits the synthesis of coagulation factors ii , vii , ix , and x in the liver and results in the production of inactive or partially active versions of these factors . inactive coagulation factors interfere with prothrombin time measurement ( quick and owren pt ) measuring the sum of coagulation activity and inhibition . the narrow therapeutic range here involves a danger of serious complications and the risk of bleeding or thrombosis . the new - generation pt method can measure coagulation activity and inhibition separately . this new technique promotes patient care and anticoagulant medication ( warfarin , dicoumarol ) based on coagulation activity in vivo . both therapy and",380,128,0.3368
dialogsum,"#Person1#: I understand your feeling. When someone is feeling at loose ends, we may show mercy on him. This is what we call the 'milk of human kindness'. #Person2#: That's right. But feeling sorry for someone is one thing, and sticking to our principles is another. We must make a clear cut between them. #Person1#: You've take the words out of my mouth.",#Person1# says people should show mercy and #Person2# thinks sticking to one's principle is another thing.,63,16,0.254
dialogsum,"#Person1#: I'd like to open a savings account. #Person2#: Fine. I'll need some information to fill out an application for you. Name? #Person1#: Alice. Alice. #Person2#: Social Security number? #Person1#: 900900999. #Person2#: OK, home address? #Person1#: 8818 Tavistock Square apartment 9C. #Person2#: Home and work phone numbers? #Person1#: My home number is 4445244, my office number is 4441616. #Person2#: OK, do you want to open a regular or temporary account? #Person1#: A temporary account. #Person2#: How much would you like to deposit to open the account? #Person1#: $5500. #Person2#: Alright, let's go over to the teller and will get you a passbook.","Alice tells #Person2# her Social Security number, home address, phone number, and deposits $5500 to open a temporary savings account.",102,20,0.1961
dialogsum,"#Person1#: What do you do? #Person2#: I'm an apprentice with a local engineering firm. My training lasts for two years. Two days a week I study Engineering at a local college. If I pass all my exams, I hope the company will take me on as an engineer.",#Person2# tells #Person1# #Person2# is an apprentice with a local engineering firm.,48,12,0.25
scientific_lay_summarisation-elife-norm,"ensuing mitochondrial dysfunction, we demonstrated the validity and relevance of this model to PD for small molecule screening purpose. Using this model to screen >1400 bioactive small molecules, we uncovered a series of compounds that protected against DA neuron loss by inhibiting different proteins in the renin-angiotensin-aldosterone system (RAAS), a pathway classically known for regulating vasoconstriction and water homeostasis (Bader, 2010). Genetic validation and molecular characterization revealed that the angiotensin receptor 1 (AGTR1) acted cell autonomously in DA neurons, the inhibition of which restored the expression of mitochondrial pathway genes disrupted by neurotoxic insults. Furthermore, we showed that RAAS inhibitors were neuroprotective in a zebrafish 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP) model and a zebrafish model of Gaucher disease, a lysosomal storage disorder with strong comorbidity of PD (Riboldi and Di Fonzo, 2019). The AGTR1 inhibitor olmesartan was also protective in a Drosophila pink1-deficient PD model (Yang et al. , 2006). Finally, utilizing the Parkinson’s Progression Marker Initiative (PPMI) database (Marek, 2018), we performed a clinical informatics analysis to uncover that RAAS inhibitors significantly slowed down PD progression. Together, our results delineate a powerful approach for neuroprotective small molecule drug discovery that leverages whole organism screening and cross-species validation. Genetic PD models in rodents generally have weak, variable, and late onset degeneration phenotypes (Dawson et al. , 2010). Modeling neurodegeneration in zebrafish is a promising approach (Paquet, 2009; Flinn, 2013; Ana Lopez, 2017; Zhang, 2017), but neuroprotective screening based on direct imaging of DA neuron integrity has not been reported, in large part because high content screening needs assays that are sufficiently robust, sensitive, and scalable. Neurotoxins such as MPTP are highly toxic to experimenters and not scalable. We have therefore used an inducible chemogenetic DA neuron ablation model, employing the nitroreductase-metronidazole (NTR-MTZ) system (Williams, 2015; Pisharath and Parsons, 2009; Curado et al. , 2008): NTR was expressed as a transgene in tyrosine hydroxylase (TH+) DA neurons to convert the pro-drug MTZ (a commonly used antibiotic) to the toxic nitroso radical form in vivo. Twenty-four hours (hrs) after adding MTZ to 5 days post fertilization (dpf) larval zebrafish, we observed at 6 dpf robust DA neuronal loss in the ventral forebrain region (1A), the homologous group to mammalian substantia nigDA (Rink and Wullimann, 2001). The specificity of ventral forebrain DA neuron labeling in","Parkinson’s disease is caused by the slow death and deterioration of brain cells, in particular of the neurons that produce a chemical messenger known as dopamine. Certain drugs can mitigate the resulting drop in dopamine levels and help to manage symptoms, but they cause dangerous side-effects. There is no treatment that can slow down or halt the progress of the condition, which affects 0. 3% of the population globally. Many factors, both genetic and environmental, contribute to the emergence of Parkinson’s disease. For example, dysfunction of the mitochondria, the internal structures that power up cells, is a known mechanism associated with the death of dopamine-producing neurons. Zebrafish are tiny fish which can be used to study Parkinson’s disease, as they are easy to manipulate in the lab and",380,128,0.3368
dialogsum,"#Person1#: I'd like to check in, PLS. #Person2#: Awfully sorry, sir. There are no rooms available now. #Person1#: But I'Ve reserved a room the day before yesterday. #Person2#: Sorry, may I have your name? #Person1#: Tony Bush. #Person2#: Pls wait a minute, let me check. Excuse me, but I can't seem to find your name on our list. Are you sure you have a reservation for tonight? #Person1#: Of course, I did it myself. #Person2#: I am terribly sorry. There must have been some mistakes. Let me check it again. Oh, yes, there is a name listed as Tommy Bush. It must be the fault of the clerk who registered your name. I apologize. #Person1#: Don't worry about that. #Person2#: According to the records, your reservation is for a single room with shower and air conditioners for two nights. The room rate will be 110 dollars per night, including 10 % tax and 4 % service charge. Is this right? #Person1#: Yes, that's right. I'd like to pay my bill by credit card. #Person2#: May I make a copy of your card? #Person1#: Here you are. #Person2#: Ok, now could you fill out this registration form? #Person1#: All right. #Person2#: Your room number is 707. Here is your key. The bellhop will help you carry the suitcases to your room. Have a nice evening!",Tony Bush has a reservation at #Person2#'s hotel. #Person2# can't find his name on the list first and apologize that there must have been some mistakes. Then #Person2# helps Tony check-in after confirming Tony's information.,224,35,0.1562
pubmed-summarization,"cardiovascular disease ( cvd ) is the main cause of death in maintenance hemodialysis ( mhd ) patients . both aortic artery calcification ( aac ) and cardiac valve calcification ( cvc ) have a high incidence in dialysis patients . the diagnosis of vascular calcification is usually based on very expensive and highly technical devices such as electron beam computed tomography ( ebct ) or multislice spiral computed tomography ( ct ) . however , lateral lumbar x - ray is a useful approach to detect aac with cheap price and low radiation . in addition , the use of plain radiographic films of bone has already been suggested in kidney disease improve global outcomes ( kdigo ) chronic kidney disease mineral and bone disorder ( ckd - mbd ) clinic practice guideline . our previous studies have already showed the high incidence of aac and cvc in dialysis patients and increased fgf23 ( fibroblast growth factor 23 ) was associated with aac and cvc . now , in this study , we aimed to investigate the relationship among aac , cvc , and mortality , and to out that , which factor could predict the outcome of mhd patients . two hundred forty - seven mhd patients were treated in ruijin hospital affiliated to shanghai jiao tong university , school of medicine in july 2011 . two hundred seventeen patients met the following inclusion criteria : ( 1 ) age over 18 years , ( 2 ) patients received hemodialysis 3 times a week , on a 4 h schedule , using a dialysate calcium concentration of 1.5 mmol / l , ( 3 ) no rapidly progressive kidney disease . among these patients , 74 patients refused to take part in this study , 18 patients with cancer , 15 patients dialysis vintage less than 3 months . this study was approved by the institutional review board of the ruijin hospital , shanghai jiao tong university , school of medicine and was in accordance with the principle of the helsinki declaration . all clinic data of mhd patients were collected , including blood pressure , which were recorded using the mean of the previous 1-month , height and weight , and medical history . predialysis blood tests","background : this study was to investigate the relationship among aortic artery calcification ( aac ) , cardiac valve calcification ( cvc ) , and mortality in maintenance hemodialysis ( mhd ) patients.methods:all mhd patients in shanghai ruijin hospital in july 2011 were included . to follow up for 42 months , clinical data , predialysis blood tests , echocardiography , and lateral lumbar x - ray plain radiography results were collected . plasma fgf23 level was measured using a c - terminal assay.results:totally , 110 mhd patients were involved in this study . of which , 64 ( 58.2% ) patients were male , the mean age was 55.2 1.4 years old , and the median dialysis duration was 29.85 ( 3.0225.5 ) months . about 25.5%",380,128,0.3368
scientific_lay_summarisation-elife-norm,"1993; Powers and Walter, 1997). Despite wide and careful study, a consistent understanding of the initial step of the targeting reaction, in which SRP binds to translating RNCs, remains elusive. Equilibrium measurements of SRP binding affinities to RNCs stalled with nascent chains up to 35 amino acids in length indicated very tight binding (∼1–100 nM binding constants) (Bornemann et al. , 2008). An estimate based on ribosome profiling of the ∼2000 most expressed proteins in E. coli indicates that at any given moment ∼10% of RNCs have a nascent chain less than 35 amino acids long (Oh et al. , 2011). Considering that the SRP concentration in E. coli is ∼400 nM (100-fold less than the ribosomal concentration) (Jensen and Pedersen, 1994), such tight binding affinities would result in 75–100% of the SRP to be bound to these RNCs that are not exposing a signal sequence, and the majority of which (∼95%) never will (Bornemann et al. , 2008). SRP binding to these RNCs would thus result in a large unproductive sink on the targeting reaction. Kinetic studies attempted to resolve this issue and concluded that, regardless of nascent chain length, SRP arrives at RNCs very quickly (arrival rates on the order of 106 M−1 sec−1) and that nascent chain length mostly affects dissociation rates (although different studies have determined a wide range of dissociation rates: ∼10–0. 01 s−1 for RNCs with no nascent chain and ∼0. 1 to 2 × 10−4 s−1 for RNCs with an exposed signal sequence) (Holtkamp et al. , 2012; Noriega et al. , 2014; Saraogi et al. , 2014). The models that emerged had SRP non-specifically, and quickly arriving to RNCs as soon they begin translating and remaining bound until a nascent chain without a signal sequence becomes long enough to emerge from the ribosomal peptide tunnel and sterically displace SRP. Alternatively, the possibility of an additional factor (such as the co-translational chaperone trigger factor) was proposed to bind the RNC and displace SRP (Holtkamp et al. , 2012; Bornemann et al. , 2014). In either model, a large pool of SRP would be unproductively bound for a significant amount of time until displaced. Prior studies of SRP-RNC binding were performed on RNCs that had been stalled while translating the nascent chain. This approach","Genes contain the instructions needed to make proteins from smaller building blocks called amino acids. These instructions are first transcribed to produce molecules of messenger RNA, which are then translated by a ribosome. This ‘molecular machine’ translates the instructions in the messenger RNA into the sequence of amino acids needed to make the protein. For some proteins to carry out their role, they need to be delivered to the outside of the cell, or inserted into one of the cell' s membranes. As they are being built, these proteins are identified by a so-called ‘signal recognition particle’, which is often called an SRP for short. The SRP attaches to the new protein when it is still joined to the ribosome, and pulls the protein-ribosome complex to an opening",380,128,0.3368
dialogsum,"#Person1#: Did you hear about car accident on Spring Road yesterday? #Person2#: Yes, I did. I heard that they took both drivers to hospital. One needed surgery. #Person1#: Yes. I heard he had a few broken bones too, but that the doctors have set the fractures without any problems. #Person2#: The second driver was luckier. He had a concussion and needed some stitches for his head wound. #Person1#: Yes. He was released from hospital yesterday evening. The other man could be there for weeks. #Person2#: I understand that he's connected to a heart monitor and breathing apparatus. His condition can't be very good. #Person1#: The hospital announced this morning that his condition is poor but stable. What does that mean? #Person2#: It means he's really badly injured, but he will almost certainly survive. #Person1#: His family will be pleased to hear that. They must have been so worried.",#Person1# and #Person2# discuss the car accident on Spring Road yesterday. They heard one driver was released from the hospital yesterday and the other's condition is poor but stable.,148,29,0.1959
scientific_lay_summarisation-elife-norm,"During differentiation SEs lose most of their cellular components, including their nucleus (Oparka and Turgeon, 1999; Furuta et al. , 2014). Ontogenetically related, metabolically active companion cells (CCs) support the adjacent enucleate SEs throughout their lifespan (Lucas et al. , 1996; Pritchard, 1996; van Bel and Knoblauch, 2000; Lalonde et al. , 2001; Otero and Helariutta, 2017). The pressure flow model of phloem transport, originally proposed by Münch (1930), envisages that an osmotically generated pressure differential drives the bulk flow through the SEs that connect photosynthetic tissues (sources) with those in which carbon consumption occurs (sinks). The loading of solutes in source tissues results in a high osmotic potential within SEs. The reduction of turgor pressure in sink organs due to carbon consumption leads to a pressure gradient that provides the energy to overcome viscous resistance within the SEs, resulting in a passive phloem flow from source to sink (Münch, 1930). Phloem sap collected from excised aphid stylets contains a complex mixture of macromolecules and low-molecular weight solutes (Atkins et al. , 2011). In a recent study, Paultre et al. (2016) showed that many proteins, including those with targeting sequences, can move across a graft union and be unloaded near the root tip. Significantly, these proteins entered a post-phloem domain beyond which their movement was restricted. This observation begs the question as to how the phloem is able to discriminate between macromolecules and solutes during unloading. Besides the central function in resource allocation, it is now well established that the phloem also serves as network for transmission of chemical (Kramer and Boyer, 1995a; Mullendore et al. , 2015) and electrical (Hedrich et al. , 2016) signals. Phloem unloading in actively growing tissues such as the shoot or root apex occurs through the protophloem, a transient tissue that connects the conducting phloem with the receiver cells in sink tissues (Oparka et al. , 1994). Initial investigations of phloem unloading in the root tip of Arabidopsis (Oparka et al. , 1994,1995; Wright and Oparka, 1996) provided evidence that unloading occurs through plasmodesmata (PD), the specialized pores that connect plant cells. Due to cell division and growth in the apical region of the root the demand for assimilates is high. Protophloem sieve elements (PSEs) become mature in such regions to accommodate this demand","A mechanism called photosynthesis allows plants to use energy from sunlight to make sugars from carbon dioxide gas and water. These sugars can then be used as fuel, or as building blocks for wood and other plant structures. Every part of the plant requires sugars, but most photosynthesis happens in the leaves and stems, so the sugars need to be able to move around the plant to wherever they are needed. Phloem tubes form a network that transports sugar, proteins and other molecules around the plant within a fluid known as sap. Because this network is so extensive, it is very difficult to study, which has left researchers with major questions about how it works. For example, it is not clear how the sugar and other molecules leave",380,128,0.3368
dialogsum,"#Person1#: ( Before Christmas Party ) Are you ready for the Christmas party tonight #Person2#: Almost. I have to get dressed. It's a formal party and I have special party make up! #Person1#: Use this lipstick and it will make your lips shine! #Person2#: Great! Uh, remember that there's a gift exchange, too. We all have to bring a gift. #Person1#: I've already got mine. #Person2#: ( At the Party ) It's Christmas Eve! Time to open presents! #Person1#: Here! Open mine first. #Person2#: Wow! It's just what I wanted! #Person1#: Hey! Why don't I have any presents!",#Person1# suggests #Person2# using the lipstick and #Person2# reminds #Person1# of bringing a gift to the party. Later #Person2# gets what she wants but #Person1# gets nothing.,98,27,0.2755
dialogsum,"#Person1#: You experimented with a lot of musical styles. What's next? #Person2#: It's hard to say where I'm going next, because my next record isn't finished. #Person1#: You used to go to acting classes before you got into music. Did you ever consider becoming an actress? #Person2#: That's what I wanted to do initially. I left school and joined a traveling theater company. We didn't have money for hotels. So we used to camp in parks. It was brilliant. Then I met William. He liked my voice and decided I should be a singer. It was queer because singing was something I never had in mind. #Person1#: Is it true that the best time of a woman's life is in her thirties? #Person2#: Well. Someone's been telling me that it really starts at forty. She is a wonderful woman. And she says the 30s are just as hard as the 20s, hut in a different way. They are just confusing. But when you get to forty, it's just extraordinary. Apparently, the whole world opens up. #Person1#: What would you like to achieve before you're... say.., sixty? #Person2#: I'd love to learn how to play the violin but not before I'm sixty. I'd like to do it in the next year or so. One of the first instruments I learned was the drums. And I am quite good at that coordination in a strange way.",#Person2# tells #Person1# #Person2#'s next record isn't finished. #Person2# wanted to be an actress initially but now she becomes a singer. #Person2# thinks the best time of a woman's life is in her forties and wants to learn to play the violin in the next year.,234,46,0.1966
dialogsum,"#Person1#: I've got a complaint about the noise next door. #Person2#: Yes, it's most irritating. #Person1#: Some people aren't very considerate. #Person2#: We're going to do something about it. #Person1#: Yes, I think so. #Person2#: We can't put up with it any more. #Person1#: We'll play the CD loud, is that all right? #Person2#: I don't think so. #Person1#: What should we do? #Person2#: Why don't we call them? #Person1#: Good idea.",#Person1# and #Person2# think the people next door are noisy so they decide to call them.,72,16,0.2222
dialogsum,"#Person1#: Jack, why don't you go to work by bike? #Person2#: I used to, but the weather today is so nice, and I decide to walk to my company. It's a good way to take exercise though I have to leave home an hour earlier than usual.",Jack tells #Person1# why he walks to work today.,47,9,0.1915
dialogsum,"#Person1#: Why do all girls appear feminine after sophomore year? #Person2#: Because they are full-grown. Look at their curvy figures. #Person1#: I feel they all talk and behave in a different way. #Person2#: They suddenly become shy when they speak to boys. #Person1#: Some even do make-up slightly. Are you aware that previous'small potato'Ma Xiaoxiao becomes a piece of cheese cake recently? #Person2#: She is certainly not my kind of girl. #Person1#: Stop preaching your dream love Marilyn Monroe to me. I know those sexy women are your tastes. #Person2#: You are so Platonic. Those naive girls will eventually grow into real women. They can't resist love, and men cannot resist their attraction either. #Person1#: I appreciate the saying'Love consists in this, that two solitude protect, border and salute each other. '","#Person1# and #Person2# talking about girls appear feminine after sophomore year, like Ma Xiapxiao. #Person2# thinks #Person1# is so platonic and #Person1# appreciates a saying about platonic love.",132,28,0.2121
dialogsum,"#Person1#: How do you arrange this summer vacation? #Person2#: I want to travel. #Person1#: Where would you like to go? #Person2#: The seaside. #Person1#: That's really a good idea. Taking a walk on the beach and lying in the sun are pretty good. I recommend you Qingdao or Dalian. #Person2#: I ' Ve been to Qingdao before, so I ' ll choose Dalian. I've heard that the environment there is very good. #Person1#: Yes, that's a good place to spend a holiday. Last year I went there. It's really. #Person2#: Thank you!","#Person2# wants to travel to the seaside this summer vacation and #Person2# recommends Qingdao or Dalian, #Person2# picks Dalian.",92,19,0.2065
scientific_lay_summarisation-elife-norm,"Ndr1) and Cyclops (Cyc, Ndr2) and that the Aplnr regulates Nodal signaling in a cell non-autonomous fashion. We propose a model in which the Aplnr fine-tunes Nodal activity during the onset of gastrulation to initiate the migration of lateral margin cells and proper heart formation. Aplnr may therefore act as a rheostat for the Nodal/TGFβ pathway. The zebrafish genome harbours two paralogues (aplnra and aplnrb) of the human APLNR gene. Only aplnrb, for which the first mutant was aptly named grinch (aplnrbs608, p. Trp90Leu), is known to be involved in early cardiogenesis (Scott et al. , 2007; Zeng et al. , 2007). In order to assess the contribution of aplnra to the process of gastrulation and heart development, we knocked it out using custom TALEN pairs targeted to its unique exon on chromosome 8 (1A). The resulting null allele, which we named max (the compliant dog companion of the Grinch), encodes a truncated 17-amino acid protein resulting from an early frameshift. The aplnramax allele (p. Thr16TrpfsX2) deletes 95% of Aplnra including its seven transmembrane domains (1A). Present at sub-Mendelian ratios, approximately 15% of mutant larvae from heterozygous aplnramax intercrosses showed pericardial edema (1B–C). As with aplnrb mutants (Scott et al. , 2007; Pauli et al. , 2014; Chng et al. , 2013), sox17-positive endodermal progenitors at 8 hr post-fertilization (hpf) and myl7-positive cardiomyocytes at 1 day post-fertilization (dpf) were significantly reduced in numbers and intensity in aplnramax fish (— 1A–D). Note that in this current study a novel aplnrbhu4145 (p. W54X) allele is being used. An independent allele, aplnrains, resulting from a viral insertion was obtained from Znomics (1A). Homozygous aplnrains embryos recapitulated the phenotype of aplnramax and aplnrbhu4145 with similar pericardial edema (1D), reduced nkx2. 5-positive cardiac mesoderm at the 15-somite stage (1F–H) and reduced myl7-positive cells at 2 dpf (1J–K). The number and spread of sox17-positive cells was significantly reduced in homozygous aplnrains when compared to wildtype (WT) and was not significantly different from aplnrbhu4145 single mutants (1M–O and — 1E–F). These aplnra mutant phenotypes suggest redundant functions for aplnra and aplnrb. 10. 7554/eLife. 13758. 003Figure 1. aplnra mutant embryos display defects in endoderm and heart formation. (A) Schematic detailing the aplnramax and aplnrains alleles. TM indicates the transmembrane domain. (B–E) Gross morphology of aplnramax, aplnrains and aplnrains;","In one of the first events that happens as an embryo develops, cells become the different stem cell populations that form the body’s organs. So what makes a cell become one stem cell type rather than another? In the case of the heart, the first important event is the activity of a signaling pathway called the Nodal/TGFβ pathway. Nodal signaling can drive cells to become many different stem cell types depending on its level of activity. Many different levels of regulation fine-tune Nodal signaling to produce these activity thresholds. Zebrafish that have a mutation in the gene that encodes a protein called the Apelin receptor have no heart. The loss of this receptor interferes with how heart stem cells (called cardiac progenitors) are made and how they move",380,128,0.3368
dialogsum,"#Person1#: Betty and I will throw a dinner party this weekend, we'd like you to come. #Person2#: That would be very nice. Only that I'll be a little late. Is that OK? #Person1#: Sure. We'll be looking forward to that day. #Person2#: So will I. Thank you.",#Person2# will come to #Person1# and Betty's dinner party.,47,9,0.1915
dialogsum,"#Person1#: Hello sir, how may I help you? #Person2#: I would like to buy some flowers, please. Something really nice. #Person1#: I see, may I ask what the occasion is? #Person2#: It's not really an occasion, it's more like I'm sorry. #Person1#: Very well. This arrangement here is very popular among regretful husbands and boyfriends. It has a dozen long stem red roses with a couple of sunflowers and a single orchid that stands out. It includes a small teddy bear to achieve the effect of immediate forgiveness. #Person2#: I think I'm gonna need more than just a dozen red roses and a bear. What else do you recommend? #Person1#: Mmm, well this is our I'm sorry I cheated on you package. Two dozen red roses lined with tulips, carnations and lilies. The fragrance and beauty of this flower arrangement is sure to make her forgive you. #Person2#: I don't think that's gonna cut it. I need something bigger and better! #Person1#: I'm sorry sir but, what exactly did you do? #Person2#: Well, I may have accidentally insinuated that she is getting chubbier. #Person1#: Get out of my store,you jerk!","#Person2# wants to buy flowers to apologize and #Person1# recommends several choices. But when knowing the reasons that #Person2# has accidentally insinuated that his girlfriend is getting chubbier, #Person1# doesn't want to sell him the flowers.",190,36,0.1895
pubmed-summarization,"worsening the risk - reward ratio and potentially choking overall investment in drug development . because approval occurs while uncertainty persists , a variety of post - approval surveillance activities are performed in case the decision must be reversed . in the five years leading up to drotrecogin 's approval in 2001 , the fda approved 597 new therapies . in other words , there is a low , but non - zero , rate of drug withdrawal . a lower rate would be preferable , but without major changes to patent laws or to the science and costs of drug development , the chilling effect of a more stringent approval process on dwindling drug pipelines would likely be considered intolerable . so , while we might lament that a sepsis drug was one of the unlucky ones , the fundamental drug approval process that led to drotrecogin approval does not seem too lenient , wrong , or unreasonable . that said , it is a shame that prowess was stopped early , something outside the control of the fda , as early stopping biases toward an overestimate of treatment effect . and it is a shame that the costs and logistics of running two concurrent phase 3 trials in critical care seem to be insurmountable obstacles in the drug development process . cheaper and easier trials could allow us to generate greater certainty without compromising drug pipeline . the usual reason for withdrawal is determination of a previously unknown yet highly undesired side effect . these studies generally reported mortality benefits similar to that seen in prowess [ 6 - 12 ] . the studies also provided greater information about bleeding risks , which led to further label restrictions . however , somewhat unusually , the withdrawal in this instance was a voluntary decision based not on safety but on failure to confirm efficacy . numerous human and animal studies suggest that it modulates coagulation and inflammatory pathways and interacts with endothelial function in the midst of intense innate immune responses to challenges such as sepsis . a previous simulation exercise of theoretical anti - tumor necrosis factor ( anti - tnf ) anti - body trials in sepsis demonstrated that modest differences in the distribution of unmeasured variables","following the failure of prowess - shock to demonstrate efficacy , eli lilly and company withdrew drotrecogin alfa ( activated ) from the worldwide market . drotrecogin was initially approved after the original trial , prowess , was stopped early for overwhelming efficacy . these events prompt consideration of both the initial approval decision and the later decision to withdraw . it is regrettable that the initial decision was made largely on a single trial that was stopped early . however , the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world . furthermore , the overall withdrawal rate of approved drugs remains very low . the decision to withdraw was a voluntary decision by eli",380,128,0.3368
scientific_lay_summarisation-elife-norm,"T cell receptor (TCR) engagement opens Ca2+ release-activated Ca2+ (CRAC) channels and triggers formation of an immune synapse between T cells and antigen-presenting cells. At the synapse, actin reorganizes into a concentric lamellipod and lamella with retrograde actin flow that helps regulate the intensity and duration of TCR signaling. We find that Ca2+ influx is required to drive actin organization and dynamics at the synapse. Calcium acts by promoting actin depolymerization and localizing actin polymerization and the actin nucleation promotion factor WAVE2 to the periphery of the lamellipod while suppressing polymerization elsewhere. Ca2+-dependent retrograde actin flow corrals ER tubule extensions and STIM1/Orai1 complexes to the synapse center, creating a self-organizing process for CRAC channel localization. Our results demonstrate a new role for Ca2+ as a critical regulator of actin organization and dynamics at the synapse, and reveal potential feedback loops through which Ca2+ influx may modulate TCR signaling. Soon after a T cell encounters cognate antigen on an antigen-presenting cell (APC), it spreads out over the cell’s surface, forming a tightly apposed structure known as the immune synapse (Bromley et al. , 2001; Yokosuka and Saito, 2010; Dustin, 2008). The synapse regulates T cell activation by maximizing the contact area and organizing the T cell receptors (TCR) and associated signaling proteins into zones. Strong antigenic stimuli create three concentric regions (Monks et al. , 1998; Grakoui et al. , 1999): a central supramolecular activation cluster (cSMAC), an intermediate zone (the peripheral SMAC, or pSMAC), and a zone at the synapse edge (the distal SMAC, or dSMAC) (Freiberg et al. , 2002). TCRs assemble with scaffolding and signaling proteins to form microclusters in the dSMAC which migrate centripetally towards the cSMAC (Grakoui et al. , 1999; Krummel et al. , 2000; Campi et al. , 2005; Varma et al. , 2006; Yokosuka et al. , 2005). As they move, TCR microclusters activate a MAP kinase cascade and Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels, both of which are essential to initiate gene expression programs that drive T cell proliferation and differentiation (Feske et al. , 2001). Signaling by TCR microclusters is terminated as they enter the cSMAC by the dissociation of signaling proteins (Yokosuka et al. , 2005; Campi et al. , 2005; Varma et al. , 2006) and endocytosis","An effective immune response requires the immune system to rapidly recognize and respond to foreign invaders. Immune cells known as T cells recognize infection through a protein on their surface known as the T cell receptor. The T cell receptor binds to foreign proteins displayed on the surface of other cells. This interaction initiates a chain of events, including the opening of calcium channels embedded in the T cell membrane known as CRAC channels, which allows calcium ions to flow into the cell. These events ultimately lead to the activation of the T cell, enabling it to mount an immune response against the foreign invader. As part of the activation process, the T cell spreads over the surface of the cell that is displaying foreign proteins to form",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Notch signaling regulates cell fate selection during development in multiple organs including the lung. Previous studies on the role of Notch in the lung focused mostly on Notch pathway core components or receptor-specific functions. It is unclear, however, how Jagged or Delta-like ligands collectively or individually (Jag1, Jag2, Dll1, Dll4) influence differentiation of airway epithelial progenitors. Using mouse genetic models we show major differences in Jag and Dll in regulation and establishment of cell fate. Jag ligands had a major impact in balancing distinct cell populations in conducting airways, but had no role in the establishment of domains and cellular abundance in the neuroendocrine (NE) microenvironment. Surprisingly, Dll ligands were crucial in restricting cell fate and size of NE bodies and showed an overlapping role with Jag in differentiation of NE-associated secretory (club) cells. These mechanisms may potentially play a role in human conditions that result in aberrant NE differentiation, including NE hyperplasias and cancer. Notch signaling is a major regulator of progenitor cell fate and differentiation during organogenesis, repair-regeneration, and cancer. In mammals, four Notch receptors (Notch1–4) and five ligands (Delta-like: Dll1, Dll3 and Dll4 and Jagged: Jag1 and Jag2) have been described. All ligands, except Dll3, are Notch activating. Signaling is triggered by ligand-receptor binding through cell-cell interactions, which leads to sequential cleavage of the Notch receptor and binding of its intracellular domain (NICD) to a CSL/RBPJk-activator complex for activation of downstream target genes, such as HEY/HES-family members (Radtke and Raj, 2003; Bray, 2006). While different Notch receptors are known to act in a variety of biological processes, evidence from genetic studies suggest that the Notch effects are not necessarily dependent on the type of NICD but rather of NICD dosage (Liu et al. , 2015). Notably, specific Notch ligand-receptor binding in mammalian cells appears to be mostly non-selective or context-dependent. Interestingly, systemic deletion of Jag1, Jag2, or Dll4 has been shown to result in distinct phenotypes, suggesting that these ligands could mediate unique functions not entirely due to the receptor they activate (D' Souza et al. , 2009; Choi et al. , 2009). Indeed, Notch ligands were reported to activate distinct targets even through binding to the same Notch receptor and ligand-specific effects have been observed in multiple contexts (Nandagopal et al. , 2018). The Notch pathway","Cells communicate with each other by sending messages through a range of signaling pathways. One of the ways cells signal to each other is through a well-studied pathway known as Notch. In this pathway, cells display molecules on their surface, known as Notch ligands, that can activate Notch receptor proteins on the surface of neighboring cells. Once the Notch receptors bind to these ligands, they trigger various responses inside the cell. Notch ligands exist in two different families: Delta-like (Dll) ligands and Jagged (Jag) ligands. The layer of cells that lines the airways in the lungs consists of several different cell types. These include secretory cells that produce the fluid covering the airway surface, multiciliated cells, and neuroendocrine cells. Together these cells work as a barrier to protect",380,128,0.3368
pubmed-summarization,"et al . , 2015 ) . a growing number of familial and sporadic forms of neurodegenerative diseases show pathological inclusions caused by abnormal aggregation of rna - binding proteins ( rbps ) . the first rbps identified in these inclusions were tar dna binding protein of 43 kda ( tdp-43 ) and fused in sarcoma ( fus ) , associated with amyotrophic lateral sclerosis ( als ) and frontotemporal lobar degeneration ( ftld ) ( arai et al . , 2006 , neumann et al . , 2009 , neumann et al . , 2006 ) . since then additional rbps such as taf15 , ewsr1 , hnrnpa2b1 , hnrnpa1 , and hnrnpa3 all of the known rbps associated with dementia contain a low - complexity ( lc ) prion - like domain enriched in glycines and uncharged polar amino acids , and similar to the sequences driving yeast prion aggregation ( alberti et al . lc prion - like domains are also present in key rbps that mediate the assembly of rna granules by liquid - liquid phase separation ( lin et al . , 2015 , significantly , a small proportion of liquid droplets made by rbps transform into solid aggregates over time in vitro ( lin et al . , 2015 , , 2015 , murakami et al . , 2015 , patel et al . , 2015 ) . for clarity , we will use the term aggregation only when referring to the formation of non - dynamic rbp aggregates . an important question is whether the special assembly properties of rbps puts them at risk of aggregating during aging in a multicellular organism and not just in the context of disease . interestingly , several rbps with lc prion - like domains were identified in the insoluble proteome of aged animals ( david et al . , 2010 ) . overall , it is imperative to know the causes and consequences of wild - type rbp aggregation during aging in order to fully understand rbp aggregation in neurodegenerative diseases . furthermore , it is likely that the organism has evolved specific mechanisms to control liquid droplet protein aggregation . in the current study , we chose to focus on key rbps responsible for stress","summarylow - complexity prion - like domains in key rna - binding proteins ( rbps ) mediate the reversible assembly of rna granules . individual rbps harboring these domains have been linked to specific neurodegenerative diseases . although their aggregation in neurodegeneration has been extensively characterized , it remains unknown how the process of aging disturbs rbp dynamics . we show that a wide variety of rna granule components , including stress granule proteins , become highly insoluble with age in c. elegans and that reduced insulin / insulin - like growth factor 1 ( igf-1 ) daf-2 receptor signaling efficiently prevents their aggregation . importantly , stress - granule - related rbp aggregates are associated with reduced fitness . we show that heat shock transcription factor 1",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and experiments that had long been imagined, but were too complex, lengthy, or tedious to have been previously realized. But there are no comparable systems for handling of experimental organisms that are larger than ~1 mm or cannot be suspended in liquid. There are large-scale systems that handle adult flies in vials, in the form of ‘fly flipping’ robots. However, these take up a whole room, generally in a core facility, and cost hundreds of thousands of dollars to purchase and maintain, and are therefore inaccessible to most labs. And while there are many examples of high-throughput phenotypic assays in Drosophila (Branson et al. , 2009; Kabra et al. , 2013; Kain et al. , 2012; Buchanan et al. , 2015; Geissmann et al. , 2017), the systems that are not single-purpose still require human intervention to load and unload individual flies. Some researchers have used flies' natural tendency to climb up (negative gravitaxis) to isolate individuals for behavioral analysis (von Reyn et al. , 2014), imaging (Medici et al. , 2015), or microsurgery (Savall et al. , 2015). But dependence on this particular behavior fundamentally caps throughput, inadvertently selects for a subset of a population, and limits eligible genotypes. An alternative approach, actively conveying flies with airflow (MacMillan and Hughson, 2014) permits moving animals on demand, and opens the door for increased throughput. The dearth of instruments for automating Drosophila experiments is representative of the situation for many other lab organisms, such as yeast and C. elegans, where there is no standard platform for automated handling of the organisms themselves. Here, we present an automated platform that is high-throughput and flexible enough to assist in conducting diverse experimental protocols in Drosophila and other species. Due to its modular design, the system can automate diverse assays in a wide variety of organisms (including yeast, C. elegans, the slime mold Physarum polycephalum, and the bumblebee Bombus impatiens, an assortment chosen to demonstrate the platform’s versatility). For fruit flies, where we developed significant capabilities, this instrument can conduct numerous protocols, including loading of individual fruit flies for circadian rhythm (Pfeiffenberger et al. , 2010; Geissmann et al. , 2017) experiments, or aiding with lab chores like collecting virgin female flies for genetic crosses or passaging individual flies in controlled culture conditions for","Biological research can, at times, be mind-numbingly tedious: scientists often have to do the same experiment over and over on many different samples. When working with animals such as fruit flies, this means researchers have to physically handle large numbers of specimens, selecting certain individuals or moving them from one container to another to perform the study. This represents a serious bottleneck that slows down discovery. Automation represents an obvious solution to this issue. In fact, it has already revolutionized fields like molecular biology, where robots can handle the liquids required for the experiments. Yet, it is not so easy to automate tasks that involve animals larger than a millimeter. To fill that gap, Alisch et al. have developed a robotic system called Modular Automated Platform for Large-scale",380,128,0.3368
pubmed-summarization,". 2004 ) and intestinal ( kaneko et al . 1975 , sing et al . however , the urogenital form is rarely seen and all of reported cases are restricted to females . so the study of men clinical manifestation as well as morphology of third instars larvae of these flies seems to be important . the aim of this paper is to report a case of man urogenital myiasis involving and to discourse the importance of its diagnosis and management in clinical science . an 18 year - old man living in zanjan city , northwest of iran , presented to ayatollah mosavi hospital at zanjan university of medical sciences with history of difficulty in urination and maggot discharging . , he was medicated by venlafazine , alpirazolam and nortriptrin . physical examination and sonography of cortex of bladder and kidneys he received mebendazole ( 2 mg tablet ) orally and washed his urogenital area with solution of xylocain ( 2% ) and iodine ( 1% ) . the urine was yellow in color and laboratory examination showed microhematuria , proteinuria and leukocyturia . the larvae were forwarded to the department of medical entomology and vector control for further studies . sonography of cortex of bladder with , small echogenous floating particles microscopic examination showed that all larvae were alive , whitish in color and pale intestinal content in the third terminal part ( . one larva was preserved in 70 % ethylic alcohol and the other cultured in nutrient rich medium to complete its life cycle but it died after 1 day . the length and width of larvae ranged from 6.8 to 6.9 and 0.68 to 0.69 mm respectively ( . precision microscopic examination of larvae revealed the presence of short spinous ( peglike ) processes on the integument . the larval head was noncapsulate , being reduced to mouth hooks and supporting cephalopharyngeal skeleton which was developed and supported large areas of the head ( . the anterior spiracles were located on each latero - posterior edge of the prothorax each had about 810 rays . a pair of posterior spiracles protruded dorsally on the 12 segment each appears with large and slender plate . in addition to their anterior and posterior union the dorsal","myiasis is the infestation of organs and tissues of human and animals with fly larvae . this article reports an 18 year - old man with urogenital myiasis , the passing of live megaselia scalaris larvae in the urine , from zanjan city , northwest of iran . we discourse the importance of diagnosis and management of urogenital myiasis in medicine .",380,62,0.1632
scientific_lay_summarisation-elife-norm,"specifically how individual species are affected by host genetics is less well understood. Because there is substantial diversity in disease location, symptoms and genetic susceptibility in IBD, understanding how specific microbial alterations occur will be important for identifying disease subtypes as well as developing precision medicine treatment options. Genetic diversity among patients is a compounding factor with respect to disease phenotype, suggesting that specific risk loci may play a role in underlying microbial community makeup. Genome-wide association studies have linked over 230 genetic risk loci to increased IBD risk (Jostins et al. , 2012; Liu et al. , 2015; de Lange et al. , 2017; Luo et al. , 2017). The microbiota and disease severity have also been linked to genetic risk (Moustafa et al. , 2018). Genetics can affect the composition of the human gut microbiome (Hall et al. , 2017b). Additionally, IBD is associated with a variety of risk alleles that affect immune activation in response to microbial recognition and handling (Davies and Abreu, 2015). Many studies have linked IBD to genetic risk variants in NOD2 (Turpin et al. , 2018), which is involved in recognition of bacterial muramyl dipeptide, but one study has linked the presence of multiple NOD2 variants to increased levels of Enterobacteriaceae (Knights et al. , 2014). A single nucleotide polymorphism (SNP) in ATG16L1 (re2241880, Thr300Ala) is associated with an increased risk of CD (Hampe et al. , 2007; Rioux et al. , 2007). ATG16L1 functions in autophagy, a cellular recycling system that aids in the sequestration of intracellular bacteria (Cooney et al. , 2010; Travassos et al. , 2010). ATG16L1 hypomorphic mice have defects in anti-microbial peptide secretion by Paneth cells (Cadwell et al. , 2008) and ATG16L1-deficient macrophages show increased secretion of pro-inflammatory cytokines (Saitoh et al. , 2008). Conditional deletion of ATG16L1 specifically in epithelial cells reduces autophagy and renders mice more susceptible to Salmonella enterica serovar Typhimurium infection and systemic translocation (Conway et al. , 2013). The Thr300Ala (T300A) variant displays enhanced degradation via active caspase 3 resulting in a reduction in the levels of ATG16L1 protein and reduced levels of autophagic flux (Murthy et al. , 2014; Lassen et al. , 2014). Moreover, microbial signatures are associated with variants in the gene for NOD2 (Xavier and Podolsky, 2007), which","Trillions of bacteria live inside the human gut. From helping to digest our food to producing vitamins, these bacteria can have a big impact on our health, yet some people tolerate these bacteria better than others. In some cases, the body reacts badly to its own bacteria, stimulating an over-exuberant immune response. The gut becomes too inflamed, causing pain and diarrhoea, which could lead to an inflammatory bowel disease such as Crohn’s disease or ulcerative colitis. The symptoms of inflammatory bowel disease can vary from person to person, and how someone responds to treatment can be as individual as the symptoms as well. The causes of inflammatory bowel disease are complex; our genes, immune system and gut bacteria all play a role. Previous research has found hundreds of",380,128,0.3368
dialogsum,"#Person1#: That was a beautiful car. It's a new car, but it's totaled. #Person2#: Well, your insurance covers sufficient money to replace it. So you don't need to worry. #Person1#: I don't think I could afford that kind of car again. I think I'll have to choose something that is not as hard to replace. #Person2#: Since you are not the one who caused the accident, your insurance cost should be the same. #Person1#: What will happen if I chose a smaller car? Would the payments be the same? #Person2#: If you got a smaller car, the cost should be a little less depending on the model, age, and size. Would you still want full coverage? #Person1#: Yes.",#Person1# discusses with #Person2# about the insurance of #Person1#'s damaged car and finally decides on full coverage.,118,17,0.1441
dialogsum,"#Person1#: I'm calling to tell you that the merchandise ordered last month has not arrived yet. #Person2#: I'm sorry, hold on a moment. I'll check it out. But we have already shipped it to you last month. Would you like us to contact the express company to know what's going on? #Person1#: Please find out the reason as soon as possible. We are in bad need of it. #Person2#: Ok, I am terribly sorry for the trouble you are getting into.We will contact you first thing, once we know the reason.","#Person1# calls #Person2# that the merchandise has not arrived, so #Person2# is going to contact the express company.",91,18,0.1978
scientific_lay_summarisation-elife-norm,"in some instances with the development of lethal complications such as chemoresistant progression or transformation into an aggressive lymphoma (Richter syndrome) (Pasqualucci et al. , 2011; Zenz et al. , 2012; Fabbri et al. , 2013). No systematic approach has been followed to disentangle and characterize the ensemble of evolutionary histories of this disease. For this purpose, we envision a dual cross-sectional and longitudinal strategy by collecting genomic information from the most common alterations in a cohort of 70 CLL patients spanning over a period of 12 years (2001–2012). To recapitulate and compare the history of genetic alterations in many patients, we propose a framework to infer TEDG by integrating longitudinal and cross-sectional genomic data of cancer patients. First, we reconstruct the sequential network of genetic alterations in each patient by analyzing genomic data from different time points. Specifically, the techniques of high-depth next generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are separately carried out to assess the mutation allele frequency (MAF) and copy number abnormalities (CNA) of selected driver genes. To unify both types of data, and to adjust the MAF of mutations in genes with CNA, we introduce mutation cell frequency (MCF, defined as the fraction of tumor cells with a particular alteration) for quantification of genetic lesions (‘Materials and methods’, — 1). Based on MCF, we investigate alterations represented in at least 5% of leukemic cells (see examples of CLL patients in — 2). First, if a given genetic lesion is observed to be temporally earlier than another lesion, we connect them with a directed edge to represent their sequential order of development (1A). Second, we pool many sequential networks from different patients to construct an Integrated Sequential Network (ISN). Third, we infer TEDG from ISN by removing indirect associations with spectral techniques and minimal spanning tree algorithm. TEDG is the backbone of ISN, representing an optimal explanation of the mutation order across many patients (1B). 10. 7554/eLife. 02869. 003Figure 1. Tumor Evolutionary Directed Graph (TEDG) framework. (A) A toy example of clonal evolution of one patient. The evolutionary history of four alterations A, B, C, and D is shown in the left panel. We then sample different time points and analyze genomic data. Specifically, for each patient, tagged-amplicon library next generation sequencing (NGS) and","A historical event is often the culmination of the preceding circumstances. The same can be said of cancer as a disease. Cancer results from genetic mutations that disrupt the normal biological processes within a cell, removing the fail-safes that prevent it from growing and reproducing uncontrollably. Cancer is not caused by just one mutation, and once one gene is malfunctioning, other genes become much more likely to mutate. Although modern sequencing methods have revealed many of the genes that mutate in several different kinds of cancer, uncovering when each of these mutations occurs has been more difficult. Knowing when each mutation occurs could make it easier to predict how the cancer will progress and could also help target cancer treatments more effectively. Wang, Khiabanian, Rossi et al. have",380,128,0.3368
dialogsum,"#Person1#: Look at this headline, Soo Mi. #Person2#: Wow! So many people in the United States get divorced! #Person1#: Is it the same in Korea? #Person2#: I don't think so. In Korea some marriages break up, but most couples stay together. #Person1#: Do people get married young? #Person2#: Not really. Very few people get married before the age of 20. #Person1#: Hmm. Do women usually work after they get married? #Person2#: No, a lot of women stay home and take care of their families. But some work.",#Person1# and #Person2# are talking about marriage and divorce in the United States and Korea.,87,15,0.1724
pubmed-summarization,"lower increases in forced expiratory volume in 1 second ( fev1 ) , compared to trials of the same investigational drug performed 5 or 10 years earlier . this may be due to evolution in trial designs , where , for example , later trials are more likely to permit concomitant treatment with other bronchodilators as part of usual care.7 additionally , there is evidence that the effect of bronchodilators varies depending on the severity of the patient s copd . patients with very severe copd show lower improvement of fev1 when treated with bronchodilators , compared with patients with moderate or severe copd.8,9 the laba olodaterol has been developed as a once - daily long - acting bronchodilator for maintenance treatment of copd . phase iii clinical trials of olodaterol have been completed , and the product , at the 5 mcg per day dose , has been approved in a number of european countries and canada , and is currently under regulatory review in the united states by the food and drug administration ( fda)10 and other regulatory agencies . to date , indacaterol is the only other once - daily laba approved and made available in many countries worldwide . indacaterol has been licensed in the united states and canada at a dose of 75 mcg per day.11,12 in most other countries , two doses are licensed : 150 mcg per day and 300 mcg per day for those patients for whom 150 mcg is not sufficient.13 in the absence of head - to - head , randomized controlled clinical trials ( rcts ) conducted on labas , the primary objective of this systematic literature review and meta - analysis was to provide estimates of relative efficacy of two new once - daily labas , olodaterol and indacaterol . a network meta - analysis was performed to indirectly compare the two treatments , linked through common treatment comparators . the review made two specific treatment comparisons : olodaterol 5 mcg compared with indacaterol 150 mcg , and olodaterol 5 mcg compared with indacaterol 75 mcg . a comprehensive and systematic literature review to identify rcts studying olodaterol and indacaterol in copd was undertaken to establish the evidence base for use in the meta - analyses . a","purposein the absence of head - to - head clinical trials comparing the once - daily , long - acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease ( copd ) , an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted.methodsa systematic literature review of randomized , controlled clinical trials in patients with copd was performed to evaluate the efficacy and safety of olodaterol and indacaterol . network meta - analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy , using outcomes based on trough forced expiratory volume in 1 second ( fev1 ) , transition dyspnea index , st george s respiratory questionnaire total score and response , rescue medication use , and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The cerebral cortex contains multiple areas with distinctive cytoarchitectonic patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modeling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas. The mammalian cerebral cortex contains a wide diversity of neuronal types heterogeneously distributed across layers and regions. The most abundant class of neurons in the cerebral cortex are excitatory projection neurons, also known as pyramidal cells (PCs). In the neocortex, PCs can be further classified into several subclasses with unique laminar distributions, projection patterns and electrophysiological properties (Greig et al. , 2013; Jabaudon, 2017; Lodato and Arlotta, 2015), and currently available data suggest that several dozen distinct transcriptional signatures can be distinguished among them (Tasic et al. , 2018). The relative abundance of the different types of PCs largely determines the distinct cytoarchitectonical patterns observed across different regions of the mammalian neocortex (Brodmann and Gary, 2006). The diversity of excitatory neurons emerges from progenitor cells in the ventricular zone (VZ) of the developing neocortex known as radial glial cells (RGCs) (Malatesta et al. , 2000; Miyata et al. , 2001; Noctor et al. , 2001). RGCs divide symmetrically to expand the progenitor pool during early stages of corticogenesis. Subsequently, they undergo asymmetric cell divisions to generate clones of PCs directly or indirectly via intermediate progenitor cells (IPCs) (Lui et al. , 2011; Taverna et al. , 2014). The characteristic vertical organization of migrating PCs in the developing neocortex led to the ‘radial unit hypothesis’, which postulates that PCs in a given radial column are clonally related (Rakic, 1988). However, the precise mechanisms through which RGCs generate diverse cytoarchitectonic patterns throughout the neocortex remain to be elucidated. The most commonly","Recognizable by its deep outer folds in humans, the cerebral cortex is a region of the mammalian brain which handles complex processes such as conscious perception or decision-making. It is organized in several layers that contain different types of ‘excitatory’ neurons which can activate other cells. The various areas of the cortex have different characteristics as they contain various proportions of each kind of neurons. Stem cells are cells capable to divide and create various types of specialized cells. The excitatory neurons in the cortex are created during development by stem cells known as radial glial cells. These cells divide several times, giving rise to different types of neurons in sucessive divisions, presumably thanks to internal molecular clocks. In the cortex, it is generally assumed that an individual",380,128,0.3368
dialogsum,"#Person1#: Hey Annie, who is this picture of? #Person2#: Oh, that's my great, great, great, great, great, great, great grandfather. #Person1#: I think you can say your seventh great grandfather! Cutie! What's his name? #Person2#: Peter Madsen. A great A if I do say so myself. #Person1#: Nice pun. What is it you active about him most? #Person2#: He loved his family and his countrymen and his freedom. #Person1#: He looks like a very personable man. #Person2#: He was. He was friendly toward and showed concern for everyone he met.",Annie tells #Person1# about the picture of Annie's seventh great grandfather who was a very personable man.,90,17,0.1889
dialogsum,"#Person1#: What characteristics should an interpreter own? #Person2#: I think he should be an expert of everything. #Person1#: Why is that? #Person2#: Because English is nothing but a tool which is used when people may negotiate in international conferences, probe into physics, release some information in a press conferrence , and do anything we can do with language. Therefore, an interpreter has to know some expertise in the field he/she serves as an interpreter. Otherwise he/she can not carry out his/her work smoothly.",#Person2# thinks an interpreter should be an expert of everything and explains #Person2#'s reasons.,83,14,0.1687
pubmed-summarization,"agriculture has been one of the primary economic avenues in the philippines contributing to about 20% to the gross domestic product ( gdp ) . crops comprise about 47.56% of the total agricultural sector and have contributed to about 510 billion pesos ( p510b ) to the country 's national income . benguet is a province in the northern portion of the philippines belonging to the cordillera administrative region . there are about 27.5 thousand farms covering 30 thousand hectares of agricultural land in benguet . it is also the largest producer of vegetables and fruits , supplying the capital cities in the philippines . the province is known as the salad bowl of the philippines as its major crops are tubers , roots , bulbs , leafy vegetables , stems , and flowers . in 2005 , benguet was the top producer of brocolli and carrots producing about 1.2 thousand and 13.7 metric tons contributing to 87.4% and 81.4% , respectively , to the national output . however , growing vegetables is considered a risk occupation in some areas in developing countries . soogarun et al . in 2003 found significantly low / abnormal mean blood cholinesterase levels among vegetable growers in thailand . health impacts of pesticide misuse on the other hand greatly affect the farming communities in the philippines questioning the economic advantages of its use . many researchers have correlated the extent of direct and indirect pesticide exposure and health hazards such as increased mortality , dermal contamination , depression in cholinesterase level , fetal abnormalities , and spontaneous abortion among pregnant women . it is a discouraging fact though , that with knowledge of health risks , many filipino families still perceive that crop yield outweighs the health risks associated with pesticide use . pesticide poisoning is one of the most prevalent health problems in the philippines . in a study by the department of health ( doh ) from 19911995 , organophosphates accounted for the highest number of poisoning cases while organochlorines caused the most number of deaths . cheng in 1994 studied 2000 benguet vegetable farmers and found that the most common complaints were allergic reactions both in the skin and the eyes , abdominal pain , dizziness , chest pain , headache","this was a cross - sectional study that investigated pesticide exposure and its risk factors targeting vegetable farmers selected through cluster sampling . the sampling size calculated with p = .05 was 211 vegetable farmers and 37 farms . the mean usage of pesticide was 21.35 liters . risk factors included damaged backpack sprayer ( 34.7% ) , spills on hands ( 31.8% ) , and spraying against the wind ( 58% ) . the top 3 pesticides used were pyrethroid ( 46.4% ) , organophosphates ( 24.2% ) , and carbamates ( 21.3% ) . those who were exposed to fungicides and insecticides also had higher total pesticide exposure . furthermore , a farmer who was a pesticide applicator , mixer , loader , and who had",380,128,0.3368
dialogsum,"#Person1#: Good evening, Madam. Could you do me a favor? #Person2#: Of course. What can I do for you? #Person1#: I am looking for a hotel. Are there any hotels near here? #Person2#: Yes, there are some in this street. The nearest one is next to the bank. It's quite modern. #Person1#: You see. I'm leaving tomorrow morning. Do you think there're any hotels not too expensive? #Person2#: Yes. Drive on for five minutes and you'll find a yellow building on your left. It's a family-style hotel, very comfortable, and the price is quite reasonable. #Person1#: It sounds nice. Thank you very much for your help. #Person2#: You are welcome.",#Person1# wants to find a cheap hotel near here. #Person2# tells #Person1# to drive on for five minutes and the yellow building is a family-style hotel.,110,26,0.2364
pubmed-summarization,"renal cell carcinoma ( rcc ) may metastasize to any site of the body , but clinically evident metastatic intestinal involvement by rcc is extremely rare . to our knowledge , simultaneous duodenal and colonic metastases have not been reported in the english literature . we report a case of pathologically proven simultaneous duodenal and ascending colonic metastases about four years after a left nephrectomy for rcc . a 76-year - old female patient who had undergone a left radical nephrectomy 4 years previously for rcc ( mixed clear and granular cell type , tnm stage iii ) presented with a 1-month history of dyspepsia , lethargy and pain in the right upper abdomen . her blood pressure was 110/70 mmhg , pulse rate 80/min , respiration rate 22/min and body temperature 36.8c . abdominal examination revealed slight tenderness but normal peristalsis ; however , a movable mass was palpated in the right upper abdomen . the hematocrit was 28.1% and the white cell count was 9700/mm with 77% polymorphonuclear cells and 14% lymphocytes . serum sodium was 134 meq / l , potassium 3.5 meq / l , chloride 101 meq / l and calcium 9.5 mg / l . the result of liver function tests were as follows : total protein 6.5 g / dl , albumin 3.5 g / dl , cholesterol 165 mg / l , bilirubin 0.6 mg / dl , alkaline phosphatase 105 iu / l , ast 28 iu / l and alt 21 iu / l . tumor marker levels , such as carcinoembryonic antigen ( cea ) , carbohydrate antigen 19 - 9 ( ca19 - 9 ) and -fetoprotein ( afp ) , were within normal limits . an abdominopelvic ct scan showed circumferential wall thickening with high enhancement at the second portion of the duodenum and additional enhancement of an irregular protruding mass into the lumen of the ascending colon with multiple lymphadenopathy in the aortocaval area ( ) . a gastroscopy showed a large , irregular multi - lobed , partially necrotic and ulcerative protruding mass nearly obstructing the second portion of the duodenum . a colonoscopy revealed a polypoid , nodular mass in the ascending colon , which was purplish in color , had sharp margins and","we report a case of pathologically proven simultaneous duodenal and colonic metastases about four years after nephrectomy for mixed clear and granular cell type renal cell carcinoma ( rcc ) . a 76-year - old female patient who had undergone a left radical nephrectomy 4 years previously for rcc presented with a 1-month history of dyspepsia and pain in the right upper abdomen . an abdominopelvic ct scan showed circumferential wall thickening with high enhancement at the second portion of the duodenum and additional enhancement of an irregular protruding mass into the lumen of the ascending colon . a gastroscopy showed a large and ulcerative protruding mass nearly obstructing the second portion of the duodenum . a colonoscopy revealed a polypoid , nodular and purplish mass in the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Animals mimicking other organisms or using camouflage to deceive predators are vital survival strategies. Modern and fossil insects can simulate diverse objects. Lichens are an ancient symbiosis between a fungus and an alga or a cyanobacterium that sometimes have a plant-like appearance and occasionally are mimicked by modern animals. Nevertheless, lichen models are almost absent in fossil record of mimicry. Here, we provide the earliest fossil evidence of a mimetic relationship between the moth lacewing mimic Lichenipolystoechotes gen. nov. and its co-occurring fossil lichen model Daohugouthallus ciliiferus. We corroborate the lichen affinity of D. ciliiferus and document this mimetic relationship by providing structural similarities and detailed measurements of the mimic’s wing and correspondingly the model’s thallus. Our discovery of lichen mimesis predates modern lichen-insect associations by 165 million years, indicating that during the mid-Mesozoic, the lichen-insect mimesis system was well established and provided lacewings with highly honed survival strategies. Modern insects have dramatic morphological specializations that match various objects of the environment. For instance, the specializations occurring in katydids and butterflies that mimic leaves, stick insects and inchworms that resemble twigs, and orchid mantids that duplicate orchid flowers, provide ecological insights for understanding mimetic associations between insect mimics and their plant models (Stevens, 2011; Gullan and Cranston, 2014; Maran, 2017). These and other fascinating cases reveal that mimesis or camouflage is highly effective when cryptic insects resemble closely the appropriate self-similar background, indicating the complexity of ecological relationships between insect mimics and their imitating models. When and how insects first evolved such an ingenious survival strategy is unclear. A Permian katydid exhibiting a mimicking pattern of wings similar to the modern relatives was considered the oldest case of insect mimicry (Garrouste et al. , 2016). However, evidence for a contemporaneous mimetic relationship in this Permian deposit was scarce, and there was no quantitative or other useful data to track the mimetic interactions among the insect, model and predator. More recent cases of insect mimicry have been recorded from the Mesozoic, indicating the existence of several such effective survival strategies. As in morphological specializations involving masterly deceit found in modern insects, several Mesozoic insect taxa developed remarkable structural adaptations resulting in highly accurate resemblances to co-existing models (Wang et al. , 2012; Wang et al. , 2014; Yang et al. ,","Many insects mimic other organisms or use camouflage to hide from predators. For example, some modern animals mimic the organism lichens, which are formed from algae and fungus, and grow almost everywhere on Earth, from the Arctic to the desert. The most iconic example of an insect mimicking a species of lichen is the peppered moth. During the industrial revolution, darker colored moths were better at surviving. But when the revolution ended and pollution levels declined, species of lichen began to re-emerge and increase the survival of paler moths. Yet, it is unclear how and when insects first evolved this ingenious survival strategy, as distinctive examples of insects mimicking lichens are missing from fossil records. To answer this question, Fang et al. set out to find fossils of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the efficiency of the basic enzyme reaction are open questions. (Kappler, 2011; Kappler, 2008) Here, we have investigated an electron transfer complex involving the periplasmic SorT sulfite dehydrogenase from the α-Proteobacterium Sinorhizobium meliloti, which represents a structurally uncharacterized type of SOE, and its electron acceptor, the c-type cytochrome SorU (Low et al. , 2011; Wilson and Kappler, 2009). In S. meliloti the SorT sulfite dehydrogenase is part of a sulfite detoxification system that is induced in response to the degradation of sulfur containing substrates such as the organosulfonate taurine (Wilson and Kappler, 2009). Electrons derived from sulfite oxidation are passed on to the SorU cytochrome, and likely then to cytochrome oxidase, as S. meliloti is capable of sulfite respiration (Low et al. , 2011). Here, we report the crystal structures of both the isolated SorT and SorU proteins and the biochemical and structural analyses of the SorT/SorU electron transfer complex. This is the first time that a crystal structure of a molybdenum enzyme in complex with its external electron acceptor has been solved. Sulfite-oxidizing enzymes, particularly those from bacteria, are known to be highly efficient catalysts (Kappler, 2011; Kappler and Enemark, 2015). Previous work has established that SorT is able to transfer electrons to the SorU cytochrome that is encoded on the same operon; however, no kinetic details of the interaction were reported (Low et al. , 2011). With the artificial electron acceptor ferricyanide, SorT was shown to have a turnover number of 338 ± 3 s-1 (Low et al. , 2011; Wilson and Kappler, 2009). Employing SorU as the substrate, we analyzed the kinetics of the interaction between SorT and SorU and found the interaction to be fast and highly specific, with a KM (SorU) of 32 ± 5 μM and a kcat of 140 ± 11 s-1, confirming that SorU is the natural electron acceptor of SorT. Measurement of the thermodynamics of the SorT/SorU interaction by isothermal titration calorimetry (ITC) revealed a dissociation constant of Kd = 13. 5 ± 0. 8 μM with a determined stoichiometry of 0. 8 ± 0. 2. These values are in the range observed for other electron transfer complexes (Dell' acqua et al. , 2008; Pettigrew et al. , 2003) and match a model where SorT sequentially transfers two electrons, derived from","A key feature of many important chemical reactions in cells is the transfer of particles called electrons from one molecule to another. The sulfite oxidizing enzymes (or SOEs) are a group of enzymes that are found in many organisms. These enzymes convert sulfite, which is a very reactive compound that can damage cells, into another compound called sulfate. As part of this process the SOE transfers electrons from sulfite to other molecules, such as oxygen or a protein called cytochrome c. In the past, researchers have described the three-dimensional structure of three SOEs using a technique called X-ray crystallography. However, it has been difficult to study how SOEs pass electrons to other molecules because of the temporary nature of the interactions. McGrath et al. studied an SOE called",380,128,0.3368
dialogsum,"#Person1#: Where do you see yourself three years from now? #Person2#: Working for your company, as the top administrative assistant in your firm! #Person1#: Good answer, B - good answer! Seriously, though, are you interested in staying in a staff-level position, or would you hope to move into management someday? #Person2#: Well, I haven't thought much about this. I think it's too early to tell. What is most important for me now is to do the best possible job for the company and learn and develop my skills as much as possible.",#Person2# tells #Person1# about #Person2#'s thoughts about #Person2#'s prospects in #Person1#'s firm.,92,12,0.1304
pubmed-summarization,"synthesis was especially noteworthy because cycloparaphenylenes form the fundamental annular segments of armchair carbon nanotubes and may serve as templates toward the rational synthesis of carbon nanotubes with specific chiralities . [ n]-cycloparaphenylenes with n = 9 , 12 , and 18 . each cycloparaphenylene is composed solely of phenyl rings sequentially connected in the para position to form a single nanoring . a peculiar feature of these cycloparaphenylenes is their unusual optoelectronic properties as a function of molecular size . specifically , as the carbon nanoring size is increased , the lowest computed absorption energy becomes larger . this result is surprising and counterintuitive to our usual expectations ! for example , our chemical intuition from organic chemistry tells us that , as the number of repeat units in a macromolecule increases , the distance between molecular energy levels diminishes , effectively decreasing the optical absorption gap . this trend ( which actually arises from quantum confinement effects ) qualitatively describes the variation of absorbance properties in -conjugated systems as the number of monomer units increase in a polymer . however , in the case of cyclic nanorings , the excitation energies as a function of size seem to contradict this quantum - confinement - effect argument . to rationalize these trends , with a view of understanding the nature of electronic excitations in these nanorings , i carried out ab initio calculations on both cyclic and linear paraphenylenes ( ) composed of 5 to 18 phenyl repeat units each . results obtained from time - dependent density functional theory ( tddft ) give electronic band gaps , optical absorption energies , and oscillator strengths that can be used to estimate exciton binding energies as a function of paraphenylene size . the tddft calculations also provide a two - dimensional real - space analysis of transition densities that represent coherent electronic transitions between ground and electronically excited states . these transition densities give a panoramic view of electronhole coherence and exciton delocalization in each of the paraphenylene systems . on the basis of overall trends in exciton binding energies and their spatial delocalization , i find that excitonic effects play a significant role in understanding the unique photoinduced dynamics of cycloparaphenylene nanoring systems . molecular structures and atom labels","the electronic structure and size - scaling of optoelectronic properties in cycloparaphenylene carbon nanorings are investigated using time - dependent density functional theory ( tddft ) . the tddft calculations on these molecular nanostructures indicate that the lowest excitation energy surprisingly becomes larger as the carbon nanoring size is increased , in contradiction with typical quantum confinement effects . in order to understand their unusual electronic properties , i performed an extensive investigation of excitonic effects by analyzing electron - hole transition density matrices and exciton binding energies as a function of size in these nanoring systems . the transition density matrices allow a global view of electronic coherence during an electronic excitation , and the exciton binding energies give a quantitative measure of electron - hole interaction",380,128,0.3368
pubmed-summarization,"lactic acid bacteria ( lab ) , in particular several strains of lactobacillus brevis ( mills et al . , 2009 ) , lactobacillus plantarum , lactobacillus delbrueckii subsp . lactis ( siragusa et al . , 2007 ; mills et al . , 2009 ; wang et al . , 2010 ) . the enterococcus spp . and streptococcus spp . also include strains that have shown gad activity ( hayakawa et al . , 1997 ) . other research has shown that these species of bacteria are also involved in the production of ba ( galgano et al . , 2001 ; linares et al . , 2012 ; lorencov et al . , 2012 ) , considered as a serious health problem when present at significant levels ( stratton et al . , 1991 ) . tyramine , -phenylethylamine , histamine , tryptamine , cadaverine , putrescine , spermine and spermidine are considered as the most important amines occurring in cheese . in cheese , ba are considered as an indicator of poor hygienic conditions of raw material and/or manufacturing practices since their production and accumulation is often associated with the activity of contaminant bacteria ( loizzo et al . , 2013 ) . in general , artisanal sheep cheeses are rich in gaba ( siragusa et al . , 2007 ) but also in ba ( loizzo et al . , 2013 ; in fact , microbial decarboxylase activity requires the availability of free amino acid precursors , produced as an outcome of proteolysis , and favourable ph and temperature conditions that can be achieved during ripening ( siragusa et al . some research has reported that gaba is also present in pecorino sardo ( siragusa et al . , 2007 ) , as are ba ( manca et al . , 2000 ) , even if these studies were limited to a very few samples . for these reasons this study has concerned the simultaneous determination of gaba and ba in pecorino sardo produced in cheese factories , pecorino produced in farmhouses , and casu marzu , made from insect larvae ( piophila casei ) , in order to assess the variability of these nitrogenous compounds important to define cheese quality , in products obtained","the bioactive compounds -aminobutyric acid ( gaba ) and biogenic amines ( ba ) , together with protein - free amino acids , were measured by high - performance liquid chromatography in ewe s milk cheeses produced in sardinia with different technological traits . the study included three types of cheese : pecorino sardo pdo , pecorino and casu marzu . farmhouse casu marzu and pecorino showed gaba content ( maximum levels : 1001.3 and 378.1 mg 100 g1 respectively ) that had never been found so high in cheese before , suggesting that these types of cheese present ideal conditions to produce gaba . these two types of cheese also showed high levels of ba ( their total maximum levels were 1035.7 and 288.0 mg 100 g1",380,128,0.3368
dialogsum,"#Person1#: How do you like your new room, Jane? #Person2#: It's not big; the rent is high. And I'm far away from work. But I enjoy myself very much. #Person1#: Why? #Person2#: I am able to get rid of that annoying roommate at last.",Jane's happy that she leaves the annoying roommate.,44,8,0.1818
dialogsum,"#Person1#: Andrei, hello, it's Laura. I'm at Kuala Lumpur Airport. #Person2#: Welcome to Malaysia. I sent my driver to pick you up, is he there? #Person1#: No, he isn't. #Person2#: I'm sorry about that. There's been a mix-up. #Person1#: You got my email about the change in the arrival time, didn't you? #Person2#: Yes, and I asked my workmate to tell my driver. But my driver got the wrong information and went to the airport this morning. #Person1#: Oh, no. #Person2#: When you didn't arrive, he came back. I told him to go out to the airport again. Maybe he's on his way now. #Person1#: OK, I'll wait for him. #Person2#: Right, shall we have dinner together this evening? I'll meet you at your hotel at about 8 o'clock if that's OK. #Person1#: That sounds good. But I am rather tired after a long flight, so I want to have a sleep first. #Person2#: OK. See you later.","Laura calls Andrei because she arrives at Kuala Lumpur Airport. Andrei invites her to have dinner together this evening, and Laura wants to have a sleep first.",158,27,0.1709
pubmed-summarization,"melamine ( 2,4,6-triamino-1,3,5-triazine , cas # 108 - 78 - 1 ) was first prepared and described by liebig in 1834 ( 1 ) and has since become an increasingly important chemical commodity . most of the melamine production is used in the fabrication of melamineformaldehyde resins ( 2 ) . the first analytical methods related to food were therefore developed to detect melamine migration from resins used in food contact materials ( 3 ) . recently , melamine has become infamous as being one of the most effective adulterants used to increase the nitrogen content in foods and feeds . melamine contains about 66.6% nitrogen , and the addition of 1% melamine to protein leads to a false increase in the kjeldahl protein content by 4.16% ( 6 ) . the first cases of melamine adulteration were detected in fish meals from italy in the late 1970s ( 7,8 ) , and methods to detect melamine in potato proteins were developed in switzerland in the 1980s ( 6 ) . since then , melamine adulteration cases have not been reported in the literature until 2004 and 2007 , when melamine was found in pet foods , causing renal failure in dogs and cats ( 9,10 ) . nephrotoxicity also appears to be the major toxic effect in humans ( 11,12 ) . with the intentional adulteration of human foods , including baby foods , with melamine , the economically motivated fraud in the food chain has reached a new dimension , for which food control systems were unprepared . the problem first became evident in china as an increase in urinary tract stone formation in infants beginning in the spring of 2008 ( 13 ) . more than 294,000 children have reportedly been affected by adulterated formula , with over 50,000 hospitalized , and at least 6 deaths ( 14 ) . twenty - two dairy companies were implicated in the melamine fraud , with the sanlu company being identified as the one that had most seriously violated the law ( 13 ) . apparently , the adulterations occurred at the raw milk collection stations , for which no systematic state surveillance had been implemented ( 13 ) . the adulterators ostensibly used relatively sophisticated techniques such as special","the recent melamine crisis in china has pointed out a serious deficiency in current food control systems , namely , they specifically focus on selected known compounds . this targeted approach allowed the presence of melamine in milk products to be overlooked for a considerable time . to avoid such crises in the future , we propose that nontargeted screening methods need to be developed and applied . to this end , nmr has an extraordinary potential that just started to be recognized and exploited . our research shows that , from the very same set of spectra , 1h nmr at 400 mhz can distinguish between melamine - contaminated and melamine - free infant formulas and can provide quantitative information by integration of individual lines after identification",380,128,0.3368
dialogsum,"#Person1#: Steven, shall we go shopping tomorrow? #Person2#: Hum... Why not go shopping the day after tomorrow? Tomorrow is Saturday. I hate all the hustle and bustle of Saturday shopping. #Person1#: But Sunday is the same with Saturday. If you don ' t mind, that's OK. #Person2#: Hum. Maybe it will be better. The most important thing is that I can have a day to relax after a week's work. #Person1#: I see. We will go the day after tomorrow. #Person2#: By the way, what kind of stores do we need to go? #Person1#: I want to buy some clothes in clothing store. When we are going back, go to the butcher's shop and buy some chicken. #Person2#: Let ' s also go to the jewelry store to buy a crystal necklace. I want to buy one for you as your birthday present. #Person1#: Thank you, darling.","#Person2# proposes going shopping tomorrow. Steven prefers the day after tomorrow because he wants a day to relax. #Person2# agrees. They decide to go to the clothing store, the butcher's shop, and the jewelry store.",147,35,0.2381
dialogsum,"#Person1#: Most of our customers are foreigners. How many foreign languages can you speak, Elizabeth? #Person2#: Two, French and Spanish. #Person1#: And how well can you speak them? #Person2#: Well, French was my best subject at school. I can read and write it pretty well. #Person1#: And how about your Spanish? #Person2#: It's not as good as my French. I can speak it well. But my written Spanish isn't good. #Person1#: I see, well, we have a lot of Spanish customers. But you don't need to write any Spanish here. #Person2#: In that case, I'm fit for the position I think.",#Person1# has many Spanish customers. Elizabeth thinks she's fit for the position because she can speak French and Spanish well.,101,20,0.198
dialogsum,"#Person1#: What did the boss say? #Person2#: He asked me if I'd like to be a newspaper salesperson? #Person1#: You are still student so I don't think you should have time for that. #Person2#: Don't worry about that. He said I can do that at spare time. Anyway, it's just a part-time job. #Person1#: Okay, then. What kind of newspaper he wants you to sell? #Person2#: It's a weekly newspaper named Olympic English. So I need to be here only on Sunday. #Person1#: Sounds interesting. Especially that we are Olympic Volunteers. #Person2#: That's exactly what I am thinking about, And also it's a good way to get social experiences. #Person1#: And a good way to get some pocket money. #Person2#: Let's do it together. #Person1#: I'll say yes. Wait a minute. I need an IC card. #Person2#: For what? You have a telephone at home, don't you? #Person1#: Yes, but I don't want my Mom to tap my phone when I call Clive.","#Person2# tells #Person1# the boss wants #Person2# to be a newspaper salesperson. #Person1# thinks it is interesting. Finally, they decide to do it together.",163,24,0.1472
scientific_lay_summarisation-elife-norm,"N6-methyladenosine (m6A) is the most abundant internal RNA modification of cellular mRNAs. m6A is recognised by YTH domain-containing proteins, which selectively bind to m6A-decorated RNAs regulating their turnover and translation. Using an m6A-modified hairpin present in the Kaposi’s sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from the ‘Royal family’ as putative m6A readers, including SND1. RIP-seq and eCLIP analysis characterised the SND1 binding profile transcriptome-wide, revealing SND1 as an m6A reader. We further demonstrate that the m6A modification of the ORF50 RNA is critical for SND1 binding, which in turn stabilises the ORF50 transcript. Importantly, SND1 depletion leads to inhibition of KSHV early gene expression showing that SND1 is essential for KSHV lytic replication. This work demonstrates that members of the ‘Royal family’ have m6A-reading ability, greatly increasing their epigenetic functions beyond protein methylation. N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic messenger RNAs (mRNAs). Despite the identification of this modification over four decades ago, only recently have major breakthroughs in our understanding of this modification been made due to the development of m6A-seq, which allows immunoprecipitation of fragmented m6A-modified RNAs followed by next-generation sequencing (NGS) analysis. m6A-seq and subsequent enhanced versions of the technique led to transcriptome-wide maps of cellular m6A modification (Dominissini et al. , 2012; Meyer et al. , 2012; Patil et al. , 2016). m6A writers have also been identified, a catalytically active methyl-transferase, METTL3 (Wang et al. , 2016), together with adapter components, catalyses m6A addition onto specific RNA sequences containing the DRm6ACH motif, where D = A, G or U; R = A or G; H = A, C or U. The RNA demethylases FTO (Jia et al. , 2011) and ALKBH5 (Zheng et al. , 2013) can erase m6A marks offering a dynamic regulation of m6A status in RNA. Importantly, a family of effector m6A readers have also been identified comprising five YT521-B homology (YTH) domain-containing proteins. YTH readers directly bind m6A in target RNAs through an aromatic cage (Liao et al. , 2018), directing their targets towards different biological fates. YTHDF2 recruits the CCR4-NOT deadenylase complex and promotes degradation of m6A-containing RNAs (Du et al. , 2016; Wang et al. , 2014) while YTHDF1, YTHDF3 and YTHDC2 stimulate mRNA translation of their targets (Wang et al. ,","When a cell needs to make a protein, it reads from the master copy of the gene in the DNA and prints out temporary duplicates called mRNA. These duplicates then act as templates for protein production. Both DNA and mRNA can be further modified by adding on chemical tags that recruit specific proteins. While chemical modifications in DNA are known to control the activity of genes, their role in mRNA is only just being uncovered. One of the most common chemical modifications in mRNA is the addition of a methyl group called m6A. This methyl group has also been found in the mRNA of certain viruses, including the Kaposi’s sarcoma-associated herpesvirus (KSHV) which causes cancer. Recent work has shown that a family of proteins, known as the YTH",380,128,0.3368
scientific_lay_summarisation-elife-norm,"D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors. Central dopamine transmission coordinates reinforcement learning, including recognition of reward-predictive stimuli and initiation of goal-directed movements. Natural rewards, reward-predictive cues, and drugs of abuse elicit a rapid increase in dopamine release from dopamine axon terminals and somatodendritic sites within the ventral midbrain. Dopamine release is negatively regulated by the activation of dopamine D2 autoreceptors on somatodendritic and axon terminals (reviewed in Ford, 2014). Loss of D2 autoreceptor-mediated inhibition results in elevated extracellular dopamine and is associated with perseverative drug-seeking, enhanced motivation for food, and novelty-induced hyperactivity (Marinelli and White, 2000; Marinelli et al. , 2003; Bello et al. , 2011; Anzalone et al. , 2012; Holroyd et al. , 2015). Chronic D2 autoreceptor activation impairs the formation of dopamine- and glutamate-releasing axon terminals (Fasano et al. , 2010). Thus, D2 autoreceptors regulate structural and functional plasticity of dopamine neurons and are essential in limiting impulsivity and reward-seeking behaviors. A prominent feature of somatodendritic D2 autoreceptors is their activation of G protein-coupled inwardly rectifying potassium (GIRK) channels, resulting in inhibition of action potential firing and subsequent dopamine release. During prolonged activation, desensitization of D2 autoreceptors reduces the D2 autoreceptor-dependent GIRK current. A component of desensitization is dependent on intracellular calcium (Beckstead and Williams, 2007). Single or repeated exposure to drugs of abuse modifies D2 autoreceptor function (Henry et al. , 1989; Wolf et al. , 1993; Jones","Dopamine is an important component of the brain' s reward system and is commonly referred to as a ‘feel-good’ chemical. It is mainly released from neurons in the brain in response to natural rewards, such as food or sex, and following exposure to, or in anticipation of, certain drugs of abuse (including cocaine). Dopamine-releasing neurons also sense dopamine, and just like someone can change the volume of their voice by hearing themselves speak, dopamine neurons regulate how much dopamine is released based on how much dopamine they sense. This feedback system is known as autoinhibition. These neurons sense dopamine when it binds to, and activates, so-called ‘dopamine D2 receptors’ on their cell surface. But not all D2 receptors are alike. Instead there are two variants called D2S and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"to form a membrane coat? How do they interact with the membrane? How do they interact with each other? Are the existing models for the outer COPII coat cages representative of the complete coat assembled on a membrane? What is the structural basis for COPII ability to transport large or elongated cargoes such as pro-collagen? Here we address these questions. We provide evidence for coordinated assembly of the two layers of the coat on a lipid membrane and suggest how this interplay may effect shape changes essential to the capture of large and unusually-shaped secretory cargo complexes and particles. To understand the architecture of the Sec13/31 outer coat we applied reference free, contrast-transfer function (CTF) corrected, subtomogram averaging to solve the 3D structure of the vertex, and of the connecting rods to resolutions of ∼40 Å (2A–B, — 1, and ‘Materials and methods’). The vertex structure was a twofold symmetric X-shape, similar to that seen in in vitro assembled Sec13/31 cages (Stagg et al. , 2006,2008) (2D, — 2). The connecting rods are consistent in shape and size with Sec13/31 heterotetramers, and are bent in the middle by approximately 15°. This same bend is seen in the solved X-ray crystal structure, which can be fitted into the densities as a rigid body (2B, C). In contrast, there is a 45° bend in the rods of in vitro-assembled protein cages (Stagg et al. , 2008; 2E, F). These data indicate that the central hinge between Sec31 molecules can adapt to assemble coats of different curvatures. 10. 7554/eLife. 00951. 004Figure 2. Structure of the outer COPII coat. (A) Isosurface representation of the outer coat vertex solved by sub-tomogram averaging of tubular membranes. ‘+’ and ‘−’ ends of Sec13/31 and alpha and beta angles are as defined by (Stagg et al. , 2008) (— 2 and panel D). (B) Structures of the rods that interconnect neighbouring vertices in left-handed (green) and right-handed (purple) helical directions, viewed from the top (upper panels), and the side (lower panels). Left-handed rods have two ‘−’ ends, whereas right-handed rods have two ‘+’ ends. (C) Atomic model of the Sec13/31 complex (Fath et al. , 2007) (PDB 2PM9 and 2PM6) fitted as a rigid body into left- and right-handed rods. (D) Isosurface representation of the Sec13/31 vertex structure","Proteins often need to move between different compartments within cells. To do this they are packaged into transport pods called vesicles. Many trafficked proteins are synthesized in an organelle called the endoplasmic reticulum, or ER; these proteins are transported away from the ER in ‘COPII’ vesicles, which are formed when the COPII proteins assemble on the ER membrane and force it to bulge outward. The bulge pinches off from the ER membrane, forming the vesicle, which can then move to, and fuse with, a different compartment in the cell. The COPII proteins assemble in a particular order to form the vesicle—Sar1 inserts into the membrane of the ER; Sec23 and Sec24 form an inner coat and capture the proteins that the vesicle will transport; and Sec13 and Sec31",380,128,0.3368
dialogsum,"#Person1#: What does your company do exactly? #Person2#: We design and assemble a wide range of electric generators for hospitals, hotels anc small factories. We specialise in medium-sized generators but we're hoping to diversify into larger models next year. #Person1#: And who do you sell to? #Person2#: We export to Eastern Europe and the Far East. The domestic market accounts for about 40 percent of our total sales.",#Person2# tells #Person1# #Person2# company sells electric generators in the domestic market and abroad.,68,14,0.2059
dialogsum,"#Person1#: Have you brought the receipt with you? #Person2#: No, I don't. I left it home. #Person1#: Sorry, but we can't do anything without the receipt. Come back with it. #Person2#: I didn't know. I'll go to get it. How late will you be open? #Person1#: Till 5:30.",#Person1# says the receipt is needed. #Person2#'ll go home and get it.,48,12,0.25
dialogsum,"#Person1#: Tell me about your school, Daniel. I'm going there next term. I start on January fourth. #Person2#: Great, Tina, but it's the fifth. No sorry, the sixth not the fourth. #Person1#: Oh right. What time do lessons start? Is it 8:50, like at my old school? #Person2#: No, we start half an hour earlier, at 8:20. #Person1#: Oh, that's much earlier. Do you usually walk to school? #Person2#: No, it's too far. I go on my bike, but there is a bus. You can take. #Person1#: I see. Is there a uniform? #Person2#: Yes, there is. They don't let us wear jeans. We have to wear boring trousers and coats, but there is a black sweater which is in bad. #Person1#: Oh, and what are the teachers like? #Person2#: Well, the maths teacher is cool. We have excellent lessons with him but I did board in history. And I don't enjoy my English lessons at all. #Person1#: Do you have any sports lessons? #Person2#: Yeah, we play football. I really prefer tennis or swimming. But we don't do those sports at all. #Person1#: I see. Well, thanks Daniel.","Daniel tells Tina that the school starts at 8:20 and he usually bikes to school. Daniel also tells Tina about the uniform, the teachers and sports lessons at the school.",189,30,0.1587
dialogsum,"#Person1#: Excuse me, could you help me pick out a lotion? #Person2#: Sure, what is the problem? #Person1#: I got poison oak while hiking, and I need something to help me with the itching. #Person2#: I can suggest a product called Techne that comes in a lotion or cream. #Person1#: Which do you prefer? #Person2#: Hikers tell me that the cream is best because it stays on longer. #Person1#: Is there anything else I can do to help with the itching? #Person2#: You can take an antihistamine. #Person1#: Thank you so much for all of the information. #Person2#: You are welcome. Please feel free to ask me a question any time you need help.",#Person1# got poison oak and wants a lotion. #Person2# recommends Techne and advises #Person1# to take an antihistamine to help with the itching.,114,23,0.2018
dialogsum,"#Person1#: Mom, what were movies like when you were a kid? #Person2#: Everything about them was different, even the theaters. #Person1#: I'm really interested. Tell me about them. #Person2#: Well, where I grew up, we saw movies at a drive-in theater in our car with the whole family. #Person1#: That's cool. I bet you could bring your own food. #Person2#: We did. On hot days, we'd take a blanket and lay in the back of dad's old pickup to watch the movie. #Person1#: Why don't we do that anymore? #Person2#: Well, the weather might have some influence, during bad weather the theater didn't make a whole lot.",#Person1#'s mom tells #Person1# about drive-in theater in her childhood and the reason of its decay.,107,16,0.1495
scientific_lay_summarisation-elife-norm,"of fluid-filled cysts developing in the kidney. This has led to the suggestion that the molecular mechanisms causing cyst formation are similar, or at least, share a common pathway (Watnick and Germino, 2003). The molecular cloning of multiple CKD mutations and the realization that the affected genes all function at the primary cilia, basal bodies or centrosomes, has given rise to the ciliary hypothesis as a unifying disease mechanism of CKDs (Yoder et al. , 2002; Mollet et al. , 2005; Fliegauf et al. , 2006). Accordingly, the primary cilia of tubule cells are thought to act as flow sensors, eliciting intracellular calcium fluxes through stretch sensitive polycystin channels in response to flow-driven bending (Praetorius and Spring, 2001,2003; Nauli et al. , 2003; Praetorius et al. , 2004). These signals are thought to constitutively dampen cell proliferation, such that loss of filtrate flow or interruptions in the signal transduction process precipitate chronic overproliferation and consequently cyst formation (Deane and Ricardo, 2012). However, major mechanistic aspects of the ciliary hypothesis remain poorly understood, including the integration of the calcium signal with downstream transcriptional regulation of cell behavior (Wilson and Goilav, 2007; Uhlenhaut and Treier, 2008; Deane and Ricardo, 2012; Kotsis et al. , 2013), the extent by which cyst development can be understood as chronic activity of endogenous repair mechanisms (Deane and Ricardo, 2012), and the identity and origins of the ectopically overproliferating cells (Murer et al. , 2002; Weimbs, 2007; Lodi et al. , 2012). Further, these questions present an investigative challenge, given the poor experimental accessibility of the mammalian kidney as an internal and essential organ. The Xenopus pronephros and zebrafish pro- and mesonephric kidneys, therefore, are increasingly being explored as model systems for human kidney disease (Drummond, 2005; Ebarasi et al. , 2011). Compounding this problem is the fact that it has not been possible to bring the full power of invertebrate models in solving fundamental cell biological processes to the analysis of human kidney disease (Igarashi, 2005; Dow and Romero, 2010). Both Caenorhabditis elegans and Drosophila melanogaster have highly derived excretory organs in which ultrafiltration is either entirely lacking (C. elegans; [Buechner, 2002]) or uncoupled from reabsorption/secretion (D. melanogaster; [Dow and Romero, 2010]). Furthermore, the excretory cells of both organisms are lacking cilia as a further requirement","Millions of people around the world are affected by cystic kidney diseases, which are amongst the most common inherited genetic disorders. Throughout their life, people with these diseases develop fluid-filled cysts in their kidneys, which stop these organs from working properly and can eventually lead to organ failure. Healthy kidneys perform many vital roles in the body, including removing waste products and keeping the concentration of salts in the blood in balance. These activities depend on the kidneys filtering the blood, and then reabsorbing useful chemicals from the filtered fluid as it passes through small tubes called tubules. Cysts disrupt both of these processes. Mutations in many different genes can cause cystic kidney diseases. Many of these genes encode proteins that are involved in the formation of cilia:",380,128,0.3368
scientific_lay_summarisation-elife-norm,"conditions (Díaz et al. , 2016; Reich, 2014; Reich et al. , 2003; Wright et al. , 2004). Thus, linking environmental conditions with relevant functional traits has become a tractable way to predict the richness and composition of communities (i. e. community structure) (Cornelissen et al. , 2003; Díaz and Cabido, 1997; Funk et al. , 2017; Kattge et al. , 2020; Lavorel and Garnier, 2002; McMahon et al. , 2011; Reich, 2014; Sundqvist et al. , 2013). The functional traits expressed by those species that are able to colonize and persist in a given location can, in turn, affect disease risk (Halliday et al. , 2019; Johnson et al. , 2013; Kirk et al. , 2019). Specifically, an infected host’s ability to transmit disease to uninfected hosts, a trait often referred to as host competence, is often related to fast-growing, poorly defended tissues and short lifespans (Becker and Han, 2021; Cronin et al. , 2014; Cronin et al. , 2010; Huang et al. , 2013; Johnson et al. , 2012; Martin et al. , 2019; Martin et al. , 2016; Parker and Gilbert, 2018; Stewart Merrill and Johnson, 2020; Welsh et al. , 2020). Importantly, these functional trait values also underlie ecological tradeoffs related to host growth and defense, resource acquisition and allocation, and survival and reproduction (i. e. life history) (Coley et al. , 1985; Herms and Mattson, 1992; Martin et al. , 2016; Reich, 2014; Reich et al. , 2003; Ricklefs and Wikelski, 2002; Stearns, 1992; Stearns, 1989; Wright et al. , 2004). Thus, host community competence (a community-level metric of host competence) is expected to correspond to the same functional traits (i. e. host pace-of-life) that link host community structure to shifting environmental conditions. A trait-based framework of host community competence may explain why biodiversity loss is consistently associated with higher disease risk (Halliday et al. , 2020b; Johnson et al. , 2013; LoGiudice et al. , 2003; Ostfeld and LoGiudice, 2003), a relationship known as the ‘dilution effect’ of biodiversity (Keesing et al. , 2010; Keesing et al. , 2006; Ostfeld and Keesing, 2000). This is because host species that are most resistant to biodiversity loss or best able to colonize newly disturbed habitats often rely on the same life-history strategies that are associated with","Climate change is causing shifts in the ecology and biodiversity of different world regions at unprecedented rates. Global warming is also linked with changes in the risk for certain infectious diseases in humans, but also in animals and plants. There are several possible mechanisms for this. For one thing, changing weather patterns may affect how pathogens grow and reproduce. For another, the distribution ranges of animal and plant hosts of certain disease-causing pathogens are changing because of global warming. This means that the distributions of pathogens are also changing, and so is the severity of the diseases that they cause. Increasing temperatures may also influence the physiological traits that make host species suitable for pathogens. This is because the traits that allow species to survive or adapt to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Acquisition of distinct neuronal identities during development is critical for the assembly of diverse functional neural circuits in the brain. In both vertebrates and invertebrates, intrinsic determinants are thought to act in neural progenitors to specify their identity and the identity of their neuronal progeny. However, the extent to which individual factors can contribute to this is poorly understood. We investigate the role of orthodenticle in the specification of an identified neuroblast (neuronal progenitor) lineage in the Drosophila brain. Loss of orthodenticle from this neuroblast affects molecular properties, neuroanatomical features, and functional inputs of progeny neurons, such that an entire central complex lineage transforms into a functional olfactory projection neuron lineage. This ability to change functional macrocircuitry of the brain through changes in gene expression in a single neuroblast reveals a surprising capacity for novel circuit formation in the brain and provides a paradigm for large-scale evolutionary modification of circuitry. Animals display a wide repertoire of complex and adaptable behaviours executed by equally complex nervous systems. Understanding how the vast number of diverse cell types is assembled into functional neural circuits in complex brains during development is a major challenge. Studies of lineage tracing and circuit mapping reveal that heterogeneous pools of neural progenitors sequentially generate series of neuronal progeny, and that such lineally related neurons with shared developmental histories often share functional connectivity in the brain. In consequence, neural lineages can be considered to form neuroanatomical units of projection that represent the developmental basis of the functional circuitry of the brain (Pearson and Doe, 2004; Cardona et al. , 2010; Pereanu et al. , 2010; Custo Greig et al. , 2013; Franco and Muller, 2013; Gao et al. , 2013; Kohwi and Doe, 2013). This is exemplified in Drosophila where the tens of thousands of neurons that comprise the adult brain are generated during development by a set of approximately 100 pairs of individually identifiable neural stem cells called neuroblasts (Truman and Bate, 1988; Urbach et al. , 2003; Urbach and Technau, 2003a, 2003b; Technau et al. , 2006). Each neuroblast gives rise to a specific, invariant lineage of post-mitotic neural cells in a highly stereotyped manner and in many cases, lineally related neurons share functional connectivity and many neuroanatomical features such as innervation of common neuropiles in the","The cells in the brain—including the neurons that transmit information—work together in groups called neural circuits. These cells develop from precursor cells called neuroblasts. Each neuroblast can produce many cells, and it is likely that cells that develop from the same neuroblast work together in the adult brain in the same neural circuit. How the adult cells develop into their final form plays an important role in creating a neural circuit, but this process is not fully understood. In many animals, the complexity of their brain makes it difficult to follow how each individual neuroblast develops. However, all of the neuroblasts in the relatively simple brain of the fruit fly Drosophila have been identified. Furthermore, the genes responsible for establishing the initial identity of each neuroblast in the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. , 2015). Here we show that Perforin-2 is a major antibacterial effector protein of the innate immune system in phagocytic and in tissue forming cells. Perforin-2 is an essential innate effector protein that kills gram-positive, gram-negative, and acid-fast bacteria. The absence of Perforin-2 enables survival of pathogenic bacteria in vitro and systemic dissemination in vivo indicating that expression of Perforin-2 in professional phagocytes and in parenchymal cells is required to eliminate pathogenic bacteria in vitro and in vivo. We demonstrate that Perforin-2 can polymerize to form pores visible by negative staining transmission electron microscopy in bacterial surfaces. The presence of Perforin-2 potentiates the antibacterial activity of other known effectors including reactive oxygen and nitrogen species. In our accompanying manuscript we report some of the molecular mechanisms of Perforin-2 activation and describe how a bacterial virulence factor blocks Perforin-2 function. Professional phagocytes avidly ingest and kill bacteria. To elucidate the contribution of Perforin-2 towards their bactericidal activity, we compared professional phagocytes from Perforin-2 deficient mice with Perforin-2 heterozygous and wild-type phagocytes. Perforin-2-deficient murine peritoneal exudate macrophages (PEM), neutrophils, and bone marrow-derived macrophages (BMDM) are unable to kill three different species of Mycobacteria (Mycobacterium smegmatis, Mycobacterium avium, M. tuberculosis), as indicated by significant intracellular bacterial replication in MPEG1 (Perforin-2) −/− compared to +/+ or +/− phagocytes (1A–C, — 1). Although BMDM express Perforin-2 constitutively, they must be activated with IFN and LPS in order to mediate Perforin-2-dependent growth inhibition of M. tuberculosis (Mtb) (— 2). This suggest that the destruction of Mtb requires both the expression and activation of Perforin-2. 10. 7554/eLife. 06508. 003Figure 1. Perforin-2 deficiency or siRNA knockdown abrogates intracellular killing of pathogenic bacteria. (A-C) Perforin-2 knockout, heterozygous, and wild-type macrophages and neutrophils were infected with Mycobacterium species (A) PEM infected with Mycobacterium smegmatis, (B) Neutrophils infected with Mycobacterium avium, and (C) BMDM infected with Mycobacterium tuberculosis. (D-H) Perforin-2 knockdown can be complemented in BV2 microglia cells infected with (D) M. avium, (E) M. smegmatis, (F) Salmonella typhimurium, and (G) MRSA. (H) Western blot demonstrating protein levels after complementation: BV2 transfected with (Lane 1) Perforin-2-RFP and Perforin-2 siRNA, (Lane 2) RFP and Perforin-2 siRNA, (Lane 3) RFP and Perforin-2 scramble siRNA, and (Lane 4) Perforin-2 siRNA alone. In western blots, Perforin-2-RFP is detected as a 105 kD band compared","An effective defense against foreign invaders is fundamental to an organism' s survival. It is likely that immunity began to develop shortly after the emergence of Earth' s first single-celled organisms and a remnant of that distant past still exists in our present day immune system in the form of Perforin-2. This ancient protein has been highly conserved throughout evolution from sea sponges to humans. Some studies have suggested that Perforin-2 may have an antimicrobial role in invertebrates (including clams, mussels, and snails) and fish. However, its mechanism of killing and its role in the mammalian immune systems has remained largely unknown. McCormack et al. now report that Perforin-2 is a crucial component of host defense against a wide spectrum of infectious bacteria in both mice and humans.",380,128,0.3368
pubmed-summarization,"each year , 200 000 inhospital cardiac arrests ( ihca ) occur in the united states , with overall survival rates of 18% to 20% . however , the extent to which hospitals vary in survival rates for ihca remains poorly understood , as prior studies have largely reported aggregate survival rates at the patient level or have had a limited sample of hospitals , and most studies have lacked detailed information on patient factors to ensure adequate casemix adjustment . furthermore , the extent of sitelevel variation in neurologic status among survivors an outcome of great importance to many patients , their family members , and providers remains unknown . defining variability in survival rates , and examining the degree to which variation persists even after adjusting for patient casemix , would provide important insights into which hospitals could improve resuscitation care and offer opportunities to identify best practices at these hospitals . if significant variability in survival exists even after adjusting for patient casemix , this may suggest that resuscitation process factors ( eg , time to defibrillation , quality of cardiopulmonary resuscitation ) and quality improvement initiatives may be the primary reasons for substantially higher survival rates in topperforming hospitals . moreover , it would suggest a greater urgency to develop appropriate research methodology to identify which factors are associated with best practices at hospitals with the highest ihca survival . accordingly , within the american heart association 's get with the guidelinesresuscitation ( gwtgr ) , a large national inhospital cardiac arrest registry , we examined the extent to which hospitals varied in rates of survival to discharge among patients with ihca . gwtgr is an ideal data source , as it contains ihca data from over 400 us hospitals and collects detailed information on a number of patient and cardiac arrest characteristics to ensure robust casemix adjustment in a specific patient cohort . this was a multicenter cohort study using data from gwtgr to calculate hospital riskadjusted survival rates for ihca . gwtgr is sponsored by the american heart association ( aha ) and is a large , comprehensive , prospective national database of ihca in the us . this dataset also has information from outcome , a quintiles company which is the data collection","backgroundinhospital cardiac arrest ( ihca ) is common and often fatal . however , the extent to which hospitals vary in survival outcomes and the degree to which this variation is explained by patient and hospital factors is unknown.methods and resultswithin get with the guidelinesresuscitation , we identified 135 896 index ihca events at 468 hospitals . using hierarchical models , we adjusted for demographics comorbidities and arrest characteristics ( eg , initial rhythm , etiology , arrest location ) to generate riskadjusted rates of inhospital survival . to quantify the extent of hospitallevel variation in riskadjusted rates , we calculated the median odds ratio ( or ) . among study hospitals , there was significant variation in unadjusted survival rates . the median unadjusted rate for the",380,128,0.3368
dialogsum,"#Person1#: Hi, Betty, where are you going for your vacation? #Person2#: Georgia. I've been waiting to go there for ages. #Person1#: Now your dream will come true. When are you off?. #Person2#: Next Wednesday evening. #Person1#: How are you getting to the airport? Is anybody seeing you off?. #Person2#: No, I will take a taxi to go there. My plane takes off at 10:30. #Person1#: Are you staying in a hotel in Georgia? Hotels there are particularly expensive and it's hard to book one at this time of year. #Person2#: No, not necessary. My aunt lives there and I'm staying with her. What about you? Are you going anywhere? #Person1#: Yeah. I'm going to Florida on Friday with my parents. #Person2#: How are you getting there? By train? #Person1#: No, by plane. #Person2#: How long are you staying there? #Person1#: It all depends. Maybe a week. See you when we get back. Have a nice time in Georgia. #Person2#: Good luck! Have a nice trip! #Person1#: Thanks. The same to you. Bye!",Betty is going to Georgia by plane next Wednesday evening and will be staying with her aunt. #Person1# is going to Florida by plane on Friday with #Person1#'s parents and maybe stay there for a week.,172,36,0.2093
dialogsum,"#Person1#: do you have any plans for Friday night? #Person2#: I don't think so. Why? #Person1#: well, my house-mates and I are having a house-warming party. Would you like to come? #Person2#: sure. Would it be alright if I brought a few friends? #Person1#: the more, the merrier! #Person2#: will there be a lot of people there? #Person1#: I sure hope so. We've each invited about 10 people. #Person2#: who else is going to be there? #Person1#: I'm inviting my friends from work, you, my sister, and a few friends from school. #Person2#: I know your sister. She's very nice. #Person1#: don't worry. You won't be sitting there by yourself. #Person2#: what time is it going to start? #Person1#: most people are working Friday night, so it's going to start around 9 pm. #Person2#: should I bring anything? #Person1#: we'll have beer and snacks, but if you want to bring a bottle of wine, that'd be great. #Person2#: I could also bring some music if you want. I've got loads of songs on my new iPod. #Person1#: that'd be great. I'll see you then!",#Person1# invites #Person2# to the house-warming party on Friday night. #Person2# agrees and #Person2#'ll bring some wine and music.,184,19,0.1033
pubmed-summarization,"intestinal helminths are among the most common and widespread of human infections , contributing to poor nutritional status , anemia and impaired growth ( 1 ) . intestinal helminthiases are also known to aggravate pre - existing anemia by decreasing appetite and thus food and iron intake ( 2 , 3 ) . worldwide , anemia is an important reproductive health problem because of its association with adverse pregnancy outcome such as increased rates of maternal and perinatal mortality , premature delivery , low birth weight , etc ( 4 ) . women in developing countries spend half of their reproductive lives pregnant and lactating and a high proportion of women in developing countries become anemic during this period . women of reproductive age who are iron deficient but not anemic may become anemic during pregnancy as a consequence of increased iron requirements and expanded plasma volume . epidemiological surveys have revealed that poor sanitation and inappropriate environmental conditions coupled with indiscriminate defaecation , geophagy and contamination of water bodies are the most important predisposing factors to intestinal worm infection ( 5 ) . practices such as hand washing , disposal of refuse , personal hygiene , wearing of shoes and others , when not done properly may contribute to the infection or picking of these worms from the environments ( 6 ) . this research investigates the prevalence of helminth infection and its hematological alterations during pregnancy findings of this study will serve as a tool in evidence based health education on the need to intensify efforts at preventing helminthiases and its attendant risk of anemia during pregnancy . two hundred and eighty - two pregnant women between the ages of 18 45 years , in their various trimesters and of various parities ( 0 10 ) were enlisted . fresh stool samples for helminth screening were collected from each of the 282 subjects in dry , clean , leak proof and sterilized sample containers . the samples were examined for consistency and presence of cysts , proglottids and adult worms . concentrated saturated sodium chloride floatation and formol - ether concentration techniques were used for fecal analysis . the total number of eggs was counted under x40 magnification of a compound microscope stool samples were processed within 8","backgroundthe incidence and hematological effects of helminth infection during pregnancy were investigated among pregnant women in isiala , mbano , southeast nigeria.methods:totally 282 pregnant women were enlisted for the study between october 2011 and september 2012 . stool samples were examined for intestinal helminths using formalin - ether sedimentation technique . hemoglobin ( hb ) and packed cell volume ( pcv ) levels were evaluated in venous blood samples using sahli s and microhaematocrit methods respectively.results:forty six ( 16.3% ) subjects were infected with at least one helminth parasite ; 24 ( 8.5% ) hookworm , 14(5.0% ) and 2(0.7% ) a. lumbricoides and trichuris trichiura infections respectively . intestinal helminthiases in pregnant women was significantly associated with age ( p<0.05 ) . the prevalence of intestinal helminthiases",380,128,0.3368
dialogsum,"#Person1#: Julia, I have good news for you. #Person2#: What's up? #Person1#: I have earned a lot of money this week, more than I do in a fortnight. #Person2#: It is really good news. How much do you earn a week now? #Person1#: My wages are six hundred dollars a week. But I find a part-time job to my income. #Person2#: Darling, I know you are a good husband. You don't have to work so hard. After all your health is the most important. #Person1#: I know, darling. I must earn enough money to buy a car. I do a part-time job to increase my income. Don't worry, I will take care of myself. #Person2#: I see. You must have more rest.",#Person1# tells Julia he finds a part-time job to his income and earned a lot this week. Julia hopes him to take care of his health.,122,26,0.2131
dialogsum,"#Person1#: How are you, Mr. Wilson? I am Tina. #Person2#: Glad to meet you, Mrs. Tina. #Person1#: Please have a seat. I know our employment of forcer has already given you the information about your employee contract, but I'd like to go over the main details again before signing. First, you'll be getting a monthly salary, with one month paid vacation after one year of service. #Person2#: That's what I understand. #Person1#: You'll be covered by our medical plan while on duty. Since you'll be middle management, you're expected to be available up to 1. 5 hours past normal working hours. Any approved time over that will be paid at time and a half, which you can take as salary or time off. #Person2#: Exactly my understanding. #Person1#: A reasonable number of sick days will be covered by the company. Any extended illness will be covered by insurance. Have you read the other terms of the contract? #Person2#: Yes, I have. #Person1#: Do you have any other questions? #Person2#: Just one. I noticed an item about flex-time. Is that a possibility for me? #Person1#: Yes, it is, but you'll have to discuss the details with your manager. #Person2#: That's acceptable. #Person1#: Good. Now, if you'll just sign here, you can start work in 3 days.","Mr.Wilson describes the elementary information about the employment contract to Tina. He mentions monthly salary, one month paid vacation, medical plans, extended working hours and flex-time.",215,26,0.1209
scientific_lay_summarisation-elife-norm,"Fossils were thought to lack original organic molecules, but chemical analyses show that some can survive. Dinosaur bone has been proposed to preserve collagen, osteocytes, and blood vessels. However, proteins and labile lipids are diagenetically unstable, and bone is a porous open system, allowing microbial/molecular flux. These ‘soft tissues’ have been reinterpreted as biofilms. Organic preservation versus contamination of dinosaur bone was examined by freshly excavating, with aseptic protocols, fossils and sedimentary matrix, and chemically/biologically analyzing them. Fossil ‘soft tissues’ differed from collagen chemically and structurally; while degradation would be expected, the patterns observed did not support this. 16S rRNA amplicon sequencing revealed that dinosaur bone hosted an abundant microbial community different from lesser abundant communities of surrounding sediment. Subsurface dinosaur bone is a relatively fertile habitat, attracting microbes that likely utilize inorganic nutrients and complicate identification of original organic material. There exists potential post-burial taphonomic roles for subsurface microorganisms. Fossils have traditionally been thought to retain little original organic material after undergoing decay and diagenesis. However, recent discoveries of relatively intact macromolecular organic material in fossils and sub-fossils challenge this view. These include ancient DNA (Meyer et al. , 2012; Orlando et al. , 2013) and peptide (Buckley, 2015; Demarchi et al. , 2016; Cappellini et al. , 2018) sequences in sub-fossils, as well as ancient biomolecules such as sterols (Melendez et al. , 2013), melanin (Vinther et al. , 2008), amino acids (Curry et al. , 1991), and porphyrins (Wiemann et al. , 2018a). These findings show that organic remains can potentially persist for thousands to millions of years, depending on the biomolecules and environmental conditions. Such remains have already provided important insights into evolution, including the origins of our species (Krause et al. , 2010) and the affinities of extinct Pleistocene megafauna (Welker et al. , 2015). In theory, millions to tens of millions of years old organic remains could offer palaeontologists new insights and a unique window into the biology of organisms distantly related to any living species. Such organic molecular fossils could potentially shed light on the biology and evolution of extinct organisms, including their coloration, structure, behavior, and phylogeny, providing unique insights into past life, and the origins of present life. However, it remains unclear how long different types of organic molecules and organic","The chances of establishing a real-world Jurassic Park are slim. During the fossilization process, biological tissues degrade over millions of years, with some types of molecules breaking down faster than others. However, traces of biological material have been found inside some fossils. While some researchers believe these could be the remains of ancient proteins, blood vessels, and cells, traditionally thought to be among the least stable components of bone, others think that they have more recent sources. One hypothesis is that they are in fact biofilms formed by bacteria. To investigate the source of the biological material in fossil bone, Saitta et al. performed a range of analyses on the fossilized bones of a horned dinosaur called Centrosaurus. The bones were carefully excavated in a manner to reduce",380,128,0.3368
dialogsum,"#Person1#: Dad, will you read to me? #Person2#: Uh, let me finish the newspaper first? #Person1#: You've been saying that forever! #Person2#: Well, how about reading the business section of the newspaper together? #Person1#: That's boring. Let's read this book. It's about a bear and cat that becomes friends. #Person2#: Okay, let's read this book. #Person1#: Great! And these books too. #Person2#: Whoa. I thought you said one book. There must be at least ten here. #Person1#: My teacher, Mrs. Green, says you have to read to me every night, and the newspaper doesn't count. And let's eat some popcorn and cookies while we're reading. #Person2#: Well, it's bedtime right now. So, okay, here we go. Once upon a time in a deep, dark forest, lived a brown bear ...","#Person1# wants #Person2# to stop reading and read a fairy-tale book for #Person1#. #Person2# agrees as it's requested by #Person1#'s teacher, and it's time for bedtime stories now.",130,28,0.2154
dialogsum,"#Person1#: Researchers in America did some experiments to try to out why some people gain weight more than others do. #Person2#: Yeah, some people can eat whatever they want and they never seem to gain a pound. #Person1#: In this study, volunteers were given 1000 extra calories a day. About 2 pieces of cheese's worth of extra intake. #Person2#: This kind of study I'd like to be in. #Person1#: Well, anyway, there're also world special equipment that recorded how much they moved. You know, walking up and down steps. Everybody gained weight. But some people gained much less than others. The secret keeping on moving. #Person2#: You mean just moving your fingers or scratching your neck or something like this? #Person1#: Any movement takes energy to perform. And little movements like rearranging things on your desk, if you do them all the time, starts to add up. We generally only think of large movements like exercise as burning calories. But people who keep on moving maybe doing a slow steady burn all day long. #Person2#: So maybe you should do more housework instead of me from now on.",#Person1# introduces to #Person2# an experiment on weight-gaining by American researchers and concludes that keeping doing little movements can also burn up many calories. Thus #Person2# asks #Person1# to do more housework.,188,32,0.1702
scientific_lay_summarisation-elife-norm,"induce RNA expression of TFIIAγ5 in IR24 or TFIIAγ5V39E in IRBB5 (1A), which correlates with the absence of predicted DNA binding motifs for known TALEs in the TFIIAγ5 promoter. In contrast, expression of known disease susceptibility genes Os8N3, TFIIAγ1, OsTFX1, and Os11N3, each of which is targeted by a different TALE (Römer et al. , 2010; Sugio et al. , 2007; Yang et al. , 2006), was always lower in IRBB5 (p<0. 01), although not necessarily completely abolished (1A). Together, these results point to TFIIAγ5 being a host co-factor for TALE-dependent induction of susceptibility genes. 10. 7554/eLife. 19605. 003Figure 1. Effects of TFIIAγ5 on the expression of disease susceptibility genes Os8N3, Os11N3, TFIIAγ1, or OsTFX1, after Xoo infection. Plants were inoculated with Xoo strain PXO99 (harbouring TALEs PthXo1, PthXo7, and PthXo6), PXO86 (harbouring TALE PthXo3) or PXO61 (harbouring TALE AvrXa7) at the booting (panicle development) stage. It is known that PthXo1, PthXo7, and PthXo6 induce Os8N3, TFIIAγ1, and OsTFX1, respectively, and PthXo3 and AvrXa7 all induce Os11N3. Each bar represents mean (three replicates) ± standard deviation. (A) Mutation of TFIIAγ5 (rice line IRBB5). b, significant difference between IR24 and IRBB5 at p<0. 01. (B) TFIIAγ5-RNAi lines. b, significant difference between wild-type (WT) and transgenic plants at p<0. 01. : http: //dx. . org/10. 7554/eLife. 19605. 00310. 7554/eLife. 19605. 004Figure 1— 1. Effects of TFIIAγ5 on rice resistance to Xoo strains known to carry TALEs. Rice plants at the booting (panicle development) stage were inoculated with Xoo. (A) The near-isogenic lines IR24 and IRBB5 showed different responses to the infection of Xoo. IRBB5 in IR24 background carries a natural mutated TFIIAγ5, TFIIAγ5V39E. Each bar represents mean (total 17 to 29 leaves from 5 plants) ± standard deviation. b, significant difference between IR24 and IRBB5 at p<0. 01. (B) The enhanced resistance of TFIIAγ5-RNAi plants to strain PXO99 was associated with reduced transcription of TFIIAγ5 but not TFIIAγ1. WT, wild-type Zhonghua 11. Each bar represents mean (3 replicates for gene expression and total 5 to 10 leaves from one plant for lesion length) ± standard deviation. b, significant difference between wild-type (WT) and transgenic plants at p<0. 01. (C) The enhanced resistance of TFIIAγ5-RNAi plants co-segregated with reduced TFIIAγ5 transcription in T1 families. Each bar represents mean (3 replicates for gene expression","Around the world, bacterial infections reduce the yields of many important crops like rice, tomatoes, peppers and citrus fruits. Xanthomonas is a particularly widespread genus of bacteria; it consists of almost 30 species that cause diseases in more than 400 plant hosts, including bacterial blight and bacterial streak in rice plants. Plants do have an immune system that is able to detect invading microbes and trigger a defensive response against them; however, many disease-causing bacteria have evolved ways to avoid or counteract this response. For example, at least five Xanthomonas species use proteins called transcription activator-like effectors (or TALEs for short) to infect their host plants. The bacterial proteins are essentially injected into the plant’s cells where they activate specific plant genes that make the host more susceptible",380,128,0.3368
dialogsum,#Person1#: Why are you walking to and fro in the room? #Person2#: I'm worrying about the children. After all this is the first time they have been out without us. #Person1#: Don't worry. They are grown-ups. #Person2#: I know. But I couldn't help.,#Person2# couldn't help worrying about the children. #Person1# comforts #Person1#.,43,10,0.2326
pubmed-summarization,"torsion of uterine adnexa is an important cause of acute abdominal pain reported in the literature.1 however , isolated torsion of fimbrial cysts has rarely been described as a cause for acute abdomen.23 we report a rare case of isolated torsion of fimbrial cysts leading to acute abdomen . a 22-yr - old female presented to the hospital with acute abdomen , amenorrhea for a half month and a half , and spotting on and off . the patient provided written consent to reproduce information or photographs . on physical examination , the patient s vital signs were found to be normal . laboratory investigations including hemoglobin , total leucocyte count , differential leucocyte count , and routine and microscopic examination of the urine were found to be normal . therefore , a serum beta human chorionic gonadotropin ( hcg ) test was done to confirm pregnancy . however , serum beta hcg levels were within normal range . the ultrasound report showed a tubo - ovarian mass in the right adnexa along with fluid in the pouch of douglas , suggestive of fimbrial cysts or ectopic pregnancy ( . on laprotomy , multiple cystic structures attached to the fimbriae were seen , which were twisted at their pedicle . many of them had ruptured leading to collection of about 200 ml of straw colored fluid . however , the fallopian tubes and ovaries were normal on both the sides , so a cystectomy was done . multiple cystic structures varying in size from 3 3 cm to 2 2 cm were seen . the cystic structures were filled with yellow colored fluid and were twisted at the pedicle ( . 2 ) . histopathology showed ciliated , columnar cells with underlying stroma and few chronic inflammatory cells , and a diagnosis of fimbrial cysts was made ( . paraovarian cysts represent approximately 10% of adnexal masses.4 they are more common in childbearing women.5 paratubal cysts arise from mllerian or wolffian structures and are common in adult females . these are hormone sensitive and are generally asymptomatic.6 malignant neoplasms arising from paratubal cysts are very rare.7 rarely , they can be associated with torsion of fallopian tubes.7 other complications include hemorrhage , rupture , and infection.3 paratubal cysts are difficult","we present a case of a 22-year - old female who presented with acute abdomen and amenorrhea . emergency laprotomy was done with a clinical diagnosis of ectopic pregnancy . on laprotomy , twisted fimbrial cysts were found . thus , although fimbrial cysts are rarely twisted , they should be considered as a cause of acute abdomen in a female of reproductive age group .",380,66,0.1737
scientific_lay_summarisation-elife-norm,"Positional information is fundamental to animal regeneration and tissue turnover. In planarians, muscle cells express signaling molecules to promote positional identity. At the ends of the anterior-posterior (AP) axis, positional identity is determined by anterior and posterior poles, which are putative organizers. We identified a gene, nr4A, that is required for anterior- and posterior-pole localization to axis extremes. nr4A encodes a nuclear receptor expressed predominantly in planarian muscle, including strongly at AP-axis ends and the poles. nr4A RNAi causes patterning gene expression domains to retract from head and tail tips, and ectopic anterior and posterior anatomy (e. g. , eyes) to iteratively appear more internally. Our study reveals a novel patterning phenotype, in which pattern-organizing cells (poles) shift from their normal locations (axis extremes), triggering abnormal tissue pattern that fails to reach equilibrium. We propose that nr4A promotes pattern at planarian AP axis ends through restriction of patterning gene expression domains. Metazoans display a large diversity of developmental modes and adult forms. Processes that govern the generation of form, collectively known as patterning, act to regulate cell identity, location, and number (Wolpert, 1969). The mechanisms by which pattern is established and maintained in adult tissues, however, are poorly understood. Planarians are freshwater flatworms capable of remarkable feats of whole-body regeneration and offer the opportunity, as a model system, to generate important insights into the molecular and cellular mechanisms that can generate and maintain adult tissue pattern. The planarian anterior-posterior (AP) axis has been a target for study of positional information in adult biology. RNA interference (RNAi) approaches have identified genes with regionalized expression domains that are important in AP patterning (Forsthoefel and Newmark, 2009; Adell et al. , 2010; Reddien, 2011). Genes with such constitutive regionalized expression and association with pathways with planarian patterning roles are called position control genes or PCGs (Witchley et al. , 2013; Scimone et al. , 2016; Fincher et al. , 2018). PCGs are predominantly expressed in planarian muscle (Witchley et al. , 2013; Scimone et al. , 2016; Fincher et al. , 2018; Scimone et al. , 2018). A number of PCGs encode evolutionarily conserved signaling proteins, such as members of the FGFRL family and Wnt/ß-catenin pathway components (Reddien, 2011). For example, inhibition of the FGFRL gene ndl-3 and the Wnt gene wntP-2 led","Many animals are able to regenerate tissue that has been lost through illness or injury. Flatworms called planarians have long been used to study tissue regeneration because of their remarkable ability to completely regenerate their whole body from small pieces of tissue. Furthermore, the stem cells of adult planarians continually produce new cells to replace dying cells in a process called tissue turnover. For regeneration and tissue turnover to be successful, it is important for the new cells to form in the right location in the body; for example, new eye cells need to form in the head. Genes known as position control genes are active in muscle at specific locations along the body of a flatworm to regulate both regeneration and tissue turnover. However, it was not",380,128,0.3368
scientific_lay_summarisation-elife-norm,"with a zipper-like morphology that connect homologs during the pachytene stage (Fraune et al. , 2012; von Wettstein et al. , 1984; Zickler and Kleckner, 1999). Within the context of the SCs, selected recombinational interactions mature into crossovers such that each pair of chromosomes attains at least one crossover despite a low number of events per nucleus. Homologs then desynapse and prepare for the meiosis-I division. The connections created by crossovers enable the stable bipolar orientation of homologs on the meiosis-I spindle, and thus accurate segregation during meiosis I. By creating new combinations of gene alleles, crossing over and independent chromosome segregation during meiosis fuels natural selection. Orchestrating the elaborate events of meiosis are regulatory networks that function at the transcriptional, post-transcriptional, translational, and post-translational levels (Bose et al. , 2014; Brar et al. , 2012; Cahoon and Hawley, 2016; Cheng et al. , 2018; Crichton et al. , 2014; Gao and Colaiácovo, 2018; Govin and Berger, 2009; Gray and Cohen, 2016; Jin and Neiman, 2016; Nottke et al. , 2017; Otto and Brar, 2018; Tresenrider and Ünal, 2018). The post-translational, SUMO (Small Ubiquitin-like MOdifier) protein-modification system (SMS) is now recognized as an essential regulator of meiotic prophase (Cheng et al. , 2007; de Carvalho and Colaiácovo, 2006; Lake and Hawley, 2013; Nottke et al. , 2017; Rodriguez and Pangas, 2016; Sakaguchi et al. , 2007; Vujin and Zetka, 2017; Watts and Hoffmann, 2011). Like ubiquitin, SUMO is conjugated to lysine (K) side-chains on target proteins via a cascade of enzymes that activate (E1) and conjugate (E2) SUMO, and provide target specificity (E3 ligases) (Jürgen Dohmen, 2004; Gareau and Lima, 2010; Jentsch and Psakhye, 2013; Johnson, 2004; Zhao, 2018). SUMOylation can also be reversed by the action of dedicated proteases (Kunz et al. , 2018). The consequences of SUMOylation are varied and target specific (Zhao, 2018), but include conformational changes, creating and masking binding interfaces to mediate protein interactions, and competing with other lysine modifications such as ubiquitylation and acetylation (Almedawar et al. , 2012; Flotho and Melchior, 2013; Liebelt and Vertegaal, 2016; Papouli et al. , 2005; Steinacher and Schär, 2005). To date, only a handful of meiotic SUMO conjugates have been identified and studied in any detail. In budding yeast, these include the SC component Ecm11 (Humphryes et","Most mammalian, yeast and other eukaryote cells have two sets of chromosomes, one from each parent, which contain all the cell’s DNA. Sex cells – like the sperm and egg – however, have half the number of chromosomes and are formed by a specialized type of cell division known as meiosis. At the start of meiosis, each cell replicates its chromosomes so that it has twice the amount of DNA. The cell then undergoes two rounds of division to form sex cells which each contain only one set of chromosomes. Before the cell divides, the two duplicated sets of chromosomes pair up and swap sections of their DNA. This exchange allows each new sex cell to have a unique combination of DNA, resulting in offspring that are genetically",380,128,0.3368
pubmed-summarization,"occur and to what extent do alterations in autophagy contribute to disease phenotype ? autophagy is generally considered to be a cell survival mechanism , and this process also contributes to cell death in several situations . sphingolipids ( sls ) are ubiquitous components of membrane structures , and renewed interest in sls has focused on sl - induced intracellular and extracellular signaling . moreover , studies have uncovered that a dynamic balance among sl metabolites is significant in cell fate determination . here we review the key aspects of bioactive sls that have emerged as important effectors in regulating the autophagic pathway , mediating the cross talk between apoptosis and autophagy , and determining the associated cell fate . a deeper understanding of the relationship between sl metabolism and autophagy explains how intact or impaired sl - related autophagic pathways are involved in the malfunctions associated with neurodegeneration , cancer , and other diseases . we also discuss how autophagy - regulating drugs work via cells ' sl metabolism and the methods that could be used to monitor sl - related autophagy . present and future investigations regarding sl - related autophagy will help to develop novel treatment strategies to control autophagy - related diseases . sls represent a significant class of lipids that contain a backbone of sphingoid bases and are ubiquitous constituents of membranes in eukaryotes . sls were first discovered in brain extracts in 1876 , and within a century of intensive research , the chemical structures of thousands of individual sls had been elucidated . the sl metabolic pathway displays an intricate network of reactions that result in the formation of multiple sls , including ceramide ( cer ) , dihydroceramide ( dhcer ) , and sphingosine-1-phosphate ( s1p ) . first , a substantial portion of sls are derived from de novo biosynthesis in most organisms , with the condensation of serine and palmitoyl - coa catalyzed by serine palmitoyl transferase to generate dehydrosphinganine . dehydrosphinganine is subsequently reduced to form dihydrosphingosine ( sphinganine ) , which is then n - acylated by dhcer synthase to produce dhcer or cer . second , through hydrolysis via a complex lipid - turnover pathway , several specific hydrolases are involved in the turnover process , including","the autophagic process involves encompassing damaged proteins and organelles within double- or multi - membraned structures and delivering these molecules to the lytic compartments of vacuoles . sphingolipids ( sls ) , which are ubiquitous membrane lipids in eukaryotes , participate in the generation of various membrane structures , including rafts , caveolae , and cytosolic vesicles . sls are a complex family of molecules that have a growing number of members , including ceramide , sphingosine-1-phosphate , and dihydroceramide , which have been associated with the essential cellular process of autophagy . this review highlights recent studies focusing on the regulation and function of sl - associated autophagy and its role in cell fate , diseases , and therapeutic interventions .",380,122,0.3211
dialogsum,"#Person1#: how did you do on your IELTS exam? #Person2#: fantastic! I got an overall score of eight. #Person1#: that's excellent! Have you received your conditional offers yet? #Person2#: yes. I'm just waiting until I offically get admitted to the university with a conditional offer to apply for my visa. #Person1#: do you know where the visa office is? #Person2#: no. #Person1#: it's just near the Dong Si Shi Tiao subway stop. #Person2#: that's not too far away. Do you think I'll get a visa? #Person1#: have you ever gone abroad before? #Person2#: yes, I've been to Tailand, Egypt, and Japan. #Person1#: have you ever been denied a visa before? #Person2#: never. #Person1#: that's good. Are you planning on immigrating to another country? #Person2#: no, I want to come back to China after I graduate. #Person1#: that's exactly what the visa officers want to hear. Do you have enough money for tuition and room and board? #Person2#: I've received a full scholarship, so I won't need any other money to live off while I'm studying. #Person1#: I think you have a very good chance of getting a visa. I can help you prepare for the visa interview if you want. #Person2#: that's be great. The more prepared I am, the better.",#Person2# got a good result on the IELTS test and #Person2#'s going to apply for the visa. #Person1# asks #Person2# some questions that visa officers would usually ask and offers to help #Person2# prepare for the visa interview.,211,38,0.1801
scientific_lay_summarisation-elife-norm,"fusions H2B-pr-mEos2 or H2B-pr-mEosFP and imaged them at different stages to observe their developmental progression. Embryos injected with mRNA encoding for H2B-pr-mEosFP showed no visible signs of developmental impairment, similar to un-injected control embryos (— 1a and 1b). In contrast, H2B-pr-mEos2-injected embryos showed partly divided, seemingly connected nuclei and prematurely arrested in development (n=30/30) (— 1b). This apparent inability to separate the nuclei during cell division is likely due to a residual tendency of mEos2 to oligomerize, as proposed previously (Zhang et al. , 2012). As a consequence, we identified primed convertible mEosFP (pr-mEosFP) as the optimal fluorescent protein variant for in vivo primed conversion in the mouse embryo followed by long-term imaging. Next, we investigated whether a single round of green-to-red photoconversion at the four-cell stage would create a sufficiently large pool of red-converted protein that could be followed throughout development until the blastocyst stage. For this purpose, we performed confined primed conversion in a confocal system as previously described (Mohr et al. , 2016) to photoconvert a single nucleus of an H2B-pr-mEosFP expressing embryo at the four-cell stage. Primed converted embryos were then transferred and monitored for 60 hours during early embryo development in a custom built SPIM suitable for long term imaging of mouse embryos (1a). To compensate for signal dilution of the H2B-pr-mEosFP signal over time primarily due to cell division, the laser power was gradually increased throughout the imaging sessions. Embryos subjected to photoconversion of a single cell developed normally and the red daughter cells of the initially primed converted cell were clearly distinguishable from non-converted green cells up to the blastocyst stage (1b; — 2a). In addition, primed conversion itself did not impede the development of photoconverted embryos compared to non-converted control embryos (— 2b). As cells converted at the four-cell stage can be visualized up to the blastocyst stage, we wondered whether such sparsely labeled subsets of cells could aid computational reorientation and automated lineage tracing in embryos that exhibit dramatic spatial and rotational drift (Videos 1,2 and 3). Of note, while we initially imaged our embryos with time intervals of 7. 5 or 15 minutes, we found that increased sampling frequency did not recover successful lineage tracing for rotating embryos: the percentage of embryos showing spatial and rotational drift prohibitive of automated","A mouse embryo starts with one cell, which divides to create identical daughters that quickly start to multiply. Within three to four days, certain cells begin to specialize and take on specific roles. Scientists want to track these early events to understand how they give rise to an individual formed of huge numbers of cells organized in specialized tissues. To do so, researchers genetically manipulate embryos so that each cell produces fluorescent molecules that ‘glow’ under light. These embryos are grown inside a special microscope for several days. Images are taken regularly and then processed by specialized software that automatically tracks the fluorescent cells and their daughters over time. This helps reconstruct the history of each cell, and which structures they give rise to. However, many embryos move",380,128,0.3368
dialogsum,"#Person1#: Ah! It hurts. Don't touch it. #Person2#: What part hurts? #Person1#: The shoulder. #Person2#: Well, maybe you broke it. But what I'm worried about is this cut. #Person1#: It's not a cut. It's a gash! It's bigger than a cut! Ah! I need a doctor. #Person2#: C'mon. Just don't move. #Person1#: I'm bleeding too much. #Person2#: We don't have a decent First Aid Kit, do we? #Person1#: Yes. My bike has one under the seat. Get it, quick! #Person2#: There's some tape, iodine, and cloth bandages. I don't think the cloth bandages can stop the bleeding. What we need is a tourniquet. #Person1#: Wrap a few loops of the bandages around my upper arm, then twist. That will work as a tourniquet. After that, you can cut more of the bandages to cover the wound. #Person2#: Good plan. Let me put some iodine on the cut. #Person1#: No, forget that! Do the tourniquet first. I'm losing too much blood. #Person2#: Alright, alright. How did you cut this so bad?",#Person1#'s got a gash in the shoulder and gives #Person2# instructions about how to make a tourniquet to stop the bleeding.,170,21,0.1235
dialogsum,"#Person1#: what are you looking for? #Person2#: I want to buy a new camcorder for my trip this summer. #Person1#: do you know what camcorder options are available? #Person2#: not really. I thought I'd just have a look today. #Person1#: would you like to look at the new digital camcorders that have just come in? #Person2#: sure. I'd like to see the smallest camcorder that you have first. #Person1#: ok. This Sony model is their newest and our most popular camcorder. Why don't you see if you like the way it feel? #Person2#: it's very light. That would be good. How is the battery life? #Person1#: it's got an above-average battery life. It lasts up tp 12 hours and can be charged in 30 minutes. #Person2#: can you also take still photos with this? #Person1#: yes, that is an option. #Person2#: how about night vision? Can you use it in the dark? #Person1#: yes. I can show you examples of some footages that was taken with this camera in the dark. #Person2#: that's not bad at all. How's the microphone? Does it pick up much sound? #Person1#: It can record any sound that's within about 8 feet of the camera. #Person2#: how does that compare with other models? #Person1#: there are models that can pick up more sound than this one, but they're much bigger and heavier than this one. #Person2#: I guess you can't have everything, can you?","#Person2# wants to buy a new camcorder for the summer trip, #Person1# recommends the newest and most popular Sony model with above-average battery life and good night vision and can take still photos and record sounds within 8 feet of the camera.",239,42,0.1757
pubmed-summarization,"elicited by questionnaire method . the item generation for this instrument was from four sources : theory , research , observation , and expert opinion . the barriers for initiating and conducting research by faculty and pg students in indian dental schools were identified from 24 questions applicable to the indian dental education , human resource and training , research and academic environment , institutional , infrastructure , resources , funding , time related issues , and other reasons . the attitude was assessed by means of five point likert scale : strongly agree , agree , no opinion , disagree , and strongly disagree . the questions were grouped in four categories that are , institutional / departmental support related barriers , financial and training support related barriers , time - related barriers , and other general barriers . the response for each question was based on selecting between no opinions , strongly agree , agree , disagree , and strongly disagree . later during analysis , strongly agree and agree were combined into one response as percentage respondents agreeing . similarly , disagree and strongly disagree were combined into one response as percentage respondents disagreeing . a pilot study was conducted to test the reliability of the questionnaire , by considering convenience sample of 50 from the faculty of jodhpur dental college general hospital . the results of the pretested questionnaire on 50 faculty members were not included in the main study , only the reliability was assessed . the data were entered into the ms excel ( ms office version 2007 developed by microsoft , redmond , wa , usa ) and intercooled stata version 9.2 ( statacorp , tx , usa ) were employed to perform statistical analysis . the data were subjected to chi - square test to check the significance of the difference between different occupational categories . the data were entered into the ms excel ( ms office version 2007 developed by microsoft , redmond , wa , usa ) and intercooled stata version 9.2 ( statacorp , tx , usa ) were employed to perform statistical analysis . the data were subjected to chi - square test to check the significance of the difference between different occupational categories . table 1 revealed","objective : research in the dental field is progressing at mightier speed worldwide , but an unfortunately representation of india at this platform is negligible . the present study was undertaken to unearth the barriers for dental research among dental professionals in indian scenario.materials and methods : a cross - sectional questionnaire study was conducted on 1514 participant 's ( master of dental surgery and bachelor of dental surgery staff ) and postgraduates in 40 dental colleges of india selected by multistage random sampling . the response rate was 75.7% . the survey was undertaken from july 2013 to december 2013 . the survey instrument was 24-item , investigator developed , self - structured , close - ended , and self - administered questionnaire grouped into four categories",380,128,0.3368
dialogsum,"#Person1#: Can I help you? #Person2#: Yes, I've got an appointment with Mr. James Larry. He said I should meet him in his office. #Person1#: That's on the fourth floor. You take the lift to the fourth floor and walk down the corridor to the end. Turn left and you'll find a conference room. Mr. Larry's office is next to it. #Person2#: Thanks very much.",#Person2# needs to meet Mr. James Larry. #Person1# tells #Person2# how to find him.,65,14,0.2154
dialogsum,"#Person1#: Shall I make some coffee, Jane? #Person2#: That's a good idea, Charlotte. #Person1#: It's ready. Do you want any milk? #Person2#: Just a little please. #Person1#: What about some sugar? Two teaspoonfuls? #Person2#: No, less than that. One and a half teaspoonfuls please. That's enough for me. That was very nice. #Person1#: Would you like some more? #Person2#: Yes, please. I'd like a cigarette, too. May I have one? #Person1#: Of course. I think there are a few in that box. #Person2#: I'm afraid it's empty. #Person1#: What a pity! #Person2#: It doesn't matter. #Person1#: Have a biscuit instead. Eat more and smoke less! #Person2#: That's very good advice!","Charlotte makes the coffee for Jane and herself. Jane wants a cigarette but there is none, and Charlotte thinks she should smoke less and eat more.",110,26,0.2364
pubmed-summarization,"( mmse ) total score of at least 21 points . face - to - face interviews were conducted by psychiatrists / psychiatric nurses ( in shanghai ) or trained research nurses ( in singapore ) , and data were collected for a wide range of variables . for the present analysis , we extracted the following variables from the databases : age , sex , functional status , chronic diseases , self - rated health status , and mmse total score . functional status was assessed by the participant 's level of dependency in performing 8 activities of daily living ( adl ) : eating , grooming , dressing , transferring , walking , toileting , bathing , and climbing stairs . the participants were asked do you have or not have any of the following illnesses or conditions at the present time ? "" in the slas , a list of 14 medical conditions was covered in the interview . the participants were asked do you have a history of this medical problem ? medical conditions that were not included in the list were recorded under any other problems . we selected ten chronic diseases on which data were available from both samples : hypertension , diabetes , heart diseases ( in singapore : defined as any of heart attack , heart failure , or atrial fibrillation ) , stroke ( in shanghai : effects of stroke ) , kidney disorder ( in singapore : kidney failure ) , chronic obstructive lung disease ( in shanghai : emphysema / bronchitis ) , asthma , arthritis ( in shanghai : arthritis or rheumatism ) , mental illness , and cancer ( in singapore , identified from any other problems ) . in statistical analysis , the number of chronic diseases was used as an objective measure of physical health . in singapore , self - rated health status was assessed using a single question : in general , would you say your health is : excellent , very good , good , fair , or poor ? in shanghai , the same question was asked but there were four choices : excellent , good , fair , poor . excellent and very good together and created a new variable","objective . we aimed to examine the independent contributions of physical health and cognitive function to disability among chinese older adults living in two asian metropolises and explore the potential influences of environment . design and participants . cross - sectional analysis based on data from two population - based studies : the shanghai survey of alzheimer 's disease and dementia ( n = 4639 ) and the singapore longitudinal ageing study ( n = 2397 ) . disability was defined as needing help in at least one activity of daily living . results . the prevalence of functional disability was higher in shanghai sample ( 5% ) than that in singapore sample ( 1.8% ) . number of chronic diseases , self - rated health status ,",380,128,0.3368
pubmed-summarization,"of > 44.4 mm / l , the serum osmolarity was 382 mm / kg ( normal : 275 - 300 mm / kg ) and the hemoglobin a1c was 0.082 hb fraction . the serum ph was 7.348 and the bicarbonate was 26.2 mm / l ( normal : 21 - 28 the c - reactive protein was normal at 3.9 mg / l ( normal : 0.1 - 4.7 mg / l ) . g / l ) , respectively . at shortly before seizure , the sledai score was 12 . the seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit mentioned above . the patient became asymptomatic and she was discharged 10 weeks after admission under maintenance therapy with prednisolone 10 mg , insulin glargine 12 unit and nateglinide 270 mg . on follow - up 1 , 2 , and 3 month after discharge , the hba1c was 0.051 , 0.049 , and 0.06 hb fraction , respectively . 1 , 2 . the patient remained asymptomatic under maintenance therapy with deflazacort 12 mg and without insulin or medication for blood sugar control . in patients with lupus nephritis , the causes of seizure are a multiplicity of different factors , such as cns involvement of sle , infections , hypertension and metabolic derangement . a large prospective study reported that infection was the most common cause of neurologic episodes and primary involvement of sle was the secondary cause ( 8) . the presence of seizure increases the risk of death in patients with sle by approximately 2-fold ( 2 , 9 ) . when seizure is noted in patients with lupus nephritis , identifying the cause and proper treatment are important to improve survival . most studies have revealed that reversible posterior leukoencephalopathy syndrome and cerebral vascular accident are other important causes of seizure in patients with lupus nephritis . by contrast , the neurologic episodes by purely metabolic derangement without infection or cns lupus are very rare , and especially hhs was a seldom cause of seizure ( 8) . steroid is associated with the risk of hyperglycemia in patients with or without diabetes ( 10 , 11 ) . this inhibit insulin signalling in skeletal muscle","a 51-yr - old female was referred to our outpatient clinic for the evaluation of generalized edema . she had been diagnosed with idiopathic thrombocytopenic purpura ( itp ) . she had taken no medicine . except for the itp , she had no history of systemic disease . she was diagnosed with systemic lupus erythematosus . immunosuppressions consisting of high - dose steroid were started . when preparing the patient for discharge , a generalized myoclonic seizure occurred at the 47th day of admission . at that time , the laboratory and neurology studies showed hyperglycemic hyperosmolar syndrome . brain mri and eeg showed brain atrophy without other lesion . the seizure stopped after the blood sugar and serum osmolarity declined below the upper normal limit .",380,128,0.3368
scientific_lay_summarisation-elife-norm,"it may be necessary for a transferred gene to confer a benefit to its new host in order to be stably maintained in the host genome over the long term. Given these evolutionary dynamics, there may be very few niche-transcending genes (Wiedenbeck and Cohan, 2011), defined as genes that are useful in different physiological capabilities, cellular structures, and ecological niches, which repeatedly increase fitness of each recipient across the whole diversity of life and can be stably and repeatedly transferred between very divergent organisms. Among the few putative cases, there is a pore-forming toxin domain that appears to have been anciently transferred between diverse lineages (Moran et al. , 2012). However, the distribution of the transfer across the tree of life is unclear because archaeal sequences were not included in phylogenetic analyses due to low support values. Other candidate genes encode proteins involved in nucleotide metabolism, intramembrane proteolysis, or membrane transport, but the transfer events defy clear interpretations due to their deep antiquity in evolutionary time and the confounding issues of ancient paralogy (Lundin et al. , 2010; Koonin et al. , 2003; McClure, 2001; McDonald et al. , 2012). Moreover, these transfers are often not functionally validated in the recipient taxa. Here we demonstrate for the first time, to our knowledge, that a functional antibacterial gene family scattered across the tree of life in diverse ecological contexts. This bacterial gene encodes a glycosyl hydrolase 25 (GH25) muramidase, a peptidoglycan-degrading lysozyme that hydrolyzes the 1,4-β-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine in the bacterial cell wall. Typically found in bacteria (Cantarel et al. , 2009), the lytic enzyme classically functions in cell division and cell wall remodeling (Vollmer et al. , 2008), while in bacteriophages they lyse bacterial peptidoglycan at the end of the phage life cycle (Fastrez, 1996). Although members of the GH25 muramidase family have been noted in other taxa (Korczynska et al. , 2010; Nikoh et al. , 2010), extensive analysis of their evolutionary history and functions have not been undertaken. We hypothesized that the transfer of antibacterial genes from bacteria to archaea and to eukaryotes bestows a niche-transcending adaptation that overcomes the barriers against repeated and evolutionarily stable HGT of the same type of gene across the tree of life. During a homology search, we uncovered 75","Living things inherit most of their genetic material from their parents, so genes tend to be passed on from one generation to the next—from ancestors to descendants. Sometimes, however, DNA is transferred from one organism to another by other means. These events, collectively called horizontal gene transfer, are fairly common in nature; genes have been passed between different species as well as between different groups of organisms. For example, genes that confer resistance to antibacterial drugs have transferred from one species of bacteria to another, and other genes have also ‘jumped’ from bacteria to plants or animals. Now Metcalf et al. have studied a gene that first arose in bacteria and that encodes an enzyme called a lysozyme. This enzyme breaks down the outer casing of a bacterial",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Hitherto, membralin has been a protein of unknown function. Here, we show that membralin mutant mice manifest a severe and early-onset motor neuron disease in an autosomal recessive manner, dying by postnatal day 5–6. Selective death of lower motor neurons, including those innervating the limbs, intercostal muscles, and diaphragm, is predominantly responsible for this fatal phenotype. Neural expression of a membralin transgene completely rescues membralin mutant mice. Mechanistically, we show that membralin interacts with Erlin2, an endoplasmic reticulum (ER) membrane protein that is located in lipid rafts and known to be important in ER-associated protein degradation (ERAD). Accordingly, the degradation rate of ERAD substrates is attenuated in cells lacking membralin. Membralin mutations or deficiency in mouse models induces ER stress, rendering neurons more vulnerable to cell death. Our study reveals a critical role of membralin in motor neuron survival and suggests a novel mechanism for early-onset motor neuron disease. The endoplasmic reticulum (ER) is a membrane-enclosed cellular organelle that plays an essential role in the folding of membrane-bound and secreted proteins, synthesis of lipids and sterols, and storage of free Ca2+. ER stress is often triggered by the accumulation of unfolded proteins due to pathological conditions, such as DNA sequence mutations, transcriptional and translational errors, or protein folding failure (Kim et al. , 2008; Lin et al. , 2008). Mammalian cells have evolved an intricate system with multiple signaling pathways to respond to ER stress, collectively termed the unfolded protein response (UPR) (Kim et al. , 2008; Lin et al. , 2008; Walter and Ron, 2011). If unchecked, ER stress eventually causes cell death, including neuronal death in neurodegenerative diseases (Lindholm et al. , 2006; Scheper and Hoozemans, 2009; Hetz and Mollereau, 2014). Increased ER stress is thought to play an early role in motor neuron diseases, including amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth (CMT) (Atkin et al. , 2006; Nagata et al. , 2007; Nishitoh et al. , 2008; Kanekura et al. , 2009; Saxena et al. , 2009). Manifestations and consequences of ER stress have been studied in the pathogenesis of SOD1 mutant mice, a commonly used model of ALS that expresses mutant human SOD1 protein as found in some inherited forms of ALS (Atkin et al. , 2006; Kanekura et al. , 2009; Saxena et al. ,","As new proteins are built inside a cell, many will pass into a structure called the endoplasmic reticulum for processing. There, the proteins are folded into the specific three-dimensional shapes that allow them to carry out their respective jobs. Sometimes the folding process goes awry, leading to a build-up of unfolded proteins that stress the endoplasmic reticulum and can kill the cell. Brain cells are particularly vulnerable to death from endoplasmic reticulum stress. To combat a deadly build-up of unfolded proteins, each cell has systems that respond when the endoplasmic reticulum is under stress. Unchecked stress on the endoplasmic reticulum has been linked to diseases like amyotrophic lateral sclerosis (called ALS for short). In diseases like ALS, the nerve cells that control muscle movements gradually die off, causing",380,128,0.3368
dialogsum,"#Person1#: My brother gave me a baby cat yesterday. I can keep it as my pet. #Person2#: I don't understand. Why do you want a cat? #Person1#: Cats are beautiful and lovely, aren't they? #Person2#: No, cats are too dirty. They are lazy and cunning. I don't like them at all. #Person1#: I don't think so. I think cats are sweet. #Person2#: You can keep the cat, but you should keep it away from me.","#Person1# got a cat and #Person1# loves it, but #Person2# doesn't like cats.",75,13,0.1733
dialogsum,"#Person1#: Senator Kirk, if you are elected again, what do you plan to do? #Person2#: Well, first, I plan to create more jobs. My office will work hard to make our state a good place for businesses. Businesses will hire more people, and more people will be able to work and feed their families here. #Person1#: What do you think about the environment? #Person2#: I am a strong supporter of protecting the environment. I think that we need to build more trains. We need more people to ride their bikes. We need to protect the air. Everybody needs clean air, and when I am elected Senator, I will make sure we protect the earth. #Person1#: In 2009, you voted to let factories put their garbage into the river. Is that correct? #Person2#: No! That's not correct. I never voted to let factories put their garbage in the river. You have your facts wrong. I am a strong supporter of business, but I am an even stronger supporter of the environment.","Senator Kirk tells #Person1# he will create more jobs and help protect the earth if elected again, and he denies he had voted to let factories put their garbage into the river.",170,32,0.1882
dialogsum,#Person1#: Why is the car before us stopping? #Person2#: What's going on? #Person1#: Look. Two cars are standing right in the middle of the road and the drivers are shouting rude words to each other. That's why that car stops. #Person2#: More and more people easily get irritated while driving. #Person1#: Yes. This is what is called road rage.,#Person1# and #Person2# witness and discuss a road rage.,59,9,0.1525
pubmed-summarization,"electrostatic interactions comprise one of the principle interatomic forces , along with exchange - repulsion , dispersion , and polarization or induction . the importance of electrostatic interactions is paramount at long range and for polar molecules . much development effort has been focused on computational treatment of long - range electrostatics , e.g. , the development of particle - meshed ewald ( pme ) methods . electrostatic interactions at short range have received less consideration until recently . at close distances , a spherical approximation of atomic charge distributions is insufficiently accurate and use of atomic multipole expansions provides much greater flexibility in modeling complex electrostatic potentials near a molecular surface , an insight which inspired the development of the amoeba force field . nonetheless , at very close interatomic distances , when electron clouds overlap , a point multipole approximation becomes inadequate . the electrostatic potential within a spherical electron cloud no longer behaves as a simple 1/r interaction potential at small separation distances . such deviation from a simple coulomb potential is referred to as a penetration effect . while the charge penetration effect leads to a negative correction to energy at typical molecular interaction distances , where the electron electron penetration is dominant , it can be repulsive at very short range . a recent study by lewis and co - workers reported the counterintuitive result that any ring substitutions of the benzene dimer ( parallel ) with electron - withdrawing or electron - donating groups yield more favorable electrostatic contributions than the unsubstituted benzene benzene dimer itself . this result is contrary to the conventional thought that such interactions are correlated with the ability to withdraw or donate electrons to the cloud as described by the hunter sanders rules . sherrill and co - workers suggested this is because the electrostatic interactions in such systems at the stacking distance exhibit a significant charge penetration effect . the multipole model , which the hunter sanders rules are based upon , can not correctly account for such effects . moreover , in a recent study of aromatic crystals , a charge penetration corrected amoeba - like model predicted better crystal properties than the uncorrected model . it was shown that point atomic multipoles consistently predict positive (","classical molecular mechanics force fields typically model interatomic electrostatic interactions with point charges or multipole expansions , which can fail for atoms in close contact due to the lack of a description of penetration effects between their electron clouds . these short - range penetration effects can be significant and are essential for accurate modeling of intermolecular interactions . in this work we report parametrization of an empirical charge charge function previously reported ( piquemalj .- p . ; j. phys . chem . a2003 , 107 , 1035326313624 ) to correct for the missing penetration term in standard molecular mechanics force fields . for this purpose , we have developed a database ( s1017 ) of 101 unique molecular dimers , each at 7 different intermolecular distances",380,128,0.3368
pubmed-summarization,"a priori assumptions of migration , displaying only the tree topology . ( b ) values of the f3 ( asian - snp vezo , x ; yoruba ) statistics are represented by dots with standard error bars . the color of each dot corresponds to the fst distances between the asian ancestry of the vezo and each asian population using a gray - yellow - red color scale from the highest ( 0.196 ) to the lowest values ( 0.02 ) . ( c ) the cumulative shared ibd ( mb ) between pairs of malagasy : asian individuals were averaged to obtain one value of ibd sharing per asian population . the numbers 115 correspond to the populations presented on the treemix dendrogram with the addition of 16 which stands for brahmin indian . localization of the asian ancestry of malagasy by ( a ) a treemix dendrogram , ( b ) fst distances and f3 statistics , all based on the asian - snp data set , and ( c ) a shared identity - by - descent ( ibd ) analysis based on haplotypes inferred from the high density of snp data set . ( a ) the treemix dendrogram was inferred imposing no a priori assumptions of migration , displaying only the tree topology . ( b ) values of the f3 ( asian - snp vezo , x ; yoruba ) statistics are represented by dots with standard error bars . the color of each dot corresponds to the fst distances between the asian ancestry of the vezo and each asian population using a gray - yellow - red color scale from the highest ( 0.196 ) to the lowest values ( 0.02 ) . ( c ) the cumulative shared ibd ( mb ) between pairs of malagasy : asian individuals were averaged to obtain one value of ibd sharing per asian population . the numbers 115 correspond to the populations presented on the treemix dendrogram with the addition of 16 which stands for brahmin indian . to explore this connection in more detail , we turned to the high density snp data set ( 551 individuals from 24 populations genotyped for 374,189 snps ; supplementary table s1 , supplementary material online )","malagasy genetic diversity results from an exceptional protoglobalization process that took place over a thousand years ago across the indian ocean . previous efforts to locate the asian origin of malagasy highlighted borneo broadly as a potential source , but so far no firm source populations were identified . here , we have generated genome - wide data from two southeast borneo populations , the banjar and the ngaju , together with published data from populations across the indian ocean region . we find strong support for an origin of the asian ancestry of malagasy among the banjar . this group emerged from the long - standing presence of a malay empire trading post in southeast borneo , which favored admixture between the malay and an autochthonous borneo",380,128,0.3368
scientific_lay_summarisation-elife-norm,"cells (Fridy et al. , 2014; Lim et al. , 2013; Morsut et al. , 2016). Co-culturing sGFP sender cells with αGFP receiver cells led to GFP transfer and labeling of the receiver cells (1A, B and — 1A). Receiver cell labeling required direct cell-cell contact, active membrane dynamics, and pairing between sGFP and its cognate αGFP receptor (1C, D and — 1B, C). Notably, sGFP transfer was accompanied by reduced GFP on the sender cells, downregulation of αGFP from the surface of the receiver cells and was partially blocked by chemical inhibitors of endocytosis – all consistent with active GFP transfer and internalization into receiver cells (— 1D–F). To characterize the kinetics of G-baToN-mediated receiver cell labeling, we performed co-culture time course experiments with time-lapse imaging and flow cytometry readouts. Time-lapse imaging showed rapid transfer and internalization of GFP by receiver cells (1E and Video 1). GFP transfer could be detected within five minutes of co-culture and was half-maximal after 6 hr (1F and — 1G-H). Importantly, GFP fluorescence in receiver cells decayed rapidly after isolation of touched receiver cells from sender cells, thus documenting the transient labeling of receiver cells (— 1I). To determine the sensitivity of this system, we co-cultured receiver cells with different ratios of sender cells. The fraction of labeled receiver cells was proportional to the number of sender cells, and even the addition of very few sender cells (representing less than one sender cell to 105 receiver cells) was sufficient to label rare receiver cells (1G, H). Thus, the transfer of GFP to αGFP-expressing cells is a rapid and sensitive method to mark cells that have physically interacted with a predefined sender population. To further characterize the interaction reporter system, we deconstructed the G-baToN design into three functional modules: (1) the transmembrane domain of αGFP on the receiver cells; (2) the pairing between GFP and αGFP; and (3) the transmembrane domain of sGFP on the sender cells. We initially used a published sGFP-αGFP pair in which the Notch1 transmembrane domain links the LaG17-αGFP nanobody onto the receiver cell surface and the PDGFR transmembrane domain links sGFP onto the sender cell surface (Morsut et al. , 2016). Replacement of the Notch1 transmembrane domain of αGFP with different transmembrane domains allowed us to quantify their impact","It takes the coordinated effort of more than 40 trillion cells to build and maintain a human body. This intricate process relies on cells being able to communicate across long distances, but also with their immediate neighbors. Interactions between cells in close contact are key in both health and disease, yet tracing these connections efficiently and accurately remains challenging. The surface of a cell is studded with proteins that interact with the environment, including with the proteins on neighboring cells. Using genetic engineering, it is possible to construct surface proteins that carry a fluorescent tag called green fluorescent protein (or GFP), which could help to track physical interactions between cells. Here, Tang et al. test this idea by developing a new technology named GFP-based Touching Nexus, or G-baToN",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19. SARS-CoV-2 is the virus causing the global pandemic ‘coronavirus diseases 2019’ (COVID-19). This is a zoonotic beta-coronavirus from bats that causes severe acute respiratory syndrome (Lu et al. , 2020). Its effects on human physiology extends well beyond the lung as it unleashes a cytokine storm to alter immune response (Chen et al. , 2020) and cause disseminated intravascular coagulation (Lillicrap, 2020). It also exhibits multiorgan tropism that impacts kidney, liver, heart and brain function (Puelles et al. , 2020). Among its structural elements, the SARS-CoV-2 Spike protein is critical for viral attachment, fusion and entry into host (Hoffmann et al. , 2020a; Li et al. , 2003; Lan et al. , 2020). The RBD region of Spike enables binding to its primary human cellular receptor, angiotensin-converting enzyme-2 (ACE2), which is ubiquitously expressed on epithelial, endothelial and blood cells (Li et al. , 2003; Hamming et al. , 2004). A role for heparan sulfates in viral entry has also been proposed (Clausen et al. , 2020). Once bound, viral fusion and entry depends on two proteolysis sites, the furin/RRAR-S site located between the Spike S1 and S2 subunits, and a second S2’/SKR-S site (Belouzard et al. , 2009). A variety of enzymes including TMPRSS2 (transmembrane protease, serine 2) and cathepsin-L may aid viral entry (Hoffmann et al. , 2020b; Matsuyama et al. , 2005; Shang et al. , 2020). While inhibitors","COVID-19 is an infectious disease caused by the virus SARS-CoV-2. To access the internal machinery necessary for its replication, the virus needs to latch onto and then enter host cells. Such processes rely on specific ‘glycoproteins’ that carry complex sugar molecules (or glycans), and can be found at the surface of both viruses and host cells. In particular, the viral ‘Spike’ glycoprotein can attach to human proteins called ACE2, which coat the cells that line the inside of the lungs, heart, kidney and brain. Yet the roles played by glycans in these processes remains unclear. To investigate the role of Spike and ACE-2 glycans, Yang et al. designed a form of SARS-CoV-2 that could be handled safely in the laboratory. How these viruses infect human kidney cells that",380,128,0.3368
scientific_lay_summarisation-elife-norm,"enhances signaling efficiency by assembly of spatially distinct subcellular complexes for different cellular tasks (Weng et al. , 1999; Pertz, 2010). The PTEN C2 domain binds the plasma membrane and interacts with the scaffold protein β-Arrestin1 (Lima-Fernandes et al. , 2011) that in turn binds and suppresses ARHGAP21 (Anthony et al. , 2011), a member of a highly conserved class of RhoGAPs (Bos et al. , 2007; Anderson et al. , 2008). ARHGAP21 regulates the small GTPases, Cdc42 (Dubois et al. , 2005) and RhoA (Anthony et al. , 2011). These GTPases have overlapping, complementary functions required for mitotic spindle orientation and consequent control of the cell division axis, cytokinetic furrow positioning, daughter cell size and tissue morphogenesis (Morin and Bellaïche, 2011). Both Cdc42 and RhoA drive actin nucleation and cortical stiffening (Ma et al. , 1998; Eisenmann et al. , 2007) required for spindle orientation (Johnston et al. , 2013). Furthermore, Cdc42 crosstalk with protein kinase c zeta [PRKCZ] (Noda et al. , 2001; Durgan et al. , 2011) localizes force generators within the cell cortex that act via astral microtubules to orientate the spindle (Hao et al. , 2010). ARHGAP21 has high GAP activity for Cdc42 (Dubois et al. , 2005) and its Pac-1 homologue regulates multicellular patterning in C. elegans by spatial regulation of Cdc42 (Anderson et al. , 2008; Klompstra et al. , 2015). Here, we investigate PTEN spatiotemporal coordination of mammalian glandular morphogenesis through conserved juxtamembrane β-Arrestin1-ARHGAP21 interactions, using 3D colorectal cancer (CRC) model systems. To substantiate physiological relevance of these processes, we also investigate their role in morphogenesis of 3D multicellular organoids isolated from normal colon. β-Arrestin1 scaffolds juxtamembrane signaling networks (Kovacs et al. , 2009), binds ARHGAP21 (Anthony et al. , 2011) and governs PTEN catalytic and noncatalytic functions (Lima-Fernandes et al. , 2011). To ascertain whether PTEN regulates membrane-associated β-Arrestin1 and ARHGAP21, we conducted expression and simple fractionation studies in PTEN-expressing [Caco-2 and HCT116] and -deficient [Caco-2 ShPTEN (ShPTEN) and PTEN -/- HCT116 (PTEN -/-) ] cells. We found near-significant or significant differences of total lysate β-Arrestin1 and ARHGAP21 between PTEN-expressing and -deficient cells [Caco-2 vs ShPTEN (1A, B) and HCT116 vs PTEN -/- cells (—supplements 1 and 2) ]. To infer subcellular localization of β-Arrestin1 and ARHGAP21, we performed membrane fractionation","The protein PTEN helps to organize cells in the body to form complex structures. In particular, it collects signals from a cells’ surroundings and changes where cells divide so new cells are produced in the right places. The control of cell division by PTEN is also thought to help limit the progression and spread of cancer. PTEN can interact with another protein called β-Arrestin1, which behaves as a so-called scaffolding protein – in other words, one that helps groups of proteins to interact with each other. β-Arrestin1 has been found to control cell division via a series of other proteins, including ARHGAP21 and Cdc42. The relationship between PTEN and these other proteins in dividing cells is still not fully understood. Javadi, Deevi et al. studied PTEN in human",380,128,0.3368
dialogsum,"#Person1#: Well, to come straight to the point, could you tell us something about your new price? #Person2#: Most willingly. It's 600 dollars per ton. #Person1#: That's a high price. #Person2#: But you know, the price of this article has soared up since last year. #Person1#: I know. But I must say it's still unacceptable. Couldn't you make a discount for me? You see, we have such a long-term cooperation. And our business could be mutually beneficial. #Person2#: OK. I can make a special offer for you. This price is based on careful calculations. And it is the lowest price we can offer to you.","#Person1# persuades #Person2# to make a discount, #Person2# agrees to offer the lowest price.",105,14,0.1333
dialogsum,"#Person1#: How good are you at sports, Bill? #Person2#: Are you kidding? I'm terrible! But I love to watch sports. I go to football or baseball games a lot. And I read sports magazines every week. #Person1#: Wow! #Person2#: Do you like sports, Janice? #Person1#: Oh, yes. I like to exercise. But I don't watch sports or buy sports magazines. I don't have much time to do those things. #Person2#: Oh, I see. You know, we spend time doing different sports. How much time do you spend exercising? #Person1#: Well, I guess I exercise about two hours a day. I do aerobics three times a week, and the other days I play badminton1 with my husband. I always feel good afterward. #Person2#: That's great! I've heard people say that before. #Person1#: Well, why don't you try to get some exercise? It's difficult, but very rewarding. #Person2#: Oh, I'm too lazy to play sports, and I'm not good at anything either. It hardly excites me.",Bill doesn't like doing sports but loves to watch sports. Janice likes to exercise but she doesn't watch sports or buy sports magazines. She suggests Bill to get some exercise.,164,30,0.1829
dialogsum,"#Person1#: Annie, some friends of mine have just moved out of this flat. It might be just what you and Jean and Emily are looking for-three bedrooms in a very quiet location. #Person2#: Well, that's important. I can't bear noise. What's the cost? #Person1#: About 450 a month, I think. Rather a strict landlady, but she keeps the house perfectly. #Person2#: Where is it? #Person1#: Five minutes' bus ride from the school, near Jean's college. There's a bus stop just outside the house. Let me know as soon as possible if you want it, or it'll be taken.",#Person1# tells Annie there's a vacant room in #Person1#'s flat and tells her the cost and location.,98,17,0.1735
pubmed-summarization,"lead is a soft , pliable , bluish - grey metal resistant to corrosion , that exists in both organic and inorganic forms . this metal does not conduct electricity and it owns antiradiation properties . lead poisoning in children is an important health problem , accounting for 0.6% of the global burden of the disease according to the world health organization . according to the national health and nutrition examination survey data , from 2007 to 2010 , approximately 535,000 children aged 1 to 5 years , meaning 2.6% , presented blood lead level above 5 g / dl . even though lead is everywhere the ways of contamination include ingestion , inhalation , prenatal exposure , and dermal exposure , but the most important and frequent ones are ingestion and inhalation . the half - life of lead is between 30 and 40 days in men , while in children and pregnant women it can be longer . it binds to the sulfhydryl group of proteins leading to toxicity for multiple enzyme systems . the clinical presentation of lead poisoning involves nervous , hematologic , and renal systems impairment , but it can also lead to gastrointestinal disorders ( anorexia , vomiting , constipation , abdominal pain ) , hypertension , and fertility impairment . neurological symptoms include ataxia , stupor , coma , convulsions , hyperirritability , reduced iq , shortened attention span , increased antisocial behavior , reduced educational attainment , and even death . impairment of the hematological system may involve either disruption of heme synthesis or hemolysis , leading to anemia with its specific clinical signs , like weakness and fatigue . the effects of lead on the renal system consist in proximal tubular function impairment leading to aminoaciduria , glycosuria , and hyperphosphaturia , interstitial nephritis in chronic exposure , and also impairment of calcium metabolism by interfering with activation of vitamin d 1,2-dihydroxy cholecalciferol . the diagnosis is established on the blood lead level , higher than 40 g / dl for occupational and 30 g / dl for nonoccupational exposure . primary and secondary preventions should be the first steps in the management of lead poisoning as public health problem . if a patient is found with high blood lead level","abstractbackground : lead is a toxic element of the environment which leads to major complications once it enters the blood stream , affecting multiple organs and systems of the body.methods:we present the case of a 16-year - old girl , diagnosed with lead poisoning after occupational exposure due to the fact that the girl was actively involved in the family 's pottery business.history revealed that the girl participated in the process of pottery , her father was also diagnosed with lead poisoning 2 years before . the patient 's personal history underlined that approximately 1 year ago she presented with severe abdominal pain , being diagnosed with acute appendicitis and she underwent appendectomy , but the pain persisted , thus due to family history of lead poisoning ,",380,128,0.3368
pubmed-summarization,"in the recent past , even many historians of medicine and science have endorsed the widespread belief that the exodus of central european scientists and physicians during the nazi period could readily be described in terms of a linear equation of the subtractions and additions of intellect . this common interpretation has simplistically viewed the massive exodus of academics , intellectuals , and scientists after 1933 as an enrichment primarily of the north american and british medical and academic communities ( see medawar & pyke , 2001 or cornwell , 2003 , for example ) . although such a perspective is not entirely wrong when a rather quantitative meta - perspective is taken , it becomes less compelling when the individual biographies of the respective physicians and scientists themselves are taken into account and are placed in their contingent work environments . this includes their work situations , skill sets , along with the personal and psychological resources of each migr neuroscientist ( cf . this contribution introduces some of those local and cultural factors which implicated the arrival , acceptance , and integration of many german - speaking migrs doctors and brain researchers into canada , following their exile between 1933 and 1945 , which have largely gone unnoticed by the relevant scholarship on twentieth - century history of neuroscience . when tracing their career paths into the 1960s , during which the scientific research landscapes in canadian biomedicine gradually came to change with the creation of the medical research council ( mrc ) , the complex cultural modes and scientific interchanges associated with the forced migration process become fairly obvious ( mrc , 2000 ) . as the main title ( learning soft skills the hard way ) of this article implies , the integration of german - speaking migrs neuroscientists can not simply be perceived in terms of a supplementation of longstanding north american scientific traditions but needs to be viewed as a very complex process of acculturation on multiple levels of the social and cultural organization of contemporary canadian and american research landscapes . it is further more of a seemingly modern interest in the cultural makeup of science to analyze and understand the process of forced migration in the neuroscientific field while mapping the often","abstractthis article is a historiographical exploration of the special forms of knowledge generation and knowledge transmission that occur along local cultural boundaries in the modern neurosciences . following the inauguration of the so - called law on the re - establishment of a professional civil service in nazi germany on april 7 , 1933 , hundreds of jewish and oppositional neurologists , neuropathologists , and psychiatrists were forced out of their academic positions , having to leave their home countries and local knowledge economies and traditions for canada and the united states . a closer analysis of their living and working conditions will create an understanding of some of the elements and factors that determined the international forced migration waves of physicians and clinical neuroscientists in the twentieth",380,128,0.3368
scientific_lay_summarisation-elife-norm,"that miR-182 targets BRCA1 (Moskwa et al. , 2011). Over-expression of miR-182 in triple negative breast tumor lines (in vitro and in vivo) suppresses HR via down-regulation of BRCA1 and sensitizes cells to PARP inhibitors. This served as a ‘proof-of principle’ that miRNAs may influence HR-mediated repair of DSBs. In this study, we used PARP inhibitor sensitivity as a marker for HR deficiency to conduct a functional screen to identify miRNAs that down-regulate HR. Over-expression of seven miRNAs significantly reduced HR-mediated DSB repair. Based on their expression in a panel of breast and ovarian lines, we focused on characterizing the mechanism and physiological relevance of miR-1255b, miR-193b*, and miR-148b*. Despite lacking canonical binding sites, miR-1255b, miR-193b*, and miR-148b* associate with the BRCA1, BRCA2, and RAD51 transcripts and regulate their expression. Remarkably, the miRNA-mediated regulation of these genes is cell cycle dependent and inhibition of miR-1255b, miR-193b*, and miR-148b* leads to enhanced expression of BRCA1, BRCA2, and RAD51 specifically in the G1 phase. A functional consequence of inhibiting these miRNAs is a basal increase in DSBs in G1 cells. This phenotype can be reversed by silencing CtIP (the BRCA1-associated DNA end resection factor) which initiates HR-mediated DSB repair. Furthermore, deletion of these miRNAs in two independent cohorts of high-grade serous ovarian tumors correlates with increase in LOH. To systematically identify miRNAs that impact PARP inhibitor sensitivity, we screened two commercially available miRNA mimic libraries (Qiagen, Valencia, CA and Applied Biosystems, Grand Island, NY). miRNA mimics are 20–22 nt, chemically modified double-stranded RNA molecules designed to mimic endogenous mature miRNAs. The miRNA mimics from Qiagen and Applied Biosystems have proprietary chemical modifications that cause inactivation of the ‘passenger’ strand, allowing the ‘active’ strand to associate with target transcripts and regulate gene expression. The goal was to identify miRNA mimics that sensitize breast tumor cells, MDA-MB231 to the clinical PARP inhibitor, ABT888 (1A, B). The miRNA mimics from Applied Biosystems impacted ABT888 sensitivity over a broad range, ∼10- to 12-fold difference between the mimics with the highest impact on viability and the control mimics. Whereas the viability range with the mimics from Qiagen was limited to 3- to 4-fold. BRCA2 siRNA served as a positive control for each plate and the mimic for miR-182 served as an internal control. BRCA2 is an important","The DNA in a cell is damaged thousands of times every day. One of the most serious types of damage involves something breaking both of the strands in the double helix. Such a double-strand break can delete genes or even kill the cell. In fact, conventional cancer therapy kills cancer cells by causing irreparable double-strand breaks. Conversely, a normal cell that is constantly exposed to DNA damaging agents can become a tumor if double-strand breaks are incorrectly repaired. An efficient and accurate double-strand break repair system needs to be in place to prevent this transformation. Therefore, an in-depth understanding of double-strand break repair and the factors involved are important for both gaining insight into the cause of cancer and to improve cancer therapy. Cells have evolved several different",380,128,0.3368
scientific_lay_summarisation-elife-norm,"RNA virus infections are detected by the RIG-I family of receptors, which induce type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion-like polymers that activate the cytosolic kinases IKK and TBK1, which in turn activate NF-κB and IRF3, respectively, to induce interferons. Here we show that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and TRAF6, through distinct TRAF-binding motifs. Mutations of these motifs that disrupted MAVS binding to TRAFs abrogated its ability to activate IRF3. IRF3 activation was also abolished in cells lacking TRAF2,5, and 6. These TRAF proteins promoted ubiquitination reactions that recruited NEMO to the MAVS signaling complex, leading to the activation of IKK and TBK1. These results delineate the mechanism of MAVS signaling and reveal that TRAF2,5, and 6, which are normally associated with NF-κB activation, also play a crucial role in IRF3 activation in antiviral immune responses. The innate immune system deploys germline-encoded pattern recognition receptors (PRRs) to detect pathogen invasion. Pathogen-associated molecular patterns (PAMPs) such as bacterial LPS and viral dsRNA are recognized by PRRs such as membrane-bound Toll-like receptors (TLRs) and cytosolic retinoic-acid-inducible gene-I (RIG-I) -like receptors (RLRs) (Akira et al. , 2006). Upon activation, the receptors trigger the production of type-I interferons (e. g. , IFNα and IFNβ) and other cytokines (e. g. , TNFα and IL-6) to rapidly restrict the infection and further activate the adaptive immune system (Pichlmair and Reis e Sousa, 2007; Stetson and Medzhitov, 2006). RLRs include RIG-I, MDA5, and LGP2 (Yoneyama et al. , 2004; Yoneyama and Fujita, 2008). All RLRs contain a DEAD/H-box RNA helicase domain, which binds to double-stranded RNA. RIG-I and MDA5, but not LGP2, harbor N-terminal tandem CARD domains that are crucial for triggering type-I IFN production. RIG-I also contains a C-terminal regulatory domain that specifically binds to RNA bearing 5′ triphosphate (Hornung et al. , 2006; Pichlmair et al. , 2006; Cui et al. , 2008). Upon binding to different viral RNA ligands, RIG-I and MDA5 activate another CARD-containing protein, mitochondrial antiviral signaling protein (MAVS, also known as IPS-1, VISA, and CARDIF), presumably through CARD–CARD interaction. MAVS in turn activates the transcription factors IRF3 and NF-κB, leading to interferon induction (Kawai et al. , 2005; Meylan et al. , 2005; Seth et al. , 2005; Xu et al. ,","The innate immune system can detect and destroy viruses, bacteria and other pathogens that enter the human body. In particular, inside cells, viral RNA can bind to and activate a protein called RIG-I. This protein switches on another protein, called MAVS, which can activate other copies of itself. These MAVS molecules then aggregate together on the membrane of mitochondria and send a signal that leads to the production of small proteins, called cytokines, which stimulate an inflammatory response and ultimately neutralize the virus. Although many of the proteins that are activated by MAVS in the innate immunity signaling pathway have been identified, precisely how MAVS transmits this signal is unknown. Now, Liu et al. explore how this protein can propagate signals in the innate immune response by monitoring",380,128,0.3368
dialogsum,"#Person1#: What's this then? #Person2#: It's my geography, sir. The Map of Africa you set us. #Person1#: But this should have been handed in last Thursday. #Person2#: Yes, I know, sir. I'm sorry. #Person1#: Well, what's your excuse then? #Person2#: My mother's been ill and I had to stay at home. #Person1#: Oh, Yes? #Person2#: It's true, sir.",#Person2# apologizes to #Person1# for handing in the geography late and explains the reasons.,58,14,0.2414
dialogsum,"#Person1#: Oh, it's already 10:30 now. I haven't finished my homework yet. #Person2#: Don't worry. The clock on the wall is 20 minutes fast. #Person1#: Great. Please tell Alice to wait for me till 11 o'clock. #Person2#: Where are you going? #Person1#: We're going to Sally's birthday party. #Person2#: When will it be? #Person1#: It will be at about 12 o'clock in the rose restaurant.","#Person1# thinks it's 10:30, but #Person2# says the clock is 20 minutes fast.",65,13,0.2
scientific_lay_summarisation-elife-norm,"models targeting fragile X syndrome and neurofibromatosis (Dolan et al. , 2013; Hayashi et al. , 2007; Molosh et al. , 2014). However, the mechanism by which PAK1 exerts such diverse therapeutic effects remains elusive. Quite interestingly, many of these same animal models of neurodevelopmental disorders also exhibit pronounced alterations in eCB signaling (Földy et al. , 2013; Jung et al. , 2012), and several reports have now suggested that, like PAK1, targeting eCB signaling may provide benefit in these conditions (Busquets-Garcia et al. , 2013; Qin et al. , 2015). As these animal models share a common deficit in E/I balance, which appear to involve critical roles of both PAK1 and eCB signaling, we have hypothesized that PAK1 might be a critical player in the regulation of E/I homeostasis through an interaction with eCB signaling. Consistent with this hypothesis, our data indicate that PAK1 restricts tonic eCB signaling in the hippocampus through the regulation of synaptosomal cyclooxygenase-2 (COX-2) expression, a non-canonical but relevant pathway in the metabolism of eCB signaling. In turn, this ability of PAK1 to restrict tonic eCB signaling confers an alteration in the E/I homeostasis of the hippocampus through the regulation of tonic GABA transmission. Given the overlapping importance of PAK1, COX-2 and eCB signaling in an array of physiological and pathophysiological processes, the identification of this functional signaling interaction likely has significant implications for a multitude of disease processes, such as autism, inflammatory conditions and cancer. Since all the animal models of brain disorders that are functionally rescued by manipulations of PAK1 share a common deficit in E/I balance (Braat and Kooy, 2015; Dolan et al. , 2013; Eichler and Meier, 2008; Gao and Penzes, 2015; Hayashi et al. , 2007; Kehrer et al. , 2008; Lewis et al. , 2005; Marín, 2012; Molosh et al. , 2014; Yizhar et al. , 2011), we therefore examined whether disrupting PAK1 would affect the E/I ratio by performing whole cell patch-clamp recordings in CA1 pyramidal neurons of hippocampal slices acutely prepared from PAK1 KO mice and their WT littermates (1a). Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) were pharmacologically isolated by using respective inhibitors specific to glutamate or GABA receptors (i. e. EPSC recorded by including 100 μM GABAα receptor antagonist picrotoxin and IPSC by including","Brain cells communicate by sending chemical signals that activate or excite neighbouring cells. However, too much signalling can be harmful. As such the brain has systems in place to inhibit brain signals, and healthy brain activity relies striking a proper balance between excitation and inhibition. In some brain mental health conditions, like autism or schizophrenia, the balance is skewed which has an impact on the brain’s activity. A chemical produced by brain cells called endocannabinoid helps maintain the appropriate balance in brain excitation and inhibition. Endocannabinoid is similar to a chemical found in cannabis, but little is known about how it works and which proteins interact with endocannabinoid. A family of proteins called p21-activated kinases (PAKs) has been implicated in autism and other disorders like Huntingtin disease and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"We show that the splicing regulator PTBP2 controls a genetic program essential for neuronal maturation. Depletion of PTBP2 in developing mouse cortex leads to degeneration of these tissues over the first three postnatal weeks, a time when the normal cortex expands and develops mature circuits. Cultured Ptbp2−/− neurons exhibit the same initial viability as wild type, with proper neurite outgrowth and marker expression. However, these mutant cells subsequently fail to mature and die after a week in culture. Transcriptome-wide analyses identify many exons that share a pattern of mis-regulation in the mutant brains, where isoforms normally found in adults are precociously expressed in the developing embryo. These transcripts encode proteins affecting neurite growth, pre- and post-synaptic assembly, and synaptic transmission. Our results define a new genetic regulatory program, where PTBP2 acts to temporarily repress expression of adult protein isoforms until the final maturation of the neuron. Compared to other cells, neurons undergo an unusually long period of maturation as they differentiate. In rodents, the time required for neuronal progenitors to become fully functional neurons can be many days, during which cells will exit mitosis, migrate to a proper location, grow initial neurites to be defined in their polarity, fully extend these axons and dendrites to their proper targets, and finally assemble active synaptic connections and circuits (Waites et al. , 2005; Craig et al. , 2006; Hamby et al. , 2008; Barnes and Polleux, 2009). A wide variety of genetic mechanisms ensure that these events occur in proper sequence and induce cell death when a process is incorrect. This developmental pathway is best understood at the level of transcriptional regulation where important signaling molecules, transcription factors, and epigenetic modifications are implicated in lineage commitment, cell survival, and establishment of synaptic connections. However, many aspects of the genetic control of neuronal development are not understood. Alternative pre-messenger RNA splicing is a common mechanism for genetic control in the nervous system, where many proteins important for neuronal differentiation and function are made in diverse isoforms through changes in splice site choice (Licatalosi and Darnell, 2006; Li et al. , 2007; Norris and Calarco, 2012; Yap and Makeyev, 2013; Zheng and Black, 2013). Changes of splicing pattern are regulated by trans-acting RNA-binding proteins that can be expressed in a temporal- or cell-type-specific manner","Cells within the developing brain undergo an extended period of maturation. A neuronal progenitor cell must first migrate to the proper place within the brain and then develop long extensions that become the axon and dendrites used by the mature neuron to communicate with other cells. Finally, the synapses that connect neurons with other neurons must be established. Multiple mechanisms are needed to ensure that all the proteins involved in this process are expressed when and where they are needed. The production of a protein begins with a region of DNA being transcribed to produce an RNA transcript that consists of segments called exons separated by segments called introns. This transcript then undergoes a process called splicing that involves the introns being removed and the exons being joined",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Kara et al. , 2015; Kreitz et al. , 2001; Mendez et al. , 2002; Ohta et al. , 2003; Siddiqui and Stillman, 2007; Tatsumi et al. , 2000). The assembly of the full ORC occurs in mid G1 phase of the cell division cycle in preparation for its role in assembly of the pre-replicative complex (pre-RC) at sites across chromosomes (Kara et al. , 2015; Siddiqui and Stillman, 2007). The ORC1-related protein CDC6 is also required for pre-RC assembly, but it is targeted for proteasome degradation by the SCFCyclin F ubiquitin ligase complex late in the cell cycle and the anaphase-promoting complex/cyclosome (APC/C) in early G1 phase and then stabilized in mid G1 phase by Cyclin E-CDK2-mediated phosphorylation (Mailand and Diffley, 2005; Petersen et al. , 2000; Walter et al. , 2016). This phosphorylation is mediated by the direct interaction between Cyclin E and CDC6 and CDC6 and Cyclin E-CDK2 cooperate to promote the initiation of DNA replication (Coverley et al. , 2002; Furstenthal et al. , 2001; Cook et al. , 2002). As proliferating cells divide, they must make a decision whether to continue to proliferate or enter into proliferative quiescence. This decision is made by a complex regulatory process known as START in yeast and the restriction point in mammalian cells (Johnson and Skotheim, 2013). Key among these regulators are the Cyclin D-CDK4/6 kinases that mono-phosphorylate the retinoblastoma (RB) protein and contributes to the release of repression of E2F-transcription factors (Narasimha et al. , 2014; Ewen et al. , 1993; Hinds et al. , 1992; Lundberg and Weinberg, 1998; Resnitzky et al. , 1994). E2F1-regulated genes include genes encoding Cyclin E (CCNE1) and CDC6 (Hateboer et al. , 1998; Ohtani et al. , 1998; Yan et al. , 1998; DeGregori et al. , 1995). Cyclin E-CDK2 amplifies the phosphorylation of RB, but how this is achieved is not known (Narasimha et al. , 2014). Here, we demonstrate that ORC1 is required for repression of the gene encoding Cyclin E and that CDC6 is involved in relieving the repression in cooperation with Cyclin E-CDK2. We suggest that ORC1 establishes a period in the newly born cells during which Cyclin E is not expressed, allowing time for the cells to decide whether to proliferate again or enter into replicative","Living cells must replicate their DNA before they divide so that the newly formed cells can each receive an identical copy of the genetic material. Before DNA replication can begin, a number of proteins must come together to form so-called pre-replicative complexes at many locations along the DNA molecules. These protein complexes then serve as landing pads for many other DNA replication proteins. One component of the pre-replicative complex, a protein called ORC1, helps to recruit another protein called CDC6 that in turn acts with Cyclin E to promote the replication of the DNA. Cyclin E is a protein that is only expressed when cells commit to divide. Previous research has shown that a lack of ORC1 causes the levels of Cyclin E to rise in human cells,",380,128,0.3368
dialogsum,"#Person1#: Have you anything to declare? #Person2#: One bottle of perfume and a watch. #Person1#: Where did you buy it? #Person2#: In Boston. #Person1#: Do you travel a lot? #Person2#: Oh. . . I go to see my sister twice a year or so. #Person1#: Twice a year? How long has your sister lived in Boston? #Person2#: Nearly ten years. #Person1#: I see, that's a long time. How much was the watch? #Person2#: I can't remember, but I've got the receipt somewhere. Would you like to see it? #Person1#: Yes, I'd like to see the receipt. Oh! I see you bought the watch last week. #Person2#: Yes. Does that mean I'll have to pay duty on it? #Person1#: Yes, I'm afraid you will. Altogether on the watch and the perfume you owe me seven pounds. #Person2#: Ok. Here you are. Is that all right now? #Person1#: Yes, that's fine. I hope you enjoyed your stay in Boston? #Person2#: Yes, I did. I had a fine time.",#Person1# asks #Person2# about the things #Person2# bought. #Person2# bought a bottle of perfume and a watch. #Person2# needs to pay #Person1# seven pounds altogether.,166,25,0.1506
dialogsum,"#Person1#: Hi, sir. Come and have a look here. We have all kinds of sweaters. #Person2#: I'm looking for a sweater for my wife. Tomorrow is her birthday. And I know she needs a woolen sweater. #Person1#: How do you like this grey one? It's pure wool, one hundred percent of Xinjiang wool. #Person2#: It feels good. Are there cowl-neck pullovers with the same color? My wife prefers a turtleneck to a V-shaped collar. #Person1#: Yes, we do. What size do you want? #Person2#: Size one. By the way, what if I bring home this sweater and my wife doesn't like it? #Person1#: Well, you can always bring it back to us for a full refund. #Person2#: All right. Could I have it gift-wrapped, please? #Person1#: Yes, just a moment, please.","#Person2# wants a sweater for his wife as a birthday present, and #Person2#'s wife prefers a turtleneck. #Person1# recommends one, and #Person2#'ll take it.",131,24,0.1832
dialogsum,"#Person1#: Steven, would you like to go dance with us tonight? #Person2#: John, I am just not in the mood for this. #Person1#: You look so upset. What's going on? #Person2#: I lost the table tennis game yesterday. #Person1#: Oh, what a pity! #Person2#: I just don't want to play table tennis any more. #Person1#: Is it that bad? It's nothing more than a game. #Person2#: My opponent bowled me with the very first ball. I was wondering if it's appropriate for me to play table tennis. #Person1#: Oh, come on! Failure is the mother of success. Don't lose heart. I'm sure you'll succeed. #Person2#: Perhaps you are right. But I still need some time to recover from the failure. #Person1#: I understand.",Steven lost the table tennis game and feels upset. John encourages him but Steven thinks he needs time to recover.,123,20,0.1626
dialogsum,"#Person1#: Scientists have found a second solar system in the universe. #Person2#: What's the second solar system? #Person1#: It's just a system like ours, with a star and a number of planets going around it. #Person2#: Is this good news or bad news? #Person1#: It's exciting news! If we find a second solar system, we might find a second earth! #Person2#: You mean with people on it? #Person1#: Yes! Isn't that exciting?",#Person1# tells #Person2# it's exciting that a second solar system has been found.,72,13,0.1806
dialogsum,"#Person1#: You'd like coffee, wouldn't you? #Person2#: I think I'd rather have tea this morning. #Person1#: What else are you going to have? #Person2#: Just an English muffin. What are you going to have? #Person1#: That sounds good. I'm going to order the same thing.",#Person2# will have tea and an English muffin. #Person1# wants the same.,45,12,0.2667
dialogsum,"#Person1#: You look tired. Didn't you get enough sleep last night? #Person2#: No, I had a bunch of friends over and we partied until midnight. #Person1#: No wonder you look so bad. #Person2#: I guess I just can't take late nights like I used to. My head is spinning. #Person1#: I think you need to go home and take a rest. #Person2#: I wish I could, but I don't think I can keep my eyes open long enough to drive home. #Person1#: Don't worry. I'll give you a ride home.",#Person2# partied until midnight so #Person2# is tired. #Person1# will give #Person2# a ride home.,90,15,0.1667
scientific_lay_summarisation-elife-norm,"motors that are targeted to the spindle by the microtubule-associated protein (MAP) Tpx2 (targeting protein for xKlp2) (Wittmann et al. , 1998). hKif15 is also recruited to the spindle microtubules by hTpx2 in human cells (Tanenbaum et al. , 2009; Vanneste et al. , 2009) with the interaction between dimeric hKif15 and hTpx2 hypothesised to enable the motor to cross-link and slide anti-parallel microtubules (Tanenbaum et al. , 2009). However, this model has been challenged by recent cell-biological studies showing that hKif15 localizes to kinetochore (k) -fibres (parallel microtubule bundles) and contributes to the generation of forces that counter those generated by hKif11 (Sturgill and Ohi, 2013; Vladimirou et al. , 2013). Understanding how hKif11 and hKif15 cooperate during mitosis has important implications for cancer therapy because the clinical efficacy of hKif11 inhibitors, currently used as monotherapy, has proven largely disappointing (Rath and Kozielski, 2012). hKif15 is therefore emerging as a potentially important therapeutic target (Groen, 2013). To understand how hKif15/hKif11 operate within the spindle, we will require a detailed mechanistic understanding of how each motor interacts with microtubules and generates force. Such information is already available for Kif11. In this study, we provide the first insight into the properties of the Kinesin-12 family motor hKif15. Full-length human His6-Kif15 (hKif15), His6-Kif15-eGFP, and His6-Tpx2 (hTpx2) were expressed in insect SF9-cells and the recombinant proteins purified to near homogeneity by sequential affinity chromatography using a cation-exchange and a Co-NTA matrix (1A). Analysis of His6-hKif15 on native PAGE revealed that the protein migrates at ∼730 KDa (1B). Given the predicted molecular weight of His6-hKif15 (164. 8 kDa) our data suggest the presence of hKif15 tetramers, although hydrodynamic analysis of the frog (xKlp2) and Sea urchin (KRP180) Kif15 orthologues indicated that the motor is dimeric with a sedimentation coefficient of 8. 1S and 8. 3S respectively (Wittmann et al. , 1998; Rogers et al. , 2000). To further characterise human Kif15, we subjected His6-hKif15 to glycerol gradient ultracentrifugation on 5–40% glycerol gradients. At physiological ionic strengths (35 mM sodium phosphate buffer, 0-150 mM NaCl) both His6-hKif15 and His6-hKif15-eGFP appear to be monodispersed and have apparent sedimentation coefficients of ∼12S (1C). However, increasing the salt concentration to 300 mM NaCl converts hKif15 into a species that runs at ∼8S (1C). Taken together, our data show","Before a cell can divide, it produces an extra copy of all its chromosomes, and it must then ensure that each daughter cell ends up with one copy of each chromosome. During the division process, a structure called the spindle forms in the cell. This spindle is made of thread-like extensions called microtubules that grow from two poles at opposite ends of the cell. These microtubules are responsible for getting the chromosomes to line up in the middle of the cell, and then pulling half of the chromosomes to one end of the cell, and half to the other end. The cell then divides into two daughter cells. Two motor proteins—so-called because they consume chemical energy to ‘walk’ along the microtubules—have important roles in this process: Kif11 motor",380,128,0.3368
scientific_lay_summarisation-elife-norm,"PARP-7 (TiPARP) is a mono (ADP-ribosyl) transferase whose protein substrates and biological activities are poorly understood. We observed that PARP7 mRNA levels are lower in ovarian cancer patient samples compared to non-cancerous tissue, but PARP-7 protein nonetheless contributes to several cancer-related biological endpoints in ovarian cancer cells (e. g. growth, migration). Global gene expression analyses in ovarian cancer cells subjected to PARP-7 depletion indicate biological roles for PARP-7 in cell-cell adhesion and gene regulation. To identify the MARylated substrates of PARP-7 in ovarian cancer cells, we developed an NAD+ analog-sensitive approach, which we coupled with mass spectrometry to identify the PARP-7 ADP-ribosylated proteome in ovarian cancer cells, including cell-cell adhesion and cytoskeletal proteins. Specifically, we found that PARP-7 MARylates α-tubulin to promote microtubule instability, which may regulate ovarian cancer cell growth and motility. In sum, we identified an extensive PARP-7 ADP-ribosylated proteome with important roles in cancer-related cellular phenotypes. Members of the poly (ADP-ribose) polymerase (PARP) family of enzymes catalyze ADP-ribosylation (ADPRylation), a posttranslational modification of proteins, through covalent transfer of ADP-ribose (ADPR) from β-nicotinamide adenine dinucleotide (NAD+) onto a variety of amino acid residues, including glutamate, aspartate, and serine (Gibson and Kraus, 2012; Gupte et al. , 2017). ADPRylation can occur as a single ADP-ribose (i. e. mono (ADP-ribose), [MAR]) or multiple ADP-ribose moieties (i. e. poly (ADP-ribose), [PAR]) (Gibson and Kraus, 2012; O’Sullivan et al. , 2019). Both MAR and PAR modifications are reversible and can be removed by a variety of ADPR hydrolases (O’Sullivan et al. , 2019; Rack et al. , 2020). Free and protein-linked ADP-ribose moieties can be bound by proteins (‘readers’) containing ADPR-binding domains (e. g. macrodomains, WWE domains), allowing MAR or PAR to be interpreted or ‘read’ (Gibson and Kraus, 2012; Teloni and Altmeyer, 2016). ADPRylation can modulate target protein functions, including enzymatic activity, interactions with binding partners, and protein stability through both direct effects resulting from chemical modification and indirect effects mediated by ADPR-binding ‘reader’ proteins (Gupte et al. , 2017; Kim et al. , 2020; Ryu et al. , 2015). In humans, the PARP family includes 17 members, each with unique structural domains, expression patterns, targets, enzymatic activity, localization, and functions (Amé et al. , 2004; Vyas et al. , 2013; Vyas et al. , 2014). In spite of the moniker,","Cancer is a complex illness where changes inside healthy cells causes them to grow and reproduce rapidly. Specialized proteins called enzymes – which regulate chemical reactions in the cell – often help cancer develop and spread through the body. One such enzyme called PARP-7 labels other proteins by attaching a chemical group which changes their behavior. However, it was unknown which proteins PARP-7 modifies and how this tag alters the actions of these proteins. To investigate this, Parsons, Challa, Gibson et al. developed a method to find and identify the proteins labelled by PARP-7 in ovarian cancer cells taken from patients and cultured in the laboratory. This revealed that PARP-7 labels hundreds of different proteins, including adhesion proteins which affect the connections between cells and cytoskeletal proteins which",380,128,0.3368
scientific_lay_summarisation-elife-norm,"al. (2004) with follow-up results in Milner et al. (2015) and Barrera et al. (2015) ), among children for whom retinopathy was assessed, 41 of 42 children dying with Ret+ CM had substantial cerebral sequestration of parasitized red blood cells in the cerebral microvasculature (defined as ≥23% of cerebral capillaries had sequestration) and mostly lacked other identified potential causes of death besides the malaria parasitemia, whereas all 15 children dying with Ret- CM lacked substantial cerebral sequestration (<23% of cerebral capillaries had sequestration) and mostly had non-malarial etiologies of death (see Appendix 1 for causes of death); these numbers update those in Taylor et al. (2004) to include patients enrolled after 2004. Incidental malaria parasitemia is common in people living in areas of high malaria transmission. Therefore, it is possible that at least some children with Ret- CM have a non-malarial etiology of coma and an incidental (asymptomatic) malaria parasitemia. The pathogenesis of Ret-CM is therefore unclear, and the role of malaria parasitemia in the etiology of the acute illness is unknown (Postels and Birbeck, 2011). Our aim of the research presented here was to assess the contribution of acute malaria infection in the pathophysiology of Ret- CM. 10. 7554/eLife. 23699. 003Table 1. Characteristics of study participants at admission, Means ± SD for continuous variables. The proportions of missing data are shown in Appendix 1. There are 3704 community controls, but their characteristics are not shown because only their genotypes and not their clinical characteristics were collected. Bold denotes p-value less than 0. 05. : http: //dx. . org/10. 7554/eLife. 23699. 003Retinopathy Positive CMRetinopathy Negative CMNon-Malaria Hospital Controlsp-value, Ret + vs. Ret -p-value, Ret + vs. Controlsp-value, Ret – vs. ControlsNumber of participants438288204Female50%52%43%0. 540. 110. 05Age (months) 40 ± 2644 ± 3046 ± 300. 100. 050. 53Mid-upper arm circumference (cm) 14. 9 ± 1. 615. 0 ± 1. 714. 8 ± 1. 80. 720. 530. 39Weight (kg) 12 ± 413 ± 513 ± 60. 370. 290. 74Height (cm) 90 ± 1691 ± 1791 ± 200. 300. 401. 00Temperature (°C) 38. 6 ± 1. 238. 4 ± 1. 437. 7 ± 1. 50. 03<0. 001<0. 001Febrile (Temperature≥ 37. 5°C) 81%77%56%0. 23<0. 001<0. 001Pulse rate – beats/minute152 ± 26148 ± 24139 ± 280. 06<0. 001<0. 001Respiratory rate – breaths/minute47 ± 1545 ±","Malaria is a life-threatening disease caused by a parasite that is transferred between people by infected mosquitoes. Most infected individuals suffer flu-like symptoms, but in rare cases malaria can affect the brain, resulting in brain damage, coma or death. The World Health Organization defines a person as suffering from cerebral malaria if the person is in a coma, has malaria parasites in his or her blood, and has no known alternative cause of the coma. Patients suffering from cerebral malaria are categorized based on whether they have damage to the back of the eyes known as retinopathy. It had previously been found that children who died of “retinopathy-positive” cerebral malaria (i. e. those who had retinopathy) had malaria parasites stuck in small vessels in their brains, which likely",380,128,0.3368
scientific_lay_summarisation-elife-norm,"in plant–herbivore interactions. As many plant organs and their associated microbial communities release CO2, it may be integrated into herbivore foraging as a marker of metabolic activity. Datura wrightii flowers, for instance, emit the highest levels of CO2 during times of high nectar availability; as hawkmoth pollinators are attracted to CO2, they may thus use this cue to locate rewarding flowers (Goyret et al. , 2008; Guerenstein et al. , 2004; Guerenstein and Hildebrand, 2008; Stange, 1996; Stange, 1999; Stange and Stowe, 1999; Thom et al. , 2004). Similarly, lesions in apples result in high CO2 release and attract Bactrocera tryoni fruit flies. As CO2 at corresponding concentrations is attractive to the flies, it has been suggested that they may use plant-associated CO2 to locate suitable oviposition sites (Stange, 1999). Root-feeding insects are highly attracted to CO2 in vitro (Bernklau and Bjostad, 1998a; Bernklau and Bjostad, 1998b; Eilers et al. , 2012; Hibbard and Bjostad, 1988; Jones and Coaker, 1978; Klingler, 1966; Nicolas and Sillans, 1989; Rogers et al. , 2013; Strnad et al. , 1986; Strnad and Dunn, 1990). Given that CO2 is produced and released by plant roots and diffuses relatively well through the soil, a likely explanation for this phenomenon is that root herbivores use CO2 as a host location cue (Bernklau and Bjostad, 1998a; Bernklau and Bjostad, 1998b; Doane et al. , 1975; Erb et al. , 2013; Johnson and Gregory, 2006; Johnson and Nielsen, 2012), However, the reliability of CO2 as a host location cue for root feeders has been questioned due to a number of reasons: (i) CO2 can be emitted by many other sources apart from host plant roots, including decaying organic matter, microorganisms, and non-host plants; (ii) there is a strong diurnal fluctuation in plant CO2 emissions that does not necessarily match with insect foraging habits; and (iii) other plant-released chemicals can be used by root herbivores for host location within a CO2 background (Agus et al. , 2010; Eilers et al. , 2012; Erb et al. , 2013; Hansen, 1977; Hibbard and Bjostad, 1988; Hiltpold and Turlings, 2012; Johnson and Nielsen, 2012; Reinecke et al. , 2008; Weissteiner et al. , 2012). A model that may reconcile these different views is that CO2 may be used as an initial cue at","Living deep in the ground and surrounded by darkness, soil insects must rely on the chemicals released by plants to find the roots they feed on. Carbon dioxide, for example, is a by-product of plant respiration, which, above ground, is thought to attract moths to flowers and flies to apples; underground, however, its role is still unclear. This gaseous compound can travel through soil and potentially act as a compass for root-eating insects. Yet, it is also produced by decaying plants or animals, which are not edible. It is therefore possible that insects use this signal as a long-range cue to orient themselves, but then switch to another chemical when closer to their target to narrow in on an actual food source. To test this idea, Arce et",380,128,0.3368
dialogsum,"#Person1#: Hello, welcome to IBA. What can I do for you? #Person2#: Do you offer a safety deposit box rental service here? #Person1#: We certainly do. May I ask you the purpose of the rental? #Person2#: I'd like to put some valuables inside, you know, documents and jewellery, things like that. #Person1#: I see. We have various rental periods. How long would you like to rent it for? #Person2#: What rental do you offer? #Person1#: You can choose a short-term or yearly rental. #Person2#: I'll have to ask my wife how long she'll need it for as it is mainly for her belongings. I'll come back after we have discussed it. Thanks for your help.",#Person1# helps #Person2# choose a safety deposit box rental service at IBA to put some valuables inside.,115,17,0.1478
dialogsum,"#Person1#: Hey, that's a really nice outfit you have on. #Person2#: Thank you. I wasn't sure if it looked okay or not. #Person1#: Oh, you look stunning. Your dress really goes well with your shoes. #Person2#: I'm glad that you think so. I thought it might be a bit too revealing. #Person1#: No, not at all. It looks really classy on you. Where did you pick that up? #Person2#: I got it on sale down at the department store. #Person1#: When did you go there? #Person2#: I was just there a couple of days ago. You know, you should go down there too. They have a lot of stylish clothes on sale. #Person1#: I might just do that. What style of clothes do they have? #Person2#: Anything you want. They have both casual and formal styles. #Person1#: I was hoping to get a few new ties for my collection. #Person2#: That's a good idea.",#Person1# appreciates #Person2#'s new outfit. #Person2# tells #Person1# that #Person2# got the dress at the department store. #Person1# will go there and buy some new ties.,154,26,0.1688
scientific_lay_summarisation-elife-norm,"The presumptive altered dynamics of transient molecular interactions in vivo contributing to neurodegenerative diseases have remained elusive. Here, using single-molecule localization microscopy, we show that disease-inducing Huntingtin (mHtt) protein fragments display three distinct dynamic states in living cells – 1) fast diffusion, 2) dynamic clustering and 3) stable aggregation. Large, stable aggregates of mHtt exclude chromatin and form' sticky' decoy traps that impede target search processes of key regulators involved in neurological disorders. Functional domain mapping based on super-resolution imaging reveals an unexpected role of aromatic amino acids in promoting protein-mHtt aggregate interactions. Genome-wide expression analysis and numerical simulation experiments suggest mHtt aggregates reduce transcription factor target site sampling frequency and impair critical gene expression programs in striatal neurons. Together, our results provide insights into how mHtt dynamically forms aggregates and disrupts the finely-balanced gene control mechanisms in neuronal cells. Poly-glutamine (PolyQ) expansion in proteins is associated with multiple neuro- and muscle- degenerative diseases such as Huntington’s disease (HD), X-linked spinobulbar muscular atrophy (SBMA) and various spinocerebellar ataxias (SCA1,2, 3,6, 7 and 17) (reviewed in [Blum et al. , 2013; Mohan et al. , 2014]). In HD, a single mutant Huntingtin allele with PolyQ tracts greater than 37 glutamines leads to selective cell death in the striatum and certain regions of the cortex, causing muscle coordination and cognitive defects (Group, 1993; Ross and Tabrizi, 2011). It has been widely observed that extended PolyQ tracts facilitate the formation of protein aggregates in the cytoplasm and nucleus of diseased cells (Bates, 2003; DiFiglia et al. , 1997; Huang et al. , 2015). Previous FRAP, FCS and in vitro super-resolution imaging provides significant insights into mHtt aggregate formation (Cheng et al. , 2013; Duim et al. , 2014; Kim et al. , 2002; Park et al. , 2012; Sahl et al. , 2012; Wustner et al. , 2012). However, the dynamics of aggregate formation or how the resulting' plaques' might influence essential molecular transactions that disrupt gene expression programs have not been investigated at the single-molecule level in living cells. Since the original discovery of mHtt aggregates in the nucleus and cytoplasm of HD cells, the relevance of these aggregates or plaques to disease pathology has been under vigorous debate (DiFiglia et al. , 1997; Scherzinger et al. , 1997; Woerner et al.","Huntington' s disease belongs to a group of human genetic disorders in which faulty proteins cause nerve cells to progressively die. All proteins are made from building blocks called amino acids, and these diseases are collectively called PolyQ expansion diseases because the faulty proteins usually have an abnormally long stretch that contains many repeats of an amino acid called glutamine. The stretches of glutamines make these mutant proteins stick to each other, which means that they aggregate in the diseased cells. Researchers have proposed several mechanisms to explain how aggregates of one such mutant protein, called mutant Huntingtin (mHtt), might contribute to Huntington' s disease. One possibility is that mHtt accumulates in the nucleus of the cell – which houses most of the cell’s DNA – and interferes",380,128,0.3368
dialogsum,"#Person1#: Good morning, madam. #Person2#: Good morning. I wonder if you can help. I've lost my coat. #Person1#: Where did you lose it, madam? #Person2#: Er... I left it on a bus yesterday morning. #Person1#: Can you describe it? Is it a raincoat? #Person2#: No. It's a long white overcoat. It's got a belt, and one of those thick furry collars that keep your ears warm. It's a very nice coat, actually. #Person1#: Hmm. I'm afraid we haven't got anything like that, madam. Sorry. But, may I have your name and your telephone number? We'll contact you as soon as we've got it.",#Person2# turns to #Person1# for help because she lost her coat. #Person1# asks for her contact.,103,16,0.1553
pubmed-summarization,"chemically , phloroglucinol ( 1,3,5-trihydroxybenzene , pg ) and its methylated derivative tri - o - methylphloroglucinol ( tmp ) , , are established pharmaceutical agents inhibit the action of catechol - o - methyl transferase , inducing relaxation of smooth muscles , and decreasing glycerol - induced abdominal pain and are also characterized by a swift and strong spasmolytic activity , hence relieving pain . therefore , pg is often used in combination with trimethylphloroglucinol as an antispasmodic drug and is regarded to be effective in decreasing smooth muscle spasm . pg / tmp combination is recommended against biliary calculi , severe pain of urinary or gastrointestinal tract , pain of abdominal region , spastic conditions of the female genital system , and pain in gynecology . literature survey reveals that some of the analytical methods for phloroglucinol are available including extraction and high - performance liquid chromatography ( hplc ) , hplc - mass spectrometry , gas chromatography - mass spectrometry , and spectrophotometry . other reported methods include titrimetry , spectrophotometry , paper chromatography , and flow injection analysis . however , there is no simple and sensitive method to be followed on industrial basis especially in general quality control laboratories . therefore , they can not be followed in the laboratories particularly those of third world countries . hence our group already developed a cost effective method for its fixed dose composition in tablet form , but still there was a need for an analytical method which would help to determine the active pharmaceutical ingredients ( apis ) in parenteral products and physiological fluid . accordingly , the purpose of this write - up is to suggest a systematic approach for the development of a validated simple , sensitive , and stability indicating rp - hplc method that should meet the current ich and regulatory requirements . the present method was designed to be easy to use , sensitive , and rapid . separation and quantification of pg and tmp in pharmaceutical drug formulations and blood were achieved with an isocratic elution and with dual wavelength technique . sil 10a autoinjector hplc system comprising of scl 10a system , controller , spd 20a prominence uv / vis detector , and shimadzu lc 20 at pump with","a reverse phase stability indicating hplc method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms ( injectable ) and in serum has been developed and validated . mobile phase ingredients consist of acetonitrile : buffer : sulfuric acid 0.1 m ( 50 : 50 : 0.3 v / v / v ) , at flow rate 1.0 ml / min using a hibar bondapak ods c18 column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol , respectively . the drugs were subjected to stress conditions of hydrolysis ( oxidation , base , acid , and thermal degradation ) . oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions . the",380,128,0.3368
pubmed-summarization,"5 cm abscess was seen related to the fistula tract on the anterior wall of the abdomen . no intestinal content was observed in the abdomen . a 10 cm mass attached to nearby tissues that contained necrotic and caseated areas covered the distal sigmoid and proximal rectum . as resection was not possible , hartman - type proximal end colostomy was performed and the operation was ended leaving a distal stubby. as adenoid structures in patches were observed by histopathological examination , the differential diagnosis was made between poorly differentiated adenocarcinoma and cc . immunohistochemically , staining with high - molecular - weight cytokeratin ( hmwck ) ( . ca 19 - 9 levels were normal ( 1.1 ng / ml and 2 iu / ml , respectively ) . three weeks after discharge from the hospital , a 5-fluorouracil + folinic acid + irinotecan regimen was started . in total , three cycles of radiotherapy and a concurrent three - drug chemotherapy regimen ( folfiri ; folinic acid , fluorouracil , irinotecan ) were administered to the patient over 6 weeks . in ct scans 3 months after therapy , an increase in mass size and hydroureteronephrosis were observed . at the end of the fifth month , in this case , failure in detecting the mass in the pelvis during laparatomy can depend on two reasons : either the mass was not formed at the time of the laparatomy or the mass could not be seen . probably it was the colonic mass that caused symptoms of appendicitis in his first surgery . however , it is normal that colon carcinoma is not suspected initially in an 18-year - old patient presenting with abdominal pain without any family history , since without the presence of familial colon cancer or ulcerative colitis history , incidence of colon cancer is very low at < 40 years of age . in this case , neither in family history nor in colonoscopic examination was any sign of polyposis coli present . furthermore , because of aggressive progression but nearly normal cea levels , no sign of liver metastasis , and no clinical answer to radiotherapy and chemotherapy , we thought that it was either undifferentiated carcinoma arising from the colonic mucosa","cloacogenic carcinoma ( cc , basaloid carcinoma ) generally occurs around the dentate line , rarely it can arise from the other sides of the colon . there are only 5 cases of cc located outside the anal canal in the literature . the first occurrence of a cc presents as intraabdominal abscess . we describe a 23-year - old male patient who was admitted with fever and severe abdominal pain . computed tomography imaging showed diffuse wall thickening about 1011 cm above the rectosigmoid junction , intraabdominal abscess and a soft tissue lession covering the pelvis with a size of 8 8.5 cm including cystic necrotic areas . we performed hartman procedure since the mass was nonresectable . histopathological examination showed cc . in total , three",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2000; Ryu et al. , 2003), and both capsaicin (Voets et al. , 2004; Matta and Ahern, 2007; Gregorio-Teruel et al. , 2014) and protons (Lee and Zheng, 2015) can sensitize the channel to activation by voltage. Conceptually, these observations can be explained by allosteric models wherein distinct stimulus-sensing domains are coupled to each other (Latorre et al. , 2007), and to an internal gate within the pore that opens and closes the ion permeation pathway (Salazar et al. , 2009; Cao et al. , 2013) (1A). 10. 7554/eLife. 13356. 003Figure 1. Substitution of extracellular Na+ with NMDG+ increases TRPV1-mediated currents. (A) Side view in ribbon representation of the transmembrane domains of two opposing TRPV1 subunits (as indicated by the black arrow, extracellular face on the top, intracellular face on the bottom) in the apo state (refined TRPV1 structural model [Bae et al. , 2016]). The dashed boxes denote the location of the two constrictions proposed to serve as gates. Side chains of residues forming the binding site for capsaicin (purple) or determining activation of TRPV1 by protons (blue) are shown as sticks. (B) Representative time-course of whole-cell TRPV1-mediated currents elicited by 100-ms voltage pulses from -90 mV (triangles) to +90 mV (circles) at 300 ms intervals and at room temperature. The colored horizontal lines signal the onset of rapid-solution exchange as indicated by the labels. The dotted red line indicates the zero-current level. (C) Normalized TRPV1 current-voltage (I-V) relations obtained from 1s-duration voltage-ramps, following the same solution-exchange sequence as in (B). The darker curves are the mean and lighter-colored envelopes the standard error (n = 8). : http: //dx. . org/10. 7554/eLife. 13356. 00310. 7554/eLife. 13356. 004Figure 1— 1. Substitution of external Na+ with NMDG+ induces channel rundown at room temperature with high cell-to-cell variability. (A) Two representative TRPV1 current time courses obtained from a train of voltage ramps in the whole-cell configuration, constructed by plotting the mean currents at -120 (triangles) and +120 mV (circles) for each ramp within the train as a function of time. Rapid switching between extracellular solutions containing either 130 mM Na+ (Nao, gray) or 130 mM NMDG+ (130 NMDGo, yellow) is indicated by the color of the symbols. The rate of channel rundown in the absence of external Na+ exhibited","Humans and other mammals sense elevated heat and other painful stimuli via a sensory ion channel protein called TRPV1. Ion channels create pores in the outer membrane of cells and act as gates that open and close to regulate the flow of ions into and out of cells. This flow of ions generates electrical signals that sensory neurons use to communicate information about the environment to the brain. The TRPV1 channel is opened by heat, but also by venom toxins, acid and the active ingredient in hot chilli peppers. The fluid that surrounds animal cells often contains high levels of sodium ions, and these ions flow through TRPV1 channels when they are open. Also, when sodium ions are removed from the fluid surrounding a cell, TRPV1 channels will",380,128,0.3368
dialogsum,"#Person1#: Do you have any plan on your mind? #Person2#: I want to see all places of renown in Suzhou. #Person1#: How are we going there, by bike or by bus? #Person2#: By bike, of course. You don't want to miss the beautiful scenery, do you?",#Person2# tells #Person1# that he wants to travel to Suzhou by bike.,46,12,0.2609
dialogsum,"#Person1#: Hello! 6896443. #Person2#: Hello! Is that Lucy? #Person1#: Speaking! #Person2#: Hi! This is Tom! Can I speak to Lily? #Person1#: Sorry. She isn't in at the moment. Can I take a message? #Person2#: Could you please tell her not to wait for me this evening? We planned to go to a party together, but something important came up and I have to rush off. I'll be back in Cairo at the beginning of next week. #Person1#: Right. I'll tell her. Are you leaving now? #Person2#: Yes, I leave at half past two. Please give my love to her. Thank you! #Person1#: You're welcome. #Person2#: Could you ask her to phone me when she gets in? #Person1#: Sure. You'd better give me your number. #Person2#: Yes, it's 13962-72854. #Person1#: OK. I've recorded it. #Person2#: Thanks very much indeed. Bye! #Person1#: Bye!",Tom asks Lucy to tell Lily that he has to leave because of some important things and will be back soon. He also wants a reply call and leaves his number.,141,31,0.2199
dialogsum,"#Person1#: Can you tell me, Ms. Smith, about the training programs you initiated this year? #Person2#: We ran a call center training service and language program to ensure that our customer service representatives are well trained. #Person1#: What ' s the result? #Person2#: We directly attribute an increase in our customer service feedback of 50 % to the increase in language skills and training that our employees have received. #Person1#: That seems very impressive. Good work! #Person2#: Thank you, but I cannot take all the credit. Our employees have all worked very hard to increase their productivity level.",Ms. Smith tells #Person1# about the training program which has greatly increased their customer service feedback.,98,16,0.1633
dialogsum,"#Person1#: Hi, Mum. #Person2#: There you are. I'm getting worried. It's so late. #Person1#: Yes. I ran into Linda and we went to a pub. She told me a funny thing. #Person2#: Oh? What was that? #Person1#: Well, she was driving home after work, and she suddenly saw an old lady on her hands and knees in the middle of the road. #Person2#: Really? #Person1#: Yes, Linda was so shocked that she stopped suddenly and the car behind crashed into hers. #Person2#: Was her hurt? #Person1#: No. #Person2#: And what was the old lady doing? #Person1#: I am just coming to that. So Linda got out of her car and saw the old lady pick up something and walk away. #Person2#: Lucky indeed. Linda didn't run her over. #Person1#: Then a policeman came. But he didn't believe what Linda said. #Person2#: Well... #Person1#: Luckily there was a witness, a man waiting for a bus. He saw it all. Guess what the old lady was doing? #Person2#: I haven't the slightest idea. #Person1#: She was looking for her gold tooth. #Person2#: A gold tooth? #Person1#: Yes, it fell out as she was crossing the road. The witness heard her saying, 'Oh, my gold tooth...'","#Person1# tells #Person1#'s mum that Linda bumped into an accident when she saw an old lady on her hands and knees in the middle of the road. Luckily, a witness told the policeman that the old lady was looking for her gold tooth.",203,43,0.2118
pubmed-summarization,"first - generation aeds ( carbamazepine , phenytoin , and phenobarbital ) are not recommended for the treatment of lgs , due to the potential for aggravation of absence and myoclonic seizures by carbamazepine and phenytoin , and exacerbation of the behavioral problems seen in patients with lgs by barbiturates . among the benzodiazepines , clobazam may be viewed as the best tolerated , although there is no head - to - head comparison to confirm this . however , for this class of drugs , development of tolerance is well documented in the literature ( levy et al 2002b ) . the only aeds which have been evaluated in a randomized , controlled trial in lgs are lamotrigine , topiramate , and felbamate , the outcomes of which are discussed later in this paper . although felbamate is licenced for the treatment of lgs in the usa and some other countries ( eg , germany ) , its use has been limited following reports of serious toxicity ( borowicz et al 2004 ) . this has led to the recommendation that , in lgs , it should be used only in patients aged over 4 years who can not be treated satisfactorily with other aeds ( schmidt and bourgeois 2000 ) . thus , there is a clear need for new options in the management of this intractable condition . rufinamide was granted orphan drug status by the european medicines agency ( emea ) and the us food and drug administration ( fda ) in 2005 . this review will evaluate the relevant pharmacologic and clinical data for rufinamide , and explore its potential role in the future management of this severe form of epilepsy in the context of other products currently available for lgs . an extensive preclinical evaluation has suggested that the principal mechanism involved in the antiepileptic activity of rufinamide is its ability to modulate the activity of sodium channels , limiting high - frequency firing of neuronal action potentials over a broad range of concentrations , as demonstrated in vitro ( mclean et al 2005 ) . in radioligand binding studies , rufinamide does not interact with other neurotransmitter systems , including monoamine , adenosine , acetylcholine , histamine , glycine , -amino-3-hydroxy-5-methyl-4-isoxazole propionate (","rufinamide , a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs ( aeds ) , is in development for the adjunctive treatment of lennox - gastaut syndrome ( lgs ) in children and adults . rufinamide is well absorbed after oral administration , demonstrates low protein binding , and is metabolized by enzymatic hydrolysis without involvement of cytochrome p450 enzymes , conferring a low drug interaction potential . in a randomized , double - blind trial involving 138 adult and pediatric patients with lgs , compared with placebo , rufinamide 45 mg / kg / day resulted in significantly superior reductions in drop attacks ( median change 42.5% vs + 1.4% with placebo ) and total seizures ( 32.1% vs 11.7% with placebo ) ,",380,128,0.3368
pubmed-summarization,"the majority of swallowed indigestible foreign bodies pass through the gastrointestinal tract without complications . however , there are three physiological narrowings involving the pylorus , duodenal c - loop and ileocecal valve . foreign bodies longer than 10 cm , such as a toothbrush , can not negotiate the duodenal c - loop due to its fixed retroperitoneal position . these objects should be endoscopically removed as soon as possible to avoid pressure necrosis and gastrointestinal perforation . if endoscopic removal fails or there is evidence of obstruction or perforation , laparoscopic gastrotomy should be performed . an 18-year - old caucasian woman with no previous history of related medical problems was admitted to the department of internal medicine , division of gastroenterology , clinical hospital split because she had accidentally swallowed a toothbrush . the patient admitted she had been using the toothbrush to induce emesis . on presentation , 2 h after ingestion , she was asymptomatic and her vital signs were within normal limits . a plain abdominal x - ray study confirmed the presence of the foreign body in the left upper abdominal quadrant ( . informed written consent for upper gastrointestinal endoscopy was obtained from the patient and her parents . esophagogastroduodenoscopy revealed the toothbrush in the stomach with its head positioned against the gastric fundus . the extracted toothbrush was 20 cm long . repeated upper gastrointestinal endoscopy was performed 4 h later and showed no evidence of mucosal lesion to the stomach or the esophagus . the patient was discharged home in excellent clinical condition after being observed for 6 hours . foreign bodies in the stomach will pass uneventfully through the gastrointestinal tract in 8090% of cases . however , foreign objects longer than 10 cm , such as a toothbrush , can not negotiate the duodenal c - loop due to its fixed retroperitoneal position . in such cases , these objects should be removed as soon as possible to avoid pressure necrosis and gastric perforation . removal of long foreign bodies from the stomach is influenced by the patient 's clinical condition and technical abilities of the endoscopist . if endoscopic removal fails or there is evidence of obstruction or perforation , surgical gastrotomy should be performed . we","most ingested foreign bodies will pass uneventfully through the gastrointestinal tract . nevertheless , long and rigid foreign bodies are associated with an increased risk of gastrointestinal impaction , perforation and bleeding . moreover , there has been no case of spontaneous passage of a toothbrush reported . therefore , the prompt removal of such ingested foreign objects is recommended before complications develop . this case report describes a case of an 18-year - old woman who accidentally swallowed her toothbrush . the toothbrush was successfully removed via flexible endoscopy using a polypectomy snare . a swallowed toothbrush is a special clinical challenge . early endoscopic retrieval of the toothbrush is critical for reducing morbidity and mortality . in cases when endoscopic removal fails , a laparoscopic surgical",380,128,0.3368
pubmed-summarization,"certain aspects of schizophrenia ( carlsson and carlsson , 1990 ; tiedtke et al . , 1990 ) . mk-801 is also known to induce neurodegeneration of hippocampal ca1 and entorhinal cortex in adult animals when administrated with high concentrations ( 10 mg / kg ) of mk-801 ( wohrl et al . , 2007 ) . in the developing rat brain , blockade of nmda receptors with low dose of mk801 during late fetal or early neonatal life triggers widespread apoptotic neurodegeneration ( 12~26% of cells ) ( ikonomidou et al . , 1999 ) . this suggests the transient blockade of nmda receptors can trigger neuronal cell death in the immature mammalian brain during a period of rapid axonal growth and synaptogenesis , and the excitatory neurotransmitter glutamate , acting at nmda receptors , controls neuronal survival . thus , neurodegenerative mk-801 model of the developing rat has relevance to human neurodevelopmental disorders involving postnatal exposure to drugs that block nmda receptors such as pediatric anesthesia . berberine has been reported to increase action potential by inhibition of voltage dependent potassium current in cat ventricular myocytes ( huang , 1990 ; sanchez - chapula , 1996 ) and in human myeloma cells ( wu et al . , 1998 ) and hepatocytes ( wang et al . , 2003 ) . berberine suppresses dopamine - induced potassium current and acetylcholine induced potassium current in acutely dissociated ca1 pyramidal neurons ( wu and jin , 1996 ; 1997 ) . it is also suggested that berberine contributes to its blockades of potassium currents in damaged ischemic brain ( wang et al . , 2004 ) . this leads us a question whether berberine reduces cell death on damaged brain of developing animal model rats induced by mk801 . we tested first the cell survival promoting effect of berberine on sh - sy5y neuronal cells damaged by oxidative stress and then examined whether berberine blocks cell death in vivo developing rat model induced by mk801 . human neuroblastoma sh - sy5y cells were acquired from atcc . as previously described , shsy5y cells were maintained in dulbecco 's modified eagle 's medium ( dmem , invitrogen , usa ) supplemented with 10% fetal bovine serum ( fbs , thermo ,","berberine is an isoquinoline alkaloid isolated from goldenthread , coptidis rhizoma and shown to have many biological and pharmacological effects . we previously reported that berberine promotes cell survival and differentiation of neural stem cells . to examine whether berberine has survival promoting effect on damaged neuronal cells , we generated a cellular model under oxidative stress and an neonatal animal model of degenerating brain disease by injecting mk-801 . mk801 , a noncompetitive antagonist of n - methyl - d - aspartate ( nmda ) receptors , acts as a neurotoxin in developing rats by inhibiting nmda receptors and induce neuronal cell death . we found that the survival rate of the sh - sy5y cells under oxidative stress was increased by 287% and 344% , when",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo remain poorly understood. In this study, we have defined such a program for multi-ciliated epithelial cells (MCCs), a cell type critical for proper development and homeostasis of the airway, brain and reproductive tracts. Starting from genomic analysis of the cilia-associated transcription factor Rfx2, we used bioinformatics and in vivo cell biological approaches to gain insights into the molecular basis of cilia assembly and function. Moreover, we discovered a previously un-recognized role for an Rfx factor in cell movement, finding that Rfx2 cell-autonomously controls apical surface expansion in nascent MCCs. Thus, Rfx2 coordinates multiple, distinct gene expression programs in MCCs, regulating genes that control cell movement, ciliogenesis, and cilia function. As such, the work serves as a paradigm for understanding genomic control of cell biological processes that span from early cell morphogenetic events to terminally differentiated cellular functions. A major goal of biology over the last several decades has been to understand the mechanisms that control differential gene expression. While recent advances in genomic technology have dramatically empowered these studies, we still know comparatively little about the mechanisms linking systems-level programs of gene expression to discrete cell biological processes in vivo. This gap in our understanding is important because organ and tissue function are ultimately executed by the specialized behaviors of individual cells (e. g. , polarized secretion in excretory organs, coordinated contraction in muscle cells). Recent studies of cilia and ciliated epithelial cells highlight the current disconnect between genomics and cell biology: it is clear that hundreds of proteins are required for cilia assembly and function (Gherman et al. , 2006; Inglis et al. , 2006), and moreover, assembly of new cilia/flagella clearly requires new transcription (Thomas et al. , 2010). Nonetheless, only a handful of transcription factors have been identified that control cilia structure and function, and their associated gene regulatory networks remain largely undefined, especially in vertebrates. In C. elegans, the sole RFX family transcription factor daf-19 is the central regulator of ciliogenesis, and dozens of target genes are known to effect its action (Efimenko et al. , 2005; Phirke et al. , 2011; Burghoorn et al. , 2012). The one Rfx factor in Drosophila is likewise well characterized (Laurencon et al. ,","Cells that have hundreds of tiny hair-like structures called cilia on their surface have important roles in our airways and also in the brain and reproductive system. By beating in a coordinated manner, the cilia cause fluid to flow in a particular direction. The development of these multiciliated cells is a complex process in which genes are expressed as proteins, with this gene expression being regulated by other proteins called transcription factors. In invertebrates the development of the cilia is controlled by transcription factors from the RFX family, which also appear to be important for development of cilia in vertebrates. However, the details of this process—in particular, the identities of the genes that are involved and how their functions are related—are not well understood in vertebrates. Chung et",380,128,0.3368
dialogsum,"#Person1#: Excuse me, do you know where the visa office is? #Person2#: Yes, I do. I'll walk you there. #Person1#: Thanks. #Person2#: Are you applying to study or work abroad? #Person1#: I want to study abroad. #Person2#: What do you want to study? #Person1#: I hope to study English Literature. #Person2#: Have you got your visa yet? #Person1#: Not yet. I have an interview with a visa official today. #Person2#: I see. Is it your first interview? #Person1#: No, I'Ve already been here for 3 interviews.",#Person1# has an interview with a visa official. #Person1# asks #Person2# the way to the visa office.,86,17,0.1977
dialogsum,"#Person1#: Morning. Can I help you? #Person2#: Well, I'm not really sure. I'm just looking. #Person1#: I see. Well, there's plenty to look at again this year. I'm sure you'd have to walk miles to see each stand. #Person2#: That's true. #Person1#: Would you like a coffee? Come and sit down for a minute. No obligation. #Person2#: Well, that's very kind of you. But... #Person1#: No, please, is this the first year you've been to the fair, Mr. ...? #Person2#: Yes. Johnson. James Johnson. #Person1#: My name's Susan Carter. Are you looking for anything in particular or are you just interested in computers in general? #Person2#: Well, actually, I have some specific jobs in mind. I own a small company. We've grown quite dramatically over the past 12 months and we really need some technological help to enable us to keep on top of everything. #Person1#: What's your line of business, Mr. Johnson? #Person2#: We are a training consultancy. #Person1#: I see. And what do you need to keep on top? #Person2#: The first thing is correspondence. We have a lot of standard letters and forms. So I suppose we need some kind of word processor. #Person1#: Right. Well, that's no problem. But it may be possible for you to get a system that does a lot of other things in addition to word processing. What might suit you is the MR5000. That's over there. It's IBM compatible. #Person2#: What about the price? #Person1#: Well, the MR5000 costs 1,050 pounds. Software comes free with the hardware. #Person2#: Well, I'll think about it. Thank you. #Person1#: Here's my card. Please feel free to contact me.",Susan Carter gives James Johnson some coffee and lets him sit down. James owns a company of training consultancy and needs some technological help to keep on top of everything. Susan recommends MR5000 to James. James will think about it.,274,40,0.146
scientific_lay_summarisation-elife-norm,"a role for thiolated tRNAs in maintaining metabolic homeostasis. More pertinently, several studies have observed that a loss of this modification alters amino acid homeostasis, and the amino-acid starvation regulator Gcn4 is induced (Laxman et al. , 2013; Zinshteyn and Gilbert, 2013; Nedialkova and Leidel, 2015). Further, thiolated tRNAs are required to maintain metabolic cycles in yeast (Laxman et al. , 2013). Finally, the amounts of thiolated tRNAs reflect the intracellular availability of sulfur-containing amino acids (cysteine and methionine), and couple the sensing of amino acid sufficiency with growth (Laxman et al. , 2013). These studies all hint that a core function of this tRNA modification may be to integrate the sensing of amino acid availability (primarily methionine/cysteine), with the coordinate regulation of overall metabolic state, in order for the cell to appropriately commit to growth. Yet, how thiolated tRNAs regulate metabolism, and the extent to which this may control cellular outcomes remains entirely unaddressed. In this study, by directly analyzing different metabolic outputs, we identify the metabolic nodes that are altered in tRNA thiolation deficient cells. We find that tRNA thiolation regulates central carbon and nitrogen (amino acid) metabolic outputs, by controlling flux towards storage carbohydrates. In tRNA thiolation deficient cells, overall metabolic homeostasis is altered, with carbon flux diverted away from the pentose-phosphate pathway and nucleotide synthesis axis, and towards storage carbohydrates trehalose and glycogen. This thereby alters cellular commitments towards growth and cell cycle progression. Counter-intuitively, we discover that this metabolic-state switch in cells lacking tRNA thiolation is achieved by down-regulating a distant metabolic arm of phosphate homeostasis. We biochemically elucidate how regulating phosphate balance can couple amino acid and carbon utilization towards or away from nucleotide synthesis, and identify trehalose synthesis as a pivotal control point for this metabolic switch. Through these findings we show how tRNA thiol-modifications regulate overall metabolic homeostasis, integrating nutrient inputs to enable optimal growth. We further present a general biochemical explanation for how inorganic phosphate homeostasis regulates commitments to different arms of carbon and nitrogen metabolism, thereby determining how cells commit to a ‘growth’ or ‘starvation’ state. Earlier studies had observed an increased expression of amino acid biosynthetic genes, and an activation of the amino acid starvation responsive transcription factor Gcn4, in cells lacking tRNA thiolation (Laxman et al. , 2013;","The building blocks of all cells are made from a handful of chemical elements, including carbon, nitrogen, sulfur and phosphorus. To grow optimally, cells need to regulate their metabolism – in other words, the biochemical reactions that keep them alive – based on the availability of these elements. As a result, cells have evolved various mechanisms to sense when usable forms of these elements are present. Proteins are chains of building blocks known as amino acids, which are assembled with the help of molecules called transfer ribonucleic acids, or tRNAs for short. Some of these molecules can be modified by attaching sulfur-containing chemical tags known as thiol groups to make “thiolated tRNAs”. Research has shown that, when there was more of an amino acid known as methionine around,",380,128,0.3368
dialogsum,"#Person1#: Let me tell you some more. The interest is settled on the 20th of the last month in each quarter, It's paid quarterly. Of course it also needs to be settled if you cancel the account. #Person2#: Miao Ping, in your opinion, should we go for the Type A or Type B Account? #Person1#: Well, the Type B Account is very restricted. If your aim is to use the account the same way as your use your Settlement Account, I would recommend the Type A Account for you. #Person2#: Thanks for your time. I'll go and discuss everything with my partner and I'll be back later.",Miao Ping tells #Person2# some information about the account types and recommends the Type A Account. #Person2# says #Person2# will decide after a discussion.,107,24,0.2243
scientific_lay_summarisation-elife-norm,"Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we investigated how manipulating neurogenesis in adult mice alters excitatory synaptic transmission to mature dentate neurons. Enhancing neurogenesis by conditional deletion of the pro-apoptotic gene Bax in stem cells reduced excitatory postsynaptic currents (EPSCs) and spine density in mature neurons, whereas genetic ablation of neurogenesis increased EPSCs in mature neurons. Unexpectedly, we found that Bax deletion in developing and mature dentate neurons increased EPSCs and prevented neurogenesis-induced synaptic suppression. Together these results show that neurogenesis modifies synaptic transmission to mature neurons in a manner consistent with a redistribution of pre-existing synapses to newly integrating neurons and that a non-apoptotic function of the Bax signaling pathway contributes to ongoing synaptic refinement within the dentate circuit. Continual neurogenesis in the adult dentate gyrus (DG) produces new granule cells (GCs) that integrate into the hippocampal circuit by establishing synapses with existing neurons (Espósito et al. , 2005; Ge et al. , 2006; Toni et al. , 2008; Dieni et al. , 2013). During a transient period of maturation, new GCs exhibit intrinsic and synaptic properties distinct from mature GCs, potentially underlying the contribution of neurogenesis to memory encoding (Schmidt-Hieber et al. , 2004; Ge et al. , 2007; Aimone et al. , 2011; Marín-Burgin et al. , 2012; Dieni et al. , 2013; Brunner et al. , 2014; Dieni et al. , 2016). Yet computational models also suggest that remodeling of pre-existing circuits by continual neurogenesis can degrade established memories (Weisz and Argibay, 2012; Chambers et al. , 2004), a possibility that has recently gained experimental support from the observation that neurogenesis facilitates ‘forgetting’ (Akers et al. , 2014; Epp et al. , 2016). Circuit remodeling could occur by synaptic redistribution, wherein existing terminals that synapse onto mature GCs are appropriated by newly integrating GCs. This possibility is supported by anatomical evidence that immature dendritic spines transiently receive a high proportion of synapses from multiple-synapse boutons (Toni et al. , 2007; Toni and Sultan, 2011). Furthermore, dramatically increasing the number of new neurons does not alter the density of spines and synapses in the molecular layer, suggesting a readjustment of synaptic connections (Kim et al. , 2009). Yet whether","Neurogenesis, the creation of new brain cells called neurons, occurs primarily before birth. However, a region of the brain called the dentate gyrus, which is involved in memory, continues to produce new neurons throughout life. Recent studies suggest that adding neurons to the dentate gyrus helps the brain to distinguish between similar sights, sounds and smells. This in turn makes it easier to encode similar experiences as distinct memories. The brain’s outer layer, called the cortex, processes information from our senses and sends it, along with information about our location in space, to the dentate gyrus. By combining this sensory and spatial information, the dentate gyrus is able to generate a unique memory of an experience. But how does neurogenesis affect this process? As the dentate gyrus accumulates",380,128,0.3368
pubmed-summarization,"obtained from noguchi memorial institute for medical research , accra , ghana , and kept in the departmental animal house . animals were maintained under laboratory conditions of temperature , humidity , and light , housed in stainless steel cages ( 34 47 18 cm ) , and allowed access to water and food ad libitum . all animals were handled in accordance to the guide for the care and use of laboratory animals and experiments were approved by the faculty ethics committee . diazepam ( dzp ) , pentylenetetrazole ( ptz ) , picrotoxin ( pct ) , 4-aminopyridine ( 4-ap ) , and strychnine ( str ) were purchased from sigma - aldrich inc . , st . flumazenil was obtained from app pharmaceuticals , llc , schaumburg , il , usa . the method as described by vellucci and webster , 1984 , and moezi et al . , 2011 , the plant extract was administered at doses of 200 , 400 , and 800 mg kg body weight orally . intraperitoneal ( i.p ) injection of diazepam ( 0.1 , 0.3 , and 1 mg kg ) was used as reference anticonvulsant drug . animals were pretreated with the plant extract thirty minutes and diazepam fifteen minutes before administration of pentylenetetrazole ( ptz ) 85 mg kg subcutaneously . control animals were pretreated with distilled water ( 10 ml kg , p.o . ) . the onset of , total duration as well as frequency of clonic seizures were measured within a thirty minute period . animals received aae at doses of 200 , 400 , and 800 mg kg ( p.o . ) body weight . picrotoxin ( pct ) was injected intraperitoneally at a dose of 3 mg kg fifteen minutes after pretreatment with diazepam and thirty minutes after aae . diazepam ( 0.1 , 0.3 , and 1 mg kg ) served as positive control . control animals received distilled water ( 10 ml kg , p.o . ) . anticonvulsant activity was scored similarly to that stated in the ptz test . tonic convulsions of hind limb extremities of mice were induced using electrical current ( 50 ma , 60 hz , and 0.2 seconds ) via ear clip electrodes . control","antiaris toxicaria ( moraceae ) was evaluated for anticonvulsant activity in rodents . animal models used include maximal electroshock test ( mest ) ; pentylenetetrazole - induced ( ptz ) convulsions ; picrotoxin - induced ( pct ) convulsions ; strychnine- ( str- ) and 4-aminopyridine - induced convulsions . increase in latency to seizures as well as reduction in duration and frequency of seizures indicated anticonvulsant activity . the extract was more effective in all models used except the maximal electroshock test and strychnine - induced convulsions . antiaris toxicaria aqueous extract ( 200 , 400 , and 800 mg kg1 ) significantly ( p < 0.05 0.01 ) shortened the duration of convulsions in ptz- and pct - induced seizures . delay in the onset of",380,128,0.3368
dialogsum,"#Person1#: I was trying to find the class on preparing for interviews. #Person2#: You have found your way to the interview class. Please come in! #Person1#: I am so happy I found this class because I was really nervous about my upcoming interview. #Person2#: When we go into an interview, what do you think our first consideration should be? #Person1#: Our dress and grooming are probably the first thing an interviewer judges us by. #Person2#: Friendliness and a good attitude are also very important. #Person1#: Yes, and they help establish a friendly tone for the rest of the interview. #Person2#: The interviewers always are interested in what you ask them about their company. #Person1#: What else should I be thinking about? #Person2#: Be yourself and be honest. Simply answer the questions put to you.",#Person1# was nervous about an upcoming interview so #Person1# takes #Person2#'s interview class. #Person2# tells #Person1# the important things #Person1# should focus on during an interview.,134,26,0.194
scientific_lay_summarisation-elife-norm,"al. , 2002; Badie and Schartner, 2001; Li and Graeber, 2012; Yang et al. , 2010; Coniglio and Segall, 2013). Instead of anti-tumoural activity, they display pro-tumoural functions and promote tumor growth. Macrophages and microglia have been shown to promote tumor cell proliferation and invasiveness, to modify the extracellular matrix, to induce angiogenesis and to induce an immunosuppressive environment promoting tumor growth (Zhai et al. , 2011; Zhang et al. , 2012; Markovic et al. , 2005; Komohara et al. , 2008; Pyonteck et al. , 2013; Wu et al. , 2010; Hambardzumyan et al. , 2016; Wang et al. , 2013; Ellert-Miklaszewska et al. , 2013). Interestingly, these pro-tumoural functions seem to be independent of the tumor grade, as they have also been described for low-grade gliomas (Daginakatte and Gutmann, 2007; Daginakatte et al. , 2008; Simmons et al. , 2011). However, the earliest responses of macrophages and microglia to cancerous cells in the brain have not been addressed so far. It is not known when macrophages and microglia respond to oncogenic transformations in the brain and which signals are involved. Furthermore, we do not know how these initial responses physically appear. Are aberrant oncogenic cells initially removed by macrophages and microglia? Do pro-tumoural activities of macrophages and microglia develop only at later tumor stages? Or is the behavior of macrophages and microglia already co-opted during the early oncogenic stages in a way that they promote tumor growth? Understanding these early events is crucial as it is tempting to speculate that similar responses of macrophages and microglia occur during tumor recurrence. Thus, identifying the underlying mechanisms is a first step toward the development of new therapeutic strategies that target macrophages and microglia within brain tumors. To address the early responses of macrophages and microglia to oncogenic alterations in the brain, we made use of the larval zebrafish model. We and others have already demonstrated that the zebrafish is a powerful tool to study microglia (Peri and Nüsslein-Volhard, 2008; Sieger et al. , 2012; Xu et al. , 2016; Oosterhof et al. , 2017; Svahn et al. , 2013; Shiau et al. , 2013; Shen et al. , 2016). Besides the genetic and optical advantages of the zebrafish larvae, the small size of the zebrafish brain allows imaging of the","Brain tumors can be aggressive, difficult to treat and are often incurable. Removing brain tumors by surgery can be challenging because the tumor cells infiltrate into the healthy tissue. Brain tumors grow in close physical contact with other cells, such as cells of the immune system. This includes cells called macrophages and microglia, which normally defend us against injuries and infections. However, instead of acting against the tumor as one might expect, macrophages and microglia actually support the growth of brain tumors. It is not clear how and when during the development of a brain tumor the macrophages and microglia start helping the tumor cells to grow. Previous studies in this area have focused on these cell types found in advance brain tumors. Chia et al. have now",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Schistosomes are parasitic flatworms infecting hundreds of millions of people. These parasites alternate between asexual reproduction in molluscan hosts and sexual reproduction in mammalian hosts; short-lived, water-borne stages infect each host. Thriving in such disparate environments requires remarkable developmental plasticity, manifested by five body plans deployed throughout the parasite’s life cycle. Stem cells in Schistosoma mansoni provide a potential source for such plasticity; however, the relationship between stem cells from different life-cycle stages remains unclear, as does the origin of the germline, required for sexual reproduction. Here, we show that subsets of larvally derived stem cells are likely sources of adult stem cells and the germline. We also identify a novel gene that serves as the earliest marker for the schistosome germline, which emerges inside the mammalian host and is ultimately responsible for disease pathology. This work reveals the stem cell heterogeneity driving the propagation of the schistosome life cycle. Flatworms include more than 44,000 parasitic species that form one of the largest groups of metazoan endoparasites (Loker and Hofkin, 2015). Their life cycles typically involve asexually and sexually reproducing stages, each with its own distinct body plan and strategy to enhance transmission between multiple hosts (Clark, 1974; Pearce and MacDonald, 2002; Viney and Cable, 2011). Although the life cycles of these parasites were established more than a century ago, they have only recently been studied in cellular and molecular terms (Matthews, 2011). Since many parasitic flatworms are pathogenic, their life cycles are also the routes for disease transmission (Hoffmann et al. , 2014). Therefore, a deeper understanding of these life cycles is significant from both basic science and medical perspectives, as blocking transmission is an effective approach to fighting parasitic diseases. Focusing on the cells that may drive such parasitic life cycles, we study Schistosoma, a parasitic flatworm infecting over 250 million people, which causes the major neglected tropical disease, schistosomiasis (Hoffmann et al. , 2014). Schistosomes are transmitted through snail intermediate and human definitive hosts. Their life cycle begins with the parasite egg excreted from the mammalian host into water, releasing a free-swimming miracidium larva. The miracidium penetrates a snail host and transforms into a mother sporocyst that undergoes asexual clonal expansion to produce many daughter sporocysts that leave the mother and colonize other snail tissues. These daughters","Parasitic flatworms called schistosomes infect around 250 million people, causing the disease schistosomiasis. Schistosomes live complex lives, spending part of their life cycle inside snails and part of it inside mammals; short-lived, water-borne stages infect each of these hosts. To thrive in such different environments, schistosomes go through several life-cycle stages. At each stage the flatworms transition to a new body plan adapted to its new environment. Understanding how these transitions occur could help researchers devise new strategies for eliminating these parasites. Previous research suggested that stem cells help schistosomes transition to new body plans. Stem cells have the ability to transform into many different cell types, and have been found in schistosome larvae and adults. However, the relationship between the larval and adult stem cells was not",380,128,0.3368
pubmed-summarization,"a 36-year - old man visited the emergency department of inje university haeundae paik hospital with severe pain in both lower limbs for 1 day . a physical examination revealed pale , pulseless , and cold lower limbs . one year ago , he had been diagnosed with kimura disease ( kd ) after excision of a right upper limb mass ( . the initial laboratory findings were as follows : leukocyte count of 45.510/l with 74% eosinophils , elevated serum fibrinogen degradation product ( fdp ) level ( 18.7 g / ml ) , elevated d - dimer level ( 5.1 g / ml ) , and extremely elevated serum immunoglobulin ( ig ) e ( > 2,500 iu / dl ) . a computed tomography ( ct ) angiogram showed total occlusion of both popliteal arteries ( pas ) ( . under the presumptive diagnosis of acute limb ischemia ( ali ) , the patient underwent an emergency thrombectomy of both femoral arteries using a fogarty catheter ( edwards laboratories , santa ana , ca , usa ) . after the operation , the pain and color changes resolved , but the right foot drop remained . to prevent thromboembolic events , immunochemical tests for autoimmune diseases , including lupus anticoagulant , anticardiolipin igg and igm antibodies , anti - beta2-glycoprotein igg and igm , and anti - phospholipid antibodies , were negative . protein s activity was low , but the levels of the total and free protein s antigen were normal , suggesting a type - ii protein s deficiency . an echocardiogram was performed ; it revealed no evidence of a cardiac thrombus or decreased systolic function of the left ventricle ( ejection fraction=47% ) . under the presumptive diagnosis of kd - related ali , the patient was administered steroid therapy . a follow - up ct angiogram on postoperative day ( pod ) brachial index ( abi ) was 0.87 on the right side and 0.62 on the left . coronary angiography ( cag ) on pod 5 showed triple - vessel disease with chronic total occlusion of the left anterior descending artery ( lad ) , left circumflex artery ( lcx ) , proximal obtuse marginal artery , and posterior descending artery","kimura disease ( kd ) is an immune - mediated chronic inflammatory disease of unknown etiology . kd has many complications associated with hypereosinophilia , including various forms of allergic reactions and eosinophilic lung disease . additionally , hypereosinophilia is associated with hypercoagulability , which may lead to thromboembolic events . a 36-year - old man with kd presented with acute limb ischemia and coronary artery occlusion . he underwent thrombectomy , partial endarterectomy of both popliteal arteries , and coronary artery stent insertion . kd is a systemic disease that affects many organs and presents with thromboembolism and vasculitis . in a patient with kd , physicians should evaluate the vascular system , including the coronary arteries .",380,119,0.3132
dialogsum,"#Person1#: Hi, the lab said that you would be getting my test results in today. #Person2#: I like you to come in and discuss some further tests that I would like to run. #Person1#: I think that this is a bad sign. #Person2#: For now, I would like to run a few more tests to look into some of the problems that you mentioned. #Person1#: Why wouldn't you tell me over the phone? #Person2#: If there is any question about test results, we always do a recheck. #Person1#: I need to come in right away. #Person2#: I would be happy to see you this afternoon. If you are feeling upset, please bring a friend or relative along. #Person1#: You are scaring me! #Person2#: Come on in this afternoon and we will talk. It will be fine!",#Person2# asks #Person1# to come in and discuss some tests that #Person2# would like to run. #Person1# is worried about the test results.,136,23,0.1691
scientific_lay_summarisation-elife-norm,"SNX6 is a ubiquitously expressed PX-BAR protein that plays important roles in retromer-mediated retrograde vesicular transport from endosomes. Here we report that CNS-specific Snx6 knockout mice exhibit deficits in spatial learning and memory, accompanied with loss of spines from distal dendrites of hippocampal CA1 pyramidal cells. SNX6 interacts with Homer1b/c, a postsynaptic scaffold protein crucial for the synaptic distribution of other postsynaptic density (PSD) proteins and structural integrity of dendritic spines. We show that SNX6 functions independently of retromer to regulate distribution of Homer1b/c in the dendritic shaft. We also find that Homer1b/c translocates from shaft to spines by protein diffusion, which does not require SNX6. Ablation of SNX6 causes reduced distribution of Homer1b/c in distal dendrites, decrease in surface levels of AMPAR and impaired AMPAR-mediated synaptic transmission. These findings reveal a physiological role of SNX6 in CNS excitatory neurons. SNX6 is a member of the sorting nexin (SNX) family that plays important roles in retromer-mediated, dynein−dynactin-driven retrograde vesicular transport from endosomes to the trans-Golgi network (TGN). The retromer complex functions in endosomal protein sorting and trafficking. It is composed of the VPS26-VPS29-VPS35 core complex and a SNX subunit or subcomplex (Gallon and Cullen, 2015). In mammalian epithelial cells, SNX6 serves as dynein adaptor in retromer-mediated vesicular transport to regulate both cargo recognition and release via its interaction with the motor and the target membrane. SNX6 contains an amino-terminal Phox Homology (PX) domain that is evolutionarily conserved among SNXs and a carboxyl-terminal Bin/Amphiphysin/Rvs (BAR) domain that allows for dimerization with BAR domains of other proteins. It dimerizes with the SNX1 subunit of retromer through its BAR domain and binds to dynactin p150Glued through its PX domain, linking the dynein−dynactin motor complex to retromer-associated vesicular cargoes (Hong et al. , 2009; Wassmer et al. , 2009). Its PX domain also interacts with the TGN-enriched phospholipid PtdIns (4) P, which inhibits the interaction between SNX6 and p150Glued to facilitate dissociation of the retrograde motor from the retromer-associated cargo at the TGN (Niu et al. , 2013). Although retromer is involved in endosomal sorting and trafficking of amyloid precursor protein (APP) (Fjorback et al. , 2012; Sullivan et al. , 2011), and transport, surface expression and endocytic recycling of AMPAR (Choy et al. , 2014; Munsie et al. , 2015; Zhang et al.","Neurons are the building blocks of the nervous system. These cells generally consist of a round portion called the cell body and a long cable-like axon. The cell body bears numerous branches called dendrites, which are in turn covered in spines. Neurons communicate with one another at junctions – or synapses – that typically form between the end of the axon of one cell and a dendritic spine on another. Specialized proteins stabilize the dendritic spines and enable the cells to exchange messages across the synapse. However, it is the cell body – rather than the dendrites – that produces most of these proteins. Structures called molecular motors transport proteins to their destinations within the cell along fixed tracks, similar to how a freight train carries cargo over",380,128,0.3368
dialogsum,"#Person1#: Do I need a visa? #Person2#: No, I shouldn't think so. But you must take your passport of course. #Person1#: Yes, I know. I must get my traveler's check and some foreign currency. #Person2#: Yes, you need the traveler's check but you needn't get any foreign currency. You can have my US Dollars, I don't need them. #Person1#: Really? That's very good of you, Helen. But I must get a new suitcase, my old one needs repairing. #Person2#: You needn't buy one. You can have mine. #Person1#: That's very kind of you, Helen. I hope you don't mind my leaving you like this. I need a holiday. It won't be long. #Person2#: Don't be silly, John. I'm going with you. It's necessary for me to have a holiday too.",Helen tells John he needs a passport and traveler's checks. He can use her dollars and suitcase. John is grateful and Helen says she'll go with him.,130,27,0.2077
pubmed-summarization,"( c ) and bone lesion ( d ) , axial ct showing lytic bone lesion in d4 vertebra ( e ) immunohistochemistry staining showing positive for chromogranin ( a ) and synaptophysin ( b ) primary nec of the breast is extremely rare with the first reported case in 1983 . the most frequent reported age varies from 40 to 70 years , with a higher incidence in women greater than 60 years . as metastatic neuroendocrine tumors of the breast are more common than that of primary neuroendocrine tumors of the breast , it is , therefore , important to differentiate primary breast neuroendocrine tumor from metastatic disease to the breast because of the differences in treatment focus . primary nec of the breast can be diagnosed if the presence of a non - mammary primary site can be clinically ruled out or if an in situ component is histologically detected or both . however , findings of certain studies have revealed that ne - differentiated tumors of the breast present as dense round or irregular masses with spiculated or lobular margins on the mammogram . definitive diagnosis is made with core needle biopsy , allowing for the immunohistochemical evaluation of the specimen for the ne markers . although the use of pet for the evaluation of ne tumors has been limited , tumors with moderate or high proliferative activity can be identified by fdg pet . there are reports of fdg pet / ct in a case of neuroendocrine differentiated breast carcinoma with pleural metastases using indium-111 octreotide . there are case reports of synchronous metastases to the liver and pancreas from a primary nec of the breast . our case is the first demonstrates that 18f - fdg pet / ct provides the most significant additional information related to the accurate detection of primary nec of breast and bone metastasis and guiding treatment .","cases of primary neuroendocrine carcinoma ( nec ) of the breast have been reported , though rare . we report the case of a 45-year - old woman presented with jaundice and evaluated to have liver metastasis from neuroendocrine origin . she underwent whole body positron emission tomography / computed tomography , which showed left breast lesion and bone metastasis . fine - needle aspiration ( fna ) of breast revealed a nec . a diagnosis of a primary nec of the breast was rendered with hepatic and bone metastasis . she was treated with peptide receptor radionuclide therapy and is on follow - up .",318,106,0.3333
pubmed-summarization,", ingelheim , germany ) was performed ( trial numbers 205.114/117,4 205.115/128,5 205.130,6 205.137,6 205.266,7 205.270,8 205.235 [ understanding potential long - term impacts on function with tiotropium ( uplift)],9 205.214,10 205.256,11 205.25912 ) , as shown in . one study was longer than one year ( uplift , which included 5993 copd patients followed over four years).9 all trials included evaluation of exacerbations and spirometry . seven trials ( trial numbers 205.114/117 , 205.115/128 , 205.130 , 205.137 , 205.235 [ uplift ] , 205.256 , and 205.259 ) included measurement using the st george s respiratory questionnaire ( sgrq).13 all trial protocols were approved by independent ethics committees , and patients in all trials provided written informed consent . all trials included in this pooled analysis had common entry criteria , ie , a clinical diagnosis of copd , age > 40 years , smoking history 10 pack - years , postbronchodilator forced expiratory volume in one second ( fev1)/forced vital capacity ratio < 0.7 , and fev1 either 65% or 70% of predicted . whilst the patients participating in these studies were classified as to the severity of their copd on the basis of post - bronchodilator fev1 measurements , exclusion criteria included a history of asthma , the need for continuous supplemental oxygen , a copd exacerbation within the previous six weeks , recent myocardial infarction or hospitalization for congestive heart failure , other unstable medical conditions that may preclude participation or interpretation of the results , and use of systemic corticosteroids in doses greater than the equivalent of prednisone 10 mg daily . we believe that this is the most dependable method for excluding patients with asthma , given that it is now well known that bronchodilator responsiveness does not discriminate between asthma and copd . the following standardized definition was used to characterize copd exacerbations in the current analysis : an exacerbation is defined by two or more ( increased or new - onset ) respiratory symptoms such as cough , sputum , wheezing , dyspnea , or chest tightness , lasting at least three days , and requiring treatment with antibiotics and/or steroids , and/or hospitalization.14 patients were grouped according to inhaled anticholinergic discontinuation , ie , d ( anticholinergic prescribed prior to","background : data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids . analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.methods:a pooled analysis of randomized , double - blind , placebo - controlled , parallel - group tiotropium trials of at least six months duration was performed . trials had similar inclusion and exclusion criteria . exacerbation definition was standardized . patients were divided into two groups , ie , d ( anticholinergics discontinued at randomization , previously prescribed ) and nd ( anticholinergics not discontinued , not previously prescribed).results : demographics were balanced between the d ( n = 5846 ) and nd ( n =",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The role of pro-inflammatory macrophage activation in cardiovascular disease (CVD) is a complex one amenable to network approaches. While an indispensible tool for elucidating the molecular underpinnings of complex diseases including CVD, the interactome is limited in its utility as it is not specific to any cell type, experimental condition or disease state. We introduced context-specificity to the interactome by combining it with co-abundance networks derived from unbiased proteomics measurements from activated macrophage-like cells. Each macrophage phenotype contributed to certain regions of the interactome. Using a network proximity-based prioritization method on the combined network, we predicted potential regulators of macrophage activation. Prediction performance significantly increased with the addition of co-abundance edges, and the prioritized candidates captured inflammation, immunity and CVD signatures. Integrating the novel network topology with transcriptomics and proteomics revealed top candidate drivers of inflammation. In vitro loss-of-function experiments demonstrated the regulatory role of these proteins in pro-inflammatory signaling. Pro-inflammatory macrophage activation plays a prominent role in a large number of disorders including cardiovascular disease (CVD) (Aikawa and Libby, 2004; Glass and Olefsky, 2012; Glass and Witztum, 2001; Gregor and Hotamisligil, 2011; Liang et al. , 2007; Randolph, 2014; Ridker and Lüscher, 2014; Tabas, 2010). Established treatments for CVD such as those dependent on the cholesterol lowering effect of statins do not completely eliminate cardiovascular risk (Aikawa and Libby, 2004; Aikawa et al. , 2001; Libby, 2005), therefore alternative novel solutions are needed to tackle such residual risk by targeting pro-inflammatory activation in CVD (Ridker et al. , 2017). Characterizing the mechanisms underlying macrophage activation itself proves to be a challenging task, given the functional heterogeneity of macrophages and the complex interplay between the pro- and anti-inflammatory phenotypes (Biswas and Mantovani, 2012; Gordon and Mantovani, 2011; Koltsova et al. , 2013; Lawrence and Natoli, 2011; Ley et al. , 2011; Moore et al. , 2013; Murray et al. , 2014; Swirski and Nahrendorf, 2013). Furthermore, it is increasingly recognized that macrophage activation has many distinct types and follows a spectrum model defined by specific stimuli rather than the bipolar model of pro- and anti-inflammatory polarization that once prevailed (Murray et al. , 2014; Nahrendorf and Swirski, 2016; Xue et al. , 2014). Nevertheless, using experimental models, where cause-effect relations are well defined, within a systems-based approach might help to","When human cells or tissues are injured, the body triggers a response known as inflammation to repair the damage and protect itself from further harm. However, if the same issue keeps recurring, the tissues become inflamed for longer periods of time, which may ultimately lead to health problems. This is what could be happening in cardiovascular diseases, where long-term inflammation could damage the heart and blood vessels. Many different proteins interact with each other to control inflammation; gaining an insight into the nature of these interactions could help to pinpoint the role of each molecular actor. Researchers have used a combination of unbiased, large-scale experimental and computational approaches to develop the interactome, a map of the known interactions between all proteins in humans. However, interactions between proteins can",380,128,0.3368
dialogsum,"#Person1#: Hello room service, This is Alice Brown in room 308. We'd like to order some drinks. #Person2#: Yes, madam. What would you like? #Person1#: We'd like to start with fruit juice, apple for me and orange for my daughter. #Person2#: Right, madam. Do you want any tea or milk? #Person1#: No, thank you. Just some lemon tea for my husband and some hot milk for my children. #Person2#: Ok, and what time do you want it brought to your room? #Person1#: About 8:00 AM. Oh, wait! Please bring it half an hour earlier. We may leave early to go sightseeing in the city. #Person2#: OK.","Alice Brown calls the room service to ask for some drinks for her family. #Person2# answers and takes her order of two juices, tea, and milk, agreeing to bring the drinks by 7:30 AM.",106,34,0.3208
dialogsum,"#Person1#: Please send this memo out to all the managerial staff. . . there will be training for all the department heads next week. Attendance for managerial staff is mandatory, except for the financial department. Financial officers may participate if their schedules allow. #Person2#: You would like me to send this to all managerial staff? I'm sorry, sir, could you please clarify? Who all is included in managerial staff? #Person1#: Managerial staff is anyone who is in a position of authority or responsibility, or who has anyone working under them. It includes all supervisors and department heads. #Person2#: What about the senior account managers? Do they count? #Person1#: No, they are in a position of leadership and have more experience than normal account managers, but they do not directly supervise others. They are not members of the managerial staff and will not be included in our training.",#Person1# asks #Person2# to send the memo to the managerial staff but #Person2# isn't sure who is included. #Person1# says it includes all supervisors and department heads without the senior account managers.,147,32,0.2177
pubmed-summarization,"and 58% yield in the presence of catalyst 2 ( entry 1 ) . gratifyingly , the z selectivity remained high ( 90% ) throughout the course of the reaction . catalyst loadings of 5 mol % afforded product 4 in 65% yield with 92% z selectivity in the presence of catalyst 2 ( entry 2 ) . increasing the concentration led to modest improvements in yields while maintaining high z selectivity ( entries 3 and 4 ) . ultimately , we found that using a catalyst loading of 7.5 mol % afforded product 4 in 76% yield with 94% z selectivity ( entry 6 ) , and these conditions proved to be optimal among the various reaction conditions explored . we next examined the solvent dependence of the activities of catalysts 1 and 2 in homodimerization , as this is an important consideration in view of the solubility profiles of many peptidic substrates ( table 2 ) . several polar and nonpolar solvents were investigated reflecting those most often used in peptide synthesis . coordinating solvents [ e.g. , acetonitrile ( mecn ) ] were less active in promoting z - selective metathesis as compared to noncoordinating solvents [ e.g. , dicholorethane ( dce ) ] ( entries 2 and 3 ) . polar solvents including dimethylformamide ( dmf ) , dimethyl sulfoxide ( dmso ) , and n - methylpyrrolidone ( nmp ) were tolerated by catalysts 1 and 2 , affording product 4 in yields ranging from 55% to 67% and 90% z selectivity ( entries 46 ) . protic solvents including methanol ( meoh ) , ethanol ( etoh ) , and aqueous tert - butanol ( t - buoh ) mixtures yielded highly enriched z - olefin products ( entries 79 ) . other polar solvents including nitromethane ( meno2 ) resulted in low conversions ( entry 10 ) , presumably by activating decomposition pathways of the cyclometalated ruthenium catalysts . it is worth noting that , across the variety of reaction conditions explored , the z selectivity remained consistently high . determined by h or c nmr spectroscopy . determined by h or c nmr spectroscopy . to probe the activities of catalysts 1 and 2 further , we investigated the homodimerization of other","olefin metathesis has emerged as a promising strategy for modulating the stability and activity of biologically relevant compounds ; however , the ability to control olefin geometry in the product remains a challenge . recent advances in the design of cyclometalated ruthenium catalysts has led to new strategies for achieving such control with high fidelity and z selectivity , but the scope and limitations of these catalysts on substrates bearing multiple functionalities , including peptides , remained unexplored . herein , we report an assessment of various factors that contribute to both productive and nonproductive z - selective metathesis on peptides . the influence of sterics , side - chain identity , and preorganization through peptide secondary structure are explored by homodimerization , cross metathesis , and ring",380,128,0.3368
scientific_lay_summarisation-elife-norm,"regenerate is lost almost completely, and the damaged tissue is instead replaced by fibrotic scarring (Porrello et al. , 2011). Other examples include appendage regeneration in developing Xenopus (Dent, 1962; Slack et al. , 2004) and the progressive loss of digit regeneration in mice and humans (King, 1979; Borgens, 1982; Reginelli et al. , 1995). The basis for this phenomenon is not well understood. In some instances where tissue re-growth is dependent on stem cell based replacement of tissue (for review see Tanaka and Reddien, 2011), the loss of a stem cell population could account for the inability to regenerate. However, this explanation cannot account for situations where regeneration is not driven by a stem cell population but rather by the proliferation and de-differentiation of adjacent tissue. In these cases the loss of regenerative capacity in a still-developing organism necessitates a mechanism that selectively inactivates regenerative processes while still allowing cell proliferation and differentiation associated with normal development. Since most genes that function during regeneration also have a variety of functions either in normal development or in maintaining homeostasis in the same tissue, it is presently unclear how their expression could be regulated so as to selectively block regeneration. Genetic studies using Drosophila have provided important insights into the genetic regulation of tissue growth. Many of these studies have examined growth of the imaginal discs, larval epithelial tissues that are precursors of adult structures, such as the wing and the eye (Cohen, 1993). Imaginal discs are capable of regenerating missing portions following damage (Worley et al. , 2012). Studies of imaginal disc regeneration were pioneered by the group of Ernst Hadorn and were mostly conducted by transplanting damaged discs into the abdomens of adult female flies (Ursprung and Hadorn, 1962). More recently, imaginal disc regeneration has been studied in intact larvae by damaging portions of the disc via brief expression of a pro-apoptotic gene in a spatially-restricted manner (Smith-Bolton et al. , 2009; Bergantiños et al. , 2010). Using either a genetic ablation system (Smith-Bolton et al. , 2009), or following X-ray irradiation (Halme et al. , 2010), it was observed that the capacity of the wing-imaginal disc to regenerate progressively diminished during the later stages of the third larval instar as the larva approached the beginning of metamorphosis. Expression","The ability of many animals to regenerate damaged tissues decreases as they age, for example, newborn mice can regenerate damaged heart tissue while older mice cannot. Researchers are trying to discover why older animals lose the ability to regenerate, which may help us to develop therapies that can regenerate damaged tissues in humans. Fruit flies are relatively simple animals that are often used as models in biology experiments. In young fruit fly larvae, there are tissues called imaginal discs that regenerate well after damage; however these discs lose this ability as the larva matures. A gene called wingless is very active in young larvae if the imaginal discs become damaged and helps them to regenerate. Previous studies show that this gene is not as strongly switched on in",380,128,0.3368
dialogsum,"#Person1#: Thanks for meeting with me today. #Person2#: Well. We're trying to finish interviews today. We need a roommate by the first of next month. #Person1#: OK. So how many of you live here? #Person2#: There are 3 of us. Mary and Rob are both nursing students. I graduated last year and I'm working in a bank. #Person1#: Oh, good. I'm a student as well. #Person2#: You don't smoke, do you? Mary refuses to live with smokers. Our last roommate claimed that she never smoked, but sometimes she would and it upset Mary a lot. #Person1#: No, no, I'm a non smoker. #Person2#: OK, good. My main concern is that you are quiet. We study a lot around here. #Person1#: I'm quiet. I'm also very clean. #Person2#: Great. Rob is the cleanest one in the house, so he'll be thrilled to hear that. #Person1#: Do you guys ever cook dinner together? #Person2#: Robin, Mary do. They're both very healthy. They eat salads and exercise every day. I work a lot, so I buy cooked food at a restaurant, then carry it away to eat at home most nights. But sometimes they share their food with me. #Person1#: I love to cook and I always make a lot, so I'd be happy to share with you. #Person2#: Awesome! Well, You seem like you'd fit in well in the house. When Mary and Rob get home this afternoon, I'll tell them that I met with you and I think they would like you. After that, I'll give you a call. #Person1#: Thanks.",#Person2# needs a roommate and #Person1# comes to apply for it. #Person2# then introduces the other two roommates here and asks about #Person1#'s living habits. #Person2# thinks #Person1# would fit in well in the house. They are satisfied with each other.,260,41,0.1577
scientific_lay_summarisation-elife-norm,"Unraveling the genetic susceptibility of complex diseases such as chronic kidney disease remains challenging. Here, we used inbred rat models of kidney damage associated with elevated blood pressure for the comprehensive analysis of a major albuminuria susceptibility locus detected in these models. We characterized its genomic architecture by congenic substitution mapping, targeted next-generation sequencing, and compartment-specific RNA sequencing analysis in isolated glomeruli. This led to prioritization of transmembrane protein Tmem63c as a novel potential target. Tmem63c is differentially expressed in glomeruli of allele-specific rat models during onset of albuminuria. Patients with focal segmental glomerulosclerosis exhibited specific TMEM63C loss in podocytes. Functional analysis in zebrafish revealed a role for tmem63c in mediating the glomerular filtration barrier function. Our data demonstrate that integrative analysis of the genomic architecture of a complex trait locus is a powerful tool for identification of new targets such as Tmem63c for further translational investigation. The analysis of the genetic basis of common diseases remains challenging due to their complex pathogenesis and genetic heterogeneity in human populations (Deng, 2015; Glazier et al. , 2002; McCarthy et al. , 2008). This applies also to elevated blood pressure (BP) or hypertension, as recent meta-analyses of genome-wide association studies (GWAS) identified more than 100 gene loci associated with BP (Hoffmann et al. , 2017; Warren et al. , 2017). The effect size of the identified gene loci, however, is in general rather modest and less than 4% of the variance of BP phenotypes can be explained by these loci (Hoffmann et al. , 2017; Warren et al. , 2017), while around 40% to 50% of the variability appears heritable (Levy et al. , 2007; Miall and Oldham, 1963). Considerable evidence supports a major role of the kidney in BP regulation, and for the renal damage such as albuminuria development as a consequence of long-term BP elevation (Coffman and Crowley, 2008; Mancia et al. , 2013). Interestingly, genetic risk scores deploying BP genetic variants predict also hypertensive target organ damage in the heart, cerebral vessels, and eye, while only little evidence exists for an effect on kidney damage (Ehret et al. , 2016). In this regard, several inbred hypertensive rat models provide valuable complementary tools to uncover the genetics of kidney damage in hypertension (Schulz and Kreutz, 2012; Yeo et al. ,","The human kidneys filter the entire volume of the blood about 300 times each day. This ability depends on specialized cells, known as podocytes, which wrap around some of the blood vessels in the kidney. These cells control which molecules leave the blood based on their size. Normally large molecules like proteins are blocked, while smaller molecules including waste products, toxins, excess water and salts pass through into the urine. If this filtration system is damaged, by high blood pressure, for example, it can lead to chronic kidney disease. A hallmark of this disease, often called CKD for short, is high levels of the protein albumin in the urine. Previous studies involving rats with high blood pressure have found several regions of the genome that contribute to high",380,128,0.3368
dialogsum,"#Person1#: Did you know it was going to rain today? #Person2#: Absolutely not. This comes as a total shock to me, especially since the paper said mostly sunny. #Person1#: Well, I guess the paper must have meant mostly sunny somewhere else. But since we've come all this way, why don't we just move the blanket under that tree? #Person2#: That's a good idea. It looks like it's still dry there as long as it doesn't start to come down any harder. #Person1#: You didn't happen to bring a spare blanket, did you? This one is all wet now. #Person2#: No. But I have got some folding chairs in the car. Will they do? #Person1#: They'll be just fine. I'm really hungry. So while you are there, how about bringing me the food? #Person2#: I thought you were bringing the food. #Person1#: This is unbelievable. So what now? #Person2#: What is the name of that restaurant you like so much?",#Person1# and #Person2# go out. It rains without warning. Their blanket is wet and they don't have food. So they decide to find a restaurant.,159,25,0.1572
dialogsum,"#Person1#: Hi, I have a reservation under the name of Sandals. #Person2#: Could I see your ID, please, sir? #Person1#: Of course! Let me take it out of my wallet. #Person2#: Thank you, sir. Now, do you have a credit card, sir? #Person1#: Yes, of course. Is American Express okay? #Person2#: I'm sorry, sir. Only VISA or MasterCard. #Person1#: In that case, here's my VISA. #Person2#: Thank you. Your room number is 507, queen bed, nonsmoking. Is that agreeable to you, sir? #Person1#: Yes, I'm easy to please. #Person2#: Very good. Here is your room key, sir. If you need anything at all, please dial 0.",#Person2# confirms #Person1#'s reservation for a room. #Person1# pays with his VISA and checks in.,106,15,0.1415
dialogsum,#Person1#: What may I help you with? #Person2#: I need to file a complaint. #Person1#: What is your complaint about? #Person2#: I got robbed. #Person1#: When did this happen? #Person2#: It happened this morning. #Person1#: What was taken? #Person2#: My wallet and cell phone. #Person1#: Did you get a good look at the person who robbed you? #Person2#: I sure did. #Person1#: Would you able to pick him out of a line-up? #Person2#: That shouldn't be a problem.,#Person2# comes to #Person1# to file a complaint that #Person2# got robbed.,78,12,0.1538
dialogsum,"#Person1#: Good morning, doctor Smith's office. What can I do for you? #Person2#: Hello, this is Bob speaking, there's a pain in my stomach. I'd like to make an appointment to see the doctor this afternoon. #Person1#: Let me see. I'm afraid he is busy at that time. #Person2#: How about tomorrow? #Person1#: Sorry, but he'll be busy too tomorrow morning, and our office won't open in the afternoon. Will the day after tomorrow be ok? #Person2#: Ok, morning please, as soon as possible. #Person1#: Then come at 9:00 o'clock in the morning, the day after tomorrow, please.",Bob has stomachache and phones to make an appointment with doctor Smith. #Person1# arranges for the appointment at 9:00 am the day after tomorrow.,98,24,0.2449
scientific_lay_summarisation-elife-norm,"Local and cross-border importation remain major challenges to malaria elimination and are difficult to measure using traditional surveillance data. To address this challenge, we systematically collected parasite genetic data and travel history from thousands of malaria cases across northeastern Namibia and estimated human mobility from mobile phone data. We observed strong fine-scale spatial structure in local parasite populations, providing positive evidence that the majority of cases were due to local transmission. This result was largely consistent with estimates from mobile phone and travel history data. However, genetic data identified more detailed and extensive evidence of parasite connectivity over hundreds of kilometers than the other data, within Namibia and across the Angolan and Zambian borders. Our results provide a framework for incorporating genetic data into malaria surveillance and provide evidence that both strengthening of local interventions and regional coordination are likely necessary to eliminate malaria in this region of Southern Africa. Renewed efforts against malaria have resulted in substantial gains in malaria control, with active plans to eliminate malaria from 35 countries (Newby et al. , 2016). Malaria elimination requires that national and regional strategies consider the impact of local and cross-border importation on local transmission (Cotter et al. , 2013; Marshall et al. , 2016a; Wangdi et al. , 2015; WHO, 2017). This is particularly important for eliminating countries that share porous borders with areas of higher transmission, where importation can play a major role in sustaining or reestablishing local transmission (Sturrock et al. , 2015). Identifying within-country and cross-border blocks of high parasite connectivity and coordinating elimination strategies accordingly will likely be required for national and regional success. Coordinating the optimal interventions to deploy when and where depends on understanding the impact of imported malaria infections on local transmission. If transmission is self-sustained locally, local control measures such as vector control will be necessary. If importation strongly connects the local parasite population to an external one, then interventions aimed at reducing malaria in these sources of importation or otherwise reducing vulnerability to importation may additionally be needed or even take precedence (Cotter et al. , 2013). Currently, the extent of importation is estimated primarily by taking recent travel histories of malaria cases (Sturrock et al. , 2015) and, less commonly, from more general estimates of human mobility. However, routine","The number of malaria cases has dropped in some Southern Africa countries, but others still remain seriously affected. When people travel within and between countries, they can bring the parasites that cause the disease to different areas. This can fuel local transmission or even lead to outbreaks in a malaria-free area. When new malaria patients are diagnosed, they are often asked to report their recent travel history, so that the origin of their infection can be tracked. In theory, this would help to spot regions where the disease is imported from, and design targeted interventions. However, it is difficult to know exactly where the parasites come from based on self-disclosed travel history. At best, this history can provide information about that persons infection but nothing further in the",380,128,0.3368
dialogsum,"#Person1#: What are your strengths and weaknesses? #Person2#: As I said, I am diligent and industrious. On the other hand, I am too hard-working and I put myself under much pressure to make things perfect. #Person1#: What is your problem in working? #Person2#: I am too introverted to let others become my friends.","#Person2# tells #Person1# about #Person2#'s strengths, weaknesses, and problems in working.",53,11,0.2075
pubmed-summarization,"examined structures have reached an ideal level of opacification ; therefore , the scan delay must be individualized to the patient by using bolus - tracking software to capture 100 hu on the abdominal aorta . at the end of the arterial acquisition , delayed images focused on the graft must be acquired , performed at least 60 s and up to 120 s after contrast material injection . the cta examination can be complemented by postprocessing reconstructions , including maximum- intensity projection ( mip ) , curvilinear reformation ( cvr ) and volume rendering ( vr ) .table 1ct acquisition protocol parametersscannerrotation time ( s)collimationtable feed ( mm / s)slice thickness ( mm)slice interval ( mm)duration ( s)4 slice0.54 1 mm251.25125 - 3016 slice0.516 0.625 mm27.50.6250.62525 - 3064 slice0.564 0.625 mm800.6250.625<15fig . 1scanning coverage of unenhanced and enhanced ct - acquisition ct acquisition protocol parameters scanning coverage of unenhanced and enhanced ct - acquisition an aortic stent - graft is a device composed of a metallic portion ( nitinol , elgiloy , and stainless steel ) and graft material ( polyester , ptfe ) . on ct images only the metallic portion is visualized . on the basis of the general morphology , there are three types of stent - grafts available for treating abdominal aortic aneurysms : straight , aorto - uni - iliac grafts and bifurcated . straight aortic tube grafts have the proximal and distal attachment sites in the aorta , above the aortic bifurcation ( aorto - aortic ) . the aorto - uni - iliac device is a stent - graft that is deployed from the supra - aneurysmal aorta to one iliac artery only ; the opposite iliac artery is then occluded with an endovascular occlusion device in order to prevent retrograde blood flow into the aneurysm sac , and a femoro - femoral crossover graft maintains blood flow into the opposite limb ( . 2 ) . bifurcated stent - grafts are extended to the iliac arteries . on the basis of proximal fixation , the suprarenal fixation device has an uncovered metallic portion placed above the ostia of the renal arteries and a covered portion placed below the renal arteries : the radiological markers placed between the uncovered and covered portion","backgroundmultidetector computed tomography ( mdct ) angiography represents the standard of reference in the follow - up of patients after endovascular abdominal aortic aneurysm repair ( evar ) , being effective in the detection of the full spectrum of possible complications on both axial and 3d images.methodsthe purpose of this article is to review the normal ct angiography findings of the different types of stent - grafts and to describe the radiological findings of early and late complications after evar on axial and reconstructed images . a selection of cases of post - evar mdct angiography is presented to learn the techniques most commonly used for endovascular treatment , the correct ct scanning technique to acquire the data , the full gamut of possible procedure - related complications",380,128,0.3368
scientific_lay_summarisation-elife-norm,"proposed in the sequential-transition model were identified in these structural studies, and direct experimental study of the transition sequence has not been reported (Dong et al. , 2019; de la Peña et al. , 2018). Transiting into the next state involves multiple changes in nucleotide status and a complex conformational rearrangement of the ATPase hexamer. We still do not know the order of these events and how the chemical energy from ATP hydrolysis may be harvested to drive these transitions. In addition, there are experimental findings that appear inconsistent with the predictions of a strict sequential-transition model. For example, mutations of the Walker-A (WA) or Walker-B (WB) motifs on an ATPase impede its nucleotide-binding or hydrolysis activity, and are therefore predicted to inactivate the proteasome by blocking the transition sequence. However, Walker mutations on some ATPases of the proteasome are in fact well-tolerated in yeast (Rubin et al. , 1998; Eisele et al. , 2018; Kim et al. , 2013). Similarly, mutations of other functional motifs on different proteasomal ATPases have varying effects on protein degradation, leading to the hypothesis that the six ATPases may have nonequivalent roles in the proteasome activities despite their high levels of similarity in sequence and structure (Rubin et al. , 1998; Beckwith et al. , 2013; Erales et al. , 2012). These functional properties of the proteasome are not interpreted by the previous models and so far no alternative model that is consistent with both structural and functional observations has been suggested. Computational approaches, such as molecular dynamics simulations, are frequently employed to decipher the structural dynamics of proteins (Brini et al. , 2020). However, despite recent advances, it is still impractical to perform a full-atom simulation of a large system such as the proteasome at a biologically relevant time scale (~100 ms) (Gecht et al. , 2020). We therefore developed a novel approach to simulate the conformational dynamics of the proteasomal ATPase hexamer by constructing a physical model based on the nucleotide-dependent free-energy landscape (FEL) of the ATPase complex. To obtain the FEL, we first performed comparative analysis on known proteasome structures to identify the primary degrees of freedom (DOFs) of proteasome’s conformational changes, and applied these DOFs as the conformational coordinates of the FEL. We then parameterized the free energy surface based","In cells, many biological processes are carried out by large complexes made up of different proteins. These macromolecules act like miniature machines, flexing and moving their various parts to perform their cellular roles. One such complex is the 26S proteasome, which is responsible for recycling other proteins in the cell. The proteasome consists of approximately 31 subunits, including a ring of six ATPase enzymes that provide the complex with the energy it needs to mechanically unfold proteins. To understand how the proteasome and other large complexes work, researchers need to be able to monitor how their structure changes over time. These dynamics are challenging to probe directly with experiments, but can be assessed using computer simulations which track the movement of individual molecules and atoms. However, currently available",380,128,0.3368
dialogsum,"#Person1#: What's all the security check about, Jimmy? Does it mean the bar may be a dangerous place? #Person2#: No, of course not. Just in case. Nothing to worry about. Don't you also do this in China? #Person1#: I don't know. Maybe the same. Actually, this is my first time being in a bar. #Person2#: Oh, then it's my honor to be here with you. I can see now why you've been so curious about the bar. You like this place? #Person1#: Sure. I love this place, especially the decoration. So tasteful! #Person2#: Yeah. Other than that, the real feature is the excellent drinks. Can I have your ticket? #Person1#: Here it is. But, what for? We're already in. #Person2#: Well, with the ticket, you can get a free drink. What would you like? Orange juice? #Person1#: Yes, orange juice will be fine for me. But how can you get the drink? It's so crowded there around the counter. You can barely move. #Person2#: I'll show you how. The bar tenders know whose turn it is. And also, I can snap my fingers to catch his attention. #Person1#: Cool. Thanks. ( Jimmy brings May a glass of orange juice. ) #Person2#: Oh, fresh juice, I love it. Well, I heard American people love hanging out in bars. Is that true? #Person1#: Not everyone. But a lot of people do, especially the young. It's a fine place to spend an evening with friends or to make some new friends. #Person2#: Interesting. Hey, look over there. The dance floor is already packed with people. Oh, the girl in red dances great. #Person1#: Yeah, a dancing queen. Wanna go and join them? #Person2#: Maybe later. I wanna take some photos first. #Person1#: OK. Let me help you to hold the drink. #Person2#: Thank you.",May comes to a bar for the first time with Jimmy. Jimmy gets her free orange juice with her ticket and they talk about the bar culture in America. Then Jimmy and May see the people on the dance floor and plan to join them after Jimmy takes some photos.,301,50,0.1661
scientific_lay_summarisation-elife-norm,"Although thrombosis has been extensively studied using various animal models, our understanding of the underlying mechanism remains elusive. Here, using zebrafish model, we demonstrated that smarca5-deficient red blood cells (RBCs) formed blood clots in the caudal vein plexus. We further used the anti-thrombosis drugs to treat smarca5zko1049a embryos and found that a thrombin inhibitor, argatroban, partially prevented blood clot formation in smarca5zko1049a. To explore the regulatory mechanism of smarca5 in RBC homeostasis, we profiled the chromatin accessibility landscape and transcriptome features in RBCs from smarca5zko1049a and their siblings and found that both the chromatin accessibility at the keap1a promoter and expression of keap1a were decreased. Keap1 is a suppressor protein of Nrf2, which is a major regulator of oxidative responses. We further identified that the expression of hmox1a, a downstream target of Keap1-Nrf2 signaling pathway, was markedly increased upon smarca5 deletion. Importantly, overexpression of keap1a or knockdown of hmox1a partially rescued the blood clot formation, suggesting that the disrupted Keap1-Nrf2 signaling is responsible for the RBC aggregation in smarca5 mutants. Together, our study using zebrafish smarca5 mutants characterizes a novel role for smarca5 in RBC aggregation, which may provide a new venous thrombosis animal model to support drug screening and pre-clinical therapeutic assessments to treat thrombosis. The erythrocytes, or red blood cells (RBCs), are highly differentiated cells produced during erythropoiesis. Mature RBCs are characterized for their abundance of hemoglobin, which can deliver oxygen to surrounding tissues. Importantly, the flexible structure of RBCs makes it capable of traveling through all blood vessels including capillaries by deformation (Rodríguez-García et al. , 2016). On the benefit of accumulated hemoglobin and the deformation ability, RBCs are essential for organism development by facilitating tissue oxygen delivery and transporting carbon dioxide into the respiration tissues. Moreover, RBCs participate in the maintenance of thrombosis and hemostasis (Weisel and Litvinov, 2019). Epigenetic regulation of RBC-related genes is fundamental for normal development and maintenance of RBCs (Hewitt et al. , 2014). In this process, the regulation of chromatin accessibility is a prerequisite for gene transcription and is regulated by chromatin remodelers. For instance, Brg1 could regulate α- and β-globin gene transcription in primitive erythrocytes in mice (Bultman et al. , 2005; Griffin et al. , 2008). The nucleosome remodeling and histone deacetylase (NuRD) is identified to activate human adult-type","After an injury, cells in our blood (called red blood cells) often stick together to form clots to stop us from bleeding and prevent infection. These clots, however, can sometimes develop in veins and arteries, resulting in a condition known as thrombosis. If left untreated, these blockages can be life-threatening and lead to a heart attack or stroke. To study the physical effects of venous thrombosis and test different treatments, researchers often use animal models. In particular, the transparent embryos of zebrafish, as it easy to see how blood flows through their circulatory system. However, it is difficult to explore the underlying mechanisms that cause red blood cells to aggregate together using these models. To overcome this, Ding et al. developed a new model for venous thrombosis by",380,128,0.3368
dialogsum,"#Person1#: Can I help you, Miss? #Person2#: No, thanks, I'm just looking. How much is that necklace? #Person1#: 2,999 dollars. #Person2#: Too expensive! My sister's birthday is tomorrow. I'm thinking what I should buy for her. #Person1#: You'll find that the prices of our goods are quite reasonable. #Person2#: Well, that's certainly nice to know. I'll take it. #Person1#: It's a good choice. I'm sure she'll love it. Cash or card, Miss? #Person2#: I hope so. Card, please. #Person1#: That comes to 3,199 dollars with tax. Please sign here.",#Person1# helps #Person2# choose a necklace for her sister as a birthday present.,89,13,0.1461
pubmed-summarization,"dess , which were specifically developed to overcome this complication . before the introduction of bare - metal stents ( bmss ) , up to 50% of the patients treated by pci experienced restenosis . even in the bms era , isr remained one of the major limitations of this technique , with an average incidence of 20% , but that could increase up to 35% in complex lesions and diabetic patients.4,5 the introduction , 10 years ago , of first- and then second - generation dess transformed the practice of pci by drastically reducing the incidence of this complication to less than 10%.3 dess prevent restenosis by inhibiting vascular smooth muscle proliferation.2331 unfortunately , they also delay re - endothelialization of stent struts , leading to the potential risk of late / very late st and thereby the need for prolonged dapt . since the appearance of dess , st has become the major safety concern in contemporary pci practice . st is a rare adverse event ( 1% at 1 year and then 0.5% per year ) but remains associated with high morbidity and mortality rates.32 the overall prognosis is poor : most patients in whom st occurs present with stemi ( st - segment elevation myocardial infarction ) or out - of - hospital death , and up to 30% of those who arrive alive at hospital die within the first month . numerous factors have been implicated in st physiopathology , but studies have also shown that these predictors vary over time . these data highlight the complex physiopathology of st , depending on the timing of event occurrence . acute ( within 24 hours ) and early st ( within 30 days ) are likely related to mechanical issues concerning the stent ( eg , minimum stent area and suboptimal stent expansion ) , inadequate platelet inhibition , or patient prothrombotic factors.33 late ( up to 1 year ) and very late st ( after 1 year ) have been attributed to incomplete vascular healing and/or inadequate neointimal coverage , which in turn , promote inflammation and activation of thrombotic pathways15 and late or acquired stent malapposition . dapt associating aspirin with an oral p2y12 inhibitor has been shown to be the standard therapy following","first - generation drug - eluting stents have raised concerns regarding the risk of late and very late stent thrombosis compared with bare metal stents and require prolonged dual antiplatelet therapy . despite extensive investigations , the physiopathology of these late events remains incompletely understood . aside from patient- and lesion - related risk factors , stent polymer has been cited as one of the potential causes . in fact , the persistence of durable polymer after complete drug release has been shown to be responsible for local hypersensitivity and inflammatory reactions . third - generation drug - eluting stents with more biocompatible or biodegradable polymers have subsequently been developed to address this problem . in this article , we evaluate and discuss the concept and clinical results",380,128,0.3368
pubmed-summarization,"it is attributed to the production of melanin , a pigment that renders color to the skin and is also an integral part of a protective barrier against ultraviolet radiations from the sun . their presence in the oral cavity , especially in the gingiva and buccal mucosa is a fairly consistent and well - documented finding , especially in the dark complexioned individuals . histologically , the melanocyte is a highly differentiated entity , with a well - endowed cellular synthetic and secretory apparatus . they are characterized by the presence of intracellular granules , also called melanosomes , which actually are a product of the cell 's golgi apparatus . it is these granules , which on maturation release melanin , an endogenous pigment into the surrounding epithelial cells through a unique cytocrine mechanism . the pigmentation is discerned clinically when melanocytes aggregate in clusters of about 1 - 3m in size . the absence of obvious pigmentation in caucasians / fair - skinned people has been associated with the presence of premelanin within the cells . melanocytes are quite rare in odontogenic tumors , but all the same , it is not unheard of . the melanotic neuroectodermal tumor of infancy was initially considered to be the only pigmented jaw tumor in existence . this was until 1964 , when the first case of odontogenic origin , that of a pigmented gingival cyst was reported by grand and marcoah . odontogenic tumors that have exhibited a pigmented variant in their ranks include : adenomatoid odontogenic tumor ( aot ) , odontoma , ameloblastic fibroodontoma , ameloblastic odontoma and calcifying odontogenic cyst . the presence of melanocytes in these tumors have not been found to relate to the location of occurrence , gender predilection or biological behavior of these lesions . but how exactly do these cells make their way into the lesion is intriguing and certainly a worthy query . thirty - seven cases of odontogenic tumors showing the presence of predominantly extracellular pigmentation have been reported till date which includes 20 calcifying cystic odontogenic tumors ( ccots ) [ figures 1 and 2 ] , four aots , three ameloblastic fibroodontomas , three odontomas [ ] , two odontoameloblastomas , two ameloblastomas and one each of","melanocytes are neural crest derivatives that exhibit a ubiquitous presence in the epidermis . they determine the complexion of an individual and most importantly , provide a barrier against ultraviolet radiations from the sun . their presence in the oral cavity is a consistent finding , especially in the gingiva and buccal mucosa of the dark complexioned . melanocytes occasionally form a part of the histology of a variety of odontogenic cysts and tumors . how these cells make their way into the lesional tissue and the diagnostic relevance of their presence remains elusive . this write up attempts to trace the path melanocytes take to find themselves within odontogenic tumors and also offer possible explanations for the same .",380,120,0.3158
scientific_lay_summarisation-elife-norm,"Gβγ subunit. The membrane-anchored Gβγ subunit binds to and activates GIRK. (B) NTA lipid (head group modified with a Ni2+ chelator NTA, DOGS-NTA) is used to anchor non-lipid modified and His-tagged Gβγ (sGβγ-His10) onto the lipid membranes. 2 μM of sGβγ-His10 was used to fully saturate all NTA lipid on the membrane. The sGβγ-His10 density on the membrane can be controlled by the NTA lipid mole fraction. 32 μM C8-PIP2 was included on the same side as sGβγ-His10. (C) Membrane-bound sGβγ-His10 activates GIRK to different levels depending on the NTA lipid mole fraction. Lipid modified Gβγ is used to fully activate GIRK at the end of each experiment. GIRK currents corresponding to different NTA lipid mole fractions are normalized to the fully activated value. A detailed description of the experiment is shown in — 1. Example current traces of activation by sGβγ-His10 and lipid modified Gβγ in liposomes are shown in — 2. : http: //dx. . org/10. 7554/eLife. 15751. 00310. 7554/eLife. 15751. 004Figure 1— 1. Details of the planar bilayer experiment. To control Gβγ density in the membrane (A) GIRK2 channel proteoliposomes containing the corresponding mole fraction of DOGS-NTA-Ni2+ lipid were fused into planar lipid bilayers containing the same density of DOGS-NTA-Ni2+ lipid. (B) A high concentration KCl solution (1 M) was applied at the membrane to facilitate complete fusion of proteoliposomes attached to the membrane. (C) 1 mM NiSO4 was applied at the membrane to ensure that all NTA groups were charged with Ni2+. (D) sGβγ-His10 and C8-PIP2 were added to the top side of the membrane. GIRK2 channels with the cytoplasmic side facing the top side began to open. (E) A Na+ titration was then performed by stepwise addition of NaCl up to 32 mM final concentration. (F) After the Na+ titration, proteoliposomes of lipid modified Gβγ was fused to the membrane to maximize GIRK activation. (G) Maximum current of for each membrane is used for normalization of currents recorded in the same membrane. : http: //dx. . org/10. 7554/eLife. 15751. 00410. 7554/eLife. 15751. 005Figure 1— 2. Example traces of GIRK2 activation by sGβγ-His10 and lipid modified Gβγ in proteoliposomes. Solution contains 10 mM potassium phosphate at pH 8. 2 with 150 mM KCl on both sides of the membrane. 2 nM NiSO4,2 mM MgCl2 and 32","Signals from outside of a cell can alter the activity inside the cell. This process often involves members of a large family of proteins called G protein-coupled receptors (GPCRs) that are found on the surface of many cells in the body. When these receptors are activated they release a G protein on the inside of the cell that then splits into two parts. One of these parts – called the Gβγ subunit – can directly bind to, and open, a protein channel called a GIRK channel in the cell membrane. Once opened, these channels allow potassium ions to flow into the cell. GIRK channels are involved in a number of processes in the body. For example, GIRK2 is a major type of GIRK channel found in nerve cells.",380,128,0.3368
dialogsum,#Person1#: What can I get you? #Person2#: A cheeseburger and an order of french fries would be great. #Person1#: Would you like anything to drink? #Person2#: I feel like having a Coke. #Person1#: That's a good idea. I think I'll join you.,#Person1# helps #Person2# order food.,42,5,0.119
dialogsum,"#Person1#: what's wrong, Jerry? You look so upset. #Person2#: to be honest, I was just dumped. #Person1#: oh, I'm sorry to hear that. You can go on a holiday to cheer you up. #Person2#: no, thanks. I'm not in the mood for traveling. #Person1#: come on. A trip will do you good. Are you doing anything this weekend? #Person2#: I was planning on doing a lot of wallowing. #Person1#: well, my friends and I are planning on going to Shangri-La on Saturday. Do you want to come with us? #Person2#: where is that? #Person1#: not very far from here. We'll fly. It's about one and a half hours. #Person2#: what's there to see? #Person1#: there is a large canyon, vast grasslands, ancient forests and mountain lakes. #Person2#: oh, sounds nice. #Person1#: yes, the scenery there is breathtaking. I have some pictures at home. You can come over and take a look if you like. #Person2#: ok. Then I can make up my mind.","Jerry tells #Person1# that he was dumped, so #Person1# asks Jerry to join the trip to Shangri-La with #Person1# and #Person1#'s friend.",163,22,0.135
dialogsum,"#Person1#: Welcome to Lincoln Bank. Are you a new customer? #Person2#: Yes, I am. I opened an account with you about a month ago, but today I'm here to see about a loan of some kind. #Person1#: I see. As you don't have a long history with us, we will have to check your credit rating with your previous bank before we can promise any loan to you. #Person2#: Yes, that's fine. My credit is good ; I banked at my former bank for many years. #Person1#: May I ask why you decided to switch your account to us? #Person2#: Haha! Actually, I felt that your array of services is much better than what my old bank had on offer. Plus, I've got plenty of friends who bank with you and they are extremely happy. #Person1#: We always welcome new business. If you can give me the details of your former bank, including your account number we can begin. #Person2#: I have everything right here. I'll let you go through that and come back. I'd like to have a good read of your materials to make sure I make the right choice.","#Person2# inquires #Person1# about loans. Since #Person2# doesn't have a long history with Lincoln Bank, #Person1# asks about #Person2#'s credit rating, then #Person2# offers the details of #Person2#'s former bank.",192,30,0.1562
scientific_lay_summarisation-elife-norm,"known about eukaryotic species. This includes yeast, a popular single cellular eukaryotic model organism, whose metabolic capacities are regularly exploited in biotechnology. Yeast cells are known to participate in multi-species communities (e. g. on human skin (Findley et al. , 2013) ), but as wild yeast isolates usually maintain similar prototrophic genomes (Jeffares et al. , 2015; Liti et al. , 2009), metagenomic data are not conclusive about yeast' s metabolite exchange strategies. In laboratory experiments, yeast cultures were, however, not effective in supporting co-growth of auxotrophs that have complementary defects in amino acid and nucleotide metabolism, unless they were genetically modified to increase metabolite export (Müller et al. , 2014; Shou et al. , 2007). This contrasts with analogous studies in bacterial species, in which such growth experiments regularly show that co-cultured cells can overcome complementary metabolic deficiencies (Foster and Bell, 2012; Oliveira et al. , 2014; Pande et al. , 2014; Vetsigian et al. , 2011). In the absence of quantitative metabolite data, this observation has triggered the conclusion that co-growing prototrophic yeast cells produce amino acid and nucleotide metabolites predominantly for themselves and export them at insufficient quantities to support growth of co-growing cells (Momeni et al. , 2013; Shou et al. , 2007). Conflicting with this interpretation, we here report that yeast colonies maintain a rich exometabolome and that cells exploit this metabolic pool preferentially over their own biosynthetic capacities, which implies that metabolite exchange establishes as a natural property of yeast growth. To test whether yeast indeed possesses the capacity for metabolite exchange at growth relevant quantities, we established an alternative method to co-culture experiments. We exploited the stochastic segregation of episomes to randomly and progressively introduce metabolic auxotrophies into a yeast population which self-establishes from an initially prototrophic cell. This strategy enabled co-growing auxotrophs to enter an efficient state of metabolic cooperation, named self-establishing metabolically cooperating communities (SeMeCos). Despite an auxotrophic cell composition of up to 97%, SeMeCos achieve metabolic efficiency, growth parameters, and cell viability similar to that of genetically prototrophic cells, revealing a natural capacity of yeast to exchange metabolites at growth relevant quantities. In a SeMeCo that possesses auxotrophies in histidine, leucine, uracil and methionine metabolism, we distinguish up to eight cell types, each of which is unable to survive on","Life is sustained by an array of chemical reactions that is collectively referred to as metabolism. Some of these reactions break down complex substances to release energy and vital compounds, while others make new molecules from smaller building blocks. Bacterial communities are regularly composed of heterogeneous species, several of which have lost one or more essential metabolic pathways. Nevertheless, these cells can still survive by making use of metabolic products released by their neighbouring cells. Yeast are single-celled fungi that also form colonies and, as eukaryotes, they possess cells that are more similar to our own. However, in the laboratory, complementary metabolically deficient yeast cells do not survive when mixed together. It was presumed this is because yeast cells make only enough of each essential metabolite for themself,",380,128,0.3368
dialogsum,"#Person1#: Hi! I see you are having fun with your new computer and internet connection. #Person2#: There's so much I want to do. I'Ve just finished sending lots of emails to friends and family all over the world. I just ran a search for music to download. #Person1#: I can give you the name of a few useful website to visit. #Person2#: Thanks. That would be very helpful. I'Ve discovered that it can take a long time to find exactly what you want. There's too much information on the net. #Person1#: When you sent your emails, did you attach any files to them? #Person2#: Yes, I did. There's an anti-virus program with my email account that scans all attachments, so I'm sure I haven't sent anything nasty to anyone. #Person1#: When you use the internet, be careful not to give out your email address very often. If you do, you might get a lot of spam-unwanted email from companies trying to sell you things. #Person2#: That's good advice. I should also be careful about giving out confidential information about myself, such as my password and credit car number. #Person1#: That's right. Another thing to remember when you are surfing is that you can add a web page to your list of favourites. Your computer will remember the page and you can return there quickly next time you want to visit. #Person2#: How do I do that? #Person1#: Take this web page for example. Press the keys ' control ' and ' d ' together. Click on ' favourites ' at the top of the screen. There you are. It has been added to you favourites list. If you click it, you will automatically go to that web page again. #Person2#: That's useful to know. Thanks. I'll just log off and shout down my computer and we can go for a coffee.",#Person1#'s exploring the new computer and internet connection. #Person2# recommends some useful websites and reminds #Person1# not to give #Person1#'s email address too often to avoid spam-unwanted emails. #Person2# teaches #Person1# how to add web pages into #Person1#'s list of favorites.,311,41,0.1318
pubmed-summarization,"the renal vein . we traced the vessels in an effort to scrutinize every segment of these two tubular structures and found that the right common iliac vein crossed the vertebra and formed the left - sided infrarenal ivc ( l - ivc ) along with the left common iliac vein . the right renal vein ( rrv ) traveled retroaortically and joined the l - ivc ( . the post - anterior diameter of the hilar portion and that of the retroaortic stenotic portion of the rrv were 8.8 mm and 2.0 mm , respectively , revealed by grey - scale ultrasound , which , with peak velocities , was demonstrated by a spectral doppler of 26 cm / s and 87 cm / s , respectively . the diameter ratio and the peak velocity ratio between the dilated portion and the stenotic portion were 4.4 and 3.4 , respectively . after collecting blood from the right and left common iliac veins and the renal veins , the l - ivc crossed the midline retroaortically and flowed into the right - sided suprarenal ivc ( r - ivc ) with turbulent , high - velocity flow ( . the diameters of the l - ivc at the level of the lrv and the dilated portion of the lrv near the hilus and the diameter of the ivc at the stenotic portion were 18.6 mm , 14.3 mm and 2.3 mm , respectively , with the peak velocities of 30 cm / s , 27 cm / s and 149 cm / s , respectively . correspondingly , the diameter ratio between the dilated portion of lrv and the stenotic portion of l - ivc was 6.2 , accompanied by the peak velocity ratio of 5.5 . 1d ) . below the level of the rrv , no tubular structure was found at the right lateral portion of the aorta . the results demonstrated that the rrv traveled retroaortically to the l - ivc . after collecting blood from the right and left common iliac veins and the renal veins , the l - ivc traversed retroaortically to join the r - ivc above the level of the celiac artery . the r - ivc ascended with the azygos instead","various anatomic anomalies have been considered the causes of nutcracker syndrome ( ncs ) . posterior ncs refers to the condition , in which vascular narrowing was secondary to the compression of the retroaortic left renal vein while it is crossing between the aorta and the vertebral column . here , we report an unusual case of posterior ncs associated with a complicated malformation of the interrupted left inferior vena cava with azygos continuation and retroaortic right renal vein , diagnosed by both color doppler ultrasonography and ct angiography .",380,90,0.2368
dialogsum,"#Person1#: Can I help you? #Person2#: Yes. I am interested in applying for graduate school in America. #Person1#: We have some catalogues from U. S. universities. You may check in the reference stacks over there. #Person2#: Can you recommend some universities with good graduate schools? #Person1#: Well, generally in the U. S. each university has its own outstanding fields. But the graduate school accepts no applications after January 29th. #Person2#: Oh, no. It's already February 5th. #Person1#: So you have to apply to begin the first semester next year. #Person2#: I will think about it.",#Person2# wants to apply for graduate school in America. #Person1# tells that #Person2# has to apply to begin the first semester next year.,95,23,0.2421
scientific_lay_summarisation-elife-norm,"Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5' cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5' UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress. Transcription start site (TSS) selection and alternative promoter (AP) usage increase transcriptome diversity and its regulation. For example the level of transcription initiation can vary between different transcription start sites (TSS) under different growth conditions, in response to a specific signal or in different cell types and tissues. In addition, mRNA isoforms with different 5’ leaders can vary in their translation efficiency or their half-lives. Likewise, AP usage can lead to the generation of protein isoforms that differ in their N-termini and as a result have different or even opposite biological functions. Recent large-scale promoter analysis in hundreds of human and mouse primary cell types shed light on the prevalence of AP usage in mammals (Forrest et al. , 2014). Several studies have examined translation and stability of transcript isoforms of the same gene (Arribere and Gilbert, 2013; Floor and Doudna, 2016; Wang et al. , 2016) but little is known about the contribution of AP usage to the translational response to stress. The process of protein synthesis is highly energy consuming and tightly regulated by the availability of nutrients, oxygen and growth factors. Downregulation of the translation machinery is a major mechanism that allows cells to preserve energy and cope with environmental deficiencies. Under these conditions translation of many mRNAs is inhibited but that of others is unchanged or even enhanced in order to survive the stress.","The production of new proteins is a complex process that occurs in two steps known as transcription and translation. During transcription, the cell copies a section of DNA to make molecules of messenger ribonucleic acid (or mRNA for short) in the nucleus of the cell. The mRNA then leaves the nucleus and enters another cell compartment called the cytoplasm, where it serves as a template to make proteins during translation. A mRNA molecule contains a sequence of building blocks known as nucleotides. There are four different types of nucleotides in mRNA and the order they appear in the sequence determines how the protein is built. Both transcription and translation consume a lot of energy so they are highly regulated and sensitive to environmental changes. However, since transcription and",380,128,0.3368
dialogsum,"#Person1#: Hi, taxi. Could you take me to the financial street, please #Person2#: Pardon, where to, sir? #Person1#: I want to go to the financial stree. #Person2#: All right. Hop in, please. #Person1#: Excuse me, how long does it take to get there? #Person2#: It usually takes about half an hour. #Person1#: Oh, does it really a long way to go. #Person2#: Yes. Moreover, since the street is heavy with traffic this time of day. I'm not sure we can make it. By the way, are you pressed for the time? #Person1#: No, I'm not. you can just drive slowly and carefully. #Person2#: OK. #Person1#: You are very skillful driver. #Person2#: Thank you. #Person1#: By the way, is the fair the same for any distance? #Person2#: No. It versa according to the distance, you can read from the meter. #Person1#: Oh, I see.","#Person1# takes a taxi to the financial street. #Person2# tells him it might take a long time because of the distance and the traffic, and the fair varies according to the distance.",143,32,0.2238
dialogsum,"#Person1#: Excuse me, could you tell me where the International Post Office is? #Person2#: Go straight on; turn right at the first traffic lights. The post office is about fifty meters away. #Person1#: I see. And is the No.13 Middle School far away from the post office? #Person2#: Not at all. It's about 150 meters. Where do you want to go? #Person1#: Oh, I only want to pick up my cousin from school. I am told that the school is next to the post office, and that is why I want to know how to get to the post office first.",#Person1# needs to pick up #Person2#'s cousin from school and asks #Person2# where the International Post Office is because #Person2# was told the No.13 Middle School is next to it.,101,30,0.297
dialogsum,"#Person1#: We don't have much time. We have to be back at work in 20 minutes. #Person2#: Really? Have you got everything you need? #Person1#: Yes. What about you? What else do you want? #Person2#: Razors, soap, a towel. Ah, and a toothbrush. #Person1#: The razors and soap are over there. #Person2#: Hmm...$ 2.75 for 10 razors. That's cheap. #Person1#: Hmm...That's nice. Look! Do you want this soap? #Person2#: No, I don't. Look at this. $ 3.80 for soap. That's expensive. There, $ 1.20, that's cheap. I'll have this kind. Now, where are the towels? #Person1#: Here they are. #Person2#: How much are they? #Person1#: These are $ 70.95 each and these, $ 9.65. #Person2#: And this one, this one is $ 5.35. #Person1#: But it doesn't feel nice. You'd better buy something better than that. #Person2#: OK, then. I'll take this one, $ 7.95. It's not too expensive and it's of better quality.",#Person1# and #Person2# are buying daily necessities. #Person2# bought 10 razors for $ 2.75 and soap for $ 1.20. #Person1# recommends #Person2# to buy a better towel.,154,27,0.1753
dialogsum,"#Person1#: I am past my stop. Would you please let me get off? #Person2#: I am sorry. It's not allowed. You have to wait till the next station. #Person1#: Well, that's OK. #Person2#: Can you please slow down? I am not in a hurry. #Person1#: OK.",#Person1# is past #Person1#'s stop but it's not allowed to get off now.,46,13,0.2826
scientific_lay_summarisation-elife-norm,"of the cerebellum and non-brain controls (Westra et al. , 2010). The current study utilizes the same techniques for DNA content analysis by flow cytometry using propidium iodide (PI). PI staining is the predominant methodology for quantitatively differentiating nuclei or cells with variable DNA content and is routinely utilized as a gold standard in multiple fields including genomic comparisons across species in botany (Dolezel et al. , 2007), studies of the cell cycle (Krishan, 1975), and DNA degradation produced by apoptosis (Riccardi and Nicoletti, 2006). Prior analyses ruled out the effects of DNA dyes, nuclear size, mitochondrial contamination, and autofluorescent lipofuscin on DNA content and validated genomic increases in DNA content using quantitation of CENP-B PNA probes against human centromere repeats (Westra et al. , 2010) which have been further substantiated by identification of copy number gains in single human neurons (Gole et al. , 2013; McConnell et al. , 2013). To further validate DCV in human neurons, whole genome amplification (WGA) was used on cortical neuronal nuclei sorted into populations of high or low DNA content based upon PI intensity. Nuclei with high or low DNA content were sorted into 12 replicates of 1000,500, or 100 and were then subject to DNA content assessment by WGA to assess starting amounts of DNA template in each sample (2A). Nuclei were denatured and amplified by multiple displacement amplification (MDA) during which DNA synthesis was continually measured by SYBR Green fluorescence (2B). In every case, nuclei with high PI intensity also showed increased DNA synthesis over those with low PI intensity. These results independently confirm, as expected, that PI staining intensity faithfully reports DNA content. 10. 7554/eLife. 05116. 004Figure 2. AD cortical nuclei show increased DNA content variation (DCV) by flow cytometry. (A) Histogram displaying gating parameters used in sorting ‘high’ and ‘low’ DNA content populations for validation of DNA content. (B) Validation of DNA content analyses using semi-quantitative MDA whole-genome amplification (WGA) on ‘high’ and ‘low’ DNA content populations of 1000,500, and 100 nuclei. (C and D) Representative DNA content histograms for lymphocytes (LYM), AD cerebellum (CBL), and AD prefrontal cortex (CTX). Each colored histogram represents a separate sample in each set; CTX and CBL samples are from paired brains. Chicken erythrocyte nuclei (CEN) were used as internal calibration controls. (E)","The instructions for living cells are contained in certain stretches of DNA, called genes, and these instructions have been largely considered to be invariant, such that every cell in the body has the same DNA. However, research has revealed that many neurons in the human brain can contain different amounts of DNA compared to other cells. When cells with varied DNA are present in the same person, it is referred to as mosaicism. The effects of this mosaicism are unknown, although by altering the instructions in brain cells, it is suspected to influence both the normal and diseased brain. The brains of patients with Alzheimer' s disease often contain deposits of proteins called amyloids. The precursor of the protein that makes up most of these deposits is produced",380,128,0.3368
pubmed-summarization,"human tgf-1 gene presents two hotspot focuses : codon 10t / c ( rs1800470 ) and codon 25c / g ( rs1800471 ) . both polymorphisms were associated with drp by bernek et al . , and el - sherbini et al ( 2014 ) associated the tt genotype of tgf-1 codon 10t / c polymorphism with dnp risk . il-6 gene polymorphism -174g / c ( rs1800795 ) was associated with dnp in study conducted by muammer et al . the few studies that evaluated the association of the polymorphism ifn- + 874t / a ( rs2430561 ) with diabetes complications found association between this polymorphism and drp and with dnr . in spite of the existence of several reports examining the association of polymorphisms in various cytokine genes , much controversy remains about their role in diabetes complications . no studies to date have examined in a single population a large number of polymorphisms ( tnf- -308g / a , il-10 -1082g / a , il-10 -819t / c , il-10 -592c / a , tgf-1 codon 10t / c , tgf-1 codon 25c / g , il-6 -174g / c , and ifn- + 874t / a ) and their association with the t2d complications and comorbidities . in this study , we investigated if these polymorphisms are associated with drp , dnp , and dnr and with comorbidities ( hypertension , dyslipidemia , and obesity ) in a group of brazilian t2d patients . this study was conducted with 102 brazilian individuals , including 19 men and 83 women with clinical and laboratory diagnosis of t2d , aged from 32 to 70 years ( 54.99 8.97 years ) , recruited from the clinic of endocrinology , santa casa hospital ( belo horizonte , minas gerais , brazil ) in the period from june 2012 to september 2013 . drp was diagnosed by ophthalmoscopic examination through fundoscopic examination and slit lamp microscopic examination with present lens . dnp was defined as albumin excretion rate ( aer ) > 30 mg/24 h and without coexisting renal diseases from causes other than diabetes ; and no dnp was defined at an aer < 30 mg/24 h , at least 2 out of 3 urine collections over a 3-month period","aims . the polymorphisms of pro- and anti - inflammatory cytokines may be involved in type 2 diabetes ( t2d ) pathogenesis and its complications . methods . we investigated in 102 t2d patients the association of the cytokine polymorphisms in the tnf- , il-10 , il-6 , tgf-1 , and ifn- genes with the t2d microvascular complications and comorbidities ( hypertension , dyslipidemia , and obesity ) . cytokine genotypes were determined by pcr using cytokine genotyping tray kit . results . diabetic retinopathy was associated with gg genotype and g allele in tgf-1 codon 25c / g polymorphism ( p = 0.004 and p = 0.018 ) and the nephropathy was associated the lower frequency of gg genotype in il-10 -1082g / a polymorphism ( p",380,128,0.3368
dialogsum,"#Person1#: So, you're going back to the United States tomorrow. #Person2#: Yes, that's correct. I'm flying home. #Person1#: I'm afraid of flying, are you? #Person2#: No, flying is fine with me. #Person1#: That's great. Er, back home, do you fly quite often for your job? #Person2#: No, I go to the work by bus and drive to different business appointments, but sometimes I take the train to go to the business conferences in other cities or things like that. #Person1#: I see. So tomorrow you will have a really long flight. #Person2#: Yes, terribly long. #Person1#: It's probably 15 or 16 hours, I suppose. #Person2#: Mmm, from Shanghai to Boston, mmm, let me see, it is about 18 hours in the air. #Person1#: So how do you pass the time on the plane? #Person2#: I like to sleep as much as possible. #Person1#: OK, do you take medicine or just have a beer or...? #Person2#: No, no, I don't take any medicine. I tend to stay up late the day before, so that I'm tired and I want a sleep on the plane. #Person1#: That's a good idea. And I hope you have a good flight. #Person2#: Thank you very much.",#Person2#'s flying home but #Person2# doesn't fly often for #Person2#'s job. #Person2# tells #Person1# it will be a long flight and #Person2# tends to stay up late the day before and sleep on the plane.,201,35,0.1741
scientific_lay_summarisation-elife-norm,"present in mandibular or maxillary bone specimens. Aside from the fragmentary rodent teeth, all dental crowns (n = 179) are hominin, recovered both from surface collection and excavation. Likewise, aside from the few bird elements, all morphologically informative bone specimens are clearly hominin. In all cases where elements are repeated in the sample, they are morphologically homogeneous, with variation consistent with body size and sex differences within a single population. These remains represent a minimum of 15 hominin individuals, as indicated by the repetition and presence of deciduous and adult dental elements. The geological age of the fossils is not yet known. Excavations have thus far recovered hominin material from Unit 2 and Unit 3 in the chamber (Dirks et al. , 2015). Surface-collected hominin material from the present top of Unit 3, which includes material derived from both Unit 2 and Unit 3, represents a minority of the assemblage, and is morphologically indistinguishable from material excavated from in situ within Unit 3. In addition to general morphological homogeneity including cranial shape, distinctive morphological configurations of all the recovered first metacarpals, femora, molars, lower premolars and lower canines, are identical in both surface-collected and excavated specimens (see later in the text). These include traits not found in any other hominin species yet described. These considerations strongly indicate that this material represents a single species, and not a commingled assemblage. The cranium of H. naledi does not have the well-developed crest patterns that characterize Australopithecus garhi (Asfaw et al. , 1999) and species of the genus Paranthropus, nor the derived facial morphology seen in the latter genus. The mandible of H. naledi is notably more gracile than those of Paranthropus. Although maxillary and mandibular incisors and canines of H. naledi overlap in size with those of Paranthropus, the post-canine teeth are notably smaller than those of Paranthropus and Au. garhi, with mandibular molars that are buccolingually narrow. H. naledi differs from Australopithecus afarensis and Australopithecus africanus in having a pentagonal-shaped cranial vault in posterior view, sagittal keeling, widely spaced temporal lines, an angular torus, a deep and narrow digastric fossa, an external occipital protuberance, an anteriorly positioned root of the zygomatic process of the maxilla, a broad palate, and a small canine jugum lacking anterior pillars. The anterior and lateral vault","Modern humans, or Homo sapiens, are now the only living species in their genus. But as recently as 100,000 years ago, there were several other species that belonged to the genus Homo. Together with modern humans, these extinct human species, our immediate ancestors and their close relatives, are collectively referred to as ‘hominins’. Now Berger et al. report the recent discovery of an extinct species from the genus Homo that was unearthed from deep underground in what has been named the Dinaledi Chamber, in the Rising Star cave system in South Africa. The species was named Homo naledi; ‘naledi’ means ‘star’ in Sotho (also called Sesotho), which is one of the languages spoken in South Africa. The unearthed fossils were from at least 15 individuals and include multiple",380,128,0.3368
scientific_lay_summarisation-elife-norm,"However, some of these reports studied skill acquisition over a course of a few days, while human skill typically evolves over weeks (and months) of practice. Therefore, including several weeks of practice might be more suitable to test whether, and at what time point, M1 develops skill-specific representations. Outside of M1, learning-related activation changes have been reported in premotor and parietal areas (Grafton et al. , 2002; Hardwick et al. , 2013; Honda et al. , 1998; Penhune and Doyon, 2002; Tamás Kincses et al. , 2008; Vahdat et al. , 2015), with activation increases commonly interpreted as increased involvement of these areas in the skilled behavior. Yet, recent studies have mostly found that, as the motor skill develops, activation in these areas predominantly decreases (Penhune and Steele, 2012; Wiestler and Diedrichsen, 2013; Wu et al. , 2004). Such reductions are harder to interpret as they could reflect a reduced areal involvement in skilled performance or, alternatively, more energy efficient implementation of the same function (1b; Picard et al. , 2013; Poldrack et al. , 2005). To complicate things further, regional activity increases and decreases could occur simultaneously in the same area (1c; Steele and Penhune, 2010). In such a scenario, the net activation in the region would not change, yet, the trained sequences would engage slightly different subpopulations of the region than untrained sequences. A variant of this idea is that each specific sequence becomes associated with dedicated neuronal subpopulation (and hence fMRI activity pattern). Such a representation would form the neural correlate of sequence-specific learning – the part of the skill that does not generalize to novel, untrained motor sequences (Karni et al. , 1995). Sequence-specific activation patterns should change early in learning (1d), when behavior improves most rapidly, and stabilize later, once the skill has consolidated and an optimal pattern is established (Peters et al. , 2017). One possible way in which sequence-specific patterns could reorganize is by becoming more distinct from one another (1e; Wiestler and Diedrichsen, 2013). Having a distinctive code for each sequence might be of particular importance to the system in a trained state, allowing it to produce different dynamical sequences, while avoiding confusion or ‘tangling’ of the different neural trajectories (Russo et al. , 2018). To systematically examine the cortical changes associated","It has famously been claimed that it takes 10,000 hours to become an expert at something. But while most of us will never become concert pianists, we can all learn new motor skills and improve existing ones – from touch-typing to tennis – by practicing. What happens in the brain to produce these improvements in performance? Researchers have tried to answer this question by scanning the brains of people as they practice motor skills, but the results have proved inconsistent. Some studies find that specific brain areas become more active as people practice. This could indicate that these areas are ‘storing’ new skills. But others report that brain activity decreases with practice. This might indicate that practice instead makes certain brain areas work more efficiently. It is also",380,128,0.3368
dialogsum,"#Person1#: May I recommend you Tsingtao beer? #Person2#: Tsingtao beer? #Person1#: Yes, sir. It's one of the best beers in China. #Person2#: Really? #Person1#: Yes. The beer is brewed by using carefully selected malts, rice, hops and natural water from the Lao Mountain. #Person2#: How about its taste? #Person1#: Fine, sir. #Person2#: That sounds great. Two Tsingtao beers, please. #Person1#: Tin or bottle? #Person2#: Tin, please. #Person1#: Would you like it on the rocks, sir? #Person2#: No, thank you. #Person1#: You're welcome.",#Person1# recommends Tsingtao beer to #Person2# and #Person2# orders two tins.,82,11,0.1341
scientific_lay_summarisation-elife-norm,"(Marder et al. , 2005; Grillner, 2006; Ritzmann and Büschges, 2007; Blitz and Nusbaum, 2011; Harris-Warrick, 2011). The proximal trigger of pattern generator activity arises from the command-like neurons, which can consist of individual neurons, or populations of neurons that induce or ‘command’ specific movements (Kupfermann and Weiss, 1978; Jing, 2009). Such neurons are also implicated in controlling different parameters of the movements that they induce, such as their speed or duration (Kupfermann and Weiss, 1978; Pearson, 1993; Kristan, 2008; Jing, 2009). However, the organizational principles underlying how such command circuitry can both initiate movements and control their parameters remain unclear. Moreover, in many cases in which the activity of command-like neurons has been experimentally manipulated (Jing, 2009), the behavioral impact of the manipulations was not assessed in intact and freely moving animals. The development of neurogenetic tools in Drosophila has led to rapid progress in identifying command-like neurons. This progress has been enabled by the use of optogenetic and thermogenetic activation of specific, genetically targeted populations of neurons in freely moving adult flies (Flood et al. , 2013a; Owald et al. , 2015). For example, activation of specific neuronal types can elicit stereotyped movements such as feeding, locomotion, courtship song, or escape (Lima and Miesenböck, 2005; von Philipsborn et al. , 2011; Flood et al. , 2013b; Gao et al. , 2013; Inagaki et al. , 2014; Bidaye et al. , 2014; von Reyn et al. , 2014). Although some of these studies have led to the identification of individual neurons and groups of neurons that command their respective behaviors, the anatomical organization of and functional connections among such groups of neurons that control these movements has been largely unexplored. Grooming movements (a. k. a. cleaning, scratching, or wiping reflexes) can be studied to determine the neuronal mechanisms by which specific movements are initiated and controlled. Grooming is ubiquitous among limbed animals as a means of protecting the body surface from different types of mechanical or chemical irritants (Sachs, 1988). Such sensory stimuli induce the movement of a limb to the irritated body part, which then scratches or wipes the surface (Stein, 1983; Dürr and Matheson, 2003). Because grooming movements can be predictably elicited by defined stimuli, they offer a way to access the sensory-connected neural circuitry that commands","Many movements that animals perform regularly—including walking and grooming—consist of stereotyped sequences of muscle contractions. For example, a dog may scratch its side in response to a fleabite or because it is itchy. But how does the nervous system trigger such specific movements from among the repertoire of different movements that the animal could perform? It also remains unclear how such movements can be produced in a reliable, yet flexible manner. Hampel et al. have now described the neural circuit that triggers and controls the stereotyped leg movements that the fruit fly Drosophila uses to groom its antennae. Such grooming movements are stereotyped yet have certain degrees of flexibility, which makes them ideal to study the neural circuits that underlie specific movements. Grooming further lends itself to this",380,128,0.3368
dialogsum,"#Person1#: Where's Bill? The ambassador is already here. The meeting is set to start at 9 am. #Person2#: He's late again. Traffic is probably holding him up. You know, he commutes from the suburbs. It's not easy commuting every day. We should cut him some slack. #Person1#: Even though the traffic is bumper-to-bumper out there, I don't think it's heavy traffic that makes Bill late. He takes the train, remember? #Person2#: Oh, that's right. Well, the train shouldn't be late. That means there is only one explanation. . . Bill must have overslept. #Person1#: Well, to be fare, since he's coming all the way from Lancaster, he's got to get up much earlier than the rest of us. He must get start on his commute about six thirty, no telling what time he actually gets up. #Person2#: That's right, because he's got to get to the train station from his house, then take the blue line into the city, then switch trains to the red line. In all, the trip's got to take more than 2 hours. #Person1#: Why doesn't he just drive to work? #Person2#: It's too difficult to park your car in the city. Also, the traffic coming in from the suburbs is a nightmare.","Bill is late and #Person2# thinks the traffic is probably holding him up, but #Person1# tells that Bill takes the train. They then think Bill must have overslept and they talk about the time it takes for Bill to commute.",207,40,0.1932
scientific_lay_summarisation-elife-norm,"The Drosophila genome contains >13000 protein-coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here, we present a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins, we created transgenic lines, and for a total of 207 lines, we assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we visualised many proteins at endogenous expression levels and found a large fraction of them localising to subcellular compartments. By applying genetic complementation tests, we estimate that about two-thirds of the tagged proteins are functional. Moreover, these tagged proteins enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will boost systematic analysis of protein expression and localisation in various cellular and developmental contexts. With the complete sequencing of the Drosophila genome (Adams et al. , 2000) genome-wide approaches have been increasingly complementing the traditional single gene, single mutant studies. This is exemplified by the generation of a genome-wide transgenic RNAi library (Dietzl et al. , 2007) to systematically assess gene function in the fly or by the documentation of the entire developmental transcriptome during all stages of the fly’s life cycle by mRNA sequencing (Graveley et al. , 2011). Furthermore, expression patterns were collected for many genes during Drosophila embryogenesis by systematic mRNA in situ hybridisation studies in different tissues (Hammonds et al. , 2013; Tomancak et al. , 2002; 2007). Particularly for transcription factors (TFs), these studies revealed complex and dynamic mRNA expression patterns in multiple primordia and organs during development (Hammonds et al. , 2013), supposedly driven by specific, modular enhancer elements (Kvon et al. , 2014). Furthermore, many mRNAs are not only dynamically expressed but also subcellularly localised during Drosophila oogenesis (Jambor et al. , 2015) and early embryogenesis (Lécuyer et al. , 2007). Together, these large-scale studies at the RNA level suggest that the activity of many genes is highly regulated in different tissues during development. Since the gene function is mediated by the encoded protein (s), the majority of proteins should display particular expression and subcellular localisation patterns that correlate with their function. However, a lack of specific antibodies","The fruit fly Drosophila melanogaster is a popular model organism in biological research. Studies using Drosophila have led to important insights into human biology, because related proteins often fulfil similar roles in flies and humans. Thus, studying the role of a protein in Drosophila can teach us about what it might do in a human. To fulfil their biological roles, proteins often occupy particular locations inside cells, such as the cell’s nucleus or surface membrane. Many proteins are also only found in specific types of cell, such as neurons or muscle cells. A protein’s location thus provides clues about what it does, however cells contain many thousands of proteins and identifying the location of each one is a herculean task. Sarov et al. took on this challenge and",380,128,0.3368
pubmed-summarization,"evolution of this dependence in order to test the theory with observations . this paper uses the quasi - linear formulation to evaluate the energy and time dependence of rep , and investigates how different parameters affect the diffusion coefficients and the energy spectrum . when applied with input wave and particle data from satellites ( e.g. , van allen probes , goes ) , the results from our model can be directly compared with balloon ( e.g. , balloon array for rbsp ( radiation belt storm probes ) relativistic electron losses ) and low - altitude satellite ( e.g. , solar anomalous and magnetospheric particle explorer ( sampex ) and polar - orbiting operational environmental satellites ( poes ) ) measurements to investigate the role of emic waves in causing rep as well as the effectiveness of the adopted theoretical model . we use quasi - linear diffusion theory to model the evolution of the distribution of electrons due to interactions with emic waves . radial and energy diffusion are ignorable because the frequency of the emic waves is well above the drift frequency and well below the gyrofrequency of the resonant particles [ kennel , 1966 ] . the bounce - averaged diffusion equation for pure pitch angle scattering can be written as [ davidson and walt , 1977 ; lyons , 1973 ; lyons and williams , 1984 ; shao et al . , 2009 ] 2where t(0)=1.38020.3198(sin(0)+ sin1/2(0 ) ) is the normalized bounce time , f0 is the trapped electron phase space density , 0 is the equatorial pitch angle , d(0,e) is the bounce - averaged pitch angle diffusion coefficient , and atm is the timescale for losses to the atmosphere . assuming that losses occur only from within the loss cone and that the loss cone is emptied twice per bounce period , we take atm to be half of the bounce period inside the loss cone and infinite outside the loss cone [ lyons , 1973 ; davidson and walt , 1977 ; lyons and williams , 1984 ; shao et al . , the differential flux is related to the phase space density through the electron momentum p as j0=pf0 . to capture the feature of the isotropic flux distribution in","previous studies on electromagnetic ion cyclotron ( emic ) waves as a possible cause of relativistic electron precipitation ( rep ) mainly focus on the time evolution of the trapped electron flux . however , directly measured by balloons and many satellites is the precipitating flux as well as its dependence on both time and energy . therefore , to better understand whether pitch angle scattering by emic waves is an important radiation belt electron loss mechanism and whether quasi - linear theory is a sufficient theoretical treatment , we simulate the quasi - linear wave - particle interactions for a range of parameters and generate energy spectra , laying the foundation for modeling specific events that can be compared with balloon and spacecraft observations . we show",380,128,0.3368
pubmed-summarization,"tissues , in intra- and periarticular fibrous tissues and along the perimisial , endomisial sarcolemma of striated muscle fibres were detected , showing immunoreactive for neurofilaments , nse , synaptophysin and to s-100 antibodies . in the articular fibrous cartilage ( articular disk ) any previously described nrec was identified ; only s-100 protein seemed to react with chondrocytes both in normal and diseased tissues . furthermore , chondrocytes of healthy individuals appeared round - shaped , with distinct cell borders and central nuclei with an evident s-100 reactivity both in nucleus and in cytoplasm . in diseased tmj , instead , chondrocytes showed a different morphoology , especially after s-100 immunostaining : they had an elongated cytoplasm with one or more thick dendritiform processes of variable length but with a strong reactivity only for s-100 protein . the number of dendritiform chondrocytes was higher in specimens of diseased patients than in healthy patients and seems undergo a reactive reparative proliferation of discal and peridiscal tissues . few studies are reported in literature on the precise identification and distribution of nrec in articular and peri - articular tissues of tmj . in the past , some authors 3 - 6 identified ruffini's - like , pacini 's like and golgi 's like receptors both in articular and periarticular tissues , using conventional or histochemical methods usually performed to identify nerve fibres and receptors 7,8 . by using immunofluorescent techniques , other authors 3 demonstrated the presence of nervous fibers in the periarticular fibrous tissues , which seemed to run along the blood vessels reaching the fibrous cartilage of tmj and ending to the inside . our study confirmed the results of other preceding reports on the presence of several different types of nrec in periarticular soft tissues of tmj , allowing additionally a precise immunohistochemical identification of ruffini's - like , pacini's- like and golgi's - like receptors in skeletal muscles and tendons , in periartcular dense fibrous connective tissues and in subsynovial tissues . in fact , nrec appeared nse , s-100 and mbp immunoreactive showing gfap and and leu-7 immunoreactivity to lower degrees . free nervous endings , immunohistochemically positive for neurofilaments , nse , and s100 protein , have been detected only in periarticular soft tissues (","aim : a study was performed on the articular disk and periarticular tissues of the temporo - mandibular joint ( tmj ) with immunohistochemical techniques to give evidence to the presence of neuroreceptors ( nrec ) in these sites . methods : the study was carried out on tissue samples obtained from 10 subjects without tmj disease and from 7 patients with severe tmj arthritis and arthrosis . we use antibodies directed against following antigens : gliofibrillary acidic protein ( gfap ) , leu-7 , myelin basic protein ( mbp ) , neurofilaments 68 kd ( nf ) , neuron specific enolase ( nse ) , s-100 protein ( s-100 ) and synaptophysin ( syn ) . results : this study revealed that ruffini's - like , pacini's",380,128,0.3368
dialogsum,"#Person1#: Did you watch television last night, Richard? #Person2#: Yes, I did. Was there anything that interested you, Laura? #Person1#: There was a good game. Did you see it? #Person2#: Oh, I didn't. I wanted to, but my wife preferred to see an old film. #Person1#: What a pity! It was quite exciting. Both teams played very well. #Person2#: How did it finish? #Person1#: It finished in a draw. What was the film like? #Person2#: It was quite good. But I missed the beginning of it because I had to eat first. #Person1#: Did your wife enjoy it? #Person2#: No, she didn't. After half an hour she stopped watching and started to read a book before going to sleep.","Laura tells Richard a good game she saw last night, and Richard tells her he watched a film with his wife.",119,21,0.1765
scientific_lay_summarisation-elife-norm,"heterotetramer that consists of two heavy chains (KHC) and two light chains (Kuznetsov et al. , 1988). Each KHC polypeptide contains two microtubule-binding domains: one ATP-dependent site in the motor domain and a second ATP-independent site at the C-terminus (Hackney and Stock, 2000; Seeger and Rice, 2010; Yan et al. , 2013). Kinesin-1 is thought to slide microtubules against each other with these two heavy chain domains; one microtubule is used as a track, while the other is transported as a cargo; kinesin light chains are not required for sliding (Jolly et al. , 2010; Yan et al. , 2013). Axons contain microtubule arrays of uniform orientation with plus-ends facing the axon tip (Baas et al. , 1988; Stone et al. , 2008). However, kinesin-1 is a plus-end motor, and therefore can only slide microtubules with their minus-ends leading and plus-ends trailing (1A), which is inconsistent with the final orientation of microtubules in mature axons. To address this apparent contradiction, we asked two questions: First, are microtubules indeed pushed with their minus-ends out at the initial stages of axon outgrowth, as would be expected if they are pushed by kinesin-1? Second, if this is the case, how are microtubules with the ‘wrong’ orientation replaced by microtubules with normal (plus-end-out) orientation in mature axons? To address these questions, we imaged and tracked markers of microtubule plus-ends and minus-ends in cultured Drosophila neurons and S2 cells at different stages of process growth. Our results showed that, at the initial stages of neurite formation, microtubules have mixed polarity with minus-ends being pushed against the plasma membrane; later, cytoplasmic dynein, attached to the actin cortex, removes minus-end-out microtubules to the cell body, creating microtubule arrays with uniform plus-end-out orientation. We speculate that regulation of dynein’s microtubule sorting activity could explain the differences in microtubule orientation between axons and dendrites. 10. 7554/eLife. 10140. 003Figure 1. Microtubule minus-ends push the plasma membrane during the initial stages of neurite outgrowth. (A) Model of microtubule-microtubule sliding driven by kinesin-1. Kinesin-1 slides antiparallel microtubules apart with their minus-ends leading (left panel). When kinesin-1 binds to parallel microtubules (right panel), forces applied by the two motors to the two microtubules are counteracted resulting in no net movement; instead, kinesin-1 crosslinks these microtubules. Large green arrows indicate direction of microtubule sliding;","Motor proteins can move along filaments called microtubules to transport proteins and other materials to different parts of the cell. Microtubules are “polar” filaments, meaning that they have two distinct ends that have different chemical properties. Motor proteins can only move along these filaments in one direction, for example, the kinesin motor proteins generally move toward the so-called “plus-end”, while dynein motors move in the opposite direction. A typical nerve cell (or neuron) is composed of a cell body, a long projection called an axon and many small branch-like structures called dendrites. Within the axon, the microtubules are arranged so that their plus-ends point outwards, but the microtubules in dendrites are arranged differently so that many minus-ends point outwards instead. This polarity is important for the neuron in",380,128,0.3368
dialogsum,#Person1#: Ten dollars? Maybe there are a lot of them. . . #Person2#: Seven dollars!!! Incredible! But I saw that the seller has kind of a bad rating. #Person1#: Was it a delivery problem or a problem with the products? #Person2#: I read that someone called him a cheat and a liar! And I noticed that he won't ship abroad. #Person1#: Some people get nasty on those comments. Maybe you should write him and ask nicely. #Person2#: OK. Wish me luck!,#Person1# and #Person2# discuss the bad rating on this seller and decide to write a letter to him.,81,18,0.2222
dialogsum,"#Person1#: How do you like the apartment? #Person2#: I like the apartment, but I see something wrong with it. #Person1#: What's wrong? #Person2#: There's a leaking faucet in the sink. #Person1#: That isn't a problem. #Person2#: That leak is going to raise my water bill. #Person1#: What can I do? #Person2#: You need to fix it. #Person1#: I can't right now. #Person2#: I won't rent it if the faucet isn't fixed. #Person1#: I will fix it for you. #Person2#: I'm glad you finally agree.",#Person2# likes the apartment but there's a leaking faucet in the sink and asks #Person1# to fix it.,84,18,0.2143
pubmed-summarization,"hybrid dx tiles do not form any large , regular assemblies . overall , the formation of tubules is preferred over two - dimensional arrays in all cases , and rna dna hybrid dx tiles are more prone than pure dna dx tiles to form tubular structures . the strategy of using dna to program rna self - assembly is a general approach and can be used for the construction of a variety of structures . to demonstrate this capability , we engineered two rna dna hybrid star motifs . symmetric dna star motifs are a family of related nanostructures that have different numbers of branches ( 3 , 4 , 5 and 6 ) . each motif is assembled from three different strands : a long repetitive strand ( l ) , a medium strand ( m ) and a short peripheral strand ( s ) . all star motifs share the same strands m and s , but differ from one another in strand l. the sequence repeating time of the l strand determines the branch number of the motif . in the current work , the m strand is replaced by an rna strand ( r ) , resulting in rna dna hybrid star motifs . rna residues comprise half of the nanomotifs . when appropriate sticky ends are present at the peripheral ends of the duplexes , the hybrid motifs can further associate with each other into two - dimensional arrays ( figs 2 and 3 ) . the l strands contain unpaired , single - stranded loops ( shown in orange in figs 2 and 3 ; three or four bases long for the three- or four - pointed star , respectively ) at the centre . the short loops are long enough to prevent the branches from stacking with one another at the centre , and short enough to prevent the tiles from being too flexible . to prevent the intrinsic curvatures of the tiles from accumulating in one direction , a corrugation strategy was also applied12,33,34 . any two interacting tiles are separated by 4.5 turns , so the two adjacent tiles are related by a twofold rotational axis that is perpendicular to the molecular plane . this arrangement cancels the intrinsic curvatures","dna has recently been used as a programmable smart building block for the assembly of a wide range of nanostructures . it remains difficult , however , to construct dna assemblies that are also functional . incorporating rna is a promising strategy to circumvent this issue as rna is structurally related to dna but exhibits rich chemical , structural and functional diversities . however , only a few examples of rationally designed rna structures have been reported . herein , we describe a simple , general strategy for the de novo design of nanostructures in which the self - assembly of rna strands is programmed by dna strands . to demonstrate the versatility of this approach , we have designed and constructed three different rna dna hybrid branched",380,128,0.3368
scientific_lay_summarisation-elife-norm,"following treatment with TLR4 ligands (Hargreaves et al. , 2009; Escoubet-Lozach et al. , 2011). Both HATs are recruited by the NF-kB subunit p65 to regulatory regions in a stimulus-dependent manner (Hargreaves et al. , 2009; Ghisletti et al. , 2010). Histone modifications are then bound by ‘readers’ such as BRD4, a protein containing two conserved N-terminal bromodomains (BD1 and BD2), which associates with most active promoters and some active enhancers, and has been proposed to couple the acetylation state at enhancers and promoters with Pol 2 elongation (Lovén et al. , 2013; Brown et al. , 2014). BRD4 occupancy correlates with acetylation marks at H4K5/8/12, H3K9/27 (Lovén et al. , 2013; Kanno et al. , 2014; Nagarajan et al. , 2014) and with gene activation, whereas chemical inhibition of BRD4 binding abrogates the induction of a subset of genes (Nicodeme et al. , 2010). Furthermore, BRD4 has been shown to associate with P-TEFb, affecting Pol 2 CTD phosphorylation, and hence, transcription elongation (Itzen et al. , 2014). These events coalesce ensuring a rapid remodeling of the inflammatory transcriptome, with hundreds of genes undergoing a dramatic upregulation (Escoubet-Lozach et al. , 2011; Chinenov et al. , 2012; Gupte et al. , 2013; Uhlenhaut et al. , 2013; Tong et al. , 2016). Although essential for host defense, unabated inflammation imposes a threat to the host and can result in tissue damage and autoimmunity. One systemic mechanism that controls acute inflammatory response is a feedback loop whereby inflammatory cytokines trigger the production of steroid hormones known as glucocorticoids (GCs) (reviewed in [Sacta et al. , 2016]). Lipophilic GCs diffuse through the cell membrane and bind the intracellular glucocorticoid receptor (GR), a transcription factor (TF), which then translocates to the nucleus and regulates gene expression. The transcriptional outcomes of GR activation are context-specific and are determined by the genomic GC response elements (GRE) to which the receptor binds. GR can bind directly to specific, usually pseudopalindromic, DNA sequences either as a homodimer or complexed with other TFs such as AP1 and STAT3 (Biddie et al. , 2011; Langlais et al. , 2012). In this context, GR recruits various coregulators such as members of the p160 family, HATs, the Mediator complex and ATP-dependent chromatin remodelers (Weikum et al. , 2017b), ultimately leading to","Inflammation is one of the body’s responses to fight infection and heal tissue damage. The response is controlled by hundreds of genes, which fall into two classes. In the first class, an injury or infection triggers the enzyme RNA Polymerase to bind to and transcribe the gene into long RNA strands, which are then translated into the proteins that play a role in the inflammation response. The second class has a more quick-fire response. RNA Polymerase binds to these genes even without an injury or infection to serve as a trigger. But most of the time the enzyme only transcribes the beginning of these genes. This is because it is inhibited by a so-called negative elongation factor, which acts like a brake. For this second class of genes,",380,128,0.3368
pubmed-summarization,"and recombinant fviii products , the benefits of primary prophylaxis were demonstrated and they became the standard of care for patients with severe factor deficiencies.8,9 the widespread use of prophylactic regimens has improved joint outcome and increased quality of life,9,10 but it has also been associated with the development of neutralizing antibodies , or inhibitors , in ~25.9%32% of these patients.11,12 additional factors contribute to the risk of inhibitor development , including genetic mutation , age , race , and intensity of exposure , and these are confounding factors to the problem . the development of inhibitors is generally considered the most frequent serious adverse event in these patients . without an effective rise in factor activity following an infusion , patients continue to bleed frequently and severely , and the benefit of prophylaxis is eliminated . low levels of inhibitors may be overcome by utilizing higher doses for infusion , but a different strategy is necessary when the inhibitor levels are high . patients who develop high levels of inhibitors may be managed effectively with bypass agents , such as activated prothrombin complex concentrate ( such as feiba [ factor eight inhibitor bypassing activity ] ) or activated fvii . these replacement products are extremely effective in the management of acute bleeds and , for some , in the long - term management of bleeds in patients with inhibitors . however , breakthrough bleeding is still common and leads to early joint damage , hemophilic arthropathy , and long - term disability . most patients who develop inhibitors will therefore be tried on immune tolerance induction ( iti ) therapy . they are exposed to high doses of a fviii product on a frequent basis . in patients who respond , the repeated exposure allows the immune system to tolerize itself to fviii and recovery of fviii activity occurs . once this is achieved , the frequency of exposure is reduced until a return to a standard prophylactic schedule is achieved . approximately 70% of patients will be able to tolerize after going through iti , and the time that is required for tolerization may be several years.13 the cost of high doses of factor can also be prohibitive for some patients.14 the human fviii protein was purified in","hemophilia a , a deficiency in the activity of coagulation factor ( f ) viii , is an x - linked bleeding disorder with an approximate incidence of one in 5,000 male infants . bleeding - related complications often result in greater severity of disease , poor quality of life , surgical interventions for severe joint destruction , and shortened life span . with the availability of plasma - derived and recombinant fviii products , the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies . current hemophilia research is focusing on the creation of new factor replacement therapies with longer half - lives ; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing activity ; and",380,128,0.3368
dialogsum,"#Person1#: I love slim girls, don't you? #Person2#: Not particularly. I like fat girls. #Person1#: And I like a girl with good skin, do you? #Person2#: I can't say I do. What I like a girl with good manners. #Person1#: Well, yes. But surely you like a girl with a nice . #Person2#: Yes. But I like a girl with a nice personality. #Person1#: But you like a girl to be rich, surely? #Person2#: Not particularly. I like a girl to be good. #Person1#: What about you, Henry? You haven't said a thing. #Person3#: I don't like girls. I think they're awful.","#Person1# likes a girl with a nice , while #Person2# likes a girl with a nice personality. Henry doesn't like girls.",102,21,0.2059
scientific_lay_summarisation-elife-norm,"molecular guidance cues directing axon outgrowth have been well-studied, an understanding of the molecular mechanisms responsible for directing target-specific connectivity has remained elusive. A primary mechanism for establishing nascent synapses is through the actions of synaptic adhesion molecules, also known as synaptic organizers (de Wit and Ghosh, 2016; Missler et al. , 2012). These organizers are often anchored to the pre- and post-synaptic membranes (e. g. neurexins, neuroligins, leucine-rich repeat transmembrane proteins/LRRTMs) and promote synapse formation through trans-synaptic adhesion and signaling. The importance of these processes in establishing proper neural circuit connectivity is highlighted by the links between mutations in genes encoding these synaptic adhesion/organizing molecules and neuropsychiatric and neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia (Kim et al. , 2008; Reichelt et al. , 2012; Rujescu et al. , 2009). Intriguingly, synaptic organizers are capable of acting in a cell-specific manner to promote synapse formation (Chen et al. , 2017; Siddiqui et al. , 2013; Zhang et al. , 2015). Thus, an exciting possibility is that individual neurons could encode connections with alternate synaptic partners through differential deployment of synaptic organizers. We have investigated this possibility in the motor circuit of the nematode Caenorhabditis elegans where individual excitatory cholinergic motor neurons form synapses with both body wall muscles and GABAergic motor neurons. Through a screen for genes that govern the formation of these divergent synaptic connections, we demonstrate that the synaptic organizer nrx-1/neurexin directs the outgrowth of previously uncharacterized dendritic spine-like structures and the formation of synaptic connections with GABAergic neurons, but is not required for synaptic connectivity with muscles. Conversely, genes previously shown to be required for cholinergic connectivity with muscles (Francis et al. , 2005; Gally et al. , 2004; Pinan-Lucarré et al. , 2014) are not required for the formation of synapses onto GABAergic neurons. Our findings demonstrate that cholinergic neurons utilize distinct molecular signals to establish synapses with GABAergic motor neurons versus body wall muscles, thus revealing that a single presynaptic neuron establishes divergent connections by employing parallel molecular strategies for the formation of connections with each postsynaptic partner. To establish a system to investigate mechanisms instructing synaptic connectivity, we labeled post-synaptic specializations on dorsally directed GABAergic DD neurons using cell-specific expression (flp-13 promoter) of the GFP-tagged acetylcholine receptor subunit ACR-12. Prior work","Nervous systems are complex networks of interconnected cells called neurons. These networks vary in size from a few hundred cells in worms, to tens of billions in the human brain. Within these networks, each individual neuron forms connections – called synapses – with many others. But these partner neurons are not necessarily alike. In fact, they may be different cell types. How neurons form distinct connections with different partner cells remains unclear. Part of the answer may lie in specialized proteins called cell adhesion molecules. These proteins occur on the cell surface and enable neurons to recognize one another. This helps ensure that the cells form appropriate connections via synapses. Cell adhesion molecules are therefore also known as synaptic organizers. Philbrook et al. have now examined the role",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2012; Bays, 2014), highlighting the flexibility of memory representations in terms of both quantity and quality (Ma et al. , 2014). These influential methods from the working memory literature have started to be applied to behavioral studies of long-term memory (Brady et al. , 2013). Importantly, it is possible to separate behaviorally the probability of recollection success from the precision with which information is retrieved (Harlow and Donaldson, 2013; Harlow and Yonelinas, 2016), which can be differentially influenced by attention and retrieval practice (Fan and Turk-Browne, 2013). Furthermore, a recent EEG study supports the idea that variations in long-term memory precision may be associated with distinct neural signatures, finding the well-established left parietal old/new effect to be graded according to recollection precision (Murray et al. , 2015). The observation that retrieval success and retrieval precision can be manipulated independently suggests that using continuous measures to differentiate such components will lead to a more detailed understanding of episodic memory retrieval at both behavioral and neural levels. Retrieval success and retrieval precision both constitute objective measures of memory performance. However, increasing research has additionally considered subjective or metacognitive measures of memory performance, such as confidence (Yonelinas, 1994) or the vividness with which retrieved memories are experienced (Kuhl and Chun, 2014; St-Laurent et al. , 2015). Research has found that subjective and objective measures of memory performance can diverge (Chua et al. , 2012; Harlow and Yonelinas, 2016). Most notably, patients with parietal cortex lesions exhibit impairment in subjective memory reports even though their objective performance appears to be intact (Simons et al. , 2010), and lateral parietal transcranial magnetic stimulation has been found to selectively reduce memory confidence but not retrieval success (Yazar et al. , 2014). One possibility is that the subjective and objective memory components that may drive mnemonic decisions are separable, with subjective aspects of retrieval, such as vividness, and objective aspects of retrieval, such as success and precision, relying on largely independent processes. Alternatively, it is possible that performance on subjective measures of memory retrieval used to date can be fully explained by subtle variations in objective memory, such as the precision with which a memory is recalled, which previous objective measures may not have been sensitive enough to detect. To summarize, memory retrieval involves a wide","Remembering is something we do countless times each day. The detail and vividness with which we can remember is part of what makes memories so precious. Given the significance and complexity of memories, it is perhaps unsurprising that several parts of the brain are needed for us to experience them. Indeed, the brain regions involved in memory all work so closely together that it is a challenge to identify what role each region plays. Richter, Cooper et al. aimed to design a memory task that could separate key characteristics of remembering, which would allow them to study links between each aspect and the different brain regions involved in memory. The resulting test involved showing people images of different objects whilst they were in an MRI medical imaging scanner.",380,128,0.3368
dialogsum,"#Person1#: Excuse me. Do you have this in blue? #Person2#: Yes, we do. That one comes in green blue and red. #Person1#: And sorry. I can't find the price. How much is it? #Person2#: Oh, that's 39 dollars and 95 cents. It's on the sale at the moment. #Person1#: OK. Do you have it in extra small? #Person2#: I'll just go and check for you.",#Person1# is buying clothes and asks #Person2# for help.,65,9,0.1385
scientific_lay_summarisation-elife-norm,"et al. , 2004; Parsch and Ellegren, 2013; Wright et al. , 2017; Mank, 2017). However, studies focusing on young sex chromosome systems suggest otherwise (Dufresnes et al. , 2015; Nozawa et al. , 2014; Alekseyenko et al. , 2013; Muyle et al. , 2012; Charlesworth et al. , 2005; Stöck et al. , 2011). Indeed, sex chromosome evolution could be driven mostly by processes resulting from suppressed recombination rather than by antagonistic selection (Branco et al. , 2018; Cavoto et al. , 2018; Branco et al. , 2017; Ma et al. , 2020). The social supergene of the red fire ant Solenopsis invicta is an excellent model for comparing how evolutionary antagonism and the consequences of suppressed recombination shape early supergene evolution. This species includes single-queen and multiple-queen colonies, which differ in behavior, physiology and ecology. This social polymorphism is controlled by a pair of ‘social chromosomes’, SB and Sb, that carry distinct supergene variants (Wang et al. , 2013). In single-queen colonies, workers and queens are SB/SB homozygotes. In multiple-queen colonies, egg-laying queens are SB/Sb heterozygotes, but workers can either be homozygous or heterozygous. Sb/Sb queens are rare and their offspring are unviable (Gotzek and Ross, 2007). Furthermore, because of at least three inversions (Stolle et al. , 2019; Huang et al. , 2018), recombination is severely repressed between SB and Sb (Wang et al. , 2013; Pracana et al. , 2017a). Similar to a Y chromosome, Sb thus lacks recombination opportunities. Importantly, the fire ant supergene system could be as young as 175,000 generations. It thus offers a rare glimpse into the evolutionary forces shaping the early stages of supergene evolution (Wang et al. , 2013). Suppressed recombination reduces the efficacy of purifying selection through Hill-Robertson interference, which can lead to gene degeneration (Charlesworth, 2016). Accordingly, Sb has accumulated non-synonymous single nucleotide substitutions and repetitive elements (Stolle et al. , 2019; Pracana et al. , 2017a). Despite Sb degeneration, gene content in SB and Sb is highly similar (Wang et al. , 2013; Pracana et al. , 2017a), likely because of the system’s young age and purifying selection in haploid males (Hall and Goodisman, 2012). Modifications in the genomic sequence can lead to gene expression changes (Denver et al. , 2005; Rifkin et al. , 2005), the","Red fire ants (Solenopsis invicta) are native to South America, but the species has spread to North America, Australia and New Zealand where it can be an invasive pest. A reason for this species’ invasiveness types of colonies: one with a single egg-laying queen and another with several queens. However, it is not possible to simply add more queens to a colony with one queen. Instead, the number of queens in a colony is controlled genetically, by a chromosome known as the ‘social chromosome’. Like many other animals, red fire ants are diploid: their cells have two copies of each chromosome, which can carry two different versions of each gene. The social chromosome is no different, and it comes in two variants, SB and Sb. Each ant can",380,128,0.3368
dialogsum,"#Person1#: Freeze! Police! Put your hands over your head. #Person2#: What crime did I commit? #Person1#: You are suspected of hiding illegal drugs, so we are taking you into custody. We ' Ve found some heroin in your house. You have the following rights while you are being interviewed. You have the right to remain silent. You don't have to make any statement against your will. You have the right to defense counsel. You have the right to request an investigation of evidence favorable to your case. Do you understand your rights? #Person2#: I am innocent.","The police found drugs in #Person2#'s house and are taking #Person2# into custody, but #Person2# claims to be innocent.",96,19,0.1979
pubmed-summarization,"the modern concept of decompression for traumatic brain injury ( tbi ) was introduced by harvey cushing before world war i . the monro - kellie hypothesis dictates that the amount of space within the skull is constant ; therefore , when the pressure is raised death occurs by herniation when the capacity for adjustment by fluid shifts from the cerebrospinal fluid and vascular compartments are already maximized . increasing the skull size by removing bone and opening the dura delays or prevents these limits from being reached . however , in the 90 years since cushing made these observations , medical , radiographic , and surgical advances in the management of tbi have obviated the need for an aggressive surgical approach in all but a minority of cases . in spite of the ability to control intracranial pressure ( icp ) elevation in most cases with removal of mass lesions , osmotic diuretics , ventricular drainage , sedative / hypnotic agents , and prevention of hypercapnea , occasional cases occur in which icp elevation accelerates in spite of maximal conservative medical therapy , and then so - called heroic measures are employed . these are considered at the ' option ' level in the american association of neurological surgeons criteria for management of severe brain injury because no large randomized trial has proven their efficacy . in the pediatric population , ruf and colleagues as well as taylor and associates have addressed the issue of using decompressive craniectomy as a more formal part of a head injury protocol before going to other ' option ' therapies once icp elevation is affirmed . bifrontal decompressive craniectomy is an aggressive approach described by kjellberg and prieto before the era of modern neuroimaging with computed tomography . this approach is particularly useful in the pediatric population , in which diffuse injury without mass lesions and with icp elevation is relatively common . hemicraniectomy represents a large cranial and dural decompression , often associated with removal of mass lesions such as subdural hematoma or traumatic intracerebral hematoma . bitemporal decompressions are unilateral or bilateral bony decompressions designed to take the pressure off the temporal lobes to prevent uncal herniation , and have been used in other cranial conditions such as pseudotumor cerebri .","more frequently than adults , pediatric victims of severe traumatic brain injury experience diffuse severe cerebral edema without mass lesions . these patients require methods to reduce intracranial pressure quickly and reliably . surgical decompression provides rapid relief of increased intracranial pressure and is an alternative to maximal medical therapy for these individuals . based on previous trials , most of which are anecdotal but now include attempts at case controlled and cohort matched investigations , ruf and colleagues describe a series of six pediatric patients treated with a prospectively implemented protocol of decompressive craniectomy for severe traumatic brain injury . the heterogeneous approaches presented ( which include hemicraniectomy , bifrontal craniectomy , and suboccipital craniectomy ) undermine the applicability of the results . however , this report",380,128,0.3368
dialogsum,"#Person1#: Aren't you going to give us a training workshop next week? How are things going on your preparation for the presentation? #Person2#: I'm having trouble narrowing down my topic for the training. I want to speak about how to improve our sales technique, but there is so much to say, it's hard to get organized. #Person3#: Our training group won't be very large, so you will have more time to focus on more areas. We can cover a lot of ground in an hour and a half, if everyone is participating and paying attention. #Person2#: I want to focus on some suggestions about making sales scores, and I was hoping to throw in a few role plays so that people get practise implementing the things I'm going to talk about. Do you think people will go for the role playing? #Person1#: I think some people may be a little shy to do role playing in front of class... but if you are enthusiastic about your topic, you can help everyone to feel more at ease and willing to give it a try.",#Person2# updates #Person1# and #Person3# about the preparation for the presentation at a training workshop. #Person3# introduces the training group. #Person2# gives some suggestions.,183,24,0.1311
dialogsum,"#Person1#: you look better today. How did your test go? #Person2#: much better than it did yesterday. #Person1#: did you pass? #Person2#: I not only passed my test, but I aced it! I'm so happy! #Person1#: you should be. You worked really hard last night preparing for it. #Person2#: thanks for helping me with it. If you hadn't encouraged me to do my best, I wouldn't have ever been able to pass. #Person1#: you don't have to thank me. It's just a part of my job as your counsellor. #Person2#: did you always do well at school? #Person1#: no, in fact, I was terrible at taking exams. #Person2#: really? #Person1#: sure, but my teachers always encouraged me to do the best that I could and that helped me a lot. When are your final exams? #Person2#: I'll get my finals in two months. #Person1#: when do you plan on studying for those exams? #Person2#: most students just cram the night forehead. #Person1#: do you think that's a good idea? #Person2#: no, I think I should study a little bit at a time, starting a few weeks before the exam. #Person1#: that sounds like a good idea. What are you going to do if you have any questions while you're studying? #Person2#: I'll go and talk to my professor or a learning support assistant. #Person1#: it sounds like you've learned something useful this year!",#Person1# helps #Person2# pass and ace #Person1#'s test. #Person2# tells #Person1# that #Person2# will prepare the final in advance and look for help when having questions.,233,26,0.1116
dialogsum,"#Person1#: When the interview finally comes to an end, the interviewee will probably breathe a sigh of relief. #Person2#: Still, you should not let down your guard. Some details should be paid attention to. #Person1#: At this moment you can thank the interviewer again for the opportunity of the interview. #Person2#: You can also ask the interviewer about your performance today. #Person1#: Don't forget to ask when you can receive a reply. #Person2#: And it's best to ask about the second interview if necessary. #Person1#: You should state politely that you will wait for the results patiently. #Person2#: You can ask questions about the position you are applying for. #Person1#: In this case, you should remember to give thanks for the reply you get. #Person2#: Of course. #Person1#: Just say goodbye to the interviewer before you leave. #Person2#: Besides, remember to make acknowledgments through an E-mail or a call.",#Person1# and #Person2# are talking about how to end an interview.,149,11,0.0738
scientific_lay_summarisation-elife-norm,"The prefrontal cortex (PFC) is thought to orchestrate cognitive dynamics. However, in tests of bistable visual perception, no direct evidence supporting such presumable causal roles of the PFC has been reported except for a recent work. Here, using a novel brain-state-dependent neural stimulation system, we identified causal effects on percept dynamics in three PFC activities—right frontal eye fields, dorsolateral PFC (DLPFC), and inferior frontal cortex (IFC). The causality is behaviourally detectable only when we track brain state dynamics and modulate the PFC activity in brain-state-/state-history-dependent manners. The behavioural effects are underpinned by transient neural changes in the brain state dynamics, and such neural effects are quantitatively explainable by structural transformations of the hypothetical energy landscapes. Moreover, these findings indicate distinct functions of the three PFC areas: in particular, the DLPFC enhances the integration of two PFC-active brain states, whereas IFC promotes the functional segregation between them. This work resolves the controversy over the PFC roles in spontaneous perceptual switching and underlines brain state dynamics in fine investigations of brain-behaviour causality. Dynamic and flexible changes are among the fundamental key properties of human cognition. Bistable visual perception has been widely used to investigate such cognitive dynamics (Brascamp et al. , 2018; Sterzer et al. , 2009), and the prefrontal cortex (PFC) —in particular, right frontal eye fields (FEF), dorsolateral PFC (DLPFC) and inferior frontal cortex (IFC) —is thought to be involved in the spontaneous perceptual switching (Brascamp et al. , 2018; Kleinschmidt et al. , 1998; Lumer et al. , 1998; Lumer and Rees, 1999; Panagiotaropoulos et al. , 2020; Panagiotaropoulos et al. , 2012; Sterzer et al. , 2009; Sterzer et al. , 2002; Wang et al. , 2013; Weilnhammer et al. , 2013). Theoretical work also indicates that top-down signals from the PFC to the visual cortex are essential to perceptual inference (Hohwy et al. , 2008; Weilnhammer et al. , 2017). These studies imply that inhibitory neural modulation of the PFC should induce behavioural changes in the bistable visual perception. However, no empirical human study has identified such behavioural causality of the PFC (Brascamp et al. , 2018) except for a recent work administering theta-burst transcranial magnetic stimulation (TMS) over the right IFC (Weilnhammer et al. , 2021). Instead, a previous TMS study reported that neural suppression of","A cube that seems to shift its spatial arrangement as you keep looking; the elegant silhouette of a pirouetting dancer, which starts to spin in the opposite direction the more you stare at it; an illustration that shows two profiles – or is it a vase? These optical illusions are examples of bistable visual perception. Beyond their entertaining aspect, they provide a way for scientists to explore the dynamics of human consciousness, and the neural regions involved in this process. Some studies show that bistable visual perception is associated with the activation of the prefrontal cortex, a brain area involved in complex cognitive processes. However, it is unclear whether this region is required for the illusions to emerge. Some research has showed that even if sections of the",380,128,0.3368
dialogsum,"#Person1#: this is tough to say, Jordan, but I think we should break up. #Person2#: are you serious? #Person1#: yes, I mean it. #Person2#: but why? Did I do anything wrong? #Person1#: no, we are just too different. This isn't working. #Person2#: hey, come on. It's too early to say that. We can fix things. #Person1#: I have thought about it for a while. I think it's time to move on for both of us. #Person2#: but I still love you. #Person1#: I'm sorry. #Person2#: I knew this would happen some day... #Person1#: then why didn't you talk to me? #Person2#: well. It's not all my fault, Anna... #Person1#: I don't want to argue with you anymore. This is going to be tough, but Let's try and be friends. #Person2#: I would like that Anna, but I think I'll need a little space for a bit. #Person1#: I think we'll be better off if we are apart. #Person2#: shall we keep Our friendship? #Person1#: sure, let's just be friends.",Anna wants to break up with Jordan because she thinks they are too different. Jordan compromises but proposes to keep the friendship. Anna agrees.,169,24,0.142
dialogsum,"#Person1#: I'm sorry to trouble you but there is a lot of noise in next room. #Person2#: Oh, is there? Which room is it? #Person1#: It. . . , I think the neighbor on the right. #Person2#: You mean the room 1818? #Person1#: I'm not sure, but I think so. I'm very exhaust but I can't sleep. #Person2#: All right madam, I'll check and tell them to be quiet. #Person1#: If the nest room is still noisy, could you give me a different room please?",#Person1# complains to #Person2# about the neighbor's noise. #Person2#'ll check and tell them to be quiet.,85,16,0.1882
scientific_lay_summarisation-elife-norm,"The straight-tusked elephants Palaeoloxodon spp. were widespread across Eurasia during the Pleistocene. Phylogenetic reconstructions using morphological traits have grouped them with Asian elephants (Elephas maximus), and many paleontologists place Palaeoloxodon within Elephas. Here, we report the recovery of full mitochondrial genomes from four and partial nuclear genomes from two P. antiquus fossils. These fossils were collected at two sites in Germany, Neumark-Nord and Weimar-Ehringsdorf, and likely date to interglacial periods ~120 and ~244 thousand years ago, respectively. Unexpectedly, nuclear and mitochondrial DNA analyses suggest that P. antiquus was a close relative of extant African forest elephants (Loxodonta cyclotis). Species previously referred to Palaeoloxodon are thus most parsimoniously explained as having diverged from the lineage of Loxodonta, indicating that Loxodonta has not been constrained to Africa. Our results demonstrate that the current picture of elephant evolution is in need of substantial revision. In the late Miocene in Africa, the last of several major radiations within Proboscidea gave rise to the family Elephantidae, which comprises living elephants and their extinct relatives including mammoths (genus Mammuthus) and various dwarf elephant species from Mediterranean islands. The three living elephant species (the African savanna elephant, Loxodonta africana, the African forest elephant, L. cyclotis and the Asian elephant, Elephas maximus), represent the last remnants of this family and of the formerly much more widely distributed and species-rich order Proboscidea. Apart from mammoths, the elephant genus with the most abundant fossil record in Eurasia is Palaeoloxodon (straight-tusked elephants; ), which appears in Eurasia around 0. 75 million years ago (Ma) (Lister, 2016). Based on morphological analyses, Palaeoloxodon is widely accepted as being more closely related to the extant Asian elephant than to mammoths or extant African elephants (Shoshani et al. , 2007; Todd, 2010) and is often subsumed into the genus Elephas (Maglio, 1973; Sanders et al. , 2010). Across its range from Western Europe to Japan, Palaeoloxodon probably comprised several species (Shoshani et al. , 2007), and, based on morphological comparisons, all of them are considered to be derived from the African Palaeoloxodon (or Elephas) recki (Maglio, 1973; Saegusa and Gilbert, 2008), which was the predominant proboscidean lineage in Africa during the Pliocene and Pleistocene but went extinct around 100 thousand years ago (ka) (Owen-Smith, 2013). Straight-tusked elephants may have survived in mainland Eurasia until around","Understanding how extinct species are related to each other or to their living relatives is often a difficult task. Many extinct species have been identified only from incomplete fragments of some of their bones. However, even if complete skeletons have been found, determining the relationships between species can be tricky because researchers often have to rely solely on the shapes of the bones. It is sometimes possible to retrieve DNA sequences from fossil bones. This is easier with younger fossils and those that have been recovered from cold environments. Ancient DNA sequences have been retrieved from only a few fossils older than 100,000 years, but such DNA sequences can be tremendously useful in determining how different species are related to each other. Today there are three living elephant",380,128,0.3368
dialogsum,"#Person1#: How was your economics class? #Person2#: Well, to be honest with you, I fell asleep during the lecture. #Person1#: Was it that boring? #Person2#: No, it wasn't the teacher's fault. The problem is that I can't stay awake for a 2 hour lecture. I had been working in the evening at the hospital. #Person1#: Isn't that going to affect your grades? #Person2#: Probably, but I need to work to pay my school fees. #Person1#: Maybe you should talk to the financial aid office. There's no point in working so hard to make money, if you were just going to fail your classes. #Person2#: But they are going to try to offer me a bunch of loans. I am trying to avoid going into debt. That's why I've been working. #Person1#: OK, then I have a better idea. Why don't you go to the student employment office and see if they can help you find another job. Even if you have to work, there's no reason why you should work at night. #Person2#: That's a great idea. I actually have a break before my next class, so I'll go there now.",#Person2# fell asleep during the economic class because #Person2# needs to work late to pay the school fees. #Person1# advises #Person2# to go to the student employment office to find another job.,191,32,0.1675
dialogsum,"#Person1#: Can I borrow your Cds for our school dance? #Person2#: Oh, you don't ask much, do you? #Person1#: I promise I will personally guard every single one and they will come back in perfect condition. #Person2#: I'll tell you what. Your class can rent them from me for the night and buy back any damaged ones. #Person1#: That sounds fair. That's still cheaper than paying a band to come play for us. #Person2#: Not as fun though. A live band is way more exciting! #Person1#: Our class doesn't have enough money. We already checked into it. #Person2#: Let me know with your next dance. I know a band that may give you a break for the publicity.",#Person1# wants to borrow #Person2#'s CDs for the school dance because #Person1# cannot afford to pay for a band. #Person2# will rent them to #Person1#.,118,25,0.2119
pubmed-summarization,"2009a ) ; t. gondii is of concern for australian native marsupials , which appear to be particularly susceptible to acute infection ( hollings et al . , 2013 ) . we review estimates of the frequency of t. gondii infection in free - ranging australian marsupial populations , and then review the extent to which the infections are associated with acute toxoplasmosis or with other effects ( such as behavioural changes and reduced reproductive success ) that may threaten population viability . t. gondii is a protozoan parasite , which can infect a wide range of endothermic vertebrates . cats ( felidae ) are the definitive host - infected cats shed environmentally resistant oocysts in the faeces . oocysts become infective in the environment , and if ingested can infect both intermediate hosts ( including australian marsupial species ) and other definitive hosts . following ingestion , sporozoites excyst from oocysts , invade the gut epithelium and transform into tachyzoites . tachyzoites multiply asexually and may colonise many host tissues , evoking a strong immune response . tachyzoites differentiate into bradyzoites , which produce tissue cysts that are resistant to the immune response . bradyzoites may be transmitted to a definitive host , or another intermediate host , upon ingestion of infected tissues . in addition , these hosts may also be infected via vertical transmission from infected mother to foetus / suckling young ( dubey , 1998 , dubey , 2010 ) . in most intermediate host species , including people , t. gondii infection tends to be subclinical ; toxoplasmosis ( clinical disease caused by t. gondii infection ) is usually associated with complicating factors such as immunosuppression ( montoya and leisenfeld , 2004 , dubey , 2010 ) . clinical toxoplasmosis may follow recent infection with t. gondii , or result from a recrudescent infection . recrudescence may be prompted by concurrent illness or immunosuppression ( ruskin and remington , 1976 , lappin et al . no published studies have investigated the incidence of t. gondii infection in free - ranging populations of australian marsupials . surveys have provided estimates infection prevalence and seroprevalence ; these are summarised in table 1 , table 2 . evidence of t. gondii infection has been found in free -","it has often been asserted that australian marsupial species are particularly susceptible to toxoplasma gondii infection and to clinical toxoplasmosis following infection . this implicates t. gondii as a potential threat to marsupial population viability , and contrasts to what is known of t. gondii in populations of several other host species . we reviewed the literature , and found a lack of scientifically robust evidence addressing the occurrence of t. gondii infection in free - ranging populations of australian marsupial species , and the impacts of the infection on population health . key limitations included a lack of studies in free - ranging marsupial populations , study findings susceptible to substantial chance influences , and selection , misclassification and confounding biases . the lack of scientifically robust",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of the Ras homolog gene family member A (RhoA). To determine whether Mfge8 regulates the force of antral smooth muscle contraction, we isolated gastric antral rings and measured the force of antral contraction in a muscle bath. Antral rings isolated from Mfge8-/- mice had increased force of contraction in response to both methacholine (MCh) and KCl as compared with wild type (WT) controls (1A and B). The thickness of antral smooth muscle was not different when comparing Mfge8-/- and WT mice indicating that the enhanced contraction was not due to smooth muscle hypertrophy (— 1A and B). Incubation with recombinant Mfge8 (rMfge8), but not a recombinant construct where the integrin-binding RGD sequence was mutated to RGE, rescued enhanced contraction indicating that the effect of Mfge8 on gastric smooth muscle was integrin-dependent (1A, B). Induction of Mfge8 expression in the smooth muscle of Mfge8-/-—Tg (Acta2-rtTA, TetO-Mfge8) transgenic mice, abbreviated Mfge8-/-sm+, where Mfge8 expression was driven by a tetracycline-inducible Mfge8 transgene coupled with an α-smooth muscle-rtTA transgene (— 1C) also rescued enhanced contraction (1C; — 1D). Of note, unlike antral rings, duodenal rings from Mfge8-/- mice did not have enhanced contraction (— 1E) consistent with our previously reported findings in jejunal smooth muscle rings (Kudo et al. , 2013). We next determined whether enhanced antrum contractility was associated with altered gastric emptying and small intestinal transit times (SIT), two in vivo measures of gastrointestinal motility. Mfge8-/- mice had significantly more rapid gastric emptying and more rapid SIT (1D–G). Administration of rMfge8 by gavage and transgenic smooth muscle expression of Mfge8 significantly reduced the rate of gastric emptying and prolonged SIT in Mfge8-/- mice (1D–G). Administration of rMfge8 by gavage also significantly reduced gastric emptying and prolonged SIT in WT mice (1D and F). 10. 7554/eLife. 13063. 003Figure 1. Mfge8 regulates gastrointestinal motility. (A–C) Force of antral smooth muscle ring contraction with and without the addition of rMfge8 or RGE construct in Mfge8-/- and WT in response to MCh (A, N = 4–5) or KCl (B, N = 4–5) or after in vivo induction of smooth muscle Mfge8 expression in Mfge8-/-sm+ mice in response to MCh (C, N = 5). (D, E) The rate of gastric emptying in Mfge8-/- and WT with and without the addition of rMfge8 or RGE construct (D, N","Animals absorb nutrients from the food they eat in a complicated process that involves multiple steps. In the mouth, teeth break down the food into smaller chunks. Then the food passes through the stomach and small intestine, where enzymes break it down into individual molecules that are small enough to be absorbed by cells that line the small intestine. These cells then package the molecules and release them into the bloodstream so that they can be distributed to the rest of the body. Muscles in the wall of the small intestine control how quickly food travels through this part of the gut. If food moves too quickly, the cells that line the intestine have less time to absorb the food molecules and may fail to absorb enough nutrients.",380,128,0.3368
pubmed-summarization,"complexity of a human biological system typically allows its relations to be expressed only in a nonlinear way . because of this complexity diabetes mellitus is a metabolic disorder of endogenous insulin allowing excessive amount of glucose to stay in blood . in general , blood glucose is transformed into energy required by human activities , such as , walking , and this transformation requires insulin functionality . however , in diabetes mellitus , since a human body fully or partially lacks the insulin functionality , unchanged glucose remains in blood . a condition of high blood glucose profiles results in several complications , such as , eye , kidney , and nerve damage , called hyperglycemia . thus , in order to avoid the hyperglycemia , a continuous supply of exogenous insulin is required , and the insulin - dependent diabetic therapy usually does this . on the contrary , too much insulin supply may lead to a condition of low blood glucose profiles resulting in drowsiness , mental malfunctioning , irritability , and loss of consciousness . thus , the insulin - dependent diabetic therapy must concern both hyperglycemia and hypoglycemia by providing an appropriate amount of exogenous insulin timely . at the beginning of the insulin - dependent diabetic therapy , it is required to obtain an approximation of the insulin - glucose relation . two methods are taken in this process , namely , empirical and fundamental methods . arguably , this process is most time consuming . based on mathematical equations representing the insulin - glucose mechanism , broadly , controlling the blood glucose levels is achieved by means of three strategies , namely , open - loop , closed - loop , and partially closed - loop schemes . in general , the fully and partially closed - loop schemes involves several medical devices but the open - loop scheme does not . while in the closed - loop scheme , a system is aimed to completely encompass the diabetic , open- and partially closed - loop require the physician 's contribution to complete the loops . therefore , typically any decisions of the insulin injections are made by a physician in open- and partially closed - loop schemes . this paper is the","we survey blood glucose control schemes for insulin - dependent diabetes therapies and systems . these schemes largely rely on mathematical models of the insulin - glucose relations , and these models are typically derived in an empirical or fundamental way . in an empirical way , the experimental insulin inputs and resulting blood - glucose outputs are used to generate a mathematical model , which includes a couple of equations approximating a very complex system . on the other hand , the insulin - glucose relation is also explained from the well - known facts of other biological mechanisms . since these mechanisms are more or less related with each other , a mathematical model of the insulin - glucose system can be derived from these surrounding",380,128,0.3368
pubmed-summarization,"maca ( lepidium meyenii walp . ) is an endemic highland crop of the central andes which is grown from central peru to bolivia and northwestern argentina . this plant has great potential as an adaptogen and appears to be promising as a nutraceutical in the prevention of several diseases . maca roots have been traditionally used to increase the rate of fertility in both humans and livestock . over the past 20 years , commercial maca products have gained popularity as dietary supplements for aphrodisiac purposes and for increasing fertility and stamina . recently , maca industry develops fast in yunnan province , china . in yunnan , until the end of 2010 , maca growing and promotion areas reached 175 hm and maca yield achieved 780 t , taking up to 90% and 93% , nationwide . mineral elements in food are very important because the quality of many functional foods and medicines depends on the content and type of minerals . in the us , national surveys show that micronutrient inadequacies are widespread and mineral helps fulfill micronutrient requirements in adults and children . up to now , only limited studies on selected elements in maca from different origins have been carried out . moreover , in some studies , no reference material had been certified for elemental analysis , so there has been doubt about accuracy of the determination . in the present study , inductively coupled plasma optical emission spectroscopy ( icp - oes ) was used to determine the contents of eight elements ( b , co , cr , cu , li , na , ni , and zn ) in maca samples , and a comparison was made between the samples from china and peru . standard sample solutions of b , co , cr , cu , li , na , ni , and zn obtained from standard material center of china were used to make a mixed calibration curve in the range of 0400 g ml . ten maca samples were collected from four places of yunnan , china , and four samples were from peru . these samples were washed with deionized water thoroughly , dried to a constant weight , grounded into powder using an agate mortar ,","contents of eight mineral elements in maca ( lepidium meyenii walp . ) from china and peru were determined by inductively coupled plasma optical emission spectroscopy . cu contents in maca samples from china ( 2.531 mg kg1 dry weight , dw ) were higher than the samples from peru ( < 2.1 mg kg1 dw ) . na in two samples from china was found to be significantly of high content ( 2400 and 2600 mg kg1 dw ) . the contents ( mg kg1 dw ) of b , co , cr , li , ni , and zn were , respectively , 8.121 , < 0.023 , < 1.1~3.5 , 0.0200.17 , 0.0854.5 , and 1039 for the samples from china , while being 6.612",380,128,0.3368
pubmed-summarization,"older adults are the chief users of emergency medical services ( ems ) , but we have paid little heed to understanding their special needs . older patients use emergency services at higher rates , require more resources once in the emergency department ( ed ) and are more likely to experience adverse health outcomes compared with younger patients . a mechanism to identify those at higher risk for adverse outcomes may lead to improvements in care . although older age groups use ems at disproportionately higher rates , paramedic training has changed little to meet the specific needs of this older demographic . moreover , there has been very little alteration in how ems systems are organized , with agencies initially established to provide care for major trauma and cardiac arrest victims . the ability of ems to cope with the influx of frail older patients may be reaching a limit , and unless changes are made in its organization , it seems inevitable that care provided to the older adult will suffer . dichotomizing older patients as fit or frail may serve to optimize pre - hospital care . the term frailty is often employed in the medical literature , including emergency medicine , and is widely recognized as a state of vulnerability or decline in physiological reserve . a definition of frailty should integrate biological , clinical , social , psychological , and environmental components , while also reflecting the multi - system impairment that is intrinsic to this concept . frailty is common with prevalence estimates of 40% or more in those aged 80 and older . geriatric interventions provided in the community setting have been shown to reduce ed utilization over relatively short intervals , likely due to improved continuity of care and access . the utility of geriatric interventions applied in the ed have demonstrated mixed results ; however , the evidence suggests benefits may be derived from targeting interventions towards high - risk clients . although a focus on frailty might usefully inform care provision in the pre - hospital and ed settings , the concept has received little attention to date . three approaches can be discerned : rules - based approaches such as the frailty phenotype , clinical frailty scales based","backgroundolder adults use more health - care services per capita than younger age groups and the older adult population varies greatly in its needs . evidence suggests that there is a critical distinction between relative frailty and fitness in older adults . here , we review how frailty is described in the pre - hospital literature and in the broader emergency medicine literature.methodspubmed was used as the primary database , but was augmented by searches of cinahl and embase . articles were included if they focused on patients 60 years and older and implemented a definition of frailty or risk screening tool in the emergency medical services ( ems ) or emergency department setting.resultsin the broad clinical literature , three types of measures can be identified : frailty",380,128,0.3368
dialogsum,"#Person1#: OK. I'll take your bet, as long as the winner gets to pick the movie. What about you, Nick? #Person2#: Sure. Do you want to go first, Sally? #Person1#: Why not! I rolled a five. The category is Best Pictures. #Person2#: OK, here's your question What movie won the 1996 Oscar for Best Picture? #Person1#: I know that, it's The English Patient. It was one of the only good American movies of the 90s. #Person2#: Well, along with Jurassic Park! Nice going, you got the right answer.",Sally takes Nick's bet and manages to answer Nick's question about the movie winning the 1996 Oscar for Best Picture.,88,20,0.2273
pubmed-summarization,"youth violence is a major international public health concern . in nearly every region of the world , adolescents and young adults comprise the majority of violent death victims , resulting in significant losses in the world 's most productive citizens . indeed , global surveillance efforts estimate that an average of 565 youth between the ages of 10 and 29 years old are victims of homicide each day , with an additional 2040 youth violence - related injuries occurring for each homicide . apart from the potential for death or serious injury , youth experiencing violence , namely , physical fighting , are more likely than their nonviolent counterparts to engage in further risk and violence - related behaviors and to suffer from a myriad of negative physical and emotional health outcomes . considering the magnitude and severity of these consequences , a growing body of the literature has sought to better understand the prevalence and risk factors for youth involvement in physical fighting both in the usa and internationally . most recently , the trends and social correlates of physical fighting among youth in 30 countries were presented . one facet of physical fighting among youth that remains underexamined , however , is the phenomenon of very frequent physical fighting . although a recent us study indicates that frequent physical fighting ( at least 12 times per year ) is a relatively rare behavior among high school students , the well - being of those youth engaged in frequent fighting is of concern ; adolescents reporting frequent physical fighting are at a heightened risk for suicide and other psychosocial problems when compared to students who engage in less frequent fighting or who do not fight . furthermore , adolescents who are frequent fighters may be more likely to become chronic offenders , a group that accounts for more than half of all the serious crimes committed by juveniles in the usa . stark gender differences in the prevalence of frequent fighting are also of note . among us , comparative studies examining the occurrence of physical fighting among youth are nearly absent from the current literature , and even fewer studies have examined frequent fighting , most of which limit analyses to youth in europe and north america","objective . using nationally representative data , this study examined the prevalence of very frequent physical fighting ( 12 times per year ) among youth in 27 countries and cities . frequent physical fighting has rarely been reported in the previous literature despite the implications for research and practice . methods . analyses were based on the global school - based student health survey ( 20032008 ) and the 2009 us youth risk behavior survey . multinomial regression analyses were conducted to determine gender differences in frequent fighting . countries were categorized into five regions ( sub - saharan africa , central and south america , asia , eastern mediterranean , and the united states ) , and one - way anova tests were used to determine regional",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect of expression quantitative trait loci (eQTLs) varies across cell types; however, the complexity of mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach in the model nematode Caenorhabditis elegans that uses single-cell RNA sequencing to map eQTLs at cellular resolution in a single one-pot experiment. We mapped eQTLs across cell types in an extremely large population of genetically distinct C. elegans individuals. We found cell-type-specific trans eQTL hotspots that affect the expression of core pathways in the relevant cell types. Finally, we found single-cell-specific eQTL effects in the nervous system, including an eQTL with opposite effects in two individual neurons. Our results show that eQTL effects can be specific down to the level of single cells. Gene expression differences have a strong genetic basis, and genome-wide studies have identified thousands of regions affecting gene expression, termed expression quantitative trait loci (eQTLs) (Albert and Kruglyak, 2015). eQTLs have been found to underlie genetic associations with complex traits and diseases (Albert and Kruglyak, 2015; Gusev et al. , 2014; Hormozdiari et al. , 2018), and genome-wide eQTL mapping holds great promise for uncovering the molecular underpinnings of phenotypic variation. Studies in purified blood cell populations (Raj et al. , 2014; Fairfax et al. , 2012; Ishigaki et al. , 2017) and computational analyses in human tissues (Donovan et al. , 2020; Kim-Hellmuth et al. , 2020) indicate that many eQTLs are cell-type specific. Studying eQTLs in relevant tissues and cell types is thus important for understanding their role in trait variation (Yao et al. , 2020). However, major challenges remain for cell-type-specific eQTL mapping. First, studying multiple tissues or cell types is laborious and expensive, and has mostly been limited to large consortia (GTEx Consortium, 2020). Additionally, diseases can be associated with specific subsets of cells that may not be readily separable from the rest of the tissue, limiting the insight that can be gleaned from studying bulk tissue samples (van der Wijst et al. , 2020). The recently developed technology of single-cell RNA sequencing (scRNA-seq) has the potential to significantly mitigate both of the above issues. In scRNA-seq, gene expression is profiled at the level of individual cells, and different cell","DNA sequences that differ between individuals often change the activation pattern of genes. That is, they change how, when, or why genes switch on and off. We call such DNA sequences' expression quantitative trait loci' , or eQTLs for short. Many of these eQTLs affect biological traits, but their effects are not always easy to predict. In fact, these effects can change with time, with different stress levels, and even in different types of cells. This makes studying eQTLs challenging, especially in organisms with many different types of cells. Standard methods of studying eQTLs involve separately measuring which genes switch on or off under every condition and in each cell. However, a technology called single cell sequencing makes it possible to profile many cells simultaneously, determining which genes",380,128,0.3368
dialogsum,"#Person1#: Look at these paintings, everybody in my family loves painting. They all go to the same painting club. #Person2#: The paintings are very good. And look at that one, it's great. #Person1#: My aunt painted it. She loves painting birds. She says their wings or special. #Person2#: Yes and their shapes are very beautiful, but I think the best painter in my family is my dad. He's excellent at painting pictures of the forest. #Person1#: Wow, I like that painting. #Person2#: Which one? #Person1#: That one there with a Woodhouse in the mountain. It looks very amazing with the sun in the sky. #Person2#: My mom painted that, she loves painting the countryside. #Person1#: And what about this one? #Person2#: My cousin painted that, she loves paintings zoo animals. #Person1#: Is this the last painting? #Person2#: Yes, my brother painted it. He likes painting different fish. #Person1#: I like the dark blue color, but the shark doesn't look very friendly.",#Person1# and #Person1# are discussing the paintings drawn by #Person1#'s family members.,161,12,0.0745
scientific_lay_summarisation-elife-norm,"their diversity is insufficient to bind and/or mount a protective response to foreign-pMHC (Vazquez-Boland et al. , 2001; Nichol, 2008; Nikolich-Zugich, 2008). Consistent with this idea, TCR diversity within both the CD4+ and CD8+ T-cell compartments contract from adult to old mice in parallel with thymic involution (Ahmed et al. , 2009; Rudd et al. , 2011; Britanova et al. , 2014), and the number of CD8+ T-cells that bind distinct foreign class I pMHC in unprimed mice decreases over the lifespan (Yager et al. , 2008; Rudd et al. , 2011; Decman et al. , 2012; Smithey et al. , 2012). Here, we explored how aging impacts the number of naive and memory phenotype CD4+ T-cells available to bind pMHC, their relative affinity for self-pMHC, and their capacity to bind foreign-pMHC. We report that, while the absolute number of CD4+ T-cells decreases over time, those that remain have an increased affinity for self-pMHC and an increased capacity to bind foreign-pMHC. Unprimed old (18–22 months) C57BL/6 mice were found to have fewer CD4+ T-cells in their secondary lymphoid organs than adults (8–12 weeks) due to a loss of naive (CD44lo) T-cells, as expected given thymic involution (1A, B) (den Braber et al. , 2012). The number of memory phenotype (CD44hi) CD4+ T-cells increased with aging (1C). This could be due to prior antigen experience and/or homeostatic proliferation (Nikolich-Zugich, 2008; Surh and Sprent, 2008). 10. 7554/eLife. 05949. 003Figure 1. The CD4+ T-cell compartment contracts but accumulates CD44hiCD5hi cells with aging. The absolute numbers of T-cells in unprimed adult (8–12 weeks) and old (18–22 months) mice are shown as (A) total CD4+ T-cells in secondary lymphoid organs, (B) CD4+ CD44lo (naïve) T-cells and (C) CD4+ CD44hi (memory phenotype) T-cells. Data are concatenated from three experiments, 4 mice/group. Horizontal bar indicates median (*p < 0. 05, ***p < 0. 0001; Mann–Whitney). (D) Relative fluorescent intensity (RFI) of CD5 expression on adult and old CD44hi and CD44lo CD4+ T-cells relative to CD5 expression on adult CD44lo CD4+ T-cells (dotted line). Data represent four experiments with 4 mice/group (***p < 0. 0001, *p < 0. 05; Mann–Whitney). (E) RFI of CD3 expression on adult and old CD44hi and CD44lo CD4+ T-cells relative to CD3 expression on adult CD44lo CD4+ T-cells (dotted line) (***p < 0.","The immune system' s T cells help the body to recognize and destroy harmful pathogens, such as viruses and bacteria. T cells ‘remember’ immunity-inducing fragments, called antigens, from the pathogens they have encountered. This memory then allows the immune system to quickly fend off infections if those pathogens, or even related pathogens, invade again. Vaccines exploit the ability to form immunological memory by exposing the body to harmless forms of the pathogen, or even just particular antigens from it. This allows the T cells to learn how to identify the pathogen without any risk of illness. Vaccines have been extremely successful and have helped to virtually eliminate some diseases. However, for reasons that are unclear, the immune systems of older adults become less functional, so vaccines often lose",380,128,0.3368
dialogsum,"#Person1#: I need to get internet. #Person2#: Which kind of internet connection do you want to get? #Person1#: What kind can I get? #Person2#: There is dial-up or DEL. #Person1#: Which one do you feel is best? #Person2#: I would get DEL if I were you. #Person1#: DEL is better than dial-up? #Person2#: It's the best choice ; plus, it won't tie up your phone line. #Person1#: I'm not sure what that means. #Person2#: Dial-up is connected through your phone, unlike DEL. #Person1#: That'll make it impossible for me to use. #Person2#: Exactly. With DEL you don't have that problem.",#Person1# needs to get the internet. #Person2# recommends #Person1# the DEL and explains that DEL won't tie up the phone line.,100,21,0.21
scientific_lay_summarisation-elife-norm,"via its cytoplasmic nuclease domain (Sidrauski and Walter, 1997). After the exons are joined by tRNA ligase, the resulting spliced mRNA (denoted HAC1i; ‘i’ for UPR ‘induced’) is now translated into Hac1ip. This active transcription factor is imported into the nucleus, where it activates the expression of UPR target genes involved in restoring protein-folding homeostasis in the ER (Chapman et al. , 1998). Intron removal is both necessary and sufficient to relieve the post-transcriptional silencing of HAC1 that otherwise prevents Hac1p accumulation (Chapman and Walter, 1997). The post-transcriptional silencing of HAC1 and its subsequent reversal by cytoplasmic splicing together enable a rapid UPR that does not depend on de novo transcription (Rüegsegger et al. , 2001). At the same time, a robust silencing mechanism is required to prevent ectopic accumulation of Hac1up from the abundant cytoplasmic pool of HAC1u mRNA that might otherwise turn on UPR target genes in the absence of ER stress. The current model for silencing is that elongating ribosomes are stalled on the mRNA during translation, thereby preventing synthesis of full-length Hac1p (Rüegsegger et al. , 2001). According to this model, the mediator of translational attenuation is a long-range base-pairing interaction between the 5′ untranslated region (UTR) and intron of HAC1u mRNA. The key data supporting the stalled elongation model is that the majority of HAC1u mRNA sediments in the polysome region of a sucrose gradient (Arava et al. , 2003; Chapman and Walter, 1997; Cox and Walter, 1996; Kuhn et al. , 2001; Mori et al. , 2010; Park et al. , 2011; Payne et al. , 2008; Rüegsegger et al. , 2001; Sathe et al. , 2015) despite no detectable Hac1up. Furthermore, the heavy-sedimenting HAC1u mRNA is distributed in a discontinuous pattern with peaks and valleys that precisely match the peaks and valleys observed for polysomes (Rüegsegger et al. , 2001). These data provide convincing evidence that heavy-sedimenting HAC1u mRNA reflects ribosome association rather than another high-molecular-weight complex that co-sediments with polysomes, or so-called ‘pseudo-polysomes’ (Thermann and Hentze, 2007). Given this apparent ribosome association of HAC1u mRNA, an alternative explanation for the absence of Hac1up is that Hac1up is synthesized but immediately degraded (Cox and Walter, 1996). However, Hac1up and Hac1ip are thought to have similar half lives (Chapman and Walter, 1997; Kawahara et","Molecular machines called ribosomes read the genetic instructions in an mRNA molecule and then translate them to make proteins. However, cells do not translate all of the template mRNAs that they have available into proteins; instead they have a number of ways to block the process to control when certain proteins are made. In budding yeast, the mRNA that codes for a protein called Hac1 is always present in the cell but the protein is normally not detected. The Hac1 protein is responsible for helping the cell deal with certain types of stress, so it only accumulates when the cell is experiencing such stresses. The mRNA that encodes Hac1 (referred to as HAC1 mRNA) contains a sequence called an intron. These sequences are normally cut out of mRNAs",380,128,0.3368
pubmed-summarization,"field emission is a quantum mechanical tunneling phenomenon in which electrons escape from a solid surface into vacuum , as explained theoretically by r. h. fowler and l. nordheim in 1928 . field emission is widely used in many kinds of vacuum electronic applications such as flat panel displays , microwave power tubes , electron sources , and electron - beam lithography . over the past decade , research groups worldwide have shown that carbon nanotubes ( cnts ) are excellent candidates for electron emission . cnts possess advantages in aspect ratios , tip radius of curvature , chemical stability , and mechanical strength . however , issues related to the placement and throughput of cnt arrays has hampered the development of such arrays for commercial applications . graphene is a two - dimensional honeycomb - structured single crystal showing ballistic transport , zero band gap , and electric spin transport characteristics [ 3 - 5 ] . in previous studies , graphene layers were randomly distributed on cathode electrodes for field emission display applications . however , further field emission studies are required using high - quality , planar graphene structure ( e.g. obtained from a highly oriented pyrolyzed graphite ( hopg ) block ) . in order to understand the fundamental behavior of graphene field emission and expand its application into vacuum nanoelectronics beyond the field emission display , the characterization and analysis of field emission from an individual graphene sheet is necessary . in this paper such a graphene triode structure can be used as a fundamental unit for vacuum nanoelectronics . the triode has an in - plane graphene tip ( emitter ) with the other in - plane electrodes used as source , drain , and gate on the substrate . depending on the gate voltage applied , electrons are emitted from the graphene tip creating an electron current that can be modulated on and off . to realize this conceptual device , the field emission characteristics of graphene layers with different thicknesses need to be characterized . conceptual schematic view of a graphene - based triode as a fundamental unit for vacuum nanoelectronics . depending on the gate voltage applied , electrons are emitted from the graphene tip creating an electron current that can","this paper describes an experimental study on field emission characteristics of individual graphene layers for vacuum nanoelectronics . graphene layers were prepared by mechanical exfoliation from a highly oriented pyrolyzed graphite block and placed on an insulating substrate , with the resulting field emission behavior investigated using a nanomanipulator operating inside a scanning electron microscope . a pair of tungsten tips controlled by the nanomanipulator enabled electric connection with the graphene layers without postfabrication . the maximum emitted current from the graphene layers was 170 na and the turn - on voltage was 12.1 v.",380,95,0.25
pubmed-summarization,"prostate cancer cell line , mat - lylu , suppresses colony formation in soft agar , decreases refractility , and increases cell - cell interactions . importantly , akap12 attenuates specialized motility , such as chemotaxis and invasiveness , rather than generic cell motility . for instance , akap12 reexpression in mat - lylu cells has no effect on short- and long - term motility in monolayer wound - healing assays . in contrast , akap12 inhibits chemotaxis via the attenuation of a pkc - raf / mek / erk pathway . in addition , upregulated akap12 facilitates hgf - induced , c - met - dependent cell motility through the upregulation of pka activity and pka - induced genes , presumably through akap12 's scaffolding function . interestingly , akap12 phosphorylation by pkc decreases akap12-pkc scaffolding but no change in akap12-pka binding or agonist - induced pka activation . it is likely that the differential pka - pkc control relates to an overlap between pkc binding and phosphorylation sites mapping to the n - terminus of akap12 , whereas the pka binding site maps to the c - terminus of akap12 lacking phosphorylation sites ( ) . the c - terminal domain of akap12 is required for akap12 to target pka to the cell periphery . however , pkc activation by phorbol esters causes translocation of the akap12/pka complex to the perinucleus . taken altogether , these data strengthen the notion that akap12 promotes the differential activation of pka and pkc in processes such as cell motility . reexpression also enhances integrin - mediated adhesion and superinduces fak autophosphorylation levels , likely by physically disengaging src from fak complexes , which , in turn , leads to less focal adhesion turnover ( bing su , lingqiu gao , fanjie meng , li - wu guo , julian rothschild , irwin h. gelman , adhesion - mediated cytoskeletal remodeling is controlled by the direct scaffolding of src from fak complexes to lipid rafts by ssecks / akap12 . in addition , mitogen - induced , fak - dependent tyrosine phosphorylation of akap12 modulates its binding to the actin - based cytoskeleton , suggesting a role for akap12 in mitogen - induced cytoskeletal reorganization . recently we discovered that akap12 negatively","cellular dynamics are controlled by key signaling molecules such as camp - dependent protein kinase ( pka ) and protein kinase c ( pkc ) . akap12/ssecks / gravin ( akap12 ) is a scaffold protein for pka and pkc which controls actin - cytoskeleton reorganization in a spatiotemporal manner . akap12 also acts as a tumor suppressor which regulates cell - cycle progression and inhibits src - mediated oncogenic signaling and cytoskeletal pathways . reexpression of akap12 causes cell flattening , reorganization of the actin cytoskeleton , and the production of normalized focal adhesion structures . downregulation of akap12 induces the formation of thickened , longitudinal stress fibers and the proliferation of adhesion complexes . akap12-null mouse embryonic fibroblasts exhibit hyperactivation of pkc , premature cellular senescence",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situactivation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single-cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation. As a proof of concept, we recapitulate immunological phenomenon such as CD4 T-cells' help to CD8 T-cells through enhanced maturation of DCs and the effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity. The field of human immunology has gained much attention in the last few decades with the increasing realisation that despite the tremendous utility of mouse models, they can only provide limited insight for advancing translational research (Wagar et al. , 2018; Council MRC, 2008). Most of the research in human immunology is based on observational studies, whereby, for example, data sets of gene expression profiles are used to identify disease biomarkers. Although these studies promote our understanding and help in developing hypotheses about disease mechanisms, they fall short, and experimental research is needed (Davis, 2008). The classical tools in experimental human immunology rely heavily on immortalised cell lines, stimulated clonal lines, peripheral blood, and more rarely humanised mouse models. Each of these tools has its limitation. Cell lines have diverged tremendously from primary cells, making their signalling machinery and response thresholds no longer representative (Colin-York et al. , 2019); bulk peripheral blood assays lack the spatial organisation of tissues; and humanised mouse models have only a portion of their system ‘humanised’, rendering the remaining parts confounding factors (Theocharides and Manz, 2018). To address these limitations, we introduce a holistic approach to allow researchers to manipulate and study human immune cells in a tissue-like environment with minimal aberrations to their natural behaviours. We report a toolkit that achieves two critical goals for engineering T-cells: (1) high efficiency TCR expression and maintenance of T-cell motility, activation dynamics and viability using mRNA electroporation and (2) a tissue-like 3D culture (). Successful engineering of T-cell specificity requires the stable expression of a functional exogenous TCR, as well as the preservation of important cellular","The human immune system protects the body from infection or cancer by detecting foreign and abnormal elements, known as antigens, and initiating a response to clear them. It relies on a type of white blood cell called a T-cell to distinguish which substances are the body’s own, and which are infectious. Each T-cell is designed to attack a specific antigen, which they recognise using a unique' T-cell receptor' . During an infection, immune cells called' antigen presenting cells' hold out antigens for the T-cells to look at. Only when an antigen matches the T-cell' s receptor can the T-cell get activated and trigger an immune response. There are still gaps in our understanding about how human T-cells interact with antigen presenting cells. Since only a small number of",380,128,0.3368
dialogsum,"#Person1#: Excuse me. May I see the manager of your store? #Person2#: I am the manager. Can I help you? #Person1#: Oh, great, I saw a job ad outside your store. I am interested in the job advertised. I am coming to see if there is any opportunity available for me. #Person2#: All right. Take a seat, please. Would you like to be a shop assistant or a cashier? #Person1#: I can do the work of shop assistant and I worked part time in a small department store during my summer vocation last year. #Person2#: So now do you want a full-time job or part-time job? #Person1#: At present, both are OK for me. What do you need most, then? #Person2#: Now we really need some part-time workers. You see, our full-time staff knocks off at five pm, but now we hope to extend the hours to eight pm. We need some part-time shop assistants to work 3 hours a day from five pm to eight pm. But I am not sure if you are qualified for the job. Since most of our customers are foreign, competence of good communication in English is necessary here. #Person1#: I think I can. I have been learning English for almost 5 years and especially I am fluent at speaking English. Also, I have made some foreigners friends during the experience of learning English. #Person2#: That is fine. I think you have the qualifications needed for the job, so I will let you have the job. Does the work schedule suit you? #Person1#: It quite suits me. I am free in the evening these days, I will have no difficulty starting at five pm. #Person2#: Good. There is only thing to be settled. Ten RMB an hour is the maximum we can pay you. Is the rate of pay acceptable to you? #Person1#: It seems reasonable. By the way, I can get my earning raised with a excellent performance, can't I? #Person2#: Sure. You will get more if you can invite more customers with your good service. #Person1#: I see. I will try my best to do the job well. #Person2#: That is good of you to say so. When can you start working? #Person1#: How about next monday? #Person2#: Ok. Let's make is",#Person1# sees a job ad outside #Person2#'s store and comes to see if there is an opportunity available. #Person1# introduces the qualifications that #Person1# has and #Person2# thinks #Person1# is suitable for the job. They reach an agreement on the payment and working hours. #Person1# will come to work next Monday.,380,51,0.1342
scientific_lay_summarisation-elife-norm,"ganglionic eminence (MGE) (Butt et al. , 2008; Xu et al. , 2008) and their specification is under the control of the TFs LHX6 (Du et al. , 2008; Liodis et al. , 2007) and SOX6 (Azim et al. , 2009; Batista-Brito et al. , 2009). MGE-derived INs develop into fast-spiking parvalbumin (PV) + basket and chandelier cells, as well as into Martinotti and multipolar somatostatin (SST) + INs (Butt et al. , 2008; Xu et al. , 2008; Du et al. , 2008; Butt et al. , 2005; Fogarty et al. , 2007; Taniguchi et al. , 2013). The second largest fraction of cortical INs arises from the caudal ganglionic eminence (CGE) (Miyoshi et al. , 2010; Nery et al. , 2002) and expresses TFs such as PROX1, SP8 and NR2F2 (Cai et al. , 2013; Ma et al. , 2012; Miyoshi et al. , 2015; Rubin and Kessaris, 2013). CGE-derived INs also express the ionotropic serotonin receptor 3A (5-HT3AR) and give rise to a large diversity of INs, including reelin+ cells, vasointestinal peptide (VIP) +/calretinin+ bipolar cells and VIP+/cholecystokinin+ basket cells (Miyoshi et al. , 2010; Armstrong and Soltesz, 2012; Prönneke et al. , 2015; Lee et al. , 2010; Murthy et al. , 2014; Vucurovic et al. , 2010). Finally, lineage-tracing experiments using Hmx3 (Nkx5. 1) -Cre (Gelman et al. , 2009) and Dbx1-Cre driver lines (Gelman et al. , 2011) have shown that a small fraction (about 10%) of cortical INs originate from the preoptic area (POA) (Gelman et al. , 2009; Gelman et al. , 2011). Among cortical INs, neurogliaform cells (NGCs) display unique characteristics. They represent the main source of ‘slow’ cortical inhibition by acting on metabotropic GABAB receptors (Tamás et al. , 2003), and are thought to be key effectors of a powerful inhibitory circuit recruited by long-range connections such as interhemispheric and thalamic projections (Craig and McBain, 2014; Palmer et al. , 2012; De Marco García et al. , 2015). Whether the current description of NGCs captures an IN subtype related to a distinct developmental specification process is unclear. Here we used in vivo genetic lineage-tracing to follow the developmental origin and trajectory of NGCs. We found that they originate from a distinct pool of 5-HT3AR-expressing Hmx3+ cells located in the rostral","Our brain contains over a 100 billion nerve cells or neurons, and each of them is thought to connect to over 1,000 other neurons. Together, these cells form a complex network to convey information from our surroundings or transmit messages to designated destinations. This circuitry forms the basis of our unique cognitive abilities. In the cerebral cortex – the largest region of the brain – two main types of neurons can be found: projection neurons, which transfer information to other regions in the brain, and interneurons, which connect locally to different neurons and harmonize this information by inhibiting specific messages. The over 20 different types of known interneurons come in different shapes and properties and are thought to play a key role in powerful computations such as learning",380,128,0.3368
dialogsum,"#Person1#: You know we went great lengths to promote the sales of your products. Through our continuous effort, consumers tend to accept your product. So, there will be a potential market for your product in this area, and would you let us act as your agent? #Person2#: We appreciate your efforts in promoting the sale of our clothes in the market of this city. But according to our record, your annual turnover is not too big, so I think it is premature for us to discuss the question of agency. #Person1#: If that's the case, we can talk about it first. What's your concept of a big amount? #Person2#: I mean to double the amount for your sales this year at least. #Person1#: I'm afraid that's too much for us. #Person2#: We know you have done a good job in building up these exports for us. However, our company has the regulation for the agency. #Person1#: All right, we accept the challenge. What about the commission? You know, we usually get a 20 % commission of the amount on every deal. #Person2#: I am sorry to say that it's a little higher. Our agents in other areas usually get a 3 % to 6 % commission. #Person1#: You may have known that we have competitors from South Korea and other countries. At the beginning of our campaign, there is sales resistance to overcome, we must send out salesmen to have the market investigation and spend a considerable amount of money on advertising in newspaper and TV programs. A 20 % commission will not leave us much. #Person2#: Our price is worked out according to the costing. A 20 % commission means an increase in our price. So, I'm afraid we have to decline your proposal of acting as our sole agent. #Person1#: Oh, that's pitiful.","#Person1# wants to act as #Person2#'s agent, but #Person2# thinks #Person1#'s annual turnover is not big enough. #Person2# asks #Person1# to at least double that amount. #Person1# accepts the challenge but demands a 20 % commission on every deal. #Person2# has to decline #Person1#'s proposal of acting as the sole agent because a 20 % commission means an increase in their price.",305,62,0.2033
dialogsum,"#Person1#: So, have you found a job yet? #Person2#: No, but, I have a few leads, so things are looking up. #Person1#: But isn't that what you always say? #Person2#: Well ... uh ... this time is different. #Person1#: What are you looking for this time, then? #Person2#: Actually, I want to work for a Web hosting company. #Person1#: What would you do there? #Person2#: Well, in a nut shell, Web hosting companies provide space for people to store and run their Websites. Does it sound like I know what I'm talking about? #Person1#: Oh, yeah, sort of. #Person2#: Well, And then, sort of? Well, they allow people to run their Web sites without having to buy and maintain their own servers, and I'd like to work in technical support, you know, helping customers resolve computer-related problems with their sites. And you know I'm a good communicator. #Person1#: So, how's the pay for that kind of job? #Person2#: Well, most people I know start out with a very reasonable salary; you can earn pay increases depending on your performance. #Person1#: So, what about benefits? #Person2#: Oh, the benefits are pretty good. They provide health insurance, two weeks of paid vacation a year, and opportunities for advancement. And in the end, I'd like to work in a management position. You know, sitting back, enjoying the view out of the twentieth-story window of the office building. Something like that. #Person1#: Well, is there any long-term job security in a job like that? #Person2#: Uhh. That's hard to tell. I mean, the Internet is booming, and these kinds of companies are sprouting up everywhere, which is a good thing, but just like the dot-com era, you never know how long things will last. #Person1#: Well, have you ever thought about going back to school to improve your job skills? #Person2#: Wait, wait. What are you suggesting? #Person1#: Well, you know, more training might help you land a better job. #Person2#: Wh ... wh ... Are you trying to say something about my current job? I mean, is there something going on here? I mean, what are you saying? #Person1#: You know, you did drop out of college. #Person2#: I know, I know, but I don't know. I'm just seeing my current job at","#Person2# tells #Person1# #Person2# wants to work in a Web hosting company that allows people to run their websites without buying their own servers. The pay is reasonable and the benefits are good, but it's hard to tell whether the job can last long. #Person1# suggests #Person2# go back to school to improve #Person2#'s job skills because more training can help, but #Person2# doesn't have the resources to go back to school.",380,72,0.1895
scientific_lay_summarisation-elife-norm,"Charcot–Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal MFN2 mutation. In mice expressing human MFN2 T105M, intermittent mitofusin activation with a small molecule, MiM111, normalized CMT2A neuromuscular dysfunction, reversed pre-treatment axon and skeletal myocyte atrophy, and enhanced axon regrowth by increasing mitochondrial transport within peripheral axons and promoting in vivo mitochondrial localization to neuromuscular junctional synapses. MiM111-treated MFN2 T105M mouse neurons exhibited accelerated primary outgrowth and greater post-axotomy regrowth, linked to enhanced mitochondrial motility. MiM111 is the first pre-clinical candidate for CMT2A. Charcot–Marie-Tooth disease (CMT) describes a family of genetically diverse and clinically heterogeneous peripheral neuropathies (Fridman et al. , 2015). Type 2A CMT (CMT2A) is caused by mutations of the mitochondrial fusion protein, mitofusin 2 (MFN2) (Züchner et al. , 2004), and is distinguished from other CMT subtypes by onset of neuromuscular signs in early childhood and progressive loss of neuromuscular coordination and strength in arms throughout the first two decades of life, thought to be the consequence of dying-back of long peripheral nerves (Fridman et al. , 2015; Feely et al. , 2011; Bombelli et al. , 2014; Yaron and Schuldiner, 2016; Berciano et al. , 2017). Because there are currently no disease-modifying treatments, CMT2A is managed with braces, wheelchairs, and social support. Over 100 different dominant missense MFN2 mutations are implicated in CMT2A (Beręsewicz et al. , 2018). MFN2 and related MFN1 are nuclear-encoded dynamin-family GTPases located at the mitochondrial outer membrane-cytosol interface where they promote mitochondrial fusion essential to mitochondrial respiratory function and repair (Chan, 2012). Dominant inhibition by MFN2 mutants of mitochondrial fusion (Chen and Chan, 2006; Pareyson et al. , 2015), mitophagy (Rizzo et al. , 2016; Filadi et al. , 2018), and/or neuronal mitochondrial transport (Pareyson et al. , 2015; Baloh et al. , 2007; Crunkhorn, 2018) are proposed to evoke neuronal degeneration in CMT2A. Because CMT2A is an autosomal dominant genetic condition, gene editing could potentially correct causal MFN2 mutant alleles, but the large number of different causal CMT2A MFN2 mutations complicates an editing approach. Alternately, forced expression of","Charcot-Marie-Tooth disease type 2A is a rare genetic childhood disease where dying back of nerve cells leads to muscle loss in the arms and legs, causing permanent disability. There is no known treatment. In this form of CMT, mutations in a protein called mitofusin 2 damage structures inside cells known as mitochondria. Mitochondria generate most of the chemical energy to power a cell, but when mitofusin 2 is mutated, the mitochondria are less healthy and are unable to move within the cell, depriving the cells of energy. This particularly causes problems in the long nerve cells that stretch from the spinal cord to the arm and leg muscles. Now, Franco, Dang et al. wanted to see whether re-activating mitofusin 2 could correct the damage to the mitochondria and",380,128,0.3368
pubmed-summarization,"of neuronal action potentials over a broad range of concentrations , as demonstrated in vitro ( mclean et al 2005 ) . in radioligand binding studies , rufinamide does not interact with other neurotransmitter systems , including monoamine , adenosine , acetylcholine , histamine , glycine , -amino-3-hydroxy-5-methyl-4-isoxazole propionate ( ampa)/kainite , n - methyl - d - aspartate ( nmda ) , and -amino butyric acid ( gaba ) systems ( bialer et al 1996 ) . rufinamide has demonstrated broad spectrum anticonvulsant activity in animal models of epilepsy , elevating both electrically and chemically induced seizure thresholds and preventing seizure spread following oral and intraperitoneal administration in mice and rats ( white et al 2005 ) . furthermore , the protective index for rufinamide ( ratio of the concentration required for 50% anticonvulsant efficacy to that for neurotoxicity ) was superior to that of each of the comparator aeds examined ( phenytoin , phenobarbital , ethosuximide , and valproate ) . the pharmacokinetic properties of rufinamide have been established both in healthy volunteers and in patients with epilepsy . in a study of 3 healthy volunteers , an oral dose of 600 mg rufinamide demonstrated high absorption , and monoexponential elimination with a mean half - life ( t ) of 9 hours ( waldmeier et al 1996 ) . excretion was largely renal ( 85% ) and complete ( 98% ) within 7 days . following administration of 400 mg rufinamide as two 200-mg tablets or 400-mg oral suspension after a standard meal , mean maximum plasma concentrations ( cmax ) of 3.03 and 3.32 g / ml were reached after 6.6 and 7.2 hours , respectively , leading to elimination with a terminal t of 8.8 and 9.1 hours , respectively ( cheung et al 1995 ) . in a further study , the absorption of a single dose of 400 mg rufinamide was accelerated in fed subjects compared with fasting conditions , resulting in a 43% increase in exposure ( 96-hour exposure ) , without affecting the t ( cardot et al 1998 ) . however , no effect of food was observed with repeat dosing ( eisai , data on file ) , and no difference in rufinamide pharmacokinetics has been found between older","rufinamide , a triazole derivative that is structurally distinct from currently marketed antiepileptic drugs ( aeds ) , is in development for the adjunctive treatment of lennox - gastaut syndrome ( lgs ) in children and adults . rufinamide is well absorbed after oral administration , demonstrates low protein binding , and is metabolized by enzymatic hydrolysis without involvement of cytochrome p450 enzymes , conferring a low drug interaction potential . in a randomized , double - blind trial involving 138 adult and pediatric patients with lgs , compared with placebo , rufinamide 45 mg / kg / day resulted in significantly superior reductions in drop attacks ( median change 42.5% vs + 1.4% with placebo ) and total seizures ( 32.1% vs 11.7% with placebo ) ,",380,128,0.3368
dialogsum,"#Person1#: What is that plastic cup for? #Person2#: Your doctor has requested a urine sample. #Person1#: Am I supposed to pee into the cup? #Person2#: We want what we call a clean sample. Urinate a drop or so into the toilet, and then stop the flow and urinate into the cup. #Person1#: Then what do I do with the cup? #Person2#: You put the cup in the little cubby in the restroom and close the door to the cubby. #Person1#: What is this test for? #Person2#: He is looking to see if you have a bladder or urinary tract infection. #Person1#: When will I know the results? #Person2#: Your doctor will call you in a few days with the results.",#Person2# gives #Person1# instructions on taking a clean urine sample and explains what this test is for.,120,17,0.1417
pubmed-summarization,"disability due to chronic pain ( dcp ) results in absence from work and is a major public health concern in japan and many western countries.14 various screening tools have been developed to identify chronic pain subgroups and comorbid factors.57 a widely used powerful tool is the start back tool ( start ) , a 9-item screening tool that was developed as a prognostic indicator of lower back pain ( lbp ) . items 14 evaluate physical factors and items 59 assess psychosocial factors ( ).5,8 the start score is often used by primary care physicians in england to make clinical decisions.5 specifically , the start results indicate the subgroup that an lbp patient falls into , which helps determine which treatment strategies may be most effective . the start has been shown to be particularly effective for individual patient management in the physiotherapy setting . patients who underwent start testing and subsequent targeted therapy had higher clinical and cost efficacy than patients who did not undergo start testing and were treated with usual care strategies.5 we previously translated the start into japanese,9 and this version was linguistically validated in a general cross - cultural adaptation process.1012 we also evaluated the reliability and validity of the start into japanese in a large number of japanese patients with lbp.13 the lower back was the most common site of chronic pain and accounted for 65% of all cases of reported chronic pain in a japanese epidemiological study.1 however , chronic pain often originates in places other than the lower back , and a generic screening tool is needed to help effectively manage chronic pain from all sites . one such tool is the generic version of the start back 5-item screening tool ( start - g ) , a modified version of the 9-item start.8 the start 9-item screening tool provides an easy way to stratify patients into three subgroups according to the probability of a poor prognosis or pain chronicity . these categories are defined as low risk , medium risk , and high risk ( ).8 on the other hand , the use of start - g ( 5-item ) screening tool has not yet been established . the start - g has also not been validated for evaluating chronic","objectivethe generic start back 5-item screening tool ( start - g ) is used to manage chronic pain in the lower back and elsewhere . this study evaluated the validity of the japanese version of this generic screening tool.materials and methodsjapanese participants between the ages of 20 and 64 years completed online surveys regarding pain . survey reliability was assessed with internal consistency , as calculated using cronbach s alpha coefficients . spearman s correlation coefficients were used to evaluate concurrent validity between the start - g score and standard reference questionnaires . associations between start - g scores and the presence of a disability due to chronic pain ( dcp ) were analyzed using receiver operator characteristic ( roc ) curves.resultsanalyses ultimately included data obtained from 52,842",380,128,0.3368
pubmed-summarization,"small number of motifs flanked by large nh2- and/or cooh - terminal extensions . except for the catalytic core motifs , which only extend over 100 amino acids along with the substrate - specific e3 ligases , usps are the only classes of ubiquitin - modifying enzymes to have expanded significantly throughout evolution ( semple et al . , 2003 ) . information on the other three classes of dubs is fairly sparse and relatively recent , preventing generalizations ; however , individual members of the ovarian tumor protease and jamm classes are involved in the regulation of protein trafficking ( as detailed below ) . protein trafficking is regulated by dubs in several ways , such as maintaining cellular levels of free ubiquitin , antagonizing the degradation of trafficking proteins in the ubiquitin proteasome system , and regulating nonproteasome - dependent functions of monoubiquitin or multiple monoubiquitin signals . secreted and membrane proteins enter the exocytic pathway at the er . the ubiquitin pathway is a major regulator of protein quality at this juncture , as misfolded proteins inserted into the er are very rapidly recognized , ubiquitylated , and degraded by proteasomes in the cytoplasm ( meusser et al . , 2005 ) . whereas some common characteristics of misfolded proteins may be recognized by the ubiquitylation machinery , it has recently been shown that one dub , usp4 , plays a very substrate - specific role at the er ( . usp4 associates with the cytosolic cooh terminus of the a2a - adenosine receptor , a gs - coupled receptor ( milojevic et al . , 2006 ) . this regulates the quality control of a2a - adenosine receptor , facilitating the passage of the receptor through the er and golgi and resulting in increased a2a - adenosine receptor at the plasma membrane . several controls showed that this increase was caused by facilitated transport through the exocytic pathway and not by recycling from the endocytic pathway ( milojevic et al . , 2006 ) . this interaction was specific , as another dub , usp14 , could not substitute for usp4 , and usp4 had no effect on the trafficking of other g protein coupled receptors . as > 50% of the a2a - adenosine receptor","ubiquitylation is a key regulator of protein trafficking , and much about the functions of ubiquitin ligases , which add ubiquitin to substrates in this regulation , has recently come to light . however , a clear understanding of ubiquitin - dependent protein localization can not be achieved without knowledge of the role of deubiquitylating enzymes ( dubs ) . dubs , by definition , function downstream in ubiquitin pathways and , as such , have the potential to be the final editors of protein ubiquitylation status , thus determining substrate fate . this paper assimilates the current evidence concerning the substrates and activities of dubs that regulate protein trafficking .",380,111,0.2921
dialogsum,"#Person1#: How may I help you? #Person2#: I'm having a problem. #Person1#: What is it? #Person2#: I apparently owe some fees, but I never got the bank statement. #Person1#: I do apologize for that. #Person2#: My fees went up, but I didn't even know I had fees to pay. #Person1#: I see your problem. #Person2#: What are you going to do about it? #Person1#: I will cancel the fees you owe. #Person2#: I don't have to pay any fees? #Person1#: You'll only have to pay the initial fee. #Person2#: That's fine. I appreciate your help.",#Person2# owes some fees but doesn't get a bank statement. #Person1# will cancel the extra fees.,95,16,0.1684
dialogsum,"#Person1#: Hello. I want to purchase an old music box. #Person2#: We have a good variety. What decade would you like? #Person1#: I was hoping I could find something made in the '20s. #Person2#: There are six on this table. #Person1#: I hope at least one of them has dancing figures. #Person2#: Many people like the dancing figures. Two of our boxes have the figures. #Person1#: So hard to choose. I think I'll take this one. #Person2#: That one will bring you many hours of pleasure. #Person1#: Does a warranty come with this music box? #Person2#: I'm sorry, but if it breaks down, you're on your own. #Person1#: I just thought I would ask. #Person2#: When you buy a Model T, you can't expect a warranty.",#Person1# is looking for an old music box made in the '20s with dancing figures. #Person2# tells #Person1# there's no warranty for the music boxes.,126,25,0.1984
dialogsum,"#Person1#: I want to find an old music box. #Person2#: We have a great selection. What decade are you looking for? #Person1#: Do you have anything made in the 1920s? #Person2#: We have six. #Person1#: Do any of them have dancing figures? #Person2#: Actually, two of them have dancing figures. #Person1#: That's fantastic. I think I like this one. #Person2#: A good choice. I prefer that one myself. #Person1#: Now, is there any warranty with this? #Person2#: Oh, no, I'm afraid not. These things are just too old to guarantee anything. #Person1#: I understand. #Person2#: Even if they break down, they're still works of art.",#Person2# shows #Person1# an old music box with dancing figures but without any warranty.,105,14,0.1333
pubmed-summarization,"clinical response of the primary tumor was observed in 28 ( 33% ) and 42 ( 49% ) patients , respectively , adding up to a total of 82% objective response rate . however , stage iv tumors the response rate was only 18% . segmental mandibulectomy was performed in the chemotherapy arm ( 31% vs. 52% in the control group ) there was no increase in the number of positive surgical margins . there was no difference in terms of locoregional recurrence , distant metastasis and os between the two arms . however , it was observed that patients achieving pathologically complete response had statistically significant higher 5 years survival rates . , with a median follow - up of 11.5 years showed no difference in the incidence of locoregional relapse between chemotherapy and control group ( p = 0.6337 ) , nor in distant metastasis development ( p = 0.1527 ) , or os ( p = 0.3402 ) . patients with a pathological complete response ( pcr ) to the nact had a higher probability of survival than those without ( 10-year os : 76.2% vs. 41.3% , p = 0.0004 ) . published the results of their prospective open - label phase iii trial of 256 untreated stages iii or iva locally advanced resectable oscc . patients were randomized into two groups who received two cycles of nact ( tpf ) ( docetaxel 75 mg / m on day 1 , cisplatin 75 mg / m on day 1 , and fluorouracil 750 mg / m on days 1 - 5 ) followed by radical surgery and postoperative radiotherapy ( 54 - 66 gy ) versus up - front radical surgery and postoperative radiotherapy . the primary endpoint was os , and the secondary endpoints included local control and safety . the pathological response rate was 13.4% . a statistically insignificant lower rate of distant metastasis in the nact arm was observed ( 5.5% vs. 8.7% ) . at a median follow - up of 30 months , there was no difference in the disease - free survival and the os between the two arms ( 68.8% vs. 68.2% ) . patients in the nact arm with a clinical response or favorable pathologic response ( <","the standard of care treatment for oral squamous cell carcinoma ( oscc ) at present , consist of surgical resection followed by adjuvant radiotherapy and chemotherapy as indicated . despite recent advances the overall prognosis remains guarded . role of neoadjuvant chemotherapy is being explored with premise of reducing extent of surgical resection , improving loco - regional control and decreasing distant metastasis , thereby improving treatment outcomes by decreasing mortality and morbidity . however , indications of neoadjuvant chemotherapy in oral cancers are not clearly defined . majority of studies have failed to demonstrate a significant benefit of neoadjuvant chemotherapy in terms of loco regional control and overall survival in resectable oscc . in a select subset of patients with locally very advanced and unresectable oscc ,",380,128,0.3368
pubmed-summarization,"sm is located in the limbs and represents appendicular sm . the same authors defined sm index ( smi ) as a % of total body mass ( sm / body weight , % ) x 100 , and smi is expressed in % units . low smi was defined as a smi below one standard deviation of young adult values according to the data from the third national health and nutrition examination survey ( nhanes iii).5 the cutoff values suggested from this study were < 37% and < 31.5% ( class i and ii sarcopenia for men ) and < 27.6% and < 22.1% ( class i and ii sarcopenia for women ) . another definition for smi was created some years later , considering smi as sm ( in kg , obtained from the same bia equation ) adjusted for the squared height ( sm / height , kg / m ) . based in physical disability risk also assessed in the nhanes iii elderly population , the authors defined the usual cutoff used to define sarcopenia with smi : moderate sarcopenia when smi is between 8.51 and 10.75 kg / m ( men ) or 5.76 and 6.75 kg / m ( women ) and severe sarcopenia when smi is 8.50 kg / m ( men ) or 5.75 kg / m ( women).6 these cutoff values are used in the european working group on sarcopenia in older people consensus , when absolute sm is estimated from bia.2 in the cachexia consensus statement , fearon et al . 3 proposed three criteria for diagnosing cancer cachexia : weight loss > 5% over past 6 months ( in the absence of simple starvation ) ; orbody mass index < 20 kg / m and any degree of weight loss > 2% ; orappendicular skeletal muscle index consistent with sarcopenia . weight loss > 5% over past 6 months ( in the absence of simple starvation ) ; or body mass index < 20 kg / m and any degree of weight loss > 2% ; or appendicular skeletal muscle index consistent with sarcopenia . sarcopenia can be assessed by several techniques , as described in the paper , including bia . the authors used the term whole body","abstractas reference methods are not available for identifying low skeletal muscle mass in clinical practice , the european group on sarcopenia in older people the asian working group for sarcopenia and the international consensus for cancer cachexia guidelines accept bioelectrical impedance analysis ( bia ) as an option for sarcopenia and cachexia assessment . using different bia equations , several components that represent muscularity can be assessed . total skeletal muscle mass or appendicular skeletal muscle mass normalized in relation to height ( skeletal muscle mass index or appendicular skeletal muscle index , respectively ) is the most common term used in the consensus . these terms are similar , but they should not be used as synonymous . both terms can be used to define sarcopenia ,",380,128,0.3368
dialogsum,"#Person1#: Oh, Ann, that was a wonderful dinner. That's the best meal I've ever had. #Person2#: Thank you. #Person1#: Can I give you a hand with the dishes? #Person2#: I'll do them myself later. Would you like some coffee? #Person1#: Thanks a lot. I'd love some. Oh, Ann, I didn't realize you were such a good cook. #Person2#: It's because I've been taking these courses. Actually, I've just learned how. #Person1#: I can't cook at all. I, I can't even boil an egg. #Person2#: You're kidding. Well, if you want to, you could take several classes at college and learn how to do it, too. #Person1#: Forget it. I was not born for that. Oh, I just remembered, I wonder if I could possibly use your phone. #Person2#: I'm sorry, but there's something wrong with my phone. It doesn't work. Is it really important? #Person1#: Well, you see, I have to call my secretary about tomorrow's work plan. So I'm afraid I have to go now. Thank you for your dinner. #Person2#: You're welcome. Good night then.",#Person1# had dinner at Ann's. #Person1# complimented Ann on her cooking skills and #Person1# cannot cook at all. #Person1# has to leave because Ann's phone doesn't work but #Person1# needs to call #Person1#'s secretary.,177,34,0.1921
pubmed-summarization,"after the first apc administration , a second round of apc treatment was administered , and hemodialysis therapy was initiated ( . a 61-year - old woman with alcoholic liver cirrhosis ( child - pugh class b ) and ckd stage v ( cr = 3.14 mg / dl ; egfr = 12.6 ml / min/1.73 m ) caused by hepatorenal syndrome was admitted to the hospital . she suffered from loss of appetite with uremia and had severe anemia ( hb = 4.8 g / dl ) despite administration of rhuepo and intravenous iron . she also had severe melena , and upper gastrointestinal endoscopy revealed diffuse antral vascular ectasia without esophageal varices or active bleeding . she was treated with apc twice , but frequent blood transfusions were required . five months after the second apc treatment , the patient was started on hemodialysis because of volume expansion ( . a 66-year - old woman with ckd stage v ( cr = 6.4 mg / dl ; egfr = 5.7ml / min/1.73 m ) presented with severe anemia ( hb = 4.8 g / dl ) and suffered from lassitude , loss of appetite , and dyspnea with uremia . the primary cause of ckd was an autosomal dominant polycystic disease with numerous and massive cysts in both the kidneys and liver . after 8 months of apc sessions , she was treated with another round of apc and started on hemodialysis ( . 1 ) . after the induction of hemodialysis , her loss of appetite and lassitude disappeared . moreover , her anemia improved , and gave has not recurred . written informed consent was obtained from all 3 patients . gave is often associated with systemic illnesses such as cirrhosis of the liver , autoimmune connective tissue disorders , bone marrow transplantation , and ckd . although the pathogenic link remains unclear , vascular ectasia is a significantly more common cause of upper gastrointestinal bleeding in patients with ckd than in those with normal renal function ( 13 vs. 1.3% , respectively ; p < 0.01 ) . it has been reported that the antral area half - time in these patients is significantly increased when compared with that of healthy controls . this finding","gastric antral vascular ectasia ( gave ) is currently recognized as an important cause of gastrointestinal bleeding . chronic kidney disease ( ckd ) is associated with a high incidence of gave . we report 3 patients with ckd who presented with severe anemia and were diagnosed with gave ; they were resistant to endoscopic argon plasma coagulation . however , remission of anemia and improvement in gave lesions were observed after the initiation of hemodialysis . the pathogenesis of gave remains largely unknown , but mechanical stress of the antrum could play an important role . this stress may be reduced by hemodialysis through improvement of uremia - associated gastrointestinal symptoms . therefore , the initiation of hemodialysis might be effective for intractable gave in ckd patients",380,128,0.3368
pubmed-summarization,"mean duration of aa was 14.5 25.4 ( range , 1 - 119 months ) . in the total of patients with aa , 46 of them were laa and 14 were at , au , or at / au group . serum tnf- levels ranged from 8.8 to 17.0 pg / ml , with the highest values observed in the au patients . the mean serum tnf- in aa patients was 10.31 1.20 pg / ml ( mean sd ) , whereas that of laa or extensive ( at , au , or at / au ) was 10.16 0.79 pg / ml or 10.40 1.03 pg / ml , respectively . patients with longer duration of the disease had higher concentration of tnf- , but not significantly [ ] . correlation between the duration of the aa and concentration of tnf-,r = 0.034 ; ( rho ) = 0.1142 ; 95% ci ( -0,144 ; 0,358 ) ; p > 0.05;-n.s serum levels of tnf- in patients with aa were significantly higher than those in controls ( p = 0.044 ) . there was no significant difference in levels of tnf- between patients with laa and the extensive group ( p=0.2272 ) . serum concentrations ( meansd ) of tnf- in patients with aa , laa , at / au and in healthy controls recent progress in the understanding of aa has shown that the regulation of local and systemic cytokines plays an important role in its pathogenesis . hair loss may occur because proinflammatory cytokines interfere with the hair cycle , leading to premature arrest of hair cycling with cessation of hair growth . this concept may explain typical clinical features of aa such as a progression pattern in centrifugal waves and spontaneous hair regrowth in concentric rings , suggesting the presence of soluble mediators within affected areas of the scalp . tnf- is a multifunctional proinflammatory cytokine which has been implicated in the pathogenesis of many infections and inflammatory disorders . however , this cytokine not only acts as mediator of immunity and inflammation , but also affects not - immune responses within tissues such as cell proliferation and differentiation . in vitro studies have shown that tnf- , along with il-1 and il- , causes","background : alopecia areata ( aa ) is a common form of localized , nonscarring hair loss . it is characterized by the loss of hair in patches , total loss of scalp hair ( alopecia totalis , at ) , or total loss of body hair ( alopecia universalis , au ) . the cause of aa is unknown , although most evidence supports the hypothesis that aa is a t - cell - mediated autoimmune disease of the hair follicle and that cytokines play an important role.aims:the aim of the study was to compare the serum levels of tumor necrosis factor - alpha ( tnf- ) in patients with aa and the healthy subjects and also to investigate the difference between the localized form of the",380,128,0.3368
dialogsum,#Person1#: What do you think of smoking? #Person2#: It's harmful not only for yourself but for others. #Person1#: What in your opinion can be done to stop smoking? #Person2#: Stop producing cigarettes. #Person1#: But that'll affect the national economy. #Person2#: That's right. But I don't think there are better ways. #Person1#: How about painting a warning on each cigarette packet? #Person2#: Maybe it can take effect.,#Person2# suggests stopping producing cigarettes to stop smoking. #Person1# suggests putting a warning on each packet.,66,16,0.2424
scientific_lay_summarisation-elife-norm,"Channelrhodopsin-2 (ChR2) has quickly gained popularity as a powerful tool for eliciting genetically targeted neuronal activation. However, little has been reported on the response kinetics of optogenetic stimulation across different neuronal subtypes. With excess stimulation, neurons can be driven into depolarization block, a state where they cease to fire action potentials. Herein, we demonstrate that light-induced depolarization block in neurons expressing ChR2 poses experimental challenges for stable activation of specific cell types and may confound interpretation of experiments when ‘activated’ neurons are in fact being functionally silenced. We show both ex vivo and in vivo that certain neuronal subtypes targeted for ChR2 expression become increasingly susceptible to depolarization block as the duration of light pulses are increased. We find that interneuron populations have a greater susceptibility to this effect than principal excitatory neurons, which are more resistant to light-induced depolarization block. Our results highlight the need to empirically determine the photo-response properties of targeted neurons when using ChR2, particularly in studies designed to elicit complex circuit responses in vivo where neuronal activity will not be recorded simultaneous to light stimulation. Optogenetics is a powerful emergent technology for investigating complex patterns of synaptic connectivity and circuit properties that underlie physiology and behavior. By selectively expressing and activating light-gated ion channels or light-driven ion pumps, optical control of neural circuitry can be accomplished with high spatial and temporal resolution (Boyden et al. , 2005; Li et al. , 2005; Nagel et al. , 2005). To date, many variants of light-sensitive proteins are available for use towards the activation or inhibition of excitable cells (Lin, 2011; Rein and Deussing, 2012). The most commonly used variant, channelrhodopsin-2 (ChR2) has become increasingly valuable in studies that exploit cell type-specific excitation. Isolated from the green algae, Chlamydomonas reinhardtii, ChR2 is a seven-transmembrane-domain, nonselective cation channel that is directly activated by blue light when bound with the chromophore all-trans-retinal (Hegemann et al. , 1991; Lawson et al. , 1991; Takahashi et al. , 1991; Nagel et al. , 2003). Absorption of photons by the chromophore induces conformational changes in the channel that allow for the passage of cations across the cell membrane in which it is expressed (Boyden et al. , 2005). This direct photo-gating makes ChR2 useful for manipulating neuronal activity in vitro (Boyden et al.","The brain is a highly complex structure composed of trillions of interconnecting nerve cells. The pattern of connections between these cells gives rise to the various brain circuits that govern how the brain functions. Understanding how the brain is wired together is important for determining how ‘faulty circuits’ contribute to various neurological disorders. New optogenetic technique tools allow neuroscientists to turn on specific neurons simply by shining light on them. These techniques involve genetically manipulating the organisms so that their neurons express proteins that are activated when they are exposed to light of a particular wavelength. However, it is important to understand the limitations of this approach—including the possibility that the light might actually turn off some neurons—when using it to study animal behavior. Now, Herman, Huang et",380,128,0.3368
pubmed-summarization,"the bowel lumen around the terminal ileum was filled with contrast media ( . 1 ) . however , we failed to control the bleeding , because the artery was too small for embolization treatment . he received transfusions of 10 units of packed red blood cells . while he was prepared for emergency surgery , his vital signs became stabilized , so he underwent colonoscopy . we found fresh blood throughout the entire colon and terminal ileum but could not find the bleeding focus . for small bowel evaluation , we performed sbe with a retrograde approach and found the dieulafoy lesion on the distal ileum , approximately 20 cm from the ileocecal valve ( . for evaluation of other small bowel lesions , we performed capsule endoscopy but could not find any abnormal lesion except the previously placed hemoclips ( . she had obstructive coronary artery disease and took aspirin and an antiplatelet agent . on admission , blood hemoglobin level was 8.7 g / dl . on the day of admission , she underwent egd and colonoscopy , but we could not find the bleeding focus . she then underwent abdominal ct , but there was no specific lesion in the gi tract suspicious for bleeding . we recommended enteroscopy for evaluation of the obscure bleeding focus , but she refused because her melena ceased . vital signs were stabilized , and she was discharged home on the ninth admission day . six days after discharge , she revisited our hospital due to recurrent fresh hematochezia . at that time , blood pressure dropped to 88/56 mm hg , and pulse was 107 beats / min . as she had underwent egd and colonoscopy , we performed sbe with a retrograde approach . we found a fresh blood clot adherent on the mucosa of proximal ileum and , after saline irrigation , we detected the active bleeding focus at a narrow point of normal - appearing mucosa ( . she was discharged home and had no evidence of recurrent gi bleeding at her 2 month follow - up visit . a 47-year - old man was admitted to our hospital for hematochezia of 8 hours . he denied previous medical history as well as taking any medication","ileal dieulafoy lesion is an unusual vascular abnormality that can cause gastrointestinal bleeding . it can be associated with massive , life - threatening hemorrhage and requires urgent angiographic intervention or surgery . ileal dieulafoy lesion is hard to recognize due to inaccessibility and normal - appearing mucosa . with advances in endoscopy , aggressive diagnostic and therapeutic approaches including enteroscopy have recently been performed for small bowel bleeding . we report two cases of massive ileal dieulafoy lesion bleeding diagnosed and treated successfully by single balloon enteroscopy with a review of the literature .",380,95,0.25
pubmed-summarization,"cytokines , mostly ifn , il-2 ; and occasionally the apc - derived il-12 or tnf were measured together with one or two of the typical th2-type cytokines il-4 , il-5 , and il-10 . generally a shift from a th1-type to a th2-type cytokine response was observed when healthy controls or women with low - grade squamous intraepithelial lesions ( lsil ) were compared with cases of high - grade sil ( hsil ) or cervical carcinoma . we previously observed manifestation of a th2-type cytokine pattern in plasma of hr - hpv - positive women during carcinogenesis of cervical cancer at the stage of cin iii . recent studies with isolated t - cell fractions stimulated with hpv16-derived oncopeptides indicate a reactivation of an inflammatory response in patients with carcinoma . these results let us assume that significant changes in the immunocompetence of circulating leukocytes are involved in the development from cervical dysplasia to cervical cancer . in the present study we used whole blood cultures from hr - hpv - negative controls , hr - hpv - positive women without cervical dysplasia and hr - hpv positive patients with different grades of cin and cervical cancer to investigate changes in immunocompetence expressed in the capacity of circulating leukocytes to release cytokines in response to a mitogenic challenge . of interest were the effect of hr - hpv infection without clinical manifestations , the special position of cin iii with a th2-type cytokine response , and a possible revival of inflammatory cytokine activity in cervical carcinoma . inclusion took place at the outpatient clinic of the obstetrics and gynaecology department of the erasmus university medical center ( rotterdam , the netherlands ) between july 2000 and august 2002 . our selection of patients for this study was based on the presence of hr - hpv and the grade of cervical intraepithelial neoplasia . histology results were defined as no dysplasia , mild dysplasia ( cin i ) , moderate dysplasia ( cin ii ) , severe dysplasia ( cin iii ) , or ( micro- ) invasive cancer . an experienced pathologist revised all histological samples . women with cin i lesions ( mild dysplasia ) were excluded since more than fifty percent of our patients with cin","aims . we investigated the effect of hr - hpv infection on the capacity of the cytokine network in whole blood cultures during carcinogenesis of cervical carcinoma . methods . thirty - nine women with moderate dysplasia , severe dysplasia , cervical carcinoma , or without dysplasia formed the study group . the control group consisted of 10 hr - hpv - negative women without cin . whole blood cultures were stimulated with phytohemagglutinin ( pha ) and concentrations of tumour necrosis factor ( tnf ) , interferon ( ifn ) , interleukin 2 ( il-2 ) , interleukin 12 ( il-12 ) , interleukin 4 ( il-4 ) , and interleukin 10 ( il-10 ) were determined by elisas . results . a significant increase in cytokine",380,128,0.3368
scientific_lay_summarisation-elife-norm,"presence and abundance of dengue mosquitoes is a necessary but not sufficient condition for dengue transmission and the occurrence of large outbreaks. Besides vector infestation, an important factor regulating transmission is the introduction of new serotypes of virus in areas with a high susceptible population. This may be facilitated by the increasing international and internal mobility across the country. Thus, large and touristic cities are prone to the introduction and maintenance of virus circulation. International mass gathering events have become an important health issue in the recent years (Abubakar et al. , 2012) as they create the opportunity for the introduction of new pathogens in a susceptible population, as well as exposing visitors to new and unknown local risks (Matos and Barcellos, 2010). Early warning systems, which take into account multiple dengue risk factors, can assist public health authorities to implement timely control measures ahead of imminent dengue outbreaks. Seasonal climate forecasts combined with early dengue surveillance system data provide an opportunity to anticipate dengue outbreaks several months in advance (Lowe et al. , 2014). To date, several studies have assessed the use of climate information in early warning systems for diseases, such as malaria and Rift Valley fever (Anyamba et al. , 2009; Thomson et al. , 2006). The incorporation of climate information for dengue early warning systems has also been explored (Degallier et al. , 2010; Lowe et al. , 2011; Stewart-Ibarra and Lowe, 2013). However, to our knowledge, real-time climate forecasts have not been previously applied to predict dengue epidemics in a practical real-life framework. From 12 June to 13 July 2014, Brazil hosted the 2014 Fédération Internationale de Football Association (FIFA) World Cup, a mass gathering of more than 3 million Brazilian and international spectators, travelling between 12 different host cities. Before the event, the potential risk of transmission of several communicable diseases, including dengue fever, was highlighted (Gallego et al. , 2014; Wilson and Chen, 2014). Several research groups published dengue outlooks ahead of the World Cup. Approaches included analysing historical time series distributions of city or state level data (Hay, 2013) and mapping of historical averages, while accounting for seasonality and areas of permanent transmission (Barcellos and Lowe, 2014a). Some groups formulated deterministic (Massad et al. , 2014) and statistical (van Panhuis et al.","Dengue is a viral infection spread by mosquitoes and is widespread in tropical and sub-tropical regions. Dengue epidemics in Brazil often occur without warning, and can overwhelm the public health services. Forecasts of seasonal climates combined with early data from a dengue surveillance system could help public health services anticipate dengue outbreaks several months in advance. However, this information has not been previously exploited to predict dengue epidemics in a practical real-life framework. Recently, a group of researchers developed a prototype of a dengue early warning system based on 13 years worth of data, and used it to predict the risk of dengue three months ahead of the 2014 FIFA World Cup in Brazil. Now Lowe et al. – including most of the researchers involved in the earlier",380,128,0.3368
pubmed-summarization,", upper extremity function , vision and work / productivity ) . each item has five response options referring to function in the previous week . the score of each item ranges from 1 to 5 points and the total ranges from 49 ( worst perception of quality of life ) to 245 ( best perception ) . in the present study , only the upper extremity function subscale was employed to analyze its association with oral health impact . although upper extremity function on this questionnaire is evaluated based on actions such as fastening a button and opening / closing a zipper , ssqol - brazil was chosen for use in the present study due to the lack of specific questionnaires in the literature for the evaluation of upper limb function in relation to oral self - care and even the function of feeding oneself . the shapiro - wilk s test was used to determine whether or not the data had a normal distribution . pearson s correlation coefficients were calculated to determine the magnitude , direction and significance of associations between variables related to upper limb function and oral health impact . the strength of the associations was classified as weak ( correlation coefficient : 0.1 to 0.3 ) , moderate ( correlation coefficient : 0.4 to 0.6 ) or strong ( correlation coefficient : 0.7 to 1 ) . a level of significance of 5% ( p < twenty - seven individuals with hemiparesis stemming from a stroke participated in the present study . the female accounted for 37.1% ( n = 10 ) of the sample and the male accounted for 62.9% ( n = 17 ) . the mean age of the subjects was 60.5 12.7 years ( range : 30 to 85 years ) and the mean time since the occurrence of stroke was 28.5 29.6 months ( range : 2 to 108 months ) . a total of 51.8% of the sample ( n = 14 ) had right side hemiparesis and 48.2% had left side hemiparesis ; 63% ( n = 17 ) had complete hemiparesis and 37% ( n = 10 ) had partial hemiparesis ; 55.5% ( n = 15 ) had brachial predominance and 44.4% ( n =",[ purpose ] the aim of the present study was to evaluate the relationship between upper limb impairment and oral health impact in individuals with hemiparesis stemming from a stroke . [ subjects and methods ] the study subjects were conducted with a sample of 27 stroke survivors with complete or partial hemiparesis with brachial or crural predominance . the 14-item short version of the oral health impact profile was used to evaluate perceptions of oral health . the brazilian version of the stroke specific quality of life scale was used to evaluate perceptions regarding quality of life . [ results ] a statistically significant association was found between the upper extremity function subscale of the ssqol - brazil and the impact of oral health evaluated using the,380,128,0.3368
scientific_lay_summarisation-elife-norm,"has a different' identity' , resulting in the bipolar distribution of Myosin II in every cell. These findings open new questions. One is what becomes of the combinatorial code and the planar polarisation of Myosin II once the cells have started intercalating and the number of cells increases along AP? Specifically, if the cell identity stripes defined by the Toll-like receptor code are one cell wide to start with as hypothesised (Paré et al. , 2014), then these would increase to two cells wide on average after one round of cell intercalation. Heterophilic interactions between Toll receptors would no longer be expected at the interfaces between pairs of cells of the same' identity' . Therefore one possibility is that these interfaces are not enriched in Myosin II at later stages of GBE. Alternatively, a secondary mechanism might be required to polarise the germband in later GBE, for example relying on a global polarising signal, more akin to PCP pathway-reliant polarisation in vertebrates (Devenport, 2014; Goodrich and Strutt, 2011). Another unsolved question is how the AP patterns established early in development are maintained during the cell movements of convergent extension (Dahmann et al. , 2011; Vroomans et al. , 2015). Cell rearrangements by intercalation are sufficient to cause mixing of adjacent cell populations (Umetsu et al. , 2014), therefore it is likely that a mechanism exists to maintain order along the AP axis of the germband. At later stages of embryonic development in Drosophila, an enrichment of actomyosin at parasegmental boundary (PSB) cell-cell interfaces is required to prevent cell intermingling caused by cell proliferation (Monier et al. , 2010; 2011). The actomyosin enrichment in this case is thought to act as a mechanical barrier, since the enriched PSB cell-cell interfaces align, indicating line tension. Supporting this notion, laser ablation experiments have demonstrated an increase in interfacial tension at compartmental boundaries in the wing disc and abdomen (Umetsu et al. , 2014; Aliee et al. , 2012; Landsberg et al. , 2009). Since parasegmental boundaries are defined genetically by pair-rule gene expression before gastrulation starts (Lawrence and Johnston, 1989), an unexplored possibility is that actomyosin enrichments at PSBs could form early, during GBE, and limit intermingling of cells during the large-scale cell rearrangements of convergence and extension. Here we take a systems","Early in development, a growing embryo elongates to form its main body (head–tail) axis. This elongation is driven by a process called cell intercalation – when cells insert between each other. The mechanism that controls this coordinated cell movement is well understood on a small scale. However, it is not known how hundreds of cells rapidly intercalate across a whole tissue without deforming a tissue or inappropriately mixing. During fruit fly development, an embryo divides into repeated segments of tissue while elongating. While this happens, cells redistribute an essential structure called the actomyosin cytoskeleton so that it is found more commonly along certain sides of the cell. This structure, which can be thought of as the cell’s “muscle”, is a contractile web made of proteins called actin and",380,128,0.3368
pubmed-summarization,"angptl2 levels were divided into quartile categories : 2.15 , 2.162.71 , 2.723.40 , and 3.41 the incidence of t2 dm was calculated by the person - year method and adjusted for age and sex by the direct method using 10-year age groupings . the adjusted hazard ratios ( hrs ) and their 95% cis in 2002 , a baseline survey for this study was performed in the town of hisayama , japan . briefly , of the total of 3,896 residents aged 40 to 79 years , 3,000 consented to participate in the survey ( participation rate , 77.0% ) . among them , 178 participants were not administered a 75-g oral glucose tolerance test ( ogtt ) : 100 refused the test , 46 had already eaten breakfast , and the other 32 were receiving insulin therapy for diabetes . consequently after further excluding 485 participants who had newly diagnosed or known diabetes and 8 for whom there was no measurement of angptl2 , the remaining 2,329 ( 953 men and 1,376 women ) were enrolled in the baseline examination . the baseline participants were followed up prospectively , from 2002 to 2009 , by yearly health examinations during which an ogtt was administered . of the baseline participants , 2,164 ( 865 men and 1,299 women ) who underwent reexaminations during the follow - up period were finally selected for this study ( follow - up rate , 92.9% ; mean follow - up period , 6.0 years ) . these participants completed the follow - up examinations an average of 4.9 times , and among them , 861 ( 39.8% of the follow - up population ) underwent all 7 annual ogtts . during the follow - up , t2 dm occurred in 221 participants ( 115 men and 106 women ) . in the baseline and follow - up examinations , the study participants underwent the ogtt after an overnight fast of at least 12 h. diabetes was defined by the 2003 american diabetes association criteria ( 7 ) . serum angptl2 concentrations were measured with the human angptl2 sandwich enzyme - linked immunosorbent assay using two mouse monoclonal antibodies that were confirmed to recognize only angptl2 and not to react with other angptls or","objectiveto examine , for the first time , the association between a novel inflammatory cytokine , angiopoietin - like protein ( angptl ) 2 , and the development of type 2 diabetes ( t2dm).research design and methodsa total of 2,164 community - dwelling japanese individuals aged 40 to 79 years without diabetes were followed up for 7 years . serum angptl2 levels were divided into quartile categories at baseline : < 2.15 , 2.162.71 , 2.723.40 , and 3.41 ng / ml . during follow - up , 221 participants developed t2dm.resultsin multivariate analyses , after adjusting for comprehensive risk factors and high - sensitivity c - reactive protein ( hs - crp ) levels , the risk of developing t2 dm was significantly higher in the highest",380,128,0.3368
dialogsum,"#Person1#: Ping-pong must be the top-ranking popular sport in China. It seems to me in every school, factory, army unit, or residential area, men and women, young and old, are swinging paddles. #Person2#: You got it! In a sense, it has become a byword for Chinese sport. #Person1#: What do you think might be the source of its popularity? #Person2#: I think its critical advantage lies in its low cost. All you need is a racket, a table and a light celluloid ball. Tables are usually available in public recreation areas, like finest rooms, and outdoor playgrounds. . . #Person1#: And sometimes a substitute table can be made out of a few desks. #Person2#: Put it there! In senior high schools, we used to play on desks in the classroom, when no vacant tables were available. Likewise, the racket may take a variety of forms, too. Anything that resembles a racket, from a plank to cardboard or even a hardcover book, may be used as a racket. #Person1#: Haha, these are very good inventions. All these speak the public's fondness for the sport #Person2#: Yeah, the sport is affordable and accessible to every Tom, Dick and Jane in this developing country. No wonder even the state leaders are known to be keen on it. #Person1#: I know President Hu Into likes playing ping-pong. #Person2#: Actually, he excels in it. Chairman Mao, too, encouraged the whole nation to play ping-pong as a part of the nationwide body building campaign. #Person1#: I see. There was also the famous ping pong diplomacy, wasn't there?","#Person1# and #Person2# are talking about the top-ranking popular sport, ping-pong, in China. #Person2# thinks its critical advantage is the low cost because it just needs a racket, a table, and a ball. #Person1# adds that sometimes substitutes also work. #Person1# and #Person2# say that many leaders are good at it.",261,51,0.1954
scientific_lay_summarisation-elife-norm,"To avoid mutations in the genome, DNA replication is generally followed by DNA mismatch repair (MMR). MMR starts when a MutS homolog recognizes a mismatch and undergoes an ATP-dependent transformation to an elusive sliding clamp state. How this transient state promotes MutL homolog recruitment and activation of repair is unclear. Here we present a crystal structure of the MutS/MutL complex using a site-specifically crosslinked complex and examine how large conformational changes lead to activation of MutL. The structure captures MutS in the sliding clamp conformation, where tilting of the MutS subunits across each other pushes DNA into a new channel, and reorientation of the connector domain creates an interface for MutL with both MutS subunits. Our work explains how the sliding clamp promotes loading of MutL onto DNA, to activate downstream effectors. We thus elucidate a crucial mechanism that ensures that MMR is initiated only after detection of a DNA mismatch. To enable the correct and complete transfer of genetic information during cell division, DNA polymerases efficiently replicate the genome by pairing nucleotide bases opposite their complementary template base. However, despite the polymerase proofreading ability, incorrect nucleotides are occasionally incorporated into the new DNA strand, resulting in mutations when left uncorrected. To reduce the number of such mismatches and maintain genomic stability, replication is followed by DNA mismatch repair (MMR) in almost all cellular organisms (Kunkel and Erie, 2005; Jiricny, 2013). The initiation of this MMR system is evolutionarily conserved, although in eukaryotes heterodimeric homologs replace the bacterial homodimeric components. Defects in MMR result in a mutator phenotype and in humans in predisposition for cancer, known as Lynch syndrome or HNPCC (Lynch and de la Chapelle, 1999). MMR is initiated when a MutS homolog binds to a mismatch. In this mismatch recognition step, the MutS dimer kinks the DNA at the site of the mismatch and stacks a phenylalanine onto the mispaired base (Lamers et al. , 2000; Obmolova et al. , 2000; Warren et al. , 2007). Upon ATP binding MutS releases the mismatch (Allen et al. , 1997; Gradia et al. , 1997) and travels as a ‘sliding clamp’ along the DNA helix (Gradia et al. , 1999; Acharya et al, 2003; Jeong et al. , 2011), and this specific state of MutS is recognized by MutL or","The genetic code of DNA is written using four letters: “A”, “C”, “T”, and “G”. Molecules of DNA form a double helix in which the letters in the two opposing strands pair up in a specific manner—“A” pairs with “T”, and “C” pairs with “G”. A cell must replicate its DNA before it divides, and sometimes the wrong DNA letter can get added into the new DNA strand. If left uncorrected, these mistakes accumulate over time and can eventually harm the cell. As a result, cells have evolved several ways to identify these mistakes and correct them, including one known as “mismatch repair”. Mismatch repair occurs via several stages. The process starts when a protein called MutS comes across a site in the DNA where the letters are",380,128,0.3368
scientific_lay_summarisation-elife-norm,"behavior (Tye et al. , 2011), thus activation of the LA/BLA is a key neural substrate of fear and anxiety. In addition to principal projection neurons, distinct interneuron populations within the BLA can also potently regulate fear memory formation and fear coding (Wolff et al. , 2014), indicating that both inhibitory and excitatory synaptic transmission within this region regulates fear-related behavior and learning. Fear generalization has been proposed to occur through a failure in an animal' s ability to define specific outcome contingencies (Grillon, 2002; Lovibond and Shanks, 2002). Thus, aberrant fear coding in the LA may be an early site of generalized fear manifestation. Consistent with this hypothesis, exposure to fear-inducing stimuli has been demonstrated to increase activity in the amygdala of human subjects (Breiter et al. , 1996; Morris et al. , 1996; Rauch et al. , 2000), and hyper-amygdala activation is observed in numerous disorders, including post-traumatic stress disorder (Rauch et al. , 2000). In rodents, increasing the intensity of an unconditioned fear stimulus increases fear generalization that correlates with enhanced activation of LA neurons to both conditioned (CS+) and non-conditioned (CS−) stimuli (Ghosh and Chattarji, 2015). In addition, suppression of GABAB-mediated signaling in the LA facilitates non-associative long-term potentiation (LTP) of excitatory synapses that correlates with generalized fear responses (Shaban et al. , 2006). Collectively, these data suggest that aberrant plasticity in the LA that facilitates non-selective potentiation of excitatory drive or suppression of inhibitory tone is an important neural substrate of generalized fear. LA neurons demonstrate short latency responses to auditory, visual, and somatosensory stimuli (Ben-Ari and Le Gal la Salle, 1971). Following fear conditioning the latency of responses to predictive auditory stimuli decreases (Quirk et al. , 1995; Maren, 2000) and the response amplitude increases selectively to predictive, but not non-predictive, stimuli (Collins and Pare, 2000), thus demonstrating acquired selectivity in responding to CS+ and CS− stimuli. Acquisition of differential coding of predictive and non-predictive fear-related information is correlated with studies investigating changes in synaptic strength in the LA after fear conditioning. Auditory fear conditioning elicits LTP-like effects in LA neurons (Rogan and LeDoux, 1995; Rogan et al. , 1997) and elicits presynaptic enhancement of inputs arriving in the LA from the medial geniculate nucleus of the thalamus and cortex (McKernan and Shinnick-Gallagher, 1997;","When we experience a situation that causes us to feel fearful, the brain processes information about the events that led up to it. This information is encoded by groups of nerve cells called neurons in a region of the brain called the lateral amygdala. The nerve cells communicate with each other through chemicals called neurotransmitters. At a junction between two neurons—called a synapse—neurotransmitters are released from one cell and influence the activity of the other cell. Long-term changes in the strength of these communications in response to specific cues underlie the formation of memories about fearful events. When these changes occur incorrectly they can lead to memories about particular events becoming inaccurate, which can lead to fear being associated with related, but non-threatening, situations. This ‘generalization’ of fear",380,128,0.3368
pubmed-summarization,"only a slight underestimation . furthermore , recorded reasons for not providing a specimen seem to be unrelated to a higher chance of having tb . the quality of the provided specimens may have been suboptimal because instructing and motivating persons to provide a sputum sample is challenging . for diagnosis of tb , microscopic examination of saliva is less sensitive than examination of sputum ; however , in 50% of saliva samples from patients with a positive sputum sample , bacilli can be demonstrated ( 12,13 ) . for 27,647 samples that appeared to be saliva , smear assuming that only 50% were detected , a maximum of 12 smear - positive tb patients may have been undetected . taking this into account results in a prevalence of 87/100,000 . using this estimate , model 1 provides a cdr of 30% and model 2 a cdr of 28% the possibility that persons who provided a saliva sample were not able to produce a sputum sample because they did not have pathologic pulmonary changes should also be taken into consideration . estimation of the incidence of smear - positive tb in eritrea is complicated by the fact that no data from tuberculin or prevalence surveys were available . the only data available for eritrea were reporting data , which experts assessed as being of low quality ( 14 ) . use of this limited information will result in an uncertain incidence estimate , which may result in an unreliable cdr . for most countries in africa , little information is available for estimating the prevalence of disease and progress towards the millennium development goals ( , accessed 2006 aug 30 ) . on the basis of case reporting , tb was rightly declared an emergency by african health ministers at the who africa regional committee in maputo in 2005 ( 15 ) . to be able to fight this emergency , more reliable information about the prevalence of tb in africa is needed . furthermore , for global tb control , reliable information about the tb epidemic in africa is needed because 28% of the incident smear - positive cases occurred in the who african region in 2004 ( 2 ) . in conclusion , the example of eritrea shows","we used results from a national tuberculosis prevalence survey in eritrea to calculate case detection rate ( cdr ) and compared it with the published cdr . the cdr obtained from the survey was 40% , whereas the cdr published by the world health organization was 3 lower ( 14% ) .",380,52,0.1368
dialogsum,"#Person1#: Hi, my name is Ted, what's yours? #Person2#: What? #Person1#: I said, I'm Ted, who are you? #Person2#: Huh? Oh, my name is Laura. #Person1#: Do you come here often, Laura? #Person2#: Huh? I can't hear you, the music's too loud. #Person1#: Let's go outside and talk. So Laura, do you come here often? #Person2#: Hold on, my ears are still ringing from the music. . . what was it you asked me? #Person1#: I asked if you come here often. #Person2#: Sometimes, usually once every few weeks. Do you? #Person1#: No, this is my first time here. #Person2#: I usually come with a group of friends. We dance a little, have a few drinks, and just have a good time. #Person1#: Yeah, that's why I'm here. My friends dragged me here, because they think I spend too much time studying. #Person2#: That's good. It's good to hit the books, but you need to get out once in a while. #Person1#: I guess so. But the music is too loud. I don't mind getting out and meeting people, but next time I'll do it in a park.",Ted and Laura meet for the first time. They tell each other how often they come to this place and they think the music here is too loud.,188,28,0.1489
dialogsum,"#Person1#: Would you like to see our new shirts? #Person2#: Sorry, but I'm not really that interested in those things. #Person1#: Well, they are very nice you know. #Person2#: Really? #Person1#: And not expensive either. #Person2#: Oh, I don't care about that. #Person1#: Everybody is buying them. #Person2#: Are they? #Person1#: Yes, they are very fashionable, you see. #Person2#: I am afraid I am not interested in fashion. #Person1#: I see. #Person2#: But thank you very much all the same. #Person1#: Sorry I couldn't help you.",#Person1# tries to convince #Person2# to see their new shirts but #Person2# shows no interest.,86,15,0.1744
dialogsum,"#Person1#: Do you have any work experience in this field? #Person2#: Yes. After my graduation from university, I worked as a Customer Service Coordinator in a foreign representative office, and then I transferred to a joint venture as a Market Development Manager. So I am familiar with the market in China. #Person1#: What have you learned from the jobs you have had? #Person2#: I learned to be patient when dealing with customers complaints and try my best to solve them. In addition, I learned at my previous jobs how to cooperate with my colleagues. #Person1#: Does your current employer know you are looking for another job? #Person2#: No, I haven't discussed my leaving plans with my current employer, but I am sure he will release me. #Person1#: What is your impression of your present company? #Person2#: Very good. #Person1#: What would your current colleague say about you? #Person2#: They would say I'm a dependable and hard worker.","#Person1# interviews #Person2# and asks about #Person2#'s work experience, what #Person2# learned from the previous jobs, #Person2#'s impressions of the current company, and what #Person2#'s colleagues would say about #Person2#.",157,30,0.1911
dialogsum,"#Person1#: Mr. Parker. When did you arrive home yesterday evening? #Person2#: At about 8:00 o'clock? #Person1#: What did you do right after you entered your flat? #Person2#: Well, I washed my hands and then watched the Sports News. #Person1#: When did you have supper? #Person2#: At about 8:45 I guess. #Person1#: Did you stay at home all evening? #Person2#: Yes. #Person1#: But your friend said, that he phoned you several times between 8:00 and 9:00. But you didn't answer. #Person2#: Well, I think I was in the bath at that time. #Person1#: No, you weren't, you were not even at home last night, you robbed a bank in James Street.",#Person1# questions Mr. Parker about Mr. Parker's whereabouts yesterday evening and accuses Mr. Parker of robbing a bank.,110,18,0.1636
dialogsum,"#Person1#: You are not looking very cheerful. What's the matter with you? #Person2#: Oh, nothing special. I'm just thinking a lot. #Person1#: About the job? #Person2#: About everything. About catching the same train every morning, sitting in the same office all day, watching the same television program... #Person1#: You need a holiday. #Person2#: It wasn't always like this, you know. #Person1#: What do you mean? #Person2#: Well, our great great grandfathers had more fun, didn't they? I mean, they hunted for their food and grew their own vegetables and did things for themselves. We do the same sort of job for years and years. There's no variety in our lives. #Person1#: You need a holiday. That's what's the matter is with you.",#Person2#'s tired of the daily routine and thinks the older generations had more fun. #Person1# advises #Person2# to take a holiday.,122,21,0.1721
scientific_lay_summarisation-elife-norm,"site: Nagongera (R2 = 0. 03, p=0. 004); Kihihi (R2 = 0. 12, p<0. 001); Walukuba (0. 01, p=0. 05). Parasite densities developed upon infection decreased with increasing age in all settings and for both symptomatic (passive detection) and asymptomatic (detected during routine visits) infections. Despite the large variability in parasite densities recorded within and between individuals, this trend is evident in the raw data (3a). A trend toward lower parasite densities was also observed among individuals living in settings with higher aEIRs (Nagongera), as compared to settings with lower aEIR (Kihihi and Walukuba). We considered multiple candidate models to describe the association between parasite density, age and aEIR (Appendix 1). Models allowing smooth (non-linear) relationships with aEIR best fit the data. Models allowing for two-way interactions between age and aEIR also outperformed models that did not include interactions. In moderate and high transmission settings (households with aEIR >5), increasing age and increasing exposure were independently and linearly associated with decreases in the parasite densities (Table 2). On average, parasite densities decreased by a factor of 0. 76 (95%CI 0. 75–0. 77) for each additional year of age and by a factor of 0. 73 (95%CI 0. 70–0. 76) for each two-fold increase in the aEIR. The relationship was less evident for the lower transmission households (aEIR <5). In these settings, there continued to be a decreasing (although smaller) association with age, but the expected parasite densities at any given age were equal or lower to those observed in the higher exposure (aEIR >10) settings. Figures 4a and 5a present the predicted parasite densities, as a function of age and aEIR, according to the best fitting model. While an individual aged 1 year exposed to an aEIR of 10 is expected to develop a parasite density of 14,610 parasites/μL (95% CI 5924–36,031 parasites/μL) upon infection, the expected parasite density goes down to 3237 parasites/μL (95% CI 1381–7586 parasites/μL) by age 10 years. In contrast, the expected parasite density in an individual living in a setting with aEIR of 150 will be similar at age 1 year (13,071 parasites/μL (95% CI 5256–32,503 parasites/μL) ), but significantly lower by age 10 years (999 parasites/μL (95% CI 398–2508 parasites/μL) ). To test whether the observed associations with age could be explained by the","Malaria kills around 500,000 children every year. The disease occurs when an infected mosquito bites a human and passes on a Plasmodium parasite. One parasite in particular, Plasmodium falciparum, is responsible for most malaria-related deaths across the globe. A person can be infected by P. falciparum many times throughout their life. However, after children have had multiple infections, they become less likely to develop symptoms of malaria, such as high fever. In other words, they gradually acquire immunity. This immunity to malaria can come in two forms: “anti-parasite immunity”, where the body fights the parasites and keeps their numbers low; and “anti-disease immunity”, where the body is more likely to tolerate an infection without developing a fever. To date, scientists do not fully understand how either kind of",380,128,0.3368
pubmed-summarization,"our hypothesis was to determine whether csa or srl had direct detrimental effects on the glomerulus and identify the possible mechanisms involved , using glomerular mesangial cells . human mesangial cells ( hmcs ) are key cells of the glomerulus and have an important role in regulating glomerular structure and function and have the potential to contribute to glomerulosclerosis by secreting profibrotic mediators , which can alter extracellular matrix ( ecm ) balance and disrupt renal function . this may be an important mechanism in renal disease progression and the upstream signalling pathways involved in csa - induced renal dysfunction are not well characterised and warrants further investigation . one intracellular pathway that may potentially be involved in immunosuppressive - induced renal damage is that of the mitogen - activated protein kinase ( mapk ) family , which has been implicated in tgf--induced cytotoxicity . the analysis of the differential activation of this pathway may provide a novel insight into the mechanisms of nephrotoxicity caused by csa . the hmcs were grown in rpmi 1640 containing 5% fcs , penicillin , streptomycin , and l - glutamine and maintained at 37c in a humidified atmosphere containing 95% air , 5% co2 . cells used in the inhibitor studies were pretreated for 1 hour with uo126 , prior to incubation with each drug treatment . mesangial cell viability was assessed using the resazurin conversion ( sigma - aldrich , 7017 ) cell viability assay . the viability of the cells was expressed as a percentage of the absorbance recorded for control cells . total rna was isolated using the trizol method from hmcs , according to the manufacturer 's protocol ( sigma - aldrich , t9424 ) . 1 g of total rna was used to synthesis cdna . a real - time pcr taqman assay was used to quantify the relative expression levels of genes of interest and has been described previously . briefly , cdna was amplified on the abi 7900ht sequence detection system at default thermal cycling conditions : 2 min at 50c , 10 min at 95c for enzyme activation , and then 40 cycles of 15 sec at 95c for denaturation and 1 min at 60c for annealing and extension . were used for all genes","end stage renal disease ( esrd ) is an ever increasing problem worldwide . however the mechanisms underlying disease progression are not fully elucidated . this work addressed nephrotoxicity induced by the immunosuppressive agents ' cyclosporine a ( csa ) and sirolimus ( srl ) . nephrotoxicity is the major limiting factor in long term use of csa . srl causes less nephrotoxicity than csa . therefore investigations into the differential effects of these agents may identify potential mechanisms of nephrotoxicity and means to prevent esrd induced by therapeutic drugs . using elisa , western blotting , quantitative pcr and a reporter gene assay we detailed the differential effects of csa and srl in human renal mesangial cells . csa treatment increased profibrotic tgf-1 secretion in human mesangial",380,128,0.3368
scientific_lay_summarisation-elife-norm,"is critical. Newly-synthesized human ribosomal proteins are subject to degradation by the proteasome in the nucleolus (Lam et al. , 2007), and we recently found that overexpressed yeast ribosomal proteins that fail to assemble are conjugated with ubiquitin and degraded by the proteasome in the nucleus (Sung et al. , 2016). Insoluble material that accumulates upon transient inhibition of the proteasome in yeast is strongly enriched for ribosomal proteins (Sung et al. , 2016), pointing to PQC of unassembled ribosomal proteins as a major pathway of proteostasis. However, the PQC pathway that mediates ERISQ remains unknown – an important gap in our understanding of PQC that we set out to address. We evaluated 115 mutant yeast strains, each lacking a different non-essential ubiquitin-proteasome system (UPS) gene, for those that accumulated non-essential ribosomal protein Rpl26a tagged with a FLAG epitope (Rpl26aFLAG) upon its overexpression from the GAL10 promoter. Accumulation of Rpl26aFLAG in most mutants was similar to wild type (WT) and well below the level detected in rpl26a∆rpl26b∆ (— 1A and B), which accumulated overexpressed Rpl26aFLAG due to lack of competition from endogenous Rpl26 (Sung et al. , 2016). Notably, Rpl26aFLAG accumulated to high levels in tom1∆ and ubc4∆ cells (1A and — 1A and B). 10. 7554/eLife. 19105. 003Figure 1. Ubc4/5 and Tom1 are the E2 and E3 enzymes responsible for ERISQ. (A) Rpl26aFLAG accumulates in tom1∆ and ubc4∆. Accumulation of Rpl26aFLAG upon galactose induction in WT, tom1∆ and ubc4∆ cells was evaluated by SDS-PAGE and immunoblotting with the indicated antibodies. n = 3 biological replicates. (B) Rpl26aFLAG ubiquitination depends on Ubc4/Ubc5. Rpl26aFLAG was induced in cells of the indicated genotypes and cell lysates were prepared and subjected to pull-down with UBA domain resin. Input and bound proteins were evaluated as in (A). n = 3 biological replicates. (C) Rpl26aFLAG accumulates in tom1CA cells. As in (A) except that the Tom1 ligase-dead (tom1CA) mutant was used. n = 3 biological replicates. (D) Rpl26aFLAG ubiquitination depends on Tom1. As in (B) except that cells expressing WT Tom1 or Tom1CA were treated with bortezomib for 45 min after addition of galactose. n = 3 biological replicates. (E) Rpl26aFLAG binds 3xHATom1. Anti-HA immunoprecipitates from cells expressing 3×HATom1 and Rpl26aFLAG were immunoblotted with antibodies to HA, FLAG, and hexokinase. n = 3 biological replicates.","Ribosomes are the molecular machines in cells that produce proteins. The ribosomes themselves are composed of almost 80 different proteins that are held together by scaffolds made from molecules of RNA. Each protein is present in one copy, and so equal numbers of all proteins are needed to assemble a ribosome. However, because it takes many steps to produce a protein and biological processes are inherently imprecise, it is essentially impossible for a cell to produce exactly the same number of copies of all the proteins in a ribosome. Much research suggests that, to overcome these issues, a cell will make more of certain ribosomal proteins than it needs, and then degrade the leftovers that are not used. However, it was not clear how this happens, nor was",380,128,0.3368
dialogsum,"#Person1#: Hi Mark. #Person2#: Hi. #Person1#: What are you planning to do today? #Person2#: I'm not sure yet. #Person1#: Would you like to have lunch with me? #Person2#: Yes. When? #Person1#: Is 11:30 AM OK? #Person2#: Sorry, I didn't hear you. Can you say that again please? #Person1#: I said, 11:30 AM. #Person2#: Oh, I'm busy then. Can we meet a little later? #Person1#: OK, how about 12:30 PM? #Person2#: OK. Where? #Person1#: How about Bill's Seafood Restaurant? #Person2#: Oh, Where is that? #Person1#: It's on 7th Street. #Person2#: OK, I'll meet you there.",#Person1# invites Mark to have lunch. They will meet at Bill's Seafood Restaurant on 7th Street at 12:30 PM.,94,19,0.2021
dialogsum,"#Person1#: I would like to order a waistcoat. #Person2#: Have you chosen the material? #Person1#: Yes, I want it to made of tweed. #Person2#: Fine. And the charge is $ 100. #Person1#: When will it be available? #Person2#: Next Wednesday.",#Person1# orders a waistcoat of tweed. #Person2# tells #Person1# it'll be available next Wednesday.,40,14,0.35
dialogsum,"#Person1#: Hey, Jordan, is that you? Long time no see! #Person2#: Oh, hey, no kidding! I haven't seen you since orientation three months ago! So how've you been? Settling into college life OK? #Person1#: Yeah, I think so! I pledged Phi Iota Alpha, so I'm living at the frat house now. #Person2#: Oh, so you're a frat boy now, huh? #Person1#: Yeah, yeah, I know, it's totally cliche, but really, I think it's been a good decision. I've got a lot of support and good suggestions from the guys. What about you? What have you been up to? #Person2#: Not much. I'm still living at home and commuting to school. I ended up dropping that metalworking class I was so excited about. It just wasn't as interesting as I'd hoped. The guidance counselor suggested that I focus on my prerequisite courses so that I can make sure the credits count. #Person1#: That sounds smart. . . but kind of boring. #Person2#: Yeah, it is, a little bit. I joined the Great Outdoors Club, though, which has been a lot of fun. We've gone on two camping trips already, and I've made some good friends. #Person1#: That's cool. Hey, so have you decided on your major yet? #Person2#: Definitely pre-med. What about you? #Person1#: I still have no clue. . . but we don't have to declare a major till our sophomore year, so I've got time! Oops, I'm late for class. Gotta run! #Person2#: OK, take care! Hey, nice running into you! #Person1#: Yeah, you too!",#Person1# runs into Jordan whom #Person1# hasn't seen for three months and they greet each other. #Person1# tells Jordan #Person1#'s a frat boy now while Jordan's still living at home and commuting to school. Jordan will choose pre-med as his major but #Person1# hasn't decided yet.,256,46,0.1797
pubmed-summarization,"root coverage . one of the problems with multiple root coverage grafting is the unavailability of the large blood supply of donor tissue . if connective tissue supply is limited , more than one surgical procedure may be needed . the purpose of the present study was to evaluate the effectiveness and the predictability of expanded mesh ctg ( e - mctg ) procedure for the treatment of multiple adjacent gingival recession defects . the study population 16 patients , ( age range 2055 years mean age 37 years ) with either dentin hypersensitivity or esthetic problems caused due to the recession defects were included in the study . prior to initiation of the study , ethical approval was obtained from institution ethical committee . all the patients agreed to the study protocol , and signed informed consent was obtained prior to inclusion in the study . the inclusion criteria are ( 1 ) the presence of at least three adjacent miller 's class i or class ii gingival recession on the buccal / facial aspect with recession depth ( rd ) of 2 mm , ( 2 ) probing depth ( pd ) of 3 mm , ( 3 ) a minimum width of keratinized gingival ( kg ) of at least 1 mm . nine subjects contributes three sites , and seven subjects contributed four sites [ ] . preoperative facial view of gingival recession the exclusion criteria are ( 1 ) the presence of severe cervical abrasion / root caries , ( 2 ) the presence of abnormal frenal attachment , ( 3 ) current smokers , ( 4 ) medically compromised patients , ( 5 ) miller 's class iii and iv gingival recession . the patients initially completed a plaque control program , so as to achieve a full mouth plaque score ( fmps ) < 25% . the following clinical measurements were taken by a single examiner at baseline and 3 months , 12 months postoperatively . ( 1 ) rd measured from the cemento - enamel junction ( cej ) to the gingival margin , ( 2 ) recession width ( rw ) measured across the buccal surface at the cej level , ( 3 ) pd measured from the gingival margin to","background : multiple approaches have been used to replace lost , damaged or diseased gingival tissues . the connective tissue graft ( ctg ) procedure is the golden standard method for root coverage . although multiple sites often need grafting , the palatal mucosa supplies only a limited area of grafting material . to overcome this limitation , expanded mesh graft provides a method whereby a graft can be stretched to cover a large area . the aim of this study was to evaluate the effectiveness and the predictability of expanded mesh ctg ( e - mctg ) in the treatment of adjacent multiple gingival recessions.materials and methods : sixteen patients aged 2050 years contributed to 55 sites , each site falling into at least three adjacent miller",380,128,0.3368
dialogsum,"#Person1#: Daddy, how are you going to spend your weekends? #Person2#: I need to finish my research paper. #Person1#: Could you go with me to climb Kiang Shan? #Person2#: Honey, I am sorry I have no time. #Person1#: Oh, Daddy, you should do more exercise. You are getting a little heavy. #Person2#: I am afraid you are right. Recently, even going upstairs makes me out of breath. #Person1#: Then go climbing with me, Daddy. Mountain climbing can build your muscles like Popeyes. #Person2#: Terrific! It is also a good exercise to keep me fit. #Person1#: I give you my word, you must feel refreshed after mountain climbing. #Person2#: OK, I'll go. #Person1#: That's a deal. #Person2#: Sure.",#Person1# persuades #Person2# to climb mountains together because #Person2# is getting heavy and mountain climbing can build muscles. #Person2# at first refuses but later gives in.,117,26,0.2222
dialogsum,"#Person1#: Welcome, sir. May I help you? #Person2#: Yes, I wanna go to America for my vacation. #Person1#: No problem. Actually, we have some great packages. The most exciting season of Hawaii is now. How about a relaxing vacation in Hawaii? #Person2#: Sounds good. Are there any group tours I can go with? #Person1#: Yes. There will be one at the end of this month. For many people, a Hawaiian vacation promises languid days filled with sunbathing and poolside cocktails. For others, it's all about non-stop action in one of the world's most extreme natural playgrounds. Whether you are in search of quiet relaxation or unbridled stimulation, Hawaii gives you the best of both. #Person2#: Great. So how long is the trip? #Person1#: 15 days. The transportation by air will take five days. #Person2#: Fine. I happen to have 20 days for holiday, so exciting! How many places will be visited and what are they? Where will be staying and how about the food there? #Person1#: Sir, let's do it step by step. First, we will visit over 25 different places. Most of the places are in Hawaii's Big Island. We will stay in Arlott's Lodge #Person2#: Well, cool. What's the price for this trip? #Person1#: Well, right now there's a special rate for 40, 000 RMB for this package, including everything such as airline ticket, tour guides, hotels and food. All you have to do is to sign up and we will take care of everything. #Person2#: Well. 40, 000 RMB that's really a lot of money. I will have to think about it. #Person1#: Sure. By the way, this special price is only good through the end of the week. #Person2#: Is it Thursday? I mean if I let the chance slide. . . #Person1#: Yes, sir. It will be a great pity! #Person2#: Well. Ok, I will take it. #Person1#: Thank you!",#Person2# wants to go to America for his vacation. #Person1# recommends a package to Hawaii at the end of this month which lasts for 15 days and introduces the places and food there. #Person2# thinks the package is expensive at first but then decides to take it.,315,47,0.1492
dialogsum,"#Person1#: Good morning, Miss Wang. How beautiful you look today! #Person2#: Thank you. I'm wearing make-up. #Person1#: Who taught you to put on make-up? #Person2#: It's me. I have studied make-up at a beauty shop. #Person1#: Can you teach me how to do make-up? #Person2#: Of course. First, use eye shadow to heighten your eyes. #Person1#: What eye shadow do you think is the most fit for me? #Person2#: I think pink eye shadow is popular among Chinese girls. #Person1#: How do you protect yourself from chapped lips? #Person2#: I suggest you use lipstick, which also accentuates your lips. #Person1#: How did you grow such long nails? #Person2#: You have to pay attention to trimming them from time to time.","#Person1# compliments Miss Wang's beauty and asks her about how to do make-up including eye shadow, lipsticks, and long nails.",120,20,0.1667
pubmed-summarization,"epithelial cells can contribute to chronic inflammatory disorders , synthesizing and secreting a variety of proinflammatory cytokines , such as il-8 , which regulates the neutrophil accumulation in the airways of chronic obstructive pulmonary disease ( copd ) subjects . in response to proinflammatory stimuli in addition , in human bronchial epithelial cells , the nfb activation may regulate il-8 release via erk / map kinase - dependent or kinase - independent processes . cigarette smoke , source of oxidative stress in the airways , is able to induce mucin synthesis in epithelial cells and a subsequent goblet cell production . the mucociliary dysfunction component of copd is due to mucus hypersecretion coupled with a decrease in mucus transport , and it is an important pathophysiological feature requiring appropriate treatment . il-17a , a major product of th17 cells , is implicated in the pathogenesis of several inflammatory and autoimmune diseases . il-17a is involved in the development and progression of inflammatory diseases of the airways , including allergic asthma , rhinitis , and copd . recent studies have demonstrated the effect of il-17a on il-8 secretion in the airway epithelial cells and in airway smooth muscle cells . furthermore , il-17a promotes the growth of airway epithelial cells through erk - dependent signaling pathway and is able to generate muc5ac by nfb in bronchial epithelial cells . acetylcholine ( ach ) it is synthesized by choline acetyl - transferase ( chat ) in different cell types ( macrophages , t - lymphocytes , fibroblasts , and epithelial cells ) acting as an autocrine / paracrine growth factor in regulating various aspects of the innate mucosal defense mechanisms including mucociliary clearance and regulation of macrophage function . nonneuronal ach is involved in the activation of bronchial epithelial cells and alveolar macrophages as well as in the release of chemotactic mediators for eosinophils and neutrophils . it contributes to the inflammatory processes of copd via the activation of muscarinic receptors ( mrs ) m1 , m2 , and m3 , and it is involved in the th17 immunity of copd patients . cholinergic agonists promote mucociliary clearance and the release of inflammatory mediators from airway epithelial cells . anticholinergic drugs , currently used in the treatment of copd , block the","il-17a is overexpressed in the lung during acute neutrophilic inflammation . acetylcholine ( ach ) increases il-8 and muc5ac production in airway epithelial cells . we aimed to characterize the involvement of nonneuronal components of cholinergic system on il-8 and muc5ac production in bronchial epithelial cells stimulated with il-17a . bronchial epithelial cells were stimulated with recombinant human il-17a ( rhil-17a ) to evaluate the chat expression , the ach binding and production , the il-8 release , and the muc5ac production . furthermore , the effectiveness of pd098,059 ( inhibitor of mapkk activation ) , bay11 - 7082 ( inhibitor of ikb phosphorylation ) , hemicholinium-3 ( hch-3 ) ( choline uptake blocker ) , and tiotropium bromide ( spiriva ) ( anticholinergic drug ) was tested",380,128,0.3368
dialogsum,"#Person1#: China is now a member of world trade organization. As a member of TO, China will have to make some changes in its economic policies so that it can follow the routines practiced by other TO members. Is it fair to China, do you think? #Person2#: It's a hard question, but I'm sure the reexamination of China's economic policies in the past may lead us to a right answer to the question. After the establishment of new China, our government employed numerous economics policies to stimulate the growth of China's economy. These policies, however, favored our domestic enterprises and protected them from international competition and these policies have contributed a lot to the rapid growth of both China economy and our domestic enterprises. After China's entry into TO, Chinese domestic enterprises will have to compete with their foreign counterparts. This new situation entails some changes of Chinese economic policies. These changes will spur Chinese enterprises to strengthen their competitiveness in the long run. #Person1#: We can infer that the non-discrimination principle is one of the most important principles of TO agreement. This principle requires equal treatment of domestic and foreign enterprise. Does the principle also apply to domestic enterprise of different ownerships? #Person2#: Yes, it does. Domestic enterprises of different ownerships enjoy equal rights for the non-discrimination principle grants equal rights to enterprises, regardless of their nationality and ownership. I have found that although changes of China's economic policies are numerous, these changes are largely based on the most important economic principle ot TO agreement-non-discrimination principle. Such an understanding of principle of the changes may help us not only to have a good insight into the changes but also to foresee the tendency of the new changes of China's economic policies.","#Person2# thinks the old economic policies stimulate the growth of China's economy and protect Chinese enterprise from global competition. But after China entered TO, it's necessary to change the economic policies. #Person1# says the TO's principle requires equal treatment of domestic and foreign enterprise and #Person2# adds the principle applies to the enterprise of different ownerships.",292,56,0.1918
dialogsum,#Person1#: When did you last go to the seaside? #Person2#: Last July. We spent all our days on the beach. #Person1#: Did you have a good time there? #Person2#: Yes. We swam and dived off the rocks into the sea. We also played game on the sand. #Person1#: The summer vacation is coming. Will you go there this year? #Person2#: I am afraid I won't. My father will go to Guangzhou on business next week. He won't back until September. #Person1#: What a pity! How long can you hold your breath under the water? #Person2#: I don't know. Perhaps more than one minute. #Person1#: That's wonderful. Let us go swimming tomorrow in the river. Is that right?,#Person2# had a good time at the beach last summer but cannot go there this year because of her father's business trip. #Person1# invites #Person2# to go swimming tomorrow.,117,29,0.2479
pubmed-summarization,"cytoscape 1 , 2 provides an environment for the visualization and analysis of networks and associated annotations . the primary audience for cytoscape is the biological community and cytoscape supports a number of standard use cases for analyzing and visualizing biological data . many of these use cases involve the selection of a number of nodes or edges based on some analysis or annotation and either performing an action on that selection or comparing those nodes or edges to a different set of nodes or edges that resulted from alternative analyses or analyses based on alternative annotations . the core capabilities for cytoscape provide some tools to facilitate these types of comparisons but they can be counterintuitive or complicated to use . setsapp is a cytoscape 3 application that provides a general set of tools for users and developers to define and maintain sets of nodes or edges and compare those sets using the standard set operations of union , intersection , and difference . in this paper , we present the implementation of setsapp , in particular , how setsapp integrates with the cytoscape command system , and then present a sample biological workflow using setsapp . cytoscape provides two approaches to implementing apps : a simple app and a bundle app . simple apps are implemented using the same general approach as in cytoscape 2.8 , but at the cost of significant flexibility . bundle apps utilize open service gateway initiative ( osgi ) interfaces through apis provided by cytoscape to interact with the cytoscape core functionality . there are three main components to the setsapp implementation : the user interface , the command interface , and the underlying data model for maintaining sets of nodes and edges . the setsapp user interface consists of menu items in the main apps menu , node and edge context menus , and a panel added to the control panel ( left or west ) section of the cytoscape user interface . the main feature of the sets panel is the list of currently defined sets . each set can be expanded to see all of the nodes or edges within that set , and context menus provide the ability to select , deselect , rename , or remove sets .","setsapp ( ) is a relatively simple cytoscape 3 app for users to handle groups of nodes and/or edges . it supports several important biological workflows and enables various set operations . setsapp provides basic tools to create sets of nodes or edges , import or export sets , and perform standard set operations ( union , difference , intersection ) on those sets . the sets functionality is also exposed to users and app developers in the form of a set of commands that can be used for scripting purposes or integrated in other cytoscape apps .",380,98,0.2579
dialogsum,"#Person1#: What do you like to do in your spare time? #Person2#: I like taking photos. #Person1#: Really? #Person2#: Yes, look at the photos I took. #Person1#: They are beautiful. You did a good job. #Person2#: Thank you for saying so. #Person1#: As a matter of fact, you are really a terrific photographer.",#Person1# compliments #Person2#'s photos taken in #Person2#'s spare time.,53,9,0.1698
pubmed-summarization,"- free outcome . a forward stepwise multiple logistic regression was used to select independent predictors to outcome . only univariate predictors attaining a p value of < 0.10 this study was approved by the regional board of medical ethics at the university of gothenburg . consent for research was obtained from all controls . for operated patients , the board considered long - term follow - up as a quality control measure not necessitating individual consent . primary research questions were as follows : are more patients seizure - free and without aed in the long term after resective epilepsy surgery compared to nonoperated patients ? this longitudinal observational study provides class iii evidence that 41% of adults and 44% of children have sustained seizure freedom in the long term after surgery compared to none of the nonoperated patients ( p < 0.0005 ) . also , 43% of seizure - free adults and 86% of seizure - free children had stopped aeds after 10 years compared to none of the nonoperated patients ( p < 0.0005 ) . this study was approved by the regional board of medical ethics at the university of gothenburg . consent for research was obtained from all controls . for operated patients , the board considered long - term follow - up as a quality control measure not necessitating individual consent . primary research questions were as follows : are more patients seizure - free and without aed in the long term after resective epilepsy surgery compared to nonoperated patients ? this longitudinal observational study provides class iii evidence that 41% of adults and 44% of children have sustained seizure freedom in the long term after surgery compared to none of the nonoperated patients ( p < 0.0005 ) . also , 43% of seizure - free adults and 86% of seizure - free children had stopped aeds after 10 years compared to none of the nonoperated patients ( p < 0.0005 ) . table 1 shows baseline characteristics of the operated patients and the controls , children ( 18 years ) and adults . the only adult who underwent hemispherectomy at age 20 was added to the pediatric hemispherectomy group . none of the baseline characteristics differed between operated and nonoperated patients","objective : to investigate prospective , population - based long - term outcomes concerning seizures and antiepileptic drug ( aed ) treatment after resective epilepsy surgery in sweden.methods : ten- and 5-year follow - ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002 , respectively . all patients had been prospectively followed in the swedish national epilepsy surgery register . ninety - three patients , who were presurgically evaluated but not operated , served as controls.results:in the long term ( mean 7.6 years ) , 62% of operated adults and 50% of operated children were seizure - free , compared to 14% of nonoperated adults ( p < 0.001 ) and 38% of nonoperated children",380,128,0.3368
pubmed-summarization,"intervention studies . the stroke subjects should have been healthy and at work before the stroke meaning that they had no known diseases but hypertonia was present among some participants . the type of stroke was obtained from medical records and self - reports ( see table 1 ) . the control participants were recruited from the local community , with no history of brain injury , stroke , psychiatric or neurological disorder , and no drug abuse , and they were fully able to work . they performed cognitive tests focused on information processing speed , attention , and working memory . the self - assessment for mental fatigue is a multidimensional questionnaire containing 15 questions and is adapted from rdholm et al . . the self - reported questionnaire covers the most common symptoms occurring after brain injury , stroke , or other neurological disorders affecting the brain . the self - assessment scale for mental fatigue and related items has been evaluated , and the 14 questions had adequate internal consistency with a cronbach 's alpha of 0.94 . the questions concern fatigue in general , lack of initiative , mental fatigue , mental recovery , concentration difficulties , memory problems , slowness of thinking , sensitivity to stress , increased tendency to become emotional , irritability , sensitivity to light and noise , and decreased or increased duration of sleep as well as 24-hour variations . this cprs scale is used here for self - assessment of depression and anxiety . the neuropsychological tests included digit symbol - coding from the wais - iii , measuring information processing speed , digit span from the wais - iii , measuring attention and working memory ; verbal fluency test , fas ; trail making test ( tmt ) a and b , measuring visual scanning , divided attention and motor speed . in order to evaluate higher demands such as dual tasks , a series of two new trail making tests was constructed with three and four factors , respectively . months were added in part c and both months and days of the week in chronological order in part d. in the latter , the order of letters and digits was switched . a new computer test","mental fatigue is for many a distressing and long - term problem after stroke . this mental fatigue will make it more difficult for the person to return to work and previous activities . the intention with this study is to investigate mental fatigue in relation to depression and cognitive functions . we examined 24 well - rehabilitated stroke subjects , who suffered from mental fatigue one year or more after a stroke , and 24 healthy controls . subjects were examined using self - assessment scales for mental fatigue , depression and anxiety , and cognitive tests . the results showed a highly increased rating for mental fatigue for the stroke group ( p < 0.001 ) . these participants also had a significantly higher rating on",380,128,0.3368
pubmed-summarization,"cytomegalovirus ( cmv ) infection still remains a major cause of morbidity and mortality in allogeneic stem cell transplantation ( sct ) recipients . while cmv infection of the central nervous system ( cns ) in acquired immune deficiency syndrome patients has been reported relatively frequently , it is an unusual presentation in allogeneic sct recipients , but fatal in all cases ( 1 - 4 ) . recently , unrelated cord blood or t - cell depleted grafts have been increasingly used as an alternative source of hematopoietic stem cells . however , the use of these grafts has been associated with an increased frequency of unusual cmv infections . here , we report a case of cmv ventriculoencephalitis after unrelated double cord blood sct with an alemtuzumab - containing preparative regimen for philadelphia - positive acute lymphoblastic leukemia . the patient had recurrent cmv dnaemia despite long - term treatment with antiviral agents ( foscarnet combined with ganciclovir ) and anti - cmv immunoglobulin . a 20-yr - old man underwent unrelated cord blood sct using two cord blood units to treat philadelphia - positive acute lymphoblastic leukemia . the patient was treated with total body irradiation ( 1,200 cgy ) , fludarabine ( 150 mg / m ) , cytarabine ( 9 g / m ) , and alemtuzumab ( 20 mg ) as a preparative regimen . for prophylaxis of cmv reactivation , acyclovir ( 10 mg / kg intravenously every 8 hr ) and anti - cmv immunoglobulin ( 150 mg / kg intravenously biweekly ) were given from day -7 until engraftment . the patients achieved successful neutrophil and platelet engraftment on day 27 and 51 , respectively . on day 33 , cmv dnaemia was detected by real - time quantitative polymerase chain reaction ( rq - pcr ) as 3,775 copies / ml and the viral load increased steadily thereafter . the patient was treated preemptively for cmv dnaemia with foscarnet ( 60 mg / kg intravenously every 12 hr for 7 days , followed by 90 mg / kg intravenously daily ) from day 39 to day 93 . during this period , foscarnet had been chosen , instead of ganciclovir , since it had less potential bone marrow toxicity .","despite the prophylaxis and preemptive strategies using potent antiviral agents , cytomegalovirus ( cmv ) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation ( sct ) recipients . delayed immune reconstitution after sct , such as cord blood and t - cell depleted sct with the use of alemtuzumab , has been associated with an increased frequency of cmv disease as well as cmv reactivation . cmv disease involving central nervous system is an unusual presentation in the setting of sct . we report a case of cmv ventriculoencephalitis after unrelated double cord blood sct with an alemtuzumab - containing preparative regimen for philadelphia - positive acute lymphoblastic leukemia .",380,116,0.3053
scientific_lay_summarisation-elife-norm,"second stimulus at the same eccentricity in the nasal field of view outside of the blind spot. The subject’s task was to indicate which of the two stimuli was continuously striped and did not present a small orthogonal inset (see 1a). Crucially, stimuli within the blind spot are filled-in and thus perceived as continuous, even when they present an inset. In the diagnostic trials, both stimuli were physically identical and continuous, and subjects were confronted with an ambiguous decision between veridical and partially inferred stimuli. 10. 7554/eLife. 21761. 003Figure 1. Stimuli and stimulation. (a) Striped stimuli used in the study. The inset was set to ~50% of the average blind spot size. The global orientation of both stimuli was the same, but in different trials it could be either vertical (as shown here) or horizontal (not shown). (b) Each stimulus was displayed individually either (partially) inside or (completely) outside the blind spot. This example presents an inset stimulus inside the subject’s left blind spot. However, due to filling-in, it is perceived as continuous (right column). The task required subjects to select the continuous stimulus, and it was designed to differentiate between two mutually exclusive predictions: First, subjects cannot differentiate between the two different types of stimuli and thus answer randomly. Alternatively, subjects have implicit or explicit knowledge about the difference between inferred (filled-in) and veridical contents and consequently select the stimulus outside the blind spot in ambiguous trials. (c) Two stimuli were displayed using shutter glasses. Each stimulus was presented to one eye only, and it is possible that both are presented to the same eye (as in the example depicted here). That is, the left stimulus could be shown either in the temporal field of view (nasal retina) of the left eye (as in the plot) or in the nasal field of view (temporal retina) of the right eye (not shown). In this case, the trial was unambiguous: The stimulus with an inset was presented outside the blind spot and could be veridically observed, therefore, the correct answer was to select the left stimulus. (d) The locations of stimulus presentation in the five experiments. All stimuli were presented relative to the blind spot location of each subject. All five experiments included the blind spot location (green). In the second","To make sense of the world around us, we must combine information from multiple sources while taking into account how reliable they are. When crossing the street, for example, we usually rely more on input from our eyes than our ears. However, we can reassess the reliability of the information: on a foggy day with poor visibility, we might prioritize listening for traffic instead. But how do we assess the reliability of information generated within the brain itself? We are able to see because the brain constructs an image based on the patterns of activity of light-sensitive proteins in a part of the eye called the retina. However, there is a point on the retina where the presence of the optic nerve leaves no space for light-sensitive receptors.",380,128,0.3368
dialogsum,"#Person1#: Would you like to come by and play bridge? #Person2#: Well, let's see. Why don't we go dancing for a change? We haven't done that for a long time. #Person1#: Well, to tell the truth, I don't really feel like it tonight. I had a pretty hard day and I'm sort of tired. #Person2#: Hmm. Well, in that case, we could go to the movies. #Person1#: Oh, we always go to the movies. Can't we do something different? #Person2#: Well, do you have any suggestions? #Person1#: Let's see. How do you feel about playing bridge? #Person2#: It's OK with me, but we don't have any beer and things. #Person1#: Well, shall I call Janet and ask her and Tom to come over, and I'll go to the store and buy some stuff. #Person2#: OK. #Person1#: Hello, Janet. It's me... Oh, fine. Just fine. Say, Janet, I was wondering if you and Tom were doing anything tonight... No? Well. would you like to come by our place and play a few hands of bridge?","#Person2# suggests dancing or going to the movies, but #Person1# prefers to play bridge although because #Person1#'s tired. #Person1# calls Janet and Tom to come over and play bridge.",174,29,0.1667
dialogsum,"#Person1#: Hey Bobby. What's going on? #Person2#: Just taking a smoke break. #Person1#: I forgot my cigarette today. Do you have another one? #Person2#: Sure. Here you go. #Person1#: Thanks. #Person2#: I didn't know you smoked. #Person1#: Really? I've been smoking for over a year now. #Person2#: Oh. You're new to smoking still. I've been smoking for 7 years. #Person1#: You ever tried to quit? #Person2#: Many times. I'm really addicted. It's harder to stop than you think. #Person1#: Yeah. I tried to quit last month, and I thought it was going to be easy, but it turns out that I'm still smoking. #Person2#: I highly recommend you quit soon. The longer you smoke, the harder it becomes to quit. #Person1#: I think you're right. Aright. Gotta go to class. Thanks for the cigarette. I'll talk to you later. #Person2#: No problem. I'll talk to you later.","Bobby, a 7-year smoker, gives #Person1#, a new smoker, a cigarette, and advises #Person1# to quit smoking as soon as possible.",147,21,0.1429
scientific_lay_summarisation-elife-norm,"Cells use phagocytosis and macropinocytosis to internalise bulk material, which in phagotrophic organisms supplies the nutrients necessary for growth. Wildtype Dictyostelium amoebae feed on bacteria, but for decades laboratory work has relied on axenic mutants that can also grow on liquid media. We used forward genetics to identify the causative gene underlying this phenotype. This gene encodes the RasGAP Neurofibromin (NF1). Loss of NF1 enables axenic growth by increasing fluid uptake. Mutants form outsized macropinosomes which are promoted by greater Ras and PI3K activity at sites of endocytosis. Relatedly, NF1 mutants can ingest larger-than-normal particles using phagocytosis. An NF1 reporter is recruited to nascent macropinosomes, suggesting that NF1 limits their size by locally inhibiting Ras signalling. Our results link NF1 with macropinocytosis and phagocytosis for the first time, and we propose that NF1 evolved in early phagotrophs to spatially modulate Ras activity, thereby constraining and shaping their feeding structures. Phagotrophic cells feed by performing large-scale endocytosis. A wide range of unicellular eukaryotes grow in this way, suggesting that it is extremely old in evolutionary terms (Stanier, 1970; Cavalier-Smith, 2002; Yutin et al. , 2009). Typically phagocytosis is used by these organisms to engulf solid particles (Metchnikoff, 1892), and nutrients are then extracted from them by lysosomal degradation (De Duve and Wattiaux, 1966). Animal cells and amoebae ingest solid material using F-actin driven projections of their plasma membrane, forming pseudopodia and ultimately cup- or crown-shaped ruffles that enclose adhered particles. These cells can also internalise bulk fluid without the guidance of a particle using a closely related process, macropinocytosis (Swanson, 2008). Phagocytosis and macropinocytosis are controlled using a large set of cytoskeletal and membrane-associated regulators, notably a variety of small G proteins (Bar-Sagi and Feramisco, 1986; Ridley et al. , 1992; Peters et al. , 1995; Cox et al. , 1997; Martínez-Martín et al. , 2011). Oncogenes such as Src and phosphatidylinositide 3′-kinase (PI3K) have also been linked with regulation of these processes (Araki et al. , 1996; Veithen et al. , 1996; Buczynski et al. , 1997; Amyere et al. , 2000). In amoebae, growth and endocytosis have obvious connections since phagocytosed material supplies essentially all their nutrients; in contrast vertebrates are specialised to digest food extracellularly in the gut, and so links are less apparent. However, large-scale endocytosis is","Dictyostelium amoebae are microbes that feed on bacteria living in the soil. They are unusual in that the amoebae can survive and grow in a single-celled form, but when food is scarce, many individual cells can gather together to form a simple multicellular organism. To feed on bacteria, the amoebae use a process called phagocytosis, which starts with the membrane that surrounds the cell growing outwards to completely surround the bacteria. This leads to the bacteria entering the amoeba within a membrane compartment called a vesicle, where they are broken down into small molecules by enzymes. The cells can also take up fluids and dissolved molecules using a similar process called macropinocytosis. With its short and relatively simple lifestyle, Dictyostelium is often used in research to study phagocytosis,",380,128,0.3368
dialogsum,"#Person1#: Honey, can you set the table? #Person2#: Um, sure. What are we having for dinner? Do I need to put out anything in particular? #Person1#: Well, make sure to put out the pepper and salt shakers. I don't know if your brother is coming tonight so set an extra place mat just in case. #Person2#: Ok, should I use the fancy silverware? #Person1#: Yeah go ahead, forks, spoons and knives. I roasted some meat so be sure to put out some steak knives as well. #Person2#: I'll also set some cups and saucers for some coffee after dinner. #Person1#: Honey? Have you seen our soup bowls? #Person2#: They are in the cupboard where you keep the gravy boat and serving dishes. Just be careful because the wine glasses are also there. #Person1#: Oops!",#Person1# asks #Person2# to set a table and tableware for dinner and reminds #Person2# to set an extra place for #Person2#'s brother.,134,22,0.1642
pubmed-summarization,"joseph disease , is the most common subtype of sca world - wide , and is caused by a pathologic cag trinucleotide repeat expansion in the atxn3 gene located on chromosome 14q32.12 . the cardinal clinical characteristics of sca3 include gait and stance unsteadiness , limb ataxia , dysarthria , oculomotor dysfunction , sensory disorder , pyramidal and extrapyramidal dysfunction , and so on . sca3 is a slowly progressive and unremitting disease , in which patients generally will become wheelchair - bound and bedridden in the end stage , and the median survival time after disease onset is approximately 21 years . the resulting loss of working ability and reduced survival confer significant disease burden to the patients , their families , and the society . thus , it is of vital importance to explore effective therapeutic options in order to alleviate the symptoms or retard the disease progression in sca3 . nerve growth factor ( ngf ) is the founding member of the neurotrophin family , and is essential for the proper development , patterning , and maintenance of the mammalian nervous system . previous studies have revealed that ngf specifically targets sensory and sympathetic neurons in the peripheral nervous system , as well as basal forebrain cholinergic neurons in the central nervous system . there is also growing evidence to support the role of ngf in the development , differentiation , and maintenance of the human cerebellar connectivity . in this context , ngf and its high - affinity receptor tachykinin receptor antagonist ( tkra ) these data imply that ngf may have neuroprotective effects on cerebellar neurons and hence might serve as a therapeutic candidate of sca3 . therefore , this clinical pilot study was set forth to examine the efficacy of ngf in patients with sca3 . this study was an open - label clinical trial assessing the efficacy of ngf in patients with sca3 ; it was conducted at the first affiliated hospital of zhengzhou university from november 2011 to november 2012 . this study was approved by the ethics committee of first affiliated hospital of zhengzhou university and registered at the chinese clinical trial registry ( www.chictr.org ; chictr - onc-11001954 ) . all study procedures were in accordance with the declaration of","background : spinocerebellar ataxia type 3 ( sca3 ) is the most common subtype of sca worldwide , and runs a slowly progressive and unremitting disease course . there is currently no curable treatment available . growing evidence has suggested that nerve growth factor ( ngf ) may have therapeutic effects in neurodegenerative diseases , and possibly also in sca3 . the objective of this study was to test the efficacy of ngf in sca3 patients.methods:we performed an open - label prospective study in genetically confirmed adult ( > 18 years old ) sca3 patients . ngf was administered by intramuscular injection ( 18 g once daily ) for 28 days consecutively . all the patients were evaluated at baseline and 2 and 4 weeks after treatment using",380,128,0.3368
dialogsum,"#Person1#: Can I help you, madam? #Person2#: Yes. I'd like to choose a sweater for my son. #Person1#: I see. Do you have any ideas so far? #Person2#: Not yet. Can you give me some suggestions? #Person1#: Sure, madam. But may l know how old he is? #Person2#: Thirteen. #Person1#: And the height? #Person2#: About 158cm. He likes to wear loose-fitting sweaters. #Person1#: I see. How about this one? It's very fashionable and popular among teenagers. #Person2#: I don't think he'll like it. He prefers simple styles. #Person1#: How about this one then? #Person2#: The style is all right, but I'm not sure about the color. Let me think for a while.",#Person2# wants to buy a sweater for her son. #Person1# asks #Person2# her son's age and height and gives some suggestions.,112,21,0.1875
pubmed-summarization,"the social background and cultural implications of the case of forced migration in the neuroscience field ( cf . an earlier process - oriented perspective developed in the 1990s by a group of scholars at the berliner wissenschaftskolleg has opened promising paths for the study of [ the ] intellectual and cultural change occurring through the forced migration of european scientific migrs ( ash & soellner , 1996 , pp . a number of american and german historians and philosophers of science ( fischer , 1996 ) have provided useful models through their scholarship on emigration - induced scientific change . these included the relevant social accounts of the historical developments , social reception , and reintegration of german - speaking migr scientists . as such , refugee - neuroscientists , like all their compatriots in exile , found themselves in the foreign environment of north america , where they had to continue their daily life , support their partners and families , become relicensed and obtain professional acceptance . they had to learn the social and cultural codes , psychological mentality , and likewise soft working skills 187197 ) when being barred from clinical work , having to close labs in order to pursue better paid jobs for their subsistence , or changing their personal research interests so as to fit more closely with the acceptable clinical and scientific paradigms of the often hands - on , capitalist , and technophile north american society . many of the migr neuroscientists , just to name the neuropathologist karl stern ( 19061975 ) , and his colleagues from the former group of kurt goldstein ( 18781965 ) , adhmar gelb ( 18871936 ) , victor franz ( 18831950 ) , and walther riese ( 18901976 ) in frankfurt am main , were influenced by interpretations of holistic neurology and the experimental culture of the weimar period , which they at first sought to continue in their american exile ( stahnisch & pow , 2015 ) . what emanates as the central problem for migr neuroscientists such as stern and goldstein , was not only personal acculturation but also the readjustment of their research and clinical activities . they had to search for new work places and integration into the preexisting canadian","abstractthis article is a historiographical exploration of the special forms of knowledge generation and knowledge transmission that occur along local cultural boundaries in the modern neurosciences . following the inauguration of the so - called law on the re - establishment of a professional civil service in nazi germany on april 7 , 1933 , hundreds of jewish and oppositional neurologists , neuropathologists , and psychiatrists were forced out of their academic positions , having to leave their home countries and local knowledge economies and traditions for canada and the united states . a closer analysis of their living and working conditions will create an understanding of some of the elements and factors that determined the international forced migration waves of physicians and clinical neuroscientists in the twentieth",380,128,0.3368
dialogsum,"#Person1#: Good morning. Are you ready to order? #Person2#: Yes, I am, thank you. I'll have three scrambled eggs with country ham, toast and jam, please. #Person1#: Would you like anything to drink? #Person2#: I'll have a tomato juice and some iced tea. #Person1#: Anything else? #Person2#: Could I have a slice of pumpkin pie? #Person1#: Sure. Coming right up.",#Person1# helps #Person2# order food and drinks.,60,7,0.1167
pubmed-summarization,"surrounding muscle , fat tissue , and intervertebral discs were completely removed from the vertebrae . each vertebra was embedded in resin ( rencast isocyanat and polyol , huntsman group , bad sckingen , germany ) up to 2 mm above and below their vertebral endplates for the purpose of biomechanical testing . the resin fixation was performed with parallel alignment of the upper and lower endplate of the vertebrae with the outer surface of the resin chock to guarantee strict axial loading conditions of the vertebrae during the uniaxial biomechanical test . for the purpose of conservation , all vertebrae were stored in the freezer at 4 celsius during the study and degassed in sodium chloride solution at least 3 h before imaging to prevent air artifacts . the vertebrae were sealed in vacuum plastic boxes filled with sodium chloride solution during imaging . multidetector computed tomography ( mdct ) images of the vertebrae were acquired by using a whole - body 256-row ct scanner ( ict , philips medical care , best , netherlands ) . scan parameters were a tube voltage of 120 kvp , a tube load of 585 mas , an image matrix of 1024 1024 pixels , and a field of view of 150 mm . the real spatial resolution was 230 230 600 m as determined at 50 of the modulation - transfer - function . a dedicated calibration phantom ( mindways osteoporosis phantom , san francisco , ca , usa ) was placed in the scanner mat beneath the vertebrae . mdct images were transferred to a remote linux workstation and loaded into an in - house developed program based on idl ( interactive data language , research systems , boulder , co , usa ) . then , transverse cross - sectional area was determined in each section to obtain the mean and minimum transverse cross - sectional area of each vertebra . second , the twenty most central slices displaying the vertebra equidistant to its endplates were identified ( (a ) ) . similar to the mrs box ( as outlined below ) , rectangular regions of interest ( rois ) with an area of 12 12 mm were manually placed in the center of the vertebra in the selected","bone marrow adiposity has recently gained attention due to its association with bone loss pathophysiology . in this study , ten vertebrae were harvested from fresh human cadavers . trabecular bmd and microstructure parameters were extracted from mdct . bone marrow fat fractions were determined using single - voxel mrs . failure load ( fl ) values were assessed by destructive biomechanical testing . significant correlations ( p < 0.05 ) were observed between mrs - based fat fraction and mdct - based parameters ( up to r = 0.72 ) and mrs - based fat fraction and fl ( r = 0.77 ) . these findings underline the importance of the bone marrow in the pathophysiology and imaging diagnostics of osteoporosis .",380,123,0.3237
scientific_lay_summarisation-elife-norm,"Foxp2, a forkhead transcription factor implicated in the development and function of neurons and required in the motor coordinating centers of the brain for the appropriate production of speech (French and Fisher, 2014). We find this embryonic parcellation interestingly persists into postnatal stages where Dbx1-derived and Foxp2+ MeA neurons are separate, non-overlapping inhibitory output neuronal subpopulations. Strikingly, both subpopulations are activated during specific innate behaviors in a sex-specific manner. Thus, our findings link developmental patterning to innate behavioral processing and further provide an embryonic developmental framework for how these behaviors may emerge. Our previous work along with the work of others revealed that the telencephalic-diencephalic border is a major source of neurons that will populate the MeA (Zhao et al. , 2008; Hirata et al. , 2009; Soma et al. , 2009; García-Moreno et al. , 2010). Our previous studies (Hirata et al. , 2009) revealed that the preoptic area (POA), which lies on the telencephalic side of this border (Flames et al. , 2007), is a source of Dbx1+ progenitors fated to generate a subpopulation of MeA inhibitory output neurons. Our previous studies further revealed that progenitors arising from ventral telencephalic Shh+ and Nkx2. 1+ domains also contributed to diverse neuronal subpopulations of the MeA (Carney et al. , 2010). Thus, while a molecular map of MeA embryonic niche diversity is beginning to emerge, the diversity of mature neurons derived from this niche and whether there is a link between embryonic identity, mature identity and function remains unknown. Moreover, as these previously identified subpopulations only generate a subset of MeA neurons, we reasoned that there must be other transcription factor marked progenitor populations within the telencephalic-diencephalic niche. Here, in addition to Dbx1+ progenitors, we observed a progenitor population comprised of Foxp2+ cells, residing primarily in the putative subventricular zone (SVZ) of the POA (1a–f, s). Interestingly, during embryogenesis, Dbx1-derived and Foxp2+ progenitor populations were non-overlapping (1a–l). Both populations were also generally distinct from OTP+ progenitors (— 1a–i), a population previously shown to define a subset of MeA-fated progenitors (García-Moreno et al. , 2010). We next investigated whether Foxp2+ progenitors overlapped with ventral telencephalic populations derived from Shh or Nkx6. 2 lineages, which also encompass the POA (Carney et al. , 2010; Fogarty et al. , 2007). We found embryonic","Within the brain, a set of interconnected structures called the limbic system is involved in emotion, motivation and memory. This system – and in particular a structure called the medial amygdala – also contributes to behavioral drives that help an animal to survive and reproduce. These include the drive to avoid predators, to defend territory, and to find a mate. Such behaviors are thought to be inborn or innate. This means that animals display them instinctively whenever specific triggers are present, without the need to learn them beforehand. However, just as a computer must be programmed to perform specific tasks, these innate behavioral responses must also be programmed into the brain. Given that animals do not learn these behaviors, Lischinsky et al. reasoned that specific events during the",380,128,0.3368
dialogsum,"#Person1#: Excuse me, can you tell me the way to Holton railway station? #Person2#: Sure. It's quite far from here. Don't worry, though. It's not difficult to get there. #Person1#: I think I'm going in the wrong direction, aren't? #Person2#: Yes. First, you need to turn around. Do you remember passing some traffic lights further up this road? #Person1#: Yes, I do. They are about two miles away, right? #Person2#: That's right. Drive back to the traffic rights and turn right. Follow the road for about a mile, until you see the plaza hotel. It's a really big hotel. You can't miss it. Turn left at the hotel. #Person1#: So, right at the traffic lights two miles up the road, then left at the plaza hotel, a mile along that road. Got it. #Person2#: Then you just go straight on until you see the station ahead of you. #Person1#: Ok. Got it. Thanks for you help. #Person2#: No problem.",#Person2# tells #Person1# how to drive to Holton railway station.,159,10,0.0629
dialogsum,"#Person1#: Here is the document you asked for this morning. #Person2#: Oh, you are so efficient. I thought you might give it to me tomorrow. Thanks. #Person1#: You're welcome. You know, these days I have been reflecting on my biggest weakness procrastination. The more I think about it, the more I hate myself for being so disorganized. I decided to change the situation as soon as possible. Otherwise I will be more regretful later. #Person2#: This is encouraging news, good for you! What is your solution, then? #Person1#: The most useful method is to make plans and set priorities. It helps me to manage time well and get the most important things done at the first place. #Person2#: Sounds not bad! Better performance isn't just about doing a lot more. It is about focusing on the right things to do.",#Person1# wants to get rid of procrastination and decides to make plans and set priorities. #Person2# thinks it's good for #Person1#.,140,21,0.15
scientific_lay_summarisation-elife-norm,"purpose is the application of a rationally designed light-sensitive domain that can allosterically control protein activity. This protein engineering approach offers several important advantages. It enables targeted regulation of one domain within a multidomain protein (Karginov et al. , 2010). Regulation is achieved ‘remotely’ without steric interference with the catalytic pocket of the enzyme and substrate binding. Also, allosteric switch domains are genetically encoded into the targeted protein simplifying the application of the tool. Only four optogenetic methods for allosteric regulation of activity have been reported so far and they suffer from critical limitations (Dagliyan et al. , 2016; Wu et al. , 2009; Hongdusit et al. , 2020; Winkler et al. , 2015; Reynolds et al. , 2011). Two of these strategies achieve subcellular control of certain targeted proteins but they cannot be applied to many other enzymes due to their design (Wu et al. , 2009; Hongdusit et al. , 2020). One approach is broadly applicable but it does not achieve local control and triggers inactivation rather than activation of the protein (Dagliyan et al. , 2016). A similar approach described by Reynolds et al achieves regulation in both directions for dihydrofolate reductase (DHFR) and PDZ domain but efficiency of this approach for applications in mammalian cells and its ability to regulate proteins at subcellular level has not been demonstrated (Reynolds et al. , 2011). Furthermore, existing allosteric switches lack the ability to tune the activation/inactivation kinetics, an important feature required for mimicking different temporal signaling modes of enzymes. Among the various potential targets of value for cell biology applications, protein kinases constitute an important family of enzymes that regulate key physiological functions and thus their activity is tightly controlled. Aberrant kinase regulation is the underpinning of many diseases, including the development and progression of malignant tumors (Lee and Yaffe, 2016). Many kinases are therefore important therapeutic targets and significant research effort is directed towards uncovering their function in cells. Such functional studies are challenging because a single kinase often induces drastically different responses depending on the location, level and timing of its activation (Marshall, 1995; Rauch et al. , 2016; Cohen-Saidon et al. , 2009; Bugaj et al. , 2018; Toettcher et al. , 2013). Furthermore, transient, sustained, or oscillatory kinase activation can result in distinct outcomes.","Cells need to sense and respond to their environment. To do this, they have dedicated proteins that interpret outside signals and convert them into appropriate responses that are only active at a specific time and location within the cell. However, in many diseases, including cancer, these signaling proteins are switched on for too long or are active in the wrong place. To better understand why this is the case, researchers manipulate proteins to identify the processes they regulate. One way to do this is to engineer proteins so that they can be controlled by light, turning them either on or off. Ideally, a light-controlled tool can activate proteins at defined times, control proteins in specific locations within the cell and regulate any protein of interest. However, current methods",380,128,0.3368
scientific_lay_summarisation-elife-norm,"common catalytic module but is regulated by distinct signaling inputs. SOS activity is enhanced by Ras•GTP, generated by RasGRP1, binding to an allosteric site. The regulatory domains from each exchange factor are distinct and are represented in gray. SOS is recruited to the membrane in part by Grb2, which interacts with phosphotyrosine residues in the adapter LAT. (B) The catalytic core of RasGRP1 includes the REM and Cdc25 domains, which are followed by a regulatory module containing the EF domain, membrane binding C1 domain and a predicted coiled coil. An alternate translational start site is present that leads to a RasGRP1 protein without the first 49 residues. The constructs used in this study are shown. : http: //dx. . org/10. 7554/eLife. 00813. 00310. 7554/eLife. 00813. 004Figure 1— 1. Domain architecture of RasGRP1 and SOS. RasGRP1 and SOS contain similar catalytic modules (REM + Cdc25 domains), but differ in the flanking regulatory domains. : http: //dx. . org/10. 7554/eLife. 00813. 004 There are three major families of Ras-specific nucleotide exchange factors in humans. The RasGRP and Ras guanine nucleotide releasing factor (RasGRF) families of exchange factors have tissue-specific expression patterns whereas SOS proteins are expressed ubiquitously (Stone, 2011). RasGRP proteins have been studied most extensively in T and B lymphocytes (Aiba et al. , 2004; Brodie et al. , 2004; Coughlin et al. , 2005; Roose et al. , 2005; Limnander et al. , 2011) where they activate Ras in a manner that is non-redundant with SOS (Dower et al. , 2000; Roose et al. , 2007). In addition, RasGRP proteins play important roles in squamous cell carcinoma and melanoma (Luke et al. , 2007; Oki-Idouchi and Lorenzo, 2007; Diez et al. , 2009; Yang et al. , 2011), T cell- and myeloid- leukemia (Reuther et al. , 2002; Yang et al. , 2002; Klinger et al. , 2005; Lauchle et al. , 2009; Oki et al. , 2012; Hartzell et al. , 2013) and prostate cancer (Yang et al. , 2010) that are distinct from those of SOS. Developing T lymphocytes pass through quality control checkpoints to generate a repertoire of protective but self-tolerant immune cells (Starr et al. , 2003) and Ras signaling plays a critical role in this progression (Swan et al. , 1995). In response to T","Individual cells within the human body must grow, divide or specialize to perform the tasks required of them. The fates of these cells are often directed by proteins in the Ras family, which detect signals from elsewhere in the body and orchestrate responses within each cell. The activities of these proteins must be tightly controlled, because cancers and developmental diseases can result if Ras proteins are not properly regulated. Binding to the small molecule GTP activates Ras and causes conformational changes that allow it to interact with other proteins in various signaling pathways in the cell. GTP is loaded into Ras by proteins called nucleotide exchange factors, which can replace ‘used’ nucleotides with ‘fresh’ ones to activate Ras. These nucleotide exchange factors are also tightly regulated. For example,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"ISWI family chromatin remodelers typically organize nucleosome arrays, while SWI/SNF family remodelers (RSC) typically disorganize and eject nucleosomes, implying an antagonism that is largely unexplored in vivo. Here, we describe two independent genetic screens for rsc suppressors that yielded mutations in the promoter-focused ISW1a complex or mutations in the ‘basic patch’ of histone H4 (an epitope that regulates ISWI activity), strongly supporting RSC-ISW1a antagonism in vivo. RSC and ISW1a largely co-localize, and genomic nucleosome studies using rsc isw1 mutant combinations revealed opposing functions: promoters classified with a nucleosome-deficient region (NDR) gain nucleosome occupancy in rsc mutants, but this gain is attenuated in rsc isw1 double mutants. Furthermore, promoters lacking NDRs have the highest occupancy of both remodelers, consistent with regulation by nucleosome occupancy, and decreased transcription in rsc mutants. Taken together, we provide the first genetic and genomic evidence for RSC-ISW1a antagonism and reveal different mechanisms at two different promoter architectures. Genomic DNA is packaged into chromatin, a dynamic material that exhibits numerous changes in post-translational modifications, composition, and protein interactions. One aspect of chromatin modulation involves the assembly or disassembly of chromatin through active remodeling, which can confer either occlusion or access to the DNA—a process that is associated with virtually all DNA-mediated transactions, including transcription, replication, and repair. Each remodeling action, either assembly or disassembly, is mediated (in part) by specialized ATP-dependent chromatin-remodeling complexes (Vignali et al. , 2000; Clapier and Cairns, 2009; Narlikar et al. , 2013; Bartholomew, 2014). Certain chromatin remodelers align with these two general categories: those that restrict DNA access by chromatin assembly and organization and those that promote DNA access by chromatin disassembly and disorganization. This broad separation in function can be partially illustrated by studies of individual chromatin remodelers and their effects on gene expression (Angus-Hill et al. , 2001; Fazzio et al. , 2001; Vary et al. , 2003); in general, remodelers associated with chromatin disassembly promote DNA access and gene expression, while remodelers associated with chromatin organization more often repress gene expression, though there are exceptions to this simplified view (e. g. , increased accessibility can promote repressor access to chromatin). The SWI/SNF family of chromatin remodelers provides a well-studied example of remodelers associated with nucleosome disorganization and/or disassembly. In yeast, the RSC chromatin-remodeling complex is an essential and abundant","The genome of an organism can contain hundreds to thousands of genes. However, these genes are not all active at the same time. Instead, mechanisms exist that control when genes are switched off or on. One such mechanism alters how tightly DNA is packaged into a structure called chromatin. To form chromatin, DNA is wrapped around histone proteins at different points along its length; these structures are known as nucleosomes. Once formed, chromatin can either adopt a tightly packed form that represses gene activity or a less compact form associated with gene activation. The proteins that control how chromatin is packed are called ‘chromatin remodelers’. These proteins work in complexes that either disassemble chromatin—for example, by repositioning nucleosomes or removing histones—or organize chromatin by replacing nucleosomes and making",380,128,0.3368
pubmed-summarization,"to limit generalized immune activation commonly seen during advanced hiv disease.(26 ) we now demonstrate a multifaceted role for treg for hiv-1-infected mp . such a role serves a range of regulatory functions acting to control disease such as suppression of viremia and modulation of hiv-1-infected macrophage neurotoxic activities . in support of such claims , we used isobaric tag for relative and absolute quantitation ( itraq ) of proteins to identify differential protein expression between hiv-1-infected bone marrow - derived macrophages ( bmm ) with and without treg . we found changes consistent with enhanced antiretroviral immunity through treg - induced upregulation of interferon ( ifn)-induced gene products . this was seen among a broad range of related protein expression changes linked to antiviral responses . second , we showed that treg utilizes caspase-3 and granzyme / perforin pathways to kill virus - infected cells . third , treg reduced neurotoxic secretions in vitro through its abilities to transform hiv-1-infected macrophages from an m1 to an m2 phenotype . these observations made in murine treg - bmm cocultures were replicated separately in human treg - monocyte - derived macrophages ( mdm ) cocultures . taken together , these data demonstrate that treg serve as effectors for virus - infected macrophages and suppressors for inflammation and as such , exert immune surveillance functions relevant to ongoing hiv infection and neuroaids . c57bl/6j male mice ( 810 wk old ) were purchased from the jackson laboratory and used for bmm and t cell isolations . all animal procedures were in accordance with the national institutes of health guidelines and were approved by the institutional animal care and use committee of the university of nebraska medical center . femurs of the mice were excised and flushed with dulbecco s phosphate buffered saline ( dpbs ) to obtain bone marrow - derived mononuclear cells . cells were passed through a 40 m cell strainer to remove the clumps and then centrifuged . erythrocytes were removed using ack lysis buffer ( gibco , grand island , ny ) . after washing twice with dbps , cells were resuspended and plated in 6-well plates at 1 10 cells / ml in 3 ml complete medium [ rpmi 1640 supplemented with 10% fetal bovine serum (","regulatory t cells ( treg ) induce robust neuroprotection in murine models of neuroaids , in part , through eliciting anti - inflammatory responses for hiv-1-infected brain mononuclear phagocytes ( mp ; macrophage and microglia ) . herein , using both murine and human primary cell cultures in proteomic and cell biologic tests , we report that treg promotes such neuroprotection by an even broader range of mechanisms than previously seen including inhibition of virus release , killing infected mp , and inducing phenotypic cell switches . changes in individual treg - induced macrophage proteins were quantified by itraq labeling followed by mass spectrometry identifications . reduction in virus release paralleled the upregulation of interferon - stimulated gene 15 , an ubiquitin - like protein involved in interferon",380,128,0.3368
dialogsum,"#Person1#: How is grandpa doing recently? #Person2#: Not good. The doctor told him not to smoke again, but it just rolls off him like water off the duck's back! #Person1#: Maybe I would talk with him someday. #Person2#: I hope it will be of some use.",#Person2# tells #Person1# #Person1#'s grandpa isn't good because he can't quit smoking.,46,12,0.2609
dialogsum,"#Person1#: Is there anything I can do for you? #Person2#: Yes. I am looking for a pair of gloves. #Person1#: What about this one? It's the latest. #Person2#: Excuse me, but I want a pair of mittens. #Person1#: I am sorry, it's out of stock right now.","#Person1# wants to buy mittens, but #Person2# says they are out of stock.",47,13,0.2766
dialogsum,"#Person1#: Hello, Mike. I hear you were doing some part time work. #Person2#: Yes, I am working 4 nights a week at a restaurant. #Person1#: What are you doing there? #Person2#: Doing some dishwashing in dusting tables. #Person1#: Do they give you decent wages. #Person2#: Not too bad. #Person1#: Well, I've been accepted for a part time job in a library. I will be working there only on weekends. #Person2#: Really? That's good. So you'll be earning some extra money, too. #Person1#: Yeah, I don't want to ask my parents for spending money anymore. Well, may I ask a personal question? #Person2#: It depends. What do you want to know. #Person1#: What do you do with the money you earn? #Person2#: Well, I spend some of it on books and movies, and I also save some for short trips. #Person1#: Good idea. What I want to get is a sports bicycle.",Mike tells #Person1# that he is doing some dishwashing in dusting tables as a part-time job because he doesn't want to ask his parents for money anymore.,151,27,0.1788
pubmed-summarization,"hemicrania continua ( hc ) is an uncommon primary headache disorder characterized by a continuous , mild to moderate intensity , unilateral headache . most patients will experience superimposed exacerbations of more severe pain , often associated with ipsilateral autonomic symptoms . headache for greater than 3 months fulfilling the following criteria : all of the following : unilateral pain without side shift , daily and continuous , without pain - free periods , moderate intensity , but with exacerbations of severe pain.at least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain : conjunctival injection and/or lacrimation , nasal congestion and/or rhinorrhea , ptosis and/or miosis.a complete response to therapeutic doses of indomethacin.finally , not attributed to another disorder . unilateral pain without side shift , daily and continuous , without pain - free periods , moderate intensity , but with exacerbations of severe pain . at least one of the following autonomic features occurs during exacerbations and ipsilateral to the side of pain : conjunctival injection and/or lacrimation , nasal congestion and/or rhinorrhea , ptosis and/or miosis . a complete response to therapeutic doses of indomethacin . finally , not attributed to another disorder . there is a group of patients that meets the above criteria for hc , but has to discontinue indomethacin secondary to adverse effects , primarily involving the gastrointestinal ( gi ) tract . the side effects can range from gastritis to severe bleeding , patients may also develop an allergy to indomethacin , see an elevation of blood pressure , or an exacerbation of asthma symptoms . gabapentin is often used in an off label fashion for the treatment of neuropathic pain and is well tolerated from a side effect profile . marinano da silva , alcantara , bordini , and speciali reported a case of a unilateral headache similar to hc that was responsive to gabapentin . institutional review board approval was obtained for the study . a retrospective chart review of nine patients with hc between october 2006 and february 1 , 2008 . inclusion criteria included men and women age 18 or above presenting to the headache center with a headache that meets ihs criteria for hc , including a response to indomethacin","the objective of this study is to examine the efficacy of gabapentin for the treatment of hemicrania continua ( hc ) in cases where patients had difficulty tolerating indomethacin due to adverse effects . a retrospective chart review of nine patients with hc between october 2006 and february 2008 . inclusion criteria included men and women age 18 or above presenting to the headache center with a headache that meets international headache society criteria for hc including a response to indomethacin , but were not able to continue on indomethacin secondary to adverse effects . four patients report being pain free , three patients report a 5080% reduction of pain , one patient reports a 10% reduction of pain , and one patient reports no change in pain",380,128,0.3368
pubmed-summarization,"according to the definition of world health organization ( who ) , quality of life ( qol ) is the individual 's perception of his / her position in life in the context of the culture , value systems in which he / she lives , and in relation to his / her goals , expectations , standards and concerns . studies have identically shown that patients with multiple sclerosis ( ms ) experience lower qol compared to healthy control group . in addition to the chronic nature of the disease , lack of prognosis and a definitive therapy besides suffering from it from early adulthood causes several psychological symptoms among which depression , anxiety , and stress are the most common . in recent years , there has been an increase in the number of studies on the relationship between these factors and qol in ms . overall , these studies have demonstrated significant relationship between fatigue and psychological symptoms with qol dimensions . in these studies , low qol has been predicted by fatigue and psychological symptoms , especially depression and anxiety . there is skepticism about the relative importance of these predictors , especially fatigue and depression , as with regard to qol of ms patients , some researches in which fatigue and depression were studied simultaneously have proved fatigue to be the more powerful predictor and some others have proved depression to be the stronger variable , while anxiety has been relevant only in some qol studies and in others it has not emerged as a significant predictor of qol . moreover , there is a shortcoming in the studies of stress in relation to qol of ms patients . for example , researchers have focused more on the effects of stress on exacerbations and relapses , new brain magnetic resonance imaging ( mri ) lesions , inflammation , radiological disease activity , and depressive symptoms of ms patients and mainly are marginalized the role of stress in reducing the physical and psychological aspects of patients qol . but in a cross - sectional investigation , we have demonstrated that qol has a negative correlation with all three symptoms of depression , anxiety , and stress ( sequenced based on the degree of significance ) .","background : although studies have demonstrated significant negative relationships between quality of life ( qol ) , fatigue , and the most common psychological symptoms ( depression , anxiety , stress ) , the main ambiguity of previous studies on qol is in the relative importance of these predictors . also , there is lack of adequate knowledge about the actual contribution of each of them in the prediction of qol dimensions . thus , the main objective of this study is to assess the role of fatigue , depression , anxiety , and stress in relation to qol of multiple sclerosis ( ms ) patients.materials and methods : one hundred and sixty - two ms patients completed the questionnaire on demographic variables , and then they were",380,128,0.3368
scientific_lay_summarisation-elife-norm,"not methylated (Ahmed et al. , 2011) and only 68% are associated with small RNAs (Hollister et al. , 2011). Thus the epigenetic modification status of TEs can be variable within the species, between different classes of elements, or even among elements of the same family. The potential role of TEs in establishing or maintaining imprinted expression coupled with the evolutionary forces that select for parent-of-origin specific expression suggest that substantial intraspecific variation in imprinting could exist. Indeed, the first imprinted gene described, the maize R gene (Kermicle, 1970), is an example of allele-specific imprinting; only alleles that have a Doppia TE inserted in the promoter are imprinted (Kermicle, 1978; Walker, 1998; Alleman and Doctor, 2000). Once imprinted gene expression arises, the kinship or parental conflict theory of imprinting (Haig, 2013) posits that it could be evolutionarily selected because asymmetrically related kin (e. g. , half-siblings that have the same mother but different fathers) compete for maternal resources. Thus, maternally and paternally inherited alleles of genes that influence maternal resource transfer to offspring have different optima for total gene expression levels. Plants adopt a range of different strategies with regards to maternal resource transfer to offspring—producing a few large seeds, or many small seeds. Intraspecific variation in this trait could potentially be linked to differences in the set of genes subject to imprinting in each strain. To systematically evaluate whether gene imprinting varies on short evolutionary time scales and to further understand the role of genetic and epigenetic polymorphisms in this process, we have investigated the conservation and variability of imprinting, DNA methylation, and small RNA production in reciprocal crosses among three strains of Arabidopsis. Arabidopsis is an ideal system in which to ask these questions because of the availability of genotyped and epigenotyped strains that have diverged for only a few thousand years. Here we discovered 12 examples of allele-specific imprinting, about half of which were associated with endosperm demethylation of a TE that was variably methylated within the strains we examined. We further evaluated intraspecific methylation variability at regions targeted for CG DNA demethylation during female reproductive development for 140 strains where vegetative methylation patterns are known (Schmitz et al. , 2013). Approximately 11% of imprinted genes are associated with an endosperm DMR that is variably methylated among","When animals or plants reproduce sexually, the DNA in a sperm or pollen is combined with that in an egg cell to generate an offspring that inherits two copies of each gene, one from each parent. For a very small number of genes, the copy from one of the parents is consistently turned off. This process—called imprinting—means that the same gene can have different effects depending on if it is inherited from the mother or the father. In plants, imprinting is vital for the production of seeds and typically occurs in the endosperm: the tissue within a seed that provides nourishment to the plant embryo. One way genes can be imprinted is by adding small chemical marks—called methyl groups—on to the DNA that makes up the gene or",380,128,0.3368
scientific_lay_summarisation-elife-norm,"used an established and biophysically plausible model of a decision making network that employs competition between neural populations to choose between two alternate response options. Rather than simulating discrete trials and reinitializing the network state at the start of each trial, we sought to emulate the serial dependency between real world choices. We therefore ran the network in continuous blocks of trials, with the final state at the end of each trial serving as the initial state of the next trial (Rustichini and Padoa-Schioppa, 2015). We confirmed that this produced choice hysteresis in the model behavior, through decaying trace activity from the previous trial biasing selection in the current trial, but only for short inter-stimulus intervals. We then conducted an analogous experiment with human participants and found a similar tendency to repeat previous choices. The model contains variables and parameters with well‐defined anatomical and physiological substrates (Rustichini and Padoa-Schioppa, 2015; Bonaiuto and Arbib, 2014; Wang, 2008,2012,2002), allowing for explicit simulation and linkage with the known neurophysiological effects of stimulation. We found that perturbation of the model’s trace activity through simulated changes in the network’s membrane potential led to predictable alterations in choice bias. In human participants, we therefore applied transcranial direct current stimulation (tDCS) to left dorsolateral prefrontal cortex (dlPFC), a region implicated in perceptual decision making (Heekeren et al. , 2004; Kim and Shadlen, 1999; Heekeren et al. , 2006; Philiastides et al. , 2011; Rahnev et al. , 2016; Georgiev et al. , 2016). TDCS is thought to alter neuronal excitability and spontaneous firing rates in brain networks by polarizing membrane potentials in a network (Rahman et al. , 2013; Nitsche and Paulus, 2011; Bikson et al. , 2004), thus providing an analogous network perturbation to our simulations. Because tDCS leads to subthreshold polarization changes, we were able to subtly alter the spontaneous fluctuations in neural activity within the targeted brain region, noninvasively in our human participants (Nitsche and Paulus, 2011,2000; Kuo and Nitsche, 2012). We found that the predictions generated by the model were closely mirrored by the modulation of choice hysteresis in human participants through application of tDCS over dlPFC. We were thus able to directionally control choice biases in perceptual decision making through causal manipulation of the neural dynamics in dlPFC. The comparison with the","When making decisions, people and other animals tend to repeat previous choices even if this is no longer the best course of action. This tendency is especially common when the choice is difficult to make. For example, when people are asked to decide whether groups of dots on a television screen are moving mostly to the left or the right, they often repeat their previous choice when the direction of motion is not clear. Recordings of brain activity in animals suggest that once a choice is made, there is brain activity left over that influences the level of activity at the beginning of the following choice. If this leftover activity is stronger in the brain cells that represent the first choice, it might give this option a head",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Perfringolysin O (PFO) is a prototypical member of a large family of pore-forming proteins that undergo a significant reduction in height during the transition from the membrane-assembled prepore to the membrane-inserted pore. Here, we show that targeted application of compressive forces can catalyze this conformational change in individual PFO complexes trapped at the prepore stage, recapitulating this critical step of the spontaneous process. The free energy landscape determined from these measurements is in good agreement with that obtained from molecular dynamics simulations showing that an equivalent internal force is generated by the interaction of the exposed hydrophobic residues with the membrane. This hydrophobic force is transmitted across the entire structure to produce a compressive stress across a distant, otherwise stable domain, catalyzing its transition from an extended to compact conformation. Single molecule compression is likely to become an important tool to investigate conformational transitions in membrane proteins. The initial demonstration that single macromolecules could be mechanically stretched with exact knowledge of the associated forces (Smith et al. , 1992; Kellermayer et al. , 1997; Rief et al. , 1997; Tskhovrebova et al. , 1997) has enabled unprecedented access to measurements of the physical and chemical inter-molecular interactions (Bippes and Muller, 2011; Bustamante et al. , 2000; Fisher et al. , 2000; Hu and Li, 2014; Zhuang and Rief, 2003). Moreover, pulling on single molecules with tensile forces has enabled detailed probing of functional and structural transitions within proteins, in particular those that involve a separation of specific structural elements (Puchner and Gaub, 2012; Zhang et al. , 2009; del Rio et al. , 2009). Yet, tensile forces cannot be used to probe transitions that involve a decrease in the distance between structural elements such as the closing of a substrate access gate, for example, as the force acts in a direction opposite to the structural movement. In these instances, what is needed is the controlled application of a compressive force at the single molecule level. Perfringolysin O (PFO) is an intriguing pore-forming toxin that undergoes a significant reduction in the distance between two of its domains during pore formation (Gilbert, 2005; Hotze and Tweten, 2012). During the prepore-to-pore transition, the distance between the D1 and D4 domains is reduced as a result of conformational changes in the D2 domain ():","Proteins are made up of chains of amino acids that need to fold into intricate three-dimensional shapes to work correctly. But some proteins also have to change their shape drastically when they work. Mechanical forces that change the shape of a protein can therefore be used to determine how a protein folds and how it changes its structure when working. Although researchers have developed techniques to analyze the effect of force on single proteins, most studies carried out so far have investigated the effect of stretching (or tensile forces) to understand structural changes that naturally involve an extension within the protein. However, many proteins undergo structural changes that involve a compaction in their shape. How these changes occur remains poorly understood because, for these, methods to apply compressive",380,128,0.3368
dialogsum,"#Person1#: Have you seen Mr. Li? #Person2#: No, I haven't. Is he looking for me? #Person1#: Yes, he is. He wants to talk to you. #Person2#: To me? About what? #Person1#: There's an opening in the sales department. He wants to talk to you about it. #Person2#: Oh, that's great! What kind of this job is it? #Person1#: He hasn't told me exactly. But it will be a better job than this. #Person2#: Thank you for your help. #Person1#: Don't thank me yet! He hasn't talked to you and he hasn't chosen you for the job yet. #Person2#: I know.",#Person1# tells #Person2# Mr. Li is looking for #Person2# to talk about a new job.,100,15,0.15
dialogsum,"#Person1#: My stay is over. Here's the key to my room. #Person2#: Thank you. And here's your receipt, sir. #Person1#: Many thanks. #Person2#: I hope your stay here was satisfactory, sir. #Person1#: This could be a great hotel, once you get rid of the insects. The city itself is great. #Person2#: I'm glad that the little problem didn't ruin your visit. Please have a pleasant trip home.",#Person1#'s stay is over. He tells #Person2# this could be a great hotel once they get rid of the insects.,67,20,0.2985
scientific_lay_summarisation-elife-norm,"Exosomes are small vesicles that are secreted from metazoan cells and may convey selected membrane proteins and small RNAs to target cells for the control of cell migration, development and metastasis. To study the mechanisms of RNA packaging into exosomes, we devised a purification scheme based on the membrane marker CD63 to isolate a single exosome species secreted from HEK293T cells. Using immunoisolated CD63-containing exosomes we identified a set of miRNAs that are highly enriched with respect to their cellular levels. To explore the biochemical requirements for exosome biogenesis and RNA packaging, we devised a cell-free reaction that recapitulates the species-selective enclosure of miR-223 in isolated membranes supplemented with cytosol. We found that the RNA-binding protein Y-box protein I (YBX1) binds to and is required for the sorting of miR-223 in the cell-free reaction. Furthermore, YBX1 serves an important role in the secretion of miRNAs in exosomes by HEK293T cells. In contrast to the normal pathways of protein secretion, the processes by which unconventional cargoes are secreted have proved diverse and enigmatic. Indeed, our understanding of unconventional secretory mechanisms is limited to a few examples of leader-less soluble and transmembrane proteins (Malhotra, 2013). Unconventionally secreted molecules may be externalized in a soluble form by translocation across various membranes. This may include direct translocation across the plasma membrane, or across an organelle membrane followed by fusion of the organelle with the plasma membrane (Zhang and Schekman, 2013). Alternatively, proteins and RNAs can be secreted within vesicles that bud from the plasma membrane, as in the budding of enveloped viruses such as HIV, or within vesicles internalized into a multivesicular body (MVB) that fuses with the plasma membrane (Colombo et al. , 2014). RNA is actively secreted into the medium of cultured cells and can be found in all bodily fluids enclosed within vesicles or bound up in ribonucleoprotin complexes, both forms of which are resistant to exogenous ribonuclease (Colombo et al. , 2014; Arroyo et al. , 2011; Mitchell et al. , 2008). Importantly, extracellular vesicle-bound RNAs appear to be enriched in specific classes of RNAs, including small RNAs and microRNA (miRNA) (Skog et al. , 2008; Valadi et al. , 2007; Kosaka et al. , 2010). Exosomes are a subclass of extracellular vesicle which can be defined as 30–100 nm","Human cells release molecules into their surroundings via membrane-bound packets called exosomes. These molecules can then circulate throughout the body and are protected from degradation. Among the cargos carried by exosomes are small molecules of RNA known as microRNAs, which are involved in regulating gene activity. Only a select subset of the hundreds of microRNAs in a human cell end up packaged into exosomes. This suggests that there might be a specific mechanism that sorts those microRNAs that are destined for export. However, few proteins or other factors that might be involved in this sorting process had been identified to date. Shurtleff et al. set out to identify these factors and started by purifying exosomes from human cells grown in the laboratory and looking for microRNAs that were",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Genomic imprinting is an epigenetic phenomenon causing parent-of-origin specific differential expression of maternally and paternally inherited alleles. While many imprinted genes have been identified in plants, the functional roles of most of them are unknown. In this study, we systematically examine the functional requirement of paternally expressed imprinted genes (PEGs) during seed development in Arabidopsis thaliana. While none of the 15 analyzed peg mutants has qualitative or quantitative abnormalities of seed development, we identify three PEGs that establish postzygotic hybridization barriers in the endosperm, revealing that PEGs have a major role as speciation genes in plants. Our work reveals that a subset of PEGs maintains functional roles in the inbreeding plant Arabidopsis that become evident upon deregulated expression. Genomic imprinting is an epigenetic phenomenon occurring in mammals and flowering plants that leads to parent-of-origin specific differential expression of maternally and paternally inherited alleles (Gehring, 2013). Recent screening of the seed transcriptome in various plant species revealed dozens to several hundreds of novel candidate imprinted genes in maize, rice, castor bean, and Arabidopsis thaliana (Gehring et al. , 2011; Hsieh et al. , 2011; Luo et al. , 2011; Waters et al. , 2011; Wolff et al. , 2011; Pignatta et al. , 2014; Xu et al. , 2014). While few reports demonstrate genes to be temporally imprinted in the plant embryo (Jahnke and Scholten, 2009; Raissig et al. , 2013), the vast majority of imprinted genes has been observed in the endosperm, the ephemeral triploid tissue derived after fertilization of the diploid central cell with a haploid sperm cell. In most angiosperms the endosperm initially develops as a syncytium and cellularizes after a defined number of mitotic divisions (Li and Berger, 2012). The right timing of endosperm cellularization is crucial for proper seed development, its failure results in deficient nutrient supply, which causes embryo arrest and eventually seed abortion (Hehenberger et al. , 2012). In Arabidopsis, endosperm cellularization is regulated by, among others, the type I MADS-box transcription factor AGL62. Loss of AGL62 leads to precocious endosperm cellularization (Kang et al. , 2008), whereas increased AGL62 expression correlates with delayed or failed cellularization (Erilova et al. , 2009; Tiwari et al. , 2010). Similar effects on endosperm development have been observed in response to interploidy hybridizations. While maternal excess hybridizations","When plants and animals reproduce sexually, their offspring inherit two copies of every gene, one from each parent, which are arranged in two sets of structures called chromosomes. In some tissues, one gene copy may be switched off—through a process called ‘genomic imprinting’—while the other copy remains active. In plants, genomic imprinting is vital for seeds to develop normally. It is particularly important in the tissue that provides nutrients for the growing embryo (the endosperm), in which one of the copies of many genes are switched off. Genes inherited from the male parent that have been imprinted are known as paternally expressed imprinted genes (PEGs). Unlike most animals, it is common for plants to have more than two sets of chromosomes. When plants with different numbers of chromosome",380,128,0.3368
pubmed-summarization,"hyperplasia refers to tissue growth into the oral cavity , located over the alveolar ridges or the soft tissues of the vestibular sulcus . its etiology is multifactorial , but some irritative factors are more commonly associated , such as periodontal disease , poor oral hygiene , smoking , and poor denture fitting . the treatment of this kind of lesion includes elimination of the causing factors and surgical removal of the lesion . if the causal factor persists , the tissue becomes more fibrous over time . the most common techniques used for removing the hyperplastic lesion are surgical scalpel , electrical scalpel , carbon dioxide laser , erbium : yag laser , neodymium : yag laser , and diode laser . the co2 laser is an appropriate option for surgical procedures in soft tissues since it operates at a wavelength of 10.6 n , which is within the medium range of the electromagnetic infrared spectrum . this wavelength is absorbed by tissues with high water content . this energy is transformed into heat , causing cell rupture from water boiling ; therefore , tissues with high water content suffer less damage . many advantages of the co2 laser include the possibility of minimal bleeding , decreasing edemas , flexibility of the wound healing tissue , reduced postoperative pain , and no need of a conventional suture . these positive aspects of the use of a co2 laser has allowed an improvement in maxillofacial surgeries . despite some disadvantages of co2 laser , such as the delay in the initial repair chronology due to heat necrosis , this technique provides suitable repair without scar formation and constitutes an alternative to the conventional incision and suture method . a sixty - three - year caucasian old female presented at the dental clinic of the university ( so jose dos campos dental school unesp ) looking for dental treatment . the clinical exam showed completely edentulous and presented a hyperplastic lesion over the alveolar ridge extending to the vestibular sulcus in the lower anterior region ( figures 1 and 2 ) . according to the patient , two previous surgeries were performed to remove the excess of mucosa , but it relapsed twice . this lesion could impair the retention and","the aim of this study was to present a case report of the surgical removal of hyperplasia in the oral cavity , using carbon dioxide ( co2 ) laser radiation and rehabilitation with a complete denture . epulis fissuratum occurs in complete denture patients , because a constant irritative action induces the mucosa to grow under poorly fitting dentures . these lesions must be removed , and to avoid a relapse , new complete dentures should be made to maintain healthy surgical tissues . the clinical sequence presented in this case shows a completely edentulous patient with epulis fissuratum on the lower alveolar ridge extending to the vestibular sulcus of the anterior region of mandible . immediate complete dentures were made prior to the lesion removal with co2",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Glycogen synthase kinase-3 (GSK-3) is a key regulator of many cellular signaling pathways. Unlike most kinases, GSK-3 is controlled by inhibition rather than by specific activation. In the insulin and several other signaling pathways, phosphorylation of a serine present in a conserved sequence near the amino terminus of GSK-3 generates an auto-inhibitory peptide. In contrast, Wnt/β-catenin signal transduction requires phosphorylation of Ser/Pro rich sequences present in the Wnt co-receptors LRP5/6, and these motifs inhibit GSK-3 activity. We present crystal structures of GSK-3 bound to its phosphorylated N-terminus and to two of the phosphorylated LRP6 motifs. A conserved loop unique to GSK-3 undergoes a dramatic conformational change that clamps the bound pseudo-substrate peptides, and reveals the mechanism of primed substrate recognition. The structures rationalize target sequence preferences and suggest avenues for the design of inhibitors selective for a subset of pathways regulated by GSK-3. Glycogen synthase kinase-3 (GSK-3) is a highly conserved kinase (Ali et al. , 2001) that in higher animals functions in insulin signaling, microtubule regulation, inflammatory pathways, and developmental programs including Hedgehog, Notch and Wnt signaling (Jope and Johnson, 2004; Kaidanovich-Beilin and Woodgett, 2011). GSK-3 has two isoforms in vertebrates, α and β, that share 97% identity in their catalytic cores but have different N- and C-terminal extensions. GSK-3 prefers pre-phosphorylated substrates, termed ‘primed’ substrates, with a phosphorylated serine or threonine residue at the position 4 residues C-terminal (P+4) to the serine or threonine to be phosphorylated (P+0) (Fiol et al. , 1987). Over 70 P+4 primed substrates for GSK-3 have been identified and confirmed as true biological GSK-3 targets (Sutherland, 2011). GSK-3 is a potential therapeutic target for diabetes and neurological disorders (Amar et al. , 2011), but its diversity of substrates complicates efforts to target a specific function. The overall structure of the GSK-3 catalytic domain is similar to other protein kinases, containing an N-terminal lobe composed primarily of β-strands in a β barrel conformation, and a C-terminal lobe composed mostly of α-helices (Dajani et al. , 2001; ter Haar et al. , 2001). At the interface of the N- and C- lobes, the C-helix and activation loop of GSK-3 form the putative substrate-binding site and help to position residues involved in the binding of ATP and substrate catalysis (Dajani et al. , 2001; ter Haar","Cells need to be able to respond to changes in the body, such as changes in hormone levels or the arrival of a pathogen such as a virus. Proteins acting in signaling pathways—where one protein switches ‘on’ or ‘off’ the next protein in the pathway—allow the detection of different changes or signals to be translated in the appropriate response. The properties of a protein often depend on its shape, and many proteins change shape when they are switched ‘on’ and ‘off’. Moreover, the ability to change shape allows a protein to interact with many other proteins and to be involved in many different signaling pathways. The enzyme GSK-3 is a protein that is involved in several pathways, and it controls other proteins by adding chemical tags, called phosphate",380,128,0.3368
dialogsum,"#Person1#: I'm not satisfied with it. #Person2#: Why not? What's wrong with it? #Person1#: Sometimes it goes fast and sometimes it goes slow, and the alarm doesn't work either. #Person2#: Would you like another one? #Person1#: No, can I have my money back? #Person2#: Emm, have you got a receipt? #Person1#: A receipt? #Person2#: Yes, I must see your receipt. You can't have your money back without a receipt. #Person1#: Though I'm not certain, but I think I've lost it.",#Person1# isn't satisfied with the product. #Person2# needs to see the receipt to give the money back.,80,17,0.2125
scientific_lay_summarisation-elife-norm,"extent in females are increased, which is probably due to additional initiation events at the LAP-AUG by ribosomes that normally would have initiated at the uORF (Calkhoven et al. , 2000). The Cebpb-mRNA levels are comparable at different ages and in the different genotypes (1D, E). Similarly, LIP expression is higher in white adipose tissue (WAT) of old female mice (WAT from males is not available) (— 1B). Since translation into LIP is stimulated by mTORC1 through phosphorylation of 4E-binding protein (4E-BP) (Zidek et al. , 2015), we reasoned that the higher LIP levels in aged livers and WAT might correlate with increased mTORC1 signalling with age. While the analysis of mTORC1-downstream phosphorylation of 4E-BP1 and p70 ribosomal protein S6 kinase 1 (S6K1) did not reveal a significant difference between young versus old or wt versus C/EBPβΔuORF mice in liver (— 1C, D), 4E-BP1 phosphorylation was significantly higher in old compared to young WAT samples from both wt and C/EBPβΔuORF females (— 1E, F). In contrast phosphorylation of ribosomal S6 protein in WAT was not significantly altered upon ageing. Thus, LIP levels increase with age and this increase is dependent on the uORF in the Cebpb-mRNA and seems to correlate with mTORC1/4E-BP1 signalling in WAT but not in the liver. We hypothesised that the C/EBPβΔuORF mutation may have positive effects on healthspan and lifespan based on the CR-like metabolic improvements in C/EBPβΔuORF mice (Zidek et al. , 2015). A lifespan experiment was set up comparing C/EBPβΔuORF mice with wt littermates (C57BL/6J) in cohorts of 50 mice of each genotype and gender. The survival curves revealed an increase in median survival of 20. 6% (difference in overall survival p=0. 0014 log-rank test, n = 50) for the female C/EBPβΔuORF mice compared to wt littermates (2A). From the 10% longest-lived females, nine out of ten were C/EBPβΔuORF mice (Supplementary file 1), showing that the maximum lifespan of C/EBPβΔuORF females is significantly increased (p=0. 0157 Fisher’s exact test). If maximum lifespan is determined by the mean survival of the longest-lived 10% of each cohort, C/EBPβΔuORF females show an increase of 9. 14% (p-value=0. 00105 Student’s t-test.). For the male cohort, we observed a modest increase in median survival of 5. 2%, however, the overall survival was not significantly increased (p=0. 4647 log-rank test,","The risks of major diseases including type II diabetes, cancer and Alzheimer’s are linked to the biological process of ageing. By finding ways to slow ageing, we can help more people to live longer healthier lives while avoiding these illnesses. Placing some animals on a diet that contains only two-thirds as many calories as they would normally eat can improve their fitness during old age and delay the onset of many age-related problems. It is unrealistic to expect people to control their diet to this extent, yet there may be other ways to bring about the same effects. Calorie restriction affects the activity of many different genes; for example, it causes a gene that produces a protein known as Liver-enriched Inhibitory Protein (LIP for short) to shut down.",380,128,0.3368
dialogsum,"#Person1#: Thanks. Sometimes talking with a friend is a great way to get over something. Do you mind if I vent a little bit? #Person2#: Of course not. If you're feeling bad and want to let your emotions out, you can just say whatever you want to me. #Person1#: Great, because I am really mad at William. I mean, what kind of an idiot wouldn't be able to appreciate a smart, beautiful woman like me? Anybody who would be friends with that guy has to be really dumb. #Person2#: Uh, A. . . you know I'm friends with William. #Person1#: Oh right. . . present company excluded, of course!","#Person1# is expressing #Person1#'s dissatisfaction with William and says everyone being friends with him is dumb, which embarrasses #Person1# since #Person1# is William's friend.",109,24,0.2202
scientific_lay_summarisation-elife-norm,"adult rodents was sufficient to induce dystonia, whereas genetic mouse models targeting the gene early in development did not produce dystonia. This provides further support for compensatory mechanisms in the rodent following the loss of certain genes early in development. We found that in adult mice, knockdown of torsinA in the cerebellum but not the basal ganglia resulted in severe and persistent dystonia. Symptoms were associated with abnormal erratic cerebellar output caused by dysfunctional intrinsic pacemaking activity of both Purkinje cells and neurons of the deep cerebellar nuclei. In contrast, mice with cerebellar knockdown of torsinA during the early post-natal period had mild symptoms with no dystonia. This observation suggests that indeed compensation of torsinA in early rodent brain development can explain the major differences in phenotype between adults and juveniles after torsinA knockdown. It is tempting based on these and previous findings (Fremont et al. , 2015) to hypothesize that abnormal cerebellar activity may be a common mechanism in some hereditary dystonias. In fact, imaging studies have implicated the cerebellum in another inherited dystonia (Carbon et al. , 2010a, 2013). Overall, by utilizing acute knockdown in adult rodents, we identified a mechanism whereby disruption of torsinA produces aberrant firing in the cerebellum and results in dystonic symptoms and provide evidence that the cerebellum may initiate symptoms in the most common inherited dystonia, DYT1. Since dystonia is often associated with changes in the basal ganglia, we first explored whether torsinA KD in this brain region results in symptoms. AAVs expressing a shRNA against torsinA with a green fluorescent protein marker (AAV-TorsinAshRNA-GFP, 1A) were stereotaxically injected into the basal ganglia (striatum and globus pallidus) of adult mice. Significant knockdown of torsinA (average torsinA levels after KD: 0. 187 ± 0. 06) was achieved and post-mortem histology demonstrated robust expression throughout the injected areas (1B, C). The behavior of these mice in the open field was assessed by observers blinded to the animals’ condition on a previously published dystonia scale (Calderon et al. , 2011). Since shRNAs take approximately two weeks to be expressed in vivo (Fremont et al. , 2015), the behavior of the animal can be compared before and after expression of the shRNA. Animals injected with a shRNA against torsinA in the basal ganglia did not develop dystonia, as","Dystonia is the third most common type of movement disorder after Parkinson’s disease and tremor. Patients with dystonia experience prolonged involuntary contractions of their muscles, often causing uncontrollable postures or repetitive movements. Almost thirty years ago, genetic studies revealed that a mutation in the gene that encodes a protein called torsinA causes the most common type of dystonia, called DYT1. Exactly how mutations that affect the torsinA protein give rise to DYT1 remains unclear, and there are still no effective treatments for the disorder. Part of the problem is that we do not fully understand how torsinA works, or which of its many proposed functions is relevant to dystonia. Moreover, attempts to study DYT1 using genetically modified mice have proved largely unsuccessful. This is because mice that simply",380,128,0.3368
pubmed-summarization,"the mesorectal plane was entered . the rectum was fully mobilized , allowing the cyst , which was adherent to it , to also be mobilized and removed intact . previous scar of incision and drainage , and mucoid color fluid on aspiration of cyst surgical excision of cyst from the posterior approach histopathology revealed a multiloculated tailgut cyst containing abundant mucoid material lined by glandular mucinous epithelium with fibrous tissue and showing intestinal glands [ ] , with no evidence of malignancy . she remains well at 1-year follow - up with no evidence of recurrence on serial pelvic imaging . histopathology showing intestinal glands within cyst wall confirming tailgut cyst ( h and e , 100 ) embryologically , tailgut cysts are believed to arise from vestigial remnants of the embryonic hindgut . the largest reported case series of 53 tailgut cysts over a 35-year period from 1950 to 1985 was described by hjermstad and helwig . they found that these cysts predominantly occurred in women ( female to male ratio , 3:1 ) . the ages ranged from 4 days to 73 years with an average age of presentation at 35 years . symptoms only occur due to the local mass effect on surrounding organs ( rectal fullness , constipation , painful defecation , lower abdominal and/or back pain or genitourinary obstruction ( dysuria ) ) , infection ( cysts with secondary infection have typical symptoms of anorectal or pelvic abscess and fistula , or perianal sinus ) , bleeding or malignant transformation / degeneration ( pain in the anorectal region ) . retrorectal cystic hamartomas in the presacral space are usually well - defined , thin - walled and multicystic or unilocular . despite the fact that the majority of tailgut cysts are benign , and can very rarely undergo malignant transformation and then most common histopathologic diagnoses are adenocarcinoma or carcinoid . they were lined by a variety of epithelia which varied not only among multiple cysts of multicystic lesions but also within the same cyst . the contents varied from clear fluid to dense mucous . due to the location of tailgut cysts , almost all of them are palpable on rectal examination as extrinsic , contained ; fluctuant masses . the differential diagnoses","retrorectal cystic hamartoma , also known as tailgut cyst , is a rare congenital developmental lesion arising from postnatal primitive gut remnants in the retrorectal space . the rarity of the lesion and its anatomical position usually leads to difficulty in diagnosis and surgical management . this cyst predominantly occurs in women ( female to male ratio , 3:1 ) . tailgut cysts can present as incidental findings during the routine examination but over half of the patients are thought to present with symptoms . computed tomography or magnetic resonance imaging has a crucial role in diagnosing these misdiagnosed cysts . complete surgical excision is the treatment of choice for tailgut cysts as this provides a definitive diagnosis , relieves symptoms , and prevents possible complications such as",380,128,0.3368
scientific_lay_summarisation-elife-norm,"reduced expression of muscle MT1-MMP greatly suppresses nerve-induced AChR cluster formation and stabilizes aneural AChR clusters against dispersal. Lastly, we show that MT1-MMP is required for the recruitment of AChR molecules from aneural to synaptic AChR clusters at developing NMJs in vitro and in vivo. Taken together, this study revealed the significance of PLS-directed MT1-MMP trafficking and surface insertion in modulating the assembly and topological remodeling of AChR clusters via focal matrix degradation at developing neuromuscular synapses. When dissociated myotomal tissues from early Xenopus embryos were cultured on glass coverslips coated with a mixture of ECM proteins, containing entactin/nidogen, collagen and laminin (ECL), topologically complex aneural AChR clusters were observed mostly on the bottom surface of muscle cells in contact with ECL-coated substratum (1A). Some aneural AChR clusters could also be found within the top surface of muscle cells but exhibited a sparsely scattered morphology. To further identify if specific ECM proteins are required for the formation of these topologically complex AChR clusters, we tested several key ECM proteins individually, including laminin, collagen, and gelatin, for their ability to induce AChR cluster formation in cultured Xenopus muscle cells. We found that the formation of bottom AChR clusters could be effectively induced by all ECM proteins tested, in contrast to the negative control using poly-D-lysine (PDL), a polypeptide commonly used to promote cell attachment (1B). In immortalized C2C12 myotubes, aneural AChR clusters can undergo a topological transformation from a plaque to a perforated pretzel-shaped, and eventually to C-shaped arrays (Kummer et al. , 2004). Hence, we further classified the aneural AChR clusters in Xenopus muscle cultures into scattered, plaque, perforated, and C-shaped based on their morphological features. A majority of ECM-induced aneural AChR clusters exhibited perforated structures. While the percentage of muscle cells with AChR clusters was largely reduced on PDL-coated substrate, the largest share of AChR clusters exhibited scattered structures (9. 59% out of 13. 33% total) (1C), similar to those structures found on the top muscle surface. As opposed to a previous study showing the topological transformation of AChR clusters in C2C12 myotubes (Kummer et al. , 2004), most AChR clusters, regardless of their topological features, were gradually dispersed over 6 days in cultured Xenopus muscle cells (— 1). Our previous study indicated that actin depolymerizing factor (ADF) /cofilin,","Voluntary movement relies on skeletal muscle cells and nerve cells being able to communicate with one another. This communication occurs at a specialized region called the neuromuscular junction, or NMJ for short. These junctions are surrounded by a meshwork of proteins, known as the matrix, which structurally supports the nerve and muscle cells. Muscle cells contain proteins called acetylcholine receptors on their cell surface. When these receptors cluster together at the NMJ, this allows nerve cells to communicate with the muscle cell and tell the muscle to contract. However, these clusters can also form spontaneously without the help of nerve cells at regions away from the communication site. Alongside these spontaneous clusters of acetylcholine receptors are dynamic actin-enriched structures. These structures are responsible for releasing enzymes that digest",380,128,0.3368
dialogsum,"#Person1#: It's nice and quiet here, away from the dust and noise of city. And our apartments are new and well-furnished. #Person2#: It's a good place except it is a bit far from the place where we work. Anyway, I'll talk with my husband tonight and give you a call tomorrow.",#Person1# promotes their apartments. #Person2# will discuss with #Person2#'s husband.,51,10,0.1961
scientific_lay_summarisation-elife-norm,"is released upon tissue damage (Lee et al. , 1997). Unlike IL-1β, which must be proteolytically processed into its active form, IL-1α is active as a zymogen and, upon secretion from epidermal keratinocytes, can play key roles in the early inflammatory phase of the wound-healing response (Bianchi, 2007). In addition, IL-1α plays an important role in mediating the reciprocal crosstalk between cells within the epidermis and dermis that stimulates the secretion of stem cell proliferation factors (Lee et al. , 2009; Szabowski et al. , 2000). The proliferative phase of the healing program rests on the ability of various epithelial stem cell pools, such as interfollicular epidermal (IFE) stem cells and hair follicle stem cells (HfSC), to contribute progenitor cells to seal the breached epidermis rapidly (Blanpain and Fuchs, 2009; Lau et al. , 2009). As a model, we used the epidermal caspase-8 knockout, which has a uniform wound-healing phenotype throughout the skin (Lee et al. , 2009), to investigate the mechanisms by which IL-1 signaling mobilizes different epithelial stem cell pools to mount an effective wound-healing response. An understanding of the regulation of stem cell proliferation within the context of an organ will advance the goal of enhancing the regenerative process or tempering diseases that have features of a chronic wound-healing response (i. e. diseases with a ‘wound signature’) (Schäfer and Werner, 2008). As we previously observed, IL-1-dependent signaling is crucial for a normal wound-healing response as mice deficient in the interleukin-1 receptor type 1 (IL1R KO) displayed a 2-day delay in wound closure (Lee et al. , 2009; Werner and Smola, 2001). Interestingly, a closer analysis of the delay in wound-closure kinetics reveals a defect that manifests itself significantly at day 3 post-wounding, suggesting a role for IL-1 signaling in the proliferative phase of the wound-healing response (— 1). This observation is consistent with previous findings that IL-1 mediates a double paracrine signaling loop wherein keratinocyte–fibroblast crosstalk generates growth factors that stimulate epidermal stem cell proliferation (Lee et al. , 2009; Werner and Smola, 2001). Extending upon this concept, we observed that the interfollicular stem cell proliferation induced by a wound is significantly impaired in the absence of IL-1 signaling (1A and — 2). In light of these observations, we investigated whether other epithelial stem cell pools that","The skin is a physical barrier that protects the body from the outside world. If the skin is injured, the body mounts a “wound healing” response to rapidly mend and restore this protective barrier. Wound healing is a complex process and relies on the different types of cells in the skin communicating with each other. Stem cells provide tissues, like the skin, with new cells. Normally, stem cells are in a resting or inactive state. Yet, during wound healing, stem cells near the injured area are awakened and start producing more cells to repair the wound. Understanding how stem cells become activated in a wound has proved challenging because only a small number of cells near a damaged site will respond, and it is difficult to distinguish their",380,128,0.3368
dialogsum,"#Person1#: Do you like Chinese food? #Person2#: Yes, Ido. #Person1#: What's your favorite Chinese food? #Person2#: Mm. It's hard to say. I like hot and sour soup a lot but I guess I like bean curd better. #Person1#: Do you eat Chinese food often? #Person2#: Once in a while.",#Person2# tells #Person1# #Person2# likes hot and sour soup.,49,9,0.1837
dialogsum,"#Person1#: Don't throw paper on the floor, Mike. #Person2#: Where shall I put it, Miss? #Person1#: Put it in the waste-paper basket, please. #Person2#: But Tom and Bill put all their paper in the basket a few minutes ago. Now it's full. #Person1#: Then take the basket outside and empty it. #Person2#: Yes, Miss. #Person1#: Where did you empty the basket, Mike? #Person2#: On the playground, Miss. #Person1#: That's not right! The dustbin is at the back of the school. Now pick up the paper and put it in the dustbin.",#Person1# asks Mike to empty the basket but Mike empties it on the playground instead of in the dustbin.,91,19,0.2088
scientific_lay_summarisation-elife-norm,"AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The mechanisms underlying this positioning have largely been ascribed to the receptor cytoplasmic C-termini and to AMPAR-associated auxiliary subunits, both interacting with the postsynaptic scaffold. Here, using mouse organotypic hippocampal slices, we show that the extracellular AMPAR N-terminal domain (NTD), which projects midway into the synaptic cleft, plays a fundamental role in this process. This highly sequence-diverse domain mediates synaptic anchoring in a subunit-selective manner. Receptors lacking the NTD exhibit increased mobility in synapses, depress synaptic transmission and are unable to sustain long-term potentiation (LTP). Thus, synaptic transmission and the expression of LTP are dependent upon an AMPAR anchoring mechanism that is driven by the NTD. AMPA receptors (AMPARs) are embedded at postsynaptic sites, aligned with the presynaptic glutamate release machinery for optimal signaling (Lisman et al. , 2007). Their activation drives propagation of presynaptic impulses through depolarization of the postsynaptic membrane (Traynelis et al. , 2010). As AMPARs have low apparent glutamate affinity, and rapidly diffuse in the plane of the membrane, they require trapping at synaptic sites in order to effectively contribute to signal transmission (Choquet and Triller, 2013; Heine et al. , 2008). Synapse strengthening, as occurs during learning, results from the recruitment of additional AMPARs and their enrichment at synapses (Chater and Goda, 2014; Huganir and Nicoll, 2013; Kessels and Malinow, 2009). Hence, the mechanisms underlying AMPAR positioning are fundamental to synaptic transmission and plasticity. Signaling properties and synaptic delivery depend on AMPAR composition. AMPARs are tetramers, assembled from the core GluA1-GluA4 (pore-forming) subunits, which associate with a varying set of auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs) (Jackson and Nicoll, 2011). Each core subunit consists of four domains – a short cytosolic C-terminus (CTD), the transmembrane ion channel domain (TMD), and two extracellular domains: the ligand-binding domain (LBD) and the distal N-terminal domain (NTD) (1A). 10. 7554/eLife. 23024. 003Figure 1. NTD deleted GluA2 is robustly expressed on the cell surface. (A) AMPA receptor schematic detailing the four-domain structure (NTD - N-terminal domain; LBD - Ligand-binding domain; TMD - Transmembrane domain; CTD - C-terminal domain). (B) Single-cell electroporated CA1","Neurons send signals via electrical impulses that are transmitted between cells by small molecules known as neurotransmitters. The information is passed from neuron to neuron at specialized points of contact termed synapses. On release of neurotransmitters from the first neuron, the molecules attach to ‘docking stations’ called receptors on the next neuron, referred to as the postsynaptic cell. One of these receptors, the AMPA receptor, transmits signals by binding to a neurotransmitter called glutamate. Previous research has shown that in order to bind glutamate effectively, these receptors need to be trapped and anchored at the correct location at the synapse. This trapping mechanism controls the number of receptors present, which strengthens the synapse, and ultimately mediates learning and memory. However, it is still not clear how AMPA receptor",380,128,0.3368
dialogsum,"#Person1#: Let's start the interview with some questions. Tell me about yourself and your past experience. #Person2#: I have 10 years financial industry experience, working for several companies. For the past two years, I have been working in an investment banking. In addition to my analytical mindset, I have a background of solid accounting principles. I am a team player and have great communication and interpersonal skills. I thrive on challenge and work well in high-stress environments. #Person1#: What finance experience have you had that qualifies you for this position? #Person2#: My background and experience include working on a variety of projects and jobs in the financial industry. Most of my experience has been behind the scenes, doing the calculations. I want to work with clients and continue to grow and be challenged. #Person1#: Why did you leave your last position? #Person2#: I'm not finding the work as challenging as I used to. I want to find a job that is stimulating, where I can grow. #Person1#: What are your strengths and weaknesses? #Person2#: One of my strengths is my ability to be flexible. I've seen companies go through many changes in structure and management philosophy. I've had to adjust my style to the new environment several times. As far as weaknesses, I really enjoy my work, and sometimes I put in too much time. But by being aware of my tendency to overwork, I have learned to pace myself more and work less overtime. #Person1#: How would your boss describe you and your work style? #Person2#: She'd say I have a lot of initiative, I see the big picture and I do what has to be done. Second, I always meet deadlines. If I say I'm going to do something, I do it. Lastly, I have the ability to focus on what I'm working on I am not easily distracted. #Person1#: What are your salary expectations? #Person2#: I'm sure whatever you offer will be a fair amount for a person with my qualifications. Salary is not the most important factor to me. I'm looking for opportunity. #Person1#: Do you have any questions? #Person2#: Yes, I do. What do you see as the future trends for the industry?","#Person2# tells #Person1# about #Person2#'s past working experience. #Person2# leaves #Person2#'s last position to find a stimulating job. Then, #Person2# talks about #Person2#'s strengths and weaknesses, work style, and salary expectations.",368,31,0.0842
dialogsum,"#Person1#: Jenny, I was wondering. . . if you. . eh are you busy this Friday? #Person2#: Yes, Friday I have a class, right after work. #Person1#: Oh, what about Saturday? Are you free then? #Person2#: Saturday my parents are coming to town. What's up? #Person1#: What about tonight? Do you have plans tonight? #Person2#: No, do you want to go and do something? #Person1#: Yes, yes, I want to take you to dinner. #Person2#: Oh, that sounds great. How about 6 o'clock?",#Person1# asks Jenny's schedule because #Person1# wants to take Jenny to dinner.,83,12,0.1446
dialogsum,"#Person1#: Hey, Terry, have all the players got here? #Person2#: Yeah, most of them have arrived. Don't worry. There are still 20 minutes left before the match. #Person1#: OK. By the way, the stadium is terrific. #Person2#: Of course. It's a newly-built one. #Person1#: We are lucky to play in a new stadium. #Person2#: Hurry up, Benjamin! Pass the ball to me. I'm good at shooting. #Person1#: Look out. Catch the ball. You should dunk besides the three-point line. #Person2#: Oh, God! I didn't touch anybody. How can I commit a foul? #Person1#: Just calm down. It's just a turnover. Make up your mind and we can shoot well. #Person2#: Yes, I got it. Come on, Benjamin, don't let him get into the paint. #Person1#: No problem, I once played a 2 - meter-high player successfully. #Person2#: Really? You must be. . . #Person1#: But that game he dunked over me for 13 times. #Person2#: That's interesting. Let's hurry up, we should beat them in the first half. #Person1#: Oh, look, what's happened to Jack? He sat down. #Person2#: He may be injured. Yes, come on, call the team doctor.","Terry and Benjamin are playing basketball in the newly-built stadium. Benjamin is confident with the shooting. Terry wants to beat the other team in the first half, but Benjamin finds Jack may be injured.",190,34,0.1789
pubmed-summarization,"coal - tar pitch is an important feedstock of carbochemical origin used for the production of i.a . carbon anodes , graphite electrodes , fireproof materials , carbon - carbon composites and carbon fibres , as coking additive and as binder in many insulating and sealing materials used in construction and road building . bitumens originating from coal , similarly as petroleum asphalts can be treated as colloidal - dispersive systems . micelles composed of 2 components and partly of 1 components form dispersed phase while oils ( components ) and partly components are the dispersing phase . because of the presence of carcinogenic aromatic hydrocarbons in coal - tar pitch , there is a need for its modification to obtain material safe for natural environment . research on the preparation of modified bituminous substances originating from coal , carried out for many years in the institute of chemistry of warsaw university of technology in plock has led to the elaboration of method reducing the level of carcinogenicity of coal - tar pitch . modification of coal - tar pitch with polymers influences also significantly its group composition and properties . the direction and scale of changes depend on chemical structure of the modifier and its amount . chemical structure is a factor directly determining properties of each of the components of bitumen - polymer compositions and simultaneously has an impact on the possibility to form a specific structure of a given composition , on which in turn its properties depend . because of profitable properties of pitch - polymer mixtures , it would be advisable to check the possibilities to use waste polymers for the modification of the pitch . it leads to the search for new techniques and methods of evaluation of their homogenicity and application properties . one of them are microscopic studies , which play significant role in the determination of the structure and colloidal stability of bitumens and bitumen - polymer systems , including pitch - polymer compositions . in the studies of bitumen - polymer systems , fluorescence microscope is used , particularly for the evaluation of polymer - asphalt materials . however , there is no significant development in the evaluation of pitch - polymer compositions with the use of such microscope .","in this work , the results of studies on the evaluation of colloidal structure of coal - tar pitch compositions with selected waste polymers by fluorescence microscope . for pitch - polymer compositions containing 1050 wt% waste polymer , softening point , coking value and content of components insoluble in toluene and quinoline were carried out . the results indicate that pitch - polymer compositions can be treated as microheterogeneous systems , colloidal and biphase , generally exhibiting uniform dispersion of particles composed of polymer macromolecules and probably of components of coal - tar pitch .",380,96,0.2526
pubmed-summarization,"integrative and motor components in this loop . presumably , during evolution , making this system work in an appropriate fashion must have taken an equally long time in itself . however , moreover , once the energy - saving advantage of having cells communicate and develop specialized activities was realized , another conservative mechanism became evident . cells were communicating , to a great extent , by chemical means , since this method of signaling reduces the size requirements for the individual communicating components ( signal molecule and its corresponding receptor ) . this method of intra- and intercellular communication allowed for a greater level of sophistication and information transfer compared to a scenario of whole cells touching , using up limited space . the significance of stereoselective chemical communication can be noted today by its presence and actions in diverse organisms . similarly , many of the same intracellular and intercellular signal molecules have been retained during evolution as well as functions associated with them first found in organisms considered primitive . this is manifest , for example , in signal molecules once associated exclusively with the nervous system now being demonstrated in the immune system , and vice versa , e.g. , neuropeptides and cytokines , respectively . if we now examine what has evolved to account for human cognitive ability , it would have to be the extent and capacity of the integrative processes . in examining any text in comparative anatomy , we are also led to the conclusion that a single structure can be traced back in time and that its presence today has been modified . the examples of this development process that retains and embellishes information as a function of a changing environment with time are now too numerous to list . since this developmental process of using and modifying existing structures and their activities is ongoing , we are on strong ground in surmising that the same holds true for a host of behaviors , including cognitive ability as noted to be present in animals other than humans by various authors , i.e. animals probably have a limited degree of cognitive ability , displaying critical fragments of the capability that exists more fully in humans . it would be foolish to","cognitive ability did not appear de novo in humans . despite our ability to recognize limited cognitive behavioral characteristics in animals , there has been no outcry to proclaim this phenomenon . the notion that humans are the only animals to possess cognition has taken advantage of the illusory potential in inter - subjectivity and placed him outside of reality . this deception , however , has positive survival value due to the fact that it is humankind s self - proclaimed responsibility to excel beyond other simple animal species . however , at this point in evolution , we must allow our cognitive ability to reform itself and , in so doing , evolve with the benefit of the knowledge that this ability is itself creating .",380,128,0.3368
dialogsum,"#Person1#: Shall I phone and tell your secretary you're not coming today? #Person2#: Yes, please, dear. Tell her I've got a cold and a headache, but I hope to be back in a day or two. You'd better say I'm staying in bed. #Person1#: But you're not in bed! Do you want me to tell a lie? #Person2#: Oh, it's only a very little one, dear. I'm not making a false excuse. I really have a bad headache. #Person1#: Then put the cigarette out. It's very foolish of you to smoke when you've got a cold. #Person2#: Very well, dear. You're quite right. #Person1#: Look, here's some boiling water. Do as I tell you now. I've put something in the water that'll do you a lot of good. Put your nose over the water. That's right. Breathe in deeply. It'll do you a lot of good. #Person2#: It smells nice.",#Person2# asks #Person1# to tell #Person2#'s secretary that #Person2# is not coming because of sickness. #Person1# advises #Person2# to put the cigarette out and put #Person2#'s nose over the water.,150,30,0.2
dialogsum,"#Person1#: Hello, could you tell me my test results? #Person2#: Your results are posted on the website. Just put in your password and you can see the exact numbers. #Person1#: Are you saying that all my results were normal? #Person2#: We always contact you by phone to come in if there is a need for follow-up. #Person1#: How will I know what the results mean on the website? #Person2#: The purpose of each test is given on the site. #Person1#: Will the numbers mean anything to me? #Person2#: The website will give you your results and then tell you what the normal range is. #Person1#: Can I see all of my test results at once? #Person2#: Yes, you can see every test for the past five years. You can compare them.","#Person2# tells #Person1# that #Person1# can search his test results, know the purpose of the result and make comparisons in the past five years on the website.",131,27,0.2061
dialogsum,"#Person1#: CFC Taxis. #Person2#: Hello. I'd like to book a taxi, please. #Person1#: Certainly. For what time? #Person2#: Five o'clock tomorrow morning. #Person1#: Where from, madam? #Person2#: From Qilu Hotel. #Person1#: Oh, I see. Where do you want to go? #Person2#: To the railway station. How much will it cost? #Person1#: About 20 dollars. #Person2#: How long will it take to get there? #Person1#: If the traffic is not too busy, it will take about 15 minutes.",#Person2# calls CFC Taxis to take her from Qilu Hotel to the railway station at 5:00 tomorrow.,77,17,0.2208
scientific_lay_summarisation-elife-norm,"neuron dendritic targeting, as well as patterning and growth during fly airway remodeling (Becam et al. , 2011; Blochlinger et al. , 1988; Bodmer et al. , 1987; Cubelos et al. , 2010; Grueber et al. , 2003; Komiyama and Luo, 2007; Ludlow et al. , 1996; Pitsouli and Perrimon, 2013; Rodríguez-Tornos et al. , 2016). Here, we show that a steep Wnt/Wingless (Wg) morphogen gradient (Clevers and Nusse, 2012; Loh et al. , 2016) at the midgut-hindgut boundary intersects with a pulse of the steroid hormone ecdysone at the onset of metamorphosis (Yamanaka et al. , 2013) to induce cut expression in a subset of midgut progenitors and reprogram them into renal progenitors. Mechanistically, the Wg morphogen gradient, through its pathway effector TCF/β-catenin, determines the pool of future renal progenitors, presumably by poising a distal cut enhancer for timely activation. On the other hand, the hormone ecdysone-induced BTB-Zinc finger protein Broad determines the timing of lineage conversion by physically interacting with enhancer-bound TCF/β-catenin complex and likely bridging the distal enhancer and promoter region of cut through its self-association. Such long-range enhancer-promoter looping could subsequently trigger timely cut transcription. Thus, integration of spatial and temporal cues by a master cell identity switch, likely through a chromatin looping mechanism, orchestrates natural lineage reprogramming with temporal and spatial precision. To identify key regulators governing midgut-to-renal lineage conversion, we carried out a genome-wide RNAi-based screen. We used temperature-sensitive, midgut and renal progenitor-specific esg-Gal4, UAS-CD8-GFP, tub-Gal80ts system to drive RNAi expression, transferred animals from permissive temperature (18°C) to restrictive temperature (29°C) at mid third instar larval stage, approximately 48 hr before the lineage reprogramming event occurs, and analyzed the renal phenotypes at early adult stages. Intriguingly, we found that midgut progenitor-specific knockdown of the transcription factor Cut resulted in lack of the entire lower ureter region (brackets in — 1B) and appearance of extra Esg- diploid cells along the renal tubules (arrowheads in — 1B). Such striking renal tubule phenotypes of cut-RNAi prompted us to carefully investigate the expression pattern of Cut in adult intestine and renal tubules. Cut has previously been found to be highly expressed in two types of post-mitotic, polyploid cells in the Drosophila digestive-excretive system: the acid-secreting copper cells in the middle midgut region (Strand and Micchelli, 2011) and the","As an embryo develops, an organism transforms from a single cell into an organized collection of different cells, tissues and organs. Regulated by genes and messenger molecules, non-specialized cells known as precursor cells, move, divide and adapt to produce the different cells in the adult body. However, sometimes already-specialized adult cells can acquire a new role in a process known as lineage reprogramming. Finding ways to artificially induce and control lineage reprogramming could be useful in regenerative medicine. This would allow cells to be reprogrammed to replace those that are lost or damaged. So far, scientists have been unable to develop a clear view of how lineage reprogramming happens naturally. Here, Xu et al. identified a cell-conversion event in the developing fruit fly. As the fly larva develops",380,128,0.3368
scientific_lay_summarisation-elife-norm,"to orient in odor gradients, however, remain poorly understood. The Drosophila larva has the smallest known olfactory system analogous to that of vertebrates (Cobb, 1999; Bargmann, 2006b; Gerber and Stocker, 2007; Vosshall and Stocker, 2007). The larva achieves robust odor gradient ascents through an alternation of approximately straight runs and turning events (Gomez-Marin et al. , 2011; Gershow et al. , 2012). The duration of runs is modulated by the sensory input: runs up the gradient are elongated while runs away from it are shortened (Gomez-Marin et al. , 2011; Gershow et al. , 2012). Although published results hint at how larval chemotaxis may be achieved (Gomez-Marin and Louis, 2012,2014), a quantitative model of the underlying sensorimotor integration is still missing. Here, we focus on the primary task of the orientation algorithm common to bacteria, C. elegans, and Drosophila: the control of run duration (Bargmann, 2006a; Lockery, 2011; Gomez-Marin and Louis, 2012). It is known that turns are preceded by stereotyped decreases in odor concentration (Gomez-Marin et al. , 2011; Gomez-Marin and Louis, 2012), but the key question of how concentration differences are computed is unresolved. In both insects and vertebrates, odor concentrations are represented by time-varying patterns of activity distributed across the olfactory sensory neuron (OSN) population (Wilson and Mainen, 2006; Wilson, 2013; Masse et al. , 2009; Mainland et al. , 2014; Uchida et al. , 2014). Nonetheless, animals with an olfactory system genetically reduced to a single functional OSN are still capable of robust chemotaxis (Fishilevich et al. , 2005; Louis et al. , 2008), implying that the mechanisms of odor concentration detection can be understood at the level of single OSNs. Here, we rely on this simplification to develop a novel larval preparation in which the neural computations underlying odor gradient ascent can be understood in unprecedented detail. We used optogenetics in larvae with a single type of functional OSNs to substitute turbulent olfactory signals with well-controlled light stimulations (Suh et al. , 2007; Bellmann et al. , 2010; Smear et al. , 2011; Gaudry et al. , 2013). This allowed us to characterize the modulatory effects of OSN firing patterns on the probability of switching from a run to a turn. Toward this goal, we developed a novel tracker to create virtual olfactory realities (Kocabas","Fruit flies are attracted to the smell of rotting fruit, and use it to guide them to nearby food sources. However, this task is made more challenging by the fact that the distribution of scent or odor molecules in the air is constantly changing. Fruit flies therefore need to cope with, and exploit, this variation if they are to use odors as cues. Odor molecules bind to receptors on the surface of nerve cells called olfactory sensory neurons, and trigger nerve impulses that travel along these cells. While many studies have investigated how fruit flies can distinguish between different odors, less is known about how animals can use variation in the strength of an odor to guide them towards its source. Optogenetics is a technique that allows neuroscientists",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Proper kinetochore-microtubule attachments, mediated by the NDC80 complex, are required for error-free chromosome segregation. Erroneous attachments are corrected by the tension dependence of kinetochore-microtubule interactions. Here, we present a method, based on fluorescence lifetime imaging microscopy and Förster resonance energy transfer, to quantitatively measure the fraction of NDC80 complexes bound to microtubules at individual kinetochores in living human cells. We found that NDC80 binding is modulated in a chromosome autonomous fashion over prometaphase and metaphase, and is predominantly regulated by centromere tension. We show that this tension dependency requires phosphorylation of the N-terminal tail of Hec1, a component of the NDC80 complex, and the proper localization of Aurora B kinase, which modulates NDC80 binding. Our results lead to a mathematical model of the molecular basis of tension-dependent NDC80 binding to kinetochore microtubules in vivo. Chromosome segregation errors lead to aneuploidy and micronuclei formation, which are closely associated with cancer, infertility, and birth defects (Santaguida and Amon, 2015). Accurate chromosome segregation is believed to result from a process that actively suppresses potential errors. The mechanism of error correction remains unclear, but extensive evidence suggests that it is based on the regulation of the attachment of microtubules to chromosome via the kinetochore, a protein complex assembled at centromeres (Godek et al. , 2015). Previous works suggested that error correction is largely due to the detachment of kinetochore microtubules (kMTs) being regulated by the tension across centromeres, which selectively destabilizes erroneous kMT attachments bearing low tension and stabilizes proper attachments under high tension (Nicklas and Ward, 1994; Liu et al. , 2009; Akiyoshi et al. , 2010; Lampson and Cheeseman, 2011; Godek et al. , 2015). However, the molecular mechanism of the tension-dependent regulation of kMT attachments is still poorly understood. The highly conserved NDC80 complex is the major coupler of the kinetochore to microtubules (Cheeseman et al. , 2006; DeLuca et al. , 2006). In human mitotic cells, ~240 NDC80 complexes are recruited at the outer layer of each kinetochore (Suzuki et al. , 2015) and interact with ~20 kMTs by directly binding to them (Cheeseman and Desai, 2008; Maiato et al. , 2004; Rieder, 1982). In vitro experiments showed that the binding affinity of NDC80 for microtubules decreases upon the phosphorylation of the N-terminal tail of Ndc80/Hec1 protein by Aurora B","When a cell divides, each new cell that forms needs to contain a complete set of DNA, which is stored in structures called chromosomes. So first, the chromosomes duplicate, and the two copies are held together. A protein structure known as a kinetochore then forms on each copy of the chromosome. The kinetochores act as a pair of hands that pull the chromosome copies apart and toward opposite sides of the dividing cell. They do this by grabbing protein ‘ropes’ called microtubules that extend toward the chromosomes from each side of the cell. Kinetochores grip the microtubule ropes more tightly when the connection is under greater tension. This helps the kinetochores to remain attached to the microtubules that will separate the chromosome copies while releasing the microtubules that",380,128,0.3368
scientific_lay_summarisation-elife-norm,"T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds) TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of αβ TCR domains with corresponding γδ TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy. T lymphocytes recognize cellular targets with extraordinary sensitivity and specificity. The T cell receptor (TCR) on the T cell surface binds to its cognate peptide antigen presented on major histocompatibility complex (MHC) molecules on the target cell surface (Reinherz, 2015). The TCR - a heterodimer that is uniquely rearranged in each T cell during its development - is the sole determinant of T cell specificity (DembiĆ et al. , 1986). Accordingly, transfer of the α and β genes encoding a tumor-reactive αβ TCR can impart anti-tumor reactivity to a cancer patient’s T cells (Clay et al. , 1999). Upon reinfusion into the patient, these engineered T cells mediate potent anti-tumor cytotoxicity (Park et al. , 2011). This approach – termed TCR gene therapy – has demonstrated clinical responses for several malignancies (Johnson et al. , 2009; Morgan et al. , 2006; Davis, 2010; Parkhurst, 2011; Robbins et al. , 2015,2011), which may be bolstered in the future through combination with complementary immunotherapies like dendritic cell-based vaccination and checkpoint blockade (Abate-Daga et al. , 2013; Brahmer and Hammers, 2015; Mellman et al. , 2011; Sharma and Allison, 2015; Topalian et al. , 2015; Chodon, 2014). Despite the promise of TCR gene therapy, there remain significant limitations to its safety and efficacy. Among these is that TCR-transduced αβ T cells express two α and two β chains, a non-physiological situation in which the","T cells enable the immune system to recognize invading microbes and diseased cells while ignoring healthy cells. The ability of a T cell to recognize a specific microbe or diseased cell is determined by two proteins that pair to form its “T cell receptor. ” The paired receptors are exported to the surface of the T cell, where they bind to infected or cancerous cells. Those T cells that produce receptors that bind healthy cells are eliminated during development. T cells can generally distinguish between the body’s own cells and the cells of invading bacteria or other microbes. However, cancer cells are more difficult to identify because they are similar to healthy cells. Efforts to develop therapies that enhance the immune system’s ability to recognize cancer cells have",380,128,0.3368
scientific_lay_summarisation-elife-norm,"digestion and cell sorting (Shamir et al. , 2016). Furthermore, cell sorting exposes cells to conditions that are different from those experienced by cells in tissues and can change metabolism in many ways. For example, sorting can induce mechanical and oxidative stress and reduce the levels of certain metabolites (Binek et al. , 2019; Llufrio et al. , 2018; Roci et al. , 2016), and even adding small amounts of bovine serum to the sorting buffer was not sufficient to prevent changes in some metabolite levels during cell sorting (Llufrio et al. , 2018). Indeed, isotopic metabolite labeling patterns can be more robust than metabolite levels when assessing metabolites from flow cytometry sorted cells, although labeling can also be affected by cell sorting (Roci et al. , 2016). Nevertheless, interpretation of metabolite labeling patterns is influenced by whether cells are at metabolic steady state (Buescher et al. , 2015), which when coupled with the rapid timescales of metabolism relative to the time needed to isolate cells suggests that new approaches are needed to better understand metabolism of individual cell types within mixed cell populations such as tumors. To overcome the challenges associated with studying cell metabolism within intact tumors and organoid co-cultures, we adapted an approach based on end-product biomass labeling (Green et al. , 2016; Hosios et al. , 2016; Le et al. , 2017; Lewis et al. , 2014; Mayers et al. , 2016; Shankaran et al. , 2016). This technique has been applied in studies of microbial metabolism and metabolic engineering to better understand mixed populations of bacteria (Gebreselassie and Antoniewicz, 2015; Ghosh et al. , 2014; Rühl et al. , 2011; Zamboni et al. , 2005). Unlike short-lived metabolic intermediates, turnover of end-product macromolecules such as protein is slow relative to the time period needed to isolate tumor cell populations. By assessing the isotope-labeling pattern of end-product biomass generated when cells are exposed to labeled nutrients in a mixed cell population, metabolic differences in nutrient use by different cells can be inferred. We used this approach to uncover a difference in glucose metabolism between cancer cells and fibroblasts in PDAC. Specifically, we find that, relative to fibroblasts, cancer cells within PDAC tumors have increased use of glucose for tricarboxylic acid (TCA) cycle anaplerosis through increased flux","Tumors contain a mixture of many different types of cells, including cancer cells and non-cancer cells. The interactions between these two groups of cells affect how the cancer cells use nutrients, which, in turn, affects how fast these cells grow and divide. Furthermore, different cell types may use nutrients in diverse ways to make other molecules – known as metabolites – that the cell needs to survive. Fibroblasts are a subset of non-cancer cells that are typically found in tumors and can help them form. Separating fibroblasts from cancer cells in a tumor takes a lot longer than the chemical reactions in each cell of the tumor that produce and use up nutrients, also known as the cell’s metabolism. Therefore, measuring the levels of glucose (the sugar that",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in living mice. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through β2-containing (β2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders. Cholinergic neurotransmission provides a widespread and diffuse signal in the brain (Picciotto et al. , 2012; Sarter et al. , 2009). ACh alters neurotransmitter release from presynaptic terminals and affects neuronal integration and network activity, by acting through two classes of membrane receptors: metabotropic muscarinic receptors and ionotropic nicotinic ACh receptors (nAChRs). nAChRs consist of hetero- and homo-pentameric arrangements of α and β subunits (9 and 3 genes, respectively), yielding a high combinatorial diversity of channel composition, localization and function (Zoli et al. , 2015). Nicotinic neuromodulation controls learning, memory and attention, and has been associated with the development of numerous neurological and psychiatric disorders, including epilepsy, schizophrenia, anxiety and nicotine addiction (Taly et al. , 2009). Understanding how nAChRs mediate such diverse functions requires tools for controlling nicotinic neurotransmission in defined brain circuits. ACh is a modulator of the VTA, a midbrain DAergic nucleus key in the processing of reward-related stimuli and in addiction (Di Chiara and Imperato, 1988; Pignatelli and Bonci, 2015; Volkow and Morales, 2015). The pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT) are the two major cholinergic inputs to the VTA (Beier et al. , 2015). Optogenetic activation of PPN and LDT neurons modulates the firing patterns of VTA DA cells and reward-associated behaviors (Lammel et al. , 2012; Dautan et al. , 2016; Xiao et al. , 2016), implicating ACh in these processes. Yet, whether ACh directly affects neuronal excitability at the","Acetylcholine is one of the most abundant chemicals in the brain, with key roles in learning, memory and attention. Neurons throughout the brain use acetylcholine to exchange messages. Acetylcholine binds to two different classes of receptors on neurons: nicotinic and muscarinic. As the name suggests, nicotinic receptors also respond to nicotine, the main addictive substance in tobacco, while muscarinic receptors respond to muscarine, present in certain poisonous mushrooms. Nicotinic and muscarinic receptors each consist of many different subtypes. But standard pharmacology techniques cannot discriminate between the effects of acetylcholine binding to these different subtypes. Likewise, they cannot distinguish between acetylcholine binding to the same receptor subtype on different neurons. Durand-de Cuttoli, Mondoloni et al. have now developed a new nanotechnology that uses light to target specific acetylcholine receptor",380,128,0.3368
dialogsum,"#Person1#: Do you like swimming? #Person2#: Yes. Swimming is one of my most favorite sports,indoors or out-doors. #Person1#: Me too. Swimming is a very good exercise for health. It combines water, bath, sunbath, and air bath together. It promotes the growth and haleness of muscles, bone, viscera and nerve systems. #Person2#: I have never thought that swimming can bring us so many benefits. I only know that swimming in great waves and deep running water can train people's spirits,and enable people to be fearless of the hardships,dangers and difficulties and become brave and staunch. #Person1#: Have you ever swum in a river or a lake? #Person2#: Yes, but not always. However, I won't let it go if I have a chance.",#Person1# and #Person2# are talking about how they like swimming and the benefits of swimming.,121,15,0.124
scientific_lay_summarisation-elife-norm,", 2003). While loss of Zeb1 function in the developing neocortex reduces proliferation in the VZ and SVZ (Liu et al. , 2008), it remains unknown how Zeb1 regulates neural progenitor populations. Studies examining Zeb1 regulation of epithelial cell polarity provide insights. Zeb1 activates stemness pathways in immature, unpolarized epithelial cells and their transformed counterparts (Spaderna et al. , 2008). It also controls transitions in epithelial differentiation and polarity plasticity: high Zeb1 expression inhibits epithelial differentiation and drives cells toward epithelial-to-mesenchymal transition (EMT), while low expression allows mesenchymal-to-epithelial transition (MET). During EMT, Zeb1 acts as a transcriptional repressor that silences adherens junction (AJ) and apical-basal polarity genes (Aigner et al. , 2007). Thus, Zeb1 simultaneously blocks differentiation, apical-basal polarity, and junction formation of epithelial cells, locking them into the mesenchymal state. In the developing nervous system, EMT-like events have been observed in the transition of polarized radial glia to their delaminating progeny (Rousso et al. , 2012; Itoh et al. , 2013). Given that neuronal progeny undergo multiple polarity transitions after delamination from a radial glial cell, it is open to question how polarity is re-acquired after delamination as nascent neurons mature (Cooper, 2014; Singh and Solecki, 2015; Barnes et al. , 2008). Do nascent neurons that undergo an EMT-like process also then transition through an MET-like process, like epithelial cells? We have known for more than a decade that persistent Sonic hedgehog (SHH) signaling blocks GNP GZ exit, but the mechanism has remained a mystery. Here we hypothesized that MET-like events control the onset of neuronal differentiation and GZ exit, which involve cell polarity and cell-cell adhesion transitions. By using gain- and loss-of-function approaches, we found that Zeb1 is necessary and sufficient to maintain GNPs in an undifferentiated, unpolarized, transiently amplifying state within the EGL and to control the onset of their GZ exit. Zeb1 represses transcription of polarity and cell adhesion genes, such as Pard6a, Pard3a and close homolog of L1 (Chl1). By using a functional screen, we found that restored expression of these genes rescues GNP differentiation, neurite extension, and GZ exit. Finally, we examined the link between morphogens and Zeb1 in controlling this process. We found that SHH, a potent GNP mitogen, maintains Zeb1 expression. Moreover, Zeb1 expression persists in MB tumor cells, the transformed GNP","During the formation of the brain, developing neurons are faced with a logistical problem. After newborn neurons form they must change in shape and move to their final location in the brain. Despite much speculation, little is known about these processes. Neurons mature via the activity of several pathways that control the activity, or expression, of the neuron’s genes. One way of controlling such gene expression is through proteins called transcription factors. At the same time, the developing neurons go through a process called polarization, where different regions of the cell develop different characteristics. However, it was not known how the maturation and polarization processes are linked, or how the developing neurons actively regulate polarization. By studying the developing mouse brain, Singh et al. found that a transcription",380,128,0.3368
dialogsum,"#Person1#: Look at this headline - Elvis Baby Born on Spacecraft. Where do these tabloids get such crazy stories? #Person2#: I've often wondered the same thing. I also wonder who reads them. Then I realize that I'm standing here reading them myself. #Person1#: It looks as though everyone in line reads them, or at least looks at the headlines. #Person2#: I think we picked the right line. This one seems to be moving more quickly than the others. #Person1#: Maybe our checker is faster at scanning the food. #Person2#: I'm glad. We have only about twenty things here, and I'm in a hurry to get home.",#Person1# and #Person2# are reading the crazy stories on the tabloids because they are attracted by the headlines.,106,18,0.1698
dialogsum,"#Person1#: Hello. May I speak to Mary, please? #Person2#: Speaking. Who's calling, please? #Person1#: Hi, Mary. This is Tom. #Person2#: Oh, hi, Tom. How've you been? #Person1#: Just fine. I say. Aren't you busy tomorrow evening? #Person2#: Let me see. Uh-huh. . . no, I guess I'll be free. #Person1#: Well, uh. . . why not dine out together and go to the movies? #Person2#: Sounds like a good idea. #Person1#: Okay. I'll pick you up at 6:00. #Person2#: Thank you for inviting me. See you then. Bye, Tom.",Tom calls Mary to invite Mary to dine out and watch a movie tomorrow evening.,89,15,0.1685
pubmed-summarization,"the global prevalence of colorectal cancer is increasing , and the incidence in south korea is rapidly increasing owing to a westernized diet . colon carcinogenesis occurs through either the adenoma - carcinoma sequence or a de novo pathway . it is known that over two - thirds of colorectal cancer cases develop from adenomas ; therefore , detection and removal of adenomas by colonoscopy is the best way to prevent colorectal cancer . according to an american study in 2008 , polyps over 9 mm in size have been detected in 6% to 7% of health screening examinations ; the reported adenoma detection rate in korea varies , but is approximately 9% during screening examinations . diagnosis and removal of colorectal polyps is increasing because of the widespread availability of colonoscopy . follow - up colonoscopy is required to reduce the risk of colorectal carcinogenesis after polypectomy for adenoma . metachronous lesions were detected in 20% to 30% of patients during follow - up colonoscopy 3 to 5 years after polypectomy to remove one or more adenomas [ 3 - 7 ] . advanced adenomas ( > 10 mm in diameter , over 25% villous component , or high - grade dysplasia ) were found in 20% of these patients [ 3 - 8 ] , and a small number had invasive colorectal cancer [ 5,9 - 14 ] . in addition , interval cancer was reported during an adequate follow - up period after screening colonoscopy [ 15 - 17 ] , and 19% to 27% of such interval cancers are known to be caused by incomplete removal of polyps . enhanced colonoscopy surveillance may be needed for screening of patients at high risk of colorectal carcinogenesis , for prediction of progressive colorectal tumor development , management of incompletely removed polyps , and appropriate follow - up . follow - up colonoscopy is required because the risk of colorectal cancer after polypectomy is higher than that in patients without polyps . an appropriate interval for follow - up colonoscopy was recommended in korea in 2012 , based on features of polyps detected by colonoscopy and the risk of progression to an advanced neoplasm during this interval . it is known that number , size , and histological characteristics","the detection and removal of adenomatous polyps and postpolypectomy surveillance are considered important for the control of colorectal cancer ( crc ) . surveillance using colonoscopy is an effective tool for preventing crc after colorectal polypectomy , especially if compliance is good . in current practice , the intervals between colonoscopies after polypectomy are variable . different recommendations for recognizing at risk groups and defining surveillance intervals after an initial finding of colorectal adenomas have been published . however , high - grade dysplasia and the number and size of adenomas are known major cancer predictors . based on this , a subgroup of patients that may benefit from intensive surveillance colonoscopy can be identified .",380,116,0.3053
pubmed-summarization,"brand , multiple lenses from each power tested rms roughness and peak - to - peak values were obtained by analysing three 20 m 20 m regions ( front curve , back curve , pigmented and non - pigmented ) of these images . four replicates of rms and peak - to - peak measurements were selected for each area within each lens at a given location or pigment status . thus , a total of 12 measurements were recorded for each lens at a given location or pigment area . data from rms and peak - to - peak responses were determined to be log - normally distributed . these responses were analysed separately using a generalised linear mixed model with a log - normal distribution . location ( front versus back curve ) , pigment area ( pigmented versus non - pigmented ) and lens brand were included as fixed effects . all two - way and three - way interactions between location , pigment and brand were also included as fixed effects . replicates nested within lens number and area number were modelled as random effects within each brand . least squares mean values and their corresponding 95% confidence intervals were estimated for each brand , location and pigment combination . results from the sem image analyses were used to determine the appropriate pair - wise comparisons between lens brands . pair - wise comparisons were made for each lens brand for pigment versus no pigment on the lens surfaces . in this study , since the analysis was completed on the log - scale , the afm estimates and their interval bounds were exponentiated to provide model - based estimates on the original , untransformed scale . since multiple comparisons were considered , a simulation adjustment for alpha was completed to control the the lens samples were removed from the manufacturer packaging , placed front ( convex ) surface down on a clean glass slide , cross - sectioned with a razor blade and mounted onto a lens holder for sem imaging with a hitachi model s-3400n sem at an iso 17025 accredited laboratory . the images were recorded at an acceleration voltage of 10 kv under variable pressure ( 3050 mpa ) operating mode and","backgroundlimbal ring ( also known as circle ) contact lenses are becoming increasingly popular , especially in asian markets because of their eye - enhancing effects . the pigment particles that give the eye - enhancing effects of these lenses can be found on the front or back surface of the contact lens or enclosed within the lens matrix . the purpose of this research was to evaluate the pigment location and surface roughness of seven types of circle contact lenses.methodsscanning electron microscopic ( sem ) analysis was performed using a variable pressure hitachi s3400n instrument to discern the placement of lens pigments . atomic force microscopy ( dimension icon afm from bruker nano ) was used to determine the surface roughness of the pigmented regions of the",380,128,0.3368
dialogsum,"#Person1#: John, I ' d like you to meet Charles Brown, our new manager at the airport. #Person2#: Yes, certainly. How can I recognize him? #Person1#: He is short, well-built, and he ' s got light blond hair. #Person2#: Is there anything else? #Person1#: He has a mustache, if I remember correctly, and a light complexion. #Person2#: How old is he? #Person1#: He is in his late thirties. #Person2#: Well. I shouldn ' t have any trouble recognizing him. What time does his flight arrive? #Person1#: At 2 thirty.",#Person1# asks John to meet Charles Brown at the airport and tells him how to recognize Brown.,89,17,0.191
dialogsum,#Person1#: How do you feel about that restaurant? #Person2#: It wasn't all that great. #Person1#: What did you dislike the most? #Person2#: I don't think that they had their act together. They didn't seem well prepared. #Person1#: Did you think that the food was any good? #Person2#: I wasn't all that impressed by the food. #Person1#: The service certainly could have been better. #Person2#: The service did not help the situation. #Person1#: Is this a restaurant that you want to come back to? #Person2#: I am not interested in trying this restaurant again.,#Person2# tells #Person1# #Person2# isn't satisfied with the restaurant and would not come again.,93,14,0.1505
dialogsum,"#Person1#: Honey, which hand should I use to hold the fork? #Person2#: Left for the fork and right for the knife. Just remember that the stronger one is for knife. #Person1#: Got it. It's so troublesome to have western food. I've been learning the table manners for hours but still can't really it. #Person2#: Sure. Rather than eating, having western food is more about western culture. #Person1#: Yeah. Which restaurant are we going to tonight? #Person2#: Cindy has reserved a table for us at a newly opened western restaurant downtown. She said the environment there was really pleasant. #Person1#: Fine. I believe in Cindy's taste. Oh, what should I wear? #Person2#: You should put on the black suit I bought for you last week. But I'm afraid it may be a bit crumpled. You'd better iron it now. #Person1#: I don't want to mess it up. Please do it for me. I'm going to the bank to cash some money. How much do we need? #Person2#: There is no need to do that. I think the restaurant accepts credit cards. But it's necessary to make a budget. #Person1#: Honey, you are a good accountant. So I'd better leave that to you, too. #Person2#: It seems that it's all about me. Then what do you do? #Person1#: I'll take care of the order. #Person2#: OK then. Well, 50 Yuan for appetizer, 200 Yuan for dinner and 200 Yuan for wine. Anything else? #Person1#: Don't forget about the dessert. #Person2#: OK, then 50 Yuan for dessert. 500 Yuan all together.",#Person1# asks #Person2# about western table manners and what to wear for their dinner in a western restaurant. #Person2# makes a budget for the dinner.,258,25,0.0969
dialogsum,"#Person1#: Bob, did you see our supervisor? I need him to sign this paper. #Person2#: He is in his office, but you'd better choose your words carefully while talking to him. #Person1#: What's up? #Person2#: Nothing. But he is in a bad mood today. #Person1#: Thanks for the warning. #Person2#: That's all right.",Bob reminds #Person1# to choose words carefully while talking to the supervisor.,53,12,0.2264
dialogsum,"#Person1#: Emily, what do you do as a trendspotter? #Person2#: Very simple. Take digital photos of youth culture and send them to my company. It's called Look-Look. #Person1#: What kind of company is it? #Person2#: It's a youth culture marketing and trend forecasting firm in Hollywood. I'm one of Look-Look's 65,000 trendspotters worldwide. #Person1#: Look-Look gets a lot of information about the ever-shifting tastes of the youth market by these images. #Person2#: Yes, its clients are mostly companies. They get information about trends from Look-Look and develop their products. They also use the images of Look-Look on their websites to impress young people and promote their newly designed products. #Person1#: But are there any people who don't like their pictures to be used on the website? #Person2#: I always have my subjects' permission before I take their pictures and put up their images onto Look-Look.com. #Person1#: Where do you find your best subjects? #Person2#: At school, in the park, at local supermarkets and near many music clubs. #Person1#: What is difficult about this job? #Person2#: To catch our original styles because so many young people try hard to stand out. You have to be able to find the difference between someone who is copying trends and someone who is truly inventing a new look. #Person1#: Thank you for talk with us, Emily.",Emily tells #Person1# about her responsibilities as a trendspotter and introduces her company called Look-Look.,222,15,0.0676
pubmed-summarization,". primary small cell carcinoma of the tonsil is rare ; only 11 cases have been reported . the prognosis of patients with epscc of the tonsil has been poor , as 6 of those 11 patients died from the disease mainly due to systemic metastasis . when a diagnosis of epscc arising in the head and neck region is made , the patient should be evaluated first to determine whether the disease is a primary or metastatic cancer . primary sclc is rarely occult because it is aggressive and fast - growing . in our case , chest and abdominal ct and fdg - pet revealed no other lesions , and the tonsillar mass was determined to be the primary lesion . the histopathological aspects of epscc include round , oval- to spindle - shaped small cells with dense chromatin , absence of nucleoli , and inconspicuous cytoplasm . mitosis , necrosis , apoptosis , and lymphatic , vascular , and perineural invasion are common . immunohistochemical staining for neuroendocrine markers , including chromogranin a , synaptophysin , and cd56 , is usually positive . in this case , histologic features and immunoreactivity for neuroendocrine markers were suggestive of epscc . although the treatment of this tumor has not been defined clearly , it can require surgical excision of the localized tumor , radiation therapy to the primary site , multiple - drug chemotherapy , or a combination of these modalities . platinum - based chemotherapy , such as the use of etoposide ( vp-16 ) and cddp , has been recognized as the standard regimen for epscc . recently , cpt-11 combined with cddp was found to be more effective than vp-16 and cddp . two cases of chemotherapy using cpt-11 and cddp have been reported for epscc arising in the head and neck region : one in the larynx and the other in the nasal cavity . both cases achieved long - term remission . in our case , radiation therapy to primary and locoregional sites followed by immediate chemotherapy with cpt-11/cddp resulted in complete remission of the tumor , although the patient later died of liver metastasis . in this report , we describe a case of small cell carcinoma of the tonsil treated by combined",we report a rare case of extrapulmonary small cell carcinoma arising in the palatine tonsil treated by combined chemotherapy with irinotecan / cisplatin following irradiation therapy . this chemotherapy regimen was recently found to be effective for small cell lung carcinoma . our case is the first report of combined irinotecan / cisplatin chemotherapy to treat extrapulmonary small cell carcinoma of the oropharynx .,380,64,0.1684
dialogsum,"#Person1#: Suiz worte me a letter. #Person2#: What did she say? #Person1#: She got a master degree, and now she is going for her doctor. #Person2#: Really? I can't believe it. #Person1#: It's not a surprise, is it? She has always been a hard working student. #Person2#: But I think a master degree is good enough for a girl.",#Person1# tells #Person2# Suiz is going for a doctor's degree. But #Person2# thinks a master's degree is enough for a girl.,59,21,0.3559
pubmed-summarization,"neglected tropical diseases ( ntds ) is an umbrella term used to describe infectious diseases that primarily affect low - income populations in tropical regions and are often widespread , chronic , and debilitating . although the number of diseases that are officially recognized as ntds by various public health authorities ranges from less than 10 to over 40 , the list of 17 diseases currently classified as ntds by the world health organization ( who ) is widely accepted as accurate and comprehensive ( 20 ) . of these 17 diseases , four are caused by bacterial pathogens ( buruli ulcer , leprosy , trachoma , and yaws ) , three are caused by protozoan parasites ( chagas disease , human african trypanosomiasis and leishmaniasis ) , two are viral ( dengue and rabies ) , and the other eight are caused by various species of parasitic worms ( 20 ) . the most recent data available indicating the estimated number of cases of each ntd are listed in table 1 . estimated number of cases of neglected tropical diseases ( ntds ) worldwide . prevalence ( total number of existing and new cases ) is reported for chronic ntds and incidence ( total number of new cases ) is reported for acute ntds or ntds with a high rate of recurrence . cdc , centers for disease control ; cfsph , center for food security and public health , iowa state university ; n / a , data not available ; who , world health organization . ntds exert an immensely deleterious effect on the public health and economies of much of the developing world . yet , by definition , ntds are issues for which the levels of awareness and resources necessary to develop effective solutions have not been sufficiently garnered . because ntds are largely confined to poor areas and have relatively low mortality rates , the policy makers and financiers of global health campaigns may underestimate or simply not be aware of the magnitude of the problem . it is for precisely these reasons ( that ntds are chronically debilitating , affect a large number of indigent people , and are often overlooked ) that it is crucial to increase the amount of education ,","neglected tropical diseases constitute a significant public health burden , affecting over one billion people globally , yet this group of diseases is underrepresented in the appropriation of both monetary and intellectual capital for developing improved therapies and public health campaigns . the topic of neglected tropical diseases has been similarly marginalized in the biology classrooms of our nation s high schools and colleges , despite offering an opportunity to teach and learn about a diverse area of microbiology with far - reaching public health , social , and economic implications . discussed herein is an argument for increasing the representation of neglected tropical diseases in microbiology education as a means to generate increased interest in these diseases among the generation of future researchers and policy - makers",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Metagenomics has revealed hundreds of species in almost all microbiota. In a few well-studied cases, microbial communities have been observed to coordinate their metabolic fluxes. In principle, microbes can divide tasks to reap the benefits of specialization, as in human economies. However, the benefits and stability of an economy of microbial specialists are far from obvious. Here, we physically model the population dynamics of microbes that compete for steadily supplied resources. Importantly, we explicitly model the metabolic fluxes yielding cellular biomass production under the constraint of a limited enzyme budget. We find that population dynamics generally leads to the coexistence of different metabolic types. We establish that these microbial consortia act as cartels, whereby population dynamics pins down resource concentrations at values for which no other strategy can invade. Finally, we propose that at steady supply, cartels of competing strategies automatically yield maximum biomass, thereby achieving a collective optimum. In this section, we present a model for the population dynamics of cell types metabolically competing for external resources (see ). Importantly, biomass production is governed by a physical model that respects flux conservation. 10. 7554/eLife. 22644. 003Figure 1. Model for metabolically competing cell types. (A) The rate of biomass production g⁢ (c1, …, cp) is a function of the internal building-block concentrations. (B) Biologically relevant growth-rate functions g⁢ (c1, …, cp) are increasing with respect to ci with diminishing returns. (C) Different cell types, i. e. metabolic strategies, are defined as specific distributions of enzymes for import αi and conversion κj⁢i, subject to a finite budget. (D) Cell types (e. g. σ1 and σ2) compete for external building blocks that are steadily and homogeneously supplied in volume V. : http: //dx. . org/10. 7554/eLife. 22644. 003 In this section, we demonstrate the possibility of stable coexistence at steady supply rates by simulating competitive population dynamics subject to continual invasion by new metabolic variants. We consider that coexistence is stable when a population of distinct cell types can resist invasion by any other metabolic variants. In our simulations, cell types have distinct metabolic strategies defined by randomly chosen enzyme distributions {αi, κj⁢i} satisfying the budget constraint Equation (2), with the universal growth-rate function Equation (1) and uniform biomass stoichiometry (bi=1). First, we show that competitive population dynamics with the continual introduction","Microbes are found in virtually every environment on Earth. Like other organisms, microbes grow by using enzymes to convert nutrients into proteins, DNA and other molecules that make up their cells. Together, these chemical transformations define the “metabolism” of a microbe. In any given environment, there is almost always a diverse variety of microbes living together. Different microbes in these communities will use different combinations of enzymes to exploit the available nutrients, and members of well-studied communities have been found to work together to make the most of the nutrient source. This is remarkable because one might expect competition between microbes to select for a single “best” microbe, rather than diverse communities. The economic concept of “division of labor” suggests that if microbes divide chemical tasks between each",380,128,0.3368
dialogsum,"#Person1#: What do you do in the evening, John? #Person2#: I go to the school Theatre club every Tuesday evening. The rest of the week I usually stay home. I don't like the city very much. #Person1#: Why don't you like the city? #Person2#: Before I moved here, I lived in a village. I knew all the people in my neighborhood. #Person1#: Life is different in the city. #Person2#: I know, but the village was quiet and there was only a little traffic. I hate the noise in the busy roads here. #Person1#: So do I. I live near a busy road. Sometimes the noise keeps me awake at night. #Person2#: I hate crossing the road the most. They're bikes, motorbikes and cars coming from every direction. They really scare me.",John tells #Person1# that he doesn't like the city life because of noisy sounds and traffic.,131,16,0.1221
scientific_lay_summarisation-elife-norm,"al. , 2006). However, the full trajectory of dynein motors in three dimensions (3D) remains unknown, because the motors are sterically prevented from moving around the circumference of surface-immobilized MTs. We next investigated the helical motility of cytoplasmic dynein. We used a tail-truncated yeast dynein artificially dimerized with glutathione S-transferase (GST-Dyn331kD), which has similar motile properties to full-length dynein (Reck-Peterson et al. , 2006). The motors were fused to GFP at the N-terminus and attached to cargo beads coated with anti-GFP antibodies (see ‘Materials and methods’). At 1 mM ATP, dynein-coated beads moved in helical trajectories with a pitch of 591 ± 32 nm (mean ± SEM, 67 rotations, 15 beads, 2A–C). This rotation corresponds to a sideways movement to a neighboring protofilament (6 nm) for every six tubulin dimers (48 nm) in the forward direction. Unlike axonemal dynein and kinesin motors, which primarily rotate along their tracks in only one direction (Vale and Toyoshima, 1988; Brunnbauer et al. , 2012), beads coated with cytoplasmic dynein exhibited both left- and right-handed helical movement on MTs (N = 67 rotations, 2A–B, —supplements 1 and 2, Videos 2,3). The speeds of left- and right-handed movements along the helical path (79 ± 4. 7 nm/s and 89 ± 17 nm/s, mean ± SEM, respectively) were statistically indistinguishable (t-test, p = 0. 28). Bidirectional helical movement was also evident from traces of single beads, which occasionally switch direction during a run (4 out of 67 rotations, 2D). In contrast, reversal of bead motility along the MT axis was never observed. 10. 7554/eLife. 03205. 006Figure 2. Dynein moves in both left- and right-handed helical paths along MT bridges. (A and B) (top) Representative three-dimensional trace of a cargo bead-driven by GST-Dyn331kD motors shows left- (A) and right-handed (B) helical motion. (bottom) Two-dimensional projections of the traces shown at top. (C) Histogram of observed pitches per complete rotation. The average pitch is 591 ± 32 nm (mean ± SEM). The average pitch of the left-handed movement (546 ± 42 nm, SEM, N = 32) was shorter (t-test, p = 0. 01) than that of the right-handed movement (749 ± 81 nm, SEM, N = 10). (D) Change in handedness of rotation during the transport of a cargo bead. An example trace shows that a cargo bead","Cells rely on ‘molecular motors’ travelling along tracks called microtubules to move proteins and other cargoes between different parts of a cell. Dynein is a molecular motor that moves along the microtubules by taking “steps” towards the slowly growing end of these tracks. The trajectories of dynein motors have been studied extensively using techniques that can follow their movements in two dimensions. However, some molecular motors can also rotate as they travel, creating a twisting force called a torque that causes the motor to spiral around the microtubule in a helix. To assess the torque that dynein can generate and to better understand its movements in three dimensions, Can et al. used a length of microtubule to build a ‘bridge’ between two polystyrene beads. The dynein motors were",380,128,0.3368
dialogsum,#Person1#: I can't decide what to do today. #Person2#: Well. Let's go swimming. #Person1#: Don't you think it's a bit cold for that? #Person2#: Then why don't we go for a walk in the hills. It'd be very good for us you know.,#Person2# invites #Person1# to walk in the hills.,43,8,0.186
pubmed-summarization,"cell for microbial killing to occur ( (b ) ) . this is thought to be mediated through perforin - generated pores in the host cell membrane . these pores facilitate the influx of extracellular ca which triggers the target cell to endocytose the damaged region of the membrane and internalize nearby granulysin . alternatively , ctl may mediate lysis of the infected host cells releasing microbes which may then be recognized and killed by nearby ctl ( (c ) ) . to acquire microbicidal activity , this priming event can occur in response to cytokines such as t cell growth factors , stimulation by a mitogen , or antigen - specific responses . the receptors and signalling pathways involved in priming may be the same , but also might be quite distinct from the receptors and signalling that lead to immediate killing . following the priming event , the microbicidal ctl is then ready to receive the signal that triggers them to kill the pathogen . t cells from mice immunized with p. aeruginosa polysaccharide were stimulated with macrophages from nonimmune mice with or without the addition of heat - killed bacteria . macrophages had to be present during the priming , but surprisingly , heat - killed bacteria did not . this suggested that the bactericidal activity of these t cells was dependent on their interaction with macrophages but did not require presentation of p. aeruginosa antigens . supernatants collected from immune t cells exposed to macrophages and p. aeruginosa were found to kill p. aeruginosa in addition to staphylococcus aureus and escherichia coli suggesting that these t cells were producing a soluble bactericidal product . ctl have also been found to mediate killing of mycobacterium tuberculosis through the release of bactericidal products . m. tuberculosis growth was reduced as much as 74% in the presence of cd4 ctl and 84% in the presence of cd8 ctl . when cd8 ctl were pretreated with strontium chloride ( which depletes granule contents ) , it caused a clear reduction in the ability to kill m. tuberculosis that correlated with a marked decrease in granulysin content . in vitro , purified granulysin was able to kill extracellular m. tuberculosis in a dose - dependent fashion . however , killing of","cytotoxic t - lymphocytes ( ctl ) are famous for their ability to kill tumor , allogeneic and virus - infected cells . however , an emerging literature has now demonstrated that ctl also possess the ability to directly recognize and kill bacteria , parasites , and fungi . here , we review past and recent findings demonstrating the direct microbicidal activity of both cd4 + and cd8 + ctl against various microbial pathogens . further , this review will outline what is known regarding the mechanisms of direct killing and their underlying signalling pathways .",380,96,0.2526
dialogsum,"#Person1#: Jack, I don't know how to write my resume. Could you tell me about that? #Person2#: You should first write your name and contact information. #Person1#: What does the contact information include? #Person2#: Such as your land line phone number, mobile phone number and e-mail box. #Person1#: Anything else? #Person2#: Then you should write your objectives, such as seeking a position in foreign trade. #Person1#: I see. It is the position desired #Person2#: Yes. After that you should emphasize your skills, educational background and related experience. #Person1#: I see. Skills are about specialty, and educational background is easy as well. But what about related experience? I have little work experience. #Person2#: Don't worry. It will take time to accumulate experience. You need to be confident for yourself. #Person1#: I see. By the way, should I write the educational background starting from elementary school? #Person2#: Generally from the college #Person1#: Thank you very much. I will write it right now.",#Person1# doesn't know how to write #Person1#'s resume and asks Jack for help. Jack instructs #Person1# and encourages #Person1# to stay confident.,160,22,0.1375
dialogsum,"#Person1#: It was so terrible yesterday. #Person2#: What happened? #Person1#: Well, everything went wrong. In the morning, I went to the hotel to pick up an important customer, but was caught in a jam on the way. When I arrived at last, the customer had already left. #Person2#: No, sorry to know that. #Person1#: When I hurried to the office, I was told that something was wrong with the fax machine. #Person2#: Oh, that was a bad luck. #Person1#: What's worse, I forgot to go to school for the parents' meeting in the afternoon. #Person2#: Oh, no. The teacher must have been angry with you. #Person1#: Yes. And that is not all. When I returned home, the kids were angry and hungry. And I found there was nothing in the refrigerator. #Person2#: Oh, my God.",#Person1# tells #Person2# about the terrible day #Person1# had yesterday. #Person2# feels sorry for #Person1#.,135,15,0.1111
dialogsum,"#Person1#: Great! I landed on Classic Movies. #Person2#: I didn't know you liked old movies. #Person1#: I love them, especially the all-time greats like Gone With the Wind. #Person2#: You're so right! Today's movies are just too commercial! #Person1#: Sometimes I think Oscars are only awarded to movies that make a lot of money.",Both #Person1# and #Person2# think today's movies are too commercial.,54,10,0.1852
scientific_lay_summarisation-elife-norm,"et al. , 1993). Ca2+ sparks are not only elicited by LTCC opening, but also occur spontaneously during diastole, where spark frequency and geometry can be measured to assess CRU function. While Ca2+ sparks are an important source of RyR-mediated Ca2+ leak from the SR, ‘silent’ or ‘non-spark’ events also occur, and involve the opening of a subset of RyRs within a CRU; so-called ‘quarky’ release (Brochet et al. , 2011). Impaired cardiomyocyte Ca2+ homeostasis is believed to importantly contribute to reduced cardiac contractility and arrhythmogenesis in heart failure (HF). SR Ca2+ release is reduced and slowed in this condition, and these changes have been linked to altered dyadic structure (Louch et al. , 2010). We and others have observed marked remodeling of the t-tubular system in failing cardiomyocytes, while RyRs remain predominantly distributed along z-lines (Song et al. , 2006; Louch et al. , 2006; Heinzel et al. , 2008). Thus, the coupling between LTCCs and RyRs is disrupted, with ‘orphaned’ CRUs exhibiting delayed Ca2+ release only after trigger Ca2+ diffuses from intact dyads. However, abnormal gaps occurring between t-tubules only account for a fraction of the overall de-synchronization of Ca2+ release in HF (Louch et al. , 2006; Øyehaug et al. , 2013). This suggests that other alterations might also occur, perhaps at the nanometer scale of CRU organization, which hinder efficient triggering of Ca2+ release. CRU reorganization could in principle contribute to increased Ca2+ leak, including silent leak, which is a hallmark of heart failure (Zima et al. , 2010; Walker et al. , 2014). Exaggerated Ca2+ leak in failing cells has been linked to reduced SR Ca2+ content and depressed contractile function, elevation of resting Ca2+ levels and impaired relaxation, pro-arrhythmic early and delayed afterdepolarizations, and energetic inefficiency as Ca2+ is redundantly cycled (Bers, 2014). Thus, a detailed understanding of CRU structure and function in failing cells is critical. The advent of super-resolution microscopy techniques has markedly improved our ability to visualize and quantify CRU organization (Baddeley et al. , 2009; Macquaide et al. , 2015; Jayasinghe et al. , 2018). However, these techniques have not previously been employed to examine RyR configuration in HF. Using direct stochastic optical reconstruction microscopy (dSTORM), we presently report that CRUs become dispersed in failing myocytes, as RyR clusters are","The muscle cells of the heart coordinate how they contract and relax in order to produce the heartbeat. During heart failure, these cells become less able to contract. As a result the heart becomes inefficient, pumping less blood around the body. For the cardiac muscle cells to contract, the levels of calcium ions in the cells needs to rapidly increase. In failing hearts, these increases in calcium ion levels are smaller, slower and less well coordinated. It was not known what causes these changes, making it difficult to treat heart failure. Calcium ions are released in cardiac muscle cells through protein channels called ryanodine receptors. These receptors form clusters that allow them to synchronize when they open and close. Could the reorganization of ryanodine receptors account for the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Rtt109. Moreover, Pkc1 also promotes H3T45 phosphorylation and this modification is important for the coordinated deposition of H3K56 acetylation. To examine whether Pkc1 has a role in protecting cells from replicative stress we first determined cell sensitivity to hydroxyurea (HU) in the presence and absence of active Pkc1. To do this we made use of strains containing temperature sensitive pkc1 alleles which could be inactivated by incubating yeast cells at 34ºC, thereby negating the confounding effects of heat shock stress response obtained using the traditionally used pkc1ts allele (Anastasia et al. , 2012). In comparison to cells containing wild-type PKC1 (DK186), temperature sensitive pkc1-14 (DK1690) cells, grown at 34ºC to inactivate Pkc1 were inviable (1A, top panel) consistent with previous studies using a pkc1Δ deletion strain (Queralt and Igual, 2005). Loss of PKC1 function results in cell lysis in the absence of osmotic support. The presence of sorbitol saved the pkc1-14 mutant phenotype (1A, middle panel) but HU sensitivity was observed under these conditions (1A, bottom panel). This suggested a role for Pkc1 other than signalling through the well studied downstream MAP kinase cascade which includes the kinase Bck1 (Lee et al. , 1993). Indeed bck1Δ (Y01328) cells were not sensitive to HU, further emphasising a new alternative mechanism of action for Pkc1 under replicative stress conditions (1A). To determine whether the kinase activity of Pkc1 is needed to protect cells from replicative stress, we attempted to rescue pkc1-14 cells by re-expressing a catalytically dead (KD) version of Pkc1 in the presence of HU. However, while wild-type (WT) Pkc1 was able to rescue the growth defect of pkc1-14 cells, the catalytically dead version was unable to do so (1B). 10. 7554/eLife. 09886. 003Figure 1. Pkc1p is required for cell viability and chromatin integrity in the presence of hydroxyurea. (A and B) Cell growth assays. (A) 10 fold serial dilutions of wild-type (WT) (DK186), pkc1-14 (DK1690) or bck1Δ (Y01328) cells were plated onto YPD media in the presence or absence of 1M sorbitol or (B) pkc1-14 (DK1690) cells containing empty vector or plasmids expressing WT or kinase dead (KD) Pkc1, were plated onto SD media in the presence 1M sorbitol. Cells were grown at 34ºC and where indicated, 100 mM HU was added to the media. : http: //dx. . org/10.","Prior to cell division, DNA must be copied so that each new cell gets a complete copy of the cell’s genetic instructions. But DNA is so long that it is stored in a heavily compacted form in the nucleus of the cell, with the strands of DNA coiled around several proteins called histones. Before the DNA is copied, it must be unfurled. Then each new copy of DNA must be repackaged to fit compactly inside the nucleus of each new cell. If errors occur in the process of copying DNA, it can lead to genetic mutations that may cause diseases like cancer. To prevent this, cells have mechanisms to identify errors and correct them before the DNA is repackaged. This requires a pause to allow the repairs to",380,128,0.3368
pubmed-summarization,"hydras ( 1 : 1 ) ( 1020 mg kg body weight ) . all animal procedures were performed according to guide for the care and use of laboratory animals published by the institute for laboratory animal research . , mice ensured to natural light - adapted state were weighted and anesthetized as above mentioned . self - modified electrodes were made of acupuncture needles , welded to the signal - recorded wire . a recording electrode ( 0.25 mm diameter silver wire configured to a semicircular loop of 2 mm radius ) reference and ground electrodes were inserted under the skin of ipsilateral pars buccalis and tail , respectively . the pupils were not dilated , and eyes were not refracted for the viewing distance since the mouse eye has a large depth of focus . visual stimuli consisted of horizontal bars with a contrast of 99% at 0.05 cycles / degree spatial frequency , 1 hz temporal frequency . perg waveforms consisted of two main waves : a positive wave with a peak latency of 90 to 100 ms ( p1 ) followed by a broad negative with peak latency in the range of 200 to 300 ms ( n1 ) . after anesthetizing , mice were dilated with tropicamide 1% and underwent spectral domain oct ( cirrus hd - oct , zeiss meditec , germany ) as reported elsewhere . in brief , mice were placed on the three - dimensional table . the mouse eyeball was coated with viscoelastic material and covered with a coverslip to form a plano - concave lens . then the 90 dpt noncontact slit lamp lens ( volk , superfield nc , volk optical inc . , macular cube scanning in the cirrus hd - oct was performed with the 512 128 scan pattern where a 6 6 mm area on the retina is scanned with 128 horizontal lines , each consisting of 512 a - scans per line with the scanning speed of 27000 a - scans per second . during the analysis procedure then retinal thicknesses are averaged in nine retinal subfields which are an area of a 6 mm diameter circle centered on the mouse optic disk . the eyes were dipped in ffa ( mixture of 95%","purpose . to describe both the functional and pathological alternations in neurosensory retina in a murine model of spontaneous type 2 diabetes ( db / db mouse ) . methods . db / db ( bks / db/ ) mice and heterozygous littermates ( as control group ) at various ages ( 12 , 16 , 20 , 24 , and 28 weeks ) were inspected with pattern electroretinogram ( perg ) , fundus fluorescein angiography ( ffa ) , and optical coherence tomography ( oct ) . histological markers of neuroinflammation ( iba-1 and f4/80 ) were evaluated by immunohistochemistry . in addition , levels of retinal ganglion cell death were measured by terminal dutp nick - end labeling ( tunel ) . results . significant alternations",380,128,0.3368
pubmed-summarization,"protocol . these fasting tests , in addition to gtts and hba1c , were considered the screening tests for this analysis . although hba1c was not an accepted test for diabetes screening during the study years , it was included in our screening profile and used in the sensitivity test since it is known that providers used hba1c for this purpose because of its recent incorporation into guidelines ( 5 ) . eight high - risk variables were defined based on the ada - designated risk factors for screening ( 5 ) . these factors include 45 years of age , ethnicity , hypertension , hypercholesterolemia , polycystic ovarian syndrome ( pcos ) , vascular disease , overweight ( bmi 25 kg / m ) , and history of prediabetes . the ada risk factors of first - degree family history , physical inactivity , and other clinical conditions associated with insulin resistance could not be obtained . definitions for high - risk variables were determined based on a combination of one or more factors , including validated international classification of diseases , 9th revision ( icd-9 ) codes ( 8) , laboratory data , and clinical information , with detailed criteria for each high - risk factor listed previously ( 6 ) . in brief , diagnosis of hypertension , pcos , prediabetes , and vascular disease was determined by presence of two validated diagnosis codes on two separate occasions within 2 years by previously established criteria ( 6 ) . age was determined as the age as of 1 january 2005 ; overweight was determined by having two icd-9 codes by the same criteria above or if last listed bmi was 25 kg / m ; and hypercholesterolemia was also defined by the presence of two icd-9 codes or by the presence of abnormal laboratory tests ( 6 ) . patients with a listed ethnicity of african american , latino , native american , asian american , or pacific islander were designated as high - risk minorities . using the defined high - risk factors , the population meeting ada screening criteria was determined . this included any patient 45 years of age or any overweight patient < 45 years with at least one additional high - risk","objectiveethnicity has been identified as a risk factor not only for having type 2 diabetes but for increased morbidity and mortality with the disease . current american diabetes association ( ada ) guidelines advocate screening high - risk minorities for diabetes . this study investigates the effect of minority status on diabetes screening practices in an ambulatory , insured population presenting for yearly health care.research design and methodsthis is a retrospective population based study of patients in a large , midwestern , academic group practice . included patients were insured , had 1 primary care visit yearly from 2003 to 2007 , and did not have diabetes but met ada criteria for screening . odds ratios ( ors ) , 95% confidence intervals ( ci ) , and",380,128,0.3368
dialogsum,"#Person1#: Frank, I want your advice on something. Some scientists I met at the conference 6 this afternoon have invited me to a party. Actually, they called it an informal get-together. #Person2#: And what's the problem? #Person1#: When I asked how people were going to dress, Dr. Lite said it was casual. #Person2#: And you want to know what to wear? #Person1#: Well, last night I went out with some journalists for a casual party, but I was overdressed. I wore what I consider casual - - an outfit of skirt, blouse, scarf, and medium heels. . . you know. #Person2#: That sounds just right to me. What was wrong with it? #Person1#: Everyone else there was wearing blue jeans. Several of the women had on running shoes. I felt out of place. So I have no idea what to wear tonight. #Person2#: My guess is you can safely wear last night's outfit to tonight's party.",#Person1# asks Frank to give some advice on what to wear for a casual party. Frank suggests #Person1# wear last night's outfit to tonight's party.,156,25,0.1603
pubmed-summarization,"soil - transmitted helminths ( sth ) or geohelminths infect more than 2 billion people worldwide , especially in developing countries located in tropical and subtropical regions . the most prevalent species are ascaris lumbricoides ( roundworm ) , trichuris trichiura ( whipworm ) , and hookworms ( necator americanus and ancylostoma duodenale ) . children and women of childbearing age are among the high - risk groups for these parasitic diseases . the morbidity caused by sth infections is highly associated with the size of the worm population residing in the intestines ( also known as worm burden ) . infections of heavy intensity are more likely to cause impaired physical growth and cognitive development as well as micronutrient deficiencies , including iron - deficiency anaemia . further , due to their chronic and insidious nature , even light intensity infections may compromise health outcomes . to reduce the morbidity caused by these parasitoses , the world health organization ( who ) recommends cyclical ( annual or biannual ) benzimidazole - based mass drug administration to groups at high - risk of infection , especially pre- and schoolchildren . the basic premise of this strategy is that even though this intervention may not decrease transmission and prevalence , it will in time reduce hosts ' worm burden with the ensuing reduction in health impact . in addition to health impact , sth infections affect the human host in more subtle manner : as extracellular metazoan parasites , helminths trigger type-2 immune response mediated by t - helper type 2 ( th2 ) cells . this response is typically characterized by expansion of mast cells , eosinophils , basophils , group 2 innate lymphoid cells ( ilc-2 ) , and alternatively activated macrophages ( aams ) , as well as increased production of th2 cytokines ( e.g. , il-4 , il-5 , il-9 , and il-13 ) and ige . on the other hand , intracellular pathogens such as viruses , bacteria , protozoa , and fungi elicit a type-1 response , characterized by increased numbers of phagocytic neutrophils and macrophages , as well as cytotoxic cd8 t cells and th1 cells . antigen - presenting dendritic cells ( dcs ) secrete interleukin- ( il- ) 12 promoting differentiation of","soil - transmitted helminth infections typically induce a type-2 immune response ( th2 ) , but no immunoepidemiological studies have been undertaken in honduras , an endemic country where the main control strategy is children 's annual deworming . we aimed to characterize the immune profile of honduran schoolchildren harbouring these parasitoses . demographic and epidemiological data were obtained through a survey ; nutritional status was assessed through anthropometry ; intestinal parasites were diagnosed by formol - ether and kato - katz ; and blood samples were collected to determine immunological markers including th1/th2 cytokines , ige , and eosinophil levels . a total of 225 children participated in the study , all of whom had received deworming during the national campaign five months prior to the study",380,128,0.3368
dialogsum,"#Person1#: Hi, how are you doing? #Person2#: I'm fine. How about yourself? #Person1#: I'm pretty good. Thanks for asking. #Person2#: No problem. So how have you been? #Person1#: I've been great. What about you? #Person2#: I've been good. I'm in school right now. #Person1#: What school do you go to? #Person2#: I go to PCC. #Person1#: Do you like it there? #Person2#: It's okay. It's a really big campus. #Person1#: Good luck with school. #Person2#: Thank you very much.",#Person1# and #Person2# greet each other and #Person2# tells #Person1# that #Person2# is in school now.,79,16,0.2025
dialogsum,"#Person1#: How did you do in the last quiz? #Person2#: I doubt if I can pass it. #Person1#: Don't be so worried, You know Professor Robert is not too strict. #Person2#: But I often skip his classes, and he doesn't like me. #Person1#: I hope you'll do better in the final. #Person2#: I must, if I want to pass the course.",#Person2# is worried that #Person2# will fail the exam. #Person1# cheers up #Person2#.,61,13,0.2131
dialogsum,"#Person1#: Daddy, I love this Happy Farmhouse. It's really fun. #Person2#: Great. But no talking, now. Don't forget that you are on a ladder. Take care! #Person1#: But you are holding it for me. Nothing to worry about. I trust you. Oops, what's that? #Person2#: Don't touch it with your stick. It's a bumble bees' hive. Get down the ladder. Be quick. #Person1#: What would happen if they started attacking you? #Person2#: You can get killed. No kidding. Remember, never stir up a hive. #Person1#: I see. Why do people come all the way here to pick apples by themselves and take them home? Isn't it easier for them to buy the apples in the supermarket? #Person2#: It's for fun. And also, the apples here are Green Food. #Person1#: Come on, daddy. You can see that people only pick the red ones. #Person2#: Silly boy. Green Food means the plants grown without using any chemicals, fertilizers, and pesticides. #Person1#: Oh, then what would happen if there were pests? #Person2#: I heard they used ultraviolet lamp to kill pests. #Person1#: Cool! Well, let's go over there to join mom. I want to tell her all about the special pests-killing method.",#Person1# and #Person2# get away from a bumblebees' hive in Happy Farmhouse. #Person2# tells #Person1# people come to pick apples here because they are Green food and it's fun.,199,29,0.1457
scientific_lay_summarisation-elife-norm,"lysozyme at 2. 9 Å resolution. Thus, a high-resolution protein structure can be determined from electron diffraction of three-dimensional protein crystals in an electron microscope. Lysozyme was chosen as a model protein because it is a well-behaved and well-characterized protein that readily forms well-ordered crystals. From the time its structure was first analyzed (Blake et al. , 1962,1965), lysozyme has been a well-studied protein and the model protein of choice for many new methods in crystallography (Boutet et al. , 2012; Cipriani et al. , 2012; Nederlof et al. , 2013). Small microcrystals of lysozyme were grown by slightly modifying the crystal growth conditions as detailed in the ‘Materials and methods’ section. 1A shows a typical crystallization drop containing microcrystals, which appear as barely visible specks (arrows) alongside the larger crystals that are typically used for X-ray crystallography. These specks are up to 6 orders of magnitude smaller in volume than the larger crystals in the drop. The solution containing these microcrystals was applied to an electron microscopy holey-carbon grid with a pipette and plunged into liquid ethane. The grids were then imaged using a 200 kV TEM under cryogenic conditions (1B). More than 100 microcrystals were typically observed per grid preparation, and these ranged in size from several microns to sub micron. The crystals typically appeared as electron dense rectangular or triangular forms with very sharp edges. 10. 7554/eLife. 01345. 003Figure 1. Images of lysozyme microrystals. (A) Light micrograph showing lysozyme microcrystals (three examples indicated by arrows) in comparison with larger crystals of the size normally used for X-ray crystallography. Scale bar is 50 μm. (B) Lysozyme microcrystals visualized in over-focused diffraction mode on the cryo-EM prior to data collection. The length and width of the crystals varied from 2 to 6 µm with an estimated thickness of ∼0. 5–1 µm. Scale bar is 1 µm. : http: //dx. . org/10. 7554/eLife. 01345. 003 Electron diffraction was used to assess the quality of the cryo-preparations. Crystals that appeared thick (estimated as >3 μm) did not yield diffraction data because the electron beam could not penetrate the sample. Crystals that appeared slightly thinner, estimated at ∼1. 5 μm, did show diffraction, but because the quality of the pattern varied depending on the sample tilt (2A), we did not use crystals","X-ray crystallography has been used to work out the atomic structure of a large number of proteins. In a typical X-ray crystallography experiment, a beam of X-rays is directed at a protein crystal, which scatters some of the X-ray photons to produce a diffraction pattern. The crystal is then rotated through a small angle and another diffraction pattern is recorded. Finally, after this process has been repeated enough times, it is possible to work backwards from the diffraction patterns to out the structure of the protein. The crystals used for X-ray crystallography must be large to withstand the damage caused by repeated exposure to the X-ray beam. However, some proteins do not form crystals at all, and others only form small crystals. It is possible to overcome this",380,128,0.3368
dialogsum,"#Person1#: I wonder if you can help me. I'm looking for a room. #Person2#: Yes. I've got a small room. #Person1#: How much is it? #Person2#: 200 Yuan a week, but smoking is not allowed. #Person1#: OK. Can I see the room now? #Person2#: Would you mind waiting? I'm on the telephone.",#Person1#'s looking for a room. #Person1# requests to see #Person2#'s small room.,52,12,0.2308
scientific_lay_summarisation-elife-norm,"leptin (Frederich et al. , 1995). This mechanism enables homeostatic regulation of feeding behavior in response to metabolic stress. Whether this mechanism represents “leptin resistance” is unclear (Myers et al. , 2010) because some biochemical aspects of leptin signaling are maintained in the obese state (Ottaway et al. , 2015). A requirement for leptin signaling may reflect the role of the leptin-stimulated JAK2-STAT3 pathway to increase expression of the negative regulator SOCS3 (Allison and Myers, 2014). Negative regulation of leptin signaling may also involve the tyrosine phosphatases PTPN1 and PTPN2 (Bence et al. , 2006; Loh et al. , 2011), reactive oxygen species (Diano et al. , 2011), the endoplasmic reticulum unfolded protein response (Zhang et al. , 2008; Ozcan et al. , 2009), autophagy (Kaushik et al. , 2011), and low-grade inflammation (de Git and Adan, 2015). The purpose of the study reported here was to test whether the cJun NH2-terminal kinase (JNK) signaling pathway regulates feeding behavior. Previous studies have established that the ubiquitously expressed JNK1 and JNK2 isoforms play an important role in the metabolic stress response of peripheral tissues (Sabio and Davis, 2010). However, loss-of-function studies have not identified a role for JNK in the control of food consumption. Here we demonstrate that the neuronal isoform JNK3 (encoded by the Mapk10 gene) plays a key role in the maintenance of energy balance during consumption of a high fat diet (HFD) by promoting leptin signaling. Mapk10 gene ablation studies identify AgRP neurons as a site of JNK3 function. JNK3 is therefore a key mediator of homeostatic regulation of energy balance in response to metabolic stress. Leptin is an anorexigenic hormone. Indeed, treatment of chow-fed mice with leptin suppressed feeding behavior and caused decreased body mass (1A). In contrast, HFD-fed mice failed to respond to leptin (1A). The mechanism that accounts for this observation is unclear, but may involve both decreased leptin signaling and reduced signaling by down-stream mediators (e. g. MC4R). Tachyphylaxis may be a contributing factor and mutational analysis of leptin signaling components implicates functions of the leptin receptor, tyrosine phosphatases, reactive oxygen species, and SOCS3 (Myers et al. , 2010). 10. 7554/eLife. 10031. 003Figure 1. JNK3 deficiency causes hyperphagia and obesity. (A) WT mice were fed (4 wk) a chow diet (CD) or a high-fat","Consuming the right amount of food is important for health. Eating too little for a long time causes damage to organs, and overeating can cause harm as well, in the form of conditions such as obesity and type 2 diabetes. Several signaling molecules and brain regions are linked to controlling food consumption and ensuring the body receives the correct amount of nutrients to fuel its activities. Previous studies have found that two proteins called JNK1 and JNK2, which are found in most tissues of the body, can reduce how much energy cells use. This can trigger insulin resistance and fat accumulation, and so suggests that blocking the activity of these proteins may help to treat type 2 diabetes and obesity. However, the role of another JNK protein –",380,128,0.3368
pubmed-summarization,"monoamine oxidases ( mao ) are mitochondrial enzymes responsible for the metabolic breakdown of monoamines ( serotonin , norepinephrine , and dopamine ) in neuronal tissues causing depletion of monoamines and clinical depression ; while mao inhibitors ( maois ) result in the clinical improvement of mood states . interestingly , drugs that possess maoi properties but are used for purposes unrelated to antidepressant activity are furazolidone ( an antiinfective ) ; procarbazine ( drug used for hodgkin 's disease ) ; and linezolid ( an antibiotic used for serious infections ) . we report a case of serious adverse drug interactions between escitalopram and linezolid precipitating near - fatal serotonin syndrome ( ss ) in an elderly female . relevant literature was retrieved via pubmed , embase , and psycinfo using the keywords ; linezolid , escitalopram , serotonin syndrome supplemented with a manual search of cross references . a 65-year - old elderly female , from urban and middle socioeconomic background , presented with history suggestive of depressed mood , middle and late insomnia , anorexia , lethargy , reduced interest in pleasurable activities since 1 year . she was diagnosed as depressive disorder as per icd-10 diagnostic criteria . she had no prior medical history of hypertension , diabetes , or any drug intake . escitalopram ( 5 mg / day ) and clonazepam ( 0.25 mg / day ) therapy showed partial improvement , fortnight later . escitalopram was increased to 10 mg / day , while clonazepam was discontinued due to drowsiness , a month later . patient had full remission of depressive symptoms with escitalopram ( 10 mg / day ) , 2 months later . patient presented with acute onset high - grade fever , cough with greenish - yellow expectoration , breathlessness , and asthenia of a week 's duration following recent travel . she had received antipyretics , mucolytics , expectorants , antibiotics ( amoxicillin and clavulanate ) for 5 days from medical practitioner but found no respite . later , she was referred to physician and hospitalized . on admission , she had 101f temperature , pulse rate of 126/min , and blood pressure ( bp ) of 136/88 mm hg . her general physical and systemic examination revealed no","linezolid is a synthetic antimicrobial agent of the oxazolidinone class with weak , nonspecific inhibitor of monoamine oxidase enzymes . concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine ( > 100 mg / day ) may induce serotonin syndrome ( ss ) . we present a case report of near - fatal adverse interaction between linezolid and escitalopram inducing ss in a 65-year - old woman with sepsis , under empirical antibiotic treatment . this report also summarizes the current relevant literature as identified via pubmed , embase , and psycinfo , supplemented with a manual search of cross references .",380,104,0.2737
scientific_lay_summarisation-elife-norm,"yeast, where the centromere is genetically defined by an ∼120-bp functional sequence on each of the 16 chromosomes. The functional centromere has a tripartite organization: the 8 bp CDEI sequence is a binding site for the Cbf1 protein, the Cse4 nucleosome maps to the 78–86 bp CDEII sequence, and the 26 bp CDEIII sequence is a binding site for the Cbf3 complex (http: //www. yeastgenome. org). Our previous native chromatin immunoprecipitation (ChIP) study has resolved all three particles at base-pair resolution, confirming that the Cse4-containing nucleosome is confined to CDEII (Krassovsky et al. , 2012). The implied single wrap of DNA around the Cse4-containing histone core is consistent with previous evidence that the Cse4 nucleosome wraps DNA in a right-handed orientation in vivo (Furuyama and Henikoff, 2009; Huang et al. , 2011), opposite to the left-handed wrap of conventional nucleosomes (Tachiwana et al. , 2011). However, conflicting structural interpretations have continued to appear, with some authors arguing for partially unwrapped octasomes (Dunleavy et al. , 2013; Hasson et al. , 2013; Miell et al. , 2013; Padeganeh et al. , 2013), others for cenH3/H4 octasomes (Lochmann and Ivanov, 2012), others for tetrasomes (Aravamudhan et al. , 2013), and others for hemisomes throughout the cell cycle but octasomes at anaphase (Shivaraju et al. , 2012). Although there have been suggestions of more than one Cse4 nucleosome per budding yeast centromere based on fluorescent microscopy (Coffman et al. , 2011; Lawrimore et al. , 2011), more recent evidence confirms that there is only one particle per centromere (Henikoff and Henikoff, 2012; Shivaraju et al. , 2012; Haase et al. , 2013). As budding yeast is the only model organism where there is a 1: 1 relationship between the cenH3 nucleosome and the microtubule attachment site (Furuyama and Biggins, 2007), any conclusion concerning its composition and structure has an unequivocal functional interpretation. To definitively settle the controversy over budding yeast centromeric nucleosome composition and structure, we have turned to an in vivo mapping method that individually characterizes every nucleosome in the genome. H4S47C-anchored cleavage mapping determines the precise position and orientation of all histone H4 molecules in an unbiased manner (Brogaard et al. , 2012a). By mapping the obligate H4 partner of Cse4, we avoid potential complications arising from the need for antibodies,","DNA is tightly packaged in cells for a variety of reasons—to allow it to fit inside the nucleus, to protect it from damage, and to help control the production of proteins from genes. The basic unit of packaged DNA is called a nucleosome, which consists of DNA wrapped around a structure formed by two pairs of four different proteins. These proteins, which are called histones, have a role that extends beyond providing structural support for DNA. When cells divide, for example, pairs of ‘sister chromosomes’ are pulled apart to ensure that the two daughter cells both have the same chromosomes as the original cell. The sister chromosomes are pulled apart from a single position called a centromere, and the nucleosomes at this position contain a histone that is",380,128,0.3368
dialogsum,"#Person1#: Mmm. . . it is delicious. #Person2#: Oh, do you really like it? #Person1#: Yes. It's superb. #Person2#: Well, it's kind of you to say so. #Person1#: In fact, could I ask you for the recipe? #Person2#: Sure. It's really very easy. First, mix together an egg, two teaspoons of salt, and two pounds of ground beef. Then, add two ounces of milk. Are you with me? #Person1#: Yes, I've got it. #Person2#: OK. Next, put the mixture into a baking pan and bake it forty-five minutes at 360 degrees. #Person1#: Wait a minute. I didn't catch you there. Could you repeat that? #Person2#: Sure. Bake it forty-five minutes at 360 degrees. #Person1#: Now, I've got it. Thank you.",#Person1# asks #Person2# for a recipe and #Person2# tells #Person1# about the ingredients and procedures.,120,15,0.125
scientific_lay_summarisation-elife-norm,"as part of an effective long-term assistive device because a stable needle-to-fibers spatial relationship cannot be maintained in a moving limb. Therefore, its use can only be limited to a single experimental session lasting a few hours at most (Vallbo et al. , 2004). Instead, implantable neural interfaces, such as Transverse Intrafascicular Multichannel Electrodes (TIMEs) (Boretius et al. , 2010), are surgically positioned and firmly stabilized to adhere to nerve fascicles and do not require an arm rest compared with needle interfaces. Therefore, implantable neural interfaces are suitable for long-term implants. In this study, we developed a novel computational model to investigate the similarities between neural effects, such as in afferent nerve recruitment curves, achieved using microstimulation with percutaneous needles and with TIME neural interfaces. This comparison allowed verification of the possibility of extending the results achieved using percutaneous needle stimulation to TIMEs. The MNT process was tested in acute conditions in four intact subjects and was validated in a TIMEs implanted subject with a transradial amputation. For the first time in human hand neuroprosthetics, these integrated approaches allowed to show that discrimination of textural features can be reliably provided to users in different experimental conditions using peripheral intraneural electrical stimulation. The range of tested tactile stimuli in the current work is on the order of millimeters (0. 5–3. 0 mm). Thus, these stimuli pertain to the lower boundary (towards the fine region) of stimuli that are typically classified as coarse (Weber et al. , 2013). The MNT process translates surface coarseness into the injection of current pulses into the nerve. It qualitatively mimics the neuronal activity recorded during human microneurographic experiments (Oddo et al. , 2011b). The MNT approach was initially tested in four intact volunteers using percutaneous electrical microstimulation of the median nerve (Vallbo et al. , 1984b; Torebjörk and Ochoa, 1980) (1a, ). The participants - without visual or acoustic cues about the stimuli - were asked to discriminate surface pairs (1b) that differed in the Spatial Period (SP) of alternating ridges and grooves (gratings), i. e. , in the distance between consecutive ridges separated by grooves (defined in 2a), which was a constant quantity in each half grating (as shown in 1b). 10. 7554/eLife. 09148. 003Figure 1. Experimental setup and performance metrics. (a) Sensorized artificial finger","Our hands provide us with a wide variety of information about our surroundings, enabling us to detect pain, temperature and pressure. Our sense of touch also allows us to interact with objects by feeling their texture and solidity. However, completely reproducing a sense of touch in artificial or prosthetic hands has proven challenging. While commercial prostheses can mimic the range of movements of natural limbs, even the latest experimental prostheses have only a limited ability to ‘feel’ the objects being manipulated. Oddo, Raspopovic et al. have now brought this ability a step closer by exploiting an artificial fingertip and appropriate neural interfaces through which different textures can be identified. The initial experiments were performed in four healthy volunteers with intact limbs. Oddo, Raspopovic et al. connected the artificial",380,128,0.3368
dialogsum,"#Person1#: Good morning, can I help you? #Person2#: We'd like to buy some furniture for our new house. #Person1#: Here are several sets of furniture, including sofa, dressing table, wardrobe, and sideboard. How about this one? #Person2#: We like a larger wardrobe.",#Person2# tells #Person1# #Person2# wants a larger wardrobe.,42,8,0.1905
dialogsum,"#Person1#: Do you enjoy your work? Do you enjoy meeting people? #Person2#: Yes. Sometimes. I've got to be honest. Sometimes. #Person1#: So, some people you like and some you don't? #Person2#: Yeah, it's like a lot of things, meeting the general public. You get good days, and you get bad days. But I do enjoy the job. I like the freedom of the job, being self-employed. #Person1#: Do you ever get difficult passengers? #Person2#: Yes, sometimes. #Person1#: What sort of things do they get up to? #Person2#: I would say sometimes a lot of difficult passengers are people who don't go in cabs a lot and they're unfamiliar with procedures, especially if you work nights. People drinking or the extras that would be included on the tariff after a certain time of night. #Person1#: You mean they argue with you over money? #Person2#: Yes, that can happen. Or the way.., the good thing is, people can argue about the way that you go to a certain route because they always know better. But nine times out of ten the route that they take you is far longer so, you know, they're the eventual losers. #Person1#: So if you do have a difficult passenger you want to get rid of what do you do? #Person2#: I'd stop the cab and tell them to get out. #Person1#: Does that often happen? #Person2#: Mmm, it's happened to me three times. And they've got out. So I, I myself haven't had a lot of problems with difficult people, you know. #Person1#: When you pick up tourists as passengers, what kind of places do they like to go to? #Person2#: Suppose the most famous landmark is Buckingham Palace, the Tower of London, maybe Harrods; but certainly Buckingham Palace.",#Person2# tells #Person1# #Person2# enjoys the job because of the freedom of being self-employed. Sometimes #Person2# meets difficult passengers who argue over money or the way.,293,26,0.0887
dialogsum,"#Person1#: Can you play tennis? #Person2#: Yes, I can. #Person1#: It is interesting, isn't it? #Person2#: Yes, it's very interesting. #Person1#: Can you teach me? #Person2#: Sure. Take the tennis racket. Now, throw the ball up, and hit it with the racket. Like this. #Person1#: Let me try. Oh, I missed! #Person2#: Throw the ball up high. #Person1#: High? #Person2#: Yes, very high. Over your head. Then you will have time to hit the ball. #Person1#: Oh! I hit it. #Person2#: Well done! #Person1#: Thank you. I think I like playing it.",#Person2# is interested in playing tennis. #Person1# teaches #Person2# how to play by throwing up and hitting.,92,17,0.1848
pubmed-summarization,"a 65-year - old man with intermittent , colicky periumbilical pain which first occurred two months earlier was admitted to hospital . he had an eight - year history of congestive heart failure caused by mitral valvular regurgitation and atrial fibrillation . he was nonalcoholic , and there was no history of diarrhea , hematochezia , or melena . vital signs at admission were stable , and laboratory findings including white blood cell count , a liver function test and electrolytic balance were within the normal ranges . electrocardiography revealed atrial fibrillation , and chest radiography demonstrated cardiomegaly ( not shown ) . to exclude acute appendicitis , initial ultrasonography ( us ) was performed , and this demonstrated diffuse , segmental , concentric wall thickening of the terminal ileum just proximal to the ileocecal valve . nonspecific ileitis , crohn 's disease , intestinal tuberculosis or ischemic enteritis were suggested as possible causes of the bowel wall thickening , and in order to evaluate the terminal ileum , colonoscopic examination was performed . the ascending colon was found to be completely obstructed by a circumferential mass lesion , and the colonoscopic fiber could not be advanced further . subsequent ct scanning showed a markedly dilated small bowel and ascending colon , with concentric , hyperattenuating , focal wall thickening in the hepatic flexure of the ascending colon ( . in addition , the terminal ileum was dilated and showed diffuse , concentric wall thickening of its long segments with heterogeneous contrast enhancement . in the thickened wall , there appeared to be several possible diagnoses , including ischemic enterocolitis caused by thromboembolism of mesenteric vessels arising from atrial fibrillation , inflammatory bowel disease involving the ascending colon and terminal ileum , and ischemic or infectious enteritis associated with colon cancer . stool culture yielded lactose - fermenting gram - negative bacillus , urine culture yielded citrobacter freundii , and gram staining of urine revealed the presence of gram - negative rods ; no organisms were isolated from blood cultures . in addition to conservative management of congestive heart failure , the patient underwent antibiotic therapy with amoxacillin , tobramycin or aztreonam for two weeks and ciprofloxacin for several days . symptoms such as abdominal pain ameliorated , the level","phlegmonous enteritis is a rare infective inflammatory disease of the intestine , predominantly involving the submucosal layer . it is difficult to diagnose and often fatal . its association with alcoholism and various liver diseases , although rarely reported , is well documented . we report a case of phlegmonous enteritis in a male patient with congestive heart failure and colon cancer , and describe the ultrasonographic and ct findings .",380,71,0.1868
dialogsum,"#Person1#: What are you going to bring to the party tonight? I was thinking about going to the grocery store to pick up some vegetables. #Person2#: Oh, there is no need to do that. I have a vegetable garden in my backyard. We can just pick some from there. #Person1#: I thought that was something only old people did. What kinds of vegetables do you have? #Person2#: I have carrots, cucumbers, tomatoes and lettuce. #Person1#: Perfect. How long have you been growing your own vegetables? #Person2#: For the last couple of years. More and more young people are doing it now. It's not just a thing for housewives. #Person1#: Can you come over tomorrow and help me get started on a garden? #Person2#: I'm busy on Friday, but I'll come the day after that.","#Person2# will bring the vegetables from #Person2#'s garden to the party, and agrees to help #Person2#, who is amazed by it, to start a garden.",134,25,0.1866
dialogsum,"#Person1#: How do you feel about wearing name logos or slogans on your clothing? #Person2#: I've never really thought about it before. I guess it doesn't bother me. #Person1#: Do you think advertising has an influence on the choices you make when you're shopping? #Person2#: I guess so. I usually buy name-brand clothing, shoes, and electronic goods. How about you? #Person1#: I actually try to avoid name-brand items. I can't stand it when big companies advertise their products all over the place! #Person2#: I know that advertisers are experts at persuading people to spend their money, I think brilliant items are usually higher quality than ~ grounds. #Person1#: I think is sensible to buy products that is high quality than others when you want to buy something that's going to last a long time, but I don't think it always makes sense. #Person2#: Do you have a brand preference for anything? #Person1#: I do for shower items like shower gel and shampoo, but I don't for higher-end items. #Person2#: What do you think about the ' impossible is nothing ' billboard on the high street? #Person1#: It's just a slogan for a famous company ; there's nothing really special about it. #Person2#: I think it's a brilliant advert! It really grabs my attention! #Person1#: To each their own!","#Person2# usually buys name-brand clothes, while #Person1# doesn't because #Person1# finds big companies' advertisement is annoying. #Person1# thinks the slogan 'impossible is nothing' is not special but #Person2# loves it.",218,30,0.1376
dialogsum,"#Person1#: Hello, Sir. Are you still there? #Person2#: Yes, I'm here. What details do you need from me? #Person1#: Did you check with reception at your hotel? #Person2#: Yes, I did. But nobody has handed it in as yet. #Person1#: OK, that's fine, Sir. We just need to ask you some questions for security purposes. #Person2#: Please, go right ahead. #Person1#: Could I have your name, please? And do you know your card number? #Person2#: I'm Mike Kowalski and my card number is 5211678 44, but there are some other numbers at the beginning. I'm not sure what they are. #Person1#: That should be fine, Mr. Kowalski. And your PIN number? #Person2#: It's 671029, my birthday. Silly to choose such a simple one, I suppose! #Person1#: That's completely natural. Most of our customers do the same thing. Could you just hold for a moment please? Thank you.","#Person1# is asking Mike Kowalski some questions for security purposes on the phone. Kowalski tells #Person1# his name, card number, and PIN number.",147,23,0.1565
pubmed-summarization,"k thermocouples ( yokogawa , tokyo , japan ) were used to measure temperature changes during drilling . a 4-channel handheld data logger thermometer that could measure temperature at 4 sites simultaneously ( yokogawa ) and allowed constant , real - time temperature readings was used to read the thermocouples . temperature measurements were made during site preparation with the diameter 2 mm twist drill ( dio inc . was drilled to a predetermined depth with a 1 mm bur using the surgical drill guide . one thermocouple was inserted vertically into the 1-mm holes prepared to a depth of 6 mm . the thermocouple was placed 1 mm away from the anticipated periphery of the osteotomy to measure the temperature without damaging the cable while drilling.( . 2 ) after fixing the thermocouple , the drill guide was placed in the block and fixed using fixation screws.( . 3 ) to duplicate clinical operating conditions , the bone blocks with the thermocouple were immersed in a 37 water bath ( . ten blocks were divided into the test and control groups ( 5 blocks each ) . in the test group , drilling was performed with the drill guide to a 10-mm depth at a rotation speed of 50 rpm without irrigation . in the control group , drilling was performed with the drill guide to a 10-mm depth at a rotation speed of 1,500 rpm with irrigation . an automated cooling system was used to deliver continuously normal saline to the external wall of the drill throughout drilling at a rate of 40 ml / min . to eliminate the effect of the drill guide on the external irrigation , additional irrigation was performed manually with a simple syringe to deliver the saline solution directly to the drill bone interface . apart from the drill speed and the irrigation , the procedures were the same for both groups . after drilling , accuracy and precision in maintaining the 1 mm distance between the thermocouple canal and the drill preparation was determined using a standard dental radiograph . the thickness of the bone substitute wall between the drill preparations and the thermocouple canals was measured . once the 1 mm wall between them was confirmed , data were included","objectivesin this study we evaluated heat generation during the low - speed drilling procedure without irrigation.materials and methodsten artificial bone blocks that were similar to human d1 bone were used in this study . the baseline temperature was 37.0. we drilled into 5 artificial bone blocks 60 times at the speed of 50 rpm without irrigation . as a control group , we drilled into an additional 5 artificial bone blocks 60 times at the speed of 1,500 rpm with irrigation . the temperature changes during diameter 2 mm drilling were measured using thermocouples.resultsthe mean maximum temperatures during drilling were 40.9 in the test group and 39.7 in the control group . even though a statistically significant difference existed between the two groups , the low - speed",380,128,0.3368
dialogsum,"#Person1#: What can I do for you? #Person2#: It's about the new clerks you need for the offices. I'm wondering how many people you want to employ. #Person1#: That depends on what you would like. #Person2#: I think I'd need about 30 hours a week, including some Saturdays. What do you think? #Person1#: That's what I was thinking too. We don't want someone who has never worked in the office before. #Person2#: Yes. It might be helpful if one could speak a second language. #Person1#: That might prevent too many people asking for the jobs. What about pay, David? #Person2#: What do you think would be the best to offer? #Person1#: I think it depends on experience. However, the lowest we could offer is about $ 9,000 per year.",#Person1# and David are discussing the requirements of the new clerks. They want the clerks to be experienced and the salary depends on experience.,129,24,0.186
dialogsum,"#Person1#: Hello miss. Can I see your ticket number? #Person2#: Sure, here you are. And here are my application forms as well. #Person1#: Thank you miss. . . Wang. I'm Bob Jones and I'll be handling your application. #Person2#: Nice to meet you Mr. Jones. #Person1#: The first step is to determine your eligibility for a U. S. visa. Let's see here. . . you're applying for a special business visa. Why is that? #Person2#: Well, my first order of business will be attending a conference in Seattle, but after that I intend to spend two weeks visiting my friends. I assumed a business visa would be required. #Person1#: I think a regular visitor's visa should suffice. With this visa, you can stay in the United States for up to 90 days. #Person2#: So I can attend conferences and do business on that visa? #Person1#: Yes. You are free to do temporary business with this visa. If you were planning on setting up a new business in the U. S. you might need to apply for a long-term visa. #Person2#: Oh, I see. I think 90 days is more than enough time.",Miss Wang will attend a conference and visit friends in the U.S. Bob Jones determines Miss Wang's eligibility for a U.S. visa and tells her a regular visitor's visa should suffice.,192,31,0.1615
dialogsum,"#Person1#: What do you think are the main causes of war today? #Person2#: I'd say the main reason is poverty. Countries and their people get frustrated because they have so little. If their neighbors have some resources, they try to steal them by military force. #Person1#: It seems that a lot of wars nowadays are really civil wars. People from different ethnic groups in the same country sometimes fight for power in that country. #Person2#: Several of those civil wars have been going on for years and years. It seems they will never end. #Person1#: How do you think they could be ended? #Person2#: I don't think that there is any easy way. The united nations could send peacekeepers into the country. At least then the warring parties could be forced to negotiate. The thing is to find the real problem form the war and solve that. #Person1#: So, if the cause is poverty, there should be a program to make the country richer. If the problem is resources, share them. #Person2#: It sounds easy when you say it like that. In reality, it's harder to make peace between countries. #Person1#: Yes. It is. One way to stop countries fighting is to cut off their financial support. Wars are very expensive. #Person2#: The problem is that many poor people might suffer.","#Person2# thinks the main cause of the war now is poverty. #Person2# argues that war is hard to end, and it's hard for countries to share the resources. #Person1# thinks cutting off the financial support may help.",221,37,0.1674
pubmed-summarization,"lesions are often sensitive to touch , cold , emotional stress , or spontaneous pain . it could be attributed to the local pressure exerted by the tumor on cutaneous nerves . the excitation of these muscles occurs via the sympathetic nervous system resulting in contraction with the influx of calcium ions . hence , nifedipine , a calcium channel blocker , has a role in relieving pain associated with cutaneous leiomyoma . this case of familial cutaneous myomatosis et uteri is reported for its rare occurrence and is rarer for being segmental type 2 variety .","reed 's syndrome or familial myomatosis cutis et uteri , an autosomal dominant inherited condition with incomplete penetrance , is characterized by multiple cutaneous and uterine leiomyomas. uterine leiomyomas usually commence earlier compared to that in the general population and cutaneous leiomyomas may precede , follow or occur concurrently . few patients may have associated renal cell carcinoma . herein we report a case of a 50-year - old female with multiple , painful cutaneous leiomyomas and who had undergone hysterectomy owing to large uterine fibroids . her 18-year - old daughter also has uterine fibroids .",97,97,1.0
scientific_lay_summarisation-elife-norm,"ability of the RING domain to promote ubiquitin transfer to substrate (Duda et al. , 2008; Saha and Deshaies, 2008; Yamoah et al. , 2008). In addition to direct effects on ubiquitin ligase activity, Nedd8 also protects Skp1/Cul1/F-box (SCF) complexes from the substrate receptor exchange factor (SREF) Cand1 (Pierce et al. , 2013; Schmidt et al. , 2009; Wu et al. , 2013; Zemla et al. , 2013). Cand1 binds unmodified SCF complexes and promotes rapid dissociation of the F-box protein (FBP) /Skp1 substrate receptor–adaptor module from the Cul1/Rbx1 core. Cand1 can subsequently be dissociated from Cul1 by a different FBP/Skp1 complex, and as a result Cand1 functions as an SREF that accelerates the rate at which Cul1/Rbx1 comes to equilibrium with different FBP/Skp1 substrate receptor–adaptor complexes (Pierce et al. , 2013). Importantly, the SREF activity of Cand1 is tightly restricted by Nedd8. Cand1 is not able to bind stably to Cul1 and promote dissociation of FBP/Skp1 when Cul1 is conjugated to Nedd8 (Liu et al. , 2002; Pierce et al. , 2013). These observations underscore the importance of neddylation not only for controlling the enzymatic activity of CRLs, but also potentially for controlling the repertoire of assembled CRLs. The key role of Nedd8 in CRL biology highlights the importance of the enzymatic pathways that attach and remove Nedd8 (Enchev et al. , 2015). Of particular significance is the rate of Nedd8 deconjugation, because it serves as the gateway for the exchange cycle; once Nedd8 is removed, a CRL complex is susceptible to the potent SREF activity of Cand1, and its substrate receptor can be exchanged (Pierce et al. , 2013). Deconjugation of Nedd8 is mediated by the COP9-signalosome (CSN), which is an eight-subunit Nedd8 isopeptidase (Lyapina et al. , 2001). The enzymatic activity of CSN resides in its Csn5 subunit, which contains a metalloprotease active site referred to as the ‘JAMM’ domain (Cope et al. , 2002). The JAMM domain has the general structure E76-Xn-H138-X-H140-X10-D151 (the subscripts refer to the sequence position of these residues in human Csn5), wherein the H and D residues coordinate a zinc ion. The fourth zinc-coordination site is occupied by a water molecule that that also forms a hydrogen bond to E76 (Ambroggio et al. , 2004; Sato et al. , 2008; Tran et","Just like you might clear out the old food in your refrigerator to make room for new groceries, cells constantly break down existing proteins to provide space for new ones. The enzymes that generally carry out the first step of this breakdown process are called ubiquitin ligases and human cells make hundreds of different ones. These ubiquitin ligases are not always active and a large group of them can be switched off by a group of proteins known as the COP9-Signalosome (or CSN for short). To achieve this, CSN recognizes and cuts off a structure called Nedd8 from these ubiquitin ligases. However, CSN itself remains inactive until it finds and binds to ubiquitin ligases that have Nedd8 attached. Mosadeghi et al. have now used biophysical techniques to study",380,128,0.3368
dialogsum,"#Person1#: Good morning, Mr. Carson, please? #Person2#: I'm afraid Mr. Carson is at a very important meeting at the moment and cannot be disturbed. May I know who's calling? #Person1#: Yes, this is Mr. Prince. I would like to talk to Mr. Carson today, if possible. #Person2#: Well, I'm afraid the meeting won't finish until one o'clock and then he has a lunch appointment. If he has time, I can ask him to ring you before he leaves. #Person1#: OK. I'd be grateful if you would. #Person2#: Not at all. Mr. Prince. Could I take your telephone number and then I'll ask Mr. Carson to ring you as soon as he's free? #Person1#: Yes, it's Hong Kong--68261427 extension 4036. #Person2#: Hong Kong--68261427 extension 4036. Right. Perhaps he has no time to ring you this morning, but I will ask him to ring you as soon as he returns from lunch. #Person1#: Thank you.",Mr. Prince phones for Mr. Carson. #Person2# tells him Mr. Carson isn't available and will ask Mr. Carson to ring him before Mr.Carson leaves.,153,24,0.1569
pubmed-summarization,"another component , non - patient revenues , made up the remaining 2 percent . over time , this relationship among the sponsors has changed . in 1965 , households were the primary sponsors of health care . since then households have been gradually paying for a smaller proportion of hss and business and the public sector has been paying for a larger proportion . however , by aggressively controlling their health care expenses , business decreased its share of hss during the 1990s . actions by the public sector were less dramatic with the result that the pubic sector share of health care costs increased significantly during this period after nearly 20 years of relative stability . by 1991 , business spent $ 249.4 billion on health care in 1995 , including $ 183.8 billion for employer - sponsored health insurance . the 1993 to 1995 average annual growth of 4.3 percent was the slowest since we began to measure business health spending in 1965 . the burden placed on business eased over the years 1993 through 1995 . during this time overall health care costs grew at a slow rate . also , enrollment in managed care plans grew . these plans generally charged lower premiums than traditional fee - for - service plans . in highly competitive markets , managed care plans also kept premiums low to increase enrollment and boost market share . this in turn forced traditional indemnity insurance companies competing with managed care plans to develop new low cost products or lose market share . these marketplace changes contributed to health care costs consuming less of the business 's compensation costs and profits . according the bureau of labor statistics ' employment cost index ( eci ) for civilian workers , the primary driver of the slowdown in benefits growth was the decline in the cost of health benefits . although a separate health insurance benefit index is not available , the eci program does publish employer compensation cost levels using current employment weights . based on that eci measure , average civilian employer health insurance costs fell 6.2 percent ( $ 1.29 to $ 1.21 per hour worked ) between march 1994 and 1995 . during the same period , wages and salary","for the period 1990 - 95 , we will present data on health care spending by business , households , and government . in addition , we will measure the relative impact of these expenditures on each sector 's ability to pay . in 1994 and 1995 , health care costs experienced the slowest growth in 3 decades . combined with healthy revenue growth , slow cost growth helped ease or stabilize the financing burden faced by business , households and government .",380,83,0.2184
pubmed-summarization,"no published studies have investigated the incidence of t. gondii infection in free - ranging populations of australian marsupials . surveys have provided estimates infection prevalence and seroprevalence ; these are summarised in table 1 , table 2 . evidence of t. gondii infection has been found in free - ranging populations of red kangaroos ( macropus rufus ) , western grey kangaroos ( macropus fuliginosus ) , common wallaroos ( marcopus robustus ) and woylies ( bettongia penicillata ) ( table 1 ) . findings suggestive of t. gondii infection ( histopathological evidence without confirmatory testing ) have also been obtained from long nosed bandicoots ( perameles nasuta ) , eastern barred bandicoots ( perameles gunnii ) , southern brown bandicoots / quenda ( isoodon obesulus ) , quokka ( setonix brachyurus ) , brushtail possums ( trichosurus vulpecula ) , brush - tailed phascogales ( phascogale tapoatafa ) and kowari ( dasyuroides byrnie ) ( table 1 ) . prevalence estimates are all limited by uncertain external validity , due to the use of non - proportionate sampling methods : reliance on culled animals , road kill or trapping for study subjects may entail selection bias . surveys involving small sample sizes have low power to detect the presence of infection , and marked imprecision in prevalence estimates ( table 1 ) . commonly , the use of diagnostic methodology that is known to be of poor sensitivity and/or specificity in other species leaves apparent prevalence estimates subject to misclassification bias . in marsupial surveys , the most commonly used diagnostic test has been the mouse bioassay , which lacks sensitivity ( piergili fioretti , 2004 ) . none of the surveys of australian marsupials using this technique also used immunohistochemistry or pcr to confirm identification of t. gondii bradyzoites . thus , the specificity of the mouse bioassay may be compromised , as t. gondii bradyzoites can appear very similar to those of neospora caninum under light microscopy ( dubey et al . , 2009 ) . as with the mouse bioassay , sample inoculation into cell culture ( in this case 13-day old chick embryos ( table 1 ) ) lacks sensitivity , often because of laboratory error ( piergili fioretti , 2004 ) . histopathological","it has often been asserted that australian marsupial species are particularly susceptible to toxoplasma gondii infection and to clinical toxoplasmosis following infection . this implicates t. gondii as a potential threat to marsupial population viability , and contrasts to what is known of t. gondii in populations of several other host species . we reviewed the literature , and found a lack of scientifically robust evidence addressing the occurrence of t. gondii infection in free - ranging populations of australian marsupial species , and the impacts of the infection on population health . key limitations included a lack of studies in free - ranging marsupial populations , study findings susceptible to substantial chance influences , and selection , misclassification and confounding biases . the lack of scientifically robust",380,128,0.3368
scientific_lay_summarisation-elife-norm,"complex to the proteasome. Importantly, this ‘holdase’ activity can also act in conjunction with other ubiquitin ligases to help degrade defective cytosolic and mislocalized proteins (Minami et al. , 2010; Hessa et al. , 2011), establishing Bag6 as a major E3-associated chaperone in protein quality control (Lee and Ye, 2013). In addition to ubiquitin ligases and associated factors, recent studies have implicated deubiquitinases (DUBs), enzymes that cleave ubiquitin conjugates, as important regulators of ERAD. However, unlike ubiquitin ligases, the functions of DUBs in ERAD are obscure. Many DUBs involved in ERAD associate with p97/VCP either directly or indirectly. These include YOD1 (Ernst et al. , 2009), ataxin-3 (Wang et al. , 2006; Zhong and Pittman, 2006), USP25 (Blount et al. , 2012), USP13, USP50, and VCPIP1 (Sowa et al. , 2009). Interestingly, although deubiquitination has often been reported to cause removal of the proteasome targeting signals and therefore inhibition of protein turnover, many p97-associated DUBs apparently serve as positive regulators in ERAD (Wang et al. , 2006; Ernst et al. , 2009; Sowa et al. , 2009). Several models have been proposed to explain these surprising findings, but experimental data in support of any of these models are lacking (Liu and Ye, 2012). In this study, we characterize a p97-associated deubiquitinase termed USP13. Our study reveals an unexpected interaction between USP13 and the ERAD-specific ubiquitin ligase gp78. Despite having opposing activities, USP13 can cooperate with gp78 to promote ERAD. Mechanistically, USP13 plays a crucial role in fine-tuning the substrate specificity of gp78 as in its absence ubiquitin chains assembled by gp78 can accumulate on an ERAD machinery component—the Bag6-Ubl4A-Trc35 complex that is associated with proteolytic processing of Bag6 and altered interaction between Bag6 and SGTA. Together, these results established that the activity of an E3 ubiquitin ligase can be safeguarded by an accompanying deubiquitinase to enhance its specificity. USP13 shares ∼80% sequence similarity to USP5 (— 1A), an isopeptidase that preferentially cleaves unanchored ubiquitin chains (Reyes-Turcu et al. , 2006). However, only USP13, but not USP5 has been implicated in ERAD. To understand how these homologous enzymes can have distinct functions, we first purified recombinant USP13 and USP5 from both mammalian cells and Escherichia coli. We tested their ability to bind free ubiquitin and to cleave ubiquitin-AFC (Ub-AFC) in vitro.","Cells make proteins inside a structure called the endoplasmic reticulum. However, some of these proteins cannot fold into the correct shape, so cells rely on a process called the ERAD pathway to degrade and eliminate these faulty proteins. First, however, the misfolded proteins must be moved from the endoplasmic reticulum to the main body of the cell (the cytosol). The process by which the misfolded proteins are moved through the membrane that encloses the endoplasmic reticulum is complex, with ‘ERAD machinery proteins’ playing an important role. Among them, a series of enzymes called E3 ligases ‘tag’ the faulty proteins with a small protein called ubiquitin, and a complex called the proteasome then recognizes and degrades those proteins that have been tagged with ubiquitin. However, it is not clear",380,128,0.3368
dialogsum,"#Person1#: It's a sunny day, isn't it? #Person2#: Yes, it is. I'm Jennifer. Nice to meet you. #Person1#: My name is David. Nice to meet you, too. #Person2#: Are you American? #Person1#: No, I'm a Britisher. Where do you come from? #Person2#: I come from America. Are you a freshman? #Person1#: Yes. What about you? #Person2#: Me, too. #Person1#: Great. Maybe we can study and play games together. I think we can be good friends. #Person2#: Yeah. Anytime.",David and Jennifer greet and introduce themselves to each other on the first meet.,78,14,0.1795
pubmed-summarization,"leg pain and back pain are the most frequent symptoms . relatively , in the secondary group ( steroid administration or endocrinopathy group ) , thoracic segments are more involved than lumbar segments and myelopathy is the main symptom . the symptoms of sel are dependent on the level of spinal canal compromise2,4 ) . in reported cases , the symptoms are gradual onset and similar to degenerative spinal stenosis . and the severity of symptoms are various from painful back pain to paraplegia . the diagnostic criterion of sel is greater than 6 mm thickness of epidural fat tissue . possible differential diagnoses include encapsulated spinal lipomas , spinal stenosis , and degenerative joint disease , which can also cause spinal compression and present with similar symptoms17 ) . conservative managements such as exogenous steroid tapering and weight loss are recommended in early sel patients while patients with severe symptoms or progressive neurologic deficits are indicated for operation1,7,9,13 ) . in a study by fogel et al.7 ) , seventy - seven percent of patients of the steroid group who underwent on decompressive laminectomy had symptom improvements . but in a study by fassett et al.6 ) , the mortality rate in these patients within 1 year after surgical decompression was 22% , because of concomitant medical problems and comorbidities . consequentially , we must make a treatment plan that considers various factors , such as neurologic severity , general health , steroid therapy and lifestyle . in patients who underwent an operation for suprasellar lesions such as pituitary adenoma , suprasellar meningioma , craniopharyngioma , and so forth , we can occasionally observe complications from corticosteroid hormone deficiency ; in which case , we start corticosteroid hormone replacement therapy without worrying about the sel . in our case , we reviewed the studies showing that long - term corticosteroid replacement therapy after neurosurgery can lead to spinal epidural lipomatosis .","spinal epidural lipomatosis ( sel ) is an abnormal localized accumulation of fat tissues in the epidural space . it is strongly related with steroid administration . the symptoms of sel are various and range from back pain to paraplegia . in severe cases , decompressive laminectomy is the choice of treatment . a 32-year - old woman who had been under long - term steroid administration after suprasellar tumor resection was admitted for both leg radiating pain and weakness . she was diagnosed with sel and had a decompressive laminectomy . during the operation , we found the nerve roots were compressed by epidural fat tissues and engorged vessels . after the operation , her radiating pain was relieved and motor weakness was improved .",322,126,0.3913
scientific_lay_summarisation-elife-norm,"regions. This is true even after manipulations of the visual input such as rearing animals with artificially induced strabismus (Hubel and Wiesel, 1965; Löwel, 1994; Löwel et al. , 1998) or monocular deprivation (Crair et al. , 1997). However, whether this relationship is a fundamental aspect of map structure that is determined by innate mechanisms (Godecke and Bonhoeffer, 1996; Crair et al. , 1998; Kaschube et al. , 2002; Katz and Crowley, 2002; Tomita et al. , 2013), and thus beyond the limits of brain plasticity, is unclear. Computational models of map formation based on Hebbian plasticity principles have played an important role in understanding the mechanisms governing visual development. In particular ‘dimension reduction’ models predict negative correlations between the local gradient magnitudes of different maps (Durbin and Mitchison, 1990; Swindale, 1996), thus explaining why pinwheels, which have a high orientation gradient, normally tend to lie near the centre of OD regions, where the ocularity gradient is small. However, such models also suggest that the spatial relationship between pinwheels and OD regions might be sensitive to visual experience (Giacomantonio et al. , 2010). Here we used a computational model to predict how rearing animals with visual input biased to vertical orientations in one eye and horizontal orientations in the other eye (cross-rearing) would change these relationships. We then confirmed this prediction by raising cats with weak (-10 dioptre) cylindrical lenses placed in front of their eyes throughout the critical period. This demonstrates a form of plasticity in the relationships between visual feature maps that has not previously been observed. The elastic net algorithm (Durbin and Mitchison, 1990) uses Hebbian learning to optimize a trade-off between coverage and continuity constraints, and can explain many aspects of visual map formation (Swindale, 1996; Goodhill, 2007). When simulating normal rearing (Erwin et al. , 1995; Carreira-Perpinan and Goodhill, 2004; Carreira-Perpinan et al. , 2005) this reproduces the experimental observations cited above that pinwheels tend to be located near the center of OD columns. However, previous simulations of map development (Giacomantonio et al. , 2010) suggested that this relationship would be disrupted when horizontal orientations were over-represented in one eye and vertical orientations were over-represented in the other (Hirsch and Spinelli, 1970; 1971; Blakemore, 1976). Here we simulated this scenario using the elastic net algorithm","The structure of the brain results from a combination of nature (genes) and nurture (environment). The brain’s ability to adapt to changes in the environment is known as plasticity, and the young brain is especially plastic. An animal’s sensory experiences in early life help to determine how its brain will process sensory input as an adult. One of the best sensory systems in which to study this process is the visual system. Within the visual system, some brain cells respond only to input from the left eye and others only to input from the right eye. Cells that respond to input from the same eye are arranged to form columns. Within each column, some cells respond only to lines with a particular orientation. Cells with different preferred orientations",380,128,0.3368
dialogsum,"#Person1#: Good morning. Wilson Association. #Person2#: This is Mr. Brown speaking. I'd like to speak to Mr. Thomas, please. #Person1#: I'm sorry, but Mr. Thomas left the office a few minutes ago. #Person2#: That's bad! I've been trying to call him for the last ten minutes, but your line has been busy. Will he be back soon? #Person1#: I'm afraid not. He's gone for the rest of the day. #Person2#: Is there anywhere I can reach him? #Person1#: I don't believe so. He's going out of town on business. May I take a message? #Person2#: I have a business appointment with him for tomorrow morning at ten o'clock, but I'm afraid I can't make it. #Person1#: Would you care to make another appointment? #Person2#: Unfortunately, I'm leaving town rather unexpectedly, and I may be gone for several days. #Person1#: I see. I can tell Mr. Thomas that you phoned. #Person2#: Thank you. #Person1#: Bye-bye.","Mr. Brown calls Wilson Association to cancel the appointment with Mr. Thomas. #Person1# answers the phone, tells him Mr. Thomas isn't available. #Person1#'ll deliver the message.",154,26,0.1688
scientific_lay_summarisation-elife-norm,"the ER, protein degradation, and, in the case of severe stress, apoptosis. In recent years, many additional components of ER stress resolution have been identified, often with roles in maintenance of metabolic homeostasis following exposure to stress. Despite the increasing number of factors involved in the ER stress response, only a few are directly responsible for ER stress resolution. Treatment of knockout mice for any of the upstream UPR pathway components, Atf6, Ire1α (product of Ern1), or Perk (product of Eifak3), with tunicamycin, a chemical stressor that primarily affects the liver, elicits a striking phenotype. All knockouts exhibit an inability to resolve ER stress upon exposure, as well as a striking metabolic phenotype of strong and persistent accumulation of hepatic triglycerides (Rutkowski et al. , 2008; Teske et al. , 2011; Zhang et al. , 2011). While tunicamycin is a supraphysiological stressor, these results are important because no other mouse models have been reported to share these phenotypes following ER stress, suggesting that the canonical UPR pathways are functionally overlapping, yet non-redundant, and also that the UPR contains the only required pathways for ER stress resolution. The orphan nuclear hormone receptor liver receptor homolog-1 (LRH-1; product of Nr5a2) is expressed in secretory tissues or tissues with high rates of protein production, including liver, pancreas, intestine, and reproductive tissue (Higashiyama et al. , 2007). None of the divergent roles of LRH-1—notably bile acid production, development and maintenance of pluripotency, and local steroidogenesis—directly imply a role in ER stress resolution. However, the fact that metabolic diseases such as type II diabetes and fatty liver disease are associated with chronic ER stress (Ozcan et al. , 2006), but can be alleviated by activation of LRH-1 (Lee et al. , 2011), suggested a potential connection. In the present study, this connection was substantiated by our discovery that LRH-1 is indispensible for ER stress resolution. In this unexpected role, LRH-1 initiates the kinase-driven activation of a CREB-like transcription factor following exposure to ER stress, specifically through polo-like kinase 3 (Plk3) induction of activating transcription factor 2 (ATF2) phosphorylation. This response is absent in Lrh-1 liver-specific knockout mice, but restoration of Plk3 induction to Lrh-1 null cells reestablishes ER stress resolution. Similarly, expression of a constitutively active Atf2 restores ER stress resolution capacity to Lrh-1 null","A protein can only work properly if it has been folded into the correct shape. However, it is estimated that about one third of new proteins have the wrong shape. This is a major challenge for cells because misfolded proteins are often toxic, and cause many neurodegenerative and metabolic disorders. In eukaryotic cells, most protein folding takes place inside a part of the cell called the endoplasmic reticulum (ER). If an incorrectly folded protein is detected, it is prevented from leaving the ER until it is refolded correctly, or destroyed. If too many proteins are misfolded, a process called the unfolded protein response helps the cell to cope with this ‘ER stress’ by expanding the ER and producing more of the molecules that assist protein folding. If this",380,128,0.3368
dialogsum,"#Person1#: We still have an important attraction. #Person2#: What is that? #Person1#: Melbourne Zoo. #Person2#: What's special about Melbourne Zoo? #Person1#: The place is a must-see. This zoo was built in 1862, and it's the oldest zoo in the world, and still among the best. There are more than 3, 000 species of animals here, including the popular kangaroos, wallabies, koalas, and wombats. #Person2#: Are the animals caged? #Person1#: Most animals are not locked up in tiny cages. Rather, they are set in almost natural surroundings or well-tended gardens. #Person2#: That's really special. #Person1#: Of course, I'm sure you will like it.","#Person1# says that Melbourne Zoo is a must-see because it's the oldest zoo in the world, and still among the best.",102,21,0.2059
dialogsum,"#Person1#: 6487258. #Person2#: May I speak to the owner please? #Person1#: Speaking. #Person2#: Good afternoon. I've just seen the advertisement in the newspaper about the furnished flat for rent. Is it still available? #Person1#: Yes, it is. Would you like me to tell you about it? #Person2#: Yes, but could you tell me the address first, please? #Person1#: Yes, it's Number 45 Station Road. #Person2#: Thank you. How big is the flat? #Person1#: Oh, it's big enough for a family of four. There are three bedrooms. #Person2#: Thanks. What about the heating and the stove? #Person1#: It's all gas -- the flat has central heating and a gas stove. #Person2#: OK. And how much is the rent? #Person1#: It's $ 200 a month, and that does not include the cost of gas. The flat will be available starting Sep. 1. #Person2#: Thank you very much.","#Person2# calls the owner to get some information about the furnished flat for rent. #Person2# asks about the address, the area, the heating and stove, and the rent.",145,28,0.1931
dialogsum,"#Person1#: How time flies! Why I always feel haven't enough time to work and study? #Person2#: Yes, I also felt that. I'm always busy, and have no time for rest. I don't know how to make use of time. #Person1#: Maybe we should make a plan and list what we should do next, and follow it. #Person2#: That's a good idea. And in this way we will know how we spend our time and spare a lot of time to do other things. #Person1#: You are right. Let's stop idling around and do something. #Person2#: Yeah, time is money. We really need to make good use of it.",#Person1# suggests making a plan and listing what should do to make use of time. #Person2# thinks it's a good idea.,108,21,0.1944
dialogsum,"#Person1#: Hey, do you know the bus company network system crashed? #Person2#: I heard about it several days ago! #Person1#: That is unbelievable! #Person3#: Daddy, can you tell me what they are talking about? #Person4#: They are talking about the network of the bus company. #Person3#: Why is their network not working? #Person4#: Because of the IC cards. #Person3#: The IC card? #Person4#: Yes, Beijing is a big city and there are about 7, 000, 000 people using IC cards on buses. #Person3#: And? #Person4#: All the people were checking the balance of their cards on the Internet at the same time, that's why the system crashed. #Person3#: Oh, that is horrible!",#Person1# tells #Person2# the bus system crashed. #Person4# explains to #Person3# that's because everyone checked the balance of their IC cards.,112,21,0.1875
dialogsum,"#Person1#: You know the party last night? Lots of old faces from college were there. #Person2#: Really? #Person1#: Yeah. Sally was there with her husband; I heard he,s something very high up and important in some business company. #Person2#: Yes, I heard that too. To tell you the truth, I never really expected her to marry someone successful. She was alway untidy and didn't like to work. #Person1#: Obviously, she has changed her attitude to life. I mean she was very smartly dressed, and she kept telling me all about how much money their new house had cost. #Person2#: Seriously. #Person1#: Yes, she was really proud of it. #Person2#: Well,she never used to be interested in money at all. #Person1#: By the way, Simon Fox was at the party. #Person2#: Was he? I haven't seen him for ages. #Person1#: Naturally, he couldn't help asking me questions about you. #Person2#: I think he still thinks that we might get back together one day. #Person1#: Exactly. #Person2#: Well, not much chance of that.",#Person1# went to a party last night and tells #Person2# about some old college friends who were there.,171,18,0.1053
pubmed-summarization,"alpha - amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( ampa ) receptor channels mediate most of the fast synaptic excitatory transmission in the brain . importantly , the glua2 subunit with its edited q / r site ( sommer et al . , 1992 ) ensures that ampa receptors containing this subunit are largely ca - impermeable ( hollmann et al . , 1991 ; burnashev et al . , 1992 ; jonas and burnashev , 1995 ; isaac et al . , 2007 ) . by contrast , glua2-lacking ampa receptor channels , i.e. , any homomeric or heteromeric assembly of glua1 , a3 , or a4 , are ca - permeable and subject to voltage - dependent block by intracellular polyamines , resulting in a characteristic doubly rectifying current - voltage ( i v ) relationship . imbalance in favor of ca permeable ampars can cause cns dysfunction ( liu and zukin , 2006 ) . in synaptic ampa channels , sensitivity to endogenous polyamines and the degree of rectification can be lessened by interaction with tarps , the transmembrane ampar regulatory proteins ( soto et al . , 2007 ) . thus , a low extent of rectification of synaptic ampar - mediated currents need not reflect a particular ampar composition , but may also indicate interaction with regulatory factor(s ) . as gleaned from the properties of ampa receptors in different neuronal populations , the current consensus would state that principal excitatory neurons operate with glua2-containing ampa receptors ( adesnik and nicoll , 2007 ; lu et al . , 2009 ) , whereas gaba - ergic inhibitory neurons often additionally feature glua2-lacking synaptic ampa receptors ( geiger et al . , 1995 ; toth and mcbain , 1998 ; liu and cull - candy , 2002 ) . while there is firm consensus , 1992 ; lu et al . , 2009 ) , conflicting evidence surrounds the possible presence of glua2-lacking ampar channels in hippocampal schaffer collateral / commissural synapses in ca1 pyramidal cells , arguably the best - studied synapses in the brain . several groups observed that the molecular identity of ampars in ca1 cell synapses is altered upon induced changes in synaptic strength . plant et al . ( 2006 ) reported that induction of","the glua2 subunit in heteromeric alpha - amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( ampa ) receptor channels restricts ca2 + permeability and block by polyamines , rendering linear the current - voltage relationship of these glutamate - gated cation channels . although glua2-lacking synaptic ampa receptors occur in gaba - ergic inhibitory neurons , hippocampal ca1 pyramidal cell synapses are widely held to feature only glua2 containing ampa receptors . a controversy has arisen from reports of glua2-lacking ampa receptors at hippocampal ca3-to - ca1 cell synapses and a study contesting these findings . here we sought independent evidence for the presence of glua2-lacking ampa receptors in ca1 pyramidal cell synapses by probing the sensitivity of their gated cation channels in wild - type ( wt ) mice and gene -",380,128,0.3368
dialogsum,"#Person1#: Thanks for inviting me to work out with you, Joan. #Person2#: Don't mention it, let's go in. #Person1#: Yeah, this place looks great. Wow, look at her, she can certainly get down, can't she? #Person2#: She sure can. Are you jealous, Leslie? #Person1#: A little, I wish I could do that. #Person2#: You can! With a little practice. #Person1#: Look at him, he's buff. #Person2#: I think he's hot too. #Person1#: How do they all get in such tiptop shape? #Person2#: Exercised over and over. Exercise is a key. #Person1#: That's it. I decided to turn over a new leaf. I'm going to exercise every single day. #Person2#: Good for you, Leslie!","Leslie sees a flexible woman and a buff man. Joan encourages her to exercise to get in shape, and Leslie'll try.",113,21,0.1858
dialogsum,"#Person1#: What kinds of Tv programs do you enjoy watching? #Person2#: I like current affairs programs and documentaries, especially wildlife ones. How about you? #Person1#: I like those kinds of programs too. They're very informative. I think that many people underrate the education value of Tv. #Person2#: I agree. People often criticize Tv for showing too much sex and violence. #Person1#: Yeah. And that's so funny because most people prefer watching sex and violence to watching something more educational! #Person2#: Right. You can't blame the tv stations for showing popular kinds of programs. They need to make money from advertisements shown during and between programs. #Person1#: In my country, there's a time limit on the advertisements that can be shown. I think it's about six minutes per hour. #Person2#: That's great idea. But don't the Tv station lose a lot of money because of that? #Person1#: No. they don't. they simply charge higher prices at peak times. Is there no limit on the amount of advertisements that can be shown on Tv in your country? #Person2#: Not as far as I know. We have so many advertisements. the interruptions are unbearable sometimes! That's one reason that many people prefer satellite or cable Tv, where you pay a fixed amount each month. #Person1#: Some people have satellite and cable Tv in my country, but people don't seem to keen to pay for their Tv programs. Besides, the terrestrial channels offer a good range of programs. #Person2#: Well, there's a wildlife documentary on Tv in a few minutes. Shall we?","#Person1# and #Person2# both think Tv programs are informative, and advertisements shown during and between programs shouldn't be blamed. In #Person1#'s country, there's a time limit on the advertisements, but there are still many advertisements in #Person2#'s country.",258,38,0.1473
scientific_lay_summarisation-elife-norm,"of the TOC complex were identified more than two decades ago (Hirsch et al. , 1994; Kessler et al. , 1994; Schnell et al. , 1994; Tranel et al. , 1995; Jarvis, 2008). However, the regulation of the activity and stability of the complex was, until recently, poorly understood. Major insights came from a forward genetic screen for suppressors of the pale-yellow Toc33 mutant, ppi1 (Ling et al. , 2012). In this screen, SP1 (SUPPRESSOR OF PPI1 LOCUS 1), a novel RING-type E3 ubiquitin ligase, was identified. A series of sp1 mutations were shown to partially suppress the phenotypic defects of ppi1 with respect to chlorosis, chloroplast development, and chloroplast protein import. In addition, SP1 function was shown to promote plastid interconversion events (e. g. , the development of the chloroplast from its precursor organelle, the etioplast). Later work demonstrated that SP1 function is also important for abiotic stress tolerance by enabling optimization of the organellar proteome via protein import regulation (Ling and Jarvis, 2015). Thus, through SP1, the ubiquitin-proteasome system promotes TOC complex degradation and reconfiguration in response to developmental and/or environmental stimuli. Ubiquitinated TOC proteins are extracted from the chloroplast outer envelope membrane and degraded in the cytosol. Recent work identified two proteins that physically associate with SP1 and promote the membrane extraction of TOC proteins (Ling et al. , 2019). These are SP2, an Omp85-type β-barrel channel protein that was identified in the same genetic screen as SP1, and Cdc48, a well-characterized cytosolic AAA+ chaperone ATPase that provides the motive force for the extraction of proteins from the chloroplast outer envelope. The three proteins – SP1, SP2, and Cdc48 – together define a new pathway for the ubiquitination, membrane extraction, and degradation of chloroplast outer envelope proteins, which has been named chloroplast-associated protein degradation (CHLORAD). In addition to CHLORAD, there exist cytosolic ubiquitin-dependent systems that also contribute to chloroplast biogenesis by regulating the levels of unimported preproteins (Lee et al. , 2009; Grimmer et al. , 2020) and by controlling the stability of the Toc159 receptor prior to its integration into the outer envelope membrane (Shanmugabalaji et al. , 2018). The discovery of SP1 and the CHLORAD pathway demonstrated that the TOC complex is not static but, instead, can be rapidly ubiquitinated and degraded in response to","All green plants grow by converting light energy into chemical energy. They do this using a process called photosynthesis, which happens inside compartments in plant cells called chloroplasts. Chloroplasts use thousands of different proteins to make chemical energy. Some of these proteins allow the chloroplasts to absorb light energy using chlorophyll, the pigment that makes leaves green. The vast majority of these proteins are transported into the chloroplasts through a protein machine called the TOC complex. When plants lack parts of the TOC complex, their chloroplasts develop abnormally, and their leaves turn yellow. Photosynthesis can make toxic by-products, so cells need a way to turn it off when they are under stress; for example, by lowering the number of TOC complexes on the chloroplasts. This is achieved by",380,128,0.3368
pubmed-summarization,"of certain honey bee viruses , additional microparasites in this complex system of host parasite interactions . in the absence of varroa mites , honey bee viruses can occur as symptomless covert infections within a colony but when varroa mites are present , a new transmission route is provided by this biological vector ( martin 2001 ; shen et al . 2005 ; gisder et al . according to theories in evolutionary epidemiology , vector - borne transmission often results in more virulent infections ( ewald 1994 ) . as the mite population grows within a colony , increasing opportunities for transmission will lead to the development of overt viral infections that ultimately result in colony mortality within one to three years if the mite population is not reduced by beekeepers ( martin 2001 ; boecking and genersch 2008 ) . therefore , the virulence of the mite is considered an indirect measure of its ability to vector these viruses . consequently , the viruses with a newly acquired vectorial transmission route will become more virulent , as their virulence is in general a measure of mite abundance . apis mellifera races in africa , a. m. scutellata , and in south and central america , of african origin ( africanized bees ) , are exceptions to the eventual mortality associated with mite infestation ( rosenkranz 1999 ; allsopp 2006 ) . wild and feral colonies under natural selective pressures in these populations have evolved resistance and are able to pass traits to managed colonies through natural mating events ( rosenkranz 1999 ) . wild and feral colonies are rare in europe and north america since the introduction of the mite ; however , a few subset populations of european honey bee races have been exposed to natural selective pressures of long - term mite infestation , as opposed to apicultural pressures or selective breeding programs . remarkably , these natural populations have been sustainably surviving mite infestation for extended periods , some over 10 years , without mite control treatments ( de jong and soares 1997 ; rinderer et al . 2001 ; kefuss et al . 2004 ; fries et al . 2006 ; le conte et al . 2007 ; seeley 2007 ) . parasite coevolution between","honey bee societies ( apis mellifera ) , the ectoparasitic mite varroa destructor , and honey bee viruses that are vectored by the mite , form a complex system of host parasite interactions . coevolution by natural selection in this system has been hindered for european honey bee hosts since apicultural practices remove the mite and consequently the selective pressures required for such a process . an increasing mite population means increasing transmission opportunities for viruses that can quickly develop into severe infections , killing a bee colony . remarkably , a few subpopulations in europe have survived mite infestation for extended periods of over 10 years without management by beekeepers and offer the possibility to study their natural host parasite coevolution . our study shows that two",380,128,0.3368
dialogsum,"#Person1#: My friend Emily recently lost 18 pounds. #Person2#: Oh, really? #Person1#: The point is that she has been persuading me to lose weight too. #Person2#: Well, it's a good thing for you. #Person1#: Good? Yes, it's good for her but not for me. You see, she tells me that I'll feel better about myself if I slim down. She keeps giving me newspaper clippings about the latest miracle diet and insists that I join a health club, as she has. #Person2#: So you don't think you are fat and need to lose weight? #Person1#: I just can't bear it that Emily made me feel like a baby who always pigs out on junk food. #Person2#: junk food is not good for your health. Too much of it will make you fat. #Person1#: But junk food is so easy. It requires no silverware or plates, no rigid mealtimes, no pleases and thank yous. #Person2#: Ok, but junk food has many disadvantages. As junk food contains high amount of oil and fat, you'll feel sleepy, but not be able to concentrate when you have a lot of it. #Person1#: Yes, but life without chips, ice cream and coca cola is boring. #Person2#: Let me see. You could exercise more to keep fit. #Person1#: Well, that sounds better than giving it up.",#Person1# hates that Emily made #Person1# feel like a baby who pigs out on junk food. #Person2# suggests exercising more and #Person1# thinks it's better than giving up.,220,28,0.1273
dialogsum,"#Person1#: Good morning, Madam. Are you being helped? #Person2#: No, I'm not. #Person1#: Where? I can certainly help you if you'd like some advice. This skirt and scarves over here are back in style. #Person2#: Oh, I'm here to look for a winter coat. #Person1#: How about this one? It's made of very high-quality wool. #Person2#: It's nice but actually I need something warmer. This would work if I were staying here in Los Angeles. But it's too light for Chicago winter. #Person1#: Ah, you need a very heavy coat. Then please follow me. This one here is a good value and is one of our warmest coats. It's also quite fashionable and very comfortable. #Person2#: Would it be possible to get a discount on it? #Person1#: Maybe we can give you a 5% discount. #Person2#: OK. I'll take it. #Person1#: Can interest you in some gloves? They are 10% percent off now. #Person2#: No, thanks. I used to live in London, so I already have some very nice gloves.",#Person2#'s looking for a very heavy winter coat for Chicago winter. #Person1# recommends one and give #Person2# a 5% discount. #Person2#'ll take it.,170,23,0.1353
pubmed-summarization,"establishment of an infrastructure for green chemistry has been provided , along with award programs , to encourage the active participation of industry . the green chemistry market of south korea ( hereafter korea ) is about us$ 96.4 billion , placing it at 13th in the world , after major developed countries such as the us , china , and japan , and accounting for about 1.8% of the entire green chemistry market , alongside canada . the global green chemistry market is expected to grow continuously to about us$3000 billion by 2020 , and efforts to monopolize the green chemistry market have swiftly centered on the major developed countries . since it is necessary for korean industries , which occupy only 1.8% of the global green chemistry market , to enter into overseas markets , various environmental changes , along with growth of the green market , may provide a chance but also a crisis for korean industries , so that a response from the korean government is very crucial ( table 1 ) . t. anastas , the epa has maintained various policies to spread green chemistry , including environmental assessments of hazardous chemicals by the federal government ; relevant research and education ; support for environment - related industries , such as prevention programs and energy saving ; the presidential green chemistry challenge awards ; and support for the reduction in use and generation of hazardous substances . the epa also developed and distributed a tool to provide information about the results of the policies related to green chemistry , including green chemistry expert system ( gces ) and green chemistry assistant ( gca ) . gces is composed of five modules that enable industries to identify information for evaluation and prediction , leading to the selection of safer green chemistry alternative chemicals . first , the synthetic methodology assessment for reduction techniques module receives inputs such as information about chemicals , number of reactions , and yield of reactions ; identifies properties of the chemical reaction process ; and estimates and assesses the amounts of products and wastes . second , the green synthetic reaction module makes it possible to identify reaction information to synthesize chemicals in a safer and less hazardous way , with","objectivesdespite the great contribution made by chemical substances to the development of modern civilization , their indiscriminate use has caused various kinds of damage to the global environment and human beings . accordingly , the major developed countries and international society have tried to ensure the safe use of chemicals and a reduction in the use of hazardous chemicals through the establishment of the united nations environment programme and various international agreements . in this reason , we tried to introduce about green chemistry progress at the present in worldwide and korea.methodswe checked and analyzed relative journals , reports using keyword as like green chemistry , alternative chemicals , eco - friendly etc . and major country s government homepage search.resultsgreen chemistry theory , which argues for the",380,128,0.3368
pubmed-summarization,"2c ) , and repeat ct showed that the mediastinal hematoma had nearly disappeared ( . the patient was discharged without complications . over the course of one year of follow - up spontaneous mediastinal hemorrhage can develop as a result of trauma , aortic dissection , the valsalva maneuver , or iatrogenic procedures . the rupture of a bronchial artery aneurysm ( baa ) is also known to result in mediastinal hemorrhage . when a baa ruptures into the mediastinum , most patients present with chest pain , hemothorax , or hemomediastinum . furthermore , if hematemesis is a prominent symptom of baa rupture , it can be confused with boerhaave s syndrome , variceal disease , or a perforated ulcer . to the best of our knowledge , only three cases of baa presenting with hematemesis have been reported in the literature . in one case , a pinhole connection between the aneurysm and esophagus was found during an endoscopic examination , but in the present case , no evidence of communication was found between the aneurysm and the esophagus . we first suspected that the mediastinal hemorrhage and hematemesis were caused by the perforation of an esophageal ulcer , but repeated gastroscopy showed a normal esophagus . the only abnormal finding was the finding of a baa without evidence of extravasation three days after the onset of symptoms . after ruling out the possibility of mediastinal hematoma , the baa was the only remaining possible source of the mediastinal hemorrhage . since the baa was regarded as the source of the mediastinal hemorrhage and hematemesis , it was embolized to avoid recurrence . the treatment of a ruptured baa depends on the patient s hemodynamic status and the presence of cardiorespiratory compromise . if the patient is hemodynamically stable , endovascular embolization is considered to be the first - line management strategy , and surgery should only be considered when embolization is contraindicated , as in patients allergic to contrast medium or when a medullary artery is involved . in patients presenting at an emergency department with hematemesis and mediastinal hemorrhage ,","hematemesis is a rare manifestation of a ruptured bronchial artery aneurysm ( baa ) in the mediastinum . it is difficult to diagnose a ruptured baa presenting as hematemesis , because it can be confused with other diseases , such as boerhaave s syndrome , variceal disease , or a perforated ulcer . in this report , we describe a case of baa resulting in hematemesis and mediastinal hemorrhage .",355,70,0.1972
pubmed-summarization,"a 42-year - old man with hcv was referred to our hospital in august 2004 because of diarrhea and bloody stool . ten years before admission , he had been diagnosed with total uc endoscopically and histologically . colonoscopic examination revealed reddish and edematous mucosa with multiple erosions through the entire colon ( . laboratory data showed thrombocytopenia ( 57,000/mm3 ) , asparate aminotransferase ( ast ) 124 iu / l , alanine aminotransferase ( alt ) 110 iu / l , and hepatitis c virus ( hcv ) rna ( genotype ib ) 757 kiu / ml . after informed consent had been obtained , he was treated with peg - ifn--2a ( 90 g / week ) for improving both colonic and liver inflammation . four weeks after initiation of peg - ifn therapy , his abdominal symptoms gradually subsided . we performed intracellular cytokine assay with peripheral cd4 t cells before and after ifn therapy . the ratio of t - helper ( th ) 1 ( ifn-?)/th 2 ( interleukin ( il)-4 ) increased ( 40.2 ) at 4 weeks after ifn therapy compared to that before ( 27.4 ) ( . however , there was no significant difference of il-10 production from cd4 t cells between before and after ifn therapy . he was uneventfully treated with peg - ifn--2a for one year . when last seen in november 2006 , he was still in remission of uc and his laboratory data showed a negative serum hcv - rna , which was suggestive of sustained virological response . inf- , through its immunomodulatory function , could have an impact on pathways in the immune system . therefore , the effect of inf- on the pathophysiology of ibd has been focused , because patients with ibd are characterized by imbalance of the th1/th2 cytokine response . previous reports showed that a treatment with inf- might be a trigger for development of th1-related intestinal disease such as celiac disease and crohn 's disease , because inf- plays an important role in t cell differentiation towards a th1 type of immune response . regard , inf- is considered to have beneficial effects in the treatment of diseases characterized by excess th2 cells such as uc . in fact","a 42-year - old man with chronic hepatitis c and ulcerative colitis ( uc ) was referred to our hospital in august 2004 because of bloody diarrhea . he was clinically and endoscopically diagnosed with flare of uc . after informed consent had been obtained , he was treated with peg - ifn--2a . four weeks after initiation of peg - ifn therapy , his abdominal symptoms gradually subsided . intracellular cytokine assay revealed that the ratio of t - helper ( th ) 1 ( ifn-?)/th 2 ( il-4 ) increased after ifn therapy . three months after starting ifn therapy , colonoscopy revealed a normal mucosal pattern . he was uneventfully treated with peg - ifn--2a for one year . when last seen in november 2006",380,128,0.3368
pubmed-summarization,"tooth were averaged to determine the gbi and pi for each subject . in addition to this examination , the hard and soft oral tissues were visually inspected for the presence of any adverse reaction by the same examiner . after the initial examination , all teeth of each subject were polished with pumice and flossed to eliminate plaque remnants . a personal "" kit "" containing a new toothbrush ( leader ; facilit odontolgica e perfumaria ltda , rio de janeiro , rj , brazil ) and the test or control dentifrice was given to all participants . they were instructed to brush their teeth for 1 min , three times a day , using the bass technique , and to refrain from any other oral hygiene procedures throughout the period of the clinical trial . verbal and written instructions about the correct use of dentifrice were given to all subjects as well . the tubes containing the dentifrices were previously coded to warrant that neither the examiner nor the volunteers knew their content , which was revealed only after completion of the study . the subjects were asked to return their dentifrice tubes , that were weighted by a digital balance ( filizola , modelo bp6 , indstrias filizola s.a . , so paulo , sp , brazil ) , previously and after the trial , so that compliance could be indirectly evaluated . student 's t - test was used to evaluate statistical differences between the weights of dentifrice tubes on days 0 and 30 ( =0.01 ) . mann - whitney test was performed to evaluate statistical differences between control and test groups on days 0 and 30 ( =0.01 ) . in each group , the mean scores of gbi and pi were compared between baseline and the end of the trial by the wilcoxon test ( =0.01 ) . the test dentifrice had a good acceptance and did not show adverse effects , such as formation of abscess and ulcerations or allergic reactions . only one subject in the test group reported unpleasant taste , but he did not drop out the clinical trial . there was a significant reduction of dentifrice tube weights between days 0 and 30 in both groups ( p<0.001","the effect of aloe vera on the reduction of plaque and gingivitis was evaluated in a randomized , parallel and double - blind clinical trial . subjects were randomly allocated to the test group ( n=15 ) dentifrice containing aloe vera - or the control group ( n=15 ) fluoridated dentifrice . plaque index ( pi ) and gingival bleeding index ( gbi ) were assessed at days 0 and 30 . subjects were asked to brush their teeth with the control or test dentifrice , three times a day , during a 30-day period . there was a significant reduction on plaque and gingivitis in both groups , but no statistically significant difference was observed among them ( p>0.01 ) . the dentifrice containing aloe vera did",380,128,0.3368
dialogsum,"#Person1#: You're looking very well. #Person2#: Thank you. I try to keep in shape. #Person1#: Do you often exercise? #Person2#: Yes, as long as I can find the time. I like swimming best. #Person1#: What style of swimming do you like best? #Person2#: I like the back best. I am good at freestyle stroke, but I usually use breast stroke as it keeps me from getting tired. #Person1#: I think butterfly stroke is the most difficult style to learn. #Person2#: I agree. I'm not good at it, either. Can you swim? How about going for a swim this Saturday? #Person1#: Oh, no. I am quite a stone in the water and cannot swim.","#Person2# often exercises and likes swimming best. #Person1# thinks butterfly stroke is the hardest, and #Person2# agrees.",113,17,0.1504
pubmed-summarization,"for even dispersion of egg counts and drug effectiveness , accurate dosing to make sure no administered drug is lost , and proper tagging of animals in each treatment group to ensure correct sampling . our study was conducted with strict adherence to the standardisation method to ensure accuracy of our data on the drugs we evaluated . the objective of this study was to evaluate resistance in west african dwarf goats to levamisole , albendazole , and ivermectin and v. amygdalina . the goat owners were interviewed before purchase to establish the treatment history of the herd . they were allowed to stabilize by giving feed , water , and mineral lick . after two weeks , the animals were divided into four treatment groups ( group a , ivermectin treatment , group b , levamisole treatment , group c , albendazole treatment , and group d , v. amygdalina treatment and group e was untreated reference group ) . the drugs ( ivermectin , levamisole , and albendazole ) were acquired from a veterinary drug store located in the study area while the plant , v. amygdalina , was collected from the environment and taken for authentication at the department of botany in the institution . the v. amygdalina leaves after identification were taken to the laboratory where the aqueous extract was prepared . two kilograms of v. amygdalina leaves was hand - washed in two litres of distilled water and passed through a 2 mm sieve and the filtrate was used within one hour . each animal in group a was given a dose of ivermectin injection of 0.2 mg / kg body weight subcutaneously individually . each animal in group b was given levamisole injection at a dose rate of 8.0 mg / kg body weight subcutaneously ; albendazole bolus was administered orally to each animal in group c at a dose rate of 10 mg / kg while the animals in group d were drenched with 5 mls per kg body weight of the plant aqueous extract . faecal samples were collected fresh from the rectum of the animals pretreatment and posttreatment in air - tight bags and taken to the laboratory for analysis . posttreatment samples were collected on days 1 , 2 ,","anthelmintic drug resistance has led to the search for alternatives in controlling helminth infections . fifty west african dwarf goats without history of anthelmintic treatment were divided equally into five groups . group a was treated with ivermectin injection subcutaneously , group b with levamisole subcutaneously , group c with albendazole orally , and group d with aqueous extract of vernonia amygdalina and group e was untreated control . faecal samples were collected before treatment from each animal and larval culture was carried out . faecal egg count reduction ( fecr ) test was carried out for each group and the data analysed using fecr version 4 to calculate percent reduction in faecal egg count . predominant helminth infections from larval culture were haemonchus contortus ( 70% )",380,128,0.3368
dialogsum,"#Person1#: Did you get your grades yet? #Person2#: Yeah. My whole GPA is screwed up now. #Person1#: Why? What happened? #Person2#: Well, I bombed my econ final and ended up with a 1. 7. #Person1#: Ouch. You must be very disappointed. #Person2#: Well, it's my fault because I didn't study as much as I should have. #Person1#: Why don't you re-take the class next year? #Person2#: That's what I plan on doing unless I keep screwing up. How did you do this semester? #Person1#: I didn't do that well either. I ended up with a 3. 2 this semester. That drops my total GPA to 3. 45. #Person2#: My GPA is pretty similar to yours. I have a 3. 1 now because of the stupid econ class. #Person1#: What was your GPA before this semester? #Person2#: I was sitting happy with a 3. 4. #Person1#: Why did it go down so much? #Person2#: Let's just say I screwed up more than my econ class. #Person1#: What happened to you? #Person2#: I started playing starcraft and ended up wasting a lot of time. #Person1#: You better stop slacking off. #Person2#: You're right. I'm not going to play games during school anymore.",#Person2# bombed the econ final because #Person2# didn't study attentively. #Person1# didn't do well this semester either and drops the total GPA to 3. 45. #Person2# says the bad scores might result from starcraft #Person2# started playing during school.,200,39,0.195
dialogsum,"#Person1#: Irene! I heard you were on a date last night! So, how how did it go? I want all the juicy details! #Person2#: Um. . . well, actually, we had a fantastic time last night. He was. . . amazing! #Person1#: Okay, now you really have to fill me in. What's he like? #Person2#: He's really good looking. he's quite tall, around 61, he's in his early thirties, and he's got the most beautiful dark brown eyes. . . #Person1#: He sounds hot! What does he do for a living? #Person2#: You know what, this is the best part. David is a junior investment banker at Fortune Bank, so he's got a great career path ahead of him! #Person1#: Hold on a sec, his name is David? #Person2#: Yeah? #Person1#: That's my brother!",Irene tells #Person1# the details of the date she had last night. #Person1# surprisingly finds the man Irene dated is #Person1#'s brother David.,134,23,0.1716
scientific_lay_summarisation-elife-norm,"and malignant cell growth (Patial and Blackshear, 2016). To determine ZFP36 functions in T cells, we employed high-throughput sequencing of UV-cross-linking and immunoprecipitation (HITS-CLIP) to generate a definitive set of ZFP36 RNA targets. HITS-CLIP utilizes in vivo UV-cross-linking to induce covalent bonds between RBPs and target RNAs, allowing stringent immunopurification and thus rigorous identification of direct binding events (Licatalosi et al. , 2008; Ule et al. , 2003). These new ZFP36 RNA binding maps pointed to roles in regulating T-cell activation kinetics and proliferation, a function confirmed in extensive functional assays, and in vivo studies demonstrating a critical role in anti-viral immunity. Our results illuminate novel functions for ZFP36 in adaptive immunity, laying groundwork for understanding and modulating its activity in disease. ZFP36 expression is induced upon T-cell activation (Raghavan et al. , 2001). We examined its precise kinetics following activation of primary mouse CD4 +T cells by Western analysis with custom ZFP36 antisera generated against a C-terminal peptide of mouse ZFP36. Protein levels peaked ~4 hr post-activation and tapered gradually through 72 hr, and were re-induced by re-stimulation 3 days post-activation (1A). ZFP36 expression depended on both TCR stimulation, provided by anti-CD3, and co-stimulation, provided by co-cultured dendritic cells (DCs) (1B). A similar pattern of transient ZFP36 induction occurred in activated CD8 +T cells (— 1A). Western blot analysis showed multiple bands at ~40–50 kD, indicating several isoforms. Notably, isoforms running above the predicted molecular weight (MW) of ZFP36 (36 kD) pre-dominated early after activation, and are consistent with previously reported hyperphosphorylation (Qiu et al. , 2012). In addition, partial conservation of the immunizing peptide in ZFP36L1 and ZFP36L2 raised the possibility of paralog cross-reactivity. Western analyses with recombinant constructs confirmed ZFP36, ZFP36L1, and ZFP36L2 are readily detected with our custom antisera (henceforth, pan anti-ZFP36; — 1B). Commercial paralog-specific antibodies were identified, and Western analysis showed that both ZFP36 and ZFP36L1 were induced by T-cell activation (— 1B–C). ZFP36L2, expected to run at ~62 kD, was not detected under any conditions examined. Analysis of Zfp36 KO T cell lysates with pan ZFP36 antisera showed ~50% reduced signal compared to WT. We conclude that the residual signal is likely due to persistent expression of ZFP36L1, which is highly homologous and of similar size to ZFP36. Collectively, these results demonstrate activation-dependent","The immune system must quickly respond to anything that may cause disease – from cancerous cells to viruses. For instance, a type of white blood cell called a T cell patrols the body, looking for potential threats. If a T cell identifies such a threat, it “activates” and undergoes various changes so that it can help to eliminate the problem. One way that T cells change is by switching on different genes to make specific proteins. The information in the genes is first used as a template to produce a molecule called a messenger RNA (mRNA), which is then translated to build proteins. So-called RNA-binding proteins help control events before, during and after the translation stage in the process. Previous studies have shown that one particular RNA-binding protein,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"burst firing. In support of this model, mice that are genetically engineered to overexpress NR2B exhibit enhanced hippocampal LTP and behavioral memory (Tang et al. , 1999). Olfactory memory in Drosophila involves a heterosynaptic mechanism driven by reinforcing dopaminergic neurons, which results in presynaptic depression of cholinergic connections between odor-activated mushroom body (MB) Kenyon cells (KCs) and downstream mushroom body output neurons (MBONs) (Schwaerzel et al. , 2003; Aso et al. , 2010; Aso et al. , 2012; Claridge-Chang et al. , 2009; Burke et al. , 2012; Liu et al. , 2012; Plaçais et al. , 2013; Owald et al. , 2015; Hige et al. , 2015; Barnstedt et al. , 2016; Perisse et al. , 2016; Aso et al. , 2014; Owald and Waddell, 2015). In addition, olfactory information is conveyed to KCs by cholinergic transmission from olfactory projection neurons (Yasuyama et al. , 2002; Leiss et al. , 2009). Although it is conceivable that glutamate is delivered to the MB network via an as yet to be identified route, there is currently no obvious location for NMDAR-dependent plasticity in the known architecture of the cholinergic input or output layers (Barnstedt et al. , 2016). The fly therefore provides a potential model to investigate other mechanisms through which dietary Mg2+ might enhance memory. The reinforcing effects of dopamine depend on the Dop1R D1-type dopamine receptor (Kim et al. , 2007; Qin et al. , 2012; Handler et al. , 2019), which is positively coupled with cAMP production (Tomchik and Davis, 2009; Boto et al. , 2014). Moreover, early studies in Drosophila identified the dunce and rutabaga encoded cAMP phosphodiesterase and type I Ca2+-stimulated adenylate cyclase, respectively, to be essential for olfactory memory (Dudai et al. , 1976; Byers et al. , 1981; Dudai and Zvi, 1984; Chen et al. , 1986; Livingstone et al. , 1984; Levin et al. , 1992). Studies in mammalian cells have shown that hormones or agents that increase cellular cAMP level often elicit a significant Na+-dependent extrusion of Mg2+ into the extracellular space (Romani and Scarpa, 1990b; Romani and Scarpa, 1990a; Romani and Scarpa, 2000; Vink and Nechifor, 2011; Vormann and Günther, 1987). However, it is unclear whether Mg2+ extrusion plays any role in memory processing. Here we demonstrate that Drosophila long-term memory","The proverbial saying ‘you are what you eat’ perfectly summarizes the concept that our diet can influence both our mental and physical health. We know that foods that are good for the heart, such as nuts, oily fish and berries, are also good for the brain. We know too that vitamins and minerals are essential for overall good health. But is there any evidence that increasing your intake of specific vitamins or minerals could help boost your brain power? While it might sound almost too good to be true, there is some evidence that this is the case for at least one mineral, magnesium. Studies in rodents have shown that adding magnesium supplements to food improves how well the animals perform on memory tasks. Both young and old",380,128,0.3368
scientific_lay_summarisation-elife-norm,"display intermediate features (Borrell and Reillo, 2012; Hutsler et al. , 2005; Kawasaki, 2014; Reillo et al. , 2011). Specifically, ferrets exhibit a gyrified neocortex and, during development, a pronounced OSVZ populated with proliferative bRG (Barnette et al. , 2009; Borrell and Reillo, 2012; Fietz et al. , 2010; Kawasaki, 2014; Kawasaki et al. , 2013; Poluch and Juliano, 2015; Reillo et al. , 2011; Sawada and Watanabe, 2012; Smart and McSherry, 1986a; Smart and McSherry, 1986b). In this context, it should be noted that in evolution, the split between the lineages leading to mouse and to human occurred a few million years later than that leading to ferret and human (Bininda-Emonds et al. , 2007). In addition to the above-mentioned features associated with neocortex expansion in general, certain specific aspects of human neocortex expansion are thought to involve human-specific genomic changes. Recent transcriptomic studies established that certain previously identified human-specific genes (Bailey et al. , 2002; Dennis and Eichler, 2016) are preferentially expressed in neural progenitor cells and have implicated these genes in human neocortex expansion (Fiddes et al. , 2018; Florio et al. , 2015; Florio et al. , 2018; Florio et al. , 2016; Suzuki et al. , 2018). Among these genes, the one that showed the most specific expression in human bRG compared to neurons was ARHGAP11B (Florio et al. , 2015). ARHGAP11B arose in evolution after the split of the human lineage from the chimpanzee lineage, as a product of a partial gene duplication of ARHGAP11A, a gene encoding a Rho GTPase activating protein (Dennis et al. , 2017; Florio et al. , 2015; Florio et al. , 2016; Kagawa et al. , 2013). Forced expression of ARHGAP11B in the embryonic mouse neocortex leads to an increase in BP proliferation and pool size (Florio et al. , 2015). However, as described above, the mouse exhibits only a minute amount of bRG, a cell type thought to be instrumental for neocortex expansion, and the role of ARHGAP11B on the pool size of bRG, therefore, remains elusive. Additionally, the role of ARHGAP11B on the production of upper-layer neurons, another hallmark of the evolutionary expansion of the neocortex, is also unknown. Here, we study the effects of forced expression of ARHGAP11B in the developing ferret neocortex, which already","The human brain owes its characteristic wrinkled appearance to its outer layer, the cerebral cortex. All mammals have a cerebral cortex, but its size varies greatly between species. As the brain evolved, the neocortex, the evolutionarily youngest part of the cerebral cortex, expanded dramatically and so had to fold into wrinkles to fit inside the skull. The human neocortex is roughly three times bigger than that of our closest relatives, the chimpanzees, and helps support advanced cognitive skills such as reasoning and language. But how did the human neocortex become so big? The answer may lie in genes that are unique to humans, such as ARHGAP11B. Introducing ARHGAP11B into the neocortex of mouse embryos increases its size and can induce folding. It does this by increasing the number",380,128,0.3368
dialogsum,"#Person1#: What do you think of our price? #Person2#: Your price has gone up sharply, hasn't it? #Person1#: Yes. We regret we cannot maintain our original price. Since the prices of the raw materials have been raised, we have to adjust the price of our products accordingly. #Person2#: I agree with you there, but your price is unreasonable. #Person1#: I don't think so. You must compare our price with that of other export houses. I'm sure our offer is in line with the prevailing market price level. #Person2#: I don't think we'll be able to pay the price. To have this business concluded, you need to lower your price at least by 3 %. #Person1#: I ' m afraid that there is no room for any reduction in price. #Person2#: Don't you agree with me that in the long run, moderate prices will bring about large sales and more profit? #Person1#: We've already cut down our price to cost level. #Person2#: Is that all? #Person1#: Yes, this is the best we can do. #Person2#: I'm sorry we can't handle the price you offered.",#Person2# thinks #Person1#'s price is unreasonable but #Person1# thinks #Person1#'s offer fits the prevailing market price level. #Person2# wants #Person1# to lower the price by 3% but #Person1# refuses. #Person2# can't handle the price.,183,34,0.1858
pubmed-summarization,"any potential increased winter fall rate and decreased levels of vitamin d has not been investigated . the winter season sees an increase in injuries from falls and in the number of accidental deaths from falls . fracture rates from falls in older adults also increase at the end of the winter season , following two to eight weeks after the nadir in serum vitamin d levels . some studies report an increased rate of falls , for both inside and outside falls ; however , significant seasonal variation in fall rates was not found in a three - year study while , in a second study , seasonal variation in fall rates was reported in women but not in men . coincident static balance changes with any potential increased fall rates in winter have not been previously reported . the data presented here forms part of a larger study , from which two other papers with the same clinical trial registration have been published . the aim of this study was to determine differences in static balance ( postural sway ) , vitamin d , incidence of falls , and type of fall serially at the end of each season over a 12-month period , in older community - living adults . we hypothesised that postural sway , falls , and vitamin d would show a seasonal variation and that there would be an inverse relationship between vitamin d and the other variables . at the end of consecutive seasons , static balance , vitamin d status , and fall rate were measured within a longitudinal study design . no intervention was implemented by study researchers , so that the study could identify natural variations that occur over the seasons . data was collected over a three - week period in each season from end of spring 2009 to the end of spring 2010 , with collection of data timed to coincide with expected peaks and troughs in serum vitamin d levels in australia at latitude 41 degrees south ( tasmania ) . after each assessment , participants were given an appointment for the next collection block in three months ' time . independently living community - dwelling adults aged between sixty and eighty - five years were recruited","introduction . low serum vitamin d levels are associated with increased postural sway . vitamin d varies seasonally . this study investigates whether postural sway varies seasonally and is associated with serum vitamin d and falls . methods . in a longitudinal observational study , eighty - eight independently mobile community - dwelling older adults ( 69.7 7.6 years ) were evaluated on five occasions over one year , measuring postural sway ( force platform ) , vitamin d levels , fall incidence , and causes and adverse outcomes . mixed - methods poisson regression was used to determine associations between measures . results . postural sway did not vary over the year . vitamin d levels varied seasonally ( p < 0.001 ) , peaking in summer",380,128,0.3368
dialogsum,"#Person1#: Hello, I'm sorry for calling this late. May I speak to Peter? #Person2#: I'm sorry. He's not in right now. #Person1#: When is he coming back? #Person2#: He should be back in ten minutes. Could 1 you call back later? #Person1#: I'll call again in thirty minutes.",#Person2# asks #Person1# to call Peter later.,48,7,0.1458
scientific_lay_summarisation-elife-norm,"regions of YAP and TAZ are found in the YAP-TFE3 and TAZ-CAMTA1 fusion proteins, detailed functional studies of YAP-TFE3 have not been performed. Furthermore, the mechanism by which these hybrid transcription factors regulate transcription and subsequent cell transformation has not been defined. Herein we identify the Ada2a-containing histone acetyltransferase (ATAC) complex as a key epigenetic modifier of the TAZ-CAMTA1 and YAP-TFE3 oncogenic transcriptional programs. The ATAC complex is one of two metazoan complexes that incorporates the GCN5 or closely related PCAF histone acetyltransferase subunit, and primarily acetylates lysine 9 of histone 3 (H3K9) and to a lesser degree lysine 14 (H3K14) (Nagy et al. , 2010). There is emerging evidence that the ATAC complex is an oncogenic driver in cancer. YEATS2, one of the subunits of the ATAC complex, has been shown to be functionally important to the pathogenesis of non-small cell lung cancer (Mi et al. , 2017). Amplification of YEATS2 has been identified in ovarian cancer, head and neck cancer, esophageal cancer, and uterine cancer (Mi et al. , 2017), as well as both well-differentiated and dedifferentiated liposarcoma (Beird et al. , 2018). Herein, we show that the ATAC complex is a key epigenetic mediator of the oncogenic properties of both the TAZ-CAMTA1 and YAP-TFE3 fusion proteins and thereby a potential therapeutic target for essentially all cases of EHE. The WWTR1 (TAZ) -CAMTA1 gene fusion fuses the end of exon 2 or exon 3 of WWTR1 to a breakpoint with exon 9 of CAMTA1 (2,3). This results in the N terminus of TAZ being fused in frame to the C terminus of CAMTA1. The N terminus of TAZ contains the TEAD binding domain and 14-3-3 protein binding site (Kanai et al. , 2000). The WW domain may be absent or present, depending on the type of gene fusion. The C terminus of CAMTA1 contributes the transactivating domain, the TIG domain, ankyrin domain, IQ domain, and nuclear localization signal (1A; Tanas et al. , 2016; Finkler et al. , 2007; Long et al. , 2014). Similarly, YAP1-TFE3 fuses exon one from YAP1 in frame to exon 4 of TFE3 resulting in the N terminus of YAP fused in frame to the C terminus of TFE3. The N terminus of YAP contains the TEAD-binding domain (Gaffney et al. , 2012;","The proliferation of human cells is tightly regulated to ensure that enough cells are made to build and repair organs and tissues, while at the same time stopping cells from dividing uncontrollably and damaging the body. To get the right balance, cells rely on physical and chemical cues from their environment that trigger the biochemical signals that regulate two proteins called TAZ and YAP. These proteins control gene activity by regulating the rate at which genes are copied to produce proteins. If this process becomes dysregulated, cells can grow uncontrollably, causing cancer. In cancer cells, it is common to find TAZ and YAP fused to other proteins. In epithelioid hemangioendothelioma, a rare cancer that grows in the blood vessels, cancerous growth can be driven by a version of",380,128,0.3368
dialogsum,"#Person1#: Hi, are you Catherine? #Person2#: Yes, Jason, right? Nice to meet you. Welcome to Taiwan. #Person1#: Thanks, good to meet you, too. #Person2#: You had a long flight, you must be tired. #Person1#: Yes, and the food was horrible! #Person2#: Oh, sorry to hear that. But, don worry! Taiwan has plenty of great things to eat. First, lets get you to the hotel. #Person1#: Great! How will we be getting there? #Person2#: My car is in the parking lot, lets go this way. Let me help you with your bags.",Catherine welcomes Jason who comes to Taiwan after a long flight.,91,11,0.1209
scientific_lay_summarisation-elife-norm,"that necrotic cell death may be accomplished by a set of signal transduction pathways and execution mechanisms (thus termed necroptosis) (Vandenabeele et al. , 2010; Linkermann and Green, 2014). Recently, the serine/threonine kinase receptor interaction protein 1 (RIP1) was identified as the crucial mediator of this process, with RIP1 phosphorylation being the key step in necroptosis (Degterev et al. , 2005; Christofferson et al. , 2014). Blockade of RIP1 phosphorylation by the specific inhibitor, necrostatin-1 (Nec-1), inhibited necroptosis (Degterev et al. , 2005; Christofferson et al. , 2014). Necroptosis plays a critical role in many pathophysiological processes, such as ischemic injury and viral infection (Vandenabeele et al. , 2010; Christofferson et al. , 2014; Linkermann and Green, 2014). In most studies, necroptosis was mainly induced by the activation of death receptors (DRs), for example, tumor necrosis factor-α (TNF-α) receptor, in the absence of caspase activation (He et al. , 2009; Vandenabeele et al. , 2010). Other endogenous initiators of necroptosis remain largely unknown. Here we report that extracellular protons trigger a novel form of necroptosis in neurons via ASIC1a, but independent of its ion-conducting function. Using RNA interference and pharmacological blockade, we identified RIP1 as a critical component in acid-induced neuronal death. RIP1 is recruited to ASIC1a within 30 min of acid stimulation, which causes RIP1 phosphorylation and triggers the downstream death events. Similarly, RIP1 became physically associated with ASIC1a and hyperphosphorylated in response to middle cerebral artery occlusion (MCAO) in mice. The enhanced RIP1 phosphorylation in response to either ischemia or acidosis was undetected in neurons from Asic1a−/− mice, demonstrating the involvement of ASIC1a-mediated RIP1 activation in ischemic brain injury. According to morphological appearance, cell death can be divided into apoptotic and necrotic death (Kroemer et al. , 2009). Either death form represents a specific set of signaling pathways and biochemical/cellular processes (Kroemer et al. , 2009). In order to classify acid-induced neuronal death, we first examined the morphological changes of cultured mouse cortical neurons exposed to acidosis using electron microscopy (EM). While most neurons treated with a pH 7. 4 solution (— 1A, upper panel) showed normal cellular morphology (1A1, left panel; 1A2, upper panel), those treated with a pH 6. 0 solution (1 hr treatment and 24 hr recovery in normal culture medium, — 1A, middle panel)","What happens in the minutes and hours after a stroke can determine how much brain damage occurs. In some types of stroke, a blood clot cuts off the blood supply to part of the brain, depriving the brain cells of oxygen and other nutrients, including glucose. One of the consequences is that the blood-starved brain becomes more acidic, which triggers cell death. Protecting brain cells from acidity-induced death could therefore reduce the damage caused by a stroke, and may also be an effective treatment for other brain disorders that involve increased brain acidity, like multiple sclerosis and Huntington' s disease. To create such treatments, researchers must first understand how increased acidity in the brain triggers cell death. A protein called the acid-sensing ion channel 1a (ASIC1a) is thought",380,128,0.3368
dialogsum,"#Person1#: Debbie, do you have a favorite place that you would like to go for your birthday dinner? #Person2#: I don't really know where I want to go. I am having trouble thinking of a particular restaurant. #Person1#: We could look online at the local Internet sites. #Person2#: Good, let's take a look. #Person1#: What kind of food would you like for your birthday? #Person2#: I like a lot of things, but Chinese or Thai would be better. #Person1#: This one, Beijing duck looks pretty good. #Person2#: Oh, yes, I've heard of that before. Everyone I've talked with says that it is great. #Person1#: Would you like to go there, then? #Person2#: I think that would be a really good choice. Let's call ahead to make sure that we can get a table for that night.",#Person1# and Debbie are looking for a restaurant online for Debbie's birthday dinner. Debbie chooses Beijing duck and will call ahead to get a table.,136,25,0.1838
dialogsum,"#Person1#: I've come to hear about your offer. #Person2#: We have the offer ready for you. Let me check. 10 boxes with 50 brooches per box, at 20, 000 yuan ; 20 boxes with 50 waistbands per box, at 30, 000 yuan ; 15 boxes with other ornaments per box, at 7, 500 yuan, for shipment in June. The offer is valid for five days. #Person1#: I can tell you right now that your prices are a little higher than we expected. #Person2#: You know that the prices of the ornaments have been rising in recent years. The prices we offer this time compare favorably with quotations you can get else where. #Person1#: I am afraid I can't agree with you there. I must point out your prices are higher than the quotations we've received from other companies. #Person2#: But you must take the design and quality into consideration. You know we are superior to others in design and quality. We have various styles, which the other companies cannot catch up with. #Person1#: I agree that yours are of the top. #Person2#: Well, since your order is large enough, can you give me a rough idea? #Person1#: To have this business concluded, I should say a reduction of least 10 % would help. #Person2#: Impossible. How about 5 % off? #Person1#: Right. A reduction of 5 % is acceptable.",#Person2# gives #Person1# an offer of ornaments. #Person1# thinks the price is higher than other companies. #Person2# asks #Person1# to consider design and quality. They agree on a 5% reduction.,229,30,0.131
scientific_lay_summarisation-elife-norm,"The computational principles by which the brain creates a painful experience from nociception are still unknown. Classic theories suggest that cortical regions either reflect stimulus intensity or additive effects of intensity and expectations, respectively. By contrast, predictive coding theories provide a unified framework explaining how perception is shaped by the integration of beliefs about the world with mismatches resulting from the comparison of these beliefs against sensory input. Using functional magnetic resonance imaging during a probabilistic heat pain paradigm, we investigated which computations underlie pain perception. Skin conductance, pupil dilation, and anterior insula responses to cued pain stimuli strictly followed the response patterns hypothesized by the predictive coding model, whereas posterior insula encoded stimulus intensity. This novel functional dissociation of pain processing within the insula together with previously observed alterations in chronic pain offer a novel interpretation of aberrant pain processing as disturbed weighting of predictions and prediction errors. Classic bottom-up views construe perception as a feedforward stream of sensory information that is passed along the neural hierarchy from receptors to high-level brain regions (Hubel and Wiesel, 1959). Accordingly, neurons are thought of as feature detectors and cortical responses to sensory stimuli are expected to scale with the presence of stimulus features, that is, activity in pain processing brain regions should reflect the activation level of nociceptors. This basic account has been extended by a wealth of findings demonstrating that top-down expectations play an important role in modulating both the pain experience and the activity in pain processing brain regions (Sawamoto et al. , 2000; Koyama et al. , 2005; Lorenz et al. , 2005; Brown et al. , 2008; Atlas et al. , 2010; Bingel et al. , 2011; Wiech et al. , 2014b). Other neuroimaging studies have shown that stimulus-response functions differ between brain regions (Davis et al. , 1998; Coghill et al. , 1999; Apkarian et al. , 2001; Bornhövd et al. , 2002; Davis et al. , 2002; Porro et al. , 2004) and that brain activation is modulated by concurrent task demands (Bantick et al. , 2002; Valet et al. , 2004; Wiech et al. , 2005; Seminowicz and Davis, 2007; Villemure and Bushnell, 2009). However, these theories cannot explain the reduction in sensory cortical activity for expected compared to unexpected stimuli (Alink et al.","All over the human body, there are receptors that help to alert the brain to potential harm. For example, intense heat on the skin elicits a signal that travels to the brain and activates many parts of the brain. Some of the same brain regions that are switched on by signals of potential bodily harm also help the brain to form expectations about events. A person’s expectations may have a strong influence on how they experience pain. For example, if a person expects that taking a pill will reduce their pain, they may feel less pain even if the pill is a fake. Exactly how the brain processes pain signals and expectations remains unclear. Does the brain activity simply reflect how intense the heat is? Some scientists think",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Many RNAs, including pre-mRNAs and long non-coding RNAs, can be thousands of nucleotides long and undergo complex post-transcriptional processing. Multiple sites of alternative splicing within a single gene exponentially increase the number of possible spliced isoforms, with most human genes currently estimated to express at least ten. To understand the mechanisms underlying these complex isoform expression patterns, methods are needed that faithfully maintain long-range exon connectivity information in individual RNA molecules. In this study, we describe SeqZip, a methodology that uses RNA-templated DNA–DNA ligation to retain and compress connectivity between distant sequences within single RNA molecules. Using this assay, we test proposed coordination between distant sites of alternative exon utilization in mouse Fn1, and we characterize the extraordinary exon diversity of Drosophila melanogaster Dscam1. One of the most important drivers of metazoan gene expression is the ability to produce multiple mRNA isoforms from a single gene. Around 58% of Drosophila melanogaster genes and >95% of human genes produce more than one transcript (Pan et al. , 2008; Wang et al. , 2008; Brown et al. , 2014), with most human genes expressing 10 or more distinct isoforms (Djebali et al. , 2012). Alternative promoter use, alternative splicing, and alternative polyadenylation all contribute to isoform diversity. In genes with multiple alternative transcription start and/or pre-mRNA processing sites, their combinatorial potential exponentially increases the number of possible products, with some human genes predicted to express >100 mRNA isoforms. In D. melanogaster, the number of isoforms observed per gene correlates with open reading frame length, suggesting that isoform complexity is a function of transcript length (Brown et al. , 2014). The current record holder in this regard is Dscam1, in which four regions of mutually exclusive cassette exons combine to generate a remarkable 38,016 distinct >7000 nt mRNAs, each encoding a unique protein isoform (Schmucker et al. , 2000). In Dscam1, the four regions of mutually exclusive cassette exon splicing are separated by one to eight constitutive exons. This feature of multiple alternative splicing regions separated by constitutive exons is shared by more than a quarter of human genes (Fededa et al. , 2005). In many cases, these regions are separated by >500 nts, the current limit for contiguous sequence output on most deep sequencing platforms. Further, high-throughput sequencing of RNA (RNA-Seq) generally","A flow chart can show how an outcome can be achieved from a particular start point by breaking down an activity into a list of possible steps. Often, a flow chart contains several alternative steps, not all of which are taken every time the flow chart is used. The same can be said of genes, which are biological instructions that often contain many options within their DNA sequences. Proteins—which perform many roles in cells—are built following the instructions contained in genes. First, the DNA sequence of the gene is copied. This produces a molecule of ribonucleic acid (RNA), which is able to move around the cell to find the machinery that can use the genetic information to make a protein. Genes and their RNA copies contain instructions with",380,128,0.3368
dialogsum,"#Person1#: What a letdown. I wanted to experience some Mafia culture firsthand. #Person2#: It's worth it just to go and eat what the mafia eat! The five-dollar tiramisu is a culinary orgasm. #Person1#: Such a thing exists? #Person2#: Fortunately, yes. You're blushing! #Person1#: Am I? Um. . . my face gets red when I walk too fast. #Person2#: You're embarrassed, aren't you? You gotta loosen up in Little Italy. The lady at the cafe will kiss you when you meet her. . .",#Person2# recommends 5-dollar tiramisu in mafia culture and asks #Person2# to lose up in Little Italy.,83,16,0.1928
pubmed-summarization,"osteoporosis is defined as a skeletal disorder characterized by loss of bone mass , decreased bone strength , and increased risk of bone fracture.1 the disease progresses with age , especially in postmenopausal women.2 japan is one of the most rapidly aging societies worldwide . according to the national institute of population and social security research ( tokyo , japan ) , japanese individuals over 65 years of age constitute 23.0% of the population in 2010 and 25.1% to 25.2% as of 2013 , meaning that more than one in four people in japan are elderly . according to population - based epidemiologic studies , the estimated number of people with osteoporosis in japan is 13 million , among which 130,000 suffer from hip fractures every year ; 20,000 of these individuals die and 60,000 experience functional decline . the prevalence rate of vertebral fractures in japan is reportedly comparable with or higher than in caucasian populations , and is approximately 30% in women in their 70 s and 40% in those in their 80 s.3 a study of the prevalence of vertebral fractures in hong kong , thailand , indonesia , and japan revealed that the prevalence of vertebral fractures in both men and women was highest in japan for the younger ( 6574 years ) and older ( 75 years ) age groups ( 36.6% and 37.6% for men , 18.8% and 28.7% for women , respectively).4 bisphosphonates are known to increase bone mineral density by inhibiting osteoclast - mediated bone resorption and thereby reduce the risk of fractures.5 several formulations containing bisphosphonates have been applied to the management of osteoporosis . alendronate sodium hydrate ( alendronate ) is a bisphosphonate that potently inhibits bone resorption and is used for the treatment of osteoporosis . alendronate produces a sustained reduction in the levels of biochemical markers of bone remodeling , returning them to the premenopausal range.6,7 it also increases bone mineral density612 and decreases the risk of osteoporotic fracture in postmenopausal women.812 long - term intervention studies have shown that continuous alendronate therapy is associated with a sustained therapeutic effect on bone density and remodeling.13,14 however , bisphosphonates including alendronate , suppress bone remodeling and thus may prevent the repair of microdamage . nine patients reportedly developed spontaneous","osteoporosis is a skeletal disorder characterized by loss of bone mass , decreased bone strength , and an increased risk of bone fracture . the disease progresses with age , especially in postmenopausal women . japan is one of the most rapidly aging societies worldwide . japanese individuals over 65 years of age constituted 23.0% of the population in 2010 and 25.1% to 25.2% as of 2013 . the estimated number of people with osteoporosis in japan is currently 13 million . bisphosphonates increase bone mineral density by inhibiting osteoclast - mediated bone resorption , thereby reducing the risk of fractures . alendronate sodium hydrate ( alendronate ) is a bisphosphonate that potently inhibits bone resorption and is used to treat osteoporosis . sufficient water is required to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"anti-inflammatory effects through the release of glucocorticoids (Tracey, 2002). A cholinergic anti-inflammatory pathway has also been reported, in which the activation of efferent vagus nerves suppresses systemic inflammatory responses (Borovikova et al. , 2000; Wang et al. , 2004). Acetylcholine attenuates cytokine production from LPS-activated macrophages in the spleen through the nicotinic acetylcholine receptor (Wang et al. , 2003). Vagus nerve stimulation also leads to the activation of the splenic nerve and release of norepinephrine in the spleen (Vida et al. , 2011). Norepinephrine inhibits cytokine production in the spleen and suppresses systemic inflammation in experimental sepsis through β2-adnenoceptors on lymphocytes (Vida et al. , 2011). Thus, the anti-inflammatory effects of the sympathetic and parasympathetic nervous systems seem to be synergistic. The hypothalamic neuropeptide orexin, which plays a crucial role in controlling sleep/wakefulness (Sakurai, 2007), regulates the hypothalamo-pituitary-adrenal axis by activating the paraventricular nucleus (PVN) (Kuru et al. , 2000) and integrates autonomic functions by interacting with brainstem centers (Zheng et al. , 2005). Recent reports show that intracerebroventricular (ICV) administration of orexin modulates heart rate and body temperature, and increases the level of adrenocorticotropic hormone (ACTH) in a murine sepsis model induced by cecal ligation and puncture (Deutschman et al. , 2013). ICV orexin also partially increases locomotor activity suppressed by a low dose of LPS in rats (Grossberg et al. , 2011). However, no information is available as to whether orexin actually improves the survival and/or suppresses the systemic inflammation. Moreover, CNS administration of therapeutic agents in human patients may often be unfeasible; clinical applications of orexin in humans require a tactic to deliver orexin into the brain. Systemic inflammation, the hallmark of sepsis, enhances the permeability of the blood-brain barrier (BBB) in rodents (Kowal et al. , 2004; Xaio et al. , 2001) and humans (Ballabh et al. , 2004); some peptides and proteins, including insulin, albumin (Xaio et al. , 2001), and antibodies (Kowal et al. , 2004), can enter the brain under the condition of systemic inflammation. In this study, we deliver orexin into the brain by taking advantage of the enhanced BBB permeability under the condition of systemic inflammation, rescuing mice with endotoxin shock by targeting the CNS. Orexin cannot normally penetrate the BBB (Fujiki et al. , 2003). Surprisingly, however, we found that","The body has a range of defenses to fight infection, which play a crucial role in keeping us healthy. However, sometimes the response to infection may damage the body’s own tissues and organs, leading to a life-threatening condition called sepsis. In the most severe stage of sepsis – known as septic shock – blood pressure drops to dangerously low levels and the individual often dies. There is currently no effective therapy for septic shock. Recent studies have revealed how the brain regulates immune responses via chemical signals and nerve impulses. A molecule called orexin is made in the brain and regulates the activity of a group of neurons that control sleep. Orexin can also alter heart rate and body temperature in rats, which suggests that it may have",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2006; Pacek et al. , 2006; Ilves et al. , 2010). GINS/Cdc45 assembly is dependent on the CDK kinase (Zegerman and Diffley, 2007), while post-translational modification of Mcm subunits 2,4, and 6 by the Cdc7/Dbf4 kinase (DDK) further contributes to CMG activation (Labib, 2010; Sheu and Stillman, 2010). Following the assembly of replicative polymerases and replisomal scaffolding factors (Gambus et al. , 2009; Muramatsu et al. , 2010), the two CMG particles split apart into discrete complexes that have been proposed to each encircle a single DNA strand during translocation (Yardimci et al. , 2010; Boos et al. , 2012). At present, multiple aspects of the Mcm2-7 loading and activation cycle remain poorly understood. Although the six homologous subunits of one Mcm2-7 complex are known to pair with a second Mcm2-7 complex through their N-terminal domains in the context of a double-hexamer (Evrin et al. , 2009; Remus et al. , 2009), the precise register by which these subunits interact with each other across the two rings is not known. How DDK phosphorylation of the Mcm2, Mcm6, and Mcm4 N-termini (Labib, 2010), or how a DDK-bypass mutation in the N-terminus of either Mcm4 (Sheu and Stillman, 2010) or Mcm5 (Jackson et al. , 1993), might aid in the switch from an inactive Mcm2-7 double hexamer state to a functional CMG is similarly unclear, particularly as Mcm4 is spatially segregated from Mcm2 and Mcm5 (Costa et al. , 2011). During unwinding and fork progression, the CMG translocates 3′→5′ along DNA. How the various components of the CMG engage nucleic acid strands during this process has remained ill-defined. Cdc45 has recently been shown to contain a RecJ exonuclease domain that can bind DNA but that is catalytically inactive (Petojevic et al. , unpublished data, as well as Sanchez-Pulido and Ponting, 2011; Krastanova et al. , 2012; Szambowska et al. , 2014). Whether or how the Cdc45 RecJ fold might bind single DNA strands formed in the context of the CMG has not been established. Conflicting models likewise exist for how Mcm2-7 engages substrate DNAs as it moves 3′→5′ during strand separation, with biochemical data from archaeal MCMs and phylogenetic relationships to superfamily III (SFIII) helicases (such as the SV40 Large T antigen and the papillomavirus E1 protein) predicting mutually exclusive binding","Before a cell divides, it must duplicate its DNA so that each new cell inherits its own copy of the genome. To do this, the DNA double helix must be unwound so that the two individual strands of DNA can serve as templates for making new DNA molecules. Unwinding begins when two helicase complexes, termed the Mcm2-7 rings, are loaded together onto the DNA. At first, the two Mcm2-7 rings encircle the double-stranded DNA and remain bound together in an inactive form. Activating the Mcm2-7 rings requires the binding of five other proteins to each ring, which forms two larger complexes called CMG helicases. When the CMG helicases form, the two DNA strands separate and an individual Mcm2-7 ring ends up encircling each of the single DNA strands.",380,128,0.3368
dialogsum,"#Person1#: I'd like to book seats for the Merchant of Venice, please. #Person2#: Yes, of course, sir. #Person1#: Have you got any seats downstairs, please? #Person2#: Yes, we have. #Person1#: How much are they, please? #Person2#: $3.75 each. #Person1#: Are there any seats at $2.50? #Person2#: Yes, there are, but upstairs. For how many? #Person1#: For 4, please. #Person2#: For which night? #Person1#: What about Saturday, October twenty-first? #Person2#: I can give you 4 seats in row 8. OK? #Person1#: Right. How long will the performance last? #Person2#: Two and a half hours. #Person1#: Thank you. How much is that altogether? #Person2#: $10 please.",#Person2# serves #Person1# to book 4 seats for the Merchant of Venice. #Person1# book 4 upstairs seats on Saturday for $10,104,21,0.2019
scientific_lay_summarisation-elife-norm,"is the accurate prediction of miRNA–target interactions. Although numerous advances have been made, accurate and specific target predictions remain a challenge. Analysis of preferentially conserved miRNA-pairing motifs within 3′ UTRs has led to the identification of several classes of target sites (Bartel, 2009). The most effective canonical site types, listed in order of decreasing preferential conservation and efficacy, are the 8mer site (Watson–Crick match to miRNA positions 2–8 with an A opposite position 1 [Lewis et al. , 2005]), 7mer-m8 site (position 2–8 match [Brennecke et al. , 2005; Krek et al. , 2005; Lewis et al. , 2005]), and 7mer-A1 site (position 2–7 match with an A opposite position 1 [Lewis et al. , 2005]). Experiments have confirmed that the preference for an adenosine opposite position 1 is independent of the miRNA nucleotide identity (Grimson et al. , 2007; Nielsen et al. , 2007; Baek et al. , 2008) and due to the specific recognition of the target adenosine within a binding pocket of Argonaute (Schirle et al. , 2014). Two other canonical site types, each associated with weaker preferential conservation and much lower efficacy (Friedman et al. , 2009), are the 6mer (position 2–7 match [Lewis et al. , 2005]) and offset-6mer (position 3–8 match [Friedman et al. , 2009]). Pairing to the 3′ end of the miRNA can canonical sites, although evidence for the use of this 3′-supplementary pairing is observed for no more than 5% of the seed-matched sites (Brennecke et al. , 2005; Lewis et al. , 2005; Grimson et al. , 2007; Friedman et al. , 2009). Some effective sites lack canonical seed pairing. For example, very extensive pairing to the 3′ region of the miRNA can compensate for a wobble or mismatch to one of the seed positions (Doench and Sharp, 2004; Brennecke et al. , 2005; Bartel, 2009), as exemplified by the two let-7 sites within the 3′ UTR of Caenorhabditis elegans lin-41 (Reinhart et al. , 2000). Although these 3′-supplementary sites can be detected above background when searching for preferentially conserved pairing configurations, they are exceedingly rare, with conserved miRNA families in mammals and nematodes each averaging <1 preferentially conserved 3′-supplementary site (Friedman et al. , 2009). Other relatively rare, yet effective sites include centered sites, which have 11–12 contiguous Watson–Crick","Proteins are built by using the information contained in molecules of messenger RNA (mRNA). Cells have several ways of controlling the amounts of different proteins they make. For example, a so-called ‘microRNA’ molecule can bind to an mRNA molecule to cause it to be more rapidly degraded and less efficiently used, thereby reducing the amount of protein built from that mRNA. Indeed, microRNAs are thought to help control the amount of protein made from most human genes, and biologists are working to predict the amount of control imparted by each microRNA on each of its mRNA targets. All RNA molecules are made up of a sequence of bases, each commonly known by a single letter—‘A’, ‘U’, ‘C’ or ‘G’. These bases can each pair up with one specific",380,128,0.3368
scientific_lay_summarisation-elife-norm,"model assumes that chromatin rapidly transitions between accessible and inaccessible states via thermal fluctuations, and that the binding of transcription factors to accessible DNA shifts this equilibrium toward the accessible state. Like all thermodynamic models, this model relies on the ‘occupancy hypothesis’ (Hammar et al. , 2014; Garcia et al. , 2012; Phillips et al. , 2019): the probability pb⁢o⁢u⁢n⁢d of finding RNA polymerase (RNAP) bound to the promoter, a quantity that can be easily computed, is linearly related to the rate of mRNA production dmRNAdt, a quantity that can be experimentally measured, such that (1) dmRNAdt=Rpbound. Here, R is the rate of mRNA production when the system is in an RNAP-bound state (see Appendix section 1. 1 for a more detailed overview). Additionally, in all thermodynamic models, the transitions between states are assumed to be much faster than both the rate of transcriptional initiation and changes in transcription factor concentrations. This separation of time scales, combined with a lack of energy dissipation in the process of regulation, makes it possible to consider the states to be in equilibrium such that the probability of each state can be computed using its Boltzmann weight (Garcia et al. , 2007). Despite the predictive power of thermodynamic models, eukaryotic transcription may not adhere to the requirements imposed by the thermodynamic framework. Indeed, Narula and Igoshin, 2010, Hammar et al. , 2014, Estrada et al. , 2016, Scholes et al. , 2017, and Li et al. , 2018 have proposed theoretical treatments of transcriptional regulation that maintain the occupancy hypothesis, but make no assumptions about separation of time scales or energy expenditure in the process of regulation. When combined with the MWC mechanism of DNA allostery, these models result in a non-equilibrium MWC model (1B). Here, no constraints are imposed on the relative values of the transition rates between states and energy can be dissipated over time. To our knowledge, neither the thermodynamic MWC model nor the non-equilibrium MWC model have been tested experimentally in eukaryotic transcriptional regulation. Here, we performed a systematic dissection of the predictive power of these MWC models of DNA allostery in the embryonic development of the fruit fly Drosophila melanogaster in the context of the step-like activation of the hunchback gene by the Bicoid activator and the pioneer-like transcription","Cells in the brain, liver and skin, as well as many other organs, all contain the same DNA, yet behave in very different ways. This is because before a gene can produce its corresponding protein, it must first be transcribed into messenger RNA. As an organism grows, the transcription of certain genes is switched on or off by regulatory molecules called transcription factors, which guide cells towards a specific ‘fate’. These molecules bind to specific locations within the regulatory regions of DNA, and for decades biologist have tried to use the arrangement of these sites to predict which proteins a cell will make. Theoretical models known as thermodynamic models have been able to successfully predict transcription in bacteria. However, this has proved more challenging to do in eukaryotes,",380,128,0.3368
dialogsum,"#Person1#: Hi, Ben! Where are you going now? #Person2#: I am going to the cinema. #Person1#: What is on today? #Person2#: Cats and Dogs. #Person1#: I saw it yesterday. It tells a story about a fight between cats and dogs. #Person2#: Sounds interesting. #Person1#: Yes. In fact, it is wonderful. All the actors in the film are real dogs and cats, not cartoons. By the way, what time is it? #Person2#: It is 3:15. #Person1#: I have got to leave now because I have got to visit my aunt in the hospital. #Person2#: See you later. #Person1#: See you.",Ben's going to the cinema to watch Cats and Dogs. #Person1# tells him the movie's wonderful.,99,16,0.1616
scientific_lay_summarisation-elife-norm,"position the pre-anaphase spindle close to the bud neck and orient it along the mother-bud axis. As the spindle elongates in anaphase, one spindle pole translocates into the bud to accomplish segregation of one set of chromosomes into the daughter cell (Pereira and Yamashita, 2011; Markus et al. , 2012; Winey and Bloom, 2012). In S. cerevisiae, the nuclear positioning and spindle orientation are regulated by two redundant pathways acting on cMTs, the Kar9 and dynein pathways (Li et al. , 1993; Miller and Rose, 1998; Winey and Bloom, 2012). Concomitant deletions in components of both pathways result in lethality, whereas loss of one pathway can be compensated by the function of the other with moderate spindle orientation defects (Miller and Rose, 1998). Survival of single deletion mutants largely relies on the function of the spindle orientation checkpoint (SPOC) that retains cells in anaphase until the spindle orientation is corrected (Bardin et al. , 2000; Pereira et al. , 2000; Caydasi and Pereira, 2012). Furthermore, MTs in S. cerevisiae are organized exclusively from the spindle pole body (SPB), which is the functional equivalent of animal centrosome. The SPB is a multilayered cylindrical organelle that is embedded in the nuclear envelope (NE) throughout the cell cycle (Byers and Goetsch, 1974; Byers and Goetsch, 1975) The outer plaque faces the cytoplasm and nucleates cMTs, whereas the inner plaque is inside the nucleus and organizes the nuclear MTs. The central plaque anchors and interconnects the outer and inner plaques (O' Toole et al. , 1999; Jaspersen and Winey, 2004). In G1 phase, some fractions of the cMTs are organized from a modified region of the NE associated with one side of the SPB known as the half-bridge (Byers and Goetsch, 1974; Byers and Goetsch, 1975). Spc72, a γ-tubulin complex (γ-TuSC) receptor, is required for nucleating MTs at both the outer plaque and the half-bridge (Chen et al. , 1998; Knop and Schiebel, 1998; Wigge et al. , 1998; Souès and Adams, 1998). Localisation of Spc72 at the outer plaque is mediated by binding to Nud1, whereas Kar1 serves as a G1 specific binding site of Spc72 at the half-bridge (Pereira et al. , 1999; Gruneberg et al. , 2000). Spc72 also has a structural role as an integral part of the outer layer","Before a cell divides, it needs to duplicate its genetic material to provide the new daughter cell with a full set of genetic information. To do so, the cell forms a complex of proteins called the spindle apparatus, which is made up of string-like microtubules that divide the chromosomes evenly. In many organisms, the position of the spindle determines where in the cell this separation happens. However, in baker’s yeast, the location where the cell will divide is determined well before the spindle is formed. Unlike many other eukaryotic cells, these yeast cells divide asymmetrically and create buds that will form the new daughter cells. The position of this bud determines where the spindle should be located and where the chromosomes separate. The spindle itself is then organised",380,128,0.3368
scientific_lay_summarisation-elife-norm,"form supramolecular activation clusters (SMACs) (Monks et al. , 1998; Griffiths et al. , 2001; Ilani et al. , 2009). TCR MCs form in the outer lamellipodia-like ‘distal’ (d) SMAC, after which signaling MCs move centripetally through the lamella like ‘peripheral’ (p) SMAC, driven by centripetal flow of F-actin (Ponti et al. , 2004; Varma et al. , 2006; DeMond et al. , 2008; Vardhana et al. , 2010; Kumari et al. , 2012; Yi et al. , 2012) to eventually reach the ‘central’ (c) SMAC. The cSMAC is an F-actin depleted zone (Stinchcombe et al. , 2006), in which TCR is destined for down-regulation via extracellular vesicle formation (Vardhana et al. , 2010; Choudhuri et al. , 2014). Actin polymerization and remodeling continues throughout the lifetime of the immunological synapse, and studies using a variety of T cell activation systems have identified a critical requirement for F-actin and its molecular effectors in optimal TCR signaling and T cell function (Valitutti et al. , 1995; Holsinger et al. , 1998; Snapper et al. , 1998; Campi et al. , 2005; Burkhardt et al. , 2008). Pharmacological disruption of global F-actin or genetic manipulations that reduce synaptic F-actin polymerization result in defects in early signaling events such as cell adhesion, TCR MC formation, early TCR signaling, TCR MC transport, as well as the TCR-distal events including intracellular calcium rise, and store operated calcium ion entry (DeBell et al. , 1992; Valitutti et al. , 1995; Campi et al. , 2005; Nolz et al. , 2006; Varma et al. , 2006). Since global actin perturbation impairs all the above steps, it has been a challenge to dissect the mechanistic role of F-actin in TCR signaling and to identify whether there exist functionally distinct F-actin networks within SMACs that may play distinct roles at various stages of the pathway. One way to investigate functional diversity within the subsynaptic F-actin network, during TCR signaling, is to utilize actin perturbations that dissociate early TCR signaling from late TCR signaling. One such context is provided by the loss of an actin effector protein—Wiscott Aldrich Syndrome Protein (WASP). F-actin polymerization relies on regulatory factors such as nucleation promoting factors (NPFs) and downstream nucleation factors such as Arp2/3 complex (Blanchoin et al. , 2000). WASP is a hematopoietic-cell-specific","The immune system is made up of several types of cells that protect the body against infection and disease. Immune cells such as T cells survey the body and when receptors on their surface encounter infected cells, the receptors activate the T cell by triggering a signaling pathway. The early stages of T cell receptor signaling lead to the formation of a cell–cell contact zone called the immunological synapse. Filaments of a protein called F-actin—which are continuously assembled and taken apart—make versatile networks and help the immunological synapse to form. F-actin filaments have crucial roles in the later stages of T cell receptor signaling as well, but how they contribute to this is not clear. Whether it is the same F-actin network that participates both in synapse formation",380,128,0.3368
pubmed-summarization,"for the appropriate resource planning and effective choice of the operation list , with the low - risk patients being scheduled for surgery before the high - risk candidates . we conducted an observational cohort study from september 2010 to january 2011 among 194 patients who were admitted to the 8-bed cardiac surgery icu of a general , tertiary hospital of athens , greece . the inclusion criteria into the study were a priori defined as follows : ( a ) patient age 18 years old and ( b ) a minimum icu - los of 24 hours . based on the predefined inclusion criteria 44 patients were excluded from the study , and 150 met the inclusion criteria and constituted our study sample . a short structured questionnaire on basic sociodemographic and clinical patient characteristics was used for data collection purposes . the collected sociodemographic data included patient age , gender , height , weight , and body mass index ( bmi ) . in addition , the collected clinical characteristics were the history of chronic pulmonary disease and diabetes , the type of surgery , the preoperative serum creatinine ( cr ) levels , the blood glucose levels during the intraoperative period , the use of intraaortic balloon pump ( iabp ) preoperatively , the application of cardiopulmonary bypass ( cpb ) , the preoperative ejection fraction of the left ventricle ( eflv ) , the duration of surgery and cpb , the presence of atrial fibrillation ( af ) preoperatively , the emergency procedure , the ischemic time , the transfusion of red blood cells ( rbcs ) , the euroscore values and the icu - los . we defined the icu - los as the duration of the hospitalization of patients from their admission to the icu until their discharge . euroscore is the most valid and reliable stratification model for predicting the perioperative risk of cardiac surgery patients in north america , europe , and japan . it was developed between 1995 and 1999 and was first introduced into clinical practice in 1999 , while the logistic algorithm of euroscore is available since 2003 . it includes three wide categories of risk factors : the patient- ( age , female sex , chronic pulmonary disease","the prediction of intensive care unit length of stay ( icu - los ) could contribute to more efficient icu resources ' allocation and better planning of care among cardiac surgery patients . the aim of this study was to identify the preoperative and intraoperative predictors for prolonged cardiac surgery icu - los . an observational cohort study was conducted among 150 consecutive patients , who were admitted to the cardiac surgery icu of a tertiary hospital of athens , greece from september 2010 to january 2011 . multivariate regression analysis revealed that patients with increased creatinine levels preoperatively ( odds ratio ( or ) 3.0 , p = 0.049 ) , history of atrial fibrillation ( af ) ( or 6.3 , p = 0.012 ) and",380,128,0.3368
scientific_lay_summarisation-elife-norm,"VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1–/– mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1–/– mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1–/– pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1–/– mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1–/– choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion. The retina is the light-sensitive tissue at the back of the eye that consists of photoreceptor cells, retinal pigment epithelium (RPE), and its basement (Bruch’s) membrane. Disorder of the retina causes vision loss. The primary nutrient source for the retina is the choroid (Bill et al. , 1980), which is a highly vascularized tissue layer surrounding the retina. The choroid consists of three layers: Haller’s layer (large blood vessel layer), Sattler’s layer (medium size blood vessels), and the choriocapillaris (Hogan et al. , 1971; Nickla and Wallman, 2010). The choriocapillaris is a unique anastomosed vascular structure with an extraretinal fenestrated capillary bed that lies in a single plane below Bruch’s membrane. In the mouse retina, choroidal development begins from embryonic day (E) 13. 5 (Marneros et al. , 2005; Saint-Geniez et al. , 2006). Vascular endothelial growth factor (VEGF) is known to be a central regulator of vascular development during embryogenesis (Coultas et al. , 2005), and VEGF secreted from RPE cells is indispensable for the vascular development and maintenance of the choroid (Saint-Geniez et al. , 2009; Le et al. , 2010; Kurihara et al. , 2012). VEGF expression is enhanced by a number of transcription factors such as hypoxia-induced factor-1α (HIF-1α), estrogen-related receptor-α (ERRα), and peroxisome proliferator-activated receptor gamma coreceptor 1α (PGC-1α) (Ziello et al. , 2007; Ueta et","The retina is the part at the back of our eyes that detects light and sends this information to our brain. Within the retina is a layered structure containing the light-sensitive cells, known as the neural retina, and another protective layer of cells called the retinal pigment epithelium. A surrounding network of blood vessels, the choroid, keeps the retina healthy by supplying oxygen and nutrients. When the choroid does not work properly, eye disease can result. A common example is age-related macular degeneration, where blood vessels in the choroid either break down or start growing uncontrollably in the wrong places. In both cases, light-sensitive cells are damaged and eventually die. This causes vision loss that worsens over time. The choroid forms early in life, within the developing embryo.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the area of forward and side scattering. JF549/TMR fluorescence was measured using a 561 nm excitation laser and a 610/20 nm emission filter. JF646 fluorescence was measured using a 640 nm excitation laser and a 670/30 nm emission filter. Each panel shows fluorescence in the JF549/TMR channel and in the JF646 channel as well as a JF549/TMR vs. JF646 scatterplot. First panel: no dye control. Second panel: 500 nM SNAP-TMR (NEB #S9105S) labeling only. Third panel: 500 nM cp-JF549 labeling only (the cp handle also labels SNAPf-Tag proteins, but more specifically than the SNAP-handle). Fourth panel: 500 nM Halo-JF549 labeling only. Fifth panel: 500 nM Halo-JF646 labeling only. Bottom panel: double 500 nM cp-JF549 and 500 nM Halo-JF646 labeling. : http: //dx. . org/10. 7554/eLife. 25776. 00410. 7554/eLife. 25776. 005Figure 1— 2. Teratoma assay demonstrates that tagging CTCF and Rad21 does not affect pluripotency in mESCs. 350,000 wild-type and C59 (FLAG-Halo-mCTCF; mRad21-SNAPf-V5) JM8. N4 mouse embryonic stem cells were injected into the testis and kidney of Fox Chase SCID-beige male 8-week-old mice (Charles River) and tumors were harvested 27–33 days after injection (top row). Tumors were fixed with 10% formalin overnight, embedded in paraffin and cut into 5 μm serial sections and then H and E stained. Representative sections from each of the three germ layers (endoderm, mesoderm and ectoderm; highlighted by black arrows) are shown for both wild-type and C59 mES cells. Black scale bar: 100 μm. : http: //dx. . org/10. 7554/eLife. 25776. 00510. 7554/eLife. 25776. 006Figure 1— 3. Tagging CTCF and Rad21 does not affect expression of key pluripotency genes or CTCF and Rad21 protein levels. (A) Expression of key mouse embryonic stem cell genes measured by qPCR was similar in wild-type (blue) and C59 (FLAG-Halo-mCTCF; mRad21-SNAPf-V5) (red) JM8. N4 mouse embryonic stem cells. (B) CTCF (red) and Rad21 (green) protein levels as measured by western blot and normalized to either H3 levels (solid bar) or TBP (hashed bar) was similar between wild-type and tagged mouse embryonic stem cells (WT, C87, C45, C59) and similar between wild-type and tagged human U2OS cells (WT, C32). Error bars show standard deviation among three replicates. : http: //dx. . org/10. 7554/eLife. 25776. 00610. 7554/eLife. 25776. 007Figure 1— 4. CTCF and Rad21 ChIP-Seq results in wt and C59 mESCs. (A) Venn","A human cell contains about 2 meters of DNA tightly packed in a compartment called the nucleus. Within the space inside the nucleus, different parts of the DNA fold into distinct bundles known as domains. These domains are important for organising the genome and are crucial for regulating gene expression, by stimulating specific DNA segments to activate certain genes. Previous research has shown that DNA segments within the same domain frequently interact, whereas DNA segments in different domains rarely do. The domains are often folded into loops that are held together by a ring-shaped protein complex called cohesin, while another protein called CTCF positions cohesin and thereby sets the boundaries between the domains. Some mutations are known to disrupt these boundaries, which allows certain DNA segments to activate",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2011), consistent with the high frequency of PTEN mutations in carcinomas. Studies on lumen morphogenesis in a three-dimensional culture system showed that PtdIns (4,5) P2 is enriched in the apical membrane, whereas PtdIns (3,4, 5) P3 is enriched in basolateral membranes (Martin-Belmonte et al. , 2007), and this was proposed to be important in tumor development (Shewan et al. , 2011). Mammalian PTEN regulates cellular processes as diverse as collective cell migration (Bloomekatz et al. , 2012) and axon regeneration (Park et al. , 2008), and some of the effects of PTEN are independent of the AKT pathway (e. g. Vasudevan et al. , 2009). PTEN is essential for viability and Pten null mouse embryos arrest at midgestation with a complex set of morphological defects (Suzuki et al. , 1998; Bloomekatz et al. , 2012). We showed previously that PTEN is required for the directional collective migration of a population of extraembryonic cells, the anterior visceral endoderm (AVE), which must move from a distal to proximal position to define the anterior-posterior body axis of the embryo (Bloomekatz et al. , 2012). PTEN is also required in the cells of the embryo proper: deletion of Pten in cells of the epiblast (the embryo proper) using the Sox2-Cre transgene (Hayashi et al. , 2002) (Pten △Epi) bypasses the requirement for AVE migration but leads arrest at midgestation (~E9. 0) with a syndrome of defects that included cardia bifida, abnormal mesoderm migration, and an abnormal open neural tube (Bloomekatz et al. , 2012). Mammalian neural tube closure requires more than 100 genes that regulate a sequence of orchestrated morphogenetic processes that transform the neural epithelium into a closed tube (Copp and Greene, 2010; Harris and Juriloff, 2010; Colas and Schoenwolf, 2001). Failure of any one of these events can cause neural tube defects, the second most common type of human birth defect after cardiac malformations. Most genetic studies of neural tube closure have focused on the cell rearrangements in the ventral midline mediated by the planar cell polarity pathway (Murdoch et al. , 2003; Ybot-Gonzalez et al. , 2007; Nishimura et al. , 2012; Williams et al. , 2014) or on the actin-mediated apical constriction of neural epithelial cells required for neural tube closure (Suzuki et al. , 2012; Grego-Bessa et al.","In mammals, the brain and spinal cord develop from a flat sheet of cells called the neural plate, which bends around to create a structure known as the neural tube. This bending process occurs through a complex sequence of cell shape changes. The cells in the neural plate are initially short and wide, but transform into long, thin cells as the neural plate forms. Problems that prevent the neural tube from forming correctly are amongst the most common birth defects in humans. Many cancer cells contain a mutation that affects a gene that produces a protein called PTEN. This protein normally activates a tumor suppressor pathway, and so cancer cells that lack PTEN divide and grow uncontrollably. Grego-Bessa et al. have now examined mouse embryos that lack this",380,128,0.3368
dialogsum,"#Person1#: I have a question about my cable. #Person2#: What do you need? #Person1#: I haven't been able to watch my cable for the past week. #Person2#: Right now the cable isn't working. #Person1#: Could you tell me when it will be back on? #Person2#: The cable should be running again in a couple of days. #Person1#: In the meantime, do I still have to pay for the cable? #Person2#: We'll just give you a credit for the inconvenience. #Person1#: Does that mean I won't have to pay for it? #Person2#: It'll be free until it comes back on. #Person1#: Thanks, I appreciate your help. #Person2#: Thank you for all your patience.",#Person2# tells #Person1# the cable isn't working and it'll be free until it comes back on.,112,16,0.1429
dialogsum,"#Person1#: May I invite you for a dance? #Person2#: With pleasure. #Person1#: You dance well. Do you breakdance? #Person2#: Me, what brought that on? #Person1#: There's a story about breakdancing in the paper. #Person2#: What does it say? #Person1#: According to the story, it's some sort of modern dance style. #Person2#: Like disco? #Person1#: Well, breakdancing is more a physical exercise than a dance. #Person2#: And disco a kind of nightclub. #Person1#: Right, a disco is a place where people dance according to nonstop recorded music. . . #Person2#: So. . . disco is what the music is called and a disco is a place where people go to dance to it. And breakdancing is a different sort of thing altogether. #Person1#: You are witty.",#Person1# introduces a story of breakdance to #Person2# when they are dancing. #Person1# also makes a comparison between disco and breakdancing.,125,21,0.168
scientific_lay_summarisation-elife-norm,"has long impeded our understanding of hearing, in particular in the case of the mammalian ear (Nam et al. , 2015). To address these problems, we used laser irradiation to stimulate hair bundles (). Because photonic force arises when photons are absorbed, reflected, or refracted upon interaction with an object, intense illumination should apply substantial force to a bundle. Our experiments confirmed the validity of the approach and demonstrated that the requisite irradiation does not jeopardize a bundle’s operation. This method allows us to probe hair-bundle physiology at previously inaccessible timescales, for the delivery time of the stimulus can accommodate the full frequency range of mammalian hearing. At the same time, this approach avoids the artifacts that bedevil current methods. The conservation of momentum entails that reflected, absorbed, and refracted photons exert force on a target. All these phenomena are likely to take place when light strikes an array of stereocilia in a hair bundle. Although an analysis based on reflection alone would indicate that a hair bundle is relatively insensitive to radiation pressure, geometric considerations reveal that multiple modes of light propagation occur in a hair bundle by virtue of the cylindrical shape of the stereocilia (see Materials and methods). Each of these modes is capable of transferring momentum and therefore of mechanically stimulating the bundle. Because the diameter of each stereocilium compares to the wavelength of light, the regular spacing of stereocilia within the hair bundle might additionally give rise to complex interference effects. We stimulated 40 hair bundles of the bullfrog’s sacculus so that radiation pressure would push them toward their tall edges—the positive direction—and reliably elicited the expected movements (see Appendix 1—1A). The bundles followed similar trajectories at the onset of irradiation (): the movement was approximately exponential with a time constant of 0. 64±0. 06⁢ms (mean ± SEM, N = 16). The responses, which reached displacements as great as 500 nm, encompassed the range of complex trajectories reported in the literature (Benser et al. , 1996; Tobin et al. , 2019; Ricci et al. , 2000). The more compliant hair bundles—those displaying initial deflections exceeding about 150 nm—displayed relatively slow movements in the direction of the photonic force, a signature of the timescale of the adaptation process that allows hair cells to reset their operating","The sense of hearing relies on specialized sensory cells in the inner ear. Each of these hair cells converts sounds into electrical signals that the brain can interpret. The hair cell takes its name from the bundle of rod-like structures that protrude from its top surface, which resemble hairs under the microscope. The hair bundle acts as an antenna that bends in response to sound waves. When a hair bundle moves in a particular direction, it opens ion channels in the hair-cell membrane. The resulting flow of ions into the cell triggers a cascade of events that ends with an electrical signal traveling to the brain. Many experiments on hearing rely on being able to manipulate the movement of a hair bundle. Researchers typically use one of two",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and as a downstream effector of Wnt-mediated proliferation, β-catenin is a mechanotransducer. Mechanical strain induces nuclear accumulation and increased transcriptional activity of β-catenin (Benham-Pyle et al. , 2015; Sen et al. , 2008), and mechanical perturbation of living tissues is associated with increased β-catenin signaling and induction of downstream transcriptional targets (Farge, 2003; Farge and development, 2011). β-Catenin transcriptional activation downstream of mechanical force or Wnt stimulation has been studied separately. It remains unknown whether β-catenin’s role as a target of mechanical force is independent, redundant or synergistic to Wnt signaling in tissue homeostasis. Previously, we showed that mechanical strain drives the re-entry of a quiescent epithelial monolayer into the cell cycle by sequential, but independent induction of Yap1 (G0 to G1) and then β-catenin transcriptional activities (G1 to S): inhibition of Yap1 and β-catenin transcriptional activities was sufficient to block cell cycle entry and G1 to S transition, respectively (Benham-Pyle et al. , 2015). However, cells that exit quiescence following mechanical strain accumulate in S/G2 and do not enter mitosis, suggesting that a further activation event is required to complete cell cycle progression. Here we show that mechanical strain-induced Src phosphorylation of β-catenin and Wnt3A pathway-dependent stabilization of cytoplasmic β-catenin synergize to increase β-catenin transcriptional activity to levels that drive cell cycle progression through S/G2 and mitosis. Physical constraints and mechanical cues regulate cell proliferation in multicellular tissues. In cell culture models of quiescent or growing epithelial cell monolayers, mechanical strain induces cell cycle re-entry and increases the number of actively cycling cells (Benham-Pyle et al. , 2015; Streichan et al. , 2014). To test directly if mechanical strain is sufficient to drive cells into mitosis, super-confluent monolayers of quiescent normal kidney epithelial (MDCK) cells (Benham-Pyle et al. , 2015) were formed on flexible silicone substrates either in a single-well biaxial cell stretching device compatible with live imaging (— 1), or in an integrated strain array (ISA) (34, see also Materials and methods). The design and fabrication of the biaxial cell stretching device compatible with live imaging allowed for direct visualization of strained monolayers with an inverted fluorescence microscope. Briefly, quiescent monolayers were formed on compliant silicone substrates in a PDMS well, surrounded by a pneumatic chamber separated by a thin silicone wall. Vacuum pressure applied to the pneumatic","Tissues and organs can both produce and respond to physical forces. For example, the lungs expand and contract; the heart pumps blood; and bones and muscles grow or shrink depending on how much they are used. These responses are possible because cells contain proteins that can respond to physical forces. One of the best studied of these is a protein called β-catenin, which increases the activity of genes that trigger cells to divide to promote the expansion of tissues. β-catenin is over-active in many types of cancer cells where it contributes to tumor growth. In addition to being switched on by mechanical force, β-catenin is also activated when cells detect a signal molecule called Wnt. Cells cycle through a series of stages known as the cell cycle to",380,128,0.3368
dialogsum,"#Person1#: I am here to tell you that the clothes are very much to taste of our market and the customers are quite satisfied with the excellent quality. #Person2#: We are very glad to hear that. We are sure that there will be a bigger market for our products in this country. #Person1#: Well, we have an extensive sales organization and a thorough knowledge of Asian market. Your products would sell very well here. We are prepared to do more business with you. We are also interested in handing a sole agent for you. #Person2#: We really appreciate your efforts. Before we go to the core of matter, can you give us some idea of them on which you would be willing to operate as our agent? #Person1#: No problem.","#Person1# tells #Person2# #Person2#'s products are popular among Asian customers, so #Person1# would like to hand a sole agent for #Person2#.",130,21,0.1615
scientific_lay_summarisation-elife-norm,"in anxiety. No effective and curative treatment has been developed for Huntington’s disease so far (Frank, 2014). A chronic drug therapy that commences early on in VFDO stages in premanifest Huntington’s disease and ameliorates early dysregulations as the potential origin of pathogenic processes and disease spreading is therefore a promising and necessary strategy. In Huntington’s disease animal models, even short-term reduction of protein load through RNA interference and antisense strategies has beneficial effects on disease phenotypes and progression lasting several months after intervention (Stanek et al. , 2014; DiFiglia et al. , 2007; Keiser et al. , 2016). We have recently shown that mRNAs carrying CAG repeats bind to a protein complex containing the ubiquitin ligase midline 1 (MID1) in a repeat size-dependent manner. Through ubiquitination MID1 regulates PP2A (protein phosphatase 2A) and mTOR (mechanistic target of rapamycin) activities and the translation of associated mRNAs (Krauss et al. , 2013; Griesche et al. , 2016). Disruption of the MID1/PP2A/mTOR protein complex leads to an increase of PP2A activity, a decrease of mTOR activity and a reduction of translation rates of mRNAs with expanded CAG repeats (Krauss et al. , 2013). We show here that the type II diabetes drug metformin interferes with the MID1/PP2A/mTOR protein complex and significantly reduces the translation rate of Htt mRNA, resulting in a reduction of aberrant Htt protein production in vitro and in vivo in the Hdh150 mouse model. Notably, in Hdh150 mice in vivo metformin, when given early in the VFDO stage, and chronically in the drinking water, fully reverses both early neuronal network dysregulations and behavioral aberrations. Since the visual cortex is one of the first regions affected by the disease (Dogan et al. , 2013; Labuschagne et al. , 2016), we focused on layer 2/3 of the visual cortex of ∼12 weeks old, heterozygous knock-in mice expressing expanded Htt with 150 glutamine repeats (Hdh150), in the lightly anesthetized mouse. This time corresponds to the VFDO in presymptomatic Huntington’s disease (1a, b). We focused our analysis on male mice, thereby minimizing the influence of hormonal fluctuations on network activity. This approach is in line with a recent study in the field of Alzheimer’s disease (Iaccarino et al. , 2016), using males only. We employed two-photon Ca2+ imaging in vivo using the synthetic Ca2+","Huntington’s disease is a devastating brain disorder that causes severe mood disorders, problems with moving, and dementia. Most people develop the condition between their thirties and fifties, and die a decade or two after the symptoms first appear. The disease emerges because of a mutation in the gene for the Huntingtin protein, which leads to neurons slowly dying in the brain. While genetic testing can reveal who carries the faulty gene, no treatment addresses the root of the disorder or prevents it from appearing. Instead, most therapies for Huntington’s disease aim to reduce brain damage once the telltale symptoms are already present. However, the disease-causing protein is expressed early during the life of a patient, which could give it time to damage the brain long before neurons die",380,128,0.3368
dialogsum,"#Person1#: Would you please weigh this letter to see what the postage is? #Person2#: Do you want to send it by ordinary or registered mail? #Person1#: By ordinary air mail, please. #Person2#: Anything of value in it? #Person1#: A postal order for four hundred dollars. #Person2#: In that case, you'd better have it registered. #Person1#: Will I be informed when my friend gets the letter? #Person2#: Yes, when your friend gets it, he'll sign a receipt, which will be sent to you by mail. Then you can be sure it's been received. #Person1#: All right, I'll have it registered, then.","#Person1# wants to send a letter by ordinary airmail. Since it contains a postal order, #Person2# recommends #Person1# to have it registered.",100,22,0.22
dialogsum,"#Person1#: Sometimes I think television is too biased. None of them are completely objective. #Person2#: That's unavoidable, but think, How would you keep up to date without television? #Person1#: Newspapers or the radio I guess. I just wish TV was more objective. #Person2#: Look, you can still learn a lot from watching television, you just need to be smart when you're watching. Filter the information and decide if you believe what you are hearing or not. #Person1#: The internet's a lot worse. #Person2#: Really? Why? #Person1#: There's no one moderating it. Anyone around the world can put information onto the net for anyone else to see. The information on the internet is mostly unsubstantiated and you can never know who has written it, or why. A lot of people get conned online. #Person2#: Again, you need to think carefully. If you don't trust others online, have nothing to do with them.",#Person1# thinks television is too biased and the internet is worse because TV isn't objective and no one moderates it. #Person2# suggests thinking carefully to filter the information.,151,28,0.1854
pubmed-summarization,". kruskal - wallis test was used to compare the groups and probability ( p ) values less than 0.05 were considered significant . the significance of the parameters in kruskal - wallis test was confirmed by mann - whitney u test and p values less than 0,016 were considered significant . kruskal - wallis test is the standard variance analysis test to compare the means of 3 or more groups . kruskal - wallis test gives us the difference between the groups , but it does not give any idea about which group is the cause of this difference . we used mann - whitney u test with bonferroni correction ( the p value for mann - whitney u test by bonferroni correction is found to be 0,05/number of groups = 0,016 for this study ) . mean ima1 levels of group i , group ii , and group iii were 0,41 0,01 ( range 0,400,45 ) , 0,46 0,16 ( range 0,440,48 ) , and 0,34 0,03 ( range 0,280,39 ) , respectively mean ldh levels were 819,71 34,53 ( range 766874 ) , 808,57 24,69 ( range 774841 ) , and 514,14 19,92 ( range 487545 ) for groups i , ii , and iii , respectively . the difference of i m a levels between group i and group ii was not significant at 6th hour ( ima2 ) ( p : 0,71 ) during acute myocardial ischemia , the ability of binding ions such as copper , zinc , and cobalt is decreased ; therefore a form of albumin is produced , which is described as ischemia modified albumin ( i m a ) . the i m a was registered by the united states food and drug administration as a marker of myocardial ischemia . the test is based on the decreased ability of albumin to bind cobalt due to the structural change of nh2 which develops in the ischemic environment . it is important to emphasise that the decreased ability of albumins to bind cobalt occurs in hypoxia , acidosis , sodium and calcium pump malfunctions , and tissue damage caused by free radicals . it has been shown that the concentration of i m a increases within a couple of minutes from","purpose . to evaluate the predictive effect of i m a in incarcerated hernias . methods . three groups ( n = 7 ) of rats were operated . group i aimed to mimic incarceration , group ii aimed the strangulation , and group iii was the sham group . i m a and ldh measurements were made . results . i m a levels were significantly higher in strangulation mimicking group and i m a levels were normal at postoperative 6th hour in incarceration mimicking group . ldh levels were significantly higher in both incarceration and strangulation mimicking groups . conclusion . i m a seems to be an effective marker in incarcerated hernias to predict necrosis . but we need further studies to generalise this hypothesis",380,128,0.3368
dialogsum,"#Person1#: What can I do? #Person2#: The system crashed when I was surfing on the internet. #Person1#: Did you go to any illegal website? #Person2#: No, But does that matter? #Person1#: Yes, your computer can be easily infected by virus if you do that. #Person2#: I see. I'd better never try. #Person1#: That's wise. #Person2#: Do you know what's wrong with my PC? #Person1#: One minute. Oh, yes, it was infected by a virus, and you had no antivirus software. #Person2#: Is anti-virus software necessary for a PC? #Person1#: Of course. You'd better learn something about it. #Person2#: I'm afraid yes. But what about the data I stored in the computer? #Person1#: Don't worry, it should have been protected automatically. And I take an anti-virus software with me. Do you want me to install it now? #Person2#: Yes, please. I'll really appreciate that.",#Person2#'s computer system crashed and #Person1# finds it was infected by the virus. #Person1#'ll install anti-virus software for #Person2#.,143,19,0.1329
scientific_lay_summarisation-elife-norm,"The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. In cats and monkeys neurons in the primary visual cortices are selective for both the orientation of the visual input (orientation preference, OP) and its eye of origin (ocular dominance, OD) (Hubel and Wiesel, 1977). These feature preferences are arranged spatially in the form of OP and OD maps, with stereotypical structure within each map, and strong spatial relationships between them (Blasdel and Salama, 1986; Bonhoeffer and Grinvald, 1991; Bartfeld and Grinvald, 1992; Obermayer and Blasdel, 1993; Hübener et al. , 1997; Nauhaus et al. , 2012). While some aspects of the structure of OD and OP maps individually are plastic in response to altered visual input, such as monocular deprivation (Hubel et al. , 1977; Shatz and Stryker, 1978; Farley et al. , 2007) or stripe rearing (Sengpiel et al. , 1999; Tanaka et al. , 2006), none of these manipulations has succeeded in modifying the overall spatial relationships between OD and OP maps, which have appeared immune from environmental influence. In particular OP map pinwheels, where domains representing all orientations meet at a point, always tend to lie close to the center of OD regions. This is true even after manipulations of the visual input such as rearing animals with artificially induced strabismus (Hubel and Wiesel, 1965; Löwel, 1994; Löwel et al. , 1998) or monocular deprivation (Crair et al. , 1997). However, whether this relationship is a fundamental aspect of map structure that","The structure of the brain results from a combination of nature (genes) and nurture (environment). The brain’s ability to adapt to changes in the environment is known as plasticity, and the young brain is especially plastic. An animal’s sensory experiences in early life help to determine how its brain will process sensory input as an adult. One of the best sensory systems in which to study this process is the visual system. Within the visual system, some brain cells respond only to input from the left eye and others only to input from the right eye. Cells that respond to input from the same eye are arranged to form columns. Within each column, some cells respond only to lines with a particular orientation. Cells with different preferred orientations",380,128,0.3368
dialogsum,"#Person1#: May I come in? #Person2#: Yes, please. I ' m Mr. Peter, the Director of Personnel. What can I do for you? #Person1#: Nice to meet you, Mr. Peter. I ' m Wang Sian. I ' Ve come for an interview as requested. #Person2#: Oh, yes. How do you do, Miss Wang? Sit down, please. #Person1#: Thank you. #Person2#: What was your major in school? #Person1#: I majored in Public Relations. #Person2#: Have you done any work in this field? #Person1#: Yes, after my graduation, I worked in a trade company in Macao for one year. #Person2#: What section did you work in? #Person1#: The export Business Section. #Person2#: So you must be very familiar with export procedures. #Person1#: Yes, very much. #Person2#: That's good.","Wang Sian comes for an interview, and Mr. Peter asks her some questions about her major and work experience.",126,19,0.1508
dialogsum,"#Person1#: Why did you decide to publicize climate change in this way? #Person2#: Well, I was really upset about some countries failure to sign up pollution control agreements. It felt like the science wasn't getting understood by the politicians, so I decided to look into what I personally could do, that led me to dream up a cartoon character called Mr. Carbon. We all know somebody like him, he's climate ignorant and makes no effort to save energy. Of course, factories are the obvious bad character in the real world, but I couldn't do much about them. #Person1#: So, are we going to see him in scenes like we get in disaster movies? #Person2#: That's pretty unlikely, it's hard to make a box office success. But he certainly gives cause for concern. People are becoming more aware of the climate change. #Person1#: So you came up with the idea of another cartoon character, Mrs. Green. #Person2#: Yes, now, she pays attention to little things, uses low energy light bulbs doesn't leave the TV on standby. Goes in for recycling. As well as making a contribution to the climate, she'll save $150,000 over her lifetime.",#Person2# tells #Person1# how #Person2# camp up with the idea to publicize climate change in creating a cartoon movie led by the characters called Mr. Carbon and Mrs. Green.,194,29,0.1495
pubmed-summarization,"rodents were captured at three sites near the riverside - orange county line : the bear canyon trailhead ( riverside county : 3336.7n , 11725.5w ) , el cariso # 1 ( orange county : 3339.8n , 11725.1w ) , and el cariso # 2 ( orange county : 3339.8n , 11725.7w ) . the rodent fauna in the study area included the dusky - footed woodrat ( neotoma fuscipes ) , desert woodrat ( n. lepida ) , brush mouse ( p. boylii ) , california mouse , cactus mouse ( p. eremicus ) , deer mouse ( p. maniculatus ) , western harvest mouse ( reithrodontomys megalotis ) , california pocket mouse ( chaetodipus californicus ) , agile kangaroo rat ( dipodomys agilis ) , california ground squirrel ( spermophilus beecheyi ) , and botta s pocket gopher ( thomomys bottae ) ( s.g . sherman traps , inc . , tallahassee , fl ) or tomahawk live traps ( tomahawk live trap co. , tomahawk , wi ) . fifty traps were set at the bear canyon trailhead on november 12 , 1998 ; 20 traps were set at both el cariso # 1 and el cariso # 2 on june 10 , 1998 . a blood sample was collected from each rodent , and the blood samples and rodent carcasses were shipped on dry ice to the university of texas medical branch . subsequently , the carcasses and samples of lung , heart , liver , and skeletal muscle were deposited in the museum of texas tech university , and mammalogists at texas tech university identified each rodent to species level on the basis of morphologic features of the animal s skin and skull . the blood samples were tested for antibody to wwav by using an enzyme - linked immunosorbent assay ( 9 ) . the test antigen was a detergent extract of vero e6 cell monolayers infected with the wwav prototype strain av 9310135 . the control ( comparison ) antigen was prepared from uninfected vero e6 cell monolayers in a manner quantitatively identical to that used to prepare the test antigen . serial fourfold dilutions ( from 1:80 through 1:5,120 ) of each blood sample were tested against both antigens . the adjusted","thirty - four rodents captured in southern california were studied to increase our knowledge of the arenaviruses indigenous to the western united states . an infectious arenavirus was isolated from 5 of 27 california mice but none of the 7 other rodents . analyses of viral nucleocapsid protein gene sequence data indicated that the isolates from the california mice are strains of a novel tacaribe serocomplex virus ( proposed name bear canyon ) that is phylogenetically most closely related to whitewater arroyo and tamiami viruses , the only other tacaribe serocomplex viruses known to occur in north america . the discovery of bear canyon virus is the first unequivocal evidence that the virus family arenaviridae is naturally associated with the rodent genus peromyscus and that a tacaribe serocomplex",380,128,0.3368
pubmed-summarization,"according to the european association of urology guidelines on urinary incontinence , concerning the treatment of female stress urinary incontinence ( sui ) , the retropubic insertion of a midurethral synthetic sling ( mus ) gives equivalent patient - reported cure of sui at 12 months , when compared to colposuspension . these guidelines also report that midurethral synthetic sling inserted by either the transobturator ( to ) or retropubic ( rp ) route gives equivalent patient - reported outcome at 12 months . with an obvious trending towards less and less invasive surgical options , single - incision vaginal slings ( sis ) have emerged . they require very limited intracorporeal dissection , proposing to further increase safety of suburethral slings , without jeopardizing the success rates reported by conventional rp and to access . these sis outcomes are comparable with conventional mus at short - term follow - up . although sparse , two - year follow - up studies are available and seem to maintain steady success rates over this time . longer follow - up time reports are needed , to ensure that , in the long run , these sis offer constant success rates . the objective of this study is to describe the outcome of women treated with mini - arc at a mean follow - up of 45 months , based on a baseline population which has already been reported in a short - term paper , after adequate long - term follow - up evaluation . previously considered cured and improved patients were evaluated to access if their condition remains stable , as reflected in a subjective satisfaction evaluation . this is a single - centre prospective evaluation of women with urodynamic stress urinary incontinence , which were submitted to mini - arc ( american medical systems , minnetonka , mn , usa ) placement as a primary surgical treatment . surgical technique , inclusion and exclusion criteria , baseline population characteristics , and short - term outcome and complications have already been described in a previous paper . on this report , on 105 women with a mean follow - up of 15 months ( and a minimum follow - up of 6 months ) , 84 patients ( 80% )","single - incision slings were introduced in the surgical treatment of female stress urinary incontinence ( sui ) to lessen the morbidity associated with traditional midurethral slings . however , long - term reports on patient satisfaction are still scarce . this study describes the outcome of women treated with mini - arc at a mean follow - up of 45 months . in a previous report on 105 women with 15-month mean follow - up , 84 ( 80% ) were found cured and 12 ( 11% ) improved . now , with a mean follow - up of 45 months , cured / improved patients were reassessed by telephone and completed patient global impression of improvement ( pgi - i ) , patient global impression of",380,128,0.3368
scientific_lay_summarisation-elife-norm,"localization schemes in a simplified, well-controlled environment, and isolate the basic biophysical and biochemical processes involved (Mullins, 2010; Holy et al. , 1997; Laan et al. , 2012; Abu Shah and Keren, 2014). A notable example is the work on localization of microtubule asters in micro-fabricated, cell-sized compartments. Early work showed that microtubule assembly and disassembly dynamics are sufficient for centering of microtubules asters (Holy et al. , 1997), while more recently the influence of cortex-bound microtubule motors was studied by attaching motors to the compartment’s interface (Laan et al. , 2012). These experiments, together with theoretical modeling (Grill et al. , 2001; Vogel et al. , 2009), showed how the interaction between the tips of microtubules and the cell boundary generates pushing and pulling forces that lead to robust centering under a variety of conditions. Localization in large cells where the cytoskeletal elements do not span the entire system, cannot rely on direct interaction between the cytoskeleton and the cell boundary. Rather, the centering mechanisms must involve indirect sensing of the cell boundary, to be able to define the cell center without directly interacting with it (Wühr et al. , 2009). Here we use a recently developed in vitro system that self organizes to form persistently contracting bulk actin networks within cell-sized compartments (Malik-Garbi et al. , 2019), to demonstrate a hydrodynamic centering mechanism that can function in very large cells in the absence of any direct interaction between the cytoskeleton and the cell boundary. Our system is based on encapsulation of Xenopus egg extracts in cell-sized water-in-oil emulsions (Abu Shah and Keren, 2014; Malik-Garbi et al. , 2019; Pinot et al. , 2012; Tang et al. , 2018). The system self-organizes to form persistently contracting actomyosin networks surrounding an aggregate that forms around the contraction center (Malik-Garbi et al. , 2019). We observe size-dependent localization of the aggregate: large droplets are symmetric with the aggregate positioned at the center, whereas smaller droplets are polar with the aggregate near the boundary. The centering and decentering of the contraction center resemble cellular centering and decentering as seen for example during nuclear centering and spindle migration in mammalian oocytes (Almonacid et al. , 2018; Uraji et al. , 2018) and plant eggs (Ohnishi and Okamoto, 2017), and can serve as a","In order to survive, cells need to react to their environment and change their shape or the localization of their internal components. For example, the nucleus – the compartment that contains the genetic information – is often localized at the center of the cell, but it can also be positioned at the side, for instance when cells move or divide asymmetrically. Cells use multiple positioning mechanisms to move their internal components, including a process that relies on networks of filaments made of a protein known as actin. These networks are constantly remodeled as actin proteins are added and removed from the network. Embedded molecular motors can cause the network of actin filaments to contract and push or pull on the compartments. Yet, the exact way these networks localize",380,128,0.3368
dialogsum,"#Person1#: Were you born in the U. S. , Melissa? #Person2#: No, I wasn't. I came here in 1992. #Person1#: How old were you? #Person2#: I was seventeen. #Person1#: So, did you go to college right away? #Person2#: No, because my English wasn't very good. I studied English for two years first. #Person1#: Wow, your English is really fluent now. #Person2#: Thanks. Your English is pretty good, too. #Person1#: Yeah, but I was born here! !",#Person1# compliments Melissa's English because Melissa isn't a native speaker.,76,10,0.1316
scientific_lay_summarisation-elife-norm,"We wish to identify determinants of endothelial lineage. Murine embryonic stem cells (mESC) were fused with human endothelial cells in stable, non-dividing, heterokaryons. Using RNA-seq, it is possible to discriminate between human and mouse transcripts in these chimeric heterokaryons. We observed a temporal pattern of gene expression in the ESCs of the heterokaryons that recapitulated ontogeny, with early mesodermal factors being expressed before mature endothelial genes. A set of transcriptional factors not known to be involved in endothelial development was upregulated, one of which was POU class 3 homeobox 2 (Pou3f2). We confirmed its importance in differentiation to endothelial lineage via loss- and gain-of-function (LOF and GOF). Its role in vascular development was validated in zebrafish embryos using morpholino oligonucleotides. These studies provide a systematic and mechanistic approach for identifying key regulators in directed differentiation of pluripotent stem cells to somatic cell lineages. Our understanding of the genetic and epigenetic processes governing endothelial development and differentiation is limited (Yan et al. , 2010; De Val and Black, 2009). Accordingly, our methodologies for obtaining endothelial cells from pluripotent stem cells are empirically driven and suboptimal (Choi et al. , 2009; James et al. , 2010; Huang et al. , 2010a, 2010b; Wong et al. , 2012). There is unexplained inconsistency in the yield of iPSC-ECs; in the stability of their phenotype; and in the fidelity of differentiation (in terms of replicating the epigenetic and genetic profile of a mature endothelial cell). Furthermore, our ability to efficiently generate specific endothelial subtypes (e. g. arterial, venous, lymphatic) is poor. Thus, a systematic approach is needed to more completely define the genetic and epigenetic programs required for differentiating pluripotent stem cells to the endothelial phenotype. Here, we propose an unbiased systematic approach to discover determinants of differentiation. We use interspecies heterokaryons, RNA sequencing and third-generation bioinformatics to discover novel candidate genes critical for proper endothelial differentiation and specification. To discover new genes involved in endothelial specification, we made heterokaryons consisting of human endothelial cells (hEC) and murine embryonic stem cells (mESC) (1a–c), which expressed cell surface markers and characteristics of both cell types. We hypothesized that the factors that are actively maintaining endothelial phenotype (transcription factors, epigenetic modifiers and non-coding RNA etc) would act on the pluripotent stem cell nuclei to induce expression of","Endothelial cells form the inner surface of blood vessels, acting like a non-stick coating. In addition to making substances that keep blood from sticking to the vessel wall, endothelial cells generate compounds that relax the vessel, and prevent it from thickening. Endothelial cells also form capillaries, the smallest vessels that provide oxygen and nutrients for all tissues. A regenerating organ, or a bioengineered tissue, requires a system of capillaries and other microvessels. Thus, regenerative medicine could benefit from a knowledge of how to generate endothelial cells from pluripotent stem cells – cells that can “differentiate” to form almost any type of cell in the body. Wong, Matrone et al. have now used a cell fusion model (named heterokaryon) to track the changes in gene expression that occur as",380,128,0.3368
scientific_lay_summarisation-elife-norm,"presence of benzamil for 24 hr and confirmed that, after a long-term MET blockage, the MET channels remain inhibited but are still functional (1B). 10. 7554/eLife. 24661. 003Figure 1. Long-term blockage of the MET channels causes selective shortening of the second and third, but not the first (tallest), rows of stereocilia in mouse outer hair cell (OHC) bundles. (A and B) Assessment of MET blockage with MET channel-permeable dye, FM1-43. (A) Left panels show maximal projection images of FM1-43 fluorescence in mouse organ of Corti explants immediately after the tissue dissection, in control conditions (top) and in the presence of non-saturating concentrations of MET blockers: amiloride (100 μM, middle) or benzamil (30 μM, bottom). Right panels show reference bright-field images of the same cochlear explants at the focal plane of the hair cell bodies. Data are representative of two independent series. (B) Similar maximal projection FM1-43 (left) and bright-field (right) images at the end of 24 hr incubation at 37°C with 30 μM of benzamil (top) and after washout of this drug (bottom). (C) Representative scanning electron microscopy (SEM) images of OHC stereocilia bundles (false-colored) in mouse organ of Corti explants cultured for 24 hr at 37°C in vehicle control conditions (top), 100 μM of amiloride (middle), or 30 μM of benzamil (bottom). Right panels show higher magnification images of OHC stereocilia. Arrows point to examples of retracted stereocilia. (D) Heights of individual stereocilia in different rows of OHC bundles in mouse organ of Corti explants cultured for 24 hr in control conditions (black; n = 103–120 stereocilia) or in the presence of the MET blockers (gray), amiloride (100 μM, n = 99–108) or benzamil (30 μM, n = 75–80). Error bars indicate mean ± SD. The data are from a single series of experiments (8–17 cells per treatment) with control and drug-treated explants processed in parallel, representative of one (amiloride) and three (benzamil) independent series. (E and F) Representative false-colored SEM images of OHC bundles (E) and quantification of stereocilia heights (F) in the first (blue), second (yellow) and third (red) rows of the bundle (n = 40–130), indicating the dose-dependent effect of a 32 hr incubation in the presence of 0,5. 5,10 and 30 μM of benzamil. Data (4–12 cells per treatment) are shown as mean ± SD.","Our sense of hearing depends on cells known as hair cells that line the inner ear. Each hair cell has tiny projections called stereocilia, which are arranged in a bundle with rows of increasing height like a staircase and are connected to each other by tiny filaments called tip-links. When sound waves hit the stereocilia, the tension on the tip-links increases, which opens “mechanotransduction” channels on the shorter stereocilia that allow calcium ions to flow into the cells. To ensure that the ears can detect even the softest sounds, the tip-links always have a small amount of tension which allows a small, but continuous flow of calcium ions into the cell. Scientists generally consider this continuous flow of calcium ions as a potentially harmful byproduct of sensitive hearing.",380,128,0.3368
dialogsum,"#Person1#: Miss, would you like to try this free sample of our new suntan cream? #Person2#: Sure, why not? #Person1#: This is a new product of company this year. It's oil-free. #Person2#: I see. It feels very light on the skin. #Person1#: It gives your skin a very natural healthy look. #Person2#: I like the cool smell, too.",#Person1# asks #Person2# try the new oil-free suntan cream.,58,9,0.1552
scientific_lay_summarisation-elife-norm,"domain of UBQLN4 (1B) and is highly conserved during evolution, suggesting its importance in structural and functional properties of the protein. 10. 7554/eLife. 25453. 003Figure 1. The UBQLN4 c. 269A>C (p. D90A) variant identified in a familial ALS case. (A) Pedigree of a family with ALS. The proband (III3, arrow) had disease onset at 55 years of age, with disease duration of 22 months. Her mother (II3) died of ALS at 62 years of age without clear information regarding disease onset. Her maternal grandfather (I2) died in a traffic accident without any known neurological problems. Her maternal aunt (II2) developed ALS with disease onset at 51 years of age, and disease duration of 36 months. Her cousin (III1) developed ALS at 56 years of age and died five years later. (B) Predicted structural and functional domains of UBQLN4 with an arrow indicating the position of the mutation site. Domains include a UBL: ubiquitin-like domain, aa 13–83; four STI1 heat-shock-chaperonin-binding motifs, aa 192–229,230–261,393–440 and 444–476; and a UBA: ubiquitin-associated domain, aa 558–597. (C) Sequencing chromatograms of UBQLN4 wild-type allele in control and mutant allele in the patient with ALS. An adenine to cytosine substitution is present in the ALS patient, resulting in the change from aspartate to alanine at the ninetieth amino acid, D90A. : http: //dx. . org/10. 7554/eLife. 25453. 003 To assess the effects of the ALS-associated variant, we expressed wild-type or disease-associated UBQLN4 in cultured mouse spinal motor neurons (2A, — 1). UBQLN4D90A-expressing cells showed a significant increase in the total number of neurites as compared to cells expressing wild-type UBQLN4, or non-transfected cells (2A, C). Importantly, these results were validated in vivo in zebrafish. When mRNAs encoding UBQLN4-WT or UBQLN4D90A were injected into zebrafish embryos, we observed abnormal motor axon branching in UBQLN4D90A but not UBQLN4-WT or uninjected embryos (2B, D). Both UBQLN4-WT and UBQLN4D90A-injected fish embryos otherwise developed normally and showed neither gross morphological abnormalities nor significant changes in motor axon length, suggesting specificity of the motor axon branching phenotype. In all experiments, expression levels of UBQLN4-WT and UBQLN4D90A were comparable (— 2A–C). These results indicate that the ALS-associated UBQLN4 variant interferes with normal motor axon morphogenesis in culture and in vivo. 10. 7554/eLife. 25453. 004Figure 2. Expression of UBQLN4D90A results in motor axon branching abnormalities","Amyotrophic lateral sclerosis, or ALS for short, is a disease in which parts of the brain and spinal cord progressively degenerate. Specifically, the condition causes the nerve cells that control movement – called motor neurons – to die. As a result, people with ALS lose control of their muscles. The cause of ALS is not known, but evidence suggests that a person’s genetics plays a role in the development of the disease. Learning which genes are involved and what they do within cells may help scientists out what goes wrong in patients with ALS and how to treat the condition. People with ALS often experience an abnormal build up of proteins in their brain and spinal cord. Cells normally rely on molecules working together in the so-called ubiquitin",380,128,0.3368
pubmed-summarization,"neurons can release small molecule neurotransmitters very rapidly in part because synaptic vesicles are docked to the membrane at active zones . docked vesicles can immediately fuse with the plasma membrane ( zenisek et al . , 2000 ) in response to a single action potential ( borst and sakmann , 1996 ; sabatini and regehr , 1996 ) . synaptic vesicle docking is defined by morphological criteria : such vesicles can be observed directly contacting the plasma membrane in electron micrographs ( couteaux and pecot - dechavassine , 1970 ; harris and sultan , 1995 ; schikorski and stevens , 2001 ; xu - friedman et al . , 2001 ; hammarlund et al . , 2007 ) . in addition to synaptic vesicles , neurons also contain secretory vesicles , called dense core vesicles , that release neuropeptides and catecholamines ( burgoyne and morgan , 2003 ) . unlike synaptic vesicles , high - frequency stimulation is required for the release of dense core vesicles ( verhage et al . , 1991 ; bruns and jahn , 1995 ; tandon et al . , 1998 ) . one possible explanation for the bashfulness of dense core vesicles is that they are not docked . dense core vesicles are usually found in the cytoplasm and these cytoplasmic vesicles must presumably translocate to the plasma membrane before release ( zupanc , 1996 ) . however , in at least two cases , dense core vesicles have been observed docked to the plasma membrane ( karhunen et al . , 2001 ; ohnuma et al . , 2001 ) and , in one case , occupied positions along the synaptic active zone ( ohnuma et al . , 2001 ) . furthermore , secretory vesicles in neuroendocrine cells , which are similar to neuronal dense core vesicles , do dock ( plattner et al . , 1997 ; steyer et al . , 1997 ) thus , the delayed release characteristics of neuronal dense core vesicles may not be caused by a requirement for translocation to the plasma membrane . alternatively , the different release characteristics of dense core and synaptic vesicles might be caused by differences in spatial organization or fusion machinery . for example , dense core vesicles and","docking to the plasma membrane prepares vesicles for rapid release . here , we describe a mechanism for dense core vesicle docking in neurons . in caenorhabditis elegans motor neurons , dense core vesicles dock at the plasma membrane but are excluded from active zones at synapses . we have found that the calcium - activated protein for secretion ( caps ) protein is required for dense core vesicle docking but not synaptic vesicle docking . in contrast , we see that unc-13 , a docking factor for synaptic vesicles , is not essential for dense core vesicle docking . both the caps and unc-13 docking pathways converge on syntaxin , a component of the snare ( soluble n - ethyl - maleimide sensitive fusion protein attachment receptor",380,128,0.3368
pubmed-summarization,"reports which had less than 80% of technically correct measurements were excluded from the study . arterial hypertension was diagnosed when mean abpm values were above the 95th centile for the corresponding age , gender , and height . this included visual acuity tests , intraocular pressure and anterior segment estimation using the slit lamp ( topcon sl-82 , japan ) . after local administration of tropicamide ( 1% solution ) , the eye fundus was examined using the + 90 d lens ( ocular instruments , usa ) . a digital camera ( topcon imaginet 2000 , japan ) was used for the fluorescein angiography . the stage of retinopathy was diagnosed according to the guidelines of the international diabetic retinopathy division . twenty - four - hour urine collection was performed three times during the period of 6 months for the evaluation of the daily albumin excretion . the urinary albumin was measured with immunoturbidimetric assay using a tina - quant kit ( boehringer mannheim gmbh , germany ) . albuminuria was diagnosed when at least two out of three urine samples displayed daily albumin excretion of between 30 and 299 mg/24 h , collected within 6 months from patients with well - controlled diabetes with no clinical or laboratory signs of ketoacidosis . glycated haemoglobin ( hba1c ) was measured with an immunoturbidometric method using a unimate 3 set ( hoffmann - la roche ag , basel , switzerland ) . one hundred and sixteen patients with t1 dm were examined and divided into four groups based on the duration of diabetes . the control group consisted of 19 healthy children and adolescents ( 11 boys and 8 girls , age range 618 yrs ) . written informed consent was obtained from all the participants in the study , or from their parents or guardians . this study was approved by the ethics committee of the medical university of gdask , and the investigation was carried out in accordance with the principles of the declaration of helsinki as revised in 1996 . the serum concentrations of tgf-1 were measured using the cytometric bead array ( cba ) as instructed by the manufacturer 's manual ( plex flex single set , becton dickinson , usa ) . the","the aim of this study was to evaluate the relationship between serum transforming growth factor 1 ( tgf-1 ) concentrations and the duration of type 1 diabetes mellitus ( t1 dm ) in children and adolescents . one hundred and sixteen patients with t1 dm and 19 healthy controls were examined . serum tgf-1 concentrations were measured using the cytometric bead array ( cba ) . a positive association between the time of diabetes duration and higher serum tgf-1 concentrations was observed . similarly , the prevalence of microvascular complications , such as retinopathy and nephropathy , increased with the duration of diabetes . logistic regression analysis showed that serum tgf-1 concentrations and the duration of the disease are independent risk factors of microangiopathy development . higher serum",380,128,0.3368
pubmed-summarization,"ch is also one of the most classic diseases in newborn screening history , the incidence of which varied from 1:2000 to 1:4000 in different areas and different ethnicities . pituitary thyroid axis , which leads to a reduction of thyroxin secretion , which , in turn , causes severe damage to the brain . according to the clinical course of the disease , ch can be classified as either permanent or transient ch ( pch / tch ) . it was reported that the incidence of pch was about 1:2000 to 1:3587 and that the incidence of tch was about 1:1580 to 1:17 000 . the major etiology of pch was linked to dysgenesis , including complications such as athyreosis , atrophy , and ectopic , but the etiology of tch was not that clear . many studies suggested that the etiology of tch was multiplicity , prematurity , low birth weight , and iodine deficiency or excessive use of antithyroid drugs . in addition , an interaction between genes and the environment may also be related to the occurrence of tch . up to now , there have been very few reports regarding the incidence and etiology of pch and tch in china . guangxi province , which is located in the southwest of china , is the largest minority nationality area for the han and zhuang nations . its geography and ethnic makeup means that it is different from other areas of china . a previous study reported the incidence of ch as detected by nsp to be about 1:835 in guangxi , which is much higher than the average for the whole country . but the incidence of confirmed cases of pch and tch among patients and the reasons of the high incidence of ch in this area are still unclear and is yet to be fully reported . the objective of this study was to confirm the high incidence of ch as detected by nsp and look at the interrelated factors linked to the major types of ch in guangxi . a total of 930 612 newborns ( 511 555 females and 419 057 males ) screened by the newborn screening program ( nsp ) at newborn screening center of guangxi , china , from","background . a newborn screening program ( nsp ) for congenital hypothyroidism ( ch ) was carried out in guangxi in order to understand the incidence of ch and the factors interrelated to major types of ch in this region of china . methods . during 2009 to 2013 , data from 930 612 newborns attending nsp in guangxi were collected . patients were classified with either permanent ch ( pch ) or transient ch ( tch ) after 2 years of progressive study . results . a total of 1210 patients were confirmed with ch with an incidence of 1/769 , including 68 pch and 126 tch cases with incidences of 1/6673 and 1/3385 , respectively . the frequency of thyroid stimulating hormone values greater than 5",380,128,0.3368
scientific_lay_summarisation-elife-norm,"NTD. Our results show that the presence of MtaLonA NTD is required to degrade damaged proteins and native proteins with degrons, but it does not play an active role in mediating the degradation by LonA of an intrinsically disordered substrate, α-casein. Here we report the crystal structure of an N-terminal fragment of MtaLonA determined at a 2. 1 Å resolution, demonstrating that it is similar to the structures of both EcLon and MacLon NTDs, but not to that of BsLon. MtaLonA NTD appears to tumble independently of the hexameric core complex, indicating that the NTD is attached to the hexameric chamber by a flexible linker thus rendering it possible for detailed chemical shift perturbation (CSP) mapping of substrate binding in the context of full-length MtaLonA. We further structurally characterize the NTD-mediated interactions with unfolded proteins, protein aggregates, and degron-tagged proteins. This work suggests that the flexibly linked NTDs can help survey, discriminate, and selectively capture damaged unfolded protein species or native protein substrates carrying exposed degradation sequence motifs. To evaluate the importance of the NTD in the proteolysis activity of MtaLonA, we constructed a MtaLonA variant, AAAP, of which the NTD (residues 1–241) was removed (1A), based on the structure of B. subtilis LonA. Substrate degradation activity of AAAP was evaluated using two protein substrates, namely α-casein and Ig2. Native α-casein is an intrinsically disordered substrate of LonA. Ig2 is an all β-stranded protein that becomes partially unfolded at 55°C (— 1) and only then is susceptible to proteolysis by MtaLonA (Higashitani et al. , 1997). Full-length MtaLonA degrades both α-casein and damaged Ig2 (Van Melderen et al. , 1996). Compared to the full-length MtaLonA, AAAP exhibited a slightly reduced degradation activity against α-casein (1B), while its proteolytic activity for thermally unfolded Ig2 was severely impaired (1C). These results showed that, despite the lack of the NTD, AAAP retains the proteolytic activity for intrinsically disordered protein substrates like α-casein. However, the NTD is essential for MtaLonA to recognize and degrade the thermally damaged substrate, Ig2, indicating the NTD may mediate specific interactions with damaged Ig2, but not α-casein. We obtained crystals of the N-terminal fragment NN206 of MtaLonA by in situ proteolysis during crystallization (2A). The structure was refined to 2. 1 Å resolution with a free R factor of","There are many different types of protein which each have different roles in biology. Most proteins are surrounded by water and are folded so that their water-attracting regions are on the outside and more fat-like regions, which repel water, are on the inside. When a protein becomes damaged or is assembled incorrectly, some of the fat-like regions end up on the outside of the protein and become exposed to water. This can prevent the protein from performing its role and harm the cell instead. LonA proteases are responsible for dismantling and recycling these harmful proteins, as well as proteins that have been labelled for destruction. They do this by unfolding the unwanted protein and transporting it into an enclosed chamber made of six LonA molecules. Once inside the",380,128,0.3368
dialogsum,"#Person1#: Sarah, what did you do today? #Person2#: I went shopping. #Person1#: Did you buy anything? #Person2#: Yes, I bought a few things. #Person1#: What did you buy? #Person2#: I bought this coat. Do you like it? #Person1#: Yeah, I like it a lot. It's very pretty. Where did you buy it? #Person2#: At the mall on 5th street. #Person1#: Was it expensive? #Person2#: No, it wasn't expensive. It was on sale for 20 dollars. #Person1#: That's cheap. #Person2#: I know. It was a really good deal. #Person1#: I don't think you'll need to wear it for a while. It's been really hot lately.",Sarah shows her new coat to #Person1# and says she bought it at the mall and it cost 20 dollars.,104,20,0.1923
dialogsum,"#Person1#: Well, what's on? #Person1#: Well, hmm. There is a reality show on at 7:00 on channel 5. #Person2#: Nah, you know I don't like reality shows. I mean, they usually show people doing crazy things like, you know, eating live fish or swimming in a pool full of snakes. I don't get into that. #Person1#: Okay. Well, how about watching a documentary on the life of panda bears in the wild? #Person2#: Personally, I'd rather watch something with a little bit more action and suspense. #Person1#: Well, then. Ah, here's something. Do you want to watch a rerun of Star Wars? #Person2#: Nah, I've seen it a zillion times. I'd like to see something different. #Person1#: Okay, let's see here. Oh, how about this? On channel 2 at 9:00, there's a home improvement show about fixing anything around the house. We do have a few things that you could repair in the bathroom ... #Person2#: Fixing things? Uh, boy, I'm beat. I think I'm going to hit the sack. #Person1#: You're going to bed? #Person2#: Yeah. I have to get up early tomorrow ... #Person1#: ... and then you're going to fix the bathroom? #Person2#: Good night. #Person1#: Okay. Too bad, though. There's a basketball game on right now, but ... but I guess you can catch the score in tomorrow's newspaper. #Person2#: Oh, okay. I'll stay up and keep you company while I ... I mean, you ... I mean, WE watch the game. #Person1#: I thought you'd change your mind. I'll get the popcorn.",#Person1# and #Person2# are watching TV. #Person1# offers many choices but #Person1# isn't interested in all these shows and wants to go to bed. #Person1# finally suggests a basketball game and #Person2# decides to stay and watch.,257,37,0.144
dialogsum,"#Person1#: How are you doing? #Person2#: I'm doing great. #Person1#: What movies have you seen lately? #Person2#: I saw Forrest Gump the other day. #Person1#: What type of movie is that? #Person2#: The movie type is drama. #Person1#: I can't believe you are watching movies. The weather is great. You should be outside. #Person2#: I hate the hot weather. I'd rather stay indoors with the air conditioner. #Person1#: What else do you like to do besides watching movies? #Person2#: I like to play computer games, read books, go shopping, and play pool. #Person1#: Out of those what is your favorite? #Person2#: My favorite is to play computer games. #Person1#: What is your favorite computer game? #Person2#: My favorite is Diablo. It used to be Star Craft, but it is getting a little old. #Person1#: If you like to play so much, when do you ever exercise? #Person2#: Although I hate to exercise, I go jogging at least twice a week. #Person1#: That's pretty good. By the way, what are you doing next Saturday? #Person2#: I am going to go to the bookstore. #Person1#: I am having a party Saturday night at my house. If you have time, you should come. #Person2#: That sounds like fun. #Person1#: Great. I'll see you on Saturday. #Person2#: Ok. See you later.","#Person2# saw Forrest Gump. #Person2# tells #Person1# that besides watching movies, #Person2# likes to play computer games, read books, go shopping, and play pool. #Person1# invites #Person2# to a party next Saturday, and #Person2# accepts.",217,35,0.1613
dialogsum,"#Person1#: Have you had any publications? #Person2#: Yes. I have published some articles in China Daily and Economist. #Person1#: How about your communication skills? #Person2#: As a journalist, I have strong communication skills. I am good at both discourse management and strategic competence.",#Person1# interviews #Person2#. #Person2# has published in China Daily and Economist and has strong communication skills.,43,16,0.3721
dialogsum,"#Person1#: How are your wedding plans going? #Person2#: Very well. We started organizing everything early to avoid a last minute rush to get things done. #Person1#: When will your wedding take place? #Person2#: At ten o'clock on the morning of next Sunday. We have invited all our relatives to the wedding. #Person1#: It will be a large church one. Is your wedding dress ready? #Person2#: Yes, its design is very elaborate and the designer took many weeks to make it. #Person1#: You will be very beautiful on your wedding day. #Person2#: Thank you! #Person1#: Which hotel will the reception be held at? #Person2#: The Palace Hotel. #Person1#: It's excellent. A friend of mine had her wedding reception there and said it was perfect, though very expensive. #Person2#: It will be expensive, but we think it will be worth. #Person1#: I think you made the right decision.",#Person2# tells #Person1# #Person2#'s wedding will be on next Sunday with a reception at the Palace Hotel and #Person2#'s dress is elaborate. #Person1# thinks that's the right decision.,146,28,0.1918
scientific_lay_summarisation-elife-norm,"Transcription is tightly regulated to maintain energy homeostasis during periods of feeding or fasting, but the molecular factors that control these alternating gene programs are incompletely understood. Here, we find that the B cell lymphoma 6 (BCL6) repressor is enriched in the fed state and converges genome-wide with PPARα to potently suppress the induction of fasting transcription. Deletion of hepatocyte Bcl6 enhances lipid catabolism and ameliorates high-fat-diet-induced steatosis. In Ppara-null mice, hepatocyte Bcl6 ablation restores enhancer activity at PPARα-dependent genes and overcomes defective fasting-induced fatty acid oxidation and lipid accumulation. Together, these findings identify BCL6 as a negative regulator of oxidative metabolism and reveal that alternating recruitment of repressive and activating transcription factors to shared cis-regulatory regions dictates hepatic lipid handling. The classical studies of Jacob and Monod on the bacterial lac operon established a central paradigm for transcriptional repression to direct metabolic responses and sustain life in an environment of discontinuous food supply (Jacob and Monod, 1961; Payankaulam et al. , 2010). In metazoans, nutrient-elicited transcription likewise coordinates the feeding to fasting transition of metabolism, yet a gap remains in our knowledge of the participating factors and their genomic coordination. In the fed state, sterol and carbohydrate regulatory element-binding proteins (SREBP and ChREBP) direct lipogenesis and glycolysis (Abdul-Wahed et al. , 2017; Horton et al. , 2002). Conversely, fasting disinhibits forkhead box transcription factors (FOXOs) and activates glucocorticoid receptor (GR) and cAMP response element binding protein (CREB) to promote gluconeogenesis (Rui, 2014). Extended fasting further stimulates peroxisome proliferator-activated receptor alpha (PPARα) to induce fatty acid oxidation, ketogenesis, and the fasting hormone FGF21 (Badman et al. , 2007; Inagaki et al. , 2007; Kersten et al. , 1999; Leone et al. , 1999). Despite progress revealing these various transcriptional activators, their dynamic genome-wide regulation and the influence of additional factors, particularly repressors, on the feeding to fasting transition remains poorly understood (Goldstein and Hager, 2015). Recently, fasting-regulated enhancers were mapped using H3K27 acetylation ChIP- and DNase I hypersensitivity sequencing and footprinting, which inferred the presence of unknown repressors at regions enriched with STAT motifs (Goldstein et al. , 2017). Our focus turned to B-cell lymphoma 6 (BCL6), a key immune cell repressor with affinity for STAT-like DNA recognition sequences (Dent et al. , 1998; Dent et al. , 1997; Zhang","Obesity has nearly tripled worldwide since the 1970s. A major health concern related to obesity is that excess fat can spill into organs such as the liver. This can lead to fatty liver disease or even liver cancer. Therefore, it is important to fully understand the mechanisms that lead to fat accumulation in the liver in order to develop new treatments. Our bodies are designed to even out the highs and lows of an unpredictable diet by storing and releasing calories. When we are well-fed, liver cells switch on genes involved in making fat. When we have not eaten for a while, they switch them off and turn on genes involved in burning fat. Each switch involves thousands of genes, controlled by proteins called transcription factors. Some work",380,128,0.3368
dialogsum,"#Person1#: I'd like to reserve a room. #Person2#: Which date would that be? #Person1#: For the night of April 18th, for one night. #Person2#: I'm afraid our hotel is fully booked on that night. Is it possible for you to change your reservation date? #Person1#: No, I'm afraid not. #Person2#: We might have cancellations. Could you call us again some other day? #Person1#: Sure, but if you do have any cancellations, could you let me know as soon as possible? #Person2#: I'm very sorry, sir, but we are unable to do that. We would appreciate it very much if you could call us instead. #Person1#: OK, thanks.",#Person1# wants to reserve a room but #Person2# tells #Person1# that their hotel is fully booked.,107,16,0.1495
pubmed-summarization,"ml kg , p.o . ) . anticonvulsant activity was scored similarly to that stated in the ptz test . tonic convulsions of hind limb extremities of mice were induced using electrical current ( 50 ma , 60 hz , and 0.2 seconds ) via ear clip electrodes . control group animals received distilled water orally ( 10 ml kg , p.o . ) . carbamazepine at doses of 3 , 10 , and 30 mg kg orally served as reference anticonvulsant . aae was tested at doses of 200 , 400 , and 800 mg kg orally . aae was administered orally at doses of 200 , 400 , and 800 mg kg body weight . strychnine was injected subcutaneously at a dose of 2 mg kg thirty minutes after aae administration . standard anticonvulsant employed was diazepam ( 0.1 , 0.3 , and 1 mg kg , i.p ) . the onset of , decrease in the total duration plus frequency of tonic convulsions were taken as indication of anticonvulsant activity . animals received aae orally at doses of 200 , 400 , and 800 mg kg body weight . 4-aminopyridine was dissolved in normal saline and injected subcutaneously at a dose of 10 mg kg body weight thirty minutes after drug treatments . control animals were pretreated with normal saline ( 10 ml kg ) and sodium valproate at 100 , 200 , and 400 mg kg served as positive control . hind limb tonic extensions and decrease in the total duration of convulsions were recorded . method as described by morales - villagrn and tapia , 1996 , was used with slight modifications . in order to investigate the mechanism of action of aae as an anticonvulsant , mice were treated with flumazenil , a benzodiazepine antagonist ( 1 mg kg , i.p ) fifteen minutes before the administration of aae ( 400 mg kg , p.o . ) . thirty ( 30 ) minutes later , convulsions were induced with pentylenetetrazole at 85 mg kg , intraperitoneally . other groups of animals received aae or flumazenil or diazepam ( 0.3 mg kg , i.p ) only . animals were observed for thirty minutes after treatment via video recording for latency and duration of convulsions .","antiaris toxicaria ( moraceae ) was evaluated for anticonvulsant activity in rodents . animal models used include maximal electroshock test ( mest ) ; pentylenetetrazole - induced ( ptz ) convulsions ; picrotoxin - induced ( pct ) convulsions ; strychnine- ( str- ) and 4-aminopyridine - induced convulsions . increase in latency to seizures as well as reduction in duration and frequency of seizures indicated anticonvulsant activity . the extract was more effective in all models used except the maximal electroshock test and strychnine - induced convulsions . antiaris toxicaria aqueous extract ( 200 , 400 , and 800 mg kg1 ) significantly ( p < 0.05 0.01 ) shortened the duration of convulsions in ptz- and pct - induced seizures . delay in the onset of",380,128,0.3368
pubmed-summarization,"nephrotic syndrome ( ns ) is characterized by massive proteinuria , hypoalbuminemia , edema and hyperlipidemia with 2 - 3/100,000 annual incidences . steroid has a main role in treatment , but patients who do not have appropriate response to steroid , have a greater chance to attain end stage renal disease ( esrd ) . therefore , detecting early stages of chronic kidney diseases ( ckd ) has greatest importance in treating patients at risk . the available standard biochemical markers are not sensitive enough to determine high - risk patients . however , a variety of factors including response to steroid , hypertension , extent of glomerular sclerosis and interstitial fibrosis have been accepted as prognostic markers of getting esrd . recently , new biomarkers have been introduced to define patients at risk . among these biomarkers , there is few data regarding the role of ngal and cystatin - c in children with ns . in this study , we evaluated serum ngal and cystatin - c in both steroid sensitive nephrotic syndrome ( ssns ) and steroid resistant nephrotic syndrome ( srns ) children . in addition , we evaluated any possible correlation between these two biomarkers and response to steroid . in this cross - sectional study , 104 participants aged 1 - 18 years were enrolled i.e. , 52 cases and an equal number of control . since normal value for these two parameters in normal children cases were selected from children with idiopathic ns who had been hospitalized from september 2008 to december 2011 in the only referral pediatric nephrology department , affiliated to isfahan university of medical sciences , isfahan , iran . histopathologic findings mostly consisted of minimal change disease and or focal segmental glomerular sclerosis ( fsgs ) . the histopathologic diagnosis of fsgs was based on the following criteria : ( i ) a lesion affecting some of the glomeruli in the renal biopsy while others remain unaffected and ( ii ) the affected glomeruli having a portion that has undergone capillary collapse with obliteration of capillary lumina with or without adhesions . control group was selected from age- and sex - matched children who had been referred to pediatric clinics for routine health examination . these data for","background : nephrotic syndrome ( ns ) is a major clinical concern in human health , especially in children . despite of the etiology , the prediction of remission in different treatment regimens based on suitable biomarkers is under development . the goal of this evaluation was the demonstration of correlation between serum level of neutrophil gelatinase associated lipocalin ( ngal ) and cystatin - c with kidney function in patients with ns.methods:during the period between september 2008 and december 2011 , 52 patients admitted to st . al zahra university hospital were selected for evaluation . the measured parameters consisted of ngal , cystatin - c , creatinine , albumin , blood urea nitrogen , urine protein , glomerular filtration rate . demographic data were collected and",380,128,0.3368
dialogsum,"#Person1#: You are looking really healthy lately. What are you doing differently? #Person2#: Thank you for noticing! I've been making a few lifestyle changes over the past year. #Person1#: Tell me about it. I'm interested. #Person2#: Well, it all started when my brother challenged me to quit smoking. #Person1#: Ha! That's right. You used to smoke. I forgot! #Person2#: When I kicked that habit, I found I had so much more energy. I started exercising. #Person1#: At the gym? #Person2#: No. I like to be outside. I took up hiking and mountain biking.","#Person2# tells #Person1# #Person2#'s been making lifestyle changes including quitting smoking and starting exercising, so #Person2# looks healthy.",93,18,0.1935
scientific_lay_summarisation-elife-norm,"improve the precision of nucleosome mapping from MNase-seq data, such as peak finding of nucleosome occupancy (Zhang and Pugh, 2011) and filtering of single-end digestion patterns (Weiner et al. , 2010), but determining the precise locations of individual nucleosomes within a cell population remains a challenge due to substantial variability in the mapped locations of digested nucleosomes – the midpoints of paired-end sequenced nucleosomes or the endpoints of single-end sequenced nucleosomes (1B). This variability may arise from a cluster of overlapping and stably positioned nucleosomes, as well as from effects causing different degrees of digestion of the same nucleosome by MNase, such as nucleosome breathing and nuclease trimming – all of which influence the distribution of the aligned reads and are difficult to disentangle (Clark, 2010). Recently, a chemical cleavage approach that uses a genetically engineered histone H4 to chemically cleave DNA sequences in contact with the nucleosome dyad allowed direct measurement of nucleosome positions with unprecedented resolution (Brogaard et al. , 2012; Moyle-Heyrman et al. , 2013). However, the requirement for genetic engineering of essential histones limits its current application to genetically tractable organisms. Therefore, novel experimental or analytical approaches that are generally applicable in eukaryotes are still needed to determine the accurate positions of nucleosomes in vivo. Here, we report a computational approach to determine in vivo nucleosome positions from paired-end MNase-sequencing data. 10. 7554/eLife. 16970. 003Figure 1. Illustration of the Template-Based Bayesian (TBB) approach for determining nucleosome positions. (A) Diagram illustrating the heterogeneous nucleosome positions and the consensus centers of nucleosomes along a genomic region in a population of cells. Blue ovals illustrate individual nucleosomes and dotted lines mark all nucleosome positions. (B) Example of digested nucleosome reads, their nucleosome positions and the overall occupancy. (C) Illustration of the computational pipeline of the TBB approach. Occupancy of sequencing read midpoints indicates the number of midpoints at every base pair for yeast Chr 8,204,500–206,500 bp. Blue ovals illustrate overlapping TBB nucleosome positions and are colored according to the magnitude of their coefficients β. Two common presentations of nucleosome sequencing data are shown for comparison: the light gray area represents the nucleosome occupancy generated by smoothing sequencing read midpoints with a Parzen window approach (band size of 20 bp) (Albert et al. , 2007; Tsankov et al. , 2010);","Plants, animals and other eukaryotes wrap their DNA around complexes of proteins called histones to form repeating units known as nucleosomes. The interaction between histones and DNA is strong, and so the DNA region inside a nucleosome has limited access to other proteins, including those that drive the expression of genes. Moving a nucleosome slightly can change the access to its DNA and significantly impact how the genes in the region are regulated. Nevertheless, determining the position of nucleosomes accurately or testing how nucleosomes are different between individual cells are challenging tasks. Most methods for identifying nucleosomes use an enzyme called micrococcal nuclease (or MNase for short) to break down the DNA that isn’t protected in nucleosomes, followed by high-throughput DNA sequencing to identify the DNA fragments that",380,128,0.3368
pubmed-summarization,"with the worldwide spread of mycobacterium tuberculosis ( mtb ) strains resistant to both isoniazid and rifampicin ( rif ) , multidrug - resistant ( mdr ) tuberculosis ( tb ) has become a major public health problem posing formidable challenges due to its complex diagnostic and treatment requirements . this highlights the need for having rapid molecular diagnostic techniques which could help facilitate early diagnosis and appropriate delivery of anti - tubercular therapy . xpert mtb / rif assay ( cepheid ) , a real - time automated nucleic acid amplification system is one such technique which detects mtb as well as mutations that confer resistance to rif in > 2 h. it was installed in our institute ( guru gobind singh medical college and hospital , faridkot ) in october 2013 under revised national tuberculosis control programme ( rntcp ) tb xpert project supported by who - stop tb partnership - unitaid . rif is a principle first line anti - tb drug and rif resistance is a surrogate marker for mdr - tb . the genetic basis of rif resistance ( in approximately 95% cases ) is the presence of mutations in 81 bp rif resistance determining region ( rrdr ) of the rpob gene , corresponding to codons 507533 ( escherichia coli numbering system ) , which codes for a beta subunit of rna polymerase of mtb . studies conducted in diverse geographical areas have shown that the burden of mdr - tb and the mutations responsible for drug resistance vary from country to country and region to region . however , there is not enough of information about this important aspect from north india and the data from malwa region of punjab is almost lacking . therefore , this retrospective study was conducted to determine the frequency of rif resistance and rpob gene mutations among the suspected tb / mdr cases of malwa region of punjab ( districts : faridkot , fazilka , firozpur , moga , bathinda , and muktsar - area approximately 14,981 km ) , using xpert mtb / rif assay . knowledge of the pattern of mutations present in rif - resistant isolates could provide insight into the epidemiology of rif - resistant mtb isolates of this particular area . a","background : xpert mtb / rif assay has revolutionized the diagnosis of tuberculosis ( tb ) by simultaneously detecting the bacteria and resistance to rifampicin ( rif ) , a surrogate marker for multidrug - resistant tb ( mdr - tb ) in < 2 h. the rif resistance pattern in malwa region of punjab , india , is not documented . here , we report the epidemiology of rif - resistant tb and mutations in rpob gene of mycobacterium tuberculosis ( mtb).materials and methods : a total of 1612 specimens received between october 2013 and february 2015 were tested by xpert mtb / rif assay following manufacturer 's instructions . the results thus obtained were analyzed using spss version 20.0.0 ( spss inc . , chicago ,",380,128,0.3368
pubmed-summarization,"blood count ; prothrombin time ; direct and indirect bilirubin ; fasting blood sugar ; serum creatinine ; liver enzymes ( serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase ) ; alanine aminotransferase . patients were treated with pegylated interferon -2a at a dose of 180 mcg injected subcutaneously once weekly for 48 weeks . all patients underwent clinical and laboratory assessments , ophthalmic examination , at 15 days , 1 month , 2 months , 3 months , 6 months , 8 months , and 9 months after the start of ifn treatment . patients were treated with pegylated interferon -2a at a dose of 180 mcg injected subcutaneously once weekly for 48 weeks . all patients underwent clinical and laboratory assessments , ophthalmic examination , at 15 days , 1 month , 2 months , 3 months , 6 months , 8 months , and 9 months after the start of ifn treatment . initially , 120 patients fulfilled the criteria for ifn therapy , but 20 of them were excluded due to non - compliance with the follow - up visits and due to the presence of diabetic or hypertensive retinopathy . also , two patients died during the study time , due to a disease not related to hepatitis , so these patients are not included . therefore , a total of 100 patients ( 68 male and 32 female ) , with chronic hcv were selected . after the start of interferon therapy , 16 out of 100 patients ( 16% ) developed retinopathy which was bilateral in 12 ( 75% ) patients and unilateral in 4 ( 25% ) patients . retinopathy was initially diagnosed by the appearance of a cotton wool spot in 14 patients . in four of the 14 patients , retinal hemorrhage two of the 16 patients who developed retinopathy were diagnosed by retinal hemorrhage without cotton wool spots . one patient ( not diabetic or hypertensive ) had cystoid macular edema , this was the only patient who complained of the visual disturbance due to interferon . all patients had bcva of ( 6/6 ) during ifn treatment except for three patients : the one who had cystoid macular edema ( bcva was 6/12 and returned to 6/6","purposeto evaluate retinopathy associated with interferon therapy in patients with chronic hepatitis c.methodsone hundred patients with chronic hepatitis c undergoing interferon therapy were examined for the presence of cotton wool spots , retinal hemorrhages , cystoid macular edema , capillary non - perfusion , and arteriolar occlusion . complete ophthalmological examination including indirect ophthalmoscopic fundus examination was carried out for all patients and colored fundus photography and fluorescein angiography were carried out for the patients with positive fundus findings . the follow - up period was 9 months.resultssixteen percent of patients developed retinopathy in the form of cotton wool spots , retinal hemorrhages , cystoid macular edema , and capillary non-perfusion.conclusioninterferon therapy can lead to retinopathy which is mostly reversible and dose related . periodic fundoscopic examinations help",380,128,0.3368
scientific_lay_summarisation-elife-norm,"prophase, HORMADs localize to chromosomes along their entire lengths, where they promote the introduction of DNA double-strand breaks and bias the repair of those breaks toward the homologous chromosome (Subramanian and Hochwagen, 2014). In both yeast and mammals, excess recombination is limited by a feedback mechanism that removes or redistributes HORMADs along the chromosome after sufficient COs have formed. The removal of HORMADs depends on a conserved AAA+ family ATPase, Pch2/TRIP13, without which the frequency and spatial distribution of COs is disrupted (San-Segundo and Roeder, 1999; Börner et al. , 2008; Joshi et al. , 2009; Wojtasz et al. , 2009; Roig et al. , 2010; Chen et al. , 2014). We have previously shown that the HORMADs assemble into higher-order oligomers through head-to-tail safety-belt interactions, and that these interactions are critical for their meiotic functions (Kim et al. , 2014). As a predominant family of AAA+ ATPases function to disaggregate or disassemble protein complexes (Erzberger and Berger, 2006; Sauer and Baker, 2011), it has been proposed that Pch2/TRIP13 mediates HORMAD removal from chromosomes through specific recognition and disassembly of chromosome-associated HORMAD complexes (Chen et al. , 2014). Recently, mammalian TRIP13 has been shown to regulate the SAC, which monitors kinetochore-microtubule attachment in both mitosis and meiosis (Musacchio and Salmon, 2007). In this pathway, unattached kinetochores generate an inhibitor of the anaphase promoting complex/cyclosome (APC/C) called the mitotic checkpoint complex (MCC), which is composed of the MAD2, CDC20, BUBR1, and BUB3 proteins (Hardwick et al. , 2000; Fraschini et al. , 2001; Sudakin et al. , 2001). MAD2 is a relative of the meiotic HORMADs, and exists in one of two conformers: an inactive ‘open’ state (O-MAD2), and an active ‘closed’ state (C-MAD2) (— 1A) that binds CDC20 through a safety-belt interaction to form the core of the MCC (Sironi et al. , 2002; Luo et al. , 2004; Shah et al. , 2004; Chao et al. , 2012). After all kinetochores become properly attached to microtubules, new MCC assembly is halted and the SAC is inactivated. Timely SAC inactivation requires two factors, TRIP13 (Wang et al. , 2014) and the HORMA domain protein p31 (comet) (Habu et al. , 2002; Xia et al. , 2004; Hagan et al. , 2011; Varetti et al. , 2011; Westhorpe et al. ,","The genetic material inside human and other animal cells is made of DNA and is packaged in structures called chromosomes. Before a cell divides, the entire set of chromosomes is copied so that each chromosome is now made of two identical sister ‘chromatids’. Next, the chromosomes line up on a structure called the spindle, which is made of filaments called microtubules. Cells have a surveillance system known as the spindle assembly checkpoint that halts cell division until every chromosome is correctly aligned on the spindle. Once the chromosomes are in place, the checkpoint is turned off and the spindle pulls the chromatids apart so that each daughter cell receives a complete set of chromosomes. A protein called MAD2 plays an important role in the spindle assembly checkpoint. It",380,128,0.3368
scientific_lay_summarisation-elife-norm,"In mammals, testicular differentiation is initiated by transcription factors SRY and SOX9 in XY gonads, and ovarian differentiation involves R-spondin1 (RSPO1) mediated activation of WNT/β-catenin signaling in XX gonads. Accordingly, the absence of RSPO1/Rspo1 in XX humans and mice leads to testicular differentiation and female-to-male sex reversal in a manner that does not requireSry or Sox9 in mice. Here we show that an alternate testis-differentiating factor exists and that this factor is Sox8. Specifically, genetic ablation of Sox8 and Sox9 prevents ovarian-to-testicular reprogramming observed in XX Rspo1 loss-of-function mice. Consequently, Rspo1 Sox8 Sox9 triple mutant gonads developed as atrophied ovaries. Thus, SOX8 alone can compensate for the loss of SOX9 for Sertoli cell differentiation during female-to-male sex reversal. During primary sex determination in mammals, a common precursor organ, the bipotential gonad, develops as a testis or ovary. In humans and mice, testicular development begins when SRY and SOX9 are expressed in the bipotential XY gonad. These transcription factors promote supporting cell progenitors to differentiate as Sertoli cells and form sex cords (Gonen et al. , 2018; Chaboissier et al. , 2004; Barrionuevo et al. , 2006), and this triggers a cascade of signaling events that are required for the differentiation of other cell populations in the testis (Koopman et al. , 1991; Vidal et al. , 2001). In XX embryos, the bipotential gonad differentiates as an ovary through a process that requires RSPO1-mediated activation of canonical WNT/β-catenin (CTNNB1) signaling in somatic cells (Parma et al. , 2006; Chassot et al. , 2008). Ovarian fate also involves activation of FOXL2, a transcription factor that is required in post-natal granulosa cells (Schmidt et al. , 2004; Ottolenghi et al. , 2005; Uhlenhaut et al. , 2009), which organize as follicles during embryogenesis in humans and after birth in mice (McGee and Hsueh, 2000; Mork et al. , 2012). For complete differentiation of testes or ovaries, an active repression of the opposite fate is necessary (Kim et al. , 2006). Inappropriate regulation within the molecular pathways governing sex determination can lead to partial or complete sex reversal phenotypes and infertility (Wilhelm et al. , 2009). Studies in humans and mice have shown that the pathway initiated by SRY/SOX9 or RSPO1/WNT/β-catenin signaling are indispensable for sex specific differentiation of the gonads. For example, in","In humans, mice and other mammals, genetic sex is determined by the combination of sex chromosomes that each individual inherits. Individuals with two X chromosomes (XX) are said to be chromosomally female, while individuals with one X and one Y chromosome (XY) are chromosomally males. One of the major differences between XX and XY individuals is that they have different types of gonads (the organs that make egg cells or sperm). In mice, for example, before males are born, a gene called Sox9 triggers a cascade of events that result in the gonads developing into testes. In females, on the other hand, another gene called Rspo1 stimulates the gonads to develop into ovaries. Loss of Sox9 in XY embryos, or Rspo1 in XX embryos, leads to mice developing",380,128,0.3368
dialogsum,"#Person1#: Shall we have some soup first? #Person2#: No, thank you. I don't like soup. I'd rather have some fruit juice to start with. #Person1#: Ok, and what about the main course? Which would you rather have, fish or meat? #Person2#: Meat, I think. #Person1#: Don't you like fish then? #Person2#: I do, but I want meat. #Person1#: Shall we have some white wine then? #Person2#: Yes, but I prefer red wine with meat. #Person1#: What would you like for dessert? #Person2#: I just want to have a coffee, I think. #Person1#: Fine, and after dinner, shall we go to a disco? #Person2#: No, thanks. I'd like to go straight home. I'm very tired.",#Person2# rejects all of #Person1#'s suggestions on the meal and disco.,114,11,0.0965
pubmed-summarization,"left lateral oblique view of radiograph showing multilocular radiolucencies a computerized tomography ( ct ) scan demonstrated buccal and lingual cortical plate expansion and a soap bubble appearance [ ] . computed tomography scan showing buccal and lingual cortical plate expansion surgical excision of the lesion the hematoxylin and eosin stained tissue section showed hypo and hyper - cellular areas with proliferation of plump fibroblasts arranged in interlacing fascicles and dense collagen . focal areas of the section also revealed dense collagenous stroma with foci of hyalinization [ ] . photomicrograph showing hypo - cellular and hyper - cellular areas with spindle cells arranged in interlacing fascicles ( h&e stain , 10 ) photomicrograph showing hyper - cellular area with proliferating plump fibroblasts , ( h&e stain , 20 ) photomicrograph showing proliferating plump , spindle - shaped fibroblasts in a collagenous stroma ( h&e stain , 40 ) photomicrograph showing a focus of dense collagenous stroma with focal areas of hyalinization ( h&e stain , 10 ) a final diagnosis of df was arrived at after histopathological examination . df is a rare , locally aggressive myofibroblastic benign tumor of connective tissue origin . as an intra - osseous lesion df was first described by jaffe in 1958 and named as df . in 1965 , the first report about a df of the jaw was presented by griffith und irby . the histologic criteria for df as defined by the world health organization is a rare benign bone tumor composed of spindle - shaped cells with minimal cytological atypia and abundant collagen production . desmoid tumor also called as aggressive fibromatosis , was described before df . about 69% of desmoid tumors are abdominal ; the extra - abdominal variety occurring in the bone is the df . although df can affect any age group , most patients are affected in the first three decades of life . in our case , the average age of patients at the time of the final diagnosis is 15.1 years . metaphysis of long bones especially tibia , scapula and femur are the most frequent sites of involvement . mandible is the fourth most common site of involvement and sex predilection remains unclear . in the mandible , the lesions tend","desmoplastic fibroma ( df ) is a benign intra - osseous neoplasm , that is , recognized as the intra - osseous counterpart of soft tissue fibromatosis in both gnathic and extra - gnathic sites . it has a propensity for locally aggressive behavior and local recurrence . an occurrence of intra - osseous lesion other than that of odontogenic origin is rare in the jaws . in this case report , we define the clinico - pathological and radiographic features of df of the mandible in a 35-year - old female , who presented to the outpatient department with a 3-year history of a slowly expanding painless mass in the left mandibular posterior region . thus , we present a classic case of df exhibiting characteristic features",380,128,0.3368
scientific_lay_summarisation-elife-norm,"literature with the creation of CircaDB, a database of tissue-specific mRNA rhythms in mice (Hughes et al. , 2009; Zhang et al. , 2014). Taken together, these projects demonstrate that publicly available functional genomics data have enduring value as a resource for the research community. Nevertheless, previous gene expression atlases have largely ignored skeletal muscle. CircaDB includes gene expression data from the heart and whole calf muscle, but it does not distinguish between their constituent tissues. Similarly, SymAtlas profiles nearly 100 different tissues, but there is only a single representative sample for either cardiac or skeletal muscle. The microRNA Atlas includes over 250 human, mouse, and rat tissues; however, skeletal muscle is entirely absent from these data. More recent human gene expression atlases have similar biases (Evangelista et al. , 2015; Lindholm et al. , 2014; Vissing and Schjerling, 2014). Many studies have compared muscle-specific gene expression in different tissues (Porter et al. , 2001), fiber-types (Chemello et al. , 2011), or disease states (Chen et al. , 2000; Colantuoni et al. , 2001), but on the whole, there is no systematic analysis of transcriptional diversity in skeletal muscle. This gap in the literature is problematic since skeletal muscle comprises a remarkably diverse group of tissues (Tirrell et al. , 2012). Skeletal muscle groups originate from different regions of the developing embryo, and they have characteristic morphological specializations (Merrell and Kardon, 2013; Murphy and Kardon, 2011; Noden and Francis-West, 2006). Their physiological functions are similarly diversified. For example, extraocular muscles govern precise eye movements, the diaphragm drives rhythmic breathing, and limb skeletal muscles are involved in either fast bursts of motion or sustained contractions underlying posture. These intrinsic differences contribute to differential susceptibility of muscle groups to injury and disease. For example, there are six major classes of muscular dystrophy, and each one afflicts a characteristic pattern of skeletal and cardiac muscle tissues (Ciciliot et al. , 2013; Emery, 2002). Since the causative mutations underlying congenital muscular dystrophies are germline and present in all cells, this observation indicates that there are properties intrinsic to different muscle tissues that regulate their sensitivity or resistance to different pathological mechanisms. Acquired diseases show similar specificity in which muscle tissues they affect and which they spare. Patients with chronic obstructive pulmonary disorder (COPD) typically","About 40% of our weight is formed of skeletal muscles, the hundreds of muscles in our bodies that can be voluntarily controlled by our nervous system. At the moment, the research community largely sees all these muscles as a single group whose tissues are virtually interchangeable. Yet, skeletal muscles have highly diverse origins, shapes and roles. For example, our diaphragm is a long muscle that contracts slowly and rhythmically so we can draw breaths, while tiny muscles in our eyes generate the short and precise movements of our eyeballs. Different skeletal muscles also respond in distinct ways to injuries, drugs and diseases. This suggests that these muscles may be diverse at the genetic level. While all the cells in our body have the same genetic information, exactly which",380,128,0.3368
scientific_lay_summarisation-elife-norm,"When choosing actions, we can act decisively, vacillate, or suffer momentary indecision. Studying how individual decisions unfold requires moment-by-moment readouts of brain state. Here we provide such a view from dorsal premotor and primary motor cortex. Two monkeys performed a novel decision task while we recorded from many neurons simultaneously. We found that a decoder trained using ‘forced choices’ (one target viable) was highly reliable when applied to ‘free choices’. However, during free choices internal events formed three categories. Typically, neural activity was consistent with rapid, unwavering choices. Sometimes, though, we observed presumed ‘changes of mind’: the neural state initially reflected one choice before changing to reflect the final choice. Finally, we observed momentary ‘indecision’: delay forming any clear motor plan. Further, moments of neural indecision accompanied moments of behavioral indecision. Together, these results reveal the rich and diverse set of internal events long suspected to occur during free choice. The study of decision making in the brain is often limited by the need to average over repeated trials. Yet if the decision process differs on different trials, we may miss the very events that would be most enlightening. To detect such events requires a moment-by-moment (Briggman et al. , 2005; Yu et al. , 2009) readout of brain states on single trials (Churchland et al. , 2007; Afshar et al. , 2011). To achieve such a moment-by-moment view in the monkey, we applied state-space analysis methods (Shenoy et al. , 2013) to simultaneous recordings from dorsal premotor cortex (PMd) and primary motor cortex (M1) —brain areas centrally involved in preparing and producing the movements that effect decisions. When a monkey is instructed about an upcoming movement but not yet allowed to make it, neurons in these areas show changes in firing rate that reflect the properties of the upcoming reach, including direction (Evarts, 1966; Tanji and Evarts, 1976; Weinrich and Wise, 1982; Godschalk et al. , 1985), distance (Riehle and Requin, 1989; Messier and Kalaska, 2000), speed (Churchland et al. , 2006a), and curvature (Hocherman and Wise, 1991; Pearce and Moran, 2012). PMd and M1 may (Pastor-Bernier et al. , 2012; Thura and Cisek, 2014) or may not be involved in actually making decisions, but these areas are known to reflect the momentary decision state (Thura et al. ,","Some decisions are easy to make. We know almost immediately what outcome we want to achieve and what actions are required to do so. But other decisions involve more deliberation: there may be more factors to consider or more at stake, or the best course of action may simply not be immediately apparent. Under such circumstances, we may hesitate, waver or even change our minds completely. To date, the majority of experiments that have explored the neural basis of decision making have been unable to detect the test subjects changing their mind as they made their decision. Instead, those experiments have measured the average brain response over multiple decisions because they lacked the power to detect what happened on each individual decision. Kaufman et al. have now addressed",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Disorders of consciousness are a heterogeneous mixture of different diseases or injuries. Although some indicators and models have been proposed for prognostication, any single method when used alone carries a high risk of false prediction. This study aimed to develop a multidomain prognostic model that combines resting state functional MRI with three clinical characteristics to predict one year-outcomes at the single-subject level. The model discriminated between patients who would later recover consciousness and those who would not with an accuracy of around 88% on three datasets from two medical centers. It was also able to identify the prognostic importance of different predictors, including brain functions and clinical characteristics. To our knowledge, this is the first reported implementation of a multidomain prognostic model that is based on resting state functional MRI and clinical characteristics in chronic disorders of consciousness, which we suggest is accurate, robust, and interpretable. Severe brain injury can lead to disorders of consciousness (DOC). Some patients recover consciousness after an acute brain insult, whereas others tragically fall into chronic DOC. The latter cannot communicate functionally or behave purposefully. Most patients remain bedridden, and require laborious care. The medical community is often confronted with an inability to meet the expectations of the chronic DOC patients' families. The social, economic, and ethical consequences are also tremendous (Bernat, 2006). In parallel, although more validations are required, recent pilot studies have proposed new therapeutic interventions, which challenge the existing practice of early treatment discontinuation for a chronic DOC patient (Schiff et al. , 2007; Corazzol et al. , 2017; Yu et al. , 2017). However, before using these novel therapeutic interventions, clinicians first need to determine whether the patient is a suitable candidate. The availability of an accurate and robust prognostication is therefore a fundamental concern in the clinical management of chronic DOC patients, as medical treatment, rehabilitation therapy and even ethical decisions depend on this information. To date, the prognostication for a DOC patient is based on physician observation of the patient' s behavior over period that is sufficient to allow determination of whether there is any evidence of awareness. On the one hand, a patient' s motor impairment, sensory deficit, cognitive damage, fluctuation of vigilance and medical complications could give rise to misjudgments; on the other hand, for the assessor,","Severe brain injury can lead to disorders of consciousness (DOC), such as a coma. Some patients regain consciousness after injury, while others do not. Those who do not recover are unable to communicate or move in purposeful ways, and need long-term care. It can be difficult for physicians to predict which patients will mend. This is mainly based on their observations of the patient’s behavior over time. But such perceptions are subjective and vulnerable to errors. More accurate and objective methods are needed. Several studies suggest that the cause of the injury, the age of the person at the time of injury, and how long the person has had a DOC may predict recovery. Recent studies have shown that using a brain-imaging tool called resting state functional magnetic",380,128,0.3368
dialogsum,"#Person1#: What are your plans for today Mark? Nick and I are going shopping. Do you want to come too? #Person2#: Well as a matter of fact. I'm eating Steve. He's writing an article and he's asked me to take some photos for it. #Person1#: An article? About What? #Person2#: Oh, just People. Anyway, I'm seeing Steve at the zoo at 10. #Person1#: Oh. well, let's meet for lunch shall we? How about that sandwich bar we went to on Friday? I'll see you there about 12:30. #Person2#: Sounds good. See you.","#Person1# invites Mark to shop, but Mark has to help Steve take photos. They'll meet for lunch then.",92,18,0.1957
scientific_lay_summarisation-elife-norm,"retained in cilia once delivered, but not how they are delivered in the first place. Two basic routes of ciliary membrane delivery have been described: first, receptors can originate from an intracellular source, through fusion of post-Golgi transport vesicles with the ciliary membrane in or near the transition zone. A number of membrane proteins are targeted to cilia by this route, and molecular machineries supporting it have been identified (Deretic and Papermaster, 1991; Geng et al. , 2006; Mazelova et al. , 2009). Second, receptors can originate from the extra-ciliary plasma membrane. This route, first described in a seminal study of flagellar agglutinins in Chalmydomonas (Hunnicutt et al. , 1990), contributes to ciliary targeting of the atypical seven-transmembrane protein Smoothened (Smo; Milenkovic et al. , 2009) in mammalian cells. Is the lateral delivery route relevant to ciliary localization of conventional GPCRs? Molecular mechanisms that underlie specific ciliary delivery pathways also remain incompletely understood. A number of proteins are already known to play a role, including the BBSome (Nachury et al. , 2007; Berbari et al. , 2008b; Jin et al. , 2010), Tulp3 (Mukhopadhyay et al. , 2010,2013), Arf4 (Deretic et al. , 2005), ASAP1 (Wang et al. , 2012), and intraflagellar transport (IFT) -B and IFT-A (Mukhopadhyay et al. , 2010; Keady et al. , 2011,2012; Crouse et al. , 2014; Kuzhandaivel et al. , 2014). Are there additional machineries not yet identified that function in targeting specific GPCRs to cilia? We addressed these questions through study of the D1-type dopamine receptor (D1R), a conventional GPCR that robustly localizes to cilia in diverse cell types (Marley and von Zastrow, 2010; Domire et al. , 2011). Here, we show that D1Rs are delivered to the cilium from the extra-ciliary plasma membrane. Further, we show that the D1R cytoplasmic tail is both necessary and sufficient to direct receptor targeting to the ciliary membrane, and this requires a distinct set of cellular proteins including the anterograde IFT-B complex and ciliary kinesin, KIF17. Moreover, we identify an essential role of the small GTP-binding protein, Rab23, in the ciliary targeting mechanism. Rab23 is not only necessary for D1R access to cilia, it is also sufficient to drive strong ciliary localization of a non-ciliary GPCR. D1Rs thus reveal a discrete route and mechanism of ciliary","Slender structures called primary cilia protrude from the outer membrane of nearly every human cell. Each cell generally has one cilium, which helps the cell to sense its environment and respond to the signaling molecules sent to the cell to influence its behavior. Proteins called receptors, which are embedded in the surface of the cilia, bind to these molecules and help to transmit information about these signals into the cell. The receptor proteins are not made in the cilia. So far, two broad ways of transporting the receptors to the cilia have been established: some receptors are carried through the interior of the cell inside small membrane-enclosed compartments, and some are pulled from another part of the cell' s membrane. However, the exact steps and molecules involved in",380,128,0.3368
scientific_lay_summarisation-elife-norm,"pores in Cry1Aa (Gómez et al. , 2014) and heptameric pores in the anthrax protective antigen (Jiang et al. , 2015) to 30–50-meric pores in cholesterol-dependent cytolysins (CDCs) (Dal Peraro and van der Goot, 2016; Hotze and Tweten, 2012). PFTs can be further divided into two groups (Iacovache et al. , 2010). PFTs of the first group perforate membranes by forming stable pores resulting in an uncontrolled influx and efflux of ions and other biomolecules. This destroys ion gradients and electrochemical gradients at the membrane. The toxins of the second group also perforate the membrane, but use the transmembrane channel to specifically translocate toxic enzymes into the host. Binary toxins, also called AB toxins (Odumosu et al. , 2010) and also recently characterized ABC toxins (Meusch et al. , 2014) belong to the latter group. A prominent AB toxin is the anthrax toxin (Collier and Young, 2003), where component B, the protective antigen, forms a translocation pore through which lethal factor or edema factor, different A components, are translocated. The members of α-PFTs show a high structural diversity. They include proteins mainly consisting of α-helical structures (bax, colicins) or β-strand motifs with a single helix responsible for membrane insertion (actinoporins) (Dal Peraro and van der Goot, 2016; Parker and Feil, 2005). Their transmembrane regions are all composed of hydrophobic or amphipathic regions buried within the core structure of the soluble monomer. Therefore, a conformational change that exposes the hydrophobic or amphipathic region is required for successful membrane insertion. The structures of cytolysin A (ClyA) (Wallace et al. , 2000; Mueller et al. , 2009) and fragaceatoxin C (FraC) (Wallace et al. , 2000; Mueller et al. , 2009) of both the monomer and oligomer gave the first structural insight into the mechanism of action of this class of PFTs. In contrast to α-PFTs, the structures of many β-PFTs, such as members of the cholesterol-dependent cytolysins (Hotze and Tweten, 2012), hemolysin and aerolysin family (Dal Peraro and van der Goot, 2016), have been determined in their monomeric and pore conformation. The transmembrane β-strands in the soluble monomers of β-PFTs are typically amphipathic with small hydrophobic patches that upon oligomerization form a hydrophobic membrane-spanning β-barrel. α-Xenorhabdolysin is a PFT that has been first isolated from the bacterium Xenorhabdus nematophila (Ribeiro et al.","Some bacteria make toxins that punch large holes into the membranes of host cells, destroying them like a puncture destroys a football. These “pore-forming toxins” allow many bacterial species to infect a variety of organisms, from insects to humans. Some sophisticated pore-forming toxins, such as the anthrax toxin, do not only form a pore but also use it to flood lethal toxins into the cell to kill it. One bacterium called Xenorhabdus nematophila punctures the membranes of insect cells, using the same type of pore-forming toxins that other bacteria use to infect humans. Previous research has shown that two proteins – components A and B – form these pore-forming toxins. Given this two-protein formation, some scientists predicted these pore-forming toxins might act like those of the anthrax bacterium:",380,128,0.3368
dialogsum,"#Person1#: Do you think chinese families have changed much in the last 50 years? #Person2#: I think families everywhere have changed a lot in the last 5 decades. #Person1#: What do you think is the biggest change? #Person2#: Well, in the past, three or four generations would live together under the same roof. Nowadays, living in the same city as one's relatives is becoming rare. #Person1#: That's true. You know, some husbands and wives don't even live in the same city any more. #Person2#: Would you consider having your parents live with you when they get older? #Person1#: I guess I'm a bit old-fashioned. I'd rather have my parents live with me than live in a retirement room. #Person2#: That's very respectable, but I could never live with my parents. I usually only see them at our christmas celebration, and that's enough! #Person1#: How about your other siblings? Do they spend a lot of time with your parents? #Person2#: Two of my sisters still live at home, even though they have already graduated from university and have good jobs. They enjoy spending their free time with my parents. I guess in that respect, I'm the black sheep of the family. #Person1#: I see. Do your parents ever ask you to come home to visit them more often? #Person2#: They're always asking me to come home, but I think our relationship is better if we keep a distance from each other. Whenever we see each other, all we do is fight.",#Person2# thinks the biggest change of Chinese families is that family members rarely live together now. #Person1# would like to live with #Person1#'s parents while #Person2# prefers keeping a distance from parents and seeing them occasionally.,250,36,0.144
dialogsum,"#Person1#: We are thinking about putting on a show this spring. #Person2#: And do you think you'll be able to make some money? #Person1#: Oh no, we just want to do it for the fun of it, you know, there are a lot of us who like to perform on a stage. #Person2#: What kind of show? #Person1#: A musical play. #Person2#: Have you decided who is going to do it? #Person1#: We have 3 people in mind, and of course we've been thinking about you. #Person2#: Me? Why me? #Person1#: You sing, don't you? Everyone says you have a wonderful voice. #Person2#: Well, I have sung a little. But I've never really appeared on a stage. #Person1#: I thought you sang in church every Sunday. #Person2#: That's different, there are so many others singing too. #Person1#: Then here's your chance to find out how good you are, and not just to sing, but to act and dance, too. #Person2#: Oh, it might be exciting.",#Person1# is thinking about putting on a musical play this spring for fun and asks #Person2# to join them. #Person2# thinks it might be exciting.,165,25,0.1515
pubmed-summarization,"on the cultivar bither with 6 cuttings types as described below : type 1 : cuttings of one - year - old shoot , length ( 30 cm ) , and diameter ( < 1.5 cm ) ; type 2 : cuttings of one - year - old shoot , length ( 40 cm ) , and diameter ( < 1.5 cm ) ; type 3 : cuttings of one - year - old shoot , length ( 60 cm ) , and diameter ( < 1.5 cm ) ; type 4 : cuttings of 2-year - old shoot , length ( 30 cm ) , and diameter ( < 1.5 cm ) ; type 5 : cuttings of 2-year - old shoot , length ( 40 cm ) , and diameter ( < 1.5 cm ) ; type 6 : cuttings of 2-year - old shoots , length ( 60 cm ) , and diameter ( > 2 cm ) . type 1 : cuttings of one - year - old shoot , length ( 30 cm ) , and diameter ( < 1.5 cm ) ; type 2 : cuttings of one - year - old shoot , length ( 40 cm ) , and diameter ( < 1.5 cm ) ; type 3 : cuttings of one - year - old shoot , length ( 60 cm ) , and diameter ( < 1.5 cm ) ; type 4 : cuttings of 2-year - old shoot , length ( 30 cm ) , and diameter ( < 1.5 cm ) ; type 5 : cuttings of 2-year - old shoot , length ( 40 cm ) , and diameter ( < 1.5 cm ) ; type 6 : cuttings of 2-year - old shoots , length ( 60 cm ) , and diameter ( > 2 cm ) . ten cuttings per replicate and per cutting types were used , with a total of 180 cuttings . during this research , cuttings were planted directly in rooting units ( 2.5 0.65 m ) under field conditions . cuttings were planted in an inclined position ( angle of 45 ) on sandy soils , where 3/4 of cutting is sinking into the soil at the professional agricultural training","this research was carried out in southeast of tunisia in 2009 and 2010 , in order to study the propagation of six ( ficus carica l. ) cultivars by using hardwood cuttings under the field conditions . the effect of the cultivars and the type of buds , shoots age , shoots length , and shoots diameter were recorded . ten cuttings per cultivar and/or cutting types with three replications were planted in rooting unit . percentage of root emergence and six morphological parameters of young plants were measured . results showed that the responses of cuttings as nursery plants presented a high variability among the five cultivars . the most widely varied characters were % root emergence ( re ) and cumulative growth of young plant (",380,128,0.3368
pubmed-summarization,"ats1-s2b . the patient underwent posterior spine surgery where decompression was done with laminotomy of s1 bilaterally and then pedicular screw fixation was done bilaterally at l5 , s1 , and s2 ( .4 ) . s1 and post - operative radiographs - anteroposterior ( a ) and lateral ( b ) view . the bladder symptoms disappeared after 3 weeks and the power of fhl / fdl improved from 4/5 to 5/5 . the patient underwent posterior spine surgery where decompression was done with laminotomy of s1 bilaterally and then pedicular screw fixation was done bilaterally at l5 , s1 , and s2 ( .4 ) . s1 and post - operative radiographs - anteroposterior ( a ) and lateral ( b ) view . the bladder symptoms disappeared after 3 weeks and the power of fhl / fdl improved from 4/5 to 5/5 . the patient underwent posterior spine surgery where decompression was done with laminotomy of s1 bilaterally and then pedicular screw fixation was done bilaterally at l5 , s1 , and s2 ( .4 ) . s1 and post - operative radiographs - anteroposterior ( a ) and lateral ( b ) view . the bladder symptoms disappeared after 3 weeks and the power of fhl / fdl improved from 4/5 to 5/5 . the deformity occurs at l4 - 5 6 times more often than at other lumbar levels and four times more often above a sacralized l5 . the lumbosacral junction and middle lumbar spine are most often involved , but the lesion is also found in cervical or rarely the thoracic vertebra . to the best of our knowledge , ds of sacral vertebrae has not been reported in the available english literature till now . the prevalence of complete lumbarization is 1.8% and to get a spondylolisthesis is even rarer . there have been many publications in the literature mentioning incidence of spondylolisthesis with sacralization but hardly any on spondylolisthesis with lumbarization . further case series or longitudinal studies of such cases may help understand better the pathomechanics related to spondylolisthesis at this level . ds of s1-s2 is a very rare entity and further case reports will help us to explore the biomechanics at this level .",introduction : degenerative spondylolisthesis ( ds ) is usually seen at l4-l5 level and less frequently at l5-s1 level . this is a rare case report of spondylolisthesis of s1 over s2 with lumbarization of s1 . lumbarization of s1 is seen in just 1 - 2% of the population and to have spondylolisthesis in this segment is even rarer . the purpose is to report a rare case of ds at s1-s2 level.case report : this is a single case report of a 66-year - old gentleman who presented with complains of lower backache for 2 years and acute retention of urine to the emergency department . detailed clinical and radiological evaluation of the spine was done which revealed lumbarization of s1 with spondylolisthesis at s1-s2 and,376,128,0.3404
pubmed-summarization,"as the number of patients with unruptured cerebral aneurysms has increased , more attention has been given to the primary prevention of the aneurysm rupture4 ) . endovascular intervention , one of the major treatment modalities , has begun to catch up with and surpass the surgery in the number of cases treated , based on the favorable outcomes and reduced morbidity / mortality21220 ) . in addition , recently , patients have shown a preference for endovascular intervention over surgery because of the cosmetic and psychological aspects . scalpel surgeons are being asked to enhance their competitiveness and develop novel surgical devices and skills , such as minimally invasive keyhole surgery81519 ) , neuroendoscopic systems7 ) , indocyanine green ( icg ) fluorescence angiography518 ) , intraoperative neurophysiological monitoring16 ) , and intraoperative cerebral angiography1 ) . microscopic icg fluorescence angiography is very helpful for detecting and readjusting unexpected arterial occlusion and incomplete clipping of cerebral aneurysms . however , the usefulness of icg fluorescence angiography is limited when the microscopic view is poorly visualized or when icg can not absorb sufficient light to emit fluorescence . therefore , these limitations can be overcome using the endoscopic systems that provide sufficient light illumination and excellent visualization of the operative fields . thus , icg fluorescence angiography would be very useful to the shortcomings of microscopic icg fluorescence . to date , there are 3 clinical reports regarding endoscopic icg fluorescence angiography from japan and europe51114 ) . we independently developed an endoscopic camera system for icg fluorescence angiography that can show the real - time simultaneous visible and fluorescent imaging . using this system , all procedures were approved by the local institutional animal care and use committee and were conducted according to international guidelines . a male crossbred swine ( landraceyorkshireduroc ) , aged 3 months and with a weight of 38.5 kg , was used in this study . anesthesia was induced intramuscularly with 5 mg / kg of zoletil and 2 mg / kg of xylazine . the swine was intubated and intravenous 0.9% normal saline was administered via the ear vein at a rate of 5 ml / kg / hr . anesthesia was maintained with 2% to 4% isoflurane at a rate of 23","objectivemicroscopic indocyanine green ( icg ) angiography is useful for identifying the completeness of aneurysm clipping and the preservation of parent arteries and small perforators . neuroendoscopy is helpful for visualizing structures beyond the straight line of the microscopic view . we evaluated our prototype of endoscopic icg fluorescence angiography in swine , which we developed in order to combine the merits of microscopic icg angiography and endoscopy.methodsour endoscopic icg system consists of a camera , a light source , a display and software . this system can simultaneously display real - time visible and near infrared fluorescence imaging on the same monitor . a commercially available endoscope was used , which was 4 mm in diameter and had an angle of 30. a male crossbred swine was",380,128,0.3368
scientific_lay_summarisation-elife-norm,"and animal models (Ivaska et al. , 2007; Yamaguchi et al. , 2005; Eckes et al. , 2000; Rogel et al. , 2011; Menko et al. , 2014). Vimentin IFs also contribute to the mechanical properties of the cytoplasm, and stabilize and localize mitochondria (Nekrasova et al. , 2011; Buehler, 2013; Guo et al. , 2013; Eckes et al. , 1998). Importantly, genetic lesions that dysregulate the IF cytoskeleton cause a wide range of human diseases, including skin and nail disorders (keratins), cardiomyopathies (desmin), lipodystrophy, muscular dystrophy and progeria (lamins), giant axonal neuropathy and Charcot-Marie-Tooth disease (neurofilaments), and cataracts (vimentin) (Omary, 2009; Omary et al. , 2004). In addition, the ectopic expression of wild type (WT) vimentin is a hallmark of the epithelial-to-mesenchymal transition, and is widely observed in human metastatic cancers (Satelli and Li, 2011; Nieto, 2011; De Craene and Berx, 2013). IFs are likely functionally important in this context, because vimentin expression levels correlate with the invasive phenotypes of breast, prostate, and other epithelial cancers (Satelli and Li, 2011; Wei et al. , 2008; Zhu et al. , 2011; Vuoriluoto et al. , 2011). Finally, the IF cytoskeleton is also intimately involved in host-microbe interactions (Geisler and Leube, 2016; Mak and Brüggemann, 2016). For example, changes in vimentin IFs are implicated in the adhesion, invasion, and replication of a wide range of bacteria, including such important pathogens as Chlamydia trachomatis (Kumar and Valdivia, 2008; Jorgensen et al. , 2011; Snavely et al. , 2014; Bednar et al. , 2011), Mycobacterium tuberculosis (Garg et al. , 2006; Mahesh et al. , 2016), Streptococcus pyogenes (Bryant et al. , 2006; Icenogle et al. , 2012; Lin et al. , 2015) and Salmonella enterica (Murli et al. , 2001; Guignot and Servin, 2008). Despite this broad pathophysiological significance, the regulation of IF cytoskeleton morphology, dynamics, and signaling functions remains incompletely understood. Several recent lines of evidence indicate that post-translational modifications (PTMs) are an important mode of IF regulation, and indeed all IFs are subject to extensive PTMs, including phosphorylation, ubiquitination, sumoylation, acetylation, farnesylation, and glycosylation (Snider and Omary, 2014). However, in most cases, the functional impact of these PTMs on IF structure and function is poorly characterized. To better understand the dynamic regulation of the IF cytoskeleton, we focused on O-linked","Like the body' s skeleton, the cytoskeleton gives shape and structure to the inside of a cell. Yet, unlike a skeleton, the cytoskeleton is ever changing. The cytoskeleton consists of many fibers each made from chains of protein molecules. One of these proteins is called vimentin and it forms intermediate filaments in the cytoskeleton. Many different types of cells contain vimentin and a lot of it is found in cancer cells that have spread beyond their original location to other sites in the body. Cells use chemical modifications to regulate cytoskeleton proteins. For example, through a process called glycosylation, cells can reversibly attach a sugar modification called O-GlcNAc to vimentin. O-GlcNAc can be attached to several different parts of vimentin and each location may have a different effect.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"four neuropil substructures, from anterior to posterior: the ellipsoid body (EB), the fan-shaped body (FB), the noduli (NO) and the protocerebral bridge (PB) (1A). In each CX substructure, neuronal processes elaborate their trajectories in precisely defined regions. They form multiple layers, or laminae, from dorsal-to-ventral within the EB, FB and NO, and other neuronal processes form 16–18 columns, medial-to-lateral, within the EB, PB and FB. More than 50 different types of ‘small-field’ and ‘large-field’ neurons innervate these CX substructures (Hanesch et al. , 1989; Young and Armstrong, 2010b). Every small-field neuron innervates one or two columns and contacts one or multiple laminae in specific CX substructures. On the other hand, each large-field neuron innervates an entire single lamina across all columns in certain CX substructures. Therefore, small- and large-field neurons collaboratively form highly organized wiring patterns and are interconnected in all four CX neuropils (Lin et al. , 2013; Wolff et al. , 2015; Yang et al. , 2013), allowing for information flow in precisely defined patterns within the CX. 10. 7554/eLife. 25328. 003Figure 1. Large-field ring neuron axons sequentially innervate the ellipsoid body. (A) Schematics showing frontal and dorsal views of the central complex (CX) in an adult Drosophila brain. The CX is composed of four substructures: from anterior (‘A’) to posterior (‘P’) the ellipsoid body (EB), the noduli (NO), the fan-shaped body (FB) and the protocerebral bridge (PB). (B–C) R15F02-GAL4 (expressed in R1/R3/R4d neurons) and R32H08-lexA (in R2/R4m neurons) driving GFP and mCherry reporters, respectively, label multiple ring neuron types in an adult fly brain. From laterally located cell bodies (arrowheads), ring neurons axons follow similar trajectories to innervate the bulb (arrows) and the ellipsoid body (dashed square) (B). Inside the EB, multiple concentric and adjacent rings are formed by dense axon projections from different R neurons (C). A smaller R1 ring is formed at more posterior EB regions and is covered by the R3 ring. (D) R32H08-lexA-driving mCherry and R15F02-GAL4-driving CD8-GFP allow for visualization of how R2/R4m and R3/R4d innervation takes place in the EB during pupal development. Strong CadN immunolabeling shows EB morphological changes (dashed lines) between 16 hr and 48 hr APF (hours after puparium formation). R2/R4m axons (red arrows) extend into the developing EB earlier than R3/R4d axons (green arrows and arrowheads), as can","The human brain contains around one hundred billion nerve cells, or neurons, which are interconnected and organized into distinct layers within different brain regions. Electrical impulses pass along a cable-like part of each neuron, known as the axon, to reach other neurons in different layers of various brain structures. The brain of a fruit fly contains fewer neurons – about 100 thousand in total – but it still establishes precise connections among neurons in different brain layers. In both flies and humans, axons grow along set paths to reach their targets by following guidance cues. Many of these cues are conserved between insects and mammals, including proteins belonging to the semaphorin family. These proteins work together to steer growing axons towards their proper targets and repel them away",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Reef-building corals depend on intracellular dinoflagellate symbionts that provide nutrients. Besides sugars, the transfer of sterols is essential for corals and other sterol-auxotrophic cnidarians. Sterols are important cell components, and variants of the conserved Niemann-Pick Type C2 (NPC2) sterol transporter are vastly up-regulated in symbiotic cnidarians. Types and proportions of transferred sterols and the mechanism of their transfer, however, remain unknown. Using different pairings of symbiont strains with lines of Aiptasia anemones or Acropora corals, we observe both symbiont- and host-driven patterns of sterol transfer, revealing plasticity of sterol use and functional substitution. We propose that sterol transfer is mediated by the symbiosis-specific, non-canonical NPC2 proteins, which gradually accumulate in the symbiosome. Our data suggest that non-canonical NPCs are adapted to the symbiosome environment, including low pH, and play an important role in allowing corals to dominate nutrient-poor shallow tropical seas worldwide. Many plants and animals cultivate symbioses with microorganisms for nutrient exchange. Cnidarians, such as reef-building corals and anemones, establish an ecologically critical endosymbiosis with photosynthetic dinoflagellate algae (Douglas, 2010) (family Symbiodiniaceae) (LaJeunesse et al. , 2018). Their symbionts reside within endo/lysosomal-like organelles, termed symbiosomes, and transfer photosynthetic products to their hosts (Muscatine, 1990; Yellowlees et al. , 2008). In addition to sugars that mostly provide energy, recent studies hint at the importance of the transfer of various lipids including sterols (Crossland et al. , 1980; Battey and Patton, 1984; Revel et al. , 2016). Sterols are essential building blocks for the cell membrane and endomembrane systems, in the form of cholesterol and other sterol variants. Cnidarians are sterol auxotrophs (Baumgarten et al. , 2015; Gold et al. , 2016) that must acquire these essential compounds from diet and/or symbionts (Goad, 1981). In line with this, non-canonical variants of the conserved cholesterol transporter Niemann-Pick Type C2 (NPC2) are among the most up-regulated genes in symbiotic Exaiptasia pallida (commonly Aiptasia) and Anemonia viridis anemones (Dani et al. , 2014; Lehnert et al. , 2014; Kuo et al. , 2010; Ganot et al. , 2011; Wolfowicz et al. , 2016). Dinoflagellates synthesize various sterols, many of which are found in symbiotic cnidarians (Bohlin et al. , 1981; Withers et al. , 1982; Ciereszko, 1989); however, the specific combinations of transferred sterols, as well as the mechanism of this transfer remain unknown.","Coral reefs are the most biodiverse marine ecosystems on our planet. Their immense productivity is driven by friendly relationships, or symbioses, between microbes called algae and the corals. Related organisms, such as anemones, also rely on these close associations. The algae use energy from sunlight to make sugars, cholesterol and other molecules that they supply to their host. In exchange, the host’s cells provide homes for the algae inside specialist, acidic structures called symbiosomes. Corals and anemones particularly need cholesterol and other ‘sterol’ molecules from the algae, because they are unable to create these building blocks themselves. In mammals, a protein known as Niemann-Pick Type C2 (NPC2) transports cholesterol out of storage structures into the main body of the cell. Corals and anemones have many different, ‘atypical’ NPC2",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Adrb3 stimulate brown adipocyte activation and beige adipocyte recruitment similarly through the activation of Adrb (Ramseyer and Granneman, 2016). Norepinephrine signaling, via Adrb3, not only stimulates thermogenic action in mature brown adipocytes but also recruits and activates beige adipocytes within WAT (Grujic et al. , 1997). Further, norepinephrine signaling through Adrb3-cAMP activation upregulates thermogenic genes such as Ucp1 potentiating the beiging process (Cao et al. , 2001). However, cellular expression studies have indicated that Adrb3 expression is restricted to mature white and brown adipocytes and is not expressed within the stromal vascular fraction (SVF), the proposed site of both white and beige progenitors (Collins et al. , 1994; Berry et al. , 2016). In contrast to Adrb3, Adrb1 is expressed in the SVF, not in mature adipocytes, and is thought to mediate the proliferation and differentiation of classical brown adipocyte progenitors (Bronnikov et al. , 1992). Thermogenically, Adrb1 null mice are unable to defend their body temperature in response to the cold (Ueta et al. , 2012); whereas, transgenic overexpression of Adrb1 showed robust cold-induced beiging potential within WAT (Soloveva et al. , 1997). Overall, several studies suggest mechanistic differences between cold- and Adrb3-induced beige adipocyte formation (Vosselman et al. , 2012). But whether these two receptors mediate or recruit beige adipocytes similarly remains unknown. Here, we show that smooth muscle/mural cells (Acta2 and Myh11) do not fate-map into Adrb3-induced beige adipocytes rather most Adrb3-induced beige adipocytes emanate from pre-existing white adipocytes. White adipocyte beiging necessity tests demonstrate the requirement of white adipocytes to form a significant percentage of beige adipocytes. Moreover, we find that that cold-induced beiging requires Adrb1 activation but not Adrb3 signaling. These data suggest that several cellular sources exist for beige adipocyte formation, which could provide mechanistic insight and clinical utility into enhancing beige adipocyte formation, function and perdurance. To begin to explore possible differences between cold-induced and Adrb3-induced beiging, we evaluated the relative appearance of in vivo beige adipogenesis. C57BL/6J-inbred mice were randomized to room temperature (23°C), cold (6. 5°C) or CL316,243 (CL, 1 mg/Kg), a Adrb3 selective agonist, for 1,3, or 7 days. After 1 day of cold exposure, beige adipocyte appearance was minimal within the subcutaneous inguinal adipose depot (IGW), the predominant beiging WAT. Conversely, 1 day of CL treatment produced some Ucp1+","Excess accumulation of a type of fat called white fat is associated with obesity and metabolic problems. White fat cells store energy. White fat tissue also contains some beige fat cells, which burn fats and sugars to produce heat. Cold temperatures trigger the production and activity of beige fat cells, which allows the body to stay warm. People with obesity tend to have less beige fat and more white fat. This has led scientists to test whether treatments that increase the number of beige fat cells a person has could reduce fat mass and improve metabolism. To develop treatments that increase beige fat, scientists must first understand where it comes from and how cold and other factors stimulate its growth. Recent studies have shown that smooth muscle cells,",380,128,0.3368
dialogsum,"#Person1#: Hello? #Person2#: Hello, Bob? This is Nancy. I got the invitation yesterday. #Person1#: Oh, can you come? #Person2#: Yes, I think so, but Tony can't. He's got to go to his parents' and help them work on their house this weekend. #Person1#: Oh, that's too bad. #Person2#: Uh, Bob. I won't have any transportation that night. Think somebody could give me a ride? #Person1#: Oh, sure! There's a group of people coming who live near you. I'm sure one of them would be glad to. If that doesn't work out, I'll drive you. #Person2#: Great! Thanks, Bob. Uh, what will people be wearing? #Person1#: Oh, you needn't dress up. It's a fairly casual party. We'll be in the yard, you know. #Person2#: Good. I can wear my new pants and sweater. Uh, what can I bring? #Person1#: Well, a side dish would be good. There'll be plenty to drink. #Person2#: OK, see you then. #Person1#: Bye!",Nancy tells Bob that she needs transportation for the party. Bob will find transportation for her and tells her what to wear and what to bring.,157,26,0.1656
pubmed-summarization,"advised not to take it again and was reviewed the next day . the repeat ophthalmic examination on the second day showed improved vision ( 6/60 ) in both the eyes , reduction in conjuctival chemosis , and improved depth of anterior chamber , while it continued to be shallow peripherally . iop measurements were repeated using applanation tonometry and were found to be 20 and 18 mmhg , in the right and left eyes , respectively . on the third day , her vision improved to 6/12 in the right eye and 6/6 partial ( p ) in the left with iop 10 and 14 mmhg , respectively . subsequent examination on the fifth day showed improved visual acuity 6/6 p in both the eyes and iop was 14 and 12 mmhg and the anterior chamber appeared well formed . she was advised to taper the anti - glaucoma medication and was examined a month later when her visual acuity was 6/6 , with iop 14 mmhg in both the eyes and was then advised via evaluation by a glaucoma specialist . all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1975 , as revised in 2008 . written informed consent was obtained from the patient for which identifying information is included in this case report . there have been 115 case reports of ocular side effects , 86 cases of secondary angle - closure glaucoma , and 7 cases of permanent visual loss reported with tpm , suggesting an association between acute onset of aacg after tpm therapy . the present case report adds evidence to show symptoms of acute onset of blurred vision associated with ocular pain to be due to adverse event associated with tpm prescribed for migraine . the ciliary body edema , uveal effusion , and relaxation of zonules along with anterior rotation of the ciliary body resulting in forward shift of the iris - lens apparatus are reported to contribute to tpm - induced aacg . in addition , these latter effects are said to produce shallow anterior chamber , leading to an increase in iop and thus precipitating the acute glaucomatous attack secondary","introductionthis case report adds supportive evidence to the development of acute angle - closure glaucoma ( aacg ) , a rare but serious adverse effect following the use of topiramate ( tpm ) for a severe headache.case reporta 25-year - old female reported with severe headache , suspected to be migraine , and was started on tpm 25 mg / day on the first day . however , she presented at the emergency clinic of a hospital with sudden blurring of vision and colored halos 5 days after stopping the drug , i.e. , day 8 . she was subjected to ophthalmic examination and was diagnosed with aacg . the intraocular pressure ( iop ) was found to be elevated and she was hence started on acetazolamide 500",380,128,0.3368
dialogsum,"#Person1#: Don't worry about your train sickness. I have brought some tablets with me that prevent train sickness. Here, take this one now. I'm sure you'll be alright on the train. #Person2#: It's very kind of you. By the way where is the dining car? #Person1#: The dining car is next to the sleeping car. Shall we eat our meals in the dining car? #Person2#: The attendant will bring some food here. But since the dining car is next to this carriage, we may just as well eat there. #Person1#: That's alright. How beautiful the scenery is. Look at the vast stretches of green fields. #Person2#: But it looks lovely only at this time of the year. It's rather dull and lonely in winter. #Person1#: That's why I prefer to travel in the summer and autumn. #Person2#: Me, too. I love summer, though it is hot. #Person1#: The train's pulling in. Do we have time to get offen stretch our legs? #Person2#: You may go out if you want. The train will stop for 1/4 of an hour before it continues on its way. Whatever you do, don't miss it.",#Person1# has brought some tablets to protect #Person2# from train sickness. #Person2# suggests eating in the dining car because it is next to the carriage. They both like traveling in the summer and autumn.,190,34,0.1789
pubmed-summarization,"fondaparinux sodium is a new synthetic , sulfated pentasaccharide , selective coagulation factor xa inhibitor , a safe and effective antithrombotic agent , which is indicated for preventing thrombus formation in patients with acute coronary syndromes , including those with st - segment elevation myocardial infarction ( stemi ) , non - stemi ( nstemi ) , or unstable angina . it is a pure , unique chemical entity consisting of five saccharide units ( pentasaccharide ) obtained entirely by chemical synthesis . however , inhibition of factor xa results in effective and linear dose dependent inhibition of thrombin generation , whether triggered by intrinsic or extrinsic pathways . unlike conventional antithrombotics such as lmwhs ( enoxaparin ) , which act on multiple targets within a coagulation cascade thereby , increasing the propensity of causing more bleeding complications . thus fondaparinux has a favorable tolerability profile , particularly with regard to the risk of major bleeding . in the oasis-5 trial , fondaparinux has been shown to reduce major bleeding with similar short - term efficacy as enoxaparin and lowers death and stroke during long - term follow - up in patients with acute coronary syndromes undergoing percutaneous coronary intervention . similarly , it has been shown superior to enoxaparin in reducing death or ischemic events at 9 days maintaining the efficacy up to 6 months in patients with unstable angina or nstemi with major bleeding occurring in fewer fondaparinux than enoxaparin recipients . on comparison with a heparin - based therapy , fondaparinux reduce mortality , ischemic events and major bleeding across the full spectrum of acute coronary syndromes . thus , it is assumed and projected from the existing knowledge that fondaparinux being more selective in its action may prove safe and efficacious . there are few reports of heparin - induced thrombocytopenia ( hit ) related to fondaparinux in a patient previously exposed to unfractionated heparin ( ufh ) and delayed - onset hit caused during its prophylaxis . in contrast , it is used sometimes off label in the management of hit with thrombosis . major bleeding is known to exist with the use of fondaparinux in previously exposed heparin user but to best of our knowledge there exist no isolated case report presenting with fondaparinux","fondaparinux sodium is a synthetic , sulfated pentasaccharide , selective factor xa inhibitor , a safe and effective antithrombotic agent indicated for preventing thrombus formation in patients with acute coronary syndromes , including those with st - segment elevation myocardial infarction ( stemi ) , non - stemi ( nstemi ) , or unstable angina . major bleeding is rarely known to exist with the use of fondaparinux and to best of our knowledge there exist no isolated case report presenting with fondaparinux - induced major bleeding prescribed for recently diagnosed nstemi . the case report highlights , a need for clinicians to have a sound understanding of anticoagulant pharmacology , dosing , toxicity , individualized approach , and predicting the risk of bleeding before they are prescribed",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2010). These findings lead to hypothesize that glucagon is responsible for the features of diabetes (Unger and Cherrington, 2012). Although suppression of glucagon action is likely to attenuate the consequences of insulin deficiency, its primary role in the hyperglycemia is uncertain. Indeed, because STZ causes an incomplete β-cell ablation due to variations in administration protocols and in genetic background-dependent sensitivity (Deeds et al. , 2011; Cardinal et al. , 1998; Gurley, 2006), it is possible that the “diabetes resistance” phenotype of Gcgr-/- mice relies on the action of insulin from residual β-cells. Thus, to determine whether lack of glucagon signaling would also prevent hyperglycemia and diabetes in the context of a more severe insulin deficiency, we used a transgenic model of diphtheria toxin (DT) -mediated β-cell ablation, termed RIP-DTR, which leads to an almost complete β-cell elimination (Thorel et al. , 2010; Chera et al. , 2014). Also, because adult RIP-DTR mice spontaneously reconstitute new insulin-producing cells by α-cell transdifferentiation in this condition of severe insulin insufficiency, we explored whether the compensatory α-cell hyperplasia due to glucagon signaling blockade (Furuta et al. , 1997; Gelling et al. , 2003; Longuet et al. , 2013) influences the reprogramming of α-cells toward insulin production. Here we show that near-total β-cell loss triggers severe hyperglycemia and all the metabolic features of type 1 diabetes (cachexia, glucose intolerance, and death) in mice with constitutive or induced glucagon signaling deficiency. We report that the absence of hyperglycemia observed in glucagon-deficient mice after STZ treatment can be explained through the persistence of a residual β-cell mass, which ensures a low level of insulin action. Recent reports indicate that Gcgr-/- mice do not develop hyperglycemia after STZ-mediated β-cell loss. Here we aimed at determining the effect of the absence of glucagon action in the context of a more extreme insulin deficiency. For this purpose, we crossed Gcgr-/- mutant animals (Gelling et al. , 2003) with RIP-DTR mice, in which diphtheria toxin (DT) injection triggers the near-total (>99%) β-cell loss (Thorel et al. , 2010). RIP-DTR; Gcgr-/- mice, like Gcgr-/- mice, displayed lower basal glucose levels than controls (RIP-DTR; Gcgr+/+ and RIP-DTR; Gcgr+/-; not shown) (Gelling et al. , 2003). Upon DT-induced β-cell ablation, both control and knockout animals developed severe hyperglycemia, with a slower kinetics in RIP-DTR;","After meals, digested food causes sugar to accumulate in the blood. This triggers the release of the hormone insulin from beta cells in the pancreas, which allows liver cells, muscle cells and fat cells to use and store the sugar for energy. Other cells in the pancreas, called alpha cells, release a hormone called glucagon that counteracts the effects of insulin by telling the liver to release sugar into the bloodstream. The balance between the activity of insulin and glucagon keeps blood sugar levels steady. Diabetes results from the body being unable to produce enough insulin or respond to the insulin that is produced, which results in sugar accumulating in the blood. Diabetes also increases the production of glucagon, which further increases blood sugar levels. Recently, some researchers",380,128,0.3368
scientific_lay_summarisation-elife-norm,"increased neuronal activity results in more myelination (Gibson et al. , 2014), and myelin remodeling in the CNS is required for motor skill acquisition (McKenzie et al. , 2014). Myelin also supplies ensheathed axons with lactate via the monocarboxylate transporter MCT1, possibly playing an important energetic support role in the CNS (Rinholm et al. , 2011; Lee et al. , 2012; Fünfschilling et al. , 2012; Morrison et al. , 2013). The emerging diversity of roles for myelin calls for a more complete understanding of its distribution among neuronal cell types and along individual axonal arbors, particularly in the gray matter of the CNS. Excitatory pyramidal neurons in cortex are known to be a main source of long-range myelinated axons connecting the two cortical hemispheres or targeting subcortical structures. Foundational EM-based studies of individual Golgi- or dye-filled neurons (Kisvárday et al. , 1986; Martin and Whitteridge, 1984; Peters and Proskauer, 1980; Tamás et al. , 1997) have revealed that the local axon collaterals of both excitatory and inhibitory neurons may also be myelinated. However, population surveys of the distribution of myelin on the axonal arbor of individual neocortical neurons have been difficult to undertake with traditional methods. Golgi labeling of neurons halts where the axon first enters a myelin sheath (Peters and Proskauer, 1980; DeFelipe et al. , 1986; Fairén et al. , 1977), and bulk labeling of myelin reveals a laminar patterned thicket (Nieuwenhuys, 2013), rather than individual neuronal arbors. Recent advances in large volume, high resolution neuroanatomy methods (Briggman and Bock, 2012; Micheva and Smith, 2007; Economo et al. , 2016) now permit cortical myelin to be directly visualized on the axonal arbors of multiple individual identified neurons for all axons within the imaged volume. Myelin tracing in large EM datasets has revealed that myelination of the axons of pyramidal neurons in cortex is distinct from the known myelination patterns in subcortical white matter, and also differs between cortical layers (Tomassy et al. , 2014). About 10–20% of neocortical neurons are inhibitory and some of these neurons may also have myelinated axons. For example, labeling of individual neocortical neurons during in vivo electrophysiological recording, followed by light-level reconstruction and electron microscopy (EM) of selected sub-arbors, has revealed that inhibitory neurons may be myelinated (DeFelipe et al. , 1986;","The brain is far away from the muscles that it controls. In humans, for example, the brain must be able to trigger the contraction of muscles that are more than a meter away. This task falls to specialized motor neurons that stretch from the brain to the spinal cord, and from the spinal cord to the muscles. Neurons transmit information (in the form of electrical nerve impulses) along their length through cable-like structures called axons. The axons of the motor neurons are so long that, if they were ‘naked’, it would take at least a second for nerve impulses to travel their entire length. Such a long delay between thoughts and actions would make rapid movement impossible. Nerve impulses are able to travel from the brain to the",380,128,0.3368
pubmed-summarization,"to determine patients who remain in the icu due to the organ failure , but do not meet the criteria of late mods . according to the authors , the clinical picture of these patients includes persistent , low intensity inflammation , protein catabolism , loss of lean body mass , impaired wound healing , suppression of the immune system , and recurrent infections . as a result of the prolonged immunosuppression and weight loss , these patients are more prone to nosocomial infections and rarely return to health . thus , the care of these patients is a major challenge for intensive care units nowadays . immunological and clinical disorders associated with sirs , cars and pics are presented in table 1 . main clinical and immunological features of sirs , cars and pics . according to sirs systemic inflammatory response syndrome ; cars the early immune response to the surgical trauma is associated with activation of innate immunity . as the first line of defense , immune cells with phagocytic properties and capability of antigen presentation migrate to the surgical wound . severe sirs and infection are accompanied by mobilization of massive amounts of immature neutrophils from the bone marrow into circulation . , after studying ability of the immature neutrophils to perform an effective immune response ( as measured by the ability to survive / perform apoptosis , expression of cd16 , toll - like receptor ( tlr ) 2 , tlr4 , cd14 , d-2 , hla - dp , and chemotaxis and phagocytosis ) in patients with sepsis and sirs , found that despite its immaturity , these cells are able to fulfill their crucial task from the point of view of innate immunity . exposure of immune cells present within infected surgical wounds expressing pattern recognition receptors ( prr ) to pathogen - associated molecular patterns ( pamps ) triggers a cascade of reactions , which results in the synthesis of proinflammatory compounds . it was observed that the systemic inflammatory response accompanying operating injuries can also occur without the presence of an infectious agent . this phenomenon can be explained by the discovery of endogenous mediators released during cell destruction damage - associated molecular patterns or danger - associated molecular patterns ( damps","surgical trauma affects both the innate and acquired immunity . the severity of immune disorders is proportional to the extent of surgical trauma and depends on a number of factors , including primarily the basic disease requiring surgical treatment ( e.g. cancer ) , often coexisting infections and impaired nutritional status . disorder of the immune response following surgical trauma may predispose to septic complications burdened with the highest mortality rate . extensive surgery in cancer patients is associated with simultaneous activation of pro- and anti - inflammatory processes defined as sirs ( systemic inflammatory immune response ) and cars ( compensatory anti - inflammatory immune response ) . however , it is generally believed that major surgical trauma is accompanied by sustained postoperative immunosuppression , which is",380,128,0.3368
pubmed-summarization,"and still plays , an important role in the evolution of these fish . thus , in the majority of recent molecular studies on species relationships within littoral tribes , especially when comparing mitochondrial and nuclear phylogenies , the explanation for the tree topologies involved the claim of introgression and hybridization between established lineages in addition to incomplete lineage sorting ( reviewed in ) . we hypothesize that this is not the case in tribes composed of deepwater species . lacking the geographic structure introduced by littoral habitat heterogeneity , deepwater species may still be spatially separated by distance , by segregation of breeding grounds , by variable hydrological conditions , or by large - scale fragmentation of the lake basin during major droughts . generally , however , the potential barriers to gene flow for deepwater species are less insurmountable than those met by stenotopic littoral cichlids . specifically in lake tanganyika , the evolution of stenotopy regarding depth , bottom type , or light intensity may have been prohibited by the seasonal upwelling of anoxic waters . we postulate that given the high potential for gene flow , diversification of lineages will either be curtailed ( as suggested by the relative species paucity ) or be attended by strong reproductive isolation right from the start . this would imply that introgression following cladogenesis occurred at much lower rates , if at all , in the deepwater species than in littoral cichlids . we test this hypothesis in the deepwater cichlid tribe bathybatini by comparing phylogenetic trees based on mitochondrial sequence data with trees obtained with nuclear multilocus aflp data , an approach which has previously revealed hybridization in littoral cichlids and other contexts . moreover , in several studies , phylogenetic inference on species relationships has benefited from the use of multilocus genetic data , and we expect that the aflp data collected in the present study will also contribute to the resolution of intergeneric relationships within the bathybatini , which are still debated due to conflicting or ambiguous molecular and morphological evidence . the tribe bathybatini ( sensu takahashi ) comprises 17 species in three genera : ( 1 ) the genus bathybates comprises six large ( 3040 cm ) , piscivorous species preying mainly on pelagic","hybridization among littoral cichlid species in lake tanganyika was inferred in several molecular phylogenetic studies . the phenomenon is generally attributed to the lake level - induced shoreline and habitat changes . these allow for allopatric divergence of geographically fragmented populations alternating with locally restricted secondary contact and introgression between incompletely isolated taxa . in contrast , the deepwater habitat is characterized by weak geographic structure and a high potential for gene flow , which may explain the lower species richness of deepwater than littoral lineages . for the same reason , divergent deepwater lineages should have evolved strong intrinsic reproductive isolation already in the incipient stages of diversification , and , consequently , hybridization among established lineages should have been less frequent than in littoral lineages .",380,128,0.3368
pubmed-summarization,"it is well known that the commutator \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$[a , b]=a^{-1}b^{-1}ab$$\end{document}[a , b]=a-1b-1ab of two elements \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$a$$\end{document}a and \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$b$$\end{document}b of a group \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$\mathbf g $ $ \end{document}g can be seen as a measure how far are \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$a$$\end{document}a and \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$b$$\end{document}b from commuting according to the group operation of \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$\mathbf g $ $ \end{document}g . thus , the normal subgroup \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$[g , g]$$\end{document}[g , g ] generated by all such commutators measures how far is the group \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$\mathbf g $ $ \end{document}g from an abelian group . namely , \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$[g , g]=0$$\end{document}[g , g]=0 if and only if \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$\mathbf g $ $ \end{document}g is abelian . the concept of commutators of normal subgroups has been generalized to a binary operation of the congruence lattice of arbitrary algebras in congruence modular varieties by smith , freese , mckenzie , hagemann , herrmann, ... one can find more details in . a malcev term of an algebra \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{mathrsfs } \usepackage{upgreek } \setlength{\oddsidemargin}{-69pt } \begin{document}$$\mathbf a $ $ \end{document}a is a ternary term operation \documentclass[12pt]{minimal }",in this note we prove that a malcev algebra is 2-supernilpotent ( = 0 ) if and only if it is polynomially equivalent to a special expanded group . this generalizes gumm s result that a malcev algebra is abelian if and only if it is polynomially equivalent to a module over a ring .,380,55,0.1447
pubmed-summarization,"described in table e-1 at neurology.org/nn . while the full characterization of the acquired immune system was performed for all 114 individuals , the innate immune system was analyzed for only 79 individuals ( table e-2 ) . the presence of anti - cytomegalovirus ( cmv ) immunoglobulin g was determined , and only 7 of the 114 participants were considered nonimmune to cmv ; no correlations were observed between cmv antibody titers and the cognitive performance of the participants . all participants presented c - reactive protein levels below the limit associated with active inflammation / infection ( 10 mg / l ) . information about anti - inflammatory / immunomodulatory medication was collected at the time of clinical interview ; 18 of the participants were receiving this type of therapy ( information provided in table e-1 ) . blood was collected to edta blood collection tubes and processed for standard hospital leukogram ( braga 's hospital ) and multiparametric flow cytometry analyses on the same day of collection ( see e - methods for details ) . leukogram analysis was conducted at the certified pathology laboratory of braga 's hospital , following standard procedures . data for mem , genexec , and gds were used in the analysis as z scores , as previously determined by santos et al . to evaluate normal distribution of the variables , skewness and kurtosis values were calculated and the approximate normal distribution was defined for variables with absolute values of skewness below 3 and of kurtosis below 8 . levene test was used to evaluate equality of variances . to compare immune systems ' cell populations ( cell counts per ml of blood ) between good and poor cognitive performance groups ( descriptive statistics of variables are presented in table e-2 ) , an independent - sample t test was performed for variables with normal distribution and a mann - whitney u test for variables with non - normal distribution . p values below 0.05 were considered significant , and to quantify the strength of the differences , cohen d was calculated as a measure of effect size ( 0.2 is considered a small effect size , 0.5 a medium effect size , and 0.8 a large effect size ) .","objective : immunosenescence and cognitive decline are common markers of the aging process . taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition , we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance.methods:in a cohort of cognitively healthy adults ( n = 114 ) , previously characterized by diverse neurocognitive / psychological performance patterns , detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry.results:better cognitive performance was associated with lower numbers of effector memory cd4 + t cells and higher numbers of naive cd8 + t cells and b cells . furthermore , effector memory cd4 + t cells were found to be predictors",380,128,0.3368
dialogsum,"#Person1#: OK class, so today we are going to continue with our anatomy class, today we will review everything we have learned. Can anyone tell me what the first major organ is? #Person2#: The brain! #Person1#: That's right, the brain! It serves as a control center for the body, handling the processes of the central nervous system as well as cognition. Then what major organ is in our chest? #Person2#: The heart! #Person1#: Very good! It pumps blood throughout the body, using the circulatory system such as blood vessels and veins. Now let's not forget that our lungs provide oxygen to our heart and body to keep us alive! Now what about the organs that help us digest food? #Person2#: The stomach and intestines! #Person1#: Very good! Let's not forget that the stomach is the one that breaks down our food and our intestines process that food and then expel the waste. Are we forgetting anything? #Person2#: Yeah! Our kidneys, liver and bladder! #Person1#: Oh yes, you are right. Very important organs indeed. #Person2#: So what do these organs do, teacher? #Person1#: Well, mumm, they. . . Time for a break! We can talk about it when you get back.","#Person2# leads students to review what they have learned, including the first major organ, the major organ in the chest, the organs helping digest food, kidneys, liver, and bladder.",200,29,0.145
dialogsum,"#Person1#: Mrs. Huang, you are on the third floor. #Person2#: It looks very comfortable. #Person1#: You have got a lovely view of Yellowstone Park. This is your private room, and just opposite is a kitchen which all six of you share. There is a common room at the end of the corridor, and a game room next door.",#Person1# shows Mrs. Huang her room. Mrs. Huang thinks it looks comfortable.,58,12,0.2069
dialogsum,"#Person1#: Aren't you going to swim? #Person2#: Are you kidding? Don't you know I can't swim? #Person1#: You are not telling me that we drove 50 miles to come here for just sunbath, are you? #Person2#: Hey, don't shout. Come here! Sit closer. Now, Jim, we'Ve had a lovely day. Don't spoil it now. #Person1#: What about your beautiful bathing suit? We shopped all day. Don't you want to show it off? #Person2#: Everybody who walks past me sees it. Besides, it's a good sunbathing suit. #Person1#: All right. Suit yourself. I am going swimming. #Person2#: Jim! #Person1#: Yes? #Person2#: Can you get me a beach umbrella and a deck chair? I am really tired of lying in thousand. #Person1#: I've got a better idea. Why don't we hire a boat and go for a ride? What do you think? #Person2#: Are you serious? That will be wonderful!","Jim wants to swim while #Person2# just wants to bathe in the sun. Finally, they decide to hire a boat and go for a ride.",148,25,0.1689
dialogsum,"#Person1#: May I help you? #Person2#: I would like an alarm clock that will awaken me with soft music. #Person1#: In that case, you'll probably be interested in this handsome electric clock radio. #Person2#: Actually, I'd like a small battery-operated clock radio. #Person1#: There's a model that should suit you perfectly. #Person2#: Can I use my credit card to pay for it? #Person1#: I'm sorry, sir, but we don't accept credit cards in this family-run store. You could try the appliance store that on Dawson Street. #Person2#: Thank you for your help. I'll see if the store you recommended has what I want.",#Person2# wants to buy a clock radio by credit card. #Person1# doesn't accept credit cards and recommends another appliance store.,103,20,0.1942
dialogsum,"#Person1#: This is tough to say, Jordan, but I think we should break up. #Person2#: Are you serious? #Person1#: Yes, I mean it. #Person2#: But why? Did I do anything wrong? #Person1#: No, we are just too different. This isn't working. #Person2#: Hey, come on. It's too early to say that. We can fix things. #Person1#: I have thought about it for a while. I think it's time to move on for both of us. #Person2#: But I still love you. #Person1#: I'm sorry. #Person2#: I knew this would happen some day. . . #Person1#: Then why didn't you talk to me? #Person2#: Well. It's not all my fault, Anna. . . #Person1#: I don't want to argue with you anymore. This is going to be tough, but Let's try and be friends. #Person2#: I would like that Anna, but I think I'll need a little space for a bit. #Person1#: I think we'll be better off if we are apart. #Person2#: Shall we keep pur friendship? #Person1#: Sure, let's just be friends.",Anna is breaking up with Jordan. Jorden doesn't want to but he accepts it at last. They are going to keep their friendship.,173,23,0.1329
dialogsum,"#Person1#: Good morning. Miss Lee. My name is Alex Jones. I'm the new assistant in the office. #Person2#: Welcome and nice to meet you. I heard you were coming today. Is today your first day here in the company? #Person1#: Yes, I'm looking forward to meeting everybody and getting started on my new job. #Person2#: First day is often exciting, isn't it? Here, let me show you to your desk. You can have this computer and telephone and share the copy machine with us in the office. How do you like it? #Person1#: This is wonderful. Thank you for doing all this for me, Miss Lee. #Person2#: You are welcome. And, please call me Betty.",Alex Jones comes to the office as a new assistant and Betty shows Alex to Alex's desk.,115,17,0.1478
dialogsum,"#Person1#: So what's the matter with you then? #Person2#: Oh, nothing. I'm just a bit led up really. #Person1#: Why's that? I thought you were pleased about the new job and going to London. #Person2#: I am, I am. It's just that I've bean here for so long in this town and it's hard to think of anywhere else as home. You know the worst thing will be not being able to take a walk with the dog whenever I feel like it. #Person1#: Yes, I can understand that. But I'm sure once you are settled in you'll be fine. #Person2#: Sure, but you know it's not the same as being here. I've got friends here, I know where the local shops and cinemas are and of course I've got you to look after me! #Person1#: Well, Tim, is that all you'll miss me for? Doing your washing and ironing...? #Person2#: No, of course not, Mum. There's your cooking as well! #Person1#: Thanks a lot, Tim. Anyway when are you leaving? #Person2#: Tomorrow evening, I've got Simon to give me a lift with all my stuff. It's a pity he's not working in London. #Person1#: That's good of your brother. And the job? #Person2#: I start on Monday. I don't know whether to wear a suit or not. What do you think? #Person1#: Probably a good idea on your first day. #Person2#: I suppose so. I can't bear wearing suits. #Person1#: You look great in a suit. #Person2#: Oh, Mum, do you have to say things like that? #Person1#: Yes, I'm here to say the most embarrassing things to my teenage son. Anyway, it's only a summer job. You'll be back in a couple of months. #Person2#: True. Thanks Mum. Can I borrow your laptop? It would be so useful. #Person1#: Tim. #Person2#: Only joking, Mum!",Tim's going to London for a summer job and he feels upset about leaving his hometown and his family. His mother comforts him that he'll soon be fine and suggests he wear suits on his first day.,306,37,0.1209
dialogsum,"#Person1#: Why don't you watch where you're going? #Person2#: Me? You're the one who pulled out in front of me! #Person1#: There was plenty of room for me to pull out. You didn't have to stay in the lane you were in. #Person2#: Hey, listen. I had every right to stay in the lane I was in. You were supposed to wait until I passed to pull out. And anyhow, you didn't give me any time to change lanes. All of a sudden--BANG--there you are right in front of me. #Person1#: I think my arm is broken. #Person2#: Sorry about your arm, but it serves you right. You need to learn how to drive. You're lucky you didn't get killed. And I'm lucky to be alive too. #Person1#: Listen, let's just wait until the police get here. Then we can decide whose fault this accident was. #Person2#: Fine with me. I know the laws of the road. I'm not worried. #Person1#: I have a cell phone in my car. Now it's probably on the floor on the passenger side. Why don't you get it for me, and then I can call the police? #Person2#: Alright. #Person1#: It doesn't work. It looks like it's broken. I need to get to a hospital. You should drive me there. #Person2#: Oh, yeah? It's better if we make a police report first. Then you can go to the hospital. #Person1#: Damn it! I'm injured here. We could wait all day for the police. #Person2#: Well, you'll just have to wait. I'm not going to move my car until the police arrive. I'll go into one of those houses over there and use their phone. Don't worry. You'll get to the hospital in time. #Person1#: It really hurts. #Person2#: Yes, maybe it does. But if you're going to drive like you did just now, you will have to get used to a little physical pain. You know what I mean? #Person1#: To hell with you. The accident was your fault. #Person2#: I'm afraid it wasn't. And when the police get here, you will also see that it wasn't. But enough of this bickering. I'm going to go find a phone. Don ' t move that arm while I'm gone. Alright? #Person1#: To hell with you.","#Person1# and #Person2# argue about who's responsible for the accident. Both of them think it's the other's fault. #Person1#'s arm is broken so #Person1# asks #Person2# to drive #Person1# to the hospital, but #Person2# won't move #Person2#'s car until the police arrive. Then, #Person2#'s going to find a phone to call the police. #Person1# keeps cursing.",380,56,0.1474
pubmed-summarization,"the emergency care system in denmark has been reorganized during recent years , and a danish quality database on emergency care has been established to assess , monitor , and improve quality . the danish quality database for prehospital emergency medical services ( qems ) is one of the three national sub - databases . the aim of the qems is to assess , monitor , and improve the quality of prehospital emergency medical service ( ems ) care in the entire patient pathway and acts as basis for clinical and health - service research . provision of prehospital emergency care is subject to variations in organization among ems providers , with domestic and regional as well as international differences . there are few uniform quality indicators and standards based on high - level evidence , and most standards are based on expert panel opinions.14 some specific diagnostic groups benefit from quality indicators and standards , such as cardiac arrest,5,6 myocardial infarction ( mi),7,8 stroke,9,10 and severe injury . the major challenge and difficulty in emergency care , especially in the prehospital setting , is that the vast majority of patients present with symptoms and not diagnoses . thus , ems care has to be initiated and delivered on the basis of the symptoms with limited knowledge about the patient s objective condition and medical history . in 2013 , a working group was established by the danish regions with medical and administrative representatives from all five health regions , with the task of formulating recommendations on indicators and standards of ems quality . the working group consisted of medical directors and administrative professionals from prehospital organizations from each of the five regions . the selection of quality indicators was a consensus process , based on literature and the actual availability of prehospital data in our system and national registries on specific emergency conditions , cardiac arrest , mi , and stroke . the danish clinical registries a national improvement program was established in 2014 with medical representatives from the five public regional ems organizations , a professor in prehospital and emergency medicine and representatives from the danish society of cardiology , the danish society of neurology , and a clinical epidemiologist and a statistician from the danish clinical registries","aim of databasethe aim of the danish quality database for prehospital emergency medical services ( qems ) is to assess , monitor , and improve the quality of prehospital emergency medical service care in the entire prehospital patient pathway . the aim of this review is to describe the design and the implementation of qems.study populationthe study population consists of all 112 patient contacts defined as emergency patients , where the entrance to health care is a 112 call forwarded to one of the five regional emergency medical coordination centers in denmark since january 1 , 2014 . estimated annual number of included 112 patients is 300,000350,000.main variableswe defined nine quality indicators and the following variables : time stamps for emergency calls received at one of the five",380,128,0.3368
scientific_lay_summarisation-elife-norm,"a mere consequence of bipolar kinetochore–microtubule attachments, as trivalent sex-chromosome align in the middle of the spindle, even though trivalent attachment does not favor an equatorial position (Nicklas and Arana, 1992). Moreover, previous studies in Chlamydomonas rheinhardtii and C. elegans showed that an asymmetry in centriole numbers at spindle poles led to an asymmetric metaphase plate position, even though chromosomes established bipolar attachments (Greenan et al. , 2010; Keller et al. , 2010). While in algae, longer half-spindles were associated with the pole containing fewer centrioles, in nematodes, longer half-spindles emanated from the pole containing more centrioles. However, whether cells react to asymmetrically located metaphase plates and the long-term consequences of this asymmetry are not known. Here, we investigated these questions in human tissue culture cells. We find that cells correct metaphase plate position before anaphase onset, we demonstrate that a centered metaphase plate position relies on the spindle assembly checkpoint (SAC) to provide sufficient time for this correction mechanisms, and we show that a failure to correct plate position leads to asymmetric cell divisions. To monitor the relative position of the metaphase plate in the spindle over time, we recorded by time-lapse imaging HeLa cells stably expressing eGFP-centrin1 (centriole marker) and eGFP-CENPA (kinetochore marker) and automatically tracked centrosomes and the metaphase plate using an in-house developed software (Jaqaman et al. , 2010; Vladimirou et al. , 2013). Metaphase or late prometaphase cells were recorded over a short period of 5 min in 3D at a resolution of 7. 5 s under conditions of low phototoxicity compatible with anaphase entry (Jaqaman et al. , 2010). By plotting the ratio R of the half-spindle lengths of metaphase cells at the onset of our recordings (first three time points), we found a broad distribution centered around median R = 0. 98, which represents nearly equal half-spindle lengths. When analyzing the subset of cells that entered anaphase during our recordings 30 s before anaphase, we found a sharp R distribution in the middle of the spindle (median R = 1. 02; 1A): less than 10% of the R values were smaller than 0. 85 or larger than 1. 15 at anaphase onset, while in the metaphase population over 24. 2% were outside of these boundaries. This suggested a centering mechanism for the metaphase","The genetic information of a cell is stored in the form of chromosomes. Before a cell divides, its entire set of chromosomes is duplicated so that the two newly formed daughter cells receive a full set. In animal cells, the chromosomes line up in the center of the cell. The two sets of chromosomes are then separated by a structure known as the spindle, which attaches long filaments of proteins to the chromosomes and pulls one set to either side of the cell. Birth defects and cancer can result from a cell ending up with too many, or too few, chromosomes. Therefore, a safety mechanism called the spindle assembly checkpoint ensures that all of the chromosomes have correctly attached to the spindle before chromosome separation begins. Although it",380,128,0.3368
pubmed-summarization,"width ( rdw ) of 17.2 ( normal 11.6 - 13.7% ) . other biochemical abnormalities were high serum cholesterol of 6.9 mmol / l ( normal 3.6 - 6.8 , hypo - thyroidism was diagnosed . in the light of the patient 's diagnosis , a second history was taken which showed that she suffered from other symptoms of hypothyroidism such as , dry skin , generalised weakness , excessive sleeping , hoarse voice , and menorrhagia . two months after the initiation of therapy , the patient had no more dysarthria or other associated symptoms . dysarthria is a disturbance of articulation that may be caused by a neuromuscular lesion , or an abnormality of the vocal cords . the first may result from damage to the central or peripheral nervous system such as head trauma , brain stem infarction , bulbar palsy , motor neuron disease , peripheral neuropathy , huntington 's chorea , parkinson 's disease , multiple sclerosis , myasthenia gravis , or muscle disease.4 the second may be attributable to congenital , traumatic , inflammatory , tumors , or post - operative lesions of the vocal cords . these causes were unlikely in this patient , because she showed no associated clinical features of these diseases besides the normal neurological examination and investigations . other causes such as congenital or aquired storage disorders such as amyloidosis , and such endocrine disorders as acromegaly or hypo - thyroidism,3 as in the presented case , may lead to an enlargement of one or more of the components of the vocal cords.56 the most likely cause for the dysarthria in this patient was hypothyroidism . this was supported by the abnormal thyroid functions and the response of the dysarthria to thyroxin . dysarthria due to hypothyroidism had been reported only once previous to this case.3 the pathophysiology of dysarthria in hypothyroidism can be explained by edematous swelling of laryngeal and hypopharyngeal structures in combination with macroglossia.3 it has been shown that macroglossia in hypothyroidism is caused by a thickening of the epithelial tissue.6 these changes can also explain the choking and the dysphagia which this patient experienced . there have been a few reports of hypothyroidism responsible for secondary dysphagia.1012 her sleep apnea may also be a","hypothyroidism is a common endocrine disorder with characteristic clinical symptoms and signs . typical symptoms of hypothyroidism are lethargy , cold intolerance , slowing of intellectual and motor activity , decreased appetite , weight gain , and dry skin . a 39-year - old female presented to the clinic with dysarthria as the chief symptom . subsequent questions revealed that other symptoms were confined to the otolaryngeal region , which were episodes of mild dysphonia , dysphagia , sleep apnea , and snoring . laboratory data revealed marked hypothyroidism and positive tests for antithyroglobulin and antimicrosomal antibodies . after administration of thyroxin , the dysarthria and the other symptoms rapidly disappeared . dysarthria may be the presenting symptom of hypothyroidism and can be resolved after hormone replacement therapy",380,128,0.3368
pubmed-summarization,"biodegradable block copolymers prepared from l - lactide , -caprolactone , 1,4-dioxan-2-one , and trimethylene carbonate have been synthesised and studied extensively during recent decades . the varying physical properties of block polymers allows for the combination of soft and hard polymers giving rise to copolymers that can be tuned for specific function such as elasticity . the sequence in which blocks are synthesised into block copolymers is specific and is determined by the choice of monomer and catalyst . for example , at the application of tin octoate as catalyst , the block copolymer structure polycaprolactone - polylactide ( pcl - pla ) is formed if the -caprolactone is polymerized first , followed by polymerization of l - lactide . however , a random copolymer is obtained when pla is initially synthesised followed by pcl . this is a result of transesterification of the pla and segmentation of the block polymer . two competing reactions during carop ( coordinated anionic ring opening polymerisation ) occur ; ( i ) ring - opening of ester bonds in molecules of the initial cyclic monomer and ( ii ) cleavage of the ester bonds in the macromolecules of the polymer . these competing reactions depend on the choice of catalyst , the existing polymer , which acts as a macroinitiator , and the type of monomer added at the second stage of polymer synthesis . atering the catalyst utilized for example , y(cf3coo)3/al(iso - bu)3 catalyst or the complex [ y(l6)-{n(sihme2)2}(thf ) ] promotes the initial synthesis of the pla block , followed by the pcl block . showed that selectivity of al(oipr)3 catalyst could be accomplished through coordination with sb(oh)2 ( ( s)-()-2,20-[1,10-binaphtyl-2,20-diylbis(nitrylomethilidyne)]diphenol ) , allowing synthesis of the block structure pcl - pla - pcl , where the pla block was synthesised by the first route . furthermore , tin octoate has been shown to result in the transesterification of polyesters in the absence of monomer ; thus , the presence of the monomer initially prevents significant transesterification of the block polymer formed . catalysts possess an ability to promote transesterification reactions , and tin octoate is known for its strong ability to break ester bonds in a macromolecule . the ability to induce transesterification is a negative property of","well - defined di- and triblock copolymers consisting of -caprolactone ( cl ) , l - lactide ( la ) , and trimethylene carbonate ( tmc ) were synthesized via pla first route in coordinated anionic ring opening polymerization / copolymerization ( carop ) with tin ( ii ) octoate as catalyst . the desired block structure was preserved by use of protective additive -methylstyrene by preventing the transesterification side - reactions . maldi - tof analysis revealed that the protection mechanism is associated with -methylstyrene and tin ( ii ) octoate complexation . additionally , it was shown that use of -methylstyrene in ring opening polymerization allowed the formation of polyesters with high molar mass .",380,117,0.3079
dialogsum,"#Person1#: Hello, JC Consulting PLC. Chris Edwards speaking. #Person2#: Mr. Edwards, this is Kristy calling from IBA. #Person1#: Hi Kristy! What's going on? #Person2#: Do you remember coming in to do the L / C amendment last week? #Person1#: Yes, I certainly do. #Person2#: The negotiating bank has just been in touch. . . #Person1#: Oh, dear! There isn't a problem, is there? #Person2#: No, Mr. Edwards, not at all. We are contacting you to let you know that everything has gone smoothly and the amendment has been accepted. #Person1#: Kristy, that's wonderful! Thanks so much for contacting me personally.",Kristy calls Edwards to inform him that everything has gone smoothly and the amendment has been accepted.,100,17,0.17
dialogsum,"#Person1#: Hello, and welcome to IBA. Which service do you require? #Person2#: Hello, Shelly, is it? I'm here on behalf of my company, so I'll need the Corporate Banking Services. #Person1#: That's no problem ; I can take care of that for you. #Person2#: I need to have a credit check done for my company. #Person1#: If it's this kind of consultancy service, I'll have to direct you to another department, I'm afraid. #Person2#: That's no problem. Do you offer any other consulting services? #Person1#: There are many services you can choose from. Why don't you take a look at this leaflet while I find someone who can help you? #Person2#: Great. I'll wait right here, thanks.",#Person2# comes to IBA to have a credit check done for #Person2#'s company. Shelly can't help with this consultancy service and will direct #Person2# to another department.,117,27,0.2308
scientific_lay_summarisation-elife-norm,"in this study how many conserved E. coli genes can successfully substitute for their yeast orthologs. We focused on those genes that are essential for viability in yeast, allowing us to assay for the complementation of otherwise lethal growth defects. We analysed many features of the proteins and ortholog pairs to identify which properties best explained replaceability, finding that replaceability was often determined at the level of specific pathways and processes, with all genes in a pathway or process similarly replaceable. Start codon choice and eukaryote-specific subcellular localization were also critical determinants of replaceability. We discovered that certain core biological processes have remained largely unchanged since the last common ancestor of bacteria, yeast, and humans. In particular, heme biosynthesis pathway enzymes appear to be generally exchangeable between prokaryotic and eukaryotic organisms, broadly retaining ancestral functions across the tree of life over 2 billion years of independent evolution, even when accompanied by evolved changes in enzyme subcellular localization. We focused our efforts on the set of genes with 1: 1 orthology between E. coli and yeast and that are known to be essential for yeast growth in standard laboratory conditions (1A). Each E. coli open reading frame (ORF) was cloned into a single-copy yeast centromeric (CEN) plasmid under the transcriptional control of a constitutive GPD promoter. Complementation assays were carried out using two types of conditionally essential yeast alleles, consisting of temperature-sensitive (TS) haploid and heterozygous diploid deletion strains. In the case of the heterozygous diploid deletion strains, the respective yeast gene null allele could be genetically segregated via sporulation, allowing selection for haploid yeast with the null allele (selected for in the presence of the antibiotic G418) or the wild-type yeast gene (in the absence of G418) (1B, Top panel). In the case of TS haploid yeast strains, the temperature sensitive yeast proteins functioned normally at the permissive temperature (25°C) but could be conditionally inactivated at the non-permissive temperature (36°C) in order to test for gene replaceability (1B, Bottom panel). Overall, we could perform informative complementation assays for 51 of the 58 orthologs, as shown for the examples in 1B. 10. 7554/eLife. 25093. 003Figure 1. Many E. coli genes efficiently complement lethal growth defects in their yeast counterparts. (A) Yeast and E. coli share hundreds of genes, 58 of which","All life on Earth – from bacteria to human beings – can be traced back to a common ancestor that lived over three billion years ago. As a result, modern-day organisms share many essential parts of life’s molecular machinery, such as certain genes and proteins. Yet there are also vital differences that allow scientists to divide almost all living things into one of two groups, known as prokaryotes and eukaryotes. Prokaryotes are all simple, single-celled organisms, such as bacteria; while eukaryotes include more complex organisms, such as plants, animals and fungi. Scientists have previously found that eukaryotes and prokaryotes have hundreds of genes in common, even though they have evolved separately for over two billion years. As different species evolve, however, their genes mutate and change, potentially affecting",380,128,0.3368
dialogsum,"#Person1#: How can I help you? #Person2#: Yes, I would like to look at some of your products. #Person1#: Did you have anything specific in mind? #Person2#: Well, to be honest, I mostly use Sarah Winter products now. But I'm not happy with them. So I would like to change companies. #Person1#: Well, you made a good choice. Coming to us, I mean. We have a full range of products from cosmetics to skin cleansers and moisturizers. #Person2#: What do you have in foundation? #Person1#: Our foundation is very high quality. Only the finest ingredients. It will moisturize your skin and it has a sun block rating of 8. #Person2#: What colors do you have in foundation? #Person1#: Let me show you. We have this rose color. We also have different shades of beige. #Person2#: The color I use now is rose. How much does this rose foundation cost? The 100ml bottle. #Person1#: In this size, we sell it for 53. 95. #Person2#: Wow! That's expensive. #Person1#: What you're paying for, Ma'am, are the ingredients. It is a very high quality product. #Person2#: I understand. I need some mascara too. Do you have a good thickening mascara? #Person1#: Of course. Here is our thickening mascara. We also have mascara designed to lengthen the eyelashes. #Person2#: Alright. And I want to consider your eye shadow too. Do you have a color chart I can look at? #Person1#: We have a very wide selection of colors. And our eye shadow is specially designed to moisturize the skin. So it is very gentle on your eyelids. Would you like to sample some? #Person2#: Oh, sure. I will need to clean off my own eye shadow first. #Person1#: I can help you with that. #Person2#: Thank you.","#Person2# used to use Sarah Winter products but is not happy with them. #Person2# wants to change companies, and #Person1# recommends her some cosmetics, including the rose foundation, thickening mascara, and eye shadow. #Person2# wants to sample some eye shadow and #Person1# helps #Person2# with it.",293,46,0.157
scientific_lay_summarisation-elife-norm,"Small nucleolar RNAs (snoRNAs) are a diverse group of non-coding RNAs that direct chemical modifications at specific residues on other RNA molecules, primarily on ribosomal RNA (rRNA). SnoRNAs are altered in several cancers; however, their role in cell homeostasis as well as in cellular transformation remains poorly explored. Here, we show that specific subsets of snoRNAs are differentially regulated during the earliest cellular response to oncogenic RASG12V expression. We describe a novel function for one H/ACA snoRNA, SNORA24, which guides two pseudouridine modifications within the small ribosomal subunit, in RAS-induced senescence in vivo. We find that in mouse models, loss of Snora24 cooperates with RASG12V to promote the development of liver cancer that closely resembles human steatohepatitic hepatocellular carcinoma (HCC). From a clinical perspective, we further show that human HCCs with low SNORA24 expression display increased lipid content and are associated with poor patient survival. We next asked whether ribosomes lacking SNORA24-guided pseudouridine modifications on 18S rRNA have alterations in their biophysical properties. Single-molecule Fluorescence Resonance Energy Transfer (FRET) analyses revealed that these ribosomes exhibit perturbations in aminoacyl-transfer RNA (aa-tRNA) selection and altered pre-translocation ribosome complex dynamics. Furthermore, we find that HCC cells lacking SNORA24-guided pseudouridine modifications have increased translational miscoding and stop codon readthrough frequencies. These findings highlight a role for specific snoRNAs in safeguarding against oncogenic insult and demonstrate a functional link between H/ACA snoRNAs regulated by RAS and the biophysical properties of ribosomes in cancer. Non-coding RNAs (ncRNAs) encompass a large group of functionally diverse non-protein coding transcripts that are emerging as important regulators of biological processes (Cech and Steitz, 2014; Esteller, 2011). Small nucleolar RNAs (snoRNAs) are abundant, often intron-encoded, short ncRNAs classified based on specific sequence and secondary structure features (Kiss, 2002; Matera et al. , 2007). The most well-characterized functions of snoRNAs relate to their roles in ribosome biogenesis, wherein structurally distinct C/D and H/ACA snoRNAs directly base pair to complementary regions of ribosomal RNA (rRNA) (Filipowicz and Pogacić, 2002). In doing so, C/D and H/ACA snoRNAs modulate the chemical landscape of the ribosome by directing ribonucleoprotein complexes to modify up to two hundred site-specific ribose methylations (2’-O-Me) and pseudouridine (Ψ) modifications, respectively (Sloan et al. , 2017; Watkins and Bohnsack, 2012). Unlike nucleotide modifications performed by stand-alone RNA modifying enzymes, the function of","Ribosomes are cellular machines responsible for translating the genetic code into proteins. Research has shown that changes in ribosome activity can contribute to healthy cells becoming cancerous. Ribosomes consist of proteins and other molecules known as ribosomal RNAs (or rRNAs for short). Before they can become part of a ribosome, another type of molecule called snoRNAs must modify new rRNAs. Indeed, many of the modifications that allow rRNAs to accurately translate genetic information into proteins are introduced by snoRNAs. As such, it is possible that changes to snoRNAs could contribute to the creation of cancerous cells by affecting how ribosomes operate. To explore this possibility, McMahon, Contreras et al. examined snoRNAs in healthy cells grown in the laboratory that have been given pro-cancer signals, in cancer from mice,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Strelkowa and Lässig, 2012). Specifically, early work by Fitch et al. (1997) found the number of nonsynonymous changes on tip branches of the HA phylogeny to be higher than expected, indicative of either strain selection bias or the presence of transiently circulating deleterious mutations in the influenza viral population. In more recent work, Pybus et al. (2007) performed a comprehensive phylogenetic analysis of over 140 viruses, including influenza A/H3N2. For H3N2' s M1 protein, as well as for the majority of the other viral proteins examined in the study, they found heightened ratios of non-synonymous-to-synonymous substitutions on external tree branches relative to those found internally. This finding again points towards transiently circulating deleterious mutations in influenza and, more generally, across RNA virus populations. Other recent work on predicting the short-term evolution of influenza has highlighted the necessity of accounting for fitness costs associated with sublethal deleterious mutations when projecting the frequencies of influenza clades into the next season (Łuksza and Lässig, 2014). Together, these results indicate that purifying selection is not sufficiently strong to immediately eliminate deleterious mutations from the influenza A/H3N2 virus population that circulates among humans. As a result of genetic linkage within genes and, to a lesser extent, across genes, these deleterious mutations have the potential to interact with beneficial mutations in determining which viral lineages will persist and which ones will ultimately be lost. Indeed, a recent statistical analysis of HA sequences from influenza A/H3N2 has suggested that interference effects largely determine the fates of viral mutants, rather than their inherent selective effects (Illingworth and Mustonen, 2012). These interference effects are possible because of an extensive genetic linkage across influenza' s HA (Strelkowa and Lässig, 2012) and arise from variation in the background fitness of viral strains and from variation in the fitness effects of subsequent mutations. Taken together, this body of work indicates that sublethal deleterious mutations commonly arise and circulate for sufficiently long periods of time to be able to impact the trajectories of influenza A/H3N2 strains. However, the impact that these deleterious mutations have on the population dynamics and long-term evolutionary patterns of this subtype has to date not been explored. Here, we address this question with a set of increasingly complex population genetic and population dynamic models, under the common assumption that","Each year, up to 15% of the world' s population experience symptoms of an influenza infection, also commonly known as flu. The most common culprit is a strain of the virus called influenza type A subtype H3N2. One reason that so many people become infected each year is that this virus evolves rapidly. Within a few years, proteins on the surface of the virus known as antigens become less recognizable to the immune system of a person who has been previously infected. This means that the person can become ill with the virus again because their immune system cannot mount an effective response to the evolved virus strain. Influenza virus strains evolve rapidly because their genetic material accumulates mutations quickly. Although some of these mutations are beneficial to",380,128,0.3368
dialogsum,"#Person1#: Hey, Jane. #Person2#: Oh Hi John, nice to see you. I'm doing a presentation for my company at your hotel today. #Person1#: Oh nice. You sure did bring a lot of things with you. What's it all for? #Person2#: I need to show people all of our new game products, so I brought all of our games with me. #Person1#: All the games? I never knew that your company made so many games. #Person2#: Yes, and I'll be giving it all away to people who come to my presentation. #Person1#: Sounds like fun, do you need a hand taking things inside? #Person2#: That would be great. #Person1#: OK, just wait here for a minute. I'll be right back with a luggage cart.",Jane is doing a presentation for her company at John's hotel. She'll give new game products away to people. John'll help her take things inside.,123,25,0.2033
pubmed-summarization,"providing the transcriptional signatures of two categories of primary sensory neurons , our study expands the molecular characterization of c - ltmrs and suggests that this particular subset of primary sensory neurons shares many molecular features of ltmrs . as a functional readout , we used electrophysiological recording to unravel the specific and exclusive functional expression of the low - voltage - gated ca channel cav3.3 in c - ltmrs , where it very likely plays a key role in shaping their functional specialization . in a recent study , we generated a mouse model that expresses the fluorescent protein m - cherry from the ginip locus ( gaillard et al . , 2014 ) . double - labeling experiments using anti - ginip antibody in combination with ib4 staining showed that drg neurons can be split into four distinct categories : ginip / ib4 ; ginip / ib4 ; ginip / ib4 ; and ginip / ib4 neurons . the ginip / ib4 double - positive ( dp ) population corresponds to the cutaneous free nerve endings mrgprd neurons ( figures 1a and 1b ) , the ginip / ib4 population corresponds to tafa4-expressing c - ltmrs ( figures 1a and 1b ) , the ginip / ib4 population contains the 20% remaining ib4 neurons ( 1a ) , and the ginip / ib4 double negative ( dn ) neurons represents a heterogeneous population of neurons composed of peptidergic nociceptors , a subset of ret neurons and trkb and trkc neurons ( 1a ) . as ginip mouse model allows high - fidelity expression of m - cherry in ginip neurons , we sought to combine live m - cherry fluorescence with ib4 cell surface staining and facs to purify the four categories of drg cells ( figures 1c and 1d ) . neurons with a cell body size above 70 m were eliminated by filtering the suspension , and axonal debris was removed by using a percoll gradient . negative gating was used to exclude dead or dying cells that incorporated sytox blue dye and cells that were autofluorescent in v500 channel ( figures 1c and s1 ) . next , we gated on m - cherry - positive and m - cherry - negative cells that we","summarycutaneous c - unmyelinated mrgprd+ free nerve endings and c - ltmrs innervating hair follicles convey two opposite aspects of touch sensation : a sensation of pain and a sensation of pleasant touch . the molecular mechanisms underlying these diametrically opposite functions are unknown . here , we used a mouse model that genetically marks c - ltmrs and mrgprd+ neurons in combination with fluorescent cell surface labeling , flow cytometry , and rna deep - sequencing technology ( rna - seq ) . cluster analysis of rna - seq profiles of the purified neuronal subsets revealed 486 and 549 genes differentially expressed in mrgprd - expressing neurons and c - ltmrs , respectively . we validated 48 mrgpd- and 68 c - ltmrs - enriched genes using",380,128,0.3368
dialogsum,"#Person1#: That's right. And I'm going to be Vice President of Marketing. #Person2#: Way to go, Mary. A lot has happened during the last few months, hasn't it? #Person1#: You can say that again! #Person2#: What's up with Vince and Elvin? #Person1#: They work for Zina now. #Person2#: And they're happy with that? #Person1#: They're in awe of her. After they saw how she crushed WebTracker. . . but I guess you know all about that.",Mary tells #Person2# that she'll become Vice President of Marketing as Vince and Elvin work for Zina now.,76,18,0.2368
dialogsum,"#Person1#: Hello, Daisy, how are you doing? #Person2#: Fine, thank you. I haven ' t seen you for quite some time. What have you been up to recently? #Person1#: I have been spending a lot of time watching movies at home, so you wouldn't have seen me. Recently, I've been obsessed with horror films. #Person2#: Oh, how can you be infatuated with horror films? They're so scary. #Person1#: Yeah, you are right I used to not watch horror films, but after seeing Silence of the Lamb with Mike last month, I fell in love with them. #Person2#: It's amazing. But if I were you, I wouldn't have the courage to watch the first one. #Person1#: But it's really exciting. #Person2#: Maybe, but I would rather watch romance, science fiction, crime or even disaster movie instead of a horror picture. I wouldn't dare sleep at night after watching one. #Person1#: Basically. you'll watch any type of movie except horror. #Person2#: Yep. #Person1#: I think you should have a try someday. Maybe you'll change your mind. #Person2#: Maybe. After all, I am grown up now.","#Person1# has been spending a lot of time watching movies and has been obsessed with horror films. Daisy thinks they're scary. #Person1# thinks Daisy should have a try, and Daisy agrees.",183,31,0.1694
scientific_lay_summarisation-elife-norm,"lack of the Hsd17b4 gene (also called multifunctional protein 2; Mfp2 gene) that encodes a central enzyme of peroxisomal β-oxidation. In MFP2-deficient cells, the β-oxidation of virtually all peroxisome-specific substrates, including VLCFA, is inhibited (Verheijden et al. , 2013). A complete disruption of the organelle is observed in the absence of peroxisome biogenesis factor peroxin 5 (PEX5). This cycling receptor recognizes proteins with a peroxisomal targeting sequence type 1 (PTS1) and is involved in their transfer into peroxisomes. PEX5-dependent protein import applies to the majority of peroxisomal enzymes. Thus, PEX5-deletion disrupts peroxisomal function substantially (Waterham et al. , 2016). Schwann cell lipid metabolism is rate-limiting for myelination and is important for maintenance of axonal integrity (Saher et al. , 2011; Viader et al. , 2013), which requires in addition to membrane wrapping the assembly of nodal, paranodal, and juxtaparanodal membrane proteins (Rasband and Peles, 2015). The juxtaparanodal domain of myelinated axons harbors voltage-gated shaker-type potassium channels, Kv1. 1 (KCNA1) and Kv1. 2 (KCNA2; Chiu and Ritchie, 1980; Robbins and Tempel, 2012), which also align the inner mesaxon as a thin band (Arroyo et al. , 1999). Associated with connexin-29 hemichannels (Rash et al. , 2016), their clustering and anchoring at juxtaparanodes requires the neuronal membrane proteins CASPR2 and TAG-1, the latter expressed by glia and neurons (Poliak et al. , 1999b; Traka et al. , 2003). Kv1 channels have been proposed to play a role in regulating fiber excitability (Baker et al. , 2011; Glasscock et al. , 2012), but the exact in vivo function of these fast-opening/slowly inactivating channels remains unknown (Arancibia-Carcamo and Attwell, 2014). Cnp-Cre: : Pex5flox/flox mice, termed cKO or' mutants' in the following, lack peroxisomal protein import in Schwann cells (1a; — 1a). The PNS of these mice is well myelinated and unlike the CNS (Kassmann et al. , 2007) without immune-mediated injury, in agreement with pilot observations (Kassmann et al. , 2011). Upon closer inspection, we determined about 50% genomic recombination, corresponding to the fraction of Schwann cell (SC) nuclei in sciatic nerves (— 1b). Teased fiber preparations, stained for PMP70, revealed peroxisomes as puncta. In mutant nerves, these were import-deficient' ghosts' , as evidenced by cytoplasmic catalase, normally a luminal peroxisomal marker (1b). 10. 7554/eLife. 23332. 003Figure 1. Schwann cell-specific PEX5-deficiency causes peroxisome dysfunction","Nerve cells transmit messages along their length in the form of electrical signals. Much like an electrical wire, the nerve fiber or axon is coated by a multiple-layered insulation, called the myelin sheath. However, unlike electrical insulation, the myelin sheath is regularly interrupted to expose short regions of the underlying nerve. These exposed regions and the adjacent regions underneath the myelin contain ion channels that help to propagate electrical signals along the axon. Peroxisomes are compartments in animal cells that process fats. Genetic mutations that prevent peroxisomes from working properly can lead to diseases where the nerves cannot transmit signals correctly. This is thought to be because the nerves lose their myelin sheath, which largely consists of fatty molecules. The nerves outside of the brain and spinal cord",380,128,0.3368
dialogsum,"#Person1#: OK, I just want to brief you all on the travel market in Taiwan. To start with, generally speaking, the travel industry in Taiwan focuses mainly on tours. This segment of the industry is well developed. #Person2#: Sorry to interrupt, Doris, but can you tell me more about these tour groups, what kind of things they enjoy, and so on? #Person1#: Yes, of course. Most of the time, when they travel, they prefer to do so in large groups accompanied by a guide, who usually takes care of everything, for instance, choosing the restaurants, the itinerary, the mode of transport, and things like that. Another thing is that most travelers to the UK tend to be middle aged, around 40 to 50 or so. This age group is less adventurous ; they like good hotels, and have money to spend. They kind of prefer to stay in the cities where they feel safer. They are not into mountain climbing in Wales or anything. #Person2#: I don't mean to interrupt, but can you tell me what plans you have for growing the youth market? #Person1#: Just a moment. I'll tell you about that in a minute. Where was I? Oh yes. By way of illustration, let's look at the top five destinations in the UK for this kind of traveler over the last five years. If you look at page ten you can see what I mean. In spite of these characteristics of the market, I still think there is room for growth in the youth sector. #Person2#: So how do you intend to do that? #Person1#: OK, let me tell you what we'Ve been doing. We'Ve been in touch with the Wales and Scottish Tourist development offices here in Taiwan and they're interested in working with us to promote their regions to the youth segment. We'Ve decided to implement an advertising campaign focusing on the excitement of the activities in those regions. #Person2#: May I interrupt you for a moment? #Person1#: Go ahead. #Person2#: How much is it going to cost, and who is going to pay? #Person1#: Well, at the moment we are trying to work out those details. We haven't managed to come up with a concrete plan yet, but we are working on it. #Person2#: I","Doris introduces the travel market in Taiwan to #Person2#. Doris tells #Person2# that the tour groups tend to be middle-aged and prefer to do travelling in large groups accompanied by a guide. Despite these characteristics of the market, she still thinks there is room for growth in the youth sector. Doris has found a potential cooperator to develop the youth segment and tells #Person2# the promotion plan.",380,67,0.1763
dialogsum,"#Person1#: Well, it's a lovely room. It's quite a nice size, but I don't like green paint very much. Would it be all right if I painted the walls a different color? #Person2#: Yes, that's fine, as long as you don't paint them a very dark color. One of my hirers painted them black a few years ago. That was terrible. #Person1#: Is there anything I should know? #Person2#: Well, I don't allow cat to go upstairs at all. #Person1#: Oh? Not at all? #Person2#: No, absolutely not. I don't like animals and I don't allow people to smoke in bedrooms. #Person1#: Oh, no, no. I agree with that. I don't smoke anywhere. Can I use the kitchen if I want to cook something? #Person2#: Yes, but only before 7 o'clock in the evening. And I don't allow people to stick pictures on the walls. You know when you take the pictures, marks leave on the wall. #Person1#: OK. I see. #Person2#: And one more thing if you don't mind. I don't want any big noisy parties, so only two or three friends at the same time, please. #Person1#: Oh, right. I'll do that. Well, it sounds fair. Thank you very much.","#Person2# tells #Person1# some rules about the room: #Person1# can paint the walls with no dark color, cats are not allowed to go upstairs, the kitchen can be used before 7 in the evening, no pictures can be stuck on the walls, and no big noisy parties are allowed.",202,49,0.2426
dialogsum,#Person1#: Who is it? #Person2#: Supervisor. Open the door. #Person1#: Wait a sec. #Person2#: What are you doing here? #Person1#: We're watching a football match. What's the matter? #Person2#: Your neighbors complained that you were so noisy that they can't sleep. #Person1#: I'm sorry about this. #Person2#: Please turn down the TV. And not another shout or I'll have to report you to the school administration. #Person1#: You can rest assured that we won't disturb others anymore.,"The supervisor warns #Person1# not to make noise, which disturbs their neighbors' sleep.",77,13,0.1688
dialogsum,"#Person1#: Hi, Tess. What are you going to do tomorrow? #Person2#: Hi, Tom. I don't have much to do. Why? #Person1#: Shall we go for a picnic tomorrow? Let's go to National Park. It's beautiful there. #Person2#: A good idea. When shall we start? #Person1#: At six in the morning. I've got some drinks and several kinds of food. #Person2#: Good. I've just bought some bread. And I'll go to buy a roast duck. We'll certainly have a good time. #Person1#: Wonderful. Shall we ask Jack and Mary? #Person2#: OK! They are free tomorrow, too. I think they would be glad to go with us. Will you tell them about it? #Person1#: I'm sorry. I am going to a birthday party this evening. So it would be kind of you to do it. #Person2#: All right.",Tess and Tom plan to go for a picnic with drinks and food tomorrow. Tess will ask whether Jack and Mary can come.,136,23,0.1691
dialogsum,"#Person1#: What are you doing? #Person2#: Look at me. I look so old! I look as if I were thirty. #Person1#: Come on! Stop being so vain. You look great! You are beautiful! #Person2#: Yes, I am, but I think it's time for some plastic surgery I'm tired of these wrinkles and sagging skin. See? #Person1#: I don't see any wrinkles or sagging skin! You are stop beings ridiculous. Besides, I think that people who get Boto, have facelifts, or tummy tucks look weird. It doesn't look natural. #Person2#: Whatever, I think I'm gonna get liposuction and a nose job and some breast implants as well. #Person1#: I think you need to get brain surgery. I honestly don't think you need cosmetic surgery. You look amazing. #Person2#: I thought you were my friend and would support me on this! I just want to feel better about myself and feel more attractive. #Person1#: You don't need plastic surgery to do that. You are fine the way you are and you have guys drooling all over you! Plus, plastic surgery hurts! #Person2#: Really? #Person1#: Yeah! When I got my nose job I was black and blue for a week!",#Person2# is not satisfied with #Person2#'s appearance and wants to have plastic surgery. #Person1# tells #Person2# #Person2# looks good and plastic surgery hurts.,197,23,0.1168
dialogsum,"#Person1#: Mrs. Daniels, I'm confused about this essay. I thought I was supposed to write about my own life. #Person2#: You're supposed to write about the book. But if you'd like to relate it to your own life, you can. The main part of your essay should be about the book. #Person1#: I see. I think I will have to rewrite what I've already written, since most of my essay doesn't have anything to do with the book. #Person2#: That's probably a good idea.","Mrs. Daniels gives #Person1# advice to rewrite the essay, which is supposed to focus on the book.",84,17,0.2024
scientific_lay_summarisation-elife-norm,"rigorous methods are needed to quantify the three-dimensional (3D) phenotypes of gene expression patterns. A useful tool for tracing back development should be able to perform a quantitative statistical comparison of normal and disease-altered embryogenesis and to detect the earliest signs of genetic misregulation leading to organ malformation. The shape of developing organs is regulated by gene activity in space and time (Andrey and Mundlos, 2017). Cascades of gene regulatory networks provide the detailed instructions necessary to organize cell behavior and to orchestrate tissue growth and differentiation. Gene expression patterns can be readily mapped within tissues in a true 3D framework combining whole-mount-in-situ hybridization (WMISH) (Rosen and Beddington, 1993) with Optical Projection tomography (OPT) (Sharpe et al. , 2002). WMISH is a standard molecular technique for detecting the expression of a specific gene using a labeled complementary RNA probe (de la Pompa et al. , 1997; Correia and Conlon, 2001), and OPT is a mesoscopic imaging procedure that can produce high-resolution 3D reconstructions of whole developing embryos processed by WMISH (Sharpe, 2003; Boot et al. , 2008). These technologies represented breakthroughs in developmental biology and have provided invaluable qualitative insights into gene function and development (Sharpe, 2003). However, methods for quantifying the 3D distributions of gene expression in a systematic, objective manner are still lacking. Expanding the potential of OPT from qualitative to quantitative analysis of gene expression patterns is challenging. Gene expression is characterized by highly dynamic patterns, with fast rates of change and fuzzy boundaries that usually do not correspond to well-defined anatomical structures but rather to tissue regions where cells have dynamically up- and downregulated genes. Gene expression patterns have rarely been quantified (Jernvall et al. , 2000; Airey et al. , 2006; Salazar-Ciudad and Jernvall, 2010; Mayer et al. , 2014; Hu et al. , 2015; Xu et al. , 2015; Martínez-Abadías et al. , 2016). We propose to quantify the shape of developing organs in association with their underlying gene expression patterns by applying Geometric Morphometrics (GM), a set of statistical tools for measuring and comparing shapes with increased precision and efficiency (James Rohlf and Marcus, 1993; Klingenberg, 2002; Klingenberg, 2010; Adams et al. , 2013; Hallgrimsson et al. , 2015). Previous attempts had analyzed the phenotypic and gene expression patterns of variation independently (Jernvall","Our development in the womb is complex. Genes need to switch on and off in a precise order, controlling the activity of millions of cells as they work together to form different tissues. For everything to happen smoothly, cells must use instructions provided by each gene exactly at the correct moment and in the correct place. In this biological assembly line, the slightest change can lead to a defect. Certain genetic mutations can change when and where cells use particular genes, and this can cause errors in development. These kinds of mutations are a common cause of birth defects, but we cannot always pinpoint how they begin. For example, a single mutation in a gene called FGFR2 causes malformations in the head, the heart and the limbs in",380,128,0.3368
pubmed-summarization,"tumors with apocrine and eccrine differentiation ( n=14 ) , malignant tumors with follicular differentiation ( n=1 ) , benign tumors with follicular differentiation ( n=17 ) , and tumors with sebaceous differentiation ( n=12 ) . the rest were retrieved from mature cystic teratoma ( n=2 ) and normal scalp tissues biopsied for therapeutic reasons ( n=2 ) . to analyze cd99 expression patterns in fetal skin , gestational ages of the collected cases were 16 , 17 , 19 ( 2 cases ) , 20 , 25 , 26 , and 28 weeks . all tissues were immediately fixed in 10% buffered formalin , and then processed in paraffin wax using standard procedures . sections were serially cut into 4-m sections and stained with hematoxylin and eosin for examination . the study protocol was approved by the institutional review board ( project number 2009 - 440 ) of asan medical center . all hematoxylin and eosin stained slides were reviewed to ensure quality . when multiple blocks were available in a single case , one block containing representative tissue was selected . ihc staining for cd99 was performed using a benchmark xt autoimmunostianer ( ventana medical systems , tucson , az , usa ) according to the manufacturer s instructions and using the reagents supplied with the kit . in brief , 4-m sections were mounted on silanized charged slides , dried for 10 minutes at room temperature and then further dried for 20 minutes at 65c . after deparaffinization , heat - induced epitope retrieval using standard cell conditioning solution 1 was performed for 24 minutes . subsequently , primary anti - cd99 ( 1:100 , clone dn16 , dinona , seoul , korea ) was applied by an automated immunostaining system with the ultraview dab detection kit ( ventana medical systems ) . analysis of whole tissue section slides stained for cd99 by ihc was performed under a light microscope as previously described [ 14 - 16 ] . the results of cd99 immunostaining were classified into the following groups : consistently complete and strong membrane staining was assigned a value + + , weak to moderate membrane staining was assigned a value of + , variable membrane staining was assigned a value of + /","backgroundcd99 is a cell surface transmembrane glycoprotein expressed in various tissues . cd99 is differentially expressed between subpopulations of each tissue and is highly expressed in certain hematopoietic and precursor cells . however , there has been no comprehensive study of cd99 expression in normal skin . we evaluated cd99 expression in normal human skin and developing fetal skin . methodsseventy - five adult skin samples containing normal skin and eight fetal skin samples of different gestational ages were collected . cd99 immunohistochemical staining was performed to evaluate expression pattern in adult and fetal skin samples . cd99 and cd34 expression were compared by double immunofluorescence . resultsin normal adult skin , cd99 was strongly expressed in the membrane of epidermal basal keratinocytes , hair follicle bulges and",380,128,0.3368
dialogsum,"#Person1#: Hi, Dave. Nice of you to take the trouble to get here. Come in. #Person2#: Wow. Looks as if the party is going strong. #Person1#: Yeah. And they're eating all my food. Oh, I'd like you to meet my sister, Carol. She's visiting for the weekend. #Person2#: Oh. Which one is she? #Person1#: She's sitting on the sofa over there. #Person2#: You mean the woman with long black hair? #Person1#: That's right. Let me introduce her to you. You're very similar people, both so friendly and adventurous. #Person2#: And who's the man sitting next to her? Uh, the man wearing the jacket. #Person1#: Oh, that's Bob, my ballet teacher. #Person2#: Ballet teacher! I never knew you were into ballet. #Person1#: I started about two months ago. Come on. I'd like you to meet them. #Person2#: I'm coming.",Dave comes to #Person1#'s party. #Person1# introduces #Person1#'s sister and ballet teacher to #Person2# and wants him to meet them.,138,20,0.1449
scientific_lay_summarisation-elife-norm,"The COP9-Signalosome (CSN) regulates cullin–RING ubiquitin ligase (CRL) activity and assembly by cleaving Nedd8 from cullins. Free CSN is autoinhibited, and it remains unclear how it becomes activated. We combine structural and kinetic analyses to identify mechanisms that contribute to CSN activation and Nedd8 deconjugation. Both CSN and neddylated substrate undergo large conformational changes upon binding, with important roles played by the N-terminal domains of Csn2 and Csn4 and the RING domain of Rbx1 in enabling formation of a high affinity, fully active complex. The RING domain is crucial for deneddylation, and works in part through conformational changes involving insert-2 of Csn6. Nedd8 deconjugation and re-engagement of the active site zinc by the autoinhibitory Csn5 glutamate-104 diminish affinity for Cul1/Rbx1 by ~100-fold, resulting in its rapid ejection from the active site. Together, these mechanisms enable a dynamic deneddylation-disassembly cycle that promotes rapid remodeling of the cellular CRL network. Cullin–RING ubiquitin ligases comprise one of the largest families of regulatory enzymes in eukaryotic cells (Deshaies and Joazeiro, 2009). With as many as 240 different enzyme complexes, these E3s control a broad array of biological processes (Skaar et al. , 2013). CRLs comprise seven distinct cullin–RING cores, each of which interacts with its own dedicated set of adaptor–substrate receptor complexes. Although ubiquitination by CRL enzymes is often regulated by covalent modifications of the substrate that stimulate binding to the substrate receptor, the CRL enzymes themselves are also subject to regulation. A key mechanism that controls the activity of all known CRLs is the conjugation of the ubiquitin-like protein Nedd8 to a conserved lysine residue in the cullin subunit (e. g. K720 in human Cul1) (Enchev et al. , 2015). The available structural and biochemical data indicate that Nedd8 conjugation (neddylation) stabilizes a profound conformational change in the C-terminal domain of the cullin. It loosens the interaction of the WHB domain with the RING subunit, allowing both of them to sample a greater conformational space (Duda et al. , 2008), thereby enhancing the ability of the RING domain to promote ubiquitin transfer to substrate (Duda et al. , 2008; Saha and Deshaies, 2008; Yamoah et al. , 2008). In addition to direct effects on ubiquitin ligase activity, Nedd8 also protects Skp1/Cul1/F-box (SCF) complexes from the substrate receptor exchange factor (SREF) Cand1 (Pierce et","Just like you might clear out the old food in your refrigerator to make room for new groceries, cells constantly break down existing proteins to provide space for new ones. The enzymes that generally carry out the first step of this breakdown process are called ubiquitin ligases and human cells make hundreds of different ones. These ubiquitin ligases are not always active and a large group of them can be switched off by a group of proteins known as the COP9-Signalosome (or CSN for short). To achieve this, CSN recognizes and cuts off a structure called Nedd8 from these ubiquitin ligases. However, CSN itself remains inactive until it finds and binds to ubiquitin ligases that have Nedd8 attached. Mosadeghi et al. have now used biophysical techniques to study",380,128,0.3368
dialogsum,"#Person1#: hi. Could you give me a hand with this report? #Person2#: sure. I'd be happy to give you some hints and advice. #Person1#: thanks. Would you mind taking a look at the layout? Do you think it's appropriate? I want it to be formal, but not boring to look at. #Person2#: it looks good to me. I would suggest that you put the client's logo and our logo on each page. The bosses seem to like that. #Person1#: that's an excellent suggestion. I can easily do it on the computer. #Person2#: why don't you use a different font the headings? They'll be more distinct. #Person1#: I'll take that suggestion too. How about the content? #Person2#: I think you'Ve included all the essential things. You might want to make the conclusion a little longer. Restate your reasons clearly. #Person1#: is it ok to include the pictures? #Person2#: definitely! I would include one or two on each page if possible. Remember that you should make the report as eye-catching as possible. #Person1#: thanks for those ideas. I'll get to work on them right away.",#Person1# asks for feedback on a report. #Person2# gives some suggestions on the layout. #Person1# is grateful and will start to work on them right away.,183,26,0.1421
dialogsum,"#Person1#: Could you have my car ready at 5:00 please? #Person2#: The damage is very serious. #Person1#: But I have to use it this afternoon. How about 5: 30? #Person2#: Well, I'll do my best. I promise you can take it at 5:15.",#Person2# promises #Person1# to have #Person1#'s car ready at 5:15.,43,10,0.2326
dialogsum,"#Person1#: You must like to dance, right. #Person2#: I'd love to. Do you often come here to dance? #Person1#: Yes, I like the old style dance, such as waltz , rumba and so on. They are quite graceful. #Person2#: You are waltzing quite wonderfully. It's great to dance with a experience and talent partner. #Person1#: Thank you for saying. I think you are light on your toes too. Oh, the music starts again, would you like to have another dance, miss? #Person2#: Ok, that would be great. Do you like modern dance? I don't care for it. #Person1#: Neither do I. I don't like any kind of modern dances all.",#Person1# and #Person2# are dancing. #Person1# likes old-style dance. They both don't like modern dance.,110,15,0.1364
scientific_lay_summarisation-elife-norm,"Parkinson' s disease (PD) genes PINK1 and parkin act in a common pathway that regulates mitochondrial integrity and quality. Identifying new suppressors of the pathway is important for finding new therapeutic strategies. In this study, we show that MUL1 suppresses PINK1 or parkin mutant phenotypes in Drosophila. The suppression is achieved through the ubiquitin-dependent degradation of Mitofusin, which itself causes PINK1/parkin mutant-like toxicity when overexpressed. We further show that removing MUL1 in PINK1 or parkin loss-of-function mutant aggravates phenotypes caused by loss of either gene alone, leading to lethality in flies and degeneration in mouse cortical neurons. Together, these observations show that MUL1 acts in parallel to the PINK1/parkin pathway on a shared target mitofusin to maintain mitochondrial integrity. The MUL1 pathway compensates for loss of PINK1/parkin in both Drosophila and mammals and is a promising therapeutic target for PD. Parkinson' s disease (PD) is the second most common neurodegenerative disorder and there is no cure for this progressive illness (Guo, 2012). Mutations in PINK1, a mitochondria-localized serine–threonine kinase, and Parkin, an E3 ubiquitin ligase, lead to autosomal recessive forms of the disease (Kitada et al. , 1998; Valente et al. , 2004). Genetic studies in Drosophila first demonstrated that PINK1 and parkin act in the same genetic pathway, with PINK1 positively regulating parkin, to regulate mitochondrial integrity and function (Clark et al. , 2006; Park et al. , 2006; Yang et al. , 2006). Mitochondrial morphology is maintained by a balance between two opposing actions, mitochondrial fusion that is promoted by mitofusin (mfn) and mitochondrial fission that is controlled by Dynamin-related protein 1 (Drp1) (Chan, 2012; Nunnari and Suomalainen, 2012). Genetic studies in Drosophila have shown that downregulation of mfn or overexpression of drp1 suppresses multiple phenotypes associated with lack of PINK1 or parkin, including defects in mitochondrial integrity, cell death, tissue health, and flight ability (Deng et al. , 2008; Poole et al. , 2008; Yang et al. , 2008). Parkin ubiquitinates Mfn and promotes Mfn degradation (Poole et al. , 2010; Ziviani et al. , 2010). However, it is not clear if increased mfn or decreased drp1 levels are sufficient to cause the phenotypes observed in PINK1 or parkin mutants. In addition to mitochondrial dynamics, the PINK1/Parkin pathway promotes mitophagy, selective autophagic degradation of defective mitochondria in","Parkinson' s disease is the second most common neurodegenerative disorder. Symptoms include tremors, rigidity, and slowness, as well as dementia and depression. While most cases of Parkinson' s disease have no known genetic cause, mutations in either of two genes—PINK1 or parkin—are known to lead to the disease. PINK1 and parkin belong to a single pathway that regulates the structure and function of mitochondria, the organelles that generate energy inside cells. Identifying inhibitors of this pathway is critically important for development of future therapies. In addition, previous studies showed that mice with mutations in PINK1 or parkin, as opposed to those in humans and flies, display subtle signs of Parkinson' s disease: the fact that these are weak suggests that other unknown proteins or cellular pathways might compensate",380,128,0.3368
dialogsum,"#Person1#: No. Just let me see a doctor. I'm worried about my arm. #Person2#: Be brave, sir. It won't be long. I will fill out the form for you. What is your name? #Person1#: Steve Schliessman. S C H L I E S S M A N. #Person2#: Alright Steve. Your social security number? #Person1#: 349-95- 8821. #Person2#: Do you have medical insurance? #Person1#: Yes, I do. Blue Cross. #Person2#: Do you have your insurance card with you? #Person1#: No, I don't. #Person2#: Well, you can call it in later. You can phone us. #Person1#: Can I sit down now? #Person2#: First I need to get your address. Try to move your arm as little as possible.","#Person2# helps Steve Schliessman, who worries about his arm, to fill out the form before Steve sees the doctor.",117,19,0.1624
scientific_lay_summarisation-elife-norm,"Bioluminescence imaging (BLI) is ubiquitous in scientific research for the sensitive tracking of biological processes in small animal models. However, due to the attenuation of visible light by tissue, and the limited set of near-infrared bioluminescent enzymes, BLI is largely restricted to monitoring single processes in vivo. Here we show, that by combining stabilised colour mutants of firefly luciferase (FLuc) with the luciferin (LH2) analogue infraluciferin (iLH2), near-infrared dual BLI can be achieved in vivo. The X-ray crystal structure of FLuc with a high-energy intermediate analogue, 5’-O-[N- (dehydroinfraluciferyl) sulfamoyl] adenosine (iDLSA) provides insight into the FLuc-iLH2 reaction leading to near-infrared light emission. The spectral characterisation and unmixing validation studies reported here established that iLH2 is superior to LH2 for the spectral unmixing of bioluminescent signals in vivo; which led to this novel near-infrared dual BLI system being applied to monitor both tumour burden and CAR T cell therapy within a systemically induced mouse tumour model. Bioluminescence imaging (BLI) is used extensively for the sensitive, longitudinal and high-throughput monitoring of biological processes in vivo (Xu et al. , 2016; Paley and Prescher, 2014; Mezzanotte et al. , 2017; Yao et al. , 2018; Yeh and Ai, 2019). Bioluminescence light emission is produced through the catalysis of a small molecule substrate, most commonly D-luciferin (D-LH2), by a luciferase enzyme. The mutagenesis of bioluminescent enzymes has improved the sensitivity and accuracy of BLI in small animals (Branchini et al. , 2010), (Iwano et al. , 2018). However, despite its widespread use in scientific research, BLI is still largely restricted to tracking a single parameter in vivo. The ability to discretely monitor two biological parameters (dual-BLI) simultaneously within a single animal is highly desirable (Xu et al. , 2016) with potential uses ranging from the monitoring of tumour burden alongside cellular therapy, to the visualisation of dynamic biological processes such as protein-protein interactions (Prescher and Contag, 2010). Previous approaches to dual-BLI have been disappointing. The use of multiple bioluminescent proteins which catalyse different substrates is the most frequently used method but suffers from a number of limitations. Sequential substrate administration is normally required, in addition this method commonly employs a combination of a coelenterazine and a D-LH2 utilising luciferase (with the blue emission from the former being heavily absorbed compared to the yellow-green emission","Fireflies and some other insects glow to attract mates or prey. This so-called bioluminescence occurs when an enzyme called luciferase modifies the molecule luciferin, which can then emit bright yellow-green light. The gene that encodes the luciferase enzyme has been introduced into cells from mammals, including cancer cells. In the presence of luciferin, these cells begin to glow. The brightness of the bioluminescence depends on how many cancer cells are growing and dividing. The light is bright enough for the cancer cells making luciferase to be transplanted into mice so their behaviour can be examined. However, blood and other tissues absorb the yellow-green light, making it hard to see the cancer cells deep within a mouse. To circumvent this problem, researchers designed a new type of luciferin, called",380,128,0.3368
dialogsum,"#Person1#: Where do you wish me to take you, sir? #Person2#: Please take us to Harvard University. By the way, is it far from here? #Person1#: It takes about half an hour to get there. #Person2#: OK. #Person1#: Here we are, sir. #Person2#: How much do I owe you? #Person1#: It's 35 dollars on the meter. #Person2#: Here's 50 dollars. Keep the change. #Person1#: Thank you. Have a nice day.",#Person1# drives #Person2# to Harvard University. #Person2# pays the bill.,70,10,0.1429
dialogsum,"#Person1#: I feel absolutely horrible. My temperature is 41 degrees Celsius, and I've got a headache and a runny nose. #Person2#: Do you have any other symptoms? #Person1#: I've also got a terrible stomach-ache. Is my face still swollen? #Person2#: Just a little. Has your toothache gone now? #Person1#: Yes, for the most part. It doesn't feel as bad as my other ailments, anyway. #Person2#: How about your tongue? Does it still hurt? #Person1#: No, the burn ointment seemed to take effect right away. I think it's already healed. #Person2#: How did you get that burn again? #Person1#: I scalded on the hot coffee a few days ago. #Person2#: You haven't had much luck lately, have you? #Person1#: No, but I'm sure I'll get better soon. #Person2#: When's the last time you took your tablets? #Person1#: I took the red ones just before lunch and the white ones just after lunch. #Person2#: I think it's time you took another dose of each. What would you like to drink with them? #Person1#: Just some water, please. Do you have any ointment for my nose? It feels so itchy after blowing my nose so much. #Person2#: Sure, I'll just go and get it now. what would you like to eat? Some soup? #Person1#: that sounds good. #Person2#: soup always makes me feel better when I'm sick. I hope it makes you feel better, too.","#Person1# tells #Person2# about #Person1#'s symptoms of a headache, a runny nose, a terrible stomach-ache and a toothache. Then #Person2# asks #Person1# to take another dose of tablets and suggests some soup for #Person1#'s itchy nose.",232,36,0.1552
dialogsum,"#Person1#: Excuse me, I'm looking for the Alanis Morrissette album Supposed Former Infatuation Junkie. #Person2#: Let's see. If we have it, it should be over there under M. ( He looks through the CDs. ) Hmm, it looks like we've sold out of that one, but we should be getting some more copies in soon. If you want, we can order it for you. #Person1#: That's okay, I'll just check back later. Do you have the new Sting album? #Person2#: Yes, it's right over here. #Person1#: Great. One last question, where is your jazz section? #Person2#: Back there against that wall. #Person1#: Oh, I see it. Thanks for your help. #Person2#: No problem.","#Person1# looks for a particular CD, but it's sold out. #Person2# could order it for #Person1#. #Person1# then asks for the new Sing album and the jazz section.",113,28,0.2478
pubmed-summarization,". after centrifugation , serum samples were divided into aliquots and immediately stored at 80c at the local site . participants who reported being pregnant or using exogenous hormones within 6 months of enrollment were not eligible for the nyuwhs cohort or for case - control selection from nshds . in the nshds , cohort linkages to regional and national cancer registries and to all - cause mortality registries were used to capture cases of incident invasive epithelial ovarian cancer . in the nyuwhs cohort , case ascertainment was achieved through self report on followup questionnaires and through linkages with state tumor registries in new york , new jersey , and florida . medical records were obtained to verify reported events . as of november 1 , 2005 , a total of 192 invasive ovarian cancer cases ( 107 from the nshds and 85 from the nyuwhs ) had been identified . twenty - two nonepithelial ovarian cancer cases ( 8 from the nshds and 14 from the nyuwhs ) were excluded from this study because they did not meet the criteria of being invasive epithelial ovarian cancer . for the current study , there were a total of 170 invasive eoc cases ( 71 from nyuwhs and 99 from nshds ) . however , two cases from the nshds cohort had only dna available for analysis , and were only included in the main vdr genotyping analysis . for each case , two controls were randomly selected from cohort members who were alive and free of cancer at the time of diagnosis of the case . controls were also matched to the case on cohort ( nyuwhs or nshds ) , age at entry ( 6 months ) and date of blood donation ( 15 days ) . seventeen cases from the nyuwhs cohort had only one eligible matched control because 10 controls had a complete bilateral oophorectomy before the diagnosis date of the case and seven cases could not be sufficiently closely matched to a second control on date of blood donation ( strict matching is required to control for seasonal effects of vitamin d ) . of the potential 323 eligible controls in total ( 198 from the nshds , 125 from the nyuwhs ) , seven","we conducted a nested case - control study within two prospective cohorts , the new york university women 's health study and the northern sweden health and disease study , to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin d ( 25(oh)d ) and the risk of subsequent invasive epithelial ovarian cancer ( eoc ) . the 25(oh)d levels were measured in serum or plasma from 170 incident cases of eoc and 373 matched controls . overall , circulating 25(oh)d levels were not associated with the risk of eoc in combined cohort analysis : adjusted or for the top tertile versus the reference tertile , 1.09 ( 95% ci , 0.592.01 ) . in addition , there was no evidence of an interaction effect between vdr",380,128,0.3368
pubmed-summarization,"study was to investigate the effects of an 8-week mat - based pilates exercise training program on the static and dynamic balance abilities of patients with chronic stroke . thirty participants were initially recruited from the rehabilitation center for the disabled located in uijeongbu , gyeonggi province , korea . the inclusion criteria stated that each participant must be at least 2 years post stroke , medically stable with a physician release granting approval to initiate and complete an exercise program , able to walk independently without an assistive device , and willing to participate in a pilates exercise class . participants were excluded if they had visual impairment , hearing damage , uncontrolled high blood pressure , or were unable to understand the nature of the experiment . participants who were receiving physical therapy separately were also excluded from this study . in total , 10 participants were excluded because they were participating in individual physical therapy sessions , and one participant dropped out of the control group due to hospital admission during the intervention period . finally , nineteen individuals with chronic hemiparetic stroke participated in the study ( age , 64.7 6.9 years ; height , 161.7 7.9 ; and weight , 67.0 11.1 ) . the research protocol was approved by the institutional review board of sahmyook university . following participant selection , they were randomized into two groups , a pilates exercise training group ( pg ) and a control group ( cg ) . during the intervention period , the pg was given pilates exercise training , while the cg was not given any exercises or treatment at the center for the disabled . the pilates training program was based on mat classes lasting one hour per class , three times a week for 8 weeks . in this study , two certified pilates instructors and one physical therapist were in charge of the class . one instructor demonstrated movements for patients to follow and the other instructor and the physical therapist assisted patients with the exercise . all movements included in the pilates training was based on 8 1 set of 8 repetitions per exercise . to improve core stability , breathing exercises were conducted in a sitting position before and after all","[ purpose ] the purpose of this study was to analyze the effects of pilates exercise on static and dynamic balance in chronic stroke patients . [ subjects and methods ] nineteen individuals with unilateral chronic hemiparetic stroke ( age , 64.7 6.9 years ; height , 161.7 7.9 cm ; weight , 67.0 11.1 kg ) were randomly allocated to either a pilates exercise group ( pg , n=10 ) or a control group ( cg , n=9 ) . the pg attended 24 exercise sessions conducted over an 8-week period ( 3 sessions / week ) . center of pressure ( cop ) sway and cop velocity were measured one week before and after the exercise program and compared to assess training effects . [ results",380,128,0.3368
dialogsum,"#Person1#: Hello, this is the International Student Office. This is Leah. How may I help you? #Person2#: This is Nathaniel Brown, from English Department. I'd like to speak to Miss Collins about my accommodation situation. #Person1#: Well, I'm sorry. She is out for lunch at the moment. Can I take a message? #Person2#: Sure. Can you have her call me back on my cell phone number? #Person1#: OK. What's your number? #Person2#: It's 07787367688. #Person1#: Let me repeat that to you. That's 077873676688, right? #Person2#: No, there's no double 6. It's just 07787367688. #Person1#: I got it. When should I have her call you back? #Person2#: Anytime before 6:00 PM tonight. #Person1#: OK, Nathaniel. I'll have Miss Collins call you back sometime tonight before 6:00 PM.","Nathaniel Brown calls to speak with Miss Collins, but she's out. Thus, #Person1# notes down his number and will have Collins call him back.",126,24,0.1905
pubmed-summarization,"diabetes mellitus is a growing health problem worldwide causing severe and costly complications including blindness , cardiac and kidney diseases ( 1 ) . according to shaw et al ( 2010 ) , the world prevalence of diabetes among adults will increase to 7.7% , and affect 439 million adults by 2030 . between 2010 and 2030 , there will be a 69% increase in number of adults with diabetes in developing countries and a 20% increase in developed countries ( 2 ) . approaches to the control of blood glucose and prevention of hyperglycemia are central to the treatment of diabetes mellitus . appetite suppressants , inhibitors of digestion , insulin secretagogues , insulin potentiators , insulin mimetics , stimulants of glucose utilization , inhibitors of gluconeogenesis and glucogenolysis are used to balance blood glucose . at present , none of these therapies either alone or in combination can redraw normal blood glucose homeostasis . additionally many limitations exist in the use of anti - diabetic drugs ; medicines available for management of diabetes exert serious side effects such as hepatotoxicity , abdominal pain , flatulence , diarrhea , and hypoglycemia . also after prolonged treatment , drug resistance traditional medicines play an important role as starting material for drug discovery . for documentation of ethnopharmacological knowledge , many comprehensive field surveys have been conducted all over the world for years and many plants used against diabetes have been recorded ( 710 ) . antidiabetic activities of plants used against diabetes in turkey as folk medicine were studied in detail by our research group . in our research on in vivo antidiabetic activity of traditional medicines from 2000 , seven plant species including gentiana olivieri griseb ( gentianaceae ) , helichrysum graveolens ( bieb . ) austriacum ) ] ( loranthaceae ) were evaluated for their antidiabetic activity ( 1116 ) . due to their promising antidiabetic effect in in vivo studies the plants used in this study are well known and widely consumed as food and medicine in different regions of anatolia . aerial parts of g. olivieri are used as bitter tonic , appetizer , antidiabetic , antipyretic , stomachic , and for mental disorders . gentians are also used in small amounts as food and beverage","objective(s):ethnopharmacological field surveys demonstrated that many plants , such as gentiana olivieri , helichrysum graveolens , helichrysum plicatum ssp . plicatum , juniperus oxycedrus ssp . oxycedrus , juniperus communis var . saxatilis , viscum album ( ssp . album , ssp . austriacum ) , are used as traditional medicine for diabetes in different regions of anatolia . the present study was designed to evaluate the in vitro antidiabetic effects of some selected plants , tested in animal models recently.materials and methods:-glucosidase and -amylase enzyme inhibitory effects of the plant extracts were investigated and acarbose was used as a reference drug . additionally , radical scavenging capacities were determined using 2,2-azino - bis(3-ethylbenzothiazoline-6-sulphonic acid ) abts radical cation scavenging assay and total phenolic content of the extracts",380,128,0.3368
pubmed-summarization,"ideas were exchanged within the design team ( two program officers and one computer experts ) and final design principles of the system were derived . the development team and the program officers assessed the responses from field staff in the current system , which were stored in a microsoft structured query language server , to identify patterns that could be used to define relevant answers . the output was a list of possible automatic sms text message replies through symbian supported mobile . eid follow - up system was designed as a web - based tool using java swing framework which generates automated sms and e - mails for reminding the field level staff for follow - up of hiv - exposed babies 7 days prior to the follow - up date . the information was collected through field tested excel - based hiv positive pregnant women line - list format incorporating the major key indicators of pptct program . this line list is generated at the hiv testing facilities where the pregnant woman is detected hiv positive . format is then shared through e - mail with hiv treatment facilities to update the treatment details of the pregnant women . the line list is further updated on periodic basis whenever the pregnant women is accessing the pptct services at hiv facilities . the individual records in the line list are monitored and crossverified by district and state level officials during the supervisory visits to these centers on periodic basis . the data collected through line list from different districts is then compiled by the state . for the software , we used the variables like name of mother and child , date of birth of baby , mobile number of counsellor and district supervisor , email of district official , and name of the hiv testing facility . database of hiv positive mother and her exposed child with date of birth was updated on monthly basis . deliberation with various stakeholders on development of tracking system led to use of mobile technology in follow - up mechanism . the software developed sends required information ( name of mother / child , facility name , and follow - up date ) to the counsellor of the respective facility and","objectivethe purpose of this study is to assess the utility of web - based mobile technology monitoring tool , for ensuring linkages , and tracking of hiv - exposed child until 18 months of age.methodsthe early infant diagnosis ( eid ) follow - up system was designed as a tool for reminding the field level staff for follow - up of hiv - exposed babies . using java swing framework , software was developed which generates automatic advance sms alerts regarding patient information to the counsellor of the respective integrated counselling and testing center and district supervisor , 7 days prior to due dates . simultaneously , system generated e - mail is sent to district program officer for monitoring and updating the line-list.resultsbefore the introduction of eid",380,128,0.3368
scientific_lay_summarisation-elife-norm,"(SC) (Dorris et al. , 1997). Since variability in the onset and rate of accumulation of low-frequency activity is correlated with eventual saccade reaction times (Hanes and Schall, 1996; Ratcliff and Rouder, 1998; Usher and McClelland, 2001), it is thought that this activity primarily dictates when the movement is supposed to be initiated. However, it is unclear how (or if) downstream motor networks distinguish activity related to movement preparation from the command to execute one. One possibility is that the activity of premotor neurons undergoes a transformation from representing preparation into movement-related commands at a discrete point in time (Thompson et al. , 1996; Juan et al. , 2004; Schall et al. , 2011), when the activity reaches a movement initiation criterion, thereby acquiring the potential to generate a movement. Indeed, this is the basis for stochastic accumulator models of saccade initiation, in which premotor activity must reach a threshold level in order to generate the movement (Hanes and Schall, 1996; Ratcliff and Rouder, 1998; Zandbelt et al. , 2014). Recent work in the skeletomotor system has also suggested that neuronal population activity undergoes a state space transformation just prior to the movement, thus permitting movement preparation without execution before the transformation (Churchland et al. , 2012; Kaufman et al. , 2014; Elsayed et al. , 2016). These related views dictate that movement planning and execution are implemented as serial processes in the motor system. Alternatively, it is possible that neurons in sensorimotor structures represent these signals concurrently, gearing up to execute a movement in proportion to the strength of the planning activity. In other words, preparatory build-up of neural activity can multiplex higher order signals while simultaneously relaying those signals to effectors; we call this latter property the ‘motor potential’ of preparatory activity. This idea is in fact the premise of the premotor theory of attention (Rizzolatti et al. , 1987; Hoffman and Subramaniam, 1995), and represents a latent behavioral manifestation of movement preparation. How might we test for the presence of a motor potential in low frequency preparatory activity? The following thought experiment helps illustrate one approach. Consider the activity of a premotor neuron accumulating over time. Under normal circumstances, inhibitory gating on the saccadic system is released at an internally specified time, possibly when activity crosses a","Most of us are familiar with the experience of revving up the engine in anticipation of a red traffic light turning green. The revving, which enables us to move forward as soon as the brakes are released, reflects our ability to plan actions in advance. The brain shows broadly analogous behavior when preparing to move parts of the body. A few hundred milliseconds before we move our eyes, for example, brain regions responsible for eye movements start to gradually ramp up their activity. Returning to the car analogy, revving up the engine will not cause the vehicle to move until we also release the brakes. In the brain, inhibitory mechanisms analogous to a brake prevent the increasing neural activity from triggering movement. The brain is thought to apply",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1- (MOF) -containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters and TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome, yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA. MSL depletion leads to decreased Tsix expression, reduced REX1 recruitment, and consequently, enhanced accumulation of Xist and variable numbers of inactivated X chromosomes during early differentiation. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs. Histone acetyl transferases (HATs) are among the key architects of the cellular epigenetic landscape as the acetylation of histones is unanimously associated with transcriptionally active domains. Many HATs also have the ability to acetylate non-histone proteins extending their influence to diverse cellular pathways inside and outside of the nucleus (reviewed in Sapountzi and Cote, 2011). Based on their catalytic domains, the HATs are classified into two major families, GCN5 N-acetyl transferases (GNATs) and MYST HATs (named after the founding members MOZ, Ybf2/Sas3, Sas2, Tip60), that encompass diverse sets of protein complexes. The individual complex members enhance and modulate the enzymes' activities, guiding the versatile HATs towards specific functions. GCN5, for example, is part of SAGA, ATAC, and SLIK complexes that are associated with distinct histone tail modifications and differential gene regulation (reviewed in Lee and Workman, 2007; Nagy et al. , 2010). In contrast, one of the well-known members of the MYST family, MOF (also known as: KAT8, MYST1), is rather substrate-specific for lysine 16 of histone H4 (H4K16) (Akhtar and Becker, 2000) and its interaction partners are thought to mainly alter the specificity and extent of MOF' s H4K16 acetylation (H4K16ac). As part of the male-specific lethal (MSL) complex (MSL1, MSL2, MSL3, MOF, MLE, roX1 and roX2 lncRNAs) in Drosophila melanogaster, MOF is recruited to the single X chromosome of male flies. The subsequent spreading of H4K16 acetylation results","Gene expression is controlled by a complicated network of mechanisms involving a wide range of enzymes and protein complexes. Many of these mechanisms are identical in males and females, but some are not. Female mammals, for example, carry two X chromosomes, whereas males have one X and one Y chromosome. Since the two X chromosomes in females contain essentially the same set of genes, one of them undergoes silencing to prevent the overproduction of certain proteins. This process, which is called X-inactivation, occurs during different stages of development and it must be tightly controlled. An enzyme called MOF was originally found in flies in two distinct complexes—the male-specific lethal (MSL) complex, which forms only in males, and the non-specific lethal (NSL) complex, which is ubiquitous in both males",380,128,0.3368
pubmed-summarization,"used in this study for the determination of rheumatoid factor . radiographic evaluation of the tmj was carried out using the conventional projections , transcranial and opg and advanced computed tomography ( ct ) . transcranial views of right and left tm joints of all patients were taken using siemens vertix 100 extraoral radiographic machine with a setting of 70 - 72 mas and 74 - 82 kvp on an average . orthopantomographs were taken using the villa rotograph machine with a machine setting of 70 - 75 kvp and 60 mas . ten patients were subjected to ct scans using the toshiba 2d ct scanner model- 300 s and with a machine setting of 150 kvp and 250 mas on an average . pa views of the hand and wrist were made with the siemens vertix 100 extra oral radiographic machine with a setting of 55 kvp and 6 - 8 mas on an average . detailed analysis of the hand and wrist radiographs was performed based on larsen 's gradings [ table 1 ] . for the tmj , the gradings were restricted to the condyle proper , as the glenoid fossa could not be clearly visualized in all the radiographs . since the anatomy of the tmj is different from that of the hand and foot joints , a modification of the grading system proposed by larsen et al . these radiographs were assessed individually by a medical and oral radiologist . during the process of deliberation the conclusion arrived at by the examiners were noted . radiographic interpretation ( gradings ) of hand and wrist joints from pa view modified grading system for evaluation of tmj radiographs radiographic interpretation ( gradings ) of tmj from transcranial , opg and ct student 's t - test was applied for the statistical analysis of the data obtained . patients with a diagnosis of ra according to the american rheumatism association 's revised criteria for rheumatoid arthritis . only patients over the age of 18 patients with joint involvement other than the tmj / hand ( mcp ) and wrist joint were not included . patients with myofascial pain , tmj ankylosis , headache , patients with known history of previous trauma , cervical spondylosis and pregnant females were","background : a review of literature revealed that , although the involvement of temporomandibular joint ( tmj ) in rheumatoid arthritis ( ra ) patients is not uncommon , variation in presentation persist . comparative studies of bony changes in the right and left tmj with the right and left peripheral hand ( metacarpophalangeal - mcp)/wrist joints have not been done , to the best of our knowledge.materials and methods : in this cross - sectional study , the temporomandibular and hand ( mcp ) and wrist joints of fifteen rheumatoid arthritis patients were evaluated with questionnaires , clinical and lab assessment and radiographically using conventional radiographs and computed tomography . students t - test was applied for the statistical analysis of the data obtained and a p",380,128,0.3368
dialogsum,"#Person1#: Does anyone need a drink? #Person2#: I'll take one. How's the cooler situation? #Person1#: It's still stocked, and there's plenty of ice. Here you are-cheers! #Person2#: Cheers. You guys didn't drive, did you? #Person1#: No, we walked. Why, do you need us to carry some stuff home later? #Person2#: No, it's just that it's a holiday. With everyone out partying, there's a lot of drunk driving.",#Person1# and #Person2# are drinking happily at a party.,67,9,0.1343
dialogsum,"#Person1#: You've packed so many clothes Ben. #Person2#: Well, it is a business trip, and the weather will be different everywhere I go. #Person1#: I suppose on Sunday you'll travel in your jeans. #Person2#: Yes, that on Monday I'm going to meet the company boss, so will need my suit then, I can't wear jeans. #Person1#: What is happening on Tuesday? #Person2#: I'm visiting a factory in the south so I've packed these gray trousers, they are light and I won't need a jacket. It'll be 35 degrees. #Person1#: Oh then you're in the mountains on Wednesday. #Person2#: Yes, a jacket will be warm enough. I've got my coat for that day. #Person1#: Are you taking a sweater as well? #Person2#: There was an room in the suitcase. On Thursday I'll be by the sea where we spent our honeymoon. So I'm taking my swim shorts. #Person1#: And what about Friday? #Person2#: I'm having lunch with some colleagues. I'll wear that blue shirt you bought me. Look here it is, under the suit. #Person1#: Oh good.",Ben is packing clothes for a business trip and tells #Person1# what he is going to wear for each day.,176,20,0.1136
scientific_lay_summarisation-elife-norm,"changing expression noise and average expression level. Here, we directly estimate the effects of changing expression noise on fitness independently from changes in average expression level for the TDH3 gene of Saccharomyces cerevisiae. TDH3 encodes an isozyme of the yeast glyceraldehyde-3-phosphate dehydrogenase (GAPDH) involved in glycolysis and gluconeogenesis (McAlister and Holland, 1985) as well as transcriptional silencing (Ringel et al. , 2013), RNA-binding (Shen et al. , 2014) and possibly antimicrobial defense (Branco et al. , 2014). Variation in this gene’s promoter affecting expression noise has previously been shown to be a target of selection in natural populations (Metzger et al. , 2015). To assess the impact of changes in expression noise on fitness at different expression levels, we generated mutant alleles of the TDH3 promoter that covered a broad range of average expression levels and expression noise. We find that increases in expression noise are detrimental when the average expression level of a genotype is close to the fitness optimum, but beneficial when the average expression level of a genotype is further from this optimum. This pattern was reproduced by a simple computational model that links expression in single cells to their doubling time​ to predict population fitness. We used this ​individual-based ​model to explore the fitness effects of a broader ​combination of average expression levels and expression noise than were explored empirically, showing that not only do the fitness effects of changing expression noise depend on the average expression level, but that the​ fitness effects of changing average expression level also depend upon the amount of expression noise. To disentangle the effects of changes in average expression level and expression noise on fitness, we examined a set of TDH3 promoter (PTDH3) alleles with a broad range of activities. For each allele, we measured the average expression level and expression noise by cloning the allele upstream of a yellow fluorescent protein (YFP) coding sequence, integrating this reporter gene (PTDH3-YFP) into the HO locus, and quantifying fluorescence in living cells using flow cytometry in six replicate populations per genotype (1A). The fluorescence value of each cell was transformed into an estimated mRNA level (1A) based on the relationship between fluorescence and YFP mRNA abundance (1B, C). The average expression level of a genotype was then calculated by averaging the median","Single-celled organisms that reproduce by dividing, like yeast, can create whole populations of genetically identical cells. However, some differences will exist among such cells, even when they have all experienced the same environment. These differences are known as “noise”. By definition, noise is not caused by differences in DNA sequence, but some DNA sequences are noisier than others (i. e. they cause more differences among cells). Because the amount of noise can be under genetic control, noise could evolve due to natural selection. Scientists often study noise at the level of gene expression – in other words, how many RNA or protein molecules are produced from each gene within each cell. Prior work has suggested that this type of noise can affect how often individual cells divide in",380,128,0.3368
dialogsum,"#Person1#: Doctor, what is the best way to stay healthy? #Person2#: Having a good diet is probably the most important thing. #Person1#: It is very confusing to know what to eat. #Person2#: You need plenty of fruits and vegetables, small amounts of protein, and whole grains. #Person1#: Are there certain things that I should avoid? #Person2#: You shouldn ' t consume too much sugar or caffeine. Also, watch your intake of fatty food. #Person1#: After watching my diet, what else should I do? #Person2#: You need to stop smoking, and make sure that you get 30 minutes of exercise every day. #Person1#: Can I have a glass of wine now and then? #Person2#: As long as you don ' t overdo it, a glass of wine a day should be OK.",#Person2# tells #Person1# the best way to stay healthy is having a good diet and advises #Person1# to stop smoking and get exercise.,131,23,0.1756
dialogsum,"#Person1#: Hello, Sunshine Flower Shop. This is Shareen speaking. #Person2#: This is Tom Hanks. I'd like to order some flowers for my mother and have them sent to her apartment. #Person1#: Fine, Mr. Hanks. What kind of flowers do you want? #Person2#: I'd like to send a dozen red carnations. #Person1#: A dozen red carnations? Our long stem red carnations are selling for 12 pounds a dozen this weekend. They are really quite nice. #Person2#: Alright then, I'll take those. #Person1#: I need your complete address, Mr. Hanks. #Person2#: The address is number 84 MW Street. For the card, just write something simple. How about 'dear mom, all my love, Tom'? #Person1#: Of course. OK, when should they arrive? #Person2#: They should be there before 5 o'clock in the afternoon on June seventeenth. My mom's telephone number is 8456086363. Please call her first before you deliver them. #Person1#: That should be no problem. Just one more question, Mr. Hanks. How do you intend to pay for it? #Person2#: You can put it on my visa card. The number is KH 3272645. #Person1#: Got it. Bye. #Person2#: Bye, thanks.",Tom Hanks phones to order a dozen red carnations for his mother and then pays for them with #Person2#'s assistance.,188,20,0.1064
pubmed-summarization,"characteristics of the subjects are shown in table 1table 1.general characteristics of the subjects ( n=32)eg ( n=16)cg ( n=16)age ( years)50.9 ( 9.9)49.3 ( 10.7)weight ( kg)62.5 ( 11.0)63.5 ( 9.1)height ( cm)165.4 ( 6.9)166.9 ( 5.2)gender ( male / female)11/510/6affected side ( right / left)7/95/11lesion ( infarction / hemorrhage)10/69/7period since the onset of stroke ( months)7.9 ( 2.5)8.0 ( 2.4)values are presented as mean ( standard deviation ) ; eg : experimental group ( underwater treadmill walking training ) ; cg : control group ( overground treadmill walking training ) . values are presented as mean ( standard deviation ) ; eg : experimental group ( underwater treadmill walking training ) ; cg : control group ( overground treadmill walking training ) there were no significant differences in homogeneity of the subjects in general characteristics . the inclusion criteria were as follows : mini - mental state examination - korea score > 24 points ; able to walk independently for 20 minutes ; and no history of orthopedic or neurologic problems other than a stroke . all subjects provided written informed consent for participation in the study prior to its initiation . the patients participated in the training for 30 minutes / session , 3 sessions / week , for 6 weeks , from november 3 to december 12 , 2014 . warm - up exercises were performed for 5 minutes to induce muscle relaxation , and these were followed by utwt for 20 minutes , and cool - down exercises and stretching for the final 5 minutes to reduce muscle fatigue . hydro physio ( syspal limited , england ) , an underwater treadmill , was used at a velocity that was 36% of the overground gait speed at the start , and the velocity was gradually increased by 0.1 m / s until the subjects were walking as fast as possible7 . the subjects wore aqua shoes for safety . water temperature and depth were 34 c and up to the xiphoid process , respectively6 . rtm 500 ( biodex , usa ) , an overground treadmill , was used following the same procedure as the utwt . the isokinetic dynamometer ( biodex , usa ) was used to assess knee extension peak torque ( kept","[ purpose ] this study investigated the effects of underwater treadmill walking training on the peak torque of the knee in hemiplegic patients . [ subjects and methods ] thirty - two subjects , who were randomly allocated to an experimental group ( n=16 ) and a control group ( n=16 ) , performed underwater treadmill walking training and overground treadmill walking training , respectively , for 30 minutes / session , 3 sessions / week , for 6 weeks . an isokinetic dynamometer was used to assess the peak torque . [ results ] the subjects in the experimental group showed an increase in the peak knee extension torque compared to the control group . [ conclusion ] the results suggested that underwater treadmill walking training has",380,128,0.3368
pubmed-summarization,"increased compared with her previous brain imaging done 2 months back . her mental status continued to improve , and she had only one mild episode triggered by cough during the next two days before her discharge . repeat surgical resection of the tumor was recommended by the otolaryngology team , which the patient declined . based on the clinical features and eeg findings , the episodes observed in our patient are most consistent with cough syncope . the mechanism underlying cough syncope is not definitively established , but it is postulated that coughing increases intrathoracic and intraabdominal pressures leading to a transient increase in icp . increased icp , in turn , causes a decrease in cerebral perfusion pressure which , if it drops below a critical level , may result in global cerebral hypoperfusion leading to syncope . transient cerebral circulatory arrest has been demonstrated by transcranial doppler measurements during cough syncope . our patient also had a drop in blood pressure and heart rate but probably not sufficient to cause syncope by itself . cough syncope has been associated with posterior fossa mass lesions or tonsillar herniation and with hydrocephalus . it may be speculated that bouts of cough caused transient herniation of cerebellar tonsils obstructing csf flow that further contributed to the increase in icp during coughing . decrease in frequency of events following placement of evd to relieve icp lends support to this notion . paragangliomas are rare tumors of extraadrenal chromaffin cell origin that most commonly occur in the head and neck region . catecholamine - hypersecreting paraganglionomas are uncommon in the head and neck region , and most patients ( 95% ) with hypersecreting paraganglionomas have hypertension . hypotension accompanying syncope observed in our patient was not orthostasis - related ( the patient was always supine during spells ) and was most likely related to cough . identified a subset of patients with cough syncope who lacked a blood pressure overshoot ( expected response ) after the relief of straining during valsalva maneuver . the authors postulate that cough syncope in these patients might be the result of delayed recovery from hypotension that follows a paroxysm of cough , and this was likely contributing to global cerebral hypoperfusion in our patient . this","we present an unusual case of recurrent cough syncope in a 43-year - old woman , which was initially thought to be seizures . syncopal episodes were triggered by paroxysms of cough and were characterized by unresponsiveness and myoclonic jerks in her extremities . she had a left - sided glomus jugulare tumor that extended into the posterior cranial fossa with evidence of worsening communicating hydrocephalus on brain imaging . we postulate that bouts of cough produced increased intracranial pressure both by raising intrathoracic and intraabdominal pressures as well as by transient obstruction to cerebrospinal fluid flow secondary to intermittent tonsillar herniation during cough . this resulted in diffuse decrease in cerebral blood flow causing syncope . the patient 's syncopal episodes decreased in frequency once an external",380,128,0.3368
dialogsum,"#Person1#: Hello? #Person2#: Hi Vicky. #Person1#: Are you there yet? #Person2#: Yes. #Person1#: I just got off the subway. I'm almost there. Sorry I'm late. #Person2#: That's no problem. I just wanted to tell you I'm inside. #Person1#: Where are you? #Person2#: On the second floor. #Person1#: Should I come to the second floor or do you want to come to the first floor? #Person2#: Come upstairs. #Person1#: What? #Person2#: Oh, Can you hear me OK? I said, come to the second floor. #Person1#: Oh, OK. What are you doing there? #Person2#: Just looking at some books on how to learn English. #Person1#: Do you want to get something to eat later? #Person2#: No, I'm still full from dinner. #Person1#: What do you want to do? #Person2#: I don't know for sure. When you get here we'll talk about it. #Person1#: OK, see you soon. #Person2#: Bye.",Vicky tells #Person2# she got off the subway and almost arrives. #Person2# is on the second floor looking at some books. They will discuss what to do later when they meet.,147,31,0.2109
pubmed-summarization,"to personalize the process of monitoring someone activated sensors , generated alarms , and danger zone . the use of computers to help people stay at home has been the subject of many research projects . some of them are quite ambitious and regroup many partners . in this section , we describe a selection of three projects designed to assist people in their living environment . we expect to give the reader an overview of the advancement in this area and also the bases our project is laying on . the selection shows different hardware and software problematics ( communication networks , system interoperability , data analysis , emergency handling , and alerts filtering ) . the prosafe project attempts to automatically identify the daily activities of the monitored person . the processing of collected data is carried out on doctor 's request with an adapted interface . the final operational objective is to detect any abnormal behaviour such as a fall , a runaway , or an accident . the research objective is to gather characteristic data about the nightly or daily activities of the patient . more precisely , the system can describe events that took place during monitoring time time spent in bed or in the toilets , entering or leaving the bedroom , moving inside the home , build a database with all abnormal situations detected , andbuild statistics about past activities . at the hardware level , the system configuration uses a ground network ( a mobile version is also usable ) . currently acquisition and data processing are local , and monitoring is both local and distant . describe events that took place during monitoring time time spent in bed or in the toilets , entering or leaving the bedroom , moving inside the home , build a database with all abnormal situations detected , and build statistics about past activities . the interface for nurses allows them visualizing the patient state and abnormal situations ( alerts and alarms ) in the bedroom . as soon as an alarm is raised , a beeper calls a nurse . in the same time , doctors can access a database updated in real time with statistical data about the patient behaviour . experiments have been","this research takes place in the s(ma)2d project which proposes software architecture to monitor elderly people in their own homes . we want to build patterns dynamically from data about activity , movements , and physiological information of the monitored people . to achieve that , we propose a multiagent method of classification : every agent has a simple know - how of classification . data generated at this local level are communicated and adjusted between agents to obtain a set of patterns . the patterns are used at a personal level , for example to raise an alert , but also to evaluate global risks ( epidemic , heat wave ) . these data are dynamic ; the system has to maintain the built patterns and has",380,128,0.3368
scientific_lay_summarisation-elife-norm,"A key step in the de novo formation of the embryonic vasculature is the migration of endothelial precursors, the angioblasts, to the position of the future vessels. To form the first axial vessels, angioblasts migrate towards the midline and coalesce underneath the notochord. Vascular endothelial growth factor has been proposed to serve as a chemoattractant for the angioblasts and to regulate this medial migration. Here we challenge this model and instead demonstrate that angioblasts rely on their intrinsic expression of Apelin receptors (Aplr, APJ) for their migration to the midline. We further show that during this angioblast migration Apelin receptor signaling is mainly triggered by the recently discovered ligand Elabela (Ela). As neither of the ligands Ela or Apelin (Apln) nor their receptors have previously been implicated in regulating angioblast migration, we hereby provide a novel mechanism for regulating vasculogenesis, with direct relevance to physiological and pathological angiogenesis. In the vertebrate embryo, the formation of the large axial vessels, namely the dorsal aorta (DA) and the cardinal vein (CV), establishes a first circulatory loop and thereby the core of the developing cardiovascular system. Angioblasts are initially specified in the lateral plate mesoderm and migrate between the somites towards the midline, where they coalesce and assemble the DA and the CV underneath the notochord (NC) (1A, B–F, Video 1). 10. 7554/eLife. 06726. 003Figure 1Angioblast migration to the midline is not regulated by Vegf. (A–F) Schematic (A) and confocal (B–F) in vivo time-lapse imaging of angioblasts (green) and their migration in a Tg (fli1a: EGFP) y1 embryo, injected with H2B-mCherry mRNA (purple, all nuclei), dorsal views at indicated time points. Arrows indicate the initial migration to the midline, and the coalescing into the dorsal aorta (DA). (G–J) Loss of Vegf-signaling components by vegfaa/vegfab double morpholino (MO) injection (H) or in vegf receptor 2 (kdrl) mutants (J) does not affect angioblast migration. Confocal projections of Tg (fli1a: EGFP) y1 embryos in dorsal views at 17 hpf. For each condition, n > 15. : http: //dx. . org/10. 7554/eLife. 06726. 00310. 7554/eLife. 06726. 004Figure 1—source movie 1. Time-lapse movie showing angioblast (green) migration to the midline analyzed using Tg (fli1a: EGFP) y1 embryos injected with H2B-mCherry mRNA (purple, all nuclei). : http: //dx. . org/10. 7554/eLife. 06726. 00410. 7554/eLife. 06726. 005Figure 1— 1. Inhibition","The circulatory system enables blood to move around the body and deliver substances including nutrients and oxygen to the cells that need them. In the embryos of animals with a backbone, blood flows from the heart through the aorta into branching smaller vessels to the cells. The blood then gets collected by progressively bigger vessels and flows back to the heart via the cardinal vein. The cells that make up these blood vessels develop from cells called angioblasts—but first, during development these angioblasts must move to the place where the vessels will form. A protein called Vascular endothelial growth factor (VEGF) had been suggested to help guide and align the angioblasts as the embryo develops. Now, Helker, Schuermann et al. have examined developing zebrafish embryos using new technologies.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"lethal infection by hematopoietic cells during Listeria infection. In contrast, HOIL-1 knock-out (KO) mice, with null mutations in the Rbck1 gene that encodes HOIL-1, were resistant to infection with murine γ-herpesvirus 68 (MHV68) and Mycobacterium tuberculosis. Although HOIL-1 KO mice raised in a barrier facility did not display signs of auto-inflammation, chronic infection with MHV68 or M. tuberculosis resulted in elevated inflammatory cytokines circulating in the serum, similar to that observed in some patients with mutations in RBCK1 (HOIL1). Interestingly, latent infection with MHV68 rescued HOIL-1 deficient mice from lethality during Listeria infection and induced high levels of the protective cytokine, interferon-gamma (IFNγ). MHV68 latency also protected IL-6, Caspase-1 and Caspase-1; Caspase-11 deficient mice from Listeria-induced lethality, indicating that the ability of latent infection to complement a genetic immunodeficiency is not restricted to mutation of Hoil-1. These data indicate that chronic infections can modify the clinical presentations of genetic variations, thereby opening a new avenue for the analysis and interpretation of human genotype-phenotype association studies. We speculate that the protective effect of chronic herpesvirus infection is due to the stimulation of the function of the innate immune system in a manner that compensates for deficient early cytokine responses associated with multiple immunodeficiencies. HOIL-1 KO mice (Tokunaga et al. , 2009) were born at Mendelian ratios and, in contrast to SHARPIN-deficient mice, failed to develop TNFα-driven inflammatory skin disease (Ikeda et al. , 2011; Gerlach et al. , 2011; Tokunaga et al. , 2011; Tokunaga and Iwai, 2012) and exhibited normal histology of lymphoid organs, liver, lung, and kidney, and the presence of Peyer' s patches along the small intestine (not shown). Aged HOIL-1 KO mice exhibited deposits of material that stained with periodic acid-Schiff reagent and was resistant to digestion with diastase, similar to the amylopectin-like material observed in humans with HOIL-1 deficiency (— 2) (Boisson et al. , 2012). Importantly, these barrier-raised mice showed minimal signs of baseline hyper-inflammation. In this regard, HOIL-1 KO mice exhibited normal numbers of lymphoid and myeloid cells in the spleen and thymus, normal complete blood counts (— 3A, B, D), and no detectable increase of tumor necrosis factor alpha (TNFα) or interleukin 6 (IL-6) in serum (discussed below). However, in the peritoneum, HOIL-1 KO mice contained about twofold more B cells, T cells","The immune system protects an individual from invading bacteria, viruses and parasites, as well as malfunctioning or cancerous host cells. However, some people inherit genetic defects that cause part of the immune system to be missing or to not work properly. This is called a genetic immunodeficiency, and puts individuals at a higher risk of infection and disease. The symptoms of immunodeficiencies can vary substantially between individuals, even when they have defects in the same gene. For example, only some of the individuals who have defects in both of their copies of a gene called HOIL-1—which has been linked to several roles in the body' s immune response—are reported to suffer from an altered susceptibility to bacterial infections and chronic (persistent) inflammation. Gaining a clear understanding of the",380,128,0.3368
dialogsum,"#Person1#: Have we sold out all the newspapers for today? #Person2#: Yes. What a good job we have done! #Person1#: Why are so many extra gifts left here? #Person2#: Many customers didn't want them. #Person1#: How about giving them to that old man? #Person2#: Good idea. #Person1#: By the way, do you think it's a good idea to give free gifts to attract customers? #Person2#: I'm not sure, but still it did attract a large crowds today. #Person1#: I think it should be more useful to hand out some fliers which is also cheaper. #Person2#: But people can just throw them into the trash can as they turn around. #Person1#: That's true. #Person2#: Anyway, let's just finish out job and get back home. #Person1#: Okay. How tiring the job is!",#Person1# and #Person2# have sold out all the newspapers for today. They're talking about strategies to attract more customers.,130,19,0.1462
dialogsum,"#Person1#: I need a room for a few days. #Person2#: That won't be a problem. Could you please tell me your name? #Person1#: John Sandals. That's S A N D A L S. #Person2#: Sir, I'm Michelle, and I run the front desk. Please tell me the days you'll be here. #Person1#: I'll be there in April Friday through Monday, the 14th through the 17th. #Person2#: We recently changed many things here, sir, including our prices. Do you mind, sir? #Person1#: Possibly. What's the actual price? #Person2#: The price will be $ 308 a night. #Person1#: $ 308! That's not bad. #Person2#: Very good. Now, Mr. Sandals, about the room, smoking or nonsmoking? #Person1#: Nonsmoking, definitely! #Person2#: Most of our clients prefer nonsmoking. Now, does a queen sound okay? #Person1#: Yes, that'll be just fine. #Person2#: One more second, sir. Your reservation is now verified, so all I need is your phone number. #Person1#: It's 626-555-1739. #Person2#: Let me repeat that 626-555-1739. Okay, sir, we look forward to seeing you in April!",John Sandals makes a reservation for a nonsmoking room for several days with Michelle's assistance.,172,15,0.0872
scientific_lay_summarisation-elife-norm,"by the AAA-ATPases (ATPases associated with diverse cellular activities) PilF (extension) and PilT1/PilT2 (retraction) (Salzer et al. , 2014b). It has been suggested that mature PilA4 assembles into pili extending from the inner membrane by action of PilF (Collins et al. , 2013; Salzer et al. , 2014b). The outer membrane channel of the T4P machinery is formed by the dodacemeric ∼1 MDa secretin complex PilQ (Burkhardt et al. , 2011) (). Other proteins, in particular PilM, PilN, and PilO, are hypothesized to be a central part of the pilus assembly platform and may couple the cytoplasmic and periplasmic sides of the T4P machinery (Karuppiah et al. , 2013). Some proteins of the complex have been implicated to play a dual role in both pilus assembly and natural competence (Friedrich et al. , 2002; Averhoff and Friedrich, 2003; Friedrich et al. , 2003; Rumszauer et al. , 2006). Recent results indicate that T4P themselves are not directly involved in DNA uptake (Burkhardt et al. , 2012; Salzer et al. , 2014a). T4P are essential for pathogenesis by mediating adhesion, biofilm formation, and twitching motility (Burrows, 2012). Thus, both secretins and T4P play important roles in virulence of different pathogenic bacteria, which has fostered their use as new targets for drug development (Baron, 2010). To date, there is no information on the in situ structure of either the T4P machinery or DNA translocator. Determining structures of T4P complexes in whole bacterial cells is therefore of paramount importance and will enable further study of bacterial resistance and disease. Electron cryo-tomography (cryoET) has the unique ability to determine protein structures in cells at molecular resolution. We have applied cryoET to whole T. thermophilus HB27 cells, in order to visualize the T4P machinery in situ. We determine the helical structure of the pilus and find that the secretin complex PilQ is a central dynamic component of this system. CryoET and subtomogram averaging of the T4P machinery with and without pili reveal a ∼30 Å conformational change as the gates in the complex open. T. thermophilus has an unusual cell architecture with deep surface clefts, formed by invaginations of the outer membrane (2A). By cryoET, these clefts are seen to be constrictions that run around the cell body (2D). Distal to the most polar outer","Gram-negative bacteria can cause serious diseases in humans, such as cholera and bacterial meningitis. These bacteria are surrounded by two membranes: an inner membrane and an outer membrane. Proteins called secretins are components of several large molecular complexes that are embedded within the outer membrane. Some secretin-containing complexes form pores in the bacterial membranes and allow molecules to pass in or out of the cell. Some secretins also form part of the machinery that allow Gram-negative bacteria to grow fibre-like structures called type IV pili. These pili help bacteria that cause infections to move and stick to host cells, where they can also trigger massive changes in the host cells' architecture. Multiple copies of a secretin protein called PilQ form a channel in the outer membrane of the",380,128,0.3368
dialogsum,"#Person1#: I can't sleep. #Person2#: What's wrong dear? #Person1#: I don't know. I just can't sleep. #Person2#: Is there anything bothering you? #Person1#: Maybe. I have a test on Friday and I'm worried I won't get a good grade. #Person2#: Well. You have a few days left the study. Is there anything I can do to help? #Person1#: Yeah. Can you help me understand some of the ideas I just can't get? #Person2#: Sure. we can start when you get home from school. For now though, close your eyes and think about nicer things. Then you'll be ready to learn tomorrow. #Person1#: Thanks, Daddy. You're always there for me when I need you.",#Person1# can't sleep because #Person1#'s worried about a test. Dad will help #Person1# understand some ideas #Person1# can't get.,113,19,0.1681
scientific_lay_summarisation-elife-norm,"Schistosomiasis is a debilitating parasitic disease infecting hundreds of millions of people. Schistosomes use aquatic snails as intermediate hosts. A promising avenue for disease control involves leveraging innate host mechanisms to reduce snail vectorial capacity. In a genome-wide association study of Biomphalaria glabrata snails, we identify genomic region PTC2 which exhibits the largest known correlation with susceptibility to parasite infection (>15 fold effect). Using new genome assemblies with substantially higher contiguity than the Biomphalaria reference genome, we show that PTC2 haplotypes are exceptionally divergent in structure and sequence. This variation includes multi-kilobase indels containing entire genes, and orthologs for which most amino acid residues are polymorphic. RNA-Seq annotation reveals that most of these genes encode single-pass transmembrane proteins, as seen in another resistance region in the same species. Such groups of hyperdiverse snail proteins may mediate host-parasite interaction at the cell surface, offering promising targets for blocking the transmission of schistosomiasis. Schistosomiasis is a chronic and debilitating disease suffered by over 200 million people worldwide (Evan Secor, 2014; Lo et al. , 2018). It is caused by infection with schistosome trematode parasites that are transmitted by aquatic snails (Lo et al. , 2018). Infection can be treated with regular doses of a single drug, praziquantel (Doenhoff et al. , 2009). However, it has become increasingly clear that mass drug administration alone will not adequately control schistosomiasis, and that successful elimination of transmission requires intervention at the snail stage (Lo et al. , 2018; Sokolow et al. , 2018). Immunogenetic interactions between snails and schistosomes represent a crucial stage in the parasite life cycle that can be targeted to block transmission. Parasite resistance is highly heritable in snails, and there is substantial strain-by-strain interaction between hosts and parasites (Richards and Shade, 1987; Richards et al. , 1992; Knight et al. , 1999; Webster et al. , 2004; Webster and Woolhouse, 1998; Theron et al. , 2014). Genetically diverse parasite cultures can infect nearly all snails, while bottlenecked laboratory strains of parasite can only infect a subset (Theron et al. , 2008), suggesting a ‘trench warfare’ model in which numerous alleles are maintained in both host and parasite populations because each matches a different phenotype in the other species (Seger, 1988; Stahl et al. , 1999). There are likely to be snail","Schistosomiasis is a widespread parasitic disease, affecting over 200 million people in tropical countries. It is caused by schistosome worms, which are carried by freshwater snails. These snails release worm larvae into the water, where they can infect humans – for example, after bathing or swimming. Treatment options for schistosomiasis are limited. Eliminating the freshwater snails is one way to control the disease, but this is not always effective in the long term and the chemicals used can also harm other animals in the water. Another way to manage schistosomiasis could be to stop the worms from infecting their snail host by breaking the parasites’ life cycle without killing the snails. It is already known that some snails are naturally resistant to infection by some strains of schistosomes.",380,128,0.3368
dialogsum,"#Person1#: I really need to apply for a driving permit. #Person2#: Do you have your ID with you? #Person1#: I may have left my ID in my car. #Person2#: Well, I need your ID and $ 27. #Person1#: I'll go get it really quick. #Person2#: Please hurry. #Person1#: Here it is. #Person2#: Thank you very much. Please fill out this paperwork. #Person1#: I need to use a pen. #Person2#: Here you go. #Person1#: Thank you very much. #Person2#: Thank you. Now turn in your application at Window B.",#Person2# asks for #Person1#'s ID when helping #Person1# apply for a driving permit.,88,13,0.1477
dialogsum,"#Person1#: Steven, we are preparing a martial arts show for the New Year's party. Would you like to join us? #Person2#: I'd love to! But I have never learned martial arts, and there is only a month left before the New Year. #Person1#: That's OK. A month is enough for you to learn the basic movements. It would be great to have you with us on the show. #Person2#: Sounds great! Shall I learn the actions that Jet Li did in the movies? #Person1#: No. You know, there are many schools and styles of kung fu. What we will perform is a set of Chinese shadow boxing. #Person2#: Whatever! I'm glad to learn something of Chinese kung fu. Thanks for asking me. #Person1#: Thank you for joining us! Now let's see some pictures and know more about kung fu. #Person2#: Good!",#Person1# invites Steven to prepare a set of Chinese shadow boxing for the New Year's party. Steven is willing to join.,141,21,0.1489
scientific_lay_summarisation-elife-norm,"rate, mutations may be available as standing genetic variation (pre-existing variation) or be generated anew every generation, allowing the population to adapt to its environment rapidly. If adaptive mutations are rare, because the population is small, the mutation rate is low, or only few specific mutations (or combinations of mutations) can help a population adapt, the population will likely adapt to its environment much more slowly. The availability of adaptive mutations does not only change the rate of adaptation, it also changes how adaptation affects genetic diversity in a population. If adaptive mutations are rare, i. e. , less than one adaptive mutation occurs per generation in the population, the first successful mutation is likely to rise to high frequency before any subsequent adaptive mutations reach appreciable frequencies (see 1A). This results in a hard selective sweep, in which the single adaptive mutation and the nearby linked mutations becomes fixed in the population (1B). Hard selective sweeps sharply reduce genetic diversity in the population (1C) (Smith and Haigh, 1974; Kaplan et al. , 1989) in a similar manner to a strong genetic bottleneck. 10. 7554/eLife. 10670. 003Figure 1. Prediction of drug resistance acquisition with more and less effective treatments. Among patients treated with more effective treatments (top), we predict HIV populations to have a lower probability of acquiring resistance per generation. As a result, the population must wait a long time for a beneficial genotype, so when resistance does occur, it will spread through the population in a hard selective sweep before other resistant genotypes emerge (A). Since resistance only occurs on a single genetic background (background mutations in grey), all sequences with resistance will be similar (B) and diversity following this type of selective sweep will be reduced (C). We can use the reduction of diversity to determine that a selective sweep is hard. In patients treated with less effective treatments (bottom), we predict HIV populations should have a higher probability of acquiring resistance per generation, so resistance will be acquired more quickly and selective sweeps of drug resistance mutations will be soft (D). We can detect these soft selective sweeps, because diversity remains high when resistance mutations on different genetic backgrounds rise in frequency simultaneously (E, F). : http: //dx. . org/10. 7554/eLife. 10670. 003 In contrast, when","In the early days of HIV therapy, the strains of the virus that infected patients frequently evolved drug resistance and the therapies would often eventually fail. These treatments generally involved using a single anti-viral drug. Nowadays, better therapies involving combinations of several anti-viral drugs are available and drug resistance in HIV is a much rarer occurrence. This means that now a particular therapy may be an effective treatment for an HIV-infected individual over much longer periods of time. A theory of population genetics predicts that when it is easy for a population to acquire a beneficial genetic mutation – like one that provides drug resistance – multiple versions of that mutation may spread in the population at the same time. This is called a soft selective sweep. However,",380,128,0.3368
dialogsum,"#Person1#: How many examinations do you have, Tom? #Person2#: Three, two this week, and one next Monday. How about you? #Person1#: Two, both are in this week. Then I have to write two papers. I'd rather have examinations. #Person2#: What do you mean? #Person1#: Well, you only recite a lot for examinations. You can work really hard for a couple of days, then that's all. #Person2#: Yeah, I know. But I like papers better than examinations. Urn, where did I put my I.C. card? #Person1#: Is it in your desk? #Person2#: No, where is it? #Person1#: Did you take it back? #Person2#: I don't know. Oh, God! I don't know what's wrong with me.","#Person1# prefers examinations, while Tom likes papers better. Then Tom finds his I.C. card lost.",114,15,0.1316
scientific_lay_summarisation-elife-norm,"Endophytic insects provide the textbook examples of herbivores that manipulate their host plant’s physiology, putatively altering source/sink relationships by transferring cytokinins (CK) to create ‘green islands’ that increase the nutritional value of infested tissues. However, unambiguous demonstrations of CK transfer are lacking. Here we show that feeding by the free-living herbivore Tupiocoris notatus on Nicotiana attenuata is characterized by stable nutrient levels, increased CK levels and alterations in CK-related transcript levels in attacked leaves, in striking similarity to endophytic insects. Using 15N-isotope labeling, we demonstrate that the CK N6-isopentenyladenine (IP) is transferred from insects to plants via their oral secretions. In the field, T. notatus preferentially attacks leaves with transgenically increased CK levels; plants with abrogated CK-perception are less tolerant of T. notatus feeding damage. We infer that this free-living insect uses CKs to manipulate source/sink relationships to increase food quality and minimize the fitness consequences of its feeding. Insect herbivores are under constant pressure from their host plants: they must adapt to toxic or anti-digestive defense compounds whose levels often dramatically increase in response to insect feeding; and their food source has low nitrogen to carbon ratios and a dietary value which decreases as leaves mature and senesce. Some herbivorous insects have developed strategies to overcome the low nutritional contents of their host plants and have evolved specialized mechanisms to tolerate, or even co-opt toxic plant defense metabolites for their own uses, in an apparent evolutionary arms race (Strong et al. , 1984; Després et al. , 2007; Heckel, 2014). Phytophagous insects can be categorized as either endophytic or free-living depending on the relationships that they establish with their host plant. This distinction is not binary and many transitional forms exist even within the same taxa. Consequently, the large differences in herbivorous lifestyles has selected for plant defense responses that counter different herbivory strategies (Kessler and Baldwin, 2002; Schuman and Baldwin, 2016). Free-living insects are mobile on their host plants, moving among plants, and frequently among different plant species. As a consequence of this mobility, they can freely choose tissues that are most nutritious or least defended, but the most nutritious tissues are often highly defended, resulting in a potential trade-off for herbivores (Ohnmeiss and Baldwin, 2000; Brütting et al. , 2017). To avoid herbivore-induced defenses, free-living insects often","Many insects use plants for food and for shelter. To protect themselves, plants often develop defense mechanisms that deter or debilitate their attackers, such as producing toxins or storing nutrients away from the attacked tissues. But some insects manage to counter the plants’ defense responses. Such species are often less mobile and spend a large part of their life in a restricted area of the plant, for example, inside plant tissues. Also known as ‘endophytic’ animals, these insects can even manipulate the signaling system in a plant, such as a class of plant hormones called cytokinins, which help plants to grow and to develop seeds and nutrient-storing fruits or young leaves. Researchers have previously assumed that endophytic animals target cytokinins because they are restricted to living in certain",380,128,0.3368
pubmed-summarization,". determine the number of instances when noise could have been identified as one of the potential causes , and 4 . though not presented in this paper , the fifth aim was to determine the worth of fatality reports as a potential surveillance data source . the assumption of a causal or contributive impact of occupational noise on the occurrence of occupational accidents has been addressed in several studies . recent publications except one suggest an exposure - response relationship between noise exposure or hearing impairment and accident risk . according to three explanatory models and empirical data , there is a biological plausibility for a causal relationship between noise exposure and occupational accident risk . nevertheless , the extent to which noise does act as a causal or contributive factor in fatal workplace accidents remains unclear and is subject to debate . potential effects of occupational noise on the risk of injuries based on interaction between the worker and his / her workplace [ institut national de sant publique du qubec ( inspq ) , adapted from htu 1993 , wilkins 1981 and le cocq 2010 ] through a review of work - related fatality reports , this study sought to : 1 . determine the number of instances when noise was identified as one of the potential causes and retained as such , 3 . determine the number of instances when noise could have been identified as one of the potential causes , and 4 . though not presented in this paper , the fifth aim was to determine the worth of fatality reports as a potential surveillance data source . similar to a multiple case studies design , this population - based descriptive study is based on a thorough analysis of the content found in the 788 fatal accident reports completed by various inspectors from the commission de la sant et de la scurit du travail du qubec [ workers compensation board ( wcb ) ] during the 1990 - 2005 period . for the investigation of the causes of a fatal injury , was adopted in 2000 , the reports were divided into the following two blocks : main block covering accident reports issued between 2000 and 2005 ( n = 284 ) and a","noise exposure in the workplace is a common reality in qubec , canada as it is elsewhere . however , the extent to which noise acts as a causal or contributive factor in industrial work - related accidents has not been studied thoroughly despite its plausibility . this article aims to describe the importance or potential importance , during investigations looking into the specific causes of each work - related fatal accident , of noise as an explanatory factor . the written information contained in the accident reports pertaining to contextual and technical elements were used.the study used multiple case qualitative content analysis . this descriptive study was based on the content analysis of the 788 reports from the commission de la sant et de la scurit du",380,128,0.3368
pubmed-summarization,"focal segmental glomerulosclerosis ( fsgs ) is a clinicopathologic entity responsible for up to 20% of all cases of end - stage kidney disease in the united states . the incidence of fsgs is estimated at 7 per million individuals annually , has a slight male predominance ( male : female ratio 1.52 ) , and now represents the leading cause of idiopathic nephrotic syndrome in adults . although the pathogenesis of fsgs has not yet been fully described , the lesions that are induced include tuft collapse , segmental hyalinosis , and effacement of foot processes as revealed by electron microscopy . fsgs may also occur secondarily to certain genetic predispositions as well as disorders such as sickle cell disease , hiv nephropathy , and obesity ; in these instances , plasma exchange would not be considered a primary therapeutic option and treatment would instead be directed at the underlying driver . clinically , patients with fsgs manifest significant , nephrotic - range proteinuria , reduced renal function , and hypertension . eighty percent of fsgs cases are characterized as primary and are suspected to be caused by a circulating fsgs permeability factor , a low - molecular weight anionic protein . this same factor may be responsible for the recurrence of fsgs in the renal allograft , a scenario that occurs in approximately 2050% of primary allografts , most commonly within the first 3 months following transplant . plasmapheresis removal of this factor appears to effectively treat many such cases . recurrent fsgs can be suspected in patients who develop impaired graft function and significant proteinuria , defined as > 1 g/24 h in the posttransplant period . in many cases early recognition is therefore critical in properly diagnosing and managing this disorder . if recurrent fsgs is suspected ( even in the absence of a pretransplant history of fsgs ) then it is important to inform the pathology department of this suspicion so that biopsy specimens can be properly processed for electron microscopy , which is needed to evaluate for the foot process effacement characteristic of fsgs . the american society for apheresis guidelines designate recurrent fsgs in the renal allograft as a category i indication for therapeutic plasma exchange ( grade 1b , strong recommendation )","focal segmental glomerulosclerosis ( fsgs ) causes glomerular lesions that can progress to end - stage renal disease . it is suspected to be caused by a circulating factor that is amenable to plasmapheresis removal and exhibits a risk for recurrence in the renal allograft . we present two patients with fsgs recurrence in their allograft kidneys diagnosed by biopsy after significant proteinuria developed in the posttransplant setting . treatment with therapeutic plasma exchange induced long - term remission in both patients . spot urine protein : creatinine ratios were monitored and treatment was continued until a target of < 0.5 was achieved . in patient number two , a second peak in proteinuria and azotemia was ultimately attributable to ureteral stenosis and these values normalized following repair",380,128,0.3368
dialogsum,"#Person1#: Have you chosen the music for the party yet? #Person2#: I was going to just let people bring their own. #Person1#: Oh, I don't think you should do that. One person needs to be in charge. Otherwise, people will start disagreeing. Sony's really good at music. You could ask her. #Person2#: OK. Have you got her number? #Person1#: Yeah, it's on my mobile. I'll text it to you.","#Person2# wanted people to bring music, but #Person1# suggests putting Sony in charge.",69,13,0.1884
dialogsum,"#Person1#: Do a lot of people do mountain running? #Person2#: Yes, the runs take place in the countryside. The areas like the Lake District in the Highlands of Scotland are very popular. But this doesn't stop people from the city taking part. For example, I drive to my club for my city apartment. #Person1#: Can you tell me the history of mountain running? #Person2#: Well, there are records of people doing this going back nearly 1000 years. It was always been connected with country fairs and festivals. Overtime it became official, and nowadays a run is operated usually on its own. #Person1#: Hmm, what are the tougher courses like? #Person2#: There is a race called the Dragons Back, which takes place over 5 days and over a distance of 200 miles. But before you sign up for it, I should point out that only people with lots of experience are allowed to enter. #Person1#: How can you get started in the sport? #Person2#: Well, you start with something easy and work your way up to more challenging runs. If you want to enter races, you'll find their graded in terms of distance and height. But just as people who do road running won't necessarily run a marathon, you don't have to enter mountain running races.",#Person2# tells #Person1# the mountain running takes place in the countryside and introduces its history. #Person2# tells that Dragons Back is only for experienced people and people should start with something easy and work their way up to more challenging runs.,215,41,0.1907
dialogsum,"#Person1#: Hey, what's new? #Person2#: Not much. Just sitting here eating some Chinese food. Is that the paper? Why don't you open it and tell me my horoscope? #Person1#: Ok, wait a minute... let's see. I'm a Taurus, and it says, Mars is in the third house, and is soon to eclipse Venus. I don't know what that means, but then it says, Your charm and drive will win others over to your way of thinking. Remember to be positive. Sounds good to me. #Person2#: What about Gemini? What's the prediction? #Person1#: Since Mercury has crossed paths with Jupiter, your fortunes are falling. Bad luck will follow you today, and you will lose that which you value. Be careful. #Person2#: That sounds bad! I'm really worried, what should I do? Maybe I should go home and stay in the rest of the day. #Person1#: But we have a date tonight! You can't stay at home because of a stupid horoscope.","#Person1# and #Person2# talk about the horoscope, which says #Person1#'s charm will win others over while #Person2#'s fortunes are falling. #Person2#'s worried.",160,22,0.1375
dialogsum,"#Person1#: What's the area of your country? #Person2#: It's not very big. It's a little over half a million square kilometers. #Person1#: That sounds quite big! How many people live there? #Person2#: There are about 30 million people in my country. Most of them live in the north. #Person1#: What's the average income? #Person2#: That's the really hard to say. I think most people earn about two thousand dollars a month, if you convert the money from our currency into dollars. #Person1#: So your country is fairly rich. #Person2#: I think we are richer than most countries, but not as rich as countries in western Europe. Our biggest problem at the moment is unemployment, which is roughly 8%. It has doubled over the last four years. #Person1#: Unemployment in my country is a fraction of that.","#Person1# asks #Person2# about the area, population, and the average income of #Person2#'s country. #Person2# also mentions unemployment is the biggest problem in #Person2#'s country.",136,25,0.1838
pubmed-summarization,"endometrial carcinoma is the most common cancer of the female genital tract in the western world . endometrial carcinomas are generally thought to have a favorable prognosis due to early detection , and the majority of tumors are detected in early stages . however , in fact this is not fully true , and there are important subgroups within this diagnosis with poor prognosis and outcome of treatment . therefore , the first step to improve the situation has been to find predictive and prognostic factors , then to define clinically relevant risk groups , and finally to design clinical trials and treatment options for these risk groups . unfortunately , no consensus exists on which predictive or prognostic factors that should be used and how to combine them in the definition of suitable - risk groups . as a result of this , the randomized phase iii trials presented during the last decades are difficult to compare since these definitions have varied , more or less , in most of them . another problem has been the small size and low power of most studies in the literature dealing with prognostic and predictive factors . despite more or less sophisticated statistical methods with multivariate technique , the results are not reliable enough for definitive conclusions from such small series analyzing multiple variables . a few exceptions do exist but then with data from large registry studies , but then with other problems of selection and bias built in . six prospective randomized studies have been presented since 1980 to elucidate the value of external beam pelvic radiotherapy after surgery in early - stage endometrial carcinoma ( aalders , portec-1 , gog#99 , astec / en.5 , portec-2 , and sorbe ) . the treated populations varied in all these studies from no risk groups defined ( aalders ) to a mixture of low - risk ( portec-1 , gog#99 ) , medium - risk ( portec-1 , gog#99 , astec / en.5 , and portec-2 ) , or high - risk cases ( astec / en.5 ) . type of primary surgery and staging also varied from no staging at all ( aalders , portec-1 , astec / en.5 , and portec-2 ) to staging with lymph node sampling","background . the aim was to evaluate predictive and prognostic factors in a large consecutive series of endometrial carcinomas and to discuss pre- and postoperative risk groups based on these factors . material and methods . in a consecutive series of 4,543 endometrial carcinomas predictive and prognostic factors were analyzed with regard to recurrence rate and survival . the patients were treated with primary surgery and adjuvant radiotherapy . two preoperative and three postoperative risk groups were defined . dna ploidy was included in the definitions . eight predictive or prognostic factors were used in multivariate analyses . results . the overall recurrence rate of the complete series was 11.4% . median time to relapse was 19.7 months . in a multivariate logistic regression analysis , figo grade",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR) -driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17. 5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies. Immune cells eliminate pathogens and diseased cells while limiting damage to healthy cells. Macrophages, professional phagocytes and key effectors of the innate immune system, play an important role in this process by engulfing opsonized targets bearing ‘eat me’ signals. One of the most common ‘eat me’ signals is the immunoglobulin G (IgG) antibody, which can bind foreign proteins on infected cells or pathogens. IgG is recognized by Fcγ receptors (FcγR) in macrophages that drive antibody-dependent cellular phagocytosis (ADCP) (DiLillo et al. , 2014; Erwig and Gow, 2016; Nimmerjahn and Ravetch, 2008). ADCP is a key mechanism of action for several cancer immunotherapies including rituximab, trastuzumab, and cetuximab (Chao et al. , 2010; Uchida et al. , 2004; Watanabe et al. , 1999; Weiskopf et al. , 2013; Weiskopf and Weissman, 2015). Exploring the design parameters of effective antibodies could provide valuable insight into the molecular mechanisms driving ADCP. Activation of multiple FcγRs is required for a macrophage to engulf a three-dimensional target. FcγR-IgG must be present across the entire target to drive progressive closure of the phagocytic cup that surrounds the target (Griffin et al. , 1975). In addition, a critical antibody threshold across an entire target dictates an all-or-none engulfment response by the macrophage (Zhang et al. , 2010). Although the mechanism of this thresholded response remains unclear, receptor clustering plays a role in regulating digital responses in other immune cells (Berger","The word ‘phagocytosis’ means cellular eating. It is the process by which cells extend their membranes around foreign particles and engulf them. Macrophages, a type of immune cell found in every tissue of the body, perform phagocytosis to eat pathogens and diseased cells. To avoid eating healthy cells, macrophages focus on targets marked by proteins called antibodies. They look for cells coated with high levels of a type of antibody called immunoglobulin G, or IgG for short, but only eat cells coated with enough IgG, raising the question, can macrophages count? Macrophages recognize IgG antibodies using cell surface receptors called Fc-gamma Receptors. When these receptors bind to IgG, they cluster together. Researchers do not yet know how the number of IgG antibodies per cluster, or the spacing between",380,128,0.3368
dialogsum,"#Person1#: Hi, I'm Josephine Chen, the tour guide for the Jade Agency. We have a reservation of twenty rooms for tonight. #Person2#: Please to meet you, Miss Chen. My name is Joey. Welcome to the hotel. Here are the keys, registration slips and breakfast vouchers. Break-fast will be served from seven tomorrow morning. Is there any change in your schedule? #Person1#: No, our check-out time will still be 8: 30 tomorrow. #Person2#: Then we will arrange a morning call at 7:30. Will that be fine? #Person1#: That's alright. #Person2#: Please put your luggage outside your room by eight. The bellboy will pick them up. #Person1#: Thank you. #Person2#: Thank you very much. Hope you enjoy your stay.","Joey helps Josephine Chen, a tour guide, to check in at their hotel and confirms the arrangement tomorrow before checkout.",117,20,0.1709
dialogsum,"#Person1#: Mary, this company is pretty good. I really want to have an interview. #Person2#: Have you made an appointment with this company? #Person1#: Not yet. Do I have to? #Person2#: Yes, it's very important to make an appointment before the interview. #Person1#: Why? #Person2#: If you go to the company without appointment, the interviewers may happen to be busy with other things, and have no time to give you an interview. #Person1#: Yes, you are right. #Person2#: If the interviewers are not in the company, you will go there for nothing. #Person1#: Sure. Why didn't I think of that? #Person2#: So you should make an appointment in advance with the company for the interview. #Person1#: Then how can I make the appointment? #Person2#: You could directly call the company and arrange the time and place for the interview. #Person1#: Ok, I see. #Person2#: If you succeed in doing that, you must attend the interview on time.",#Person1# wants to have an interview. Mary suggests #Person1# make an appointment before the interview because the interviewers might be busy.,157,21,0.1338
dialogsum,"#Person1#: Hi Jane, can you let me know the best way to get to your house this evening? #Person2#: Certainly, where will you be coming from? #Person1#: I need to be in the city centre this afternoon so I will be coming straight from there. #Person2#: Ok. Take the Underground (the Circle line) to High Street Kensington. Make sure you take the High Street Kensington exit. #Person1#: Got that. #Person2#: Ok - when you leave the Underground, cross the road and you should see Hornton Street. WAk up that street to the crossroads. As you wAk you should see a fast food place on your right. #Person1#: Hold on, I am looking at the map now. Ok, I can see Hornton Road. Do I go straight at the intersection? #Person2#: No, you need to turn left into Philimore WAk and take the next right. #Person1#: Ok, I can see that road. #Person2#: That's fine. You will not miss it because it's just next to the Kensington CentrA Library. #Person1#: Good, I can see the library on the map. #Person2#: Ok, we live in the third building on your left. Will we see you around 7 pm? #Person1#: That's great, see you at seven.","Jane tells #Person1# the best way to get to her house by 7 pm from the city centre by underground, her place is in the third building on the left after turning right next to the Kensington Centre library.",203,39,0.1921
dialogsum,"#Person1#: Have you got any certificate of technical qualification? #Person2#: Yes, I have obtained an accountant's qualification and a driver's license. #Person1#: How long did it take you to get your driver's license? #Person2#: I spent a year to get my license.",#Person2# has obtained an accountant's qualification and a driver's license.,42,10,0.2381
dialogsum,"#Person1#: How do you usually spend your time, now that you'Ve retired? #Person2#: Well, I nearly always get up at dawn. I don't like sleeping in late. The days are longer in summer than in winter, so I get up in summer. I usually do some exercise when I get up. #Person1#: What do you have for breakfast? #Person2#: I usually have cereal, but sometimes I cook a traditional English breakfast. #Person1#: that sounds nice. How do you spend your mornings? #Person2#: I usually do housework in mornings. I go shopping occasionally. I like to do all my shopping in one bag trip to the supermarket. I always drive to the big supermarket in the city center. It takes about 20 minutes to drive there. #Person1#: How do you spend your afternoons? #Person2#: I usually meet some friends and we play sports together or I might spend some time alone on my hobbies. I spend winter evening watching tv, but I spend summer evening at cultural events if I have time.","#Person2# tells #Person1# how #Person2# spends #Person2#'s mornings and afternoons after retirement. #Person2# usually gets up early, does housework in the morning, and plays sports with friends in the afternoon.",171,30,0.1754
scientific_lay_summarisation-elife-norm,"al. , 2008; Mamvura et al. , 2011; Matoulkova et al. , 2012). As wort is boiled prior to fermentation, the primary reservoir for spoilage microorganisms in beer production is the brewery environment. Lactic acid bacteria (LAB) are of particular concern, as some members of this clade resist hop antimicrobial compounds, enabling growth and spoilage of beer through acidification, hazes, and off-flavors (Suzuki et al. , 2006; Bokulich and Bamforth, 2013). Hop iso-alpha-acids, the primary antimicrobial compounds in beer, kill most Gram-positive bacteria by acting as ionophores, dissipating proton-motive force across cell walls (Simpson and Fernandez, 1992,1994; Simpson, 1993a), and via oxidative stress (Behr and Vogel, 2010). Very few resistance mechanisms have been proposed (Suzuki et al. , 2006), primarily being the multi-drug transporters horA (Sami et al. , 1997; Sakamoto et al. , 2001) and horC (Suzuki et al. , 2005; Iijima et al. , 2006), the transcriptional regulator of horC, horB (Suzuki et al. , 2005; Iijima et al. , 2006), and hitA, a divalent cation transporter (Hayashi et al. , 2001) that imports manganese into the cell. These genes are all located on plasmids and transmit via horizontal gene transfer (Suzuki et al. , 2005,2006). The frequency and transmission of these and other beer-spoilage genes within processing environments—or any other reservoir for spoilage microbes—have yet to be tested. Here, we employ mixed molecular approaches (Bokulich and Mills, 2012b) and a Bayesian modeling method to interrogate the seasonal sources, reservoirs, and transmission of bacteria, fungi, and beer-spoilage genes within a North American brewery over the course of one year. Given the inherent role of environmental microbiota in conducting coolship ale fermentations, this serves as a model system for studying mechanisms for microbial transfer within food-processing systems. Information on population and gene flow extends to other food-processing systems where environmental microbiota are involved positively or negatively in the production, stability, and safety of human nutrition. Short-amplicon marker-gene sequencing was employed to survey the bacterial and fungal consortia inhabiting the entire brewery environment. A total of 501 samples were collected during three seasons, representing the main processing surfaces and equipment used throughout the brewing process (). Beta-diversity (between sample) comparisons provide useful assessments of the taxonomic similarity between different sites. Bray–Curtis dissimilarity of complete microbial profiles reveals that many samples","Many microbes—including bacteria and fungi—can affect the food and drink we consume, for better and for worse. Some spoil food, making it less tasty or even harmful to health. However, microbes can also be important ingredients: for example, yeast ferments malted barley sugars to make the alcohol and flavor of beer. Nowadays, many beers are made under carefully controlled conditions, where the only microbes in the beer should be the strain of yeast added to the barley sugars. A more traditional ‘coolship’ method can be used to make sour beers; the barley sugars cool in an open-topped vessel and are fermented by the yeast and bacteria found naturally on the raw ingredients and in the surrounding environment. Relatively little was known about how microbes spread around and adapt",380,128,0.3368
scientific_lay_summarisation-elife-norm,"test of Disc1 mice (TST: p = 0. 015,22 Disc1 and 14 control mice; forced swimming: p = 0. 049,22 and 20 mice; Cohen' s d of 0. 82 and 0. 65 corresponding to a strong and moderate effect size, respectively [Table 1]). Both genotypes reached similar movement speeds in the open field arena, indicating that high immobility in the behavioural despair tests cannot be caused by motor impairment (1D). 10. 7554/eLife. 04979. 003Figure 1. Disc1 mice show depression-related behavioural despair. (A) Disc1 mice show similar sucrose preference as controls (146 ± 7 vs 144 ± 15% sucrose intake, n = 10 each group). (B and C) Enhanced behavioural despair of Disc1 mice in TST (37. 8 ± 3. 3 vs 25. 8 ± 2. 9%, n = 22 Disc1,14 control mice) and forced swim test (44. 1 ± 2. 6 vs 37. 3 ± 2. 0%, n = 22,20). (D) Unaltered locomotion of Disc1 mice. Left, examples of the path of a Disc1 and a control mouse during a 10 min exploration period (n = 19 Disc1,18 control mice). Right, Disc1 mice move slower during the initial phase of the task but reach similar movement speeds as controls during the later phase. (E) Radial arm water maze to probe spatial reference and working memory. The animals were released from a random start arm and had to find the hidden platform in the southern arm. Green line shows the path of one representative animal during one trial. Arm entries were detected by a threshold-crossing algorithm (bottom, N = 6,9). (F) Path length and reference memory errors plotted against the five subsequent test days. Identical shortening of the swim path length (left) and identical number of reference memory errors (entries in wrong arms; middle) of Disc1 and control mice indicates intact spatial learning. Time spent in the target arm is identical between genotypes (n = 6,9). (G) The number of working memory errors (re-entries in previously explored arms within a trial, 14 ± 2 vs 17 ± 3) did not depend on the genotype. *p < 0. 05, **p < 0. 01. Data are mean ± SEM. : http: //dx. . org/10. 7554/eLife. 04979. 00310. 7554/eLife. 04979. 004Figure 1— 1. Additional assessment of working memory performance. (A) Working memory assessment in","Our thoughts and emotions are produced and processed by complex networks of neurons inside our brains. Signals are sent from one neuron to another via chemical messengers, and pass through the neuron as an electrical signal. The electrical signals produced by a brain region often show steady rhythms, or oscillations. In the brains of many people diagnosed with certain mental disorders, such as schizophrenia and major depression, these oscillations are disrupted, but how these changes in rhythm are linked to defects in the networks of neurons behind the electrical activity is not well understood. Studies of a family in Scotland over several decades revealed that a gene called DISC1 was shortened in family members who had been diagnosed with mental illnesses. Recently, scientists have been able to create",380,128,0.3368
scientific_lay_summarisation-elife-norm,"During infection, CD8+ T cells initially expand then contract, leaving a small memory pool providing long lasting immunity. While it has been described that CD8+ T cell memory formation becomes defective in old age, the cellular mechanism is largely unknown. Autophagy is a major cellular lysosomal degradation pathway of bulk material, and levels are known to fall with age. In this study, we describe a novel role for autophagy in CD8+ T cell memory formation. Mice lacking the autophagy gene Atg7 in T cells failed to establish CD8+ T cell memory to influenza and MCMV infection. Interestingly, autophagy levels were diminished in CD8+ T cells from aged mice. We could rejuvenate CD8+ T cell responses in elderly mice in an autophagy dependent manner using the compound spermidine. This study reveals a cell intrinsic explanation for poor CD8+ T cell memory in the elderly and potentially offers novel immune modulators to improve aged immunity. Upon successful clearance of a pathogen, the majority of short-lived effector T cells die and the remaining cells differentiate into a memory T cell population that provides long lasting immunity. While the cytokines, surface molecules, and signaling components involved in T cell memory formation have been extensively studied, the molecular pathways supporting these cell fate decisions are poorly understood. The T memory population is (1) quiescent, (2) long-lived and actively maintained, and (3) relies on mitochondrial respiration (Pearce and Pearce, 2013). Both reduced cell cycling and longevity of this stem cell-like population demand rigorous maintenance of the cytoplasm as debris cannot be diluted to daughter cells, reminiscent of true stem cells (Mortensen et al. , 2011; Guan et al. , 2013; Warr et al. , 2013). Across mammalian cell types, clearance of debris and damaged organelles such as mitochondria is typically executed via autophagy (Choi et al. , 2013). A recent study showed that formation of the influenza-specific B cell memory pool requires autophagy (Chen et al. , 2014). However, while the role of autophagy in the homeostasis of naïve T cells is well studied (Puleston and Simon, 2014), nothing is known about the requirement of autophagy in antigen-experienced T cells. The T cell memory pool has previously been shown to be controlled by PI3K/Akt and AMPK signaling as well as mTOR (mammalian Target Of Rapamycin) inhibition","In the face of an infection, the immune system mounts an aggressive response by producing many copies of killer immune cells called CD8+ T cells that recognize and destroy any cells infected with the invading pathogen. The number of killer cells produced depends on the extent of the infection. Once the infection has been brought under control, most of the CD8+ T cells die off. The small numbers that are retained—called memory cells—‘remember’ the pathogen, so that if it invades the body again, they can help the immune system to respond more quickly and effectively. Memory cells are also critical to the effectiveness of vaccines, many of which introduce a dead or weakened pathogen into the body. This does not cause an infection, but does allow the immune",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The unfolded protein response (UPR) is a cellular homeostatic circuit regulating protein synthesis and processing in the ER by three ER-to-nucleus signaling pathways. One pathway is triggered by the inositol-requiring enzyme 1 (IRE1), which splices the X-box binding protein 1 (Xbp1) mRNA, thereby enabling expression of XBP1s. Another UPR pathway activates the activating transcription factor 6 (ATF6). Here we show that murine cytomegalovirus (MCMV), a prototypic β-herpesvirus, harnesses the UPR to regulate its own life cycle. MCMV activates the IRE1-XBP1 pathway early post infection to relieve repression by XBP1u, the product of the unspliced Xbp1 mRNA. XBP1u inhibits viral gene expression and replication by blocking the activation of the viral major immediate-early promoter by XBP1s and ATF6. These findings reveal a redundant function of XBP1s and ATF6 as activators of the viral life cycle, and an unexpected role of XBP1u as a potent repressor of both XBP1s and ATF6-mediated activation. The endoplasmic reticulum (ER) is responsible for synthesis, posttranslational modification, and folding of a substantial portion of cellular proteins. When protein synthesis is increased or ER function is compromised, the folding capacity of the ER may get out of balance, leading to an accumulation of unfolded or misfolded proteins in the ER. To alleviate ER stress and restore homeostasis, the cell activates three ER-to-nucleus signaling pathways, collectively called the unfolded protein response (UPR), which lead to a reduced protein synthesis and an increased expression of folding chaperones and ER-associated degradation (ERAD) factors (Walter and Ron, 2011). Subsequently, ER folding capacity increases and terminally misfolded protein species are exported from the ER and targeted for proteasomal degradation (Christianson and Ye, 2014). In mammalian cells, the UPR comprises three main signaling pathways named after the initiating ER stress sensors: PERK (PKR-like ER kinase), ATF6 (activating transcription factor 6), and IRE1 (inositol-requiring enzyme 1) (Walter and Ron, 2011). Upon activation by ER stress, PERK phosphorylates the translation initiation factor eIF2α, which leads to a massive attenuation of protein synthesis and an immediate reduction of the protein load in the secretory system. However, phosphorylated eIF2α selectively supports the translation of selected cellular proteins such as the transcription factor ATF4, which activates a negative feedback loop resulting in dephosphorylation of eIF2α (Novoa et al. , 2001). Upon activation by ER stress, ATF6 travels to the","Cells survive by making many different proteins that each carry out specific tasks. To work correctly, each protein must be made and then folded into the right shape. Cells carefully monitor protein folding because unfolded proteins can compromise their viability. A protein called XBP1 is important in controlling how cells respond to unfolded proteins. Normally, cells contain a form of this protein called XBP1u, while increasing numbers of unfolded proteins trigger production of a form called XBP1s. The change from one form to the other is activated by a protein called IRE1. Viruses often manipulate stress responses like the unfolded protein response to help take control of the cell and produce more copies of the virus. Murine cytomegalovirus, which is known as MCMV for short, is a herpes-like",380,128,0.3368
dialogsum,"#Person1#: What are you doing? #Person2#: I'm working on my college application. I just started writing my personal statement, but I'm having a hard time. #Person1#: What does it have to be about? #Person2#: It's basically just an essay about why I want to go to college and what I hope to do there. It's difficult to write, because I don't know what to major in yet. I know I want to go to college. I just don't have an idea of why I want to go. #Person1#: Why not just tell the truth in your essay? #Person2#: You mean I should write about the fact that I don't know what to do with my life? #Person1#: Yeah. I mean, I doubt if anyone really knows what career they want to have when they first go to college. You have years to that out. #Person2#: I guess I could write about that. #Person1#: What else do you need to do to finish your application? #Person2#: I need 2 recommendation letters. I asked my English teacher and my math teacher. Mrs. Watson turned hers in, but I'm waiting on my math teacher. I wanted to ask my drama teacher, Mr. Bennett, but I've only had one class with him, so I decided not to. I already turned in my grades and my SAT score. #Person1#: How did you do on the SAT? #Person2#: Not as well as I had hoped. I have really good grades, though, and I'm in all honors classes so that should help.",#Person2# is working on a college application but has difficulties in writing the personal statement. #Person1# reminds #Person2# that #Person2# has years to out the career. #Person2# also needs recommendation letters and grades for the application.,255,36,0.1412
dialogsum,"#Person1#: Today we have Jane Couch with us. Good evening and welcome, Jane. #Person2#: Good evening. #Person1#: Now this is a question that everyone would like to ask you. How did you get interested in boxing? #Person2#: I saw a little television program about women boxing about 6 years ago. And at that moment, I said to myself, I'm going to do that. And it just changed my life. But my parents disagreed at first. #Person1#: And were you interested in sport at school? #Person2#: No, nothing. I wasn't ever fit or anything. I just don't look after myself at all. #Person1#: What do you think is the most important for a top boxer? #Person2#: Believe it or not, anyone can fight. But to make it to the top, you have to know your skills. And you have to have a quick brain and the fitness. The fitness side of it is the most important. #Person1#: And just lastly, when is your next big fight? #Person2#: The next one is going to be the end of February, and I will have another 2 at the beginning of April, and at the end of May. #Person1#: Well, that's great. We're looking forward to seeing your performance. Thank you very much Jane.",Jane Couch tells #Person1# she got interested in boxing when she saw a little television program about 6 years ago. She tells #Person1# about important quality for a top boxer and her next fight plans.,210,35,0.1667
dialogsum,"#Person1#: Do you like music? #Person2#: Well, it depends. #Person1#: Do you think the music is well-matched? #Person2#: No, I think the music is too fast. #Person1#: How about the words of the song? #Person2#: It sounds nice. #Person1#: I like it. Naturally it can arouse your feelings. #Person2#: Yes, I think so. It's very emotional. #Person1#: Of course, and I also like the rhythms. #Person2#: Full of energy and hope. #Person1#: Really. It's worth listening to and enjoying. #Person2#: Certainly it is. It's worth an Academy Award.",#Person1# and #Person2# talk about a song. They both enjoy it because it's emotionaland full of energy and hope.,88,19,0.2159
dialogsum,"#Person1#: Well, Betty. Since you'Ve done well during the probation period, we decided to employ you formally. And now we need to sign the formal agreement. #Person2#: Thank you very much, Mr. Smith. I am very happy that I'll be a member of your team. May I see the agreement first? #Person1#: Of course. If you have any questions, just bring them out. #Person2#: OK, thank you. Well, I find that the salary level in this agreement is not like what you have said in the interview. Can you give me some explanations? #Person1#: Well, it's like this, during your first year, you will enjoy this salary level, a year later, we'll increase your salary by 20 %. #Person2#: Can we add up this item to the agreement? #Person1#: Yes, maybe the personnel department made some mistakes in making the agreement. Do you have any other questions? #Person2#: No, thank you. Shall we sign the agreement now? #Person1#: Yes, welcome to our company. I hope we can cooperate happily. #Person2#: Thank you. I'll work hard.","Betty finds the salary rate in the agreement is different from what Mr. Smith said in the interview. Mr. Smith explains and will modify it, then Betty's willing to sign the agreement.",175,32,0.1829
scientific_lay_summarisation-elife-norm,"of viral and cellular membranes, to allow the bilayers to fuse. On the virion, the Gn and Gc residues involved in intra- and inter-spike interactions have not been identified. These interactions control the fusion activity of Gc (Guardado-Calvo and Rey, 2017), by maintaining it at neutral pH in a functional metastable conformation (Harrison, 2015). Here, we show that the 2-fold Gc: Gc contacts between adjacent (Gn/Gc) 4 spikes at the surface of the hantavirus particles are mediated by the same interface observed in a crystallographic dimer revealed by the available X-ray structure of Gc in a pre-fusion form. These contacts regulate viral assembly together with spike stability and subsequent disassembly for entry. We further demonstrate that at physiological temperature, the spikes exhibit a dynamic temperature-dependent equilibrium between a ‘closed’ form in which the fusion peptides are masked by Gn, and an ‘open’ form that allows the particle to bind to liposomes at neutral pH. The X-ray structure of the Hantaan virus Gc ectodomain at neutral pH (PDB: 5LJY) (Guardado-Calvo et al. , 2016) revealed a pre-fusion monomer which, among other crystal contacts, presented two Gc molecules packing about a crystallographic 2-fold axis. The two Gc monomers in this dimer cross at an angle of roughly 50 degrees (1a) similar to the 2-fold related spike interactions in the cryo-ET map (Li et al. , 2016). The ‘dimer’ interaction observed in the hantavirus Gc crystals is reminiscent of the crystallographic dimer contacts presented by class II alphavirus fusion protein E1 (Roussel et al. , 2006), which is recapitulated by the 2-fold related contacts between hetero-hexameric (E2/E1) 3 spikes at the surface of alphavirus particles (Sun et al. , 2013; Voss et al. , 2010) (1a). To test whether the Gc: Gc interface observed in the crystallographic dimer is involved in contacts between adjacent spikes at the surface of hantavirus particles, we introduced cysteine substitutions of candidate Gc residues at the putative 2-fold interface, such that they could form inter-spike disulfide bonds. We surveyed residues facing each other across the crystallographic Gc dimer interface with Cα-Cα distances ranging between 4 and 10 Å and selected the highly conserved His303 and Gly187 for single cysteine substitutions. These residues face their counterpart on the 2-fold axis of the crystallographic dimer with Cα-Cα distances of 8.","Hantaviruses infect rodents and other small mammals, but do not harm them. When transmitted to humans, often through rodent urine, feces or saliva, they can cause serious and even fatal diseases. Currently, there are no known methods that effectively prevent hantavirus infections or treat the diseases that they cause. During an infection, viruses invade the cells of their host. A hantavirus interacts with target cells through proteins on its surface called Gn and Gc glycoproteins. Previous work has shown that these glycoproteins are organized in bundles of four Gn and four Gc proteins, termed spikes, which project from the membrane that surrounds the virus. The Gc protein changes shape when it is activated and exposes a hidden region that can insert into the membrane of the target cell.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"activation of ATM by chloroquine (CQ) promotes DNA damage clearance, rescues age-related metabolic shift, and alleviates cellular senescence. Mechanistically, ATM phosphorylates and stabilizes pro-longevity protein SIRT6. Extra copies of Sirt6 attenuate metabolic abnormality and extend lifespan in Atm-/- mice. Importantly, long-term treatment of CQ restores metabolic reprogramming and extends the lifespan of nematodes and a progeria mouse model. In searching for genes/pathways that drive senescence, we employed human primary endothelial cells, which underwent replicative senescence at passage 21, with increased p21 expression and β-galactosidase activity (— 1a–b). By RNAseq analysis, a gradual decline of ATM-centered DNA repair machinery was identified (— 1c–e). Western blotting analysis confirmed progressively downregulated protein levels of ATM and its downstream target NBS1 and RAP80 in senescent human skin fibroblasts (HSFs) (1a). Mouse embryonic fibroblasts (MEFs) with limited growth capacity and senescent phenotypes when cultured in vitro (Parrinello et al. , 2003; Samper et al. , 2003; Sherr and DePinho, 2000), and brain tissues from aged mice also showed progressive decline of ATM, NBS1, and RAP80 (1b–c). Concomitantly, upregulation of γH2AX, indicating accumulated DNA damage, and an increase in p16Ink4a were observed in senescent HSFs, MEFs, and aged brain tissues (1a–c). Knocking down ATM via shRNA accelerated senescence in HSFs, evidenced by increased β-galactosidase activity (1d–e), enlarged morphology (— 2a), accumulated γH2AX (1f), and reduced cell proliferation (— 2b). These data indicate that ATM decline retards DDR and drives senescence. Other than DNA damage, ATM is activated by chloroquine (CQ), an antimalarial drug that modulates chromatin confirmation (Bakkenist and Kastan, 2003). We confirmed that a low dose of CQ increased the level of pS1981 auto-phosphorylation of ATM but not γH2AX (— 2c). We then investigated whether activating ATM by CQ can ameliorate senescence. As shown, the CQ treatment activated ATM (pS1981), promoted clearance of DNA damage (γH2AX), and inhibited apoptosis (cleaved Casp3) in HSFs (1g). Also, the CQ treatment suppressed β-galactosidase activity, which was abrogated if ATM was knocked down (1h–i). Importantly, CQ treatment extended the replicative lifespan of HSFs (1j). Likewise, CQ treatment activated Atm, cleared up accumulated DNA damage, suppressed β-galactosidase activity (1k and — 2d–e), and prolonged replicative lifespan in MEFs (1l). Although both 10 μM and 1 μM of CQ activated ATM, a dose-dependent toxicity assay showed that 1 μM is suitable","As cells live and divide, their genetic material gets damaged. The DNA damage response is a network of proteins that monitor, recognize and fix the damage, which is also called DNA lesions. For example, an enzyme called ATM senses when DNA is broken and then begins a process that will get it repaired, while another enzyme known as SIRT6 participates in the actual mending process. When organisms get older, the repair machinery becomes less efficient, and the number of DNA lesions and errors increases. The accumulation of DNA damage may cause the ‘symptoms’ of old age – from cancer, to wrinkles and the slowing down of the body’s chemical processes. In fact, individuals with defective ATMs (who thus struggle to repair their DNA) age abnormally fast; conversely, SIRT6",380,128,0.3368
scientific_lay_summarisation-elife-norm,"are associated with a modulation of dopamine release such that, for instance, immediate early gene activation is triggered only by bursting patterns of activity (Kitai et al. , 1999). From a biophysical point of view, regular tonic activity seems to rely mainly on SNc dopaminergic neuron intrinsic conductances while both irregular and bursting patterns necessitate the release of various neurotransmitters (glutamate, acetylcholine) by SNc synaptic inputs (Kitai et al. , 1999; Grace et al. , 2007). In vitro however, mature SNc dopaminergic neurons mainly display a regular tonic (also called pacemaker) firing behavior (Grace and Onn, 1989; Liss et al. , 2001; Seutin et al. , 2001; Puopolo et al. , 2007; Guzman et al. , 2009; Putzier et al. , 2009b; Tateno and Robinson, 2011; Amendola et al. , 2012). The irregular pattern of spontaneous activity is observed in immature SNc DA neurons in vitro (postnatal days 9–16, P9–P16) and seems to be due to transient spontaneous activation of T-type calcium channels (Seutin et al. , 2000; Cui et al. , 2004) and subsequent activation of calcium-activated potassium channels (SK) (Seutin et al. , 1998; Wolfart and Roeper, 2002; Cui et al. , 2004). Finally, the spontaneous bursting pattern of activity is usually absent from mature SNc DA neurons in vitro, but can be observed in juvenile neurons (P15–P21) and depends on the activation of NMDA receptors (Mereu et al. , 1997), or can be promoted by pharmacological blockade of T-type calcium channels and SK potassium channels (Wolfart and Roeper, 2002). Although these different studies suggest that the activity pattern of SNc dopaminergic neurons changes during the first three postnatal weeks, involving modifications in both intrinsic and synaptic input properties, our knowledge of the precise timecourse of their electrophysiological development is still fragmented. In the current study, we have performed a detailed analysis of the development of the intrinsic properties of SNc dopaminergic neurons over the first four postnatal weeks (from P2 to P29). We measured 16 electrophysiological parameters, exhaustively characterizing the passive and active properties of SNc dopaminergic neurons. Applying multi-variate statistical analyses (agglomerative hierarchical clustering and principal component analysis) to the measured electrophysiological parameters revealed that the acquisition of mature regular pacemaking involves biphasic changes occurring mainly during the first two postnatal weeks: intrinsic electrophysiological maturity is","The brain contains hundreds of types of neurons, which differ in size and shape, and also in the chemicals that they use to communicate with each other. However, one thing all neurons have in common is that they all carry electrical signals that depend on the flow of ions through specialized channels in the membranes that surround each neuron. Nevertheless, the number and identity of these channels also vary markedly from one type of neuron to the next. This biophysical diversity underlies a variety of complex patterns of electrical activity observed in different types of neurons. This complexity often makes it difficult to pinpoint which of the myriad features of a neuron are most important for determining its function, and which ones are most affected by processes such",380,128,0.3368
dialogsum,"#Person1#: Where are you going to take your vacation? #Person2#: Hawaii. #Person1#: That sounds like a great place to visit. Is your family going? #Person2#: Yes. We plan to go mountain climbing, fishing, swimming, and windsurfing. But most of all, we're planning to relax. My wife is taking a whole bunch of books to read. #Person1#: Your children must all be excited about it. #Person2#: Yes, they are. They're counting the days. Are you going to Europe again this summer? #Person1#: No, not this time. We're going to visit some old friends in Egypt.",#Person2# plans to go to Hawaii to relax and #Person1# is going to Egypt.,94,14,0.1489
scientific_lay_summarisation-elife-norm,"very different membrane curvatures: the central cisterna part, which is almost flat with the seldom presence of fenestrations or pores; and the highly bent rim of the cisterna. How the different functions of the Golgi membranes (namely, protein processing and transport) are organized between these two regions is not yet fully understood. We previously reported that disruption of sphingomyelin (SM) organization specifically at the Golgi membranes –by SM synthase-mediated formation of short-chain SM at the trans-Golgi membranes– leads to inhibition of transport carrier formation (Duran et al. , 2012) and also to defects in transmembrane protein glycosylation and localization (van Galen et al. , 2014). Interestingly, we showed that these effects occur concomitantly with an overall reduction in the lateral lipid order of the Golgi membranes (Duran et al. , 2012) as well as with striking alterations in the morphology of Golgi cisternae, which abandon their typical flat morphology and become highly curled (van Galen et al. , 2014). Based on our findings, we suggested that short-chain SM might not be able to generate liquid-ordered nanodomains at the Golgi membranes (Duran et al. , 2012). However, it is still unclear whether there is any causal relation between the ability of SM to control lateral Golgi membrane organization and the observed changes in the morphology of the Golgi cisternae. Motivated by these experimental observations, we decided to investigate the physical mechanisms by which SM metabolism controls Golgi cisternae morphology, with a general aim at understanding whether the shape and the function of the Golgi complex are two sides of the same coin and how they relate to each other. Curling of a flat Golgi cisterna has, from a physical point of view, severe consequences. A flat cisterna has a large surface area at its rim with a very high membrane curvature thereby bearing large elastic stresses (Shibata et al. , 2009). Hence, cisterna curling is accompanied by a change in the distribution of the membrane elastic stresses. The quantitative analysis of the extent of these stresses and how they can be sustained within the overall cisterna morphology requires a physical description of the Golgi cisterna free energy. Here we present a biophysical model that describes the free energy of a Golgi cisterna to elucidate the mechanisms by which SM homeostasis mechanically","The Golgi complex is a hub inside cells that transports many proteins to various parts of the cell. It also receives freshly made proteins and modifies them to help them mature into their final active forms. The complex is made up of a stack of disc-like membrane structures called cisternae. Are the shapes of the cisternae important for the Golgi complex to work properly? Membranes are made of mixtures of molecules known as lipids and proteins. Previous experiments show that when the mixture of lipids in the Golgi membranes changes in a specific manner, the cisternae curl into an onion-like shape and the Golgi cannot process or send out proteins anymore. Campelo et al. used mathematics and experimental approaches to investigate what causes the Golgi to change shape",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2009), via inhibitory phosphorylation of Cdc42 guanine exchange factor (GEF) Gef1 (Das et al. , 2015). Here, we describe a novel role for Orb6 kinase, genetically separable from its control of the Cdc42 pathway, in promoting polarized cell growth by inhibiting translational repression. Translational repression, carried out in part by the assembly of cytoplasmic granules of ribonucleoprotein particles (RNPs), is a quick and reversible cellular strategy for inhibiting cell growth in response to stress, such as nutritional deprivation, oxidative stress, or osmotic stress (Coller and Parker, 2005; Decker and Parker, 2012; Kedersha et al. , 2005; Jud et al. , 2008). P-bodies, stress granules, and other RNPs such as neuronal transport granules and germ granules play important roles in mRNA regulation with implications for human diseases such as ALS, frontotemporal lobar degeneration, and viral infection (Ramaswami et al. , 2013; Chahar et al. , 2013). P-bodies in particular contain mRNA decay machinery and serve as sites of storage or degradation for mRNAs during times of cellular stress (Decker and Parker, 2012). In this work, we describe a novel mechanism whereby NDR kinase Orb6 negatively regulates the recruitment of mRNA-binding protein Sts5 into RNP particles and Sts5 localization to P-bodies at least in part by promoting Sts5 interaction with 14-3-3 protein Rad24. This mechanism of control prevents the degradation of mRNAs encoding proteins important for polarized cell growth and cell morphogenesis during exponential cell growth, and promotes morphological adaptation during nutritional stress. We observed that loss of Orb6 kinase activity by chemical inhibition of analog-sensitive Orb6-as2 kinase by the ATP analogue 1-NA-PP1 leads to cell separation defects (1A, c; B) and slow growth, in addition to polarity defects (Das et al. , 2009; Das et al. , 2015). By complementation screening of the orb6-as2 allele with mutants of other orb genes (Snell and Nurse, 1994; Verde et al. , 1995), we found that sts5 mutants (allelic to orb4; see — 1A) suppress the cell-separation defect associated with chemical inhibition of Orb6-as2 kinase (1A, d; 1B; Verde et al. , 1995) as compared to control cells (1A, c; 1B). sts5 encodes an mRNA-binding protein with significant sequence homology to Ribonuclease II (RNB) –domain and Ribonuclease R–domain proteins (Toda et al. , 1996; Jansen et al. , 2009). Closest homologues of Sts5 include","Living cells can grow to adopt a range of different shapes. For example, fission yeast cells maintain their rod-like shape by growing from their ends and then splitting in the middle to produce two new cells of an equal size. Like many other cells, fission yeast often responds to shortages of nutrients or other environmental stressors by growing more slowly or stopping its growth altogether. One way that this stress response is achieved is by preventing certain growth-promoting proteins from being made by storing or degrading the RNA molecules that are needed to make these proteins. Fission yeast uses an enzyme called Orb6 to control its growth and its overall shape. This enzyme is a kinase, meaning that it adds phosphate groups on to other proteins. Orb6 controls",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Structural modeling showed that ADs interact with Med15 without shape complementarity (‘fuzzy’ binding). ADs shared no sequence motifs, but mutagenesis revealed biochemical and structural constraints. Finally, a neural network trained on AD sequences accurately predicted ADs in human proteins and in other yeast proteins, including chromosomal proteins and chromatin remodeling complexes. These findings solve the longstanding enigma of AD structure and function and provide a rationale for their role in biology. Transcription factors (TFs) perform the last step in signal transduction pathways. They thus serve key roles in central processes such as growth, stress response, and development, and their mutation or misregulation underlies many human diseases (Spitz and Furlong, 2012). A TF includes a sequence-specific DNA-binding domain (DBD) and an effector domain that regulates nearby gene transcription. Activation domains (ADs) – effector domains that increase transcription – have long been of particular interest due to their roles as oncogenic drivers and use as scientific tools (Bradner et al. , 2017; Brückner et al. , 2009; Dominguez et al. , 2016). ADs were discovered as regions that could independently stimulate transcription when ectopically recruited to a gene promoter (Brent and Ptashne, 1985). Early experiments showed that ADs were unlike structured domains because progressive truncations showed graded reductions in activity (Hope and Struhl, 1986; Hope et al. , 1988). Subsequent studies showed that ADs were disordered and had few similarities in their primary sequence (Mitchell and Tjian, 1989). Instead, ADs were classified based on their enrichment of certain residues, whether acidic, glutamine-rich, or proline-rich. Acidic ADs are the most common and best characterized. Acidic ADs retain activity when transferred between yeast and animals, pointing to a conserved eukaryotic mechanism (Fischer et al. , 1988; Struhl, 1988). While some have found that acidic residues are necessary for activation, others have found that they are dispensable (Brzovic","Cells adapt and respond to changes by regulating the activity of their genes. To turn genes on or off, they use a family of proteins called transcription factors. Transcription factors influence specific but overlapping groups of genes, so that each gene is controlled by several transcription factors that act together like a dimmer switch to regulate gene activity. The presence of transcription factors attracts proteins such as the Mediator complex, which activates genes by gathering the protein machines that read the genes. The more transcription factors are found near a specific gene, the more strongly they attract Mediator and the more active the gene is. A specific region on the transcription factor called the activation domain is necessary for this process. The biochemical sequences of these domains vary",380,128,0.3368
dialogsum,"#Person1#: Hi, Claire. How does it feel to be back on campus? #Person2#: Hi, Gee. Well, to tell you the truth, I have mixed feelings. #Person1#: Oh, why? #Person2#: I have this great summer job that I really hated to leave I worked at the wild life research center in Maryland. #Person1#: That makes sense for a genetic major. What did you do? Clean the cages? #Person2#: This is a wild life center, not a zoo. This place breeds endangered species and tries to prepare them for life in the wild. #Person1#: You mean the endangered species like the tiger and the panda? #Person2#: Well, endangered species, yes. But not tigers or pandas. I work with whooping cranes and sandhill cranes. I taught the baby crane how to eat and drink, and I help the vets to give medical check-ups. #Person1#: I can see it was hard to leave that job. But how did you teach a bird how to eat and drink? #Person2#: We covered ourselves up with cloth and used puppets made out of stuffed crones to show the baby chicks what to do. Then the chicks copied what the puppets did. #Person1#: Cloth? Puppets? Sounds like fun. #Person2#: It was. The cloth and puppets are the key tools. We all covered ourselves up, the scientists, the vets, the junior staff, everybody. You see, baby cranes will become attached to their caretakers. #Person1#: So if the caretaker is a person, the crane will stay in places where people are. #Person2#: Yeah. And their chances for survival aren't very good. But by covering ourselves and using cloth and puppets the chicks are more likely to seek out other birds rather than people. And their transition to the wild has a better chance of being successful. #Person1#: A chance of being successful? Hasn't this been done before? #Person2#: It's been done with sandhill cranes and everyone is optimistic about its work with whooping cranes too. #Person1#: If this works, it should increase the number of cranes in the wild. #Person2#: Yeah. It's exciting, isn't it?","Claire has mixed feelings to be back on campus because she hated to leave her summer job. She worked at the wildlife research center, where she helped to breed cranes and prepare them for life in the wild. Claire then shares her experience in detail.",345,45,0.1304
dialogsum,"#Person1#: What's wrong? #Person2#: I have a headache. These past few days I've been living off painkillers. Man, I feel like my head is going to explode. #Person1#: You should get acupuncture treatment. My mom was always having headache issues and it was acupuncture that cured her. #Person2#: The results are too slow. On top of that, just the thought of smoking needles poking into my flesh frightens me. #Person1#: They don't just randomly stick you, they find your pressure points. The heat allows the body to immediately respond to the treatment, restoring the body's ' chi '. #Person2#: But I get scared the moment I see a needle. How could I stand having needles in my body for hours on end? #Person1#: The needles are very thin, and as long as the doctor's technique is good, and the patient himself is relaxed, it won't hurt-on the contrary it will actually alleviate pain. Now there are high-tech needles that are micro thin ; they don't hurt at all. However, if you are really scared of acupuncture, scraping or cupping are also options. #Person2#: Scraping is too terrifying. When they finish scrapping, your body is all red, as if you were just tortured. Cupping is the same, your body ends up with red circles all over. It looks like someone beat you up. #Person1#: This only signifies that the toxins have left the body. Actually, there is only discomfort during the treatment process. Once it's over you feel very comfortable. #Person2#: Chinese medicine is strange. The patients are already ill, and then the doctor makes them suffer more. #Person1#: This is the only way to get at the problem. Anyway, if you want to relieve the pain, you are just going to have to be tough and do it. #Person2#: Forget it. I don't want to inflict any more pain on myself. In a little while I'll go and buy some more painkillers and take a nap.",#Person2# suggests #Person1# getting acupuncture treatment to treat #Person1#'s bad headache but #Person2# is afraid of needles. Then #Person2# suggests #Person1# trying scraping or cupping but #Person2# prefers to take painkillers.,326,31,0.0951
dialogsum,"#Person1#: So next year, you're going to start A levels, which subject are you going to choose? #Person2#: I'm surely going to do Spanish because it is my favorite subject and then I'm not really sure. I'd like to do art but I don't know if it's very useful for my career. #Person1#: What do you want to do? #Person2#: A journalist, that has been my dream since my childhood, so I guess history or psychology or something is probably more useful for my career. #Person1#: Do you want to go to university? #Person2#: Yeah, but I'm not going to start university straight after I leave school. I'm planning to have a gap year, you know, a break from studying for a while. #Person1#: And what would you like to do in your gap year, any ideas? #Person2#: I want to travel. I'd like to go to Italy and learn Italian. I don't know if it's really practical, but that's my dream.",#Person2# will start A levels next year. #Person1# asks #Person2# about #Person2#'s future plan. #Person2# wants to choose Spanish and wants to be a journalist and wants to take a gap year before college.,162,34,0.2099
dialogsum,"#Person1#: I'd like to try this on, please. Where is the fitting room? #Person2#: This way, please. #Person1#: How do I look in this skirt, Gucci? Am I Spice Girl, or what? #Person3#: No, you look ridiculous. I suggest you try some other colors. #Person1#: OK, I will try on that green one. ... Now, how do I look? #Person3#: You look like a Christmas tree. Why not try on the red one? #Person1#: But red doesn't go with my green sweater. #Person3#: It surely does. Trust me, red is the global fashion now. #Person1#: All right, I will try on the red one. ... Now, what do you think? #Person3#: Terrific! #Person1#: But I feel I look like a pepper in green and red. #Person3#: That makes you a Spice Girl. #Person1#: Don't be kidding! Anyway I will take this one. #Person2#: Thank you. I will wrap it up for you. You can pay at the front counter. It's 500 yuan.","#Person1# tried the skirts on, and Gucci thinks #Person1# looks ridiculous. Gucci advises #Person1# to try on the red one which makes #Person1# look like pepper, and finally #Person1# takes the one.",162,32,0.1975
dialogsum,"#Person1#: I heard you received a prize for you book. #Person2#: yes, I did. I won a prize for best local history book at the annual book awards. #Person1#: congratulations! You must be very proud of your achievement. #Person2#: actually, I was happy just to get the book published. Winning the prize was an added bonus. #Person1#: what was the prize? #Person2#: I won $200 to spend on any books of my choice. #Person1#: that's a great prize for a person who writes books! Have you ever won a prize before? #Person2#: I shared a prize with some friends last week. We won a bottle of whisky at a pub quiz. #Person1#: I won $10 in the lottery last month. Perhaps next time, I'll be luckier and win the jackpot!",#Person1# congratulates #Person2# on winning the prize for #Person2#'s book. Then they share their own experience of winning a prize before.,130,21,0.1615
scientific_lay_summarisation-elife-norm,"of various factors that influence gut microbiota structure (Cowley et al. , 2015; Friedman et al. , 2017; Dhall et al. , 2014). Much of our knowledge for how gut redox potentials are determined involves host-associated pathways (Spees et al. , 2013; Rivera-Chávez et al. , 2016). Passive diffusion of oxygen from the epithelium increases redox potential and stimulates growth of aerobic microbes (Espey, 2013; Albenberg et al. , 2014). Secretion of redox-active immune molecules such as reactive oxygen species or nitrate is known to be a feature of inflammation that imposes oxidative stress on commensal microbes and can be exploited by select pathogens to colonize the intestine (Winter et al. , 2010; 2013; Faber et al. , 2016; Spees et al. , 2013; Rivera-Chávez et al. , 2016; Kelly et al. , 2015; David et al. , 2015). Maintenance of redox homeostasis in host tissue can also have spillover effects on luminal redox state (Circu and Aw, 2011). Yet, redox potential is likely to also be shaped by microbial metabolism. In free-living microbial communities, variation in available electron acceptors dictates where microbes that employ respiration can thrive; the differential microbial metabolism that follows can produce further changes in electron acceptor availability (Morris and Schmidt, 2013; Chen et al. , 2017; Noll et al. , 2005; Orcutt et al. , 2011). Moreover, microbial metabolism has been proposed as a mechanism for low redox potential states in the lung of cystic fibrosis patients (Cowley et al. , 2015). Here, we investigated the nature of redox potential dynamics under antibiotic treatment to assess the importance of host and microbial processes in structuring gut bacterial communities. Antibiotics directly disturb the microbiota but are also expected to alter host biology related to redox potential. Specifically, antibiotics have been found to increase gut epithelium oxygenation as a result of altered microbial composition and metabolic signaling to the host (Kelly et al. , 2015; Rivera-Chávez et al. , 2016). Increases in luminal oxygen due to diffusion from the microvasculature supplying the epithelium would lead to a higher redox potential under antibiotic treatment. In addition, host inflammation responses to antibiotic treatment and antibiotic-associated pathogen colonization have been shown to produce electron acceptors and other redox active molecules that cause oxidative stress (Faber et al. , 2016; Winter","The gut is home to a large and diverse community of bacteria and other microbes, known as the gut microbiota. The makeup of this community is important for the health of both the host and its residents. For instance, many gut bacteria help to digest food or keep disease-causing bacteria in check. In return, the host provides them with nutrients. When this balance is disturbed, the host is exposed to risks such as infections. In particular, treatments with antibiotics that kill gut bacteria can lead to side effects like diarrhea, because the gut becomes recolonized with harmful bacteria including Clostridium difficile and Salmonella. Reese et al. have now investigated what happens to the gut environment after antibiotic treatment and how the gut microbiota recovers. Mice treated with broad-spectrum",380,128,0.3368
dialogsum,"#Person1#: Hello, Is this EYE computers? #Person2#: Yeas, It is. Sewen Jes speaking. How can I help? #Person1#: Actually, I'm calling to complain about your service. The computer I bought last week is faulty. #Person2#: Oh, I'm sorry to hear that, sir. What exactly is problem? #Person1#: Well, easily, It doesn't work. It doesn't even start probably. #Person2#: Oh, dear! I'll do whatever I can.",#Person1# calls Sewen Jes about the faulty computer #Person1# bought last week.,65,12,0.1846
scientific_lay_summarisation-elife-norm,"perform a comprehensive analysis of the functionality, chemical and electrical compartmentalization as well as Ca2+ signaling in short spines (<2 µm), long spines (2–5 µm) and shaft synapses. In addition, we tested the influence of subthreshold voltage changes on spine Ca2+ during slow pacemaking, a characteristic firing pattern of dopamine neurons. We demonstrate the presence of functional dendritic spines on SNc dopaminergic neurons and provide evidence that activation of spines during pacemaking leads to novel enhancement of spine Ca2+ that occurs periodically in a window starting at the middle phase and lasts throughout remainder of the spike cycle. We analyzed the density and morphology of dendritic spines on dopaminergic neurons in live brain slices obtained from juvenile (P6–25) mice. shows a typical example of an Alexa-594-filled dopamine neuron. Dendritic spines were clearly visible on all dendrites that were imaged, including on proximal and distal dendrites (1A). However, the density of spines varied widely across the population of dendritic segments from 0. 5 spines/10 µm up to 4. 4 spines/10 µm, with the average density on segments at 2. 08 ± 0. 10 spines/10 µm (n = 76; 1B). Plotting the spine density versus age (1B), we observed a weak but statistically significant correlation indicating a reduction in density with age (Pearson’s R = -0. 23569, p=0. 040, n = 76 dendritic segments). 10. 7554/eLife. 13905. 003Figure 1. Dendritic spines on SNc dopamine neurons visualized in live slices. (A) SNc dopamine neuron filled with Alexa-594 via patch pipette, visualized on a two-photon microscope. Higher magnification of selected dendritic segments are shown in green, blue and red boxes. (B) Plot of spine density versus age for dendritic segments visualized in live slices. (C) Cumulative histogram showing distribution of spine lengths for P6 – P11 (green) and P14 – P25 (purple) mice. (D) Distribution of spines (indicated by vertical lines) along continuous stretches of dendrite from 20 different cells. (E) Plot of spine density versus distance from the 20 dendrites in previous panel (gray dashed lines) and averages with s. e. m. (white boxes). : http: //dx. . org/10. 7554/eLife. 13905. 003 Analysis of spine morphology showed many of the typical spine shapes (e. g. stubby and mushroom spines) similar to those reported on more traditional spiny neurons like pyramidal cells. In addition,","When a nerve cell is viewed under the microscope, its structure looks a little like that of a tree. Each nerve cell, or neuron, has an array of ‘branches’ known as dendrites, which receive chemical messages from other cells. These messages are converted into electrical signals in the cell body and then travel down the main nerve fiber, which is the output of the cell. At the end of the nerve fiber, the signals are converted into chemical messages again and passed on to the dendrites of the next neuron. The dendrites of most neurons are covered with spines that resemble thorns on a stem. These are the sites that typically connect neurons with other cells. However, neurons that release a chemical messenger called dopamine have largely smooth",380,128,0.3368
pubmed-summarization,"for extensive multifocal lesions have been proposed as treatment modalities in lch,9 however spontaneous regression has been reported in some unifocal lch cases.1 herein , we report a case of unifocal lch presenting as an unusual limbal lesion which recurred after primary excision . a 24-year - old man was referred to our center for a recurrent and painless limbocorneal lesion in his left eye . the primary lesion had been removed 10 months earlier with a clinical impression of limbal papilloma at another eye care center . the histopathological diagnosis had been acute bullous inflammation with granulation tissue composed of scattered single- and multi - nucleated histiocytes . uncorrected visual acuity was 20/20 in the right eye and 20/80 in the involved left eye . on slit lamp biomicroscopy , there was an elevated vascular mass extending from the temporal limbus to the central cornea in the left eye . intraocular pressure was within normal limits and fundus examination was unremarkable . with a clinical diagnosis of a recurrent limbocorneal papillomatous / dermoid - like lesion , the patient underwent mass resection together with corneoscleral patch grafting and lateral tarsorrhaphy . slit lamp photography was overlooked preoperatively since the lesion was thought to be a simple recurrent limbal papilloma . after surgery the patient received topical betamethasone 0.1% and chloramphenicol 0.5% eye drops along with non - preserved lubrication four times a day for four weeks . on gross histopathological examination , light microscopy disclosed non - keratinized stratified squamous epithelium overlying a diffuse inflammatory background composed of nests and clusters of large histiocytes with indented and grooved nuclei intermixed with lymphocytes , plasma cells and eosinophils ( figures 1a and 1b ) . the histopathological features were characteristic of lch with incomplete surgical excision . during follow - up and after four months , no signs indicative of recurrence lch results from proliferation of langerhans cells normally present in the epidermis.10 the condition is characterized by a wide clinical spectrum varying from spontaneous regression to rapid progression , recurrence and long - lasting sequelae.11 lch encompasses three main clinical subtypes ; unifocal lch ( eosinophilic granuloma ) , multifocal lch ( hand - schuller - christian disease ) and systemic lch ( abt - letterer - siwe disease).1","purposeto report a rare presentation of unifocal langerhans cell histiocytosis ( lch ) simulating a limbal papilloma.case reporta 24-year - old man presented with a limbal mass in his left eye which had initially been suspected to be a papilloma based on clinical findings . the mass was excised and a histopathological diagnosis of acute bullous inflammation with granulation tissue was made . the lesion relapsed 10 months later which necessitated repeat resection along with corneoscleral patch grafting . histopathological studies of the excised lesion led to a final diagnosis of lch.conclusionto the best of our knowledge , this is the second report of a rare presentation of lch in the limbus which recurred after excision of the primary mass . the recurrent lesion was diagnosed based on",380,128,0.3368
pubmed-summarization,", was dissolved in dmso ( 3 g/l ) and was injected into the fourth ventricle at a volume of 1 l per rat 1015 min before 2dg injection . at this the ampk activator aicar ( sigma - aldrich ) was dissolved in saline and injected into the fourth ventricle at a dose of 20 , 100 , 300 ( or 500 ) nmol per rat in 3 ( or 5 ) l saline . the immunotoxin dsap ( 82 ng/200 nl ; advanced targeting systems , san diego , ca ) or control unconjugated saporin ( sap ) ( 17.2 ng/200 nl ) , dissolved in 0.1 mol / l pbs ( ph 7.4 ) , was infused bilaterally through a pulled - glass capillary pipette ( 30-m tip diameter ) positioned stereotaxically just dorsal to the targeted site in the paraventricular hypothalamic nucleus ( pvh ) . stereotaxic coordinates for the pvh injection site were 1.8 mm caudal and 0.45 mm lateral to bregma and 7.37.4 mm ventral to dura mater ( 29 ) . the amount of unconjugated sap in the control solution approximated the amount of sap present in the dsap conjugate ( 21% ) , as indicated in the manufacturer s product information . previous work comparing sap and uninjected controls demonstrated that sap did not produce behavioral or significant histological signs of toxicity ( 2 ) . glucoprivic feeding induced by 2dg ( 200 mg / kg ) was tested 3 weeks after dsap or sap injections . one week later , expression of pampk and total ampk in hindbrain after the 2dg injection was measured . the dsap lesion was evaluated by western blot analysis of tyrosine hydroxylase ( th ) expression in hindbrain sites of interest and in a separate group of lesioned rats using immunohistochemistry ( ihc ) staining to detect dbh - positive cell bodies . two methods were used to confirm the dsap lesion because we knew that western blot analysis would detect the th present in the punched sample from terminals and processes of unlesioned catecholamine neurons not targeted by pvh dsap injection . thus , western blots of th would not reflect the destruction of catecholamine cell bodies in the lesion site as accurately as ihc","objectiveto examine the role of amp - activated protein kinase ( ampk ) in the control of glucoprivic feeding by hindbrain catecholamine neurons.research design and methodsmicropunched hindbrain samples were collected from control and 2-deoxy - d - glucose ( 2dg)-injected rats for western blot analysis of phosphorylated ( activated ) ampk ( pampk ) . samples also were collected from 2dg - injected rats pretreated with anti - dopamine--hydroxylase conjugated to saporin to lesion hindbrain catecholamine neurons . in a second experiment , rats were given a fourth - ventricle injection of compound c ( cc ) or 5-aminoimidazole-4-carboxyamide ribonucleoside ( aicar ) , an inhibitor and activator of ampk , to identify a role for ampk in hindbrain neurons required for elicitation of 2dg - induced feeding.resultssystemic",380,128,0.3368
dialogsum,#Person1#: Is Alice available? #Person2#: You're talking to her. #Person1#: I've called you a hundred times today. #Person2#: I was busy doing something. I apologize. #Person1#: No problem. #Person2#: Did you need something? #Person1#: Did you want to do something tomorrow? #Person2#: Is there somewhere special you wanted to go? #Person1#: How about a movie? #Person2#: A movie sounds good. #Person1#: Call me tomorrow then. #Person2#: I will see you tomorrow.,#Person1# calls Alice to invite her to watch a movie together tomorrow.,71,12,0.169
scientific_lay_summarisation-elife-norm,"were excluded. Second, we excluded any remaining transcripts with conserved protein coding potential, including the potential to produce small peptides, by performing stringent codon-substitution frequency (CSF) analysis (Lin et al. , 2011). We previously demonstrated that this algorithm is capable of discriminating known functional small peptides down to 11 amino acids (Guttman and Rinn, 2012; Guttman et al. , 2013). Using selective criteria, we restricted candidate lincRNAs to those with CSF scores <−200 (ranging from −205 to −14,771, 1A). Then, we examined existing ribosome profiling datasets to quantitate the ability of these transcripts to engage the ribosome (— 1). None of the tested candidates were shown to have clear translation efficiency or codon bias according to proposed standards (Guttman et al. , 2013). Finally, through genome lift-over of our mouse lincRNAs to the human genome (build hg19), we examined mass spectrometry data by Gascoigne et al. (2012) to discard transcripts with mapped peptides. We kept transcripts with only two or less mass spectrometry tags, consistent with low levels of background ribosome association observed by Guttman et al. (2013) (Supplementary file 1B). Thus, based on an exhaustive analysis of existing annotations, standard evolutionary and ribosome profiling metrics, as well as mass spectrometry data, these candidates do not appear to contain protein coding potential. 10. 7554/eLife. 01749. 003Figure 1. Properties of the 18 lincRNA candidates and Mendelian inheritance. (A) List of the 18 lincRNA candidates for targeted deletion in mouse and overview of criteria used for their selection. (B) Heatmap of log10 FPKM+1 expression levels of the 18 lincRNAs in a panel of adult mouse tissues and cell lines via RNA-Seq. (C) Guilt-by-association (GBA) analysis for 17/18 lincRNA candidates. Individual tiles represent significant (p<1. 0 × 10−6) gene sets from the CP Reactome collection at MSigDB. Tiles are filled based on the Z-score of the Pearson correlation values between a given lincRNA and the genes within the gene set across a compendium of RNA-Seq samples. (D) Mendelian inheritance of the 18 lincRNA mutant alleles from the progeny of heterozygote intercrosses. Numbers of observed and expected (in parenthesis) wild-type (+/+), heterozygote (+/−) and homozygote (−/−) mice are indicated. Mice were genotyped at weaning age. The p value is based on X2 test. † The Spasm gene is located on the X chromosome. :","The mammalian genome is comprised of DNA sequences that contain the templates for proteins, and other DNA sequences that do not code for proteins. The coding DNA sequences are transcribed to make messenger RNA molecules, which are then translated to make proteins. Researchers have known for many years that some of the noncoding DNA sequences are also transcribed to make other types of RNA molecules, such as transfer and ribosomal RNA. However, the true breadth and diversity of the roles played by these other RNA molecules have only recently begun to be fully appreciated. Mammalian genomes contain thousands of noncoding DNA sequences that are transcribed. Recent in vitro studies suggest that the resulting long noncoding RNA molecules can act as regulators of transcription, translation, and cell cycle. In",380,128,0.3368
pubmed-summarization,"pathophysiological cycles of denervation and impaired reinnervation , the loss of entire motor units , unloading due to prolonged periods of disuse , and excitation - contraction uncoupling may trigger a substantial loss in skeletal muscle mass and function . although considerable interindividual differences exist in the functional decline of the musculature during aging , most elderly people experience a general loss in skeletal muscle strength . while regular physical activity and a protein - rich diet can partially counteract severe muscle wasting , a sedentary life style and certain medical conditions , such as diabetes , cancer , renal failure , chronic obstructive pulmonary disease , or congestive heart failure , clearly promote muscle degeneration . skeletal muscle wasting plays a crucial role in physical disability , frailty , and loss of independence in aged people . skeletal muscle wasting in the elderly has been termed sarcopenia of old age , whereby this muscular impairment is probably due to multiple factors , as outlined in . on the cellular level , a variety of abnormal structural , physiological , and biochemical processes have been identified that are directly or indirectly associated with age - dependent muscle wasting . this includes a severe decline in contractile efficiency , increased apoptosis , denervation - associated atrophy , bioenergetic changes , impaired ion homeostasis , excitation - contraction uncoupling , decreased capacity for fibre regeneration , a partially diminished cellular stress response , and an altered equilibrium of hormones and growth factors crucial for the maintenance of contractile function , as well as oxidative stress and mitochondrial abnormalities . although individual muscles in aged humans and animal models of sarcopenia exhibit alterations in the molecular composition of contractile fibres and changes in their glycolytic and aerobic capacity , findings on distinct shifts in fibre types with aging are highly variable . however , since mitochondrial functions are clearly impaired in senescent muscle tissues , it was of interest to summarize the impact of recent mass spectrometry - based proteomic studies on the molecular fate of mitochondrial enzymes in senescent fibres . this paper briefly outlines the proposed role of mitochondria in cellular senescence and recent achievements of mitochondrial proteomics and then focuses on findings from proteomic profiling studies of aged skeletal muscle","mitochondria are of central importance for energy generation in skeletal muscles . expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis , fibre maturation , and various neuromuscular pathologies , as well as natural fibre aging . mass spectrometry - based proteomics suggests itself as a convenient large - scale and high - throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease . this paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles . changes in the abundance , biochemical activity , subcellular localization , and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2008). Importantly, extracellular vesicle-bound RNAs appear to be enriched in specific classes of RNAs, including small RNAs and microRNA (miRNA) (Skog et al. , 2008; Valadi et al. , 2007; Kosaka et al. , 2010). Exosomes are a subclass of extracellular vesicle which can be defined as 30–100 nm vesicles with a buoyant density of ~1. 10–1. 19 g/ml that are enriched in specific biochemical markers, including tetraspanin proteins (Colombo et al. , 2014). It is often assumed that vesicles fitting this description are derived from the multivesicular body, but some evidence suggests that physically and biochemically indistinguishable vesicles bud directly from the plasma membrane (Booth et al. , 2006). Numerous studies have reported the presence of RNAs, especially miRNAs, from fractions containing exosomes, though many of these studies have relied on isolation techniques (e. g. high speed sedimentation) that do not resolve vesicles from other cellular debris or RNPs (Bobrie et al. , 2012). Thus, it is difficult to know in which form RNAs are secreted and even more challenging to determine which miRNAs may be specifically secreted as exosome cargo. The use of many different cell lines, bodily fluids and isolation methods to identify which miRNAs are specifically packaged into exosomes further complicates the establishment of widely accepted exosomal miRNA cargo. Even with the crude preparations that have been characterized, it is clear that RNA profiles from exosomes are distinct from those of the producer cells. Thus RNA capture or stabilization in exosomes is likely to occur through a selective sorting mechanism. RNA packaging may occur by specific interactions with RNA binding proteins that engage the machinery necessary for membrane invagination into the interior of an MVB or by interaction of RNAs with lipid raft microdomains from which exosomes may be derived (Janas et al. , 2015). In order to probe the mechanism of exosome biogenesis, we developed procedures to refine the analysis of RNA sorting into exosomes. Using traditional means of membrane fractionation and immunoisolation, we identified unique miRNAs highly enriched in exosomes marked by their content of CD63. This miRNA sorting process was then reproduced with a cell-free reaction reconstituted to measure the packaging of exosome-specific miRNAs into vesicles formed in incubations containing crude membrane and cytosol fractions. Among the requirements for miRNA sorting in","Human cells release molecules into their surroundings via membrane-bound packets called exosomes. These molecules can then circulate throughout the body and are protected from degradation. Among the cargos carried by exosomes are small molecules of RNA known as microRNAs, which are involved in regulating gene activity. Only a select subset of the hundreds of microRNAs in a human cell end up packaged into exosomes. This suggests that there might be a specific mechanism that sorts those microRNAs that are destined for export. However, few proteins or other factors that might be involved in this sorting process had been identified to date. Shurtleff et al. set out to identify these factors and started by purifying exosomes from human cells grown in the laboratory and looking for microRNAs that were",380,128,0.3368
pubmed-summarization,"vitamin a deficiency is the leading cause of preventable childhood blindness in the developing world . although rare in the united states , vitamin a deficiency has been known to occur as a result of poor dietary intake , liver diseases , and gastrointestinal malabsorption . vitamin a is a fat - soluble vitamin ingested in the diet in two forms : as retinol itself from animal sources , such as milk , meat , fish , liver , and eggs , or as the provitamin carotene from plant sources , such as green leafy vegetables , yellow fruits , and red palm oil . on the ocular surface , vitamin a deficiency has a wide range of ocular manifestations including conjunctival and corneal xerosis , keratomalacia , retinopathy , visual loss , and nyctalopia , also called night blindness , which is the earliest and most common symptom . we report a case of bilateral sequential corneal ulceration in a patient with severe vitamin a deficiency in the context of eosinophilic gastroenteropathy . a 29-year - old man was referred to our cornea unit with a left corneal ulcer of 6 weeks ' duration . he was previously diagnosed with eosinophilic gastroenteropathy ( biopsy proven ) , skin atopy and atopic keratoconjunctivitis . he had been treated with peroral steroids 15 mg / day and methotrexate 6 mg / week since the age of 11 years for his gastroenteropathy . he had surgery for steroid - induced cataracts with toric intraocular lens implantation at the age of 27 years . in addition , he had a number of food intolerances and subsisted mostly on a diet of potatoes . prior to his presentation , he had noted irritation , itchiness , and a decrease in vision in his left eye for 6 weeks and was treated with topical anti - allergic and topical steroid drops ; however , no improvement could be observed . polymerase chain reaction testing for herpes simplex virus was negative , and the cultures did not show any growth . acuity without correction was 20/80 od , improved by pinhole to 20/50 , and 20/150 os with a manifest refraction of 0.25/-2.5/5 , not improved by pinhole . the intraocular pressure was 19 mm hg","purpose : vitamin a deficiency is a very rare condition in the developed world and can lead to a variety of ocular changes from xerosis and xerophthalmia to corneal ulcer and perforation . the treatment of this devastating disease is simple and inexpensive . it is therefore important to recognize and treat accordingly , especially in the event of ulcers unresponsive to treatment or in the presence of severe malnutrition / malabsorption syndromes . the purpose of this case report is to remind physicians of the potentially devastating effects of vitamin a deficiency on the eyes and to demonstrate outcomes after vitamin a treatment . methods : single observational case report . results : a 29-year - old male with known eosinophilic gastroenteropathy was treated with oral steroids",380,128,0.3368
dialogsum,"#Person1#: What do you want to do tonight? #Person2#: How about going to the cinema? I haven't seen a movie for a long time and I really miss it. #Person1#: What do you want to see? #Person2#: There's a good film at the Green House Cinema,The Speed and Passion 8. I've watched all the former movies in that series and I really like them. The movie starts at 6:15 pm. #Person1#: I don't think I can make it. I won't be able to leave the office until 6:00 pm. #Person2#: Then let's watch the one that starts at 8:20 pm. We can eat first and then go to the cinema. #Person1#: That sounds better.","#Person2# suggests going to the cinema. Since #Person1# can't leave the office until 6:00 pm, they will watch the one starting at 8:20 pm.",114,24,0.2105
pubmed-summarization,"in the mouse genome . serum concentrations of il-1 , il-1 , il-2 , il-3 , il-4 , il-5 , il-6 , il-9 , il-10 , il-12(p40 ) , il-12(p70 ) , il-13 , il-17 , eotaxin , g - csf , gm - csf , ifn- , kc , mcp-1 , mip-1 , mip-1 , rantes , tnf- , il-15 , fgf - basic , lif , m - csf , mig , mip-2 , pdgf , vegf , alanine aminotransferase ( alt ) , and aspartate aminotransferase ( ast ) were not significantly different in the presence or absence of b cell lymphomas . interestingly , the average sil-2r level was significantly higher in the sera from rzcd19cre mice with b cell lymphomas ( 830.3 533.0 pg / ml ) than in that from tumor - free control groups , including the rzcd19cre , rz , cd19cre , and wild - type ( wt ) mice ( 499.9 110.2 pg / ml ; p < 0.0057 ) ( (d ) ) . the difference in the average sil-2r levels between the sera from groups with tumors other than b cell lymphomas ( 430.46 141.15 pg / ml ) and that from tumor - free control groups was insignificant ( p > 0.05 ) . moreover , all rzcd19cre mice with a relatively high level of sil-2r ( > 1000 pg / ml ) presented with b cell lymphomas . a significant increase in sil-2r was also observed in mxcre / cn2 - 29 mice that expressed the hcv cn2 gene and had b cell lymphomas , compared with tumor - free control ( cn2 - 29 ) mice . to examine whether sil-2r was derived from lymphoma tissues , we quantified il-2r concentrations in splenocytes , peripheral blood lymphocytes ( pbls ) , and b cell lymphoma tissues . the concentration of il-2r was significantly higher in splenocytes from rzcd19cre mice than in splenocytes from cd19cre mice . moreover , the concentration of il-2r in b cell lymphoma tissues from rzcd19cre mice was higher than that in splenocytes . these results strongly suggest that b cell lymphomas directly contribute to the elevated serum concentrations of sil-2r in rzcd19cre mice . they also strongly support the possibility that persistent","b cell non - hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis c virus ( hcv ) infection . the mechanism by which hcv infection leads to lymphoproliferative disorder remains unclear . our group established hcv transgenic mice that expressed the full hcv genome in b cells ( rzcd19cre mice ) . we observed a 25.0% incidence of diffuse large b cell non - hodgkin lymphomas ( 22.2% in male and 29.6% in female mice ) within 600 days of birth . interestingly , rzcd19cre mice with substantially elevated serum - soluble interleukin-2 receptor -subunit ( sil-2r ) levels ( > 1000 pg / ml ) developed b cell lymphomas . another mouse model of lymphoproliferative disorder was established by persistent expression of hcv structural",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2013). There was no difference between the weights of control (19. 8 ± 2. 3 g; n = 14) and dI3OFF mice (19. 0 ± 2. 7 g; n = 9, p>0. 44). Footprint and inter-limb coordination analysis revealed subtle alterations in locomotion in adults (1A). The hind paws, but not the forepaws, of dI3OFF mice were more widely spaced than those of control mice (1B), and dI3OFF mice had a greater propensity to make coincident contact with the ground with three or four paws (1A, C, and Video 1), however inter-limb coordination was similar in dI3OFF and control mice (— 1). During treadmill locomotion (Video 1), dI3OFF mice had longer stance times on average, and a steeper relationship between stance duration and cycle period than seen in controls (1D, E). Collectively, the shorter swing phases, increased time with more paws in contact with the treadmill, and more widely spaced hind paws in dI3OFF mice could result from a reduction in extensor activity and/or compensation for a reduction in stability. Taken together, these results show that while dI3 INs sculpt hind limb movement, they are not critical for the fundamental rhythm and/or pattern of locomotion. 10. 7554/eLife. 21715. 003Figure 1. dI3 INs are subtly involved in locomotion. (A) Footprint snapshots in control (cyan) and dI3OFF (magenta) littermates at 30 ms intervals starting from the onset of the stance of right hindlimb (top) running at 30 cm/s. Coloured lines represent hindlimb feet spacing, circles indicate foot contact. (B) Front and rear foot spacing for control (cyan, n = 6) and dI3OFF (magenta, n = 3) animals running between 10 and 50 cm/s. Mean +/− Standard Deviation. (C) Proportion of time with indicated number of feet contacting the treadmill belt in same animals running between 10 and 18 cm/s. (D) Percentage of swing (light shades) and stance (dark shades) in same animals running between 10 and 18 cm/s. (E) Correlation between swing or stance duration and cycle period in same animals running between 9. 5 cm/s and 72 cm/s. Each data point represents a single step cycle. Analysis of Covariance (ANCOVA) on slopes. (B, C, D) Two-way ANOVA followed by Sidak post-hoc multiple comparison test. *p<0. 05, **p<0. 01, ***p<0. 001, and ****p<0. 0001, ns non-significant. : http: //dx. . org/10.","Circuits of nerve cells, or neurons, in the spinal cord control movement. After an injury to the spinal cord, the connections between the brain and spinal neurons may be severed, meaning that the spinal circuits can no longer work properly. This loss of communication between the brain and the spinal cord often leads to paralysis below the level of the injury. There are currently no effective treatments for individuals who have lost the ability to walk following spinal cord injury. However, the spinal cord retains circuits that are sufficient to restore walking and these circuits can be activated with training. That is, rehabilitative training can lead to improvements in movement by promoting spinal cord plasticity – the ability of other neurons in the spinal cord to take over",380,128,0.3368
scientific_lay_summarisation-elife-norm,"this mathematical method fails, and as a result the claims are without any basis. We will see that the data on human olfaction are equally consistent with a trillion discriminable odors and with just 10 (and anything in between). Moreover, if the same method were applied to human color vision, one would conclude that humans can distinguish at least 1027 colors, in dramatic conflict with experimental evidence. Beyond correcting the erroneous claims, the analysis of failure in the Bushdid et al. study yields useful insights about the nature of the olfactory code. I follow with some suggestions for an approach to estimate the number of distinguishable odors. The reader is encouraged to read the original report by Bushdid et al. (2014). The following is a brief summary of the procedures used in that study. The space of all possible odor stimuli is huge. There are likely several hundred thousand distinct chemicals that smell. Any mixture of those chemicals is a point in odor space. The goal is to find how many of those mixtures produce distinct sensations. What is the largest collection of odors such that any one is discriminable from all the others? The reported experiments were limited to a subspace spanned by 128 substances. From these primary odors the authors made mixtures by drawing a number (N) of primary odors and mixing those in equal parts. Each primary odor is either present or absent in the mixture. Some of these mixtures are very similar to each other, for example if they share 29 of the 30 primary components. Others are very different, for example when they share none of the primary components. For any two mixtures the number of unshared components can be defined as their ‘distance’. The authors assume that the ability of humans to discriminate two odors improves systematically with this distance. The next step is to determine the critical distance at which two odors become discriminable. The authors probe this systematically by making pairs of mixtures with N components of which M are unshared, and testing those for discrimination by human subjects. Indeed they find that the probability of discrimination increases with M (3B of Bushdid et al. , 2014). They define the critical distance D as that separation M at which 50% of the","Scientists are interested in the number of colors, sounds and smells we can distinguish because this information can shed light onto how our brains process these senses both in health and disease. It is relatively straightforward to determine how many colors we can see or sounds we can hear because these stimuli are well defined by physical properties such as wavelength. We know the range of wavelengths that the eye can see or the ear can hear, and we can also understand how two such stimuli (e. g. , red and blue) are arranged perceptually (think of a color wheel). It is harder, however, to do the same for smell because most ‘olfactory stimuli’ consist of mixtures of different odor molecules. Moreover, we understand much less about how",380,128,0.3368
dialogsum,"#Person1#: Hi, Bill, you look happy. #Person2#: Yes, I've just seen a very funny film on TV. #Person1#: What was it about? #Person2#: It was about a careless man who got into trouble wherever he went. He couldn't do anything right. #Person1#: So you like it? #Person2#: Yes, I do. It made me laugh a lot. #Person1#: But I'd rather see something not only interesting but also instructive. #Person2#: Oh, Jane, don't be so serious. People sometimes need relaxation. #Person1#: That's true. But I just think that watching TV is not just for entertainment.","Bill saw a funny movie. Jane thinks it's not instructive, but Bill thinks people need relaxation.",94,16,0.1702
dialogsum,#Person1#: What? You want to leave early? #Person2#: Yes. Can I? #Person1#: Do you really need to? #Person2#: Yes. Is it OK with you? #Person1#: Is it important? #Person2#: Yes. Do you mind? #Person1#: You really have to? #Person2#: Yes. Will you let me? #Person1#: I guess so.,#Person2# wants to leave early. #Person1# is reluctant but agrees.,48,10,0.2083
scientific_lay_summarisation-elife-norm,"Al Olama et al. , 2009; Yeager et al. , 2009). For example, the polymorphism rs6983267 linked to colorectal (Tomlinson et al. , 2007) and prostate (Yeager et al. , 2007) cancers contributes more to cancer morbidity and mortality than any other known inherited variant or mutation, including the inherited mutations in classic tumor suppressors such as RB, TP53 and APC. Through computational and experimental analyses, we and others have shown that the risk allele G of rs6983267 creates a strong binding site for the colorectal-cancer associated transcription factor Tcf7l2 (Pomerantz et al. , 2009; Tuupanen et al. , 2009). This binding site is located within the Myc-335 enhancer element that is dispensable for mouse viability, but required for efficient Tcf7l2-driven intestinal tumorigenesis (Sur et al. , 2012b). More recently, another enhancer element, located 1. 47 Mb downstream of Myc was shown to be required for formation of acute lymphoblastic leukemia (ALL) in mice (Herranz et al. , 2014). However, in contrast to the Myc-335 element, this element is also required for normal T-cell development. Thus, the mechanism by which individual Myc enhancer elements contribute to normal development and tumorigenesis is still unclear. Several studies have shown that the 8q24 region contains a large number of additional enhancer elements (see, for example [Hallikas et al. , 2006; Ahmadiyeh et al. , 2010; Yan et al. , 2013; Yao et al. , 2014]) and super-enhancers that are active in many different types of human cancer (Hnisz et al. , 2013; Lovén et al. , 2013; Zhou et al. , 2015). The MYC-associated super-enhancers are activated during the process of tumorigenesis (Hnisz et al. , 2013), and downregulation of super-enhancer activity leads to selective inhibition of MYC expression (Lovén et al. , 2013). Thus, MYC-associated super-enhancer activity is required for tumorigenesis, but the role of these elements in normal tissue morphogenesis and homeostasis has been unclear. To address this problem, we have in this work generated multiple mouse strains deficient of regulatory elements upstream of the Myc promoter. Since this region contains multiple tumor type and tissue -specific enhancers and super-enhancers, for the sake of clarity we refer to the deleted region here as the `super-enhancer region´. By analysis of the mice, we found that the entire super-enhancer region conferring multi-cancer susceptibility","Our cells each contain close to 20,000 genes, which provide the instructions needed to build our bodies and keep us alive. At any one time in the life of the cell, only some of these genes are active. The activity of each gene is constantly regulated to allow the cell to respond to changes in its environment. Enhancers are sections of DNA, outside of the genes, that act as molecular switches controlling the activity of genes. A gene can have many such enhancers; each enhancer is linked to a particular set of signals and having multiple enhancers allows the same gene to be activated by different signals in different tissues in the body. Changes to enhancers can have serious consequences. By altering the activity of genes, an enhancer",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2000; Rosen et al. , 2000; Farmer, 2006; Rosen and MacDougald, 2006; Siersbæk and Mandrup, 2011]), most notably the early-expressed CCAAT/enhancer binding proteins beta (C/EBPβ) and delta (C/EBPδ), which induce C/EBPα and the adipogenic master regulator nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ). C/EBPα and PPARγ cooperate to activate adipogenic genes and cross-regulate each other in a positive feedback loop to maintain the terminally differentiated state of mature adipocytes (Wu et al. , 1999). Several studies have revealed the importance of other TFs in regulating adipogenesis both in vitro and in vivo (Soukas et al. , 2001). These include members of the Krüppel-like family (KLF4 [Birsoy et al. , 2008], KLF5 [Oishi et al. , 2005], and KLF15 [Mori et al. , 2005]), ADD1/SREBP1c (Fajas et al. , 1997; Kim et al. , 1998), the E2F (Fajas et al. , 2002), and the interferon regulatory factor (IRF) families (Eguchi et al. , 2008), STAT5A/B (Floyd and Stephens, 2003) and GATA2/3 (Tong et al. , 2000). Efforts are therefore underway to integrate this information into comprehensive adipogenic regulatory networks (aGRNs) (Rosen and MacDougald, 2006, Siersbæk et al. , 2012), to which new nodes such as the early regulators ZFP432 (Gupta et al. , 2010), TCF7L1 (Cristancho et al. , 2011), or EVI1 (Ishibashi et al. , 2012) keep being added. This suggests that many important components of this aGRN remain to be discovered. To systematically identify novel aGRN members, we performed a large-scale overexpression screen with 734 full-length mouse TFs in 3T3-L1 cells, which led to the identification of 26 pro-adipogenic TFs. We found that the top ranking TF, ZEB1, previously known for its role in epithelial to mesenchymal transition (EMT) and tumor metastasis (Vandewalle et al. , 2009; Gheldof et al. , 2012), is a critical mediator of in vitro and in vivo adipogenesis, as it directly controls the majority of aGRN genes. To systematically identify TFs enhancing adipogenesis in an unbiased manner, we tested the effect of overexpressing almost half (48%) of all predicted mouse TFs on 3T3-L1 fat cell differentiation. We transferred 750 available mouse TF open reading frames (ORFs) (Gubelmann et al. , 2013) into Tet-On Gateway-compatible inducible lentiviral expression vectors and obtained 734 clones (— 1A). Using a robotic platform, lentiviral particles containing each TF","The growing rates of obesity and related metabolic diseases are a major public health concern worldwide. People who are overweight or obese are at increased risk for a range of diseases including diabetes and heart disease, which may reduce their quality of life and shorten their lifespans. Obese people have more, larger fat cells than individuals of healthy weight, and so understanding how the body creates fat cells may provide new insights into ways to prevent or treat obesity. Fat cells arise from a population of stem cells that can also give rise to bone cells and cartilage. Some of the proteins—called transcription factors—that work together to turn on the expression of genes needed for a stem cell to become a fat cell have been identified. However, the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"major organ growth, after which they reach a steady low proliferative capacity that contributes to maintain normal homeostasis and physiological adaptation of the pituitary gland (Levy, 2002; Nolan et al. , 1998). Contrary to other organs, where somatic stem cells are shown to be able to become transformed into cancer stem cells, the roles of SOX2+ PSCs in tumourigenesis remain poorly understood, possibly due to the patchy knowledge of the pathways regulating SOX2+ PSC fate and proliferation. Pituitary tumours are common in the population, representing 10–15% of all intracranial neoplasms (Bronstein et al. , 2011; Daly et al. , 2006). Adenomas are the most common adult pituitary tumours, classified into functioning, when they secrete one or more of the pituitary hormones, or non-functioning if they do not secrete hormones. In children, adamantinomatous craniopharyngioma (ACP) is the most common pituitary tumour. Targeting oncogenic beta-catenin in SOX2+ PSCs in the mouse generates clusters of senescent SOX2+ cells that induce tumours resembling ACP in a paracrine manner, that is the tumours do not derive from the targeted SOX2+ PSCs (Andoniadou et al. , 2013; Gonzalez-Meljem et al. , 2017). Up to 15% of adenomas and 50% of ACP display aggressive behaviour with invasion of nearby structures including the hypothalamus and visual tracts, associated with significant morbidity and mortality (Lasolle et al. , 2017). Pituitary carcinomas exhibiting metastasis are rare but can develop from benign tumours (Veldhuis, 2013; Pernicone et al. , 1997; Heaney, 2014). Whether SOX2+ cells can cell autonomously contribute to pituitary neoplasia has not been hitherto demonstrated. The Hippo pathway controls stem cell proliferation and tumourigenesis in several organs such as in the liver (Zhou et al. , 2009; Lu et al. , 2018), intestines (Zhou et al. , 2011) and lung (Lin et al. , 2015; Nantie et al. , 2018). In the core phosphorylation cascade, STK3/4 kinases phosphorylate and activate LATS1/2 serine/threonine-protein kinases, which in turn phosphorylate co-activators Yes-associated protein (YAP1, a. k. a. YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, a. k. a. TAZ) that are subsequently inactivated through degradation and cytoplasmic retention (Meng et al. , 2016). Active YAP/TAZ associate with TEAD transcription factors, promoting the transcription of target genes such as Cyr61 and Ctgf (Zhao et al. , 2008; Zhang et al. , 2009;","The pituitary is a gland inside the head that releases hormones that control major processes in the body including growth, fertility and stress. Diseases of the pituitary gland can prevent the body from producing the appropriate amounts of hormones, and also include tumours. A population of stem cells in the pituitary known as SOX2 cells divide to make the specialist cells that produce the hormones. This population forms as the pituitary develops in the embryo and continues to contribute new hormone-producing cells throughout life. Signals from inside and outside the gland control how the pituitary develops and maintain the correct balance of different types of cells in the gland in adults. In 2016, Lodge et al. reported that a cascade of signals known as the Hippo pathway is",380,128,0.3368
dialogsum,"#Person1#: Look at this picture! Is it the Great Pyramid? #Person2#: You've got it. I took many pictures of it. #Person1#: You mean you have been in Egypt? When did you go there? #Person2#: Last summer. It was so interesting. #Person1#: Tell me something about the Great Pyramid. #Person2#: It was very high, about 137 meters. The sides are as long as 230 meters. #Person1#: And it's very old? #Person2#: Yes, it has a long history of about 4500 years. #Person1#: Really? I can't believe it! #Person2#: Yes, seeing is believing. You must go and see it by yourself. #Person1#: It sounds nice. So Egypt is the place where I'm going to spend my next holiday. #Person2#: By the way, where did you spend your vacation last summer? #Person1#: I went to Japan and it's not so much fun. #Person2#: I bet you'll have great fun in Egypt.",#Person2# tells #Person1# about #Person2#'s trip to Egypt and #Person2#'s impression of the Great Pyramid. #Person1# decides to spend #Person1#'s next vacation in Egypt.,148,24,0.1622
scientific_lay_summarisation-elife-norm,"of weekly influenza-like patient visits (transformed into an estimated rate of infection) as a response variable in a regression analysis of climate data. They concluded that the bulk of explained variation (57%) was attributed to the depletion of susceptible hosts during the disease season and non-weather-related ‘between-season effects, ’ with only 3% explained by absolute humidity, represented as a continuous predictor variable. Additionally, this study observed that school holidays did not have a statistically significant effect on influenza transmission. As all causality detection methods come with dissimilar limitations and are imperfect in unique ways, we designed our study intentionally to attack the same target problem using three different statistical approaches: Approach 1: A non-parametric Granger analysis (Granger, 1980) focusing on infection flows’ directionalities across the US and whether influenza propagates via long- vs. short-distance travel (we run analysis across all pairs of air- and land-travel county neighbors, respectively). Approach 2: A mixed-effect Poisson regression (Hedeker and Gibbons, 2006) explicitly accounting for the auto-correlation of infection waves in time and space, along with the full set of socioeconomic, climate, and geographic predictors. Approach 3: A county-matching, non-parametric analysis to identify the minimum predictive set of factors that distinguish those counties associated with the onset of the influenza season (Morgan and Winship, 2015). Our study became possible through access to several, very large longitudinal datasets: (1) a nine-year collection of insurance records capturing the dynamics of influenza-like illnesses (ILIs) in the United States (Truven MarketScan database, see Materials and methods); (2) temporally collinear, high-resolution weather measurements over every US county; (3) detailed air travel (The United States Bureau of Transportation Statistics, 2010) and geographic proximity data (The United States Census, 2016) showing connectivity between US counties; (4) billions of geo-located Twitter messages reflecting long- and short-distance human movement patterns, and; (5) US census data accounting for US county and county-equivalent population distribution, demographic, and socioeconomic properties (HRSA, 2016). An explicit comparison of the ILI data in the insurance claims to the influenza records provided by the Center for Disease Control and Prevention (CDC, 2016) showed that the two sources agree well (ρ=0. 91, p=3. 5×10-201), with insurance claims providing higher data resolution, see — 1. Curiously, the relationship between the two sources of ILI observations is not linear: We attribute this to","Influenza – or ‘the flu’ – is a contagious disease which sweeps across the globe like clockwork, claiming tens of thousands of lives. This is known as ‘seasonal flu’. Many scientists have tried to identify the factors that spark these yearly outbreaks. Some past studies have found that seasonal flu occurs when air that is normally humid turns dry, suggesting weather patterns play an important part. Other research has shown that air travel contributes to the flu spreading across the world. However, these studies typically focus on just one or two factors on their own. It is still not clear how exactly these factors combine to drive outbreaks, and then sustain the wave of infection. To address this, Chattopadhyay et al. analyze the medical histories of 150 million",380,128,0.3368
dialogsum,"#Person1#: Sir, the plane will be landing in Moscow in 20 minutes. Please remain seated. #Person2#: I'm sorry. I just wanted to get something to drink. I'm so thirsty, can you bring me a glass of water? #Person1#: Sure, I'll be back with it in just a minute. Please wait for a moment. #Person2#: Thank you very much, by the way, what's the weather like in Moscow now? #Person1#: It's very cold. You should probably put on your coat before you get off the plane. #Person2#: Thanks for reminding me. #Person1#: You're welcome.",#Person1# tells #Person2# to remain seated. #Person2# asks for water and asks #Person1# about the weather in Moscow.,93,18,0.1935
scientific_lay_summarisation-elife-norm,"III, V (Birk and Mayne, 1997), XII, XIV (Ansorge et al. , 2009), fibronectin and small proteoglycans such as decorin (Berenson et al. , 1996; Zhang et al. , 2006). Therefore, the expression of these transcription factors and structural proteins, and the presence of particular signalling pathways, does not, in itself, provide information on the development of tendon structure and function. The defining event that signifies the onset of functional tendon development is the appearance of collagen fibrils in the ECM. The distribution of collagen fibril diameters distinguishes two stages in tendon development. In mouse, stage 1 begins at E12. 5 when narrow (∼35 nm) diameter collagen fibrils are formed within actin-dependent fibripositors at the cell surface (Canty et al. , 2004,2006; Kalson et al. , 2013). The length and width of the tissue doubles in a few days, and is accompanied by two-orders of magnitude increases in elastic modulus and ultimate tensile strength (McBride et al. , 1985,1988). Serial section transmission electron microscopy (ss-TEM) of chick embryonic tendon showed that the tendon matrix contains bundles of collagen fibrils that undergo gradual rotation over several microns (Birk and Trelstad, 1986; Birk et al. , 1989). Moreover, the collagen fibril bundles are stabilised by cell–cell connections containing cadherin-11 (Richardson et al. , 2007). During stage 1 there is a modest increase in fibril diameter (to ∼40 nm), which has been replicated in vitro by slow stretching of a 3-dimensional (3D) tendon-like construct containing embryonic tenocytes (Kalson et al. , 2011). At birth (in the mouse), the unimodal distribution of narrow fibrils is quickly (within a few days) replaced by a bimodal distribution of fibril diameters with a range of 35–400 nm (Goh et al. , 2012). The transition from unimodal to bimodal distributions specifies the onset of stage 2. In addition to increased fibril diameter and changes to cell morphology, the collagen fibrils in tendon develop regular undulations, known as crimp (Diamant et al. , 1972). Crimp becomes evident early in embryonic development (Shah et al. , 1982) and provides the biomechanically important ‘toe-region’ to the force–extension curve (Shah et al. , 1982). Crimp structure has been investigated by plane polarised light microscopy and by SEM (Raspanti et al. , 2005; Franchi et al. , 2007), but the structure of crimp","Young animals are able to grow in a way that allows them to maintain roughly the same shape until they reach their adult size. The growth of embryos is driven by increases in cell size and number, but it is less clear how the body grows after birth. By this point, many of the cells in the body are part of tendons and other fibrous tissues, where they are surrounded by a mesh of fibres made of collagen and other proteins. These fibres provide strength to the tissue, but may also restrict its ability to grow. Tendons connect muscles to bones. They contain fibres of collagen that run along their length, which enables them to cope with very strong pulling forces. Kalson et al. used electron microscopy to",380,128,0.3368
dialogsum,"#Person1#: Did you hear the news? #Person2#: What happened? #Person1#: Our cousin went into labor and had her baby last week. #Person2#: She did? Why didn't anyone tell me? #Person1#: I would've thought that somebody would have told you. #Person2#: No, I had no idea. #Person1#: Well, she did, her baby was 8 pounds 6 ounces. #Person2#: Oh my God, that's great! #Person1#: Are you going to go and visit her and the baby? #Person2#: I think that I might. #Person1#: Good! I just thought I'd let you know. #Person2#: Thanks for telling me.",#Person1# tells #Person2# their cousin had a baby and they are going to visit her and the baby.,94,18,0.1915
dialogsum,#Person1#: Some people pile on their agonise and try to seek other's sympathy by telling them how miserable they are. #Person2#: Yeah. They take the advantage of other people's hospitality and generosity. #Person1#: I was fooled once. A lady told me she needed some money to keep the pot boiling. So I gave her some money and bailed her out of the situation. But later I learned that she had lied to me. #Person2#: You are still wet behind the ears. You should have seen through her. #Person1#: Nothing rang a bell.,#Person1# tells #Person2# the experience of being cheated by a lady who piled on her agonize and sought #Person1#'s sympathy.,92,20,0.2174
scientific_lay_summarisation-elife-norm,"HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02: 01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1–30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F’ pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions. CD8 T-cells mediate immunity to Toxoplasma gondii infection (Khan et al. , 1988; Suzuki and Remington, 1988) through recognition of peptide antigens presented by the MHC class I (MHC I) molecules of infected cells (Brown and McLeod, 1990; Deckert-Schlüter et al. , 1994). The majority of peptide ligands identified to date are derived from parasite surface proteins, proteins localized to dense granules, or the rhoptry proteins which are specialized secretory granules whose contents are released either into the host cell cytoplasm or the parasitophorous vacuole (Blanchard et al. , 2008; Cardona et al. , 2015; Cong et al. , 2011). These secreted proteins are thought to be optimal candidates for MHC I presentation because they have the best access to conventional antigen processing and presentation machinery in the host cell. However, this is a large pathogen, and the full array of parasite proteins that might be sampled and presented remains unknown. Recent advances in immunology and proteomics highlight that non-canonical ligands are presented to T cells by MHC I molecules. While a majority of peptides are 8–11 amino acids in length, MHC I molecules present a considerable number of peptides >11 amino acids (Hassan et al. , 2015; Schittenhelm et al. , 2014) that elicit T-cell responses (Hassan et al. , 2015; Burrows et al. , 2006). Structural characterizations suggest that these long ligands interact with the MHC I molecule much like canonical peptides:","Toxoplasma gondii is a parasite that can infect most warm-blooded animals and cause a disease called toxoplasmosis. In humans, toxoplasmosis generally does not cause any noticeable symptoms, but it can cause serious problems in pregnant women and individuals with weakened immune systems. T. gondii is one of many parasites that hide within human cells in an attempt to avoid detection by the immune system. However, proteins called Human Leukocyte Antigens, or HLAs, can reveal hidden parasites by carrying small sections of them from the inside the infected cell to the cell’s surface. The immune system can then recognize the fragments as foreign and attack the parasite. HLAs typically pick up parasite fragments of a certain length, which enables the immune system to recognize that what is being displayed",380,128,0.3368
pubmed-summarization,"in the reduced nicotinamide adenine dinucleotide dehydrogenase subunit 6 gene ( ) . a - d , brain magnetic resonance imaging ( mri ) obtained at 3 years 2 months of age shows high signal intensity lesions with partially cystic lesions in the bilateral putamina on fluid - attenuated inversion recovery images ( a - c ) and diffusion diffusion - weighted imaging ( d ) . e - h , brain mri obtained at 5 years 2 months of age show a high signal intensity lesion that is newly detected in the left caudate nucleus on fluid - attenuated inversion recovery images ( e - g ) . diffusion - weighted imaging shows that the bilateral putamina are iso- or hypointense and the left caudate nucleus is hyperintense ( h ) . i - l , brain mri obtained at 6 years 11 months of age shows high signal intensity lesions spread to bilateral caudate nuclei and the midbrain ( right substantia nigra ) on fluid - attenuated inversion recovery images ( i - k ) and diffusion - weighted imaging ( l ) , in addition to the putaminal hyperintensities . m - o , brain mri obtained at 8 years 6 months of age shows high signal intensity lesions in the bilateral putamina and caudate nuclei on t2-weighted ( m - o ) and diffusion - weighted imaging ( p ) . q - t , brain mri obtained at 10 years 5 months of age shows high signal intensity lesions in the bilateral putamina and caudate nuclei on t2-weighted ( q - s ) and diffusion - weighted imaging ( t ) . a - c , e - g , i - k : fluid - attenuated inversion recovery images ; m - o , q - s : t2-weighted images ; and d , h , l , p , t : diffusion - weighted images . sequence analysis of the white blood cell mitochondrial dna from this patient shows the presence of a homoplasmic g > a transition mutation at nucleotide position 14 459 in the reduced nicotinamide adenine dinucleotide dehydrogenase subunit 6 gene . the patient had been treated with coenzyme q10 ( 2 mg / kg / d ) , l","this article reports the case of an 11-year - old boy with progressive dystonia caused by the homoplasmic g14459a mitochondrial dna mutation . the patient presented with focal dystonia in the right upper limb at 3 years of age , which progressed over 4 years to exhibit dystonia in both the upper and lower limbs . at 7 years of age , high signal intensity lesions in the bilateral striata and the midbrain were observed on fluid - attenuated inversion recovery images . it was observed on diffusion - weighted images that with time , these high signal intensity lesions migrated from the putamen to the caudate nuclei , which closely correlated with disease progression . because his symptoms and abnormal magnetic resonance imaging findings progressed despite treatment",380,128,0.3368
scientific_lay_summarisation-elife-norm,"harboring the endobacteria does. Thus, it was proposed that the beneficial effects for the plant result directly from the presence of bacteria (Sharma et al. , 2008). The rice seedling blight fungus, Rhizopus microsporus, and its endosymbiont bacterium, Burkholderia rhizoxinica represent a particularly noteworthy example of a bacterial-fungal endosymbiosis (Partida-Martinez and Hertweck, 2005; Lackner and Hertweck, 2011). The fungus harbors endosymbionts of the genus Burkholderia, which reside within the fungal cytosol, as shown by confocal laser scanning microscopy, transmission electron microscopy (EM) and freeze–fracture EM (Partida-Martinez et al. , 2007a, 2007b, 2007c). The bacteria are harnessed by the fungus as producers of highly potent antimitotic macrolides (Scherlach et al. , 2006), which are then further processed by the host into the phytotoxin rhizoxin (Scherlach et al. , 2012). The toxin represents the causative agent of rice seedling blight, which weakens or kills the rice plants (Lackner et al. , 2009b). Both the saprotrophic fungus and the endofungal bacteria benefit from the nutrients released, and R. microsporus provides a protective shelter for the bacterial partner. The Rhizopus-Burkholderia association also stands out as it employs an elegant mechanism that allows the persistence and spreading of the symbiosis through spores containing the endosymbionts (Partida-Martinez et al. , 2007c) (). Yet it is unknown how the vegetative reproduction of the fungus has become totally dependent upon the presence of the endobacteria (Partida-Martinez et al. , 2007c). Insights into the genome of B. rhizoxinica and mutational studies have unveiled several symbiosis factors (Leone et al. , 2010; Lackner et al. , 2011a, 2011b). 10. 7554/eLife. 03007. 003Figure 1. Microscopic image of Burkholderia rhizoxinica (green) residing in the cytosol of Rhizopus microsporus. The GFP encoding B. rhizoxinica cells can re-colonize the sterile R. microsporus, then induce fungal sporulation. The endobacterium is transmitted via fungal vegetative spores (upper right corner). : http: //dx. . org/10. 7554/eLife. 03007. 003 A plausible scenario for the evolution of the symbiosis is a shift from antibiosis or antagonism to mutualism. The rhizoxin complex secreted by the bacteria arrests mitosis in almost all eukaryotic cells. Yet, Rhizopus, amongst other zygomycetes, has gained resistance to this toxin due to a mutation at the β-tubulin binding site (Schmitt et al. , 2008). Furthermore, phylogenetic analyses point to host switching events during evolution (Lackner et","Many organisms live in what are known as symbiotic relationships, whereby two or more different species share a close and often long lasting association. Examples of symbiosis abound in nature, with well-studied examples including the sea anemone and the clownfish, corals and their photosynthetic algae, and nitrogen-fixing bacteria that live in association with legumes. In some cases, each member of the relationship benefits from the symbiosis. One such example is the rice seedling blight fungus Rhizopus microsporus and its bacterial symbiont Burkholderia rhizoxinica, which work together to produce toxins that kill rice plants. This frees up nutrients that nourish both the fungus and the bacteria. B. rhizoxinica lives inside the tissues of the fungus, but to do so the bacterial cells must first travel through the tough cell",380,128,0.3368
dialogsum,"#Person1#: You're going to have coffee, aren't you? #Person2#: Yes. I could use a cup of coffee. #Person1#: Are you going to have anything to eat? #Person2#: French toast sounds good. What are you going to order? #Person1#: I'll have that too.",#Person2# are going to have a cup of coffee. French toast for both #Person1# and #Person2#.,42,16,0.381
dialogsum,"#Person1#: Hey, Ann, I am really sorry about last night. I shouldn't have said those things to you. #Person2#: I am sorry too. I know we've been talking about this beach trip for a while. I should have told Bob I was busy this weekend. #Person1#: don't be silly. You guys should spend as much time together as you can. Besides we can go to the beach anytime. #Person2#: thanks for understanding. #Person1#: well that's what being friends is about, isn't it? #Person2#: hey, what if the three of us go to the beach together? Besides, you and Bob haven't seen each other for a while. I don't want my best friend and my boyfriend to be complete strangers. #Person1#: Nah, I wouldn't worry about that. But I don't want to be the third wheel. You two should have some quiet time to yourselves. #Person2#: I know Bob won't mind. You can bring a date, like that guy from the bar you keep talking about. #Person1#: maybe. . . I'll think about it. #Person2#: well, I think you should come and have some fun. Besides you never know maybe he likes you as well. You should at least try.",Ann says sorry to #Person1# because she can't go to the beach with #Person1# as planned. She invites #Person1# and the guy from the bar to join her and Bob to go to the beach together. #Person1# will think about it.,199,41,0.206
scientific_lay_summarisation-elife-norm,"2003); and age-related cognitive decline (MacDonald et al. , 2006). The association between behavioral variability and cognitive performance suggests that adolescent stabilization of behavior reflects the continuing alteration of fundamental aspects of brain processing that support the transition to adult-like levels of performance. Mechanistically accounting for the stabilization of behavior is critical to our understanding of adolescent neural development. Thus, in the present study, we examine the neural processes that underlie behavioral variability. Behavioral variability has been found to be associated with fluctuations in neural (Newsome et al. , 1989; Cohen et al. , 2009; Nienborg and Cumming, 2009) or blood-oxygen-level dependent (BOLD) signals occurring within individual brain areas (Wagner et al. , 1998; Ress and Heeger, 2003; Yarkoni et al. , 2009), and networks of brain areas (Rosenberg et al. , 2016). Several lines of research suggest that these brain/behavior relationships are driven, at least in part, by trial-to-trial variability in gain modulating signals (Fox et al. , 2006; Eldar et al. , 2013; Rabinowitz et al. , 2015) that enhance the activity of individual neurons or brain areas experiencing net excitation and further suppress the activity of neurons or areas experiencing net inhibition (Servan-Schreiber et al. , 1990). Recent electrophysiological evidence indicates that some gain modulating signals are shared across cortical areas and that moment-to-moment variation in such distributed gain signaling may account for a significant portion of neural and behavioral variability (Rabinowitz et al. , 2015). Additionally, the structure of neural covariance within populations of simultaneously recorded sensory neurons is best explained as the result of multiple ongoing gain modulating signals (Rabinowitz et al. , 2015), raising the possibility that different sources of gain variability affect neural activity in a functionally targeted way. Widespread or global gain modulating processes would not, by definition, change the spatial distribution or ‘pattern’ of task evoked neural activity. Rather, they would influence the amplitude with which they are expressed, manifesting as trial-to-trial variability in the amplitude of expression of whole-brain patterns of activity that support task-relevant processes. We refer to this hypothesized phenomenon here as ‘brain state’ variability. With this operationalized definition of gain modulation, once an average pattern of task-evoked activity is known, the occurrence of fluctuations in global gain signals may be determined by measuring trial-to-trial differences in the","Adolescence is a period of change: physically, socially and intellectually. During the teenage years, the brain undergoes changes in structure and connectivity that lead to improvements in areas such as self-control, social skills and cognition. Adolescence is also a time during which cognitive skills, such as problem solving and memory, become more stable. Whereas a child will perform a task markedly better on some days or trials than others, adolescents become increasingly consistent. But why does cognitive performance fluctuate at all? Studies in monkeys suggest that momentary fluctuations in processes like attention and alertness are linked to changes in the level of activity within brain regions that are active during a task. Areas of the brain that are relatively active tend to become even more active, whereas those",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The striatum and the subthalamic nucleus (STN) constitute the input stage of the basal ganglia (BG) network and together innervate BG downstream structures using GABA and glutamate, respectively. Comparison of the neuronal activity in BG input and downstream structures reveals that subthalamic, not striatal, activity fluctuations correlate with modulations in the increase/decrease discharge balance of BG downstream neurons during temporal discounting classical condition task. After induction of parkinsonism with 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine (MPTP), abnormal low beta (8-15 Hz) spiking and local field potential (LFP) oscillations resonate across the BG network. Nevertheless, LFP beta oscillations entrain spiking activity of STN, striatal cholinergic interneurons and BG downstream structures, but do not entrain spiking activity of striatal projection neurons. Our results highlight the pivotal role of STN divergent projections in BG physiology and pathophysiology and may explain why STN is such an effective site for invasive treatment of advanced Parkinson' s disease and other BG-related disorders. State-of-the-art basal ganglia (BG) computational models (Gurney et al. , 2015; Schultz et al. , 1997) divide the BG network into two functionally related subsystems. First, the main axis (or' actor' in machine learning terminology) which corresponds to the BG structures that connect state-encoding thalamo-cortical areas to cortical and brainstem motor centers. Second, the neuromodulators (machine learning' s' critics' , e. g. , the midbrain dopaminergic neurons and striatal cholinergic interneurons) that adjust activity along the BG main axis by encoding a prediction error signal capable of modulating the efficacy of cortico-striatal transmission (Deffains and Bergman, 2015; Reynolds et al. , 2001; Shen et al. , 2008). The input structures of the BG main axis (the striatum and subthalamic nucleus, STN) receive considerable glutamatergic inputs from the cortex and the thalamus. The striatum and STN provide major inhibitory GABAergic and excitatory glutamatergic drive respectively to the external segment of the globus pallidus (GPe) and the BG output structures (internal segment of the globus pallidus and substantia nigra reticulata, GPi/SNr) (Parent and Hazrati, 1995a, 1995b). In return, the GPe emits feedback GABAergic projections to the STN (Carpenter et al. , 1981) and the striatum (Hegeman et al. , 2016; Mallet et al. , 2012) as well as massive feedforward GABAergic projections to the GPi/SNr (Parent and Hazrati, 1995b). Thus, aside from the action of the BG neuromodulators and lateral","The symptoms of Parkinson’s disease include tremor and slow movement, as well as loss of balance, depression and problems with sleep and memory. The death of neurons in a region of the brain called the substantia nigra pars compacta is one of the major hallmarks of Parkinson’s disease. These neurons produce a chemical called dopamine, and their death reduces dopamine levels in another area of the brain called the striatum. This structure is one of five brain regions known collectively as the basal ganglia, which form a circuit that helps to control movement. The most effective treatment currently available for advanced Parkinson’s disease entails lowering electrodes deep into the brain in order to shut down the activity of part of the basal ganglia. However, the target is not",380,128,0.3368
dialogsum,"#Person1#: it seems the department still has some money left in the budget. Do you have any suggestions how to use it before the budget is renewed? #Person2#: what about renting a restaurant and treating the employees to a nice dinner? #Person1#: but we've done that many times. We want something fresh this time. #Person2#: okay, let me think. What about a party-and-movie night? We can rearrange our reference room, invite a band to play some music, order in some food and watch a movie later. #Person1#: sounds like a good idea, but a band sounds too expensive. #Person2#: well, we can ask people to make small contributions. #Person1#: I don't think so. I don't think people are going to like it if they have to pay to come. But we certainly can cut costs in other ways, such as make the party BYOB. #Person2#: BYOB? What's that? #Person1#: bring your own beverage. We can provide food, but people have to bring their own drinks. #Person2#: so we're just going to have a party where they bring their own drinks and we just give them some snacks? I don't know how well that will go over. #Person1#: maybe you have a point. How about having a party on a Friday afternoon? We'll stop early, order some pizza, and serve drinks. There'll be music but no band. Having the party in the office will make #Person2#: oh, that sounds like fun!","#Person1# and #Person2# are discussing how to spend money left in the budget of the department. They finally decide to have a party on a Friday afternoon with pizza, drinks, and music but no band in the office.",240,38,0.1583
pubmed-summarization,"recruited from the john hunter hospital diabetes clinic , hunter new england area health service , nsw , australia . the median duration ( interquartile range ) of disease was 10.0 ( 5.017.0 ) years . these were age- and gender - matched to plasma samples from 33 lean ( body mass index ( bmi ) 2025 kg m ) and 33 obese ( bmi>25 kg m ) healthy controls sourced from previously collected plasma samples from 400 healthy red cross blood donors . the study was approved by the university of newcastle and hunter new england area human research ethics committees , and informed consent was obtained from all the participants . peripheral blood samples were collected into 3.2% na citrate vacuette containers ( greiner bio - one gmbh , frickenhausen , germany ) and platelet - free plasma was prepared by serial double centrifugation ( 15 min at 2100 g ) within 2 h of collection . aliquoted samples were stored at 80 c , then thawed at 37 c immediately before analysis . staining and analysis of mps was performed essentially as previously described and according to guidelines established by the international society on thrombosis and haemostasis vascular biology ssc on the standardisation of fmc - based pmp enumeration by flow cytometry incorporating modifications suggested for the bd facs canto ( bd biosciences , san jose , ca , usa ) . to calibrate the cytometer , a blend of 2:1:1 0.5- , 0.9- and 3-m diameter fluorescent beads ( megamix , biocytex , marseille , france ) was used to ensure adequate fsc resolution and set the lower mps ' detection limit according to the manufacturer 's instructions . a 10-l aliquot of platelet - free plasma was incubated at room temperature for 30 min with an antibody against cd36 ( clone 11h5 ) conjugated to dylight-488 in various combinations with cd41-phycoerythrin ( cd41-pe ; clone pl2 - 49 , biocytex ; platelet marker ) , cd14-pe ( clone tk4 , miltenyi biotec , teterow , germany ; monocyte marker ) , cd235a - allophycocyanin ( cd235a - apc ; clone ga - r2 ( hir2 ) , bd pharmingen , san diego , ca , usa ; erythrocyte marker ) , cd105-pe ( clone 1g2","objective : elevated plasma levels of the fatty acid transporter , cd36 , have been shown to constitute a novel biomarker for type 2 diabetes mellitus ( t2 dm ) . we recently reported such circulating cd36 to be entirely associated with cellular microparticles ( mps ) and aim here to determine the absolute levels and cellular origin(s ) of these cd36+mps in persons with t2dm.design:an ex vivo case - control study was conducted using plasma samples from 33 obese individuals with t2 dm ( body mass index ( bmi)=39.96.4 kg m2 ; age=579 years ; 18 male:15 female ) and age- and gender - matched lean and obese non - t2 dm controls ( bmi=23.61.8 kg m2 and 33.55.9 kg m2 , respectively ) . flow cytometry",380,128,0.3368
pubmed-summarization,"solid organ imaging . development of such devices facilitates the translation of oct to clinical applications and allows clinicians to use the enhanced imaging capabilities of this technique to benefit the patients . 2a shows the schematic of a representative oct catheter / endoscope device consisting of a hollow cable carrying a single - mode ( sm ) optical fiber . the beam from the distal end of the fiber is focused by a gradient - index ( grin ) microlens and is directed perpendicular to the catheter axis by a microprism or micromirror . the beam can be scanned either circumferentially ( by rotating the cable ) or linearly ( by translating the cable ) to form a cross - sectional oct image . the outer diameter of the catheter / endoscope can be made small enough to image inside a human coronary artery ( see 2b ) . jude medical , inc . ) combined with a modified vacuum - pumped biopsy needle . this modified core - needle biopsy device includes the addition of a transparent front window for real - time oct guidance , the addition of a long steel / plastic tube through which the oct catheter is inserted , and a y - valve to allow both linear access for the oct catheter and the vacuum / pressure tube connection . 2d depicts a custom laparoscopic oct device imaging the ovaries in patients undergoing oophorectomy . ( a ) schematic of the distal end of an oct probe . ( b ) photograph of an intravascular imaging catheter ( 0.4 mm in diameter ) . ( c ) schematic of a modified core - needle biopsy device with a catheter - based oct probe ( figures are adapted from reference with permission ) and photographs of modified tip . ( d ) the photograph of a custom laparoscopic oct probe for imaging human ovary . figures are adapted from reference 21 with permission . since its invention in 1991 , oct has rapidly developed as a non - invasive biomedical imaging modality that enables cross - sectional visualization of tissue microstructures in vivo . the resolution of oct is one to two orders of magnitude higher than conventional ultrasound , approaching that of histopathology","since optical coherence tomography ( oct ) was first demonstrated in 1991 , it has advanced significantly in technical aspects such as imaging speed and resolution , and has been clinically demonstrated in a diverse set of medical and surgical applications , including ophthalmology , cardiology , gastroenterology , dermatology , oncology , among others . this work reviews current clinical applications in urology , particularly in bladder , urether , and kidney . clinical applications in bladder and urether mainly focus on cancer detection and staging based on tissue morphology , image contrast , and oct backscattering . the application in kidney includes kidney cancer detection based on oct backscattering attenuation and non - destructive evaluation of transplant kidney viability or acute tubular necrosis based on both",380,128,0.3368
dialogsum,"#Person1#: I'd like to have this cashed, please. #Person2#: Please put your name and address here. May I see your passport. #Person1#: Yes. #Person2#: How would you like it? #Person1#: Ten hundreds and Ten Twenties and the rest of small changes please. #Person2#: Ok, here you are.",#Person2# helps #Person1# to have things cashed.,47,7,0.1489
dialogsum,"#Person1#: Ten sheets of rice paper, 25 brushes, two boxes of oil color and two boxes of water color. All these come up to $35. 50, sir. #Person2#: Ok, here is $50. Oh, can you make out an invoice for me? #Person1#: Sure, just a minute. Are you an artist, sir? #Person2#: No, I am a teacher. I teach art. #Person1#: That must be a very interesting job. #Person2#: It is. You must be new here. I do my shopping here regularly, once a week. #Person1#: Do you? Nice to meet you! And here is the invoice and your change. #Person2#: Thank you. Nice to meet you, too.","#Person2# buys some paper, brushes, oil color and watercolor from #Person1#. #Person2# tells #Person1# that #Person2# is an art teacher.",108,20,0.1852
dialogsum,"#Person1#: Hi, Jeannie, why have you come to school an hour early? #Person2#: I wanted to get a front row seat and review one more time before the test, because I failed a course last term. Why you here so early, Jack? #Person1#: I get out of my car here at this time everyday. You seem to be nervous about your lessons. Have you finished your review? #Person2#: I've only been studying night and day for the last week. If I don't get an A in this class, I won't get the support of my country. Why do you seem so calm? #Person1#: This class is really just a review for me. I've been learning it for 2 years. #Person2#: That's lucky for you. #Person1#: Jeannie, can you guess what the test will be like? Will it be difficult? #Person2#: I hope not, but I'm still worried about it. #Person1#: Well, cheer up. Hope for good luck. #Person2#: Thanks for wishing me luck. I'm going to need it.",Jeannie comes to school early because she wants to review for the test and is worried she wouldn't get the support of her country if she failed. #Person1# feels relaxed because #Person1# has learned for two years.,168,37,0.2202
scientific_lay_summarisation-elife-norm,"Wharton, 1999). Hence, combinatorial hb mRNA repression requires the sequence specificity of Pum and the spatial information provided by the Nos gradient. Nos and Pum also regulate germline and neurological processes (Forbes and Lehmann, 1998; Mee et al. , 2004; Menon et al. , 2009,2004; Ye et al. , 2004). Nos and Pum collaborate to repress expression of Cyclin B mRNA (CycB) in primordial germ cells and germline stem cells (Asaoka-Taguchi et al. , 1999) and the sodium channel paralytic (para) in the nervous system (Muraro et al. , 2008). Like hb mRNA, CycB and para mRNAs possess NREs with PRE-like motifs. Furthermore, genome-wide analyses have identified hundreds of Pum-associated mRNAs, suggesting that Pum may play an expansive regulatory role beyond the few validated target RNAs (Gerber et al. , 2006; Laver et al. , 2015). While collaboration between Nos and Pum is firmly established, the mechanism by which they do so remains to be determined. Here, we report the crystal structures of Nos-Pum-RNA complexes, which reveal that Nos acts as a molecular clamp that embraces both Pum and RNA. The C-terminal region of Pum undergoes conformational changes to make new contacts with the RNA and Nos. We explored the hypothesis that Nos promotes repression by modulating the RNA-binding activity of Pum. We show that Nos enhances the cellular repression activity and in vitro RNA-binding affinity of Pum. Moreover, Nos contacts nucleotides upstream of the PRE. In doing so, Nos alters the specificity of the repression complex and promotes repression of RNAs that are not stably bound by Pum alone. We performed RNA target selection and high-throughput sequencing, which, together with RNA-binding and cellular repression assays, demonstrate that Nos diversifies Pum RNA regulatory networks. We established a cell-based hb reporter mRNA assay, wherein exogenous Nos robustly repressed reporter protein and RNA expression in a manner dependent on the PREs () and Pum (Weidmann and Goldstrohm, 2012). We used D. mel-2 cells, which do not express Nos and express insufficient Pum to repress the reporter efficiently in the absence of exogenous Nos (Weidmann and Goldstrohm, 2012), and a Renilla luciferase (RnLuc) reporter containing the 3´UTR of hb with two NREs, each of which possesses a PRE (1A). Halo-tagged, full-length Nos protein, comprising N-terminal, tandem ZF (Z), and C-terminal regions (NZC, 1B),","Molecules of DNA contain the instructions needed to make proteins inside cells. Proteins perform many different roles and each needs to be produced at the right time and in the right amounts to enable the cells to survive. The DNA is first copied to make molecules of ribonucleic acid (RNA), which are then used as templates to make the proteins. One way to control protein production is to regulate the RNA molecules. A family of proteins called RNA-binding proteins can recognise and bind to specific RNA molecules and determine whether a RNA molecule is destroyed, used to produce proteins, or stored for later use. In effect, these RNA-binding proteins act as switches that turn protein production on or off. Nanos and Pumilio are two RNA-binding proteins that are",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Subgenomic flaviviral RNA (sfRNA) accumulates during infection due to incomplete degradation of viral genomes and interacts with cellular proteins to promote infection. Here we identify host proteins that bind the Zika virus (ZIKV) sfRNA. We identified fragile X mental retardation protein (FMRP) as a ZIKV sfRNA-binding protein and confirmed this interaction in cultured cells and mouse testes. Depletion of FMRP elevated viral translation and enhanced ZIKV infection, indicating that FMRP is a ZIKV restriction factor. We further observed that an attenuated ZIKV strain compromised for sfRNA production was disproportionately stimulated by FMRP knockdown, suggesting that ZIKV sfRNA antagonizes FMRP activity. Importantly, ZIKV infection and expression of ZIKV sfRNA upregulated endogenous FMRP target genes in cell culture and ZIKV-infected mice. Together, our observations identify FMRP as a ZIKV restriction factor whose activity is antagonized by the sfRNA. Interaction between ZIKV and FMRP has significant implications for the pathogenesis of ZIKV infections. Zika virus (ZIKV) is a mosquito-borne flavivirus that is closely related to dengue (DENV) and yellow fever viruses (YFV). There are three ZIKV genotypes: one from Asia, which has caused the recent pandemic in the Americas, and two from Africa (East and West African) (Lanciotti et al. , 2016). ZIKV infection is characterized by fever, arthralgia and conjunctivitis (Goeijenbier et al. , 2016) and was considered an exceedingly rare human infection since only 14 cases were reported prior to 2007 (Faye et al. , 2014). In 2007, the first ZIKV outbreak caused by an Asian lineage was reported in Micronesia, followed by epidemics in French Polynesia in 2013 and the recent pandemic (2015–2016) in the Americas (Weaver et al. , 2016; Aliota et al. , 2017). During this period, it has been estimated that 1. 5 million cases occurred in Brazil and more than 25,000 cases in Colombia (Focosi et al. , 2016; Samarasekera and Triunfol, 2016). As of January 2018, the virus was widely distributed in 50 countries in the Americas (PAHO/WHO, 2018). The public health concern about Zika has been primarily driven by its maternal-fetal (Brasil et al. , 2016a; Yockey et al. , 2016; Driggers et al. , 2016) and sexual modes of transmission (Deckard et al. , 2016; Davidson et al. , 2016; Hills et al. , 2016) as well as its association with congenital abnormalities,","Certain mosquitoes can carry pathogens that are able to infect humans, including Zika and dengue viruses. Most people infected with Zika virus only develop mild symptoms, or no symptoms at all. But if the virus infects a pregnant woman, it can lead to miscarriage and other pregnancy complications, or cause severe birth defects in her unborn baby. Viruses must infect the cells of a host to multiply. To do so, they hijack the cellular machinery to make proteins needed to copy their genetic material and assemble new virus particles. The genetic material of Zika virus is made of ribonucleic acid (RNA). When the Zika virus infects cells, pieces of the virus RNA, known as subgenomic flavivirus RNAs (or sfRNAs for short), accumulate in the cell. Cells infected with",380,128,0.3368
dialogsum,"#Person1#: Hey Mike. What are you doing tonight? #Person2#: Nothing planned. How about you? #Person1#: Work is kicking my ass. I'm so stressed. Let's go grab a drink. #Person2#: I'm always up for a drink. To tell you the truth, it's been quite stressful here too. #Person1#: I say we get drunk tonight. I don't want to think about all this stuff. #Person2#: But we have to work tomorrow. #Person1#: We won't stay out too late. I just need to forget about work. #Person2#: I hear ya. Let's do it.",#Person1# invites Mike to grab a drink and promises not to stay out too late. Mike agrees.,90,17,0.1889
scientific_lay_summarisation-elife-norm,"regeneration/maintenance. To determine the effect of age on cellular self-organization and alveolosphere formation, L-MSCs and AEC2s were isolated from the lungs of young (2–3 months) and aged (22–24 months) mice and seeded in various combinations (1H, upper panel). L-MSCs and AEC2s from young mice generated normal alveolospheres, whereas L-MSCs and AEC2s from the lungs of aged mice showed impaired self-organization with condensed, poorly formed organoids. Interestingly, combining aged AEC2s with young L-MSCs resulted in relatively normal-appearing alveolospheres, while the reverse combination (young AEC2s and old L-MSCs) did not (1H, middle and lower panels; — 1B). Quantitative analyses revealed that, while the number of alveolospheres formed was not significantly different between groups (1I), the size of alveolospheres was critically dependent on the age of L-MSCs, and not that of AEC2s (1J). These findings indicate that secreted factor (s) from young L-MSCs are capable of supporting the self-organizing behavior of alveolospheres, while aged L-MSCs do not. Cellular senescence accumulates in tissues with advancing age (Krishnamurthy et al. , 2004) and has been proposed as a key driver of aging and aging-related disease phenotypes (Baker et al. , 2016; Kennedy et al. , 2014). Based on our observation that aged L-MSCs were incapable of supporting alveolosphere formation, we explored whether the emergence of cellular senescence may account for this finding. First, we confirmed the senescent features of L-MSCs from aged mice in monolayer 2D cell culture (2A, — 1) and in 3D alveolospheres (2B) by staining for β-galactosidase (β-gal) (Dimri et al. , 1995) and lipofuscin (Georgakopoulou et al. , 2013), respectively. To characterize secreted factors that may account for the age-associated dysregulation of cell-cell communication, we first measured cytokines/growth factors secreted from both young and aged L-MSCs using antibody arrays (2C). A number of cytokines that have been associated with the senescence-associated secretory phenotype (SASP) were found to be released at higher levels by aged L-MSCs, including IL-6, CCL12/MCP-5, CCL11/Eotaxin, and WISP-1/CCN4; in contrast, IGFBP1 was the only secreted protein that was statistically more elevated in young L-MSCs in this cytokine array (2D and E). In addition to predefined cytokine array analyses, we employed an unbiased approach to identification of secreted proteins from young and aged L-MSCs by mass spectrometry-based discovery proteomics (2F). After adjustments for false discovery rates, 503 high-confidence proteins","Many tissues in the body are capable of regenerating by replacing defective or worn-out cells with new ones. This process relies heavily on stem cells, which are precursor cells that lack a set role in the body and can develop into different types of cells under the right conditions. Tissues often have their own pool of stem cells that they use to replenish damaged cells. But as we age, this regeneration process becomes less effective. Many of our organs, such as the lungs, are lined with epithelial cells. These cells form a protective barrier, controlling what substances get in and out of the tissue. Alveoli are parts of the lungs that allow oxygen and carbon dioxide to move between the blood and the air in the lungs. And",380,128,0.3368
dialogsum,"#Person1#: Good morning, madam. Can I help you? #Person2#: I want to buy some cleansing milk. What would you recommend? #Person1#: Your complexion is on the oily side. I suggest you use cleansing gel. #Person2#: Anything that can keep my skin clean will do. #Person1#: How do you prefer this one? It cleans thoroughly without striping your natural protective oil. The gentle formula keeps skin soft and healthy. #Person2#: Hm. . . the smell is too strong, I can't stand it. I'm very sensitive to fragrance. #Person1#: We've also got a fragrance-free one, specially designed for sensitive skin. I'm sure you'll like it. #Person2#: I'll try that. Do you have facial cream to go with that? #Person1#: Yes, sure. This line of products is fragrance-free. We have a facial mask, moisturizing lotion, eye cream and tonic. #Person2#: I'll buy the moisturizing lotion and cleansing gel first. If they suit me, I'll come back for the others later. #Person1#: Thank you very much, madam. Here are some samples of our products. Do try them out.","#Person2# wants to buy cleansing milk and #Person1# recommends a fragrance-free cleansing gel. #Person2# buys the fragrance-free cleansing gel and moisturizing lotion, and #Person1# gives her some products' samples.",174,29,0.1667
dialogsum,"#Person1#: Next, please. #Person2#: Yes, I just received a telephone bill and there's a problem with it. #Person1#: And what exactly is the problem? #Person2#: There is a call to Finland on there, and I don't know anyone in Finland. I'm upset. Could you please take the charge off my bill? #Person1#: May I see your bill please? #Person2#: Certainly, there it is, on July first. I really don't know anybody in Finland. #Person1#: OK, don't worry. I'll take the call off. Let's see it was $60. Your bill was $84, minus 60 dollars. So, your new total is $24. I'm very sorry about the fault. #Person2#: And that's OK.",#Person2# claims there's a problem with #Person2#'s telephone bill. #Person1# takes the call off and takes the charge off #Person2#'s bill.,110,21,0.1909
dialogsum,"#Person1#: Excuse me, What time does the next bus for Boston leave? #Person2#: It leaves at 8 o' clock. #Person1#: I see. Are there any seat available? #Person2#: Just a moment please. Yes. You can have a seat. #Person1#: Good. How much is it when we take it? #Person2#: It thirty eight dollars. #Person1#: All right. Here's forty dollars. #Person2#: Here's your ticket and change. #Person1#: Thank you. Which gate should I go to for the bus? #Person2#: Go to gate No. 2, please. #Person1#: Thank you very much. #Person2#: Don't mention it.",#Person2# checks the bus ticket to Boston for #Person1# and #Person1# buys one.,93,13,0.1398
scientific_lay_summarisation-elife-norm,"Mineral malnutrition stemming from undiversified plant-based diets is a top global challenge. In C3 plants (e. g. , rice, wheat), elevated concentrations of atmospheric carbon dioxide (eCO2) reduce protein and nitrogen concentrations, and can increase the total non-structural carbohydrates (TNC; mainly starch, sugars). However, contradictory findings have obscured the effect of eCO2 on the ionome—the mineral and trace-element composition—of plants. Consequently, CO2-induced shifts in plant quality have been ignored in the estimation of the impact of global change on humans. This study shows that eCO2 reduces the overall mineral concentrations (−8%, 95% confidence interval: −9. 1 to −6. 9, p<0. 00001) and increases TNC: minerals > carbon: minerals in C3 plants. The meta-analysis of 7761 observations, including 2264 observations at state of the art FACE centers, covers 130 species/cultivars. The attained statistical power reveals that the shift is systemic and global. Its potential to exacerbate the prevalence of ‘hidden hunger’ and obesity is discussed. The first empirical evidence of lower mineral content in plants exposed to eCO2 appeared at least over a quarter century ago (e. g. , Porter and Grodzinski, 1984; Peet et al. , 1986; O’Neill et al. , 1987). Physiological mechanisms responsible for the overall decline of plant mineral content—with expected changes being non-uniform across minerals—have been proposed: the increased carbohydrate production combined with other eCO2 effects such as reduced transpiration (Loladze, 2002; McGrath and Lobell, 2013). However, most of the experimental evidence showing CO2-induced mineral declines came from artificial facilities, mainly closed chambers and glasshouses, and many results were statistically non-significant. This led some research groups to challenge altogether the notion of lower mineral content in plants exposed to eCO2 in field conditions. Such conditions are most accurately represented in Free-Air Carbon dioxide Enrichment (FACE) centers, which have been established in at least 11 countries. In the grains of rice harvested at four FACE paddies in Japan, Lieffering et al. (2004) found no decline in any of the minerals but lower N content. The result disagreed with Seneweera and Conroy (1997), who were the first to report lower iron (Fe) and zinc (Zn) in grains of rice grown at eCO2 and warned that altered rice quality can negatively affect developing countries. Lieffering et al. (2004), however, argued that the result of Seneweera and Conroy (1997) could","Rice and wheat provide two out every five calories that humans consume. Like other plants, crop plants convert carbon dioxide (or CO2) from the air into sugars and other carbohydrates. They also take up minerals and other nutrients from the soil. The increase in CO2 in the atmosphere that has happened since the Industrial Revolution is thought to have increased the production of sugars and other carbohydrates in plants by up to 46%. CO2 levels are expected to rise even further in the coming decades; and higher levels of CO2 are known to lead to lower levels of proteins in plants. But less is known about the effects of CO2 levels on the concentrations of minerals and other nutrients in plants. Loladze has investigated the effect of rising",380,128,0.3368
scientific_lay_summarisation-elife-norm,"has been shown to dictate clonal recruitment and expansion (Fulton et al. , 2015; Tabbekh et al. , 2013). To date, the impact of non-heritable influences such as human chronic viral infection on the quantitative and qualitative aspects of the preimmune repertoire remains unknown. In our study, we focused on patients with chronic hepatitis C virus infection (cHCV), which show CD8+ T cell dysfunction (Park and Rehermann, 2014; Rehermann and Nascimbeni, 2005). In particular, HCV-specific responses are typically (i) weak – both in term of numbers and function, (ii) of low avidity, and (iii) blocked in their differentiation into central memory cells, despite the availability of cognate pMHC complexes (Park and Rehermann, 2014). cHCV is to date the only chronic viral infection that can be cured, offering the unique possibility to interrogate the reversibility of immune perturbations post-viral clearance (Pol et al. , 2013). Herein, we applied the highly sensitive tetramer-associated magnetic enrichment (TAME) technique for investigating at the antigen-specific level the impact of chronic viral hepatitis infection on the CD8 T cell preimmune repertoire (Alanio et al. , 2010). Although precursor frequencies were similar to healthy controls, we observed significant impairments of the preimmune repertoire in cHCV patients. Inexperienced T cell populations contained increased proportions of MP cells. This correlated with naïve-phenotype CD8+ T cells having lower surface expression of CD5, which accounted for a lower threshold for TCR signaling and the generation of potent immune responses from cHCV patients. Importantly, the positive effect of chronic infection on naïve T cell recruitment into immune responses is transient, as cHCV patients who clear their virus following successful therapy (referred to as Sustained Virologic Responders or SVR) can experience a reversion towards a healthy naïve T cell repertoire within 2 years. These data provide the first evidence for chronic infection resulting in the bystander dysregulation of the antigen-specific preimmune repertoire in humans, and highlight the added benefit of early viral clearance in patients with chronic HCV infection. To test the hypothesis that chronic viral infection perturbs preimmune repertoire homeostasis, we evaluated the influence of cHCV infection on the phenotype of circulating CD8+ T cells. 29 cHCV and 37 Sustained Virologic Responders (SVR, i. e. patients achieving clearance of the virus after therapy) patients were included in the study (Table 1). 62%","Long-lasting or “chronic” infections massively perturb the immune system as a way to favor their own growth. In particular, they can stop T cells – a subtype of immune cells that help to destroy viruses – from working well. For example, HIV and hepatitis C viruses can overwork T cells and cause them to die. This can make individuals vulnerable to other infections. In healthy people, T cells that have participated in the fight against particular infections continue to live to provide a memory of those past infections. Groups of “naïve” T cells that have not yet encountered an infected cell also patrol the body, ready to respond to infections by a new virus. There are relatively few virus-specific naïve T cells in the body, so until recently",380,128,0.3368
scientific_lay_summarisation-elife-norm,"7554/eLife. 08362. 003 How does the grid system represent spatial location and what function does the modular variation in grid scale serve? Here, we propose that the grid system provides a hierarchical representation of space where fine grids provide precise location and coarse grids resolve ambiguity, and that the grids are organized to minimize the number of neurons required to achieve the behaviorally necessary spatial resolution across a spatial range equal in size to the period of the largest grid module. Our analyses thus assume that there is a behaviorally defined maximum range over which a fixed grid represents locations. Our hypotheses, together with general assumptions about tuning curve shape and decoding mechanism, explain the triangular lattice structure of two-dimensional grid cell firing maps and predict a geometric progression of grid scales. Crucially, the theory further predicts that the ratio of adjacent grid scales will be modestly variable within and between animals with a mean in the range 1. 4–1. 7 depending on the assumed decoding mechanism used by the brain. With additional assumptions the theory also predicts that the ratio between grid scale and individual grid field widths should lie in the same range. These predictions naturally explain the structural parameters of grid cell modules measured in rodents (Barry et al. , 2007; Giocomo et al. , 2011a; Stensola et al. , 2012). Our results follow from general principles, and thus, we expect similar organization of the grid system in other species. The theory makes further predictions including: (a) the number of grid scales necessary to support navigation over typical behavioral distances (i. e. , a logarithmic relation between number of modules and navigational range), (b) possible deficits in spatial behavior that will obtain upon inactivating specific grid modules, (c) the structure of one- and three-dimensional grids that will be relevant to navigation in, for example, bats (Yartsev et al. , 2011), (d) an estimate of the number of grid cells we expect in the mEC. Remarkably, in a simple decoding scheme, the scale ratio in an n-dimensional environment is predicted to be close to en. As we will explain, our results and their apparent experimental confirmation in Stensola et al. (2012), suggest that the grid system implements a two-dimensional neural analog of a base-b number system. This provides","In the 1930s, neuroscientists studying how rodents find their way through a maze proposed that the animals could construct an internal map of the maze inside their heads. The map was thought to enable the animals to navigate between familiar locations and also to identify shortcuts and alternative routes whenever familiar ones were blocked. In the 1960s, recordings of electrical activity in the rat brain provided the first clues as to which nerve cells form this spatial map. In a region of the brain called the hippocampus, nerve cells called ‘place cells’ are active whenever the rat finds itself in a specific location. However, place cells alone are not able to support all types of navigation. Some spatial tasks also require cells in a region of the brain",380,128,0.3368
dialogsum,"#Person1#: I still have a question to ask you. #Person2#: It's my pleasure! #Person1#: How much luggage can I take for my flight? #Person2#: It is allowed to carry 55 pounds for each passenger. #Person1#: But if I have more than 55 pounds, what can I do? #Person2#: You will have to pay some for every extra pound. #Person1#: How about my hand carry luggage? #Person2#: You can bring one, if you want to.",#Person1# asks #Person2# how much luggage can #Person1# take for the flight.,74,12,0.1622
dialogsum,"#Person1#: Hey, Jessica, there is a new fun test in the paper. I love to fill these things out. #Person2#: What's this one about? #Person1#: It's about health. #Person2#: OK. Read it to me. I'll keep score. #Person1#: OK. No. 1: Do you smoke more than ten cigarettes a day? #Person2#: That's easy. I gave up smoking three years ago. #Person1#: Right. You know, I should too. #Person2#: Yeah, I've heard that before. #Person1#: No, No, really. I'm going to. But for now I'd have to say, yes. OK. No. 2: Do you have a check-up at your doctor's office at least once a year? #Person2#: Yeah, the company makes us go to the doctor every year. How about you? #Person1#: Well, I went to the doctor...let's see...about three years ago. #Person2#: You should go more often. #Person1#: Well, let's move on to No. 7: Do you work more than ten hours a day? #Person2#: No, but you've been working a lot lately. #Person1#: I'm really tired. I should work a lot less. But we've been busy though. #Person2#: You really should slow down. #Person1#: It's not that easy. Last question: Do you worry a lot in your life? #Person2#: Worry a lot? Yeah. I guess I'd have to say yes. I should rest more. #Person1#: I definitely should rest more. You know what? It's surprising I'm not dead already.","#Person1# reads a test about health to Jessica. Jessica gave up smoking, goes to the doctor every year, and doesn't work overtime, but #Person1# smokes, seldom goes to the doctor, and is quite busy. They both worry a lot in life and they should rest more.",230,46,0.2
scientific_lay_summarisation-elife-norm,"Familial Advanced Sleep Phase (FASP) is a heritable human sleep phenotype characterized by very early sleep and wake times. We identified a missense mutation in the human Cryptochrome 2 (CRY2) gene that co-segregates with FASP in one family. The mutation leads to replacement of an alanine residue at position 260 with a threonine (A260T). In mice, the CRY2 mutation causes a shortened circadian period and reduced phase-shift to early-night light pulse associated with phase-advanced behavioral rhythms in the light-dark cycle. The A260T mutation is located in the phosphate loop of the flavin adenine dinucleotide (FAD) binding domain of CRY2. The mutation alters the conformation of CRY2, increasing its accessibility and affinity for FBXL3 (an E3 ubiquitin ligase), thus promoting its degradation. These results demonstrate that CRY2 stability controlled by FBXL3 plays a key role in the regulation of human sleep wake behavior. Sleep is vital for all animals. Sleep-wake timing is regulated by the internal biological clock driving physiological rhythms with a period of approximately 24 hr (Takahashi, 1995). The circadian clock is composed of interlocked transcriptional and translational negative feedback loops (Lowrey and Takahashi, 2004; Reppert and Weaver, 2001). In mammals, a CLOCK-BMAL1 heterodimer binds to E-boxes and activates gene expression of the Period (Per) and Cryptochrome (Cry) genes. Translated PERs and CRYs proteins form a complex that enters the nucleus to inhibit their own transcription through direct interaction with CLOCK-BMAL1 heterodimers. PER and CRY proteins accumulating in the nucleus are then degraded over time. As protein levels fall (depending on rate of degradation), the transcription-translation feedback loop begins anew. CRY2 is a principal component in mammalian circadian clocks (Shearman et al. , 2000; van der Horst et al. , 1999; Vitaterna et al. , 1999). While Drosophila and plant CRY proteins act as photoreceptors contributing to photoentrainment of the circadian clock and other biological processes by binding to flavin adenine dinucleotide (FAD) (Partch and Sancar, 2005), mammalian CRY2 has light-independent transcriptional repressor activity and strongly inhibits E-box-regulated gene expression (Griffin et al. , 1999; Kume et al. , 1999; Shearman et al. , 2000). The protein stability of CRY2 is fine-tuned by post-translational modification including phosphorylation and ubiquitylation. In addition, various enzyme modifications play a role in CRY2 regulation (Reischl and Kramer, 2011; Stojkovic et al. , 2014).","Sleep is an essential process in animals. In humans, the disturbance of normal sleep-wake cycles through shift-work or long-term sleep disorders increases the risk of developing conditions including mental illness, cancer and metabolic syndromes. Understanding how sleep-wake behavior is controlled within cells may help researchers to develop effective therapies to reduce the ill effects of disturbed sleep-wakLouise cycles on health. To understand how our sleep-wake cycles are regulated in cells, researchers have been looking for genetic mutations that affect human sleep schedules. For example, some people have a ‘morning lark’ schedule that makes them prone to go to sleep early and rise early the next day. Others are prone to be ‘night owls’, staying up later at night and waking up later in the morning. By studying the",380,128,0.3368
dialogsum,"#Person1#: Can you believe the school year is almost here? #Person2#: I know. Every time I walk by our new school, I get a little anxious. #Person1#: Why? Everything is going to be so much better. #Person2#: Really? I heard it is a lot of extra work. #Person1#: Relax. We'll get used to it. Apparently, there was a huge computer room we can study in. Also they have just finished building a new running track and put in artificial grass. #Person2#: Cool. We'll have lots of fun on the playground. #Person1#: You think that's cool? There are 2 gyms and a indoor swimming pool. Anyway, we have to choose 2 arts courses this year. Any thoughts? #Person2#: At first I thought about dance and music, but I changed my mind. I think I'm going to try acting instead. And since I'm joining the school newspaper, I'll take something related to that. #Person1#: Good for you. I'm going to improve my drawing and learn how to play the drums. #Person2#: Hey, maybe if you become a famous musician, I can interview you.",#Person1# tells #Person2# their new school has finished building a new running track and put in artificial grass. Then they discuss two art courses they need to choose.,181,28,0.1547
scientific_lay_summarisation-elife-norm,"2001) and colonial (Volvox) (Drescher et al. , 2010) species, in order to maintain optimum light levels for photosynthesis. Volvocalean phototaxis is deterministic, requiring precise tuning between the internal biochemical timescales and the rotation period of the organism as a whole. Although S. rosetta colonies also rotate around an internal axis, due to the variable colony morphology and the independent beating of the individual flagella, this rotation rate will itself be random (Kirkegaard et al. , 2016), rendering a strategy similar to that of the Volvocales unlikely in S. rosetta. An alternative strategy is stochastic taxis, sometimes referred to as kinesis. The classic example of stochastic taxis is the run-and-tumble chemotaxis of certain peritrichous bacteria (Berg, 1993). By spinning their left-handed helical flagella in different directions, such bacteria can alternate between swimming in straight lines (running) and randomly reorienting themselves (tumbling). Through biasing tumbles to be less frequent when going up the gradient, the bacteria exhibit biased motion towards a chemoattractant without directly steering towards it (Berg, 1993). Here, we study S. rosetta and show that it exhibits aerotaxis, i. e. navigation along gradients of oxygen. We further examine and statistically analyse aerotaxis of S. rosetta colonies under spatio-temporal variations of oxygen at the level of total colony populations and at the level of the trajectories of individual colonies. From these experiments we establish two key features of the aerotactic response of choanoflagellates: they employ a stochastic reorientation search strategy and the sensing of oxygen concentration gradients is logarithmic. Finally, we render these results quantitative through the use of mathematical analysis of a modified Keller-Segel model (Keller and Segel, 1971). The study of aerotaxis in bacteria has led to numerous methods for creating spatial oxygen gradients (Shioi et al. , 1987; Wong et al. , 1995; Zhulin et al. , 1996; Taylor et al. , 1999), one of which is the exploitation of soft lithography techniques (Adler et al. , 2012; Rusconi et al. , 2014). Since PDMS, the most commonly used material for microfluidic chambers, is permeable to gases, gas channels can be introduced in the devices to allow gaseous species to diffuse into the fluid. For example, an oxygen gradient can be created using a source channel flowing with normal air and a sink channel flowing with pure","Most animals are made up of millions of cells, yet all animals evolved from ancestors that spent their whole lives as single cells. Today the closest single-celled relatives of animals are a group of aquatic organisms called choanoflagellates. Certain species of choanoflagellates can also form swimming colonies. This kind of multicellularity might resemble that seen in the earliest of animals. As such, studies into modern-day choanoflagellates can give insights into how the first animals to evolve might have behaved. Many organisms can find their way towards favorable areas using different strategies. For instance, bacteria can bias their tumbling to gradually swim towards food, and algae can turn and move directly towards light. While choanoflagellates require oxygen, it was not known if they could also actively navigate towards it,",380,128,0.3368
dialogsum,"#Person1#: I can't sleep very well. Could I take some sleeping pills, please? #Person2#: Is anything worrying you? #Person1#: Well, perhaps... I'm working very hard. We're very busy at the moment. #Person2#: Well. I don't really like giving patients sleeping pills. You must have a good rest. Forget all about work. If you can't sleep, have a hot bath before you go to bed, and then read a boring book. Don't choose exciting ones. #Person1#: Oh, but I like a drink before I go to bed. #Person2#: OK, have a glass of milk. Have some fruit or bread but don't have a big meal in the evening.",#Person1# tells the doctor #Person1# cannot sleep and asks for sleeping pills. The doctor refuses and suggests #Person1# do something relaxing.,107,21,0.1963
pubmed-summarization,"simple obesity is currently one of the most common metabolic diseases and its incidence has been increasing every year . this is mainly due to changes in lifestyle and dietary habits of contemporary society as well as the development of inappropriate nutrition and physical activity patterns already in early childhood . obesity increases the risk of hypertension , dyslipidemia and abnormal glucose tolerance , which results in an increased risk of heart and metabolic diseases . obesity as a disease of affluence affects the youngest patients increasingly frequently . over the last decades a gradual increase in the prevalence of excessive body weight and obesity has been observed around the world . this is true not only for the adult population , but for children as well . it is thought that if this trend is not stopped , the present generation of children , despite the considerable progress in medical sciences , will probably be the first generation to live shorter than the parents . the additional tests for children with simple obesity most commonly ordered by primary care physicians include the assessment of thyroid function conducted in order to exclude hormonal imbalances that cause obesity . obese individuals relatively often have elevated levels of the thyroid - stimulating hormone ( tsh ) in the blood serum , called hyperthyrotropinemia , which has a tendency to rise with age . the substance which is responsible for this is leptin , which regulates body weight and hunger , influencing the level of tsh in the blood serum by modifying its synthesis in the pituitary gland . another mechanism accounting for the elevated levels of this hormone in obese patients consists in the possible resistance to thyroid hormones at the level of the pituitary gland and disruption of the negative feedback phenomenon . as a result , the tsh concentration is observed to decrease following the reduction of body weight to a normal level . an attempt at broadening the diagnostic investigation by conducting an imaging examination of the thyroid gland , in addition to tests of free thyroxine , triiodothyronine and antibodies against thyroid peroxidase and thyroglobulin seems to be an obvious course of action . according to them one of the indications for the ultrasound examination of the thyroid",obesity as a disease of affluence also affects younger children . numerous observations suggest a link between excessive body weight and thyroid function disorders . subclinical hypothyroidism has been diagnosed increasingly frequently in patients with obesity . a growing number of papers also point to morphological changes of the thyroid gland in the ultrasound examination in obese children . these reports mainly concern changes in echogenicity . the present paper discusses the most important aspects of this topic on the basis of the literature as well as containing a brief analysis based on own experiences .,380,96,0.2526
pubmed-summarization,", furanolabdane , and labdane types , triterpenes including ursolic and oleanolic acids , nitrogen - containing compounds such as leonurine and stachydrine , and phenylpropanoids such as lavandulifolioside , as well as flavonoids , phenolic acids , volatile oils , sterols , and tannins . pharmacological reports have established antimicrobial , antioxidant , and anti - inflammatory effects , as well as the effects of the herb on the heart and circulatory system . sedative and hypotensive properties since pharmacological studies are limited , the use of motherwort is mainly based on traditional suggestions . analgesic drugs are one of the most products that are used in numerous diseases for alleviating the pain . most analgesic drugs , accessible in the market , exhibit an extensive range of adverse effects including gastrointestinal disorders , kidney problems , and other unwanted effects . this situation highlights the need for advent of safe , novel , and effective analgesic compounds . the aim of the present study was to investigate the analgesic activities of aerial part of leonurus cardiaca using three analgesic tests in mice . the animals were handled in accordance with the criteria outlined in the guide for the care and use of laboratory animals ( nih us publication 86 - 23 revised 1985 ) . 68 weeks of age , were kept in a controlled environment ( 22 2c , 50 5% humidity ) under a 12-hour light / dark cycle ( light on 08:0020:00 ) and had free access to a standard pellet chow and tap water throughout the study . all experiments were conducted at tehran university of medical sciences according to the recommendations of the ethics committee for animal welfare and have been approved by institutional animal care and utilization committee . one hundred grams of aerial parts was placed into a flask ; one liter of 96% ethanol was then added . after 24 hours , when the solution had become clear , this was transferred into another flask . one liter of 70% ethanol was then added to the solid residue and after 12 hours the supernatant was again decanted into another flask . both solutions were then combined and concentrated by vacuum distillation at a temperature of 50c and 70 rpm rotation","leonurus cardiaca , commonly known as motherwort , is a member of the lamiaceae family . it has a number of interesting biological activities , for example , sedative and hypotensive , antioxidant , anti - inflammatory , and antimicrobial activities . the aim of the present study was to investigate the effect of alcoholic extract of aerial part of leonurus cardiaca on nociceptive response using formalin , tail flick , and hot plate tests in mice . the acute treatment of mice with an ethanolic extract at doses of 500 and 250 mg / kg by intraperitoneal administration produced a significant antinociceptive in the first and second phases of formalin test , respectively . the hot plate and tail flick tests showed an increase in the antinociceptive",380,128,0.3368
scientific_lay_summarisation-elife-norm,"amyotrophic lateral sclerosis 4 (Chen et al. , 2004), and spinal muscular atrophy can be caused by mutations in SMN (Clermont et al. , 1995). The neuronal ELAV-like (ELAVL) and NOVA RBPs are targeted by the immune system in paraneoplastic neurodegenerative disorders (Buckanovich et al. , 1996; Szabo et al. , 1991). Mammalian ELAVL proteins include the ubiquitously expressed paralog ELAVL1 (also termed HUA or HUR) and the three neuron-specific paralogs, ELAVL2,3 and 4 (also termed HUB, C, and D, and collectively referred to as nELAVL; Ince-Dunn et al. , 2012). nELAVL proteins are expressed exclusively in neurons in mice (Okano and Darnell, 1997), and they are important for neuronal differentiation and neurite outgrowth in cultured neurons (Akamatsu et al. , 1999; Kasashima et al. , 1999; Mobarak et al. , 2000; Anderson et al. , 2000; Antic et al. , 1999; Aranda-Abreu et al. , 1999). Redundancy between the three nELAVL isoforms complicates in vivo studies of their individual functions. Nevertheless, even haploinsuffiency of Elavl3 is sufficient to trigger cortical hypersynchronization, and Elavl3 and Elavl4 null mice display defects in motor function and neuronal maturation, respectively (Akamatsu et al. , 2005; Ince-Dunn et al. , 2012). ELAVL proteins have been shown to regulate several aspects of RNA metabolism. In vitro and in tissue culture cells, nELAVL proteins have been implicated in the regulation of stabilization and/or translation of specific mRNAs, as well as in the regulation of splicing and polyadenylation of select transcripts [reviewed in Pascale et al. (2004) ]. A more comprehensive approach was taken by immunoprecipitating an overexpressed isoform of ELAVL4 in mice, although such RNA immunoprecipitation experiments cannot distinguish between direct and indirect targets (Bolognani et al. , 2010). Recently, direct binding of nELAVL to target RNAs in mouse brain was demonstrated by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP; Ince-Dunn et al. , 2012); these data, coupled with transcriptome profiling of Elavl3/4 KO mice, demonstrated that nELAVL directly regulates neuronal mRNA abundance and alternative splicing by binding to U-rich elements with interspersed purine residues in 3’UTRs and introns in mouse brain (Ince-Dunn et al. , 2012). While genome-wide approaches have been applied to studying nELAVL proteins in mice, the targets of nELAVL in the human brain remain largely unknown. This is of particular","When a gene is active, its DNA is copied into a molecule of RNA. This molecule then undergoes a process called splicing which removes certain segments, and the resulting ‘messenger RNA’ molecule is then translated into protein. Many messenger RNAs go through alternative splicing, whereby different segments can be included or excluded from the final molecule. This allows more than one type of protein to be produced from a single gene. Specialized RNA binding proteins associate with messenger RNAs and regulate not only their splicing, but also their abundance and location within the cell. These activities are crucially important in the brain where forming memories and learning new skills requires thousands of proteins to be made rapidly. Many members of a family of RNA binding proteins called ELAV-like",380,128,0.3368
scientific_lay_summarisation-elife-norm,"time a clear dichotomy among the skin-resident macrophages based on their differential sensitivity to γ-irradiation. Radio-resistant and radio-sensitive skin macrophages are distinctively polarized already in steady state as revealed by transcriptional analysis. Consequently, these two macrophage subsets are functionally specialized in a cell-autonomous manner even though both subsets are exposed to mostly shared environmental cues. In particular, the radio-resistant macrophage subset comprises a novel type of perivascular macrophages that gain access to the vascular lumen, are highly phagocytic and possess anti-inflammatory properties even in the presence of pro-inflammatory stimuli. Moreover, they are renewed from a local Bmi1+ progenitor and become outcompeted over time by bone marrow-derived resident macrophages. Finally, the preferential depletion of these skin transendothelial radio-resistant anti-inflammatory macrophages (STREAMs) using diphtheria toxin-OVA nanoparticles evidences their involvement in tissue repair and remodeling, as well as the inability of their radio-sensitive counterparts to act as functional surrogates. To visualize the microvascular network of the skin, we performed intravital imaging of the upper dermis of the mouse ear under steady-state conditions using a minimally invasive model based on confocal microscopy (Auffray et al. , 2007). The vasculature was highlighted by injecting i. v. a non-permeable vascular tracer, high molecular weight (HMw; 2 MDa) TRITC-dextran. Remarkably, a population of perivascular cells became readily visible during the first hours after HMw dextran injection, suggesting that these mostly sessile cells were constantly taking up intravascular dextran (1A and Video 1). This observation was further confirmed by monitoring the uptake of two differently labeled HMw dextrans injected with a lapse of 24 hr (— 1A). Dextran administration followed by the subsequent injection of a non-phagocytosable tracer (vivotag) revealed the presence of dextran+ protrusions as non-stained regions in the vivotag channel projecting into the vessel lumen (1B). The protrusions were flapping inside the vessels, presumably deflected by the vascular flow, and even contacting circulating cells (— 1B and Videos 2–4). The phenotypic characterization of the TRITC-dextran+ perivascular cells identified them mostly as macrophages (i. e. , they were either CD45+ F4/80high CD11c- CD11b+ or CD45+ F4/80high CD11c- CD64+ cells by FACS [1C and — 1C] and CD68+ cells by whole-mount immunofluorescence staining [— 1D]). Flow cytometry analysis of skin single-cell suspensions from 12-week-old animals showed that the 96. 67% ± 1. 02% of all TRITC-dextran+ cells were","The skin forms an essential barrier that defends our body from external damage. For this reason, it is important to understand the complex mechanisms involved in healing wounds and maintaining healthy skin. This could allow us to find effective treatments for skin diseases such as atopic dermatitis and psoriasis. Immune cells called macrophages can protect the body in different ways depending on the signals they receive. Their protective roles include killing microbes that may cause disease, and helping to repair damaged tissues. Barreiro et al. have now investigated the roles of the macrophages in the skin by means of a number of complementary techniques, including a method called intravital microscopy that can image cells in a living organism. The experiments revealed that a division of labor exists among",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the compendium of genetic determinants of the NCC lineage and characterize how they act in concert in time and space. During neuroectoderm development, transcriptional programs are initiated successively in response to morphogen induction to specify neural stem cell (NSC) subdomains along the dorsal-ventral axis in the neuroepithelium (Briscoe et al. , 2000; Vokes et al. , 2007; Kutejova et al. , 2016). NCCs also arise from the neuroepithelium, at the border with the surface ectoderm through the pre-epithelial-mesenchymal transition (pre-EMT) which is marked by the activation of Tfap2a, Id1, Id2, Zic1, Msx1 and Msx2 (Baker et al. , 1997; Mayor et al. , 1997; Saint-Jeannet et al. , 1997; Marchant et al. , 1998; Etchevers et al. , 2019). In the migratory NCCs, gene activity associated with pre-EMT and NCC specification is replaced by that of EMT and NCC identity (Marchant et al. , 1998). NCC differentiation progresses in a series of cell fate decisions (Lasrado et al. , 2017; Soldatov et al. , 2019). Genetic activities for mutually exclusive cell fates are co-activated in the progenitor population, which is followed by an enhancement of the transcriptional activities that predilect one lineage over the others (Lasrado et al. , 2017; Soldatov et al. , 2019). However, more in-depth knowledge of the specific factors triggering this sequence of events and cell fate bias is presently lacking. Twist1 expression is initiated during NCC delamination and its activity is sustained in migratory NCCs to promote ectomesenchymal fate (Soldatov et al. , 2019). TWIST1 mediates cell fate choices through functional interactions with other basic-helix-loop-helix (bHLH) factors (Spicer et al. , 1996; Firulli et al. , 2005; Connerney et al. , 2006) in addition to transcription factors SOX9, SOX10, and RUNX2 (Spicer et al. , 1996; Hamamori et al. , 1997; Bialek et al. , 2004; Laursen et al. , 2007; Gu et al. , 2012; Vincentz et al. , 2013). TWIST1 therefore constitutes a unique assembly point to identify the molecular modules necessary for cranial NCC development and determine how they orchestrate the sequence of events in this process. To decipher the molecular context of TWIST1 activity and identify functional modules, we generated the first TWIST1 protein interactome in the NCCs. Leveraging the proximity-dependent biotin identification (BioID) methodology, we captured TWIST1 interactions in the","Shaping the head and face during development relies on a complex ballet of molecular signals that orchestrates the movement and specialization of various groups of cells. In animals with a backbone for example, neural crest cells (NCCs for short) can march long distances from the developing spine to become some of the tissues that form the skull and cartilage but also the pigment cells and nervous system. NCCs mature into specific cell types thanks to a complex array of factors which trigger a precise sequence of binary fate decisions at the right time and place. Amongst these factors, the protein TWIST1 can set up a cascade of genetic events that control how NCCs will ultimately form tissues in the head. To do so, the TWIST1 protein interacts with",380,128,0.3368
pubmed-summarization,"for patients with acute coronary syndrome ( acs ) , the key to increased survival and the preservation of myocardial function is rapid diagnosis followed by appropriate early intervention , which will enable timely management strategies and intervention to be carried out . delays at any level of management , from the prehospital setting to the emergency department ( ed ) and , subsequently , to the cardiac catheterisation laboratory , must be minimised . the diagnosis of acute myocardial infarction requires the combination of a good and prompt clinical history , a 12-lead electrocardiogram ( ecg ) and also appropriate cardiac markers ( in cases of st - elevation ami [ stemi ] , the results of cardiac markers will not be required for decisions on management and intervention ) . prehospital 12-lead ecgs are now being performed and transmitted to eds to save precious time in diagnosis . institutions set targets where the door - to - ecg time should not exceed 10 min , the door - to - needle time must be within 30 min and the door - to - intervention time should be within 90 min of arrival . the acquisition of a 12-lead ecg is an important step to assess the cardiac status in routine and emergency situations . in a cardiac emergency , the time and accuracy of information are important elements that have a critical effect on patient outcomes . accurate ecg measurements are essential for diagnostic purposes , as well as serial comparison to evaluate changes in cardiac status and help in the prediction of future events . in clinical practice , the relevance of the ecg depends upon its reproducibility in an individual . with all of these points in mind the application of single - lead electrodes to the torso for standard 12-lead ecg acquisition takes time . a relatively new praecordial v1v6 , v - quick patch , has been developed and it provides a one - piece template for the placement of all six praecordial leads , which makes application easy . the person performing the 12-lead ecg need only to reach out for one single item to be applied to the patient s torso , instead of six separate pieces of items , as in","introductionthe v - quick patch template system is compared with the standard 12-lead electrocardiogram ( ecg ) acquisition technique in this paper . the objectives of the study were : ( a ) to study and compare the time taken to produce the printed 12-lead ecg and ( b ) to look at the level of agreement when the ecgs were compared by two blinded , independent assessors.methodsone hundred and fifty each of male and female volunteers signed an informed consent form to participate in the clinical study . nurses were put through a 4-h training session to familiarise themselves with the v - quick patch system . the timings were measured with a stopwatch with the specific start and end points defined . the final ecg printouts",380,128,0.3368
scientific_lay_summarisation-elife-norm,"brain metabolism (Owen et al. , 1967; Hasselbalch et al. , 1994). During the neonatal period, the developing human brain has high energy requirements and also relies on ketone bodies as a major fuel (Cunnane and Crawford, 2003; Cahill, 2006). Given their importance in fueling large, energetically expensive brains, it has been posited that ketone bodies do not only have an important role during fasting, but have also been crucial for brain expansion during human evolution (Cunnane and Crawford, 2003; Wang et al. , 2014). Ketone bodies comprise acetoacetate, acetone, and d-β-hydroxybutyrate (1A) and are mainly produced in the liver by ketogenesis. This metabolic process occurs in the mitochondria and uses fatty acid-derived acetyl-CoA to generate the water-soluble, acidic ketone bodies, which are secreted into the blood. The rate limiting step of ketogenesis is the production of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by HMG-CoA synthase (Hegardt, 1999). Mammals possess two HMG-CoA synthases that originated by gene duplication. While the cytosolic enzyme, encoded by HMGCS1, is broadly expressed and is necessary to produce cholesterol (Hegardt, 1999), the mitochondrial HMG-CoA synthase, encoded by HMGCS2, is primarily expressed in the liver and is only used for ketone body production. HMGCS2 is required for ketogenesis, as mutations in the human gene and mouse gene-knockdown experiments abolish or greatly reduce ketogenesis (Bouchard et al. , 2001; Ramos et al. , 2013; Thompson et al. , 1997; Wolf et al. , 2003; Pitt et al. , 2015; Cotter et al. , 2014). HMG-CoA synthase-2 deficiency in human can lead to coma after fasting for more than 22 hours due to low glucose levels (Thompson et al. , 1997; Morris et al. , 1998). Human individuals with HMGCS2 mutations therefore require regular carbohydrate intake but show no other symptoms, suggesting that this deficiency is probably underdiagnosed. Here we investigated the evolution of HMGCS2 in mammals. Unexpectedly, we identified three independent losses of this gene in cetaceans (dolphins and whales), pteropodids (Old World fruit-eating bats) and Elephantimorpha (elephants and mastodons). Remarkably, these species have relatively large brains, suggesting that, unlike in humans, ketone bodies are not strictly required for fueling complex brains. Furthermore, we show that in the cetacean and Elephantimorpha clades HMGCS2 was lost before brain size expansion happened, suggesting that the lack of ketogenesis did not prohibit the evolution","Our brain requires a lot of energy to work properly. Sugars are usually the main type of fuel for the body, but when they run low – for example during a food shortage – fat, in the form of fatty acids, can be used instead. However, the brain cannot directly process these molecules; instead, fatty acids need to go through ketogenesis, a process that turns fat into ketone bodies, which the organ can then burn. Scientists believe that the ability to create ketone bodies was essential for us to evolve large brains. Yet, it is still unclear if all mammals can transform fatty acids into ketone bodies. One way to look into this question is to track whether other species have HMGCS2, the main enzyme that drives ketogenesis.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Many transcription factors co-express with their homologs to regulate identical target genes, however the advantages of such redundancies remain elusive. Using single-cell imaging and microfluidics, we study the yeast general stress response transcription factor Msn2 and its seemingly redundant homolog Msn4. We find that gene regulation by these two factors is analogous to logic gate systems. Target genes with fast activation kinetics can be fully induced by either factor, behaving as an' OR' gate. In contrast, target genes with slow activation kinetics behave as an' AND' gate, requiring distinct contributions from both factors, upon transient stimulation. Furthermore, such genes become an' OR' gate when the input duration is prolonged, suggesting that the logic gate scheme is not static but rather dependent on the input dynamics. Therefore, Msn2 and Msn4 enable a time-based mode of combinatorial gene regulation that might be applicable to homologous transcription factors in other organisms. Homologous transcription factors (TFs) often co-exist in eukaryotic cells, resulting in seemingly redundant regulation of their target genes. Although a large number of TF homologs have diversified over time to obtain distinct target genes from their partners, others have remained relatively conserved and share the same DNA binding motif, which limits their downstream interactions to identical target genes. Recent studies suggest that some closely related TF homologs or isoforms, which regulate a shared set of target genes, might have diverged expression patterns, dynamic responses or gene regulatory functions. For example, the yeast transcriptional regulator Dig1 inhibits the expression of mating response genes to pheromone stimulation, whereas its homolog Dig2 exhibits both negative and positive regulation depending on the conditions (Chou et al. , 2008; Houser et al. , 2012). In mammalian cells, two TF isoforms NFAT1 and NFAT4 display distinct nuclear translocation dynamics in response to stimuli. It has been suggested that this dynamic diversity of isoforms might enhance the temporal signal processing function of the cell (Yissachar et al. , 2013). In addition, a very recent study showed that the TF homologs STAT5A and STAT5B differentially contribute to the immune transcriptional response due to their different expression levels (Villarino et al. , 2016). Here we use the yeast homologous stress responsive TFs Msn2 and Msn4 as a model to quantitatively study the functional relevance of closely related TFs in the same","Cells respond to environmental signals by activating proteins called transcription factors. These bind to the DNA that is stored in the cell nucleus and turn on specific genes to make gene products. Many of these transcription factors move in and out of the nucleus once activated. Different environmental signals affect the amount of transcription factor that appears in the nucleus in different ways, and this is important in determining which genes should be turned on and how many copies of gene products should be made. Many transcription factors co-exist with a similar version of themselves in the same cell. These closely related proteins, called homologous transcription factors, respond to the same signals and bind to the same place on the DNA to turn on the same genes. It",380,128,0.3368
dialogsum,"#Person1#: OK, boys. It's time that you learn how to do your own laundry. Who can tell me the first thing that you need to do? #Person2#: Separate the whites from the dark colours. #Person1#: Good job, Matt. Now, what do you do after you put the clothes in the washer? #Person2#: Choose the speed, size of the load and water temperature that you want. #Person1#: Excellent, Matt. You're almost ready to do this yourself. You just forgot one thing, put in the soap, before you start the machine. Then press the start button and wait until the washer makes the short high sound. That means the cycle is complete, then what do we do? #Person2#: Clean out the dryer and then put the clothes in it, choose the temperature level and timing and press start. #Person1#: Good job, Matt. You sound like you're ready to go. Be sure never to leave the machines going if you're not at home and make sure to take out the clothes and fold them as soon as their dry, so they don't wrinkle. Now you can do this all by yourselves!",#Person1# asks Matt the steps of doing laundry. #Person1# reminds Matt to put in the soap before starting the machine and asks Matt to do it all by himself.,188,29,0.1543
dialogsum,"#Person1#: Hello, Miss Wu, This is Dan Robson calling from OTC limited. I'd like to check my last order. When exactly was it sent out? #Person2#: I can check that for you right now. Would you mind holding? #Person1#: Sure. No problem. #Person2#: Mr. Robson, I'm sorry. Our computer system is down. Could I call you back later? #Person1#: Sure. Do you have my number? #Person2#: Yes, I have it right here. I'm so sorry about this. #Person1#: No problem. I'll wait for your call.",Miss Wu will call Mr. Robonson back to check his order because now the system is down.,85,17,0.2
dialogsum,"#Person1#: Good afternoon! Can I help you? #Person2#: Could you show me where the Chinesc-style clothing is located? I want to buy a silk coat. #Person1#: This way, please. Here they are. They're all handmade. #Person2#: Oh, they look nice. May I try that black one on? #Person1#: Of course. The fitting room is right over there. #Person2#: Do you have a medium in the same color? This one is a little tight. #Person1#: l'm sorry. All the black of that size are sold out. Would you like a red one? #Person2#: OK. Let me try it on. What do you think? #Person1#: Oh, that suits you very well. Besides it is believed in China that the red color brings happiness and good luck. #Person2#: Really? I'II take it and I'm leaving here tomorrow. Is it possible for you to send one in black to me by mail when you get it in? #Person1#: Our pleasure. Please fill out this form, leaving your address and telephone number. #Person2#: Thanks. How much would that come to? #Person1#: Let me see. . .",#Person1# assists #Person2# in buying silk coats. #Person2# buys a red one in the shop and orders a black one to be delivered.,181,23,0.1271
dialogsum,"#Person1#: Is there anything I can do for you? #Person2#: Yes. I am looking for a pair of gloves. #Person1#: What about this one? It's the latest. #Person2#: Excuse me, but I want a pair of mittens. #Person1#: I am sorry, it's out of stock right now.",#Person2# wants mittens. #Person1# says it's out of stock.,47,9,0.1915
dialogsum,"#Person1#: May I take your order now? #Person2#: Yes, bring me a bottle of wine and filet steak. #Person1#: Do you want some salad dressing? #Person2#: Yes, what kind do you have? #Person1#: We have Italian, French, thousand island and blue cheese. #Person2#: I think French will be fine.","#Person2# orders some wine, filet steak, and French salad dressing with #Person1#'s assistance.",49,13,0.2653
dialogsum,"#Person1#: Hello, Jenny. Are you going to California? #Person2#: Yes, I have decided to live abroad. #Person1#: Why? #Person2#: I think life there is more comfortable. The cost of living is not so high like here and the environment there is better. #Person1#: But you will leave all of your friends here. Then you have to find a new job. #Person2#: That's no problem. I can still be a painter. #Person1#: If you insist on living there, I hope you can be happy everyday. #Person2#: I will. Anyway, I have bought the air ticket. I can come back if I'm unhappy there, so don't worry about me. #Person1#: OK, I plan to hold a farewell party for you this Sunday. We can invite our friends. #Person2#: Thank you. That's very kind of you.",Jenny is going to live in California due to the lower cost of living and a better environment there. #Person1# will hold a farewell party for her.,133,27,0.203
dialogsum,"#Person1#: Hi. Mike. How did your weekend go? #Person2#: Fine. I went back to visit my grandma in the countryside. #Person1#: Lucky you. What did you do there? #Person2#: I went for a walk in the hills with some of my friends. #Person1#: Was it good? #Person2#: Yes. the scenery was amazing. The whole hillside was very red. #Person1#: How wonderful! Do anything else? #Person2#: We went on a picnic on Sunday. #Person1#: Did you like it? #Person2#: Very enjoyable. By the way, Lisa. what about your Weekend? #Person1#: Don't ask me. Mike. #Person2#: What happened? #Person1#: I have got a cold. I could do nothing but lie in bed. #Person2#: Oh. dear.","Mike thinks that his weekend was good because he visited his grandma in the countryside and walked with his friends in the hills, while Lisa has got a cold.",113,29,0.2566
pubmed-summarization,"( erp ) in an oddball task discriminated between children with down syndrome , fasd , and typically developing controls ( kaneko et al . auditory processing delays have also been observed in a meg study of preschool children with fasd ( stephen et al . , 2012 ) . the present study utilized meg to investigate brain dynamics of adolescents with fasd during the performance of an auditory oddball task . perceptual expectation for a set of repeated ( standard ) tones , detection of target tones that elicit behavioral responses and processing of novel digital sounds in cortico - hippocampal circuits ( halgren et al . , 1998 ) . sex - related differences in brain structure are known to emerge in typically developing adolescents , with increased volume of the amygdala in males and of the hippocampus in females ( for a review , see blakemore , 2012 ) . since prenatal ethanol exposure is known to produce sex - specific deficits in hippocampus in rodent models ( coleman et al . , 2012 ; see also helfer et al . 2014 ) , we hypothesized that meg measures of brain activation in the oddball data may reveal sex - specific differences for adolescents with fasd . consideration of potential sexual dimorphism in neuroimaging and neurophysiological studies in adolescents with fasd is rare ( although see kaneko et al . , 1996a ) . the present effort will contribute novel information on sex - specific effects on brain function and motivate further attention to potential sexual dimorphism in studies of adolescents with fasd . forty eight adolescents and young adults in the age range 1222 years were recruited for this study . for the participants utilized in the meg analysis , twenty two of the participants ( 9 male , age 15.0 yrs , sd = 3.6 yrs ; 13 female , age 15.5 yrs , sd = 2.8 yrs ) were identified as fasd according to the modified institute of medicine criteria ( stratton et al . , , 9 were diagnosed with fas ( 6 male and 3 female ) and 13 with alcohol - related neurodevelopmental disorder ( arnd ) ( 3 male and 10 female ) . twenty - two age- and sex","children exposed to substantial amounts of alcohol in utero display a broad range of morphological and behavioral outcomes , which are collectively referred to as fetal alcohol spectrum disorders ( fasds ) . common to all children on the spectrum are cognitive and behavioral problems that reflect central nervous system dysfunction . little is known , however , about the potential effects of variables such as sex on alcohol - induced brain damage . the goal of the current research was to utilize magnetoencephalography ( meg ) to examine the effect of sex on brain dynamics in adolescents and young adults with fasd during the performance of an auditory oddball task . the stimuli were short trains of 1 khz standard tone bursts ( 80% ) randomly interleaved",380,128,0.3368
dialogsum,"#Person1#: Bob! #Person2#: Anne! I haven't seen you for ages. How ' Ve you been? #Person1#: Fine, just fine. And you? #Person2#: Not bad. It really is great to see you again. Where have you been? #Person1#: Guangzhou. I've got a cousin there.",Bob and Anne who haven't seen each other for ages greet each other.,43,13,0.3023
scientific_lay_summarisation-elife-norm,"In mouse embryo gastrulation, epiblast cells delaminate at the primitive streak to form mesoderm and definitive endoderm, through an epithelial-mesenchymal transition. Mosaic expression of a membrane reporter in nascent mesoderm enabled recording cell shape and trajectory through live imaging. Upon leaving the streak, cells changed shape and extended protrusions of distinct size and abundance depending on the neighboring germ layer, as well as the region of the embryo. Embryonic trajectories were meandrous but directional, while extra-embryonic mesoderm cells showed little net displacement. Embryonic and extra-embryonic mesoderm transcriptomes highlighted distinct guidance, cytoskeleton, adhesion, and extracellular matrix signatures. Specifically, intermediate filaments were highly expressed in extra-embryonic mesoderm, while live imaging for F-actin showed abundance of actin filaments in embryonic mesoderm only. Accordingly, Rhoa or Rac1 conditional deletion in mesoderm inhibited embryonic, but not extra-embryonic mesoderm migration. Overall, this indicates separate cytoskeleton regulation coordinating the morphology and migration of mesoderm subpopulations. In mice, a first separation of embryonic and extra-embryonic lineages begins in the blastocyst at embryonic day (E) 3. 5 when the trophectoderm is set aside from the inner cell mass. A second step is the segregation of the inner cell mass into the epiblast, the precursor of most fetal cell lineages, and the extra-embryonic primitive endoderm (Chazaud and Yamanaka, 2016). At E6, the embryo is cup-shaped and its anterior-posterior axis is defined. It comprises three cell types, arranged in two layers: the inner layer is formed by epiblast, distally, and extra-embryonic ectoderm, proximally; the outer layer, visceral endoderm, covers the entire embryo surface. The primitive streak, site of gastrulation, is formed at E6. 25 in the posterior epiblast, at the junction between embryonic and extra-embryonic regions, and subsequently elongates to the distal tip of the embryo. The primitive streak is the region of the embryo where epiblast cells delaminate through epithelial-mesenchymal transition to generate a new population of mesenchymal cells that form the mesoderm and definitive endoderm layers. All mesoderm, including the extra-embryonic mesoderm, is of embryonic epiblast origin. At the onset of gastrulation, emerging mesoderm migrates either anteriorly as so-called embryonic mesodermal wings, or proximally as extra-embryonic mesoderm (Arnold and Robertson, 2009; Sutherland, 2016). Cell lineages studies showed that there is little correlation between the position of mesoderm progenitors in the epiblast and the final localization of mesoderm descendants (Lawson","As an embryo develops, its cells divide and specialize to form different tissues and organs. Early in development the cells arrange into so-called germ layers, which each produce particular types of tissue. One of these layers, called the mesoderm, develops into the muscles, bones and circulatory system of the embryo. It also contributes to the support structures that feed and protect the embryo, such as the placenta, umbilical cord and yolk sac. If these ‘extra-embryonic’ structures do not develop correctly, the embryo may not grow properly. Much of what we know about how the cells of the mesoderm move around to form different tissues comes from studies of species that lay eggs; for example, chicks, frogs and fish. The initial steps of embryo development in these animals are",380,128,0.3368
scientific_lay_summarisation-elife-norm,"During translation elongation, the ribosome ratchets along its mRNA template, incorporating each new amino acid and translocating from one codon to the next. The elongation cycle requires dramatic structural rearrangements of the ribosome. We show here that deep sequencing of ribosome-protected mRNA fragments reveals not only the position of each ribosome but also, unexpectedly, its particular stage of the elongation cycle. Sequencing reveals two distinct populations of ribosome footprints, 28–30 nucleotides and 20–22 nucleotides long, representing translating ribosomes in distinct states, differentially stabilized by specific elongation inhibitors. We find that the balance of small and large footprints varies by codon and is correlated with translation speed. The ability to visualize conformational changes in the ribosome during elongation, at single-codon resolution, provides a new way to study the detailed kinetics of translation and a new probe with which to identify the factors that affect each step in the elongation cycle. To accomplish the huge task of translation elongation—in each cycle, accurately incorporating a new amino acid into a nascent peptide every 1/6th of a second, then moving precisely three nucleotides along the mRNA template—the ribosome undergoes a series of major structural rearrangements () (reviewed in Chen et al. , 2012 and Noeske and Cate, 2012). During the initial decoding step of elongation, aminoacylated tRNAs are delivered to the decoding site (A site) as part of a ternary complex with EF-Tu (in prokaryotes) or the orthologous eEF1A (in eukaryotes). When the anticodon of one of these aminoacylated tRNAs is able to base-pair stably with the specific mRNA codon in the decoding site (A site), a new peptide bond is formed between the nascent polypeptide and the specified amino acid. The ribosome then undergoes a massive rearrangement in which the ribosomal subunits rotate relative to each other (Frank and Agrawal, 2000; Zhang et al. , 2009). Along with this rotation, the A and P site tRNAs move from ‘classic’ to ‘hybrid’ states: the anticodon ends stay in their original A and P sites and the acceptor ends move to the P and E sites (Moazed and Noller, 1989; Munro et al. , 2007). This rotated state of the ribosome undergoes additional conformational changes in preparation for translocation (Zhang et al. , 2009; Fu et al. , 2011). The ribosome can fluctuate between rotated","To make a protein from a gene, the gene is first transcribed to produce a molecule of messenger RNA (mRNA), which then passes through a molecular machine called a ribosome. The ribosome reads the genetic code in the mRNA in groups of three letters at a time, and each triplet of letters (or codon) represents an amino acid. The ribosome then joins the relevant amino acids together to build a protein. The ribosome processes about six amino acids per second, on average, but the mRNA is not fed through at a constant rate. Instead, the ribosome changes its shape to ratchet along the mRNA from one codon to the next: it then reads the new codon and adds another amino acid to the protein. However, many of the",380,128,0.3368
dialogsum,"#Person1#: What can we do for you today? #Person2#: Uh, hi. Yes, I'm having a problem with my car, and it doesn't seem to run right. I mean every time I start it up, the engine runs for a minute or so, sputters like it isn't getting enough gas, and then dies. #Person1#: Hmmm. Okay. Let's open the hood, and let's take a look... Okay, start her up. [Engine starting...] Okay, Okay. Shut her off. Hmmm. [So...] Let me look at the book here... [It] sounds like a possible fuel line, a dirty carburetor, bad alternator, or even a weak battery. #Person2#: So, which one is it? #Person1#: Uhh. Difficult to say. Let me try this... Uh, alright... You need to talk to the mechanic. #Person2#: The mechanic! So, who are you? #Person1#: Well, I'm the assistant, and I've only been here on the job for two days. #Person2#: So, why didn't you tell me that in the first place? I mean, I wouldn't have wasted all this time! #Person1#: You didn't ask. #Person2#: Okay, so how much is it going to cost? #Person1#: Ah. Difficult to say. [That's what you said about the last thing!] Are you a local or from out of town? #Person2#: I'm just passing through, and this is the only place for miles. [Yeah, that's right.] Man, can't you see my license plate? [Sure did!] #Person1#: Okay. The out-of-town rate. Let's see. Okay, here we go. If it's a fuel line, that'll be $100... No, no, That's the local rate. Here, $200 for the pre-screening check, $150 for parts, plus or minus $100, and $75 an hour for labor. Oh, oh yeah. Today's a holiday, so labor is actually $50 more per hour. #Person2#: Huh? Those prices are outrageous, and what holiday is it today? #Person1#: Oh, it's the local pumpkin festival. #Person2#: Ah, come on. I can't believe this. Of all my luck, my car breaks down in an out-of-the-way town [That's right.], and it'll cost an arm and a leg to get my car fixed. #Person1#: Ah, we'll take care of you. Just bring the car back on Tuesday so Mike, our mechanic, can take a look at it. #Person2#: Why not today? It's only 11:00 a.m.! #Person1#: Ahh, we close at 11:30","#Person2#'s car seems to have some problems. #Person1# checks the car but #Person1# is just an assistant so #Person1# cannot repair the car. Because of the pumpkin festival, #Person2# has to pay more money and wait until next Tuesday to have the car repaired.",380,44,0.1158
scientific_lay_summarisation-elife-norm,"nucleoplasm into condensates (Banani et al. , 2016; Wheeler et al. , 2016). Scaffold proteins that drive phase transitions have distinct features, the most prominent being multivalency of folded domains or Short Linear amino acid Motifs (SLiMs) (Banani et al. , 2017; Li et al. , 2012; Brangwynne et al. , 2015; Csizmok et al. , 2016; Kato et al. , 2012). Valency quantifies the number of interaction domains or SLiMs. Ligands of multivalent proteins can be other multivalent proteins or polynucleotides. The simplest multivalent proteins are linear polymers that consist of multiple protein-protein/protein nucleic acid interaction domains or SLiMs connected by intrinsically disordered linkers that lack specific interaction motifs (1a). Linear multivalent proteins may be classified as associative polymers (Tanaka, 2011; Semenov and Rubinstein, 1998), with specific intra- and intermolecular associations being mediated by non-covalent interactions amongst domains or motifs. Unlike generic homopolymers where the interactions are isotropic, uniform, and typically short-range (Flory, 1942a; Flory, 1974), the interactions involving associative polymers span a range of length scales and can be directional in nature (Brangwynne et al. , 2015; Tanaka, 2011). This includes a hierarchy of so-called weakly polar interactions involving charges, dipoles, and quadrupoles (Nott et al. , 2015; Brangwynne et al. , 2015; Burley and Petsko, 1988; Brady et al. , 2017; Lin et al. , 2016), hydrogen bonds, screened charge-charge interactions (Pak et al. , 2016), and hydration-mediated interactions (Boeynaems et al. , 2017; Schneider et al. , 2002; Pochan et al. , 2003). This hierarchy of interactions will enable non-covalent interactions known as physical crosslinks that involve associative domains/motifs that enable the formation of system-spanning networks known as gels (Semenov and Rubinstein, 1998; Schneider et al. , 2002; Pochan et al. , 2003; Rubinstein and Colby, 2003). Associative polymers can undergo two types of reversible gelation transitions. These are gelation without phase separation or gelation driven by phase separation (Tanaka, 2011; Semenov and Rubinstein, 1998; Rubinstein and Semenov, 1998). Our work focuses on the differences between the distinct gelation transitions and the molecular determinants of these differences in linear multivalent proteins. Gelation without phase separation refers to a switch from a solution of dispersed monomers and oligomers – a sol – to a system-spanning network – a gel (1b). This networking transition is characterized by a","Our cells contain a variety of structures called organelles that perform specific roles within a cell. Some organelles are surrounded by a membrane, while others float inside the cell as spherical droplets made of proteins. These proteins contain several sticky regions, which are connected by flexible linker proteins. It is thought that the level of stickiness and the number of sticky regions, or domains, determine whether a protein will form a membraneless organelle. Often, proteins with similar sticky domains have different linkers, and until now, it was assumed that the linkers do not have any other purpose than stringing the domains together. To test this further, Harmon et al. used a combination of computer simulations and physics-based theory. In these simulations, the domains were kept the same, but",380,128,0.3368
dialogsum,"#Person1#: Doris, I'm glad you're home. I'm terrified. I don't know what to do! #Person2#: What is it? What happened? #Person1#: I think someone is stalking me. #Person2#: No, it can't be. Really? Who? #Person1#: I don't know. I saw him the first time Tuesday. He was at the cafe. I noticed he was looking at me a lot. Not just the usual looking, but staring. He just kept staring at me. He didn't stop. #Person2#: What did you do? #Person1#: I didn't do anything. Finally, he left. But then I saw him again today. Outside the shoe store. Near the cafe. I went into a CD store and pretended I was looking at CD's. But then he came in too. #Person2#: Did he leave when you left? #Person1#: Yes. Then I noticed he was on the sidewalk behind me. He was following me. #Person2#: What did you do?",#Person1# tells Doris that someone is stalking #Person1# and #Person1# has seen the stalker twice. #Person1# is terrified.,149,18,0.1208
dialogsum,"#Person1#: Hey, Louise, where can I get some lunch around here? #Person2#: There are several places. What would you like to eat? #Person1#: I'd really like a cheeseburger and some French fries. #Person2#: Well, there's a coffee shop on the next corner. It serves good food. #Person1#: OK. I'll try it. Can I get you something? #Person2#: No, I think I'll come with you. I'm longing for a nice salad. #Person1#: Do you often have lunch at this coffee shop? #Person2#: No, I usually bring my lunch from home and eat at my desk.",#Person1# wants to get some lunch. Louise recommends a coffee shop and they will go there together.,94,17,0.1809
dialogsum,"#Person1#: Even if our company didn't have a dress code, I still think people would wear formal clothing to work. #Person2#: I wouldn't be so sure... People want to wear what they feel most comfortable in. #Person1#: Maybe that's true for some positions, but I think the marketing and sales staff would definitely not agree. They dress for success! You can't go out on a sales call if you are dressed in jeans. It's just not respectful to you client. #Person2#: I think what you wear is so overrated. I would rather have a down-to-earth, honest and solid sales person than a painted, patent leather, designer suite salesman. #Person1#: It's not as simple as that. People judge you by your appearance, whether you like it or not. So dressing professional is being professional. The image that you portray to others is so important in business. It's your image and how others perceive you that makes the difference between landing or losing a sale. #Person2#: Maybe you're right, but I'll take my sneakers and jeans any day!","#Person1# thinks the marketing and sales staff should wear formal clothing to work because dressing professionally is important for business, while #Person2# would prefer a down-to-earth salesman and wear comfortable clothing to work.",176,33,0.1875
dialogsum,"#Person1#: A lovely day, isn't it? #Person2#: It is. #Person1#: It seems it will be fine all day. #Person2#: I think it will be a dry day. There's hardly a cloud in the sky. #Person1#: We'll have a heat wave in the afternoon. I'm afraid. #Person2#: It's very hot today. No wind at all. #Person1#: You're fight. There's hardly a breath of air. #Person2#: By the way, did you watch the weather forecast on the television? #Person1#: Yes, it is said a high pressure area would remain to the southwest of England. There would be a little rain or showers here or there, but bright weather the rest of the day.",#Person1# and #Person2# think it's a hot lovely day. #Person1# watched the weather forecast and tells #Person2# about the weather.,111,20,0.1802
dialogsum,"#Person1#: Excuse me. But are you Mrs. Smith from America? #Person2#: That's it. I am Maria Smith. You must be Zhang Lin from Tianjin Sports Facility Co. Ltd. #Person1#: Yes. Nice to meet you, Mrs. Smith. #Person2#: Nice to meet you too, Mr. Zhang.",Mrs. Smith and Zhang Lin meet for the first time and greet each other.,44,14,0.3182
pubmed-summarization,"exaggerated innate immune / inflammatory responses in the brain are now thought to be a common core in the etiology of numerous psychiatric disorders such as depression , ptsd and bipolar disorder ( jones and thomsen , 2013 ) . seemingly unrelated to neuroinflammation , the experience of life stressors is a predisposing factor in the development of psychiatric disorders ( kessler , 1997 ) . however , the clinical literature contains numerous instances in which stress predisposes individuals to inflammatory disorders such as cardiovascular disease ( albus , 2010 ) , which have a high comorbidity with psychiatric conditions that include depression ( sansone and sansone , 2008 ) . indeed , recent evidence from several laboratories , including our own , suggests that stressors sensitize or prime the neuroinflammatory response to subsequent pro - inflammatory challenges , thereby providing a mechanism that can link the impact of stressors and a pivotal role for neuroinflammatory processes in the development of psychiatric disorders . the central notion explored here is that exposure to stressors can induce a vulnerable phenotype characterized , in part , by a sensitized neuroimmune microenvironment . thus , prior stress can lead to a potentiated neuroinflammatory cascade upon exposure to pro - inflammatory challenges that include bacterial or viral infection and sterile injury . this exaggerated neuroinflammatory response can then manifest as changes in cognitive ( e.g. memory ) , affective ( e.g. mood ) , sensory ( e.g. pain ) and vegetative ( e.g. sleep and eating ) endophenotypes , typically observed in a spectrum of psychiatric disorders . several neuroimmune mechanisms , by which stress sensitizes / primes the neuroinflammatory response to pro - inflammatory challenges , have been characterized in recent years . first , a brief overview of neuroinflammatory processes will be provided as a basis for exploring mechanisms of neuroinflammatory priming . neuroinflammatory processes are characterized , in large part , by the activation of cns innate immune effector cells including microglia , which secrete an array of inflammatory mediators including pro - inflammatory cytokines , chemokines , prostaglandins and reactive oxygen / nitrogen species ( ransohoff and perry , 2009 ) . when elaborated under a variety of neuropathological conditions , including neurodegeneration , brain trauma , ischemia and seizure","stress and glucocorticoids ( gcs ) have universally been considered to be anti - inflammatory , however in recent years , stress and gcs have been found to exert permissive effects ( immunological priming ) on neuroinflammatory processes . this phenomenon of priming is characterized by prior stress or gc exposure potentiating the neuroinflammatory response to a subsequent immune challenge . a considerable body of evidence is discussed here that supports this permissive effect of stress and gcs.in light of this evidence , a mechanism of neuroinflammatory priming is proposed involving a signal cascade in the brain involving danger - associated molecular patterns ( hmgb-1 ) and inflammasomes ( nlrp3 ) , which results in an exaggerated or amplified neuroinflammatory response and subsequently , the amplification of the",380,128,0.3368
dialogsum,"#Person1#: Put all baggage on the conveyor belt. Walk through the detector gate one at a time, please. Excuse me, ma'ma. Could you walk back through the doorway again, please? #Person2#: What for? #Person1#: Airport security. Could you empty your pockets over here, please? #Person2#: Really? I'm in a hurry. All right. #Person1#: Ah, a set of keys. #Person2#: I'm embarrassed! I forgot completely about them. I'm terribly sorry. #Person1#: That's all right. Enjoy your flight. #Person2#: Thank you.",#Person1# asks #Person2# to walk through the doorway again for airport security and #Person2# embarrassedly finds a set of keys in her pockets.,79,23,0.2911
scientific_lay_summarisation-elife-norm,"(RNAPII) in both yeast and mammalian cells (Abernathy et al. , 2015; Braun and Young, 2014; Haimovich et al. , 2013; Sun et al. , 2013). In yeast, a buffering system exists in which Xrn1 plays a major role in connecting mRNA synthesis and decay, presumably allowing cells to maintain an appropriate overall mRNA abundance. Mammalian cells also have a mechanism to sense mRNA levels, though the pathway appears to operate differently than in yeast. Here, accelerated cytoplasmic mRNA degradation does not lead to a compensatory increase in mRNA synthesis, as might be predicted by the homeostatic model, but instead decreases cellular RNAPII promoter recruitment, thereby amplifying the restrictive gene expression environment (Abernathy et al. , 2015). Significant transcriptional repression as measured by nascent mRNA production was reported to occur at approximately 9% of host genes, although validation experiments suggested this number is likely to be an underestimate (Abernathy et al. , 2015). The mRNA decay-transcription feedback pathway is activated in mammalian cells infected with gammaherpesviruses like Kaposi’s sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), as well as upon expression of virally encoded mRNA endonucleases in uninfected cells. Herpesviral endonucleases, including the muSOX protein of MHV68, cleave mRNA but do not impact the abundance of noncoding RNAs transcribed by RNA polymerase I (RNAPI) or III (RNAPIII) (Covarrubias et al. , 2011). Correspondingly, muSOX-induced mRNA decay elicits a significant decrease in RNA polymerase II (RNAPII) recruitment to cellular promoters (Abernathy et al. , 2015). Notably, depletion of Xrn1 from muSOX-expressing cells prevents the ensuing RNAPII transcriptional repression. This suggests that the initial mRNA cleavage and translational inactivation are insufficient to restrict RNAPII recruitment, and that subsequent exonucleolytic degradation of the cleaved mRNA fragments is a critical signaling step. Little is currently known about this pathway linking cytoplasmic mRNA decay to RNAPII activity in mammalian cells, including the nature of the signal that is transmitted between the two cellular compartments. An attractive hypothesis is that one or more RNA binding proteins (RBPs) differentially traffics between the cytoplasm and the nucleus when basal rates of mRNA decay are perturbed, thereby conveying global mRNA abundance information. Recent analyses indicate that mammalian cells contain hundreds of RBPs that bind polyadenylated mature mRNAs, and proteins within this group have been shown to regulate all stages","The nucleus of a cell harbors DNA, which contains all information needed to build an organism. The instructions are stored as a genetic code that serves as a blueprint for making proteins – molecules that are important for almost every process in the body – and to assemble cells. But first, the code on the DNA needs to be translated with the help of a ‘middle man’, known as messenger RNA. These molecules carry information to other parts of the cell, wherever it is needed. Messenger RNA is produced in the nucleus of a cell, and then exported into the material within a cell, called the cytoplasm, as a template to produce proteins. Once this process has finished, the template is destroyed. The rate at which the messenger",380,128,0.3368
pubmed-summarization,". application of mr reporter gene imaging to the heart could transform cardiac regeneration research by enabling direct correlation of injected cell survival with important therapeutic outcomes such as restoration of contractile function and perfusion . paradoxically , studies of cell based cardiac regeneration therapy now number in the thousands , yet studies utilizing mr reporter gene imaging of cell survival following intramyocardial transplantation number in the single digits ( . research into the field of cardiac regeneration with cell therapy has undergone explosive growth since 1990 as evidenced by the large number of publications ( blue columns ) . an emerging consensus view considers in vivo imaging of cell fate decisions as a key tool for improving future therapeutic strategies . mri cell tracking following cell labeling with exogenous contrast agents ( red columns ) has emerged over the prior decade as a potential method by which to monitor the survival and viability of injected cells . more recently , the use of mri reporter genes ( green columns ) has been explored for in vivo imaging of cell survival , proliferation , and differentiation . in the context of mr reporter gene cell tracking in the heart , only four studies have to date been published on imaging the survival of reporter gene expressing cells following intramyocardial injection suever plot of relevant publications . research into the field of cardiac regeneration with cell therapy has undergone explosive growth since 1990 as evidenced by the large number of publications ( blue columns ) . an emerging consensus view considers in vivo imaging of cell fate decisions as a key tool for improving future therapeutic strategies . mri cell tracking following cell labeling with exogenous contrast agents ( red columns ) has emerged over the prior decade as a potential method by which to monitor the survival and viability of injected cells . more recently , the use of mri reporter genes ( green columns ) has been explored for in vivo imaging of cell survival , proliferation , and differentiation . in the context of mr reporter gene cell tracking in the heart , only four studies have to date been published on imaging the survival of reporter gene expressing cells following intramyocardial injection in this review we seek","research into cell therapy based cardiac repair and regeneration has experienced explosive growth over the last decade , however further progress is hindered by an inability to serially and non - invasively image cell survival and fate decisions following implantation . recent advances in magnetic resonance imaging ( mri ) reporter gene techniques have enabled in vivo imaging of cell survival , proliferation , migration , and differentiation , however this has mostly been performed in stationary tissues . a small series of recent studies has examined the possibility of using mri reporter genes to track the survival of cells injected into the heart following myocardial infarction . in this review , we seek to frame the emerging field of mri reporter gene based cardiac cell tracking within",380,128,0.3368
dialogsum,"#Person1#: Sara, I've been looking forward to our yearly camp out for three weeks. [Me too] It's going to be a wonderful day for hiking tomorrow. The great outdoors. Camping under the stars. This is the life. #Person2#: Yeah, but Paul, I'm a little bit worried about the weather though. The weatherman said it was going to rain later tonight. #Person1#: Ah, nonsense. Nothing can spoil our adventure. Those weather reports are never right. #Person2#: And it said there was a chance of high winds. #Person1#: Ah. Don't worry. #Person2#: [thunder] Paul. Paul. Did you remember to bring our raincoats just in case, like I told you? [light rain] #Person1#: Uh ... no. I left them on the front porch. [heavy rain] #Person2#: What are we going to do now? #Person1#: We'll have to sleep in the car! Hurry get in! [door shut] #Person2#: So, Paul, what are we going to do now? #Person1#: How about playing a card game? #Person2#: Uhh. I left them next to the picnic table. [Hmmm] Hey, you don't want me to go out in this rain and get them, do you? #Person1#: No. That's okay. So what now? #Person2#: Well, we could head down the mountain and stay at that hotel we passed on the way up, or go home. #Person1#: Hmm, why don't we just make the best of it here and hope the weather clears. #Person2#: That's a good idea.","Paul's excited about the hiking tomorrow but Sara's worried about the weather. When it's time for hiking, it begins to rain, but they left the raincoats at home. They finally decide to stay in the car and wait for the weather to clear.",238,43,0.1807
scientific_lay_summarisation-elife-norm,"pyloric and gastric mill rhythms differs because they target distinct cells within the respective CPGs (Blitz et al. , 1999; Wood et al. , 2000). Proctolin principally excites the pyloric circuit and can activate it from quiescence, while CabTRP is required for the gastric mill rhythm and acts on a key neuron in its CPG in addition to neurons of the pyloric circuit. Activation of MCN1 by mechanosensory inputs from the stomach, induces a gastric mill rhythm via the action of CabTRP and alters the pyloric rhythm in response to the actions of both peptides (Beenhakker and Nusbaum, 2004; Blitz et al. , 2004). Sensory information, conveyed by two neuromodulators, thus produces coordinated changes in two functionally related circuits. The significance and adaptive value of many neuromodulatory effects characterized in the STG remains unknown, and, in general, the sheer abundance of circuit neuromodulation revealed by studies of this and other small systems challenges the simple idea of ‘chemical coding’ of behavior by neuromodulators. This complexity is also underscored by analyses of neuromodulator receptor-distributions, first undertaken by ligand autoradiography in the 1980s. On the one hand, these studies supplied strong evidence that neuromodulators could act at many sites and over long distances, but they also highlighted the difficulty of establishing which sites were relevant for performance of specific behaviors without knowledge of where and under what circumstances each neuromodulator was released (Herkenham, 1987). For neuromodulators already implicated in specific behaviors, however, the receptor distributions sometimes spectacularly confirmed the idea that neuromodulators target ethologically significant circuits (Insel and Young, 2000). For example, cross-species differences in striatal expression of vasopressin receptors in two closely related vole species were shown to correlate with, and in fact cause, monogamous and polygamous predispositions in mating (Hammock and Young, 2005; Young et al. , 1997). Based on these and other examples, variations in neuromodulator receptor expression during speciation have been proposed to be a major driver of behavioral evolution (Katz and Lillvis, 2014). The recent development of genetic techniques for targeting and functionally manipulating neurons in genetic model animals has facilitated the functional characterization of neuronal populations on which neuromodulators act (Spangler and Bruchas, 2017). This work again provides examples of neuromodulators that coordinate activity in broadly distributed circuits. The evidence is particularly compelling for conserved neuromodulators,","Why do animals behave the way they do? Behavior occurs in response to signals from the environment, such as those indicating food or danger, or signals from the body, such as those indicating hunger or thirst. The nervous system detects these signals and triggers an appropriate response, such as seeking food or fleeing a threat. But because much of the nervous system takes part in generating these responses, it can make it difficult to understand how even simple behaviors come about. One behavior that has been studied extensively is molting in insects. Molting enables insects to grow and develop, and involves casting off the outer skeleton of the previous developmental stage. To do this, the insect performs a series of repetitive movements, known as an ecdysis sequence. In",380,128,0.3368
pubmed-summarization,"of gastrointestinal and respiratory tract can occur due to aspiration of infected amniotic fluid that culminates in candidial septicemia manifesting as bronchopneumonia , meningitis , arthritis , endocarditis with microabcess in liver , brain , kidneys , or spleen . features like respiratory distress , leucocytosis with left shift , persistent hyperglycemia , glycosuria , positive cultures from blood , urine , cerebrospinal fluid ( csf ) , and burn - like skin lesions suggest systemic involvement . neonatal candidiasis typically manifests after 6 days of life and differs clinically from cc [ table 1 ] . cc should be differentiated from various other diseases presenting with pustules in the newborn [ table 2 ] . comparision of congenital and neonatal candidiasis causes of neonatal pustular disorders diagnosis was established by koh mount of skin lesions showing budding yeasts and pseudohyphae and culture revealing candidial growth . blood , urine , and csf cultures should be obtained to rule out systemic involvement if there is clinical suspicion . amphotercin b is the first line agent given in doses of 0.5 - 1 mg / kg / day and liposomal amphotericin b is less toxic and preferred if there is preexisting renal insufficiency . fluconazole at 6 - 12 mg / kg / day dose is effective alternative if organism is susceptible . topical therapy is given till the resolution of skin lesions and systemic therapy continued for minimum of 21 - 28 days if systemic involvement is present . cc is very rare and needs to be differentiated from various diseases presenting with generalized maculopapular or pustular lesions at birth in order to avoid complications .","congenital candidiasis ( cc ) is a rare disease with less than 100 cases being reported in the literature . it presents within six days of life with manifestations ranging from localized skin disease to systemic involvement in the form of respiratory distress , sepsis , and death . we report a neonate who presented with diffuse pustular eruption on erythematous background involving face , trunk , and palms within 24 h after birth . candida albicans was identified in 10% potassium hydroxide ( koh ) smear and culture from the pustules . intravenous fluconazole and topical ketoconazole were given and the condition improved completely in two weeks . cc is rare and needs to be differentiated from other conditions presenting with pustular lesions at birth in order",276,128,0.4638
scientific_lay_summarisation-elife-norm,"RESISTANT 2), two bHLH transcription factors acting as major regulators of BR-induced transcriptional changes, which then become active (Wang et al. , 2002; Yin et al. , 2002). Treatment with the chemicals LiCl and bikinin, which inhibit GSK3-like kinases (De Rybel et al. , 2009; Yan et al. , 2009), resulted in impaired flg22-triggered ROS burst (1A, B), as observed upon genetic or ligand-induced activation of the BR pathway. Furthermore, a triple mutant in BIN2 and the two closest related GSK3-like kinases, BIL1 (BIN2-LIKE 1) and BIL2 (triple GSK3 mutant; Vert and Chory, 2006), shows a similar impairment in response to either flg22 or chitin (1C). Interestingly, in spite of regulating MAPKs involved in stomata development (Kim et al. , 2012; Khan et al. , 2013), neither BR treatment nor loss of function of BIN2 affect flg22-triggered MAPK activation (— 2), contrary to what has been recently suggested (Choudhary et al. , 2012; Zhu et al. , 2013). These results indicate that the BR-PTI crosstalk occurs downstream of BIN2. 10. 7554/eLife. 00983. 003Figure 1. Activation of BZR1 is sufficient to inhibit the PAMP-triggered ROS burst. (A) and (B) Flg22-triggered ROS burst after LiCl (A) or bikinin (B) treatment. Leaf discs were pre-treated with a 10 mM LiCl solution for 5 hr or with a 50 μM bikinin solution for 16 hr. (C) Flg22- or chitin-triggered ROS burst in Col-0 and the triple GSK3 mutant plants. (D) Flg22- or chitin-induced ROS burst in Col-0 and BZR1Δ plants. (E) Elf18-triggered ROS burst in bri1-5 and bri1-5/BZR1Δ plants. In all cases, bars represent SE of n = 28 rosette leaf discs. Asterisks indicate a statistically significant difference compared to the corresponding control (mock treatment [A and B], Col-0 [C and D] or bri1-5 [E]), according to a Student’s t-test (p<0. 05). Leaf discs of four- to five-week-old Arabidopsis plants were used in these assays. Flg22 and elf18 were used at a concentration of 50 nM; chitin was used at a concentration of 1 mg/ml. Total photon counts were integrated between minutes two and 40 after PAMP treatment. All experiments were repeated at least three times with similar results. : http: //dx. . org/10. 7554/eLife. 00983. 00310. 7554/eLife. 00983. 004Figure 1— 1. The BR-mediated suppression of PTI can be triggered independently of a competition","Like all organisms, plants must perform a careful balancing act with their resources. Investing in the growth of new roots or leaves can allow a plant to better exploit its environment—but it must not be at the expense of leaving the plant vulnerable to attack by pests and pathogens. As such, there is an obvious trade-off between allocating resources to growth or defense against disease. This trade-off must be finely balanced, and must also be responsive to different cues in the environment that would favor either growth or defense. The plant’s immune system is able to detect invading microbes, and trigger a defensive response against them. At the surface of plant cells, proteins called pattern recognition receptors are able to recognize specific molecules that are the tell-tale signs",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Mesial temporal lobe epilepsy (mTLE) is the most common focal epilepsy in adults and is often refractory to medication. So far, resection of the epileptogenic focus represents the only curative therapy. It is unknown whether pathological processes preceding epilepsy onset are indicators of later disease severity. Using longitudinal multi-modal MRI, we monitored hippocampal injury and tissue reorganization during epileptogenesis in a mouse mTLE model. The prognostic value of MRI biomarkers was assessed by retrospective correlations with pathological hallmarks Here, we show for the first time that the extent of early hippocampal neurodegeneration and progressive microstructural changes in the dentate gyrus translate to the severity of hippocampal sclerosis and seizure burden in chronic epilepsy. Moreover, we demonstrate that structural MRI biomarkers reflect the extent of sclerosis in human hippocampi. Our findings may allow an early prognosis of disease severity in mTLE before its first clinical manifestations, thus expanding the therapeutic window. Epilepsy is a devastating disease, with a prevalence of about 1%, which makes it one of the most common neurological disorders. Of particular clinical significance is mesial temporal lobe epilepsy (mTLE), in which seizures arise from mesial temporal limbic structures, as it is the most frequent form of epilepsy in adults (40%) and particularly resistant to pharmacological treatment (Engel, 2001). Hippocampal sclerosis (HS), characterized by the loss of CA1 and CA3 pyramidal cells, gliosis and associated with granule cell dispersion (GCD), represents the most common pathological hallmark of intractable mTLE (Thom, 2014; Walker, 2015). HS can emerge secondary to an initial precipitating insult, e. g. status epilepticus (SE), head trauma, febrile seizures or limbic encephalitis (Engel, 2001). To date, resection of the lesioned, epileptogenic tissue is the only therapeutic intervention. However, not all patients remain seizure-free (Ryvlin and Kahane, 2005). In this context, non-invasive MRI techniques have become an important method to identify sclerotic tissue as a biomarker in both human patients (Gomes and Shinnar, 2011; Urbach et al. , 2014) and rodent TLE models (Nehlig, 2011; Shultz et al. , 2014; Sierra et al. , 2015a). Up to now, this has been, however, restricted to the chronic stage of epilepsy when seizures have already emerged. A promising notion is to start medical treatment during early epileptogenesis before the first seizure arises. This stands in contrast to current anti-epileptic treatments","Roughly one percent of people in the world suffer from epilepsy, a disorder in which individuals experience seizures due to abnormal electrical activity in the brain. Seizures can vary from brief episodes of amnesia or déjà-vu to convulsions and loss of consciousness. In adults, the most common form of epilepsy is known as temporal lobe epilepsy. As the name suggests, this type of epilepsy originates in a region of the brain called the temporal lobe, usually within a structure called the hippocampus. Many patients who develop temporal lobe epilepsy will have experienced a head injury or infection earlier in life that damaged their hippocampus. However, damage to the hippocampus does not always lead to epilepsy. Moreover, many years may pass between the damage and the onset of regular",380,128,0.3368
dialogsum,"#Person1#: how was your job at the state-owned enterprise? #Person2#: oh, I no longer work there. I'm working with a multi-national corporation. #Person1#: you changed jobs again? Why do you move so frequently? #Person2#: I want to try different things before I find the one I really like. #Person1#: why don't you stick with one job for a bit longer? #Person2#: I could handle everything pretty well in the old position, so I decided to move around and learn something new. #Person1#: how's your current job going? #Person2#: I'm pretty satisfied with it. I can broaden my experience, learn lots of new things, and have more development opportunities. #Person1#: sounds good, but I still think perhaps you should first have a clear career path to follow and then decide whether to change your job or not. #Person2#: yes, you're right. When I graduated, I didn't know what I really wanted to do or what I could do. Now things are growing much clearer. #Person1#: do you have a definite career path yet? #Person2#: I'm not sure. I just like the job I'm doing now. #Person3#:",#Person2# changes #Person2#'s job again because #Person2# wants to try different things before #Person2# finds the one #Person2# really likes. #Person1# suggests #Person2# should have a clear career path.,185,29,0.1568
scientific_lay_summarisation-elife-norm,"During eukaryotic evolution, genome size has increased disproportionately to nuclear volume, necessitating greater degrees of chromatin compaction in higher eukaryotes, which have evolved several mechanisms for genome compaction. However, it is unknown whether histones themselves have evolved to regulate chromatin compaction. Analysis of histone sequences from 160 eukaryotes revealed that the H2A N-terminus has systematically acquired arginines as genomes expanded. Insertion of arginines into their evolutionarily conserved position in H2A of a small-genome organism increased linear compaction by as much as 40%, while their absence markedly diminished compaction in cells with large genomes. This effect was recapitulated in vitro with nucleosomal arrays using unmodified histones, indicating that the H2A N-terminus directly modulates the chromatin fiber likely through intra- and inter-nucleosomal arginine–DNA contacts to enable tighter nucleosomal packing. Our findings reveal a novel evolutionary mechanism for regulation of chromatin compaction and may explain the frequent mutations of the H2A N-terminus in cancer. Genome size, defined as the haploid DNA content of a cell, has increased as eukaryotes evolved from single-cell species to more complex, multicellular organisms. Within the same evolutionary timeframe, nuclear volume has also increased but at a slower rate than genome size expansion (Maul and Deaven, 1977; Olmo, 1982). While the ratio of nuclear to cell size has remained essentially constant in eukaryotes (Cavalier-Smith, 2005), the disproportional increase in genome size relative to the nuclear volume has required organisms with larger genomes to compact their chromatin to greater extents than organisms with small sized genomes. Indeed there is a positive correlation between genome size and native chromatin compaction as measured by dye incorporation into chromatin (Vinogradov, 2005). In most eukaryotes, the genome is organized into chromatin by the repeating nucleosomal structure (Luger et al. , 1997). The nucleosomes stack and fold into higher order structures, serving to systematically compact the genome (Lieberman-Aiden et al. , 2009; Duan et al. , 2010) and to regulate molecular processes that are based on DNA (Celeste et al. , 2002; Vogelauer et al. , 2002; Fischle et al. , 2005; Kouzarides, 2007; Fussner et al. , 2011). The surface of the histone octamer has 14 DNA interaction sites. Each interaction is mediated by an arginine residue that intercalates into the minor groove of the DNA to stabilize the nucleosomal structure (Luger et al.","There are up to three meters of DNA in a human cell. To fit this length into the cell' s nucleus in an organized manner, DNA is wrapped around proteins called histones and then tightly packaged to form a structure called chromatin. The interaction between the histones and the DNA is helped by certain amino acids on the surface of the histones fitting snugly into the DNA molecule. Plants and animals have genomes that are significantly larger than those of single-celled organisms. However, although genome size has increased gradually during the evolution of complex organisms, the size of the nucleus has not undergone a similar expansion. Large genomes are therefore packaged more tightly than small genomes. However, we do not fully understand how different species evolved the ability",380,128,0.3368
dialogsum,#Person1#: He has lots of hobbies. #Person2#: And he's always busy with his pictures and roses. #Person1#: He's won a dozen prizes for his pictures and roses. #Person2#: But as for his business in the city. . . #Person1#: He lets his cousins look after his business. #Person2#: He sounds more like an artist than a businessman.,#Person1# and #Person2# are talking about a businessman's hobbies.,57,9,0.1579
pubmed-summarization,"laboratories ( molins de rei - barcelona , spain ) , respectively . the labeled and unlabeled preparations of plasminogen used in this study had the characteristics of previously described preparations from our laboratory . fluorescein isothiocyanate ( fitc ) conjugated goat anti - mouse monoclonal antibodies were from sera - lab , ltd . neutrophils , monocytes , and lymphocytes were isolated from blood collected into heparin ( 5 u / ml ) as described . other cell lines were from the american type tissue culture collection ( atcc ) and cultured in rpmi-1640 ( bio - whitakker / ma bioproducts ) containing 1 mm na pyruvate and 510% fetal bovine serum . blast cells from peripheral blood were analyzed from a patient with acute nonlymphoblastic leukemia ( anll ) , categorized according to the fab classification . ligand binding analyses were performed as previously described by separating bound from free ligand by centrifugation over 20% sucrose . molecules of ligand bound per cell were calculated based on the specific activities of the radiolabeled ligands . plasminogen activation studies were carried out in microtitre plates in reaction volumes of 100 l as previously described . briefly , 20 l of plasminogen activators ( tpa or upa ) ( final concentration 70 and 37 pmol / l , resp . ) were mixed with 40 l of cells ( final concentration 1.5 10 cells / ml ) and 40 l of substrate mix containing glu - plasminogen ( final concentration 100 nmol / l ) and chromogenic substrate s-2251 ( val - leu - lys - p - nitroanilide ; chromogenix ) ( final concentration 0.15 mmol / l ) . reactions were performed in assay buffer consisting of tris - hcl , ph 7.4 , at 37c , and a final ionic strength of 0.12 , containing 1 mg / ml human serum albumin . absorbance was monitored at 405 nm , using a thermomax thermostatted plate reader ( molecular devices corporation , stanford , ca ) . cells were washed with pbs containing 1% bsa and 0.1% sodium azide ( pba ) , incubated with pba containing 10% heat - inactivated normal rabbit serum , washed again , and incubated with mab49 ( 130 nm ) or isotype","the nb4 promyelocytic cell line exhibits many of the characteristics of acute promyelocytic leukemia blast cells , including the translocation ( 15 : 17 ) that fuses the pml gene on chromosome 15 to the rar gene on chromosome 17 . these cells have a very high fibrinolytic capacity . in addition to a high secretion of urokinase , nb4 cells exhibit a 10-fold higher plasminogen binding capacity compared with other leukemic cell lines . when tissue - type plasminogen activator was added to acid - treated cells , plasmin generation was 2026-fold higher than that generated by u937 cells or peripheral blood neutrophils , respectively . we found that plasminogen bound to these cells can be detected by fluorescence - activated cell sorting using an antiplasminogen monoclonal",380,128,0.3368
pubmed-summarization,"rectal varices are not an uncommon manifestation in cirrhosis with portal hypertension . however , serious bleeding from rectal varices is uncommon . because of its rarity , several authors have reported the utility of transjugular intrahepatic portosystemic shunt ( tips ) placement to control such bleeding when local therapy , such as endoscopic sclerotherapy or banding , fails . however , we experienced a case of massive bleeding from large rectal varices that could not be controlled by tips placement , despite normalization of the portosystemic pressure gradient . furthermore , we observed rapid decompensation of the cirrhosis that led to severe encephalopathy and death after the tips placement . we report this case to highlight and discuss potential pitfalls of tips placement when using this technique to treat rectal variceal bleeding . a 59-year - old man with a history of alcoholic cirrhosis was hospitalized at an outside facility for massive hematochezia and fainting . he underwent upper endoscopy and tagged red blood cell scan , both of which were negative for active bleeding . a computed tomography of the abdomen was performed and did not reveal the source of the gastrointestinal bleeding ; a nodular liver with splenomegaly consistent with liver cirrhosis was seen , and a markedly dilated inferior mesenteric vein was also noted . during his 5-day hospitalization , he had approximately 1015 bloody bowel movements and received a total of 6 units of packed red blood cells and 2 units of fresh frozen plasma . the patient was then transferred to our institution for further management of his persistent hematochezia . his admission laboratory tests showed a hemoglobin level of 8.3 g / dl , a serum ammonia level of 45 g / dl , a total bilirubin level of 2.8 mg / dl and a model for end - stage liver disease ( meld ) score of 18 . however , he had another episode of massive hematochezia on the following day , with a decrease in hemoglobin level to 5.0 g / dl . therefore , the decision was made to proceed with emergent tips placement . a tips was successfully created with a 10 90 mm viatorr stent - graft ( gore & associates , flagstaff , ariz . this resulted","in patients with portal hypertension , bleeding from rectal varices is rare . however , it can be life - threatening . we report a case of massive bleeding from large rectal varices in a 59-year - old man with alcoholic cirrhosis . emergent transjugular intrahepatic portosystemic shunt ( tips ) placement was performed following failed local endoscopic therapy . despite normalization of the portosystemic pressure gradient , the patient had another episode of massive bleeding on the following day . embolization of the rectal varices via tips successfully stopped the bleeding . after the procedure , rapid decompensation of the cirrhosis led to severe encephalopathy , and death was observed . although tipss have been reported to be useful in controlling bleeding from rectal varices , our",380,128,0.3368
scientific_lay_summarisation-elife-norm,"of cytonemes is dependent on the glypicans present in the membranes of neighbouring cells. Thus, cytonemes cannot properly extend across Dally or Dlp mutant cells. In addition, cytonemes can cross smo (smoothened) and ptc mutant clones, which cannot internalize Hh, providing a bridging mechanism and allowing Hh delivery to adjacent wild type cells. Finally, we describe discrete cell-cell contact structures between Hh-sending and Hh-receiving cytonemes, where the morphogen may be transferred from one cytoneme to the other for its reception. Hh-producing cells in the P compartment of the wing imaginal disc extend cytonemes that transport Hh to the A compartment cells and that are essential for the restricted distribution of Hh during Drosophila epithelial development (Callejo et al. , 2011; Bilioni et al. , 2013; Bischoff et al. , 2013). In addition, the Hh-receiving cells of the anterior compartment also extend cytonemes towards the Hh-secreting cells of the P compartment. Here we have characterized the cytonemes from the signal-receiving cells and investigated their role in Hh morphogen reception. In previous studies on Hh signalling filopodia in the abdominal histoblasts we showed that the P compartment generated highly dynamic protrusions that reached anteriorly the Hh-receiving cells (Bischoff et al. , 2013). The Hh-receiving cells also produce highly dynamic protrusions oriented towards the Hh-producing cells, easily visualized when expressing the actin-binding domain of moesin (GMA) fused to GFP (1A, Video 1A). These GMA-labelled filopodia are less dynamic when they co-express Ihog (1B, Video 1B), as was previously described for the Hh-producing histoblasts (Bischoff et al. , 2013). Here we show that both Hh-presenting and Hh-receiving histoblast cells emit protrusions with similar dynamics (Video 1 and Video 2). In a more detailed analysis of filopodia dynamics, we have been able to distinguish two different dynamic behaviours: one of filopodia that elongate and immediately retract, which we have classified as ‘triangle dynamics’ and another one with a ‘stationary’ interphase between the elongation and retraction phases, which we have classified as ‘trapezoid dynamics’ (— 1; see Materials and methods). Both Hh-producing and Hh-receiving cell filopodia have similar values of average maximum extent, lifetime, elongation (Ve) and retraction (Vr) velocities (1C–E, — 2). 10. 7554/eLife. 24045. 003Figure 1. Cytonemes emanating from the A compartment cells. (A, B) Dynamic behaviour of cytonemes emanating from the A compartment","When an embryo develops, it is critical that tissues and organs form properly and at the right time. For this, cells need to be able to communicate over long distances by using signalling molecules called morphogens. Morphogens disperse via extensions that protrude from the surface of a ‘source’ cell. Previous research has shown that these extensions called cytonemes can transport the morphogens to ‘receiver’ cells, and depending on the distance from the source, build a concentration gradient that will either be higher or lower. These gradients then help unspecialized cells to develop into different specialized ones. One of the key morphogens during the development is the Hedgehog protein. Researchers have previously shown that vesicles along cytonemes of cells that produce Hedgehog transport the morphogen to the receiver cells.",380,128,0.3368
dialogsum,"#Person1#: Wow! What's the hold up? #Person2#: It's probably just people trying to get an early start out of the city for the weekend. Nobody sticks around in the summer. #Person1#: Really? Then, I guess I won't have a hard time finding a room or getting a cab? #Person2#: Actually, you might because there's a big convention in town this weekend. #Person1#: I'm not too worried about it. I always seem to find something.",#Person2# tells #Person1# it's probably people getting out of the city that causes the holdup. #Person2# thinks it might be hard to find rooms or get cabs because of the big convention.,74,32,0.4324
dialogsum,"#Person1#: What is wrong with Peter? He sure looks unhappy. #Person2#: His girlfriend dumped him, and he is tearing his heart out over her. #Person1#: How foolish he is. The girl is inviting. She often makes a pass at boys. #Person2#: Love is blind, you know.",#Person1# and #Person2# talk about Peter who is unhappy.,46,9,0.1957
pubmed-summarization,"some estimates may be obtained when a fossil record is available that permits information on relatively specific ecological changes . for example , it has been estimated that reductions in selective behavioral responsivity to rattlesnakes and in resistance to the venom of these snakes by california ground squirrels both decline over periods measured in the tens of thousands of years after rattlesnakes have disappeared from the squirrels habitats ( coss et al . , 1993 ) . as this example suggests , when ecological changes make some of the existing characteristics of species less adaptive than previously , the replacement of these by more adaptive characteristics can be a lengthy and variable process ; moreover , maladaptive as well as adaptive aspects of the emerging behaviors may be relevant to the patterns that ultimately emerge . with complex behavior patterns such as those involved in social relationships an even longer time - frame might be needed than for venom resistance and other purely physiological adaptations . however , following long - term exposure to diverse situations , even closely related species would be expected to show behavioral differences based on what is most adaptive in their particular habitats : rubenstein ( 2009 , p. 243 ) gives the example of plains zebras ( equus burchelli ) , living in an environment in which close proximity of food and water allow female zebras to consistently form groups , in turn permitting males to vie for harems in this home range . in contrast , grevy 's zebra ( equus grevyi ) inhabit locales where food and water are widely dispersed and scarcer , such that females forage alone and must travel between feeding and watering areas . in this species males form territories along the traveling routes , gaining breeding access to females that pass through or linger within the territory . in both the harem and territorial social systems , zebra males attempt to control access to females in breeding condition , but the time - frame and the location of these efforts vary with the conditions under which these animals have evolved . some of these considerations may be relevant to a question that was raised at the very beginning of the scientific study of the evolution of behavior","the function of manes in lions has been a topic of scientific interest since darwin ( 1871 ) suggested that it provides protection in intraspecific fights . recent experimental studies on wild lions have emphasized the role of female selection , but analyses of specific attack behaviors and targets , and the social consequences of manelessness for lions living in very hot climates suggest that male manes may indeed mitigate the outcomes of intraspecific male attack and thus serve a permissive function for multi - male + female groups , facilitating protection of prides against take - overs and infanticide by nomadic males . humans also have unusual structural protections for the head , face and neck , areas that are especially accessible during intraspecies attack , and",380,128,0.3368
dialogsum,#Person1#: It's too hot to read. #Person2#: We'd better go out for a walk. #Person1#: Which season do you like best? #Person2#: Spring. #Person1#: How about summer? #Person2#: I dislike it most. #Person1#: Why? #Person2#: Because the hottest season is summer in a year. #Person1#: But sometimes summer is more charming than the other seasons.,"#Person2# and #Person1# will go for a walk, #Person2# hates summer while #Person1# disagrees.",55,14,0.2545
dialogsum,"#Person1#: Are you ready to order? May I suggest a veal? #Person2#: No, I'll have the fish please. #Person1#: The chicken is also nice. #Person2#: No, I want the fish. #Person1#: Our special tonight is lobster. #Person2#: Thank you, but I prefer the fish. #Person1#: Perhaps you'd enjoy the lamb. #Person2#: No, I like the fish. #Person1#: What ever you say?",#Person1# gives several recommendations but #Person2# insists on ordering the fish.,61,11,0.1803
scientific_lay_summarisation-elife-norm,"Most behaviors such as making tea are not stereotypical but have an obvious structure. However, analytical methods to objectively extract structure from non-stereotyped behaviors are immature. In this study, we analyze the locomotion of fruit flies and show that this non-stereotyped behavior is well-described by a Hierarchical Hidden Markov Model (HHMM). HHMM shows that a fly' s locomotion can be decomposed into a few locomotor features, and odors modulate locomotion by altering the time a fly spends performing different locomotor features. Importantly, although all flies in our dataset use the same set of locomotor features, individual flies vary considerably in how often they employ a given locomotor feature, and how this usage is modulated by odor. This variation is so large that the behavior of individual flies is best understood as being grouped into at least three to five distinct clusters, rather than variations around an average fly. There are many approaches to the study of neural underpinnings of behavior: One large body of work is rooted in the psychophysical literature where an animal is forced to choose between a few discrete behaviors (Green and Swets, 1974). This approach allows stimulus control and rigorous analysis of behavior based on an established framework (Gold and Shadlen, 2000), but sacrifices a full analysis of behavioral dynamics, leaving critical issues unexplored. Other studies have focused on behaviors that are reflexive (albeit with some flexibility) such as saccades (Laurutis and Robinson, 1986) and collision avoidance in insects (Tammero and Dickinson, 2002). Another large body of work has focused on the control processes involved in goal-directed behaviors such as reaching movements and has revealed many fundamental principles of motor control. Yet, another popular behavioral motif that has received much attention is behaviors that require meticulous sequencing (Graybiel, 2008). Finally, much work has been done to elucidate the workings of central pattern generators that underlie the rhythmic motor activity during walking and running (Grillner, 1979). Although many of these relatively stereotypical behavioral motifs are at play during most behaviors, they are not helpful in describing the structure underlying most everyday activities such as making a cup of coffee or a peanut-butter sandwich or walking to a car which consist of a sequence of actions, but neither the sequence nor each sub-action is stereotyped. These activities and","Many behaviors that we perform everyday, including something as familiar as making a peanut-butter sandwich, consist of a sequence of recognizable acts. These acts may include, for example, holding a knife and opening a jar. Yet often neither the sequence nor the individual acts are always performed in the exact same way. For example, there are many ways to hold a knife and there are many ways to open a jar, meaning neither of these actions could be called “stereotyped”. A lack of stereotypy makes it difficult for a computer to automatically recognize the individual acts in a sequence. This same problem would apply to other common behaviors, such as walking around somewhere you have not visited before. While we easily recognize it when we see it, walking",380,128,0.3368
dialogsum,"#Person1#: This section of the store is called Junior. Why is that? #Person2#: It means young girls. That's where you'll find clothes for young girls. #Person1#: But I can't find anything in my size here. #Person2#: You're small, but you're not a child. #Person1#: Well, there's nothing I can do about my height! #Person2#: There's a petite section that you an check out. #Person1#: What's in the petite section? #Person2#: It has clothes in small sizes for small women.",#Person1# can't find anything in her size in the Junior section. #Person2# recommends her to check out in the petite section.,79,21,0.2658
dialogsum,"#Person1#: Hello, Mrs. White, what can I do for you? #Person2#: I don't know what's the matter with me. I'm always feeling tired, I'm usually worn out at the end of the day. #Person1#: I see. Let me take your pulse rate first.",Mrs. White feels tired and #Person1# takes her pulse rate.,43,10,0.2326
dialogsum,"#Person1#: John, it's time to get up. #Person2#: It can't be time to get up yet. #Person1#: It is. Hurry up! You'll be late for school. #Person2#: What's the time? #Person1#: It's nearly half past seven. #Person2#: My watch says ten past. #Person1#: It's slow. Hurry up! The bus goes at twenty to eight. #Person2#: Are you sure half past seven? #Person1#: Positive. I'll put the radio on. #Person2#: ( And here is the seven o'clock news ) It's only seven o'clock. Your watch is fast. #Person1#: No, it isn't. It's stopped. I forgot to wind it up last night. #Person2#: I could have stayed in bed for another half hour.","#Person1# wakes up John, saying he'll be late for school. However, it's actually pretty early because #Person1#'s watch has stopped.",111,20,0.1802
pubmed-summarization,"examination of the variety of physiologically occurring antioxidant systems , that use cysteine as a major component of their antioxidant activity or as part of a redox sensor , clearly demonstrates the sensitivity and evolutionary significance of cysteine as part of a protein 's active center . for example , glutathione ( gsh ) consists of glutamate , glycine , and cysteine and is the major antioxidant found in brain . it is found at millimolar levels and is a major determinant of intracellular redox conditions . further examples of cysteines ' critical role in redox balance can be found in other enzymatic systems including the multiple enzymes involved in the maintenance of peroxiredoxins , glutaredoxins , and thioredoxins among others . the natural role of cysteines as redox sensors is further observed by the observation that throughout evolution , cysteines are found in transcriptional regulators that are modulated by oxidative stress such as oxyr and nrf2/keap . due to the varying microenvironments that exist for cysteine within a given protein structure , cysteines are not equally reactive . for example , as discussed further below , the parkinson 's disease - linked protein , dj-1 cysteine at position 106 , appears to be highly sensitive to oxidative attack , while two other cysteines within its structure are not as easily modified . such apparent specificity of cysteines within the same protein is also observed among many other proteins . in terms of the macroenvironment , cysteine - dependent enzymes require a reducing environment for activity , which is the condition maintained in the cytoplasm in contrast to the extracellular space that is oxidizing . however , the lysosomal compartment is variable , and changes in redox state have been shown to modulate enzymatic activities located within it . for example , cathepsin activity was found to be altered through redox state as detected by a change in cleavage pattern produced under varying redox conditions . thus , the location of the cysteine within the overall tertiary / quaternary structure as well as its macroenvironment ( e.g. , intracellular versus extracellular or organelle ) plays major roles in the extent to which a cysteine is stabilized in the anionic transition state , thereby affecting its reactivity to a change in","evidence of increased oxidative stress has been found in various neurodegenerative diseases and conditions . while it is unclear whether oxidative stress is a cause or effect , protein , lipid , and dna have all been found to be susceptible to oxidant - induced modifications that alter their function . results of clinical trials based on the oxidative - stress theory have been mixed , though data continues to indicate that prevention of high levels of oxidative stress is beneficial for health and increases longevity . due to the highly reactive nature of the sulfhydryl group , the focus of this paper is on the impact of oxidative stress on cysteine - dependent enzymes and how oxidative stress may contribute to neurological dysfunction through this selected group",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Humans have relied on sourdough starter microbial communities to make leavened bread for thousands of years, but only a small fraction of global sourdough biodiversity has been characterized. Working with a community-scientist network of bread bakers, we determined the microbial diversity of 500 sourdough starters from four continents. In sharp contrast with widespread assumptions, we found little evidence for biogeographic patterns in starter communities. Strong co-occurrence patterns observed in situ and recreated in vitro demonstrate that microbial interactions shape sourdough community structure. Variation in dough rise rates and aromas were largely explained by acetic acid bacteria, a mostly overlooked group of sourdough microbes. Our study reveals the extent of microbial diversity in an ancient fermented food across diverse cultural and geographic backgrounds. Sourdough bread is a globally distributed fermented food that is made using a microbial community of yeasts and bacteria. The sourdough microbiome is maintained in a starter that is used to inoculate dough for bread production (1A). Yeasts, lactic acid bacteria (LAB), and acetic acid bacteria (AAB) in the starter produce CO2 that leavens the bread. Microbial activities including the production of organic acids and extracellular enzymes also impact bread flavor, texture, shelf-stability, and nutrition (Arendt et al. , 2007; De Vuyst et al. , 2016; Gobbetti et al. , 2014; Hansen and Schieberle, 2005; Salim-ur-Rehman et al. , 2006). Starters can be generated de novo by fermenting flour and water or acquired as established starters from community members or commercial sources. Home-scale fermentation of sourdough is an ancient and historically important practice (Cappelle et al. , 2013) that experienced a cultural resurgence during the COVID-19 pandemic (Easterbrook-Smith, 2020). Despite being an economically and culturally significant microbiome, a comprehensive survey of sourdough starter microbial communities has not yet been conducted. Previous studies have primarily focused on starters from regions within Europe (De Vuyst et al. , 2014; Gänzle and Ripari, 2016; Hammes et al. , 2005; Minervini et al. , 2014) and the diversity of sourdough starters in North America is poorly characterized (Kline and Sugihara, 1971; Sugihara et al. , 1971). Most previous studies have applied a range of culture-based techniques to characterize sourdough microbial diversity (De Vuyst et al. , 2014; Gänzle and Ripari, 2016) making it difficult to understand distributions of sourdough bacterial and fungal","Sourdough bread is an ancient fermented food that has sustained humans around the world for thousands of years. It is made from a sourdough ‘starter culture’ which is maintained, portioned, and shared among bread bakers around the world. The starter culture contains a community of microbes made up of yeasts and bacteria, which ferment the carbohydrates in flour and produce the carbon dioxide gas that makes the bread dough rise before baking. The different acids and enzymes produced by the microbial culture affect the bread’s flavor, texture and shelf life. However, for such a dependable staple, sourdough bread cultures and the mixture of microbes they contain have scarcely been characterized. Previous studies have looked at the composition of starter cultures from regions within Europe. But there has never",380,128,0.3368
scientific_lay_summarisation-elife-norm,", 2002), whereas Hop1 has preferential affinity for G-rich sequences and specific DNA topologies in vitro (Kironmai et al. , 1998). However, on meiotic chromosomes, Hop1 and Red1 binding coincides with cohesin binding sites and regular distribution of Hop1 requires cohesin (Panizza et al. , 2011), suggesting that cohesin is a major determinant of axis attachment sites. The yeast meiotic cohesin complex consists of Smc1, Smc3, Scc3, and the kleisin Rec8, which replaces the mitotic kleisin Scc1/Mcd1 (Klein et al. , 1999; Watanabe and Nurse, 1999). Despite the different subunit composition, the cohesin-associated chromosomal sites are highly conserved between mitosis and meiosis (Blat and Kleckner, 1999; Glynn et al. , 2004). A strong correlation between cohesin sites and regions of convergent transcription has been observed (Lengronne et al. , 2004), and changes in transcriptional activities can result in altered cohesin localization (Lengronne et al. , 2004; Bausch et al. , 2007). Because cohesin can encircle DNA from two sister-chromatids (Ivanov and Nasmyth, 2005,2007) it is hypothesized to be pushed along genes ahead of the RNA polymerase II (RNAPII) complex, thus accumulating at convergent regions (Ocampo-Hafalla and Uhlmann, 2011). However, sliding has not been addressed in meiotic prophase, where cohesin may be stably incorporated in the axial element. Moreover, the mechanisms of meiotic axis protein loading and the functional link to cohesin remain to be elucidated. Here, we probed axis assembly using high-resolution chromatin binding studies of axis protein distribution and in vivo detection of physical associations between axis proteins. We found that axis proteins dynamically accumulate between convergent genes in a distinctive two-peak pattern, which we demonstrate to be a direct consequence of the underlying transcriptional activity. We show that cohesin is responsible for this behavior and that Rec8 interacts closely with both axis proteins via Red1. In the absence of Rec8, Hop1 becomes essential for chromosomal Red1 recruitment, defining a cohesin-independent mode of axis protein recruitment. Intriguingly, Hop1 but not Rec8 is required for the preferential loading of Red1 to short chromosomes, possibly by preventing excess Red1 accumulation on large chromosomes and at centromeres. Our findings demonstrate that the well-dispersed binding and chromosome size-biased enrichment of axis proteins are controlled by two independent recruitment modes and provide important insight into the mechanistic hierarchy of meiotic axis assembly. We used","Chromosomes are long molecules of DNA that represent the genetic material of an organism. In most animal cells, chromosomes are found in pairs; with one inherited from the mother and the other from the father. Sex cells—egg cells and sperm—contain half the normal number of chromosomes, so that when they fuse, the resulting single-celled embryo inherits the full set. When sex cells are being produced, a ring made from a protein called cohesin encircles each pair of chromosomes and holds them together until they are ready to be separated. The paired chromosomes also swap sections of DNA via a process called recombination. Structures, referred to as axial elements, compact the chromosomes in each pair and bring them in close contact so that recombination can take place. In the",380,128,0.3368
dialogsum,#Person1#: Is it me or is it really hard to understand this speaker? #Person2#: You're right. It's not that he has an accent like some of the other speakers from another country. It's just that he is speaking too softly. Do you think it would be rude to ask him to turn his microphone up a little bit? #Person1#: I don't think he's wearing one either that or he's turned it off. #Person2#: That's crazy. There must be 400 people here. #Person1#: This part of the conference has turned into such a waste of time. Maybe we should leave and try to find another lecture. #Person2#: I can't do that. I come here specifically to hear this guy's speech. I think I'll just go up to him at the end of the speech and try to ask him some questions. #Person1#: Good idea. Would you mind if I followed you up there? It might be the only way to get anything out of this hour. #Person2#: No problem.,#Person1# and #Person2# couldn't understand the speaker because he speaks too softly. #Person1# thinks this conference is a waste of time. #Person2# decides to ask some questions in the end. #Person1# agrees.,168,32,0.1905
dialogsum,"#Person1#: I can't believe the cost of apartments in New York City. #Person2#: Oh, you didn't know that apartments here are considered valuable, even if they are small and crowded? #Person1#: Of course I had heard about that, but now I know how expensive it is to rent a place here. #Person2#: I don't mind paying high rent to live in New York. #Person1#: Why? You pay so much for such a tiny space to live. #Person2#: Yeah, but so what! I'm proud to live in the world's most exciting city. And, the salaries here are the highest in the nation, too.","#Person1# is surprised at the expensive rent in New York, but #Person2# thinks the city is exciting and the salary is high.",102,22,0.2157
scientific_lay_summarisation-elife-norm,"Despite extensive research on the role of the rodent medial and lateral entorhinal cortex (MEC/LEC) in spatial navigation, memory and related disease, their human homologues remain elusive. Here, we combine high-field functional magnetic resonance imaging at 7 T with novel data-driven and model-based analyses to identify corresponding subregions in humans based on the well-known global connectivity fingerprints in rodents and sensitivity to spatial and non-spatial information. We provide evidence for a functional division primarily along the anteroposterior axis. Localising the human homologue of the rodent MEC and LEC has important implications for translating studies on the hippocampo-entorhinal memory system from rodents to humans. The entorhinal cortex (EC) —defining the interface between the hippocampus and the neocortex (Munoz and Insausti, 2005) —plays a pivotal role in the integration of different sensory inputs into higher order mnemonic representations (Eichenbaum et al. , 2007; Moser and Moser, 2013). In rodents—and on the basis of cytoarchitectonics—the EC is typically (Kerr et al. , 2007; Canto et al. , 2008; Van Strien et al. , 2009) subdivided into two major subregions, the medial- and the lateral entorhinal cortex (MEC and LEC, respectively). The MEC receives inputs about spatial information from parahippocampal cortex (PHC) and the LEC receives item-related information from perirhinal cortex (PRC) (Van Strien et al. , 2009; Deshmukh and Knierim, 2011; Ranganath and Ritchey, 2012; Knierim et al. , 2013). Similar functional roles of the PHC and PRC have been described in humans (Epstein and Kanwisher, 1998; Davachi et al. , 2003; Eichenbaum et al. , 2007; Ekstrom and Bookheimer, 2007; Litman et al. , 2009; Duarte et al. , 2011; Staresina et al. , 2011; Martin et al. , 2013; Vilberg and Davachi, 2013) and relate to distinct visual processing streams (Kravitz et al. , 2011). The differential input pattern into the rodent LEC and MEC also dovetails with a cell-type specific functional specialisation (Eichenbaum and Lipton, 2008). The MEC contains a high proportion of head-direction and grid cells, whose activity is modulated by running direction and spatial location, respectively (Hafting et al. , 2005; Sargolini et al. , 2006). In contrast, cells in the LEC respond to individual objects in the environment rather than to specific locations (Deshmukh and Knierim, 2011; Tsao et al. , 2013; Knierim et al. , 2013).","In the early 1950s, an American named Henry Molaison underwent an experimental type of brain surgery to treat his severe epilepsy. The surgeon removed a region of the brain known as the temporal lobe from both sides of his brain. After the surgery, Molaison' s epilepsy was greatly improved, but he was also left with a profound amnesia, unable to form new memories of recent events. Subsequent experiments, including many with Molaison himself as a subject, have attempted to identify the roles of the various structures within the temporal lobes. The hippocampus—which is involved in memory and spatial navigation—has received the most attention, but in recent years a region called the entorhinal cortex has also come to the fore. Known as the gateway to the hippocampus, the entorhinal",380,128,0.3368
dialogsum,"#Person1#: Which countries have you been to? #Person2#: I've been to most of the countries in Europe, several countries in asia-china, Japan, korea, and Thailand-and to the united states and Canada. #Person1#: I thought you had been to Australia too. #Person2#: No, but I'm planning on visiting Australia and new Zealand soon. I've heard that they are beautiful countries. Which is the most beautiful country you've been to? #Person1#: I think I'd say norway. It has many picturesque fjords, waterfalls, and mountains. #Person2#: Isn't it really cold there? #Person1#: Well, the north of Norway is almost always cold, but further south it can be fairly warm in summer. It's a wet country, so there's snow almost everywhere in winter. #Person2#: I've been to other Scandinavian countries, but not to Norway. Perhaps I should go and do some winter sports there.",#Person1# and #Person2# share the countries they have been to. #Person2# also tells #Person1# about #Person2#'s plan on visiting Australia and New Zealand. #Person1# plans to travel to Norway.,140,29,0.2071
pubmed-summarization,"piece template for the placement of all six praecordial leads , which makes application easy . the person performing the 12-lead ecg need only to reach out for one single item to be applied to the patient s torso , instead of six separate pieces of items , as in the traditional case . the patch has characteristics that enable it to conform to variations in thoracic dimensions while retaining the ability of providing accurate electrode placement . training in the use of this new patch requires a minimal amount of time , as the template provides cues to the user on placement as it is being performed . the v - quick patch has the potential to be used anywhere and in any setting where a 12-lead ecg is carried out . this study will assess : the time required to obtain a 12-lead ecg using the v - quick patch system versus the standard single - electrode systemthe agreement between the 12-lead ecgs acquired by both techniques as assessed by two assessors the time required to obtain a 12-lead ecg using the v - quick patch system versus the standard single - electrode system the agreement between the 12-lead ecgs acquired by both techniques as assessed by two assessors the null hypothesis would be that there is no difference between the times taken and the level of agreement or quality of the ecgs acquired by the two different techniques . one hundred and fifty each of healthy male and female volunteers , at least 18 years of age , with various body builds and weights were enrolled . any volunteer who was incidentally found to have significant ecg changes were given an appointment with a cardiologist for the necessary evaluation . preparation consisted of cleaning the skin with alcohol wipes at the site for lead placement . electrodes were placed in the routine standard positions for the single - electrode 12-lead ecg . following the removal of the standard electrodes , the v - quick template was attached to the praecordium for the acquisition of the next 12-lead ecg . this was done using their unique identification number ( in ) and if this number ended with an even digit , they would have the v - quick","introductionthe v - quick patch template system is compared with the standard 12-lead electrocardiogram ( ecg ) acquisition technique in this paper . the objectives of the study were : ( a ) to study and compare the time taken to produce the printed 12-lead ecg and ( b ) to look at the level of agreement when the ecgs were compared by two blinded , independent assessors.methodsone hundred and fifty each of male and female volunteers signed an informed consent form to participate in the clinical study . nurses were put through a 4-h training session to familiarise themselves with the v - quick patch system . the timings were measured with a stopwatch with the specific start and end points defined . the final ecg printouts",380,128,0.3368
pubmed-summarization,"the prevalence of diabetes is increasing rapidly worldwide with the influence of expanding economy , abrupt transition of living styles , and social aging . in 2014 , there were 387 million people living with diabetes worldwide . the number is predicted to reach 592 million by 2035 of which 46% will still be un - diagnosed . throughout the world , there exists a large amount of diversity with respect to diabetes prevalence , deaths , and health expenditure . according to the 6th edition ( 2014 update ) of the international diabetes federation ( idf ) diabetes atlas , the western pacific ( wp ) has the largest population with diabetes ( 137.8 million ) , which means that 7.9% of the population in this region has diabetes . the region with the second highest prevelance is southeast asia ( sea ) with 75.0 million patients ( table 1 ) . another fact of spatial distribution is that the prevalence rate of diabetes in developing countries is higher . more than 80% of diabetic patients live in low- and middle - income countries . globally , 90% of diabetic patients have type 2 diabetes , of which 77% live in developing countries . in china , the number of diabetes patients in china was 96.3 million , 29.5 million more compared to india , in 2014 . the prevalence rate of diabetes had reached 9.3% .table 1regional estimates for diabetes ( 2079 years old ) in 2014idf regionpopulation ( millions)number of people with diabetes ( millions)comparative diabetes prevalence ( % ) afr407.921.55.9eur658.752.06.2mena374.536.811.3nac334.938.89.9saca300.524.88.2sea883.275.08.8wp1,613.2137.87.9world4,572.9386.78.2 idf international diabetes federation , afr africa , eur europe , mena middle east and north africa , nac north america and caribbean , saca south and central america , sea southeast asia , wp western pacific regional estimates for diabetes ( 2079 years old ) in 2014 idf international diabetes federation , afr africa , eur europe , mena middle east and north africa , nac north america and caribbean , saca south and central america , sea southeast asia , wp western pacific china carried out five large - scale epidemiological surveys to understand better the prevalence of type 2 diabetes . the prevalence rate of diabetes has been increasing in china from 0.67%","backgroundtype 2 diabetes is associated with acute and chronic complications and poses a large economic , social , and medical burden on patients and their families as well as society.objectivethis study aims to evaluate the direct economic burden of type 2 diabetes in china . data source : systematic review on cost of illness , health care costs , direct service costs , drug costs , and health expenditures in relation to type 2 diabetes was conducted up to 2014 using databases such as pubmed ; ebsco ; elsevier sciencedirect , web of science ; and a series of chinese databases , including wanfang data , china national knowledge infrastructure ( cnki ) , and the china science and technology journal database . factors influencing hospitalization and drug",380,128,0.3368
dialogsum,"#Person1#: Good morning Mike! #Person2#: Morning Sally! What's up? you seem in a hurry! #Person1#: I am having an exam at nine, It's already eight thirty. #Person2#: Don't worry, I'll drive you. #Person1#: Thank you very much! #Person2#: How are your cases coming along? #Person1#: Very well, thanks , I will probably finish next week, but this is still a lot of work , I have been worked on in for six months, and i 'm so closed to end. I can feel it. #Person2#: Wow, Good for you. It sounds like a lot of work. I'm proud of you! Is this the right building? #Person1#: Yes , It's only eight forty. Thanks so much! #Person2#: You're welcome. Good luck, bye! #Person1#: Have a nice day, bye!",Sally's in a hurry for an exam. Mike offers to drive her. Sally tells Mike her cases will be finished soon.,127,21,0.1654
scientific_lay_summarisation-elife-norm,"Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here, we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes; however, activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release. Oxytocin (OT) is a nine amino acid peptide synthesized almost exclusively in hypothalamic neurons of the supraoptic and paraventricular nucleus (SON, PVN). Despite the highly localized nature of OT synthesizing neurons, OT receptors (OTRs) are distributed widely throughout the CNS. Significant evidence indicates an important modulatory role for central oxytocinergic signaling in a wide variety of processes including fear conditioning, stress responding, anxiety-related behaviors, maternal behavior, sexual behavior, and social recognition (e. g. see Bosch et al. , 2005; Knobloch et al. , 2012; Jurek et al. , 2015; Veening et al. , 2015; Neumann and Slattery, 2016; Lin et al. , 2018; Tan et al. , 2019; Valtcheva and Froemke, 2019; Winter and Jurek, 2019). Numerous studies have demonstrated effects of OTR agonists and antagonists delivered intracerebrally or intraventricularly on social, stress, and anxiety-related behaviors, while conversely, animal models with genetic disruptions in OT signaling systems exhibit a range of social and behavioral deficits (e. g. see Jin et al. , 2007; Young, 2007; Lee et al. , 2008; Higashida et al. , 2010; Pobbe et al. , 2012; Kent et al. , 2013; Morales-Rivera et al. , 2014; Peters et al. , 2014; Burkett et al. , 2016; Caldwell et al. , 2017; Lee et al. , 2018). Collectively, these types of data implicate the central OT signaling system as a promising therapeutic target for a variety of conditions impacting mental health.","Oxytocin is often referred to as a ‘love hormone’ because it can be released during activities such as hugging, snuggling, or sex. Reality, of course, can be a bit more complicated. In the brain, oxytocin can have powerful and diverse effects on mood, stress, anxiety, and social interactions. In the body it helps regulate fluid balance, promotes contractions during childbirth, and stimulates the letdown of milk during breastfeeding. Much of the oxytocin produced in both humans and rodents comes from oxytocin-synthetizing magnocellular neurons located in an area of the brain called the hypothalamus. These very specialized neurons have separate, but overlapping, mechanisms for releasing oxytocin into the brain and into the rest of the body. This means that while certain signals cause the neurons to release oxytocin into",380,128,0.3368
pubmed-summarization,"ionic calcium ( ca ) controls multiple cellular signaling processes in all eukaryotic cells , including proliferation , gene expression , and neurotransmitter release . ca - binding proteins such as calmodulin play a pivotal role in ca signal transmission and amplification . increases in the concentration of intracellular ca activate specific protein targets , among which the ca / calmodulin - dependent protein kinase ii ( camkii ) is a critical signal mediator . in response to an increase in intracellular ca , thr-286 of camkii the coupling of ca - calmodulin to one of the camkii subunits allows for the phosphorylation of an adjacent subunit at thr . calmodulin trapping , confers ca - calmodulin - independent kinase activity to the complex and thus prolongs the ca signal . thus , calmodulin trapping represents a molecular mechanism of memory , which is defined as the capacity to acquire , store ( consolidate ) , and retrieve ( evocate ) information . camkii is a major synaptic protein that is activated during the induction of long - term potentiation ( ltp ) by ca influx through n - methyl - d - aspartate ( nmda ) receptors . calmodulin trapping allows camkii to remain activated long after the initial ca signal has dissipated , suggesting that camkii is a memory molecule crucial for ltp . consistent with this notion , camkii - null mice present with impaired memory formation , and camkii is essential for genesis and maintenance of ltp in postsynaptic neurons . following presynaptic stimulation , camkii is activated in postsynaptic neurons , which creates a physiological imprint of the initial ca signal , and increases translocation of nmda receptors to the plasma membrane . because of its capacity to remain activated long after the initial pulse of ca signaling , camkii perpetuates ca effects and modulates gene expression and the epigenetic profile of postsynaptic neurons . camkii also participates in glucose - stimulated insulin secretion ( gsis ) , as multiple insulin secretagogues increase camkii activity . in the perfused rat pancreas , the dynamics of camkii activation correlate with the amplitude of gsis , and camkii activation is temporally associated with insulin secretion . camkii is essential for appropriate gsis and is involved in several","ca2+/calmodulin - dependent protein kinase ii ( camkii ) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators . therefore , we hypothesized that pancreatic - cells acquire and store the information contained in calcium pulses as a form of metabolic memory , just as neurons store cognitive information . to test this hypothesis , we developed a novel paradigm of pulsed exposure of - cells to intervals of high glucose , followed by a 24-h consolidation period to eliminate any acute metabolic effects . strikingly , - cells exposed to this high - glucose pulse paradigm exhibited significantly stronger insulin secretion . this metabolic memory was entirely dependent on camkii . metabolic memory was reflected on the protein level by increased expression",380,128,0.3368
pubmed-summarization,"m6 and a telomeric one in l2 . a large part of the eukaryotic genome is formed by repetitive dna , including tandem sequences mainly comprising satellite dna and multigene families . ribosomal dna and histone gene families include a variable number of copies with various genome locations ( charlesworth et al . fluorescence in situ hybridization ( fish ) with rdna and histone genes probes has proven useful for mapping and their location and in clarifying the genome organization of several organisms . among invertebrates , rdna gene mapping has been used in several groups , including worms ( vitturi et al . , 2002 ) , mollusks ( colomba et al . , 2002 ) , insects ( cabrero and camacho , 2008 ; cabral - de - mello et al . , 2011a ; panzera et al . , 2012 ) , the studies involving histone genes mapping in grasshoppers included some species of the acrididae family ( cabrero et al . , 2009 ; oliveira et al . , 2011 ) and four species of the proscopiidae family ( cabral - de - mello et al . , 2011b ) were mapped . this study aimed at understanding the pattern of organization of multigene families in two species of radacridium . our results showed a great variability in the number and location of rdna clusters in both species , whereas the histone h4 genes were highly conserved in number . these results are compared with data from other grasshopper species and are discussed based on the possible mechanisms involved in repetitive dna diversification . we analyzed ten individuals of r. mariajoseae from gravat ( 081204 s ; 353353 w ) and bezerros ( 081400 s ; 354749 w ) and ten adult males of radacridium nordestinum from surubim ( 074959 s ; 354517 w ) , all located in the agreste region of the state of pernambuco , brazilian northeast . specimens were processed and their testes were fixed in carnoy solution ( 3:1 ethanol : acetic acid ) . chromosome preparations were obtained by the testicular follicles squashing technique , in one drop of 45% acetic acid . the slides were stained with cma3 ( 0.5 mg / ml ) for one hour , washed","in this study , two species of romaleidae grasshoppers , radacridium mariajoseae and r.nordestinum , were analyzed after cma3/da / dapi sequential staining and fluorescence in situ hybridization ( fish ) to determine the location of the 18s and 5s rdna and histone h4 genes . both species presented karyotypes composed of 2n = 23 , x0 with exclusively acrocentric chromosomes . cma3 + blocks were detected after cma3/da / dapi staining in only one medium size autosome bivalent and in the x chromosome in r. mariajoseae . on the other hand , all chromosomes , except the l1 bivalent , of r. nordestinum presented cma3 + blocks . fish analysis showed that the 18s genes are restricted to the x chromosome in r. mariajoseae , whereas these",380,128,0.3368
scientific_lay_summarisation-elife-norm,"the 3′ end, depending on the library protocol employed). When considering the 5′ end of sequences, the excess of C-to-T substitutions is highest at the first base and decreases exponentially towards the center (1A). This pattern is the result of cytosine deamination to uracil in single stranded overhangs (Briggs et al. , 2007). Since it is present in aDNA-derived sequences but absent in much younger samples, it has been used as an authentication criterion in aDNA experiments (Krause et al. , 2010; Prüfer and Meyer, 2015). 10. 7554/eLife. 10005. 003Figure 1. Patterns of cytosine to thymine (C-to-T) substitutions at the 5′end of known modern and ancient DNA. (A) C-to-T substitutions at the 5′ end from a whole library of historic Solanum tuberosum (ancient DNA). The line shows the fit with the exponential distribution and the box the goodness-of-fit p-value. (B) C-to-T substitutions at the 5′ end from a whole library of present-day Triticum aestivum (modern DNA). Line and box as in (A). : http: //dx. . org/10. 7554/eLife. 10005. 003 Smith et al. analyzed sediments from Bouldnor Cliff, a submerged archeological site in the United Kingdom, and suggested the presence of domesticated wheat 8000 years ago based on sedimentary ancient DNA (sedaDNA). This is 2000 years earlier than expected based on archeological remains in the British Isles and 400 years earlier than in nearby European sites (reviewed in Smith et al.). Since Smith et al. did not find wheat pollen or archeological remains associated with wheat cultivation, they conclude that the wheat presence in Bouldnor Cliff was the result of trading. In total they produced ∼72 million Illumina reads, of which they robustly assigned 152 to wheat (Triticum), with dozens more (160 reads) to higher taxonomic ranks that include wheat. Smith et al. took state-of-the art preventive measures to avoid contamination and exercised great effort to ensure the accuracy and robustness of their phylogenetic assignments. The authors attempted to authenticate the aDNA molecules based on the expected excess of C-to-T substitutions, but because of the very small number of reads assigned to wheat, they failed to do so using standard approaches. As a result of that, the authors did not present any positive evidence for the ancient origin of their reads. Here we present an approach that compares the pattern","Ancient DNA, that is to say DNA extracted from fossils and ancient remains, provides a window into the past lives of humans, animals and plants. But working with ancient DNA is challenging; DNA decomposes with time, and so ancient DNA is often fragmented, damaged and present in tiny quantities. Furthermore, ancient DNA is also easily contaminated by modern DNA from those handling it and its surroundings. Researchers have therefore developed special protocols for working with ancient DNA and tests for its contamination. One approach used to check that DNA is of ancient origin identifies a pattern of damage that is specific to ancient DNA. This damage changes the building blocks that make up DNA, causing one (called cytosine or C) to be misread as another (thymine or T).",380,128,0.3368
pubmed-summarization,"the p38-dependent stress pathway and the p53-dependent cell cycle checkpoint . we have previously shown that depletion of the protein pcm-1 leads to defects in the assembly of the centrosomal components centrin , ninein , and pericentrin , and to an altered organization of the microtubule network in interphase cells ( dammermann and merdes , 2002 ) . to investigate the consequences of pcm-1 depletion on the cell cycle , we performed rna silencing experiments in primary human fibroblasts , mrc-5 . depleted cells were tested for incorporation of brdu into the nucleus , as an indicator of dna synthesis ( . we determined that in pcm-1depleted cells only 15 4% incorporated brdu , as compared with 35 3% in controls , as expected for a normal cycling population ( . this is consistent with previous reports on microinjection of pcm-1inhibiting antibodies ( balczon et al . , 2002 ) and on centrosome removal by microsurgery or laser ablation , which prevent cells from entering s phase ( hinchcliffe et al . several years ago , experiments on cells treated with the microtubule drugs colcemid , nocodazole , and taxol indicated that untransformed cells are arrested in g1 phase , when microtubules are depolymerized or when microtubule dynamics are altered ( trielli et al . , 1996 ; di leonardo et al . , 1997 this raises the question of whether dna replication in pcm-1depleted cells is inhibited because of an altered microtubule network , or whether defects at the centrosome itself suffice to induce a cell cycle arrest . 1 a ) , which in contrast to pcm-1 , only slightly reduces microtubule density but seems to have no significant effect on microtubule anchoring at the centrosome ( dammermann and merdes , 2002 ) . consistently , ( a ) immunofluorescence of mrc-5 fibroblasts treated with control rna or sirna against pcm-1 and pericentrin , respectively . graphs depict the percentages of cells lacking pcm-1 or pericentrin expression after treatment with control or silencing rnas . cells were scored as negative if they lacked centrosomal staining of pcm-1 or pericentrin , only displaying diffuse background fluorescence . ( b ) percentages of cells incorporating brdu after treatment with control rna or silencing rna against pcm-1 or pericentrin . data","previous evidence has indicated that an intact centrosome is essential for cell cycle progress and that elimination of the centrosome or depletion of individual centrosome proteins prevents the entry into s phase . to investigate the molecular mechanisms of centrosome - dependent cell cycle progress , we performed rna silencing experiments of two centrosome - associated proteins , pericentriolar material 1 ( pcm-1 ) and pericentrin , in primary human fibroblasts . we found that cells depleted of pcm-1 or pericentrin show lower levels of markers for s phase and cell proliferation , including cyclin a , ki-67 , proliferating cell nuclear antigen , minichromosome maintenance deficient 3 , and phosphorylated retinoblastoma protein . also , the percentage of cells undergoing dna replication was reduced by > 50%",380,128,0.3368
dialogsum,"#Person1#: What's your city like? #Person2#: It's quite an interesting place to live. The best thing to do in my city is go shopping. There are several indoor and outdoor markets, department stores and shopping malls. #Person1#: Is the traffic bad in the city centre? #Person2#: Not really. Cars are not permitted in several parts of city centre, especially in the main shopping areas. The public transport system is pretty good. #Person1#: What about restaurants and entertainment? #Person2#: There are restaurants with food from all over the world. We have a small china-town near the city centre. There are many Indian, thai, and Italian restaurants all over the city centre. There are many s #Person1#: Is there a lot of nightlife in your city? #Person2#: There are several good clubs near the city centre. Many people in my city prefer something more cultural, so we several theatres and venues for classical music concerts and operas. #Person1#: It sounds like a really exciting city to live in. #Person2#: It is. I hope you'll have time to come for a visit soon. You really should come during the summer, when the weather is better and there's more happening outdoors.",#Person2# tells #Person1# #Person2#'s city is interesting. The best thing is to go shopping and the public transport system is good. There are restaurants with food from all over the world. #Person2# hopes #Person1# to come for a visit.,197,39,0.198
dialogsum,#Person1#: Good afternoon. British Airline. Is there any thing I can do for you? #Person2#: Can I make a reservation for flight FW58 to San Marino? #Person1#: Sure. When do you want to take the plane? #Person2#: Next Monday. #Person1#: Will that be first class or economy seat? #Person2#: What's the fare for a first class seat? #Person1#: $ 200. #Person2#: Oh. I am not a wall streeter. Give me an economy one please.,#Person2# asks #Person1# to book an economy class ticket on the flight FW58 because #Person2# thinks the ticket of first-class is too expensive.,74,23,0.3108
pubmed-summarization,"therapeutic transrectal or transcolonic drainages with endosonography ( ( endoscopic ultrasound ) eus ) are now considered as a mini - invasive option for the treatment of pelvic abscesses . the aim of our case series is to confirm that eus transrectal drainage is effective , safe , and induces a short duration of hospitalization . we did a single - center retrospective analysis of seven patients with pelvic abscess treated by eus transrectal drainage between january 2010 and august 2014 . there were four men and three women , with a median age of 50 years ( range 22 - 68 ) . a concomitant intravenous antibiotic treatment was always administered be for eus and for a minimum of 7 days after drainage . the method of drainage was done with a linear interventional echoendoscope ( pentax ) ( eg 3870utk pentax - hitachi , hambourg , germany ) . eus - doppler evaluation was first performed to exclude the presence of intercalated blood vessels before puncture with a 19-gauge access needle ( cook ) ( 19 g , echotip access needle , cook ireland ltd . , limerick , ireland ) . the puncture tract was then enlarged with a 10 french diathermic cystostomy over a tetrafluoroethylene ( tfe)-coated 0.035-inch guidewire ( cook endoscopy , winston - salem , nc , usa ) . a second guidewire was then put into the cavity , and two 7 french double pigtail plastic stents were positioned ( 4 or 7 cm length ) . eus drainages were done for a majority of abscesses post surgery ( n = 5/7 ) . the treatment was feasible and effective in 100% of cases [ figures 17 ] , without supplementary radiological or surgical intervention [ table 1 ] . the median time of hospitalization was 10 days ( range 4 - 25 days ) . the main difficulty related to this technique is the positioning of the double pigtail plastic stents , induced by pus outflow that can reduce the endoscopic visibility . two of our patients were embarrassed by the length of the double pigtail plastic stents which protruded in the anal canal . pelvic abscess before drainages pelvic abscess after drainage sagittal view of pigtail stent in pelvic abscess fluoroscopic","background and objective : pelvic abscesses are a well - known complication of intestinal diseases or abdominal surgery . we report our case series concerning transrectal drainage by endoscopic ultrasound ( eus).methods : between january 2010 and august 2014 , seven patients received transrectal drainage by endoscopic ultrasound ( eus ) were selected and analyzed.results:two pigtails was positioned under fluoroscopic and eus control . the success rate was 100% and complication rate was 0% . the median time of hospitalization was 10 days [ range 4 - 25].conclusions : the technique appears to be safe and feasible in all etiologies . in our experience , we can considerate transrectal drainage by eus like a first - line technique in experienced hands .",380,122,0.3211
dialogsum,"#Person1#: I thought it was a great movie, so visually exciting. #Person2#: I hate to admit it, but I jumped in my seat a few times, too. #Person1#: The shark looked so real at times! #Person2#: I guess recent advances in camera technology helped a lot.",#Person2# and #Person1# discuss how exciting the movie was.,46,9,0.1957
scientific_lay_summarisation-elife-norm,"an AAA-ATPase that has essential functions in ubiquitin-dependent proteolysis. But, pathogenic mutations in VCP do not seem to impair the UPS or ERAD protein degradation pathways (Tresse et al. , 2010a; Chang et al. , 2011). More recently, VCP has been implicated in autophagy. Specifically, over-expression of VCP mutant transgenes with disease causing mutations leads to an accumulation of autophagosomes (Ju et al. , 2009; Tresse et al. , 2010a), suggesting that VCP functions in processes related to the maturation or fusion of autophagosomes with lysosomes. Lysosomes are the major cellular degradation sites for clearing damaged proteins and organelles. Lysosomes are classically thought to be vesicular organelles, where they serve as depots for cargo delivered via endosomes or autophagosomes. However, in certain systems lysosomes have been observed to adopt non-vesicular morphologies. A particularly dramatic example has been observed in a subset of bone-derived cultured macrophages, where lysosomes form abundant, extended tubules that radiate from the cell center and, in some cases, form an interconnected web throughout the cytoplasm (Swanson et al. , 1987a; Knapp and Swanson, 1990). Additionally, there are examples where cellular stress, particularly the induction of high levels of autophagy, induces lysosomal membranes to tubulate and undergo scission to produce new vesicular lysosomes, a process referred to as autophagic lysosome reformation (ALR) (Yu et al. , 2010). Despite these observations, lysosome tubules have received little attention and it remains unclear to what extent lysosome tubulation occurs in different cell types and what purpose it serves in vivo. Moreover, the molecular repertoire of factors required for lysosome tubule formation is virtually unknown. Here, we employ fluorescently tagged lysosomal and autophagic markers to study the autophagy-lysosome system in Drosophila muscle cells and investigate the muscle pathology of VCP-related diseases. Remarkably, we find that lysosomes adopt a dynamic, tubular morphology that ramifies throughout the entire sarcoplasm of Drosophila muscle, in vivo. We find that VCP is required for the integrity and dynamics of this tubular network. Disruption of lysosome tubules correlates with defects in autophagosome-lysosome fusion, increased poly-ubiquitin aggregates and the accumulation of lipofuscin material in the sarcoplasm. We show that the human VCP homolog can rescue lysosomal tubulation following loss of VCP in Drosophila muscle, indicating that the functions of VCP in lysosome tubulation are conserved. Finally, we demonstrate that","Mutations in a gene that produces a protein called Valosin-containing protein (VCP for short) causes degenerative diseases that affect the brain, muscle and bone. In nearly half of the individuals with these VCP-related diseases—which can also result in dementia, Paget' s disease of the bone and amyotrophic lateral sclerosis (ALS) —the first symptom is muscle weakness. Currently, very little is known about how VCP affects muscles. Patients with VCP-related diseases often have problems clearing damaged proteins from their cells, and recent research suggests that VCP is important for forming a cellular structure known as a lysosome. Lysosomes contain powerful enzymes that destroy damaged proteins and other cellular structures that would otherwise accumulate in the cells. In most cells, lysosomes look like bubble-like compartments called vesicles. However, in some",380,128,0.3368
scientific_lay_summarisation-elife-norm,"both be handled in a bottom-up way by the combined action of auditory cortical oscillations in distinct frequency ranges, enabling parallel computations at syllabic and phonemic timescales (Ghitza, 2011; Giraud and Poeppel, 2012). Intrinsic coupling across cortical oscillations of distinct frequencies, as observed in electrophysiological recordings of auditory cortex (Lakatos et al. , 2005; Fontolan et al. , 2014), could enable the hierarchical combination of syllabic- and phonemic-scale computations, subsequently restoring the natural arrangement of phonemes within syllables (Giraud and Poeppel, 2012). The most pronounced energy fluctuations in speech occur at about 4 Hz (Zion Golumbic et al. , 2012) and can serve as an acoustic guide for signalling the syllabic rhythm (Mermelstein, 1975). Since the syllabic rate coincides with the auditory cortex theta rhythm (3–8 Hz), syllable boundaries could be viably signalled by a given phase in the theta cycle. The relevance of speech tracking by the theta neural rhythm (Henry et al. , 2014) is highlighted by experimental data showing that speech intelligibility depends on the degree of phase-locking of the theta-range neural activity in auditory cortex (Ahissar et al. , 2001; Luo and Poeppel, 2007; Peelle et al. , 2013; Gross et al. , 2013). By analogy with the spatial and mnemonic oscillatory processes that take place in the hippocampus (Jensen and Lisman, 1996; Lisman and Jensen, 2013; Lever et al. , 2014), the theta oscillation may orchestrate gamma neural activity to facilitate its subsequent decoding (Canolty et al. , 2007): the phase of theta-paced neural activity could regulate faster neural activity in the low-gamma range (>30 Hz) involved in linguistic coding of phonemic details (Ghitza, 2011; Giraud and Poeppel, 2012). The control of gamma by theta oscillations could hence both modulate the excitability of gamma neurons to devote more processing power to the informative parts of syllabic sound patterns, and constitute a reference time frame aligned on syllabic contours for interpreting gamma-based phonemic processing (Shamir et al. , 2009; Ghitza, 2011; Kayser et al. , 2012; Panzeri et al. , 2014). Compelling as this hypothesis may sound, direct evidence for neural mechanisms linking speech constituents and oscillatory components is still lacking. One way to address a causal role of oscillations in speech processing is computational modelling, as it permits to directly test the efficiency of cross-coupled","Some people speak twice as fast as others, while people with different accents pronounce the same words in different ways. However, despite these differences between speakers, humans can usually follow spoken language with remarkable ease. The different elements of speech have different frequencies: the typical frequency for syllables, for example, is about four syllables per second in speech. Phonemes, which are the smallest elements of speech, appear at a higher frequency. However, these elements are all transmitted at the same time, so the brain needs to be able to process them simultaneously. The auditory cortex, the part of the brain that processes sound, produces various ‘waves’ of electrical activity, and these waves also have a characteristic frequency (which is the number of bursts of neural activity per second).",380,128,0.3368
dialogsum,"#Person1#: Where are you going? #Person2#: Take me to the center station, please #Person1#: OK, here we go. #Person2#: Do you think you can get me there seven thirty? #Person1#: We shouldn't have any trouble if we don't get stuck in the traffic jam. #Person2#: Hope we have good luck. #Person1#: Here we are, you still get plenty of time. That's 8. 15$, please. #Person2#: Thank you very much. Here's 10$, keep the change, please.",#Person2# drives #Person1# to the central station before seven-thirty. #Person1#'s grateful and pays for the fee.,75,16,0.2133
pubmed-summarization,"- nonbc , both hbsag , and hcvab negative . the significance of age , sex , body mass index ( bmi ) , alcohol intake , diabetes mellitus , underlying liver disease child - pugh score , platelet count , prothrombin time ( pt ) , albumin ( alb ) , total bilirubin ( bil ) , aspartate aminotransferase ( ast ) , alanine aminotransferase ( alt ) , afp , dcp , and tumor - node - metastasis ( tnm ) stage were examined to identify possible relationships with hcc - nonbc using logistic regression analysis . patients diagnosed with hcc were assessed for surgery based on the extent of lobar involvement and liver function status . the extent of lobar involvement was evaluated based on a combination of usg , ct , mri , and hag findings . patients were considered to be poor candidates for resection if they met any of the following criteria : ( 1 ) bilobar involvement , ( 2 ) evidence of tumor infiltration into the main portal vein or thrombosis of the vein , ( 3 ) evidence of extrahepatic metastases , ( 4 ) child s grade c cirrhosis , or ( 5 ) poor cardiac and/or respiratory status . if surgery was contraindicated or the patient refused to undergo an operation , rfa or pei therapy was the second treatment choice , offered to those with hccs less than 3 cm in diameter . the remaining patients without main portal vein thrombosis or extrahepatic metastasis were advised to undergo tace , regardless of tumor size or number . after initial treatment , the afp levels and liver functions of the patients were assessed every 1 to 3 months , and usg imaging was performed every 3 to 6 months during the follow - up period . the assessment of treatment for recurrent hcc was based on lobar involvement and liver function status as described for the initial treatment . rfa or liver transplantation to treat hcc was started at our institution in 2002 . furthermore , none of the subjects in our study received either of these treatments for recurrent hcc during the follow - up period . the survival duration was the time from the diagnosis of hcc","backgroundthe incidence of hepatocellular carcinoma ( hcc ) continues to increase in japan , but the clinical characteristics of japanese patients with hcc have not been well described . the aim of this study was to determine the frequencies and utilities of elevated -fetoprotein ( afp ) and des - gamma - carboxy prothrombin ( dcp ) levels as biomarkers in cryptogenic hcc.material/methodsa total of 2638 patients with hcc diagnosed between 1999 and 2010 in the nagasaki association study of liver ( nasld ) were recruited for this study . the cause of hcc was categorized into 4 groups ; hcc - b , hcc - c , hcc - bc , and hcc - nonbc . the significance of factors was examined for hcc - nonbc using",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2014). In one study, co-expression network analyses of autism-linked genetic mutations suggested that layer 5 in prefrontal and sensorimotor cortex is a key site of convergence for pathogenesis (Willsey et al. , 2013). Whether aberrant ERK/MAPK signaling might result in cortical layer disorganization and defective long-range connectivity is unknown. To address questions of cell type specificity and consequences for circuit formation, we have defined the effects of ERK/MAPK loss- and gain-of-function on the development of cortical pyramidal neurons. Pyramidal neuron-specific functions of ERK/MAPK signaling were assessed by deleting the upstream kinases Map2k1/Mek1 and Map2k2/Mek2 (hereafter referred to as Map2k1/2) or overexpressing hyperactive Map2k1. Conditional deletion of Map2k1/2 led to major disruption of layer 5 with noticeably fewer CTIP2-expressing large neurons compared to controls. Further, long range axon extension of layer 5 corticospinal projection neurons during early development was markedly impaired. Subsequent to delayed entry of axons into the cervical spinal cord, many layer 5 projection neurons in sensorimotor cortices underwent apoptosis. Gain-of-function ERK/MAPK signaling also affected layer 5 CST neurons with a resultant decrease in axon elongation and associated increase in axon branching. The morphological requirement for ERK/MAPK signaling was specific for layer 5, as layer 2/3 was not disrupted and callosal projection neurons in upper cortical layers do not exhibit overt changes in axon extension or targeting following Map2k1/2 deletion. In contrast to the layer-specific functions of ERK/MAPK on axonal development, we found that ERK/MAPK was required for the expression of ARC and other plasticity-associated genes across all cortical lamina. Further, loss of ERK/MAPK signaling in pyramidal neurons disrupted excitatory and inhibitory neurotransmission and altered intrinsic excitability in both layers 2/3 and 5. Our data reveal unexpectedly specific requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on the excitability of cortical pyramidal neurons in multiple layers. Previous work has shown that MAPK1/3 (aka ERK1/2) is activated in embryonic cortical neurons, albeit at much lower levels than in the ventricular zone (Faedo et al. , 2010; Li et al. , 2014; Pucilowska et al. , 2012; Toyoda et al. , 2010). In western blots of sensorimotor cortical lysates from P1,2, 7,14, and 21 day old mice, we found that the levels of pan-MAPK1/3 (ERK1/2) and pan-MAP2K1/2 show a steady but evident increase from","In the nervous system, cells called neurons form networks that relay information in the form of electrical signals around the brain and the rest of the body. Typically, an electrical signal travels from branch-like structures at one end of the cell, through the cell body and then along a long fiber called an axon to reach junctions with another neurons. The connections between neurons start to form as the nervous system develops in the embryo, and any errors or delays in this process can cause severe neurological disorders and intellectual disabilities. For example, genetic mutations affecting a communication system within cells known as the ERK/MAPK pathway can lead to a family of syndromes called the “RASopathies”. Abnormalities in this pathway may also contribute to certain types of autism.",380,128,0.3368
scientific_lay_summarisation-elife-norm,"(B) Z-scores for fold-change of proliferation of MDA-MB-453-eGFP cells infected with multiple shRNAs targeting the indicated genes and treated for 9 days with GDC0941 (0. 625 μM; red), or vehicle (DMSO; blue). Cells infected with five different control shRNAs (shCTRLs) were used to calculate Z-scores. Bars indicate standard deviation between the different shRNAs targeting each gene. Data shown are representative of three independent experiments. (C–D) MDA-MB-453 cells were infected with the indicated shRNAs, and then treated for 4 days with GDC0941 (0. 625 μM) (C) or left untreated (D). Adherent and floating cells were collected and subjected to immunoblot analysis for induction of PARP cleavage. Cells infected with a shRNA targeting ZNF565 and treated with GDC0941 (0. 625 μM) for 4 days were used as positive control for PARP cleavage (D). Data shown are representative of two independent experiments. (E) MDA-MB-453 cells were infected as in B and treated for 4 days with GDC0941 (0. 625 μM). Adherent and floating cells were collected and analyzed for DNA content by flow cytometry. Bars indicate standard deviation between the different shRNAs targeting each gene. : http: //dx. . org/10. 7554/eLife. 24523. 00310. 7554/eLife. 24523. 004Figure 1— 1. Supporting information for shRNA screen setup and scoring. (A) MDA-MB-453 cells were counted at the indicated time points after initiation of treatment with either DMSO or GDC0941 at the indicated concentrations. Experiments were performed in triplicates, with error bars representing standard deviation. Data shown are representative of two independent experiments. (B) MDA-MB-453 cells were seeded and treated as in A. Seventy-two hours after treatment initiation, cells were lysed and Western blotting analysis was performed using the indicated antibodies. Staurosporine (STS, 1 μM, 6 hr) was used as a positive control for cleaved-Caspase3 antibody. (C–D) MDA-MB-453 cells were seeded and treated as in A. Adherent and floating cells were collected and fixed at the indicated time-points. Cells were then stained with cleaved-cPARP antibody and analyzed by flow cytometry. At least 30,000 cells were acquired per sample. (E) Scoring of individual shRNAs according to a T-statistic. Each dot represents an individual shRNA T-statistic value. Red dots represent shRNAs that contributed to the nomination of genes by STARS. (F) Venn diagram summarizes the gene calling by either RIGER or STARS algorithms. (G) qPCR was used to measure the","When cells become cancerous, they accumulate mutations in their DNA that switch on some genes at the wrong time and to higher levels than normal. These over-active genes help cancer cells to survive, grow and evade death. One of the genes that is often mutated and over-active in breast cancer encodes an enzyme called PIK3CA. There are several drugs that bind to and inhibit the mutant version of PIK3CA. Recent experiments show that inhibiting over-active forms of this enzyme can stop cancer cells from growing, but it does not cause them to die. This means that the cells have the opportunity to become resistant to the drug, which can subsequently lead to tumor relapse. Therefore, researchers have been looking for other drugs that, when combined with the PIK3CA-inhibiting",380,128,0.3368
dialogsum,"#Person1#: Now people are talking about world recession which started more than a year ago. Can you give us your personal assessment of the situation of the global economy? #Person2#: As you know, we are in a very special time. This is a very hard time for many countries ' economics, both developed and developing. I think the current economic situation could be described as synchronized slowdown of major economies. #Person1#: What is the direct impact of the terrorist attack upon your country's economy? #Person2#: Once the US economy is in trouble due to the terrorist attack, the impact could be quickly felt in the rest of the world. #Person1#: What challenges is your country's economy facing at the moment? #Person2#: We do face a lot of challenges because there is still much uncertainty about the world economy. It's very important for us to strike a proper balance between investment in fixed assets and household consumption.",#Person2# thinks there is a synchronized slowdown of major economies and the US economy is in trouble due to the terrorist attack. They face many challenges because there is still much uncertainty.,156,32,0.2051
pubmed-summarization,"primary treatment receive prophylactic cranial radiation ( pci ) to reduce the risk of brain metastases . additionally , if a patient is not a good candidate for or refuses chemotherapy , they may receive radiation to symptomatic sites . evidence - based care for the elderly lung cancer population is lacking due to the underrepresentation of this population in clinical trials . cancer trials tend to consider 70 years of age as the reference point for being elderly ; however , there is not a specific minimum age that clearly defines the term . the tendency to exclude elderly patients from cancer treatment clinical trials on the basis of chronological age is largely because older patients are more likely to have serious comorbid conditions and have reduced organ function which can lead to higher drug - related toxicities . many elderly people , however , do not have any measurable loss of functional capacity and are free from significant medical problems . in canada , it has been estimated that 45% of those 7584 years of age and 22% of those 85 years of age and older are in overall good health . in addition , studies have shown that age alone is not significantly associated with adverse prognosis . this suggests that elderly patients should not be excluded from therapeutic opportunities solely on the basis of age . the care of elderly patients is , however , often complicated by comorbidities , frailty , and decreased organ function . the purpose of this study was to describe the receipt of chemotherapy provided to elderly patients with sclc in alberta , canada , and assess their chemotherapy tolerance and survival . we also sought to identify the reasons for not recommending chemotherapy and for dose reductions and assess the relationship of patient age in these decisions . in the absence of clear evidence from clinical trials , the analysis of the elderly sclc population through retrospective population - based studies such as this one helps assess and quantify the value of treating elderly cancer patients with chemotherapy . a retrospective , population - based study was conducted on all residents of alberta , canada , diagnosed with sclc at the age of 75 years or older in years 20042008","the treatment of elderly cancer patients is complicated by many factors . we sought to assess the uptake and tolerance of chemotherapy among patients 75 years and older diagnosed with small cell lung cancer ( sclc ) in years 20042008 in alberta , canada , and assess their survival . all patients who met the above criteria and had an oncologist - consult were included . data were obtained from the alberta cancer registry and chart review . a total of 171 patients were included in the study , 117 ( 68% ) of whom began chemotherapy . of those , 52% completed all cycles , 66% did not have any dose reductions , and 31% completed all cycles at the recommended dose . the risk of death",380,128,0.3368
pubmed-summarization,"cm in size . the wide upper portion of the mass has 2 small appendages at either corner that are each 1 cm long ( . the narrow lower end of the mass was firm in consistency ( arrow in . 2 ) . we opened the mass and observed amniotic fluid and two dead fetuses , each 6 cm in length ( . the mass wall was thin in the upper segment and thick in the lower segment . the portion of the mass representing the cervix was solid and did not have an internal opening or cervical canal , as confirmed using a fistula probe . tissue samples taken from the upper and lower portions of the specimen for histopathological analysis both exhibited the smooth muscle fiber arrangement of uterine tissue . one year later , a hysterosalpingogram showed a normal uterine cavity and two patent fallopian tubes ( . a few months later , she became pregnant , and she had a full term pregnancy with normal vaginal delivery . she had four subsequent pregnancies over 9 years that all reached full term and all resulted in normal vaginal deliveries . there was a lack of a full medical history and poor communication between the gynecologist and the ultrasonographist . thus , despite the proficiency of the ultrasonographist , during two examinations , he did not thoroughly examine all pelvic organs once he detected a twin miscarriage in what appeared to be a uterine cavity . if he had examined all pelvic organs , he should have detected the empty normal uterus just beside the gravid abnormal uterus as it is clear in the post - operative hystersalpingography ( . hysteroscopy could have been useful in this case , but unfortunately , the only available hysteroscope in the hospital was broken - down . most of the congenital anomalies of the uterus are due to a fault in one or more step in the fusion process of the mullerian ducts . in this case , however , the accessory uterus most probably developed as a growth from the right mullerian duct generating an incompletely developed separate accessory uterus ( non - communicating , cavitated accessory uterus ) acum . most probably , the ovum entered the accessory","highlightsobtaining a detailed medical history is important , and we should not depend on examination tools when dealing with patients.unexplained findings should raise suspicions regarding other possible diagnoses , and the same non - conclusive procedures should not be repeated.following this advice can prevent unnecessary operative procedures and the complication of perforation of the uterus .",380,56,0.1474
dialogsum,"#Person1#: Have you ever witnessed any crimes or accidents? #Person2#: I don't quite remember. Why did you ask that? #Person1#: I was taking a walk in the park early this morning when suddenly I heard someone calling ' help '. I rushed over and saw a man beating a woman. #Person2#: Oh, my. What did you do? #Person1#: I guess I was stunned for a moment, then I quickly ran away to get help. #Person2#: Did you call the police? #Person1#: Yes. Fortunately, I had my cell with me this morning. I called the police as I was running to get people to come to help.",#Person1# tells #Person2# the experience of witnessing a crime this morning.,106,11,0.1038
scientific_lay_summarisation-elife-norm,"(Valitutti et al. , 1995; Varma et al. , 2006; Rivas et al. , 2004; Babich et al. , 2012; Yi et al. , 2012). Thus, the mechanisms that control actin organization and flow at the synapse are key to understanding synapse formation as well as T-cell signaling. TCR stimulation is known to drive actin reorganization by activating the Rho-family GTPases Rac1 and Cdc42, which function via Wiscott-Aldrich syndrome protein (WASp) and WASp-family verprolin homologous protein (WAVE2) to initiate actin nucleation through the Arp2/3 complex (Billadeau et al. , 2007). Recent studies have shown that actin polymerization collaborates with myosin IIA contractility to drive retrograde actin flow from the lamellipod to the ADZ, although there is some disagreement as to their relative contributions (Babich et al. , 2012; Yi et al. , 2012). The mechanisms that control retrograde flow at the synapse are still not fully understood, and the possibility remains that a master regulator of some kind may act on a global scale to organize this process. Indirect evidence suggests that intracellular Ca2+ may regulate actin organization and dynamics at the synapse. Elevated intracellular Ca2+ ([Ca2+]i) in T cells has been associated with such cytoskeleton-dependent processes as motility arrest (Negulescu et al. , 1996; Bhakta et al. , 2005), cell rounding (Donnadieu et al. , 1994), cell spreading (Bunnell et al. , 2001) and synapse stabilization (Negulescu et al. , 1996; Krummel et al. , 2000; Delon et al. , 1998). In addition, T cells express a range of Ca2+-sensitive proteins known to regulate actin depolymerization, severing, bundling, and capping (Babich and Burkhardt, 2013; Joseph et al. , 2014; Janmey, 1994). TCR engagement is known to elicit Ca2+ influx through CRAC channels via a cascade in which PLCγ generates inositol 1,4, 5-trisphosphate (IP3), releasing Ca2+ from the ER and causing the ER Ca2+ sensor STIM1 to redistribute to ER-plasma membrane (PM) junctions (Wu et al. , 2006; Luik et al. , 2006) where it traps and activates Orai1, the pore-forming subunit of the CRAC channel (Luik et al. , 2006; Wu et al. , 2014). STIM1 and Orai1 colocalize at early times at the immune synapse (Lioudyno et al. , 2008; Barr et al. , 2008) and later at the distal pole of the cell (Barr et al. ,","An effective immune response requires the immune system to rapidly recognize and respond to foreign invaders. Immune cells known as T cells recognize infection through a protein on their surface known as the T cell receptor. The T cell receptor binds to foreign proteins displayed on the surface of other cells. This interaction initiates a chain of events, including the opening of calcium channels embedded in the T cell membrane known as CRAC channels, which allows calcium ions to flow into the cell. These events ultimately lead to the activation of the T cell, enabling it to mount an immune response against the foreign invader. As part of the activation process, the T cell spreads over the surface of the cell that is displaying foreign proteins to form",380,128,0.3368
scientific_lay_summarisation-elife-norm,"must be particularly important for the proper proliferation of human neural progenitors (Siller and Doe, 2009; Megraw et al. , 2011). In support of this possibility, mutations in the centriolar components CPAP (DSas-4 in Drosophila, here called dCPAP) and STIL (Ana2 in Drosophila, here called dSTIL) in flies lead to defects in the asymmetric division of larval neural stem/progenitor cells (Basto et al. , 2006). Mutations in MCPH proteins in mice, however, lead to complex phenotypes that can include, but are not restricted to, microcephaly (McIntyre et al. , 2012). Moreover, compelling genetic links are now emerging between centrioles/centrosomes and DNA damage repair (DDR) pathways: mutations in certain MCPH genes and in genes encoding other centriole/centrosome proteins can lead to Seckel syndrome and MOPD, pathologies normally associated with defects in DDR (Megraw et al. , 2011). Thus, the cellular mechanisms that lead to pathology when centriole/centrosome proteins are mutated in humans remain unclear. Centrioles are complex structures, but work in several model systems revealed only a small number of conserved proteins to be important for centriole assembly. These include PLK4/SAK, SAS-6, STIL/Ana2, CPAP/CenpJ/SAS-4, Cep152/Asl, and CEP135 (Brito et al. , 2012; Gonczy, 2012). Several studies have identified a complex web of putative interactions between these proteins (Cizmecioglu et al. , 2010; Dzhindzhev et al. , 2010; Hatch et al. , 2010; Tang et al. , 2011; Vulprecht et al. , 2012; Lin et al. , 2013). However, an understanding of centriole architecture and its assembly mechanisms will ultimately require high-resolution structures of the key centriolar components and their complexes. The power of combining structural studies with protein biochemistry and functional in vivo experiments has been demonstrated by work on SAS-6. These studies revealed how SAS-6 homo-oligomerises to organise the central cartwheel (Kitagawa et al. , 2011b; van Breugel et al. , 2011), the earliest structurally defined intermediate in centriole assembly (Brito et al. , 2012; Gonczy, 2012), and suggested how SAS-6 might interact with SAS-5, the proposed STIL homologue in worms (Qiao et al. , 2012). Additionally, high-resolution structures of Sak/Plk4 fragments have recently been solved (Leung et al. , 2002; Slevin et al. , 2012). However, equivalent studies with other core centriolar components or especially their complexes are currently missing, and how any of these proteins might be structurally","Organisms—and individual tissues—grow and develop by dividing their cells. However, the process of cell division does not have to be symmetric, and the fates of the cells can be very different if cellular contents, including RNAs or proteins, are exclusively retained in the ‘mother’ or passed to her ‘daughter’. Organelles known as centrioles can play an important part in influencing whether cell division is symmetric or asymmetric. Centrioles contain ordered assemblies of various proteins, and mutations in some of these proteins can cause developmental defects in humans. For example, mutations in the centriolar proteins CPAP and STIL cause a syndrome known as microcephaly, in which the brain is smaller than normal. Although CPAP and STIL are known to bind each other, how they interact on a molecular level",380,128,0.3368
dialogsum,"#Person1#: What's the weather like in your city? #Person2#: In the summer it gets very hot. The temperature is between often 37 and 40 centigrade. When it is hot we often get rains. The winters are drier. #Person1#: The summer temperature usually often reaches about 20 or25 in my city. The rain falls mostly in the winter. And we often get snow. #Person2#: What are the temperatures in winter? In my city it is about 15 or 20 degrees. #Person1#: In winter temperature often falls to zero at night temperature can be below that. The streets are often icing in the morning. With high such temperatures you must get some thunderstorms. #Person2#: Yeah, we do. In the middle of summer there can be found storms every day usually in the afternoon. I heard your city has a lot of fog, is that true? #Person1#: We do have a few fog days in winter. But I would not say we have a lot of fogs. The sky are usually clearly in your city, are they? #Person2#: Yes, they are like I said we have thunderstorms. But each one usually last a few hours. Then the skys are clear again. #Person1#: Have you ever had snow in your city? #Person2#: My grandmother said there was snow once when she was a child. But my parents and I never see it outside of my city. #Person1#: The river in my city sometime freeze over. People go ice-skating on it. In summer people go boating on the river. But few people go swimming because it is not very clean. #Person2#: As you know, my city is on the coast. the water is also not clean. But people still go swimming all year around. I prefer to sand bath on the beach when the weather is hot and sunning.","#Person1# and #Person2# compare the weather of summer and winter in their cities. #Person1# disagrees with #Person2#'s idea that #Person1#'s city has a lot of fog. The water in both cities is not clean. Few people in #Person1#'s city go swimming, while people in #Person2#'s city go swimming all year round.",304,51,0.1678
scientific_lay_summarisation-elife-norm,", 2003). Absorption of photons by the chromophore induces conformational changes in the channel that allow for the passage of cations across the cell membrane in which it is expressed (Boyden et al. , 2005). This direct photo-gating makes ChR2 useful for manipulating neuronal activity in vitro (Boyden et al. , 2005; Li et al. , 2005; Zhang and Oertner, 2007) and in vivo (Markram et al. , 2004; Li et al. , 2005; Nagel et al. , 2005; Petreanu et al. , 2007; Douglass et al. , 2008; Huber et al. , 2008; Mahoney et al. , 2008; Ayling et al. , 2009; Baier and Scott, 2009; Guo et al. , 2009; Liu et al. , 2009; Zhu et al. , 2009; Katzel et al. , 2011; Schultheis et al. , 2011; Boyd et al. , 2012; Britt et al. , 2012; English et al. , 2012; Beltramo et al. , 2013; Chen et al. , 2013; Chiu et al. , 2013; Owen et al. , 2013). Coupled with genetically-targeted expression, ChR2 affords exquisite functional control of specific neuronal subpopulations. Many studies to date that utilized ChR2 for in vivo manipulation of behavior and/or circuit function have largely focused on the activation of principal excitatory neurons, particularly in the cortex (Petreanu et al. , 2007; Huber et al. , 2008; Ayling et al. , 2009; Boyd et al. , 2012; Britt et al. , 2012; Beltramo et al. , 2013; Chen et al. , 2013). As the experimental applications of ChR2 move to include biophysically diverse interneurons (Markram et al. , 2004; Katzel et al. , 2011; Schultheis et al. , 2011; English et al. , 2012; Chiu et al. , 2013; Owen et al. , 2013), a fuller understanding of its possibilities and limitations becomes essential. Although ChR2 expression, trafficking, and activation has been achieved in most types of nervous tissue (Li et al. , 2005; Nagel et al. , 2005; Bi et al. , 2006; Schroll et al. , 2006; Adamantidis et al. , 2007; Zhang et al. , 2007; Douglass et al. , 2008; Mahoney et al. , 2008; Baier and Scott, 2009; Guo et al. , 2009; Han et al. , 2009; Liu et al. , 2009; Zhu et al. , 2009; Gourine et al.","The brain is a highly complex structure composed of trillions of interconnecting nerve cells. The pattern of connections between these cells gives rise to the various brain circuits that govern how the brain functions. Understanding how the brain is wired together is important for determining how ‘faulty circuits’ contribute to various neurological disorders. New optogenetic technique tools allow neuroscientists to turn on specific neurons simply by shining light on them. These techniques involve genetically manipulating the organisms so that their neurons express proteins that are activated when they are exposed to light of a particular wavelength. However, it is important to understand the limitations of this approach—including the possibility that the light might actually turn off some neurons—when using it to study animal behavior. Now, Herman, Huang et",380,128,0.3368
scientific_lay_summarisation-elife-norm,"P-selectin glycoligand-1 (PSGL-1) and CD40, respectively, on leukocytes (Lievens et al. , 2010; Mayadas et al. , 1993; Palabrica et al. , 1992). As platelets must be potently activated to facilitate P-selectin/CD40L exposure, such interactions unlikely mediate the early platelet-leukocyte interactions that occur in the murine DVT model. Consistent with this, lack of platelet P-selectin has no effect upon either leukocyte recruitment or thrombus formation in murine DVT (von Brühl et al. , 2012). Leukocytes can also indirectly interact with platelets through Mac-1 (integrin αMβ2), which can associate with activated αIIbβ3 via fibrinogen (Weber and Springer, 1997), or directly via GPIbα (Simon et al. , 2000). Interactions are also possible through lymphocyte function-associated antigen 1 (LFA-1/integrin αLβ2) that can bind intercellular adhesion molecule 2 (ICAM-2) on platelets (Damle et al. , 1992; Diacovo et al. , 1994). In both instances though, leukocyte activation is necessary to activate Mac-1 or LFA-1 integrins before interactions can occur. Although it is often assumed that only activated platelets bind leukocytes, recent studies have revealed that platelets captured under flow by VWF released from activated endothelial cells can recruit leukocytes (Doddapattar et al. , 2018; Zheng et al. , 2015). If VWF-GPIbα-dependent signaling is capable of promoting leukocyte binding, this may be highly relevant to the non-hemostatic platelet functions (particularly when other agonists are not available/abundant), but may also provide major mechanistic insights into the early recruitment of leukocytes during the initiation of DVT. Genome wide association studies (GWAS) on venous thromboembolism (VTE) have identified a panel of genes (ABO, F2, F5, F11, FGG, PROCR) with well-described influences upon coagulation and thrombotic risk, as well as those with well-established causative links (e. g. PROS, PROC, SERPINC1) (Germain et al. , 2015; Germain et al. , 2011; Rosendaal and Reitsma, 2009). This is consistent with the efficacy of therapeutic targeting of coagulation to protect against DVT with anticoagulants (Chan et al. , 2016). However, although the use of anticoagulants is effective, dosing and efficacy are limited by the increase in the risk of bleeding in treated individuals (Chan et al. , 2016; Schulman et al. , 2014; Schulman et al. , 2009; Schulman et al. , 2013; Wolberg et al. , 2015). Therefore, alternative targets that inhibit DVT disease processes, but that do not modify bleeding","Platelets in our blood form clots over sites of injury to stop us from bleeding. Blood clots can also occur in places where they are not needed, such as deep veins in our legs or other regions of the body. Developing such clots – also known as deep vein thrombosis (or DVT for short) – is one of the most common cardiovascular diseases and a major cause of death. Although certain inherited factors have been linked to DVT, the underlying mechanisms of the disease remain poorly understood. In addition to platelets, the pathological (or dangerous) clots that cause DVT also contain immune cells called neutrophils which fight off bacterial infections. Platelets are recruited to the wall of the vein by a protein called “von Willebrand Factor” (or VWF",380,128,0.3368
pubmed-summarization,"dl , and a significantly elevated alkaline phosphatase level at 65.3 g / l . preoperative mri , t1 with contrast , showing an ethmoid mass extending through the cribriform intracranially . the patient underwent a combined endoscopic endonasal approach to the anterior skull base with tumor resection . the cribriform defect and intraoperative cerebrospinal fluid ( csf ) leak pathology revealed a vascular neoplasm with a uniform cluster of ovoid cells arranged around the vessels and moderate focal nuclear enlargement ( . tumor cells stained positive for cd31 and smooth muscle actin ( sma ) but negative for cd34 , s100 , and pan - cytokeratin on immunohistochemistry ( . the patient reported near - complete resolution of bone pain and improvement in smell , and he had normalization of phosphate , alkaline phosphatase , vitamin d , and other laboratory values . repeat mri showed gross total resection of the mass and no detectable recurrence ( . 4 ) . postoperative mri , t1 with contrast , showing gross total resection of the mass with nasoseptal flap reconstruction of the skull base . osteomalacia is a disease of the bone characterized by defective mineralization of osteoid from decreased levels of available phosphate and calcium or increased bone resorption . it often presents with diffuse joint and bone pain , easy fracturing , difficulty walking , weakness , and other nonspecific symptoms . oo is a rare , disabling , and curable form of osteomalacia that affects both sexes equally and usually presents around 40 years of age.6 it is not well described in glomangiomas but has been detailed several times in relation to glomangiopericytomas and other soft tissue and bone tumors , with more than 300 reported cases7 since its debut in 1947.8 it predominantly occurs in the context of mesenchymal tumors and is thought to be due to neoplastic overexpression of fgf23 . this protein inactivates the sodium - phosphate pump in the proximal tubule ( prohibiting phosphate reabsorption and inducing renal phosphate wasting ) and reduces 1-hydroxylation of 25-hydroxy vitamin d.9 accordingly , common oo laboratory abnormalities include hypophosphatemia , normal or decreased calcium , decreased 1,25-dihydroxy vitamin d3 with resistance to vitamin d supplementation , and elevated alkaline phosphatase , which our patient exhibited .","oncogenic osteomalacia ( oo ) is an uncommon but treatable cause of osteomalacia related to tumor production of fgf23 , usually caused by benign mesenchymal neoplasms . paranasal sinus glomangiomas are a rare cause of oo , with only one previously reported case . here we describe a second case ( first reported in english ) of paranasal sinus glomangioma - induced osteomalacia in a 42-year - old man . he presented with weakness and multiple spontaneous fractures , and was found to have an ethmoid sinus glomangioma with intracranial extension . the tumor was removed via endoscopic endonasal approach to the anterior skull base , which resulted in complete resolution of symptoms and no further evidence of disease 1 year postoperatively .",380,123,0.3237
scientific_lay_summarisation-elife-norm,"The mammalian heartbeat is thought to begin just prior to the linear heart tube stage of development. How the initial contractions are established and the downstream consequences of the earliest contractile function on cardiac differentiation and morphogenesis have not been described. Using high-resolution live imaging of mouse embryos, we observed randomly distributed spontaneous asynchronous Ca2+-oscillations (SACOs) in the forming cardiac crescent (stage E7. 75) prior to overt beating. Nascent contraction initiated at around E8. 0 and was associated with sarcomeric assembly and rapid Ca2+ transients, underpinned by sequential expression of the Na+-Ca2+ exchanger (NCX1) and L-type Ca2+ channel (LTCC). Pharmacological inhibition of NCX1 and LTCC revealed rapid development of Ca2+ handling in the early heart and an essential early role for NCX1 in establishing SACOs through to the initiation of beating. NCX1 blockade impacted on CaMKII signalling to down-regulate cardiac gene expression, leading to impaired differentiation and failed crescent maturation. The heart is the first organ to form and function during mammalian embryonic development. In the mouse, mesoderm originating from the primitive streak forms a bilateral pool of progenitor cells that at E7. 5 give rise to the cardiac crescent (CC). The CC subsequently expands and migrates to the midline whereupon, between E8. 25 and E8. 5, the two sides of the CC fuse and form the linear heart tube (LHT) (reviewed in Buckingham et al. , 2005). The first cardiac contractions have been described during the transition from CC to LHT. Studies of heart development in model organisms have historically focused on the origin and spatial-temporal allocation of cardiac progenitors and cardiovascular lineage determination (Buckingham et al. , 2005; Saga et al. , 1996; Cai et al. , 2003; Meilhac et al. , 2004; Wu et al. , 2006; Moretti et al. , 2006; Evans et al. , 2010; Devine et al. , 2014). Whilst insight into the identification and regulation of cardiac cell types is important for improved understanding of congenital heart disease (Bruneau, 2008), an anatomical and cellular bias has overlooked a role for the onset of cardiac function. Early descriptions of initial cardiac contractions (Navaratnam et al. , 1986), including suggested pacemaker activity on either side of the embryonic midline (Goss, 1952), as well as optical mapping of spontaneous action potentials performed in both chicken (7","The heart is the first organ to form and to begin working in an embryo during pregnancy. It must begin pumping early to supply oxygen and nutrients to the developing embryo. Coordinated contractions of specialised muscle cells in the heart, called cardiomyocytes, generate the force needed to pump blood. The flow of calcium ions into and out of the cardiomyocytes triggers these heartbeats. In addition to triggering heart contractions, calcium ions also act as a messenger that drives changes in which genes are active in the cardiomyocytes and how these cells behave. Scientists commonly think of the first heartbeat as occurring after a tube-like structure forms in the embryo that will eventually develop into the heart. However, it is not yet clear how the first heartbeat starts or",380,128,0.3368
dialogsum,"#Person1#: hello, do you remember me? I bought some vases from you yesterday. #Person2#: yes, you sent them to New York, right? #Person1#: that's right. I thought I'd come back to buy some more souvenirs. #Person2#: what did you in mind? #Person1#: well, first, I'd like to buy a few postcards. My sister used to always send a postcard to herself whenever she went anywhere. I want to do that, too. #Person2#: we have plenty of postcards to choose from here. The same designs can be found on these posters. #Person1#: posters are difficut to travel with. I think I'll just buy the postcards. I heard that you might also have some of the masks that are made in Venice. #Person2#: yes, we do. They're on the wall behind you. #Person1#: how much do they cost? #Person2#: the prices are clearly marked on the back of each mask. Would you like me to get one down for you to look at? #Person1#: yes, I think I'd like the green mask in the middle. #Person2#: here you go. #Person1#: I'll take it, I'd also like to buy some chocolate. #Person2#: are you looking for some homemade chocolate as a gift. #Person1#: yes, it's my girlfriend's birthday today and she loves chocolate. #Person2#: we've got plenty to choose from here. #Person1#: they look delicious. I think she'll be pleased.","#Person1# comes back to #Person2#'s shop where #Person1# bought vases yesterday to buy more souvenirs. #Person2# assists #Person1# to choose a few postcards for #Person1#'s sister, some masks made in Venice and some chocolate for #Person1#'s girlfriend.",227,37,0.163
scientific_lay_summarisation-elife-norm,", 2004; Shah et al. , 2000; Bowman et al. , 2000; Berg et al. , 2000; Barkus et al. , 2008; Hendricks et al. , 2010; Rosa-Ferreira and Munro, 2011; Maday et al. , 2012; Kamal et al. , 2000; Lazarov et al. , 2005; Fu and Holzbaur, 2013; Almenar-Queralt et al. , 2014; Rao et al. , 2017), including autophagosomes (Ravikumar et al. , 2005; Katsumata et al. , 2010; Cheng et al. , 2015), mitochondria, and ionotropic glutamate receptors (Horak et al. , 2014). Defects or perturbations in dynein function lead to mislocalization of these cargoes, and results in an accumulation of protein aggregates at the neurite tip (Ravikumar et al. , 2005; Levy et al. , 2006). In fact, accumulation of misfolded protein aggregates in the neuronal cytoplasm is a common pathological hallmark for motor neuron disease (He et al. , 2005; LaMonte et al. , 2002; Lin and Schlaepfer, 2006). Consistent with an important role for dynein in neuronal health (Schiavo et al. , 2013), mouse models with dynein mutations exhibit severe neuropathy, and decreased rates of retrograde axonal transport, among other defects (Hafezparast et al. , 2003; Chen et al. , 2007; Ori-McKenney et al. , 2010). In addition to its key role in the retrograde trafficking of cargoes, dynein also plays a critical and conserved role during neuronal development by promoting interkinetic nuclear migration (INM) in neuronal progenitor cells, and in the subsequent migration of young postmitotic neurons. During the former process, which is critical for neurogenesis, nuclear envelope anchored dynein motors promote migration of the nucleus from the basal to the apical surface of the neuroepithelium where mitotic divisions occur (Tsai et al. , 2010; Hu et al. , 2013; Del Bene et al. , 2008). Thus, defects in dynein-mediated nuclear migration can lead to defects in early brain development. Given its myriad roles in neuronal processes, it is unsurprising that mutations within the catalytic component of the dynein complex (the dynein heavy chain, or DHC, which is encoded by the DYNC1H1 gene) are found in individuals suffering from a wide array of neurodegenerative diseases. For instance, mutations in dynein underlie many cases of malformations of cortical development (MCD), spinal muscular atrophy with lower extremity dominance (SMA-LED), congenital muscular dystrophy (CMD), and","Motor proteins maintain order by transporting biomolecules and various structures within living cells. Dynein is one such motor that moves many types of cargoes along tracks called microtubules, which are spread across the cell’s interior. This motor is particularly important in nerve cells, which can be very long and thus depend heavily on motor proteins to ensure cargoes end up where they are needed. This becomes especially apparent in human diseases that arise as a consequence of mutations in the genes that produce components of the dynein motor. It is assumed that these genetic changes simply prevent dynein from working properly, which ultimately affects the health and survival of cells. However, it is currently unknown what specific effect these mutations have on dynein’s role within the cell, and",380,128,0.3368
dialogsum,"#Person1#: Hi, what're you reading? #Person2#: An old book Death on the Nile. Have you read it? #Person1#: Not yet, but I saw the movie. Could I borrow it when you finish reading? #Person2#: Sure. But you need to be patient.",#Person2# is reading an old book and will lend it to #Person1#.,41,12,0.2927
dialogsum,"#Person1#: I've been worried that Richard is frozen. #Person2#: What sounds to be a problem? #Person1#: Well, he has trouble concentrating when getting along with other children. I was wondering there might be something on his mind. Some problem at home?",#Person1# tells #Person2# Richard has trouble concentrating when getting along with other children.,41,13,0.3171
dialogsum,"#Person1#: Thank you, Thank you and welcome to everyone's favorite game show, Unbelievable Trivia. Today's contestant, Julie Jones, has just entered our bonus round and is trying to win our grand prize, $30,000 in cash and an all-expense paid, six-day vacation to China. Okay, Julie. In order to win the grand prize, you must answer all four of the bonus questions correctly. All of the questions are true or false. If false, you must make the statement true by giving the correct information. If not, you go home with our consolation prize: a fine set of encyclopedias on home repairs. [Oh] Remember. When the buzzer goes off, you must give your answer. Are you ready? #Person2#: I'm ready. #Person3#: The first question: A cat has 32 muscles in each ear. #Person2#: Uh. True. #Person3#: You are correct! Question number two: A tuna is the only fish that can blink with both eyes. #Person2#: True, I mean, I mean, I mean false. A SHARK is the only fish that can blink with both eyes. #Person3#: Correct. Only two more questions. Number three: An elephant has the largest eyes in the world. #Person2#: I know that one. False. The giant squid has the largest eyes. #Person3#: Super. This is the last question Julie. The national anthem of Greece has 134 verses. #Person2#: False. The national anthem of Greece has 158 verses. #Person3#: You are right! #Person2#: Did I win? #Person3#: Yes, Julie, pack your bags, and we'll pack your wallet. [Alright!] You're off to China. Well, that's all for today's show. See you next time #Person2#: Thank you, Thank you.","Julie Jones participates in the game show, Unbelievable Trivia. #Person1# introduces the rules of the game and asks Julie four questions. Julie answers correctly and gives the correct information, so she'll enjoy the all-expense paid to China.",268,37,0.1381
scientific_lay_summarisation-elife-norm,"and control we need to model the underlying system. First, the nature of the representation matters: although saccades are often simplistically viewed as ballistic (or open-loop) movements, these movements are monitored online through the corollary discharge (Van Gisbergen et al. , 1981; West et al. , 2009; Goossens and Van Opstal, 2000; Xu-Wilson et al. , 2011; Sommer and Wurtz, 2008; Optican, 2009). Second, sensory feedback matters: we are not ‘blind’ during saccades. There is no peripheral interruption of sensory inflow, and information about specific spatiotemporal frequency or color is still good (Burr et al. , 1994; Burr and Morrone, 1996). Moreover, target jumps during long saccades can influence movement (Gaveau et al. , 2003). We should thus model saccades as driven by closed-loop control (1a). 10. 7554/eLife. 25073. 003Figure 1. Model architecture and simulations of eye movements. (a) Schematic representation of the control and estimation architectures. We consider a closed loop controller based on optimal feedback control and state estimation. The dynamics of the eye plant corresponded to a second order system with time constants taken from the literature (13 ms and 224 ms). Bottom: Optimal state estimator based on usual Kalman filtering, and augmented with the extrapolation of sensory feedback to compensate for sensorimotor delays (Sensory Extrapolation, red box). The symbolic representation of the signals in blue follows the same notations as in the Materials and methods: y (t) is the sensory feedback, x^ (t|y) is the extrapolation of sensory feedback, u (.) is the sequence of previous and current control commands, x^P (.) and x^ (.) are the prior and posterior estimates at the corresponding time steps. (b) Top: Modeled saccadic eye movement from the first (x1*) to the second fixation target (x2*). Bottom: Associated control function. Time zero corresponds to the end of the fixation period to the first target. (c) Illustration of the sensory extrapolation performed in the state estimator. The simulated task is to track the target, which suddenly starts moving (velocity jump) with or without position jump in the opposite direction. The simulated eye trajectory shows how the extrapolation of target motion over the delay interval generates a catch up saccade (black arrow). This compensatory movement is also illustrated in the velocity trace. : http: //dx. . org/10. 7554/eLife. 25073. 003 To describe","Although we have the impression that our eyes move smoothly from place to place, we in fact perform rapid eye movements called saccades several times per second. Experiments have shown that our ability to perceive contrast and flashes decreases before and during each saccade. This phenomenon is known as saccadic suppression. A prevailing hypothesis to explain saccadic suppression suggests that by making vision temporarily less sharp for the rapid eye movement, the nervous system discards visual information about movement and helps us to perceive the world as stable. However, this does not explain the timing of saccadic suppression. Indeed, for saccades of about 50 milliseconds, the brain begins to reduce the sharpness of vision roughly 100 milliseconds before each eye movement begins. Why does the brain discard so",380,128,0.3368
dialogsum,"#Person1#: Mr. Black, I ' d like to take some time off. I ' Ve been feeling exhausted these days. #Person2#: That's no problem. Let me see... You still have ten days annual leave left, is that right? #Person1#: Yes. I was wondering if I could take another two weeks off. #Person2#: That's long leave. How's your project coming along? #Person1#: The project I'm in charged of now will be done by the end of this week. I'd like to take my leave from next Monday on. #Person2#: Well, all right. But you make sure to tie up loose ends before you leave. #Person1#: Thank you, Mr.Black. There are no immediate projects coming up at the moment. Mr.Smith will be in charge during my absence. He is taking part in several projects as my assistant and knows how to maintain relationships with our clients. #Person2#: Great! I hope you have a good relaxation and come back refreshed. #Person1#: I will. Many thanks, Mr.Black.",#Person1# would like to take some time off. Mr. Black asks #Person1# about the progress of #Person1#'s project. #Person1# tells Mr. Black that Mr. Smith will be in charge during #Person1#'s absence. Mr. Black agrees.,163,35,0.2147
scientific_lay_summarisation-elife-norm,"whether these changes were due to a general activity increase for all reading conditions, we computed a whole-brain ANOVA interaction analysis of the signal change following the course for reading visual words, visual Braille words and tactile Braille words versus their respective control tasks ([tactile Braille vs. tactile control - (visual Braille vs. visual Braille control+visual words vs. visual words control) ] x (after course-before course) ) (see' Materials and methods' ). Relative to visual reading, tactile reading led to increased activation in the VWFA (1F; MNI -45 -61 -12, Z = 4. 05) and other parietal and frontal areas (Table 1). The results demonstrated that this pattern of activation in visual cortex was observed specifically for tactile reading. Indeed, we found no increase in activation to visual words following the course. The only increases in activation to visual Braille were found in the default mode network nodes in the parietal and prefrontal cortices (— 3C, Table 2, Appendix 1. 3). Importantly, the analyses mentioned in this section (1D–F), including the whole-brain ANOVA, did not reveal any activation in the primary and secondary somatosensory cortices, even at an exploratory threshold of p=0. 01 voxel-wise. Our subjects' progress in tactile reading was not homogeneous, with some subjects being entirely unable to learn Braille at all (0 WPM) and other subjects reaching a speed of 17 WPM (Appendix 1. 1). We therefore used regression to ask which fMRI responses to tactile Braille reading were modulated by the subjects’ tactile reading speed. This regression analysis revealed one significant cluster, located in the left inferior occipital gyrus (1G; MNI = -45 -76 -12, Z = 3. 69, Table 3). A similar result was obtained when we correlated single letter recognition speed with tactile Braille activations, which further supports the significance of the visual cortex in learning to read Braille (Table 3, Appendix 1. 4). We found no such correlations for other reading speed measures (e. g. visual Braille reading speed) or imagery activations (e. g. imagining tactile Braille; see Appendix 1. 5). These observations indicate that the ventral visual activations for tactile reading cannot be explained as a by-product of imagery. Visual words, visual Braille and tactile Braille all elicited activity in the VWFA. How similar are the neural representations of these three scripts?","According to most textbooks, our brain is divided into separate areas that are dedicated to specific senses. We have a visual cortex for vision, a tactile cortex for touch, and so on. However, researchers suspect that this division might not be as fixed as the textbooks say. For example, blind people can switch their' leftover' visual cortex to non-visual purposes, such as reading Braille – a tactile alphabet. Can this switch in functional organization also happen in healthy people with normal vision? To investigate this, Siuda-Krzywicka, Bola et al. taught a group of healthy, sighted people to read Braille by touch, and monitored the changes in brain activity that this caused using a technique called functional magnetic resonance imaging. According to textbooks, tactile reading should engage the tactile",380,128,0.3368
dialogsum,"#Person1#: What do you say we stop in at that Burger King over there and grab a bite? #Person2#: Forget it! If you think I'd ever set foot that inferior restaurant again, you gotta be nuts. Last time I ate that food, almost vomited. The service in there is terrible. It was the first time I ever stiffed a waiter #Person1#: Yeah, not seeing a single person anywhere informed me. Hey! How about that one over there? #Person2#: Oh, give me a break! That place is too lavish for us. #Person1#: Easy. It's on me. #Person2#: In that case, I'm right behind you.",#Person1# suggests going to Burger King but #Person2# refuses. #Person1# will treat #Person2# in a lavish place.,103,17,0.165
pubmed-summarization,"part of the proximal tubule . since the start of the 20 century , phlorizin , a toxic 2-glucoside of phloretin , has been known to increase glycosuria , and has been used in the study of renal function.16,17 during the 1930s , phlorizin was used in non - invasive human experiments that revealed some of the fundamental mechanisms of renal hemodynamics and metabolic transport.18 in the 1950s , studies delineated phlorizin s mechanism of action on inhibition of glucose transport in the kidney and small intestine at the cellular and molecular levels . renal micropuncture studies conducted with phlorizin in the 1970s showed that the transporter was located in the brush border of the proximal tubule , and that sodium was required for the renal absorption of glucose.11,19,20 studies performed since then confirmed that phlorizin is a competitive inhibitor of glucose transport , with a binding affinity for the transporter that is 1000- to 3000-fold greater than that of glucose.21 the rabbit homolog of the human type 1 sodium - glucose transporter ( sglt1 ) , which is coded by the slc5a gene , was the first mammalian cotransporter carrier protein to be identified , cloned , and sequenced.22 a family of slc5a gene sodium - dependent transporters has since been sequenced and identified in a broad range of tissues.23,24 sglt1 and sglt2 are , perhaps , the slc5a family members that have received greatest coverage within the literature . the high affinity , low capacity slgt1 is the main gastrointestinal glucose transporter the relatively widespread distribution of sglt1 is contrasted by the almost exclusive expression on the luminal surface of proximal tubules ( mainly in the renal cortex ) of the low glucose affinity , high capacity sglt2 , responsible for most renal tubular glucose reabsorption.2226 cellular glucose and sodium uptake occurs in a 1:1 ratio ( ) . the sodium : potassium adenosine triphosphatase ( atp ) pump transports sodium across the basolateral surface into the intracellular fluid , maintaining the physiological levels of sodium in the cell . cellular glucose concentrations are maintained by facilitative glucose outflow through transporters in the basolateral membrane of the cell . after binding intracellular glucose the transporters undergo a conformational change that subsequently moderates the movement of glucose ( down","there is a recognized need for new treatment options for type 2 diabetes mellitus ( t2 dm ) . recovery of glucose from the glomerular filtrate represents an important mechanism in maintaining glucose homeostasis and represents a novel target for the management of t2 dm . recovery of glucose from the glomerular filtrate is executed principally by the type 2 sodium - glucose cotransporter ( sglt2 ) . inhibition of sglt2 promotes glucose excretion and normalizes glycemia in animal models . first reports of specifically designed sglt2 inhibitors began to appear in the second half of the 1990s . several candidate sglt2 inhibitors are currently under development , with four in the later stages of clinical testing . the safety profile of sglt2 inhibitors is expected to be",380,128,0.3368
pubmed-summarization,"il ; minneapolis , mn ; and oakland , ca . recruitment balanced enrollment at each site by sex , age ( 1824 years vs 2530 years ) , race , and education . serial followup of participants at years 2 , 5 , 7 , 10 , 15 , 20 , and 25 ( 20102011 ) after enrollment has been performed , with 72% retention of surviving participants at year 20 and 25 . clinical assessments were performed at each cardia visit as described.11 , 12 , 13 , 14 , 15 from an initial cohort of 5115 individuals , we excluded individuals with selfreported congenital heart disease , congestive heart failure , cardiomyopathy , myocarditis , rheumatic heart disease , valvular heart disease ( all assessed at baseline study visit ) , prior myocardial infarction reported at baseline or final study visit , bariatric surgery by final study visit , or withdrawn consent for study participation , leaving 4941 cardia participants ( 97% of the study cohort ) for analysis . to reflect current metrics for metabolic risk assessment in the clinic,16 we defined a metabolic risk score by assigning + 1 point for each of the following 5 highrisk features , based on the third report of the adult treatment panel ( atp iii ) definition of metabolic syndrome17 : ( 1 ) triglyceride concentration 150 mg / dl ; ( 2 ) highdensity lipoprotein concentration 40 mg / dl ( in men ) or 50 mg / dl ( in women ) ; ( 3 ) waist circumference 102 cm ( in mend ) or 89 cm ( in women ) ; ( 4 ) systolic bp 135 mm hg ( mean of two different readings ) , selfreported history of hypertension , or current or former use of bp medication ; and ( 5 ) selfreported diabetes or fasting glucose concentration 100 mg / dl . selfreported diabetes only was used for the fifth criteria in examinations at year 2 and year 5 , as glucose was not measured on these visits . we did not include bmi in the metabolic risk score , as we sought to measure metabolic risk development independent of obesity status . ( cumulative bmi adjustment was performed in logistic","backgrounddespite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk , current guidelines focus on risk assessments later in life , missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease.methods and resultsin 4420 young adults in the coronary artery risk development in young adults ( cardia ) study , we defined a metabolic risk score based on components of the third report of the adult treatment panel 's definition of metabolic syndrome . using latent class trajectory analysis adjusted for sex , race , and timedependent body mass index , we identified 6 distinct metabolic trajectories over time , specified by initial and final risk : lowstable , lowworsening , highstable , intermediateworsening , intermediatestable , and highworsening .",380,128,0.3368
dialogsum,"#Person1#: You know, Mary, I feel we meet somewhere before. Where were you born? #Person2#: I was born in Beijing, but I spent most of my childhood in London. #Person1#: What was your childhood like? #Person2#: I had a pretty strict upbringing, and my parents taught at universities so they have extremely high expectations for me. #Person1#: Where did you go to university? #Person2#: My parents wanted me to stay in Beijing, but I decided to go back to England. I graduated from University of Newcastle upon Tyne with a degree in Cross Culture Communication. #Person1#: What is your current occupation? #Person2#: I am a journalist. I write for China Daily. #Person1#: Did you know that you wanted to be a journalist right after your graduation? #Person2#: No, I didn't. I started working at a university in London but as time went by, I found I did not really like my job. I decided to explore other fields. Journalism is great fit for me as well as a challenge. #Person1#: Do you like your current job? #Person2#: Yes, I came to Beijing two years ago looking for new opportunities. I was lucky because my friend introduced me to my current company.","#Person1# asks Mary some questions about her birthplace, her childhood, her university, and her current occupation. Mary worked at a university in London but decided to explore other fields. Now, she is a journalist and works in Beijing.",201,38,0.1891
dialogsum,"#Person1#: This is the Bell Captain's Desk. May I help you? #Person2#: Yes, I've been waiting for my bags to be sent up for the last half hour. Where are they? #Person1#: I'm very sorry to hear that. May I have your name and room number, please? #Person2#: Yes, it's Yao Lan. Room 406. #Person1#: And how many pieces did you have? #Person2#: Two suitcases and a handbag. The suitcases are blue and the shoulder bag is red. #Person1#: Is there a name tag attached to them? #Person2#: Yes, there is. #Person1#: We're very sorry for the delay. I'll check immediately and call you back.",Yao Lan calls the Bell Captain's Desk to hasten the delivery of her package. #Person1# apologizes and will check for her immediately.,105,22,0.2095
pubmed-summarization,"the main structures related to human memory are the papez circuit , the basolateral limbic circuit , and the basal forebrain , which communicate with each other through white - matter tracts . damage to these structures ( including the communication tracts ) from hemorrhages , infarctions , and tumors can result in memory disturbances.1,2 in addition to these structures , valenstein et al . suggested that the retrosplenium could be a supplementary pathway of the limbic system connecting the anterior thalamus and medial temporal lobe structures.3 the retrosplenium is located in the posterior cingulate cortex surrounding the splenium , and is a cytoarchitecturally distinct structure forming brodmann areas 29 and 304 ( . we report on a patient who developed both verbal and visual memory deficits after an acute infarction of the retrosplenial cortex . a 57-year - old right - handed man who had suffered from diabetes mellitus for 10 years was admitted to an emergency room due to acute memory loss . one month prior to admission he was diagnosed with syphilis and began treatment with penicillin g. on the day of his symptom onset , his daughter noted that he asked repeatedly over the phone about an appointment time for a clinic visit . after the conversation , he asked his daughter what day of the week it was . two days later , accompanied by his daughter , he went to the hospital in order to receive treatment for syphilis , but he did not know why he was there or where he was . therefore , he was transferred to the emergency room for further evaluation . on initial evaluation at the emergency room , his blood pressure was 103/63 mmhg and his heart rate was 75 beats / min and regular . his score on the initial mini - mental state examination ( mmse ) was 22/30 ( memory registration , 3/3 ; memory recall , 0/3 ; orientation to time , 4/5 ; orientation to place , 3/5 ; calculation and concentration , 4/5 ; and reading , 0/1 ) . the visual fields of both eyes were constricted due to a previous panretinal photocoagulation procedure for diabetic retinopathy , but all the other cranial nerve examinations were normal . a cerebrospinal","the retrosplenial cortex is a cytoarchitecturally distinct brain structure located in the posterior cingulate gyrus and bordering the splenium , precuneus , and calcarine fissure . functional imaging suggests that the retrosplenium is involved in memory , visuospatial processing , proprioception , and emotion.we report on a patient who developed reversible verbal and visual memory deficits following a stroke . neuropsychological testing revealed both anterograde and retrograde memory deficits in verbal and visual modalities . brain diffusion - weighted and t2-weighted magnetic resonance imaging ( mri ) demonstrated an acute infarction of the left retrosplenium .",380,96,0.2526
dialogsum,"#Person1#: May I help you? #Person2#: I would like to return this book. #Person1#: May I do anything else for you? #Person2#: I would also like to check out this magazine. #Person1#: I can't let you do that. #Person2#: Why is that? #Person1#: Our policy doesn't allow anyone to check out the magazines. #Person2#: What things am I allowed to check out? #Person1#: You are only allowed to check out books or videos. #Person2#: I really need to check out this magazine. #Person1#: I'm sorry, but that's our policy. #Person2#: That's stupid.",#Person2# wants to check out a magazine. #Person1# refuses because it's against the policy.,92,14,0.1522
dialogsum,#Person1#: Anyone home? Jen! #Person2#: I'm in the kitchen. . . let yourself in! #Person1#: Wow! You're really working up a storm! #Person2#: I know. I've even worked up a sweat. #Person1#: You look like a cooking show host--only messier.,#Person1# visits Jen and Jen's working up a storm in the kitchen.,40,12,0.3
pubmed-summarization,"/ dl ) . most of them developed hypoglycemia ( mean = 60.6 mg / dl ) on day 6 which returned to normal ( mean = 67.3 ) after stoppage of l - asp treatment . similarly , patients in hyperglycemia group had a mean plasma glucose of 86.5 mg / dl . on day 6 , majority of the patients hyperglycemia persisted even after the stoppage of l - asp treatment ( mean = 121.6 mg / dl ) . when the mean plasma glucose levels before the start of treatment with l - asp were compared with the values on day 6 by paired t - test , the p values for the hypo- and hyper - glycemia groups were found to be 0.0012 and 0.0309 , respectively . l - asp , an enzyme , has a wide application in many therapeutic protocols , including all . during all treatment , glucose levels are routinely monitored because many patients develop hyperglycemia , presumably because of glucocorticoids and l - asp . unexpectedly , many of our patients experienced repeated fasting hypoglycemia during induction and maintenance therapy . since altered fpg level can change the clinical outcome of patients , it was thought imperative to probe the exact course of hypo / hyperglycemia so that appropriate measures can be taken . most patients were given native l - asp and only a few were given pegylated l - asp , may be due to cost factor . approximately , one - fifth of the patients on l - asp therapy developed abnormal plasma glucose levels . most of the patients who developed hyperglycemia belonged to higher age group ( median age = 19.5 years ) compared to patients who have developed hypoglycemia ( median age = 5.5 years ) . this may be due to the fact that , in patients with higher age group , pancreatic reserve is less compared to younger age group . however , there is no significant difference between male to female ratio so far l - asp - induced abnormal plasma glucose levels ( hypo- or hyper - glycemia ) are concerned . in this study , as per the american diabetes association 2016 guidelines , fpg 100125 mg / dl","objectives : the objective of this study was to evaluate any abnormal change in plasma glucose levels in patients treated with l - asparaginase ( l - asp)-based chemotherapy regimen in patients of acute lymphoblastic leukemia ( all).materials and methods : this retrospective , hospital - based study was conducted in patients of all , admitted to the clinical haematology department of a tertiary care hospital of odisha from august 2014 to july 2015 . indoor records of 146 patients on multi - centered protocol-841 were evaluated for any alteration in plasma glucose level , time of onset of hypo / hyperglycemia , and persistence of plasma glucose alteration.results:twenty-one percent of patients showed abnormal plasma glucose level . most of these patients developed hypoglycemia and were of lower",380,128,0.3368
pubmed-summarization,"traditionally , this has been via the abdominal or vaginal routes . in the present era , hysterectomies are undertaken using minimal access techniques . total laparoscopic hysterectomy ( tlh ) is performed entirely by the laparoscopic route , including closure of the vaginal vault , with the uterus being removed vaginally or by morcellation . today , lap hysterectomy is a safe and feasible technique to manage benign uterine pathology as it offers minimal postoperative discomfort , shorter hospital stay , rapid convalescence , and early return to the activities of daily living . considerable technical advances in this procedure have occurred during the last few years . in our study , we have modified the steps and started with the ligation of the uterine artery at its origin from the internal iliac artery on both sides causing transient uterine ischemia as most blood enters the uterus through these vessels especially its ascending branch . the hypothesis of this study proposes that , soon after occlusion , blood within the myometrium clots and the myometrium becomes hypoxic . the aim of this study was to compare conventional tlh to prior uterine artery ligation at its origin . total of 52 cases were included in the study of which 26 underwent conventional total laparoscopic hysterectomy and another 26 , underwent uterine artery ligation at its origin prior to total laparoscopic hysterectomy . patients were kept nil by mouth 12 hours before the procedure and no bowel preparation was done prior to surgery . a veress needle is inserted at the umbilicus or supraumbilical site depending on the size of the uterus and abdomen is insufflated with carbon dioxide at initial pressure of 20 mm hg and maintenance at 15 mm hg . a 10 mm trocar is inserted blindly and 10 mm telescope is introduced through this port . three additional 5 mm ports are introduced : one along the left spinoumbilical line at the junction of medial 2/3rd and lateral 1/3rd , second port at right angles to the previous port two ports , and a third 5 mm port placed around 2 cm below and to the right of umbilicus . the entire abdomen is surveyed before starting the procedure . the size of the uterus , presence","we compared the duration of surgery , blood loss , and complications between patients in whom both uterine arteries were ligated at the beginning of total laparoscopic hysterectomy ( tlh ) and patients in whom ligation was done after cornual pedicle . using a prospective study in a gynecologic laparoscopic center , a total of 52 women who underwent tlh from june 2013 to january 2014 were assigned into two groups . in group a , uterine arteries were ligated after the cornual pedicles as done conventionally . in group b , tlh was done by ligating both uterine arteries at the beginning of the procedure . all the other pedicles were desiccated using harmonic scalpel or bipolar diathermy . uterus with cervix was removed vaginally or by",380,128,0.3368
dialogsum,"#Person1#: Hi, Ann. #Person2#: Hi. You look excited. What's happening? #Person1#: I just heard that our school will hold a singing contest in 5 days. #Person2#: And you're planning to enter? #Person1#: Of course. This is a great chance for me to show off my beautiful voice. #Person2#: Is there a prize? #Person1#: I heard that the winner gets a Panda Radio. #Person2#: Do you think you have a chance? #Person1#: A chance? Not just a chance, I'm a hundred percent certain. Everyone says my voice is beautiful. #Person2#: But you haven't practised all that much. #Person1#: I still have 5 days to practise. It's in the bag! #Person2#: Don't be too sure. You're still going to need some help. #Person1#: Yeah, maybe.",Ann tells #Person1# that she's going to enter the singing contest and is confident of winning. #Person1# asks Ann to ask for some help.,123,24,0.1951
pubmed-summarization,") the influence of transmembrane potential ( aksimentiev and schulten 2005 ; mathe et al . 2005 ; kathawalla et al . 1989 ; heng et al . 2005 ; keyser et al . 2006 ) , ( v ) pore geometry ( howorka and bayley 2002 ) as well as ( vi ) interaction with pore walls ( wiggin et al . 2008 ; wanunu et al . 2008 covalently attaching dna to the pore wall is an attractive variation in single - molecule research . in previous studies aimed at dna sensing , one or multiple single stranded dna ( ssdna ) molecules were end - tethered to the pore wall of protein ( howorka et al . complementary or mismatched dna molecules showed that dna duplexes between the free and tethered strands form inside the nanopore . as the perfect and mismatched duplexes , respectively , had different lifetimes , the dna - modified nanopores could be used as biosensor elements to distinguish nucleic acids with single - point mutations ( howorka et al . the covalent attachment of dna strands has also been exploited to control the electronic properties of a pore . in general , artificial pores that exhibit engineered properties such as voltage gating or ion selectivity are attractive model systems for biological voltage - gated ion channels ( hille 2001 ) . ( 2004 ) were the first to demonstrate that dna - modified nanopores can function as ionic switches . a single gold nanotube carrying thiol - terminated dna strands was shown to preferentially transport cations in one direction , while hindering transport in the other . the ion current rectification was explained by assuming that dna molecules deflect by the external electric field and cause voltage - dependent pore opening . the attached dna strands were not localized to a single subnanoscale position but covered the entire pore . additionally , the length of the fully extended dna molecules was smaller than the pore diameter ; hence , it was not possible to completely block the current ( e.g. , 59-nm - diameter gold tube was modified with 30-mer dna ) . with the aim of achieving a greater pore blockade and ion current modulations , this study attempts to tune","single nanopores attract a great deal of scientific interest as a basis for biosensors and as a system to study the interactions and behavior of molecules in a confined volume . tuning the geometry and surface chemistry of nanopores helps create devices that control transport of ions and molecules in solution . here , we present single conically shaped nanopores whose narrow opening of 8 or 12 nm is modified with single - stranded dna molecules . we find that the dna occludes the narrow opening of nanopores and that the blockade extent decreases with the ionic strength of the background electrolyte . the results are explained by the ionic strength dependence of the persistence length of dna . at low kcl concentrations ( 10 mm ) the",380,128,0.3368
scientific_lay_summarisation-elife-norm,"allele BRI1sud suppresses PTI outputs (Belkhadir et al. , 2012). One such output, the PAMP-triggered callose deposition, could be restored by over-expression of BAK1-HA, suggesting that BAK1 is a limiting factor (Belkhadir et al. , 2012). However, exogenous BR treatment of wild-type plants does not affect the FLS2-BAK1 complex formation upon FLS2 activation, while it results in decreased PTI responses (Albrecht et al. , 2012). In order to clarify the role of BAK1 in the BR-PTI crosstalk, we investigated FLS2-BAK1 complex formation in the transgenic Arabidopsis lines overexpressing BRI1 or DWF4 or expressing BRI1sud (Belkhadir et al. , 2012). Upon treatment with flg22, FLS2 associated normally with BAK1 in these transgenic plants, and neither FLS2 nor BAK1 accumulation was altered (— 1A). Moreover, these plants displayed a weaker reactive oxygen species (ROS) burst in response to chitin (— 1B), whose signaling pathway is BAK1-independent (Shan et al. , 2008; Ranf et al. , 2011). This result is consistent with the previous finding that exogenous BR treatment can also inhibit the chitin-induced ROS burst (Albrecht et al. , 2012). BAK1-HA is not fully functional in BR signaling and exerts a dominant-negative effect on the endogenous BAK1 (— 1C), which may explain that introduction of the BAK1-HA transgene can override the suppression of immunity triggered by overexpression of BRI1 (Belkhadir et al. , 2012); BAK1-HA does not exert such a dominant negative effect, however, on PTI signaling (— 1D). Taken together, these results indicate that the BR-mediated suppression of PTI is triggered independently of a competition between BRI1 and PRRs for BAK1. We sought to determine at which level of the BR signaling pathway the antagonism initiates. After BR perception by BRI1 and activation of the BRI1-BAK1 complex, the BR signal transduction cascade includes inactivation of BIN2 (BR INSENSITIVE 2) and BIN2-like kinases, a family of GSK3-like kinases acting as negative regulators of the pathway (Vert and Chory, 2006). This leads to dephosphorylation of BZR1 (BRASSINAZOLE RESISTANT 1) and BES1/BZR2 (BRI1-EMS-SUPPRESSOR 1/BRASSINAZOLE RESISTANT 2), two bHLH transcription factors acting as major regulators of BR-induced transcriptional changes, which then become active (Wang et al. , 2002; Yin et al. , 2002). Treatment with the chemicals LiCl and bikinin, which inhibit GSK3-like kinases (De Rybel et al. , 2009; Yan et al. , 2009),","Like all organisms, plants must perform a careful balancing act with their resources. Investing in the growth of new roots or leaves can allow a plant to better exploit its environment—but it must not be at the expense of leaving the plant vulnerable to attack by pests and pathogens. As such, there is an obvious trade-off between allocating resources to growth or defense against disease. This trade-off must be finely balanced, and must also be responsive to different cues in the environment that would favor either growth or defense. The plant’s immune system is able to detect invading microbes, and trigger a defensive response against them. At the surface of plant cells, proteins called pattern recognition receptors are able to recognize specific molecules that are the tell-tale signs",380,128,0.3368
dialogsum,"#Person1#: Excuse me, please. I seem to have lost my purse. #Person2#: Oh, I see. Well, I'll have to fill out this lost and found report for you. It was a purse, you say? #Person1#: That's right. #Person2#: What is it like, ma'am? #Person1#: Well, it's a black leather one with my driver's license, some name cards, and about fifty dollars in it. #Person2#: Where did you last have it? #Person1#: I'm pretty sure I had it when I was in the coffee shop. #Person2#: When was that? About 1:30 I think. Where did you go after that? #Person1#: To the shoe department, and then I came here. #Person2#: I'm sure it will turn up. Now could you give me your name, address and phone number? #Person1#: Mrs. Jane Thomas, 20 King Street, and my phone number is 89362124.","Mrs. Jane Thomas claims she lost her purse. She tells #Person2# what it's like, when and where she last had it, and her name, address, and phone number.",139,28,0.2014
pubmed-summarization,"reports have described the increasing use of endoscopic ultrasound - guided hepaticogastrostomy ( eus - hg ) to treat malignant biliary obstruction in patients with endoscopic retrograde cholangiopancreatography ( ercp ) failure . however , a previous review article noted that despite its high success rate , eus - hg is associated with a relatively high rate of adverse events 1 , which is attributable to the lack of standardized protocols and specialized equipment . previously at our institution , eus - hg was performed on three patients using a biliary dilation catheter for hepaticogastric fistula dilation and a 7-cm , straight plastic stent or 8-cm fully covered metal stent . however , in two of the three patients , achieving fistula dilation was time - consuming and the stent migrated into the peritoneal cavity in two of the three patients . recently , we introduced a 6f cystotome ( cysto gastro set ; endo - flex , gmbh , voerde , germany ) for fistula dilation and an 8-mm , 12-cm covered stent with a 1-cm uncovered portion at the distal , intrahepatic end ( bare - end type , niti - s biliary s - type ; taewoong medical , seoul , korea ) ( . , we present our experience with four cases of eus - hg in which our institutional procedure ( 6f cystotome and 8-mm , 12-cm covered metal stent ) was used , and evaluate the safety of this procedure . bare - end type niti - s biliary s - type stent with a 1-cm uncovered portion at the distal end ( red arrow ) ; the remaining portion is fully covered . between october 2014 and august 2015 , we treated four consecutive cases of malignant biliary obstruction via eus - hg with a 6f cystotome and 8-mm , 12-cm covered metal stent . procedural consent was obtained from each patient , and the institutional review board granted permission to review the patients records . m , male ; f , female ; bd , bile duct ; hgs , hepaticogastrostomy ; fu , follow - up ; eus , endoscopic ultrasound all procedures were performed using a convex - type echoendoscope ( gf - uct260 ; olympus medical systems , tokyo","background and study aims : an iincreasing number of reports describe endoscopic ultrasound - guided hepaticogastrostomy for malignant biliary obstruction in patients with endoscopic retrograde cholangiopancreatography failure . however , this procedure has not yet been standardized ; as a result , the rate of adverse events , including bile leakage and stent migration , is relatively high . here , we report our experience with four cases of endoscopic ultrasound - guided hepaticogastrostomy performed according to our institutional procedure .",380,81,0.2132
scientific_lay_summarisation-elife-norm,"in a very far from disease onset (VFDO) premanifest stage (1a). This stage reaches back more than 15–20 years before motor symptoms become visible in patients and far before protein aggregates and neurodegeneration are observed. In Huntington’s disease occurrence of such very early changes is supported by the observation of early deficits in premanifest Huntington’s disease mutation carriers, such as loss of phosphodiesterase 10A in the occipital lobe up to 47 years prior to disease onset (summarized in Wilson et al. , 2017). Also, the ability to perform complex visuospatial orientation, such as visual search, seems to be altered even in pre-manifest stages far from clinical diagnosis (Labuschagne et al. , 2016). We hypothesize that primal functional changes in the VFDO stage of premanifest Huntington’s disease open up very early vulnerable windows for disease development and preventive therapy prior to neuronal loss and may also provide promising early biomarkers for therapy development (Mehler and Gokhan, 2000; Kerschbamer and Biagioli, 2015; Humbert, 2010; Cepeda et al. , 2003). It seems that the visual cortex is one of the first regions that are functionally affected during disease development in Huntington’s disease (Labuschagne et al. , 2016; Dogan et al. , 2013). In order to identify primal network changes, we have here established a network-centered approach and focused on microcircuit function in layer 2/3 of the visual cortex at an early premanifest stage in a mouse model of Huntington’s disease corresponding to the VFDO stage in premanifest Huntington’s disease. We have used two-photon imaging using fluorescent indicators of intracellular Ca2+ in order to resolve the functional architecture of intact cortical microcircuits in vivo with single neuron resolution (Grienberger and Konnerth, 2012). We show that even at the early age of 10 – 15 weeks (young adults compared to humans), the entire cortical microcircuit shifts towards a more excitable state characterized by a complex change in neuronal activity pattern and hyperactive neurons. These findings are accompanied by changes in animal behavior, including a decrease in anxiety. No effective and curative treatment has been developed for Huntington’s disease so far (Frank, 2014). A chronic drug therapy that commences early on in VFDO stages in premanifest Huntington’s disease and ameliorates early dysregulations as the potential origin of pathogenic processes and disease spreading is therefore a promising","Huntington’s disease is a devastating brain disorder that causes severe mood disorders, problems with moving, and dementia. Most people develop the condition between their thirties and fifties, and die a decade or two after the symptoms first appear. The disease emerges because of a mutation in the gene for the Huntingtin protein, which leads to neurons slowly dying in the brain. While genetic testing can reveal who carries the faulty gene, no treatment addresses the root of the disorder or prevents it from appearing. Instead, most therapies for Huntington’s disease aim to reduce brain damage once the telltale symptoms are already present. However, the disease-causing protein is expressed early during the life of a patient, which could give it time to damage the brain long before neurons die",380,128,0.3368
pubmed-summarization,"type rbp aggregation during aging in order to fully understand rbp aggregation in neurodegenerative diseases . furthermore , it is likely that the organism has evolved specific mechanisms to control liquid droplet protein aggregation . in the current study , we chose to focus on key rbps responsible for stress granule formation . stress granules are a specific type of rna granule that protect the cell by sequestering mrna from the translational machinery during periods of stress . importantly , stress granule proteins are often found to co - localize with pathological inclusions of tdp-43 and fus ( bentmann et al . whether these stress granule proteins are innocent bystanders transiently interacting with tdp-43 and fus or whether they co - aggregate and accelerate disease - associated rbp aggregation remains intensely debated ( bentmann et al . , 2013 , li et al . , 2013 ) . we show that key stress - granule - related rbps ( sgrbps ) accumulate in aberrant stress granule - like puncta and in large solid aggregates in aged c. elegans . proteomic analysis revealed that long - lived animals with reduced daf-2 signaling preferentially abrogate the insolubility of rna granule components . importantly , sgrbp aggregates are associated with reduced animal size , motility , and lifespan . we show that sgrbp aggregation is triggered at an earlier age by their co - aggregation with other misfolded proteins , a process that is prevented by daf-16 in daf-2 mutants . in addition , the proteostasis network established by heat shock transcription factor 1 ( hsf-1 ) during development is required to maintain dynamic stress granule proteins throughout the animal s life . to identify and quantify changes in aggregation - prone proteins in animals with reduced daf-2 signaling , we performed an in - depth proteomic analysis of the insoluble proteome from both control and long - lived animals ( 1a ; table s1 ) . because protein misfolding and aggregation is highly abundant in aged c. elegans gonads and masks changes in other somatic tissues ( david et al . , 2010 , goudeau and aguilaniu , 2010 , zimmerman et al . , 2015 ) , we used a gonad - less mutant to focus our analysis on protein insolubility","summarylow - complexity prion - like domains in key rna - binding proteins ( rbps ) mediate the reversible assembly of rna granules . individual rbps harboring these domains have been linked to specific neurodegenerative diseases . although their aggregation in neurodegeneration has been extensively characterized , it remains unknown how the process of aging disturbs rbp dynamics . we show that a wide variety of rna granule components , including stress granule proteins , become highly insoluble with age in c. elegans and that reduced insulin / insulin - like growth factor 1 ( igf-1 ) daf-2 receptor signaling efficiently prevents their aggregation . importantly , stress - granule - related rbp aggregates are associated with reduced fitness . we show that heat shock transcription factor 1",380,128,0.3368
dialogsum,"#Person1#: Well, Mr. Brown, we've settled everything in connection with this transaction except the question of payment in yen. Now can you explain to me how to make payment in yen? #Person2#: Many of our business friends in England, France, Switzerland, Italy and Germany are paying for our exports in Japan currency. It is quite easy to do so. #Person1#: I know some of them are doing that. But this is new to me. I've never made payment in yen before. It is convenient to make payment in pound sterling, but I may have some difficulty in making payment in yen. #Person2#: Many banks in Europe now carry accounts in yen. They are in a position to open letters of credit and effect payment in yen. Consult your banks and you'll see that they are ready to offer you this service. #Person1#: Do you mean to say that I can open a letter of credit in yen with a bank in London or Bonn? #Person2#: Sure you can. Several of the banks in London, such as the National Westminster Bank and Barclays Bank are in a position to open letters of credit in yen. They'll do so against our sales confirmation or contract. #Person1#: I see.",Mr. Brown teaches #Person1# how to make the payment in yen and recommends #Person1# to consult the bank.,206,18,0.0874
scientific_lay_summarisation-elife-norm,", 2008; Mitchell et al. , 2009; Guirao et al. , 2010; Vladar et al. , 2012; Kunimoto et al. , 2012). If cilia are oriented, synchronisation emerges by hydrodynamic coupling as adjacent cilia engage by flow (Brumley et al. , 2014; Elgeti and Gompper, 2013). In addition, basal body coupling can also contribute to beat synchronisation as demonstrated in green algae (Wan and Goldstein, 2016). However, biophysical mechanisms alone cannot explain all aspects of ciliary beat synchronisation. For example, the flow-networks generated by ependymal cilia show complex reorganisation that is under circadian regulation (Faubel et al. , 2016). In mucociliary surfaces, changes in ciliary beat frequency are coordinated to regulate flow rates. Some of these changes are due to locally secreted diffusible molecules, including serotonin (Maruyama et al. , 1984; König et al. , 2009; Walentek et al. , 2014) and neuropeptides (Conductier et al. , 2013). However, long-range ciliary coordination is often under neuronal control (Doran et al. , 2004; Tamm, 2014; Arkett et al. , 1987; Kuang and Goldberg, 2001). Ciliary swimmers display the most elaborate forms of neuronal ciliary coordination. In the ctenophore Pleurobrachia, prey-capture triggers a rapid synchronised beating of all eight ciliary comb-rows resulting in fast forward swimming (Tamm, 2014). In gastropod veliger larvae, the normal beating of velar cilia is periodically interrupted by coordinated, velum-wide ciliary arrests, triggered by calcium-spikes (Arkett et al. , 1987). Similarly, annelid larvae show regular and coordinated arrests of the entire prototroch ciliary band (Conzelmann et al. , 2011). Such coordinated changes in ciliary activity, often triggered throughout the whole body, require neuronal control. The neuronal circuits coordinating whole-body ciliary activity have not been described in any animal. Here we reconstruct and functionally analyse the complete ciliomotor circuitry in the planktonic nectochaete larva of the marine annelid Platynereis dumerilii. Platynereis has emerged as a powerful model to study neural cell types and development (Tomer et al. , 2010; Marlow et al. , 2014; Tessmar-Raible et al. , 2007) and the whole-body circuit bases of larval behaviour, including conical-scanning and visual phototaxis (Jékely et al. , 2008; Randel et al. , 2014). Platynereis nectochaete larvae (Fischer et al. , 2010) have three trunk segments and use segmentally arranged ciliary bands to swim and muscles to turn while swimming (Randel","The oceans contain a wide variety of microscopic organisms including bacteria, algae and animal larvae. Many of the microscopic animals that live in water use thousands of beating hair-like projections called cilia instead of muscles to swim around in the water. Understanding how these animals move will aid our understanding of how ocean processes, such as the daily migration of plankton to and from the surface of the water, are regulated. The larvae of a ragworm called Platynereis use cilia to move around. Like other animals, Platynereis has a nervous system containing neurons that form networks to control the body. It is possible that the nervous system is involved in coordinating the activity of the cilia to allow the larvae to manoeuvre in the water, but it was",380,128,0.3368
pubmed-summarization,"in diameter to cause obstruction . as shown by reisner and cohen , impaction of the stone can occur at any part of the bowel including ileum ( 60.5% ) , jejunum ( 16.1% ) , stomach ( 14.2% ) , colon ( 4.1% ) , and duodenum ( 3.5% ) . it most frequently occurs in the terminal ileum and the ileocecal valve because of their narrow lumen and potentially less active peristalsis . the most common complications of gallstone disease are acute cholecystitis , acute pancreatitis , choledocholithiasis with or without cholangitis , and a gangrenous gallbladder . morbidity from gallstone ileus in the past , it was difficult to clinch the diagnosis , but the advent of ct and mri has made it easier to diagnose gallstone ileus . in 50% of cases , the classic rigler 's triad of radiography includes mechanical bowel obstruction , pneumobilia , and an ectopic gallstone within bowel lumen . however , air in the gallbladder , small bowel obstruction , and gallstone ileus imply the presence of biliary enteric fistula . the choice is between performing simple enterolithotomy with longitudinal incision on the antimesenteric border proximal to the site of obstruction , or a single - stage procedure involving enterolithotomy , cholecystectomy , and closure of the fistula . the choice of the surgical procedure is largely determined by the clinical condition of the patient . if the patient is hemodynamically stable , then single - stage procedure can be performed . however , in unstable patients with renal failure , enterolithotomy alone is considered sufficient ( table 2 ) . we thus performed enterolithotomy since our patient suffered from renal failure , diabetics , and brain infarcts . the laparoscopy - assisted techniques have been reported by sarli et al . who successfully treated three women with gallstone ileus . however , one should remember that laparoscopy is somehow more challenging in cases of dilated and edematous bowel and may require gentle mobilization of the bowel to prevent perforation . the final technical issues to remember are milking the stone and taking the enterotomies away from the site of impaction because it is often edematous . in addition , resection of a segment of the bowel might be necessary","background : gallstone ileus is an uncommon complication of gall stones associated with potentially serious morbidity and mortality.case report : we reported a 60-year - old male case who presented with renal failure and pain in right hypochondriac region . he also had a history of brain infarcts along with diabetes which is an additional factor for mortality . on computed tomography of the abdomen , he was diagnosed to have cholecystocholedochal fistula including air in the gall bladder and obstruction in the distal part of the ileum . computed tomography plays an important role to make the proper diagnosis and in treatment.conclusions:as in our case , diagnosis was challengeable because of renal failure , diabetes , septicaemia and intestinal obstruction ( peritonitis ) . we did surgery",380,128,0.3368
dialogsum,"#Person1#: How's everything, Janice? #Person2#: I sent my resume to a computer company and am waiting for their call. #Person1#: Which company? #Person2#: Pineapple Computer Company. A secretary is needed there, and it is worth a try. Do you get any information or advertisement for employment? #Person1#: Yep! I got some, in which I am interested. But. . . #Person2#: But what? You always act like this, when you face difficulties. #Person1#: YOU GET ME! #Person2#: All the fears are nothing. You can make it. There is no other choice for you. Be brave. #Person1#: Seemingly there is no turning back. I have to face it somehow. #Person2#: It's all or nothing.","Janice tells #Person1# she sent her resume to Pineapple Computer Company. #Person1# gets some employment information, but #Person1# fears. Janice encourages #Person1#.",112,22,0.1964
scientific_lay_summarisation-elife-norm,"et al. , 2013; Madsen and Surlykke, 2013). As whales and bats close in on prey, both are thought to concurrently decrease signal intensity and auditory sensitivity to partially compensate for reduced transmission loss (Hartley, 1992; Au and Benoit-Bird, 2003; Supin et al. , 2004; Linnenschmidt et al. , 2012; Madsen and Surlykke, 2013), while increasing the signal emission rate for faster updates on prey location (Griffin, 1958; Morozov et al. , 1972; Au, 1993). Both groups terminate prey pursuits with a low intensity, high repetition rate sequence of echolocation signals called a buzz (see ref. [Madsen and Surlykke, 2013] for review). Signal production rates characteristic of buzzes have likely evolved in these echolocators to facilitate close range prey tracking. However, for a given sonar beam, effective beam diameter will decrease as the distance between predator and prey diminishes. Thus, while a directional sound beam enables longer detection range by restricting the acoustic field of view (FOV), it may be disadvantageous to the echolocator at short ranges, as moving prey may easily vanish at the periphery of the FOV. Directionality increases with aperture size (e. g. , a bat' s gape) and signal frequency (Au, 1993) and both factors appear to be exploited by some bats to modify their beam (Surlykke et al. , 2009; Jakobsen and Surlykke, 2010). Unlike bats, whales do not generate echolocation signals in the larynx nor do they emit them through the mouth or the nares (Ridgway et al. , 1980; Cranford et al. , 1996). Instead, whales have evolved specialized sound-producing structures, the phonic lips, located high in the blowhole (). An echolocation click is generated by pneumatic actuation of the phonic lips as pressurized air is forced past them (Cranford et al. , 1996). The resulting sound pulse propagates into the fatty melon and is transmitted into the water as a directional beam (Au et al. , 1986). While the exact function of the melon is not known, its size and properties are expected to affect the radiation pattern of sound from the head (Varanasi et al. , 1975; Aroyan et al. , 1992; Harper et al. , 2008). As the bulbous melon fills a large proportion of the forehead (), the diameter of the head has come to be considered indicative of","Bats and toothed whales such as porpoises have independently evolved the same solution for hunting prey when it is hard to see. Bats hunt in the dark with little light to allow them to see the insects they chase. Porpoises hunt in murky water where different ocean environments can quickly obscure fish from view. So, both bats and porpoises evolved to emit a beam of sound and then track their prey based on the echoes of that sound bouncing off the prey and other objects. This process is called echolocation. A narrow beam of sound can help a porpoise or bat track distant prey. But as either animal closes in on its prey such a narrow sound beam can be a disadvantage because prey can easily escape to",380,128,0.3368
dialogsum,"#Person1#: Can I help you? #Person2#: Yes, I'm looking for a house. #Person1#: To buy or to rent? #Person2#: Oh, to rent. #Person1#: How much do you want to pay? #Person2#: About 300 a month. #Person1#: Well, I've got one here. It's 260 a month. #Person2#: How big is it? #Person1#: It's got a kitchen, a bathroom, and one bedroom. #Person2#: Well, actually I prefer something a bit bigger if that's possible. #Person1#: Yes, I think so. There is also an interesting one.It ' s opposite the park. #Person2#: How much is it? #Person1#: It's 325 a month. It's the biggest we've got in this area. #Person2#: What's it like? #Person1#: Well, There're two bedrooms, a sitting room, a kitchen and a bathroom. #Person2#: It sounds interesting. Can I go and see it? #Person1#: Of course, Sir.",#Person2# wants to rent a big house and #Person1# recommends one opposite the park for 325 a month. #Person2# decides to go and see it.,137,25,0.1825
dialogsum,"#Person1#: Good afternoon, everyone. The experiment is to start at 3. Have you gone through the instructions? #Person2#: Yes, sir. #Person1#: Ok, now some points for attention. First of all, pay attention to safety. . . Now, sign your names on the lab record, and after that you can start. If there is any question, just let me know. #Person2#: Excuse me, sir. This air compressor doesn't work. #Person1#: Have you turned it on? #Person2#: Yes, I have. #Person1#: Ok, I will get you another one. #Person2#: Thank you.","#Person1# explains some points about the experiment that need attention before it starts. #Person2# reports to #Person1# that the air compressor doesn't work, so #Person1#'ll get #Person2# another one.",89,29,0.3258
scientific_lay_summarisation-elife-norm,"Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM. Organs arise from precisely defined territories containing progenitor cells with specific developmental potential. Distinct progenitor territories often abut one another, and communication at the interfaces between neighboring territories acts to refine their boundaries (Dahmann et al. , 2011). This process delineates the final dimensions of each territory and, subsequently, influences the sizes of the derived organs. Boundary refinement is generally thought to be mediated by interplay between opposing inductive and suppressive factors (Briscoe and Small, 2015). In many cases, however, the identification of and interactions among these factors remain elusive. Kidney progenitor cells originate from the intermediate mesoderm (IM), a pair of narrow bilateral stripes within the posterior mesoderm, flanked by lateral mesoderm that gives rise to vessels and blood and by paraxial mesoderm that gives rise to bone, cartilage, and skeletal muscle. The mechanisms that determine the dimensions of the stripes of IM are not fully understood. Several conserved transcription factors are expressed in the IM and are required for its development, including Lhx1/Lim1, Pax2, and Osr1/Odd1 (Dressler and Douglass, 1992; James et al. , 2006; Krauss et al. , 1991; Toyama and Dawid, 1997; Tsang et al. , 2000; Wang et al. , 2005). Studies in chick have indicated essential roles for the lateral mesoderm, paraxial mesoderm, and surface ectoderm in regulating the expression of these transcription factors (James and Schultheiss, 2003; Mauch et al. , 2000; Obara-Ishihara et al. ,","The human body is made up of many different types of cells, yet they are all descended from one single fertilized egg cell. The process by which cells specialize into different types is complex and has many stages. At each step of the process, the selection of cell types that a cell can eventually become is increasingly restricted. The entire system is controlled by switching different genes on and off in different groups of cells. Balancing the activity of these genes ensures that enough cells of each type are made in order to build a complete and healthy body. Upsetting this balance can result in organs that are too large, too small or even missing altogether. The cells that form the kidneys and bladder originate within a tissue",380,128,0.3368
dialogsum,"#Person1#: Please point out the painful place with your finger. Is there any relation between the pain and the weather? #Person2#: Yes, the pain comes more intense when the weather is bad. And the pain comes more intense when I walk too much. #Person1#: Have you ever had any trauma? #Person2#: Yes, I have. #Person1#: Does the pian become more intense at night? #Person2#: Yes, it does. Just like a needle prick. Besides, the place that hurts often feels cold, too. #Person1#: Do you have the sensation of ants crawling over the painful part? #Person2#: Yes, I do. #Person1#: I'd like to treat you with acupuncture if you agree. #Person2#: By the way, does acupuncture hurt? #Person1#: Acupuncture may cause just a little pain, but it also causes a certain feeling of numbness and distension. We'll try it every day for seven days. Will that be all right? #Person2#: Yes. Let's start today.",#Person2# tells #Person1# #Person2#'s pain comes more intense when the weather is bad and at night. #Person1# decides to treat #Person2# with acupuncture and #Person2# agrees.,153,26,0.1699
dialogsum,"#Person1#: Mother's birthday is getting close. Have you thought about what to buy for her this year? #Person2#: Oh, I totally forgot. It's already May tenth. Her birthday is the day after tomorrow, right? #Person1#: Yes, I will get mom a beautiful dress. It will make her look younger. What do you want to buy? #Person2#: Since you will buy her a dress, I'll buy her something else. What do you think of a pair of shoes? #Person1#: Do you know what size she wears? It may not fit her if she doesn't try them on first. #Person2#: You're right. Do you have any suggestions? #Person1#: Well, she saw a handbag when I was shopping with her last week. She seemed to like it very much. #Person2#: Why didn't she buy it? #Person1#: She couldn't accept the price, but she really liked it. #Person2#: How about going downtown tomorrow morning? We can get the present for her there. #Person1#: OK.",The birthday of #Person2# and #Person1#'s mother is the day after tomorrow. #Person2# will get her a beautiful dress and suggests #Person1# get mom a handbag which she seemed to like it very much.,160,34,0.2125
dialogsum,"#Person1#: Well, I'm afraid my cooking isn't to your taste. #Person2#: Actually, I like it very much. #Person1#: I'm glad you enjoy it. Let me serve you some more fish. #Person2#: No, thank you. I've had enough fish, but I'd like some soup. #Person1#: Here it is. Help yourself! #Person2#: Thanks. I didn't know you were so good at cooking. If only my wife could learn to cook from you. #Person1#: Why not bring your wife next time? I haven't seen her for quite a while. #Person2#: OK, I will. She will be very glad to see you, too. Thank you for the wonderful meal.",#Person2# likes #Person1#'s fish very much. #Person1# suggests #Person2# bring his wife for a meal next time. #Person2# agrees.,105,19,0.181
pubmed-summarization,"tailgut cysts , also known as retrotrectal cystic hamartomas , are rare congenital developmental lesions arising from postnatal primitive gut remnants , that generally occur in the retrorectal space , but have also been described in prerectal and perirenal locations . the retrorectal space is a potential space bound anteriorly by the mesorectum and posteriorly by the sacrum . the superior border is formed by the peritoneal reflection while the inferior border is formed by the rectosacral fascia . the lateral borders of the retrorectal space are formed by the ureters , the iliac vessels , the sacral nerve roots , and the lateral stalks of the rectum . the retrorectal space contains loose connective tissue , the middle sacral , iliolumbar and middle hemorrhoidal vessels , branches of the sympathetic and parasympathetic nervous systems , and lymphatics . the anatomical position and rarity of the lesion lead to difficulty first in diagnosis ( the lesion is often misdiagnosed ) and second in surgical management ( the condition is often suboptimally managed ) . these tailgut cysts predominantly occur in women , with average age of presentation at 35 years . rertrorectal tumors are frequently asymptomatic and are found incidentally during evaluation for unrelated physical complaints . half of the patients present with symptoms such as low back or rectal pain , pain during defecation , rectal bleeding , urinary frequency , etc . furthermore , retrorectal lesions in women can mimic gynecological pathology , and the risk of malignant transformation of a tailgut cyst always exists . despite that , the role of preoperative biopsy for retrorectal tumors is very controversial , but most authors agree that it can be a more harmful than a useful option . this is why preoperative high - resolution modern imaging techniques ( pelvic computed tomography [ ct ] or magnetic resonance imaging [ mri ] ) play such a crucial role in differential diagnostics between retrorectal tumors and planning the surgical management of retrorectal lesions , including tailgut cysts . complete surgical resection with negative margins still remains the cornerstone of surgical treatment , as this eliminates the potential of recurrence , hemorrhage , infection , compression , and malignant changes . a 40-year - old female was referred to our institution","retrorectal cystic hamartoma , also known as tailgut cyst , is a rare congenital developmental lesion arising from postnatal primitive gut remnants in the retrorectal space . the rarity of the lesion and its anatomical position usually leads to difficulty in diagnosis and surgical management . this cyst predominantly occurs in women ( female to male ratio , 3:1 ) . tailgut cysts can present as incidental findings during the routine examination but over half of the patients are thought to present with symptoms . computed tomography or magnetic resonance imaging has a crucial role in diagnosing these misdiagnosed cysts . complete surgical excision is the treatment of choice for tailgut cysts as this provides a definitive diagnosis , relieves symptoms , and prevents possible complications such as",380,128,0.3368
scientific_lay_summarisation-elife-norm,"may function as an environmental cue. Lightning generates the major abiotic source of environmental NO (Navarro-González et al. , 2001). Despite its prevalence in the environment, it remains unclear if NO is utilized as a sensory cue by terrestrial animals to elicit behavioral responses. sGCs are the only described sensors for biosynthetically produced NO, mediating NO-evoked muscle relaxation and vasodilation (Gow et al. , 2002; Stoll et al. , 2001). However, it is unclear if sGCs also play a role in NO-evoked sensory responses. In vertebrates, NO modulates the activities of various ion channels, either directly through S-nitrosylation or indirectly through sGCs. NO regulation of ion channels alters neuron and muscle excitability (Bolotina et al. , 1994; Broillet and Firestein, 1996,1997; Koh et al. , 1995; Wang et al. , 2012; Wilson and Garthwaite, 2010). For example, in salamander olfactory sensory neurons, S-nitrosylation of a cysteine residue in cyclic nucleotide-gated (CNG) channels activates these channels, thereby directly altering odor-evoked responses in these cells (Broillet and Firestein, 1996,1997). CNG channels are highly conserved among invertebrates and vertebrates. Because both CNG channels and guanylate cyclases are essential for transducing responses for many sensory modalities, these results suggest that CNG channels and guanylate cyclases may also play a role in NO-evoked sensory responses. Unlike most metazoans, the nematode C. elegans lacks genes encoding NOS (Gusarov et al. , 2013) and consequently cannot synthesize NO. Nonetheless, C. elegans is exposed to several potential environmental sources of NO, including NO produced by bacteria, which regulates C. elegans stress responses and aging (Gusarov et al. , 2013). C. elegans lives in rotting organic matter, where it feeds on diverse microbes, including the gram-negative bacteria from the Pseudomonas and the Bacillus genera (Samuel et al. , 2016). C. elegans exhibits a rich repertoire of behavioral interactions with Pseudomonas aeruginosa, Serratia marascens, and Bacillus subtilis (Brandt and Ringstad, 2015; Garsin et al. , 2003; Reddy et al. , 2009; Styer et al. , 2008; Zhang et al. , 2005). A few bacterially derived metabolites have been shown to mediate these behavioral responses (Brandt and Ringstad, 2015; Meisel and Kim, 2014; Pradel et al. , 2007). Here we test the idea that bacterially produced NO is an ecologically significant environmental cue for C. elegans-pathogen interactions. When cultured with a","Nitric oxide is a colorless gas that contains one nitrogen atom and one oxygen atom. Found at very low levels in the air, this gas is produced by the intense heat of lightning strikes and by combustion engines. Almost all living organisms also produce nitric oxide. In animals, for example, nitric oxide regulates blood pressure and signaling between neurons. However, it was not known if animals could detect nitric oxide in their environment and respond to it. Caenorhabditis elegans is a worm that has been intensively studied in many fields of biology. Unlike most animals, it cannot make nitric oxide. Yet, living in the soil, C. elegans does come into contact with many microbes that can, including the bacterium Pseudomonas aeruginosa. These bacteria can infect and kill C.",380,128,0.3368
dialogsum,"#Person1#: Would you mind giving me a hand? #Person2#: Okay, Bob, What is it? #Person1#: Help me hang up this picture, please. Would you hold it straight while I put in the nail? #Person2#: All right. #Person1#: Now, hand me the hammer and those nails, please. #Person2#: Yes, here you are. #Person1#: There! How does it look? Tell me if I've got it straight. #Person2#: Well, it's straight, but it's upside down I'm afraid.","#Person2# helps Bob to hang up the picture, but it's upside down.",74,12,0.1622
scientific_lay_summarisation-elife-norm,"Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in response to many physiological cues. CaAR leads to transient immobilization of organelles, drives reorganization of actin during cell cortex repair, cell spreading and wound healing, and induces long-lasting changes in gene expression. Our findings suggest that CaAR acts as fundamental facilitator of cellular adaptations in response to acute signals and stress. Actin organization and dynamics are critical for most morphogenetic processes, including cell polarization, migration and division. The prominent role of the actin cytoskeleton is reflected in a host of regulators that mediate dynamic assembly of complex actin structures from filament bundles and networks. These structures in turn provide protrusive and contractile forces during physiological and pathological processes such as differentiation, wound healing and tumor metastasis (Lecuit et al. , 2011; Pantaloni et al. , 2001; Pollard and Cooper, 2009). While many studies in the past have focused on the molecular characterization of specific actin assemblies and their local function within cells, recent work has elegantly shown that a balance between different actin assemblies is established in cells by distinct actin nucleators. These nucleators constantly compete for a common pool of actin monomers (Burke et al. , 2014), and the balance between actin assemblies can be tightly controlled by regulatory factors such as profilin (Rotty et al. , 2015; Suarez et al. , 2015). In addition, cellular F- and G-actin levels have been linked to profound and long-lasting changes in cell physiology through regulation of transcriptional cofactors such as myocardin-related transcription factors (MRTF), the Yes-associated protein (YAP) or transcriptional co-activator with PDZ-binding motif (TAZ) (Halder et al. , 2012; Miralles et al. , 2003). Finally, the rapidly expanding field of mechanobiology has highlighted global integration of actomyosin-mediated forces across the","Our skeleton plays a vital role in giving shape and structure to our body, it also allows us to make coordinated movements. Similarly, each cell contains a microscopic network of structures and supports called the cytoskeleton that helps cells to adopt specific shapes and is crucial for them to move around. Unlike our skeleton, which is relatively unchanging, the cytoskeleton of each cell constantly changes and adapts to the specific needs of the cell. One part of the cytoskeleton is a dense, flexible meshwork of fibers called the cortex that lies just beneath the surface of the cell. The cortex is constructed using a protein called actin, and many of these proteins join together to form each fiber. When cells need to adapt rapidly to an injury or",380,128,0.3368
pubmed-summarization,"in the atomic spectra . according to the new theory derived by bigeleisen later on , similar odd even isotope effects were found in gd , zn , nd and cd . lanthanides and actinides are known to have deformed nuclei , which cause the charge distribution effects in the isotope shifts of the atomic emission spectral lines . therefore , the field shift is expected to have a great effect on their isotope effects . in case of cd , the contribution of the nuclear field shift effect to the observed isotope enrichment factor was estimated to be 530% . another supporting proof for the importance of the field shift on isotope effects was given by the study of temperature effect on eu isotope effects . it was shown that the separation coefficient of eu isotopes increases with the increase in temperature , which could be explained by the field shift effects . kim et al . studied the isotope effects of uranyl complexes by means of ion exchange chromatography and reported that the malic acid eluent system had the largest separation coefficient among some selected uranyl carboxylate complexes . therefore , the purpose of the work is to study the isotope effects of neodymium in ligand exchange system using glycolic , malic and citric acids as mono , di and tri carboxylic acid to compare the effect of different ligands on the isotope effects of nd in nd - ligand exchange system . it is aimed to find the most suitable ligand that gives the highest separation coefficient and to get more information that may lead to more understanding of the theory of isotope effects . the cation exchange resin used in the ligand exchange system , lxs , was a macroporous strongly acidic cation exchange resin , ( sqs , 100200 mesh size ) obtained as a gift from asahi chemical co. japan , nd2o3 of purity 99.99% was supplied by alfa - aesar , usa , and converted to ndcl3 by dissolving in 2 m hcl solution followed by well gentle evaporation , drying the obtained solid salt , washing several times with distilled water followed by evaporation till neutrality , then used without further purification . neodymium isotope separation experiment based on the ligand complex","the isotope effects of neodymium in nd - glycolate ligand exchange system were studied by using ion exchange chromatography . the separation coefficients of neodymium isotopes , s , were calculated from the observed isotopic ratios at the front and rear boundaries of the neodymium adsorption band . the values of separation coefficients of neodymium isotopes , s , for the nd - glycolate ligand exchange system were compared with those of nd - malate and nd - citrate , which indicated that the isotope effects of neodymium as studied by the three ligands takes the following direction malate > citrate > glycolate . this order agrees with the number of available sites for complexation of each ligand . the values of the plate height , hetp of",380,128,0.3368
dialogsum,"#Person1#: Excuse me, Mr. Brooke, I almost forgot there was a phone message here for you. Professor Johnson called and asked you to call him back. #Person2#: Where is he now? Do you know? #Person1#: He's staying in the Blackwood Hotel room 509. #Person2#: Thank you. Do you happen to have the number of the Blackwood Hotel? #Person1#: I'm sorry I don't, but you can get it from information just dial 114. #Person2#: Oh, and could I trouble you to change a dollar? #Person1#: Alright. Here is your change. By the way, the public phone is over there on your right. #Person2#: I see, thanks.",#Person1# tells Mr. Brooke Professor Johnson called and asked him to call back. #Person1# suggests dialing 114 to get Johnson's hotel's number and changes a dollar for him to use the public phone.,105,33,0.3143
scientific_lay_summarisation-elife-norm,"During transcription initiation, RNA polymerase (RNAP) binds to promoter DNA, unwinds promoter DNA to form an RNAP-promoter open complex (RPo) containing a single-stranded ‘transcription bubble, ’ and selects a transcription start site (TSS). TSS selection occurs at different positions within the promoter region, depending on promoter sequence and initiating-substrate concentration. Variability in TSS selection has been proposed to involve DNA ‘scrunching’ and ‘anti-scrunching, ’ the hallmarks of which are: (i) forward and reverse movement of the RNAP leading edge, but not trailing edge, relative to DNA, and (ii) expansion and contraction of the transcription bubble. Here, using in vitro and in vivo protein-DNA photocrosslinking and single-molecule nanomanipulation, we show bacterial TSS selection exhibits both hallmarks of scrunching and anti-scrunching, and we define energetics of scrunching and anti-scrunching. The results establish the mechanism of TSS selection by bacterial RNAP and suggest a general mechanism for TSS selection by bacterial, archaeal, and eukaryotic RNAP. During transcription initiation, RNA polymerase (RNAP) and one or more transcription initiation factor bind to promoter DNA through sequence-specific interactions with core promoter elements, unwind a turn of promoter DNA to form an RNAP-promoter open complex (RPo) containing an unwound ‘transcription bubble, ’ and select a transcription start site (TSS). The distance between core promoter elements and the TSS can vary. TSS selection is a multi-factor process, in which the outcome reflects the contributions of promoter sequence and reaction conditions. TSS selection by bacterial RNAP and the bacterial transcription initiation factor σ involves four promoter-sequence determinants: (i) distance relative to the promoter −10 element (preference for TSS selection at the position 7 bp downstream of the promoter −10 element; Aoyama and Takanami, 1985; Sørensen et al. , 1993; Jeong and Kang, 1994; Liu and Turnbough, 1994; Walker and Osuna, 2002; Lewis and Adhya, 2004; Vvedenskaya et al. , 2015; Winkelman et al. , 2016a; Winkelman et al. , 2016b); (ii) identities of the template-strand nucleotide at the TSS and the template-strand nucleotide immediately upstream of the TSS (strong preference for a template-strand pyrimidine at the TSS and preference for a template-strand purine immediately upstream of the TSS; Aoyama and Takanami, 1985; Sørensen et al. , 1993; Jeong and Kang, 1994; Liu and Turnbough, 1994; Walker and Osuna, 2002; Lewis and Adhya, 2004; Vvedenskaya et al. , 2015; Winkelman","Genes store the information needed to build and repair cells. This information is written in a chemical code within the structure of DNA molecules. To make use of the information, cells copy sections of a gene into a DNA-like molecule called RNA. An enzyme called RNA polymerase makes RNA molecules from DNA templates in a process called transcription. RNA polymerase can only make RNA by attaching to DNA and separating the two strands of the DNA double helix. This creates a short region of single-stranded DNA known as a “transcription bubble”. RNA polymerase can start transcription at different distances from the sites where it initially attaches to DNA, depending on the DNA sequence and the cell’s environment. It had not been known how RNA polymerase selects different transcription",380,128,0.3368
scientific_lay_summarisation-elife-norm,"bound, making the transfer of torque from TonB to the core unlikely (Sarver et al. , 2018). Pulling models have been explored using steered molecular dynamics (MD) (Gumbart et al. , 2007) as well as single-molecule AFM (atomic force microscopy) pulling experiments (Hickman et al. , 2017), and these studies indicate that an N-terminal region of the core (up to residue 73) is preferentially unfolded to permit the movement of vitamin B12 into the periplasm. This work concludes that the C-terminal region of the core is static and does not unfold during transport, a result that is consistent with denaturation experiments on BtuB (Flores Jiménez and Cafiso, 2012). An important caveat to almost all the structural work on BtuB is that it has been carried out on purified or partially purified protein where the native OM environment is no longer present. Since transport in this family of transporters has never been reconstituted, it has never been established that the isolated, purified, and membrane reconstituted BtuB is capable of transport. Recently, we developed an approach to attach spin labels to either extracellular or periplasmic sites on BtuB in intact cells, thereby permitting EPR measurements to be made under conditions where the protein is known to be functional (Joseph et al. , 2019; Nilaweera et al. , 2019). Preliminary measurements made on BtuB indicate that it behaves differently in the intact cell than it does in a purified reconstituted phospholipid system. For example, a substrate-dependent change in the core domain of BtuB involving substrate binding loop 3 (SB3) is observed in situ but is not seen in a detergent-treated OM preparation (Nilaweera et al. , 2019). Moreover, the extracellular loops of BtuB are also highly constrained in the intact cell, and substrate-induced structural changes and structural heterogeneity that is observed for BtuB in proteoliposomes are not observed for BtuB in situ (Nyenhuis et al. , 2020a). In the present work, we perform double electron-electron resonance (DEER) on BtuB in intact cells to determine whether structural changes take place in the core domain that are associated with substrate binding and transport. Upon substrate binding, a movement of the core is observed involving sites 90 and 93 in SB3. No other movements in the core are detected. When the ionic lock is broken between","Bacteria must obtain nutrients from their surrounding environment in order to survive. In Gram-negative bacteria, proteins in the outer membrane surrounding the cell actively transport carbohydrates and trace nutrients like iron into the cell’s interior. Although the structures of many of these transport proteins have been determined, the mechanism they use to move molecules across the membrane is poorly understood. To better understand this process, Nilaweera, Nyenhuis and Cafiso examined the structure of BtuB, a transport protein found in the outer membrane of Escherichia coli that is responsible for absorbing vitamin B12. Previous experiments analyzing the structure of BtuB, and other similar transporters, have been carried out on purified proteins that were extracted from the outer membrane. However, these isolated proteins fail to replicate the transport activity observed",380,128,0.3368
dialogsum,"#Person1#: I'm here with Margaret Seabrook, the CEO of creative toys. In today's show, we're going to discuss the hottest new toy of two thousand seventeen, the Super Spinner. Margaret, welcome. #Person2#: Thank you, Brian. It's great to be here. #Person1#: OK, so tell us about this new toy. #Person2#: Well. It's similar to a relaxation ball in its function, but it's useful for anyone who has problems focusing. #Person1#: So how does it work? #Person2#: It's about the size of a cookie and it has 3 small round parts that can move in any direction. Basically, you just hold it in between your thumb and middle finger and spin it. That's it. #Person1#: That's it? #Person2#: Yeah, it's very popular. Not only with children, but with adults as well. #Person1#: A professor at MIT by the name of Jill Mean Lee has publicly stated there is no scientific or medical evidence for your claims about its benefits. Many schools also have banned the toy, saying it leads to a lack of focus in the classroom. #Person2#: Well, that professor is allowed to have her opinion. #Person1#: Fair enough, and who invented it? #Person2#: Catherine Hettinger, a chemical engineer, was first believed to be its creator. But then we found that an IT professional named Scott McCoskry was the actual inventor. #Person1#: It's time for a commercial break. More with Margaret Seabrook in a moment.","Margaret Seabrook is telling the audience about the new toy, the Super Spinner. It is similar to a relaxation ball in its function, but it's useful for anyone who has problems focusing. It's popular with children as well as adults.",235,40,0.1702
pubmed-summarization,"birth , and psychiatric diagnoses in the national registers was similar among participants and nonparticipants . for detailed information about the part study see the technical report . for the purpose of this study we restricted our analyses to the 8387 subjects that participated in both baseline and the first followup , with information on symptoms of depression and anxiety . definitions of anxiety and depressive disorders were made according to dsm - iv criteria , including research criteria , using validated diagnostic scales based on the questionnaire . the included scales were the sheehan patient - rated ( panic ) anxiety scale and the major ( icd-10 ) depression inventory , mdi . social phobia was assessed using the avoidance part of an instrument developed by marks and mathews and for obsessive - compulsive disorders screening questions suggested by the swedish psychiatric association and swedish institute for health services development were used . anxiety disorders included panic syndrome with agoraphobia , agoraphobia without panic syndrome , social phobia , obsessive - compulsive disorder , panic syndrome without agoraphobia , anxiety syndrome due to somatic cause , specific phobia , posttraumatic stress syndrome , general anxiety disorder , and acute stress syndrome . some of the persons affected by major depressive disorder may have a bipolar disorder since there was no scale for manic episodes in the questionnaire . three mutually exclusive groups were created : any depressive disorder ( n = 465 ) , any anxiety disorder ( n = 751 ) , and coexistent depressive and anxiety disorder ( n = 810 ) . in total 2 026 persons ( 24% ) fulfilled the criteria for any depressive or anxiety disorder . health care is accessible to everyone living in sweden , and because of tax subsidies , costs are limited for individuals . both private- and public - funded outpatient clinics are under the same regulations and the patient can choose their preference for the same cost , with exception for those private clinics without affiliation to the public health care system . with regards to psychologists and psychotherapists , there are also private practices without affiliation , and thus not subsidized , a more expensive alternative for the patient . the health care system is organized","background . in primary care , a vast majority of patients affected with depression and anxiety present with somatic symptoms . detection rate of psychiatric symptoms is low , and knowledge of factors influencing care seeking in persons affected by depressive and anxiety disorders on a population level is limited . objective . this study aims to describe if persons , affected by depression and anxiety disorders , seek care and which type of care they seek as well as factors associated with care seeking . method . data derives from a longitudinal population - based study of mental health conducted in the stockholm county in 19982010 and the present study includes 8387 subjects . definitions of anxiety and depressive disorders were made according to dsm - iv",380,128,0.3368
dialogsum,"#Person1#: Hi, I'm checking in. The last name is Rama. #Person2#: Yes, here is your reservation. You have a standard room reserved for two nights. Is that right? #Person1#: Actually, no. It should be a suite. I had booked a non-smoking king. #Person2#: Oh, my mistake. The reservation is for a suite and it is a non-smoking room with a king bed. I'm sorry for the error. #Person1#: That's okay. I'm here a little early. Is it possible to check in right now? #Person2#: Sure, that's no problem. May I have your credit card? We need a credit card on file for your room charges and incidentals. #Person1#: Here it is. #Person2#: Okay, now if you could please verify the room rate here, initial next to the X, and sign right here. How many keys will you need? #Person1#: Oh, just one. #Person2#: Okay, you're all set. You're in room 1201. Take the elevators to the 12th floor and it will be on your left. Do you need any help with your bags? #Person1#: No, I'm fine. Thanks. #Person2#: Enjoy your stay.",Rama has booked a non-smoking king for two nights and is checking in. #Person2# makes a mistake of the reservation but corrects instantly. And #Person2# helps Rama follow the procedures for check-in.,182,32,0.1758
dialogsum,"#Person1#: Where is that? #Person2#: Take me to the airport, please. #Person1#: Are you in a hurry? #Person2#: I have to be there before 1700. #Person1#: We'll make it except a jam. You know it's rush hour. #Person2#: There's an extra ten in it for you if you can get me there on time. #Person1#: I'll do my best. #Person2#: Here's twenty dollars. #Person1#: Do you have small bills? #Person2#: No. If you can't break it , keep the change. But can you give me a receipt? #Person1#: Here is your receipt. Thank you.","#Person1# is happy to pay an extra $10 if #Person2# can take #Person1# to the airport by 17:00, #Person2# pays $20 and tips #Person1# the change.",94,26,0.2766
scientific_lay_summarisation-elife-norm,"representative neuron exhibited suppressed responses to a tone presented as a standard (gray raster and PSTH) compared to the same tone presented as a deviant (red raster and PSTH). Left: responses to tone A, presented as a deviant in oddball stimulus 1, and a standard in oddball stimulus 2. Right: responses to tone B. Shaded regions indicate standard (gray) and deviant (red) tones trials. Gray dashed lines indicate tone onset and offset times. (D) Population histogram of stimulus-specific adaptation (SSA) index exhibited by all neurons included in the analysis. Gray and white bars indicate neurons expressing significant and non-significant SSA, respectively. Spike count for response to deviant tones was significantly greater than for response to standard tones (Wilcoxon rank sum test, one tail, p < 0. 05). The black marker indicates the population average SSA index. (E) Left: diagram of electrode spanning A1. Right: representative peri-stimulus current source density (CSD). Top: mean response to deviant tones. Bottom: mean response to standard tones. Gray dashed lines indicate tone onset and offset. Green dashed lines indicate the location of the granular layer. Negative CSD values (blue) indicate current sinks, while positive CSD values (red) indicate current sources. (F) Mean CSD collected from the thalamo-recipient layer, in response to standard (gray) and deviant (red) tones. Gray dashed lines indicate tone onset and offset. (G) Mean SSA index across sessions measured from thalamo-recipient granular layer CSD, infra- and supra-granular layer cortical CSD and mean neuronal spiking activity SSA index averaged over sessions. : http: //dx. . org/10. 7554/eLife. 09868. 00310. 7554/eLife. 09868. 004Figure 1— 1. Local field potentials recorded in A1 exhibit SSA. (A) Representative peri-stimulus local field potentials (LFPs) across cortical layers. Top: mean response to deviant tones. Bottom: mean response to standard tones. Gray dashed lines indicate tone onset and offset. Green dashed lines indicate the margins between cortical layers. (B) Mean LFP collected from the thalamo-recipient granular layer, in response to standard (gray) and deviant (red) tones. Gray dashed lines indicate tone onset and offset. : http: //dx. . org/10. 7554/eLife. 09868. 004 Auditory cortex, like other sensory cortices, contains morphologically and physiologically diverse inhibitory interneurons, which form dense interconnected networks with excitatory neurons (DeFelipe, 2002; Douglas and Martin, 2004). While different interneuron types have been hypothesized to carry out specialized","In everyday life, we are often exposed to a mix of different sounds. An essential task for our brain is to separate the important sounds from the unimportant ones. For example, stepping out onto a busy street, you may at first be very aware of the noise of traffic. Later, you may start to ignore the din and instead only notice sounds that break the monotony: a honking car horn or maybe a stranger' s voice. This is because the neurons in the auditory pathway respond differently to common and rare sounds. In particular, excitatory neurons in the region termed the ‘auditory cortex’ send fewer nerve impulses in response to frequent sounds, but respond vigorously to rare sounds. This phenomenon is called ‘stimulus-specific adaptation’, but it is not",380,128,0.3368
scientific_lay_summarisation-elife-norm,"et al. , 2008; Nadell et al. , 2009; Queller and Strassmann, 2009; Rainey and Kerr, 2010; Ratcliff et al. , 2012; Celiker and Gore, 2013). Microbial societies can be highly regulated, such as in the multicellular fruiting bodies of slime moulds and myxobacteria, where cells within the collective commit to a developmental program analogous to that of permanent multicellular organisms, including the soma-like' suicide’ of a part of the population. At a lesser degree of sophistication, many other forms of collectives are known in microbial organisms, ranging from colonies to biofilms (Grosberg, 2007; Nadell et al. , 2009; Niklas, 2014). A central feature of most microbial aggregates is their ability to persist long enough to affect the survival of their composing units. Such persistence is mediated by various forms of adhesion (Jiang et al. , 1998; Gresham, 2013) ensuring local cohesion between cells of the same or different kind. For instance, cells that fail to completely separate at the moment of division are selected for in regimes favoring increased aggregate size (Ratcliff, 2013), a feature reinforced by genetic homogeneity within groups (Nadell et al. , 2010). Although apparently an achievable initial step to foster multicellularity (Kirk, 2005), incomplete division is however unlikely to be the only mechanism at play in the emergence of multicellular organization in the tree of life, as some biological populations form aggregates from dispersed cells and can be composed of multiple genetically distinct strains (Nanjundiah and Sathe, 2011). Such cases turn out to be particularly challenging for the different theoretical solutions to the evolution of collective function (Tarnita et al. , 2013). Here, we focus on populations where groups disperse after individual reproduction and emerge anew from a well-mixed pool at the next generation. By affecting group formation as well as the performance of a group, differential attachment is an established means to create positive assortment, which enables the concomitant evolution of adhesive traits and sizeable groups in idealized, well-mixed populations (Simon et al. , 2013; Garcia and De Monte, 2013) as well as more realistic, spatially explicit settings (Garcia et al. , 2014). These models address the binary competition between more adhesive ‘cooperators’ and less adhesive ‘defectors’ and demonstrate that segregation between types can be generated even if encounters among players occur at random.","Throughout the living world, organisms work together in groups and help each other to survive. Indeed, multicellular organisms such as plants and animals owe their existence to cooperation. Life on Earth was initially made up of single cells, some of which evolved the ability to stick to each other and work together to form tissues and organs. However, developing the ability to adhere to other cells costs energy that could otherwise be used by the cell to ensure its own survival and proliferation. How multicellularity emerged, despite such costs, remains puzzling, in particular in groups of cells that do not share a common ancestor. Now, Garcia, Doulcier and De Monte have produced a mathematical model that shows how large cohesive groups of cells can evolve. Over long periods",380,128,0.3368
pubmed-summarization,"that eg was due to methicillin - resistant staphylococcal infection in contrast to all the four reports where there was pseudomonas infection . the case also highlights the need of early surgical intervention in such circumstances so as the probable sequelae of scarring of upper eye lid , resulting in mechanical ptosis which can result in stimulus deprivation amblyopia can be prevented . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .","ecthyma gangrenosum ( eg ) is a cutaneous infection which usually occurs in immunocompromised patients . we report a case of eg of the eyelid treated with escharotomy and skin grafting , highlighting the importance of surgical management . a 2-year - old asian indian female presented to us with right upper lid edema with a large necrotic area . the child received intravenous cefotaxime for a week and the necrotic area turned to a well - defined eschar . escharotomy with wound debridement and skin grafting was done . the present case highlights the importance of surgical intervention to prevent the sequelae of scarring of upper lid .",217,109,0.5023
dialogsum,"#Person1#: Excuse me, are you Dr. Smith? #Person2#: Yes I am. And you. . . #Person1#: I'm David, Joanna's husband. She has to be at work late today. So she asked me to pick you up here. #Person2#: So nice to meet you, David. Call me Bill. It's very nice of you to come here. #Person1#: My pleasure.",Joanna's husband David picks up Bill because Joanna works late.,58,10,0.1724
pubmed-summarization,"the highest number of poisoning cases while organochlorines caused the most number of deaths . cheng in 1994 studied 2000 benguet vegetable farmers and found that the most common complaints were allergic reactions both in the skin and the eyes , abdominal pain , dizziness , chest pain , headache , and nose bleed . meanwhile , a study on pesticide poisoning in selected hospitals in four philippines regions in 2001 found that cases of acute poisoning were more prevalent than chronic cases . this study aimed to identify the pesticide exposure and risk factors among vegetable farmers . the data can be used as baseline data on the vegetable industry in the philippines . this was a cross - sectional study to investigate the prevalence of pesticide exposure and its risk factors . target population consisted of vegetable farmers in the largest vegetable producing community in the philippines . the inclusion criteria were farmers living in the community for at least one year from the time of interview , and practicing farmers who own or work a farm in the community . those who were involved in organic farming and the migrant farmers who have been in the area for less than one year were excluded . there were 211 respondents from the identified municipalities selected as the study population using cluster sampling . the sampling size calculated with p = .05 was 211 vegetable farmers and 37 farms . data gathering was done using the following : ( 1 ) questionnaire structured personal interview with farm workers / farmers was done by research assistants who were trained prior to the data collection . details included personal information , health history , pesticide usage , work practices , work conditions , risk factors associated with pesticide exposure , and health data ; ( 2 ) exposure assessment monitoring on work conditions , work practices , and pesticide concentration ; ( 3 ) work analysis in each farm was also done to validate work practices related to pesticide preparation and application . recall bias was dealt with by confining the health data questionnaire to the last one year from the time of interview . the health data were also collected by medical doctors who simultaneously conducted physical assessment of the","this was a cross - sectional study that investigated pesticide exposure and its risk factors targeting vegetable farmers selected through cluster sampling . the sampling size calculated with p = .05 was 211 vegetable farmers and 37 farms . the mean usage of pesticide was 21.35 liters . risk factors included damaged backpack sprayer ( 34.7% ) , spills on hands ( 31.8% ) , and spraying against the wind ( 58% ) . the top 3 pesticides used were pyrethroid ( 46.4% ) , organophosphates ( 24.2% ) , and carbamates ( 21.3% ) . those who were exposed to fungicides and insecticides also had higher total pesticide exposure . furthermore , a farmer who was a pesticide applicator , mixer , loader , and who had",380,128,0.3368
dialogsum,"#Person1#: I hate to say goodbye, but it's late. #Person2#: Can't you stay for a little bit longer, it's only 8. #Person1#: I wish I could. But I'm afraid I can't. I've got some serious studying to do. I have to go. #Person2#: OK. See you on Today. #Person1#: See you on Moday. Have a great weekend. #Person2#: You too. Thanks for dropping in.",#Person2# wants #Person1# to stay but #Person1# has to leave.,64,10,0.1562
pubmed-summarization,") , is a hypermutable phenotype caused by impaired dna mismatch repair ( mmr ) system to correct errors such as single - base mismatches and insertion - deletion loops that spontaneously occur during dna replication ( 2324 ) . msi arises from impaired dna mmr genes , such as mutl homolog 1 ( mlh ) 1 , muts homolog ( msh ) 2 , and to a lesser degree msh6 ( 2526 ) . faulty dna fidelity caused by defects in dna mmr causes frameshift and point mutations , mainly in repetitive sequences ( microsatellites ) ( 26 ) . lynch syndrome is a well - established hereditary predisposition to colorectal cancer caused by a germline mutation in a dna mmr gene . however , 12% of msi exhibit sporadic crc with cin ( 27 ) . because pathways are not mutually exclusive , crc can display features of multiple pathways . i colon cancer , surgery is the definitive treatment without the use of adjuvant chemotherapy . benefit of adjuvant chemotherapy for patients with a stage ii disease is highly debatable due to minimal gains in overall response . however , adjuvant chemotherapy is generally acceptable for the use patients with node - positive cancer following surgery ( high - risk stage ii disease ) ( 29 ) . adjuvant chemotherapy is required for all patients with a stage iii colon cancer after surgical resection , which have a high risk of recurrence of 15~50% ( 30 ) . conventional chemotherapeutic agents include 5-fluorouracil ( 5-fu ) with leucovorin ( lv ) , capecitabine ( an orally administered prodrug of 5-fu ) , oxaliplatin , and irinotecan . adjuvant chemotherapy using the 5-fu / lv regimens following surgery provides significant reduction in mortality by 22% and improves event - free survival by 35% ( 31 ) . to improve disease - free survival ( dfs ) and overall survival ( os ) , currently , folfox ( 5-fu / lv and oxaliplatin ) or folfiri ( 5-fu / lv and irinotecan ) is widely used for standard first- or second - line treatment in patients with node - positive colon cancer following surgical resection ( 3233 ) . however , folfox and folfiri demonstrated greater toxicities , including","colorectal cancer is the third leading cancer worldwide . although incidence and mortality of colorectal cancer are gradually decreasing in the us , patients with metastatic colorectal cancer have poor prognosis with an estimated 5-year survival rate of less than 10% . over the past decade , advances in combination chemotherapy regimens for colorectal cancer have led to significant improvement in progression - free and overall survival . however , patients with metastatic disease gain little clinical benefit from conventional therapy , which is associated with grade 3~4 toxicity with negative effects on quality of life . in previous clinical studies , cell - based immunotherapy using dendritic cell vaccines and sentinel lymph node t cell therapy showed promising therapeutic results for metastatic colorectal cancer . in our",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling. The first two lineages to segregate during mammalian development are the inner cell mass (ICM) and the trophectoderm (TE). The TE is an extraembryonic tissue, giving rise to the trophoblast lineages of the placenta. The ICM will form two additional lineages before implantation - the pluripotent epiblast (EPI), giving rise to all germ layers of the embryo, and the primitive endoderm (PE), largely forming the endoderm layers of the yolk sacs (Cockburn and Rossant, 2010). At the blastocyst stage, the TE forms a monolayer tight junction-coupled epithelium enclosing the blastocoelic cavity, at one end of which lies the ICM. Inside and outside cell populations first form following the 8 to 16 cell divisions (Anani et al. , 2014; Dietrich and Hiiragi, 2007; Watanabe et al. , 2014). During the 16 cell stage and during the 16 to 32 cell divisions, division-independent and dependent cell internalization leads to dynamic morphological rearrangements (Anani et al. , 2014; Maître et al. , 2016; Morris et al. , 2010; Samarage et al. , 2015; Watanabe et al. , 2014; Yamanaka et al. , 2010). From the 32 cell stage onwards, apart from the relatively rare event of division-independent cell internalization, inside and outside positioning is generally a good indicator of ICM and TE lineage fates, respectively (McDole et al. , 2011; McDole and Zheng, 2012; Pedersen et al. , 1986; Watanabe et","In female mammals, conception is a complex process that involves several stages. First, an egg is released from the ovary and travels along a tube called the oviduct, where sperm from a male may fertilize it. If the egg is fertilized, the newly formed embryo moves into the womb, where it will then implant into the walls. In mice, it takes around four days for the embryo to implant and during this time, the cells in the embryo divide several times and start to specialize to form distinct cell types called lineages. The first two lineages to form are known as the inner cell mass and the trophectoderm. The inner cell mass forms a ball of cells within the embryo and contains the precursors of all cells that",380,128,0.3368
scientific_lay_summarisation-elife-norm,"upon conditioning injury. In support of this, Wnd/DLK is transported in axons (Xiong et al. , 2010) and is required acutely in injured axons for the generation of signals that are retrogradely transported to the cell body (Xiong et al. , 2010; Shin et al. , 2012). DLK/Wnd is required for axonal regeneration in many types of neurons, including motoneurons in mammals, flies and worms, and CNS neurons where regeneration is ectopically induced by PTEN mutations (Yan et al. , 2009; Hammarlund et al. , 2009; Xiong et al. , 2010; Shin et al. , 2012; Watkins et al. , 2013). Conversely, in mammalian CNS neurons that do not regenerate (eg. retinal ganglion cells, RGCs), DLK activation after injury mediates cell death (Welsbie et al. , 2013; Watkins et al. , 2013). Collectively, these findings support the model that a conserved function of the Wnd/DLK kinase is to ‘sense’ axonal damage. Through a yet unknown mechanism, axonal damage leads to activation of Wnd/DLK’s kinase function. Once activated, downstream signaling mediates both beneficial and deleterious outcomes in neurons, depending upon the context. The high stakes outcomes of regeneration or death, combined with additional findings that DLK mediates cell death in models for nerve growth factor withdrawal (Huntwork-Rodriguez et al. , 2013; Ghosh et al. , 2011), glaucoma (Welsbie et al. , 2013), MPTP toxicity (Mathiasen et al. , 2004) and excitotoxicity (Pozniak et al. , 2013), have inspired much interest in understanding the unknown pathways that lead to the activation of DLK/Wnd in injured axons. Here we identify a direct upstream activator of DLK/Wnd in injured axons, in the form of the cAMP effector kinase PKA. We find that PKA phosphorylates evolutionarily conserved serines within the activation loop of DLK, which is sufficient to activate DLK independently of its downstream signaling mechanisms. In addition, our functional studies in both Drosophila motoneurons and adult mammalian DRG neurons indicate that the ability of cAMP and PKA to promote axonal regeneration depends entirely upon the ability of PKA to activate the DLK/Wnd kinase. These findings present a unified and evolutionarily conserved molecular pathway, from cAMP to PKA to DLK, which plays a central role in stimulating the ability of injured axons to regenerate. Previous studies in mammalian and C. elegans neurons suggest that cAMP","Adult mammals typically cannot repair damage to the nerve fibers in their brain or spinal cord. This is because these nerve cells cannot generally grow new nerve fibers. However this inability to regenerate nerve fibers is not set in stone. Instead, it can be unlocked by a second injury in nerves elsewhere in the body, the so-called “peripheral nervous system”. This process relies on an enzyme called DLK, which becomes activated in damaged nerve fibers. But how does DLK ‘sense’ damage to nerve fibers? Injuring the peripheral nervous system causes the levels of a molecule called cAMP to increase in the damaged nerve cells, and the elevated cAMP levels stimulate the nerve fibers to regenerate. However, it was not known if cAMP activates DLK, or if the two",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Trade-offs between protein stability and activity can restrict access to evolutionary trajectories, but widespread epistasis may facilitate indirect routes to adaptation. This may be enhanced by natural environmental variation, but in multicellular organisms this process is poorly understood. We investigated a paradoxical trajectory taken during the evolution of tetrapod dim-light vision, where in the rod visual pigment rhodopsin, E122 was fixed 350 million years ago, a residue associated with increased active-state (MII) stability but greatly diminished rod photosensitivity. Here, we demonstrate that high MII stability could have likely evolved without E122, but instead, selection appears to have entrenched E122 in tetrapods via epistatic interactions with nearby coevolving sites. In fishes by contrast, selection may have exploited these epistatic effects to explore alternative trajectories, but via indirect routes with low MII stability. Our results suggest that within tetrapods, E122 and high MII stability cannot be sacrificed—not even for improvements to rod photosensitivity. Nature-inspired strategies are increasingly recruited toward engineering objectives in protein design (Khersonsky and Fleishman, 2016; Jacobs et al. , 2016; Goldenzweig and Fleishman, 2018, a central challenge of which is to successfully manipulate backbone structure to modulate stability without introducing undesirable pleiotropic effects on protein activity (Khersonsky and Fleishman, 2016; Goldenzweig and Fleishman, 2018; Starr and Thornton, 2017; Tokuriki and Tawfik, 2009). Engineering protein stability and activity requires an understanding of a protein’s sequence-function relationship, or landscape (Pál and Papp, 2017; Wu et al. , 2016; Starr et al. , 2017), where billions of possible pair-wise and third-order interactions can exist between amino acids (Starr and Thornton, 2017; Storz, 2016), and only a limited number of amino acid combinations will confer the function of interest (Wu et al. , 2016; Starr et al. , 2017; McMurrough et al. , 2014; Mateu and Fersht, 1999; Tarvin et al. , 2017). To understand the context-dependence of amino acid functional effects (also known as intramolecular epistasis [Starr et al. , 2017; Storz, 2016; Echave et al. , 2016]), approaches such as deep mutational scanning (Wu et al. , 2016; Starr et al. , 2017; Sailer and Harms, 2017) can explore a subset of sequence-function space formed in response to a limited set of artificial selection pressures (Starr and Thornton, 2017). By contrast, natural protein sequence variation reflects the range of protein function","People can see in dim light because of cells at the back of the eye known as rods. These cells contain two key components: molecules called retinal, which are bound to proteins called rhodopsin. When light hits a rod cell, it kicks off a cascade of reactions beginning with the retinal molecule changing into an activated shape and ending with a nerve impulse travelling to the brain. The activated form of retinal is toxic, and as long as it remains bound to the rhodopsin protein it will not damage the rod or surrounding cells. The toxic retinal also cannot respond to light. It must be released from the protein and converted back to its original shape to restore dim light vision. As with all proteins, rhodopsin’s structure comprises",380,128,0.3368
pubmed-summarization,"pancreatic acini and dialated ducts interspersed by smooth muscle bundles ( . photomicrograph showing pancreatic acini and ducts ( h&e , x100 ) the patient had an uneventful recovery and remains asymptomatic postoperatively . as stated by hunt and bonesteel ( 5 ) the first case of heterotopic pancreas was reported by schultz in 1729 , and klob provided its histological confirmation in 1859 ( 6 ) . the reported incidence in autopsy studies is 0.5 - 13% ( 3 ) . in adults it is found mainly in the stomach , duodenum and jejunum , in much smaller proportions in the ileum and meckel s diverticulum , and it is rarely found in the esophagus , liver , gallbladder , omentum , lungs , mediastinum , fallopian tubes and umbilicus ( 2 ) . in adults the incidence is higher in males , while in pediatric patients the female gender prevails . the proposed theory is that during rotation of foregut in a fetus and fusion of dorsal and ventral parts of pancreas , small islands of pancreas are carried away and continue to develop at its aberrant location ( 2 ) . most patients with ectopic pancreas are asymptomatic and diagnosis is usually performed during radiological examination or endoscopy of the digestive tract or during surgical explorations motivated by other diseases ( 2 ) . when symptomatic , about 30% of total mimic clinical symptoms similar to diseases that affect the organ in which the heterotopia is located ( 3 ) . usually they present in the form of small yellowish nodules , ranging from 1 mm to 5 cm , typically covered by intact mucosa , and often exhibit a central hole representing exteriorization of the rudimentary pancreatic duct . however , lesions smaller than 1.5 cm do not usually show such an orifice ( 8) . the ectopic pancreatic tissue is detected more frequently in the submucosa and muscularis propria layers of the gastrointestinal tract and may be observed in the sub - serosa or even in the serosa of the affected segment ( 2 ) . the heinrich classification system is frequently used to classify heterotopic pancreas : type 1 ( containing acini , islets and ducts ) , type 2 ( acini and ducts","heterotopic , aberrant or ectopic pancreas is defined as the presence of pancreatic tissue in topographic anomaly , with no anatomical , neural or vascular connection to the normal pancreas . it is a rare condition found mainly in stomach , duodenum and jejunum . ileal heterotopic pancreas is an uncommon condition and has been rarely reported in children so far . hereby we report a case of heterotopic pancreas presenting as ileal poyp leading to ileoileal intussusception in a 12 year child .",380,84,0.2211
scientific_lay_summarisation-elife-norm,"between the replicated sister chromatids is established from S phase until the onset of mitotic anaphase, which ensures that an identical set of genetic information is inherited by both daughter cells. Sister chromatid cohesion is mediated by a conserved multi-subunit ring-shaped protein complex called cohesin, which consists of four subunits: the coiled-coil proteins Smc1 and Smc3 are linked by the globular SMC hinge domains at one end, at the other end, the ATPase head domains bind to Scc1–Mcd1–Rad21–Klesin together with Scc3 (Haering et al. , 2002,2004; Michaelis et al. , 1997; Tóth et al. , 1999). Cohesin is proposed to hold DNA topologically (Haering et al. , 2008). The cohesin complex is loaded onto chromosomes in late G1 by the cohesin-loading complex Scc2–Scc4 (Ciosk et al. , 2000) through opening of the SMC hinge region (Gruber et al. , 2006; Nasmyth, 2011). In budding yeast, cohesin preferentially accumulates between convergently transcribed genes and at centromeres (Lengronne et al. , 2004; Tanaka et al. , 1999). Establishment of sister chromatid cohesion during S phase requires an essential acetyltransferase, Eco1/Ctf7, which acetylates the cohesin subunit Smc3 at K112 and K113 (Rolef Ben-Shahar et al. , 2008; Skibbens et al. , 1999; Tanaka et al. , 2000; Tóth et al. , 1999; Unal et al. , 2008) to inhibit cohesin’s interaction with the Wpl1–Pds5 complex, which destabilizes the cohesin on chromatin (Rolef Ben-Shahar et al. , 2008; Kueng et al. , 2006; Rowland et al. , 2009; Sutani et al. , 2009; Terret et al. , 2009). In addition, two non-essential cohesion establishment pathways, including Ctf4 and Ctf18, contribute to cohesion establishment (Hanna et al. , 2001; Mayer et al. , 2001). Cohesion can no longer be established once replication is complete (Uhlmann and Nasmyth, 1998), except during DSBs in G2, when cohesin is recruited to DSBs for Eco1-dependent cohesion establishment and efficient break repair by homologous recombination (HR) (Ogiwara et al. , 2007; Ström et al. , 2004,2007; Unal et al. , 2007). The destruction of cohesion at the onset of anaphase is mediated by separase-induced proteolysis of Scc1, thereby triggering the segregation of sister chromatids (Nasmyth and Haering, 2009; Peters et al. , 2008). Emerging evidence suggests that establishment of cohesion between sister chromatids is coupled to replication fork progression. A","Most of the DNA in a cell is stored in structures called chromosomes. During every cell cycle, each cell needs to replicate its chromosomes, hold the two chromosome copies (also known as “sister chromatids”) together before cell division, and distribute them equally to the two new cells. Each step must be executed accurately otherwise the new cells will have extra or missing chromosomes – a condition that is seen in many cancer cells and that can cause embryos to die. Since these processes are so essential to life, they are highly similar in a range of species, from single-celled organisms such as yeast to multicellular organisms like humans. However, it was not clear when and how sister chromatids first join together, or how this process is linked to",380,128,0.3368
pubmed-summarization,"infusion . but bp was dropped from 160/100 mm hg to 70/40 mm hg and her consciousness was impaired . chest x - ray showed cardiomegaly and patchy increased opacities in right upper and lower lobes ( . 1 ) . arterial blood gas analysis showed a metabolic acidosis ( ph : 7.24 , pao2 : 70 mm hg , paco2 : 39 mm hg , hco3- : 16.7 mmol / l ) . a diffusion - weighted magnetic resonance brain imaging showed localized encephalomalacic lesions in left parietal lobe and right temporal pole region with peripheral old blood product deposition . division of cardiology was called for suspecting st elevation myocardial infarction ( stemi ) since an electrocardiogram ( ecg ) showed precordial v2 - 4 st segment elevation and she was found to have elevated cardiac enzymes on serial measurements ( troponin i levels 0.62 2 ) . there was no evidence of pericarditis or pheochromocytoma from her history , clinical symptoms , laboratory findings and echocardiographical features . an emergency transthoracic echocardiography ( tte ) showed an apical ballooning of the left ventricle ( lv ) with severe systolic dysfunction ( lv ejection fraction = 23% by simpsons methods ) and focal hypokinesia of right ventricular ( rv ) apex with decreased rv systolic function . fractional area change ( fac ) , [ ( rv end diastolic area - rv end systolic area ) / rv end diastolic area 100 ] was 22 % , tricuspid annular plane systolic excursion was 20 mm . despite tte finding was accordant with tc , emergency coronary angiography was done since we suspected stemi . there was no significant stenosis in left anterior descending artery , left circumflex artery and right coronary artery . however , hypokinesia of the mid to apical lv and rv from tte were discordant with coronary artery lesion . she had no further epileptic seizures during hospitalization with sodium valproate 300 mg every 12 hours and initial metabolic acidosis was resolved . after supportive care with standard heart failure therapy ( aspirin , - blocker , angiotensin converting enzyme inhibitor , 3-hydroxy-3-methylglutaryl - coenzyme a reductase inhibitor , diuretics and anti - convulsant ) , her clinical condition was getting better and moved from","we describe a case of takotsubo cardiomyopathy in an elderly woman after status epilepticus . in an emergency echocardiography , not only left ventricular apical ballooning but also right ventricular apical hypokinesia was observed . after a medical management , the patient 's condition was improved and a follow - up echocardiography showed substantial recovery of left and right ventricular apical ballooning .",380,63,0.1658
pubmed-summarization,"history of body weight status to clarify the effect of past obesity on diabetic nephropathy . we examined subjects with type 2 diabetes whose estimated glomerular filtration rate ( egfr ) was 30 ml / min/1.73 m or more and who were admitted to saiseikai central hospital from january 1999 to december 2004 ( n = 1834 ) or keio university hospital from april 1998 to september 2010 ( n = 1093 ) for the management of metabolic control . the study protocol was reviewed and approved by the ethics committee of both hospitals . those subjects in whom the etiology of renal disease was strongly suspected to be other than diabetic nephropathy were excluded . according to the history of body weight status and the japanese criteria for obesity , we defined current obesity as bmi on hospitalization of 25 or more , previous obesity as bmi on hospitalization of less than 25 and self - reported maximum bmi in the past of 25 or more , and continuously lean as maximum bmi of less than 25 . hba1c level on admission was determined by high - performance liquid chromatography ( hplc : arkray inc . , kyoto , japan ) according to the recommended method by the japan diabetes society ( jds ) at that time and converted to the national glycohemoglobin standardization program ( ngsp ) value . egfr ( ml / min/1.73 m ) was calculated as 194 cr age ( with further multiplication by 0.739 for female subjects ) using the equation provided by the japanese society of nephrology . subjects with albumin excretion rate ( aer ) of 20 g / min or more in 24-hour urine were considered to have diabetic nephropathy . hypertension was defined as systolic blood pressure > 140 mmhg , diastolic blood pressure > 90 mmhg , or the prescription of antihypertensive medication . < 1.04 mmol / l , or the prescription of lipid - lowering medication . continuous variables are expressed as mean sd . differences in baseline characteristics among the obesity categories were analyzed by anova and chi - squared test . chi - squared test was also performed to evaluate differences in prevalence , with bonferroni 's correction for post hoc multiple comparisons . as","aims . we analyzed the prevalence of nephropathy according to past body weight status in japanese subjects with type 2 diabetes because the influence of past obesity on diabetic complications is not certain . methods . we examined the prevalence of nephropathy in 2927 subjects with type 2 diabetes mellitus according to current bmi and maximum bmi in the past . we defined current obesity as bmi on hospitalization of 25 or more , previous obesity as bmi on hospitalization of less than 25 and self - reported maximum bmi in the past of 25 or more , and continuously lean as maximum bmi of less than 25 . results . the prevalence of nephropathy was significantly higher in subjects with current obesity ( 40.6% ) or previous",380,128,0.3368
pubmed-summarization,"basal cisterns with severe cerebral edema [ ] . the bar penetrated the third ventricle and suprasellar cistern ; adjacent to the right carotid artery and branches , the dense hemorrhage observed within the suprasellar cistern was likely the result of injury to the right internal carotid artery . angiography could not be performed because the patient rapidly worsened neurologically ( gcs 3 : e1m1v1 ) . lateral skull radiograph shows the bar penetrating the orbit and emerging from the occipital bone . computed tomography demonstrates the bar 's trajectory into the sellar and suprasellar region via the superior orbital fissure . the right internal carotid artery was found to be lacerated , and the right optic nerve and optic chiasm transected near the superior orbital fissure . the bar penetrated the superior orbital fissure , anterior clinoid process , suprasellar cistern , third ventricle , and cerebrum . incidentally , if a metal bar is fixed at the superior orbital fissure , it can usually be mobilized and removed , retracting it carefully from the entry site under direct visualization and avoiding resistance or leverage . severe bleeding from the right internal carotid artery occurred despite this maneuver ; the carotid artery required ligation . the patient died 10 days postoperatively due to ischemic brain injury , diencephalic injury , and intractable increased intracranial pressure with brainstem herniation . . most reports are by pens , knives , or chopsticks . due to its thin wall , the orbit is the most vulnerable structure in the cranium ; penetrating orbital injuries are often associated with traumatic brain injury . the cranium can be violated via the transorbital route through the superior orbital fissure and optic canal . the degree of neurologic damage is related to orbital bone anatomy , as well as the size , shape , and trajectory of the object . intracranial penetration may occur through the orbital roof , superior orbital fissure or optic canal . therefore , medial or canthal injuries , associated with severe visual loss , strongly suggest optic canal damage . the most frequent site of penetration is through the orbital roof because the superior orbital plate of the frontal bone is thin and fragile . this frequently leads to frontal lobe","transorbital intracranial injury is uncommon , representing 0.04% of penetrating head trauma with a high mortality rate . orbital penetrating injuries may cause severe brain injury if the cranium is entered , typically via the orbital roof , the superior orbital fissure , or the optic canal . a 13-year - old male sustained a severe brain injury due to penetration of the right orbit with an iron bar . the bar entered the inferiomedial aspect of the orbit and emerged from the left occipital bone . neurological examination revealed deep coma ( gcs : e1m2v1 ) with fixed , dilated , and non - reactive pupils . the bar followed an intracranial trajectory , through the third ventricle and suprasellar cistern . the patient underwent an immediate",380,128,0.3368
pubmed-summarization,"medical history and prior treatment , as well as details of the procedure , was limited to that provided by the patient himself or the accompanying procedure report . the patient reported that he had previously received esis on the left side of his lower back ; this was the second injection in a series of 3 . correct needle placement in the left l5-s1 neural foramen was verified with epidurography immediately after the injection , the patient felt his legs going dead ; paraplegia of the lower extremities was noted . because of the concern for intrathecal injection with resultant motor blockade , the patient was monitored for 4 hours . when no clinical improvement was observed , he was transferred to a nearby community hospital emergency department for neurologic examination . although the initial magnetic resonance imaging ( mri ) study performed in the emergency department was unremarkable ( . however , a second mri study to evaluate the possibility of vascular complications obtained 48 hours after the injection showed a conus infarct ( . 2 ) . five hours after esi in a 47-year - old man , magnetic resonance imaging scans performed at the emergency department were unremarkable , showing a normal appearing conus . ( a ) ( b ) t1-weighted sagittal image ( repetition time , 416.7 ; echo time , 15.0 ) . magnetic resonance images ( about 48 hours after the procedure ) showing extensive signal abnormalities within the lower thoracic spinal cord and conus compatible with the clinical diagnosis of conus infarct . ( a ) t1-weighted sagittal image ( repetition time , 675.0 ; echo time , 9.6 ) . ( b ) t2-weighted sagittal image ( repetition time , 3640.0 ; echo time , 102.0 ) . ( c ) short tau inversion recovery ( stir ) sagittal image ( repetition time , 4000.0 ; echo time , 58.0 ) . at 1-month follow - up , the patient could walk without assistance with a slow and calculated gait , had symmetric lower - extremity strength , and had dorsiflexion strength of 4 of 5 bilaterally . his urinary urge sensation had returned , and occasional episodes of fecal incontinence occurred in relation to bladder overdistention . our search","backgroundgiven the risk of paralysis associated with cervical transforaminal injection , is it time to reconsider transforaminal injections of the lumbar spine ? arguments for discontinuing lumbar injections have been discussed in the anesthesia literature , raising concern about the risks of epidural steroid injections ( esis).methodsin a 47-year - old man , paraplegia of the lower extremities developed , specifically conus medullaris syndrome , after he underwent an esi for recurrent pain . correct needle placement was verified with epidurography . immediately after the injection , the patient felt his legs going dead ; paraplegia of the lower extremities was noted.resultsan initial magnetic resonance imaging study performed after the patient was transferred to the emergency department was unremarkable . however , a later neurosurgical evaluation showed conus",380,128,0.3368
dialogsum,"#Person1#: Mom, you know that Andrea and I sometimes worry about you. #Person2#: Really? Why would you worry about me? I'm just fine. #Person1#: You're almost 70 years old, Mom! Don't you think it would be better for you if you moved in with us? #Person2#: No way! I like my apartment, and I like to be independent. #Person1#: Do you ever get lonely living alone? #Person2#: Not at all. I see you and your family twice a week, and I enjoy seeing my own friends. I'm too busy to feel lonely!","#Person1# and Andrea worry about #Person1#'s mom living alone, so #Person1# asks #Person1#'s mom to move in. #Person1#'s mom refuses.",92,20,0.2174
scientific_lay_summarisation-elife-norm,"alignment of the 21 leucine-rich repeats in HAESA with the plant LRR consensus sequence shown for comparison. Conserved hydrophobic residues are shaded in gray, N-glycosylation sites visible in our structures are highlighted in blue, cysteine residues involved in disulphide bridge formation in green. (D) Asn-linked glycans mask the N-terminal portion of the HAESA ectodomain. Oligomannose core structures (containing two N-actylglucosamines and three terminal mannose units) as found in Trichoplusia ni cells and in plants were modeled onto the seven glycosylation sites observed in our HAESA structures, to visualize the surface areas potentially not masked by carbohydrate. The HAESA ectodomain is shown in blue (in surface representation), the glycan structures are shown in yellow. Molecular surfaces were calculated with the program MSMS (Sanner et al. , 1996), with a probe radius of 1. 5 Å. : http: //dx. . org/10. 7554/eLife. 15075. 00410. 7554/eLife. 15075. 005Figure 1— 2. Hydrophobic contacts and a hydrogen-bond network mediate the interaction between HAESA and the peptide hormone IDA. (A) Details of the IDA binding pocket. HAESA is shown in blue (ribbon diagram), the C-terminal Arg-His-Asn motif (left panel), the central Hyp anchor (center) and the N-terminal Pro-rich motif in IDA (right panel) are shown in yellow (in bonds representation). HAESA interface residues are shown as sticks, selected hydrogen bond interactions are denoted as dotted lines (in magenta). (B) View of the complete IDA (in bonds representation, in yellow) binding pocket in HAESA (surface view, in blue). Orientation as in (A). (C) Structure based sequence alignment of leucine-rich repeats in HAESA with the plant LRR consensus sequence shown for comparison. Residues mediating hydrophobic interactions with the IDA peptide are highlighted in blue, residues contributing to hydrogen bond interactions and/or salt bridges are shown in red. The IDA binding pocket covers LRRs 2–14 and all residues originate from the inner surface of the HAESA superhelix. : http: //dx. . org/10. 7554/eLife. 15075. 00510. 7554/eLife. 15075. 006Figure 1— 3. The IDA-HAESA and SERK1-HAESA complex interfaces are conserved among HAESA and HAESA-like proteins from different plant species. Structure-based sequence alignment of the HAESA family members: Arabidopsis thaliana HAESA (Uniprot (http: //www. uniprot. org) ID P47735), Arabidopsis thaliana HSL2 (Uniprot ID C0LGX3), Capsella rubella HAESA (Uniprot ID R0F2U6), Citrus clementina HSL2 (Uniprot ID V4U227), Vitis vinifera HAESA (Uniprot ID F6HM39).","Plants can shed their leaves, flowers or other organs when they no longer need them. But how does a leaf or a flower know when to let go? A receptor protein called HAESA is found on the surface of the cells that surround a future break point on the plant. When its time to shed an organ, a hormone called IDA instructs HAESA to trigger the shedding process. However, the molecular details of how IDA triggers organ shedding are not clear. The shedding of floral organs (or leaves) can be easily studied in a model plant called Arabidopsis. Santiago et al. used protein biochemistry, structural biology and genetics to uncover how the IDA hormone activates HAESA. The experiments show that IDA binds directly to a canyon shaped pocket",380,128,0.3368
pubmed-summarization,"cancer is one of the most common malignancies worldwide ; it is the leading cause of death in economically developed countries and the second leading cause of death in developing countries . approximately 12.7 million new cases of cancer and 7.6 million cancer - related deaths were reported in 2008 . despite the efforts exerted by many researchers to elucidate the mechanism of carcinogenesis , environmental factors , diet , lifestyle , and smoking and drinking habits have been implicated in the development of cancer . various epidemiological studies have revealed that inflammation - associated factors , such as interleukin- ( il- ) 1 , il-6 , il-10 , and tumor necrosis factor- , are associated with cancer tumorigenesis . interleukin-17 ( il-17 ) is a proinflammatory cytokine that serves important functions in inflammation , autoimmune disorders , and cancer . the il-17 cytokine family consists of six members ( il-17a to il-17f ) and five receptors ( il-17ra to il-17rd and sef ) . these cytokines are primarily produced from a subset of cd4 + effector cells known as th17 cells . clinical studies have shown increased il-17 expression in malignant tumors . single nucleotide polymorphisms ( snps ) can alter gene functions and protein expression , which influence cell proliferation and increase cancer risk . the il-17a rs2275913g > a and il-17f rs763780t > c polymorphisms are the most common loci associated with il-17 activity and cancer risk . in 2009 , shibata et al . conducted the first study and reported a positive relationship between gastric cancer and the il-17a rs2275913g > a polymorphism in a japanese population . but no significant association was found between gastric cancer and polymorphisms of il-17f rs763780 t > c . many epidemiological studies have focused on the association of the il-17a rs2275913g > a and il-17f rs763780t > c polymorphisms with cancer risk therefore , we performed a meta - analysis to clarify the possible association of the il-17a rs2275913g > a and il-17f rs763780t > c polymorphisms with cancer risk . the pubmed , embase , and chinese national knowledge infrastructure databases were searched using the terms cancer , tumor , the related articles option was also used in each research article to find potential relevant studies on the","epidemiological studies have suggested that interleukin-17 ( il-17 ) polymorphisms are associated with cancer risk . however , the results of these studies are inconsistent . therefore , we performed a meta - analysis to obtain a precise conclusion . odds ratios ( ors ) with 95% confidence intervals ( cis ) were used to assess the association of the il-17a rs2275913g > a and il-17f rs763780t > c polymorphisms with cancer risk . publication bias and sensitivity analyses were performed to ensure the statistical power . overall , 10 relevant case - control studies involving 4,516 cases and 5,645 controls were included . the pooled ors with 95% cis indicated that the il-17a rs2275913g > a polymorphism was significantly associated with increased cancer risk ( for a",380,128,0.3368
pubmed-summarization,"correct placement of each endotracheal tube was verified by auscultation during independent ventilation and later confirmed by bronchoscopy and/or autopsy . additional doses of pentobarbital were given to ensure adequate anesthesia ( titrated to achieve a heart rate of < 160 beats / min , systolic blood pressure 140 mmhg , and absence of withdrawal to painful stimuli ) . each lung was independently mechanically ventilated ( bp 200 , bear medical systems , riverside , california , usa ) simultaneously with identical settings . pulmonary function tests ( pfts ) were recorded for each lung at baseline while on heliox and nitrox using an infant / pediatric pulmonary function computer ( peds , medical associated services , inc . , hatfield , pennsylvania , usa ) , calibrated for the gas mixture being delivered to derive tidal volume , resistance and compliance . airflow data were obtained by a fleisch 0 ( pediatric ) tachometer ( oem medical , richmond , virginia , usa ) . while ventilating both lungs with nitrox , methacholine ( 10 mg / ml 1.5ml diluted to 3 ml with buffer ) was aerosolized continuously to both lungs simultaneously over 3 min until airway resistance of each lung at least doubled from baseline . one lung was then randomized to receive nitrox and the other to receive heliox . fio2 was not adjusted to either lung , but remained at 30% throughout the experiment . pulmonary function testing was performed every 2 min , alternating lungs until the resistance of one lung returned to within 15% of baseline or until 16 min had elapsed . as approximately 2 min was required to complete each pulmonary function assessment and because of differences in calibration between the two gases used , right and left lung pfts were not obtained simultaneously . therefore , the order for each lung to be tested was determined randomly and data were compared by pulmonary function assessment number . results of pfts obtained at 2 min and 4 min are reported as assessment number 1 ; the results of pfts performed at 6 min and 8 min are reported as assessment number 2 ; the results of pfts performed at 10 and 12 min as assessment number 3 ; and the","background : a helium - oxygen gas mixture ( heliox ) has low gas density and low turbulence and resistance through narrowed airways . the effects of heliox on pulmonary mechanics following severe methacholine - induced bronchospasm were investigated and compared to those of a nitrogen - oxygen gas mixture ( nitrox ) in an innovative pediatric porcine , independent lung , mechanical ventilation model.results:all of the lungs showed evidence of severe bronchospasm after methacholine challenge . prospective definition of ' heliox response ' was a 15% or greater improvement in lung function in the lung receiving heliox compared with the matched lung receiving nitrox . seven out of 10 pigs responded to heliox therapy with respect to resistance and eight out of 10 pigs responded to heliox",380,128,0.3368
scientific_lay_summarisation-elife-norm,"N-glycosylation – the sequential addition of complex sugars to adhesion proteins, neurotransmitter receptors, ion channels and secreted trophic factors as they progress through the endoplasmic reticulum and the Golgi apparatus – is one of the most frequent protein modifications. In mammals, most organ-specific N-glycosylation events occur in the brain. Yet, little is known about the nature, function and regulation of N-glycosylation in neurons. Using imaging, quantitative immunoblotting and mass spectrometry, we show that hundreds of neuronal surface membrane proteins are core-glycosylated, resulting in the neuronal membrane displaying surprisingly high levels of glycosylation profiles that are classically associated with immature intracellular proteins. We report that while N-glycosylation is generally required for dendritic development and glutamate receptor surface expression, core-glycosylated proteins are sufficient to sustain these processes, and are thus functional. This atypical glycosylation of surface neuronal proteins can be attributed to a bypass or a hypo-function of the Golgi apparatus. Core-glycosylation is regulated by synaptic activity, modulates synaptic signaling and accelerates the turnover of GluA2-containing glutamate receptors, revealing a novel mechanism that controls the composition and sensing properties of the neuronal membrane. Most membrane and secreted proteins are N-glycosylated during their synthesis and processing in the secretory pathway (Moremen et al. , 2012). During this process, as nascent proteins emerge in the lumen of the endoplasmic reticulum (ER), a mannose-rich precursor is first transferred en bloc to specific aspargine residues. These immature' core-glycans' are then trimmed down and modified by the sequential addition of diverse monosaccharides as proteins exit the ER and progress through the Golgi apparatus before they are sent to their final destination (Moremen et al. , 2012; Aebi et al. , 2010). This sequential and combinatorial modification results in a huge potential diversity of N-glycans and regulates virtually every aspect of membrane protein biology, in particular protein folding, trafficking, stability, ligand-binding and interaction with the extracellular matrix (Moremen et al. , 2012; Aebi et al. , 2010; Scott and Panin, 2014; Miller and Aricescu, 2014). Consequently, congenital N-glycosylation defects, especially in the brain, result in severe and often lethal developmental disorders (Cylwik et al. , 2013). Although the primary organelles of the secretory pathway were first described in neurons (Golgi, 1989; Nissl, 1903), little is known about the N-glycosylation of neuronal membrane proteins. Numerous mRNAs encoding surface and","Information is carried around the nervous system by cells called neurons. The ability of neurons to communicate with each other relies on many proteins that are found on the surfaces of the cells. Like in all animal cells, surface proteins are made inside the cell in a compartment called the endoplasmic reticulum. During this process, one or several complex sugar molecules are usually added to newly made proteins. These sugar molecules are then modified as the proteins leave the endoplasmic reticulum and pass through another compartment called the Golgi apparatus on the way to the cell membrane. The precise number and structure of the sugar molecules attached to the protein define its glycosylation profile. Neurons receive information from other neurons at branch-like structures called dendrites, which trigger electrical",380,128,0.3368
dialogsum,"#Person1#: Hi, Albert. You know, John won first place during the chess competition and we've been asked to organize a party for him. #Person2#: Yeah, sure. It's about time we started to prepare it. #Person1#: Exactly. And when is the best time to hold it? #Person2#: Well, John will leave for Boston next Tuesday. #Person1#: So what about 2 days before he leaves on May thirteenth? That's a Sunday. #Person2#: Sounds nice. #Person1#: What about the place, at school or at a restaurant? #Person2#: I think it'll be expensive if we hold it at a restaurant. John said his grandparents welcome us to their big house. #Person1#: Great. And then, we ought to be thinking about invitations. Who must we invite? #Person2#: Well, John's chess coach. #Person1#: And John's parents? #Person2#: Yes. Besides, we'll invite at least 5 teachers and 20 students. #Person1#: OK. By the way, what gift will you give John? #Person2#: A book or a pen. What about you? #Person1#: Well, I will buy a dictionary for him. I heard him say that he needed a good one. #Person2#: Yeah, that's a good idea.",#Person1# and Albert will organize a party for John for his winning first place during the chess competition. They are going to invite some people to John's grandparent's house to celebrate it.,187,32,0.1711
dialogsum,"#Person1#: we'd like to rent a flat near the university. #Person2#: are you looking for somewhere for two people? #Person1#: yes, we are. obviously, we'd like something as cheap as possible. we've heard that there are places for 80 to 100 pounds a month. #Person2#: yes, there are several place available in that price range near the university. do you have any other requirements? #Person1#: net really, no. we'd preferably like to live in a quiet street. #Person2#: how many rooms do you need in the flat? #Person1#: we'll need two bedrooms. the kitchen and dining room can be separate or combined. #Person2#: ok. i've got a list of place that fit your requirements. let's just go through them. the first on the list costs 80 pounds a month, but it's on a noisy street and it's a little far from t #Person1#: how far away is it from the campus? #Person2#: it's about two miles away. that might be a little far to walk. here's one that's about half a mile from the campus. the cost is 100 pounds a month and it's on a small street, just off a #Person1#: that sounds ideal. can we go to have a look at it? we'd like to see it before making a final decision. #Person2#: of course. i'm not very busy at the moment. if you can wait for about 15 or 20 minutes. i can take you there. #Person1#: thank you. that would be great.",#Person1# wants to rent a cheap flat near the university for two people in a quiet street. #Person2# has a flat that fits #Person1#'s requirements. #Person1# wants to see it so #Person2# will take #Person1# there.,246,36,0.1463
pubmed-summarization,fu ) - 600 mg / m intravenous ( iv ) day 1.adriamycin - 50 mg / m iv day 1.cyclophosphamide - 600 mg / m iv day 1 . ac t adriamycin - 60 mg / m iv day 1.cyclophosphamide - 600 mg / m iv day 1paclitaxel - 175 mg / m iv day 1 cmf cyclophosphamide - 600 mg / m iv day 1.methotrexate - 40 mg / m iv day 1.5 fu - 600 mg / m iv day 1 . 5 fluorouracil ( fu ) - 600 mg / m intravenous ( iv ) day 1.adriamycin - 50 mg / m iv day 1.cyclophosphamide - 600 mg / m iv day 1 . 5 fluorouracil ( fu ) - 600 mg / m intravenous ( iv ) day 1 . adriamycin - 60 mg / m iv day 1.cyclophosphamide - 600 mg / m iv day 1paclitaxel - 175 mg / m iv day 1 adriamycin - 60 mg / m iv day 1 . cyclophosphamide - 600 mg / m iv day 1 paclitaxel - 175 mg / m iv day 1 cyclophosphamide - 600 mg / m iv day 1.methotrexate - 40 mg / m iv day 1.5 fu - 600 mg / m iv day 1 . clinical response ( cr ) to nact was assessed according to world health organization criteria . patients with positive or close margins were given boost with ir 192 implant or electron beam or conformal radiotherapy . postmastectomy radiation dose was 35 gy/15 # to chest - wall and 40 gy/15 # to the supraclavicular fossa . tamoxifen or letrozole was given to hormone receptor positive patients for 5 years according to the menopausal status . fac 5 fluorouracil ( fu ) - 600 mg / m intravenous ( iv ) day 1.adriamycin - 50 mg / m iv day 1.cyclophosphamide - 600 mg / m iv day 1 . ac t adriamycin - 60 mg / m iv day 1.cyclophosphamide - 600 mg / m iv day 1paclitaxel - 175 mg / m iv day 1 cmf cyclophosphamide - 600 mg / m iv day 1.methotrexate - 40 mg / m iv day 1.5 fu - 600 mg / m iv day 1 . 5,"background : introduction of neoadjuvant chemotherapy ( nact ) has dramatically changed the management of locally advanced breast cancer ( labc ) . however , very few randomized trials of nact have been carried out specifically in labc patients in our country . in this retrospective analysis , we presented our experience with nact in labc patients.materials and methods : medical records of 148 patients of stage iii labc patients treated with nact , followed by surgery and radiotherapy from january 2006 to december 2010 were reviewed . clinical and pathological responses to different chemotherapy regimens were assessed according to world health organization criteria . various factors influencing response to nact and clinical outcome were identified and analyzed.results:a total of 90 ( 60.8% ) patients received anthracycline -",380,128,0.3368
scientific_lay_summarisation-elife-norm,"gastric cancer. Xer recombinases are members of the tyrosine site-specific recombinase superfamily, a large group of enzymes that catalyze DNA breakage and rejoining using a conserved tyrosine nucleophile (Grindley et al. , 2006; Guo et al. , 1997; Midonet and Barre, 2014; Nunes-Düby et al. , 1998). Tyrosine recombinases promote various programmed DNA rearrangements including the monomerization of phage, plasmid and chromosome multimers, resolution of hairpin telomeres, and the movement of virulence and antibiotic resistance carrying integrative mobile genetic elements (including phages and transposons) (Grindley et al. , 2006; Jayaram et al. , 2015; Midonet and Barre, 2014). In addition, tyrosine recombinases (as exemplified by Cre and Flp) provide powerful genetic engineering tools that are widely used to carry out mutagenesis and DNA insertion in eukaryotic chromosomes (Nagy, 2000; Turan et al. , 2011). Tyrosine recombinases share a common chemical mechanism that involves step-wise breakage and exchange of four DNA strands in pairs, proceeding through a characteristic four-way Holliday junction (HJ) DNA intermediate (1B) (Gopaul and Duyne, 1999; Grindley et al. , 2006; Holliday, 2007). They cut each DNA strand with a polarity creating a covalent 3’ phosphotyrosyl protein-DNA linkage and a free 5’ hydroxyl group. The DNA ends then go on to join with the complementary ends of the partner DNA strand generating the recombined products. All DNA cleavage and rejoining reactions take place in an ordered protein-DNA synaptic complex, comprising four recombinase molecules holding the two recombination partner DNA molecules together. An unusual feature of Xer recombination at dif is that it requires an accessory factor, FtsK (Aussel et al. , 2002; Debowski et al. , 2012a; Le Bourgeois et al. , 2007; Leroux et al. , 2013; Nolivos et al. , 2010; Steiner et al. , 1999). This DNA motor protein localizes to the bacterial cell division septum and contributes to segregating the sister chromosomes into the daughter cells by translocating towards their replication termini. On chromosome dimers, FtsK stops at the Xer-bound dif sites and activates recombination, triggering resolution of the dimers to monomers (Aussel et al. , 2002; Grainge et al. , 2011; May et al. , 2015). Without FtsK, Xer-dif synaptic complexes are formed, but do not lead to final recombination products (Aussel et al. , 2002; Diagne et al. , 2014; Grainge et","Similar to humans, bacteria store their genetic material in the form of DNA and arrange it into structures called chromosomes. In fact, most bacteria have a single circular chromosome. Bacteria multiply by simply dividing in two, and before that happens they must replicate their DNA so that each of the newly formed cells receives one copy of the chromosome. Occasionally, mistakes during the DNA replication process can cause the two chromosomes to become tangled with each other; this prevents them from separating into the newly formed cells. For instance, the chromosomes can become physically connected like links in a chain, or merge into one long string. This kind of tangling can result in cell death, so bacteria encode enzymes called Xer recombinases that can untangle chromosomes. These enzymes",380,128,0.3368
scientific_lay_summarisation-elife-norm,"tissues (Ueda et al. , 1990), little has been done to study what roles Ftz-f1 plays in adult flies, particularly in oogenesis. Drosophila oogenesis is an excellent model for studying many cell biology questions in the last few decades. Drosophila oogenesis occurs in the ovariole, ~16 of which bundle together to form an ovary. At the anterior tip of the ovariole, germline and follicle stem cells proliferate to produce daughter cells to form a stage-1 egg chamber (also named follicle in this paper), which develop through 14 morphologically distinct stages into a stage-14 egg chamber [also named mature follicle; (Spradling, 1993). Each follicle contains a layer of somatic follicle cells encasing 16 interconnected germ cells, one of which differentiates into an oocyte, while the rest become nurse cells to support oocyte growth and are eventually degraded in mature follicles. Somatic follicle cells proliferate at stages 1–6 and transition into endoreplication at stages 7-10A induced by Notch signaling (Klusza and Deng, 2011). At stage 10B, a pulse of ecdysone signaling induces follicle cell transition from endoreplication to synchronized gene amplification via zinc-finger transcription factor Ttk69 (Sun et al. , 2008). This is also accompanied by the downregulation of the zinc-finger transcription factor Hindsight (Hnt) and the upregulation of the homeodomain transcription factor Cut in stage-10B follicle cells. As follicles develop from stage 10B onwards, Ttk69 and Cut are diminished. By stage 14, another critical follicle cell transition occurs, accompanied by re-upregulation of Hnt and complete loss of Cut and Ttk69 (Knapp et al. , 2019). This transition is critical for the follicle to gain ovulatory competency via upregulation of Octopamine receptor in mushroom body (Oamb) and Matrix metalloproteinase 2 (Mmp2) (Deady and Sun, 2015; Deady et al. , 2015; Deady et al. , 2017; Knapp et al. , 2019). In addition, stage-14 follicle cells upregulate NADPH oxidase (Nox) expression, downregulate EcR. B1 and EcR. A, and receive another ecdysteroid signaling via EcR. B2 to become ovulatory competent (Knapp and Sun, 2017; Li et al. , 2018). However, it is largely unknown how follicle cells differentiate from stage 10B to stage 14. In this study, we demonstrate that Ftz-f1 is transiently expressed in Drosophila follicle cells at stages 10B-12 and this expression is induced by ecdysteroid signaling in stage-10B follicle cells, independent","When animals reproduce, females release eggs from their ovaries which then get fertilized by sperm from males. Each egg needs to properly mature within a collection of cells known as follicle cells before it can be let go. As the egg matures, so do the follicle cells surrounding it, until both are primed and ready to discharge the egg from the ovary. Mammals rely on a protein called SF-1 to mature their follicle cells, but it is unclear how this process works. Most animals – from humans to fruit flies – release their eggs in a very similar way, using many of the same proteins and genes. For example, the gene for SF-1 in mammals is similar to a gene in fruit flies which codes for another protein",380,128,0.3368
scientific_lay_summarisation-elife-norm,"1691 ± 1791 ± 200. 300. 401. 00Temperature (°C) 38. 6 ± 1. 238. 4 ± 1. 437. 7 ± 1. 50. 03<0. 001<0. 001Febrile (Temperature≥ 37. 5°C) 81%77%56%0. 23<0. 001<0. 001Pulse rate – beats/minute152 ± 26148 ± 24139 ± 280. 06<0. 001<0. 001Respiratory rate – breaths/minute47 ± 1545 ± 1345 ± 150. 120. 170. 93Liver size – cm below costal margin2. 0 ± 1. 91. 5 ± 1. 91. 1 ± 1. 7<0. 001<0. 0010. 04Spleen size – cm below costal margin1. 7 ± 2. 11. 6 ± 2. 10. 9 ± 1. 60. 56<0. 001<0. 001Deep breathing33%25%30%0. 030. 590. 18Blantyre Coma Score: 0 1 2 3 4 514% 35% 49% 1% 0% 0%19% 38% 43% 0% 0% 0%28% 40% 23% 3% 0% 5%0. 010. 080. 90CSF opening pressure – mm of water176 ± 75152 ± 82176 ± 990. 0010. 960. 07Hematocrit -- %19. 8 ± 6. 928. 2 ± 7. 528. 1 ± 9. 6<0. 001<0. 0010. 86Platelets81,220± 67,219161,600± 124,747248,400± 162,287<0. 001<0. 0010. 86Malaria parasitemia – parasites/mm3230,500± 321,924180,500± 280,6763,619± 28,9170. 03<0. 001<0. 001White blood cells13,040± 916313,020± 892313,930± 95440. 970. 290. 31Lactate – mmol/liter8. 6 ± 5. 07. 3 ± 4. 45. 5 ± 3. 90. 05<0. 0010. 007Blood glucose – mmol/liter6. 1 ± 3. 96. 8 ± 4. 47. 6 ± 5. 30. 03<0. 0010. 05CSF white cell count – % ≥ 516%20%24%0. 310. 060. 37Blood culture positive for pathogen4%2%14%0. 51<0. 001<0. 001HIV positive18%17%15%0. 910. 590. 66OutcomesDischarge outcome: Full recovery Neurological Sequalae Died69% 10% 21%78% 10% 12%57% 15% 28%0. 0030. 01<0. 001 depicts three possible pathways to clinically-defined (WHO-defined) CM (Postels and Birbeck, 2011). One pathway is to Ret+ CM for which there is evidence that malaria parasites play a primary role. As noted above, at autopsy, Ret+ CM is associated with the sequestration of parasitized red cells in the cerebral microvasculature (Taylor et al. , 2004). Compared to children with Ret- CM, those who are Ret+ have increased concentrations of P. falciparum HRP2, a parasite-produced protein reflecting total body parasite burden (Seydel et al. , 2012). Ocular funduscopic findings in Ret+ CM mirror the microvascular pathology observed on fluorescein angiography (MacCormick et al. , 2015) and are correlated with the severity of sequestration in both the retina and the brain at autopsy (Barrera et al. , 2015).","Malaria is a life-threatening disease caused by a parasite that is transferred between people by infected mosquitoes. Most infected individuals suffer flu-like symptoms, but in rare cases malaria can affect the brain, resulting in brain damage, coma or death. The World Health Organization defines a person as suffering from cerebral malaria if the person is in a coma, has malaria parasites in his or her blood, and has no known alternative cause of the coma. Patients suffering from cerebral malaria are categorized based on whether they have damage to the back of the eyes known as retinopathy. It had previously been found that children who died of “retinopathy-positive” cerebral malaria (i. e. those who had retinopathy) had malaria parasites stuck in small vessels in their brains, which likely",380,128,0.3368
dialogsum,"#Person1#: I think that show biz stars have a really easy life. They have lots of money, so they can buy almost anything they want. They're famous, so everyone loves them. #Person2#: I think they must have horrible lives. All the paparazzi take photos of them wherever they go and whatever they do. They must get sick of it. #Person1#: I bet they love it really. Sure, they complain about it, but that just gets them more publicity, doesn't it? #Person2#: I think that few of the show biz stars want any publicity for themselves. They only want it for their films. #Person1#: No way! They want publicity for themselves, so that they get invited to make more films, go to lots of cocktail parties, and even make albums! They have such an easy life. They don't even pay for drinks when they go to a cocktail party. #Person2#: Show biz stars have plenty of expenses. That's why they need so much money. They need million of dollars to buy big, seclude houses and wonderful dresses. I bet most show biz stars would prefer to wear jeans and a t-shirt, but they can't because their managers force them to wear clothes they don't like. #Person1#: I don't understand how you can have any sympathy for show biz stars. They're overpaid, over-ambitious, and over-adored. #Person2#: I think you should give them some credit. They're very talented people and they deserve all the money they earn. They even donate money to charity to help people who are less fortunate than themselves. #Person1#: Come on! They only do that to get even more publicity for their films and themselves.","#Person1# thinks show biz stars have a really easy life. #Person2# thinks they must have horrible lives. #Person1# wonders why #Person2# has sympathy for the stars who are overpaid, over-ambitious, and over-adored. #Person2# thinks they are talented people and deserve all the money they earn.",276,45,0.163
scientific_lay_summarisation-elife-norm,"space. Instead, sensations that arise from whisker self-motion –' reafferent' signaling – is thought to play an important role in determining whisker position and object localization (Kleinfeld and Deschênes, 2011). Although earlier studies suggested that reafferent signaling is encoded in parallel to afferent (touch-related) signals via posterior medial (POm) thalamus (Yu et al. , 2006), recent evidence suggests that reafferent signaling is also processed along the same lemniscal (VPM-S1) pathway to cortex as afferent input from whisker-object contact (Moore et al. , 2015). Many studies of reafferent sensory signaling have used an' artificial whisking' paradigm to elicit whisker movements in anesthetized rodents by electrical stimulation of the buccal branch of the facial motor nerve (Zucker and Welker, 1969; Brown and Waite, 1974; Szwed et al. , 2003). Artificial whisking produces whisker protractions with amplitude and frequency that can be well controlled experimentally. This paradigm has drawbacks, however, including the necessity to perform experiments in anesthetized subjects, which makes it difficult to relate reafferent signaling to behavior; and the inability to stimulate certain muscle groups, which means that only whisker protractions, not retractions, can be evoked. Recently, optogenetic studies of motor nerves and muscles have used the hindlimb as a model system (Liske et al. , 2013; Towne et al. , 2013; Bryson et al. , 2014; Magown et al. , 2015). While various central elements of the whisker system have been targeted for optical control in behaving mice (Poulet et al. , 2012; O' Connor et al. , 2013; Sachidhanandam et al. , 2013; Matyas et al. , 2010), peripheral optogenetic stimulation have not been used to investigate control of whisker movements. In this study, we report that optogenetic stimulation of the whisker pad in Emx1-Cre; Ai27D transgenic mice evokes whisker movements due to channelrhodopsin-2 (ChR2) expression in select intrinsic and extrinsic muscles. We first characterize the amplitude and frequency of whisker protractions evoked by anterior whisker pad stimulation in anesthetized mice. We then compare the electrophysiological responses in S1 to optogenetic and mechanical whisker stimulation. Finally, we show that awake, head-fixed mice are able to perceive optical whisker pad stimulation in a behavioral detection task. The results suggest that optogenetic stimulation of whisker pad muscles leads to sensory perception through reafferent signaling. In initial screens of adult Emx1-Cre; Ai27D","Mice use their whiskers to sense their environment and to detect nearby objects. Rather than simply allowing their whiskers to brush passively against objects, mice move them in rhythmic bursts in a process called whisking. Whisking enables neuroscientists to study how the brain gathers and processes actively acquired sensory information. However, controlling active whisker movements in the laboratory has proven challenging. Park et al. now offer a solution based on a technique called optogenetics. The new procedure involves introducing the gene for a light-sensitive ion channel into the facial muscles of the mouse. Shining blue light onto the area of skin where the whiskers grow – the whisker pad – activates these ion channels. Park et al. were able to use this technique to trigger the contraction of",380,128,0.3368
dialogsum,#Person1#: Hey Bob. Whatchy doing? #Person2#: I'm at home painting. #Person1#: I didn't know you paint. What type of painting is it? #Person2#: I enjoy oil painting. I learned it in one of my extra classes in college. #Person1#: That sounds so interesting. I wish I learned a hobby. #Person2#: Hobbies are never too late to learn. They offer a variety of classes at the local community college. You should look into it. #Person1#: I think I will. Thanks for the info.,Bob likes oil painting. #Person1# wishes #Person1# learned a hobby. Bob recommends the local community college.,82,16,0.1951
dialogsum,"#Person1#: Today, I'd like to find out what people are doing to keep healthy. Excuse me, you look so good. What do you do to keep in shape? #Person2#: Nothing special. I ride my bike to work every day except when it rains. I love to eat out, so I eat whenever I want. I just try not to eat after 9 at night. #Person1#: Really? How long does it take you to go to work by bike? #Person2#: About 45 minutes. #Person1#: Do you do any other sports after work? #Person2#: No, I usually go home to have dinner. #Person1#: I see, thank you. Let me ask someone else. Excuse me...",#Person1# interviews #Person2# about how to keep in shape. #Person2# says #Person2# goes to work by bike and avoids eating after 9 pm.,112,23,0.2054
pubmed-summarization,". the hearing problem as perceived by the patient 's friends and relatives was basically a misinterpretation of the patient 's problem secondary to his psychiatric illness . also the patient was unable to express his actual problem at the time of presentation . the patient used to ask for repetition of the spoken sentences multiple times in order to grasp the components of interaction because of his significantly impaired attention . however , there could be the other possibility that this behavior could be a compulsive act of the patient to confirm his doubts . the patient could not express his problem elaborately , which was one of the reasons for not being able to make an early diagnosis . there were multiple factors that had complicated and hindered the narration of history by the patient . lack of clarity of thoughts and associated clinical symptoms of ocd ( especially predominantly obsessive type ) , indecisiveness , anxiety , lack of confidence , along with impaired memory and attention , were the possible factors in this case , as also reported in different studies . the patient could express details of his illness comprehensively once his above - mentioned signs and symptoms improved significantly . his wife and relatives also reported improvement in his hearing , which was actually the improvement in his attention and ocd symptoms . such an atypical presentation may lead to misdiagnosis , delay in diagnosis , loss of time and money as the patient may present to other specialties instead of psychiatry . high suspicion for diagnosis of ocd and response to treatment may help in managing such cases . obsessive compulsive disorder is usually easily recognized , but sometimes its presentation is so atypical or bizarre that the problem comes to notice as being a psychiatric disorder after multiple consultations in different specialties . but if proper evaluation is done , such cases can easily be recognized and treated effectively .","obsessive compulsive disorder ( ocd ) is a common psychiatric disorder which is easily recognized . however , sometimes patients of ocd present in such an atypical or bizarre way that their problem comes to notice as being a psychiatric disorder after multiple consultations in different specialties . we are reporting a case of a man who had first sought opinion in the department of ear , nose and throat ( ent ) for hearing impairment . he was then referred to a neurologist and a general physician for evaluation of neurological cause of his symptom . as no pathology related to ent or neurology could be detected , he was referred to the department of psychiatry . the patient 's chief complaints were difficulty in hearing and",328,128,0.3902
dialogsum,"#Person1#: Hi, you look upset. What's up? #Person2#: I haven't been sleeping well, recently. #Person1#: What's the problem? #Person2#: I tried to go to bed early, but I just couldn't fall asleep in bed with the other girls' lights on, and noises now and then. I'm a light sleeper. #Person1#: I understand, I used to live in a dorm with 3 People. It was great in some aspects. We always went out and had fun together. But on the other hand, when I wanted some quiet time they kept talking and laughing aloud. It was really painful. #Person2#: Living in a dorm means that you have to learn to be considerate of others. #Person1#: Yeah, but you can at least talk with them and find a solution. #Person2#: Ok. Maybe I really should have a talk with them about this matter.",#Person2# says #Person2# hasn't been sleeping well recently with other girls' lights on and noises. #Person1# suggests #Person2# talk about this problem with them.,141,24,0.1702
scientific_lay_summarisation-elife-norm,"and computational approaches, we generate a plausible model for how two rib segments form during development. Lineage-tracing studies indicate that the sternum and ribs have different developmental origins. The sternum, like the appendicular skeleton, arises from the lateral plate mesoderm (Cohn et al. , 1997; Bickley and Logan, 2014), while the ribs and vertebrae arise from the somites (reviewed in [Brent and Tabin, 2002]). Studies using chicken-quail chimera grafts have shown that the thoracic somites contribute to all portions of the ribs (Huang et al. , 1994), with a the medial somite contributing to the proximal ribs while lateral somite contributes to the distal ribs (Olivera-Martinez et al. , 2000). These results suggest that the proximal and distal progenitor populations of the rib are distinct at early somite stages rather than being intermixed. As the whole somite matures, it separates into distinct dorsal (dermomyotome and myotome) and ventral (sclerotome) compartments (1C). Initially, there was some debate on the precise embryological origin of the ribs within the somite (Kato and Aoyama, 1998; Huang et al. , 2000). However, using retroviral lineage labeling which avoids the challenges of transplantation experiments, both the proximal and distal segments of the rib were shown to arise from the sclerotome compartment (Evans, 2003). It has been still unclear though, how the sclerotome becomes patterned along the proximal-distal axis. Through studies particularly of Drosophila wing/leg disc and of vertebrate limb development over the past decades, several patterning models have been conceived to explain how proximal-distal, dorsal-ventral, and anterior-posterior pattern arises (Briscoe and Small, 2015). For example, compartments could become specified based on: (1) the presence of cellular determinants, (2) the concentration of a morphogen, (3) the duration of exposure to a signaling molecule, and/or (4) the action of local relay or mutual inhibition signaling. Specification could gradually emerge over the course of organogenesis or via a biphasic process with specification occurring early in a small population of cells followed later by expansion into compartments (recently reviewed in [Zhu and Mackem, 2017]). In this study, we first use genetically modified mice in which the Hedgehog (Hh) and apoptosis pathway is disrupted to provide clues for how two rib segments are patterned and grow. Our experiments produced unexpected results which led us to seek an explanation using Agent-Based Modeling,","During animal development, the ribs grow from the back of the embryo around towards the chest. In fish, these bones simply terminate. Yet in land animals, cartilage forms at the end of the rib where it connects to the breastbone, or sternum. This encloses the chest cavity. Fogel, Lakeland et al. have now asked how the progenitor cells that develop into the ribs form these two skeletal elements – the bone element and the cartilage element – in land animals. Their approach involved genetic analysis in mice and a simple computing model. It revealed that two elements could form if the progenitor cells decide which element they will belong to based on the concentration of the diffusible protein called Hedgehog. This protein controls many aspects of animal development,",380,128,0.3368
pubmed-summarization,", il-1 , and tumor necrosis factor ( tnf)- have been reported to stimulate parvocellular and magnocellular neurons to secrete more adh ; thus causing siadh . fluid restriction is the main treatment modality in siadh , with a suggested goal intake of less than 800 ml / day . further treatment options depend on the severity of hyponatremia and the presence of other related symptoms . in the presence of severe or symptomatic hyponatremia , hypertonic saline goal should be to raise serum sodium less than 10 - 12 meq / lin 24 h to ovoid the potential complication of osmotic demyelination with rapid correction . oral salt tablets and loop diuretics may also be added if optimum response is not seen with fluid restriction alone . our patient 's siadh was thought to be secondary to influenza , which was treated with oseltamivir and led to steady improvement in the patient 's serum sodium levels . in conclusion , clinicians should be cognizant of the association between influenza and siadh to allow for accurate diagnosis and treatment of this condition . further studies are needed in future to find out the incidence and pathogenesis of siadh in patients with influenza . although treatment depends on the severity of hyponatremia and associated symptoms , fluid restriction remains the cornerstone of therapy .","context : syndrome of inappropriate secretion of antidiuretic hormone ( siadh ) is a common cause of hyponatremia . although it has been associated with different pulmonary infections , there have been only few case reports describing the association of siadh with influenza.case report : we report a case of siadh in a patient with influenza who was successfully treated with fluid restriction.conclusion:it is essential for clinicians to be aware of the association between influenza and siadh .",223,78,0.3498
scientific_lay_summarisation-elife-norm,"is poorly understood, in large part because direct transcriptional targets for only very few of these transcripts have thus far been identified (Chu et al. , 2011; Ng et al. , 2013; Simon et al. , 2011; Vance et al. , 2014). Moreover, it is not clear whether these transcripts commonly act directly, or within ribonucleoprotein complexes, and how they might modify their target genes’ regulatory landscape such as by regulating their DNA methylation profiles. Many thousand mammalian intergenic lncRNAs have now been identified. Not all lncRNA transcript models will be functional, however. Single exon models, in particular, can be artefacts arising from genomic DNA contaminating sequencing libraries, and transcripts that are expressed at average levels lower than one copy per cell are less likely to confer function. Highly and broadly expressed, and bona fide monoexonic intergenic lncRNAs, such as Neat1 and Malat1/Neat2, however, appear not to have essential roles because their knockout mouse models are viable and fertile (Eissmann et al. , 2012; Zhang et al. , 2012). Transcript sequences and levels are thus not reliable predictors of mechanism. Instead, the significant temporal and spatial co-expression of genomically adjacent intergenic lncRNA and transcription factor genes might suggest that such lncRNAs commonly modulate transcriptional programmes that are initiated by these transcription factors (Ponjavic et al. , 2009). Indeed, several intergenic lncRNAs have well-documented cis-acting regulatory roles (Wang et al. , 2011; Zhang et al. , 2012; Berghoff et al. , 2013). Spatiotemporal co-expression of intergenic lncRNA and transcription factor genes is most pronounced during the development of the mouse central nervous system (CNS) (Ponjavic et al. , 2009). To investigate the mechanistic basis of this physical linkage we chose to study a 3. 5-kb, CNS-expressed, monoexonic, intergenic lncRNA termed Dali (DNMT1-Associated Long Intergenic), owing to its conservation of sequence and transcription across therian mammals and its genomic proximity to a transcription factor gene, Pou3f3 (also known as Brn1 or Oct8), which encodes a class III POU family transcription factor. Dali is transcribed in the sense orientation, relative to Pou3f3, from a locus 50 kb downstream of Pou3f3 within the flank of an extended genomic region (1A) that is characterised by near pervasive transcription in neuronal lineages (Ramos et al. , 2013). Sauvageau et al. recently generated mouse knockout models for","Traditionally genes are considered to contain all the instructions necessary to build proteins. For these instructions to be followed they need to be ‘transcribed’ into molecules called messenger RNA, which are then ‘translated’ to form the protein. Messenger RNAs are not the only type of RNA molecule made in a cell; long non-coding RNAs (or lncRNAs), for example, are transcribed but never translated into proteins. Instead, some lncRNAs control the expression of nearby genes and some alter how the DNA is packaged within the cell. Several lncRNAs have been found to control their neighbouring genes, but it is unclear how many of these molecules can also regulate genes that are much further away, even on other chromosomes. One lncRNA called Dali is made in cells of the nervous",380,128,0.3368
dialogsum,#Person1#: We hope that there will be no repetition of this kind of trouble in the future. #Person2#: Yes. I promise it will not happen again. #Person1#: We look forward to your settlement at an early date. #Person2#: We will inform you as soon as possible.,#Person2# promises #Person1# no repetition of the trouble.,46,8,0.1739
dialogsum,"#Person1#: Thanks for the advice, Mr. Macmillan. I'll keep it in mind. I had better head off though. I'm meeting my husband for dinner. #Person2#: Sure, I'm heading out myself. Enjoy your evening. #Person1#: Thanks, sir. You too. Drive safely, I hear there's a lot ice on the roads. #Person2#: Thanks for the warning! See you tomorrow!",#Person1# thanks for Mr. Macmillan's advice and heads off.,57,9,0.1579
pubmed-summarization,"healthcare costs between cohorts in the lhid2000 and the enrollees were reported by the nhri . the international classification of diseases revision ninth clinical modification ( icd-9-cm ) was used for the diagnoses . the study was approved by the institutional review board of china medical university and hospital ( cmuh104-rec2115 ) . a retrospective cohort study was conducted to determine the association between renal stone ( rs ) ( icd-9-cm 592.0 : calculus of kidney , icd-9-cm 592.1 : calculus of ureter , icd-9-cm 592.9 : urinary calculus , icd-9-cm 594.1 : other calculus in bladder ) and stroke ( icd-9-cm 430 : subarachnoid hemorrhage , icd-9-cm 431 : intracerebral hemorrhage , icd-9-cm 432 : other and unspecified intracranial hemorrhage , icd-9-cm 433 : occlusion and stenosis of precerebral arteries , icd-9-cm 434 : occlusion of cerebral arteries , icd-9-cm 435 : transient cerebral ischemia , icd-9-cm 436 acute , but ill - defined , cerebrovascular disease , icd-9-cm 437 other and ill - defined cerebrovascular disease , icd-9-cm 438 : late effects of cerebrovascular disease ) . the claims data between1998 and 2010 were used to identify patients aged 20 years with a first diagnosis of rs . a comparison cohort was randomly selected from among the patients without rss during the same period , frequency matched 1:4 for age ( every 5 years ) , sex , comorbidities ( diabetes , hyperlipidemia , hypertension , coronary artery disease [ cad ] , congestive heart failure [ chf ] , and atrial fibrillation ) , and index year . patients with a stroke history and with missing information for age or sex were excluded from the data analysis . a follow - up for stroke occurrence was performed until the date of follow - up loss , withdrawal from the insurance system , or end of 2010 , whichever occurred first . the baseline comorbidities were diabetes ( icd-9-cm 250 ) , hyperlipidemia ( icd-9-cm 272 ) , hypertension ( icd-9-cm 401 to 405 ) , cad ( icd-9-cm 410 to 414 ) , chf ( icd-9-cm 398.91 , 402 , 404.01 , 404.03 , 404.10 , 404.11 , 404.13 , and 404.9 ) , and atrial fibrillation ( icd-9-cm 427.31 ) . surgical procedures for rs removal","abstractnephrolithiasis is highly prevalent and has been associated with vascular diseases such as cardiovascular events . few studies have comprehensively associated renal stones with stroke.this study explored whether patients with renal stones were at a higher stroke risk than those without renal stones . a national insurance claim dataset of 22 million enrollees in taiwan was used to identify 53,659 patients with renal stones , and 214,107 were selected as age- , sex- , and comorbidity - matched controls for a 13-year follow-up.the relative stroke risk for the rs cohort was 1.06-fold higher than that for the non - rs group ( 95% confidence interval [ ci ] = 1.011.11 ) . age - specific analysis revealed that the adjusted stroke risk for the rs cohort increased as",380,128,0.3368
scientific_lay_summarisation-elife-norm,"downstream mediator of the DNA damage response pathway, activated by both the double-strand break and ATMIN-dependent responses, is the tumor suppressor TP53. Precancerous lesions in which the DNA damage response is activated are under selective pressure to lose or mutate TP53, and loss of TP53 is known to cooperate with several genes to accelerate tumorigenesis (as summarized in the IARC database [Petitjean et al. , 2007]). Among these cooperating changes is loss of ATM, which induces rapid T-cell lymphoma development (Westphal et al. , 1997). TP53 is also one of the most commonly mutated genes in human GBM. Consequently, the majority of available mouse models of GBM use deletion of one or both copies of the Trp53 gene in combination with other mutations (Chen et al. , 2012). Overexpression of the Pdgf receptor ligand Pdgfrb in adult Nestin-positive neural stem cells, for instance, results in glioma formation, which is accelerated in a Trp53-mutant background (Squatrito et al. , 2010). In this study, we demonstrate that congenital loss of Trp53 in the mouse brain is sufficient to precipitate spontaneous glioblastoma formation, and that this correlates with upregulation of Pdgfra. Further, we show that ATMIN plays a critical role in GBM formation, promoting Pdgfra protein and gene expression in a Trp53-deficient background, using an in vivo glioma model as well as neural stem cell and primary tumor cell cultures. Importantly, we find that these results are translatable to therapeutic ATM inhibition in human patient-derived GBM stem cells, and that combining ATM inhibition with PDGFRA inhibition results in synergistic tumor cell killing with minimal effects on untransformed cells. Loss of TP53 is one of the earliest occurring events in human GBM initiation (Maher et al. , 2001; Wang et al. , 2009; Ohgaki et al. , 2004; Mazor et al. , 2015; Johnson et al. , 2014). This inevitably results in the accumulation of a plethora of secondary hits, which, after a long latency period, leads to tumor formation. To recapitulate this chain of events in mice, we deleted Trp53 as an initial driver during neural development (using p53f/f; Nestin-Cre (p53ΔN) mice) and monitored brain tumor formation in late adult life. After 8 months, brain tumors arose in p53ΔN mice with high penetrance (1A and B), similar to previous observations using an hGFAP-Cre","Glioblastomas are the most common and aggressive brain cancers in adults, and currently lack efficient treatment options. Glioblastoma cells contain genetic mutations that enable them to grow and divide more quickly than they would under normal conditions. The occurrence of these mutations often leads to a functional impairment in so-called' tumor suppressor' proteins that may have a range of roles, including repairing genetic damage or controlling the rate of cell division. Blake et al. have now studied how some of these tumor suppressor proteins interact. Deleting a prominent tumor suppressor called TP53 from the brain of mice caused these animals to develop glioblastomas. If, however, both TP53 and another tumor suppressor called ATMIN were deleted at the same time, the majority of mice did not develop any brain",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Non-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeast Schizosaccharomyces pombe, the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the γ-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146. Although Mto1 is not a nuclear export cargo, it binds Crm1 via a nuclear export signal-like sequence, and docking requires both Ran in the GTP-bound state and Nup146 FG repeats. In addition to determining the mechanism of MTOC formation at the NE, our results reveal a novel role for Crm1 and the nuclear export machinery in the stable docking of a cytoplasmic protein complex at NPCs. Non-centrosomal microtubule organizing centers (MTOCs) are critical to the morphology and function of many types of cells (Petry and Vale, 2015; Sanchez and Feldman, 2017; Wu and Akhmanova, 2017), especially cells in which interphase microtubules (MTs) are arranged in linear rather than radial arrays (Bartolini and Gundersen, 2006). Examples include differentiated animal cells such as neurons (Kapitein and Hoogenraad, 2015), muscle (Mogessie et al. , 2015; Tassin et al. , 1985), and epithelial cells (Wu and Akhmanova, 2017), and many higher plant cells (Masoud et al. , 2013; Oda, 2015), as well as some single-celled eukaryotes, such as fission yeast Schizosaccharomyces pombe (Chang and Martin, 2009; Sawin and Tran, 2006). The mechanisms underlying non-centrosomal MTOC formation are just beginning to be understood. Some non-centrosomal MTs are thought to be generated by nucleation-and-release from the centrosome, followed by minus-end stabilization and anchoring elsewhere in the cell (Bartolini and Gundersen, 2006; Sanchez and Feldman, 2017; Wu and Akhmanova, 2017). However, in many cases, MTs are nucleated directly from non-centrosomal sites by the γ-tubulin complex, the primary microtubule-nucleation complex in eukaryotic cells (Kollman et al. , 2011; Petry and Vale, 2015). Understanding how the γ-tubulin complex is recruited to these sites is thus key to deciphering the fundamental mechanisms of non-centrosomal MT organization (Lin et al. , 2015). Sites of non-centrosomal γ-tubulin complex recruitment include pre-existing microtubules themselves, as well as membrane-bound compartments such as","Nearly all cells contain networks of filaments called microtubules that play many different roles. They provide internal structure; they serve as ‘tracks’ for transporting materials from one region of the cell to another; and they help to separate chromosomes during cell division. To understand how microtubules work, it is important to know how they are organized and distributed in cells. In several types of cells, including muscle cells in humans, and most plant cells, microtubules form on the surface of the cell nucleus – the membrane-bound compartment that stores genetic information. A key protein involved in microtubule formation, called Mto1, is present on the surface of the nucleus, but it was not clear how Mto1 localizes there. Using fission yeast cells, Bao et al. have devised a new",380,128,0.3368
scientific_lay_summarisation-elife-norm,"2008; Gupta et al. , 2008; Thomas et al. , 2008; Zhong and Jin, 2009; Li et al. , 2012). HATs can be classified into two predominant families: the GCN5-related N-acetyltransferase (GNAT) family (i. e. Gcn5 and p300) and the Moz-Ybf2/Sas3-Sas2-Tip60 (MYST) family (i. e. , Tip60 and Mof [male absent on the first]) (reviewed in Kimura et al. , 2005). These enzymes often function as part of multi-protein co-activator complexes (reviewed in Lee and Workman, 2007). Mof (also known as Kat8 or Myst1), is a MYST-type HAT specific for histone H4 lysine 16 acetylation (H4K16ac) (Hilfiker et al. , 1997; Smith et al. , 2001,2005; Taipale et al. , 2005) and has been shown to be the catalytic subunit of two distinct protein complexes in Drosophila (d) and mammals: the male-specific lethal (MSL) and the non-specific lethal (NSL) complexes (Smith et al. , 2005; Mendjan et al. , 2006; Cai et al. , 2010; Raja et al. , 2010). In Drosophila, the dMSL complex is targeted to transcribed regions of male X-chromosomal genes, where it mediates dosage compensation (reviewed in Straub and Becker, 2007; Gelbart and Kuroda, 2009; Conrad and Akhtar, 2011). In contrast, dNSL is present at gene promoters of male and female chromosomes, where it regulates transcription of housekeeping genes (Prestel et al. , 2010; Raja et al. , 2010; Feller et al. , 2012; Lam et al. , 2012). Mof itself and subunits of the Mof-containing dMSL and dNSL HAT complexes are required for the binding of the two Drosophila Mof-containing complexes at promoters and gene bodies, which leads to H4K16 acetylation and gene expression (Raja et al. , 2010; Kadlec et al. , 2011). Inactivation of Mof in mice (m) leads to early embryonic lethality as Mof−/− embryos fail to develop beyond the expanded blastocyst stage and die at implantation (Gupta et al. , 2008; Thomas et al. , 2008). Mof deletion correlated with cell cycle defects and cell death. Moreover, mESCs could not be derived from Mof−/− mouse embryos. In agreement, it was shown that Mof plays an essential role in the maintenance of mESC pluripotency (Li et al. , 2012). H4K16 acetylation levels were undetectable in Mof−/− embryos, whereas the acetylation of other histone lysine residues was unaffected (Thomas et al. , 2008).","Embryonic stem cells are special cells that have the ability to become many different types of cells, such as skin, muscle, or neuronal cells. This process is called differentiation. They can also undergo a process called self-renewal to produce more embryonic stem cells. These processes are controlled by a complex network of enzymes, and the production of these enzymes depends on various genes within the organism being expressed as proteins. The DNA that holds the genetic information inside cells spends most of its time wrapped around proteins called histones: this allows the DNA molecules—which can be up to several metres long in some species—to fit inside the cell nucleus; it also protects the DNA molecules, which are quite fragile, from damage. Enzymes that attach chemical groups called acetyl",380,128,0.3368
dialogsum,"#Person1#: Excuse me. Are you in charge here? #Person2#: Yes, sort of. #Person1#: Then perhaps you can help me. I need to use a computer to type an assignment. #Person2#: Well, are you a student? #Person1#: Yes, I am. First year. #Person2#: Ok. Have you used a computer before? #Person1#: Yes, I've done a bit of word processing. #Person2#: That's good. You can use a computer for 2 hours at a time. #Person1#: Mm. What can I do if something goes wrong with the computer? #Person2#: There's usually someone here from 9 o'clock. You can ask him for help.",#Person1# asks for #Person2#'s help because #Person1# needs a computer to type an assignment.,99,14,0.1414
pubmed-summarization,"the international cancer genome consortium ( icgc ) is a multidisciplinary , multi - institutional collaborative effort aiming to systematically and comprehensively characterize somatic mutations in 50 different cancer types and subtypes ( 1 ) . five hundred tumor genomes , as well as matched normal control genomes for each cancer type , will be analyzed using high - throughput next - generation sequencing technologies to detect a wide range of somatic mutations , including single nucleotide mutations , small insertions / deletions , copy number alterations , translocations and other chromosomal structural rearrangements . genome - wide methylation state analysis and whole - transcriptome sequencing have also been planned to provide additional molecular - level characterizations . to make the effort more scalable each member institution specializes in generating data for a particular tumor type . at the time of writing , .international cancer genome consortium ( icgc ) projects ( march 2011 ) . international cancer genome consortium ( icgc ) projects ( march 2011 ) . one of the major goals of icgc is to rapidly bring these data to the cancer research community in order to accelerate studies on the discovery of cancer causes , to enhance the accuracy of diagnoses and to improve treatments . in order to achieve this task , the data generated by the consortium members have to be managed efficiently . amongst the most important data management challenges faced by the consortium is the high complexity and heterogeneity of the data types involved , the necessity to link different data types , and the need to protect controlled data . furthermore , the high volume of data and the distributed nature of the sources make traditional centralized approaches to data management impractical . consequently , the icgc has adopted federated data architecture to address their data management needs . the scalability of the system is improved by having each member institution store and process data locally ; the data federation software then presents these separate sources as a single access point for remote data access . biomart , an open source data federation system ( 2 ) , has been chosen as the icgc data management platform . biomart s flexible data model makes it generally applicable to a wide range","the international cancer genome consortium ( icgc ) is a collaborative effort to characterize genomic abnormalities in 50 different cancer types . to make this data available , the icgc has created the icgc data portal . powered by the biomart software , the data portal allows each icgc member institution to manage and maintain its own databases locally , while seamlessly presenting all the data in a single access point for users . the data portal currently contains data from 24 cancer projects , including icgc , the cancer genome atlas ( tcga ) , johns hopkins university , and the tumor sequencing project . it consists of 3478 genomes and 13 cancer types and subtypes . available open access data types include simple somatic mutations ,",380,128,0.3368
scientific_lay_summarisation-elife-norm,"In order to regenerate tissues successfully, stem cells must detect injuries and restore missing cell types through largely unknown mechanisms. Planarian flatworms have an extensive stem cell population responsible for regenerating any organ after amputation. Here, we compare planarian stem cell responses to different injuries by either amputation of a single organ, the pharynx, or removal of tissues from other organs by decapitation. We find that planarian stem cells adopt distinct behaviors depending on what tissue is missing to target progenitor and tissue production towards missing tissues. Loss of non-pharyngeal tissues only increases non-pharyngeal progenitors, while pharynx removal selectively triggers division and expansion of pharynx progenitors. By pharmacologically inhibiting either mitosis or activation of the MAP kinase ERK, we identify a narrow window of time during which stem cell division and ERK signaling produces pharynx progenitors necessary for regeneration. These results indicate that planarian stem cells can tailor their output to match the regenerative needs of the animal. When faced with injury or disease, many animals can repair or even replace damaged tissue. This process of regeneration is observed across animal species, and is often fueled by tissue-resident stem cells (Bely and Nyberg, 2010; Sánchez Alvarado and Tsonis, 2006; Tanaka and Reddien, 2011). In response to injury, stem cells accelerate the production of specific types of differentiated cells to repair damaged tissues. For example, in adult mammals, injuries to the intestine, skin, or lung induce stem cells to increase proliferation rates and alter their differentiation potential (Buczacki et al. , 2013; Stabler and Morrisey, 2017; Tetteh et al. , 2015; Tumbar et al. , 2004). These findings suggest that injury can modify the behavior of stem cells to promote repair, but how these changes contribute to tissue regeneration remains unclear. The freshwater planarian Schmidtea mediterranea is an ideal model organism to study the interaction between injury and tissue repair due to their virtually endless ability to regenerate (Ivankovic et al. , 2019). This ability is driven by an abundant, heterogeneous population of stem cells (Adler and Sánchez Alvarado, 2015; Reddien, 2018; Zhu and Pearson, 2016). Defined by ubiquitous expression of the argonaute transcript piwi-1 (Reddien et al. , 2005), the planarian stem cell population consists of pluripotent stem cells capable of reconstituting the entire animal (Wagner et al. , 2011)","Many animals can repair and regrow body parts through a process called regeneration. Tiny flatworms called planaria have some of the greatest regenerative abilities and can regrow their whole bodies from just a small part. They can do this because around a fifth of their body is made of stem cells, which are cells that continuously produce new cells and turn into other cell types through a process called differentiation. Measuring the gene activity in stem cells from planaria shows that these cells are not all the same. Different groups of stem cells have specific genes turned on which are needed to regrow certain body parts. It is unclear whether all stem cells respond to injuries in the same way, or whether the stem cells that respond are",380,128,0.3368
dialogsum,"#Person1#: Lisa, I'm going shopping downtown this afternoon. Would you like to go with me? #Person2#: I'd like to but I have arranged to discuss the project with Mister Cook. I'm also going to a party with Bill this evening. #Person1#: But you know, I'm not good at bargaining. How I wish you could help me. #Person2#: Why not ask Mary to go with you. She loves shopping. She can help you. #Person1#: Good idea. I'll go and ask her. Thank you. #Person2#: You're welcome.",#Person1# invites Lisa to go shopping. Lisa can't go and advises #Person1# to ask Mary.,85,15,0.1765
pubmed-summarization,"consequently improve patient s outcome.16,17 despite the successful role of the use of l - asp in childhood all treatment , its use is limited and constantly re - evaluated due to serious side effects mainly caused by toxicity . interestingly , most of the observed side effects arise from a second substrate specificity of asparaginase , which can also deplete the concentration of glutamine due to its structural similarity.18,19 among the side effects provoked by this glutaminase side activity of l - asp are pancreatitis , hemostasis abnormalities , thrombotic and neurological complications , and hypersensitivity reactions ( eg , clinical allergy ) due to antibody production . usually , children are more tolerant to l - asp - induced side effects , whereas adolescents and young adults are more sensitive and often develop significant morbidity.2022 innumerous studies have reported that delivery of concomitant vincristine and prednisone and shorter time intervals between l - asp doses reduces the probability of hypersensitivity reactions23 ; however , concomitant therapy with anthracyclines and/or steroids may increase the risk of pancreatitis.4 to overcome toxicity and severe side effects , different asparaginase formulations have been constantly modulated , and the best approach to deal with such an administration schedule has been the main focus of clinical investigation studies in the last decades . for instance , the risk for pancreatitis or thromboembolism seems to be similar among different l - asp preparations.4,24 aspects of different asparaginases formulations are listed in table 1 . one of the major concerns during l - asp treatment is the development of drug resistance mechanisms which are mainly derived through antibodies production in response to l - asp , since all asparaginase sources are from a variety of microorganisms.1,7 yet , unnecessary doses are also a challenge to be defeated . repeated administration of l - asp leads to the development of specific antibodies and hypersensitivity reactions.25,26 for example , in case of allergic reactions to native e. coli - asparaginase , patients are usually switched to either peg - asparaginase or erwinia - asparaginase,27,28 although similar incidence rates of hypersensitive reactions have been reported for both native l - asp and peg - asparaginase . reactions to erwinia - asparaginase , however , may be less frequent.24 in","great improvements have been made in acute lymphoblastic leukemia ( all ) treatment in the past decades , especially due to the use of l - asparaginase ( l - asp ) . despite the significant success rate , several side effects mainly caused by toxicity , asparaginase silent inactivation , and cellular resistance , encourage an open debate regarding the optimal dosage and formulation of l - asp . alternative sources of asparaginases have been constantly investigated in order to overcome hypersensitivity clinical toxicity . additionally , genomic modulation as gene expression profiling , genetic polymorphisms , and epigenetic changes is also being investigated concerning their role in cellular resistance to l - asp . understanding the mechanisms that mediate the resistance to l - asp treatment",380,128,0.3368
dialogsum,"#Person1#: Amanda, could you make a call to the cinema to see if there are still some seats left for the movie this afternoon? #Person2#: I've already booked tickets online for the 2:00 o'clock movie. I'm thinking of picking them up from the ticket office on the way to the restaurant. What do you think? #Person1#: OK. Well, the Smiths want to move our appointment forward by half hour earlier. That means we should be there at 11:30. #Person2#: Then we don't have enough time. We'd better get moving. Oh, before I forget, can you remind me to stop by the bookstore on the way back home? I have to order a book there. #Person1#: OK.",#Person1# asks Amanda to check the seats for the movie. Amanda has already booked tickets online. They'd better get moving because the Smiths want to move the appointment forward.,116,29,0.25
dialogsum,"#Person1#: Hoo, thanks for stopping. Sometimes it can be impossible to get a cab in the rain. #Person2#: No worries. Where to? #Person1#: I'm going to fifth avenue and east twenty second street, no rush at all though. #Person2#: Well, that's good because it looks like we're not going to be able to move more than a few feet per minute. #Person1#: Well, that's what happens when it starts to rain during rush hour. I'm one of the lucky ones. Usually I would have an appointment around this time, but today I get to go home early. #Person2#: That's great, ma'am. I'll try to get you home as early as possible.",#Person1# feels lucky to get #Person2#'s cab in the rain and doesn't mind the traffic jam.,111,16,0.1441
scientific_lay_summarisation-elife-norm,"can have functions as regulatory sRNAs. sRNAs commonly base pair with trans-encoded mRNAs, frequently with the assistance of the RNA chaperone protein Hfq, resulting in changes in the stability or translation of the target mRNA (reviewed in Hör et al. , 2020). Most sRNAs characterized to date are transcribed independent of other genes or are processed from mRNA 3´ UTRs, though a few 5´ UTR-derived sRNAs have been reported (reviewed in Adams and Storz, 2020). RNA fragments entirely internal to coding sequences (Dar and Sorek, 2018a) also have been suggested to function as regulators, though this has not been tested. While sRNAs generally base pair with mRNA targets, a few small transcripts have been shown to have roles as competing endogenous RNAs (ceRNAs) also known as ‘sponges’, which base pair primarily with sRNAs, targeting the sRNAs for degradation or blocking their interactions with mRNA targets (reviewed in Denham, 2020; Figueroa-Bossi and Bossi, 2018; Grüll and Massé, 2019). To systematically identify new regulatory elements in E. coli, we globally mapped RNA 3´ ends, and specifically characterized those ends in 5´ UTRs and ORF-internal regions. We compared this 3´ end dataset with another dataset where BCM treatment was used to identify sites of Rho termination. Using these approaches, we detected hundreds of RNA 3´ ends within 5´ UTRs and internal to ORFs, likely generated by premature transcription termination or RNase processing. We propose the majority of these 3´ ends are the consequence of regulatory events, and we document regulation for multiple examples. For instance, we show 3´ ends are associated with the translation of uORFs, or result from the binding of some sRNAs to mRNA 5´ UTRs. Furthermore, we demonstrate that RNA fragments generated by premature transcription termination and from within coding sequences function as independent sRNA regulators; one as part of an autoregulatory loop and another that connects cell division to the cell envelope stress response. These findings reveal extensive and diverse regulation through premature transcription termination and RNase processing of mRNAs, which can lead to the generation of RNA by-products with independent functions. Two independent cultures of wild-type E. coli MG1655 (WT) were grown to OD600 ~0. 4 in rich (LB) medium, OD600 ~2. 0 in LB, and OD600 ~0. 4 in minimal (M63) glucose medium. Total RNA was isolated","In most organisms, specific segments of a cell’s genetic information are copied to form single-stranded molecules of various sizes and purposes. Each of these RNA molecules, as they are known, is constructed as a chain that starts at the 5´ end and terminates at the 3´ end. Certain RNAs carry the information present in a gene, which provides the instructions that a cell needs to build proteins. Some, however, are ‘non-coding’ and instead act to fine-tune the activity of other RNAs. These regulatory RNAs can be separate from the RNAs they control, or they can be embedded in the very sequences they regulate; new evidence also shows that certain regulatory RNAs can act in both ways. Many regulatory RNAs are yet to be catalogued, even in simple, well-studied",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Smith et al. , 2011), yet less is known about the thalamostriatal projections from other thalamic subregions. The lack of systematic anatomical maps of corticostriatal and thalamostriatal inputs has stymied efforts to dissect the cortico-thalamo-striatal triangular circuits. For example, recent functional studies suggest that corticostriatal and thalamostriatal axons differ in their release probability and plasticity properties (Ding et al. , 2008; Smeal et al. , 2007), but the precise differences have been controversial (Ding et al. , 2008; Smeal et al. , 2007). This controversy raises the possibility of heterogeneity within axons originating from different cortical or thalamic subregions in their synaptic properties (Kreitzer and Malenka, 2008). A comprehensive excitatory input wiring diagram will provide a road map to enable systematic examination of the differential function of individual inputs. In addition, since the excitatory input patterns are thought to be stereotypic in the striatum, we reasoned that the striatal subregions and their boundaries may be revealed by systematic analysis of these input patterns from individual cortical and thalamic subregions. Here, we provide a quantitative and comprehensive description of cortical and thalamic inputs to the mouse striatum. This is achieved by integrating an in-house comprehensive thalamic anterograde projection dataset (Hunnicutt et al. , 2014) and a selected cortical projection dataset from the Allen Institute for Brain Sciences (AIBS) (Oh et al. , 2014). Analyses of this striatal excitatory input wiring diagram revealed clear boundaries separating the three traditional striatal domains and uncovered a fourth subdivision in the posterior striatum. The dorsomedial striatum exhibited the highest degree of cortical input heterogeneity, suggesting that this subdivision serves as an information hub. In addition, thalamic subregions receiving basal ganglia outputs are preferentially interconnected with motor-related cortical subregions. With all the pathways tested, the anatomically described corticostriatal and thalamostriatal projections were confirmed to be functional using optogenetic approaches. Importantly, striatal inputs originating from different cortical or thalamic subregions form synapses in the striatum with distinct plasticity properties. Our findings lay the foundation for understanding the function of the striatum and its interactions with the cortex and the thalamus. In order to obtain a comprehensive excitatory map of the striatum, two viral-based anterograde fluorescent-tracing datasets (Hunnicutt et al. , 2014; Oh et al. , 2014) were analyzed and combined (). The cortex has large, well-defined subregions.","To fully understand how the brain works, we need to understand how different brain structures are organized and how information flows between these structures. For example, the cortex and thalamus communicate with another structure known as the basal ganglia, which is essential for controlling voluntary movement, emotions and reward behaviour in humans and other mammals. Information from the cortex and the thalamus enters the basal ganglia at an area called the striatum. This area is further divided into smaller functional regions known as domains that sort sensorimotor, emotion and executive information into the basal ganglia to control different types of behaviour. Three such domains have been identified in the striatum of mice. However, the boundaries between these domains are vague and it is not clear whether any other",380,128,0.3368
dialogsum,"#Person1#: Oh, Eric. Could you please turn the TV off? I'm trying to study. #Person2#: Oh, come on. I've just got home from work. I need to relax. #Person1#: That's not the point. You don't have to relax with the sound so loud. #Person2#: Well, do you mind closing your bedroom door? So I won't have to turn the TV off. #Person1#: No, sorry, I can't. The door is broken, no remember? #Person2#: OK. I'll turn the TV off now, but I want to watch my favorite program in an hour. #Person1#: Sure, no problem.",#Person1# asks Eric to turn the TV off and Eric finally agrees to watch later.,95,15,0.1579
dialogsum,"#Person1#: May I speak to Mr. Smith? #Person2#: He is at the warehouse this morning. #Person1#: What time do you expect him back? #Person2#: Sorry, I have no idea. You can call him there if you like. #Person1#: Ok, I have the number. Bye!",#Person1# calls Mr. Smith but #Person2# says Mr. Smith is unavailable now.,44,12,0.2727
pubmed-summarization,"in all well developed societies there tend to be barriers between different organizations and different professions , even when those professions want to co - operate to help individuals to satisfy their needs . health and social services today face groups of patients who have composite problems and are often unstable . they include , very obviously , elderly persons with multiple problems , chronically ill children , and persons suffering mental ill - health . they have continuing need of care and in search of care they move between primary care , hospital care and municipality care , such as that provided for elderly persons . their situation demands some form of integration between health and social services , the benefits of which have been identified as including reduced hospital use , a strong focus on prevention and keeping patients healthy , and the provision of care closer to home . from the perspective of the person seeking care , medical and social needs are connected . individuals do not see themselves as multi - ill , but as needing support for their needs as they know them . it must be said that from the 1970s onwards a number of integrative approaches have been tried out , not least in education . although there are exceptions to learn from , generally speaking european health and social services are fragmented and poorly equipped to take care of patients with composite needs . so far , and to a great extent , the task of integrating different delivery systems , of managing the transitions from one provider to another , has fallen on the shoulders of patients themselves or their relatives . much of the evidence indicates that the problem we face is a result of the prevailing mindset . how can we increase our understanding of health and social services that are located in different organizations ? in all well developed societies there tend to be barriers between different organizations and different professions , even when those professions want to co - operate to help individuals to satisfy their needs . health and social services today face groups of patients who have composite problems and are often unstable . they include , very obviously , elderly persons with multiple","introductionorganizations can be regarded as systems . the traditional model of systems views them as machines . this seems to be insufficient when it comes to understanding and organizing complex tasks . to better understand integrated care we should approach organizations as constantly changing living organisms , where many agents are interconnected in so - called complex adaptive systems ( cas).theory and discussionthe term complex emphasizes that the necessary competence to perform a task is not owned by any one part , but comes as a result of co - operation within the system . adaptive means that system change occurs through successive adaptations . a cas consists of several subsystems called agents , which act in dependence of one another . examples would be the ant -",380,128,0.3368
dialogsum,"#Person1#: Hmm... Here's one of a crowd of people moving. I think that's pretty stressful. #Person2#: Well, I don't think it's so bad. But I do think that going to the dentist is stressful. #Person1#: Oh, so do I! It's stressful because you have no control. #Person2#: That's right. Look at this one. This poor boy is sitting in an exam. I think exams are the most stressful. Sometimes you just can't think of anything to write. #Person1#: Yes, I agree with you there. What about these people here? #Person2#: Mmm... I'm not sure. They seem to be in a hurry, don't they? I think being late is stressful. #Person1#: That's true. It can be terrible, especially when you're late for something important. #Person2#: Like an interview. Look at this picture here: here's someone in an interview. Do you think interviews are stressful? #Person1#: No. I think they're quite exciting, a challenge. #Person2#: Oh, I hate interviews.","#Person1# and #Person2# are talking about stressful things. They both think that going to the dentist, taking exams, and being late are stressful. #Person2# thinks interviews are stressful while #Person1# thinks it challenging.",157,33,0.2102
scientific_lay_summarisation-elife-norm,"proxy for nanostructural dimensions, since structural colors and pigments often co-occur and covary. While recent studies (Parnell et al. , 2018; Matsuoka and Monteiro, 2018; Brien et al. , 2018) have made early headway toward describing genetic regulation of structural colors, much work remains to decipher the evolutionary, developmental, and genetic bases of structural coloration, and lab-tractable systems with intraspecific variation in structural coloration are needed. We present a promising system, the butterfly genus Junonia, with extensive variation in a simple structural color, and show how structural simplicity is a tactical advantage when seeking to unravel mechanisms for the biological production of nanostructures. In butterflies, photonic nanostructures occur within the architecture of scales. Scales are the fundamental coloration unit on butterfly wings and have a Bauplan consisting of a grid of ridges and crossribs, supported by a lower lamina that is a simple plane (1A). Scales are composed of chitin and may also have embedded pigments. Intricate architecture and a high refractive index make scales a pliable substrate for photonic innovations, and indeed scales have been evolutionarily elaborated in many ways for impressive optical effects (Ghiradella, 1985). Even the simplest butterfly scales can produce structural color, via the lower lamina acting as a thin film reflector. Thin films are the simplest photonic structure and consist of a layer of high refractive index material, on the order of hundreds of nanometers thick, surrounded by a material with a contrasting refractive index, such as air (1B). Light is reflected from each surface of the film, and these two reflections interfere with each other. If the two reflections remain in phase, which depends on the extra distance traveled through the film and the wavelength, then they interfere constructively to produce observable color (Mason, 1927; Yeh et al. , 1978). Conversely, wavelengths (colors) that undergo destructive interference have decreased brightness. While it is known that the thickness of the lower lamina is one parameter that controls structural color wavelength (Stavenga et al. , 2014) and that thickness can respond to artificial selection in the laboratory (Wasik et al. , 2014), it is not known how general this mechanism is in natural evolution. It is also unknown how lamina structural colors are genetically regulated and whether any recognized butterfly wing patterning genes regulate lamina thickness.","From iridescent blues to vibrant purples, many butterflies display dazzling ‘structural colors’ created not by pigments but by microscopic structures that interfere with light. For instance, the scales that coat their wings can contain thin films of chitin, the substance that normally makes the external skeleton of insects. In slim layers, however, chitin can also scatter light to produce color, the way that oil can create iridescence at the surface of water. The thickness of the film, which is encoded by the genes of the butterfly, determines what color will be produced. Yet, little is known about how common thin films are in butterflies, exactly how genetic information codes for them, and how their thickness and the colors they produce can evolve. To investigate, Thayer et al. used",380,128,0.3368
pubmed-summarization,"subsequent applications , the approximation must be done on a fine data set , meaning that many more points require approximation , again incurring a larger computational cost . the solution is to make use of the convolution - deconvolution properties of stochastic interpolation combining the densification step with the approximation step . however , we introduce an approximate means for doing the interpolation that interpolates for smooth data , but which approximates for noisy data , thus avoiding the costly need to construct the inverse operator needed for interpolation . consider the task of sampling a known function f(u ) at points f(uk ) = vk with uk so as to determine its value at xj . the stochastic interpolant to the data { ( uk , vk ) } , k = 1 , , n is given by ( 1)bmnann1v , where v = ( v1 , v2 , , vn ) is the data vector , and where ann is a row stochastic matrix whose coefficients consist of the n n values ajk . choosing the generator of the row space of ann to be the bernstein functions ( named after bernstein as the derivation of this form that can be obtained from the bernstein polynomials ) , we have ( 2)ajk=12[erf(uk+1xjn)+erf(xjukn ) ] with > 0 on the partition wk = ( uk+uk+1)/2 , with w0 = and wn = yielding a stochastic matrix . setting xj = uj generates the entries of ann , and setting xj to any set of m consecutive values in generates the coefficients of bmn , that is , the coefficients of bmn are constructed in the same manner as for ann , except that the nodes xj at which bjk is evaluated may differ from the values at which the data are given . while any probability density function ( pdf ) can be used , appropriately replacing the mean and variance of the gaussian in ( 2 ) , a pdf based on the normal distribution is consistent with the problem of filtering gaussian noise . in stochastic interpolation , with the coefficient of ann generated by ( 2 ) , we can interpret ann as the discrete deconvolution of the data yielding the preimage generated by","determining the outline or boundary contour of a two - dimensional object , or the surface of a three - dimensional object poses difficulties particularly when there is substantial measurement noise or uncertainty . by adapting the mathematical approach of stochastic function recovery to this task , it is possible to obtain usable estimates for these boundaries , even in the presence of large amounts of noise . the technique is applied to parametric boundary data and has potential applications in biomedical imaging . it should be considered as one of several techniques to improve the visualization of images .",380,100,0.2632
dialogsum,"#Person1#: Do you have a swimming pool in this hotel? #Person2#: We don't have a swimming pool, sir, but we do have swim stations in the gym. #Person1#: I never heard of a swim station. Is that like a train or bus station? #Person2#: It's just a deep bathtub with a current of water that you swim against. #Person1#: Holy cow! I never heard of such a thing. How much do they cost? #Person2#: As a guest, sir, you pay nothing. #Person1#: This sounds better every second. Now, when can I use the stations? #Person2#: If you want to swim, you can visit the gym any day between 7 a. m. and 10 p. m. #Person1#: Oh, boy! This is going to be great. I'm going to the gym right now! #Person2#: I'm sure you'll enjoy your workout, sir. Everyone seems to like the swim stations.",#Person2# introduces #Person1# to the swimming stations in the gym which is free for the hotel guests. #Person1# is impressed and decides to go there now.,146,26,0.1781
dialogsum,"#Person1#: This is the good life! We have it good don't you think? #Person2#: Yeah of course! Although, don't you ever wonder what could have been? #Person1#: What do you mean? #Person2#: Well, sometimes I think of how things could have turned out if I had done things a little differently. #Person1#: For example? #Person2#: Like for example, if I hadn't studied architecture, I would have become an artist like I wanted to. #Person1#: I see. Yeah now that I think of it, I wouldn't have gotten married if I hadn't moved to this town and met Sally. #Person2#: You see! Everything happens for a reason! We wouldn't even have met if I hadn't been in that car accident ten years ago! #Person1#: Well, I have no regrets! #Person2#: I'll drink to that!",#Person1# and #Person2# talk about how their life would be if they had done things differently. They are content with their current life.,133,23,0.1729
pubmed-summarization,"acute generalized exanthematous pustulosis ( agep ) is a rare acute reaction that is drug - induced in 90% of the cases , characterized by a widespread , sterile pustular rash . cefepime is a fourth generation cephalosporin antibiotic used to treat febrile neutropenia , severe infections related to the urinary tract , skin , nosocomial pneumonia , brain abscess , and intra - abdominal and septic lateral / cavernous sinus thrombosis . a 67-year - old man with renal failure who had been on dialysis during the last 2 years and with an 8-year history of cardiac insufficiency was admitted to the hospital complaining of 6 days of diarrhea . the patient was taken to the semi - intensive care unit and treated with ciprofloxacin . as a consequence , his long - term medications had not been changed and consisted of acetylsalicylic acid , furosemide , captopril , carvedilol and clonazepam . on the seventh day , the patient became dyspneic and his chest radiograph showed a left lower lobe opacity . treatment for nosocomial pneumonia was promptly initiated with cefepime ( 1 g / day ) . five days later , he presented with a pruritic , erythematous , maculopapular eruption affecting the abdomen , neck and skin folds . one day later , he developed disseminated pustular lesions ( . 1 ) and his temperature was 37c . laboratory exams evidenced c - reactive protein 136 mg / l , white blood cells 14,700 cells/l ( normal 3,50010,500 cells/l ) with 11,995 cells/l neutrophils ( normal 1,7008,000 cells/l ) . histology showed a toxic pustuloderma with spongiform subcorneal pustules , edema in the papillary dermis and perivascular inflammatory infiltrate consisting of neutrophils ( . after withdrawal of cefepime and introduction of imipenem , the disseminated skin nonfollicular pustules cleared within 4 days following a desquamation . the patient denied previous adverse reaction to other drugs and no personal or family history of psoriasis was evident . agep is a disease characterized by the rapid onset of many sterile , nonfollicular pustules usually arising on an edematous erythema and frequently accompanied by leukocytosis and fever . skin symptoms usually arise rapidly after an insult and resolve spontaneously ( within a few days ) . agep often starts","acute generalized exanthematous pustulosis ( agep ) is a rare cutaneous rash characterized by widespread sterile nonfollicular pustules . cefepime is a fourth generation cephalosporin , used to treat severe infections . a 67-year - old man was admitted with acute gastroenterocolitis . on the seventh day , the patient developed a nosocomial pneumonia and cefepime was initiated . on the fourth day of cephalosporin treatment , he presented with a maculopapular , pruritic eruption affecting the face , neck , abdomen and limbs . one day later he developed disseminated pustular lesions and his temperature was 37c . laboratory analysis evidenced leukocytosis and skin biopsy showed subcorneal pustule , edema in the papillary dermis , perivascular inflammatory infiltrate consisting of neutrophils , leukocytoclasia and red cell extravasation",380,128,0.3368
dialogsum,"#Person1#: Cindy! Are you getting take-out? #Person2#: Yeah, do you want something? #Person1#: Yeah, thanks. Could you pick me up a chicken salad sandwich, an order of fries, and a large diet coke? #Person2#: No problem. Do you have any cash on you? I don't think I have enough.",#Person1# asks Cindy to pick #Person1# up some take-out.,49,9,0.1837
dialogsum,"#Person1#: How about this floor lamp? #Person2#: Fine, just get it! We have been shopping for furniure for five hours! I'm so tired! #Person1#: We still need to find an armoire and a dresser. #Person2#: Fine! I am going to go home and drop off this nightstand, coffee table and love seat while you look for the rest of the things. #Person1#: Great! Pick me up in about an hour because I think I'll also get a bean bag and a dining set. #Person2#: While you are at it can you pick out a nice recliner? I really want one so I can watch TV. #Person1#: Recliner? In my beautifully decorated living room? I don't think so!",#Person1# and #Person2# have been shopping for furniture for five hours. #Person2# will go home first and pick up #Person1# in an hour because #Person2# is tired.,117,27,0.2308
scientific_lay_summarisation-elife-norm,"Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signalling in Drosophila. Like many mammalian cytokines, unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for unpaired-JAK signalling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes (Drosophila macrophages) are an important source of this tonic signal. Loss of the dome receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis. JAK/STAT activating signals are critical regulators of many biological processes in animals. Originally described mainly in immune contexts, it has increasingly become clear that JAK/STAT signalling is also central to metabolic regulation in many tissues (Dodington et al. , 2018; Villarino et al. , 2017). One common consequence of activation of JAK/STAT pathways in inflammatory contexts is insulin resistance in target tissues, including muscle (Kim et al. , 2013; Mashili et al. , 2013). However, it is difficult to describe a general metabolic interaction between JAK/STAT and insulin signalling in mammals, due to different effects at different developmental stages, differences between acute and chronic actions, and the large number of JAKs and STATs present in mammalian genomes (Dodington et al. , 2018; Mavalli et al. , 2010; Nieto-Vazquez et al. , 2008; Vijayakumar et al. , 2013). The fruit fly Drosophila melanogaster has a single, well-conserved JAK/STAT signalling pathway. The unpaired (upd) genes upd1-3 encode the three known ligands for this pathway; they signal by binding to a single common GP130-like receptor, encoded by domeless (dome) (Agaisse et al. , 2003; Brown et al. , 2001; Chen et al. , 2002). Upon ligand binding, the single JAK tyrosine kinase in Drosophila, encoded by hopscotch (hop), is activated; Hop then activates the single known STAT, STAT92E, which functions as a homodimer (Binari and Perrimon, 1994; Chen et al. , 2002; Hou et al. , 1996; Yan et al. , 1996).","The immune system helps animals fend off infections, but it also has a role in controlling the body’s metabolism – that is, the chemical reactions that sustain life. For instance, in fruit flies, high-fat diets can trigger the immune system, which results in cells becoming resistant to the hormone insulin and not being able to process sugar properly; this in turn leads to problems in sugar levels and shorter lifespans. This mechanism involves the release of an immune signal called unpaired-3 (upd3), which then binds to a receptor known as dome. Yet, it was unclear how exactly the immune system and metabolism work together, and whether their interactions are also important in flies on a normal diet. To investigate, Kierdorf et al. stopped the activity of the dome",380,128,0.3368
scientific_lay_summarisation-elife-norm,"transform of their inputs remains unknown. Controlling the timing and precision of movements is considered to be one of the main functions of the cerebellum. In the cerebellum, the firing frequency of Purkinje cells (PCs) (Heiney et al. , 2014; Herzfeld et al. , 2015; Hewitt et al. , 2011; Medina and Lisberger, 2007; Payne et al. , 2019; Sarnaik and Raman, 2018; Witter et al. , 2013) or the timing of spikes (Brown and Raman, 2018; Sarnaik and Raman, 2018) have been shown to be closely related to movement. Indeed, cerebellar pathology impairs precision in motor learning tasks (Gibo et al. , 2013; Martin et al. , 1996) and timing of rhythmic learning tasks (Keele and Ivry, 1990). These functions are executed by a remarkably simple neuronal network architecture. Inputs from mossy fibers (MFs) are processed by GCs and transmitted via their parallel fiber (PF) axons to PCs, which provide the sole output from the cerebellar cortex. GCs represent the first stage in cerebellar processing and have been proposed to provide pattern separation and conversion of the MF input into a sparser representation (recently reviewed by Cayco-Gajic and Silver, 2019). These MF inputs show a wide variety of signaling frequencies, ranging from slow modulating activity to kilohertz bursts of activity (Arenz et al. , 2008; Rancz et al. , 2007; Ritzau-Jost et al. , 2014; van Kan et al. , 1993). Interestingly, in most cellular models of the cerebellum, each MF is considered to be either active or inactive with little consideration for this wide range of frequencies (Albus, 1971; Marr, 1969). Furthermore, in these models, GCs are generally considered as a uniform population of neurons. Here, we show that the biophysical properties of GCs differ according to their vertical position in the GC layer. GCs located close to the white matter (inner-zone) preferentially transmit high-frequency MF inputs, have shorter action potentials, and a higher voltage threshold to fire an action potential compared with GCs close to the PC layer (outer-zone). These gradients in properties of GCs enable a Fourier-like transformation of the MF input, where inner-zone GCs convey the high-frequency, and outer-zone GCs the low-frequency components of the MF input. The different Fourier-like components are sent to PCs by specialized downstream signaling pathways, which differ in PF axon","The timing of movements such as posture, balance and speech are coordinated by a region of the brain called the cerebellum. Although this part of the brain is small, it contains a huge number of tiny nerve cells known as granule cells. These cells make up more than half the nerve cells in the human brain. But why there are so many is not well understood. The cerebellum receives signals from sensory organs, such as the ears and eyes, which are passed on as electrical pulses from nerve to nerve until they reach the granule cells. These electrical pulses can have very different repetition rates, ranging from one pulse to a thousand pulses per second. Previous studies have suggested that granule cells are a uniform population that can",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Nixon, 2016; David et al. , 2010; Sun et al. , 2016; Tiku et al. , 2017). In budding yeast mitosis, age-induced damage is asymmetrically retained by the mother cell resulting in the formation of an aged mother cell and a young daughter cell (Mortimer and Johnston, 1959). In contrast, meiotic cells reset aging symmetrically such that all of the meiotic products are born young, independent of their progenitor’s age (Unal et al. , 2011). Importantly, senescence factors originally present in the aged precursor cells, including protein aggregates, nucleolar damage, and rDNA circles, are no longer present in the newly formed gametes (Ünal and Amon, 2011; Unal et al. , 2011). How gametes avoid inheriting age-associated damage and how this event is coupled to the meiotic differentiation program remains unknown. Meiotic differentiation, also known as gametogenesis, is a tightly regulated developmental program whereby a progenitor cell undergoes two consecutive nuclear divisions, meiosis I and meiosis II, to form haploid gametes. Meiotic differentiation requires extensive cellular remodeling to ensure that gametes inherit the necessary nuclear and cytoplasmic contents. In yeast gametogenesis, the nucleus undergoes a closed division, with the nuclear envelope remaining continuous until karyokinesis forms four new nuclei (Moens, 1971; Moens and Rapport, 1971; Neiman, 2011). Mitochondria and cortical endoplasmic reticulum also undergo regulated morphological changes, separating from the cellular cortex and localizing near the nuclear envelope at the transition between meiosis I and II (Gorsich and Shaw, 2004; Miyakawa et al. , 1984; Sawyer et al. , 2019; Stevens, 1981; Suda et al. , 2007). Around the same time, new plasma membranes, also known as prospore membranes, grow from the centrosome-like spindle pole bodies embedded in the nuclear envelope. This directed growth of plasma membrane ensures that nascent nuclei and a fraction of the cytoplasmic contents are encapsulated to form gametes (Brewer et al. , 1980; Byers, 1981; Knop and Strasser, 2000; Moens, 1971; Neiman, 1998). Subsequently, the uninherited cellular contents are destroyed by proteases released upon permeabilization of the progenitor cell’s vacuole, the yeast equivalent of the mammalian lysosome (Eastwood et al. , 2012; Eastwood and Meneghini, 2015). Whether these cellular remodeling events are integral to the removal of age-induced damage has not been characterized. In this study, we aimed to determine the mechanism by which nuclear senescence","The cells of living organisms accumulate damage as they age. Some of this age-associated damage is found around the organism’s DNA. However, when genetic material is passed on during sexual reproduction, newly born offspring avoid inheriting this age-induced damage. This ensures that the progeny are ‘re-set’ with a fresh lifespan that is independent from their parents’ age. A lot of what is known about aging has come from studying budding yeast. Yeast cells can undergo a process called meiosis and divide into four cells known as gametes, which are the equivalents of human sperm and egg. During meiosis, the structure that surrounds the cell’s genetic material – known as the nuclear membrane – remains intact, surrounding the DNA as it separates into four distinct parts. As the cell",380,128,0.3368
dialogsum,"#Person1#: Hello, Ann. #Person2#: Oh, hello. Come on in. Let me take your coat. You managed to find us then. #Person1#: Well, I got a bit lost coming off the ring road. Sorry I'm a bit late. #Person2#: Oh, don't worry. The dinner hasn't been ready yet. Martin is still in the kitchen. #Person1#: So he is cooking, isn't he? #Person2#: He is quite an expert in the kitchen. Fortunately for me, I can't boil an egg myself. #Person1#: Oh, I brought you this. I wasn't sure what you liked. But obviously, it's meant to be quite a good year. #Person2#: Oh, thanks. Lovely.",#Person1# visits Ann and Martin and brings them a gift. Ann tells #Person1# Martin's still cooking.,104,16,0.1538
dialogsum,"#Person1#: How do you like Korea? #Person2#: I like it. It's a beautiful country. #Person1#: What part of the visit excited you most? #Person2#: The best island of Korea-Jizhou island. #Person1#: Why? #Person2#: Attractive scenery, pleasant climate, these make it charming. #Person1#: Yes, I think so. But there is also something terrible. #Person2#: What do you mean? #Person1#: Sometimes the traffic is too busy. #Person2#: Yes, you are right.","#Person2# likes the attractive scenery and pleasant climate of Korea-Jizhou island, but #Person1# thinks the traffic there is busy.",69,19,0.2754
pubmed-summarization,"blood pressure : 118.6 7.3 mmhg ; diastolic blood pressure : 72.6 8.4 mmhg ) volunteered as subjects for the present study . the study was conducted in accordance with the standards set by the latest revision of the declaration of helsinki , and all the subjects provided written informed consent in accordance with the department of sport for all studies at soongsil university guidelines . anthropometric measurements included height , body composition , resting heart rate , and blood pressure . height and body composition were measured using a stadiometer ( seca213 ; seca , germany ) and a bioimpedance analysis device ( inbody720 ; biospace , korea ) , respectively . resting heart rate and blood pressure were measured in a seated position , using a heart rate monitor ( polar a5 ; polar , finland ) and a mercury sphygmomanometer ( trimline ; pymah , usa ) , respectively . the 9 subjects participated in control and experimental tests , both involving 60 min of running on a treadmill at an exercise intensity of 75% heart rate reserve in a laboratory with temperature and humidity of 18.5 0.5 c and 36.0 1.0% , respectively . the clothing worn by each subject consisted of a half - sleeve t - shirt and short pants . during the control test , the participants wore conventional clothing ( which had not received functionality treatment ) ; during the experimental test , they wore ge - coated functional clothing ( which had been prepared by coating the same clothing used for the control test with ge ) . according to the result of a comparison test using fourier transform infrared spectroscopy ( ft - ir ) and a black body at 37 c , which is almost the same as body temperature , the far infrared rays emitted by the ge - coated functional clothing characteristically showed an emission rate of 0.893 m and a wavelength of 3.44 10 w / mm . tympanic temperature was measured using infrared ear thermometry ( thermoscan irt-4520 ; braun , germany ) as a surrogate for core temperature . thermal sensation was measured using a disc score7 . using a 22-gauge needle , a serum separator tube ( becton dickinson , usa ) ,","[ purpose ] the present study investigated the effects of wearing germanium - coated functional clothing on tympanic temperature , thermal sensation , heat shock protein 70 ( hsp70 ) , and lactate during endurance exercise . [ subjects and methods ] nine healthy and untrained male subjects were enrolled . subjects ran for 60 min on a treadmill ( 75% heart rate reserve ) in the following 2 tests : 1 ) control test ( wearing conventional clothing ) and 2 ) experimental test ( wearing germanium - coated functional clothing ) . during each test , the tympanic temperature and thermal sensation were measured , and blood samples were collected immediately before exercise and immediately after exercise . thermal sensation was measured using a disc score",380,128,0.3368
dialogsum,"#Person1#: Hi. #Person2#: Hi, Mary. #Person3#: Hi, Ken I hate to bring this up, but that new stereo, system you got. . . #Person2#: Yeah? #Person3#: You were playing it very late last night. #Person2#: Yeah? #Person3#: It kept me awake. #Person2#: Oh, I'm sorry. #Person3#: It kept me awake a couple of hours. #Person2#: I'm so sorry, I. . I didn't realize it was that loud. #Person3#: It was that loud, and it was pretty late, and check with Mary if you don't believe me. #Person1#: It's true. It was a bit loud. #Person2#: I'm very sorry. I didn't realize it. I promise I'll keep it down in the future. #Person1#: Oh, it's no problem. It's OK. You know, it only happened once. #Person2#: I am glad we've straightened everything out.",#Person3# tells Ken that they play their stereo system very late last night. Ken feels sorry and promises to keep it down next time.,132,24,0.1818
dialogsum,"#Person1#: Good morning, everyone. In the studio today we have Steve Jackson, who's going to tell us about his recent trip to the Antarctic. So Steve, what was it like? Did you freeze? #Person2#: No, I didn't. While I was there, the temperature was about 7 degrees and I found it quite comfortable. It can get storming in the Antarctic but the seas were calm. #Person1#: I guess you should take warm clothes. #Person2#: Well, you really need that. But what I found most useful was dark sunglasses. The sun can get really strong with the reflection of the snow and the ice. #Person1#: What were the other passengers like? #Person2#: All the atmosphere aboard the ship was great. The crews were mainly American and they did their best to get everyone to mix. #Person1#: Did you come across any people apart from your fellow tourists? #Person2#: Yes, a few of the scientists at a research station. They gave his coffee and biscuits one morning. #Person1#: What's your best memory of the trip? #Person2#: Hard to say really. There are so many. We saw a lot of wildlife, but I guess what I most treasured is the large variety of birds we saw. #Person1#: I guess the area was totally untouched before the scientists arrived. #Person2#: Well, actually there used to be a booming fishing industry in the area at one time. But all that's left are some deserted buildings now. No old boats are machines or anything like that, though.",Steve Jackson comes to #Person1#'s studio and introduces his recent trip to the Antarctic. Jackson says the temperature was comfortable and the atmosphere aboard the ship was great. Jackson treasured the view of various birds most.,251,36,0.1434
scientific_lay_summarisation-elife-norm,"relies on different brain structures. Imprinted sounds activate the mediorostral nidopallium/mesopallium (MNM) (Bock and Braun, 1999; Wallhäusser and Scheich, 1987), where neural responsiveness increases after training (Bredenkötter and Braun, 1997). In contrast, the intermediate medial mesopallium (IMM, former IMHV) (Horn, 2004; McCabe et al. , 1982) is required for visual imprinting, where neural responses shift to favor the imprinted object (Horn et al. , 2001). While the brain circuits and neurophysiological changes have been uncovered (Horn, 2004; Scheich, 1987), much less is known about the molecular machinery linking experience and the formation of imprinted memories in each sensory modality. While imprinting requires protein synthesis (Gibbs and Lecanuet, 1981), little is known about the underlying translational control mechanisms. The translation of mRNA into protein occurs in three steps: initiation, elongation and termination and can be regulated through several signaling pathways (Sonenberg and Hinnebusch, 2009). Translation initiation is believed to be the rate-limiting step and a key target for translational control (Sonenberg and Hinnebusch, 2009; Buffington et al. , 2014). A major way in which translation initiation is regulated is by modulating the formation of the ternary complex via phosphorylation of the translation-initiation factor eIF2α. In rodents, protein synthesis controlled by phosphorylation of eIF2α is critically required for long-lasting forms of synaptic plasticity (Costa-Mattioli et al. , 2007; Di Prisco et al. , 2014) as well as long-term memory storage in several systems (Costa-Mattioli et al. , 2007,2005; Zhu et al. , 2011; Stern et al. , 2013; Ounallah-Saad et al. , 2014; Ma et al. , 2013). Here we asked whether this central translational control mechanism plays a role in imprinting in newborn chickens and can be used to restore imprinting outside of the CP. Dark reared chickens were placed in a running wheel in front of an LCD screen and a speaker for training. Visual and auditory imprinting were tested separately 24 hr after training (1a). Stimuli consisted of animated movies showing a virtual object, and artificial sounds synchronized to movements of the object in the screen (1b, see supplementary materials). The imprinting was assessed by the preferential approach to the imprinted stimuli, either visual or auditory, compared to the approach to novel stimuli. The preference for imprinted stimuli is commonly used as an index of long-term memory storage (Horn,","Shortly after hatching, a chick recognizes the sight and sound of its mother and follows her around. This requires a type of learning called imprinting, which only occurs during a short period of time in young life known as the “critical period”. This process has been reported in a variety of birds and other animals where long-term memory formed during a critical period guides vital behaviors. In order to form imprinted memories, neurons must produce new proteins. However, it is not clear how new experiences trigger the production of these proteins during imprinting. Unraveling such mechanisms may help us to develop drugs that can recover plasticity in the adult brain, which could help individuals with brain injuries relearn skills after critical periods are closed. It is possible to",380,128,0.3368
dialogsum,"#Person1#: You know, smoking does do harm to your health. #Person2#: Yes, you're right. #Person1#: Why don't you try to give it up? #Person2#: I've tried to give up smoking several times, but it's no good. Smoking relaxes me. #Person1#: Have you ever thought of just cutting down? You could do it gradually. #Person2#: Yes, maybe I should have another try.",#Person1# advises #Person2# to cut down smoking gradually.,61,8,0.1311
scientific_lay_summarisation-elife-norm,"was loaded. (C4) 1% of the amount of hAxin1-GFP lysate was loaded. One representative immunoblot of 3 independent experiments. Details of calculations used are in the Results and Materials and methods—full data is in Table 1. (D) Measuring the levels of APC2 overexpression in SW480 cells. Immunoblot analysis of cells transfected with Flag-tagged truncated human APC1-1338 (see 1B) or fly APC2 with the indicated antibodies. γ-Tubulin was used as a loading control. (D1, D2) Equal volumes of cell lysate were loaded. (D3) 10% the amount of Flag-flyAPC2 lysate loaded. (D4) 10% the amount of Flag hAPC1-1338 lysate was loaded. One representative immunoblot of 3 independent experiments. : http: //dx. . org/10. 7554/eLife. 08022. 00410. 7554/eLife. 08022. 005Figure 1— 2. Human APC' s Arm repeat domain colocalizes with Axin. (A) Diagrams of fly APC2 and APC2Arm rpts only. (B) SW480 cells expressing GFP-APC2Arm rpts only. APC2Arm rpts only forms cytoplasmic puncta and is unable to reduce βcat levels (insets = box in B). (C) Diagrams of hAPC1 and hAPC1Arm rpts only mutant. (D) GFP-hAPC1Arm rpts only expressed in SW480 cells. hAPC1Arm rpts also forms cytoplasmic puncta and is unable to reduce βcat levels (insets = box in D). (E) GFP-hAxin1 expressed in SW480 cells forms cytoplasmic puncta, and does reduce βcat levels, but βcat accumulates in the puncta (insets = box in D). : http: //dx. . org/10. 7554/eLife. 08022. 005 Despite this attractive model, several key issues remain. APC and Axin are destruction complex core components. Both are protein interaction hubs, combining folded domains with intrinsically disordered regions carrying peptide motifs that bind protein partners. APC was initially thought to be the scaffold templating βcat phosphorylation but subsequent work revealed that Axin plays this role (Hart et al. , 1998; Ha et al. , 2004). Axin has binding sites for βcat, APC, GSK3, CK1 and PP2A, and self-polymerizes via its DIX domain (1A), which allows it to locally increase the concentration of proteins mediating βcat phosphorylation (Ikeda et al. , 1998; Fagotto et al. , 1999; Liu et al. , 2002; Fiedler et al. , 2011). Thus while APC is essential for destruction complex function, its role in the complex remained a mystery. APC combines an N-terminal Armadillo repeat domain (Arm rpts) with a more C-terminal intrinsically disordered region; each","An embryo starts off as a small ball of stem cells, each of which has the potential to become any type of cell in the body. Adult organs and tissues also contain small numbers of stem cells that can replace old or damaged cells. In both of these processes, stem cells need to ‘decide’ when they should start to change into a more specialized cell type, and which cell fate to choose (e. g. , liver cell vs kidney cell). A signaling pathway involving Wnt proteins helps to direct many of these decisions. But if the ‘Wnt signaling pathway’ becomes activated at the wrong time, it can lead to cancer. For example, the first step in development of colon cancer is the inappropriate activation of Wnt signaling, and",380,128,0.3368
dialogsum,"#Person1#: I wonder if you could help me find something for my daughter. #Person2#: Do you think she'd like a laptop? #Person1#: I think that would be perfect. #Person2#: A Mac is something most people appreciate. #Person1#: In fact, she prefers Macs. How much is one? #Person2#: Our 15-inch Pro will cost you only $2, 100. #Person1#: She's going to be so happy. Let me have one. #Person2#: You've made a good decision. How would you like to pay? #Person1#: I'll pay for it with my VISA. #Person2#: It's all yours after you sign here, please. #Person1#: Are there any extras that she needs? #Person2#: This is good to go. If she wants accessories, just visit us again. #Person1#: You've been so helpful. Thank you. #Person2#: Have a nice day, and thank you for shopping here.","#Person1# purchases a 15-inch Pro Mac for #Person1#'s daughter which costs $2, 100 with #Person2#'s assistance.",136,16,0.1176
scientific_lay_summarisation-elife-norm,"T-cells per µL, was used to scale all CD4+ T-cell count observations for adults on ART (zi= xi, jy). Our analysis was restricted to patients with available baseline (i. e. at antiretroviral treatment initiation) CD4+ T-cell counts and sufficient observations to estimate all model parameters (). We categorized as baseline any CD4+ count measurement that was taken within 15 days before or after the ART initiation date. Two model-fitting scenarios were defined based on the availability of enough observations to estimate the model parameters: Scenario 1: In which baseline scaled CD4+ T-cell counts were estimated, including 1312 children and 12,238 adults, with a minimum of five CD4+ T-cell counts measurements and no missing values for our variables of interest (specified below). Scenario 2: Where baseline scaled CD4+ T-cell counts were used as a predictor, including 1616 children and 14,542 adults, with a minimum of four CD4+ T-cell counts measurements and no missing values for our variables of interest. These variables were CD4+ T-cell counts since ART initiation; viral load, age and body mass index at ART initiation; sex and suppression (or not) of viral load within 12 months of ART initiation. In this paper we will mostly discuss results of scenario 1, where all parameters are estimated. The methodology used and most of the obtained results are applicable for scenario 2, when baseline CD4+ T-cells counts data are available. We also present results of scenario 2. Under both scenarios, in the initial model fitting, all parameters were assumed to vary per individual (i. e. there were random effects on all parameters) and their distributions was set as log-normal. Thus, for each parameter θ, the distribution of individual values was log (θi) ∼ ℵ (μ, ω2), with mean μ and variance ω2. Random effects were assumed to be independent and the identity diagonal matrix was used for the variance–covariance structure. This assumption was later relaxed and different variance–covariance structures were subsequently evaluated. To compare models, the Akaike and Schwarz information criteria (AIC and BIC respectively), computed by importance sampling, were used (see Comets et al. , 2017). Models with a full variance–covariance matrix were retained as this structure gave the lowest AIC and BIC values. Our choice of covariates was based on literature reviews (Pinzone et al. , 2012; Sempa et","The human immunodeficiency virus (HIV) remains an ongoing global pandemic. There is currently no cure for HIV, but antiretroviral therapies can keep the virus in check and allow individuals with HIV to live longer, healthier lives. These drugs work in two ways. They block the ability of the virus to multiply and they allow numbers of an important type of infection-fighting cell called CD4+ T cells to rebound. As more patients with HIV survive and transition from one life stage to the next, it is critical to understand how long-term antiretroviral therapies will affect normal age-related changes in their immune systems. The health of an immune system can be evaluated by looking at the number of CD4+ T cells an individual has, though this will vary by age",380,128,0.3368
dialogsum,"#Person1#: Good morning. This is Shanghai Car Rental. #Person2#: Good morning, Miss. A friend of mine suggested I call you to hire a car. #Person1#: Oh, yes. A lot of people do this these days. #Person2#: Yes, we are just on holiday here for a few days and they said it would be a good idea to hire a car to get around the city. #Person1#: Well, it certainly is. What kind of car do you want to hire? #Person2#: What can you suggest? #Person1#: We have a variety of choice, such as Xiali, which is the cheapest, 200 yuan a day, Citroen, Jatta, Elysee, but Santana sedans are the big favorite these days. #Person2#: How much if I hire a Santana for three days? #Person1#: Oh, that will be 1,200 yuan. #Person2#: On, it sounds a bit too expensive. What about a Jetta? #Person1#: It will be 300 yuan a day. #Person2#: Then I'd better hire a Jetta tomorrow morning, would there be any problem? #Person1#: No problem at all. Now let me take down your name and telephone number.",#Person2# wants to hire a car from Shanghai Car Rental and asks for suggestions. #Person2# finally decides to hire a Jetta instead of Santana because Santana is too expensive.,181,29,0.1602
pubmed-summarization,"a recent report published by the american association of colleges of nursing ( aacn ) noted that over 67,000 qualified applicants were not accepted into baccalaureate and graduate nursing programs in the usa in 2010 . the report also noted that almost two - thirds of the nursing schools participating in the survey noted that faculty shortage is the primary reason for not accepting all qualified applicants into baccalaureate programs . the consequence of a nursing shortage is nurses work longer hours under stressful conditions , which leads to nurses being more prone to making mistakes and medical errors . schools of nursing are increasingly using hospital - based nurses to precept students during clinical rotations . these nurse preceptors extend the faculty at a time when a shortage of nursing faculty limits nursing school enrollment . combined with initiatives already in place , such as using master 's prepared nurses at the hospital as loaned faculty , compressing students ' clinical rotations and assigning clinical rotations to off - shifts or , in less popular nursing units , using nurse preceptors as clinical faculty helps in two ways : it increases the number of available clinical nursing slots and it provides qualified clinical instructors . as little quantitative research on the effectiveness of using preceptors as clinical instructors early in a nursing program has been reported , this study looks at the question given baccalaureate students in their second medical - surgical class , do precepted students perform as academically well as traditionally prepared students ? clinical groups in texas traditionally have a ratio of one master 's prepared instructor to 10 students . the instructor 's role is to monitor students in the clinical setting and instruct them in meeting their educational learning objectives . when class size is extended to increase enrollment , procuring a sufficient number of qualified clinical instructors is often difficult . that nurses qualified for teaching can make higher salaries working as a nurse in a hospital than as faculty in a university exacerbates the faculty shortage problem additionally , as the number of clinical slots dedicated to nursing students is limited , schools in the region compete with each other . students often demand accessible and timely information , and they want","the shortage of nursing faculty has contributed greatly to the nursing workforce shortage , with many schools turning away qualified applicants because there are not enough faculty to teach . despite the faculty shortage , schools are required to admit more students to alleviate the nursing shortage . clinical groups in which preceptors are responsible for student learning extend faculty resources . purpose . to determine the effectiveness of an alternative clinical experience ( preceptorship ) . methods . quasi - experimental , randomized , longitudinal design . students were randomized to either the traditional or precepted clinical group . the clinical experience was a total of 12 weeks . groups were compared according to several variables including second semester exam scores , hesi scores , and quality",380,128,0.3368
pubmed-summarization,"to amniotic fluid and fetal heart ( 8) . . summarized placental findings associated with influenza infections in publications from 1987 and 1994 , describing perivillous and villous inflammation with concurrent amniotic fluid immunofluorescence for influenza virus ( 9 ) . in another study ( 10 ) , researchers from beijing , people s republic of china , reported autopsy findings for 2 patients ( 1 of whom was 4 months pregnant ) who died of avian influenza a ( h5n1 ) . viral antigens were present in the maternal pulmonary system , and virus was detected in placental hofbauer cells ( histiocytes ) , cytotrophoblast , fetal lung , circulating mononuclear cells , and liver macrophages ( 10 ) . their documentation of tropism of the influenza virus to placental tissue is similar to the histopathologic features in our report . our unexpected discovery of viral production in placental , maternal , and fetal histiocytes is another example of transplacental passage of influenza . adverse fetal outcomes have reportedly included congenital malformation and schizophrenia , but factors that determine these effects remain unclear ( 11,12 ) . fetal consequences of influenza exposure may be an effect of systemic inflammatory response to the infection , which could represent direct action of the virus on the placenta , the maternal fetal interface , or the fetus . reported the inflammatory response of decidual and fetal tissue in the presence of influenza virus infection and demonstrated expression of mrna for a set of proinflammatory cytokines such as interleukin-6 , tumor necrosis factor- , and granulocyte macrophage colony - stimulating factor , secreted in substantial amounts in response to exposure to influenza virus in vitro ( 13 ) . as our case suggests , a complex interaction of maternal and fetal responses at the interface is a more likely explanation . a total of 15%20% of pregnancies end in spontaneous miscarriage , most before gestational week 12 ( 3 ) . approximately 50% of miscarriages are associated with chromosomal defects , which leaves many other miscarriages unexplained ( 14 ) . examined first trimester miscarriages not associated with chromosomal abnormality , observing histologic changes of chronic intervillositis and increased perivillous fibrin ( 15 ) . the mechanism of loss was thought to be","a second trimester fetal demise followed influenza - like illness in early pregnancy . influenza a virus ( h1n1 ) was identified in maternal and fetal tissue , confirming transplacental passage . these findings suggested a causal relationship between early exposure and fetal demise . management of future influenza outbreaks should include evaluation of products of conception associated with fetal loss .",380,62,0.1632
pubmed-summarization,"malignant unilateral or bilateral ureteral obstruction may be secondary to direct tumor invasion , extrinsic compression , or encasement by metastatic retroperitoneal or pelvic lymph nodes . the selection of cancer patients for diversion should take into account factors such as tumor stage , prognosis of the primary cancer , likelihood of additional antineoplastic therapy , and quality of life . contemporary management options include external drainage via percutaneous nephrostomy ( pcn ) and internal drainage via the insertion of double - j stents . regular double - j stents used to relieve ureteral obstructions that are secondary to extrinsic causes , such as malignancies , have high rates of failure . pcn is commonly used as an alternative , either as a primary procedure or after the failure of transurethral procedures . however , pcn is more invasive than double - j stent insertion and may also have a greater incidence of accidental tube dislodgement . the invasiveness of the procedure and the high incidence of tube dislodgement may result in a reduction in patient quality of life . in addition , some patients are unwilling to accept a pcn tube because it requires an external collecting device . the limitations associated with conventional treatments for ureteral obstructions highlight the need for a novel treatment that can maintain ureteral patency while minimizing the deterioration of patient quality of life . several types of metallic stents have been used in the palliative treatment of malignant ureteral obstructions , but implantation of these stents has yielded results that are not uniform and the stents have been associated with various complications . a novel polytetrafluoroethylene ( ptfe ) membrane - covered metal mesh stent prevents obstruction from tissue ingrowth and reduces stent migration as a result of its unique structure . here we report our initial experience with a ptfe membrane - covered self - expandable metallic stent ( uventa stent ) for the palliative care of malignant ureteral obstruction . between october 2010 and november 2011 , 18 consecutive patients ( 5 men and 13 women ; mean age , 57 years ) underwent placement of uventa stents ( taewoong medical , seoul , korea ) for unilateral or bilateral malignant ureteral obstruction . the ureteral obstructions were caused by compression","purposewe assessed the efficacy and safety of insertion of a polytetrafluoroethylene membrane - covered self - expandable metallic stent ( uventa stent ) for palliation of malignant ureteral obstruction on the basis of our early results.materials and methodseighteen patients underwent uventa stent insertion for extrinsic malignant ureteral obstructions of 20 ureters . the uventa stents were deployed retrogradely under cystoscopy and fluoroscopy . candidates for the procedure had preexisting double - j stents that were nonfunctional or caused excessive bladder irritation . we recorded the success and patency rate in addition to any complications associated with the procedure.resultsthe mean length of obstruction was 10.6 cm ( range , 2 to 20 cm ) . two ureters were obstructed in the upper ureter , 9 in the lower ureter",380,128,0.3368
pubmed-summarization,"= 33,285 ; 7497 families ) and both sexes , with 49.4% males ( n = 16,428 ) and 50.6% females ( n = 16,857 ) , were screened by three neurologists , in addition to 15 female social workers ( for sociodemographic data collection ) via a door - to - door survey . a standardized questionnaire , the sensitivity and specificity of which are 96% and 93.2% , respectively,3 was applied by three neurologists to every member of each family ( children and elderly were questioned through their caregivers ) . a total population of 31,754 ( 95.4% ) were free from any neurological disorder , versus 1531 ( 4.6% ) of both sexes ( 3.9% [ n = 647 ] males and 5.2% [ n = 884 ] females ) had different neurological disorders . full history data and examinations ( general , systemic , and neurological ) were carried out by the three neurologists in collaboration with nine other senior staff members from neurology departments in assiut , al - azhar , sohag , and qena universities . all neurological disorders were finally diagnosed after evaluation by the three neurologists , each separately , as well as specific investigatory tools . diagnoses of different neurological disorders were based on the accepted definition and diagnostic criteria given by the world health organization.4,5 the definition of incidence rate , prevalence , and lifetime prevalence in this study are according to those provided by abramson.6 ethical approval for the study was obtained from the research ethics committee of assiut university and from the ministry of health to carry out this project in al quseir city , red sea governorate . each participant provided written informed consent ( children , illiterate , and disabled individuals consented through the responsible person in the family or their caregivers ) . data management was carried out by two specialists in data entry and three medical statisticians using spss software ( v 16 ; ibm corporation , armonk , ny , usa ) , excel ( microsoft corporation , redmond , wa , usa ) , and epicalc 2000 ( microsoft corporation ) . the project was designed to assess major neurological disorders in al quseir city as a representative coastal city lying on","a door - to - door survey , including every household , was conducted for all inhabitants of al quseir city ( 33,283 ) , red sea governorate , egypt by three specialists of neurology as well as nine senior staff members of neurology and 15 female social workers to assess the epidemiology of major neurological disorders . over six phases , from july 1 , 2009 to january 31 , 2012 , screening of all eligible people in the population was carried out , by which case ascertainment of all major neurological disorders included in the study was done according to the accepted definitions and diagnostic criteria of the world health organization . the order of frequency of prevalence of the studied neurological disorders was dementia (",380,128,0.3368
pubmed-summarization,"due to increasing life expectancy of the dentition , older adults are experiencing root caries and gingival recession , putting them at even higher risk for periodontal disease . root caries is the major cause of tooth loss in older adults , and tooth loss is the most significant oral health - related negative variable of quality of life for the elderly . one prominent goal of the dental profession is to preserve and maintain dentitions throughout life . population projections suggest that the proportion of the population aged 65 years and older will nearly double between 2000 ( 12.6 percent ) and 2030 ( 20.0 percent ) , and that the proportion of those aged 85 years and older will increase dramatically over the next 10 to 15 years . this population trend coupled with compelling evidence that people are retaining their teeth into old age suggests that there will be an increased number of older adults with many more natural teeth in the years to come . there are known clinical and behavioral risk factors involved in the production and progression of root caries in the elderly . risks are described in a number of levels , from socioeconomic status to salivary flow to presence of dentures . data have shown correlations of dietary and oral habits and other variables on root caries . many risk factors can compromise an older adult 's systemic health such as sociodemographic variables , nutrition / diet , and weakened immune system . this paper examines salivary hypofunction , the systemic and oral immune system ( immunoglobulins found in saliva ) in older adults , and their manifestations . there are several indicators that provide insight into the incidence and prevalence of caries in healthy people and the medical or disability conditions that place individuals at increased caries risk . one indicator is the presence of mutans streptococci , an established etiologic agent for caries activity . one of the main oral behaviors to reduce the amount of bacteria in the oral cavity is regular tooth brushing with a fluoride - containing dentifrice . conditions that compromise good oral hygiene behaviors and oral health are also positively associated with caries risk . these include certain illnesses , physical and mental disabilities ,","root caries is one of the most significant dental problems among older adults today . many studies have demonstrated that older adults are at greater risk for developing root caries . here we examine what risk factors older adults are prone to and explain how they contribute to higher rates of oral disease , in particular root caries . the elderly are at risk for root caries due to dentures , lack of dexterity , a shift from complex to simple sugars , and poor oral hygiene . decreased salivary flow and its manifestations with other social / behavioral and medical factors may provide a more comprehensive explanation to a higher frequency of root caries in older adults .",380,119,0.3132
dialogsum,"#Person1#: Good afternoon, madam. How can I help you? #Person2#: Well, I am a bit out of shape. I'm thinking about getting some exercises to keep fit. #Person1#: Oh, that's good news for us. #Person2#: So what do you provide? #Person1#: First of all, we'll design a custom-made work-out plan according to your habits. #Person2#: How can you get that done? #Person1#: Well, we give each of our customers a personal trainer who is qualified. And he will give you a fitness assessment and then come up with the work-out plan for your needs. #Person2#: What else? #Person1#: Since everyone is different, your personal trainer will find you a suitable type of exercise equipment and teach you all the techniques to help you achieve your fitness level and goal. #Person2#: Sounds pretty good. What about the charge? #Person1#: That depends. We offer membership for one month, half a year and one year. #Person2#: Maybe one month. Just have a try first. Not too tough at the beginning. #Person1#: Wise decision. You'll find it's totally worth it.","#Person2# wants to exercise and consults #Person1#. #Person1# tells her about the custom-made work-out plan, personal trainers, and the charge. #Person2# decides to try for one month.",176,27,0.1534
pubmed-summarization,"q . air - q ila was introduced with a gentle inward and downward pressure using the curvature of the device as a guide till a fixed resistance to further advancement was felt . the cuff was inflated with air as per manufacturer 's recommendation , 18 ml for size 3.5 and 25 ml for size 4.5 . the proximal connector of the air - q ila was connected to etco2 probe along with the breathing circuit . initiating positive pressure ventilation , proper insertion of device was confirmed by observing bilateral chest rise along with audible breath sounds on auscultation and capnographic trace on the monitor . the vital parameters ( pulse rate , blood pressure , peripheral oxygen saturation [ spo2 ] ) were recorded after successful insertion of the air - q ila . the pre - lubricated appropriate size endotracheal tube was then advanced through the air - q ila blindly to intubate the trachea . the endotracheal tube was then connected to etco2 probe along with the breathing circuit and placement of the endotracheal tube in trachea was again confirmed by auscultation of breath sounds along with bilateral chest rise and capnographic trace . on the first attempt , if trachea was not intubated , the endotracheal tube was withdrawn up to 18 cm mark for number 7.0 endotracheal tube and 20 cm mark for number 8.0 endotracheal tube followed by re - advancement of the endotracheal tube with adequate external laryngeal manoeuvre over the cricoid cartilage . after confirmation of endotracheal placement , the connector of endotracheal tube was removed and the tube was stabilised using the air - q removal stylet . the cuff of the air - q was deflated and air - q withdrawn over the endotracheal tube - stylet assembly . the placement of endotracheal tube was reconfirmed to rule out endobronchial advancement and then the tube was secured . after removal of air - q following tracheal intubation , the device was observed for visible macroscopic blood stains to rule out airway trauma . the following data were recorded : number of attempts to insert air - q , post - insertion heart rate ( hr ) , blood pressure and spo2 , number of attempts to intubate the","background and aims : air - q intubating laryngeal mask airway ( ila ) is used as a supraglottic airway device and as a conduit for endotracheal intubation . this study aims to assess the efficacy of the air - q ila regarding ease of insertion , adequacy of ventilation , rate of successful intubation , haemodynamic response and airway morbidity.methods:sixty patients presenting for elective surgery at our medical college hospital were selected . following adequate premedication , baseline vital parameters , pulse rate and blood pressure were recorded . air - q size 3.5 for patients 50 - 70 kg and size 4.5 for 70 - 100 kg was selected . after achieving adequate intubating conditions , air - q ila was introduced . confirming adequate ventilation",380,128,0.3368
dialogsum,"#Person1#: How may I help you? #Person2#: I need to buy some clothes for my daughter. I don't know what size to get. Can you help me? #Person1#: Certainly. How old is she? How tall is she? #Person2#: She is 9 years old and 4 feet tall. #Person1#: We have a great selection of clothes for young girls. Pants start at $10 and shirts start at $7. #Person2#: Great. I will take 3 pairs of pants and 2 shirts, please. #Person1#: If they're gifts, I can wrap each item for $1 each. #Person2#: Please do, thank you.",#Person2# buys 3 pairs of pants and 2 shirts for #Person2#'s daughter with #Person1#'s help.,97,15,0.1546
dialogsum,"#Person1#: It's a vicious circle, really. It takes me the best part of an hour to get here in the morning, so I honestly never have time for breakfast. #Person2#: But you should always have something. According to nutrition experts, it's the most important meal of the day. #Person1#: That's a load of rubbish, if you ask me. It's all very well for them. They've probably got time for it. I haven't. Anyway, when I get to work, I'm plunged into the usual stressful day, and my hunger just sort of evaporates. #Person2#: Yes. I only live around the corner, but I often skip breakfast myself, but I suppose you could always make up for it at the lunch time. #Person1#: I should, but more often than not I just grab a cup of coffee and a few biscuits, or a sandwich. #Person2#: There's nothing wrong with that. That's all I ever have when I'm busy. #Person1#: Fine, but what happens as the day wears on is that the less you eat, the less you want to eat. Abstinence seems to suppress the appetite, somehow. #Person2#: Well, I suspect what we ought to be doing is establishing a regular pattern of eating, instead of just grabbing what we can when we can. #Person1#: Em, a sensible conventional diet. There's no doubt that's the way to go, so shall we now go and do something for a change? You name the restaurant and I'll treat you to lunch. #Person2#: That will be nice.",#Person1# gets to work with no time to eat breakfast and just grab what #Person1# can when #Person1# can for lunch. #Person2# sometimes does the same. #Person2# thinks they should establish a regular pattern of eating.,252,36,0.1429
dialogsum,#Person1#: There will be another sandstorm here tomorrow. #Person2#: It's the fourth one this year. Isn't it horrible. #Person1#: Yes. We should plant more trees and grass to stop the sand from spreading. #Person2#: It may take many years for the trees to grow. I hope people will stop cutting down trees. #Person1#: But we need the wood. #Person2#: But we can't destroy our forests to get the wood.,"In terms of the sandstorm, #Person1# prefers to plant more trees and grass, but #Person2# thinks stopping cutting down trees is quicker.",69,22,0.3188
pubmed-summarization,"case , where a female patient developed aacg after 8 days , following tpm 25 mg / day , once a day ( od ) , for 3 days as an adverse reaction to tpm . she was started on tpm 25 mg / day ; however , she stopped the treatment after 3 days without consultation as her headache was not relieved . after 5 days of stopping the treatment with tpm , she presented at the emergency clinic of a hospital with complaints of blurred vision and severe pain in both the eyes , which were of a few hours in duration . she also complained of colored halos and headache associated with nausea with no family history of eye - related disorders . on ophthalmic examination , the visual acuity was found to be 3/60 in both the eyes , and did not show improvement in visual acuity in the pinhole test . both anterior chambers were found to be shallow , appeared occluded in the periphery , and pupils were reactive . applanation tonometry revealed high intraocular pressure ( iop ) of 34 and 32 mmhg , in the right and left eyes , respectively ( . 1). . 1a photograph of normal ( a ) and glaucomatous ( b ) eyes a photograph of normal ( a ) and glaucomatous ( b ) eyes a diagnosis of aacg , precipitated following oral administration of tpm , was made . while , laser peripheral iridotomy would have been an ideal procedure for aacg , due to presence of choroidal effusion along with anterior migration of anterior structures this treatment option was not considered in this case . she was hence started on acetazolamide tablets 250 mg four times a day ( qid ) , pilocarpine 2% eye drops qid , travoprost 0.004% od , and dorzolamide 2% eye drops three times a day ( tid ) . since she had already stopped tpm , she was advised not to take it again and was reviewed the next day . the repeat ophthalmic examination on the second day showed improved vision ( 6/60 ) in both the eyes , reduction in conjuctival chemosis , and improved depth of anterior chamber , while it continued to be shallow","introductionthis case report adds supportive evidence to the development of acute angle - closure glaucoma ( aacg ) , a rare but serious adverse effect following the use of topiramate ( tpm ) for a severe headache.case reporta 25-year - old female reported with severe headache , suspected to be migraine , and was started on tpm 25 mg / day on the first day . however , she presented at the emergency clinic of a hospital with sudden blurring of vision and colored halos 5 days after stopping the drug , i.e. , day 8 . she was subjected to ophthalmic examination and was diagnosed with aacg . the intraocular pressure ( iop ) was found to be elevated and she was hence started on acetazolamide 500",380,128,0.3368
dialogsum,"#Person1#: What is this eviction notice for? #Person2#: The notice you received is a 30 - day notice to vacate. #Person1#: Are you kidding me? #Person2#: I mentioned to you before that you need to keep up with your rent. This notice to evict is letting you know that I mean business. #Person1#: You can't just throw me out on the street! #Person2#: You have 30 days to catch up on your rent, or a sheriff will evict you. #Person1#: Will you still throw me out if I make the rent payment? #Person2#: You can stay, but you might think about looking for a less expensive living arrangement if you are having trouble making the payments. #Person1#: I am going to take care of the rent payment right now. #Person2#: Thank you. The payment needs to be in the form of cash or a cashier's check.",#Person1# got an eviction notice and #Person2# tells #Person1# #Person1# has 30 days to pay the rent or a sheriff will evict #Person1#. #Person1# pays the rent right now.,146,29,0.1986
dialogsum,"#Person1#: You say he was around average height. #Person2#: Yes, that's right, around five nine five ten. #Person1#: Weight? #Person2#: I'm not sure. Medium I suppose. Maybe a little on the heavy side. #Person1#: Any marks on his face? #Person2#: No, I don't think so. #Person1#: Glasses? #Person2#: No. #Person1#: What about his hair? #Person2#: Black or dark brown. #Person1#: Long or short? Straight? Curly? #Person2#: Straight, I think, and about average length #Person1#: Boy, this sure doesn't help us much. It could be anybody. How about his cloth? What was he wearing?",#Person1# is describing the appearance of a certain man to #Person2#.,93,11,0.1183
dialogsum,"#Person1#: I am considering going for the new job that was posted yesterday. #Person2#: Are you certain that that is what you want to do? #Person1#: It may not be the best choice for me, but I am considering it. #Person2#: Why do you think that this would be a good move? #Person1#: I believe that this job would allow me to move up but might be a little boring for me. #Person2#: Yes, there are always pros and cons to making a career change. #Person1#: Also, the matter of pay is also a consideration. #Person2#: I think the slight pay decrease might be worth it. The benefits are much better. #Person1#: Yes, sometimes giving up a little to move forward is the best choice. #Person2#: I think you should definitely apply for the position.","#Person1# tells #Person2# the job might be a good move for #Person1# but might be boring. Though the pay decreases, #Person2# thinks the benefits are better.",135,26,0.1926
dialogsum,"#Person1#: This is going to surprise you, but I'm happy. I think you're making the right move. #Person2#: You do? #Person1#: Look, maybe I shouldn't tell you this, but I'v going over to WebTracker, too. #Person2#: No way! That's great! Then we'll still be together! #Person1#: Actually, I'm already working for WebTracker. Vince never wanted to give me what I was worth, so I figured, what the heck. #Person2#: No kidding! I can't believe this. You devil! #Person1#: It's kind of cool, isn't it? I'm sort of like a secret agent.","#Person1# is going over to WebTracker with #Person2#, which surprises #Person2#.",91,11,0.1209
scientific_lay_summarisation-elife-norm,"Env trimers or to gp120 (Scheid et al. , 2011; Zhou et al. , 2010; Diskin et al. , 2012; Scharf et al. , 2013; Hoot et al. , 2013; Ota et al. , 2012; McGuire et al. , 2013). In previous studies, we investigated VRC01-class germline recognition of Env by solving a crystal structure of the clade A/E 93TH057 gp120 core bound to a half germline, half mature chimeric VRC01-class Ab (NIH45-46CHIM) in which the inferred germline HC was paired with the mature LC to permit binding to an unmodified gp120 (Scharf et al. , 2013). Two forms of designed gp120-based immunogens were subsequently engineered to bind and activate germline HC/LC VRC01-class B cell receptors: gp120 outer domain-only constructs (eOD-GT6 and eOD-GT8) (Jardine et al. , 2013; 2015) and gp120s modified from the clade C 426c Env (McGuire et al. , 2013; 2014; 2016). Crystal structures of the inferred germline Fab of VRC01 complexed with eOD-GT6 and NIH45-46CHIM complexed with gp120 revealed a similar angle of approach for binding as mature Fabs and conservation of the signature VRC01-class interactions with gp120 residues (Scharf et al. , 2013; Jardine et al. , 2013). However, questions concerning germline B-cell receptor recognition of gp120 remained because neither structure represented a complex between a fully germline VRC01-class Ab and a complete gp120 core. Here, we present crystal structures of inferred germline VRC01-like Abs alone and complexed with 426c-based gp120 immunogen cores and compare and contrast their gp120 recognition with structures of mature VRC01-class Ab/gp120 complexes. The analyses shed insight on the evolution pathway by which Abs derived from VH1-2*02 germline mature towards broad recognition of the CD4bs on gp120 and provide structural information that will facilitate design of immunogens to elicit VRC01-class bNAbs. The antigen-binding Fabs of two VRC01-class Abs isolated from different patients, NIH45-46 and 3BNC60 (Scheid et al. , 2011), were generated in their inferred germline forms (NIH45-46GL and 3BNC60GL) using sequences described in previous studies (Scharf et al. , 2013; Hoot et al. , 2013; McGuire et al. , 2013; Dosenovic et al. , 2015). Compared with mature NIH45-46 (NIH45-46MAT), NIH45-46GL contained 40 HC and 23 LC substitutions in addition to a two-residue insertion in CDRL1. 3BNC60GL contained 38 HC and 25 LC substitutions in addition to a four-residue deletion","When human immunodeficiency virus-1 (HIV-1) infects humans it can cause a serious disease that damages the immune system. Currently there is no cure for this disease and there are no vaccines available to halt the spread of the virus. Researchers are hoping to be able to develop a single vaccine that can protect individuals against every form (or strain) of HIV-1, but this has proved difficult because many different versions of the virus exist. An effective vaccine triggers long-lasting immunity to a particular virus or microbe by activating the production of proteins called antibodies that identify and help to destroy the threat. Research has shown that most individuals infected with HIV-1 produce antibodies that can only recognize a few HIV strains. However, there are rare individuals who produce",380,128,0.3368
dialogsum,"#Person1#: What can I do for you? #Person2#: I would like to buy two exquisite watches for me and my girlfriend. #Person1#: We have many pairs for couples. Look at this counter. #Person2#: This pair is Rolex, right? #Person1#: You have a very good taste, this pair is the latest product. #Person2#: What function does this watch have? #Person1#: Both of them are luminous with a time reminder function. They don't need battery, because they can absorb energy from the sun. #Person2#: Sounds good. #Person1#: In addition, they are waterproof and shockproof. #Person2#: How long is the guarantee? #Person1#: We guarantee the quality of the product for 12 months. We also provide a worldwide warranty. #Person2#: How much does the pair cost? #Person1#: 2, 200 $. #Person2#: It is a bit expensive. But it is worth buying one's favorite. I will take them.",#Person2# asks #Person1# of watches for couples. #Person2# takes a fancy to Rolex and decides to buy them after #Person1#'s introduction.,143,21,0.1469
dialogsum,"#Person1#: I need to buy a bus pass. #Person2#: What kind of bus pass would you like to buy? #Person1#: What are the different kinds? #Person2#: You can get a day, weekly, monthly, or student pass. #Person1#: Could I get a student pass, please? #Person2#: Sure, can I see your student ID? #Person1#: Sure, here it is. #Person2#: Very good. #Person1#: How much for the pass? #Person2#: It's free, but the monthly sticker is $ 24. #Person1#: Okay, I'll take it. #Person2#: Thank you for your purchase. #Person1#: You are welcome.",#Person1# wants to buy a student bus pass. #Person2# checks #Person1#'s student ID. #Person1# pays $24 for the monthly sticker.,91,20,0.2198
scientific_lay_summarisation-elife-norm,"et al. , 2008). The IL-6 receptor complex consists of the ligand-binding subunit, the IL-6Rα chain, and the signal-transducing subunit, gp130 (Taga et al. , 1989), which is a common signaling transducer for several cytokines including IL-6, IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin-1 (CT-1), and IL-35. Homodimerization of gp130 upon IL-6 binding results in the activation of the gp130-associated tyrosine kinases JAK1, JAK2 and TYK2 and the subsequent phosphorylation of the transcription factors STAT1 and STAT3 (Kamimura et al. , 2003). In addition to the membrane-bound receptor, a soluble form of the IL-6Rα chain can be generated through either alternative splicing or proteolytic cleavage and is capable of binding to IL-6 and activating cells through association with gp130 (Kamimura et al. , 2003). Although both IL-6-deficient mice and mice bearing a T cell-specific deletion of gp130 have been used to examine the in vivo function of IL-6 in T cell responses, the pleiotropic nature of IL-6, as well as the promiscuous use of the gp130 signaling subunit, has complicated these analyses (Kamimura et al. , 2003). Thus, the T cell-specific role of IL-6 signaling in vivo has remained poorly understood. In the present study, we therefore used mice carrying a T cell-specific ablation of the IL-6Rα chain, in order to investigate the role of IL-6 in the induction of CD4+ T cell responses following TLR activation. Our data not only confirm an important function for IL-6 in Th17 cell differentiation, but also reveal a critical role for IL-6 in the induction of the Th1 cell response in vivo. IL-6 enables T cell activation by acting on responder CD4+ T cells to make them less sensitive to the suppressive activity of Tregs, in part by blocking Treg-mediated inhibition of IL-2Rα expression in responder CD4+ T cells in cooperation with IL-1β. Although not absolutely required for the generation of Tfh cells, we also found that IL-6 signaling is important for the ability of these cells to provide help to B cells. In addition, we reveal a role for IL-6 in the generation of functional memory CD4+ T cells. To examine the function of IL-6 in CD4+ T cell responses in vivo, we generated mice in which T cells were specifically deficient of the IL-6Rα by crossing a floxed allele","The human body' s ability to defend itself against pathogens relies on two distinct but connected systems: the innate and the adaptive immune systems. Innate immune cells survey their environment and use receptors located on their surface to distinguish between molecules that are harmless and molecules that stem from pathogens. When the cells of the innate immune system detect a pathogen, they secrete signaling molecules to alert adaptive immune cells to the invaders. Both sets of immune cells then mount a coordinated attack that usually kills the pathogen. The adaptive immune system also produces memory cells that retain information about the pathogen: this allows the organism to mount a fast and efficient immune response the next time the same type of pathogen strikes. However, it is not completely",380,128,0.3368
scientific_lay_summarisation-elife-norm,"The amyloid precursor protein (APP), whose mutations cause familial Alzheimer’s disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function. The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer’s disease, alterations of this synaptic role of APP could contribute to dementia. Human genetic evidence and studies in App-knock-out (KO) mice indicate that the amyloid precursor protein (APP) plays an important physiological role in the central nervous system. In humans, a polymorphism in APP that reduces APP processing protects from sporadic Alzheimer’s disease (AD) and normal aging-dependent cognitive decline (De Strooper and Voet, 2012, Jonsson et al. , 2012). In contrast, mutations in APP and in genes that regulate APP processing – such as PSENs and BRI2/ITM2B – cause familial AD (FAD) and the AD-like familial British dementia and familial Danish dementia (De Strooper, 2007, De Strooper et al. , 2010, De Strooper and Voet, 2012, Garringer et al. , 2010, Matsuda et al. , 2005, Giliberto et al. , 2008, Matsuda et al. , 2009, Tanzi, 2012, Vidal et al. , 1999,2000). Analysis of App-KO mice has also suggested a synaptic role for APP (Korte et al. , 2012, Marcello et al. , 2012, Octave et al. , 2013, Randall et al. , 2010, Turner et al. , 2003, Venkitaramani et al. , 2007). For example, hippocampal App-KO neurons in culture show enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission and increased size of the readily releasable synaptic vesicle pool (RRP). In addition, long-term potentiation (LTP), a form of synaptic plasticity that underlies memory formation, is impaired in App-KO mice; and these LTP deficits are clearly noticeable in","Alzheimer’s disease has been linked to mutations in a gene encoding the amyloid precursor protein (APP). Mutations in this gene cause early onset Alzheimer’s disease in some families. Studies in animals suggest this mutant form of the protein may interfere with the messages sent between brain cells. But it remains unclear how this protein works even when it isn’t mutated. One reason it has been difficult to out how APP works is because it is a long protein and is often cut into smaller, but still functional proteins. It is unclear which parts of the protein are involved in sending messages between brain cells, but previous research has allowed scientists to zero in on one stretch of the protein containing just 50 amino acids. Now, Fanutza, Del Prete",380,128,0.3368
dialogsum,"#Person1#: New York Airport. May I help you? #Person2#: Yes. I am calling to make sure if flight CG877 will arrive on time? #Person1#: Hold on a moment please. . . Sorry, the flight from London has been delayed. It departed two hours later than scheduled. The whether in London was really bad. #Person2#: You mean it will arrive two hours later than usual? #Person1#: So far we could only deduce this way. If you want further information, would you please call us 1 hour later? #Person2#: OK, thank you.",#Person1# from New York Airport tells #Person2# on the phone that #Person2#'s flight has been delayed because of the weather.,90,20,0.2222
dialogsum,"#Person1#: What are you doing, awake? #Person2#: I can't sleep. . . #Person1#: But it's almost midnight! #Person2#: Exactly. I'm too excited for Christmas morning. Also, I thought I heard Santa. #Person1#: Really? How do you know it was Santa? #Person2#: Well, I heard that naughty boys and girls get coal in their stockings, so I thought I'd be nice and make Santa cookies. I even left out some milk. I heard someone in the kitchen eating the cookies, so I came downstairs! #Person1#: Hmm. . . well I know that Santa won't come down the chimney with you hiding behind the tree, spying on him! #Person2#: Really? #Person1#: Really! Let's go back upstairs and get back to bed. That way, we can let Santa do his job. Then when you wake up, it will be Christmas already! #Person2#: O-K. . . #Person1#: Hey, honey! Is that you? Don't eat all the cookies, I want some, too!",#Person2# can't sleep because of Christmas coming. #Person1# persuades #Person2# to go back to bed and sleep. Both #Person1# and #Person2# want to eat the cookies.,157,26,0.1656
dialogsum,"#Person1#: Has everything been OK with you lately? #Person2#: I haven't been able to get a good night's sleep lately. I'm exhausted! #Person1#: Have you been too busy to get enough sleep? #Person2#: I try to go to sleep, but I just can't stay asleep. #Person1#: How late do you try to go to sleep? #Person2#: I go to bed when I finish my work. #Person1#: Has anything in your day-to-day life been bothering you lately? #Person2#: I am worried about how I am going to pay my tuition. #Person1#: You might consider listening to relaxing music as you go to sleep to clear your head. #Person2#: Doing something relaxing before I go to sleep sounds like a plan.",#Person2# hasn't been able to sleep well lately because #Person2#'s worried about paying #Person2#'s tuition. #Person1# suggests listening to relaxing music.,119,21,0.1765
scientific_lay_summarisation-elife-norm,"to be derived from the African Palaeoloxodon (or Elephas) recki (Maglio, 1973; Saegusa and Gilbert, 2008), which was the predominant proboscidean lineage in Africa during the Pliocene and Pleistocene but went extinct around 100 thousand years ago (ka) (Owen-Smith, 2013). Straight-tusked elephants may have survived in mainland Eurasia until around 35 ka, although the youngest reliably dated remains are from the last interglacial, 115–130 ka (Stuart, 2005). 10. 7554/eLife. 25413. 003Figure 1. Palaeoloxodon antiquus, geographic range based on fossil finds (after Pushkina, 2007). White dots indicate the locations of Weimar-Ehringsdorf and Neumark-Nord. : http: //dx. . org/10. 7554/eLife. 25413. 003 Recent technological progress has pushed back the temporal limit of ancient DNA research, enabling, for example, recovery of a low coverage genome of a ~700,000 year-old horse preserved in permafrost (Orlando et al. , 2013). For more temperate regions, however, evidence of DNA preservation reaching far beyond the last glacial period is still limited to a single locality, Sima de los Huesos in Spain, where DNA has been recovered from ~430 ka old hominin and bear remains (Dabney et al. , 2013; Meyer et al. , 2016). While genetic analyses of the extinct interglacial fauna remain a challenging undertaking, recent advances in ancient DNA extraction (Dabney et al. , 2013) and sequencing library construction (Meyer et al. , 2012) have improved access to highly degraded DNA. To better understand the evolutionary relationships between the extinct straight-tusked elephants and other elephant species, we attempted DNA extraction and sequencing from several P. antiquus fossils, four of which we investigated in depth. Three of these, which were all unambiguously assigned to P. antiquus based on their morphology, were from Neumark-Nord (NN) 1 in Germany, a fossil-rich site that has been proposed to date to MIS 5e (~120 ka) or MIS 7 (~244 ka) or both (Mania, 2010; Schüler, 2010; Penkman, 2010). This site has yielded one of the largest collections of P. antiquus remains known to date. The fourth fossil was recovered during recent active mining in the travertine deposits of Weimar-Ehringsdorf (WE), Germany, a quarry that has for more than a century yielded a rich collection of fossils representing a typical European interglacial fauna (Kahlke, 1975). Weimar-Ehringsdorf is best known for the discovery of Neanderthal remains in the early 20th century, and","Understanding how extinct species are related to each other or to their living relatives is often a difficult task. Many extinct species have been identified only from incomplete fragments of some of their bones. However, even if complete skeletons have been found, determining the relationships between species can be tricky because researchers often have to rely solely on the shapes of the bones. It is sometimes possible to retrieve DNA sequences from fossil bones. This is easier with younger fossils and those that have been recovered from cold environments. Ancient DNA sequences have been retrieved from only a few fossils older than 100,000 years, but such DNA sequences can be tremendously useful in determining how different species are related to each other. Today there are three living elephant",380,128,0.3368
pubmed-summarization,"a 19-year - old female with no significant past medical history or medication use presented to our hospital in april 2010 with severe nephrotic syndrome characterized by marked fluid retention , heavy proteinuria ( protein : creatinine ratio of 1244 mg / mmol ) , hypoalbuminaemia ( 13 g / l ) and elevated total serum cholesterol ( 9.3 mmol / l ) . renal function was preserved with a serum creatinine of 42 mol / l , and there was no haematuria evident on urine microscopy . lupus and vasculitis markers , hepatitis serology and serum electrophoresis were negative . a renal biopsy was performed which revealed normal glomeruli , tubules and interstitium . the patient was commenced on prednisolone 50 mg daily ( 1 mg / kg ) in addition to ramipril 5 mg daily , simvastatin 10 mg daily and warfarin therapy . complete remission was achieved within 2 months and prednisolone dose was reduced to 25 mg daily . soon after , and against medical advice , the patient abruptly ceased her prednisolone and within 72 h had a relapse of disease with recurrence of gross peripheral oedema , hypoalbuminaemia of 13 g / l ) and proteinuria of 1030 mg / mmol ( from 0.06 mg / mmol ) . despite recommencing high - dose steroids ( 60 mg / day ) , the disease thereafter remained refractory to steroid therapy with persistent gross oedema , nephrotic - range proteinuria and hypoalbuminaemia ( albumin of 9 g / l ) . after failing to respond to 3 months of high - dose steroids , the patient was commenced on cyclophosphamide . in light of the patient 's history of non - compliance and in an effort to reduce drug exposure and toxicity , pulse intravenous cyclophosphamide was administered in incremental doses of 0.5 , 0.75 and 1.0 g / m 1 month apart . during this period two months after the third pulse of cyclophosphamide was administered , there was no evidence of disease response with ongoing gross oedema , hypoalbuminaemia ( albumin 14 g / l ) and heavy proteinuria ( 1476 mg / mmol ) . at this point , it was decided to trial the monoclonal anti - cd20 antibody rituximab (","we report a case of steroid- and cyclophosphamide - resistant nephrotic syndrome secondary to minimal - change disease occurring in an otherwise healthy 19-year - old female , responding rapidly to two doses of rituximab therapy . complete disease remission has been sustained up to last follow - up ( 32 months ) despite cd19 recovery . literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal - change disease .",380,79,0.2079
dialogsum,"#Person1#: I need to order new business cards. #Person2#: Do you have any idea how many you'd like? #Person1#: I think 2, 000 would be enough. #Person2#: Would you fill out this form, please? #Person1#: I don't want to make any changes to my old card. #Person2#: If you detect any difference, I'll take you out to dinner. #Person1#: . . . Okay, that's it. Here's the form, and here's my old card to use as a model. #Person2#: Thank you. Your order will be ready seven days from now. #Person1#: I need it sooner. Let me have it in three days, okay? #Person2#: We can certainly give you faster turnaround, but it will cost you extra.","#Person1# orders 2,000 new business cards with #Person2# assistance. #Person1# wants them sooner. #Person2# tells #Person1# it will cost more.",117,20,0.1709
dialogsum,"#Person1#: May I come in? #Person2#: Yes, please. #Person1#: How are you doing, Madam? My name is During Wu. I am coming to your company for an interview as requested. #Person2#: Fine, thank you for coming. Mr. Wu, Please take a seat. I am Anne Smith, the assistant manager. #Person1#: Nice to see you, Mrs. Smith. #Person2#: Nice to meet you, too.",During Wu comes to the company for an interview and the assistant manager Anne Smith introduces herself.,62,17,0.2742
pubmed-summarization,"and backcrossed for at least seven generations into the c57bl/6 background . lfa1 and c57bl/6 wildtype ( wt ) mice were provided by charles river ( sulzfeld , germany ) . all mice were maintained as breeding colonies at the central animal facility of the university of heidelberg , germany . the animal experiments were approved by the animal care and use committee of the regierungsprsidium karlsruhe , germany . in certain experiments , recombinant murine tnf ( r&d systems , minneapolis , usa ) was injected intrascrotally at a dose of 500 ng per mouse 3 hours before intravital microscopy . in some experiments , recombinant murine chemokine cxcl1 ( keratinocyte - derived chemokine kc ; peprotech , london , uk ) was injected systemically at a dose of 600 ng per mouse . blocking antibodies against murine mac1 ( tib128 , clone m1/70 , rat igg2b ) and murine lfa1 ( tib217 , clone m17/4 , rat igg2a ) were obtained from american type culture collection ( atcc , manasses , usa ) and systemically administered with a dose of 100 g per mouse . bordetella pertussis ptx was purchased from sigma - aldrich ( taufkirchen , germany ) and administered in certain experiments at a dose of 4 g per mouse 3 h prior to preparation in the trauma model . mice were prepared for intravital microscopy as reported recently . briefly , after intraperitoneal ( i.p . ) injection of ketamine ( 125 mg / kg body weight , ketalar ; parke - davis , morris plains , usa ) and xylazine ( 12.5 mg / kg body weight ; phoenix scientific , inc . joseph , usa ) mice were placed on a heating pad to maintain body temperature . intravital microscopy was conducted on an upright microscope ( leica ; wetzlar , germany ) with a saline immersion objective ( sw40/0.75 numerical aperture , zeiss , jena , germany ) . mice were intubated , and the left carotid artery was cannulated for blood sampling and the right jugular vein for glucose and systemic mab administration . d - glucose ( 200 mg / ml ) was administered in doses of 0,25 g , 0,5 g , and 1 g / kg body weight","it is well acknowledged that proinflammatory stimulation during acute hyperglycemia is able to aggravate inflammatory diseases . however , the mechanisms of proinflammatory effects of glucose are controversially discussed . we investigated leukocyte recruitment after intravenous injection of glucose in different inflammatory models using intravital microscopy . flow chamber experiments , expression analysis , functional depletion , and knockout of key adhesion molecules gave mechanistic insight in involved pathways . we demonstrated that a single injection of glucose rapidly increased blood glucose levels in a dose - dependent manner . notably , during tumor necrosis factor ( tnf ) -induced inflammation leukocyte recruitment was not further enhanced by glucose administration , whereas glucose injection profoundly augmented leukocyte adhesion and transmigration into inflamed tissue in the trauma model ,",380,128,0.3368
dialogsum,"#Person1#: Can I help you? #Person2#: Yes. My daughter bought this camera here for my wife's birthday. But it doesn't work. So I'd like to change it for another one. #Person1#: I see. Let me have a look. Well, we'll be happy to change it for you. But I am afraid we don't have another pink one. #Person2#: Oh? What will I do then? #Person1#: Would you like to choose a different color? We do have this camera in black and orange. #Person2#: My wife doesn't like either of those colors. #Person1#: If you want, we can order another camera just like this one. There wouldn't be any extra charge for it. #Person2#: That sounds fine. Would you please go ahead and do that? #Person1#: We'd be very happy to but it'll take at least a week. Maybe ten days. We'll call you when it comes in. #Person2#: Thank you very much. #Person1#: You are welcome.",#Person2# wants to change the camera his daughter bought for his wife because it doesn't work. #Person1# says they don't have another pink one but could order one. #Person2# agrees.,156,30,0.1923
scientific_lay_summarisation-elife-norm,"X syndromes (Budworth and McMurray, 2013). Consequently, the high mutability of some DNA regions may accelerate the evolution of specific traits. Examples are the fast-evolving dog head shape (Fondon and Garner, 2004) or the recurrent pelvic fin reduction in sticklebacks (Chan et al. , 2010; Xie et al. , 2019). In the second case, the higher mutational variance of a phenotype may be due to a larger mutational target size rather than a high mutation rate at a given locus: the mutational variance increases with the number of genes (and size of gene regions) whose mutation alters the phenotype. This may be the case for a phenotype that is sensitive to small quantitative alterations, for example in biochemical pathways. The construction of such a trait may indeed be affected by mutations at many loci, many of which may only affect the trait at low penetrance. In another case, bacterial tolerance to antibiotics, mutations to tolerance are frequent because mutations affecting bacterial growth or lag time result in tolerance (Girgis et al. , 2012; Girgis et al. , 2009; Fridman et al. , 2014; Brauner et al. , 2016; Khare and Tavazoie, 2020). Some traits are indeed known to be highly polygenic in natural populations. Some authors even proposed an ‘omnigenic’ model, where phenotypic variation may result from variation at many genes outside the core pathways known to regulate the phenotype (Boyle et al. , 2017). This model fits quantitative genetic data of human diseases (Liu et al. , 2019). However, the number of loci segregating in natural populations also depends on factors such as population structure and selection. To address the origin of a high mutational variance, a more direct approach is needed and more data need to be collected to evaluate how much and in which context each of the above scenarios - highly mutable loci versus a broad mutational target - contributes to a fast rate of phenotypic evolution. We use the nematode vulva to explore this question. This developmental system relies on six precursor cells, with several useful features: (1) the developmental fate of the six homologous cells can be followed in a wide range of species; (2) the mutational variance of the different precursor cells can be compared on the same scale; (3) much knowledge has","Heritable characteristics or traits of a group of organisms, for example the large brain size of primates or the hooves of a horse, are determined by genes, the environment, and by the interactions between them. Traits can change over time and generations when enough mutations in these genes have spread in a species to result in visible differences. However, some traits, such as the large brain of primates, evolve faster than others, but why this is the case has been unclear. It could be that a few specific genes important for that trait in question mutate at a high rate, or, that many genes affect the trait, creating a lot of variation for natural selection to choose from. Here, Besnard, Picao-Osorio et al. studied the roundworm Caenorhabditis elegans",380,128,0.3368
dialogsum,"#Person1#: I am kind of nervous. #Person2#: Nervous? Why? #Person1#: I don't know. I never went to a church before. I was not raised as a Christian, so I don't know what to do. #Person2#: Don't worry. You don't have to do anything. All you have to do is listen. You will enjoy it. #Person1#: Maybe. I know I agreed to go with you, but now I don't feel right about it. #Person2#: Listen, Ryan. Catholics welcome people who aren't Catholics to visit the church. You don't have to pretend to be Catholic. It's okay if you just come to listen. #Person1#: Really? #Person2#: Yes. We are kind and welcoming people. It is not a secret society or something like that. #Person1#: Alright. But will we sing? #Person2#: Yes, but you don't even have to sing. If you want to sing along, you can. #Person1#: I don't know the words. #Person2#: There is a songbook. All the words are in the songbook. Many people have to read the words. #Person1#: And will I go up to the front to have the bread and wine? #Person2#: No. That is something only true Catholics do. So if you come to the church as a visitor, you only listen to the service. But you shouldn't go up to the altar for the bread and wine. Only after someone joins the church, then they go up for the Eucharist. #Person1#: Eu-char-ist? What is that? #Person2#: That is the special word for the ritual of the bread and wine. The Catholics call it the Eucharist. #Person1#: It doesn't sound like an English word. #Person2#: It's not. It's an ancient Greek word. It means gratitude. #Person1#: Alright. Well, I feel more comfortable now. Now I understand I am welcome as a visitor. #Person2#: Of course you are. I wouldn't ask you otherwise.","Ryan is nervous about going to a church because he wasn't raised as a Christian, so he doesn't know what to do. #Person2# tells him Catholics welcome people who aren't Catholics to visit their church and tells him what he should and shouldn't do. Ryan feels more comfortable now.",306,49,0.1601
dialogsum,"#Person1#: Julia, I want to talk to you. #Person2#: What? #Person1#: I am wondering if you are dating anyone now? #Person2#: No, so what? #Person1#: What do you think of me? #Person2#: I think you're great. But what on earth do you want to say? #Person1#: I think I have fallen in love with you. #Person2#: Really? #Person1#: Yes, I have been in love with you since the first time I saw you. #Person2#: Why do you love me? #Person1#: You're my kind of woman. I'm happy to have known you. #Person2#: Are you sure? #Person1#: Of couse. I've never felt like this before. #Person2#: OK, but I hope that you can remember that love me, love my dog.","#Person1# tells Julia #Person1# fell in love with her. Julia hopes #Person1# can remember that love her, love her dog.",119,20,0.1681
scientific_lay_summarisation-elife-norm,"generalization, such as transitive inference and acquired equivalence, the associative relationship among stimuli determines similarity. This relationship can be established for example by sensory preconditioning (e. g. , train stimuli A-B and B-C, test whether A comes to predict C) or by a common associate (e. g. train A-C and B-C, test whether A and B are associated). In contrast, in stimulus generalization the relationship among stimuli is based on the similarity along one or more perceptual dimensions (frequency of sounds, color, line orientation, etc.). Most of what we know about stimulus generalization comes from behavioral experiments utilizing intradimensional stimulus discrimination (Dunsmoor and LaBar, 2013; Ghirlanda and Enquist, 2003; Guttman and Kalish, 1956; Hanson, 1959). In these paradigms, one stimulus (e. g. one particular line orientation) is paired with reward (rewarded conditioned stimulus, CS+), while a second stimulus (e. g. a slightly different line orientation), which differs from the first in only one dimension, is paired with no reward (unrewarded conditioned stimulus, CS−). Generalization is then tested using a range of stimuli that vary along the defining stimulus dimension (e. g. line orientation). Although the test stimuli have never been paired with reward, animals and humans show robust generalization in that they respond to test stimuli that are similar to the CS+. Several psychological models have been developed based on these experiments (Ghirlanda and Enquist, 1998; Pearce, 1987; 1994; Shepard, 1987; McLaren et al. , 2012), but the neurobiological mechanisms regulating the width of stimulus generalization have remained unknown. Early research suggested a role for dopamine in mediating generalization by demonstrating that blockade of dopamine receptors during generalization tests alters response gradients in rats and pigeons (Lyons et al. , 1973a; 1973b; Terrace, 1963). While the effects of dopamine have not been investigated in humans, evidence from neuroimaging suggests that dopaminoceptive and dopaminergic regions such as the striatum and the midbrain are involved in generalization (Kahnt et al. , 2012; Wimmer et al. , 2012; Wimmer and Shohamy, 2012). However, because standard neuroimaging relies on indirect measurements of neural responses, these studies were unable to inform questions about neurotransmitter-specific activity. A candidate brain region for a prominent role in stimulus generalization is the hippocampus, based on its involvement in learning, memory, and associative generalization (Dickerson and Delgado, 2015; Eichenbaum, 2000;","In the 1920s, two psychologists taught a young child known as ‘Little Albert’ to fear a white rat. They did so by striking a metal bar with a hammer whenever the rat was present. After experiencing the rat and noise together on multiple occasions, Little Albert eventually began to cry whenever the rat appeared. However, he also showed a similar response to a number of other white furry objects, including a rabbit and even a fur coat. By applying knowledge about a familiar object to other similar stimuli, humans and other animals avoid having to learn about each and every stimulus from scratch. However, this stimulus generalization is only effective if it occurs to the correct degree: under- or over-generalization (as shown by Little Albert) can lead to",380,128,0.3368
pubmed-summarization,"silica nanoparticles have attracted much attention for industrial and biomedical applications , such as for use as additives and in printer toners , varnishes , pharmaceutics , cosmetics , and coating materials.1,2 these wide - ranging applications stem from the properties of silica nanoparticles , which include easy synthesis , low toxicity , hydrophilicity , and the ease with which their surfaces can be modified or functionalized.35 hence , silica nanoparticles have been extensively developed for biological purposes for use as biomarkers , biosensors , dna or drug delivery , and cancer therapy.610 in this context , many studies have recently focused on biological effects of silica nanoparticles at different levels , such as on their cytotoxicities , blood compatibilities , acute and repeat dose toxicities , and biokinetics,1119 which are currently hot issues in the nanotoxicology field . however , the kinetic behaviors of silica nanoparticles at the systemic level , including their pharmacokinetics , tissue distributions , and clearances , remain unclear . in vivo biokinetic studies can be conducted by systematic and quantitative analyses of plasma , tissues , urine or feces , and other biological samples in whole animals after exposure to assess absorption , distribution , metabolism , and excretion . an understanding of the kinetic behaviors of silica nanoparticles is of importance in the context of determining absorption amounts , target organs , and residence times , which are essential for the prediction of potential adverse effects in the short- and long - term . some researchers have recently described the biodistribution and excretion kinetics of silica nanoparticles.2025 however , most of this information was obtained after intravenous injection , which introduces nanoparticles directly into the circulatory system . in practice , oral administration is important , for example , in food or water , and results in kinetic behaviors unlike those associated after intravenous injection because nanoparticles must encounter stomach acid and cross the epithelium of the gastrointestinal ( gi ) tract in order to reach the blood circulation . in addition , even after gi transit , nanoparticles are carried to the liver via the portal vein before entering the systemic circulation and , thus , are subject to metabolic processes that evidently reduce bioavailability . the biokinetics of silica nanoparticles at","purposethe effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats.methodssilica nanoparticles of two different sizes ( 20 nm and 100 nm ) were orally administered to male and female rats , respectively . tissue distribution kinetics , excretion profiles , and fates in tissues were analyzed using elemental analysis and transmission electron microscopy.resultsthe differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post - administration and , to some extent , to lungs and spleen for 2 days post - administration , regardless of particle size or sex . transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles",380,128,0.3368
scientific_lay_summarisation-elife-norm,"Cerebellar climbing fiber activity encodes performance errors during many motor learning tasks, but the role of these error signals in learning has been controversial. We compared two motor learning paradigms that elicited equally robust putative error signals in the same climbing fibers: learned increases and decreases in the gain of the vestibulo-ocular reflex (VOR). During VOR-increase training, climbing fiber activity on one trial predicted changes in cerebellar output on the next trial, and optogenetic activation of climbing fibers to mimic their encoding of performance errors was sufficient to implant a motor memory. In contrast, during VOR-decrease training, there was no trial-by-trial correlation between climbing fiber activity and changes in cerebellar output, and climbing fiber activation did not induce VOR-decrease learning. Our data suggest that the ability of climbing fibers to induce plasticity can be dynamically gated in vivo, even under conditions where climbing fibers are robustly activated by performance errors. The cerebellum is thought to implement a supervised learning algorithm, with the climbing fiber input to the cerebellum providing error signals that induce learning. According to this model, performance errors activate neurons in the inferior olive and their climbing fiber axons, which in turn trigger the induction of plasticity in the cerebellar cortex to produce adaptive changes in behavior (Marr, 1969; Albus, 1971). Previous work has shown that this process is regulated by a feedback loop from the cerebellar cortex to the inferior olive (Andersson and Armstrong, 1987; Hesslow and Ivarsson, 1994; Medina et al. , 2002; Rasmussen et al. , 2008; Yang and Lisberger, 2013; reviewed in Apps, 1999; Gibson et al. , 2002). In this study, we describe a second level of regulation in animals undergoing learning: even when climbing fibers are robustly activated by performance errors, the ability of that climbing fiber activity to trigger plasticity can be regulated by the state of the cerebellar circuit. Thus, the cerebellum is not a slave to its climbing fiber ‘teachers’, but rather plays an active role in determining whether it will adapt in response to the error signals it receives from the climbing fibers. The question of whether error signals carried by climbing fibers are the trigger for learning has been controversial, since the evidence from different studies has been inconsistent. Climbing fibers are activated by performance errors during","The cerebellum (or ‘little brain’) is located underneath the cerebral hemispheres. Despite comprising around 10% of the brain’s volume, the cerebellum contains roughly half of the brain’s neurons. Many of the functions of the cerebellum are related to the control and fine-tuning of movement, and people whose cerebellum has been damaged have problems with balance and coordination, and with learning new motor skills. One of the roles of the cerebellum is to control a reflex known as the vestibulo-ocular reflex, which enables us to keep our gaze fixed on an object as we turn our heads. The cerebellum relays information about head movements to the muscles that control the eyes, instructing the eyes to move in the opposite direction to the head. This keeps the image of the",380,128,0.3368
pubmed-summarization,"the internal globus pallidus ( gpi ) and substantia nigra pars reticulata ( snr ) are the basal ganglia ( bg ) output nuclei . besides projecting to the thalamus to form the cortico - bg loops ( chevalier et al . , 1985 ; smith and bolam , 1989 ; alexander and crutcher , 1990 ; delong , 1990 ; smith et al . , 1998 ; haber , 2003 ) , output nuclei also project to pons and brain stem to control descending pathways and central patterns generators ( cpgs ) that regulate muscular tone and automatic or rhythmic motor responses ( takakusaki et al . , 2003 , 2004 ; grillner et al . , 2008 ) . in birds , reptiles , and lower vertebrates in which the cortex is not well developed , the control of brain stem nuclei is a main function of the bg ( reiner et al . , 1998 ; grillner et al . , 2005 , 2008 ; gale and perkel , 2010 ) . in the snr , inhibitory postsynaptic currents ( ipscs ) are in part provided by striatonigral direct pathway terminals ( grofov and rinvik , 1970 ; chevalier et al . , 1985 ; smith and bolam , 1991 ; , 1996 ; matuszewich and yamamoto , 1999 ) , which possess functional presynaptic dopamine d1-receptors whose activation increases direct pathway inhibition ( porceddu et al . , 1986 ; altar and hauser , 1987 ; floran et al . , 1990 ; radnikow and misgeld , 1998 ; chuhma et al . , enhancement of direct pathway inhibition facilitates movements while its reduction represses them ( albin et al . , 1989 ; in contrast , subthalamonigral afferents compose the last step of the indirect pathway ( nakanishi et al . presynaptic modulation of subthalamonigral terminals by dopamine uses both classes of dopamine receptors : d1 and d2 ( ibez - sandoval et al . , 2006 ) . activation of d1 enhances while activation of d2 depresses subthalamonigral excitatory postsynaptic currents ( epscs ) . interestingly , simultaneous blockade of both receptors induced larger evoked epscs , suggesting that d2-receptors have more influence than d1-receptors in the modulation of transmission ( ibez - sandoval","previous work has shown the functions associated with activation of dopamine presynaptic receptors in some substantia nigra pars reticulata ( snr ) afferents : ( i ) striatonigral terminals ( direct pathway ) posses presynaptic dopamine d1-class receptors whose action is to enhance inhibitory postsynaptic currents ( ipscs ) and gaba transmission . ( ii ) subthalamonigral terminals posses d1- and d2-class receptors where d1-class receptor activation enhances and d2-class receptor activation decreases excitatory postsynaptic currents . here we report that pallidonigral afferents posses d2-class receptors ( d3 and d4 types ) that decrease inhibitory synaptic transmission via presynaptic modulation . no action of d1-class agonists was found on pallidonigral synapses . in contrast , administration of d1-receptor antagonists greatly decreased striatonigral ipscs in the same preparation ,",380,128,0.3368
pubmed-summarization,"in vivo imaging of cell survival , proliferation , and differentiation . in the context of mr reporter gene cell tracking in the heart , only four studies have to date been published on imaging the survival of reporter gene expressing cells following intramyocardial injection in this review we seek to discuss existing methods for mri cell tracking and the results of early studies of mr reporter gene cell tracking in the heart . given the small number of studies performed to date , each study is discussed in detail in order to highlight the important contributions made to the nascent field , and further questions that have arisen as a result of such studies . finally , we will discuss how important findings from mr reporter gene studies in stationary organs and tumors can potentially lead to more dynamic cmr reporter gene imaging . mri cell tracking has historically relied upon labeling of cells with chemical agents that generate contrast via modulation of either t1 ( bright contrast ) or t2 ( dark contrast ) relaxation times , or through selective excitation and transfer of saturated magnetization ( false color contrast ) . for example , labeling of fibroblasts with gadolinium - dtpa , a t1-shortening contrast agent , has been used to track the recruitment of fibroblasts to ovarian carcinoma tumors , and to track macrophage migration to the forming scar after myocardial infarction in the mouse heart . the recruitment of gadolinium labeled cells can either be visualized as positive contrast on heavily t1-weighted images , or can be measured by quantifying changes in tissue t1-relaxation times between areas with and without labeled cells . a more widely used cell labeling technique has involved the use of a large variety of iron oxide nanoparticles with a range of sizes and relaxivities . once internalized , iron oxide nanoparticles de - phase the surrounding magnetic field , leading to significantly shortened t2 relaxation times in the vicinity of labeled cells . labeled cells can then be easily tracked as signal voids on t2 * weighted images , or more quantitatively as areas of reduced t2-relaxation on t2-maps . while detection of cells labeled with t1 or t2 shortening contrast agents can be accomplished using conventional pulse sequences ,","research into cell therapy based cardiac repair and regeneration has experienced explosive growth over the last decade , however further progress is hindered by an inability to serially and non - invasively image cell survival and fate decisions following implantation . recent advances in magnetic resonance imaging ( mri ) reporter gene techniques have enabled in vivo imaging of cell survival , proliferation , migration , and differentiation , however this has mostly been performed in stationary tissues . a small series of recent studies has examined the possibility of using mri reporter genes to track the survival of cells injected into the heart following myocardial infarction . in this review , we seek to frame the emerging field of mri reporter gene based cardiac cell tracking within",380,128,0.3368
pubmed-summarization,"curcumin,1,7-bis(4-hydroxy-3-methoxypheny l)- 1- 6- heptadiene- 3 , 5-dione , commonly known as diferuloylmethane , is the yellow pigment component of the curry or turmeric ( curcuma longa ) ( 1 ) . turmeric extracts have been extensively used for the treatment of several diseases in ayurvedic medicine in india for several centuries . curcumin was first extracted from turmeric in its impure form in 1815 , but it was not until 1910 when it was crystallized and its structure was elucidated ( 2 ) . it has antimicrobial , antioxidant , immunomodulatory , anti - inflammatory , anti - alzheimer and anticancer activity ( 38 ) . it has shown no toxicity in vitro in numerous cell culture systems , and in vivo in animal models and over 13 phase i human clinical trials . it is generally recognized as safe by the united states food and drug administration ( fda ) ( 2 , 4 , 5 ) . curcumin has been shown to affect several targets in somatic cells for its biological activity ( 38 ) . it inhibits nf-b activity , cox-2 , and 5-lox expression and modulates release of several cytokines ( 3 , 4 ) . it also binds to a number of other proteins including thioredoxin reductase , protein kinases and several receptors ( 3 , 4 ) . however , most of these proteins / factors may not be expressed/ present in terminally non - transcriptional sperm . also , the sperm has a unique characteristic , the motility , that is not present in other cells . thus , curcumin may have different molecules/ mechanism(s ) for its action that are unique to sperm . recently , our laboratory reported , for the first time ever , that the curcumin affects sperm function ( motility / capacitation and acrosome reaction / fertilization ) in vitro and fertility in vivo . intravaginal administration of curcumin caused a significant , but reversible reduction in fertility ( 9 ) . the molecular mechanism(s ) by which curcumin inhibits / blocks sperm motility has not been delineated . since modulation of intracellular ph ( phi ) and plasma membrane polarization has been shown to be involved in sperm motility and capacitation / acrosome reaction of several","backgroundcurcumin has shown to affect sperm motility and function in vitro and fertility in vivo . the molecular mechanism(s ) by which curcumin affects sperm motility has not been delineated . since modulation of intracellular ph ( phi ) and plasma membrane polarization is involved in sperm motility , the present study was conducted to investigate the effect of curcumin on these sperm ( human and murine ) parameters.methodsthe effect of curcumin on sperm forward motility was examined by counting percentages of forward moving sperm . the effect of curcumin on intracellular ph ( phi ) was measured by the fluorescent ph indicator 2,7-bicarboxyethyl-5,6-carboxyfluorescein - acetoxymethyl ester ( bcecf - am ) . the effect of curcumin on plasma membrane polarization was examined using the fluorescence sensitive dye",380,128,0.3368
pubmed-summarization,"a 60-year - old man was admitted because of visual disturbances and ocular pain following penetrating keratoplasty in the right eye for a corneal chemical burn . on slit lamp examination , we observed a feather - like corneal opacity , corneal infiltrations , and epithelial defects . subconjuctival amphotericin b ( 1 mg ) , topical amphotericin b 0.125% , and levofloxaxin 0.5% were subsequently administered every hour for 16 weeks . the patient was restarted on and maintained on a topical amphotericin b treatment ( 0.125% twice daily ) for 1 year . in addition , levofloxaxin 0.5% ( three times daily ) and fluorometholone 0.1% ( twice daily ) were administered for 1 year . the lesion did not progress , but there was no change in corneal infiltration . on examination one year later , an elevated corneal lesion and increased corneal infiltration with a yellow color were observed despite the topical amphotericin b treatment . seven days later anterior chamber hypopyon and vitreous opacity on a b - scan were observed ( . we immediately performed an intravitreal injection of amphotericin b 5 g/0.1ml and vancomycin 1 mg/0.1ml . intravitreal voriconazole 80 g/0.1ml and ceftazidime 2 mg/0.1ml were injected and topical voriconazole 1% was administered every 2 hours . the patient discontinued the oral voriconazole because of abdominal pain , dry mouth , and scaling of the oral mucosa . the patient was treated topically for 6 weeks , after which the corneal lesion and endophthalmitis had improved . the patient subsequently underwent another penetrating keratoplasty and demonstrated a visual acuity of 0.1 at 10 months follow - up with no signs of recurrence . a 60-year - old man was referred to us because of a lack of improvement after a month of empiric treatment with topical amphotericin b for fungal keratitis . on our initial examination after 10 days the culture revealed no growth and the corneal epithelium appeared healed ; however , there was no change in corneal infiltration ( . because of a lack of improvement in the corneal lesion a month later , a new treatment regimen was initiated with topical voriconazole 1% administered every hour . six weeks later we observed a decreasing density of the infiltrate and healing","we describe two patients with fungal keratitis refractory to standard antifungal therapy whose conditions were managed with voriconazole.the first case is a patient with endophthalmitis and corneal ulcer due to candida parapsilosis after receiving a corneal transplant . the patient was treated with amphotericin but showed no signs of improvement . topical voriconazole , oral voriconazole , and intravitreal voriconazole yielded signs of improvement . the second case is a 63-year - old male who underwent a month of empiric treatment with 0.2% topical amphotericin for fungal keratitis but showed no signs of improvement . treatment was then provided with 1% voriconazole . both cases showed effective treatment with voriconazole.voriconazole may be considered as a new method to treat fungal keratitis refractory to standard antifungal therapy .",380,127,0.3342
pubmed-summarization,"highly active antiretroviral therapy ( haart ) has improved the prognosis of patients with human immunodeficiency virus ( hiv ) infection by significantly reducing related morbidity and mortality.1,2 early treatment protocols , many of which are still recommended , contain two nucleoside reverse transcriptase inhibitors ( nrti ) and one nonnucleoside reverse transcriptase inhibitor ( nnrti ) or a protease inhibitor ( pi).35 nnrtis currently included in treatment regimens comprise nevirapine ( npv ) , efavirenz , and rilpivirine . although npv is used mostly to substitute pis in patients with high cardiovascular risk in developed countries,5 it is still included in first - line treatment regimens in low - income countries.3 given its short plasma half - life , nvp immediate - release ( nvp - ir ) must be administered twice a day to achieve a 24-hour effective plasma level.6 in order to simplify art regimens and improve adherence to prescribed medications , the extended - release formulation of nvp ( nvp - xr ) , which allows a single daily intake , has been developed and tested in two phase iii clinical trials . the aim of the current review is twofold : ( 1 ) to highlight the clinical utility and efficacy of nvp - xr ; ( 2 ) to assess the impact of nvp - xr on patients safety by shedding light on the main side effects of nvp - xr and the expected gain in term of treatment adherence . nevirapine is a member of the nnrti family that was introduced as a component of the triple art in 1996 ( viramune ; boehringer ingelheim pharmaceuticals , inc , ridgefield , ct , usa ) . since then , it has been used in its immediate - release ( ir ) form alongside nrtis . following an induction phase at 200 mg in a single intake per day for 2 weeks , nvp - ir is administered twice per day at 200 mg per intake during the continuation phase.7 early clinical trials comparing a single daily dose of nvp - ir 400 mg vs 200 mg twice per day , or vs another nnrti with longer half - life , revealed high rates of virologic failure among patients treated with single daily intake.810",an extended - release formulation of nevirapine ( nvp - xr ) has been developed with the aim of simplifying antiretroviral treatment regimens and improving patients adherence with a single daily intake . the verxve and tranxition clinical trials have demonstrated the noninferiority of nvp - xr compared with nevirapine immediate - release ( nvp - ir ) on viral load after 24 and 48 months of treatment . the tolerance profiles of nvp - xr and nvp - ir are similar . simplifying the treatment dosage for nvp would likely improve adherence to antiretroviral treatments .,380,97,0.2553
pubmed-summarization,"patients underwent argon laser therapy and the remaining half was observed . the vision in both groups improved , but the laser group experienced a greater gain.7 approximately 16%27% of rams occlude with lasers , but there is a risk of vascular occlusion , early increase in exudates from selective reabsorption of fluid , arteriovenous shunts , macular pucker , and scotomas.7,8 other treatment options for rams include yellow dye laser and indocyanine green dye - enhanced photocoagulation.9,10 anti - vascular endothelial growth factor ( vegf ) therapy has recently been reported in the treatment of patients with exudative or hemorrhagic rams . chanana and azad11 published the first case report in 2009 , and subsequent case reports have shown encouraging results ( table 1).1219 cho et al18 described 23 patients with rams who were either observed or received intravitreal bevacizumab . both groups experienced statistically significant improvements in visual acuity and central macular thickness , but the bevacizumab group regained vision faster . a larger , prospective study of 38 eyes with hemorrhagic and exudative rams underwent three monthly injections of bevacizumab , with the vision and retinal thickness improving in both groups.19 the role of vegf and the mechanism of action of anti - vegf therapy in rams are not fully understood . in a study that compared the vegf levels in 500 l vitreous samples from patients with vitreous hemorrhage from nondiabetic etiologies ( including four patients with ram ) with those from patients with proliferative diabetic retinopathy , the vegf levels were significantly lower in the former than in the latter groups ( 2.75 pg / ml vs 821 pg / ml , respectively).20 however , these were small vitreous samples obtained up to 3 weeks after the initial hemorrhage and may not have been representative of the vitreous and microenvironment around the ram . the role of vegf in intracranial aneurysms and other biological systems has been more clearly elucidated . in intracranial aneurysms , vegf levels were found to be significantly higher than the levels in controls.20 in particular , patients with intracranial aneurysms had higher expressions of vegf receptor 2 ( vegfr2 ) and lower levels of vegf receptor 1 ( vegfr1 ) . vegfr1 is associated with angiogenesis , while vegfr2 is","an 84-year - old female with a history of hypertension and dyslipidemia was referred for a retinal artery macroaneurysm with exudation that had extended into the macula . she underwent a total of six injections of bevacizumab , with some improvement in visual acuity and retinal thickness . due to persistent macular edema , focal laser photocoagulation was performed around the macroaneurysm . the vision remained at 20/30 during 20 months of follow up . although anti - vascular endothelial growth factor therapy may improve vision and decrease retinal thickness in retinal artery macroaneurysm , recalcitrant cases may be treated with laser photocoagulation to seal the leaking vessel .",380,109,0.2868
dialogsum,"#Person1#: Hi, how're you doing? #Person2#: Terrible. #Person1#: Oh, what's the matter? #Person2#: I'Ve got a fever and really a bad headache. #Person1#: Oh, that's too bad. Why don't you take some aspirin? #Person2#: I'Ve already tried some but it didn't help. #Person1#: Well, it's necessary for you to see a doctor. #Person2#: Yeah, I guess I should. #Person1#: Well, you'd better get some rest. #Person2#: Thank you very much. #Person1#: Bye.",#Person2# is sick and #Person1# suggests #Person2# see a doctor.,72,10,0.1389
pubmed-summarization,"it seems that complications of vitamin d deficiency have been completely removed by having enriched food by vitamin d , but rachitism is the top of iceberg of vitamin d deficiency . vitamin d deficiency can also causes osteopenia , osteoporosis , and muscle weakness and increases risk of hip fracture in adults . the most important effect of vitamin d is on parathyroid and bone and also plays a key role on the calcium absorption from the gut . the discovery of vitamin d receptor in most tissues and organs has developed a new perception from effects of vitamin d. for instance , vitamin d can decrease risk of many chronic diseases , cancers , autoimmune disease , infectious , and cardiovascular disease . it has been estimated that one billion people are vitamin d deficient in the world . this deficiency is common in all different cities with the same level of the sea or cities with lower geographic latitude . 20 ng / ml is the level of vitamin d deficiency and 20 < 25 ( oh ) d < 30 ng / ml is recognized as a vitamin d insufficiency . there are different ways to detect cut - off points for vitamin d deficiency . for instance , based on inverse relation between 25 ( oh ) d and pth , a direct relation between 25 ( oh ) d and 1 , 25 ( oh ) d and effect of vitamin d on fracture risk . the level of 25 ( oh ) d that would be enough for pth suppression , probably , is a suitable criterion for bone health and cut - off point for vitamin d deficiency . the aim of this study was detection of prevalence of vitamin d deficiency in secondary students in arak , a centrally located city in iran , and also detection of cut - off points for vitamin d deficiency . in a cross - sectional study in november 2010 , 420 students including 220 girls and 200 boys from secondary students from 10 to 16 years old were selected by a multistage sampling . first , all of the secondary schools were divided into two areas and then 21 schools including 11 girls schools","introduction : vitamin d has a basic role in bone growth and metabolism and has been noticed for its important role in many diseases , such as diabetes , depression , hypertension , and cardiovascular disease . regarding some studies , detection of vitamin d deficiency in different places has important implication for health . this study determined prevalence of vitamin d deficiency in arak , a centrally located city in iran.materials and methods : based upon a cross - sectional study in 2010 , 420 students 10 - -16 years old including 220 girls and 200 boys , studied at arak secondary schools , were selected by a multistage sampling . the level of 25 ( oh ) d and pth ( parathormone ) was measured and",380,128,0.3368
dialogsum,"#Person1#: I've been invited to a dinner party tomorrow. What time should I arrive for that? #Person2#: On time, or even a few minutes late, but not early. #Person1#: Why? #Person2#: Because the host and Hostess are running around finishing last minute chores. #Person1#: I never thought of that. But what the dinner get cold if people come several minutes late? #Person2#: No. Generally it's planned so that when you arrive you get a drink and then chat with people for a while. When all the guests have arrived and finish their drinks, you sit down to dinner or go to the buffet table. #Person1#: What are they get caught in a traffic jam, or the subways late or something else happens? And I'm going to be really late. #Person2#: You must call and say you're coming, but you'll be late. #Person1#: Oh, I see. #Person2#: By the way, a dinner invitation doesn't call for you to eat and run. #Person1#: What do you mean? #Person2#: People do talk to each other during the meal. But after dinner, they also sit around and talk. If the conversation is good, it might go on until 11:00 or 12:00 or even late into the night. I think it's a good opportunity to practice your oral English. #Person1#: I agree. I'll tell mom, maybe I will be late back home.","#Person1# got invited to a dinner party, and #Person2# tells #Person1# to arrive on time or a bit late because the hose and hostess are preparing. If late, contacting the host to let them know the situation.",227,37,0.163
dialogsum,"#Person1#: Hi, my name is Christa and I have a friend Mary, whose son is taking guitar lessons from you, and she suggested I call you. #Person2#: OK. Will the lessons be for yourself or your son? #Person1#: I want to learn. My son is only three. #Person2#: Fine. Have you had any musical experience before? #Person1#: Well, I studied the piano for about three months but that was 6 years ago. #Person2#: That's good. So we needn't start right from the beginning again. #Person1#: When can I take lessons and how much do they cost? #Person2#: Well, that depends on you. We have a small group that meets on Monday and Wednesday evenings for two hours, that costs $4 an hour. Then on Tuesdays and Thursdays I give private lessons which cost $8 an hour. #Person1#: I'm afraid that I can't make it on Mondays but I can come on Wednesdays.","Christa wants to learn the guitar from #Person2#, who is recommended by Mary. #Person2# tells Christa the time for the lesson and the cost. Christa'll come on Wednesdays.",152,28,0.1842
dialogsum,"#Person1#: Hi, James, do you think it's possible for us to have a talk sometime today? #Person2#: I'd love to, Maggie. But you see, I've got a very very tight schedule today. #Person1#: Oh, what have you got to do? #Person2#: Well, I've got to finish a report by 10. Then I have to drive to the airport and pick up my boss at 11. After that, we'll have a meeting over lunch. I guess I won't have a break until 2 o'clock. But then from 3 until 5 I have to attend another meeting. #Person1#: Wow, that's really tough. So we cannot make it today, can we? #Person2#: I think I've got some time tomorrow. How about talking tomorrow afternoon? #Person1#: That's fine with me. But don't push yourself too hard. I can always wait. #Person2#: Tomorrow afternoon after four should be all right with me. How about us meeting at the cafe on the comer of Peter Street and William Street? We can talk over coffee, all right? #Person1#: Good. That sounds great to me. #Person2#: See you then. #Person1#: Sure, take care and don't work too hard.",James has a busy schedule today from 10 am to 5 pm. So he decides to meet Maggie tomorrow afternoon at the cafe.,190,23,0.1211
dialogsum,"#Person1#: Excuse me, bags aren't permitted inside the supermarket. #Person2#: Oh, I'm sorry. #Person1#: Don't worry. Just check in your bag before entering. #Person2#: Thanks. Could you tell me where I should deposit my bag? #Person1#: The checkroom is just behind the front door. #Person2#: OK. I will deposit my bag right now.",#Person1# tells #Person2# bags aren't permitted inside the supermarket. #Person2#'ll deposit it.,53,12,0.2264
dialogsum,#Person1#: How long do you plan on staying? #Person2#: I don't know! Can I park my car now? #Person1#: We are open from nine to nine. So be sure to be back by then. #Person2#: Fine! I'll be back by nine then. Don't worry. #Person1#: Alright. There's a spot open at the far end of the lot. Here's your parking stub. #Person2#: Finally! #Person1#: Please drive slowly.,#Person2# want to park. #Person1# gives #Person2# a parking stub. #Person2# will be back by nine.,67,16,0.2388
dialogsum,"#Person1#: Come on, why do you stop your car here? It's still a long way from the town. #Person2#: I didn't stop the car. The car stopped itself. Let me have a look and find out what the matter is. #Person1#: Is it out of gas? It was running so well. #Person2#: Out of gas? Yeah, it's possible. Oh, yes, it is. #Person1#: But there is no one around and not a building in sight. How can we get some gas? #Person2#: Don't worry. Just stand by the road. Wave your hands when the next car comes. We are sure to get some gas from others. #Person1#: It's getting dark. I'm afraid we can't get to the town before dark. #Person2#: Take it easy. We are sure to get to the town and spend our night in a comfortable hotel.",#Person1# and #Person2#'s car is out of gas. #Person1# is worried but #Person2# thinks they'll get some gas from the next car.,140,22,0.1571
dialogsum,"#Person1#: . . . so, I said, let's take a break. And since that night, I've been waiting for him to call, but I still haven't heard from him. You don't think he's seeing someone else, do you? #Person2#: Come on, don't be so dramatic! I'm sure everything is going to work out just fine. #Person1#: You think so? Oh, no! How can he do this to me? I'm sure he's cheating on me! Why else wouldn't he call? #Person2#: But, you two are on a break. Theoretically he can do whatever he likes. #Person1#: He's the love of my life! I've really messed this up. #Person2#: Come on, hon. Pull yourself together. It's going to be alright. #Person1#: But I. . . I still love him! And it's all my fault! I can't believe how immature and selfish I was being. I mean, he is a firefighter, it's not like he can just leave someone in a burning building and meet me for dinner. I've totally messed this up! #Person2#: You know what, Veronica, I think you should make the first step. I'm sure he'll forgive you. . . #Person1#: No, this is not gonna happen! I. . . I've ruined everything. . . . #Person2#: do you hear something?","Veronica is waiting for someone's call, but she still hasn't heard from this person. #Person2# comforts her and suggests her make the first step.",211,24,0.1137
pubmed-summarization,"abdominal cavity , the serosa of uterine body was noted to be diffusely thickened by multiple - to - coalescing white villous projections ( ) . formalin - fixed perimetrial surface of uterine body revealing diffuse - to - coalescing polypoid lesions there was a small amount of mildly flocculent abdominal fluid present . the cat recovered uneventfully and follow - up examinations in a 6 month period , including ultrasound at 3 months postsurgery , detected no abdominal abnormalities . microscopic examination of the uterine body confirmed the presence of multiple nodular perimetrial proliferations of moderately loose connective tissue forming irregular polyps or plaques blending into the myometrium ( figures 3 and 4 ) . most polyps contained multifocal randomly distributed lymphocyte and plasma cell infiltrations , and regions of neovascularisation . polyps were covered by a combination of normal , attenuated and moderately swollen mesothelial cells . at sites of mesothelial cell loss , the stratum vascularis was moderately oedematous containing both congested medium - to - large size blood vessels and dilated lymphatics . endometrium and uterine epithelium appeared unremarkable with a low glandular content , intact mucosal epithelium and minimal - to - no inflammatory cell infiltrations . the lesion was characterised as a diffuse , chronic , polypoid , fibrotic perimetritis and parametritis . cross - section of uterine body ( u ) revealing multiple polypoid perimetrial projections ( p ) ( haematoxylin and eosin ) polypoid structures blending with myometrium and containing ( a ) foci of angiogenesis and ( b ) regions of active fibroplasia ( haematoxylin and eosin ) uterine prolapse has rarely been documented in cats , with individual case reports citing complete or unilateral uterine prolapse with or without uterine mucosal eversion . the majority have occurred in association with the periparturient period , one of which was proposed to be associated with oestrus . furthermore , a novel lesion inducing extensive perimetrial fibrosis , not previously reported in cats , was noted and could potentially be implicated as the cause . however , other factors have been suggested including uterine atony or excessive abdominal contractions , including tenesmus . for the uterus to prolapse there is a requirement for laxity , stretching or rupture of uterine ligaments , and","case summarythis case describes a young non - pregnant cat that presented with uterine prolapse in association with an unusual diffuse , polypoid , fibrosing perimetritis and parametritis . following ovariohysterectomy the cat recovered fully . no intra - abdominal complications were seen on ultrasound examination 3 months postsurgery . at the time of writing , the cat remains healthy.relevance and novel informationuterine prolapse in the cat is relatively rare and usually associated with the periparturient period . inflammatory polypoid perimetritis and parametritis have not previously been documented in cats , and in dogs have only been reported in association with the administration of oestrogenic compounds . the polypoid inflammation affecting the uterus and parametrium may have contributed to increased laxity of the uterine ligaments and predisposed to",380,128,0.3368
scientific_lay_summarisation-elife-norm,"stochastic dynamics of the incubation process, as the pathogen invades, multiplies, and competes with itself and the cells of the host in a structured network topology. The theory predicts that under a broad range of circumstances, incubation periods should follow a right-skewed distribution that resembles a lognormal, but is actually a Gumbel, one of the universal extreme value distributions (Kotz and Nadarajah, 2000). Heterogeneity is not required, but it is allowed; it does not qualitatively alter our results when included. We model the incubation process using the formalism of evolutionary graph theory (Lieberman et al. , 2005; Nowak, 2006; Ohtsuki et al. , 2006; Ashcroft et al. , 2015). A network of N≫1 nodes is used to represent an environment within a host where a pathogenic agent, such as a harmful bacterium or a cancer cell, is invading and reproducing. The network could represent several plausible biological scenarios, for example the intestinal microbiome, where harmful typhoid bacteria are competing against a benign resident population of gut flora in a mixing system (modeled as a complete graph); or it could represent mutated leukemic stem-cells vying for space against healthy hematopoietic stem cells within the well-organized three-dimensional bone marrow space (modeled as a 3D lattice); or a flat epithelial sheet with an early squamous cancer compromising and invading nearby healthy cells (modeled as a 2D lattice). For the sake of generality, we will refer to the two types of agents as healthy residents and harmful invaders. While Sartwell’s law has been applied to many different types of diseases with diverse etiologies, the model we propose makes the most sense for asexually reproducing invaders, like cancer cells or bacteria. Viruses, on the other hand, often reproduce with a ‘one-to-many’ dynamic, which is not faithfully captured in this model. So, while the general phenomenon of network invasion seems to apply to viruses as well, the model in its present form is not well suited to describe their dynamics. Considering asexually reproducing and competing invaders, then, we choose to model the invasion dynamics as a Moran process (Moran, 1958; Williams and Bjerknes, 1972; Lieberman et al. , 2005; Nowak, 2006). Invaders are assigned a relative fitness r (suggestively called the carcinogenic advantage by Williams and Bjerknes, 1972). The fitness of residents is normalized to 1.","When one child goes to school with a throat infection, many of his or her classmates will often start to come down with a sore throat after two or three days. A few of the children will get sick sooner, the very next day, while others may take about a week. As such, there is a distribution of incubation periods – the time from exposure to illness – across the children in the class. When plotted on a graph, the distribution of incubation periods is not the normal bell curve. Rather the curve looks lopsided, with a long tail on the right. Plotting the logarithms of the incubation periods, however, rather than the incubation periods themselves, does give a normal distribution. As such, statisticians refer to this kind",380,128,0.3368
dialogsum,"#Person1#: Where did you go to school? #Person2#: I went to university in New York and studied computer, and then I went to a business school in Sydney and stayed there for 2 years. #Person1#: OK, but you grew up in the UK, right? #Person2#: Well, kind of. I was born in London but moved to New York with my family when I was 6. My dad got a job there. #Person1#: What did your father do? #Person2#: He was a teacher.",#Person2# tells #Person1# about #Person2#'s personal experience.,82,7,0.0854
dialogsum,"#Person1#: Excuse me, sir, may I talk to you? #Person2#: Bill! Sure, come on in. What can I do for you? #Person1#: Well sir, as you know, I have been an employee of this prestigious firm for over ten years. #Person2#: Yes. #Person1#: I won ' t beat around the bush. Sir, I would like a raise. I currently have three companies after me and so I decided to talk to you first. #Person2#: A raise? Son, I would love to give you a raise, but this is just not the right time. #Person1#: I understand your position, and I know that the current economic downturn has had a negative impact on sales, but you must also take into consideration my hard work, pro-activeness and loyalty to this company for over a decade. #Person2#: Taking into account these factors, and considering I don ' t want to start a brain drain, I ' m willing to offer you a ten percent raise and an extra five days of vacation time. How does that sound? #Person1#: Great! It ' s a deal! Thank you, sir! #Person2#: Before you go, just out of curiosity, what companies were after you? #Person1#: Oh, the electric company, gas company and water company!","Bill wants a raise in the economic downturn for his hard work, pro-activeness, and loyalty. #Person2# finally agrees to offer a ten percent raise and an extra five days of vacation time. Bill accepts the deal.",207,36,0.1739
dialogsum,"#Person1#: Hi, Sarah How is everything? #Person2#: Nothing new here. I was just wondering if you want to go out tonight? #Person1#: Well, I was thinking about reading a book at home tonight. What exactly have you got in mind? #Person2#: I thought we could just go for a walk. Maybe down to the bridge. #Person1#: Sorry, but I worked out in the gym this afternoon. I don't feel like going for a walk tonight. #Person2#: Oh, then let's go to the cinema. There is a new movie playing in theaters. How about going to see it? #Person1#: Sounds great. What time does it start? #Person2#: At 8:20. What about having supper together before going to the movie? #Person1#: Sorry. But my mother will make chicken and potatoes tonight, which are my favorite. So I'd rather eat at home and then go to the cinema. #Person2#: OK, so let's meet in front of the cinema 20 minutes before the movie begins. OK? #Person1#: OK. See you then. #Person2#: See you then.",Sarah invites #Person1# to go out tonight. #Person1# doesn't want to go for a walk but agrees to go to the cinema after eating at home.,171,26,0.152
dialogsum,"#Person1#: Are there many idioms in English? #Person2#: There are hundreds and hundreds. English is particularly rich in idiomatic expressions. #Person1#: Can you give us an example? #Person2#: I'll look up the rate. To look up doesn't mean to look high into the sky or to look at the roof. It means to search for and find some information. #Person1#: What about the expression 'goodbye'? Is that an idiom? #Person2#: That is just a natural, grammatical English expression. It has a direct translation in other languages. #Person1#: This is interesting, Ms. Parker.",Ms. Parker tells #Person1# about English idioms and offers examples.,92,10,0.1087
scientific_lay_summarisation-elife-norm,"et al. , 2016; Jeltsch et al. , 2014). Alternative activation by plasmin has been shown in vitro, but its significance under physiological settings is unknown (McColl et al. , 2003). VEGF-D is the closest paralog of VEGF-C (Achen et al. , 1998). Similar to VEGF-C, it is lymphangiogenic (Veikkola et al. , 2001), but appears to have a higher angiogenic potential than VEGF-C (Byzova et al. , 2002; Rissanen et al. , 2003). The proteolytic activation of VEGF-D is very similar to that of VEGF-C (Stacker et al. , 1999a), but it deploys distinct, so far unknown proteases (Bui et al. , 2016). Many kallikrein-related peptidases are highly expressed in the prostate, and some prostate-derived cell lines, such as the immortalized human normal prostate epithelial (NPrEC) or PC-3 cells — from which VEGF-C was originally cloned — express high amounts of VEGF-C (Grennan, 2006; Joukov et al. , 1996). In a peptide library scan, Matsumura et al. (2005) identified VEGF-C as a potential substrate for KLK4. Based on these observations, we tested human kallikrein-related peptidases for their ability to activate VEGF-C. In this study, we show that KLK3, the major protease in human semen, is able to specifically activate VEGF-C and VEGF-D. We further show that cathepsin D cleavage of VEGF-C results in a novel, predominantly VEGFR-3-binding form of VEGF-C, and that cathepsin D cleavage of VEGF-D at the homologous site results in a VEGFR-2-specific (minor mature) form of VEGF-D. We could not demonstrate robust VEGF-C activation by KLK4 as predicted by Matsumura et al. (2005) (data not shown), but purified KLK3 cleaved pro-VEGF-C, resulting in a mature protein that migrated at about 20 kDa in Western blotting analysis (1A, lane 2). To confirm that KLK3 was responsible for the cleavage, we inhibited its protease activity by using the monoclonal antibody 5C7 (Stenman et al. , 1999) in 2-fold molar excess (1A, lane 1 versus lane 2). We probed the polypeptide bands resulting from the cleavage with rabbit antiserum 6 and antiserum 3/4, which were raised against full-length and mature VEGF-C, respectively (1A and B, compare the second lanes). Probing with antiserum 3/4, which recognizes both pro-VEGF-C and mature VEGF-C, showed that the majority of pro-VEGF-C had been cleaved by KLK3. We tested the KLK3-processed VEGF-C for its biological","The lymphatic system is composed of networks of vessels that drain fluids from the body’s tissues and filter it back into the blood. Growing these vessels depends on a factor known as VEGF-C, which is released in an inactive form and must be cut by enzymes before it can work. One enzyme that is known to activate the VEGF-C signal when the early embryo is developing is ADAMTS3. If this signal fails to switch on this can result in a condition known as lymphedema – whereby problems in the lymphatic system cause tissues to swell due to insufficient drainage. However, it is unknown whether the VEGF-C signal can be activated by enzymes other than ADAMTS3. To investigate this Jha, Rauniyar et al. tested a specific family of proteins",380,128,0.3368
dialogsum,"#Person1#: Did you even bother to go to school today? #Person2#: Yeah, I went. Did you go? #Person1#: No, I didn't feel like it. #Person2#: That's nice, have you been to the movies lately? #Person1#: No, but that was a random change of subject. #Person2#: It may have been random, but have you? #Person1#: I haven't lately. #Person2#: I would love to catch a movie this weekend. #Person1#: So then, why don't you just go? #Person2#: I don't want to see a movie by myself. #Person1#: Okay, so are you going to school tomorrow? #Person2#: I think I might just go to the movies.",#Person1# didn't go to school today. #Person2# might go to see the movies rather than going to school tomorrow.,104,19,0.1827
pubmed-summarization,"a range of 5 cm in between . the first category included the height under 150 cm and the last with height over 186 cm ( the largest number of respondents , 30% of them were in the range of 170 - 175 cm ) . the weight of the patients was also of an open type , and after all the given number there has been a classification with a total of six categories , with a range of 10 kg , the first one considering all the values under 49 kg and the last all the values above 90 kg . the largest number of respondents were in the range 70 - 79 kg ( 32% ) . in the survey while asking the examinee of their body mass index ( bmi ) , this number was only approximate considering the height and weight of the examinee and was nt taken in a professional manner . bmi index of examinees after evaluating these basic information on phenotype characteristics of the examinees , the next group of questions referred to risk factors on diabetes type 2 and it s possible manifestation . did any of your close relatives have diabetes is the basic information in every family history which can roughly show us the history of this disease amongst the closest relatives of our examinee ( ) . family history of examinees our further questions were related to the risk factors concerning the environment but which have the effect on the progress of diabetes . these questions are as follows : do you have at least 30 minutes of physical exercise daily ( including regular daily activities ) and how often do you eat fruit , vegetables , grains . the question : do you suffer from high blood pressure is a manifestation of some other chronic disease for which the examinee also has got or not genetic predispositions . risk environment factors was a high blood sugar level ever detected earlier ( e.g. during regular testing in pregnancy or during other illness ) is a question from the patients history and can also roughly show us the history of blood sugar levels in our patients ( answer yes was given from 35% of examinees ) . the last","introduction : diabetes is a group of metabolic diseases characterized by hyperglycemia , and represents a disease of the modern age , disease of the 21st century . prevention of this disease is listed as imperative . aim of this article was to evaluate questionnaires on the assessment of risk factors for diabetes mellitus type 2.material and methods : a total of 540 questionnaires handed out randomly to citizens of canton sarajevo of all ages , sexes and educational levels ( in january 2016 ) were analyzed.results:analyzed questionnaires showed relatively low risk of getting diabetes in the next ten years in the majority of the population . these results are rather encouraging but may in some way be in confrontation with the statistics which show a rapid outburst",380,128,0.3368
dialogsum,"#Person1#: Look, Jimmy's report came today. #Person2#: Let's have a look. What is this? Where are all the grades? #Person1#: He's in the third grade Sam! You see under each subject that he is being taught in school, he receives a mark from one to three. A one means his achievement or work is excellent. Here in Science for example he got a two, which means its satisfactory. #Person2#: What about here in physical education? #Person1#: He got a three here which means it's unsatisfactory. We should work on that with him. #Person2#: So confusing! In my day we got an A or B if we were doing well and if we failed an exam we would get an F!",#Person1# and #Person2# are looking at Jimmy's report and talking about his grades. #Person2# is confused about the number that stands for grades.,120,23,0.1917
scientific_lay_summarisation-elife-norm,"the Old and New Worlds. For example, the mean rate of tooth fracture on a per tooth basis is 2. 3 ± 1. 3% among 13 extant large (>21 kg) felids, canids, and hyaenids, whereas the same is 8. 1 + 3. 5% for a sample of five large North American late Pleistocene felids and canids that represent distinct geographic locations (Alaska, California, Mexico, Peru) (Van Valkenburgh, 2009). Similarly, a study of temporal variation in dental wear and breakage in Pleistocene gray wolves of Great Britain found that per tooth fracture rates ranged from 2. 5% to 8%, and noted that the higher rate was associated with lower prey diversity and the presence of a likely competitor, the brown bear (Ursus arctos) (Flower and Schreve, 2014). In both studies, the authors suggested that elevated tooth fracture frequencies in large Pleistocene carnivorans reflect intensified competition for kills and consequent increases in heavy carcass utilization and scavenging. However, the inference of an association between prey availability, competition, increased bone consumption and higher tooth fracture rates is complicated by several factors. First, because the probability of having at least one broken tooth increases with age (Van Valkenburgh, 2009), populations dominated by older individuals are likely to have higher rates of tooth fracture and heavier tooth wear than those dominated by younger individuals. Most museum collections of skulls do not have associated age data so it is difficult to control for this potential bias. Second, museum collections almost never have data on levels of prey availability or carcass consumption behavior for the sampled predators. Third, the most commonly broken teeth are canines, and these teeth have multiple functions as weapons in combat and predation as well as in feeding. Consequently, increases in canine tooth breakage are more problematic to interpret than increases in premolar or molar breakage. To better understand the causes of variation in tooth fracture frequency among fossil and living large carnivorans, we collected dental wear and fracture data from gray wolves (Canis lupus) representing three well-studied populations that had associated data on prey availability, and in some cases the degree of carcass consumption and age of death for each wolf. These include samples of wolves from Isle Royale National Park (USA), Yellowstone National Park (USA) and Scandinavia. In both Isle Royale","Gray wolves roam many European and American landscapes, where they prey on large animals such as elk and moose. A healthy dentition is essential for these predators to kill, eat and defend themselves. As a result, they tend to avoid biting down on tough body parts, such as bones, so that their teeth do not break. If food becomes scarce however, the wolves may resort to consuming these hard elements, eating more of the carcasses and leading to more damaged teeth. It could therefore be possible to assess the food levels available to existing (or even extinct) wolf populations based on how many broken teeth the animals have. However, older individuals are also more likely to have more damaged teeth, so age would need to be taken into",380,128,0.3368
dialogsum,"#Person1#: Is this our bus stop? #Person2#: I think this is it. Get off. #Person1#: Dude, where are we at? #Person2#: I have no idea. #Person1#: I thought this was the right stop. #Person2#: It doesn't look right to me. #Person1#: Did you make us get off early? #Person2#: I think we did. #Person1#: I should not have listened to you. #Person2#: I really thought this was our stop. #Person1#: Now we have to walk. #Person2#: Maybe we should just wait for the next bus.",#Person2# makes #Person1# and #Person2# get off the bus early. #Person1# blames #Person2#.,85,13,0.1529
scientific_lay_summarisation-elife-norm,"is the most frequently used method but suffers from a number of limitations. Sequential substrate administration is normally required, in addition this method commonly employs a combination of a coelenterazine and a D-LH2 utilising luciferase (with the blue emission from the former being heavily absorbed compared to the yellow-green emission from the latter) (Maguire et al. , 2013), (Stacer et al. , 2013). Differences in biodistribution and reaction kinetics of two substrates can make image co-registration and interpretation difficult. The development of orthogonal luciferase-luciferin pairs has solved some of these limitations but this approach still requires multiple substrate administrations (Rathbun et al. , 2017). An ideal dual-BLI approach would use two spectrally distinct bioluminescent proteins utilising a single substrate followed by spectral unmixing of the signal. However, this approach is not currently feasible using LH2. Although luciferases can be mutated to alter the colour of their emission, a limit appears to have been reached for mutational colour modulation of firefly and related luciferases. The most red-shifted of these enzymes have maximal peak emissions between 610 and 620 nm (Branchini et al. , 2010). This is insufficient for dual BLI in vivo. Due to the differential attenuation of light by biological tissue spectral unmixing of a red-shifted luciferase paired with a standard or green-shifted enzyme is challenging, especially in deeper tissue models (Mezzanotte et al. , 2011). Shifting the emission of both enzymes into the near infrared must be achieved to allow adequate unmixing. To further red-shift peak emission we and others have turned to chemical modification of the D-luciferin (LH2) substrate (Adams and Miller, 2014). We recently described the LH2 analogue infraluciferin (iLH2) which has a luciferase dependent red-shifted peak emission of up to 706 nm (Jathoul et al. , 2014) (1a). We hypothesised that combining colour modulation of bioluminescence through mutagenesis of the FLuc protein along with red-shifting bioluminescence by chemical modification of LH2 would allow dual-BLI, an approach that has not been described previously. In this work, we explored the possible structural interactions in the enzyme that may account for the near infrared emission of iLH2 and its application to dual-BLI in vivo. First, the X-ray crystal structure of FLuc in complex with a high-energy intermediate analogue, 5’-O-[ (N-dehydroinfraluciferyl) -sulfamoyl] adenosine (iDLSA) was determined to provide insight into","Fireflies and some other insects glow to attract mates or prey. This so-called bioluminescence occurs when an enzyme called luciferase modifies the molecule luciferin, which can then emit bright yellow-green light. The gene that encodes the luciferase enzyme has been introduced into cells from mammals, including cancer cells. In the presence of luciferin, these cells begin to glow. The brightness of the bioluminescence depends on how many cancer cells are growing and dividing. The light is bright enough for the cancer cells making luciferase to be transplanted into mice so their behaviour can be examined. However, blood and other tissues absorb the yellow-green light, making it hard to see the cancer cells deep within a mouse. To circumvent this problem, researchers designed a new type of luciferin, called",380,128,0.3368
dialogsum,"#Person1#: So what kind of job did you find for this summer? #Person2#: I'm working for a marketing company. I'm doing telephone marketing. #Person1#: Oh, so you are one of those people who drive me crazy by calling me up in trying to persuade me to buy something that I have no need for. Do you like it? #Person2#: Believe it or not, I do. There are a lot of students working there and we have a lot of fun when we're not making calls. It's really easy since we just have to read from a text. #Person1#: Are you doing this full time? #Person2#: Yeah, but I work from 2:00 in the afternoon until 11:00 at night so I can sleep as late as I want to in the morning.",#Person2# tells #Person1# #Person2# enjoys his job of telephone marketing because he gets along well with colleagues and has enough sleeping hours.,131,22,0.1679
pubmed-summarization,"a 15-year - old female developed fever , stinging eyes and headache , followed one day later by sudden appearance of flaccid blisters on the face with subsequent dissemination to more than 70% of the whole integument and development of mucosal erosions . thirty days before , she had been operated on the nose and medicated with cefuroxime ( for 8 days ) , paracetamol ( for approx . 10 days ) and metamizol ( for approx . 10 days ) , the latter of which was later identified by lymphocyte transformation test as the most likely causative compound . four days before admission , she had taken acetylsalicylic acid and paracetamol for flu - like symptoms including conjunctival irritation and rhinitis . upon physical evaluation , disseminated flaccid blisters filled with serous liquid were present on 70% of her skin surface . her eye- , mouth- , pharyngeal- and genital mucosae were also affected by erosive lesions . she received intravenous immunoglobulins ( ivigs ) , in total 3 g / kg body weight over three consecutive days , hydration and nutritional support as well as careful wound care . topical therapy included silver - coated dressings on erosions , and after reepithelialization , skin washes with water and wax emulsion were performed , followed by the application of hydrocortisone 0.5% in hydrophilic unguent . from day 1 after onset of ivig therapy onwards , no new development of blisters was observed . during the clinical course , desquamation of dusky areas of skin leaving an intact epidermis below was observed . we noted frequent spontaneous bleeding upon changes of the silver - coated dressings during reepithelialization period in the second week . the remaining detached skin fragments that overlied the progressively regrowing epidermis as of day 7 were progressively shed between day 7 and day 28 . the patient was discharged from the intensive care unit ( icu ) at day 28 after admission , with almost complete skin reepithelialization . at the last follow - up control 6 months later , the patient showed full recovery , except for residual alopecia and dry eyes . to date , no specific treatment with a high evidence level of efficacy has been reported for ten . the standard of","toxic epidermal necrolysis is a rare but clinically well - described dermatological pathology . however , clinical pictures of this disorder in text books do not reflect its dynamic evolution . usually , the desquamative post - bullous stage is represented , neglecting the initial bullous stage as well as the skin healing . with one clinical case , we provide a day - after - day illustration of the evolution of a patient suffering from toxic epidermal necrolysis . during one month , a skin area of a limb was regularly photo - documented .",380,96,0.2526
pubmed-summarization,"activated within vascular smooth muscle cells , cardiac myocytes , and renal tubular epithelial cells , generating superoxide , a reactive oxygen species with unfavorable effects . more importantly , nitric oxide release by endothelium may be disturbed in the presence of superoxide and reactive oxygen species . as many as 50% of patients with ahfs present with a systolic blood pressure > 140 mm / hg . elevated blood pressure is present in patients either with systolic heart failure or heart failure with preserved ejection fraction . avp is a hormone that is secreted from the posterior pituitary and is normally suppressed by hypoosmolality . in the failing heart , however , even in the presence of hyponatremia , and thus hypoosmolality , there is a marked increase in avp secretion secondary to nonosmotic baroreceptor - mediated release of the hormone . avp activates the v2 receptor on the basolateral surface of principal cell of the collecting duct . this increases expression and trafficking of the aquaporin 2 water channel to the apical surface . the resultant increased water permeability of the collecting duct allows osmotic water equilibrium with the hypertonic interstitium and urinary concentration . also , avp stimulates the v1a receptors of the vascular smooth muscle that results in vasoconstriction of the arterial and venous system . thus , avp potentially may result in further remodeling of the myocardium by these pathways ( ) . it is evident that the neurohormonal storm and worsening kidney function in ahfs ultimately ensue to venous congestion and elevated central venous pressure ( cvp ) , which results in a vicious cycle . in a prospective cohort of 145 patients from the cleveland clinic , cvp was the most important hemodynamic factor causing worsening renal function in patients with ahfs . in addition , in a retrospective analysis of 2557 patients who underwent cardiac catheterization for hemodynamic assessment , elevated cvp remained as the single most important prognostic factor for worsening renal function and mortality . there is growing evidence that hypervolemia , that is , increased pulmonary capillary wedge pressure , independently correlates with mortality and may predict an urgent need for cardiac transplantation . furthermore , improvement in cardiac output / index in patients with ahfs has little impact","impaired cardiac function leads to activation of the neurohumoral axis , sodium and water retention , congestion and ultimately impaired kidney function . this sequence of events has been termed the cardiorenal syndrome . this is different from the increase in cardiovascular complications which occur with primary kidney disease , that is , the so - called renocardiac syndrome . the present review discusses the pathogenesis of the cardiorenal syndrome followed by the benefits and potential deleterious effects of pharmacological agents that have been used in this setting . the agents discussed are diuretics , aquaretics , natriuretic peptides , vasodilators , inotropes and adenosine 1 receptor antagonists . the potential role of ultrafiltration is also briefly discussed .",380,119,0.3132
dialogsum,"#Person1#: you are dressed to kill. You look gorgeous, Alexander. #Person2#: thanks. This is my power suit. I have a dinner date tonight. #Person1#: how did you meet each other? #Person2#: she's a friend of Amy. We met at Amy's birthday party. #Person1#: is this your first date? #Person2#: yes. I hope it pans out. Cross your fingers, Lily. #Person1#: sure it will. Oh, no, it's seven fifteen already. I'm going to be late for my date. #Person2#: oh. . . so you buried the hatchet with Steven? #Person1#: absolutely not! He's a cheater. I will never talk to him again. I'm over with him. He's history! #Person2#: then who will you meet tonight? #Person1#: a guy I met on the internet three month ago. #Person2#: really? Are you sure this is a good idea? #Person1#: please don't be so fussy! I didn't just meet him yesterday. #Person2#: I know, but remember to meet in a public place and don't give out your personal information.",Alexander met Amy's friend at Amy's birthday party and they'll go on a date tonight. Lily broke up with Steven and will date with a guy she met online.,165,29,0.1758
scientific_lay_summarisation-elife-norm,"the antiviral cytokine, IFN-α, for others (Zhou et al. , 2016). Typically, the presence of viral RNA or DNA in the cytoplasm of mammalian cells will induce secretion of type I interferon proteins (IFN-α and IFN-β), which promote expression and translation of interferon-stimulated genes (ISGs) in neighboring cells and render them effectively antiviral (Stetson and Medzhitov, 2006). In some bat cells, the transcriptomic blueprints for this IFN response are expressed constitutively, even in the absence of stimulation by viral RNA or DNA (Zhou et al. , 2016). In non-flying mammals, constitutive IFN expression would likely elicit widespread inflammation and concomitant immunopathology upon viral infection, but bats support unique adaptations to combat inflammation (Zhang et al. , 2013; Ahn et al. , 2019; Xie et al. , 2018; Pavlovich et al. , 2018) that may have evolved to mitigate metabolic damage induced during flight (Kacprzyk et al. , 2017). The extent to which constitutive IFN-α expression signifies constitutive antiviral defense in the form of functional IFN-α protein remains unresolved. In bat cells constitutively expressing IFN-α, some protein-stimulated, downstream ISGs appear to be also constitutively expressed, but additional ISG induction is nonetheless possible following viral challenge and stimulation of IFN-β (Zhou et al. , 2016; Xie et al. , 2018). Despite recent advances in molecular understanding of bat viral tolerance, the consequences of this unique bat immunity on within-host virus dynamics—and its implications for understanding zoonotic emergence—have yet to be elucidated. The field of ‘virus dynamics’ was first developed to describe the mechanistic underpinnings of long-term patterns of steady-state viral load exhibited by patients in chronic phase infections with HIV, who appeared to produce and clear virus at equivalent rates (Nowak and May, 2000; Ho et al. , 1995). Models of simple target cell depletion, in which viral load is dictated by a bottom-up resource supply of infection-susceptible host cells, were first developed for HIV (Perelson, 2002) but have since been applied to other chronic infections, including hepatitis-C virus (Neumann et al. , 1998), hepatitis-B virus (Nowak et al. , 1996) and cytomegalovirus (Emery et al. , 1999). Recent work has adopted similar techniques to model the within-host dynamics of acute infections, such as influenza A and measles, inspiring debate over the extent to which explicit modeling of top-down immune control can","Bats can carry viruses that are deadly to other mammals without themselves showing serious symptoms. In fact, bats are natural reservoirs for viruses that have some of the highest fatality rates of any viruses that people acquire from wild animals – including rabies, Ebola and the SARS coronavirus. Bats have a suite of antiviral defenses that keep the amount of virus in check. For example, some bats have an antiviral immune response called the interferon pathway perpetually switched on. In most other mammals, having such a hyper-vigilant immune response would cause harmful inflammation. Bats, however, have adapted anti-inflammatory traits that protect them from such harm, include the loss of certain genes that normally promote inflammation. However, no one has previously explored how these unique antiviral defenses of bats",380,128,0.3368
pubmed-summarization,"structures according to the boltzmann probability distribution , the trnascan - se gene finder for trna ( 12 ) , multiple sequence alignment for the statistical detection of rna secondary structure msari ( 13 ) , dynamic programming pairwise sequence - structure alignment dynalign ( 14 ) , tertiary structure modeling tool mc - sym ( 15 ) , etc . only a few of the many important computational tools for rna structure prediction , gene finding , alignment , etc . have been listed . in this paper , we describe the web server rnaloss , based on the algorithm of clote ( 16 ) , which computes an aspect of the folding landscape of an rna nucleotide sequence s = s1 , , sn . given s , this algorithm runs in time o(n ) and space o(n ) , and computes for each k , the number of k - locally optimal secondary structures ( explained below ) . work by clote ( 16 ) was motivated by the following question , as has been suggested for proteins ( 17 ) : is it the case that rna has been under selective pressure to fold rapidly ? using the algorithm of the web server rnaloss , it appears that structural rna has a different folding landscape than random rna of the same dinucleotide frequency ; specifically , for small values of k , there appear to be fewer k - locally optimal secondary structures than in random rna . related , but distinct work has appeared in ( 1821 ) , for discussion see ( 16 ) . a secondary structure for an rna sequence s = s1, ,sn is an expression s = s1, ,sn involving dot , left and right parenthesis , which is well balanced , such that nucleotides corresponding to matching parentheses are either watson crick complements or gu wobble pairs . a secondary structure s on rna sequence s = s1, ,sn is defined to be a set of ordered pairs ( i , j ) , such that i + 3 < j and the following conditions are satisfied . watson crick or gu wobble pairs : if ( i , j ) belongs to s , then pair ( ai","rnaomics , analogous to proteomics , concerns aspects of the secondary and tertiary structure , folding pathway , kinetics , comparison , function and regulation of all rna in a living organism . given recently discovered roles played by micro rna , small interfering rna , riboswitches , ribozymes , etc . , it is important to gain insight into the folding process of rna sequences . we describe the web server rnaloss , which provides information about the distribution of locally optimal secondary structures , that possibly form kinetic traps in the folding process . the tool rnaloss may be useful in designing rna sequences which not only have low folding energy , but whose distribution of locally optimal secondary structures would suggest rapid and robust folding",380,128,0.3368
scientific_lay_summarisation-elife-norm,"demonstrated that inbred Solanum carolinense L. display reduced flower size, pollen and scent production, and receive fewer visits from diurnal generalists. It is necessary to broaden such integrated methodological approaches to other plant-pollinator systems (e. g. , nocturnal specialist pollinators) and further floral traits (e. g. , flower colour). The magnitude and slope of inbreeding effects in plants can vary across environments, since local conditions partly determine the selective value of recessive alleles unmasked by inbreeding (Fox and Reed, 2011). While the influence of environmental stress on the expression of inbreeding depression is well studied, the effects of plant sex, which considerably shapes an individual’s interaction with its environment, remain largely unexplored. Individuals of dioecious plant species invest into either male or female reproductive function. This partitioning goes along with different life histories, resource demands, stress susceptibilities, and consequently sex-specific selection regimes in identical habitats (Moore and Pannell, 2011; Barrett and Hough, 2013). Sex-specific selection may modify the magnitude of inbreeding depression in dioecious plants. Studies on animals reported higher inbreeding depression in females than males resulting from higher reproductive investment and prolonged life cycles in the former (Ebel and Phillips, 2016). In plants, such relations have rarely been investigated (Teixeira et al. , 2009), and if so, not with a focus on floral traits. If inbreeding effects on floral traits are more pronounced in female than male plants, the relative frequency of pollinator visits may be biased towards the latter sex, with devastating consequences for the effective size and persistence of populations. Studies on sex-specific inbreeding effects on floral traits are thus needed to improve the risk assessment for the conservation of dioecious plant species. Plant populations may escape progressive retractions under increased inbreeding rates by purging. Inbreeding unmasks deleterious recessive mutations, which facilitates their selective removal from the population gene pool and may result in a rebound of fitness when the demographic bottleneck is intermediate (Crnokrak and Barrett, 2002). Plant species that have successfully colonised distant geographic regions provide perfect models for studying the relevance of purging in natural plant populations. As colonisation events are associated with successive demographic bottlenecks, purging is expected to be one determinant for the successful establishment and proliferation of plant populations in novel habitats (Facon et al. , 2011; Schrieber and Lachmuth, 2017).","Destroying habitats can reduce the size of local populations of many plants and animals. For plants, a smaller population means a greater chance of inbreeding, where individual plants that are closely related to each other mate and produce offspring. Inbreeding often results in offspring that are weaker than their parents which can reduce the plant’s chance of survival. Many plants rely on animals to help them to breed. For example, bees carry pollen – containing the male sex cell – to other flowers which then fertilize the plant to produce seeds. Flowers use a wide range of attributes to attract animals such as their colour, scent and providing them with food. However, inbreeding may alter these characteristics which could make it harder for inbred plants to reproduce, meaning",380,128,0.3368
pubmed-summarization,"clients . although a focus on frailty might usefully inform care provision in the pre - hospital and ed settings , the concept has received little attention to date . three approaches can be discerned : rules - based approaches such as the frailty phenotype , clinical frailty scales based on clinical judgment , and the frailty index based on deficit count . ( table 1 ) some describe frailty as a medical syndrome , while others believe that it is derived from the accumulation of age - related changes over time . while this will be a particular challenge for defining frailty in emergency services , it is also the case that the special needs in the emergency setting not just for reliable and valid measures , but for feasible measures that can be used rapidly usefully will resolve some of the more esoteric considerations that are often at play in the debate about frailty measurement . in fact , data from the medicare current beneficiary survey confirmed that the rockwood - mitnitski frailty index was a robust predictor of serious adverse events ( death , nursing home admission , hospital admission ) in the first 30 days following an older individual s visit to the emergency department . the primary objectives of this review were : 1 ) to identify measures of frailty used by emergency medical services ; and 2 ) to describe frailty measures used in emergency medicine . we limited our discussion to the pre - hospital and ed environments , with their unique time , resource , and system constraints . here , we undertook a narrative review of the ems and emergency medicine literature to understand how the concept of frailty is being applied , which measures have been validated for use in this population , and what can be recommended . the primary objectives of this review were : 1 ) to identify measures of frailty used by emergency medical services ; and 2 ) to describe frailty measures used in emergency medicine . we limited our discussion to the pre - hospital and ed environments , with their unique time , resource , and system constraints . here , we undertook a narrative review of the ems and emergency medicine literature","backgroundolder adults use more health - care services per capita than younger age groups and the older adult population varies greatly in its needs . evidence suggests that there is a critical distinction between relative frailty and fitness in older adults . here , we review how frailty is described in the pre - hospital literature and in the broader emergency medicine literature.methodspubmed was used as the primary database , but was augmented by searches of cinahl and embase . articles were included if they focused on patients 60 years and older and implemented a definition of frailty or risk screening tool in the emergency medical services ( ems ) or emergency department setting.resultsin the broad clinical literature , three types of measures can be identified : frailty",380,128,0.3368
dialogsum,"#Person1#: Are you planning on voting? #Person2#: Yes. What about you? #Person1#: Yes, but this will be my first time voting. #Person2#: Really? #Person1#: Yes, and I have no idea how to do it. #Person2#: Voting is simple. #Person1#: I don't know any of the laws they're trying to pass. #Person2#: That's okay. They describe everything on the ballot. #Person1#: I didn't know that. #Person2#: Don't worry. You'll be fine. #Person1#: That's good to know. #Person2#: Congratulations on your first voting day.",#Person1# is going to vote for the first time and asks #Person2# how to do it. #Person2# says voting is simple and encourages #Person1#.,82,24,0.2927
dialogsum,"#Person1#: What happened to your brother? #Person2#: It seems that he has gone ape over the girl. #Person1#: Your parents must be worrying about him. #Person2#: Yes, he's been like this for two weeks. We don't know what to do. #Person1#: Have you talked to him? #Person2#: Yeah. But he just didn't listen.",#Person2# tells #Person1# #Person2#'s brother may go ape over a girl.,53,11,0.2075
scientific_lay_summarisation-elife-norm,"octamer, are catalyzed by ATP-dependent chromatin remodeling enzymes (Zhou et al. , 2016). Underscoring their central role in chromatin regulation, remodeling enzymes play essential roles in many processes including transcription, DNA replication, and DNA repair (Falbo and Shen, 2006; Hota and Bruneau, 2016; Price and D' Andrea, 2013). How a relatively small number of remodeler types carry out such diverse regulatory functions remains an area of active research, not least because much remains unknown regarding remodeler mechanisms for substrate recognition and the coupling of that recognition to activity. Chromatin remodelers are members of the SF2 superfamily of nucleic acid motors, which catalyze noncovalent changes to nucleic acid substrates (Zhou et al. , 2016). Chromatin remodelers, however, are unique in that they specifically mobilize DNA in the context of the nucleosome, where DNA is tightly bound to histone proteins. Remodelers are further classified into families based on the domain architecture of their ATPase subunit. These families differ in their specific biochemical activities (Zhou et al. , 2016). Substantial progress in our general understanding of remodeling mechanisms has been made by asking what elements of the nucleosome are important for remodeling in different families. For example, maximal remodeling by ISWI family remodelers, which primarily slide nucleosomes, requires DNA flanking the nucleosome and the N-terminal tail of histone H4 (Clapier et al. , 2001; Yang et al. , 2006). Conversely, maximal remodeling by SWI/SNF family remodelers, which carry out the most diverse set of changes to nucleosome structure, does not require these nucleosomal epitopes (Guyon et al. , 1999). Less is known about how these substrate cues are recognized and mechanistically coupled to remodeling. Some important insights have come from biochemical analyses and structures of remodelers in the absence of nucleosomes, which suggest that in the ground state, chromatin remodelers are held in an inactive conformation by family-specific autoinhibitory motifs (Clapier and Cairns, 2012; Hauk et al. , 2010; Xia et al. , 2016; Yan et al. , 2016). Binding to specific nucleosomal epitopes is thought to relieve this autoinhibition via conformational changes in the remodeler, but the details of this process remain unclear. At the same time, structures of several nucleosome-protein complexes are revealing that many of these proteins interact with a conserved acidic patch formed by histones H2A and H2B on","Every human cell contains nearly two meters of DNA, which is carefully packaged to form a dense structure known as chromatin. The building block of chromatin is the nucleosome, a unit composed of a short section of DNA tightly wound up around a spool-like core of proteins called histones. The tight structure of the nucleosome prevents the cell from accessing and ‘reading’ the genes in the packaged DNA, effectively switching off these genes. So the exact placement of nucleosomes helps manage which genes are turned on. Changing the position of the nucleosomes can ‘free’ the DNA and make genes available to the cell. Enzymes called chromatin remodelers move nucleosomes around – for example, they can make the histone core slide on the DNA strand. However, it is still",380,128,0.3368
scientific_lay_summarisation-elife-norm,"We have developed an open-source software called bi-channel image registration and deep-learning segmentation (BIRDS) for the mapping and analysis of 3D microscopy data and applied this to the mouse brain. The BIRDS pipeline includes image preprocessing, bi-channel registration, automatic annotation, creation of a 3D digital frame, high-resolution visualization, and expandable quantitative analysis. This new bi-channel registration algorithm is adaptive to various types of whole-brain data from different microscopy platforms and shows dramatically improved registration accuracy. Additionally, as this platform combines registration with neural networks, its improved function relative to the other platforms lies in the fact that the registration procedure can readily provide training data for network construction, while the trained neural network can efficiently segment-incomplete/defective brain data that is otherwise difficult to register. Our software is thus optimized to enable either minute-timescale registration-based segmentation of cross-modality, whole-brain datasets or real-time inference-based image segmentation of various brain regions of interest. Jobs can be easily submitted and implemented via a Fiji plugin that can be adapted to most computing environments. The mapping of the brain and neural circuits is currently a major endeavor in neuroscience and has great potential for facilitating an understanding of fundamental and pathological brain processes (Alivisatos et al. , 2012; Kandel et al. , 2013; Zuo et al. , 2014). Large projects, including the Mouse Brain Architecture project (Bohland et al. , 2009), the Allen Mouse Brain Connectivity Atlas (Oh et al. , 2014), and the Mouse Connectome project, have mapped the mouse brain (Zingg et al. , 2014) in terms of cell types, long-range connectivity patterns, and microcircuit connectivity. In addition to these large-scale collaborative efforts, an increasing number of laboratories are also developing independent, automated, or semi-automated frameworks for processing brain data obtained for specific projects (Fürth et al. , 2018; Ni et al. , 2020; Niedworok et al. , 2016; Renier et al. , 2016; Wang et al. , 2020a; Iqbal et al. , 2019). With the improvement of experimental methods for dissection of brain connectivity and function, development of a standardized and automated computational pipeline to map, analyze, visualize, and share brain data has become a major challenge to all brain connectivity mapping efforts (Alivisatos et al. , 2012; Fürth et al. , 2018). Thus, the implementation of an efficient and reliable method","Mapping all the cells and nerve connections in the mouse brain is a major goal of the neuroscience community, as this will provide new insights into how the brain works and what happens during disease. To achieve this, researchers must first capture three-dimensional images of the brain. These images are then processed using computational tools that can identify distinct anatomical features and cell types within the brain. Various microscopy techniques are used to capture three-dimensional images of the brain. This has led to an increasing number of computational programs that can extract data from these images. However, these tools have been specifically designed for certain microscopy techniques. For example, some work on whole-brain datasets while others are built to analyze specific brain regions. Developing a more flexible, standardized",380,128,0.3368
scientific_lay_summarisation-elife-norm,"tailing by Rqc2p—are functionally related. Although many studies have identified Rqc1p/TCF25 as a core component of the yeast and mammalian RQC required for nascent-chain degradation (Brandman et al. , 2012; Defenouillère et al. , 2013; Shao and Hegde, 2014), Rqc1p’s precise structural and functional roles in the complex remain unclear. Previous work in yeast suggested that Rqc1p acts after Ltn1p to promote nascent-chain degradation. This hypothesis emerged from two lines of evidence: The presence of polyubiquitinated proteins in purified RQC depends on Ltn1p (and to a lesser extent on Rqc2p) but not on Rqc1p or Cdc48p (Brandman and Hegde, 2016; Brandman et al. , 2012); and recruitment of Cdc48p to the 60S subunit requires Rqc1p and nascent-chain ubiquitination (Defenouillère et al. , 2013). However, these studies did not determine whether Rqc1p is necessary for ubiquitination of the nascent chain itself or whether recruitment of Cdc48p requires a direct interaction with Rqc1p. Therefore, the mechanism by which Rqc1p promotes nascent-chain degradation in vivo has remained unclear. In this study, we provide an in vitro characterization of the RQC in a budding-yeast extract that uniquely recapitulates ubiquitination by Ltn1p and CAT tailing by Rqc2p, providing new insights into RQC action in promoting degradation of stalled translation products. Because CAT tails have thus far only been observed in S. cerevisiae (Choe et al. , 2016; Defenouillère et al. , 2016; Shen et al. , 2015; Yonashiro et al. , 2016), we used S. cerevisiae extracts to recapitulate Rqc2p-mediated elongation in vitro. Although S. cerevisiae has long been used for in vitro translation (Hussain and Leibowitz, 1986; Iizuka et al. , 1994; Rojas-Duran and Gilbert, 2012; Tarun and Sachs, 1995), these reactions are notoriously inefficient. Further exacerbating this problem, we aimed to program these reactions with truncated mRNA substrates that trigger quality control, which are translated less efficiently because they lack poly (A) tails that normally enhance translation. Thus, we found it necessary to first establish an optimized protocol that could reproducibly generate translation products that were detectable by immunoblotting (see Materials and methods). Critical aspects of our protocol included: (1) lysing cells with a freezer mill under cryogenic conditions rather than by bead beating in the cold; (2) minimizing the number of lysis cycles; (3) removing small molecules by dialysis rather than by","Cells make proteins by reading instructions encoded in molecules called messenger RNAs. Structures called ribosomes move along the messenger RNAs and translate the coded instructions to build new proteins from building blocks known as amino acids. Normally, a ribosome will encounter a stop signal on the messenger RNA, which ends translation and allows the newly built protein to be released. Sometimes, however, ribosomes stall before they reach the genuine stop signal, which can happen due to defects in the messenger RNAs or ribosomes. To prevent incomplete proteins from accumulating and causing damage, cells contain a group of other proteins called the Ribosome-associated Quality-control Complex (or RQC for short). This quality-control complex is composed of three components that assemble on stalled ribosomes and attach two different tags to the",380,128,0.3368
dialogsum,"#Person1#: Hi, Daisy! #Person2#: Hi Simon. Nice to meet you again #Person1#: I hope you are Settling in at school! #Person2#: I am! I've made lots of friends and I really enjoy my courses. #Person1#: Good! Me too! By the way. you didn't tell me what you are studying here. #Person2#: Didn't I? I'm doing business studies. #Person1#: Really? That's great. You hope to join a company after graduating? #Person2#: Maybe. My parents moved to Canada the year when I was born. We are living in Toronto. Isuppose I might get a job in Toronto when I graduate. It's too soon to say really. #Person1#: What about your friend Zoe #Person2#: She's from Australia. She lives in Sydney. Her father runs a hotel business there and she is doing a degree in accountancy. #Person1#: Accountancy? Really? She must be very good at figures. #Person2#: I guess so. What about you, Simon? #Person1#: I'm studying law. #Person2#: Great! So I'll know who to call if I ever need a lawyer. #Person1#: Sure, welcome anytime",Daisy tells Simon she's doing business studies and may get a job in Toronto after graduation. They also talk about Zoe who is now studying accountancy. Simon tells Daisy he's studying law.,173,32,0.185
dialogsum,"#Person1#: How do you like other films starring Charlie Chaplin? #Person2#: Well, I like others very much, but I really don't think much of this one. #Person1#: You don't like the performance, do you? #Person2#: Yes, but I don't like the story.",#Person1# and #Person2# discuss films starring Charlie Chaplin.,42,8,0.1905
dialogsum,"#Person1#: Hi, Jane. It's nice to see you again. I heard that you went to the United Kingdom during the vacation. #Person2#: Yes. I paid a visit to London and attended a summer course in English. #Person1#: Wow. It sounds so good. How long did you stay there? #Person2#: Well, I went there on July 5th and came back on August 15th. #Person1#: What about the course? #Person2#: I think the course was well organized. The teachers were nice. They taught us to listen, speak, read and write in English, but it mostly focused on speaking. One interesting thing I found was that the English classes were different from ours because they were very free. You can sit anywhere you like in the classroom. You can ask the teacher questions at any time during the class, and you are welcome to share your ideas with the classmates and teachers. I really enjoy this kind of class. #Person1#: How interesting! Maybe our teachers should try that.","Jane shares with #Person1# the summer course in English that she attended in London, which was well organized but mostly focused on speaking. She enjoys the class.",165,27,0.1636
dialogsum,"#Person1#: I am looking for a blouse. Can you show me the way, please? #Person2#: OK, what style do you want? #Person1#: I have no idea. Could you recommend me one? #Person2#: What about this one? It fits you. #Person1#: Well, the style is quite good, but I think it's too showy. I would like to try on the lighter one.",#Person2# recommends a blouse to #Person1#. #Person1# would like a lighter one.,61,12,0.1967
pubmed-summarization,"this period , their diurnal cortisol profiles normalized , and most of the subjects reported that their sleep improved and their pain and stress levels declined . the results of the experiment led to these conclusions : 1 ) grounding the body during sleep yields quantifiable changes in diurnal or circadian cortisol secretion levels that , in turn , 2 ) produce changes in sleep , pain , and stress ( anxiety , depression , and irritability ) , as measured by subjective reporting . the cortisol effects described by ghaly and teplitz5 are particularly significant in the light of recent research showing that prolonged chronic stress results in glucocorticoid receptor resistance.6 such resistance results in failure to downregulate inflammatory responses , which can thereby increase risks of a variety of chronic diseases . this effect complements the findings described in the effects on pain and the immune response section . a pilot study on the effects of grounding on pain and the immune response to injury employed delayed - onset muscle soreness ( doms).7 doms is the muscular pain and stiffness that takes place hours to days after strenuous and unfamiliar exercise . the phase of contraction that occurs when a muscle shortens , as in lifting a dumbbell , is referred to as concentric , whereas the phase of contraction as a muscle lengthens , as in lowering a dumbbell , is referred to as eccentric . eight healthy subjects performed an unfamiliar , eccentric exercise that led to pain in their gastrocnemius muscles . this was done by having them perform two sets of 20 toe raises with a barbell on their shoulders and the balls of their feet on a 2-inch 4-inch wooden board.7 all subjects ate standardized meals at the same time of day , and adhered to the same sleep cycle for 3 days . at 5.40 pm on each day , four of the subjects had conductive grounding patches adhered to their gastrocnemius muscles and the bottoms of their feet . they remained on the grounded sheets except for visits to the bathroom and meals . as controls , four subjects followed the same protocol except that their patches and sheets were not grounded . the following measurements were taken before the exercise","multi - disciplinary research has revealed that electrically conductive contact of the human body with the surface of the earth ( grounding or earthing ) produces intriguing effects on physiology and health . such effects relate to inflammation , immune responses , wound healing , and prevention and treatment of chronic inflammatory and autoimmune diseases . the purpose of this report is two - fold : to 1 ) inform researchers about what appears to be a new perspective to the study of inflammation , and 2 ) alert researchers that the length of time and degree ( resistance to ground ) of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation , wound healing , and tumorigenesis",380,128,0.3368
pubmed-summarization,"the development and survival of offspring within the breeding pools utilized by this species . this study was conducted to measure and perform a risk analysis of the bioavailable concentrations of pahs present within breeding pools utilized by puerto rican crested toads at sites used for vehicular parking compared to those that are not . the psds used in this study were composed of a single strip of dichloromethane - extracted ldpe tubing with the dimensions of 25 cm 7.5 cm , an effective surface area of 375 cm , and an average weight of 4.3 g. during deployment , these strips were housed between two rectangular fenestrated aluminum plates with the dimensions of 30 cm 9 cm , which were curved along the longitudinal axis to form a cylindrical housing for the device . six small slices were made along the edges of each ldpe strip to allow conventional plastic ties to hold the strip in place within the aluminum plates . these plates allowed the strips to be positioned at their respective deployment sites , provided shade , and elevated the strips above the sediment and within the water column . small plastic placards were placed on each device and secured with plastic ties to deter theft during the deployment period . the components of the devices were stored wrapped in baked aluminum foil at 20c until the time of the deployment . deployment of the devices was scheduled for the first adequate rainfall of the rainy season , which occurred on november 8 , 2009 . recovery of the devices was performed 14 days following the initial deployment of each device to ensure that analytes remained in the linear uptake phase for appropriate modeling purposes . devices were deployed into the ephemeral pools located at the three breeding sites : tamarindo , aroma , and atolladora . device placement was based on the specific pool configuration at each site favoring deep depressions to ensure that devices were not exposed to air as the pools evaporated during the deployment period . 15 devices were deployed at the tamarindo site and were divided between its two major pools . 8 of these devices were deployed at the tamarindo south pool , and 7 devices were deployed at the tamarindo","habitat preservation and management may play an important role in the conservation of the puerto rican crested toad , peltophryne lemur , due to this species ' small geographic range and declining native wild population . bioavailable water concentrations of polycyclic aromatic hydrocarbon ( pah ) contaminants within breeding pools at 3 sites were established using passive sampling devices ( psds ) and gas chromatography - mass spectrometry ( gc / ms ) . a more diverse population of pah analytes were found in higher concentrations at the breeding site that allowed direct vehicular access , but calculated risk quotients indicated low risk to toad reproduction associated with the current pah analyte levels .",380,114,0.3
dialogsum,"#Person1#: Would you like some tea or coffee? #Person2#: No, thank you. It's very late now. I won't be able to sleep well if I drink some tea or coffee. #Person1#: Then what about some water? #Person2#: Yes, please. #Person1#: Don't work too late since you are not in good health. You should be careful with your health. #Person2#: I know, but I have to finish these reports tonight. Our manager will use them at the meeting tomorrow morning. #Person1#: Can I help you with something? #Person2#: No, I'm afraid you can't. Just turn down the TV set a little so that it won't be so noisy. #Person1#: I will. I do hope that you will finish the report soon and get some sleep. #Person2#: Don't worry. It won't take me too long.",#Person2# has to finish the reports and #Person1# wants to help. But #Person2# only wants the TV sounds to be lower.,133,21,0.1579
dialogsum,"#Person1#: Would you like to stretch your legs? #Person2#: Why not? #Person1#: Let's get a soft drink. #Person2#: Do we have enough time? #Person1#: Yes, we do. #Person2#: The performance is excellent. #Person1#: It's a new concert hall and the acoustics are great. #Person2#: I couldn't agree more. #Person1#: Is this your first time to come to a symphony concert? #Person2#: Yes, it is. #Person1#: Do you have concert halls in your city? #Person2#: Yes, but it's much smaller. #Person1#: Well, we'd better get back to our seats. It's about to start. #Person2#: OK.",#Person1# and #Person2# take a break for drinks during the symphony concert.,94,12,0.1277
dialogsum,"#Person1#: Do you remember John from head office? #Person2#: Yes. #Person1#: Have you heard what happened to him? #Person2#: No, what? #Person1#: He had his car stolen. Actually he was kidnapped while he was in the car. #Person2#: What do you mean? #Person1#: Well, apparently, he was just getting into his car-he'd parked it in one of those underground multi-story things-he was just getting in and suddenly three guys with guns opened the back doors of the car and got in. #Person2#: Crikey. Where did this happen? #Person1#: In Taichung, I think. #Person2#: Oh, right, I hear they have a lot of this kind of problem down there. #Person1#: Really? Well, anyway, they pointed their guns at him and said, you know, keep calm and drive out. . . . we don't want to hurt you. . . we just want your car. #Person2#: So what happened? #Person1#: Well, he drove out, and when he got to the booth to pay the attendant, he pretended to have an epileptic fit, you know, to scare the thieves away. The attendant was no help at all, even though the guys were holding guns in plain view, he did nothing. #Person2#: That's terrible. #Person1#: Yes, makes you think, doesn't it? #Person2#: So what happened next? #Person1#: Well, he kept on pretending to have a fit, so they freaked out and just ran away. #Person2#: Well, he sure was lucky. #Person1#: I'll say.",#Person1# tells #Person2# about John's experience of being kidnapped in Taichung. He was pointed at with guns by three guys but he scared away the thieves by pretending to have an epileptic fit.,239,33,0.1381
scientific_lay_summarisation-elife-norm,"for preclinical therapy development. The mouse glioma cell line GL261 was purchased from National Cancer Institute (NCI Tumor Repository, Frederick, MD) and cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% FBS, 100 U/ml penicillin, and 100 µg/ml streptomycin (all from Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany). The 1x105 GL261 cells diluted in 2-µl sterile phosphate buffered saline (PBS, Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany) were stereotactically implanted into the right brain hemisphere of 6- to 8-week-old female C57Bl/6J mice (n=45 mice, Charles River Laboratories, Sulzfeld, Germany) using a Hamilton syringe, driven by a fine step motor (coordinates: 2 mm lateral and 2 mm ventral of bregma; injection depth: 3 mm below the dural surface). Animals were deeply anesthetized with ketamine/xylazine and unresponsive to stimuli during the intracranial injection; GL261 cells were routinely tested for viral or mycoplasma contamination, and mouse cell identity was confirmed by the multiplex cell contamination test (Multiplexion GmbH, Heidelberg, Germany, Schmitt and Pawlita, 2009). The human S24 cell line was derived as a primary glioblastoma culture from a resected glioblastoma (after informed consent) and GBM typical genetic changes were confirmed by comparative genomic hybridization (Lemke et al. , 2012; Osswald et al. , 2015). For the S24 glioma model, 5x104 S24: td-tomato cells (stably transduced by lentivirus) were transplanted orthotopically in 8- to 10-week-old male NMRI nude mice (Charles River, Sulzfeld, Germany, n=3 mice). The cells were cultivated under serum-free conditions in DMEM-F12 as sphere cultures (Thermo Fisher Scientific Inc. , Waltham, MA) supplemented with 2% B-27 (Thermo Fisher Scientific Inc.), 5 µg/ml human insulin (Sigma-Aldrich Corporation, St. Louis, MO), 12. 8 ng/ml heparin (Sigma-Aldrich Corporation), 0. 4 ng/ml EGF (R&D Systems Inc. , Minneapolis, MN) and 0. 4 ng/ml FGF (Thermo Fisher Scientific Inc.). Cell lines were regularly checked for mycoplasma infections and authenticity (species control). Mycoplasma testing was done using the LookOut Mycoplasma PCR Detection Kit (Sigma-Aldrich, Germany) according to the manufacturer’s instructions. All animal experiments were approved by the regional animal welfare committee (permit number: G187/10, G188/12 and G145/10, Regierungspräsidium Karlsruhe). MR imaging was performed on a 9. 4 Tesla horizontal bore small animal NMR scanner (BioSpec 94/20 USR, Bruker BioSpin GmbH, Ettlingen, Germany) with a four-channel phased-array surface receiver coil. MR imaging included a standard RARE T2-w and T1-w post-Gd-contrast sequence to monitor","Blood vessels are the body’s highways that allow blood to transport oxygen, nutrients, hormones and waste products quickly and efficiently around the body. Tumors are made up of particularly active cells and so their growth heavily depends on blood vessels. Indeed, a fundamental hallmark of tumor progression is for nearby blood vessels to form more quickly. Tumor blood vessels also differ in structure from their normal counterparts for reasons that need to be investigated in more detail. Compounds that block the formation of blood vessels have been developed for treating highly malignant brain tumors called gliomas. However, although many of these compounds show promising effects in preclinical trials, clinical trials on humans have been less successful. Having the ability to image the blood vessels in high detail during",380,128,0.3368
dialogsum,"#Person1#: There will be a party in my company ; what shall I wear? #Person2#: Is it formal or informal? #Person1#: I guess it is a formal one because the general director will give a speech there, and most of the staff will take part in. #Person2#: In that case, formal suit with a nice tie will be better. #Person1#: You are right. What about shoes? #Person2#: The brown leather shoes are OK. #Person1#: Thanks a lot. #Person2#: Don't mention it.",#Person2# advises #Person1# on dressing for a formal company party.,81,10,0.1235
scientific_lay_summarisation-elife-norm,"is the G2019S amino acid substitution, which activates the kinase two- to threefold (West et al. , 2005; Khan, 2005; Jaleel et al. , 2007). Since protein kinases are attractive pharmacological targets, this finding has raised hopes that selective LRRK2 inhibition can prevent or delay the onset of PD (Yao et al. , 2013). Extensive studies of LRRK2 have associated it with diverse cellular processes such as Wnt signaling, mitochondrial disease, cytoskeleton remodeling, vesicular trafficking, autophagy, and protein translation (Taymans et al. , 2015; Cookson, 2015; Schapansky et al. , 2014; Papkovskaia et al. , 2012). Moreover, several LRRK2 substrates have been reported previously; however, evidence that they are phosphorylated by LRRK2 in a physiological context is generally lacking and proofs are confined to in vitro approaches or to cellular systems using overexpressed kinase (Jaleel et al. , 2007; Kumar et al. , 2010; Ohta et al. , 2011; Kawakami et al. , 2012; Bailey et al. , 2013; Martin et al. , 2014; Qing et al. , 2009; Chen et al. , 2012; Gloeckner et al. , 2009; Imai et al. , 2008; Gillardon, 2009; Kanao et al. , 2010; Matta et al. , 2012; Xiong et al. , 2012; Yun et al. , 2013; Yun et al. , 2015; Krumova et al. , 2015). Significant off-target effects for LRRK2 compounds that have been used previously further complicate interpretation of the data (Schapansky et al. , 2015). Overall, there is little consensus on the cellular roles of LRRK2; thus, identification of definitive and verifiable physiological LRRK2 substrates is considered to be one of the greatest challenges in the field (Schapansky et al. , 2015). Besides mutations in LRRK2, other genetic risk variants for PD map to the Park16 locus. Among the five genes within this locus is Rab7L1 (also known as Rab29), which together with LRRK2 increases nonfamilial PD risk. Depletion of Rab7L1 recapitulates the dopaminergic neuron loss observed with LRRK2-G2019S expression and its overexpression rescues mutant LRRK2 phenotypes (MacLeod et al. , 2013). Rab GTPases comprise ~70 family members in humans, and they are key players in all forms of intracellular vesicular trafficking events (Stenmark, 2009; Rivero-Ríos et al. , 2015). Apart from Rab7L1, several other family members have been associated with PD pathogenesis. For example, mutations in","Parkinson’s disease is a degenerative disorder of the nervous system that affects approximately 1% of the elderly population. Mutations in the gene that encodes an enzyme known as LRRK2 are the most common causes of the inherited form of the disease. Such mutations generally increase the activity of LRRK2 and so drug companies have developed drugs that inhibit LRRK2 to prevent or delay the progression of Parkinson’s disease. However, it was not known what role LRRK2 plays in cells, and why its over-activation is harmful. Steger et al. used a' proteomics' approach to find other proteins that are regulated by LRRK2. The experiments tested a set of newly developed LRRK2 inhibitors in cells and brain tissue from mice. The mice had mutations in the gene encoding LRRK2 that",380,128,0.3368
pubmed-summarization,"shock programmed to 24 j was delivered , and had to be confirmed . if unsuccessful , a system revision was recommended , and the df testing procedure was repeated . the primary end point was the fse to terminate all true episodes of vt / vf during follow - up . a blinded two - member clinical event committee reviewed the diagnostic information of the vt / vf treated with icd shocks . safety end points included procedural serious adverse events , vt / vf conversion rate , and all - cause , cardiac , or arrhythmic mortality during follow - up . all adverse events were reviewed and adjudicated by a data and safety monitoring board ( dsmb ) , consisting of three members . all patient deaths were adjudicated by the dsmb according to a classification originally described by epstein et al . the goal of the nordic icd trial was to demonstrate the non - inferiority of no df testing when compared with df testing with respect to the primary endpoint of fse . this margin was chosen because the variation of fse in published trials was in the range of 8392% . after a pre - specified blinded re - assessment , the sample size was increased to 1080 patients recruited over a period of 28 months , with a follow - up of at least 12 months . the intention - to - treat ( itt ) population which included all randomized patients , the evaluated - for - safety population which included randomized patients who received an icd , and the per protocol ( pps ) population which included randomized patients who received an icd and did not have a major protocol violation . however , for time - dependent outcomes , these patients were included up to the date of the protocol violation . the primary analysis was performed in the per protocol episode data set ( p - pps ) , which included all sufficiently documented shocked episodes in pps patients . baseline characteristics are presented group wise for the itt population as mean ( sd ) or frequency ( % ) . to compensate for the dependence structure induced by recurrent episodes with similar outcome in some of the patients","aimsthis trial was designed to test the hypothesis that shock efficacy during follow - up is not impaired in patients implanted without defibrillation ( df ) testing during first implantable cardioverter - defibrillator ( icd ) implantation.methods and resultsbetween february 2011 and july 2013 , 1077 patients were randomly assigned ( 1 : 1 ) to first time icd implantation with ( n = 540 ) or without ( n = 537 ) df testing . the intra - operative df testing was standardized across all participating centres , and all icd shocks were programmed to 40 j irrespective of df test results . the primary end point was the average first shock efficacy ( fse ) for all true ventricular tachycardia and fibrillation ( vt / vf",380,128,0.3368
dialogsum,"#Person1#: I'm looking for a white purse as a gift. Could you show what you have in stock? #Person2#: You are in luck. We just receive a shipment of several different styles of white purses. #Person1#: They must be popular again this season. #Person2#: Yes, I believe they are. Here are something that might interest you. #Person1#: Wow. this is nice. I'll take this one. I guess if she doesn't like it she can return it, right? #Person2#: Sure. Let me ring this up for you at the register. If you would like, this can be gift-wrapped for free. Just take it to the customer service department.",#Person1# purchases a white purse as a gift with #Person2#'s assistance. #Person2# tells #Person1# it can be returned if the gift-recipient doesn't like it.,107,24,0.2243
scientific_lay_summarisation-elife-norm,"differences across molecular, behavioral, and metabolic levels (Bangasser and Wicks, 2017; Brivio et al. , 2020; Hodes, 2018; Hodes and Epperson, 2019; Young and Pfaff, 2014). Very few studies, however, have looked into the interaction between pre-existing differences in social behavior between the sexes and stress. Considering that abnormalities in social functioning are an essential part of the symptomatology of stress-related disorders, differences in social behavior and social cognition prior to disorder onset are likely to contribute to disorder susceptibility. Here, we explored how social context shapes the response to chronic stress. We focused specifically on social dominance, an essential characteristic of rodent social groups. Wild and laboratory rodents form complex and dynamic social structures which typically involve the formation of dominance hierarchies (Kondrakiewicz et al. , 2019). These have been observed in the lab in group sizes ranging from three to over a dozen individuals (Horii et al. , 2017; Varholick et al. , 2019; Wang et al. , 2014). Hierarchies are thought to improve social stability and reduce severe conflicts and aggression (Curley, 2016). As a consequence, an individual’s position in the dominance hierarchy has important consequences, including preferential access to food, shelter, and mates (Drews, 1993). Social rank within male hierarchies is also known to influence health, hormonal profile, brain function, metabolism, and mortality (Pallé et al. , 2019; Razzoli et al. , 2018). For instance, subordinate individuals display increased anxiety-like behavior, a suppressed immune response, higher basal corticosterone levels, and reduced life span (Bartolomucci, 2007). These types of relationships have classically been studied in male animals, as female mice have usually appeared more communal and displayed limited aggression (König and Lindholm, 2012). Recent work, however, has demonstrated that female laboratory mice also form hierarchies that appear quite similar to those seen in males, accompanied by some of the same dominance-related physiological markers, such as differences in corticosterone levels (Schuhr, 1987; van den Berg et al. , 2015; Varholick et al. , 2019; Varholick et al. , 2018; Williamson et al. , 2019). Thus, we examined social dominance status as a putative mediator of sex differences in the response to adverse events. To do so, we took advantage of a high-throughput automated behavioral monitoring system (the Social Box, SB) to assess and better understand the hierarchies of","Most people experience chronic stress at some point in their life, which may increase their chances of developing depression or anxiety. There is evidence that chronic stress may more negatively impact the well-being of women, placing them as higher risk of developing these mental health conditions. The biological factors that underlie these differences are not well understood, which leaves clinicians and scientists struggling to develop and provide effective treatments. The social environment has a powerful influence on how people experience and cope with stress. For example, a person’s social and socioeconomic status can change their perception of and reaction to everyday stress. Researchers have found differences in how men and women relate to their social standing. One way for scientists to learn more about the biological processes involved",380,128,0.3368
dialogsum,"#Person1#: Are you from England? #Person2#: No, I'm from America. How about you? #Person1#: I live here in Paris, but I'm not French. I'm from Australia. #Person2#: Are you a student? #Person1#: No. I'm a news reporter for a TV station. #Person2#: Wow, that's a good job.",#Person1# is a news reporter from Australia. #Person2# is from America.,47,11,0.234
pubmed-summarization,"intestinal lesions has revealed a variety of entities such as streptococci , gram - positive cocci , and gram - negative or -positive rods . the mortality rate associated with this disease continues to be high due to delayed diagnosis ( 1 - 5 ) . thus , most cases reported in the literature were discovered at autopsy or after the examination of surgical specimens following surgery ( 1 - 6 ) . some reports have suggested that earlier diagnosis and surgical resection of diseased bowel , together with the use of broad- spectrum antibiotics , has led to a good outcome ( 1 , 6 ) . the pathogenesis of this disease entity is not clear : ito et al . first , the direct toxic effect of alcohol may affect the gastrointestinal tract , and prolonged alcohol ingestion leading to changes in the intestinal mucosa , with increased intestinal permeability ; subsequent penetration of the lamina propria by antigens ( organisms ) from the intestinal lumen results in a local antibody response . second , in chronic alcoholism , the systemic and mucosal immune mechanisms are impaired , and this may exacerbate bacterial infection . it is not known why the organisms involved in phlegmonous enteritis are confined to the submucosa . bowel wall edema associated with portal hypertension has been described in liver cirrhosis , and the loose connective tissue in the submucosa can be excellent soil for the rapid and diffuse spread of the organisms involved in an episode of bacteremia ( 5 ) . first , the patient was not alcoholic and had no evidence of liver disease or septicemia . second , his clinical course was silent for a long period , being discovered only at surgery ; previously reported cases , on the other hand , manifested an acute and serious clinical course , one which led even to sudden death . in our case , the early use of broad - spectrum antibiotics might have helped his condition to persist . the literature in english includes only one case report dealing with the radiologic findings pertaining to this disease . mooney et al . ( 6 ) reported the ct findings in one case , in which only nonspecific small bowel wall","phlegmonous enteritis is a rare infective inflammatory disease of the intestine , predominantly involving the submucosal layer . it is difficult to diagnose and often fatal . its association with alcoholism and various liver diseases , although rarely reported , is well documented . we report a case of phlegmonous enteritis in a male patient with congestive heart failure and colon cancer , and describe the ultrasonographic and ct findings .",380,71,0.1868
dialogsum,"#Person1#: Where are you from? #Person2#: The United States. I live in New York. #Person1#: Oh, really? That's a big city with a large population, right? By the way, do you like it there? #Person2#: Yeah. I think it's the only suitable place to live. #Person1#: Why do you say that? #Person2#: You see, there's always something exciting to do, and it's never boring. #Person1#: My place isn't boring, either. You can fish, hike, grow vegetables, and do all kinds of things, although it's small and quiet. #Person2#: It sounds like you really like it here in New Zealand.",#Person2# thinks New York is a suitable place to live. #Person1# thinks #Person1#'s place New Zealand isn't boring either.,99,19,0.1919
dialogsum,"#Person1#: What's your major? #Person2#: Hotel management. #Person1#: What do you want to do when you graduate? #Person2#: I'd like to work for a hotel or a travel agency in this area. How about you? #Person1#: At first I wanted to major in French or history, but I realized I might have a hard time finding a job, so I major in computer science. With the right skills, getting a job shouldn't be so difficult. #Person2#: Do you have a part-time job to support yourself through school? #Person1#: Fortunately for me, I received a four-year academic scholarship. #Person2#: Wow. That's great. #Person1#: Are you working your way through school? #Person2#: Yeah. I work as a cook in a restaurant near campus three times a week.","#Person1# and #Person2# talk about their majors, their career plans, and how they support themselves through school.",125,17,0.136
pubmed-summarization,", there is no study in the open scientific literature that has reported on the exact bioactive abortifacient agent(s ) in s. alata leaves . therefore , the present study aimed to validate the speculation that the alkaloids in aqueous extract of s. alata leaves are responsible for its abortifacient activity . the focus on alkaloid was a follow - up from our previous study that speculated on alkaloids to be responsible for the abortifacient activity of the crude extract of s. alata leaves and from several studies that implicated the phytochemical property of colchicine , quinazoline alkaloids , e.g. vasicine and vasicinone in several botanicals such as xylopia aethiopica , peganum harmala epigeal parts , areca catchu nuts and gloriosa superba roots as abortifacient bioactive agents and/or their role in the contraction and relaxation of uterine muscles ( 912 ) . the plant leaves , obtained from herb sellers at oja tuntun , ( new market ) in ilorin , nigeria , was authenticated at the herbarium unit of the forestry research institute of nigeria ( frin ) in ibadan , nigeria . a voucher specimen ( fhi 10845 ) was deposited at the herbarium of the institute . assay kits for both glucose and cholesterol were products of randox laboratories , ltd , united kingdom , while those of progesterone , follicle stimulating and luteinizing hormones were products of inteco uk ltd , united kingdom . thin layer chromatographic ( t lc ) plates and silica gel were products of merck ( darmstadt , germany ) . para - nitrophenyl phosphate and other reagents were products of sigma- aldrich inc . , st . male and female wistar rats ( rattus norvegicus ) weighing 178.913.07 and 143.99 1.21 g , respectively , were obtained from the animal holding unit of the department of biochemistry , university of ilorin , ilorin , nigeria . the animals which were housed individually in plastic cages and placed in a well - ventilated room ( temperature : 28 - 31c ; photoperiod : 12 hr natural light and 12 hr darkness ; humidity : 50 - 55% ) were provided with unrestricted access to rat pellets ( bendel feeds and flour mills , ewu , nigeria ) and water . the animals","backgroundthe abortifacient claim of senna alata ( s. alata ) was scientifically validated recently with alkaloids speculated to be the bioactive agent . this speculation is yet to be substantiated or refuted by scientific evidence . the present study was aimed to investigate the pregnancy terminating effects of the alkaloids from s. alata leaves.methodstwenty four pregnant rats ( 143.991.21 g ) allocated randomly to four groups : a , b , c and d respectively received , 0.5 ml of distilled water , 250 , 500 and 1000 mg / kg body weight of the s. alata extracted alkaloids orally , once daily from day 10 until day 18 post - coitum . the indices of abortifacient were evaluated at the end of the exposure period . the",380,128,0.3368
dialogsum,"#Person1#: I would appreciate it if you could go to the store for me. #Person2#: No problem. What do you want me to get? #Person1#: Here's a list with a few things that I need you to get. #Person2#: Did you forget to put anything on the list? #Person1#: I don't think I forgot anything. #Person2#: Would you like me to go anywhere else for you? #Person1#: If you don't mind, I would appreciate it if you would pick up my prescription. #Person2#: Has your prescription been filled yet? #Person1#: Someone at the pharmacy called and told me it was ready. #Person2#: Sure, I'll go get it for you. #Person1#: Thank you. #Person2#: Anything for you.","#Person1# asks for #Person2#'s help to get things on the list and pick up #Person1#'s prescription, and #Person2# agrees.",116,19,0.1638
dialogsum,"#Person1#: Who put this pile of magazines in my office? #Person2#: Alice. She said you were going to take them back to the library. #Person1#: Oh, that's right. She did ask me to take some magazines back for her. I completely forgot.",#Person2# reminds #Person1# that Alice asked #Person1# to take magazines back to the library.,42,14,0.3333
scientific_lay_summarisation-elife-norm,", 2014). 10. 7554/eLife. 16886. 003Figure 1. Domain diagram of complexin-1, mutants, and truncations. (A) Domain diagram for full-length wildtype complexin-1 (Cpx [1–134]) and complexin-1 mutants (SC, superclamp; NC, no-clamp; 4M, mutation of the central helix that prevents binding to ternary SNARE complex). (B) Domain diagrams for truncation mutants of complexin-1 (Cpx [26–134], Cpx [48–134]). : http: //dx. . org/10. 7554/eLife. 16886. 003 The central domain of complexin-1 binds to the groove formed by the synaptobrevin-2 and syntaxin-1A α-helices in the complexin-1 / ternary SNARE supercomplex (PDB ID 1KIL) (Chen et al. , 2002). This interaction is antiparallel, i. e. , the direction of the α-helix of the accessory domain of complexin-1 is antiparallel to the direction of the α-helices in the ternary SNARE complex. Functional studies, along with molecular modeling suggested that complexin-1 may inhibit full ternary SNARE complex formation by preventing the C-terminal part of synaptobrevin-2 from binding to the syntaxin-1A / SNAP-25A components of the ternary SNARE complex (Giraudo et al. , 2006,2009). However, a subsequent crystal structure of the' superclamp' mutant of complexin-1 (D27L, E34F, R37A) (1A) in complex with a partially truncated SNARE complex (containing a truncated synaptobrevin-2 fragment, amino acid range 25–60), along with isothermal titration calorimetry (ITC) and light scattering experiments instead found that complexin-1 bridges two partially truncated SNARE complexes: one partial SNARE complex binds to the central domain of complexin-1 while another partial SNARE complex weakly binds to the accessory domain of the same complexin-1 molecule (PDB IDs 3RK3 and 3RL0) (Kümmel et al. , 2011; Krishnakumar et al. , 2015). However, this weak interaction of the accessory domain was not observable by NMR (Trimbuch et al. , 2014), and its relevance has been debated (Trimbuch et al. , 2014; Krishnakumar et al. , 2015). Regardless of the ongoing studies of the biophysical interactions involving the accessory domain of complexin-1, this domain is essential for regulation of spontaneous fusion both in neurons and in reconstituted systems. For example, in rescue experiments with complexin knockdown in cultured neurons, the complexin-1 superclamp mutant slightly decreased the mEPSC (miniature excitatory postsynaptic current) frequency, while a' poor-clamp' mutant (K26E, L41K, E47K) of complexin increased the mEPSC frequency compared to wildtype control (Yang et al. , 2010). Similarly, genetic rescue experiments in Drosophila showed that the","Nerve cells communicate via electrical signals that travel at high speeds. However, these signals cannot pass across the gaps – called synapses – that separate one nerve cell from the next. Instead, signals pass between nerve cells via molecules called neurotransmitters that are released from the membrane of the first cell and recognized by receptors in the membrane of the next. Prior to being released, neurotransmitters are packaged inside bubble-like structures called vesicles. The synaptic vesicles must fuse with the cell membrane in order to release their contents into the synaptic cleft. Proteins called SNAREs work together with other proteins to allow this membrane fusion to occur rapidly after the electrical signal arrives. Complexin is a synaptic protein that binds tightly to a complex of SNARE proteins to",380,128,0.3368
pubmed-summarization,"the aids epidemic which has hit southern africa with such devastating force affects a variety of reproductive issues among infected people . these include whether or not to become pregnant , when and which type of contraception to use , and decisions on whether to continue or try to terminate a pregnancy . findings from studies in both developing and developed nations indicate that a significant proportion of hiv infected adults still desire or intend to have children . with the advent of highly active antiretroviral therapy ( haart ) and its impact on the health of the infected as well as its impact on lowering mother to child transmission of hiv , the number of hiv infected people considering childbearing has increased . while much attention has been paid to the reproductive choices and intentions of the infected as well as to some factors that influence these , most studies are silent on the role of health professionals in the reproductive and sexual lives of hiv infected people . there are few studies that mention the role of health professionals in the reproductive sphere of hiv positive people , yet these are the people who usually play a significant role in the decision making process of hiv positive people . this is because of their medical expertise and that most hiv infected people make their reproductive decisions within a biomedical and health institution context . there are some studies that have involved health professionals and they found that biomedical considerations usually dominate health care providers ' attitudes towards reproduction by hiv infected people . findings from this study indicate that there are three dominant discourses concerning childbearing by people with hiv among health professionals . the first two are rooted in the biomedical model of health where biomedical considerations are prominent while the third takes a human rights perspective . taped in - depth interviews were conducted with 12 health professionals in two opportunistic infections clinics in bulawayo . health professional interviewees were selected for their involvement in the care , treatment , and counselling of hiv positive people . this research among health professionals was part of a broader study that explored reproductive decisions among hiv positive couples in bulawayo , zimbabwe , in 2010 . interviews with",objective . the role of health professionals in the decision making process of patients is usually heard or seen from the perspective of the patients . this paper gives the usually silent and invisible health professionals voice and visibility . it describes their views and attitudes towards reproduction by couples who are hiv positive and attempts to understand their perspectives . methods . in - depth interviews were conducted with twelve health professionals at an opportunistic infections clinic . transcribed interviews were analysed using the grounded approach to identify patterns and themes concerning views and attitudes of health professionals towards reproduction by hiv positive people . results . the study found that most health professionals generally had a negative attitude towards childbearing by hiv positive couples . their,380,128,0.3368