cameron-git/pile_test_val · Datasets at Hugging Face

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Barbara Ingram School for the Arts Barbara Ingram School for the Arts is a magnet high school that opened its doors for gifted art students in August 2009. Currently there are eight different majors: Theatre, Musical Theatre, Technical Theatre, Vocal Music, Instrumental Music, Dance, Creative Writing, and Visual Arts. The Literary Arts program was added at the start of the 2011-2012 school year. The school building is located adjacent to the Maryland Theatre in the arts and entertainment district of downtown Hagerstown, Washington County, Maryland, United States. Despite being a public school, applications and auditions are part of a process needed in order to be accepted and then enrolled. Barbara Ingram School is also unique in that it will accept students not only from all of Washington County but also from proximate Maryland counties and areas in nearby Pennsylvania and West Virginia. Rob Hovermale is the current Principal. There are no sports teams originating from the school. BISFA is named for late Barbara Ingram, a Hagerstown native and former public school art teacher. Performances and exhibitions All-School Musicals 2009-2010 The first all school musical was Thoroughly Modern Millie and received rave reviews. 2010-2011 The all school musical The Phantom of the Opera was performed during the 2010 to 2011 school year. Barbara Ingram School for the Arts was one of the first high schools to perform this musical. Not only was the performance well received, it is also considered a milestone in the revival of downtown Hagerstown. 2011-2012 The 2012 all school musical was Disney's Beauty and The Beast and ran for two weekends at the Maryland Theatre. 2012-2013 The 2013 Barbara Ingram was Legally Blonde and received some of the highest praise for acting. It was the final musical for the first full graduating class. 2013-2014 In August 2013, Barbara Ingram announced that its fifth all-school musical will be the classic The Wizard of Oz. It was performed in April 2014. 2014-2015 In April 2015, Shrek the Musical was performed by students from all departments. 2015-2016 In April 2016, Barbara Ingram performed "The little Mermaid" as their 7th all school musical. 2016-2017 In April 2017, Barbara Ingram presented "Seussical" at the Maryland Theater as their 8th musical. 2017-2018 In April 2018, Barbara Ingram presented “Hairspray” at the Maryland Theater as their 9th musical. 2018-2019 In April 2019, Barbara Ingram presented "Mamma Mia!" at the Maryland Theater as their 10th musical. Additional Performances In the summer of 2010 thirty-seven vocalists traveled to New York City to perform in Eric Whitacre's Paradise Lost: Shadows and Wings at Carnegie Hall. The dance department has also traveled to perform at the Orange Bowl. In 2010, the choral ensemble had the opportunity to sing as the backup choir for Todd Rundgren's fall tour. The Barbara Ingram Music Theatre Ensemble, the "Phantasmics", performed at Downtown Disney in Orlando Florida in the summer of 2011 and in Disney and Universal theme parks in 2012. There are many performances year-round at the school, including the yearly Holiday Spectacular, in which all disciplines participate. Performances have occurred in The Maryland Theatre, in the downstairs "Black Box" of the main building, and at other locations around the community. Mascot The Barbara Ingram school mascot is 'The Phantom,' alluding to the alleged ghost that haunts the lower level of the building. The school colors are purple, black and silver. Notable Alumni Nathaniel Philp, Former Volunteer Firefighter, Former Assistant Manager of Moe's Southwest Grill (Hagerstown) References External links Official site Washington County Public Schools: Barbara Ingram School for the Arts Category:Public high schools in Maryland Category:Public schools in Washington County, Maryland Category:Buildings and structures in Hagerstown, Maryland Category:Magnet schools in Maryland Category:Performing arts in Maryland Category:2009 establishments in Maryland Category:Educational institutions established in 2009	{ "pile_set_name": "Wikipedia (en)" }
Lolita, the whale, has been living at the Miami Seaquarium since her capture off the northern Pacific Coast in 1970. © Flickr / Ross Cobb The tank measures 80 x 60 feet wide and 20 feet deep. People for the Ethical Treatment of Animals (PETA), the Animal Legal Defense Fund and other groups had sued the US Department of Agriculture in 2012, claiming the tank Lolita lives in violates the Animal Welfare Act and that regulators have been "rubber-stamping" an aquarium’s license to keep her. "Lolita is being held in the smallest orca tank in America, she has no shelter from the hot sun in Miami, she has no company of a single other orca. And all of those violate the basic standards of the Animal Welfare Act," PETA attorney Delcianna Winders said. The tank measures 80 x 60 feet wide and 20 feet deep. The Judge dismissed the lawsuit in March 2014, on the terms that the agency is allowed to reissue licenses without re-inspecting facilities. Activists argue now that the US District Court should have looked into the animal rights abuses before approving the USDA’s license renewal. "It’s absurd to give out licenses where you know there are blatant violations going on and that undermines the purpose of the animal welfare act," said Winders. But Seaquarium and USDA lawyers beg to differ. Renewing the license only required an annual application, an annual report from the aquarium and a $100 fee, said Assistant US Attorney Anthony Erickson-Pogorzelski. In another attempt to free Lolita, the federal government agreed to list her as an endangered species in February, which would allow for her release into the wild. However, seaquarium officials are skeptical, fearing she would see the fate of Keiko, the orca in the 1993 movie "Free Willy." Keiko was released into the waters off Iceland in 2002 but died a year later after being rejected by wild orcas.	{ "pile_set_name": "OpenWebText2" }
Subungual melanoma--case report and literature review. Subungual melanoma is an infrequent malignant tumor which, despite its visibility and easy accessibility, is often misdiagnosed and thus inappropriately treated. This delay in recognition often results in a worsened prognosis. All persistent nail lesions which do not respond to conservative treatment, whether pigmented or not, should undergo excisional biopsy and pathologic examination. A case of subungual melanoma is presented to illustrate the typical presentation and clinical characteristics.	{ "pile_set_name": "PubMed Abstracts" }
(a) Field of the Invention The present invention relates to a channel state feedback method by quantizing time domain channel coefficients. (b) Description of the Related Art In a multiple-user multiple-antenna communication system, communication between a plurality of terminals and base stations is simultaneously performed at the same time and same frequency through a spatially identified signal. In this instance, a terminal must not be interfered with by a signal transmitted to another user during communication through a single receiving antenna. For this, a base station performs an appropriate beamforming process based on channel information with the terminal. In detail, one part of information to be known by the base station in the multiple-user multiple-antenna communication system is channel information with the terminal to be simultaneously communicated by the base station. In the frequency division duplex (FDD) system, the terminal measures channel information between the base station and the terminal and transmits a measured channel coefficient (a channel value) to the base station so that the base station knows the channel information. Considering the existing multiple-user multiple-antenna communication system, the terminal transmits a quantized direction of a channel vector for the base station and the terminal and a corresponding signal-to-noise ratio (SNR) value to the base station. Here, the channel vector indicates a channel state between the base station and the terminal. The channel state is expressed as a channel vector assuming that the base station has a plurality of transmitting antennas and the terminal has a single receiving antenna. The base station selects a plurality of appropriate terminals from among many terminals in consideration of the channel state, and transmits data to the selected terminals. In this instance, what is to be considered when the terminals are selected is selection of the terminals having less interference between the quantized directions of the channel vectors of the selected terminals and having a great SNR. The orthogonal frequency division multiplexing (OFDM) system is widely used for transmitting signals in the current communication system. However, the above-noted scheme is difficult to apply to the OFDM system because it is proposed for a single-carrier system. This is because channel state transmission in the frequency domain from the terminal to the base station is not performed by all subcarriers, but several subcarriers are sampled by considering the limited feedback resource and the channel state is then transmitted on the sampled subcarrier in the OFDM system. The base station uses the channel state on the sampled subcarrier, and performs an interpolation process for checking state information of the subcarrier receiving no channel state value to know the channel state on the subcarrier. However, the above-noted existing method transmits not the channel vector but the quantized value of the channel vector direction to the base station. Therefore, it is difficult to know directions of other subcarriers by using the quantized direction of the channel vector on a specific sampled subcarrier. The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.	{ "pile_set_name": "USPTO Backgrounds" }
When you subscribe we will use the information you provide to send you these newsletters. Sometimes they’ll include recommendations for other related newsletters or services we offer. OurPrivacy Noticeexplains more about how we use your data, and your rights. You can unsubscribe at any time. Read More Related Articles Restrictions not imposed While at the secure facility on Merseyside, Arnold gradually improved and was moved to the lower-security Edenfield Centre in Prestwich, Manchester, in late 2011. Dr Andrew Haddock, a forensic psychiatrist who was involved in Arnold’s care three years prior to the murder, recommended in January 2013 that should Arnold leave care it should be under special legal orders requiring supervision to prevent a relapse. The court heard when Arnold was eventually released a specialist tribunal chose not to impose such a restriction, called a Community Treatment Order. While the details of that hearing were not discussed, Arnold’s treatment history - including that offered through what is now the Greater Manchester Mental Health NHS Foundation Trust - is under the scope of Coroner Kevin McLoughlin’s investigation. Read More Related Articles Double tragedy Earlier in the day Maureen Lound, Mr Lound’s mum, called for Arnold’s past care - and his involvement with the police and courts, to come under scrutiny. She said: “I bear no malice towards Arnold, he was a very sick man and was moved within days of his arrest to Ashworth special hospital, where he remained until his conviction. “I do not blame Arnold for Will’s death. Unfortunately Arnold did not receive the care and treatment he needed to live safely in the community. A man like Arnold should not have been allowed to roam the streets unsupervised.” Ms Lound also paid tribute to her daughter, Gini, who tragically took her own life just months after her brother’s died. Read More Related Articles Mistakes followed by murder Jurors were told Arnold, homeless when he killed Mr Lound on February 7, 2016, was on the streets despite breaching bail conditions. He was bailed by magistrates following a theft charge in December 2015. He failed to reside at a specific address but was then arrested over shoplifting allegations and breach of bail the following month. William Lound Despite an application by Greater Manchester Police for him to be remanded in custody, magistrates re-bailed him with stricter conditions. He failed to comply with them but an “administrative error” by the force meant the bail condition was not registered. This meant officers were not aware of the further breach and no effort to arrest Arnold over it was made. Ms Lound said she believed an arrest would have presented magistrates with another opportunity to remand him - therefore taking him off the streets before he murdered her son.	{ "pile_set_name": "Pile-CC" }
The ethics of using AOL search data Can researchers ethically use the search data that AOL released last week? Like one of the forest fires that each summer consumes a major chunk of California real estate, the AOL data release scandal has quickly exploded from a campfire into an inferno. Giving the search history of 650,000 users to researchers seemed like a good idea when Abdur Chowdhury first posted it, but the move quickly claimed Dr. Chowdhury's job, as well as that of a supervisor. Maureen Govern, the company's CTO, also resigned the same day. Now the flames of controversy have spread into academia, where researchers desperately want to use the new data set but feel caught in an ethical dilemma. Given that AOL has already pulled the data, and given that it can be used to uniquely identify some individuals, should researchers refuse to use the data for their work? Jon Kleinberg, a computer science professor at Cornell, told the New York Times that he won't touch the hundreds of megabytes of search query data. "Now it's sitting there, in cold storage," he said. "The number of things it reveals about individual people seems much too much. In general, you don't want to do research on tainted data." It would be much easier for the researchers to turn down this forbidden fruit if apples grew on every tree. But when it comes to quality search data, options are limited unless you work for one of the major search engines (or are with the government). For researchers who have been stuck with the same search data for almost 10 years, the new information comes like rain to a Dust Bowl farmer. Jeffrey Seglin, author of a syndicated ethics column called "The Right Thing" (and a book by the same name), tells Ars that, in his view, the ethical obligation "here falls upon the companies that are releasing the data. If these companies have made a commitment to keep individual behavior private, then they have an obligation to make sure that the data they release can't be manipulated to discover the identities of the users." When it comes to research, though, Seglin has no problem with people who want to use the data for their own projects—provided they do not cross one important boundary. "If researchers are using the data to identify individual users, I believe they've crossed an ethical line," Seglin says. But if they don't try to match up the data with actual people, he believes that they are (ethically) in the clear. One unfortunate side effect of the entire AOL debacle is that search engines will now be more wary about releasing data— and they were already stingy to begin with. On the other hand, when they do release data in the future, search engines will certainly pay far more attention to the privacy implications of what they're doing.	{ "pile_set_name": "Pile-CC" }
NEW YORK — "The Daily Show" is unveiling the Donald J. Trump Presidential Twitter Library this weekend. "He is a damn fine twitterer," "Daily Show" host Trevor Noah said. The pop-up exhibit will be at 3 West 57th Street in Manhattan, not far from Trump Tower, Comedy Central announced. It will feature some of the president's better known one-shots, organized around such categories as "SAD! A Retrospective" and "The Commander-In-Tweet." The "Daily Show" will highlight Trump's insults and contradictions and allow "verified survivors" to remember being on the receiving end of his social media outbursts. "I think it's a chance for us to really understand the way in which our commander in chief communicates," said show correspondent Jordan Klepper. The twitter library also features an interactive Trump nickname generator. There's a locked vault jokingly marked as 'Trump's Tax Returns.' But the true highlights are all in 140 characters or less. Daily Show Correspondent Hasan Minhaj's favorite tweet is Trump's well known Cinco de Mayo tweet featuring the taco bowl at Trump Tower. He calls it the Mona Lisa tweet. "It's both pandering to minorities while also plugging his business," Minhaj said. Favorites could change as President Trump is a frequent tweeter. A siren will sound in the library every time Trump tweets. "Whenever he does tweet, a siren will go off bing bing bing bong bing, letting everyone know in the building that he is tweeting, so to either run outside and call loved ones or run underneath a table," Minhaj said. The exhibit runs Friday through Sunday, and will be open from 11 a.m. to 7 p.m. Admission is free.	{ "pile_set_name": "OpenWebText2" }
Introduction {#s1} ============ Chinese herbal medicines (CHMs) were the main treatment method used in ancient times by the Chinese to combat disease. As early as the Qin and Han Dynasty (around 221 BCE to 220 CE), Sheng Nong\'s Herbal Classic recorded 365 medicines. By the time of the Ming Dynasty (1368--1644), the number of CHMs listed in the book of Compendium of Materia Medica had increased to 1892. Most herbal medicines in such publications have been used constantly throughout medical history and are still applied in practice today. For example, according to Sheng Nong\'s Herbal Classic, Coptis chinensis Franch. was found to relieve abdominal pain and diarrhea and this herb is still widely used in China for the treatment of diarrhea or dysentery. Further, Panax notoginseng (Burk.) F. H. Chen, a traditional herb was initially used to stop bleeding, promote blood circulation and ease pain, was recorded in the Compendium of Materia Medica. It is now commonly used in cases of trauma and cardiovascular, and cerebrovascular diseases. A recent meta-analysis further demonstrated that several P. notoginseng preparations are beneficial for patients with unstable angina pectoris (Song et al., [@B121]). Despite the positive effects of CHMs, little is known about their effective constituents, bioactive ingredients, and mechanisms of action. Therefore, in addition to the clinical applications mentioned in classic texts, understanding the specific active ingredients and clarifying the mechanisms of action of these compounds would facilitate the improved application of CHMs. The discovery of the drug artemisinin best illustrates the importance of CHM to the world (Tu, [@B133]), inspiring the notion that, through study of their bioactive ingredients, CHMs can help people around the world to conquer life-threatening diseases. Non-coding RNA molecules (ncRNAs), which mainly comprise miRNA, lncRNA, and circRNA, do not encode proteins; however, as the most abundant class of RNA (at least 90%) (Sana et al., [@B113]), ncRNAs have important functions in gene regulation and are involved in pathological processes contributing to many diseases (Batista and Chang, [@B4]; Memczak et al., [@B97]; Zhang et al., [@B177]), particularly cancer, and cardiovascular and nervous system diseases. Moreover, circRNA and lncRNA act as competitive endogenous RNAs (ceRNA), which are natural miRNA sponges that influence miRNA-induced gene silencing via miRNA response elements (Tay et al., [@B127]). Thus, complex regulatory networks exist, comprising circRNA, lncRNA, miRNA, and target genes. Unraveling of this complexity has laid the foundation for a comprehensive understanding of the pathology and treatment of diseases influenced by gene regulatory networks, rather than only core disease-related genes (Boyle et al., [@B9]). Excitingly, recent studies (Feng et al., [@B30]; Tian F. et al., [@B128]; Zhou Y. et al., [@B196]) have revealed that some miRNA, lncRNA, circRNA, and ceRNA crosstalk can be regulated by bioactive ingredients from CHMs, which often have multiple targets ([Table 1](#T1){ref-type="table"}). By influencing regulatory mechanisms, including pro-apoptosis (Feng et al., [@B30]), anti-proliferation and anti-migration (Liu T. et al., [@B83]), anti-inflammation (Fan et al., [@B28]), anti-atherosclerosis (Han et al., [@B42]), anti-infection (Liu et al., [@B79]), anti-senescence (Zhang J. et al., [@B178]), and suppression of structural remodeling (Liu L. et al., [@B81]), these ingredients exert protective functions in cancer, cardiovascular disease, nervous system disease, inflammatory bowel disease, asthma, infectious diseases, and senescence-related diseases. ###### Detailed information on bioactive ingredients targeting ncRNAs. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ No. Name of ingredient Original plant ncRNA target Gene/protein/pathway Disease --------- ------------------------------------------ ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------ ---------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- 1 Berberine Coptis chinensis Franch., Berberis soulieana Schneid, Berberis poiretii Schneid., Berberis vernae Schneid, Berberis wilsoniae Hemsl., and Platycladus orientalis (Linn.) Franco. miR-99a\~125b (Feng et al., [@B30])\ RAC1, NFκB1, MYC, JUN, and CCND1 (Feng et al., [@B30])\ Multiple myeloma (Luo et al., [@B89]; Feng et al., [@B30]; Yin et al., [@B166]) miR-21 (Luo et al., [@B89])\ IL6/STAT3, PDCD4 (Luo et al., [@B89])\ miR-19a/92a (Yin et al., [@B166]) P53 signaling pathway (Luo et al., [@B89])\ P53, ERB, and MAPK signaling pathways (Feng et al., [@B30]) miR-23a (Wang N. et al., [@B141]) NEK6, P53, P21, GADD45α (Wang N. et al., [@B141]) Hepatocellular carcinoma (Wang N. et al., [@B141]) miR-152\ DNMT1, DNMT3A, DNMT3B, CDK4\ Colorectal cancer (Su et al., [@B123]; Huang et al., [@B48]) miR-429\ (Su et al., [@B123]; Huang et al., [@B48])\ miR-29a (Huang et al., [@B48])\ Pin1-β-catenin-cyclin D1 signaling pathway (Su et al., [@B123]) miR-296-5p (Su et al., [@B123]) miR-34a\ CDK4, CyclinD1, CyclinE, CDK2 (Yang L. H. et al., [@B159]) Melanoma (Yang L. H. et al., [@B159]) miR-154\ miR-26a\ miR-124 (Yang L. H. et al., [@B159]) miR-93 (Chen et al., [@B17]) miR-93/PTEN/AKT signaling pathway (Chen et al., [@B17]) Ovarian cancer (Chen et al., [@B17]) miR-203 (You et al., [@B167]) BCL-w (You et al., [@B167]) Gastric cancer (You et al., [@B167]) miR-27a miR-27b (Wu et al., [@B154]) PPAR-γ (Wu et al., [@B154]) Obesity (Wu et al., [@B154]) lncRNA MRAK052686 (Yuan et al., [@B172]) NRF2 (Yuan et al., [@B172]) Steatotic liver (Yuan et al., [@B172]; Li C. H. et al., [@B69]) miR-373 (Li C. H. et al., [@B69]) EGR1, AKT1\ AKT-mTOR-S6K signaling pathway (Li C. H. et al., [@B69]) miR-29a-3p (Mao et al., [@B94]) IRS1 (Mao et al., [@B94]) Insulin resistance (Mao et al., [@B94]) 2 Artesunate Artemisia annua L. lncRNA UCA1\ lncRNA UCA1/miR-184/BCL-2 axis (Zhou S. et al., [@B194]) Prostate cancer (Zhou S. et al., [@B194]) miR-184 (Zhou S. et al., [@B194]) 3 Triptolide/ Triptonide Tripterygium wilfordii Hook. f miR-21 (Li et al., [@B74]) Caspase-3 and 9, PTEN (Li et al., [@B74]) Non-small cell lung cancer (Li et al., [@B74]) 227 miRNAs (Reno et al., [@B109]) Focal adhesion kinase (Reno et al., [@B109]) Lung cancer (Reno et al., [@B109]) miR-17-92\ c-MYC, BIM, PTEN, and P21 (Li S. G. et al., [@B71]) Hepatocellular carcinoma (Li S. G. et al., [@B71]) miR-106b-25 (Li S. G. et al., [@B71]) lncRNA THOR (Wang et al., [@B143]) IGF2BP1, Myc, IGF2, and Gli1 (Wang et al., [@B143]) Nasopharyngeal carcinoma (Wang et al., [@B143]) 4 Ailanthone Ailanthus altissima (Mill.) Swingle miR-21 (Yang P. et al., [@B160]) caspase 3, caspase 9, Beclin-1, LC3-II, p62, and cyclin D1\ Vestibular schwannomas (Yang P. et al., [@B160]) Ras/Raf/MEK/ERK and mTOR pathways (Yang P. et al., [@B160]) 5 Cordycepin/Soya-cerebroside Cordyceps militaris miR-21 (Yang et al., [@B157]) PTEN, Akt (Yang et al., [@B157]) Renal cell carcinoma (Yang et al., [@B157]) miR-432 (Liu S. C. et al., [@B82]) MCP-1\ \ AMPK and AKT signaling pathways (Liu S. C. et al., [@B82]) Osteoarthritis\ (Liu S. C. et al., [@B82]) 6 Tubeimoside I Bolbostemma paniculatum (Maxim) Franquet miR-126-5p (Shi et al., [@B118]) VEGF-A/VEGFR-2/ERK signaling pathway (Shi et al., [@B118]) Non-small cell lung cancer (Shi et al., [@B118]) 7 Oridonin Rabdosia rubescens (Hemsl.) Hara 105 miRNAs (Gui et al., [@B37]) / Laryngeal cancer (Gui et al., [@B37]) 8 Curcumin Curcuma longa L. miR-208 (Guo H. et al., [@B38]) CDKN1A (Guo H. et al., [@B38]) Prostate cancer (Guo H. et al., [@B38]; Cao et al., [@B11]; Liu W. L. et al., [@B84]; Zhang et al., [@B176]) miR-145\ CCND1, CDK4, OCT4, CD44, and CD133 (Liu W. L. et al., [@B84]) lncRNA-ROR (Liu W. L. et al., [@B84]) miR-770-5p\ DLK1-DIO3 (Zhang et al., [@B176]) miR-1247 (Zhang et al., [@B176]) miR-143 (Cao et al., [@B11]) PGK1, FOXD3 (Cao et al., [@B11]) miR-98 (Liu W. L. et al., [@B84]) LIN28A, MMP 2, MMP9 (Liu W. L. et al., [@B84]) Lung cancer (Tang et al., [@B126]; Liu W. L. et al., [@B84]) miR-186\* (Tang et al., [@B126]) / miR-203 (Saini et al., [@B112]) AKT2, SRC (Saini et al., [@B112]) Bladder cancer (Saini et al., [@B112]) miR-33b (Sun et al., [@B124]) XIAP (Sun et al., [@B124]) Gastric cancer (Sun et al., [@B124]) miR-192-5p (Jin et al., [@B57]) PI3K/AKT signaling pathway (Jin et al., [@B57]) Non-small cell lung cancer (Jin et al., [@B57]) miR-7 (Ma et al., [@B92]) SET8 (Ma et al., [@B92]) Pancreatic cancer (Ma et al., [@B92]) miR-30c (Lu et al., [@B87]) MTA1 (Lu et al., [@B87]) Paclitaxel-resistant non-small-cell lung cancer (Lu et al., [@B87]) miR-29b-1-5p (Zhou S. et al., [@B194]) PPARG, RRM2, SRSF1, EPAS1, MAPK, mTOR, PI3K-AKT, AMPK, TNF\ Adriamycin-resistant breast cancer (Zhou S. et al., [@B194]) RAS signaling pathways (Zhou S. et al., [@B194]) lncRNA AK294004 (Wang Q. et al., [@B142]) Cyclin D1(Wang Q. et al., [@B142]) Radioresistant nasopharyngeal carcinoma (Wang N. et al., [@B141]) miR-146a (Wu et al., [@B152])\ NF-κB signaling (Wu et al., [@B152])P38 (Li et al., [@B73]) Glioblastoma (Wu et al., [@B152]; Li et al., [@B73]) miR-378 (Li et al., [@B73]) miR-34a (Guo et al., [@B39]) BCL-2, BMI-1 (Guo et al., [@B39]) Breast cancer (Guo et al., [@B39]; Zhou et al., [@B195]) miR-29b-1-5p\ DDIT4, EPAS1, VEGFA, RPS14, and DCDC2 (Zhou et al., [@B195]) miR-29b-3p\ miR-6068\ miR-6790-5p\ miR-4417 (Zhou et al., [@B195]) miR-122\ FGF2, MMP2, VEGF, HGF, TF, FVII (Zhang S. et al., [@B184]) Hepatocellular Carcinoma (Guo Y. et al., [@B40]; Liu W. L. et al., [@B84]) miR-221 (Zhang S. et al., [@B184]) lncRNA AK125910 (Guo Y. et al., [@B40]) miR-155 (Ma F. et al., [@B91]) TNF-α, IL-6\ LPS-induced inflammatory response (Ma F. et al., [@B91]) PI3K/AKT pathway (Ma F. et al., [@B91]) miR-17-5p (Tian L. et al., [@B129]) WNT signaling pathway effector TCF7l2 (Tian L. et al., [@B129]) Adipogenic differentiation (Tian L. et al., [@B129]) 9 Shikonin Lithospermum erythrorhizon Sieb. et Zucc. miR-106b (Huang and Hu, [@B47]) miR-106b/PTEN/AKT/mTOR signaling pathway (Huang and Hu, [@B47]) Endometrioid endometrial cancer (Huang and Hu, [@B47]) miR-128 (Wei et al., [@B148]) BAX (Wei et al., [@B148]) Breast cancer (Wei et al., [@B148]) miR-143 (Liu et al., [@B80]) BAG3 (Liu et al., [@B80]) Glioblastoma (Liu et al., [@B80]) 10 Paeoniflorin Paeonia lactiflora Pall. miR-16 (Li W. et al., [@B72]) MMP-9 (Li W. et al., [@B72]) Glioma (Li W. et al., [@B72]) 11 Honokiol Magnolia grandiflora miR-34a (Avtanski et al., [@B3]) STAT3\ Breast tumor (Avtanski et al., [@B3]) WNT1-MTA1-β-catenin signaling (Avtanski et al., [@B3]) 12 Schisandrin B Schisandra sphenanthera Rehd. et Wils. miR-150\ miR-150/ lncRNA BCYRN1/ cell proliferation axis (Zhang X. Y. et al., [@B185]) Asthma (Lu et al., [@B85]) lncRNA BCYRN1 (Zhang X. Y. et al., [@B185]) 13 Resveratrol Grapes, blueberries, Morus alba L.,\ lncRNA MALAT1 (Ji et al., [@B52]) c-MYC, MMP-7\ Colorectal cancer (Ji et al., [@B52]; Karimi Dermani et al., [@B60]) Polygonum cuspidatum Sieb. et Zucc. and Rubus idaeus L. WNT/β-catenin signaling (Ji et al., [@B52]) miR-200c (Karimi Dermani et al., [@B60]) Vimentin, ZEB-1, E-cadherin (Karimi Dermani et al., [@B60]) miR-221 (Wu and Cui, [@B151]) NF-κB, TFG (Wu and Cui, [@B151]) Melanoma (Wu and Cui, [@B151]) miR-21\ P53, PTEN, EGFR, STAT3, COX-2, NF-κB\ Glioma (Wang G. et al., [@B136]) miR-30a-5p\ PI3K/AKT/mTOR pathway (Wang G. et al., [@B136]) miR-19 (Wang G. et al., [@B136]) miR-155 (Ma C. et al., [@B90]) TNF-α, IL-6, MAPKs, STAT1/STAT3, and SOCS1 (Ma C. et al., [@B90]) LPS-induced inflammatory response (Ma C. et al., [@B90]) miR-663\ JUNB, JUND, activator protein-1 (Tili et al., [@B130]) Malignancies (Tili et al., [@B130]) miR-155 (Tili et al., [@B130]) miR-96 (Bian et al., [@B6]) BAX (Bian et al., [@B6]) Hypoxia/ischemia-induced brain injury (Bian et al., [@B6]) miR-13\ CREB, BDNF (Zhao et al., [@B190]) Alzheimer\'s disease (Zhao et al., [@B190]) miR-124 (Zhao et al., [@B190]) 14 Soybean Isoflavones Glycine max (Linn.) Merr. miR-29a\ TRIM68, PGK-1 (Li et al., [@B75]) Prostate cancer (Li et al., [@B75]) miR-1256 (Li et al., [@B75]) 15 Matrine Sophora flavescens Ait miR-19b-3p (Wei et al., [@B149]) PTEN (Wei et al., [@B149]) Melanoma (Wei et al., [@B149]) 16 Corylin Psoralea corylifolia Linn lncRNA GAS5 (Chen et al., [@B14]) / Hepatocellular carcinoma (Chen et al., [@B14]) 17 Tanshinone IIA/Magnesium lithospermate B Salvia miltiorrhiza Bge. miR-155\ TLR4, MyD88, GM-CSF, sICAM-1, CXCL-1, MIP-1α, TNF-α, IL-1β, COX-2\ LPS-induced inflammation (Fan et al., [@B28]) miR-147\ TLR4-NF-κB pathway (Fan et al., [@B28]) miR-184\ miR-29b\ miR-34c (Fan et al., [@B28]) miR-146b\ CRP, ox-LDL, IL-1β, IL-6, IL-12, TNF-α, CCL-2, CD40, and MMP-2 (Xuan et al., [@B156]) Atherosclerosis (Xuan et al., [@B156]) miR-155 (Xuan et al., [@B156]) miR-133 (Zhang et al., [@B180]) MAPK ERK1/2 (Zhang et al., [@B180]) Hypoxia (Zhang et al., [@B180]) miR-1 (Shan et al., [@B116]; Zhang et al., [@B187]) SRF, Kir2.1 (Shan et al., [@B116]) Arrhythmias post-AMI (Shan et al., [@B116]) Cx43, SRF, MEF2,\ Myocardial infarction (Zhang et al., [@B187]) P38 MAPK signal pathway (Zhang et al., [@B187]) miR-107 (Yang et al., [@B164]) GLT-1, glutamate (Yang et al., [@B164]) Cerebral I/R injury (Yang et al., [@B164]) 18 Baicalin Scutellaria baicalensis Georgi miR-191a (Wang L. et al., [@B140]) ZO-1 (Wang L. et al., [@B140]) Inflammatory bowel disease (Wang L. et al., [@B140]) miR-294 (Wang J. et al., [@B146]) c-jun and c-fos (Wang J. et al., [@B146]) Inhibition of proliferation (Wang J. et al., [@B138]) 19 Cinnamaldehyde Cinnamomum cassia Presl. miR-21\ TNF-α, IL-1β, IL-6, AKT, mTOR, COX2 (Qu et al., [@B107]) Ulcerative colitis (Qu et al., [@B107]) miR-155 (Qu et al., [@B107]) has-circ-0043256, miR-1252 (Tian F. et al., [@B128]) has-circ-0043256/miR-1252/ITCH axis\ Non-small cell lung cancer (Tian F. et al., [@B128]) WNT/β-catenin pathway (Tian F. et al., [@B128]) 20 Geniposide Gardenia jasminoides Ellis miR-145 (Su et al., [@B122]) IL-6, TNF-α, MCP-1,\ Inflammation in cardiomyocyte (Su et al., [@B122]) MEK/ERK pathway (Su et al., [@B122]) 21 Carvacrol/ Thymol Origanum vulgare L. or wild bergamot miR-155\ TLR2, TLR4, SOCS1, SHIP1 (Khosravi and Erle, [@B61]) Asthma (Khosravi and Erle, [@B61]) miR-146a\ miR-21 (Khosravi and Erle, [@B61]) 22 3-acetyl-11-keto-β-boswellic acid Boswellia serrata miR-155 (Sayed et al., [@B114]) P-IκB-α, carbonyl protein, SOCS-1 (Sayed et al., [@B114]) Neuroinflammation (Sayed et al., [@B114]) 23 Sinapic acid Sinapis alba L. LncRNA MALAT1 (Han et al., [@B42]) ET-1, IL-1β, ASC, NRLP3, Caspase-1 (Han et al., [@B42]) Diabetic atherosclerosis (Han et al., [@B42]) 24 Polydatin Polygonum cuspidatum Sieb. et Zucc. miR-214 (Zhou et al., [@B192]) Blood glucose, ALT, AST, TC, TG, LDL-C, HDL-C, MDA, SOD (Zhou et al., [@B192]) Atherosclerosis with liver dysfunction (Zhou et al., [@B192]) 25 Ampelopsin Ampelopsis grossedentata miR-21 (Yang D. et al., [@B158]) eNOS, DDAH1, NO, and ADMA (Yang D. et al., [@B158]) Endothelial dysfunction (Yang D. et al., [@B158]) miR-34a (Kou et al., [@B64]) SIRT1-mTOR signal pathways (Kou et al., [@B64]) Neurodegenerative diseases (Kou et al., [@B64]) 26 Icariine Epimedium brevicornu Maxim. miR-34c (Liu et al., [@B79]) RUNX2, JNKs, and p38,\ Bacteria-induced bone loss diseases (Liu et al., [@B79]) NF-kB pathways (Liu et al., [@B79]) miR-21 (Li J. et al., [@B70]) PTEN, RECK, Caspase-3, and BCL-2 (Li J. et al., [@B70]) Ovarian cancer (Li J. et al., [@B70]) 27 Ginsenosides Panax ginseng C. A. Mey. miR-15b (Chan et al., [@B13]) IP-10 (Chan et al., [@B13]) H9N2/G1 infection (Chan et al., [@B13]) 28 Salidroside Rhodiola rosea L let-7c\ p53, transcription factor CREB\ Senescence (Zhang J. et al., [@B178]) let-7e\ \ miR-3620\ \ miR-411\ \ miR-24-2-5p\ \ miR-485-3p (Zhang J. et al., [@B178]) AKT/mTOR signaling (Zhang J. et al., [@B178]) 29 Phlorizin Acanthopanax senticosus (Rupr. et Maxim.) Harms miR-135b (Choi et al., [@B24]) p63, PCNA, integrin α6, integrin β1, and type IV collagen (Choi et al., [@B24]) Skin aging (Choi et al., [@B24]) 30 Osthole Cnidium monnieri (L.) Cuss. miR-107 (Xiao et al., [@B155]) Aβ, BACE1, and LDH (Xiao et al., [@B155]) Alzheimer\'s disease (Xiao et al., [@B155]) 31 Panax Notoginseng Saponins Panax notoginseng (Burk.) F. H. Chen. miR-29c (Liu L. et al., [@B81]) Collagen (Col) 1a1, Col1a2, Col3a1, Col5a1, FBN1, TGFβ1 (Liu L. et al., [@B81]) Myocardial injury and fibrosis (Liu L. et al., [@B81]) miR-146b-5p (Wang J. et al., [@B146]) / Oxidative damage (Wang J. et al., [@B146]) miR-34a (Lai et al., [@B66]) miR-34a/SIRT1/p53 pathway (Lai et al., [@B66]) Senescence (Lai et al., [@B66]) miR-18a (Yang Q. et al., [@B162]) CD34, VWF (Yang Q. et al., [@B162]) Tumor complicated with myocardial ischemia (Yang Q. et al., [@B162]) miR-222 (Yang Q. et al., [@B161]) p27 and PTEN\ Lewis lung carcinoma (Yang Q. et al., [@B161]) Met/miR-222 axis (Yang Q. et al., [@B161]) 32 Tetrandrine Stephania tetrandra S. Moore. miR-27b\ VEGFC, BCL2L12, COL4A3, FGFR2 (Ning et al., [@B103]) Hypertrophic scar (Ning et al., [@B103]) miR-125b (Ning et al., [@B103]) 33 Leonurine Leonurus artemisia (Laur.) S. Y. Hu F. miR-1 (Lu et al., [@B86]) ANP, ET-1, p38 MAPK, p-p38 MAPK, myocyte enhancer factor 2, β-myosin heavy chain, and α-myosin heavy chain protein (Lu et al., [@B86]) Cardiomyocyte hypertrophy (Lu et al., [@B86]) 34 Calycosin/\ Astragalus membranaceus (Fisch.) Bunge. miR-375 (Wang Y. et al., [@B145]) ER-α and Bcl-2 and RASD1 (Wang Y. et al., [@B145]) Cerebral I/R injury (Wang Y. et al., [@B145]) Astragaloside IV/Total flavonoids lncRNA EWSAT1 (Kong et al., [@B63]) / Nasopharyngeal carcinoma (Kong et al., [@B63]) miR-34a (Zhang C. et al., [@B174]) LDHA, MCT1, MCT4, HIF-1α, CD147, TIGAR and p53 (Zhang C. et al., [@B174]) Gastric carcinoma (Zhang C. et al., [@B174]) miR-378\ / Viral myocarditis (Wan et al., [@B134]) miR-378\* (Wan et al., [@B134]) 35 Paeonol Paeonia suffruticosa Andr. and Cynanchum paniculatum (Bunge) Kitagawa miR-1 (Zhang and Xiong, [@B179]) / Ischemic arrhythmia (Zhang and Xiong, [@B179]) 36 Salvianolic acid A Salvia miltiorrhiza Bge. miR-101 (Yu D. S. et al., [@B168]) tight junction proteins, HO-1, p-caveolin-1, ZO-1, occluding, Nrf2, and Cul3 (Yu D. S. et al., [@B168]) Spinal cord injury (Yu D. S. et al., [@B168]) miR-3686\ MDR1 (Chen et al., [@B15]) Lung cancer (Chen et al., [@B15]) miR-4708-3p\ miR-3667-5p\ miR-4738-3p (Chen et al., [@B15]) 37 Andrographolide Andrographis paniculata (Burm. f.) Nees miR-222-3p\ signaling pathways of miRNAs in cancer, MPAKs, and focal adhesion (Lu et al., [@B85]) Hepatoma tumor (Lu et al., [@B85]) miR-106b-5p\ miR-30b-5p\ miR-23a-5p (Lu et al., [@B85]) 38 Puerarin Radix Puerariae Lobatae miR-22 (Wang L. et al., [@B139]) caveolin-3, amphiphysin-2, and junctophinlin-2 (Wang L. et al., [@B139]) Cardiovascular diseases (Wang L. et al., [@B139]) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Methodology {#s2} =========== The bioactive ingredients of CHMs and their interactions with ncRNA targets are the subject of intensive and rapidly expanding research. In this study, we undertook a comprehensive review of this research. The PubMed database was searched using the terms: "(ncRNA) AND herbal medicine", "(((miRNA) OR lncRNA) OR circRNA) AND herbal medicine," "(((miRNA) OR lncRNA) OR circRNA) AND active ingredient," "(((miRNA) OR lncRNA) OR circRNA) AND Chinese herb," "(((miRNA) OR lncRNA) OR circRNA) AND natural agent," "(((miRNA) OR lncRNA) OR circRNA) AND natural compound," or "(((miRNA) OR lncRNA) OR circRNA) AND traditional Chinese medicine." In addition, the China National Knowledge Infrastructure (CNKI) was also searched with terms as follows: "FT = 'Chinese herbal medicine' AND SU = 'ncRNA' NOT (TI = 'Review' OR TI = ' Progress\' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Chinese herbal medicine' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = ' Progress\' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Active ingredient' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Natural compound' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," "FT = \'Natural ingredient' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Traditional Chinese medicine extract' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," or "FT = 'Traditional Chinese medicine' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')." "FT" means full text; "SU" means subject; "TI" means title. Articles included in "Guide to Core Journals of China," "Chinese Science Citation Database" and "Chemical Abstracts" simultaneously, were selected to ensure high quality of literature. According to the above searching method, English and Chinese original articles related to bioactive ingredients of CHMs and any ncRNA (miRNA, lncRNA, or circRNA) were selected manually. Pro-apoptosis Effects of CHMs {#s3} ============================= Apoptosis is programmed cell death, which is a normal physiological process of cells. Imbalance of apoptosis is closely associated with various diseases, particularly cancer. Proteins that inhibit apoptosis are over-expressed in various cancers, and are considered to be related to tumorigenesis and chemotherapy resistance (Mohamed et al., [@B100]); therefore, the induction of apoptosis is a promising method for cancer management (Fulda and Vucic, [@B31]). Recently, several bioactive ingredients of CHMs have been reported to promote apoptosis by targeting miRNA, lncRNA, or ceRNA crosstalk, indicating their potential as complementary therapies for cancer. Berberine --------- Berberine \[BBR, 9,10-Dimethoxy-2,3-(methylenedioxy)-7,8,13,13a-Tetrahydroberbinium; [Chem. 1](#T2){ref-type="table"}\] is an isoquinoline alkaloid extracted from the roots of several species including: Coptis chinensis Franch., Berberis soulieana Schneid., Berberis poiretii Schneid., Berberis vernae Schneid., Berberis wilsoniae Hemsl., and Platycladus orientalis (Linn.) Franco. These herbs are considered to have antipyretic and detoxification effects, based on the theory of traditional Chinese medicine (TCM), and were mainly used to treat diseases of the digestive and urinary systems, such as diarrhea, ulcer, jaundice, and urinary infection, as well as dermatological diseases, including eczema. Newly reported researches (Luo et al., [@B89]; Chai et al., [@B12]) have found the anti-cancer activity of two extracts from Coptis chinensis Franch. one of which is BBR. It\'s indicated that BBR affects apoptotic pathways in various cancers through regulation of multiple miRNAs. For example, BBR exerts significantly protective effects in multiple myeloma (MM) through targeting several miRNAs. BBR down-regulates the expression of miR-99a\~125b, miR-17\~92, miR-106\~25 (Feng et al., [@B30]), and miR-21 (Luo et al., [@B89]), thereby influencing the P53, ERB, and MAPK signaling pathways, leading to acceleration of apoptosis and growth inhibition. Moreover, BBR suppresses MM cell viability through down-regulating miR-19a/92a expression (Yin et al., [@B166]). Further, BBR can up regulate miR-23a in hepatocellular carcinoma (HCC) (Wang N. et al., [@B141]), as well as miR-152, miR-429, and miR-29a in colorectal cancer (Huang et al., [@B48]) in a P53-dependent manner. By inducing NEK6 inhibition and transcriptional activation of the P53-associated tumor suppressor genes, P21 and GADD45α, BBR induces cell death, G2/M cell cycle arrest, and tumor growth suppression in HCC cells; in contrast, miR-23a inhibition can attenuate these BBR-mediated functions (Wang N. et al., [@B141]). Besides, BBR also regulates cell cycle and inhibits cell proliferation in melanoma A375 cells through promoting miR-34a, miR-154, miR-26a, and miR-124 expression, as well as suppressing target genes CDK4, CyclinD1, CyclinE, and CDK2 (Yang L. H. et al., [@B159]). Additionally, BBR can enhance cellular sensitivity to chemotherapeutic drugs, helping to address the problem of drug resistance. In ovarian and gastric cancers, BBR can enhance cisplatin sensitivity by regulating the expression of miR-93 (Chen et al., [@B17]) and miR-203 (You et al., [@B167]), respectively, thus inducing apoptosis. Furthermore, there is evidence that BBR can function together with other compound. It has a synergistic antiproliferative effect on colorectal cancer when combined with NVP-AUY922. The potential mechanism underlying this phenomenon was reported to be suppression of CDK4 and induction of miR-296-5p-mediated inhibition of Pin1-β-catenin-cyclin D1 signaling, resulting in cell growth arrest (Su et al., [@B123]). Interestingly, BBR also has protective effects against obesity, steatotic liver and insulin resistance. It inhibits cell viability, cell differentiation, and triglyceride content in a dose- and time-dependent manner, through marked induction of miR-27a and miR-27b; while miR-27a and miR-27b inhibitors can counteract this repressive function of BBR (Wu et al., [@B154]). Steatotic liver results from disordered lipid metabolism, where lncRNA MRAK052686, NRF2 (Yuan et al., [@B172]), and miR-373 (Li C. H. et al., [@B69]) are down-regulated. BBR can reverse the abnormal expression of these genes in steatotic liver, thereby inhibiting the AKT-mTOR-S6K signaling pathway and preventing the development of hepatic steatosis (Li C. H. et al., [@B69]). In addition, through downregulating miR-29a-3p in insulin resistant HepG2 cells, BBR can increase the mRNA and protein expression of IRS1, leading to regulation of the insulin receptor signaling pathway protein (Mao et al., [@B94]). Based on the above results, it is clear that BBR possesses different pharmacological effects via targeting miRNAs. Particularly, it shows obvious advantages for treatment of MM and digestive cancers, mainly through its activities in promotion of apoptosis and inhibition of cell growth. More importantly, its direct anticancer properties are strongly associated with P53 signaling. Therefore, BBR presents as promise for potential future use in cancer treatment. Artesunate ---------- Artesunate (ART, dihydroartemisinin-12-alpha-succinate; [Chem. 2](#T2){ref-type="table"}) is a sesquiterpene lactone extracted from the leafy portions of the Chinese herb, Artemisia annua L. It\'s the semisynthetic derivative of artemisinin which is widely known to be a natural antimalarial medicine (Tu, [@B133]). Recently, the function of ART in cancer therapy, by targeting lncRNA and promoting cell apoptosis, was newly identified. The lncRNA, UCA1, is up-regulated in prostate cancer tissues and positively correlated with poor prognosis (Zhou Y. et al., [@B196]). ART significantly decreased the expression of lncRNA UCA1, thereby regulating the downstream miR-184/BCL-2 axis, inducing apoptosis, and inhibiting metastatic ability. Furthermore, these protective effects could be reversed by overexpression of lncRNA UCA1, indicating that it is a target of ART (Zhou Y. et al., [@B196]). Hence, ART exhibits anticancer properties through regulating the ceRNA crosstalk of the lncRNA UCA1/miR-184/BCL-2 axis in prostate cancer. Nevertheless, additional evidence to support these findings is lacking and the stability of this regulatory network requires validation. Triptolide/Triptonide --------------------- Triptolide (TP, (3bs,4as,5as,6r,6ar,7as,7bs,8as,8bs)-6-hydroxy-6a-isopropyl-8b-methyl-3b,4,4a,6,6a,7a,7b,8b,9,10-decahydrotrisoxireno\[6,7:8a,9:4b,5\]phenanthro\[1,2-c\]furan-1(3h)-one; [Chem. 3](#T2){ref-type="table"}) and Triptonide (TN,(3bS,4aS,5aS,6aS,7aS,7bS,8aS,8bS)-6a-isopropyl-8b-methyl-3b,4,4a,7a,7b,8b,9,10-octahydrotrisoxireno\[6,7:8a,9:4b,5\]phenanthro\[1,2-c\]furan-1,6(3H,6aH)-dione; [Chem. 4](#T2){ref-type="table"}) are both diterpene lactone components originated from Tripterygium wilfordii Hook. f. (TwHf) that has traditionally been used for treatment of rheumatoid arthritis (RA). A recent study has revealed that TwHf exerts its anti-rheumatic effects through regulation of miR-146a, which is over-expressed in patients with RA and negatively correlated with prognosis. TwHf treatment could significantly decrease miR-146a expression. Moreover, miR-146a could be used as a predictor of patient clinical response to TwHf (Chen Z. Z. et al., [@B21]). Researches about TP and TN broaden the traditional application and generate new pharmacological effect for cancer treatment. TP has been found to exert anticancer activities in lung cancer. It can induce apoptosis and suppress proliferation through inhibiting miR-21 and increasing expression of phosphatase and tensin homolog (PTEN) protein in non-small cell lung cancer. Moreover, miR-21 upregulation could reverse the effect of TP on cell viability and PTEN (Li et al., [@B74]). Furthermore, TP treatment is also reported to regulate 227 miRNAs and markedly decrease the migration, invasion, and metastasis of lung cancer cells (Reno et al., [@B109]). In addition, TP can promote apoptosis and suppress cell proliferation in hepatocellular carcinoma, potentially via inhibition of miR-17-92 and miR-106b-25, in a c-MYC-dependent manner, leading to an increase of BIM, PTEN, and P21 levels (Li S. G. et al., [@B71]). However, TN shows significant therapeutic advantages in human nasopharyngeal carcinoma (NPC). It promotes NPC apoptosis and cell cycle arrest, as well as inhibition of cell migration and invasion, without toxicity to nasopharyngeal epithelial cells. This anti-cancer activity is attributed to suppression of lncRNA THOR, followed by downregulation of IGF2BP1 mRNA targets involving Myc, IGF2, and Gli1. Furthermore, lncRNA THOR knockout enhances the protection of TN on NPC; while lncRNA THOR overexpression reverses TN-induced treatment in cells. In vivo, TN administration also obviously impedes subcutaneous NPC xenograft growth in mice. Similarly, lncRNA THOR knockout inhibits xenograft growth (Wang et al., [@B143]). Therefore, TP and TN are attractive candidate chemotherapeutic agents against the above cancers. With regard to TP, PTEN is an important target; while TN possesses anti-cancer activity in vitro and in vivo through regulating lncRNA THOR/IGF2BP1 signaling. Nevertheless, as the extracts from TwHf with general toxicity (Chen et al., [@B16]; Luo et al., [@B88]), the effectiveness and safety of TP and TN require additional confirmation. Ailanthone ---------- Ailanthone (AIL, Picrasa-3,13(21)-diene-2,16-dione, 11,20-epoxy-1,11,12-trihydroxy-, (1-beta,11-beta,12-alpha)-; [Chem. 5](#T2){ref-type="table"}) is a water-soluble quassinoid extracted from the root bark of Ailanthus altissima (Mill.) Swingle. Traditionally, the root bark was used for improvement of itching, bleeding and diarrhea in TCM theory. However, AIL has been newly found to possess anti-tumor activity in different tumors (Chen Y. et al., [@B20]; Peng et al., [@B105]; Yang P. et al., [@B160]). Among those, inhibitory effect of human vestibular schwannomas (VSs) induced by AIL is correlated with miRNA. A research has demonstrated that AIL cleaves caspase 3 and caspase 9, promotes Beclin-1, LC3-II accumulation, and decreases p62, cyclin D1 expression, thus increasing apoptotic cell rate. The upstream mechanism may be suppression of miR-21, and the Ras/Raf/MEK/ERK and mTOR pathways, leading to apoptosis and autophagy in AIL-treated cells. In addition, miR-21 overexpression can attenuate the regulation of AIL on Ras/Raf/MEK/ERK and mTOR pathways, as well as apoptosis and autophagy, indicating miR-21 can be the treatment target of AIL in VSs (Yang P. et al., [@B160]). Cordycepin ---------- Cordycepin (COR, 9-(beta-D-3′-Deoxyribofuranosyl)adenine; [Chem. 6](#T2){ref-type="table"}) is the main bioactive ingredient of Cordyceps militaris, a precious CHM. The medicinal herb has immunity-strengthening effect, and has been already used as a health care product in clinical practice. Modern researches broaden the application of COR in various cancers (Wang et al., [@B135]; Liang et al., [@B77]; Yu X. et al., [@B170]). Specifically, treatment of COR for renal cell carcinoma (RCC) is attributed to regulation of miR-21 and PTEN phosphatase. It\'s indicated that COR down-regulates miR-21 expression and Akt phosphorylation, yet promotes PTEN phosphatase in RCC Caki-1 cells, resulting in induction of apoptotic cell death and suppression of cell migration. Furthermore, miR-21 mimic or PTEN siRNA can markedly abolish the above effects induced by COR (Yang et al., [@B157]). Therefore, it\'s confirmed that COR possesses pro-apoptosis and anti-migration function through regulating miR-21/PTEN axis. In addition, soya-cerebroside ([Chem 7](#T2){ref-type="table"}), another extracts from Cordyceps militaris is demonstrated to be anti-inflammatory for osteoarthritis (OA). It suppresses AMPK and AKT signaling pathways, and then promotes miR-432 expression in OA synovial fibroblasts, leading to inhibition of monocyte chemoattractant protein-1 (MCP-1), monocyte migration and infiltration, as well as cartilage degradation (Liu S. C. et al., [@B82]). As a result, soya-cerebroside exerts protective effect for OA partially via regulating miR-432, MCP-1, AMPK and AKT pathways; while in this study a clear functional relationships among those factors are not reported. Tubeimoside I ------------- TubeimosideI (TBMSI, nosyl\]-β-D-glucopyranosyl\]oxy\]-2,23-dihydroxy-,28-(O-β-D-xylopyranosyl-(1 → 3)-O-6-deoxy-α-L-mannopyranosyl-(1 → 2)-α-L-arabinopyranosyl)ester, intramol. ester, \[2β,3β(S),4α\]- Tubeimoside TUBEIMOSIDE A(P); [Chem. 8](#T2){ref-type="table"}) is the main triterpenoid saponin originated from Bolbostemma paniculatum (Maxim) Franquet. which has detoxification and detumescent activities. Recent studies have revealed the pharmacological action of TBMS1 as a potential anti-cancer agent (Wang et al., [@B144]; Gu et al., [@B36]). A research demonstrated that TBMS1 can promote apoptosis, and attenuate migration, invasion of non-small cell lung cancer cells. The underlying mechanism is attributed to upregulation of miR-126-5p, followed by inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. MiR-126-5p inhibitor can reverse the downregulated VEGF-A and VEGFR-2 induced by TBMS1 treatment; moreover, both miR-126-5p inhibitor, and VEGF-A, VEGFR-2 overexpression upregulate the mRNA expression and phosphorylation of MEK1 and ERK. Significantly, apoptosis, migration and invasion of TBMS1-treated cells can be reversed by either miR-126-5p inhibitor or ERK activator (Shi et al., [@B118]). From the above results, it can be concluded that miR-126-5p/VEGF-A/VEGFR-2/ERK signaling is the protective pathway of TBMS1 for cancer therapy. Oridonin -------- Oridonin (ORI, (14R)-7-alpha,20-Epoxy-1-alpha,6-beta,7,14-tetrahydroxykaur-16-en-15-one, [Chem. 9](#T2){ref-type="table"}) is a ent-kaurane diterpenoid compound mainly originated from Rabdosia rubescens (Hemsl.) Hara. Traditionally, the herb was convinced to have the effect of detoxification, circulation promotion and pain relief in China. Currently, ORI is illustrated to participate in the treatment of several tumors via different regulatory pathways. It\'s reported that human laryngeal cancer cell is accelerated to apoptosis after ORI treatment through inhibiting EGFR signaling. Similarly, EGFR suppression increased ORI-induced apoptosis by the promotion of oxidative stress, and activation of intrinsic and extrinsic apoptotic pathways (Kang et al., [@B59]). Moreover, 105 miRNAs are involved in the regulation of ORI-treated pancreatic cancer (Gui et al., [@B37]). Therefore, it\'s possible that miRNAs involve in the anti-cancer activity of ORI; however, whether EGFR is the downstream target of miRNAs deserves more researches. Anti-proliferation and Anti-migration Effects of CHMs {#s4} ===================================================== Abnormal cell proliferation is involved in the pathogenesis of many diseases. In particular, the proliferation and invasion of cancer cells are primary contributors to poor patient outcomes (Gao et al., [@B33]). In addition, asthma is also associated with the cell proliferation and migration in airway smooth muscle (Zhao et al., [@B189]). Hence, suppression of cell proliferation and migration are critical methods for treatment of these diseases. Excitingly, some bioactive ingredients of CHMs have been found to inhibit the proliferation and migration of both cancer and asthma cells through targeting miRNA, lncRNA, or ceRNA crosstalk. Curcumin -------- Curcumin (CUR, (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione; [Chem. 10](#T2){ref-type="table"}) is a phenolic compound extracted from Curcuma longa L., which was traditionally used as painkiller in rheumatism and other bone and joint diseases. Recent studies have found that CUR can also act as an anticancer agent, via miRNA and lncRNA targets. CUR inhibits miR-208 and activates expression of the cell cycle suppressor, CDKN1A, resulting in dose-dependent suppression of prostate cancer cell proliferation (Guo H. et al., [@B38]). Further, CUR can significantly increase miR-143 and decrease PGK1 expression, while ectopic expression of FOXD3 can enhance the regulatory effect of CUR on miR-143, thereby inhibiting the proliferation and migration of prostate cancer cells (Cao et al., [@B11]). Further studies reveal that CUR also acts on human prostate cancer stem cells (HuPCaSC). CUR treatment increases the expression of miR-145 and decreases levels of lncRNA-ROR, the cell cycle proteins CCND1, CDK4, and the stem cell markers OCT4, CD44, and CD133. The tumorigenicity of these cells is thereby significantly reduced through inhibition of their proliferation, invasion, and cell cycle arrest (Liu T. et al., [@B83]). Moreover, expression levels of miR-770-5p and miR-1247 in the DLK1--DIO3 imprinted gene cluster were significantly up-regulated, leading to suppression of HuPCaSC proliferation and invasion in vitro (Zhang et al., [@B177]). CUR also promotes the expression of miR-98 in lung cancer, thus inhibiting cell growth and migration (Liu W. L. et al., [@B84]). By reducing miR-186^\^ expression, it induces apoptosis and decreases cell viability in lung cancer cells as well (Tang et al., [@B126]). Furthermore, CUR inhibits both proliferation and accelerates apoptosis in bladder, gastric, non-small cell lung, pancreatic cancers, and hepatic carcinoma via the up-regulation of miR-203 (Saini et al., [@B112]), miR-33b (Sun et al., [@B124]), miR-192-5p (Jin et al., [@B57]), miR-7 (Ma et al., [@B92]), and lncRNA AK125910 (Guo Y. et al., [@B40]), respectively. CUR has also been reported to increase the sensitivity of non-small-cell lung cancer (Lu et al., [@B87]), breast cancer (Zhou S. et al., [@B194]), and nasopharyngeal carcinoma (Wang Q. et al., [@B142]) to chemotherapy drugs by targeting ncRNAs including miR-30c, miR-29b-1-5p, and lncRNA AK294004, respectively, along with their downstream genes. Moreover, CUR can exert synergistic effects in combination with other compounds, to suppress cell proliferation and invasion and induce apoptosis in glioblastoma (Wu et al., [@B152]), breast cancer (Guo et al., [@B39]), and hepatocellular carcinoma (Zhang S. et al., [@B184]). In glioblastoma, miR-378 was found to promote the anticancer effect of CUR by regulating p38 expression, demonstrating the mutual interaction of miRNA and CUR (Li et al., [@B73]). Furthermore, CUR is reported to exert anti-inflammatory effects (Ma F. et al., [@B91]) and to inhibit adipogenic differentiation (Tian L. et al., [@B129]). Notably, as liposome technology is a good method for targeting drug delivery system that can solve the solubility problems of poorly soluble drugs (Allen and Cullis, [@B2]). A research has used this technology to produce CUR-loaded liposome, increasing solubility and oral bioavailability of CUR, as well as reducing first pass effect of hepar. This drug combination can also promote sensitivity of breast cancer cells to chemotherapy, through regulating different miRNAs of miR-29b-1-5p, miR-29b-3p, miR-6068, miR-6790-5p, and miR-4417, as well as their target genes involving DDIT4, EPAS1, VEGFA, RPS14, and DCDC2 (Zhou et al., [@B195]). These data demonstrate that CUR can suppress cell proliferation, growth, and metastasis in various cancers by targeting ncRNAs. In particular, CUR has obvious advantages for the treatment of prostate cancer through its regulation of cancer and cancer stem cells. Moreover, the synergistic effects of CUR with other chemotherapies provide new alternative strategies to address drug resistance. Excitingly, structural improvement of CUR not only ensures its anti-cancer effect, but also promotes the bioavailability. Shikonin -------- Shikonin (SHK, 5,8-dihydroxy-2-((1R)-1-hydroxy-4-methyl-3-penten-1-yl)-1,4-naphthalen-edione; [Chem. 11](#T2){ref-type="table"}) is a naphthoquinone derivative compound. SHK is extracted from the root of the natural herbal medicine, Lithospermum erythrorhizon* Sieb. et Zucc. This plant was generally used to treat rash, pox, measles, and urticaria in TCM. Modern studies have discovered broader applications for this compound in cancer, by revealing its anti-proliferation function, which is reported to be associated with targeting of miRNAs. SHK can inhibit proliferation and promote apoptosis by modulating the miR-106b/PTEN/AKT/mTOR signaling pathway in endometrioid endometrial cancer (Huang and Hu, [@B47]). Moreover, SHK inhibits the proliferation of breast cancer cells through down-regulation of tumor-derived exosomal miR-128 (Wei et al., [@B148]). In addition, the anticancer activity of SHK in glioblastoma is enhanced by miR-143 by reducing the expression of the anti-apoptosis regulator, BAG3, which is a functional target of miR-143 (Liu et al., [@B80]). Overall, the regulatory relationships between SHK and miRNAs are mutual. SHK could target miR-106b and miR-128 in endometrioid endometrial cancer and breast cancer to prevent cell proliferation. Further, miR-143 expression influences the anticancer activity of SHK in glioblastoma. Finally, the results reviewed above demonstrate that the anti-proliferation activity of SHK in cancers can be attributed to its interactions with miRNAs. Paeoniflorin ------------ Paeoniflorin\[PF,5b-((Benzoyloxy)methyl)tetrahydro-5-hydroxy-2-methyl-2,5-methano-lH-3,4-dioxacyclobuta(cd)pentalen-1a(2H)-yl-beta-D-glucopyranoside; [Chem. 12](#T2){ref-type="table"}\] is the main active ingredient of Paeonia lactiflora Pall., which was commonly used to regulate blood circulation and relieve pain in TCM theory. Recent investigations have revealed roles for PF in vasodilation (Goto et al., [@B35]), anti-inflammation (Chen et al., [@B19]; Hu et al., [@B45]), microcirculation improvement (Zhou et al., [@B193]), anti-oxidation (Chen et al., [@B18]), and anti-cancer (Wang et al., [@B137]) activities. Specifically, PF exhibits protective activity in glioma via suppression of cell proliferation and promotion of apoptosis. The potential underlying mechanism may involve upregulation of miR-16 and downregulation of matrix metalloproteinase-9 (MMP-9), which are differentially expressed in glioma tissues and cells compared with healthy controls (Li W. et al., [@B72]). This result lays the foundation for treatment of cancer using PF; however, supporting evidence is insufficient and more investigations are needed. Honokiol -------- Honokiol (HNK, 5,3′-Diallyl-2,4′-dihydroxybiphenyl; [Chem. 13](#T2){ref-type="table"}) is a bioactive polyphenol isolated from Magnolia grandiflora. Although the flower was traditionally valued as ornamental, it contains the phenolic ingredient, HNK, which has been shown to have antimicrobial activity (Clark et al., [@B25]). A recent study discovered that HNK has anti-tumor activity; it can markedly inhibit the growth, invasion, and migration of breast cancer cells, and breast-tumor-xenograft growth induced by leptin. HNK promotes the expression of miR-34a, and inhibits WNT1-MTA1-β-catenin signaling, through suppression of STAT3 phosphorylation and recruitment of STAT3 to the promoter of miR-34a (Avtanski et al., [@B3]). Hence, HNK has demonstrated a protective effect on breast cancer in a diet-induced-obese mouse model with high leptin levels and could serve as a new endocrine therapy drug for patients with obesity-related breast cancer accompanied by negative estrogen and progesterone receptors; however, the research described above was limited to animal experiments, and further evidence in humans is required, thus clinical trials are warranted to further investigate HNK. Schisandrin B ------------- SchisandrinB (SchB, 7-dimethyl-ethoxy-stereoisomer;benzo(3,4)cycloocta(1,2-f)(1,3)benzodioxole,5,6,7,8-tetrahydro-1,2,3,13-tetram; [Chem. 14](#T2){ref-type="table"}) is a type of lignan, extracted from Schisandra sphenanthera Rehd. et Wils. The original fruit was commonly used to relieve symptoms of cough, gasp, abnormal sweating, nocturnal emission, thirst, and palpitations, under TCM theory. Although it was widely used to treat various diseases in ancient China, its specific target and underlying mechanism of action were unclear. A recent study of Sch B provided information about the involvement of ncRNA. Sch B may increase the expression of miR-150 and subsequently reduce levels of the lncRNA BCYRN1 in airway smooth muscle cells (ASMCs) of asthmatic rats. By regulating these two ncRNAs, Sch B suppresses the proliferation, viability, and migration of ASMCs; therefore, the study generated evidence that partially explains the mechanism underlying the activity of Sch B against asthma (Zhang X. Y. et al., [@B185]). Moreover, Sch B can mediate ceRNA crosstalk between miR-150 and lncRNA BCYRN1, further establishing an miR-150/lncRNA BCYRN1/cell proliferation axis; however, as a new regulatory mechanism influencing asthma, the stability of the ceRNA crosstalk requires further investigation. Resveratrol ----------- Resveratrol (RES, 3,4′,5-trihydroxystilbene; [Chem. 15](#T2){ref-type="table"}) is a natural phenol stilbenoid that is mainly found in food, including the skin of grapes and blueberries, and several CHMs, including Morus alba L., Polygonum cuspidatum Sieb. et Zucc., and Rubus idaeus L. It is considered to protect individuals from cardiovascular diseases, as well as dietary and metabolic diseases (Bradamante et al., [@B10]; Baur et al., [@B5]; Lagouge et al., [@B65]). Recently, its anticancer properties have also been evaluated by researchers and RES has been used as a dietary supplement (Garvin et al., [@B34]; Kalra et al., [@B58]; Roy et al., [@B111]). RES can down-regulate the lncRNA, MALAT1, and up-regulate miR-200c, as well as inhibiting WNT/β-catenin signaling, leading to suppression of cell invasion, metastasis, and migration in colorectal cancer (Ji et al., [@B52]; Karimi Dermani et al., [@B60]). Moreover, by significantly decreasing oncogenic miR-221 and regulating NF-κB and TFG, RES exerts inhibitory effects on melanoma cells, both in vitro and in vivo (Wu and Cui, [@B151]). In glioma, RES inhibits cell proliferation, arrests the cell cycle in S phase, and induces apoptosis in vitro, through down-regulation of miR-21, miR-30a-5p, and miR-19, as well as regulating their targets, including P53, PTEN, EGFR, STAT3, COX-2, NF-κB, and the PI3K/AKT/mTOR pathway (Wang G. et al., [@B136]). RES also has anti-inflammatory effects. It can reduce expression of miR-155 and promote that of its target gene, suppressor of cytokine signaling 1 (SOCS1), leading to subsequent inhibition of the inflammatory factors, TNF-α, IL-6, MAPKs, and STAT1/STAT3 (Ma C. et al., [@B90]). Interestingly, by increasing miR-663 expression, RES down-regulates miR-155, thus acting as both an anti-inflammatory and an anticancer agent (Tili et al., [@B130]). Furthermore, RES exhibits neuroprotective effects. It promotes miR-96 and inhibits its target gene, BAX, resulting in prevention of oxygen/glucose deprivation/re-oxygenation-induced apoptosis and brain damage, while this protective function can be reversed by miR-96 inhibitor (Bian et al., [@B6]). In Alzheimer\'s disease, RES also improves long-term memory formation and induction of long-term potentiation of hippocampus CA1 neurons, through down-regulation of miR-134 and miR-124, and up-regulation of CREB and BDNF (Zhao et al., [@B190]). Therefore, RES is a potential therapeutic agent against cancers, cerebral ischemia, Alzheimer\'s disease, and other inflammatory conditions. Soybean Isoflavones ------------------- Soybean isoflavones (SIF, 3-phenyl-4h-1-benzopyran-4-one; [Chem. 16](#T2){ref-type="table"}) are extracted from Glycine max (Linn.) Merr. They act as phytoestrogens in mammals and have been used as dietary supplements. SIF are associated with breast cancer (Douglas et al., [@B27]; Takagi et al., [@B125]). Recently, they have also been demonstrated to suppress cell growth and invasion in prostate cancer. A potential mechanism underlying the anti-prostate cancer activity of SIF is its promotion of miR-29a and miR-1256, leading to down-regulation of TRIM68 and PGK-1 by inhibiting methylation of the miR-29a and miR-1256 promoters (Li et al., [@B75]). Nevertheless, as a controversial ingredient with weak estrogen-like properties, the influence of SIF on hormone-receptor-positive cancers has caused widespread concern. Therefore, research is needed to determine the effectiveness and safety of SIF in the context of different cancers. Matrine ------- Matrine (MAT, (7aS,13aR,13bR,13cS)-Dodecahydro-1H,5H,10H-dipyrido\[2,1-f:3′,2′,1′-ij\](Memczak et al., [@B97]; Song et al., [@B121])naphthyridin-10-one; [Chem. 17](#T2){ref-type="table"}) is the main alkaloid extract from Sophora flavescens Ait which was commonly used for diseases of dysentery, eczema and jaundice in China. Modern pharmacological research shows that MAT has protective activity in melanoma, as evidenced by inhibition of proliferation and invasion, and promotion of apoptosis in melanoma cell lines. By downregulating miR-19b-3p expression, MAT increases the protein and mRNA expression of PTEN, a direct target of miR-19b-3p. Similarly, miR-19b-3p downregulation can imitate the effect of MAT; while PTEN silencing reverses the protection induced by MAT (Wei et al., [@B149]). As a result, MAT can exert anti-cancer activity in melanoma via regulating miR-19b-3p/PTEN axis. Corylin ------- Corylin (CL, 3-(2,2-dimethylchromen-6-yl)-7-hydroxychromen-4-one; [Chem. 18](#T2){ref-type="table"}) is the flavonoid compound extracted from Psoralea corylifolia Linn. In TCM practice, Psoralea corylifolia Linn. was often used for degenerative bone and joint diseases. Newly reported studies have revealed its application in inflammation (Kim et al., [@B62]; Hung et al., [@B51]) and cancer (Chen et al., [@B14]). The anti-cancer activity induced by CL is related to upregulation of tumor suppressor lncRNA GAS5 and its downstream anticancer pathways activation. As a result, the proliferation, migration, and invasiveness, as well as epithelial-mesenchymal transition are all inhibited in hepatocellular carcinoma cells. Moreover, lncRNA GAS5 silencing can attenuate the above inhibitory effect of CL. In an animal experiment, CL is observed to obviously retard tumor growth as well, with no significant physiological toxicity (Chen et al., [@B14]). Taken together, lncRNA GAS5 may act as the treatment target of CL in hepatocellular carcinoma; however, specific downstream gene of lncRNA GAS5 still needs further study. Anti-inflammatory Effects of CHMs {#s5} ================================= Inflammation is a common pathological process involved in many diseases, including coronary heart disease, inflammatory bowel disease, myocarditis, asthma, and neuroinflammatory disorder (Harrington, [@B43]; Robinson et al., [@B110]; Mahajan et al., [@B93]); however, both non-steroidal anti-inflammatory drugs and immunosuppressive agents have clear side effects (Shah and Gecys, [@B115]; Ahmad et al., [@B1]). Consequently, safe and effective anti-inflammatory drugs for the treatment of the basic pathologies underlying the above diseases are still needed. Several bioactive ingredients of CHMs are reported to target miRNA or ceRNA crosstalk, thereby exerting anti-inflammatory effects. Tanshinone IIA -------------- Tanshinone IIA (Tan IIA, Phenanthro \[1, 2-b\]furan-10, 11-dione, 6, 7, 8, 9-tetrahydro-1, 6, 6-trimethyl; [Chem. 19](#T2){ref-type="table"}) is a lipophilic diterpenoid extracted from the root of Salvia miltiorrhiza Bge. Under TCM theory, the original herb is considered to promote blood circulation. Recent studies have illustrated that Tan IIA has cardioprotective activity (Shang et al., [@B117]; Feng et al., [@B29]) and injection of sodium Tan IIA sulfonate has been widely used as an adjunctive therapy for cardiovascular diseases in China (Yu M. L. et al., [@B169]). A potential mechanism underlying its inhibition of inflammation (Pan et al., [@B104]; Cheng et al., [@B22]), and an upstream regulator, is miRNA. Tan IIA can reduce the expression levels of cytokines, chemokines, and acute-phase proteins, including TLR4, MyD88, GM-CSF, sICAM-1, CXCl-1, and MIP-1α. Moreover, it significantly inhibits the mRNA expression levels of IL-1β, TNF-α, and COX-2, thereby suppressing lipopolysaccharides (LPS) -induced activation of the TLR4-NF-κB pathway. Furthermore, expression of miR-155, miR-147, miR-184, miR-29b, and miR-34c is also reduced by Tan IIA, and these may be upstream regulators in anti-inflammation processes (Fan et al., [@B28]). In addition, by down-regulation of miR-146b and miR-155, Tan IIA significantly reduces the levels of inflammatory factors, including CRP, ox-LDL, IL-1β, IL-6, IL-12, TNF-α, CCL-2, CD40, and MMP-2, thereby exerting protective functions in atherosclerosis induced by Porphyromonas gingivalis (Xuan et al., [@B156]). Another study indicated that Tan IIA can also inhibit apoptosis caused by hypoxia. Through increasing miR-133 expression and activating the stress-induced protein kinase, MAPK ERK1/2, Tan IIA enhances resistance to hypoxic exposure in neonatal cardiomyocytes (Zhang et al., [@B180]). Treatment with Tan IIA has also been illustrated to reverse the abnormal expression of miR-1, SRF, and MEF2, and participates in suppression of the p38 MAPK signaling pathway, restoring declined I(K1) current density and Kir2.1 and Cx43 protein levels, thus lowering the incidence of arrhythmogenesis and mortality after myocardial infarction, and improving cardiac function (Shan et al., [@B116]; Zhang et al., [@B187]). These results provide a partial explanation for the anti-inflammatory and anti-hypoxia activity of Tan IIA via miRNAs in cardiovascular diseases; in particular, miR-155 may be a specific target of Tan IIA in inflammation. Additionally, an aqueous extract from Salvia miltiorrhiza Bge., named magnesium lithospermate B (MLB, magnesium (2R)-3-(3,4-dihydroxyphenyl)-2-\[(E)-3-\[(2S,3S)-2-(3,4-dihydroxyphenyl)-3-\[(2R)-3-(3,4-dihydroxyphenyl)-1-oxido-1-oxopropan-2-yl\]oxycarbonyl-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl\]prop-2-enoyl\]oxypropanoate; [Chem. 20](#T2){ref-type="table"}), has neuroprotective effect in ischemia/reperfusion (I/R) injury. I/R injury can lead to miR-107 upregulation, glutamate transporter 1 (GLT-1) suppression and glutamate accumulation, increasing neurological deficit score, infarct volume and cellular apoptosis (Yang Z. B. et al., [@B165]). MLB treatment improves I/R-induced cerebral injury through reversing the abnormal expressions of miR-107, GLT-1 and glutamate (Yang et al., [@B164]). The above results may help to throw light on the underlying mechanisms of Tan IIA and MLB for the treatment of cardiovascular and cerebrovascular diseases from the perspective of miRNA; however, it should be noted that the pharmacological action of Salvia miltiorrhiza Bge. is not limited to ncRNAs (Zhu et al., [@B197]). Baicalin -------- Baicalin (BA, 7-D-glucuronic acid-5,6-dihydroxy-flavone; [Chem. 21](#T2){ref-type="table"}) is a flavone glycoside extracted from Scutellaria baicalensis Georgi, which was commonly applied for the treatment of respiratory and digestive diseases in CHM. The traditional treatment effects may be related to regulation of inflammatory responses. TNF-α stimulation promotes the expression of miR-191a, causing downregulation of ZO-1 mRNA and protein. BA pretreatment could reverse the effects of ZO-1 and miR-191a expression induced by TNF-α, leading to improved viability and migration of rat small intestine epithelial cells. Furthermore, knockdown of miR-191a expression significantly increased BAL-induced ZO-1 protein expression, thereby enhancing the protective effect of BA on cell motility (Wang L. et al., [@B140]). These data suggest that miR-191a may be an upstream target of BA in the treatment of inflammatory bowel disease; moreover, the therapeutic effects of BA can also be influenced by miR-191a. Also, another research illustrates the proliferative inhibition of mouse embryonic stem cells induced by baicalin. Baicalin suppresses the expression of miR-294, c-jun and c-fos; while miR-294 overexpression could significantly reverse the above effect of baicalin, indicating miR-294 may be the treatment target (Wang J. et al., [@B138]). Therefore, BA exerts anti-inflammatory and anti-proliferative effects by targeting miRNAs and emerges as a potential treatment agent for digestive disease. Further, as BA remains one of the most frequently used medicines for the treatment of cough and phlegm, the activity of BA in respiratory disease warrants similar studies. Cinnamaldehyde -------------- Cinnamaldehyde (CA, 3-phenylprop-2-enaldehyde; [Chem. 22](#T2){ref-type="table"}) is a conjugated aromatic aldehyde extracted from the bark of the Chinese herb, Cinnamomum cassia Presl. According to TCM theory, the traditional plant can enhance the function of "yang qi" (a substance with excitatory function in TCM) and is often used to relieve symptoms of weakness. Recent studies have broadened the application of this preparation to the treatment of cerebrovascular diseases, ulcerative colitis, and cancer (Zhao et al., [@B188]; Tian F. et al., [@B128]; Qu et al., [@B107]), where it acts by exerting anti-inflammatory or ncRNA regulatory functions. CA improves symptoms of weight loss, disease activity index, and infiltration of inflammatory cells, by decreasing the levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, as well as the NLRP3 inflammasome, miR-21, and miR-155, in both colon tissue and macrophages. Moreover, levels of reactive oxygen species were also reduced, along with the phosphorylation of AKT, mTOR, and COX2 proteins. Further experiments revealed similar suppression of IL-1β and IL-6 in response to miR-21 or miR-155 inhibitors, demonstrating that these inflammatory factors are positively regulated by miR-21 or miR-155 (Qu et al., [@B107]). As a result, CA suppresses the miR-21/miR-155/IL-1β/IL-6 axis to exert its protective function in ulcerative colitis. CA also has anti-cancer activity through regulation of ceRNA crosstalk and can suppress cell proliferation and induce apoptosis in non-small cell lung cancer. Through upregulation of has-circ-0043256 and ITCH expression, CA inhibits the WNT/β-catenin pathway, while this function can be partially abolished by miR-1252, indicating that miR-1252 may participate in has-circ-0043256-related regulation. Moreover, has-circ-0043256 knockdown can reverse the effects of CA on cells (Tian F. et al., [@B128]). Consequently, has-circ-0043256/miR-1252/ITCH crosstalk may contribute to the anticancer activity of CA. Geniposide ---------- Geniposide (GEN, methyl (1S,4aS,7aS)-7-(hydroxymethyl)-1-\[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl\]oxy-1,4a,5,7a-tetrahydrocyclopenta\[c\]pyran-4-carboxylate; [Chem. 23](#T2){ref-type="table"}) is derived from Gardenia jasminoides Ellis, a traditional antipyretic and detoxifying CHM. A recent research reported GEN has effects of anti-inflammatory and cardiomyocyte protection in LPS-injured H9c2 cells. It up-regulates miR-145 expression, inhibits pro-inflammatory factors of IL-6, TNF-α, and MCP-1, and then suppresses the MEK/ERK pathway, thus promoting cell viability and inhibiting apoptosis. Moreover, miR-145 inhibitor could reverse the above protective function induced by GEN pretreatment (Su et al., [@B122]). Therefore, GEN becomes a potential therapeutic agent for myocarditis in practice by targeting miR-145 and anti-inflammation in cardiomyocyte. Carvacrol/Thymol ---------------- Carvacrol (Car, 5-Isopropyl-2-methylphenol; [Chem 24](#T2){ref-type="table"}) and Thymol (Thy, 2-Isopropyl-5-methylphenol; [Chem. 25](#T2){ref-type="table"}) are isolated from the essential oil of Origanum vulgare L. or wild bergamot. They are isomers and belong to monoterpenoid phenol. Traditionally, Origanum vulgare L. was applied for the treatment of cold and heatstroke. Bergamot can relieve pain and vomit under TCM theory. A research further expanded the applicable scope of these herbs by studying the two bioactive ingredients. Car/Thy can suppress the allergic inflammation in asthma by regulating miRNAs and inflammatory factors. In chitin-induced model, expression levels of miR-155, miR-146a and miR-21, promotor of pro-inflammatory cytokines, are upregulated. Furthermore, SOCS1 and SHIP1, targets of miR-155 and negative regulators of TLR-mediated inflammation, are demonstrated to be inhibited by chitin. However, Car/Thy treatment can reverse the abnormal expressions of TLR2, TLR4, SOCS1, SHIP1, and miR-155, miR-146a, miR-21 (Khosravi and Erle, [@B61]). These results preliminarily establish the relationships between anti-inflammation effect of Car/Thy and miRNAs; but the specific target and corresponding regulatory network are not reported regrettably. Boswellic Acids --------------- Boswellic acids are extracted from oleo-gum-resin of Boswellia serrata, a traditional CHM with promoting blood circulation and pain relief function. Boswellic acids contain different ingredients, among which 3-acetyl-11-keto-β-boswellic acid (AKBA, (3R,4R,6aR,6bS,8aR,11R,12S,14bS)-3-acetyloxy-4,6a,6b,8a,11,12,14b-heptamethyl-14-oxo-1,2,3,4a,5,6,7,8,9,10,11,12,12a,14a-tetradecahydropicene-4-carboxylic acid; [Chem. 26](#T2){ref-type="table"}) possesses the most potent anti-inflammatory activity (Siddiqui, [@B120]; Sayed et al., [@B114]). AKBA can attenuate the behavioral dysfunction in LPS-induced neuroinflammation, similarly with that effect of dexamethasone. Moreover, AKBA lowers expression of miR-155, P-IκB-α, and carbonyl protein, and increases contents of normal cytokine and SOCS-1, resulting in effects of anti-apoptotic and anti-amyloidogenic (Sayed et al., [@B114]). Therefore, regulation of miR-155 and downstream protein helps to reveal the possible mechanism underneath AKBA\'s positive role in neuroinflammatory disorders; however, the specific target deserves more verification. Anti-atherosclerosis Effects of CHMs {#s6} ==================================== Atherosclerosis is the basic pathology underlying coronary artery disease, cerebral infarction, and other vascular diseases (Pothineni et al., [@B106]; Li Q. et al., [@B76]). Medicines with anti-atherosclerosis activities are therefore highly significant for the prevention and treatment of these diseases. Statins are currently the main drugs used against atherosclerosis; however, when taken for long periods of time, they risk impairing liver function and causing muscle lysis, particularly in elderly patients (Guyton, [@B41]; Ramakumari et al., [@B108]). Therefore, better drugs with relatively few side effects are needed and CHMs represent a good resource in this context. Recent studies have identified three bioactive ingredients of CHMs as regulators of atherosclerosis through targeting miRNA or lncRNA. Sinapic Acid ------------ Sinapic Acid (SA, 3,5-dimethoxy-4-hydroxycinnamic acid; [Chem. 27](#T2){ref-type="table"}) is the bioactive ingredient isolated from seeds of the Chinese herb, Sinapis alba L. The seeds were commonly used to treat cough, phlegm, limb numbness, and chronic abscess. A recent study reported protective effects of SA in atherosclerosis, which helped to partially explain the original application of the seed to treat limb numbness. The lncRNA MALAT1 is significantly up-regulated in rats with diabetic atherosclerosis and low-dose SA treatment can suppress this abnormal expression. Subsequently, pyroptotic death of bone marrow derived macrophages is inhibited, accompanied by decreased expression of ET-1 and IL-1β, and the pyroptotic proteins, ASC, NRLP3, and Caspase-1 (Han et al., [@B42]). Hence, SA exerts anti-inflammatory activity and prevents pyroptosis, thus exerting anti-atherosclerosis effects, through targeting lncRNA MALAT1; however, the efficacy and safety of SA as a potential treatment agent require verification by additional studies. Polydatin --------- Polydatin (PLD, 3,4,5-trihydroxystilbene-3-beta-monoglucoside; [Chem. 28](#T2){ref-type="table"}), also known as Piceid, is the bioactive ingredient from Polygonum cuspidatum Sieb. et Zucc. This herb was traditionally used for the treatment of jaundice and cough. However, PLD has also been found to exert protective effects against cardiac hypertrophy (Zhang et al., [@B181]), insulin resistance, and hepatic steatosis (Zhang et al., [@B182]). Further, a recent study has revealed the underlying regulatory action of PLD in atherosclerosis with liver dysfunction. The findings indicated that PLD treatment can markedly lower increased blood glucose, serum ALT, AST, TC, TG, and LDL-C in mice with high-fat diet. Simultaneously, changes in HDL-C, MDA, SOD, and miR-214 were also improved in liver tissue (Zhou et al., [@B192]). This study indicates that PLD can be therapeutically effective in complex diseases by regulating various factors. In addition, PLD shows great potential as a complement to treatment for statin-induced liver damage via its anti-atherosclerosis and liver protection properties; however, the above study only reported the expression levels of various factors induced by PLD, rather than systematically studying the relationships between miR-214 and its target genes. Therefore, further in-depth investigations are required in the future. Ampelopsin ---------- Ampelopsin \[(2r,3r)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chroman-4-one; [Chem. 29](#T2){ref-type="table"}\], alsocalled dihydromyricetin (DHM), is the main flavonoid compound from Ampelopsis grossedentata. The original herb has effects of detoxification, anti-inflammatory and analgesic, commonly used as a dietary supplement. DHM is now demonstrated to impede atherosclerotic process by regulating endothelial dysfunction (Yang D. et al., [@B158]), and exert anti-aging effect against neurodegenerative diseases (Kou et al., [@B64]). It inhibits miR-21 expression and then improves endothelial dysfunction induced by TNF-α, accompanied by suppression of abnormal expression of eNOS, DDAH1, NO, and ADMA, as well as improvement of tube formation and migration. Furthermore, miR-21 blockade can produce similar effects with DHM treatment; while miR-21 overexpression abolishes the above protection. Additionally, improvement of endothelial dysfunction can be reversed by a non-specific NOS inhibitor, indicating DHM ameliorates vascular endothelial function and inhibits atherosclerosis by targeting miR-21-mediated DDAH1/ADMA/NO signal pathway (Yang D. et al., [@B158]). Another study reveals that miR-34a is upregulated in D-gal-induced brain aging rats; while DHM management can inhibit the abnormal expression. Moreover, DHM suppresses apoptosis and ameliorates impaired autophagy of neurons in D-gal-injured hippocampus tissue, by up-regulating SIRT1 and down-regulating mTOR signal pathways (Kou et al., [@B64]). Therefore, DHM possesses anti-aging effect partially through regulating miR-34a-mediated SIRT1-mTOR signal pathway, showing important role for the treatment of neurodegenerative diseases. From the above results, it can be seen that DHM exerts not only anti-atherosclerosis effect, but also anti-aging function by targeting miRNAs and downstream signaling pathways. Anti-infection Effects of CHMs {#s7} ============================== Antibiotics and antiviral drugs are basic treatments for infectious diseases; however, a deteriorating situation caused by antibiotic abuse, drug-resistance, and viral mutations is shifting the focus of research attention to other therapeutic and complementary drugs for treatment of these conditions (Miyoshi et al., [@B99]; Jiang et al., [@B55]). To date, two bioactive ingredients of CHMs have been found to contribute to the treatment of infection through regulation of miRNAs. These substances can protect the human body from pathological damage, although they do not directly induce pathogen resistance. Icariine -------- Icariine \[ICA, 2-(4′-methoxyphenyl)-3-rhamnosido-5-hydroxyl-7-glucosido-8-(3′-methyl-2-butylenyl)-4-chromanone; [Chem. 30](#T2){ref-type="table"}\] is the main bioactive flavonoid glucoside extracted from Epimedium brevicornu Maxim. Under TCM, this herb was considered to nourish "yang qi" and generally applied for treatment of osteoarticular and reproductive diseases. ICA can suppress osteoclast bone resorption and bone loss, indicating great potential for use as a treatment agent for both aseptic loosening and bacteria-induced bone loss (Zhang et al., [@B186]; Liu et al., [@B79]). Specifically, ICA can restore LPS-induced bone loss, without obvious cytotoxicity. This product can down-regulate expression of the osteogenic inhibitor, miR-34c, while it up-regulates levels of the key transcription factor, RUNX2, thereby inducing osteogenic differentiation and mineral nodule formation. Moreover, miR-34c overexpression can reverse these effects of ICA. Additionally, ICA markedly suppresses LPS-induced activation of JNK, p38, and NF-kB pathways, leading to therapeutic effects in diseases causing bacteria-induced bone loss, such as osteomyelitis and septic arthritis (Liu et al., [@B79]). Interestingly, ICA also exhibits anticancer activity in ovarian cancer via down-regulation of miR-21 expression. This subsequently induces PTEN, RECK, and Caspase-3 activity, while BCL-2 protein expression is inhibited, leading to suppression of cell proliferation and increased apoptosis (Li J. et al., [@B70]). Based on these findings, miR-34c appears to facilitate the mechanisms underlying the role of ICA in infectious bone loss. Furthermore, the identification of miR-21 suggests a potential new application of ICA in cancer therapy. Therefore, there is promise that additional currently unknown functions of this medicinal herb could be determined by studying ncRNA and related regulatory networks. Ginsenosides ------------ Ginsenosides (GS,(3S,5R,8R,9R,10R,14R,17S)-17-(2-hydroxy-6-methylhept-5-en-2-yl)-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta\[a\]phenanthren-3-ol; [Chem. 31](#T2){ref-type="table"}), also referred to as panaxosides, are a class of natural steroid glycosides and triterpene saponins. These products include various active components, such as ginsenoside Re, Rg, Rh, Rb, and Rc. GS are mainly isolated from Panax ginseng C. A. Mey., a valuable herb with nourishing effects and a long history of use in ancient China. At present, GS products are not only used to promote health, but also for their activity as immune regulators in many diseases (Jiang Z. et al., [@B56]; Shin et al., [@B119]; Yu X. et al., [@B171]). GS exert a cytoprotective effect, thereby promoting cell viability on avian influenza H9N2/G1 infection. During this process, the expression of miR-15b was up-regulated, while production of IP-10 was markedly inhibited. Furthermore, cytometry and TUNEL analyses indicated that ginsenoside Re prevents apoptosis and DNA damage in human endothelial cells caused by H9N2/G1 (Chan et al., [@B13]). These results are inconsistent with the traditional concept that GS is only suitable for treatment of sub-optimal health status or chronic diseases and greatly expand the potential for application of GS for treatment of acute infectious diseases in the future. Anti-senescence Effects of CHMs {#s8} =============================== Cell senescence is the irreversible state in which cells undergo cycle arrest responding to various factors (Watanabe et al., [@B147]). It participates in biological processes involving embryonic development, wound healing and aging, closely relating to organismal aging and diseases, and thus arousing widespread concerns in researchers (Watanabe et al., [@B147]; de Magalhães and Passos, [@B26]). Currently, several bioactive ingredients of CHMs have been found to act positive roles in anti-senescence. Salidroside ----------- Salidroside \[SAL, 2-(4-Hydroxyphenyl)ethyl beta-D-glucopyranoside; [Chem. 32](#T2){ref-type="table"}\] is the main bioactive extract from Rhodiola rosea L. with effects of nourishing "yang qi" and promoting blood circulation under TCM theory. Modern pharmacological study further revealed that the medicinal herb not only exerts anti-fatigue ability, but also improves resistance to hypoxia (Li et al., [@B68]). Moreover, SAL has been supported to possess anti-senescence activity. The potential mechanism is related to regulation of multiple miRNAs expression. Through upregulating let-7c, let-7e, miR-3620, and decreasing expression of miR-411, miR-24-2-5p and miR-485-3p in the aging cells, SAL participates in several pathways involving p53, transcription factor CREB and AKT/mTOR signaling (Zhang J. et al., [@B178]). As is known that both let-7 and mTOR are aging-related (Marasa et al., [@B95]; Wu et al., [@B153]), and the former factor can directly inhibit the expression of the latter (Marcais et al., [@B96]). Therefore, it\'s possible that SAL possesses anti-senescence effect by regulating let-7 and mTOR; however, the predicted regulatory relationship requires more validation in the future. Phlorizin --------- Phlorizin (PZ, Phloretin-2′-O-beta-glucoside; [Chem. 33](#T2){ref-type="table"}) is the main active ingredient of Acanthopanax senticosus (Rupr. et Maxim.) Harms which is a traditional CHM with functions.of nourishing and enhancing strength. PZ is convinced to exert effects of anti-fatigue, learning improvement and immune-enhancing (Huang et al., [@B49]). Researches further reported that PZ can act as a promising agent for skin aging (Zhai et al., [@B173]; Choi et al., [@B24]). By promoting epidermal cell proliferation and self-renewal, PZ thickens epidermis to maintain skin structure and resistance to aging. Moreover, PZ increases expression of p63 and proliferating cell nuclear antigen (PCNA), as well as integrin α6, integrin β1 and type IV collagen. Particularly, the mRNA of type IV collagen is also increased and possibly regulated by downregulation of miR-135b (Choi et al., [@B24]). As a result, miR-135b/type IV collagen axis may be the underlying regulatory mechanism of anti-senescence induced by PZ. Osthole ------- Osthole (Ost, 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one; [Chem. 34](#T2){ref-type="table"}) is mainly extracted from Cnidium monnieri (L.) Cuss. which was commonly used for nourishing "yang qi" and relieving itching in TCM practice. Current pharmacological researches newly revealed that Ost can improve memory, delay senescence and resist cell damage in Alzheimer\'s disease (AD) (Hu et al., [@B46]; Zheng et al., [@B191]). As it\'s clear that beta-amyloid peptide (Aβ) is the critical pathology of AD, inhibition of Aβ deposition thereby becomes an important treatment strategy for the disease (Wilcock et al., [@B150]). Ost was reported to enhance cyclic AMP response element-binding protein (CREB) phosphorylation and then inhibit Aβ cytotoxicity on neural cells (Hu et al., [@B46]). Further mechanism study indicates that it upregulates miR-107, and then promotes cells viability of neuron, resulting in suppression of the protein expression of Aβ and BACE1, as well as LDH (Xiao et al., [@B155]). Therefore, Ost exertes obvious neuroprotective effect through targeting miR-107 and impeding Aβ deposition, presenting as a potential treatment agent for neurogenic aging and neurodegenerative disease. Inhibitory Effects of CHMs on Structural Remodeling {#s9} =================================================== Structural remodeling is an important factor that can impede the normal functions of tissues and organs. It is also the main pathological change during the late stages of various diseases, making poor prognosis and difficult treatment (Bijkerk et al., [@B7]; Bittencourt et al., [@B8]; Zhuang et al., [@B198]). Encouragingly, three CHM ingredients have been demonstrated to exert protective effects on this pathological change through regulation of miRNAs. Panax Notoginseng Saponins -------------------------- Panax notoginseng saponins (PNS, notoginsenoside-fe, 98%; [Chem. 35](#T2){ref-type="table"}) are a chemical mixture extracted from the root of Panax notoginseng (Burk.) F. H. Chen. According to TCM theory, the traditional herb can simultaneously promote blood circulation and prevent bleeding; therefore, it was commonly used to treat coronary artery disease, stroke, gastrointestinal bleeding, irregular menstruation, and bruises. Currently, several PNS preparations, including xuesaitong injections and xuesetong capsules, are widely used to treat cardiovascular diseases (Song et al., [@B121]). The improvement in cardiac prognosis caused by PNS has been attributed to its regulation of miRNAs and suppression of structural remodeling. PNS was reported to increase expression of the anti-fibrotic factor, miR-29c, which is clearly reduced in mice with isoproterenol-induced myocardial fibrogenesis, leading to downregulation of its target genes: collagen (Col) 1a1, Col1a2, Col3a1, Col5a1, Fbn1, and TGFβ1, thus exerting protective effects against myocardial injury and fibrosis (Liu L. et al., [@B81]). In addition, PNS has obvious resistance to H~2~O~2~-induced oxidative damage, showing anti-apoptosis activity in vascular endothelial cells (VECs) by suppressing miR-146b-5p expression (Wang J. et al., [@B146]). Moreover, notoginsenoside R1, one main component of PNS, can delay the process of senescence in VECs by regulating miR-34a/SIRT1/p53 pathway (Lai et al., [@B66]). As a result, through repairing VECs damages, PNS inhibits vascular pathological process. PNS also has an active role in tumors complicated by myocardial ischemia where paradoxical treatment strategy existed. PNS and its major components, Rg1, Rb1, and R1, are implicated in tissue-specific regulation of angiogenesis, and can inhibit tumor growth, as well as attenuating myocardial ischemia. The potential underlying mechanism may be the down-regulation of miR-18a and vascular markers (CD34 and vWF) in tumor, with simultaneous up-regulation of these factors in heart (Yang Q. et al., [@B162]). Notably, by modulating Met/miR-222 axis, and then increasing target genes of tumor suppressor p27 and PTEN expression, PNS selectively inhibits the survival of lewis lung carcinoma cells and attenuates tumor growth in mice (Yang Q. et al., [@B161]). Based on the above results, PNS appears to exert its cardioprotective function by preventing fibrosis, improving vascular endothelium, and promoting angiogenesis in the heart. Simultaneously, considering the cardioprotection and anti-tumor effects through targeting miRNAs, PNS is especially suitable for patients with heart disease and tumor. Tetrandrine ----------- Tetrandrine (TET, 6,6′,7,12-tetramethoxy-2,2′-dimethyl-1 beta-berbaman; [Chem. 36](#T2){ref-type="table"}) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore. The medicinal plant was often used for treatment of rheumatism and edema under the theories of TCM. Notably, the source plant should not be confused with Radix Aristolochiae Fangchi which causes nephrotoxicity, despite their similar Chinese names. A recent study identified a new pharmacological effect of TET in treatment of anti-hypertrophic scarring. The underlying mechanism was suggested to be repression of DNA and collagen synthesis in scar-derived fibroblasts (Liu et al., [@B78]). Furthermore, by upregulating miR-27b and downregulating miR-125b, TET influenced the expression of putative targets, including VEGFC, BCL2L12, COL4A3, and FGFR2, predicted to contribute to several scar and wound healing-related signaling pathways (Ning et al., [@B103]). Consequently, TET has therapeutic potential for the inhibition of skin tissue hyperplasia after wounding or surgery. Leonurine --------- Leonurine (LEO, 4-Guanidino-n-butyl syringate; [Chem. 37](#T2){ref-type="table"}) is the alkaloid compound from Leonurus artemisia (Laur.) S. Y. Hu F, which was commonly used for gynecological diseases in TCM. Newly reported results have indicated the cardioprotective effect by studying LEO activity, namely anti-atherosclerosis (Jiang T. et al., [@B54]), anti-oxidation (Gao et al., [@B32]) and resistant to cardiomyocyte hypertrophy (Lu et al., [@B86]). LEO treatment can significantly reduce the surface area of hypertrophic cardiomyocytes, decrease the content of atrial natriuretic peptide (ANP), endothelin-1 (ET-1), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated p38 MAPK (p-p38 MAPK), myocyte enhancer factor 2 and β-myosin heavy chain. Moreover, it also up-regulates the expression levels of α-myosin heavy chain protein and miR-1. Thus, by upregulating miR-1 expression and then inhibiting the activation of p38MAPK signaling pathway, LEO may inhibit AngII-induced cardiomyocyte hypertrophy and structural remodeling (Lu et al., [@B86]). Other Effects of CHMs {#s10} ===================== Bioactive ingredients of CHMs can exert various protective effects through targeting different miRNA, lncRNA, or circRNA. Besides the above mentioned mechanisms, some ingredients also play positive roles in anti-I/R injury, anti-arrhythmia, recovery of blood-spinal cord barrier, and promotion of cardiac differentiation by targeting lncRNA and miRNA. Calycosin/Astragaloside IV -------------------------- Calycosin (CAL, 7,3′-dihydroxy-4′-methoxyisoflavone; [Chem. 38](#T2){ref-type="table"}) is a natural phytoestrogen derived from Astragalus membranaceus (Fisch.) Bunge. which can nourish "yang qi" and was commonly used for cardiovascular and cerebrovascular diseases in TCM practice. It\'s indicated that the neuroprotection effect of CAL is related to miRNA. CAL markedly improves the infarcted volume, brain water content, and neurological deficit in cerebral I/R injury rats, by upregulating miR-375, ER-α and Bcl-2, and inhibiting RASD1 expression (Wang Y. et al., [@B145]). Regrettably, a systematic mechanism of miR-375 and those downstream targets has not been revealed in this study. Moreover, CAL also possesses positive role in anti-cancer, enriching the pharmacological effect and application of Astragalus membranaceus extracts (Tseng et al., [@B131]; Kong et al., [@B63]). It\'s demonstrated that CAL significantly impedes lncRNA EWSAT1 expression in nasopharyngeal carcinoma (NPC), followed by influenced downstream factors and pathways, leading to inhibitory growth. Furthermore, lncRNA EWSAT1 overexpression can reverse CAL-induced effect, indicating lncRNA EWSAT1 act as the specific target of CAL promisingly (Kong et al., [@B63]). Additionally, Astragaloside IV (ASIV, 3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosylcycloastragenol; [Chem. 39](#T2){ref-type="table"}), another bioactive compound of Astragalus membranaceus (Fisch.) Bunge., can ameliorate precancerous lesions of gastric carcinoma (PLGC) markedly. It lowers mRNA and protein expressions of LDHA, MCT1, MCT4, HIF-1α, and CD147, as well as increasing TIGAR and p53 content. Furthermore, ASIV treatment promotes miR-34a expression. As a result, ASIV improves abnormal glycolysis and dysplasia possibly via regulation of miR-34a/LDHA pathway (Zhang C. et al., [@B174]). Interestingly, the total flavonoids of Astragalus membranaceus (Fisch.) Bunge. (TFA) can improve heart function damaged by viral myocarditis. By upregulating the expression of miR-378 and miR-378^\^ in cardiomyocytes infected with coxsackie B3 virus, TFA may inhibit cardiac hypertrophy and improve prognosis (Nagalingam et al., [@B102]; Wan et al., [@B134]). Therefore, it can be speculated that the heart protection of TFA is attributed to inhibition of myocardial pathology by regulating miR-378 and miR-378^\^. From the above results, it can been seen that although CAL, ASIV and TFA are extracted from the same herb, they have different targets and are applicable for distinct diseases, demonstrating the study necessity of identified ingredients and targets from CHMs. Paeonol ------- Paeonol (PAE, 2′-Hydroxy-4′-methoxyacetophenone; [Chem. 40](#T2){ref-type="table"}) is the main bioactive ingredient of Paeonia suffruticosa Andr. and Cynanchum paniculatum (Bunge) Kitagawa. The two herbs promoted blood circulation and could be used for cardiovascular diseases in TCM practice. Further pharmacological research shows PAE significantly reduces the incidence of ischemic arrhythmia in rats, including lowered frequency of ventricular premature beat, ventricular tachycardia and ventricular fibrillation. Moreover, it markedly decreases infarct size of myocardium. The potential treatment target is miR-1 which is inhibited by PAE in cardiomyocytes (Zhang and Xiong, [@B179]). Nevertheless, the above study only reveals the possible regulatory relationship between PAE and miR-1, which needs more verification and further identifies the downstream target gene of miRNA. Salvianolic Acid A ------------------ Salvianolic acid A (Sal A, (R)-3-(3,4-Dihydroxyphenyl)-2-(((E)-3-(2-((E)-3,4-dihydroxystyryl)-3,4-dihydroxyphenyl) acryloyl)oxy)propanoic acid; [Chem. 41](#T2){ref-type="table"}) is derived from water-soluble phenolic compound of Salvia miltiorrhiza Bge. It has protective effects of anti-IR injury (Jiang et al., [@B53]; Yang et al., [@B163]), recovery of neurological function (Yu D. S. et al., [@B168]) and anti-cancer activities (Chen et al., [@B15]; Lu et al., [@B85]), the latter two pharmacological actions of which are attributed to miRNA regulation. It\'s reported that Sal A significantly increases expression of tight junction proteins and HO-1, and decreases p-caveolin-1 and apoptosis-related proteins, resulting in recovery of blood-spinal cord barrier integrity after spinal cord injury (SCI). Furthermore, HO-1 inhibitor can attenuate the regulation of ZO-1, occluding, and p-caveolin-1 by Sal A. The underlying target and mechanism may be upregulation of miR-101 which promotes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1. Conversely, miR-101 inhibitor accelerates the permeability of rat brain microvascular endothelial cells, and the protein of Cul3 by targeting its mRNA. As a result, Sal A improves neurological function after SCI through targeting miR-101/Cul3/Nrf2/HO-1 signaling pathway (Yu D. S. et al., [@B168]). Another study indicated that Sal A can also down-regulate the expression of multidrug resistance gene MDR1 in lung cancer, thereby emerging as a new treatment agent for lung cancer resistance. The potential mechanism may be related to up-regulation of 4 miRNA expressions including miR-3686, miR-4708-3p, miR-3667-5p, and miR-4738-3p (Chen et al., [@B15]). This study attempts to find the upstream target of Sal A against MDR1 from perspective of post-transcriptional regulation; but current result cannot directly confirm the regulatory correlation between the 4 miRNAs and MDR1. Thus, more and deeper experiments are urgently needed in the future. Andrographolide --------------- Andrographolide (Andro, 17-hydro-9-dehydro-andrographolide; [Chem. 42](#T2){ref-type="table"}) is a diterpenoid lactone compound derived from Andrographis paniculata (Burm. f.) Nees, a natural anti-bacterial and anti-viral CHM. A recent study further demonstrates that Andro can inhibit hepatoma tumor growth. It promotes the expression of 22 miRNAs, but declines that of other 10 miRNAs in a xenograft mouse tumor model in vivo. Among those upregulated miRNAs, miR-222-3p, miR-106b-5p, miR-30b-5p, and miR-23a-5p are confirmed in cell experiments in vitro. Functional analysis reveals that those miRNAs are mainly involved in signaling pathways of miRNAs in cancer, MPAKs and focal adhesion. Moreover, 24 target genes involved in the above signaling pathways are illustrated to be consistent with miRNAs expression (Lu et al., [@B85]). As a result, Andro prevents hepatoma tumor growth partially through regulating miRNA profile; whereas the specific target and underlying mechanism still need deeper study. Puerarin -------- Puerarin (PUE, 7,4\'-Dihydroxy-8-C-glucosylisoflavone; [Chem. 43](#T2){ref-type="table"}) is the main active ingredient extracted from Radix Puerariae Lobatae which improved symptoms of fever, neck stiffness, thirst and diarrhea in ancient China. Modern researches reveal the cardiovascular protection of PUE for myocardial infarction (Zhang et al., [@B183]) and arrhythmia (Zhang et al., [@B175]). The active effects may be attributed to promotion of cardiac differentiation (Cheng et al., [@B23]; Wang L. et al., [@B139]). PUE upregulates expression of caveolin-3, amphiphysin-2 and junctophinlin-2, and then ameliorates myofibril array and sarcomeres formation, accompanied by increased t-tubules development in the embryonic stem cell-derived cardiomyocytes. Moreover, PUE suppresses the upstream regulatory factor of caveolin-3, namely miR-22, indicating miR-22/caveolin-3 axis may be the underlying mechanism of cardiomyogenesis induced by PUE (Wang L. et al., [@B139]). Conclusion {#s11} ========== CHM has long been a powerful weapon used by Chinese people to combat disease. Over thousands of years, practitioners of CHM have accumulated a wealth of knowledge which is used to prevent and cure diseases. The theoretical concepts of TCM act as the basis for scientific research into CHM today, including identification of the bioactive ingredients and underlying mechanisms of CHMs that could be of benefit internationally---a gift from the Chinese people to the world (Tu, [@B132], [@B133]). Chinese pharmacologist, Youyou Tu, and her team discovered the highly effective and low-toxicity bioactive ingredient "artemisinin" from Artemisia annua L. (also referred to as "qinghao" in Chinese), inspired by, "A Handbook of Prescriptions for Emergencies" (written around 317--420 CE), thus making an outstanding contributions to the global treatment of malaria (Tu, [@B133]). Consequently, we became convinced that study of the bioactive ingredients of CHMs is an effective way to reveal their potential mechanisms of action and further broaden their clinical application. By conducting the above comprehensive review, we found that bioactive ingredients of CHMs can play positive roles in treatment of cancer, cardiovascular, nervous system, respiratory, digestive, infectious, and senescence-related diseases. Through targeting various miRNAs, lncRNAs, circRNAs, or ceRNA crosstalk, these ingredients exert protective effects, including pro-apoptosis, anti-proliferation and anti-migration, anti-inflammation, anti-atherosclerosis, anti-infection, anti-senescence, and anti-structural remodeling. Some miRNAs, including miR-21, miR-34a, miR-34c, miR-155, miR-29a, miR-203, miR-27b, miR-184, and miR-143, contributed to the treatment mechanisms of more than one bioactive ingredient of CHMs. In particular, miR-21 was identified as targeted and regulated by BBR (Luo et al., [@B89]), TP (Li et al., [@B74]), RES (Wang G. et al., [@B136]), CA (Qu et al., [@B107]), ICA (Li J. et al., [@B70]), AIL (Yang P. et al., [@B160]), Car/Thy (Khosravi and Erle, [@B61]), DHM (Yang D. et al., [@B158]), and COR (Yang et al., [@B157]), especially in its anti-cancer activities, indicating that this miRNA is stably targetable and responsive to the pharmacological effects of various CHMs. Moreover, miR-155 was associated with inflammatory responses and could be inhibited by CUR, RES, Tan IIA, CA, Car/Thy and AKBA, in inflammatory-related diseases (Tili et al., [@B130]; Fan et al., [@B28]; Khosravi and Erle, [@B61]; Ma F. et al., [@B91]; Xuan et al., [@B156]; Qu et al., [@B107]; Sayed et al., [@B114]). Thus, it is highly likely that miR-155 could represent a new treatment target for anti-inflammation. In addition, three complex ceRNA crosstalk networks were discovered to function in the therapeutic mechanisms of ART, Sch B, and CA. Specifically, ART regulates the lncRNA UCA1/miR-184/BCL-2 axis, to inhibit prostate cancer (Zhou S. et al., [@B194]), while the has-circ-0043256/miR-1252/ITCH axis was involved in the treatment of non-small cell lung cancer by CA (Tian F. et al., [@B128]). The miR-150/ lncRNA BCYRN1 axis was targeted by Sch B treatment, leading to suppression of cell proliferation in asthma (Zhang X. Y. et al., [@B185]). All of these complex networks provide foundations for in-depth understanding and broader application of CHMs in the near future. The interactions between bioactive ingredients of CHMs with ncRNA targets are the subject of intensive and rapidly expanding research. This has helped to reveal the treatment mechanisms underlying the activities of CHMs and offers promising complementary and alternative treatments for diseases, based on scientific research. Although some previous reviews have revealed the increasing importance of bioactive ingredients (Huang et al., [@B50]; Lelli et al., [@B67]) or CHMs (Hong et al., [@B44]) in the treatment of diseases by targeting ncRNA. However, most of them mainly focused on one kind of ncRNA (particularly miRNA), or are limited to a specific disease (mostly cancer) (Mohammadi et al., [@B101]; Mirzaei et al., [@B98]); rather than overall and comprehensive ncRNA targets, ceRNA crosstalk and corresponding mechanisms. As a result, we consider it\'s necessary to make a systematic review about the treatment mechanisms of bioactive ingredients from CHMs by targeting miRNA, lncRNA, and circRNA. From our review, it can be seen that studies are currently in initial and exploratory phases, and several critical problems remain. First, various individual ncRNA molecules are targets of CHM bioactive ingredients; however, recent results are far from sufficient to allow understanding of the complex regulatory interactions between circRNA, lncRNA, miRNA, and mRNA in the treatment of diseases. Second, the metabolism of drugs in single cell lines and animals may differ from that in the human body; therefore, results based on basic research require further verification in clinical trials. Third, each CHM generally contains numerous ingredients and a TCM clinical prescription often consists of several CHMs; therefore, multiple targets and ceRNA crosstalk must occur and the study of classic TCM formulae will further complicate the picture. In conclusion, ncRNAs are potential targets of CHMs and understanding of ceRNA crosstalk has helped to reveal the complex mechanisms underlying multi-target and multi-level regulation of bioactive ingredients from CHMs. Therefore, CHM ingredients represent new and promising choices for future alternative disease treatments. Author Contributions {#s12} ==================== JW and JL designed the study. YD, HC, and JG conducted searches and extracted the data. YL and YD analyzed the data. YD wrote the manuscript. Conflict of Interest Statement ------------------------------ The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding. This study was supported by the National Natural Science Foundation of China (No. 81673847; No. 81473561). ###### Chem. 1--43 Chemical formulae of bioactive ingredients from CHMs. ------------------------------------- -------------------------------------------- ![](fphar-10-00515-i0001.jpg)\ ![](fphar-10-00515-i0002.jpg)\ Chem. 1 Berberine Chem. 2 Artesunate ![](fphar-10-00515-i0003.jpg)\ ![](fphar-10-00515-i0004.jpg)\ Chem. 3 Triptolide Chem. 4 Triptonide ![](fphar-10-00515-i0005.jpg)\ ![](fphar-10-00515-i0006.jpg)\ Chem. 5 Ailanthone Chem. 6 Cordycepin ![](fphar-10-00515-i0007.jpg)\ ![](fphar-10-00515-i0008.jpg)\ Chem. 7 Soya-cerebroside Chem. 8 Tubeimoside I ![](fphar-10-00515-i0009.jpg)\ ![](fphar-10-00515-i0010.jpg)\ Chem. 9 Oridonin Chem. 10 Curcumin ![](fphar-10-00515-i0011.jpg)\ ![](fphar-10-00515-i0012.jpg)\ Chem. 11 Shikonin Chem. 12 Paeoniflorin ![](fphar-10-00515-i0013.jpg)\ ![](fphar-10-00515-i0014.jpg)\ Chem. 13 Honokiol Chem. 14 Schiscandrin B ![](fphar-10-00515-i0015.jpg)\ ![](fphar-10-00515-i0016.jpg)\ Chem. 15 Resveratrol Chem. 16 Soybean isoflavones ![](fphar-10-00515-i0017.jpg)\ ![](fphar-10-00515-i0018.jpg)\ Chem. 17 Matrine Chem. 18 Corylin ![](fphar-10-00515-i0019.jpg)\ ![](fphar-10-00515-i0020.jpg)\ Chem. 19 Tanshinones UA Chem. 20 Magnesium lithospermate B ![](fphar-10-00515-i0021.jpg)\ ![](fphar-10-00515-i0022.jpg)\ Chem. 21 Baicalin Chem. 22 Cinnamaldehyde ![](fphar-10-00515-i0023.jpg)\ ![](fphar-10-00515-i0024.jpg)\ Chem. 23 Geniposide Chem. 24 Carvacrol ![](fphar-10-00515-i0025.jpg)\ ![](fphar-10-00515-i0026.jpg)\ Chem. 25 Thymol Chem. 26 3-acetyl-11-keto-a-boswellic acid ![](fphar-10-00515-i0027.jpg)\ ![](fphar-10-00515-i0028.jpg)\ Chem. 27 Sinapic acid Chem. 28 Polydatin ![](fphar-10-00515-i0029.jpg)\ ![](fphar-10-00515-i0030.jpg)\ Chem. 29 Ampelopsin Chem. 30 Icariine ![](fphar-10-00515-i0031.jpg)\ ![](fphar-10-00515-i0032.jpg)\ Chem. 31 Ginsenosides Chem. 32 Salidroside ![](fphar-10-00515-i0033.jpg)\ ![](fphar-10-00515-i0034.jpg)\ Chem. 33 Phlorizin Chem. 34 Osthole ![](fphar-10-00515-i0035.jpg)\ ![](fphar-10-00515-i0036.jpg)\ Chem. 35 Panax Notoginseng Saponins Chem. 36 Tetrandrine ![](fphar-10-00515-i0037.jpg)\ ![](fphar-10-00515-i0038.jpg)\ Chem. 37 Leonurine Chem. 38 Calycosin ![](fphar-10-00515-i0039.jpg)\ ![](fphar-10-00515-i0040.jpg)\ Chem. 39 Astragaloside IV Chem. 40 Paeonol ![](fphar-10-00515-i0041.jpg)\ ![](fphar-10-00515-i0042.jpg)\ Chem. 41 Salvianolic acid A Chem. 42 Andrographolide ![](fphar-10-00515-i0043.jpg)\ Chem. 43 Puerarin ------------------------------------- -------------------------------------------- [^1]: Edited by: Chandravanu Dash, Meharry Medical College, United States [^2]: Reviewed by: Zijian Zhang, Texas Tech University Health Sciences Center El Paso, United States; Yong Xu, First Hospital of Shanxi Medical University, China [^3]: This article was submitted to Pharmacogenetics and Pharmacogenomics, a section of the journal Frontiers in Pharmacology [^4]: †These authors have contributed equally to this work	{ "pile_set_name": "PubMed Central" }
SS Joplin Victory The SS Joplin Victory was the 12th Victory ship built during World War II under the Emergency Shipbuilding program. She was launched by the California Shipbuilding Company on April 25, 1944 and completed on June 15, 1944. The ship's United States Maritime Commission designation was VC2-S-AP3, hull number 12 (V-12). The 10,500-ton Victory ships were designed to replace the earlier Liberty Ships. Liberty ships were designed to be used just for World War II. Victory ships were designed to last longer and serve the US Navy after the war. The Victory ship differed from a Liberty ship in that they were: faster, longer and wider, taller, had a thinner stack set farther toward the superstructure and had a long raised forecastle. SS Joplin Victory was christened on April 26, 1944 and launched at the yards of the California Shipbuilding Corporation. The launching of The SS Joplin Victory splashed into the water of Wilmington, Los Angeles. World War II SS Joplin Victory served in the Pacific Ocean in World War II as part of the Pacific war. SS Joplin Victory Naval Armed Guard crews earned "Battle Stars" in World War II for the assault occupation of Okinawa. Ward incident SS Joplin Victory was part of a foreign relations project between the United States and China called the Ward incident, a diplomatic incident. In 1949 she streamed in to China port city of Port of Tianjin, called Taku Bar at the time, to remove US citizens at Mukden. She steamed in with the Lakeland Victory. SS Joplin Victory was in port from Dec. 5 to 7, 1949. The two ships removed the US diplomatic staff in China. US Consul General Angus Ward and nineteen other American citizens has spent time in a Communist Chinese jail. On February 3, 1949 she arrived in San Francisco with Shanghai refugees. Korean War SS Joplin Victory served as merchant marine naval ship supplying goods for the Korean War. She help move the 140th Medium Tank Battalion. About 75 percent of the personnel taken to Korea for the Korean War came by the merchant marine ships. The SS Joplin Victory transported goods, mail, food and other supplies. About 90 percent of the cargo was moved by merchant marine naval to the Korean war zone. SS Joplin Victory made trips between 18 November 1950 and 23 December 1952 helping American forces engaged against Communist aggression in South Korea. On Nov. 19, 1952 she was blown by high winds and broke loose from the Oakland Estuary pier, in Oakland, California. She ran into the side of a transport ship, the USN Navy's SS Neshoba. James River She was laid up at Astoria, Oregon in 1952 and later transferred to the James River in Virginia as part of the National Defense Reserve Fleet for years. In 1994 she was scrapped in Alang, India. See also List of Victory ships Liberty ship Type C1 ship Type C2 ship Type C3 ship References Sources Sawyer, L.A. and W.H. Mitchell. Victory ships and tankers: The history of the ‘Victory’ type cargo ships and of the tankers built in the United States of America during World War II, Cornell Maritime Press, 1974, 0-87033-182-5. United States Maritime Commission: Victory Cargo Ships Category:Victory ships Category:Ships built in Los Angeles Category:United States Merchant Marine Category:1944 ships Category:World War II merchant ships of the United States	{ "pile_set_name": "Wikipedia (en)" }
Q: Linear Interploation using two arrays I have the following arrays: List_CD = [2410.412434205376, 2287.6750893063017, 2199.2602314650626, 2124.4647889960825, 2084.5846633116403, 2031.9053600816167, 1996.2844020790524, 1957.1098650203032, 1938.4110044030583, 1900.0783178367647, 1877.6396548046785, 1868.2902104714337, 1844.9165996383219, 1816.8682911816766] List_Dose = [10.0, 12.0, 14.0, 16.0, 18.0, 20.0, 22.0, 24.0, 26.0, 28.0, 30.0, 32.0, 34.0, 36.0] what I am trying to do is to do a simple interpolation using: dsize = numpy.interp(2000., List_CD, List_Dose) the result that expect is between 20.0 and 22.0 but I keep getting a value of 10.0 Can anyone help here please? A: xp : 1-D sequence of floats The x-coordinates of the data points, must be increasing. Your List_CD is not increasing. You can sort it in the following way: d = dict(zip(List_CD, List_Dose)) xp = sorted(d) yp = [d[x] for x in xp] numpy.interp(2000., xp, yp) # returns 21.791381359216665 or: order = numpy.argsort(List_CD) numpy.interp(2000., np.array(List_CD)[order], np.array(List_Dose)[order])	{ "pile_set_name": "StackExchange" }
G Man Breaking the Ninth Commandment G Man has been saying that I have said that you can believe in a supernatural deity or God and still be an atheist…which is completely absurd. He recently was on the Drunken Peasants again lying about what I have never said, even though just a few days prior I made it very clear that you can not believe in a God and rationally consider yourself to be an atheist. LIKE, SHARE, and SUBSCRIBE 🙂 (and leave a comment!)	{ "pile_set_name": "Pile-CC" }
---------------------- Forwarded by Judy Hernandez/HOU/ECT on 11/22/2000 08:51 AM --------------------------- Daily-Blessings <dailyblessings.10@lists.postmastergeneral.com> on 11/21/2000 10:47:07 PM To: judy.hernandez@enron.com cc: Subject: Daily Blessing 11/22/00 Daily Blessing http://www.daily-blessings.com/bless147.htm Intelligence http://www.daily-blessings.com/humor54.htm FORGET PC PHONE. GET REAL LONG DISTANCE AT NO COST bigredwire is the first and only company to offer REAL long distance at no cost Switch your long distance to bigredwire and get REAL long distance at zero cost to you. Up to 100 complimentary minutes everyday when you zap your online bill. If you don't zap, pay only 5 cents a minute without fees. Switch now! find out how at http://www.daily-blessings.com/cjbigredwire.htm Hundred's of you have taken advantage of the free download available for the Work From Home folks. If you haven't checked it out yet...you should!! http://www.daily-blessings.com/cjworkfromhome.htm <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> * To remove yourself from this mailing list, point your browser to: http://inbound.postmastergeneral.com/remove?dailyblessings:10 * Enter your email address (judy.hernandez@enron.com) in the field provided and click "Unsubscribe". The mailing list ID is "dailyblessings:10". OR... * Reply to this message with the word "remove" in the subject line. This message was sent to address judy.hernandez@enron.com X-PMG-Recipient: judy.hernandez@enron.com <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>>	{ "pile_set_name": "Enron Emails" }
Social Anhedonia and Romantic Relationship Processes. Social anhedonia is a deficiency in the capacity to experience pleasure from social interactions. This study examined the implications of social anhedonia for romantic relationship functioning, including the association of social anhedonia with sentiments toward romantic partners that are central to relationship functioning (satisfaction, commitment, regard for the partner, and care for the partner's welfare) and analogous perceptions of the partner's sentiments. Data were collected from 281 participants who were involved in romantic relationships. Social anhedonia predicted less satisfaction, regard, and care, and these effects were independent of attachment insecurity and self-esteem. In addition, social anhedonia had an indirect negative effect on commitment via attachment avoidance. Social anhedonia also predicted more negative perceptions of the partner's sentiments. Results suggest that social anhedonia may undermine the functioning of romantic relationships by reducing positive sentiments toward partners and security in the partner's sentiments toward the self.	{ "pile_set_name": "PubMed Abstracts" }
Michael Arndt to Write Screenplay for Star Wars: Episode VII - jwallaceparker http://starwars.com/news/michael-arndt-to-write-screenplay-for-star-wars-episode-vii.html ====== lazugod ...you posted this eleven times. ~~~ dfc Twelve times. I flagged 11 of them.	{ "pile_set_name": "HackerNews" }
Adobe Digital Imaging How-Tos: Essential Techniques for Photoshop CS5, Lightroom 3, and Camera Raw 6 is a concise, current, and affordablefull-color guide to the key techniques for working with digital images. Choose the How-Tos guide when you want to learn the features and functions that provide immediate results. In Photoshop Lightroom 3 Advanced Techniques, photographer Chris Orwig shows how to master the subtleties of Lightroom 3 and maximize its efficiency. The course begins with an in-depth exploration of Lightroom catalogs to keep track of photos, collections, keywords, stacks, and more. Along the way, Chris shows how to integrate Bridge and Photoshop in the Lightroom workflow and shares advanced techniques, including image editing with the adjustment brush, automating actions, using plug-ins and extensions, exporting to email or an FTP server, and more. Exercise files are included with the course. Serious digital photographers, amateur or pro, who seek the fastest, easiest, most comprehensive way to learn Adobe Photoshop Lightroom 3 choose Adobe Photoshop Lightroom 3 Classroom in a Book from the Adobe Creative Team at Adobe Press.	{ "pile_set_name": "Pile-CC" }
A knifeman barricaded himself in a room with a pregnant woman at a refugee centre in Hamburg before being dramatically arrested, it has emerged. Armed police were called amid reports a man with a weapon had stormed into the facility in Hammerbrook area of the German city this morning. He is understood to have been holding a pregnant woman - believed to be his partner - hostage at the centre and was holed-up in a room. A gunman has barricaded himself in refugee centre in the German city of Hamburg, it has been reported (file picture) Footage online shows elite German officers with assault rifles storming into the building this morning at about 10.30am local time. A pregnant woman in a yellow top was seen being led away from the building a short time later. According to Bild, the man was overpowered by police and was seen on a stretcher being taken to an ambulance. Hamburg police said the man had wounded himself during the operation, but the nature of his injuries is not yet known. The police force had earlier taken to Twitter to say a major police operation was underway in the Hammerbook area. Local media reported that the man was a refugee who had been living in another state within Germany. It is not yet known why he barricaded himself in the building.	{ "pile_set_name": "OpenWebText2" }
49er & 49er FX World Championships The 49er World Championships are international sailing regattas in the 49er and 49er FX classes organized by the International Sailing Federation. It was first held in 1997. In 2013, the 49er FX class was added to the programme. The 49er is an Olympic class since 2000. The 49er FX is anan Olympics class since 2016. Editions All-time medal table 49er 49er FX Medalists 49er Open 49er Men's 49er FX Women's 49er Youth 49er FX Youth Multiple medallists 49er 49er FX See also ISAF Sailing World Championships International Sailing Federation References External links International 49er Class Association Sailing competitions Category:Recurring sporting events established in 1997	{ "pile_set_name": "Wikipedia (en)" }
Wearable UV Sensor Based on Carbon Nanotube-Coated Cotton Thread. A fabric-compatible UV sensor is presented using a cellulose-based thread coated with single-wall carbon nanotube ink. Two-terminal resistive responses of the thread were measured upon exposure to UV, and the effects of intensity, wavelength, and on/off cycling were studied. The sensor was tested in the field under direct sunlight, demonstrating practical usability for a wearable/flexible UV sensor system. The results here confirm the potential for an inexpensive wearable sensor in contrast to the conventional rigid and bulky solid-state detectors.	{ "pile_set_name": "PubMed Abstracts" }
4G Wimax Jammer 50 Meters,High Power 4G Block,4G LTE Blocker 60 Meters,Product Description This high quality signal jamming blocker will fit in the palm of your hand, or comfortably in your pocket. Our best seller has no external antennas to break, is loaded with great...	{ "pile_set_name": "Pile-CC" }
Abnormal glucose metabolism in patients treated with antipsychotics. Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical antipsychotics, although the question is still debated because of the presence of many confounding factors. A close relationship between drug-induced weight gain and risk of diabetes has been reported, emphasizing the role of insulin resistance. However, some cases of diabetes developed independently of weight gain, rather rapidly and possibly progressing to ketoacidosis, thus arguing for a severe impairment of insulin secretion. Another debated question is whether diabetes risk is a class action or a differential action. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. Interestingly, reversibility of drug-related diabetes has been reported with aripiprazole. The choice of atypical antipsychotic medication for a specific patient depends on many factors, but the likelihood of developing diabetes should become an important consideration. When prescribing an atypical antipsychotic, a commitment to careful baseline screening and follow-up monitoring is essential in order to mitigate the risk of developing diabetes and associated complications.	{ "pile_set_name": "PubMed Abstracts" }
It has been reported that Girls’ Generation member Taeyeon is in the middle of gearing up for a new solo album. Aiming for a release in the first half of the year, she is currently gathering songs to be included in the album. If all goes according to plan, Taeyeon will be the very first member of Girls’ Generation to make her debut as a solo artist. Taeyeon has already received much recognition from the public for her vocal abilities with a number of solo songs through drama OSTs, such as “If,” “Can You Hear Me,” and more. It is said that the Girls’ Generation member is joining the list of idols from SM Entertainment to take on a solo debut following SHINee’s Taemin, Super Junior’s Kyuhyun, SHINee’s Jonghyun, as well as f(x)’s Amber, who is expected to release a solo album next month. Are you excited to see Taeyeon debut as a solo artist in the near future? Source (1)	{ "pile_set_name": "OpenWebText2" }
Q: recursively traverse multidimensional dictionary and export to csv I've have a complex multidimensional dictionary that I want to export some of the the key value pairs to a csv file as a running log file. I've tried the various help with exporting to cvs functions and hacked away at most of the code example in stackoverflow on traversing multidimensional dictionaries but have failed to arrive at a solution. This problem is also unique in that it has only some key values I want to export. Here is the dictionary: cpu_stats = {'time_stamp': {'hour': 22, 'month': 5, 'second': 43, 'year': 2014, 'day': 29, 'minute': 31}, 'cpus': [[{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 39}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000}]]} I need to format the values in time_stamp into a yyyy-mm-dd hh:mm:ss and store it as the first cell of the row. I then need the values in 'cpus' for CPU_INDEX, CPU_TEMPERATURE, and CPU_FAN_SPEED in the same row as the time stamp. The csv file should look like this: time_stamp, cpu_index, cpu_temperature, cpu_fan_speed 2014-05-29, 1, 38, 12000 One example I've been hacking away on is: def walk_dict(seq, level=0): """Recursively traverse a multidimensional dictionary and print all keys and values. """ items = seq.items() items.sort() for v in items: if isinstance(v[1], dict): # Print the key before make a recursive call print "%s%s" % (" " * level, v[0]) nextlevel = level + 1 walk_dict(v[1], nextlevel) else: print "%s%s %s" % (" " * level, v[0], v[1]) I get the following output walk_dict(cpu_stats) cpus [[{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 38}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000}]] time_stamp day 29 hour 22 minute 17 month 5 second 19 year 2014 I have also been hacking away at this function as well hoping I can store the date information into variables that can then be formatted into a single string. Unfortuatly it has recursive calls which loose the local variables on subsequent calls. Using global was futile. def parseDictionary(obj, nested_level=0, output=sys.stdout): spacing = ' ' if type(obj) == dict: print >> output, '%s{' % ((nested_level) * spacing) for k, v in obj.items(): if hasattr(v, '__iter__'): # 1st level, prints time and cpus print >> output, '%s:' % (k) parseDictionary(v, nested_level + 1, output) else: # here is the work if k == "hour": hour = v elif k == "month": month = v elif k == "second": second = v elif k == "year": year = v elif k == "day": day = v elif k == "minute": minute = v print >> output, '%s %s' % (k, v) print >> output, '%s}' % (nested_level * spacing) elif type(obj) == list: print >> output, '%s[' % ((nested_level) * spacing) for v in obj: if hasattr(v, '__iter__'): parseDictionary(v, nested_level + 1, output) else: print >> output, '%s%s' % ((nested_level + 1) * spacing, v) print >> output, '%s]' % ((nested_level) * spacing) else: print >> output, '%s%s' % (nested_level * spacing, obj) if __name__ == "__main__": global year global month global day global hour global minute global second cpu_stats = {'time_stamp': {'hour': 22, 'month': 5, 'second': 43, 'year': 2014, 'day': 29, 'minute': 31}, 'cpus': [[{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 39}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000}]]} parseDictionary(cpu_stats) print '%s-%s-%s %s:%s:%s' % (year, month, day, hour, minute, second) output: { time_stamp: { hour 22 month 5 second 27 year 2014 day 29 minute 57 cpus: [ [ { metric_type CPU_INDEX value 1 { metric_type CPU_TEMPERATURE value 39 { metric_type CPU_FAN_SPEED value 12000 ] ] Traceback (most recent call last): File "./cpu.py", line 135, in <module> print '%s-%s-%s %s:%s:%s' % (year, month, day, hour, minute, second) NameError: global name 'year' is not defined Thanks, I appreciate any help in pointing me in the right direction as I'm currently at a loss. A: I agree with @desired login, however assuming you have no control of the incoming data and had to work with what you showed in your questions... You could just traverse it like so: cpu_stats = {'time_stamp': {'hour': 22, 'month': 5, 'second': 43, 'year': 2014, 'day': 29, 'minute': 31}, 'cpus': [ [{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 39}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000} ] ] } timestamp = '' for stats in cpu_stats.keys(): if stats == 'time_stamp': timestamp = '{year}-{month}-{day}'.format(**cpu_stats[stats]) if stats == 'cpus': for cpu in cpu_stats[stats]: cpu_index = '' cpu_temperature = '' cpu_fan_speed = '' for metric in cpu: if metric['metric_type'] == 'CPU_INDEX': cpu_index = str(metric['value']) elif metric['metric_type'] == 'CPU_TEMPERATURE': cpu_temperature = str(metric['value']) elif metric['metric_type'] == 'CPU_FAN_SPEED': cpu_fan_speed = str(metric['value']) print ','.join([timestamp, cpu_index, cpu_temperature, cpu_fan_speed])	{ "pile_set_name": "StackExchange" }
Inflatable Harley Quinn Bat - Suicide Squad 3 1/2in x 30in Plastic Prop \| SKU: 687576 Price: $9.99 Knock your Suicide Squad costume out of the park with this Inflatable Harley Quinn Bat. Printed to look like the bat she carries in Suicide Squad, this inflatable bat reads "Good Night". Swing it around as you get into some mischief in your Suicide Squad Harley Quinn costume.	{ "pile_set_name": "Pile-CC" }
The use of halogen lamps in light fixtures provides many advantages over the use of flourescent and incandescent lamps. Halogen light sources provide, among other benefits, pure white light, instant start-up with no flickering, and are operational at any temperature including sub freezing temperatures. However, halogen light fixtures typically employ one or more lamps having a wattage that is often 100 watts or greater. This use of high wattage lamps increases the heat generated in and around the fixture. Thus, there is a need for light fixtures that allow and provide for the efficient dissipation of the heat generated by the lamp or lamps contained therein. Not only will the dissipation of heat prevent the fixture itself from becoming dangerously hot, it also assists in protecting the fixture's internal components from heat damage as well. In addition, because of the high temperatures created by a halogen lamp, the possibility exists that objects located near the lamp may unintentionally combust. Consequently, there is a need for a fixture design that prevents objects or structures such as walls and the like from coming into close contact with the light generated by the fixture in order to reduce the risk of inadvertent combustion.	{ "pile_set_name": "USPTO Backgrounds" }
HELSINKI – Nordic governments are primed to raise suspected GPS jamming of military exercises and communications with Russia. Finland and Norway intend to launch diplomatic discussions with Moscow over suspected GPS signal-jamming by Russia’s military over recent weeks that impacted areas in northern Norway where NATO-led Trident Juncture maneuvers were being conducted. Norway’s defense intelligence agency said it tracked the source of the signal-jamming to a Russian military base on the nearby, heavily fortified Kola Peninsula. Finland’s military intelligence said Norway’s analysis mirrors its own investigations and evaluations. Scrambled GPS signals were first detected during NATO’s large-scale Trident Juncture exercises in Norway at the end of October. Defense and civil aviation chiefs in Finland and Norway warned that the GPS jamming posed a serious risk to both military and commercial aircraft using the affected airspace in the High North. Finland’s Ministry of Foreign Affairs (MFA) has presented the national parliament’s Committee on Foreign Affairs (CFA) a preliminary report on the jamming. The MFA is expected to furnish the panel with a more conclusive report by the end of November. NATO general: Europe not moving fast enough on military mobility Are there changes that NATO nations can easily make to ease the logistics challenge in Europe? The GPS signal-jamming issue is being discussed with the Russian Federation “through diplomatic channels”, said Sari Rautio, director of the MFA’s unit for security policy and crisis management. Russia will almost certainly deny any involvement in jamming military exercises, said Matti Vanhanen, the CFA’s chairman. × Fear of missing out? Sign up for the Early Bird Brief, the defense industry's most comprehensive news and information, straight to your inbox. Thanks for signing up. By giving us your email, you are opting in to the Early Bird Brief. "There is every reason to trust Norway and its intelligence. It’s unlikely that Norway will publicly disclose the methods behind its assessment. As no technical evidence will be offered in the public domain, we may end up in a situation where Russia just denies it. We need to tell Russia that we do not accept disturbances of this kind in our airspace," Vanhanen said. Initial diplomatic contacts between Nordic governments and Moscow has produced a flat denial that Russia was behind the GPS signal-jamming. "There is a tendency to blame Russia for all sins in general. As a rule, these allegations are found to have no basis in actual fact," said Dmitry Peskov, the senior press spokesman to Russian President Vladimir Putin. Norway’s civil aviation authorities opened an investigation into possible GPS signal-jamming in the High North at the end of October when several commercial aircraft reported loss of satellite navigation while flying over the Troms and Finnmark regions in the north of the country. Warnings and confusion preceded Norwegian frigate disaster: here’s what we know The disaster has far-reaching consequences for the Norwegian Navy, which now faces the loss of one of its premier warfighting assets. National aviation authorities in Finland and Norway subsequently issued a so-called notice to airmen (NOTAM) due to widespread disturbances in GPS signals in the airspace of both countries’ northern regions. In Norway, the NOTAM related to the northern airports of Kirkenes and Vadsø which are located close to the border with Russia and the Kola Peninsula. The investigation by Norway into suspected GPS signal-jamming by Russia covered the period between Oct. 16 and Nov. 7. NATO’s Trident Juncture exercises started, following months of field preparation work, on Oct. 25 and finished on Nov. 7. Norway also conducted investigations into suspected jamming of satellite navigation systems by Russia linked to the Zapad-2017 drill. These large-scale military exercises by Russia were held on and around the Kola Peninsula during September and October 2017.	{ "pile_set_name": "OpenWebText2" }
The integration of song environment by catecholaminergic systems innervating the auditory telencephalon of adult female European starlings. Mate choice is among the most consequential decisions a sexually reproducing organism can make. In many songbird species, females make mate-choice decisions based, in part, on variation between males in songs that reflect their quality. Importantly, females may adjust their choice relative to the prevalence of high quality songs. In European starlings (Sturnus vulgaris), females prefer males that primarily sing long songs over those that primarily sing short songs, and sensitivity of the auditory telencephalon to song length depends on the prevalence of long songs in the environment. Several lines of evidence suggest a role for noradrenergic innervation of the auditory telencephalon in mediating this neuro- and behavioral plasticity. To simulate variation in quality of the song environment, we exposed adult female starlings to 1 week of either long or short songs and then quantified several monoamines and their metabolites in the caudomedial mesopallium and caudomedial nidopallium (NCM) using high performance liquid chromatography. We also used immunocytochemistry to assess these areas for immunoreactive dopamine-beta-hydroxylase (DBH-ir), the enzyme that synthesizes norepinephrine. We found that long songs elevated levels of the principal norepinephrine metabolite, the principal dopamine metabolite, and the probability of DBH-ir in the NCM compared to short songs. Song environment did not appear to influence norepinephrine or dopamine levels. Thus, the quality of the song environment regulates the local secretion of catecholamines, particularly norepinephrine, in the female auditory telencephalon. This may form a basis for plasticity in forebrain sensitivity and mate-choice behavior based on the prevalence of high-quality males.	{ "pile_set_name": "PubMed Abstracts" }
Arthur Covington Arthur Edwin Covington (21 September 1913 – 17 March 2001) was a Canadian physicist who made the first radio astronomy measurements in Canada. Through these he made the valuable discovery that sunspots generate large amounts of microwaves at the 10.7 cm wavelength, offering a simple all-weather method to measure and predict sunspot activity, and their associated effects on communications. The sunspot detection program has run continuously to this day. Early life and education Covington was born in Regina and grew up in Vancouver. He showed an early interest in astronomy, and had built a refractor telescope after meeting members of the local chapter of the Royal Astronomical Society of Canada. He was also interested in amateur radio and operated station VE3CC for a time. He started his career as a radio operator on ships operated by the Canadian National Railways. He put himself through school and eventually earned a bachelor's degree from the University of British Columbia in 1938, and obtained his master's degree from the same institution in 1940 after building an electron microscope. He then moved to University of California in Berkeley where he received his doctoral degree in nuclear physics in 1942. He was still at Berkeley when he was invited to join the National Research Council (NRC) in Ottawa in 1942 as a radar technician, working at the NRC's Radio Field Station. Solar observations Immediately after the war Covington became interested in radio astronomy, and built a small telescope out of the electronic parts from a surplus SCR-268 radar combined with parts from another receiver originally built to test silicon crystal radio parts for radar applications. These electronics were attached to the 4 ft (1.2 m) parabolic dish from a Type III gun-laying radar. The system operated at a frequency of 2800 MHz, or a wavelength of 10.7 cm. Initially the instrument was pointed in the direction of various celestial objects, including Jupiter, the Milky Way, aurora borealis, and the Sun, but it proved too insensitive to pick up any source other than the Sun. So a solar study program was started. As time passed, Covington and his colleagues realized that the Sun's emission at 10.7 cm wavelength was varying, which was unexpected. Thinking at that time was that the solar emission at centimeter wavelengths would be simply black body emission from a ball of hot gas. Covington became convinced that the effect was due to sunspots, as the flux appeared to vary with the number of visible spots. The resolution of the device, about seven degrees, made it impossible to "pick out" a spot on the sun's surface for study, making a demonstration of the claim difficult. An opportunity to directly measure this possibility presented itself on November 23, 1946 when a partial solar eclipse passed over the Ottawa area, and Covington was able to conclusively demonstrate that the microwave emissions dropped off precipitously when the Moon covered a particularly large sunspot. This also demonstrated that magnetic fields were instrumental in sunspot activity. It was entirely by accident that the original instrument operated on frequencies suitable to detection of the 10.7 cm signal, and it had never been intended for "production" use. As the importance of the sunspot measurements became obvious, plans were made to continue these observations over a longer time period. As the Radio Field Station was still actively being used for radar development, and causing heavy interference as a result, a new location was selected about five miles (8 km) away at Goth Hill. Here they measured the whole-disk flux and averaged the measurements to produce three highly accurate measurements a day. He then set about designing an instrument that could directly resolve portions of the sun's disk. The new telescope consisted of a 150 ft (46 m) long section of 3 by 1½ inch metal waveguide cut with slots in locations to create a simple interferometer with a fan-shaped area of sensitivity. The amount of flux gathered was improved by placing the waveguide in metal trough, and the direction of aim could be changed slightly by rotating the waveguide inside the trough, but in general terms it was used to take measurements as the sun passed through its "beam". The new telescope started operation in 1951, allowing them to directly measure the flux from the Sun's corona and the temperature of the regions above sunspots (about 1,500,000 °C). The Goth Hill observatory also included a number of other instruments for a variety of measurements. ARO Increasing radar and radio use in the Ottawa area presented interference problems, and Covington turned his attention to finding a more suitable "radio quiet" location for the program. This led to the creation of the Algonquin Radio Observatory (ARO) in Algonquin Park, about 150 km northwest of Ottawa but relatively easy to access on major highways. A new 6 ft (1.8 m) parabolic dish solar flux telescope was built in 1960, operating in parallel before taking over duties from the Goth Hill instrument in 1962. In 1964 an identical instrument was installed at the Dominion Radio Astrophysical Observatory (DRAO) in British Columbia. This was followed by a more powerful version of the waveguide instrument, this time focused by a series of thirty-two 10 ft (3 m) dishes arranged over a 700 ft (215 m) waveguide, which opened in 1966. The ARO was greatly expanded in 1966 with the opening of the 150 ft (46 m) deep-space telescope. This was a major research site through the 1960s and 70s, although limitations in its design made it see less use in the 1980s. For some time this instrument was joined by a smaller 18 m telescope originally located at the David Dunlap Observatory outside Toronto, operated by the University of Toronto. The original solar observatories remained in use until 1990 when funding drawdowns at the NRC forced the closure of the entire Algonquin site. In 1991 the 1.8 m dish was moved to the DRAO as a backup instrument. Covington's work led to other solar-related discoveries. Observations in 1969 led to the realization that certain types of major sunspot breakouts were preceded by a particular type of radio signal, which allowed advanced prediction of upcoming solar storms. As other teams also started studying the solar flux they noticed that the different teams all came to different conclusions about the total flux, due to differences in the instruments and other effects. Covington worked on an effort to correlate these measurements and solve a single flux number, which was published in 1972. He also played a role in the construction of the Indian River Observatory, an amateur built 200 m interferometer. Retirement Covington remained director of the ARO until he retired in 1978. He died in 2001 in Kingston, Ontario, at the age of 88. One of the buildings at the Dominion Radio Astrophysical Observatory was named in his honour in 2003. He had many hobbies including a fondness for rare books, many of which have been donated to Queen's University in the Riche-Covington collection. Notes The exact location of "Goth Hill" is not known, as this term does not appear on modern maps. According to the City of Ottawa Archives, it is likely located on a plot of land south of the downtown Ottawa area, a plot formerly owned by Robert Goth that appears in the Beldon Atlas, 1878. The terms "hill" and "ridge" were commonly applied to otherwise nondescript land throughout the Gloucester Township area. The Goth plot lies off the eastern end of runway 25 of the Ottawa Macdonald-Cartier International Airport, west of CFS Leitrim. This location fits with all of the known references, which describe it as being "five miles south of Ottawa in South Gloucester". References Category:1913 births Category:2001 deaths Category:Canadian physicists	{ "pile_set_name": "Wikipedia (en)" }
Q: Can the javascript .bind go up multiple levels? I have a piano Keyboard object in JavaScript and JQuery, like so: function Keyboard(name, size, xPos, yPos, octaves) { this.name = name; this.size = size; this.setDimensions = function (){}; this.highlightKeyboard = function (){}; ... etc. } It's got a bunch of methods to set dimensions, generate the keyboard using divs for the keys, generate major and minor scales referencing the classes of the divs, etc. I wrote 4 methods to highlight a major scale when I press a certain key, a minor scale when I press a different key, major and minor triads with two other keys. They all worked, but after writing them I realized all 4 methods use a lot of the same code so I've been trying to consolidate by bringing out most of the code into separate methods in the main Keyboard object so I can call them repeatedly. The problem I'm having now that I'm consolidating is getting the $(document).keypress objects to play nice with the external code. What I want is something like this (partial code sample—I left out all the code to generate the keyboard and everything else that wasn't relevant because it seems to be working OK other than this one issue): function Keyboard(name, size, xPos, yPos, octaves) { this.getMajorTonic = (function(userNote) { // code to determine myTonic return myTonic; }); this.setMajScale = function(myTonic) { var scale = []; // code to determine scale[]; return scale; }; this.setScaleClasses = function(scale) { // code to determine scale_classes[] return scale_classes; }; this.highlightKeyboard = function (scale, scale_classes){}; // code to add highlighted classes to my divs based // on the values in scale and scale_classes }; this.findMajorScales = function(userNote); var myTonic = this.getMajorTonic(userNote); var scale = this.setMajScale(myTonic); var scale_classes = this.setScaleClasses(scale); var highlightKeyboard = this.highlightKeyboard; $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard(scale, scale_classes) } }); }; } var keys = new Keyboard("piano", 1, 0, 0, 2); keys.findMajorScales("E"); The desired effect is that when I load the page, it generates a blank keyboard, but when I press the "m" key, it highlights the E Major scale using the this.highlightKeyboard method. So I want to pass the this.findMajorScales method a this.highlightKeyboard method with no arguments, and then have the arguments filled in and the method executed when the "m" key is pressed. Most everything works, including the ($document).keypress object—it executes other code, just not the this.highlightKeyboard method with the right arguments. How do I accomplish this? Does .bind have something to do with it? I can't really figure out if it's applicable here or if I need to do something else. Thanks so much! Jake A: So I want to pass the this.findMajorScales method a this.highlightKeyboard method with no arguments, and then have the arguments filled in and the method executed when the "m" key is pressed. You are listening for M fine, so the only problem you have is invoking highlightKeyboard in the correct context. Consider var foo = {bar: function () {return this}), bar = foo.bar; What will foo.bar() return? (foo) What will bar() return? (window or null or throws an error, etc) You have a lot of options There are several ways around this, you've already mentioned Function.prototype.bind and it may be conceptually easier for you to use Function.prototype.call, Function.prototype.apply or even passing the this variable through using another identifier instead. In either case, the default this in the handler will no longer be an instanceof Keyboard as the event is coming from document Using Function.prototype.bind you have a few options var highlightKeyboard = this.highlightKeyboard.bind(this); $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard(scale, scale_classes); } }); // or binding args ahead of time too var highlightKeyboard = this.highlightKeyboard.bind(this, scale, scale_classes); $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard(); } }); // or binding the handler $(document).keypress(function (event) { if (event.which === 109) { this.highlightKeyboard(scale, scale_classes); } }.bind(this)); Using Function.prototype.call or .apply, requires ref to this var highlightKeyboard = this.highlightKeyboard; var me = this; $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard.call(me, scale, scale_classes); } }); Just using a ref to this var me = this; $(document).keypress(function (event) { if (event.which === 109) { me.highlightKeyboard(scale, scale_classes); } }); Finally, one more solution is to write a function which generates what you want, this is very similar to what .bind is doing but is supported in environments that don't support .bind (read: legacy) $(document).keypress(function (me) { // this function generates the inside one return function (event) { // this is the function used as the handler if (event.which === 109) { me.highlightKeyboard(scale, scale_classes); } }; }(this)); // passing in `this` as param `me`	{ "pile_set_name": "StackExchange" }
Q: image map software for coordinates using magic wand Quick question... there are lots of ways to create an image map (old school, I know!) for a web page, but I have a requirement for one. I want to have an interactive map showing UK counties. I have the map, I have "mapspinner" (also dreamweaver) to do the polymap... but, I was wondering if there was a way to use a magic wand to get the area's coordinates? I have tried using photoshop export to illustrator paths, but the file doesn't contain any coords (as expected really!). Does anyone know a way to do this? (I see that fireworks might do it, but I don't have that software) thanks in advance. A: GIMP can do this. See http://docs.gimp.org/en/plug-in-imagemap.html for a tutorial of exactly the task you are trying to accomplish.	{ "pile_set_name": "StackExchange" }
Instant Payment - 10:36 Papierüberweisung: Mühsam, langsam, teuer Bild: dpa Im Hochfrequenzhandel an den Börsen geht es um Mikrosekunden. Eine schlichte Überweisung aber braucht noch immer einen Tag oder länger. Das soll sich bald ändern. Bitte melden Sie sich an, um diesen Artikel auf Ihrem Merkzettel zu speichern. Viele Bankkunden könnten vom kommenden Jahr an Geldbeträge innerhalb von wenigen Sekunden auf ein anderes Konto überweisen. Für die neue Echtzeitüberweisung (Instant Payments) werde ab November europaweit ein einheitlicher Rechtsrahmen gelten, sagte der Hauptgeschäftsführer des Bundesverbandes deutscher Banken (BdB), Michael Kemmer. „Im ersten Quartal 2018 wird es die ersten Anbieter geben.“ Allerdings dämpft Kemmer die Erwartungen: „Es wird sicher noch eine Zeit lang dauern, bis sie sich durchgesetzt hat“, merkte der Verbandsvertreter an. Denn für die Kreditinstitute gebe es keine Verpflichtung, an „Instant Payments“ teilzunehmen. Gebrauchtwagen sofort bezahlt Beim Instant Payment soll der Überweisungsbetrag dem Empfänger innerhalb von zehn Sekunden auf dem Konto des Empfängers gutgeschrieben sein. Der Auftrag erfolgt per Online-Banking oder mit einer Smartphone-App. Bislang werden Überweisungen in der Regel am folgenden Bankarbeitstag gutgeschrieben. „Die Überweisung in Sekunden könnte ein Ersatz für Bargeldzahlungen werden“, sagte Kemmer. „Das wird vieles erleichtern“, etwa Probleme beim Warenkauf vermeiden, die dadurch entstehen, dass das Geld dem Verkäufer erst mit einem Tag Verzögerung gutgeschrieben wird. Ein gutes Beispiel hierfür sei der Autoverkauf privat zu privat. Die Bankenbranche reagiert mit dem System auch auf eine Reihe von Angeboten von Online-Bezahldiensten wie Paypal. „Zurzeit wechseln Payment-Dienstleister für hohe Summen den Besitzer, weil hier ein ertragreiches Geschäftsfeld erwartet wird“, erklärte Kemmer. „In Deutschland finden sie jedoch einen extrem harten Wettbewerb vor. Das macht es für die Banken schwierig, solche hohen Investitionen wieder hereinzuwirtschaften.“ Bezahlen mit der Girocard sei neben der Lastschrift das beliebteste bargeldlose Verfahren im Handel. Noch nicht im großen Stil durchgesetzt habe sich in Deutschland das kontaktlose Bezahlen mit Karte oder mit einem Smartphone plus App. „Hier gibt es verschiedene Anbieter, die sich auf dem Markt versuchen. Entscheidend ist, was sich in der Fläche durchsetzen wird“, sagte Kemmer. Mehr zum Thema Beim kontaktlosen Bezahlen muss die Plastikkarte im Abstand von weniger als vier Zentimeter an das Terminal des Händlers gehalten werden. Ohne Eingabe einer Geheimnummer ist der Betrag, der dann vom Girokonto abgebucht wird, in der Regel pro Vorgang auf 25 Euro begrenzt. Aus Sicherheitsgründen kann nur wenige Male hintereinander ohne Geheimzahl bezahlt werden. Es gibt auch ein Tageslimit, das von Bank zu Bank unterschiedlich hoch ist.	{ "pile_set_name": "OpenWebText2" }
This guy built a replica of a McLaren F1 that actually looks decent, complete with a Top Gear influenced "Hammond seat". Top Gear Fanatic Builds Replica Of £5,000,000 Supercar From Scrap Barcroft Cars - The Home Of Amazing Car Stories Online SUBSCRIBE: http://bit.ly/1sHvkD5 A Top Gear fa...More New 1,000 bhp electric supercar from Spain hits 0-62 in just 3.4 seconds and a top speed of 186 mph! Meet the VOLAR-e.. 1.000 hp and 1,500 Nm Fastest Electric Supercar in the World Spanish engineering firm Applus+Idiada has developed an electric supercar known as Volar-E. Presentation of the most p...More	{ "pile_set_name": "Pile-CC" }
Q: Force a browser's visibility setting to true I'm trying to set up some specs against a real (not headless) browser but some of the javascript on the target page only runs if the browser is visible (it doesn't need to be the active app). I've been perusing the W3C Page Visibility API docs and [MDN's] too but I can't see a way to manipulate the setting while running Watir. I know there's the option of running the spec on a headless machine but while I'm developing the specs it'd be handy to not have to switch back and forth between browser and terminal to avoid timeouts and failures. I've had a look for Chrome switches that might help and found this very helpful list but it doesn't appear to have the magic bullet either. I've also tried browser.execute_script('document.hidden = false'); but that had no effect. Any help or insight would be much appreciated. A: It's possible to force this status with a Javascript injection via execute_script. To simulate a visible document: Object.defineProperty(document, 'visibilityState', {value: 'visible', writable: true}); Object.defineProperty(document, 'hidden', {value: false, writable: true}); document.dispatchEvent(new Event("visibilitychange")); To simulate an hidden document: Object.defineProperty(document, 'visibilityState', {value: 'hidden', writable: true}); Object.defineProperty(document, 'hidden', {value: true, writable: true}); document.dispatchEvent(new Event("visibilitychange")); Note that you'll have to run it again if the page is reloaded.	{ "pile_set_name": "StackExchange" }
Q: Trying to get a count of labels used in Gmail using Gmail API I am trying to go one level deeper with the demo code that utilises labels to extract the count of each label used within my inbox. e.g label1 = 5, label2 =10 etc and with a date. Any suggestions? Demo code: function listLabels() { var response = Gmail.Users.Labels.list('me'); if (response.labels.length == 0) { Logger.log('No labels found.'); } else { Logger.log('Labels:'); for (var i = 0; i < response.labels.length; i++) { var label = response.labels[i]; Logger.log('- %s', label.name); } } } A: Using the Users.messages:list function call from the GMail API should get you your results. The trick here is to pass label.id to the labelIds argument as a list function listLabels() { var response = Gmail.Users.Labels.list('me'); if (response.labels.length == 0) { Logger.log('No labels found.'); } else { Logger.log('Labels:'); for (var i = 0; i < response.labels.length; i++) { var label = response.labels[i]; // Use the label name to get the messages that match this label var label_messages = Gmail.Users.Messages.list('me', {'labelIds': [label.id]}); Logger.log('%s = %s', label.name, label_messages.resultSizeEstimate); } } }	{ "pile_set_name": "StackExchange" }
The internet revolution BuzzFeed UK editor Luke Lewis speaks to Grace Marsh about launching in the UK, British humour and what makes the site so successful Tuesday 30 September 2014 How did you get involved in BuzzFeed? BuzzFeed launched in the UK in March 2013. It had been established in the US and actually goes back all the way to 2006. They really started ramping it up, and it started becoming more of a big deal really in 2011/12. So that’s when I became a huge fan of what they were doing so I contacted them and kind of figured that they might want to launch in the UK. So I said if you do, if you’re thinking about it, then you should consider me. And actually I was kind of right in that position because they were thinking about launching, they just hadn’t really got round to it yet. So yeah, that happened in early 2013. What was it like when you first started? Initially, it was very much kind of experimental, there was only three of us, we were sharing an office which was another company’s, you know, it was quite low key. The audience was there, and since then we’ve been building it up so the UK editorial team is about 30 people now. In terms of consumers, now we have 15 million unique users in the UK and globally 150 million per month. What makes BuzzFeed UK different from BuzzFeed US? The main thing that distinguishes BuzzFeed in the UK from in the US is our focus on humour. So if you look at all the most viral, most widely shared articles that we’ve ever done in the UK, they’re mostly funny. That’s not really true in the US; humour is a pretty big part of what they do, but it’s not like the number one priority. How have you adapted content for a UK audience? Around about the time that we launched, things that were doing very well in the US was cute animal stuff, chill, uplift articles were very popular—a really huge article around that time was ‘photos that will restore your faith in humanity’. That kind of thing was really popular in the US and we kind of experimented with that in the UK, but it didn’t work that well. But when we focused more specifically on humour, self-deprecating humour and regional identity is another one – those things worked incredibly well so we really focused on those. What do you think makes people enjoy reading things like ‘ten reasons why you’re from the north’? There is a slight element of mockery invovled, especially self-mockery, that’s an important thing. When we’re writing about a certain niche, or a certain regional identity, you want people who are part of that identity to share it themselves, so if it’s really nasty, sort of slagging off Geordies for example, then they wouldn’t share it, but if it’s sort of gently mocking in a way that they can agree with, then it works. Because you know that’s just the great British thing. Self-depreciating humour is a really big part of our identity. What makes regional identity so important? The reason that identity is really powerful I think is that British media traditionally has kind of ignored the regions beyond London. And so we were really keen to not do that on BuzzFeed. In fact we want to embrace that more actually. We’re gonna sort of ramp up the amount of regional stuff that we’re doing. How do the British public respond to articles about cute cats and Kim Kardashian? Humour is extremely important to us, then there’s also the whole news side of BuzzFeed and celebrity stuff; it’s always popular but it tends not to be shared that well. Those kind of things, Kim Kardashian, there’s a lot of entertainment value. They do quite well from the homepage and people do like to read it, but then people won’t necessarily share it. It’s part of the mix, but not necessarily our main focus. How popular is sport on BuzzFeed? It’s the same with sport as with celebrity stuff; we kind of dipped our toe in the water with sport, but it’s an area that is very, very well served in the British media, by the newspapers and we’ve not quite found a route into that. Maybe in the future, but at the moment, sport is now something we’re really focused on. Is it BuzzFeed’s unique, easy to read format that makes it so successful? Yes, absolutely. We’re thinking about impact and accessibility. For a couple of hundred years, the format of a news story has not really changed very much. It’s about 500 words of copy, with one picture at the top. Especially news online, there’s not been much kind of innovation; they’re really just taken from newspapers. They’re just repurposed, with one picture and 500 words of copy and often it’s just rewritten from the wire. What makes BuzzFeed different? We do like to think about how we like to present news stories and getting away from that classic structure of a newspaper which is often like an inverted pyramid. Newspaper journalists will try to cram as many details as they can into the first few sentences and then the story gets less and less relevant. How do you achieve this? We kind of flip it on its head and we make it more conversational, a bit more chronological. News journalists will often just start at the beginning – this is the person, this is his name, this is how old he is. And then you kind of start telling it like a story, as if you were in conversation with a friend. So I think that’s what makes our news stories a little bit less artificial and a little bit more conversational, which I think is why they work well on Facebook. Is Facebook the most popular sharing platform? It definitely is yeah, but that just reflects the fact that it’s the biggest social media platform by far. The second biggest one is Pinterest and the third is Twitter. To be honest, Twitter is slightly bigger in the UK but globally Pinterest drives significantly more interest than Twitter because it’s huge in the US. How can students get themselves noticed on the internet? You can kind of make the mistake of trying to be on every platform. I’m not personally on Pinterest; it drives a lot on interest on BuzzFeed but I’m not sure it’s a great way of selling yourself. Facebook is kind of underrated as a way of promoting yourself. I’ve always had a public facebook profile and posted lots of links there, and have now built up a bit of a following. I think sometimes people neglect Facebook and focus on Twitter. Why is the more light-hearted content so popular on BuzzFeed? It just reflects the reality of how people consume content nowadays. I think the organising principal of the web now is the kind of activity stream, especially the Facebook newsfeed. If you look at your newsfeed right now, I’m sure there’s news stories and serious stuff about what’s going on in the world, but there’s also stuff about your friends and family, throwaway entertaining stuff as well. And I think that’s just how people live their lives. So it makes sense that BuzzFeed should reflect that. So you’ve got the serious and the light-hearted, entertaining co-exisiting very closely and I think that’s just a natural reflection of life really. I think that’s great. It’s great writing about universities because all it takes is for one person to put it on Facebook and people in their year share it, then it starts to spread to people that once went to that university and it ends up as being tens of thousands of people and that’s brilliant, that’s what BuzzFeed is all about really.	{ "pile_set_name": "Pile-CC" }
Q: How to use HoC with React Native I have an listing app where users can add items for multiple categories, when they want to add new record, there are 3 related screens with this particular feature. All of those screens have <Header/> component, so i thought HoC would be nice here so that i can reuse it across 3 screens. However, i could not accomplish it. Here is what i tried so far: This is my HoC class import React, { Component } from 'react'; import { View, StyleSheet, Text, StatusBar } from 'react-native'; import Header from '../components/Header'; const NewAd = (WrappedComponent) => { class NewAdHoc extends Component { handleBackPress = () => { this.props.navigation.navigate('Home'); StatusBar.setBarStyle('dark-content', true); } render() { const {contentText, children} = this.props return ( <View style={styles.container}> <Header headerText={'Yeni ilan ekle'} onPress={this.handleBackPress} /> <View style={styles.contentContainer}> <Text style={styles.contentHeader}>{contentText}</Text> <WrappedComponent/> </View> </View> ); } } return NewAdHoc; } this is my screen: class NewAdScreen extends Component { render() { const Content = () => { return ( <View style={styles.flatListContainer}> <ListViewItem /> </View> ); } return ( NewAdHoc(Content) ) } } after that i am getting error TypeError: (0 , _NewAdHoc.NewAdHoc) is not a function(…) and i have no idea how can i fix it because this is my first time using hocs on a react-native app. I have looked why this error is popping and they suggest import components in this way: import {NewAdHoc} from '../hocs/NewAdHoc'; but even this is not solved it. any help will be appreciated, thanks. A: The main purpose of a HOC is to encapsulate and reuse stateful logic across components. Since you are just reusing some jsx and injecting nothing in WrappedComponent you should be using a regular component here: const NewAd = ({ contentText, children }) => { handleBackPress = () => { this.props.navigation.navigate('Home'); StatusBar.setBarStyle('dark-content', true); } return ( <View style={styles.container}> <Header headerText={'Yeni ilan ekle'} onPress={this.handleBackPress} /> <View style={styles.contentContainer}> <Text style={styles.contentHeader}>{contentText}</Text> {children} </View> </View> ); } And use it like this return( <> <NewAd> <Screen1 /> </NewAd> <NewAd> <Screen2 /> </NewAd> <NewAd> <Screen3 /> </NewAd> </> )	{ "pile_set_name": "StackExchange" }
The present invention relates to real-time navigation and more specifically to utilizing non-GPS information to update navigation information in real-time. Navigation devices exist today that utilize GPS information to track the location of the navigation device and thus the device's user. Existing navigation devices typically store a cartographic map of data indicative of a roadway network for a geographic area and offer various applications and features to support the user's navigation through the geographic area. One exemplary application is to provide the user with audio instructions to direct the user between source and destination locations within the roadway network. Various routing parameters exist upon which the route through the roadway network may be based, such as time, distance and the like. However, the data stored in the navigation device that is indicative of the roadway network is static in that the data is representative of the status of the roadway network only as of the last time that the navigation device was uploaded with a new cartographic map of the roadway network. The cartographic map reflects limited non-periodic or non-reoccurring information regarding the status of the roadway network. For example, while the cartographic map may store data identifying road segments that typically exhibit slow travel times (e.g. due to numerous traffic lights, rough road conditions and the like), the data is unable to identify for non-reoccurring, one time events that impact travel over the roadway network. Examples of non-reoccurring events are traffic accidents, icy road conditions, flooded roads, construction, weather conditions, temporary traffic back-ups and the like. Heretofore, travelers generally obtained information regarding these non-reoccurring events through the automobile's FM/AM radio that played various types of content, such as entertainment-related content, traffic-related content and the like. To obtain travel-related content, drivers tuned to a weather channel or traffic channel to hear local travel conditions. No system exists that is able to utilize real-time travel-related content to update navigation information and provide updated navigation information to the user. A need remains for improved navigation devices, modular electronic devices and methods for use thereof that are better suited to inform users of real-time travel-related conditions and to utilize such real-time travel-related conditions to update navigation information.	{ "pile_set_name": "USPTO Backgrounds" }
Sabres to hold part of training camp in Rochester 'The Sabres will hold daily on-ice workouts at the ESL Sports Centre from September 15th through September 20th. All workouts will be free and open to the public. "This is a great opportunity for our fans in Rochester to come see the team first hand," Regier said. "It will give them a preview of our team and should build some excitement for our preseason game versus Chicago and our regular season game against New Jersey in November."'	{ "pile_set_name": "Pile-CC" }
{ "type": "bundle", "id": "bundle--4ec75f30-2415-4ef5-81d0-c7443b8c9f9d", "spec_version": "2.0", "objects": [ { "id": "relationship--6d102ef8-c831-413d-b2cb-392517638b0b", "created_by_ref": "identity--c78cb6e5-0c4b-4611-8297-d1b8b55e40b5", "description": "[Zebrocy](https://attack.mitre.org/software/S0251) uses HTTP for C2.(Citation: Palo Alto Sofacy 06-2018)(Citation: Unit42 Cannon Nov 2018)(Citation: ESET Zebrocy Nov 2018)(Citation: Unit42 Sofacy Dec 2018)(Citation: ESET Zebrocy May 2019)(Citation: Accenture SNAKEMACKEREL Nov 2018)", "object_marking_refs": [ "marking-definition--fa42a846-8d90-4e51-bc29-71d5b4802168" ], "external_references": [ { "url": "https://researchcenter.paloaltonetworks.com/2018/06/unit42-sofacy-groups-parallel-attacks/", "description": "Lee, B., Falcone, R. (2018, June 06). Sofacy Group\u2019s Parallel Attacks. Retrieved June 18, 2018.", "source_name": "Palo Alto Sofacy 06-2018" }, { "source_name": "Unit42 Cannon Nov 2018", "url": "https://researchcenter.paloaltonetworks.com/2018/11/unit42-sofacy-continues-global-attacks-wheels-new-cannon-trojan/", "description": "Falcone, R., Lee, B. (2018, November 20). Sofacy Continues Global Attacks and Wheels Out New \u2018Cannon\u2019 Trojan. Retrieved November 26, 2018." }, { "source_name": "ESET Zebrocy Nov 2018", "url": "https://www.welivesecurity.com/2018/11/20/sednit-whats-going-zebrocy/", "description": "ESET. (2018, November 20). Sednit: What\u2019s going on with Zebrocy?. Retrieved February 12, 2019." }, { "description": "Lee, B., Falcone, R. (2018, December 12). Dear Joohn: The Sofacy Group\u2019s Global Campaign. Retrieved April 19, 2019.", "url": "https://unit42.paloaltonetworks.com/dear-joohn-sofacy-groups-global-campaign/", "source_name": "Unit42 Sofacy Dec 2018" }, { "source_name": "ESET Zebrocy May 2019", "url": "https://www.welivesecurity.com/2019/05/22/journey-zebrocy-land/", "description": "ESET Research. (2019, May 22). A journey to Zebrocy land. Retrieved June 20, 2019." }, { "description": "Accenture Security. (2018, November 29). SNAKEMACKEREL. Retrieved April 15, 2019.", "url": "https://www.accenture.com/t20181129T203820Z__w__/us-en/_acnmedia/PDF-90/Accenture-snakemackerel-delivers-zekapab-malware.pdf#zoom=50", "source_name": "Accenture SNAKEMACKEREL Nov 2018" } ], "source_ref": "malware--a4f57468-fbd5-49e4-8476-52088220b92d", "relationship_type": "uses", "target_ref": "attack-pattern--df8b2a25-8bdf-4856-953c-a04372b1c161", "type": "relationship", "modified": "2020-03-17T02:54:27.611Z", "created": "2018-10-17T00:14:20.652Z" } ] }	{ "pile_set_name": "Github" }
Q: IE reading inherited font size from computed style (currentStyle) is incorrect I've put a little test case together here: http://jsfiddle.net/D4sLk/2/ Basically I have the following font sizes set: * (everything): 12px container: 20px test element: inherit The DOM hierarchy is: container > test element. In IE9, the font size is reported as 12px using testEl.currentStyle.fontSize but is displayed as 20px. In Chrome and FF it seems fine. Are there any workarounds to this issue? Or have I done something really stupid? A: Try using font-size: 1em instead of using inherit. The reason for this is because I've found that inherit seems to have issues in IE. It rendered fine when I looked in IE9, however for some reason testEl.currentStyle.fontSize and $(testEl).css('font-size') both returned 12px as well. I've read that to use font-size: inherit in IE8, you would need to specify a !DOCTYPE, however it should be fine in IE9 (http://www.w3schools.com/cssref/pr_font_font-size.asp). For some reason, testEl.currentStyle.fontSize and $(testEl).css('font-size') are not picking up the correct values in IE9. When you set the font-size to 1em, you are sizing it up to 100% of the parent font-size, which in this case results to 20px. From http://www.w3schools.com/cssref/css_units.asp: 1em is equal to the current font size. 2em means 2 times the size of the current font. E.g., if an element is displayed with a font of 12 pt, then '2em' is 24 pt. The 'em' is a very useful unit in CSS, since it can adapt automatically to the font that the reader uses As a result, computedStyle.fontSize and $(testEl).css('font-size'), should both return 20px. Hope this helps!	{ "pile_set_name": "StackExchange" }
194 U.S. 458 (1904) MATTER OF CHRISTENSEN ENGINEERING COMPANY. No. 15, Original. Supreme Court of United States. Submitted April 25, 1904. Decided May 31, 1904. IN THE SUPREME COURT OF THE UNITED STATES. 459 Mr. W.A. Jenner for petitioner. Mr. Frederic H. Betts for respondent. MR. CHIEF JUSTICE FULLER, after making the foregoing statement, delivered the opinion of the court. The examination in Bessette v. W.B. Conkey Company, 194 U.S. 324, just decided, of the right of review in contempt cases precludes the necessity of extended discussion. In that case Bessette was not a party to the suit, and the controversy had been settled by a final decree, from which, so far as appeared, no appeal had been taken. He was found guilty of contempt of court, and a fine of $250 imposed, payable to the United States, with costs. In this case the Christensen Engineering Company was a party. The contempt was disobedience of a preliminary injunction and the judgment in contempt was intermediate the preliminary injunction and the decree making it permanent. The fine was payable, one-half to the United States, and the other half to the complainant. The distinction between a proceeding in which a fine is imposed by way of compensation to the party injured by the disobedience, and where it is by way of punishment for an act done in contempt of the power and authority of the court, is pointed out in Bessette's case, and disclosed by some of the cases referred to in the opinion. In New Orleans v. Steamship Company, 20 Wall. 387, the act in contempt was by one not then a party to the suit. No order was entered against him until the final decree in the case, 460 and then he was punished for the act of disobedience, purely as an act of a criminal nature, and without compensation to the plaintiff in whose favor the injunction was originally ordered. No review under the then existing law was allowable. In Hayes v. Fischer, 102 U.S. 121, the contempt proceeding was remedial and compensatory, and the entire amount of the fine was ordered paid to the plaintiff in reimbursement. It was held that, if the remedial feature was alone to be considered, and the proceeding regarded as a part of the suit, it could not be brought to this court by writ of error, but could only be corrected on appeal from the final decree; if to be regarded as a criminal action, then it was one of which this court had no jurisdiction, either by writ of error or appeal. In Ex parte Debs et al., 159 U.S. 251, there was nothing of a remedial or compensatory nature. No fine was imposed, but only a sentence of imprisonment. This court had no jurisdiction of a writ of error in such a case. And see O'Neal v. United States, 190 U.S. 36. In Worden v. Searls, 121 U.S. 14, the proceeding was remedial and compensatory, in that for violations of a preliminary injunction the defendants were ordered to pay the plaintiff $250 "as a fine for said violation," by one order, and, by another order, to pay a fine of $1,182 to the clerk, to be paid over by him to the plaintiff for "damages and costs," the $1,182 being made up of $682 profits made by the infringement, and $500 expenses of plaintiff in the contempt proceedings. These interlocutory orders were reviewed by this court on appeal from the final decree, and as that decree was reversed, the orders were also set aside, this being done "without prejudice to the power and right of the Circuit Court to punish the contempt referred to in those orders, by a proper proceeding." It was also said "that, though the proceedings were nominally those of contempt, they were really proceedings to award damages to the plaintiff, and to reimburse to him his expenses." These authorities show that when an order imposing a fine for violation of an injunction is substantially one to reimburse *461 the party injured by the disobedience, although called one in a contempt proceeding, it is to be regarded as merely an interlocutory order, and to be reviewed only on appeal from the final decree. In the present case, the fine payable to the United States was clearly punitive and in vindication of the authority of the court, and, we think, as such it dominates the proceeding and fixes its character. Considered in that aspect, the writ of error was justified, and the Circuit Court of Appeals should have taken jurisdiction. Petitioner entitled to mandamus.	{ "pile_set_name": "FreeLaw" }
DeLane Matthews DeLane Matthews (born August 7, 1961) is an American actress. She is best known for her role as Beth Barry in the CBS television sitcom Dave's World from 1993 to 1997. Life and career DeLane Matthews was raised in northern Florida. She moved to Manhattan after being hired to join the Kennedy Center/Juilliard School Acting Company. Acting in theater productions, she appeared Off-Broadway in City Boys at the Jewish Rep, and Pieces of Eight at The Public Theater. She also performed in The Cradle Will Rock, The Merry Wives of Windsor, and Pericles, and toured in The Bat, Grease, The Invaders and I Oughta Be in Pictures. Television Following daytime television work in The Guiding Light in New York City, Matthews transitioned into primetime television on the Peter Boyle ABC comedy series Joe Bash (1986), playing the part of the streetwalker Lorna. It was cancelled after six episodes. In 1988, she went to star opposite Scott Bakula in the CBS sitcom Eisenhower and Lutz. She later starred on the NBC sitcom FM (1989-1990) with Robert Hays and Patricia Richardson, and in 1992 landed a leading role on the ABC sitcom Laurie Hill. In 1993, Matthews landed a female leading role opposite Harry Anderson in the CBS sitcom Dave's World; the series ran to 1997. Matthews guest-starred in a number of television series, include Murphy Brown, Quantum Leap, From the Earth to the Moon, Diagnosis: Murder, Strong Medicine, Cold Case, Nip/Tuck, Castle and well as recurred on The Shield and Saving Grace. In 2001, she joined the cast of ABC soap opera General Hospital playing Janine Matthews. She was regular cast member from October 29, 2001 to June 5, 2003. References External links Category:American television actresses Category:American people of Irish descent Category:Florida State University alumni Category:Actresses from Florida Category:1961 births Category:Living people Category:20th-century American actresses Category:21st-century American actresses Category:People from Rockledge, Florida Category:Power family	{ "pile_set_name": "Wikipedia (en)" }
Subscribe to Nintendo Life on If you're a fan of in-game cross-promotion, it might be worth checking out Le Cartel's new game, Heave Ho. It's designed for up to four people and simply requires players to reach a goal without falling to their death. As Heave Ho is published by Devolver Digital, it will include a number of indie game cameos. You'll be able to select avatars based on games such as Enter the Gungeon, Hotline Miami, GRIS, The Messenger, Gato Roboto, My Friend Pedro and many more. See the full line-up below: Pre-order now on Nintendo Switch and PC, available tomorrow!pic.twitter.com/g65z7bcIiM Lose a bunch of friends but gain a new one with My Friend Pedro joining Heave Ho!Pre-order now on Nintendo Switch and PC, available tomorrow! https://t.co/HGm5pdZ4bE @deadtoast_com August 28, 2019 Pre-order now on Nintendo Switch and PC, available Thursday!pic.twitter.com/Mku5RGEZBF Enter the Gungeon is armed to the teeth but Heave Ho is mostly arms and teeth!Pre-order now on Nintendo Switch and PC, available Thursday! https://t.co/HGm5pdHsN4 @DodgeRollGames August 27, 2019 Pre-order now on Nintendo Switch and PC, available Thursday!pic.twitter.com/K5xWmhzMFh Gris faces a whole different kind of grief in Heave Ho!Pre-order now on Nintendo Switch and PC, available Thursday! https://t.co/HGm5pdZ4bE @nomadastudiobcn August 26, 2019 Pre-order now on Nintendo Switch and PC, available August 29! pic.twitter.com/1a676eIOvN "Yes that shoud work." Katana ZERO knows a little something about trying and trying until you get it just perfect!Pre-order now on Nintendo Switch and PC, available August 29! @katana_zero https://t.co/HGm5pdZ4bE August 24, 2019 Pre-order now on Nintendo Switch and PC, available August 29!pic.twitter.com/SKxQx8fHL3 Meow-ve over and provide a helping hand before we love all nine lives - Gato Roboto is making an appearance in Heave Ho!Pre-order now on Nintendo Switch and PC, available August 29! https://t.co/HGm5pdZ4bE August 23, 2019 Pre-order now on Nintendo Switch and PC, available August 29!@devolverdigital pic.twitter.com/IelstWITRo "Do you like dropping other people?" Hotline Miami joins the effort in Heave Ho!Pre-order now on Nintendo Switch and PC, available August 29! https://t.co/HGm5pdZ4bE @HotlineMiami August 21, 2019 Pre-order now on Nintendo Switch and PC, available August 29!pic.twitter.com/jDXyPO8wAS Piku proves that you don't need arms to be a hero in Heave Ho! We're overjoyed to have @PikunikuGame make an appearance in Heave Ho!Pre-order now on Nintendo Switch and PC, available August 29! https://t.co/2Id3evqa05 August 20, 2019 Our review for Heave Ho will go live soon, until then, why not view the trailer at the top of the page to get a better idea of what you can expect. It really does look like it could be a lot of fun with a group of friends or your family members. Will you be downloading this game later today? Leave a comment down below.	{ "pile_set_name": "OpenWebText2" }
A comparison of four methods of variance component estimation for heritability of embryonic mortality in turkeys. A comparison of four methods for variance component estimation to compute heritability of embryonic mortality in the early (Days 1 to 10) and late (Days 21 to 28) incubation period, was performed using Henderson's Method 3, maximum likelihood (ML), restricted maximum likelihood (REML), and minimum variance quadratic unbiased estimator (MIVQUE). Incubation records from Wrolstad Medium White turkeys divergently selected for semen ejaculate volume were the source of data for the present study. Negative sire components of variance were obtained for early mortality by both Henderson's Method 3 and the MIVQUE procedure. Estimates of the sire variance component for the late mortality period were lower (P less than .05) for ML than those obtained using Henderson's Method 3, REML, and MIVQUE. It was concluded that likelihood procedures (ML and REML) are superior for estimating variance components and genetic parameters from unbalanced data.	{ "pile_set_name": "PubMed Abstracts" }
Q: Trouble posting a JavaScript object with an array of Key Value Pairs to Web Api I have an object (mockup below) I've populated client-side with JavaScript and I need to post it to my server. There's a corresponding type of object defined in a class server-side that I'm expecting to receive. When I attempt to post the object, everything posts fine except for a single property. This property is defined server-side as a List<KeyValuePair<Guid,Bar>>. The Bar doesn't seem to be the issue, as I can post that just fine. Client-side, I've attempted to reformat the corresponding property on the JavaScript object in a few ways (as an array of object pairs, as literal properties on the object, etc.), but it's always an empty list when it arrives at the server. I'm guessing this is a syntax issue, but I'm having trouble figuring out what the proper syntax is, and I'm seeing a lot of conflicting examples online. I'm hoping someone can speak from experience as to how this should be posted. //C# Class MockUp public class Foo { public Guid FooId {get;set;} public string Description {get;set;} public bool Inactive {get;set;} public List<KeyValuePair<Guid,Bar>> FooBar {get;set;} //This comes over as null regardless of how I arrange the object client-side. } //TypeScript Class MockUp class Foo { fooId: string; description: string; inactive: boolean; fooBar: Array<KeyValuePair>; } class KeyValuePair { key: string; value: Bar } class Bar { //...Implementation here mathces Bar on the server } A: Will work if you create a dto for foobar public class FooDto { public Guid FooId {get;set;} public string Description {get;set;} public bool Inactive {get;set;} public List<FooBarDto> FooBar {get;set;} } public class FooBarDto { public Guid Key {get;set;} public Bar Value {get;set;} } The reason why KeyValuePair will not work in this case is because the properties in KeyValuePair are read only, take a look here at the msdn docs you can see that the Key and Value proerties only have getters	{ "pile_set_name": "StackExchange" }
World Online Campaigns Aim to Help Kai the Hitchhiker Beat Murder Rap The never-dull story of Kai the Hitchhiker took a dark turn last week when the viral hero was unexpectedly arrested on murder charges. Since then, a small handful of online campaigns have tried to drum up support for the man who famously referred to himself as "homefree" — not homeless — and set him back on his untethered way. Kai, less frequently known by his given name of Caleb McGillvary, was arrested at a Philadelphia bus terminal last Thursday. He is charged with killing a 73-year-old lawyer named Joseph Galfy, Jr., in Galfy's home in Clark, N.J. Police found Galfy's body in his house last Monday after he and McGillvary met in New York City. The cause of death was determined as blunt force trauma. McGillvary skyrocketed to viral Internet fame in February after using a hatchet to save a utility worker and female bystander. McGillvary had hitched a ride through Fresno, Calif., with a man named Jett Simmons McBride, who referred to himself as Jesus. After pulling into a gas station, McBride allegedly ran his car into a African American Pacific Gas and Electric worker, pinning him to his truck. He then proceeded to get out of his car and beat the 37-year-old worker. At this point, McGillvary found a hatchet in the car and used it to save the worker. A local TV interview shot at the scene quickly became an online sensation. McGillvary found brief national fame, appearing on Jimmy Kimmel Live, where the talk show host presented him with a new surfboard for his act of valor. Shortly thereafter, McGillvary began corresponding with a Georgia man named Terry Ratliff via Facebook and email, according to Ratliff. Ratliff, who made a YouTube remix of McGillvary's local TV interview, said they mostly talked about music and made plans to produce an original song. Ratliff said he was shocked to learn of the murder charge against McGillvary this month. It inspired him to start a GoFundMe campaign with the lofty goal of raising $3 million for McGillvary — the amount prosecutors set for bail upon his arrest. Ratliff realizes that number is likely a pipe dream, but said any money raised will go toward helping McGillvary's legal defense. "I've spoken to some lawyers that might be willing to help, or might take his case pro bono," Ratliff told Mashable. "A public defender would be the worst thing for him, someone with 50 or 100 clients and no time to really work on his case." So far, Ratliff's GoFundMe campaign has raised just over $1,200 online in a week. Similar efforts by others have met similarly meager success. Much of the sympathy for McGillvary stems from a Facebook post he wrote a day after Galfy's alleged murder, but before the story became national news. In the post, which includes graphic language but little detail, McGillvary intimates that he'd been drugged and sexually assaulted. It finishes with a question: "What would you do?" In interviews following his initial rise to fame, McGillvary said that he'd been abused as a kid as well. “You look in his eyes,” Miller, who started the Change.org petition, told NJ.com, “and you can see he’s a good kid.” For all his support, meanwhile, Ratliff acknowledges that he doesn't truly know McGillvary, with whom he'd corresponded extensively before the arrest but never met in person. "Personally, he always seemed alright to me," Ratliff told Mashable. "He seemed like a happy person who wasn't angry at anything. He seemed like a cool guy but, I mean, you never really know what anyone is capable of." What's Hot More in World What's New What's Rising What's Hot Mashable is a leading global media company that informs, inspires and entertains the digital generation. Mashable is redefining storytelling by documenting and shaping the digital revolution in a new voice, new formats and cutting-edge technologies to a uniquely dedicated audience of 42 million monthly unique visitors and 24 million social followers.	{ "pile_set_name": "Pile-CC" }
Pharmaceutics Professor Mandip Sachdeva from the Florida A&M University (FAMU) has led a research project to 3D print a cornea in what is reportedly the first example of high throughput printing of human cells, particularly in America. The project was undertaken in two research laboratories in the Dyson Pharmacy Building on the FAMU campus using the Cellink Bio X bio printer. Sachdeva, research assistant Paul Dinh, and Shallu Kutlehria, a graduate assistant in the College of Pharmacy and Pharmaceutical Sciences, will be submitting a white paper detailing the project later this month for journal publication. Potentially, the results of the project could lead to advancements in the medical field for applications related to the cornea, like transplants and treatments. Sachdeva tells Speaking to the Tallahassee Democrat, Sachdeva explained the significance of this breakthrough: “High throughput cornea printing means that we can print multiple corneas in a matter of minutes using a specially designed scaffold by our laboratory.” “This will save time, and hence, will increase efficiency.” Towards 3D printed corneal transplants Sachdeva has been teaching at FAMU for 26 years, and in his time has been awarded $25 million in research funding. The most recent research for 3D bioprinted corneas follows a 2017 grant from the National Science Foundation. Alongside two FAMU-FSU College of Engineering professors, Sachdeva was awarded the grant to research applications for bioprinting, aerospace materials and energy. After initially focusing on materials/devices for biological applications, this research led to ocular research and the 3D printing of corneas. The project began around the beginning of 2018, and centered on replicating the collagen matrix of real cornea with 3D printing by using stromal cells or keratocytes. These cells help develop and maintain normal corneal structure and transparency, as well as helping to repair tissue after injury. “The starting point was, we have to have print the cornea,” Sachdeva added. “A lot of things went into it. When you print the cornea, the bio-ink is very important. You have to formulate a bio-ink to use for the cornea that simulates the human characteristics.” Potential applications for the tissues include cornea transplants, a long-term goal of the project, and creating an in-vitro model for research and drug screening drug. Currently, the team is developing a prototype of a blinking eye model utilizing the 3D printed cornea, which is an upgrade of a basic in-vitro model. The first 3D printed cornea As the potential impact of artificial ocular tissues is realized several efforts in 3D bioprinted corneas have emerged in recent years. Since 2017 the Instituto de Investigación Biomédica del Hospital La Paz (IdiPAZ) in Madrid, Spain, has been working toward the goal of 3D printing viable human corneas by the year 2020. Pandorum Technologies Pvt., a Bangalore-based biotechnology company, has also used 3D bioprinted cornea tissue to promote the scarless healing of wounds in the eye. In 2018, scientists at Newcastle University (NCL) successfully 3D printed human corneas for the first time. Che Connon, Professor of Tissue Engineering at Newcastle University, and his research team created a printable bioink solution from donor stem cells, alginate, and collagen. This was used to successfully 3D print a cornea in under ten minutes. Sachdeva explains the difference between the research project at FAMU to the NCL study, however, “They printed one cornea. [Dinh] said it takes so much time, if you want to print six corneas, or 12 corneas, how do we do that?” “My team developed a high throughput printing system where in about 10 minutes, you can print about six corneas.” Subscribe to the 3D Printing Industry newsletter for the latest 3D bioprinting research. Stay connected by following us on Twitter and liking us on Facebook. Looking for a career in additive manufacturing? Visit 3D Printing Jobs for a selection of roles in the industry. Featured image shows Florida A&M University biology student Paul Dinh holding a 3D printed cornea on the tip of his finger. Photo via Tori Schneider/Tallahassee Democrat.	{ "pile_set_name": "OpenWebText2" }
Poly(4-vinylpyridinium)hydrogen sulfate: a novel and efficient catalyst for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes under conventional heating and ultrasound irradiation. A simple and convenient procedure for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes is described through a one-pot condensation of 2-naphthol with aryl aldehydes in the presence of poly(4-vinylpyridinium)hydrogen sulfate as an efficient, cheap, readily synthesized and eco-friendly catalyst in a solvent free media using conventional heating and ultrasound irradiation.	{ "pile_set_name": "PubMed Abstracts" }
The New Mind Control: How the Internet Flips Elections and Alters Our Thoughts - Jerry2 https://aeon.co/essays/how-the-internet-flips-elections-and-alters-our-thoughts ====== dc2 "Google and its top executives donated more than $800,000 to President Barack Obama and just $37,000 to his opponent, Mitt Romney." Did you just Alter My Thoughts? How much of that $837,000 was Google versus its top executives (based on their personal preferences)?	{ "pile_set_name": "HackerNews" }
Take a trip back in time to when Tallinn was a wealthy city in the Hanseatic league - one which has miraculously preserved its medieval aura right up to the present day! We take you on a stroll along the winding cobblestone streets of the Old Town, recounting legends and stories of medieval life, stopping off for food-tasting along the way – marzipan in the oldest continuously operating pharmacy in Europe; starters at the medieval eatery The Third Dragon; a feast at the Waggehus restaurant; and dessert at the medieval restaurant Olde Hansa, in the setting of an historical rich merchant's home.	{ "pile_set_name": "Pile-CC" }
Oh god farking dammit. This new line of proposed Bruce Crow laws in the south aren't enough, right-wing shiatheads here are trying to further influence an already unhinged country into going full-on Nazi in regard to gays? You know who else made it a crime to not report gay people? THE NAZIS. THAT'S NOT EVEN THE JOKE. That dude sounds almost resonable. If scientists tells him that being gay isn't a lifestyle choice, then he won't sign the law. Obviously his own scientists have told him it is a choice, but he seems inclined not to believe that, probably due to diplomatic preasure. Its like he he's going "hold on, all this stuff you told me was bullshiat, people are born like that?". To a lot of homophobic people, the choice part doesn't matter. I mean, it's not like Hitler killed the gays because he thought they were like that just to piss him off. spawn73:That dude sounds almost resonable. If scientists tells him that being gay isn't a lifestyle choice, then he won't sign the law. Obviously his own scientists have told him it is a choice, but he seems inclined not to believe that, probably due to diplomatic preasure. Its like he he's going "hold on, all this stuff you told me was bullshiat, people are born like that?". To a lot of homophobic people, the choice part doesn't matter. I mean, it's not like Hitler killed the gays because he thought they were like that just to piss him off. I think it's more a thing of:He's scared of US cutting their foreign aid and he's looking for an out. Satanic_Hamster:spawn73: That dude sounds almost resonable. If scientists tells him that being gay isn't a lifestyle choice, then he won't sign the law. Obviously his own scientists have told him it is a choice, but he seems inclined not to believe that, probably due to diplomatic preasure. Its like he he's going "hold on, all this stuff you told me was bullshiat, people are born like that?". To a lot of homophobic people, the choice part doesn't matter. I mean, it's not like Hitler killed the gays because he thought they were like that just to piss him off. I think it's more a thing of:He's scared of US cutting their foreign aid and he's looking for an out. Bloody William:The law would also make it a crime not to report gay people. Oh god farking dammit. This new line of proposed Bruce Crow laws in the south aren't enough, right-wing shiatheads here are trying to further influence an already unhinged country into going full-on Nazi in regard to gays? You know who else made it a crime to not report gay people? THE NAZIS. THAT'S NOT EVEN THE JOKE. Well the thing is everyone in a country like that should be scared of laws like that, even the homophobes. It seems unlikely Uganda's court system is infallible, so if someone doesn't like them and decides to report them as gay, are they so sure they could prove they aren't to a jury probably full of people like themselves? Alphax:markfara: Alphax: FirstNationalBastard: Will they eat da poopoo for lunch? I'm sure it was American conservatives who told that guy to say that. Yes. They had an awesomely advanced civilization until the conservatives got involved. Or something. /Not the least bit conservative.//But, you know, come on, here. . . . I've heard the American conservatives were telling the same stories about gay people in the 1950's. So, yeah, pack up the old 'textbooks' and mail them overseas.. and they say the same shiat again. No argument here. My point is that the conservatives didn't jump into some advanced, well-developed culture and make it all anti-gay. They're exploiting a market-niche, absolutely, but they didn't create it. And it would most likely still exist if they hadn't gotten involved. Ever notice how when the Fark Islamophobes are comparing Muslims to Christians, the Christians they use as examples of comparison are not these third world Christians, whose economic and educational circumstances are actually similar to those of most Muslims? Always nice, safe, tame Christians from America?That's because it would be a valid comparison, and Christians wouldn't come out looking any better.	{ "pile_set_name": "Pile-CC" }
Springlands, Queensland Springlands is a rural locality in the Whitsunday Region, Queensland, Australia. In the , Springlands had a population of 45 people. Geography The suburb completely surrounds the town of Collinsville. The Collinsville coal mine is located in the suburb. The majority of the western and southern boundary is aligned with the Bowen River. Sonoma State Forest covers 8,800 hectares in the north east of Springlands. Heritage listings Springlands has a number of heritage-listed sites, including: Strathmore Road: Strathmore Homestead References Category:Whitsunday Region Category:Springlands, Queensland Category:Localities in Queensland	{ "pile_set_name": "Wikipedia (en)" }
1. Field of the Invention The present invention relates in general to a monitor, and more particularly, to a monitor improved in tilting structure of the monitor against a base member, and improved in combining structure of the base member and an inclined plane. 2. Description of the Related Art As shown in FIG. 1, a conventional monitor includes a base member 201 laid on a horizontal plane, a monitor main body 202 to display a picture thereon, and a link member 210 to link the base member 201 with the main body 202. A lower part of the link member 210 is rotatably combined to the base member 201 by a pair of fixing brackets 204 and 206, and an upper part of the link member 210 is fixed with the main body 202. Thus, along a direction of an arrow “A” in FIG. 1, the link member 210 is vertically rotated against the base member 201, but the main body 202 cannot be tilted against the link member 210. Therefore, with the conventional monitor, it is inconvenient to adjust an angle of the main body 202 as necessary. Contrary to the monitor shown in FIG. 1, it is possible that the upper part of the link member 210 is rotatably combined to the main body 202, and the lower part of the link member 210 is fixed with the base member 201. Accordingly, the angle of the main body 202 is more efficiently adjusted. As computer systems rapidly spread, demand of various monitor capabilities are also being rapidly increased. In relation to the increased demand of the monitor, there has been provided an arm stand to support the monitor, which is manufactured separately from the monitor and combined to the monitor, to thereby meet a user's preference. A combining structure of the monitor and the arm stand has been regulated by VESA (VIDEO ELECTRONIC STANDARD ASSOCIATION). However, in the conventional monitor, because the base member 210 must be laid on the horizontal plane, it is impossible to install the monitor onto an inclined plane such as a wall, the arm stand, etc. Because the main body 202 is not folded to the base member 201, the monitor is packed in a state as shown in FIG. 1, or in a state that the link member 210 is folded to the base member, which is not shown. Thus, a packing volume of the monitor cannot be decreased, thereby increasing costs to keep and carry the monitor. Furthermore, if regulations regarding the angle adjustment of the main body 202 are different in various nations, it is difficult to adaptively meet regulation requirements for the angle adjustment.	{ "pile_set_name": "USPTO Backgrounds" }
DayZ Standalone SNViolent – 3v3 NW Airfield – Score.. 3-0 Quite a long siege at the NW Airfield. Apologies for some trash talk.. It wasn't me! If you like the video don't forget to press that subscribe button... DayZ Standalone SNViolent – Hacking Piece of S*** I'm not one to usually shout the H word, but what do you think? Keep it legit, brothers. If you like the video don't forget to press that subscribe bu... DayZ Standalone SNViolent – You know what to do with that big fat butt… A random guy we met lightened up our night. Bit creepy. If you like the video don't forget to press that subscribe button. Also, all my gameplay i... DayZ Standalone SNViolent – Guardian Angels – Electro Overwatch Sitting on a rooftop helping out some new spawns get some gear! If you like the video don't forget to press that subscribe button. Also, all my gamepl... Welcome to my channel guys and girls. All my games are streamed through Twitch so drop by and see what i’m playing today! http://www.twitch.tv/snviolent If you like the video don’t forget to press that subscribe button. You can also follow me on twitter for updates on streaming and more YouTube videos. This website is not affiliated with or authorized by Bohemia Interactive a.s. Bohemia Interactive and DAYZ and all associated logos and designs are trademarks or registered trademarks of Bohemia Interactive a.s. DAYZ is created by Dean Hall.	{ "pile_set_name": "Pile-CC" }
Nebraska Supreme Court Online Library www.nebraska.gov/apps-courts-epub/ 10/11/2019 01:06 AM CDT - 933 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 State of Nebraska on behalf of K aaden S., a minor child, appellee, v. Jeffery T., appellant, and M andy S., appellee. ___ N.W.2d ___ Filed August 30, 2019. No. S-17-1210. 1. Paternity: Appeal and Error. In a filiation proceeding, questions con- cerning child custody determinations are reviewed on appeal de novo on the record to determine whether there has been an abuse of discretion by the trial court, whose judgment will be upheld in the absence of an abuse of discretion. 2. Judges: Words and Phrases. A judicial abuse of discretion exists if the reasons or rulings of a trial judge are clearly untenable, unfairly depriv- ing a litigant of a substantial right and denying just results in matters submitted for disposition. 3. Evidence: Appeal and Error. In a de novo review, when the evidence is in conflict, the appellate court considers, and may give weight to, the fact that the trial court heard and observed the witnesses and accepted one version of the facts rather than another. 4. Child Custody: Visitation. The Parenting Act does not require any particular parenting time schedule to accompany an award of either sole or joint physical custody, and there exists a broad continuum of possible parenting time schedules that can be in a child’s best interests. 5. Child Custody: Visitation: Words and Phrases. An alternating week- on-week-off parenting time schedule requires the child to spend roughly the same amount of time at each parent’s residence and allows both parents to exert continuous blocks of parenting time for significant periods of time, and thus meets the statutory definition of joint physi- cal custody. 6. Child Custody: Visitation. Where a parenting plan effectively estab- lishes a joint physical custody arrangement, courts will so construe it, regardless of how prior decrees or court orders have characterized the arrangement. - 934 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 7. Divorce: Child Custody. The Parenting Act authorizes a trial court to award joint custody in dissolution actions if the court specifically finds, after a hearing in open court, that joint physical custody or joint legal custody, or both, is in the best interests of the minor child regardless of any parental agreement or consent. 8. Courts: Appeal and Error. The doctrine of stare decisis requires that appellate courts adhere to their previous decisions unless the reasons therefor have ceased to exist, are clearly erroneous, or are manifestly wrong and mischievous or unless more harm than good will result from doing so. The doctrine is entitled to great weight, but it does not require courts to blindly perpetuate a prior interpretation of the law if it was clearly incorrect. 9. Child Custody: Judges. A blanket rule disfavoring joint physical cus- tody is inconsistent with the Parenting Act and unnecessarily constrains the discretion of trial judges in some of the most important and difficult decisions they are called upon to make. 10. Child Custody. Joint physical custody is neither favored nor disfavored under Nebraska law. In fact, no custody or parenting time arrangement is either favored or disfavored as a matter of law. 11. ____. When determining the best interests of the child in deciding cus- tody, a court must consider, at a minimum, (1) the relationship of the minor child to each parent prior to the commencement of the action; (2) the desires and wishes of a sufficiently mature child, if based on sound reasoning; (3) the general health, welfare, and social behavior of the child; (4) credible evidence of abuse inflicted on any family or household member; and (5) credible evidence of child abuse or neglect or domestic intimate partner abuse. 12. Visitation. The Parenting Act provides that the best interests of a child require a parenting plan that provides for a child’s safety, emo- tional growth, health, stability, physical care, and regular school attend ance, and which promotes a child’s continued contact with his or her families and parents who have shown the ability to act in the child’s best interests. 13. ____. When determining the allocation of parenting time that is in a child’s best interests, a trial court should consider the parties’ ability to communicate on issues such as transportation, homework, discipline, medical and dental appointments, and extracurricular activities. Other relevant considerations include stability in the child’s routine, mini- malization of contact and conflict between the parents, and the general nature and health of the individual child. The fact that one parent might interfere with the other’s relationship with the child is also a factor to consider, but is not a determinative factor. - 935 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 14. Child Support: Rules of the Supreme Court. The Nebraska Child Support Guidelines require child support orders to address how the par- ents will provide for the child’s health insurance. 15. ____: ____. Neb. Ct. R. § 4-215(B) of the Nebraska Child Support Guidelines estimates $480 as an ordinary amount of nonreimbursed medical expenses, and that figure is then subsumed within the amount of child support that is ordered. Any nonreimbursed expenses exceeding $480 are prorated between the parties. 16. ____: ____. Child support payments should generally be set according to the child support guidelines. Petition for further review from the Court of Appeals, Pirtle, R iedmann, and Welch, Judges, on appeal thereto from the District Court for Jefferson County, R icky A. Schreiner, Judge. Judgment of Court of Appeals affirmed in part as modi- fied, and in part reversed and remanded with directions. Ronald R. Brackle for appellant. Angelica W. McClure, of Kotik & McClure Law, for appel- lee Mandy S. Heavican, C.J., Miller-Lerman, Cassel, Stacy, Funke, Papik, and Freudenberg, JJ. Stacy, J. In this paternity action, the district court awarded primary legal and physical custody of a minor child to the father and awarded the mother nearly equal parenting time. Child support was calculated using a joint custody worksheet, and the father was ordered to pay monthly support. The father appealed, assigning multiple errors, including that the award of nearly equal parenting time was, in effect, an award of joint physical custody and was an abuse of discretion. The Nebraska Court of Appeals agreed, and it reversed and remanded with directions to modify the mother’s parenting time so it was “consistent with an award of primary physical custody” to the father.1 In 1 State on behalf of Kaaden S. v. Jeffery T., 26 Neb. App. 421, 430, 920 N.W.2d 39, 48 (2018). - 936 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 doing so, the Court of Appeals relied on Nebraska precedent holding that joint physical custody is disfavored and should be reserved for rare cases.2 We granted the mother’s petition for further review to reexamine that precedent.3 We now hold that a blanket rule disfavoring joint physical custody is inconsistent with the Parenting Act,4 which requires that all determinations of custody and parenting time be based on factors affecting the best interests of the child. We thus disapprove of our prior rule disfavoring joint physical custody, and we clarify that Nebraska law neither favors nor disfa- vors any particular custody arrangement and instead requires all such determinations to be based on the best interests of the child. When the custody and parenting time in the instant case are reviewed under this standard, we find no abuse of discretion. We thus reverse the Court of Appeals’ determination to the contrary and remand the matter with directions to affirm the judgment of the district court as it regards custody, parenting time, and child support. I. FACTS Kaaden S. was born to Mandy S. and Jeffery T. in June 2014. The parents did not have a dating relationship either before or after conception. Mandy notified Jeffery of her pregnancy, and Jeffery was at the hospital on the day Kaaden was born. In February 2015, the State filed a paternity action against Jeffery in the district court for Jefferson County, including Mandy as a third-party defendant. Jeffery’s answer admitted paternity, and he filed a cross-claim against Mandy seeking 2 State on behalf of Kaaden S., supra note 1, citing Erin W. v. Charissa W., 297 Neb. 143, 897 N.W.2d 858 (2017). 3 See, e.g., Erin W., supra note 2; Zahl v. Zahl, 273 Neb. 1043, 736 N.W.2d 365 (2007); Trimble v. Trimble, 218 Neb. 118, 352 N.W.2d 599 (1984); Aguilar v. Schulte, 22 Neb. App. 80, 848 N.W.2d 644 (2014). 4 Neb. Rev. Stat. §§ 43-2920 to 43-2943 (Reissue 2016 & Cum. Supp. 2018). - 937 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 joint legal and physical custody of Kaaden and asking that Kaaden’s surname be changed. Mandy’s responsive pleading admitted Jeffery was Kaaden’s father and requested sole legal and physical custody of Kaaden. Genetic testing later con- firmed Jeffery was Kaaden’s biological father. In July 2015, the district court entered an order finding Jeffery was Kaaden’s father, but reserved the issues of custody, parenting time, and child support pending further hearing. Approximately 1 year later, when Kaaden was nearly 2 years old, the district court entered an order establishing temporary child support and parenting time. The temporary order allowed Jeffery supervised, nonovernight visits for 60 days and then progressed to give Jeffery parenting time every other weekend and on Wednesday evenings. Mandy did not comply with the temporary order and con- sistently refused to allow Jeffery overnight parenting time with Kaaden. Jeffery sought to have Mandy held in contempt of court for failing to comply with the temporary order, and the contempt matter was set to be taken up at the time of trial. Generally, as Jeffery’s parenting time with Kaaden increased, the quality of the interaction between Mandy and Jeffery decreased. In November 2016, Jeffery made an audio recording of a particularly contentious interaction with Mandy that occurred during an exchange of Kaaden. In the record- ing, Mandy can be heard yelling at Jeffery and belittling his attempts to build a relationship with Kaaden. During this interaction, Mandy pepper-sprayed Jeffery in the face and then called police to report she had been assaulted. Jeffery played the recording for the officers, and no arrest was made. After this incident, it became even more difficult for Mandy and Jeffery to communicate. Exchanges for parenting time occurred at the sheriff’s office, but remained contentious. The parties twice attempted to mediate the issues of custody, parenting time, and child support, but both times, Mandy refused to sit in the same room with Jeffery and no agreement was reached. - 938 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 1. Trial In May 2017, trial was held on the issues of custody and parenting time, child support, and contempt of the temporary order. Jeffery, whose pleadings originally had requested joint custody, sought primary physical custody of Kaaden at trial. He testified that if awarded primary custody, he would support Mandy and Kaaden’s relationship and adhere to any parenting time order imposed. He also asked that Kaaden’s surname be changed to his surname. Mandy testified that she did not think joint custody would work because she and Jeffery did not communicate well, though she thought that would improve once the litigation was concluded. She asked to be awarded sole legal and physical custody of Kaaden and proposed that Jeffery have parenting time every other weekend. She requested continued child sup- port and opposed changing Kaaden’s surname. Mandy admitted she had not adhered to the parenting plan under the temporary order, but she testified that Kaaden was scared and did not want to have visits with Jeffery. She said that around the time that Jeffery’s parenting time was to increase under the tempo- rary order, Kaaden began exhibiting behavioral problems, so she took him to see a counselor. Kaaden’s counselor testified at trial. She initially diagnosed Kaaden with “separation trauma and extreme anxiety,” but testified he showed significant growth over the 5 months she worked with him. The counselor had no concerns about Mandy as a custodial parent, but offered the opinion that it was best for Kaaden that contact between Mandy and Jeffery be limited. According to the counselor, Mandy had “significant unresolved issues” toward Jeffery, and she recommended Mandy partici- pate in treatment to address it. The counselor had no opinion on the feasibility of joint custody, but did have a recommenda- tion regarding future parenting time. She recommended that after a transition period, Jeffery’s parenting time should be “week on, week off . . . until [Kaaden] reaches middle school grade age.” - 939 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 Before trial, the court appointed an attorney to serve as the guardian ad litem (GAL) for Kaaden. The GAL attended trial but did not testify. Instead, she was ordered by the court to sub- mit a recommendation and written report, which was received into evidence after trial. No party objected to this procedure before the trial court. The GAL’s report detailed that she had met with both par- ties and their counsel, visited Kaaden at both parties’ homes, observed exchanges of Kaaden during parenting time, and interviewed more than a dozen people including a nationally recognized expert in the area of parental alienation, members of Mandy’s family, and friends and acquaintances of Jeffery. The GAL described the case as “one of the most difficult cases [she had] worked on in 20 years of being appointed as a [GAL].” Her report stated she was “completely confident in making the recommendation that Kaaden’s primary physical custody be awarded to . . . Jeffery.” The GAL believed that Mandy’s “loathing” of Jeffery was harmful to Kaaden and that Mandy’s pattern of “parental alienation” was unlikely to change. The GAL expressed the opinion that “it would be in Kaaden’s best interests to be in a parent’s custody [who] is going to make a good faith effort to work with the other parent and not sabotage Kaaden’s relationship with that parent.” (a) Custody and Parenting Time The trial court’s order summarized the evidence adduced at trial and generally found that both parents were fit and had formed a good relationship with Kaaden. But the court noted: The complicating factor in this matter is the lack of a relationship between the parents, both prior to Kaaden’s conception and continuing, and the obvious resentment Mandy has towards Jeff[er]y and the situation in which she now finds herself. Mandy testified that she believes Kaaden needs his father in his life and does not believe that Jeffery abuses Kaaden in any fashion, although she . . . appears to do everything she can to limit or monitor Jeff[er]y and Kaaden’s relationship. The record reflects - 940 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 that she has done everything in her power to prevent Jeff[er]y from being a father to Kaaden by contesting and litigating every attempt he has made to do so. Mandy’s testimony at trial indicated that while she wanted to be a mother at some point in her life she did not envi- sion it happening in this fashion nor was this part of her plan. That said, it’s obvious she loves Kaaden. Her anger towards Jeff[er]y, unfortunately, clouds her judg- ment regarding what is in Kaaden’s best interests at times, especially when it comes to allowing Jeffery to be involved in his life. Mandy and Jeff[er]y both provide safe and appropriate homes for Kaaden where he enjoys a healthy diet, has a bed to sleep in, and toys and activities to keep him occu- pied and engaged. .... The court has addressed the parties, on the record, dur- ing the pendency of this matter. Each time I addressed them I tried to remind them that Kaaden’s interests are best served by having both of his parents involved in his life, and tried to encourage Mandy to see past her hurt, fear, and anger and allow Kaaden to have his father in his life. Unfortunately, the report from [the GAL] indicates those words went in one ear and out the other because nothing has changed with her behavior. It appears she is still putting more value on her hate and anger than she is on Kaaden’s ability to have a father actively engaged in his life and the benefits of that relationship. For the reasons stated above, as well as the firm belief that doing so best ensures compliance with the order of custody so that Kaaden can enjoy the full benefits of having both parents involved in his life to the greatest degree possible, the court finds that it is in Kaaden’s best interests that primary legal and primary physical custody be awarded to . . . Jeff[er]y . . . subject to liberal parenting time with . . . Mandy . . . . - 941 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 The decree awarded Jeffery “primary legal and primary physical care, custody and control” of Kaaden, pursuant to a court-created parenting plan. The parenting plan described the custody award as follows: The father shall have sole legal and physical custody of the minor child and, as such, shall have the legal respon- sibility and authority to make final decisions concerning the parenting functions necessary to raising the child. . . . The principal place of residence (physical custody) of the child shall be with the father, (custodial parent) subject to the terms of this Plan. The court-created parenting plan provided that after a brief transition period, Mandy and Jeffery would have parenting time in alternating 1-week blocks. Exchanges were to occur each Friday at 6 p.m. at the sheriff’s office. The plan addressed holidays and gave each parent 2 uninterrupted weeks of sum- mer parenting time. (b) Child Support and Nonreimbursed Health Care Costs The court used worksheet 3 of the Nebraska Child Support Guidelines, the joint custody worksheet, to calculate child sup- port, and the completed worksheet was attached to the decree. In allocating the number of overnights for each parent (line 5 on the worksheet), the court attributed 182 days to Mandy and 183 days to Jeffery. Jeffery was ordered to pay child sup- port of $93 per month and to provide health insurance for Kaaden. He was also ordered to pay the first $480 of Kaaden’s nonreimbursed reasonable and necessary health care expenses each year, and Mandy was ordered to pay 50 percent of such expenses in excess of $480. (c) Name Change, Contempt, and Attorney Fees Jeffery’s request to change Kaaden’s surname was denied. The court found Mandy in willful contempt for failing to comply with the terms of the temporary order and imposed a - 942 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 sanction of $50, but did not impose a purge plan. Finally, the court declined to award attorney fees and ordered the parties to pay their own fees and costs. 2. Court of A ppeals Jeffery appealed, assigning that the district court erred in (1) ordering equal parenting time, (2) calculating child sup- port using the joint custody worksheet, (3) ordering him to pay the first $480 in nonreimbursed health care expenses, (4) refusing to change Kaaden’s surname, (5) imposing a nominal fine for Mandy’s contempt, and (6) denying his request for attorney fees. The Court of Appeals found no merit to the arguments regarding the name change or attorney fees. But it agreed with Jeffery that the district court erred in its determinations regard- ing parenting time, child support, nonreimbursed health care expenses, and contempt. We summarize the court’s reason- ing below. (a) Custody and Parenting Time Before the Court of Appeals, Jeffery claimed the district court’s parenting plan was “essentially a Joint Physical Custody Plan,”5 which he argued was an abuse of discretion. The Court of Appeals agreed. It acknowledged that the district court had awarded primary physical custody to Jeffery, but it concluded that by giving Mandy nearly equal parenting time, the district court effectively imposed “the standard joint physical custody arrangement.”6 In considering whether such an arrangement was an abuse of discretion, the Court of Appeals relied on this court’s precedent which holds: Joint physical custody should be reserved for those cases where, in the judgment of the trial court, the parents are of such maturity that the arrangement will not operate to 5 Brief for appellant at 22. 6 State on behalf of Kaaden S., supra note 1, 26 Neb. App. at 431, 920 N.W.2d at 49. - 943 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 allow the child to manipulate the parents or confuse the child’s sense of direction, and will provide a stable atmos phere for the child to adjust, rather than perpetuating tur- moil or custodial wars.7 The Court of Appeals found that Mandy and Jeffery had “vir- tually no ability to communicate with each other regarding Kaaden”8 and concluded it was an abuse of discretion to estab- lish a parenting time schedule that amounted to joint physi- cal custody. It thus affirmed the award of primary legal and physical custody to Jeffery, but reversed the parenting plan and remanded the matter to the district court to implement a parent- ing time schedule “consistent with an award of primary physi- cal custody to Jeffery.”9 It did not indicate what the parameters of such a plan must be. (b) Child Support and Medical Expenses Because the matter was being remanded to reduce Mandy’s parenting time, the Court of Appeals also found the trial court’s use of the joint custody worksheet to calculate child support was in error. It therefore reversed the child support award and remanded the matter for recalculation “using the appropriate worksheet.”10 The Court of Appeals also reversed the provision in the decree requiring Jeffery to pay the first $480 of Kaaden’s nonreimbursed health care expenses. It rea- soned that children’s health care expenses are specifically included in the child support guidelines amount of up to $480 per child per year11 and that consequently, any nonreimbursed health care costs up to $480 were subsumed within the amount of child support ordered.12 It directed the trial court, upon 7 Id., citing Erin W., supra note 2. 8 Id. at 433, 920 N.W.2d at 50. 9 Id. at 430, 920 N.W.2d at 48. 10 Id. at 433, 920 N.W.2d at 50. 11 See Neb. Ct. R. § 4-215(B) (rev. 2011). 12 See, id.; State on behalf of Martinez v. Martinez-Ibarra, 281 Neb. 547, 797 N.W.2d 222 (2011). - 944 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 recalculating child support to reflect Mandy’s reduced parent- ing time, to then allocate nonreimbursed health care costs in excess of $480 accordingly. (c) Name Change, Contempt, and Attorney Fees Although not directly relevant to this petition for further review, we note that the Court of Appeals affirmed the dis- trict court’s refusal to change Kaaden’s surname, affirmed the district court’s denial of Jeffery’s request for attorney fees, and found that the district court committed plain error with respect to the unconditional sanction imposed for Mandy’s contempt. Our opinion on further review does not affect those findings. We granted Mandy’s petition for further review. II. ASSIGNMENTS OF ERROR On further review, Mandy assigns, restated, that the Court of Appeals erred in (1) reversing the parenting plan and remand- ing the matter with instructions to reduce Mandy’s parenting time, (2) finding the record did not support joint physical custody when the district court created a parenting plan that gave Mandy “de facto”13 joint physical custody, and (3) revers- ing the child support calculation and the requirement that Jeffery pay the first $480 of Kaaden’s nonreimbursed health care expenses. III. STANDARD OF REVIEW [1,2] In a filiation proceeding, questions concerning child custody determinations are reviewed on appeal de novo on the record to determine whether there has been an abuse of discretion by the trial court, whose judgment will be upheld in the absence of an abuse of discretion.14 A judicial abuse of discretion exists if the reasons or rulings of a trial judge 13 Brief for appellee Mandy S. in support of petition for further review at 2. 14 Cesar C. v. Alicia L., 281 Neb. 979, 800 N.W.2d 249 (2011). - 945 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 are clearly untenable, unfairly depriving a litigant of a sub- stantial right and denying just results in matters submitted for disposition.15 [3] In such de novo review, when the evidence is in con- flict, the appellate court considers, and may give weight to, the fact that the trial court heard and observed the witnesses and accepted one version of the facts rather than another.16 IV. ANALYSIS In her first two assignments of error, Mandy argues the Court of Appeals erred in reversing the parenting time schedule and remanding the matter with directions to reduce her parent- ing time. After reexamining our jurisprudence, we agree. As noted, the district court awarded Jeffery “primary” legal and physical custody of Kaaden and imposed a parenting plan that gave Mandy nearly equal parenting time. The Court of Appeals relied on its own precedent17 and precedent from this court18 to conclude that an award of nearly equal parenting time amounted to an award of de facto joint physical custody. It found such a custody arrangement was an abuse of discre- tion, relying on the legal proposition that joint physical cus- tody is disfavored and should be reserved for rare cases.19 We granted further review to reexamine that proposition. Before doing so, we set out the legal framework that governs child custody determinations in Nebraska. 1. Legal Custody Under the Parenting Act adopted by the Nebraska Legislature, the concept of child custody encompasses both “legal custody and physical custody.”20 “Legal custody” focuses entirely on 15 Leners v. Leners, 302 Neb. 904, 925 N.W.2d 704 (2019). 16 Cesar C., supra note 14. 17 Hill v. Hill, 20 Neb. App. 528, 827 N.W.2d 304 (2013). 18 Elsome v. Elsome, 257 Neb. 889, 601 N.W.2d 537 (1999). 19 See, Erin W., supra note 2; Aguilar, supra note 3. 20 § 43-2922(7). - 946 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 decisionmaking authority and is defined as “the authority and responsibility for making fundamental decisions regard- ing the child’s welfare, including choices regarding education and health.”21 Here, Jeffery was awarded Kaaden’s legal custody, and no party disputes that award. As such, Jeffery has the final say on fundamental decisions regarding Kaaden’s welfare, such as where he attends school, his religious upbringing, and how his health and medical needs are met.22 Because Kaaden’s legal custody is not at issue in this appeal, we focus our analysis on the issues of physical custody and parenting time. 2. Physical Custody and Parenting Time “Physical custody” is defined by the Parenting Act as “authority and responsibility regarding the child’s place of residence and the exertion of continuous parenting time for significant periods of time.”23 As such, although the Parenting Act does not speak in terms of “sole” or “primary” physical custody, it contemplates that an award of physical custody will determine the child’s primary residence and identify the parent who will exert “significant” and “continuous” parenting time over the child.24 “Joint physical custody” as defined by the Parenting Act means “mutual authority and responsibility of the parents regarding the child’s place of residence and the exertion of continuous blocks of parenting time by both parents over the child for significant periods of time.”25 The Parenting Act does not further define either “significant periods of time” or “con- tinuous blocks,” but it does define “parenting time.”26 21 § 43-2922(13). 22 See id. 23 § 43-2922(20). 24 See id. 25 § 43-2922(12). 26 See id. - 947 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 “Parenting time” is defined under the Parenting Act as “communication or time spent between the child and parent.”27 And the Parenting Act makes clear that regardless of the physi- cal custody arrangement, when parents are exercising parenting time, they are performing “[p]arenting functions.”28 Parenting functions are defined to include maintaining a safe, stable, consistent, and nurturing relationship with the child; attending to the child’s ongoing developmental needs, including feed- ing, clothing, grooming, emotional stability, and appropriate conflict resolution skills; attending to adequate education for the child; assisting the child in maintaining a safe, positive, and appropriate relationship with each parent and other family members; minimizing the child’s exposure to harmful parental conflict; assisting the child in developing skills to maintain safe, positive, and appropriate interpersonal relationships; and exercising support for social, academic, athletic, or other spe- cial interests.29 [4] The Parenting Act does not require any particular par- enting time schedule to accompany an award of either sole or joint physical custody, and there exists a broad continuum of possible parenting time schedules that can be in a child’s best interests. Nebraska has a number of appellate cases in which the parties disagreed over whether a particular custody and parenting time arrangement was properly characterized as sole physical custody with liberal parenting time or as joint physi- cal custody.30 But in this case, that analysis is not difficult, and both parties concede the court effectively imposed a joint physical custody arrangement. We agree. [5] The district court awarded the parents nearly equal par- enting time in the form of an alternating week-on-week-off 27 § 43-2922(19). 28 § 43-2922(17). 29 Id. 30 See, e.g., Dooling v. Dooling, ante p. 494, ___ N.W.2d ___ (2019); Donald v. Donald, 296 Neb. 123, 892 N.W.2d 100 (2017); McDonald v. McDonald, 21 Neb. App. 535, 840 N.W.2d 573 (2013); Hill, supra note 17. - 948 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 schedule. Such a schedule requires Kaaden to spend roughly the same amount of time at each parent’s residence and allows both parents to exert continuous blocks of parenting time for significant periods of time, and thus meets the statutory defini- tion of joint physical custody.31 [6] Where a parenting plan effectively establishes a joint physical custody arrangement, courts will so construe it, regardless of how prior decrees or court orders have charac- terized the arrangement.32 In several cases, we have looked past the labels used by the trial court when describing the physical custody arrangement and have focused instead on the actual terms of the parenting plan adopted by the court.33 Such cases illustrate that it is the trial court’s allocation of parent- ing time that drives the physical custody label, not the other way around. We therefore agree with the parties and the Court of Appeals that regardless of the label used in the decree and parenting plan to describe physical custody, the trial court here effec- tively imposed a joint physical custody arrangement by creat- ing a week-on-week-off parenting time schedule.34 For the sake of clarity, we modify the language of the decree and parenting plan to reflect this holding. We turn next to the question whether, by effectively impos- ing a joint physical custody arrangement, the trial court abused its discretion. The Court of Appeals concluded it did, citing our 31 Becher v. Becher, 299 Neb. 206, 908 N.W.2d 12 (2018) (parenting plan establishing every-other-week parenting time schedule with equal time over summer break meets statutory definition of joint physical custody regardless of label used by trial court). 32 See, id.; Elsome, supra note 18. 33 See, e.g., Dooling, supra note 30, ante at 517, ___ N.W.2d at ___ (“the label that a court uses is not controlling and . . . the classification of a custody arrangement is ultimately dictated by parenting time”); Becher, supra note 31, 299 Neb. at 225, 908 N.W.2d at 29 (“the labels make little difference” when parenting plan sets forth parent’s rights and responsibilities). 34 See id. - 949 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 cases that generally disfavor joint physical custody arrange- ments, especially when there is evidence the parents have diffi- culty communicating.35 The time has come to reexamine those cases, and we turn to that discussion now. 3. Trimble v. Trimble One of the first times this court addressed the concept of joint physical custody was in Trimble v. Trimble,36 decided in 1984. In that case, the trial court awarded physical custody of two young children to the mother, finding she had “spent a great deal more of her time with the children, has the more pre- dictable work and leisure schedule, and was more concerned with the children’s education.”37 On appeal, the father argued it was error not to award joint physical custody. Trimble noted that “in a given case joint custody might very well act to preserve the parent-child bond for both parents and thus avoid the severance of either of the attachments.”38 But without citation or further explanation, Trimble opined: We believe, however, that such arrangements must be reserved for the most rare of cases, i.e., where in the judg- ment of the trial court the parents are of such maturity that the arrangement will not operate to allow the child to manipulate the parents or confuse the child’s sense of direction. A collateral question exists as to why those most ideal of parents, who would satisfactorily cope with the conflicts inherent in a joint child custody arrange- ment, came to be divorced in the first instance. . . . We are not prepared to reject the concept of joint custody, but are not prepared to state that it should be a regular tool in the remedies of the district courts.39 35 See, e.g., Erin W., supra note 2; Zahl, supra note 3; Trimble, supra note 3; Aguilar, supra note 3. 36 Trimble, supra note 3. 37 Id. at 119, 352 N.W.2d at 600. 38 Id. at 119, 352 N.W.2d at 600-01. 39 Id. at 120, 352 N.W.2d at 601. - 950 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 Trimble was decided at a time when Nebraska law did not distinguish between legal and physical custody, so many of our opinions applying Trimble described a blanket rule that “joint custody” is disfavored and must be reserved for the rar- est of cases.40 More recently, articulation of the Trimble rule has focused on joint physical custody; in Zahl v. Zahl,41 we described the rule this way: [J]oint physical custody must be reserved for those cases where, in the judgment of the trial court, the parents are of such maturity that the arrangement will not operate to allow the child to manipulate the parents or confuse the child’s sense of direction, and will provide a stable atmos phere for the child to adjust, rather than perpetuating tur- moil or custodial wars. Trimble and Zahl use different phrasing but stand for the same blanket proposition—that joint custody arrangements are generally disfavored and should be reserved for rare or spe- cial cases. 4. R evisiting Trimble [7] Recently, in Leners v. Leners,42 we cited the rule dis- favoring joint custody but cautioned that it should not be viewed as a “hard-and-fast rule.” We emphasized that the Parenting Act authorizes a trial court to award joint custody 40 See, e.g., Ensrud v. Ensrud, 230 Neb. 720, 727, 433 N.W.2d 192, 197 (1988) (“[t]his court has frequently and consistently expressed disapproval of joint custody as a purported solution for the difficulty confronted by a court in determining a question concerning child custody”); Wilson v. Wilson, 224 Neb. 589, 590, 399 N.W.2d 802, 803 (1987) (“[w]e have . . . stated explicitly that joint custody is not favored and must be reserved for only the rarest of cases”); Korf v. Korf, 221 Neb. 484, 486, 378 N.W.2d 173, 174 (1985) (“[a]n award of joint custody of minor children is not favored. Such an award must be reserved for the most rare of cases”). 41 Zahl, supra note 3, 273 Neb. at 1053, 736 N.W.2d at 373. Accord, Erin W., supra note 2; Schmeidler v. Schmeidler, 25 Neb. App. 802, 912 N.W.2d 278 (2018); Hill, supra note 17. 42 Leners, supra note 15, 302 Neb. at 913, 925 N.W.2d at 712. - 951 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 in dissolution actions “‘if the court specifically finds, after a hearing in open court, that joint physical custody or joint legal custody, or both, is in the best interests of the minor child regardless of any parental agreement or consent.’”43 In Leners, we affirmed an award of joint legal and physi- cal custody, finding it was in the child’s best interests, despite evidence the parents had a contentious relationship. In doing so, we analyzed the parents’ relationship as one of many fac- tors bearing on the child’s best interests. We noted that both parents were fit and that the child had a good relationship with each. We ultimately concluded that by establishing a parent- ing plan that afforded roughly equal parenting time, the trial court had fashioned a schedule that maximized the child’s time with both parents, accommodated the father’s unusual work schedule, and minimized the number of transitions and the need for communication and coordination between the parents. We found this plan served the child’s best interests. Leners did not expressly disapprove of the Trimble rule,44 but our analysis highlighted tension between the best interests analysis required under the Parenting Act and a blanket rule that disfavors joint custody and reserves it only for rare cases. We are persuaded the time has come to expressly reexam- ine the proposition that joint custody arrangements are disfa- vored and “reserved” for rare or special cases.45 The Wyoming Supreme Court recently engaged in a similar reevaluation of its judicial rule disfavoring joint custody. In Bruegman v. Bruegman,46 Wyoming acknowledged that its longstanding rule had been to disfavor joint custody “‘“absent good reason”’” based on the rationale that “‘“stability in a child’s environment is of utmost importance to the child’s 43 Id. at 913-14, 925 N.W.2d at 712, quoting Neb. Rev. Stat. § 42-364(3)(b) (Cum. Supp. 2018). 44 See Trimble, supra note 3. 45 See id. at 120, 352 N.W.2d at 601. 46 Bruegman v. Bruegman, 417 P.3d 157 (Wyo. 2018). - 952 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 well-being”’”47 and out of concern that joint custody could be successful only when “‘“the parents are able to communicate and agree on the matters relevant to the children’s welfare.”’”48 In evaluating whether it should change its rule disfavoring joint custody, the Wyoming court did not analyze the evolv- ing social science on parenting and child development, nor did it discuss arguments advanced for or against joint custody. Instead, it found that its blanket rule disfavoring joint custody was inconsistent with Wyoming statutes that require child cus- tody to be determined based on the best interests of the child. It noted that courts in Iowa49 and Maryland50 had previously criticized application of a blanket rule disfavoring joint physi- cal custody, reasoning that the question whether joint physical custody is appropriate should be based on the individual cir- cumstances of each case and not on general presumptions that may or may not be applicable.51 Wyoming ultimately rejected its precedent disfavoring joint custody and held instead that the fundamental consideration governing all child custody deter- minations is the best interests of the child. Citing the proposi- tion that “‘“joint custody, in any of its multiple forms, is but another option available to the trial judge,”’”52 the Wyoming court concluded that “shared custody should be considered on an equal footing with other forms of custody.”53 47 Id. at 162. 48 Id. 49 In re Marriage of Hansen, 733 N.W.2d 683, 695 (Iowa 2007) (concluding “the joint physical care issue must be examined in each case on the unique facts and not subject to cursory rejection based on a nearly irrebuttable presumption found in our prior cases”). 50 Taylor v. Taylor, 306 Md. 290, 302, 508 A.2d 964, 970 (1986) (reexamining rule that joint physical custody is “an arrangement ‘to be avoided, whenever possible, as an evil fruitful in the destruction of discipline, in the creation of distrust, and in the production of mental distress in the child’”). 51 Bruegman, supra note 46. 52 Id. at 163. Accord Taylor, supra note 50. 53 Id. at 164. - 953 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 5. Joint Custody No Longer Disfavored [8] The doctrine of stare decisis requires that we adhere to our previous decisions unless the reasons therefor have ceased to exist, are clearly erroneous, or are manifestly wrong and mischievous or unless more harm than good will result from doing so.54 The doctrine is entitled to great weight, but it does not require us to blindly perpetuate a prior interpretation of the law if we conclude it was clearly incorrect.55 We can conceive of no principled justification for continu- ing to apply a blanket rule that disfavors joint legal or physi- cal custody, especially when the rule is based on generalized concerns regarding parental maturity and possible behavioral consequences to a child from spending substantial amounts of time with each parent. Such concerns may well be valid in any given case and in that event should be considered in light of all the other factors and circumstances in arriving at a custody and parenting time arrangement that serves the best interests of the child at issue. But a blanket rule disfavoring joint legal or physical custody is difficult to reconcile with the Parenting Act, under which the best interests of the child are the polestar of all child custody and parenting time determinations.56 We see nothing in the Parenting Act that either favors or disfavors any particular custody or parenting time arrange- ment. The Parenting Act simply requires that all custody and parenting time arrangements be determined based on the best interests of the child.57 The Parenting Act “presumes the criti- cal importance of the parent-child relationship in the welfare and development of the child and that the relationship between the child and each parent should be equally considered unless it is contrary to the best interests of the child.”58 The Parenting 54 Davis v. State, 297 Neb. 955, 902 N.W.2d 165 (2017). 55 See id. 56 See §§ 43-2921 to 43-2923. See, also, § 42-364(2) (Reissue 2016). 57 § 43-2923(6). 58 § 43-2921 (emphasis supplied). - 954 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 Act also states that the best interests of the child require, among other things, “appropriate, continuing quality contact” between the child and parents who have shown the ability to act in the child’s best interests.59 The Parenting Act neither expresses nor suggests a default position favoring or disfavor- ing any particular custody arrangement, even one agreed to by the parents,60 and instead requires that all such determinations be based on the best interests of the child.61 We note that, in dissolution actions where the parents have not agreed to joint custody, § 42-364(3) requires that before joint custody may be ordered, there must be a hearing in open court and an express finding that joint custody is in the child’s best interests.62 But we do not understand the provisions of § 42-364(3) to indicate the Legislature either favors or disfa- vors joint custody. All cases governed by the Parenting Act 63 require a judicial determination, whether expressly stated or not, that the custody and parenting time arrangement ordered by the court is in the child’s best interests.64 And a hearing on the record is routinely held to facilitate that judicial determina- tion, whether the parents are submitting an agreed-upon parent- ing plan for approval65 or have contested the issues of custody and parenting time such that a trial is necessary. [9] We conclude that a blanket rule disfavoring joint cus- tody is inconsistent with the Parenting Act and unnecessarily 59 See § 43-2923(3). 60 See § 43-2923(4). 61 §§ 43-2923(6) and 43-2935(1). 62 See, also, State ex rel. Amanda M. v. Justin T., 279 Neb. 273, 280, 777 N.W.2d 565, 571 (2010) (in paternity case, it is preferable to make express finding that order of joint custody is in best interests of child, but it is “not error under the Parenting Act in a paternity case to fail to make a specific finding of best interests”). 63 See § 43-2924. 64 See §§ 43-2921, 43-2923(4) and (6), and 43-2935. See, also, Dooling, supra note 30. 65 See §§ 43-2923(4) and 43-2935. - 955 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 constrains the discretion of trial judges in some of the most important and difficult decisions they are called upon to make. To ensure that custody and parenting time determina- tions are focused on the best interests of the child, trial judges must be able to base their determinations on actual, not pre- sumed, facts. [10] Because a blanket rule disfavoring joint custody limits judicial discretion and may constrain the best interests of the child analysis required by the Parenting Act, we now disap- prove of the Trimble rule and hold that joint custody is nei- ther favored nor disfavored under Nebraska law.66 In fact, we emphasize that no custody or parenting time arrangement is either favored or disfavored as a matter of law, and we disap- prove of prior cases suggesting otherwise. Our holding today necessarily calls into question some of our reasoning in other cases, to the extent such reasoning was premised on the rule disfavoring joint custody.67 But today’s holding does not alter the fact that whether parents come to court having agreed to a joint custody arrangement, or dis- puting the issues of custody and parenting time, the court is required to independently determine that any parenting plan being ordered is in the child’s best interests and must reject or modify parenting plans that are not in the child’s best inter- ests or which do not meet the requirements of the Parenting Act.68 And today’s holding does not change in any respect the various factors courts should consider when deciding what sort of custody and parenting time arrangement is in a child’s best interests;69 it merely eliminates the need to also consider a blanket rule premised on generalized concerns of parental 66 See Trimble, supra note 3. 67 See, e.g., State ex rel. Amanda M., supra note 62 (noting that factual inquiry for awarding joint physical custody is substantially different from that required for making sole custody determination); Zahl, supra note 3. See, also, Aguilar, supra note 3; Hill, supra note 17. 68 See §§ 43-2921, 43-2923(4) and (6), and 43-2935. 69 See §§ 42-364(2), 43-2921, and 43-2923. - 956 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 maturity, manipulative behavior by the child, and perpetuat- ing turmoil and instability. Of course when such concerns are supported by the evidence, they will still be factors for the court to consider, along with all the other factors bearing on the child’s best interests. We discuss those factors next. 6. Equal Parenting Time Was Not A buse of Discretion We turn now to the primary question on further review: whether the district court abused its discretion in creating a parenting plan that gave Mandy and Jeffery nearly equal parenting time, effectively imposing a joint physical custody arrangement. We address that question in light of the evidence adduced regarding Kaaden’s best interests and disregarding our prior case law to the extent it disfavored joint physi- cal custody. (a) Best Interests [11] When determining the best interests of the child in deciding custody, a court must consider, at a minimum, (1) the relationship of the minor child to each parent prior to the commencement of the action; (2) the desires and wishes of a sufficiently mature child, if based on sound reasoning; (3) the general health, welfare, and social behavior of the child; (4) credible evidence of abuse inflicted on any fam- ily or household member; and (5) credible evidence of child abuse or neglect or domestic intimate partner abuse.70 In this case, the trial court analyzed the evidence in light of each of these factors. [12] The Parenting Act also provides that the best inter- ests of a child require a parenting plan that provides for a child’s safety, emotional growth, health, stability, physical care, and regular school attendance71 and which promotes a child’s 70 § 43-2923(6). See, also, Gress v. Gress, 271 Neb. 122, 710 N.W.2d 318 (2006) (reciting rule before amendments to § 43-2923(6)). 71 § 43-2923(1). - 957 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 continued contact with his or her families and parents who have shown the ability to act in the child’s best interests.72 [13] In addition to considering these statutory factors, our case law instructs that when making determinations as to the allocation of parenting time that is in a child’s best interests, a trial court should also consider the parties’ ability to commu- nicate on issues such as transportation, homework, discipline, medical and dental appointments, and extracurricular activi- ties.73 Other relevant considerations include stability in the child’s routine, minimalization of contact and conflict between the parents, and the general nature and health of the individual child.74 The fact that one parent might interfere with the other’s relationship with the child is also a factor to consider, but is not a determinative factor.75 By reciting these factors, we do not suggest that each will be relevant in every case; nor do we imply that a court is prohib- ited from considering other factors not mentioned. No single factor is determinative, and different factors may weigh more heavily in the court’s analysis depending on the evidence pre- sented in each case. The one constant is that “[i]n any proceed- ing involving a child, the best interests of the child shall be the standard by which the court adjudicates and establishes . . . any custody, parenting time, visitation, or other access determina- tions as well as resolution of conflicts affecting each child.”76 (b) Kaaden’s Best Interests Here, the district court, after observing the parties and considering the evidence in light of the factors set out above, 72 § 43-2923(3). 73 See, generally, Coffey v. Coffey, 11 Neb. App. 788, 661 N.W.2d 327 (2003). 74 See State on behalf of Maddox S. v. Matthew E., 23 Neb. App. 500, 873 N.W.2d 208 (2016). 75 Kamal v. Imroz, 277 Neb. 116, 759 N.W.2d 914 (2009); Maska v. Maska, 274 Neb. 629, 742 N.W.2d 492 (2007). 76 § 43-2921. - 958 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 expressly found that an alternating week-on-week-off parent- ing time schedule was in Kaaden’s best interests. This was the parenting time schedule recommended by Kaaden’s counselor, and it is consistent with the court’s express factual findings that both parents are fit and provide a safe and appropriate home environment for Kaaden. Moreover, nearly equal parenting time furthered the court’s stated goal of allowing Kaaden to “enjoy the full benefits of having both parents involved in his life to the greatest degree possible.” In arguing that the award of nearly equal parenting time was an abuse of discretion, Jeffery focuses almost exclusively on evidence of Mandy’s animosity toward him and their dif- ficulty communicating. In our de novo review, we neither ignore nor minimize evidence that the parties have difficulty communicating effectively regarding Kaaden’s welfare, or that Mandy has significant unresolved anger toward Jeffery and actively interfered with his parenting time while the case was pending before the district court. But when all of the evidence is considered in light of Kaaden’s best interests, we cannot find the parenting time awarded here was an abuse of discretion. The trial court was appropriately concerned about Mandy’s interference with Jeffery’s parenting time and her unresolved anger toward him, and it addressed those concerns by award- ing Jeffery sole legal custody. This minimized the need for the parties to confer regularly because Jeffery has the sole author- ity and responsibility to make fundamental decisions regarding Kaaden’s welfare, including choices regarding his education and health. The trial court also explained that placing primary legal custody with Jeffery was the best way to ensure compli- ance with the parenting plan. And despite the tense relationship between Mandy and Jeffery, the record fully supports the trial court’s findings that both Mandy and Jeffery are fit and proper parents who love Kaaden and that both provide him safe and stable homes. The evidence shows both parents have developed a nurturing, - 959 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 positive bond with Kaaden, and it fully supports the trial court’s conclusion that it is in Kaaden’s best interests to have both parents involved in his life to the greatest degree possible. The trial court’s alternating week-on-week-off parenting schedule served to maximize Kaaden’s time with both parents and was directly supported by the testimony of his treating counselor. At the same time, the parenting schedule minimized the need for direct interaction between the parents by limiting exchanges of Kaaden to one time per week at a neutral site. An abuse of discretion occurs when a trial court bases its decision on reasons that are untenable or unreasonable or if its action is clearly against justice or conscience, reason, and evi- dence.77 Here, the trial court made detailed and specific factual findings which were fully supported by the record, and it pro- vided a carefully reasoned explanation for why it considered the custody and parenting time arrangement to be in Kaaden’s best interests. The trial court’s goal was not to find a custody and parent- ing time schedule the parents thought was fair, but to find one that was actually in Kaaden’s best interests. That required the court to create a parenting plan for a child who has a positive and nurturing relationship with both his parents, but whose parents do not have a good relationship with each other. On this record, we find no abuse of discretion in developing a par- enting plan that gave Jeffery sole legal custody and effectively imposed a joint physical custody arrangement with a week-on- week-off parenting time schedule. 7. Nonreimbursed Medical Expenses [14] The Nebraska Child Support Guidelines require child support orders to address how the parents will provide for the child’s health insurance.78 Here, Jeffery was ordered to pro- vide health insurance for Kaaden, and no party challenges that on appeal. 77 Randy S. v. Nicolette G., 302 Neb. 465, 924 N.W.2d 48 (2019). 78 § 4-215. - 960 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 The district court also ordered Jeffery to pay the first $480 of Kaaden’s nonreimbursed reasonable and necessary health care expenses per year, and it ordered Mandy to pay 50 per- cent of such expenses in excess of $480. We understand this language to have effectively allocated responsibility for non- reimbursed health care expenses equally between Mandy and Jeffery. No party contends otherwise, and no party challenges the court’s allocation of expenses in excess of $480. Instead, the parties focus on whether the trial court erred in ordering Jeffery to pay the first $480 of Kaaden’s nonreimbursed health care expenses. We limit our analysis accordingly. Before the Court of Appeals, Jeffery argued it was error to order him to pay the first $480 of nonreimbursed health care expenses. The Court of Appeals agreed, reasoning that the first $480 of nonreimbursed health care expenses was “subsumed within the amount of child support that is ordered.”79 The Court of Appeals thus reversed that portion of the decree. On further review, Mandy argues the Court of Appeals improperly reversed on this issue. We conclude the Court of Appeals cor- rectly interpreted the child support guidelines. [15] Nonreimbursed health care expenses are governed by § 4-215(B) of the child support guidelines, which states, in part, “Children’s health care expenses are specifically included in the guidelines amount of up to $480 per child per year.” As we have explained, “the guidelines estimate $480 as an ordi- nary amount of such nonreimbursed medical expenses, and that figure is then subsumed within the amount of child support that is ordered. Any nonreimbursed expenses exceeding $480 are [then] prorated between the parties.”80 The guidelines do not require the trial court to expressly identify any party as being responsible for the first $480 of nonreimbursed health care expenses, but they do require a 79 State on behalf of Kaaden S., supra note 1, 26 Neb. App. at 434, 920 N.W.2d at 50. 80 State on behalf of Martinez, supra note 12, 281 Neb. at 552, 797 N.W.2d at 222. - 961 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 court to allocate nonreimbursed health care expenses in excess of $480 per year “to the obligor parent as determined by the court.”81 Such allocation “shall not exceed the proportion of the obligor’s parental contribution (worksheet 1, line 6).”82 The guidelines’ reference to an “obligor” refers to the party ordered to pay child support. We therefore agree with the Court of Appeals that under the child support guidelines, the trial court erred in making Jeffery, who is the obligor under its child support calculation, responsi- ble for paying the first $480 of Kaaden’s nonreimbursed health care expenses, when such amounts are already subsumed in the monthly child support payment. The trial court may have had a sound reason for wanting Jeffery to pay such costs, but no explanation was provided in the decree, so we have no basis upon which to review a deviation from the guidelines.83 We affirm the Court of Appeals’ reversal of that portion of the decree requiring Jeffery to pay the first $480 of Kaaden’s non- reimbursed health care costs. 8. Child Support Because the Court of Appeals found the parenting time schedule was an abuse of discretion and remanded the matter to reduce Mandy’s parenting time, it also concluded the trial court erred in using worksheet 3, the joint custody worksheet, to calculate child support. It thus reversed the child support award and remanded the matter for recalculation “using the appropriate worksheet.”84 Mandy assigns this as error. She argues the trial court’s use of worksheet 3 to calculate support was appropriate given the 81 § 4-215(B). 82 Id. 83 See, generally, Neb. Ct. R. § 4-203 (rev. 2011) (child support guidelines shall be applied as rebuttable presumption, and deviations should be supported by specific findings). 84 State on behalf of Kaaden S., supra note 1, 26 Neb. App. at 433, 920 N.W.2d at 50. - 962 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 amount of parenting time she was awarded,85 and she seeks affirmance of the child support as ordered by the district court. No party challenges any other aspect of the child support award, so we confine our analysis to whether it was error to use worksheet 3. [16] Child support payments should generally be set accord- ing to the child support guidelines.86 Section 4-212 of the guidelines explains when, and how, worksheet 3 is to be utilized: When a specific provision for joint physical custody is ordered and each party’s parenting time exceeds 142 days per year, it is a rebuttable presumption that support shall be calculated using worksheet 3. When a specific provi- sion for joint physical custody is ordered and one party’s parenting time is 109 to 142 days per year, the use of worksheet 3 to calculate support is at the discretion of the court. . . . For purposes of these guidelines, a “day” shall be generally defined as including an overnight period. Here, the award of nearly equal parenting time effectively created a joint physical custody arrangement, and we have modified the decree and parenting plan to so describe it. Moreover, under the parenting plan, Mandy’s parenting time far exceeds the rebuttable presumption of 142 overnights per year referenced in § 4-212, and Jeffery has presented no evi- dence or argument that would rebut the presumptive use of worksheet 3. As such, we find no abuse of discretion in the trial court’s decision to use worksheet 3 to calculate child sup- port. We reverse the Court of Appeals’ holding to the contrary, and remand the matter with directions to affirm the district court’s child support award. V. CONCLUSION For the foregoing reasons, we modify the language of the decree and the parenting plan to reflect an award of joint 85 See Neb. Ct. R. § 4-212 (rev. 2011). 86 See Hotz v. Hotz, 301 Neb. 102, 917 N.W.2d 467 (2018). - 963 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 physical custody. We find no abuse of discretion in the custody and parenting time arrangement ordered by the district court, and we reverse the Court of Appeals’ decision to the contrary and remand the matter with directions to affirm that award as modified. We find no abuse of discretion in using worksheet 3 to calculate child support, and we reverse that aspect of the Court of Appeals’ decision as well and remand the matter with directions to affirm the child support award. In all other respects, we affirm the decision of the Court of Appeals. A ffirmed in part as modified, and in part reversed and remanded with directions.	{ "pile_set_name": "FreeLaw" }
Many organizations wish to gain better control over their print environment because printing is a significant source of expenses, and one that is often difficult to manage. These costs come from a variety of printing practices, including the use of inkjets (which are relatively cheap to buy, but relatively expensive to run), inappropriate use of color (e.g., for draft documents, emails, personal files, etc.), and inappropriate use of devices (e.g., large runs sent to small workgroup printers rather than high volume reprographics centers). A number of products in the market allow organizations to track the type of printing that occurs (such as Lexmark Markvision™, HP WebJetAdmin, Xerox® CenterWare™ Web and Pharos Blueprint®). Using this information, organizations can begin to phase out devices with a poor fit with respect to system usage requirements. However, changing user behavior is difficult when users are able to directly access printers on the network. Some existing approaches (e.g., Pharos® Uniprint®, EnvisionWare® LP:TOne, Equitrac® XYZ) can prevent users from accessing printers directly, and instead force them to print via these products' print servers—enabling the system administrator to set appropriate print policies. All of these products have a potential disadvantage, namely that they require changes to the organization print environment, such as through installing components on the workstation, changing the print destination, installing software on the print server, and/or changing the print server queue configuration. Such products may also require the customer to make changes to the printer itself to remove the capability of users to print directly thereto.	{ "pile_set_name": "USPTO Backgrounds" }
HT Motorsports HT Motorsports was an American truck racing team from Martinsville, Virginia, owned by trucking company owner Jim Harris. It fielded entries for the nine years in the Camping World Truck Series before suspending operations early in 2010. Truck No. 24 history This team debuted at a test session at Homestead-Miami Speedway as the No. 92 with Terry Cook driving. He started fifteenth and finished 20th. The No. 24 originally was intended to be the No. 11 Toyota for Red Horse Racing but driver David Starr and Zachry Holdings parted ways with the team in December. This team became the No. 24 for 2009 and Starr had fourteen top-ten finishes. Zachry and Starr left the team after the 2009 season for Randy Moss Motorsports. Truck No. 25 history HT Motorsports made its NASCAR debut at New Hampshire International Speedway in 2001 as the No. 92 Learnframe Dodge. It made four starts that season with Stacy Compton and finished in the top ten in each race. The team then ran at Martinsville Speedway in 2002 as the No. 17 Duck Head Footwear Dodge Ram driven by Darrell Waltrip. He qualified eighteenth but finished thirty-eighth. Waltrip returned at Indianapolis Raceway Park with Tide sponsorship, and finished sixth. Stacy Compton would drive three additional races that season, posting a best finish of eighth at Richmond. In 2003, HT switched to the No. 59 and hired Robert Pressley to drive. Driving with associate sponsorship from Melling Engine Parts, Pressley finished in the top-five four times and finished thirteenth in points. Randy LaJoie ran the first two races of 2004, followed by rookie Mark McFarland. McFarland finished sixth at Mansfield Motorsports Speedway before being cycled out by LaJoie, who had an eighth-place finish at Gateway. Andy Houston drove for three races, but did not finish higher than 14th. Sammy Sanders, Bobby Hamilton, Jr., and Scott Lynch finished out the year in the 59. Pressley returned to HT in 2005, but had only three top-ten finishes and finished 20th in the standings. He was released and replaced by Mike Wallace at the beginning of 2006, but wrecked out of the two races in which he drove for the team. Steve Park became the team's new driver, as the team switched to Ford. Despite a tenth-place finish at Mansfield, he was released after ten races and replaced by Chad Chaffin. After a slow start, the team switched to Toyota and Chaffin finished eighth at Talladega Superspeedway. Terry Cook was named the driver of the 59 for 2007, and had two top-tens and finished fourteenth in points. He was released at the end of the season for Whelen Modified driver Donny Lia, who raced the last race of the season. For 2008, Ted Musgrave will move to the No. 59 team, bringing along his ASE sponsorship. In August 2008 ASE announced they will be leaving NASCAR. After 18 races in season, and a wreck in the 1st practice at Las Vegas Motor Speedway, Musgrave & HT Motorsports parted ways. Stacy Compton replaced him later in the day. Joey Logano made his truck series debut at Talladega starting sixth but crashing early. Terry Cook, recently released from Wyler Racing, drove the No. 59 for the rest of the '08 season. The team switched to the No. 25 for 2009 with Cook returning. He had nine top-tens but was replaced in the final two races by Mike Bliss. References External links Official Website Category:American auto racing teams Category:Companies based in Virginia Category:Defunct NASCAR teams Category:Auto racing teams established in 2001 Category:Sports clubs disestablished in 2010	{ "pile_set_name": "Wikipedia (en)" }
package cn.neural.common; import lombok.Getter; import java.util.concurrent.; /* * A specialized <em>semaphore</em> implementation that provides a number of permits in a given time frame. * <p> * TimedSemaphore sem = new TimedSemaphore(1, TimeUnit.SECOND, 10); * * @author lry / @Getter public class TimedSemaphore { /* * Constant for a value representing no limit. * If the limit is set to a value less or equal this constant, * the {@code TimedSemaphore} will be effectively switched off. / public static final int NO_LIMIT = 0; /* * Constant for the thread pool size for the executor. / private static final int THREAD_POOL_SIZE = 1; /* * The executor service for managing the timer thread. / private final ScheduledExecutorService executorService; /* * Stores the period for this timed semaphore. / private final long period; private final TimeUnit unit; /* * A flag whether the executor service was created by this object. / private final boolean ownExecutor; /* * A future object representing the timer task. / private ScheduledFuture<?> task; /* * Stores the total number of invocations of the acquire() method. / private long totalAcquireCount; /* * The counter for the periods. This counter is increased every time a period ends. / private long periodCount; private int limit; /* * The current counter. / private int acquireCount; /* * The number of invocations of acquire() in the last period. / private int lastCallsPerPeriod; /* * A flag whether shutdown() was called. / private boolean shutdown; public TimedSemaphore(long timePeriod, TimeUnit timeUnit, int limit) { this(null, timePeriod, timeUnit, limit); } public TimedSemaphore(ScheduledExecutorService service, long timePeriod, TimeUnit timeUnit, int limit) { if (timePeriod < 1) { throw new IllegalArgumentException("Time period must be greater than 0!"); } this.period = timePeriod; this.unit = timeUnit; if (service != null) { this.executorService = service; this.ownExecutor = false; } else { ScheduledThreadPoolExecutor timerExecutor = new ScheduledThreadPoolExecutor(THREAD_POOL_SIZE, r -> { Thread t = new Thread(r); t.setDaemon(true); t.setName("MANAGING_TIMER_THREAD"); return t; }); timerExecutor.setContinueExistingPeriodicTasksAfterShutdownPolicy(false); timerExecutor.setExecuteExistingDelayedTasksAfterShutdownPolicy(false); this.executorService = timerExecutor; this.ownExecutor = true; } setLimit(limit); } /* * Returns the limit enforced by this semaphore. The limit determines how * many invocations of {@link #acquire()} are allowed within the monitored period. * * @return the limit / public final synchronized int getLimit() { return limit; } /* * Sets the limit. This is the number of times the {@link #acquire()} method * can be called within the time period specified. If this limit is reached, * further invocations of {@link #acquire()} will block. Setting the limit * to a value <= {@link #NO_LIMIT} will cause the limit to be disabled, * i.e. an arbitrary number of{@link #acquire()} invocations is allowed in the time period. * * @param limit the limit / public final synchronized void setLimit(final int limit) { this.limit = limit; } /* * Initializes a shutdown. After that the object cannot be used any more. * This method can be invoked an arbitrary number of times. All invocations * after the first one do not have any effect. / public synchronized void shutdown() { if (!shutdown) { if (ownExecutor) { // if the executor was created by this instance, it has to be shutdown getExecutorService().shutdownNow(); } if (task != null) { task.cancel(false); } shutdown = true; } } /* * Tests whether the {@link #shutdown()} method has been called on this object. * <p> * If this method returns <b>true</b>, this instance cannot be used any longer. * * @return a flag whether a shutdown has been performed / public synchronized boolean isShutdown() { return shutdown; } /* * Acquires a permit from this semaphore. This method will block if * the limit for the current period has already been reached. If * {@link #shutdown()} has already been invoked, calling this method will * cause an exception. The very first call of this method starts the timer * task which monitors the time period set for this {@code TimedSemaphore}. * From now on the semaphore is active. * * @throws InterruptedException if the thread gets interrupted * @throws IllegalStateException if this semaphore is already shut down / public synchronized void acquire() throws InterruptedException { prepareAcquire(); boolean canPass; do { canPass = acquirePermit(); if (!canPass) { wait(); } } while (!canPass); } /* * Tries to acquire a permit from this semaphore. If the limit of this semaphore has * not yet been reached, a permit is acquired, and this method returns * <strong>true</strong>. Otherwise, this method returns immediately with the result * <strong>false</strong>. * * @return <strong>true</strong> if a permit could be acquired; <strong>false</strong> otherwise * @throws IllegalStateException if this semaphore is already shut down / public synchronized boolean tryAcquire() { prepareAcquire(); return acquirePermit(); } /* * Returns the number of (successful) acquire invocations during the last * period. This is the number of times the {@link #acquire()} method was * called without blocking. This can be useful for testing or debugging * purposes or to determine a meaningful threshold value. If a limit is set, * the value returned by this method won't be greater than this limit. * * @return the number of non-blocking invocations of the {@link #acquire()} method / public synchronized int getLastAcquiresPerPeriod() { return lastCallsPerPeriod; } /* * Returns the number of invocations of the {@link #acquire()} method for * the current period. This may be useful for testing or debugging purposes. * * @return the current number of {@link #acquire()} invocations / public synchronized int getAcquireCount() { return acquireCount; } /* * Returns the number of calls to the {@link #acquire()} method that can * still be performed in the current period without blocking. This method * can give an indication whether it is safe to call the {@link #acquire()} * method without risking to be suspended. However, there is no guarantee * that a subsequent call to {@link #acquire()} actually is not-blocking * because in the mean time other threads may have invoked the semaphore. * * @return the current number of available {@link #acquire()} calls in the * current period / public synchronized int getAvailablePermits() { return getLimit() - getAcquireCount(); } /* * Returns the average number of successful (i.e. non-blocking) * {@link #acquire()} invocations for the entire life-time of this {@code * TimedSemaphore}. This method can be used for instance for statistical * calculations. * * @return the average number of {@link #acquire()} invocations per time * unit / public synchronized double getAverageCallsPerPeriod() { return periodCount == 0 ? 0 : (double) totalAcquireCount / (double) periodCount; } /* * Starts the timer. This method is called when {@link #acquire()} is called * for the first time. It schedules a task to be executed at fixed rate to * monitor the time period specified. * * @return a future object representing the task scheduled / protected ScheduledFuture<?> startTimer() { return getExecutorService().scheduleAtFixedRate(this::endOfPeriod, getPeriod(), getPeriod(), getUnit()); } /* * The current time period is finished. This method is called by the timer * used internally to monitor the time period. It resets the counter and * releases the threads waiting for this barrier. / private synchronized void endOfPeriod() { lastCallsPerPeriod = acquireCount; totalAcquireCount += acquireCount; periodCount++; acquireCount = 0; notifyAll(); } /* * Prepares an acquire operation. * <p> * Checks for the current state and starts the internal timer if necessary. / private void prepareAcquire() { if (isShutdown()) { throw new IllegalStateException("TimedSemaphore is shut down!"); } if (task == null) { task = startTimer(); } } /* * Internal helper method for acquiring a permit. * * @return a flag whether a permit could be acquired */ private boolean acquirePermit() { if (getLimit() <= NO_LIMIT \|\| acquireCount < getLimit()) { acquireCount++; return true; } return false; } }	{ "pile_set_name": "Github" }
For an amazing selection of original sculptures, statues, prints and DVDs be sure to check out ShiflettBrothers.com. On September 6, 2011, Fabulous Films, with distribution from Shout! Factory, will unleash AIRWOLF: The Movie on DVD for the first time in the U.S. and Canada. Written and directed by Donald P. Bellisario and starring Jan-Michael Vincent, Ernest Borgnine and Alex Cord, AIRWOLF: The Movie boasts full-throttle action, daring high-speed aerial stunts and captivating storylines mixed with international espionage and intrigue. A futuristic high action adventure about a billion dollar helicopter (named Airwolf) equipped with a twin-turbine drum rotor system capable of propelling it to 300 knots, plus 14 firepower options. When the helicopter is purloined by Libyan mercenaries, project director of the CIA (Alex Cord) enlists the help of Vietnam veteran Stringfellow Hawke (Jan-Michael Vincent) and his father’s best friend Dominic Santini (Ernest Borgnine) in an attempt to recover it. The deadly mission takes them to the Middle East where they must battle the enemy to repossess the deadliest aerial weapon ever made.	{ "pile_set_name": "Pile-CC" }
[Current prenatal care with reference to state of the art knowledge]. Every physician taking care of pregnant women believes to be well acquainted with the state-of-the-art requirements. However, changes imposed by the new Swiss health insurance legislation (KVG) and by the pressure of Evidence Based Medicine brought these into a new scope. In Switzerland there is no general agreement on optimal pregnancy-care. We propose a care-standard, based on rational and efficient clinical, laboratory and sonographic checks, which allow a timely diagnosis of pregnancy-at-risk. Targeted laboratory investigations as well as the anti-D-immunoprophylaxis, and screening for diabetes mellitus efficiently help to avoid long-term sequelae for mother and child. Screening for toxoplasmosis, HIV, and hepatitis B are compulsory. A vaginal pH below 4.5 prevents premature birth. Diagnosis and treatment of vaginal chlamydial and candida infection are also very important in this respect. The number of sonographies to be performed during pregnancy is a highly political issue, and we have to comply with our dirigistic governmental regulations. However, sonography including search for increased nuchal translucency done early in pregnancy is a key procedure for quality assurance. Supplementation of folic acid started before conception, almost entirely prevents neural tube defects. Hence women need appropriate advice before conception. A new information brochure is available for future parents in Switzerland, and makes all former self-made guidelines unnecessary. UNICEF declared 1998 as the year of safe motherhood. Worldwide still too many women die from pregnancy and delivery. Care for normal pregnancy, and not only for at-risk-pregnancy will therefore continue to make sense.	{ "pile_set_name": "PubMed Abstracts" }
Article content continued Black Friday The symbolism of announcing the drastic measures on a Friday night wasn’t lost on many Venezuelans. In 1983, President Luis Herrera Campins devalued the bolivar for the first time in 22 years after oil prices crashed. The day became to be known locally as “Black Friday.” When in 1989 Venezuela raised gasoline costs, lifted foreign-exchange controls and let the currency plunge, prices soared 21 per cent in one month alone, leading to riots known as the “Caracazo” that killed hundreds and eventually paved the way for Chavez’s rise to power. Military Alliance It’s not clear how the shock measures announced by Maduro will sit with one of his key allies: the military. Top ranking generals have been handed the keys to ministries, the state-run oil company and the lucrative business of food imports. Myriad exchange rates created juicy arbitrage opportunities that enriched many close associates of the state. “Clearly this will hit Maduro’s popularity, but power is being sustained with bullets and not with votes,” Naim said. “As long as the military continues to have access to lucrative businesses it will continue to grant support to the government.” The opposition, a fragmented group of parties whose leaders are either in hiding or in jail, called for protests against the measures Tuesday. Several labour unions also called for a 24-hour national strike. In Caracas this weekend, many small shops were closed while people flocked to supermarkets and gasoline stations to stock up. Online banking services will be suspended for 24 hours starting at 6 p.m. local time in anticipation of the redenomination. Many private companies, already dealing with hyperinflation, years of brain drain, price controls and threats of seizure, now must deal with even faster inflation and mandatory wage hikes. It’s also possible that the exodus of Venezuelans to other countries will increase, even as Ecuador and Peru announced entry restrictions and tensions flared along the border with Brazil. “People are leaving because of a feeling of despair, and the desperation will now increase,” Naim said. Bloomberg.com	{ "pile_set_name": "OpenWebText2" }
Q: @InitBinder in spring boot not working with @RequestBody If I use @InitBinder without limiting it,it is working fine with @RequestBody to validate my objects. @InitBinder private void initBinder(WebDataBinder binder) { binder.setValidator(validator); } @RequestMapping(method=RequestMethod.POST) public CustomerQuickRegisterEntity saveNewCustomer(@Valid @RequestBody CustomerQuickRegisterEntity customerEntity,BindingResult result) { if(result.hasErrors()) { return new CustomerQuickRegisterEntity(); } return customerQuickRegisterRepository.save(customerEntity); } But problem is that when i limit it to just one object by doing it as @InitBinder("customerEntity") it is not validating the object. So I have searched through stackoverflow and found that @InitBinding only works with objects annotated with @ModelAttribute. Then my question is that it is working fine with @RequestBody when I use it as @InitBinder but does not work well when I use it as @InitBinder("customerEntity") ...why is it so? Is there any other way to validate Objects(Not properties of object Individually) associated with @RequestBody A: This is an old question, but I've managed to get the @InitBinder annotation to bind my custom Validator to a @Valid @RequestBody parameter like this: @InitBinder private void bindMyCustomValidator(WebDataBinder binder) { if ("entityList".equals(binder.getObjectName())) { binder.addValidators(new MyCustomValidator()); } } If you try to filter the bound argument by setting the value of the annotation, then it won't work for a @RequestBody argument. So here I check the object name instead. My method parameter is actually called entities, but Spring had decided to call it entityList. I had to debug it to discover this. A: From the docs, Default is to apply to all command/form attributes and all request parameters processed by the annotated handler class. Specifying model attribute names or request parameter names here restricts the init-binder method to those specific attributes/parameters, with different init-binder methods typically applying to different groups of attributes or parameters. Please have a look here	{ "pile_set_name": "StackExchange" }
Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach. Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs. Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2 alpha, AP-2 gamma). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2 alpha and HER2 in contrast to MCs (CK7: 91% of IDCs versus 77% of MCs; AP-2 alpha: 77% versus 57%; and HER2: 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05). Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2 alpha overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs.	{ "pile_set_name": "PubMed Abstracts" }
The standard way of assigning file permissions on Unix systems is so tied into how people think of Unix that many of us seem to forget that this scheme was expanded many years ago to accomodate more than just file owners, groups, and everyone else. The setfacl (set file access control lists) and getfacl (get file access control list) commands were designed to allow more than the traditional limited assignment of privileges. While not disturing the customary owner-group-other permissions, you could, for example, give another account holder the same permissions as the owner or allow more than one group to have special access while not giving that access to just everyone. Everything comes at some cost, however, and to use the setfacl and getfacl commands, a file system has to be mounted with a special option that allows these commands and the underlying expansion of priviledges to be used. After all, there is overhead associated with keeping track of the extra permissions, so you have to opt in by adding an option to the file system in the /etc/fstab file -- the acl option. If you don't, anyone trying to use these commands will likely be confronted with an "operation not supported" error. You may also have to check whether your kernel provides support for this feature. To mount a file system with the acl option, you will need to use a command like this: # mount -t ext4 -o acl /dev/hdb3 /data In the /etc/fstab, this same operation might look like this: /dev/hdb3 /data ext4 defaults,acl 0 1 Indications that the extended permissions are in use are rather subtle. You'll just see a + sign at the end of the normal permissions field. For example: -rw-r-----+ 1 smitten admins 22088 Oct 26 recipe That little + at the end of -rw-r-----+ tells you that there are more permissions than the rw-r----- permissions string is letting on. And, if you want to know more, you just have to use the getfacl command to display the complete permissions for the file. For a file with only standard permissions, you will see something like this: $ getfacl beerlist # file: beerlist # owner: smitten # group: admins user::rw- group::r-- other::--- This shows us what we normally see in a long listing, but in a different format. For a file with the extended permissions, on the other hand, the getfacl command might show you any additional permissions that have been set -- like this: $ getfacl beerlist # file: beerlist # owner: smitten # group: admins user::rw- user:tsmiley:rw- group::r-- mask::rw- other::--- Notice that we now see another user (tsmiley) with read and write permissions and a new field -- the "mask" field that sets default permissions for the file. You can set extended permissions using the setfacl command. Here are some examples where we give a user read, write and execute or add write permission. setfacl -m u:tsmiley:rwx /data/example setfacl -m u:tsmiley:+w /data/example The -m stands for modify. The "u" in u: stands for user. You can assign permissions to groups as well as to individuals. You would assign a group permissions with a "g" as in the examples shown below. setfacl -m g:devt:rwx /data/testcase setfacl -R -m g:devt:+x testcases/ setfacl -m d:g:admins:rwx /data/scripts In the third line in this example, the d: before the g: makes the new settings (rwx) the default for this directory. When files or direcxtories are created under the /data/scripts directory, the admins group will have rwx permission to them as well. After setting a default, you can expect to see these values when you use the getfacl command in the form of an additional line that looks like this: default:group::rwx One of the other complexities that you are likely to run into is the idea of the effective mask setting. If the mask is more restrictive than the permissions that you grant, the mask will take precedence. In the example below, the mask is r-- and reduces the privileges given to the groups to r--. $ getfacl /data/jumping.jar # file: /data/jumping.jar # owner: dbender # group: users user::rw- group::rwx #effective:r-- group:devt:rwx #effective:r-- mask::r-- other::r-- To remove extended permissions for a file or folder, you can use one of these commands. Remove all ACLs from a file: setfacl -b /data/example Remove the default ACL: setfacl -k testcases The mask setting is interesting. It will be set up whenever permissions beyond those of owner, group, and other are used. As you'd read in the man page for the setfacl command, the mask is the union of all permissions from the owning group, named user and group settings. It can limit the permissions that are available but you can change the mask with a command like this: $ setfacl -m mask:rw- /data/example Note that mask can be spelled (mask:) out or abbreviated to m (m:). Generally, it will be set to whatever permissions are intended for the expected collections of users and groups. You can also override this setting when you assign permissions by requesting that no mask be used with the -n or --no-mask setting. The traditional Unix permissions are easy to think about, but can be seriously confining when you need more flexibility in defining what various users or groups on your servers should be able to do. The newer ACL commands give you a lot more leeway in determining who gets what permissions. You just have to work a little harder to be sure they're right.	{ "pile_set_name": "OpenWebText2" }
If you would like to get rich in your line of work, it would be best to be an entrepreneur or a salesperson who consistently goes beyond the targets set for you. To dabble in the world of e-sports, well, only a select few will be able to make a good living out of it, and afterwards as well when they have retired. Still, if you would like to give those restless thumbs and fingers of yours a go, how about checking out the Mortal Kombat eSports tournament that boasts of a $500,000 prize pool? Advertising Half a million in cold, hard cash, now that is certainly pretty difficult to turn down, don’t you think so? Warner Bros. would be the one behind this prize money as they launch the massive Mortal Kombat X eSports program later next month April, with the prize pot being a mouth watering $500,000. This particular venture will also include the third season of ESL Mortal Kombat X Pro League, which will see the cream of the crop from around the world go up against one another this April 3rd. As for the top sixteen players, they will then stand a chance to compete in front of a live audience when June 12 rolls around, while the final eight finalists will be able to duke it out for a slice of the $200,000 from the prize pot. This is because Warner Bros. will host tournaments throughout North America, Europe, the Russian Commonwealth and Latin America at the same time. Filed in . Read more about Mortal Kombat. Source: eventhubs	{ "pile_set_name": "OpenWebText2" }
Accidental swallowing of a gold cast crown during orthodontic tooth separation. Accidental swallowing of a gold cast crown that became loose after separation with brass wire for orthodontic band placement, is reported. The intervention to remove the ingested crown subsequent to its location in the GI tract on immediate radiographic examination of chest and abdomen included endoscopic examination. Since the crown had past distal to the duodenum it was decided to keep a watch on its movement by daily radiographic examination. The crown passed with excreta on the 5th day uneventfully. Literature on ingestion of foreign bodies of dental origin is reviewed. Possible emergencies and their management is discussed.	{ "pile_set_name": "PubMed Abstracts" }
Manny Pacquiao Gabriel Bouys / AFP / Getty Manny Pacquiao was considered a savior by two groups of people this year: Filipinos and boxing aficionados. For his countrymen, the diminutive (5 ft. 6 in. and change) pugilist once again proved that their archipelago could produce more than tales of violence, poverty and natural disaster that there was some undefined quality that could produce a fighter of such speed, resiliency and charisma as to be a living legend. For boxing fans, Pacquiao defied physics, rising through six weight classes to win seven world titles and galvanizing the sport like no other boxer in years. His two bouts this year were among the most dramatic in the sport: his second-round knockout of Ricky Hatton and his terrifying demolition of the rock-solid Miguel Cotto over 11 rounds. His visceral charm or his bloody attraction will continue into next year with his expected multimillion-dollar, hugely lucrative matchup against Floyd Mayweather Jr., the only fighter remaining who can claim to be his equal.	{ "pile_set_name": "Pile-CC" }
Oskar Roehler Oskar Roehler (born 21 January 1959) is a German film director, screenwriter and journalist. He was born in Starnberg as the son of writer Gisela Elsner and the writer Klaus Roehler. Since the mid-1980s he has been working as a screenwriter, for, among others, Niklaus Schilling, Christoph Schlingensief and Mark Schlichter. Since the early 1990s he has also been working as a film director. For his film No Place to Go he won the Deutscher Filmpreis. His 2010 film Jew Suss: Rise and Fall was nominated for the Golden Bear at the 60th Berlin International Film Festival. Partial filmography Gentleman (1995) Silvester Countdown (1997) Gierig (1999) No Place to Go (2000) Suck My Dick (2001) Beloved Sister (2002) Angst (2003) Agnes and His Brothers (2004) The Elementary Particles (2006) Lulu and Jimi (2009) Jew Suss: Rise and Fall (2010) Sources of Life (2013) Punk Berlin 1982 (2015) Subs (2017) References External links Category:1959 births Category:German film directors Category:German-language film directors Category:Living people Category:People from Starnberg	{ "pile_set_name": "Wikipedia (en)" }
Whitman MS in Entrepreneurship Experience The 30-credit-hour Whitman MS in Entrepreneurship program provides a rigorous immersion into the nature of entrepreneurship and the entrepreneurial process. Combining core content with a strong commitment to experiential learning, the program is targeted to students with a passion for entrepreneurship in start-ups and larger, more established companies, and in the for-profit, non-profit, and public sector contexts. Established in 1992, Whitman's program in Entrepreneurship and Emerging Enterprises (EEE) is today one of the most comprehensive and respected in the country. Syracuse University has adopted a campus-wide initiative on entrepreneurship, where entrepreneurship is being integrated into multiple schools and courses across campus. The EEE program has earned recognition as a top-tier program in ratings by U.S. News & World Report, Bloomberg BusinessWeek, and Entrepreneur magazine/Princeton Review.	{ "pile_set_name": "Pile-CC" }
Enhancement of association rates by nonspecific binding to DNA and cell membranes. A comprehensive analytic theory is developed for the kinetics of reversible association with specific sites on DNA and receptors on cell membranes in the presence of nonspecific binding to the target surfaces. Nonspecific binding is treated as a short-range attractive potential, which is more fundamental and realistic than the surface sliding model. The presence of a surface potential around the target enhances the rate of specific association and for reversible reactions leads to deviations from single exponential relaxation.	{ "pile_set_name": "PubMed Abstracts" }
Q: How to split a page in six equally sized sectors? I'd like to split an A4 page into six equally sized sectors. I want that page to be in landscape. Each sector has a body of text and a caption. I don't really have an idea where to start. I know I can split a page in to columns, but I need like six minipages, all equally arranged on one paper. The only idea I could come up with, is to use a0poster and then size it down for print. I think however, this is overkill; isn't there a better way to do that? I'm preferably using XeLaTeX, if that is of any importance. A: You can use six minipages; I defined a \Block command using a minipage of the desired width and length with two arguments: the text and the caption (make the necessary formatting adjustments). I added some frames just for visualization purposes (and they will produce some overfull boxes); please delete the lines marked with %delete: \documentclass{article} \usepackage[landscape]{geometry} \newcommand\Block[2]{% \setlength\fboxsep{0pt}\setlength\fboxrule{0.1pt}% delete \fbox{% delete \begin{minipage}[c][.5\textheight][t]{0.333333\textwidth} #1\par #2 \end{minipage}% }% delete } \begin{document} \noindent \Block{text}{caption}% \Block{text}{caption}% \Block{text}{caption}% \par\nointerlineskip\noindent \Block{text}{caption}% \Block{text}{caption}% \Block{text}{caption} \end{document} To meet the requirements in the comment: \documentclass{article} \usepackage[margin=3cm,centering,landscape]{geometry} \newcommand\Block[2]{% \setlength\fboxsep{0pt}\setlength\fboxrule{0.1pt}% delete \fbox{% delete \begin{minipage}[c][\dimexpr.5\textheight-2pt\relax][c]{\dimexpr0.3333333\textwidth-3pt\relax} \centering #1\par #2 \end{minipage}% }% delete } \begin{document} \thispagestyle{empty}% optional: suppress page numbering \noindent \Block{text}{caption}\hfill% \Block{text}{caption}\hfill% \Block{text}{caption}% \vfill \noindent\Block{text}{caption}\hfill% \Block{text}{caption}\hfill% \Block{text}{caption} \end{document} Using some of the options for the geometry package, the text area layout can be modified at will. A: Here's a solution using the pdfpages package. It consists of two steps: First you produce a document with a small paper size, and then you produce another document that combines these small pages onto one A4 landscape page. This is your actual document, where you put all of your text etc. You might have to adapt the margins, page numbers, etc. to your needs. % This file is called sixpages-doc.tex \documentclass{article} \usepackage[paperwidth=9.9cm,paperheight=10.5cm]{geometry} % paperwidth is A4/3, paperheight is A4/2 \usepackage{lipsum}% just for filler text \begin{document} \lipsum[1-6] \end{document} This is the document that puts the six pages on one page: \documentclass{article} \usepackage[landscape,a4paper]{geometry} \usepackage{pdfpages} \begin{document} \includepdf[pages=-,nup=3x2]{sixpages-doc.pdf} % pages=- means all pages % nup "Puts multiple logical pages onto each sheet of paper. The syntax of % this option is: nup=⟨xnup⟩x⟨ynup⟩." (from the manual) % If you want this layout: % 1 3 5 % 2 4 6 % use the option "column". \end{document} This is the output of the second document: A: I know that you want to use minipages. But here is a version using \parbox. You can't have certain things like footnotes here. This answer is given just to complete the list. We ride on Gonzalo's code (thanks @Gonzalo) and modify a bit: \documentclass{article} \usepackage[landscape]{geometry} \newcommand\Block[2]{% \setlength\fboxsep{0pt}\setlength\fboxrule{0.1pt}% delete \fbox{% delete \parbox[c][.5\textheight][t]{0.3\textwidth} {#1\par #2} % }% delete } \begin{document} \noindent \Block{text}{caption}\hfill \Block{text}{caption}\hfill \Block{text}{caption}% \vfill\noindent \Block{text}{caption}\hfill \Block{text}{caption}\hfill \Block{text}{caption} \end{document}	{ "pile_set_name": "StackExchange" }
Von Ronen Steinke, Berlin Das Bundesverteidigungsministerium hat die geplante unehrenhafte Entlassung des Whistleblowers Patrick J. vorerst gestoppt. Das geht aus einem Schreiben des Personalamts der Bundeswehr hervor, das die Süddeutsche Zeitung einsehen konnte. Demnach setze man "den Vollzug" der Entlassung "bis auf Weiteres aus". Der 30 Jahre alte Unteroffizier Patrick J. hatte so viele vertrauliche Hinweise auf rechte Umtriebe abgegeben wie noch kein Bundeswehrsoldat zuvor. In den vergangenen Monaten hatte er auf eigene Initiative ein Dossier mit rechtsradikalen oder vermeintlich rechtsradikalen Äußerungen von mehr als einhundert seiner Kameraden angelegt und dem Geheimdienst der Truppe, dem Militärischen Abschirmdienst (MAD), übergeben. Interne Ermittlungen nur in neun Fällen Nach SZ-Informationen haben nur die wenigsten der Hinweise von Patrick J. bisher bundeswehrinterne Ermittlungen ausgelöst. Viele Vorwürfe waren aus Sicht des MAD zu dünn. In neun Fällen allerdings ist der MAD durch die Mitteilungen von Patrick J. tatsächlich zu Ermittlungen veranlasst worden. Zum Beispiel hatte der Whistleblower dokumentiert, wie sich ein Stabsunteroffizier im Internet mit Rechtsextremisten vernetzte, die das KZ Auschwitz mit Legosteinen nachbauten. Bei einem Oberstabsgefreiten entdeckte er Facebook-Kontakte zu sogenannten Reichsbürgern. Im Netz schrieb dieser Bundeswehrsoldat: "Wir sind eh alle Staatenlos." Das Personalamt der Bundeswehr wollte Patrick J. ursprünglich mit der Begründung entlassen, es fehle ihm an der "charakterlichen Eignung". Zahlreiche seiner Vorwürfe gegen Kameraden seien "übertrieben und haltlos". Auch hätten sich inzwischen Kameraden ihrerseits über Patrick J. beschwert, weshalb er wegen "Missbrauchs der Befehlsbefugnis" zu einer Geldstrafe von 1500 Euro verurteilt worden sei. Patrick J. hat allerdings gegen das Urteil Rechtsmittel eingelegt. Das Bundesverteidigungsministerium, dessen Staatssekretär Gerd Hoofe (CDU) sich in der vergangenen Woche mit Patrick J. getroffen hatte, wollte sich auf SZ-Anfrage nicht zu dem Fall äußern. Hoofe verwies auf den Datenschutz.	{ "pile_set_name": "OpenWebText2" }
Zeta Pavonis Zeta Pavonis, Latinized from ζ Pavonis, is an orange-hued star in the southern constellation Pavo. Its apparent magnitude is 4.01, which is bright enough to be faintly visible to the naked eye. The annual parallax shift of this star is 14.93 mas as seen from Earth, which provides a distance estimate of approximately away from the Sun. It is moving closer to the Sun with a radial velocity of −16.30. Based upon its motion through space, this star appears to be a member of the Hyades Supercluster. This is an evolved K-type giant star with a stellar classification of K0 III, which indicates it has exhausted the supply of hydrogen at its core. The measured angular diameter of this star, after correction for limb darkening, is . At the estimated distance of this star, this yields a physical size of about 19 times the radius of the Sun. The star is radiating 155 times the Sun's luminosity. Zeta Pavonis has a companion, probably optical, of apparent magnitude 12.0 at about 55.6" separation. References Category:K-type giants Category:Hyades Stream Category:Pavo (constellation) Pavonis, Zeta Category:Durchmusterung objects 171759 091792 6982	{ "pile_set_name": "Wikipedia (en)" }
Corynebacterium ulcerans, an emerging human pathogen. While formerly known infections of Corynebacterium ulcerans are rare and mainly associated with contact to infected cattle, C. ulcerans has become an emerging pathogen today. In Western Europe, cases of respiratory diphtheria caused by C. ulcerans have been reported more often than infections by Corynebacterium diphtheria, while systemic infections are also increasingly reported. Little is known about factors that contribute to host colonization and virulence of this zoonotic pathogen. Research in this field has received new impetus by the publication of several C. ulcerans genome sequences in the past years. This review gives a comprehensive overview of the basic knowledge of C. ulcerans, as well as the recent advances made in the analysis of putative virulence factors.	{ "pile_set_name": "PubMed Abstracts" }
Luo Xiangang Luo Xiangang (; born December 1970) is a Chinese engineer specializing in photoelectric technology. He is an academician of the Chinese Academy of Engineering currently serves as director of the Institute of Optics and Electronics, Chinese Academy of Sciences. Biography Luo was born in Cangxi County, Sichuan, in December 1970. He attended Qinglin Village School. He elementary studied at Baiqiao Town Middle School and secondary studied at Chengjiao High School. In 1989 he graduated from Mianyang Teachers' College. He holds a bachelor's degree from Sichuan Normal University, and master's and doctor's degrees from the Institute of Optics and Electronics, Chinese Academy of Sciences. He was a postdoctoral fellow at the Institute of Physical and Chemical Research between May 2001 and May 2002. He was also a research scientist at the institute from May 2001 to January 2005. He joined the Institute of Optics and Electronics, Chinese Academy of Sciences in December 2004. Honours and awards 2008 National Science Fund for Distinguished Young Scholars 2014 Fellow of the International Academy of Photonics and Laser Engineering (IAPLE) 2016 State Technological Invention Award (First Class) 2018 Fellow of the Chinese Optical Society (COS) 2019 Fellow of The Optical Society (OSA) 2019 Fellow of SPIE November 22, 2019 Member of the Chinese Academy of Engineering (CAE) References External links Luo Xiangang on the Institute of Optics and Electronics, Chinese Academy of Sciences Category:1970 births Category:Living people Category:People from Cangxi County Category:Engineers from Sichuan Category:Sichuan Normal University alumni Category:Members of the Chinese Academy of Engineering Category:Fellows of the Optical Society Category:Fellows of SPIE	{ "pile_set_name": "Wikipedia (en)" }
//===- llvm/TableGen/Error.h - tblgen error handling helpers ----- C++ --===// // // The LLVM Compiler Infrastructure // // This file is distributed under the University of Illinois Open Source // License. See LICENSE.TXT for details. // //===----------------------------------------------------------------------===// // // This file contains error handling helper routines to pretty-print diagnostic // messages from tblgen. // //===----------------------------------------------------------------------===// #ifndef LLVM_TABLEGEN_ERROR_H #define LLVM_TABLEGEN_ERROR_H #include "llvm/Support/SourceMgr.h" namespace llvm { void PrintWarning(ArrayRef<SMLoc> WarningLoc, const Twine &Msg); void PrintWarning(const char Loc, const Twine &Msg); void PrintWarning(const Twine &Msg); void PrintError(ArrayRef<SMLoc> ErrorLoc, const Twine &Msg); void PrintError(const char Loc, const Twine &Msg); void PrintError(const Twine &Msg); LLVM_ATTRIBUTE_NORETURN void PrintFatalError(const Twine &Msg); LLVM_ATTRIBUTE_NORETURN void PrintFatalError(ArrayRef<SMLoc> ErrorLoc, const Twine &Msg); extern SourceMgr SrcMgr; extern unsigned ErrorsPrinted; } // end namespace "llvm" #endif	{ "pile_set_name": "Github" }
Aceruloplasminemia, an inherited disorder of iron metabolism. Ceruloplasmin, a multi-copper ferroxidase that affects the distribution of tissue iron, has antioxidant effects through the oxidation of ferrous iron to ferric iron. Aceruloplasminemia is an inherited disorder of iron metabolism due to the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. It is characterized by iron accumulation in the brain as well as visceral organs. Clinically, the disease consists of the triad of retinal degeneration, diabetes mellitus, and neurological disease, which include ataxia, involuntary movements, and dementia. These symptoms reflect the sites of iron deposition. The unique involvement of the central nervous system distinguishes aceruloplasminemia from other inherited and acquired iron storage disorders. Twenty-one mutations in the ceruloplasmin gene have been reported in 24 families worldwide. In Japan, the incidence was estimated to be approximately one per 2,000,000 in the case of non-consanguineous marriages. Excess iron functions as a potent catalyst of biologic oxidation. Previously we showed that an increased iron concentration is associated with increased levels of lipid peroxidation in the serum, cerebrospinal fluid, and erythrocyte membranes. The levels of malondialdehyde and 4-hydroxynonenals, indicators of lipid peroxidation, were also elevated in the basal ganglia and cerebral cortex. Positron emission tomography showed diminished brain metabolism of glucose and oxygen. Enzyme activities in the mitochondrial respiratory chain of the basal ganglia were reduced to approximate 45% and 42%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals causes neuronal cell damage through lipid peroxidation and mitochondrial dysfunction in aceruloplasminemia brains.	{ "pile_set_name": "PubMed Abstracts" }
Influence of protein restriction on lymphoid cell populations characterized by the binding of peanut agglutinin. Cells binding peanut agglutinin (PNA) were studied in the thymus, spleen, and mesenteric lymph nodes from mice placed in the post weaning period on protein-restricted diets containing 8% (R8%) and 4% (R4%) casein. The proportion of PNA+ thymocytes and the absolute number of total and PNA+ cells in the thymus were significantly diminished in R8% and R4% mice. Larger proportion of PNA+ thymocytes showed weaker fluorescence in R8% and R4% than in normally fed (N) animals. Recovery of PNA+ thymocytes was observed in R8% but not in R4% mice at 8 weeks. The number of total and PNA+ cells was significantly diminished although the proportion of PNA+ cells was not modified in the peripheral lymphoid organs of R8% and R4% mice. Results indicate that protein restriction preferentially affected the immature cortical PNA+ cells in the thymus whereas cell depletion in the peripheral lymphoid organs occurred at the expense of both the PNA+ and PNA- subpopulations.	{ "pile_set_name": "PubMed Abstracts" }
--- abstract: 'For second countable locally compact Hausdorff groupoids, the property of possessing a Haar system is preserved by equivalence.' address: \| Department of Mathematics\ Dartmouth College\ Hanover, NH 03755\ USA author: - 'Dana P. Williams' date: 15 January 2015 title: Haar Systems on Equivalent Groupoids --- [^1] Introduction {#sec:introduction} ============ Beginning with the publication of Renault’s seminal paper [@ren:groupoid], locally compact groupoids have been an especially important way to construct operator algebras. Just as with the time honored group [$\mathcs$]{}-algebra construction, this is done by turning $C_{c}(G)$ into a convolution algebra and then completing. In the group case, there is always a (left) Haar measure on $G$ which allows us to form the convolution product. In the groupoid case, the natural convolution formula requires a family of measures $\lambda^{u}$ with support $G^{u}=\set{x\in G:r(x)=u}$ for each $u\in{G^{(0)}}$. We want the family to be left-invariant in that $x\cdot \lambda^{s(x)} = \lambda^{r(x)}$ where $x\cdot \lambda^{s(x)}(E)=\lambda^{s(x)}(x^{-1}E)$. In order that the convolution formula return a continuous function, we need the continuity condition that $$u\mapsto \int_{G}f(x)\,d\lambda^{u}(x)$$ be continuous for all $f\in C_{c}(G)$ (the necessity is the main result in [@sed:pams86]). Such a family ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$ is called a (continuous) Haar system for $G$. An annoying gap in the theory is that there is no theorem guaranteeing Haar systems exist. The only significant positive existence result I am aware of is that if ${G^{(0)}}$ is open in $G$ and the range map is open (and hence the source map as well), then the family consisting of counting measures is always a Haar system. Groupoids with ${G^{(0)}}$ open and for which the range map is open are called étale. (It is also true that Lie Groupoids necessarily have Haar systems [@pat:groupoids99]\[Theorem 2.3.1]{}, but this result is crucially dependent on the manifold structure and hence not in the spirit of this note.) It is also well known that if $G$ is any locally compact groupoid with a Haar system, then its range and source maps must be open. (This is a consequence of Remark \[rem-haar-r-sys\] and Lemma \[lem-pi-sys-open\].) Thus if a locally compact groupoid has a range map which is not open, then it can’t possess a Haar system. Such groupoids do exist; for example, see [@sed:pams86]\[§3]{}. However, to the best of my knowledge, there is no example of a locally compact groupoid with open range and source maps which does not possess a Haar system. I have yet to find an expert willing to conjecture (even off the record) that all such groupoids need have Haar systems, but the question remains open. The purpose of this note is to provide some additional examples where Haar systems must exist. The main result being that if $G$ and $H$ are equivalent second countable locally compact groupoids (as defined in [@mrw:jot87] for example), and if $G$ has a Haar system, then so does $H$. Since equivalence is such a powerful tool, this result gives the existence of Haar systems on a great number of interesting groupoids. For example, every transitive groupoid with open range and source maps has a Haar system (Proposition \[prop-trans\]). The proof given here depends on several significant results from the literature. The first is that if $\pi:Y\to X$ is a continuous, open surjection with $Y$ second countable, then there is a family of Radon measures ${\{\beta^{x}\}}$ on $Y$ such that $\operatorname{supp}\beta^{x}=\pi^{-1}(x)$ and $$x\mapsto \int_{Y} f(y)\,d\beta^{x}(y)$$ is continuous for all $f\in C_{c}(Y)$. (This result is due to Blanchard who makes use of a Theorem of Michael’s [@mic:am56].) The second is the characterization in [@kmrw:ajm98]\[Proposition 5.2]{} of when the imprimitivity groupoid of free and proper $G$-space has a Haar system. The third is the concept of a Bruhat section or cut-off function. These are used in [@bou:integrationII04]\[Chapter 7]{} to construct invariant measures. They also appear prominently in [@ren:xx14]\[Lemma 25]{} and [@tu:doc04]\[§6]{}. Since Blanchard’s result requires separability, we can only consider second countable groupoids here. I would like to thank Marius Ionescu, Paul Muhly, Erik van Erp, Aidan Sims, and especially Jean Renault for helpful comments and discussions. The Theorem {#sec:main-theorem} =========== \[thm-main\] Suppose that $G$ is a second countable, locally compact Hausdorff groupoid with a Haar system ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$. If $H$ is a second countable, locally compact groupoid which is equivalent to $G$, then $H$ has a Haar system. As in [@ren:jot87]\[p. 69]{} or [@anaren:amenable00]\[Definition 1.1.1]{}, if $\pi:Y\to X$ is a continuous map between locally compact spaces $Y$ and $X$, then a $\pi$-system* is a family of (positive) Radon measures $\set{\beta^{x}:x\in X}$ on $Y$ such that $\operatorname{supp}\beta^{x}\subset \pi^{-1}(x)$ and for every $f\in C_{c}(Y)$, the function $$x\mapsto \int_{Y}f(y)\,d\beta^{x}(y)$$ is continuous. We say that $\beta$ is full* if $\operatorname{supp}\beta^{x}=\pi^{-1}(x)$ for all $x\in X$. If $Y$ and $X$ are both (left) $G$-spaces and $\pi$ is equivariant, then we say $\beta$ is equivariant* if $\gamma\cdot \beta^{x} = \beta^{\gamma\cdot x}$ where $\gamma\cdot \beta^{x}(E)=\beta^{x}(\gamma^{-1}\cdot E)$ for all $(\gamma,x)\in GX=\set{(\gamma,x):s(\gamma)=r(x)}$. Alternatively, $$\int_{Y}f(\gamma\cdot y)\,d\beta^{x}(y)=\int_{Y} f(y)\,d\beta^{\gamma\cdot x}(y)$$ for all $f\in C_{c}(Y)$ and $(\gamma,x)\in GX$. \[rem-haar-r-sys\] It is useful to keep in mind that a Haar system on $G$ is a full, equivariant $r$-system on $G$ for the range map $r:G\to{G^{(0)}}$. In many cases, such as [@kmrw:ajm98]\[§5]{}, $\pi$-systems are reserved for continuous and open* maps $\pi:Y\to X$. In the case of full systems, the next lemma implies that there is no loss in generality. (This part of the result does not require second countability.) Conversely, if $Y$ is second countable $\pi$ is an open surjection, then Blanchard has proved that full $\pi$ systems must exist. Blanchard’s result will be crucial in the proof of the main result. \[lem-pi-sys-open\] Suppose that $\pi:Y\to X$ is a continuous surjection between second countable locally compact Hausdorff spaces. Then $\pi$ is open if and only if it admits a full $\pi$ system. Suppose that $\beta$ is a full $\pi$ system. To show that $\pi$ is open, we appeal to the usual lifting argument as in [@wil:crossed]\[Proposition 1.15]{}. Thus we assume that $x_{i}\to \pi(y)$ is a convergent net. It will suffice to produce a subnet ${\{x_{j}\}}_{j\in J}$ and elements $y_{j}\in \pi^{-1}(x_{j})$ such that $y_{j}\to y$. To this end, let $$J=\set{(i,V):\text{$V$ is an open neighborhood of $y$ and $\pi^{-1}(x_{i})\cap V\not=\emptyset$}}.$$ We need to see that $J$ is directed in the expected way: $(i,V)\ge (j,U)$ if $i\ge j$ and $V\subset U$. So let $(k,V)$ and $(j, U)$ be in $J$. Let $f\in C_{c}^{+}(G)$ be such that $f(y)=1$ and $\operatorname{supp}f\subset V\cap U$. Then $$\beta(f)(x_{i})=\int_{Y} f(y)\,d\beta^{x_{i}}(y) \to \int_{Y} f(y) \, \beta^{\pi(y)}(y)=\beta(f)(\pi(y)).$$ The latter is nonzero since $\beta^{\pi(y)}$ has full support. Hence there is a $k\ge i$ and $k\ge j$ such that $$\int_{Y}f(y)\,d\beta^{x_{i}}(y)\not=0.$$ It follows that $(i,U\cap V)\in J$. Thus if we let $x_{(i,V)}=x_{i}$, then ${\{x_{(i,V)}\}}_{(i,V)\in J}$ is a subnet. If we let $y_{(i,V)}$ be any element of $\pi^{-1}(x_{i})\cap V$, then $y_{(i,V)}\to y$. This suffices. The converse is much more subtle, and is due to Blanchard [@bla:bsmf96]\[Proposition 3.9]{}. We also need what is sometimes called a Bruhat section* or cut-off function for $\pi$. The construction is modeled after Lemma 1 in Appendix I for [@bou:integrationII04]\[Chapter 7]{}. Recall that a subset $A\subset Y$ is called $\pi$-compact if $A\cap \pi^{-1}(K)$ is compact whenever $K$ is compact in $X$. We write $C_{c,\pi}(Y)$ for the set of continuous functions on $Y$ with $\pi$-compact support. \[lem-phi-exists\] Let $\pi:Y\to X$ be a continuous open surjection between second countable locally compact Hausdorff spaces. Then there is a $\phi\in C_{c,\pi}^{+}(Y)$ such that $\pi\bigl(\set{y\in Y:\phi(y)>0} \bigr) = X$. Let $\mathscr V=\set{V_{i}}$ be a countable, locally finite cover of $X$ by pre-compact open sets $V_{i}$. Let ${\{\alpha_{i}\}}$ be a partition of unity on $X$ subordinate to $\mathscr V$. Let $\phi_{i}\in C_{c}^{+}(Y)$ be such that $\pi\bigl(\set{y\in Y:\phi_{i}>0}\bigr) \supset V_{i}$. Then we can define $$\phi(y) =\sum_{i} \phi_{i}(y) \alpha_{i}\bigl(\pi(y)\bigr).$$ Since $\mathscr V$ is locally finite, the above sum is finite in a neighborhood of any $y\in Y$. Hence $\phi$ is well-defined and continuous. Local finiteness also implies that every compact subset of $X$ meets at most finitely many $V_{i}$. Since ${\{\alpha_{i}\}}$ is subordinate to $\mathscr V$, it follows that $\phi$ has $\pi$-compact support. If $x\in X$, then there is an $i$ such that $\alpha_{i}(x)>0$. Then there is a $y$ such that $\phi_{i}(y)>0$ and $\pi(y)=x$. Hence the result. Let $Z$ be a $(G,H)$-equivalence. Then the opposite module, ${Z^{\text{op}}}$, is a $(H,G)$ equivalence. Therefore, in view of [@kmrw:ajm98]\[Proposition 5.2]{}, it will suffice to produce a full $G$-equivariant $s_{{Z^{\text{op}}}}$-system for the structure map $s_{{Z^{\text{op}}}}:{Z^{\text{op}}}\to{G^{(0)}}$. Equivalently, we need a full equivariant $r_{Z}$-system for the map $r_{Z}:Z\to{G^{(0)}}$.[^2] Hence the main Theorem is a consequence of Proposition \[prop-jean-proper-map\] below. The following proposition is even more that what is called for in the proof of Theorem \[thm-main\]: it shows that every proper $G$-space has a full equivariant $r$-system for the moment map whether the action is free or not. It should be noted that pairs $(X,\alpha)$ where $X$ is a proper $G$-space and $\alpha$ and equivariant $r$-system play an important role in the constructions in [@ren:jot87] and [@holren:xx14]. This makes the assertion that such $\alpha$’s always exist even more interesting. \[prop-jean-proper-map\] Let $G$ be a locally compact Hausdorff groupoid with a Haar system ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$. Suppose that $Z$ is a proper $G$-space. Then there is a full equivariant $r_{Z}$-system ${\{\nu^{u}\}}_{u\in{G^{(0)}}}$ for the moment map $r_{Z}:Z\to{G^{(0)}}$. Blanchard’s Lemma \[lem-pi-sys-open\] implies that there is a full $r_{Z}$-system $\beta={\{\beta^{u}\}}_{u\in{G^{(0)}}}$. The idea of the proof is to use the Haar system on $G$ to average this system to create and equivariant system. The technicalities are provided by the next lemma. Notice that since $G$ acts properly, the orbit map $q:Z\to G\backslash Z$ is a continuous open surjection between locally compact Hausdorff spaces. \[lem-phi-fcns\] Let $G$, $Z$, $\lambda$ and $\beta$ be as above. 1. If $F\in C_{c}(G\times Z)$, then $$\Phi(F)(g,u)=\int_{Z} F(g,z)\,d\beta^{u}(z)$$ defines an element of $C_{c}(G\times{G^{(0)}})$. 2. If $f\in C_{c}(Z)$ and $\phi\in C_{c,q}(Z)$, then $$\Psi_{\phi}(f)(g)=\int_{Z} f(g\cdot z)\phi(z) \,d\beta^{s(g)}(z)$$ defines an element of $C_{c}(G)$. \(a) This is straightforward if $F(g,z)=f(g)\phi(z)$ with $f\in C_{c}(G)$ and $\phi\in C_{c}(Z)$. But we can approximate $F$ in the inductive limit topology with sums of such functions. \(b) Let $L=\operatorname{supp}\phi\cap q^{-1}\bigl(q(\operatorname{supp}f)\bigr)$. By assumption on $\phi$, $L$ is compact. Since $G$ acts properly on $Z$, the set $$P(\operatorname{supp}f,L)=\set{g\in G:g\cdot L\cap \operatorname{supp}f\not=\emptyset}$$ is compact. It follows that $$F(g,z)=f(g\cdot z)\phi(z)$$ defines an element of $C_{c}(G\times Z)$. Then $$\Psi_{\phi}(f)(g)=\Phi(F)(g,s(g)).$$ The assertion follows. Using Lemma \[lem-phi-exists\], we fix $\phi\in C_{c,q}^{+}(Z)$ such that $q\bigl(\set{z:\phi(z)>0} \bigr)=G\backslash Z$. Then we define a Radon measure on $C_{c}(Z)$ by $$\label{eq:1} \nu^{u}(f)=\int_{G}\int_{Z} f(g\cdot z)\phi(z)\,d\beta^{s(g)}(z) \,d\lambda^{u}(g) =\int_{G}\Psi_{\phi}(f)(g) \,d\lambda^{u}(g).$$ Since $\lambda$ is a Haar system and $\Psi_{\phi}(f)\in C_{c}(G)$, we see immediately that $$u\mapsto \nu^{u}(f)$$ is continuous. Clearly, $\operatorname{supp}\nu^{u}\subset r_{Z}^{-1}(u)$. Suppose $r_{Z}(w)=u$ and $f\in C_{c}^{+}(Z)$ is such that $f(w)>0$. Then there is a $z'\in\set{z:\phi(z)>0}$ such that $q(z')=q(w)$. Hence there is a $g\in G$ such that $g\cdot z'=w$. Note that $r_{Z}(z')=s(g)$ and $r(g)=r_{Z}(g\cdot z)=r_{Z}(w)=u$. Since $\beta^{s(g)}$ has full support and since everything in sight is continuous and non-negative, $$\Psi_{\phi}(g) =\int_{Z} f(g\cdot z)\phi(z)\,\beta^{s(g)}(z)>0.$$ Hence $\nu^{u}(f)>0$ and we have $$\operatorname{supp}\nu^{u} = r_{Z}^{-1}(u).$$ Hence to complete the proof of the theorem, we just need to establish equivariance. But $$\begin{aligned} \int_{Z} f(g'\cdot z)\,d\nu^{s(g')}(z) &= \int_{G}\int_{Z} f(g'g\cdot z)\phi(z)\,d\beta^{s(g)}(z)\,d\lambda^{s(g')}(g) \\ &= \int_{G}\Psi_{\phi}(f)(g'g)\,d\lambda^{s(g')}(g) \\ \intertext{which, since $\lambda$ is a Haar system on $G$, is} &= \int_{G}\Psi_{\phi}(g) \,d\lambda^{r(g')}(g) \\ &=\int_{G}\int_{Z} f(g\cdot z)\phi(z)\,d\beta^{s(g)}(z) \,d\lambda^{r(g')}(g) \\ \intertext{which, since $g'\cdot s(g')=r(g')$, is} &=\int_{Z}f(z)\,d\nu^{g'\cdot s(g')}(z).\end{aligned}$$ This completes the proof. Proposition \[prop-jean-proper-map\] is interesting even for a group action. The result itself is no doubt known to experts, but is amusing none-the-less. \[cor-jean-group\] Suppose that $G$ is a locally compact group acting properly on a space $X$. Then $X$ has at least one invariant measure with full support. Examples and Comments {#sec:exampl-comm-future} ===================== As pointed out in the introduction, any étale groupoid $G$ has a Haar system. As a consequence of Theorem \[thm-main\], any second countable groupoid equivalent to $G$ has a Haar system (provided $G$ is second countable). In this section, I want to look at some additional examples. In some cases it is possible and enlightening to describe the Haar system in finer detail. Proper Principal Groupoids {#sec:prop-princ-group} -------------------------- Recall that $G$ is called principal if the natural action of $G$ on ${G^{(0)}}$ given by $x\cdot s(x)=r(x)$ is free. We call $G$ proper if this action is proper in that $(x,s(x))\mapsto (r(x),s(x))$ is proper from $G\times {G^{(0)}}\to{G^{(0)}}\times{G^{(0)}}$. If $G$ is a proper principal groupoid with open range and source maps, then the orbit space $G\backslash {G^{(0)}}$ is locally compact Hausdorff, and it is straightforward to check that ${G^{(0)}}$ implements an equivalence between $G$ and the orbit space $G\backslash {G^{(0)}}$. Since the orbit space clearly has a Haar system, the following is a simple corollary of Theorem \[thm-main\]. \[prop-proper-prin\] Every second countable proper principle groupoid with open range and source maps has a Haar system. \[rem-blanchard\] If $G$ is a second countable proper principle groupoid with open range and source maps, then the orbit map $q:{G^{(0)}}\to G\backslash {G^{(0)}}$ sending $u$ to $\dot u$ is continuous and open. Hence Blanchard’s Lemma \[lem-pi-sys-open\] implies there is a full $q$-system ${\{\beta^{\dot u}\}}_{\dot u\in G\backslash {G^{(0)}}}$. It is not hard to check that $\lambda^{u}=\delta_{u}\times \beta^{\dot u}$ is a Haar system for $$G_{q}:=\set{(u,v)\in{G^{(0)}}\times{G^{(0)}}:\dot u = \dot v}.$$ Since $x\mapsto (r(x),s(x))$ is a groupoid isomorphism of $G$ and $G_{q}$, we get an elementary description for a Haar system on $G$. While there certainly exist groupoids that fail to have open range and source maps — and hence cannot have Haar systems — most of these examples are far from proper and principal. In fact the examples I’ve seen are all group bundles which are as a far from principal as possible. This poses an interesting question. Must a second countable, locally compact, proper principal groupoid have open range and source maps? Transitive Groupoids {#sec:transitive-groupoids} -------------------- Recall that a groupoid is called transitive if the natural action of $G$ on ${G^{(0)}}$ given by $x\cdot s(x):=r(x)$ is transitive. If $G$ is transitive and has open range and source maps, then $G$ is equivalent to any of its stability groups $H=G_{v}^{v}=\set{x\in G:r(x)=u=s(x)}$ for $v\in{G^{(0)}}$; the equivalence is given by $G_{v}$ with the obvious left $G$-action and right $H$ action. Second countability is required to see that the restriction of the range map to $G_{v}$ onto ${G^{(0)}}$ is open.[^3] Since locally compact groups always have a Haar measure, the following is an immediate consequence of Theorem \[thm-main\]. (Similar assertions can be found in [@sed:pria76].) \[prop-trans\] If $G$ is a second countable, locally compact transitive groupoid with open range and source maps, then $G$ has a Haar system. As before, I don’t know the answer to the following. Must a second countable, locally compact, transitive groupoid have open range and source maps? Blowing Up the Unit Space {#sec:blowing-up-unit} ------------------------- While there are myriad ways groupoid equivalences arise in applications, one standard technique deserves special mention (see [@txlg:acens12] for example). Suppose that $G$ is a second countable locally compact groupoid with a Haar system (or at least open range and source maps). Let $f:Z\to {G^{(0)}}$ be a continuous and open map. Then we can form the groupoid $$\label{eq:2} G[Z]=\set{(z,g,w)\in Z\times G\times Z: \text{$f(z)=r(g)$ and $s(g)=f(w)$}} .$$ (The operations are as expected: $(z',g',z)(z,g,w)=(z',g'g,w)$ and $(z,g,w)^{-1} = (w,g^{-1},z)$.) The idea being that we use $f$ to “blow-up” the unit space of $G$ to all of $Z$. If $\phi:G[Z]\to G$ is the homormorphism $(z,g,w)\mapsto g$, then we get a $(G[Z],G)$-equivalence given by “the graph of $\phi$” (see [@kmrw:ajm98]\[§6]{}): $$W = \set{(z,g)\in Z\times G:f(z)=r(g)}.$$ The left $G[Z]$-action is given by $(z,g,w)\cdot (w,g')=(z,gg')$ and the right $G$-action by $(w,g')\cdot g = (w,g'g)$. The openness of the range map for $G$ are required to see that the structure map $r_{W}:W\to Z$ is open, while the openness of $f$ is required to see that $s_{W}:W\to {G^{(0)}}$ is open. Assuming $G$ has a Haar system and $Z$ is second countable, Theorem \[thm-main\] implies $G[Z]$ has a Haar system. However in this case we can do a bit better and write down a tidy formula for the Haar system on the blow-up. We still require Blanchard’s Lemma \[lem-pi-sys-open\] that there is a full $f$-system for any continuous open map $f:Z\to {G^{(0)}}$ (provided that $Z$ is second countable). \[prop-blow-up-haar\] Suppose that $G$ is a locally compact Hausdorff groupoid with a Haar system ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$, and that $Z$ is second countable. Let $f:Z\to{G^{(0)}}$ be a continuous open map, and let $$G[Z]=\set{(w,g,z)\in Z\times G\times Z: \text{$f(w)=r(g)$ and $s(g)=f(z)$}}$$ be the “blow-up” of $G$ by $f$. If ${\{\beta^{u}\}}_{u\in{G^{(0)}}}$ is a full $f$-system, then we get a Haar system ${\{\kappa^{z}\}}_{z\in Z}$ on $G[Z]$ given by $$\kappa^{z}(f)=\int_{G}\int_{Z} f(z,g,w)\,d\beta^{s(g)}(w)\,d\lambda^{f(z)}(g).$$ The proof is relatively straightforward. Imprimitivity Groupoids {#sec:impr-group} ----------------------- If $X$ is a free and proper right $G$-space, then assuming $G$ has open range and source maps, we can form the imprimitivity groupoid $G^{Z}$ as in [@muhwil:plms395]\[pp. 119+]{}. Specifically we let $G^{Z}$ be the quotient of $X_{s}X=\set{(x,y)\in X\times X:s(x)=s(y)}$ by the diagonal right $G$-action. Then $G^{Z}$ is a groupoid with respect to the operations $[x,y][y,z]=[x,z]$ and $[x,y]^{-1}=[y,z]$. Furthermore $X$ implements an equivalence between $G^{Z}$ and $G$. Again we can apply Theorem \[thm-main\]. \[prop-imprimitivity\] Suppose that $G$ is a second countable, locally compact Hausdorff groupoid with a Haar system. Let $X$ be a free and proper right $G$-space. Then the imprimitivity groupoid $G^{Z}$ has a Haar system. \[rem-kmrw\] In [@kmrw:ajm98]\[§§9-10]{}, we associated a group $\operatorname{Ext}(G,\T)$ to any second countable, locally compact Hausdorff groupoid $G$. In [@kmrw:ajm98]\[Theorem 10.1]{} we showed that $\operatorname{Ext}(G,\T)$ was naturally isomorphic to the Brauer group $\operatorname{Br}(G)$. The definition of $\operatorname{Ext}(G,\T)$ required we consider the space $\mathcal{P}(G)$ of all free and proper right $G$-spaces $X$ such that $G^{X}$ has a Haar system. In view of Proposition \[prop-imprimitivity\], $\mathcal{P}(G)$ becomes simply the collection of all free and proper right $G$-spaces. \#1 [^1]: This work was supported in part by a grant from the Simons Foundation. [^2]: The gymnastics with the opposite space is just to accommodate a preference for left-actions. This has the advantage of making closer contact with the literature on $\pi$-systems. [^3]: Proving the openness of $r\restr{G_{v}}$ is nontrivial. It follows from [@ram:jfa90]\[Theorem 2.1]{} or Theorems 2.2A and 2.2B in [@mrw:jot87]. The assertion and equivalence fail without the second countability assumption as observed in [@mrw:jot87]\*[Example 2.2]{}. It should be noted that in both [@ram:jfa90] and [@mrw:jot87] openness of the range and source maps on a topological groupoid is a standing assumption.	{ "pile_set_name": "ArXiv" }
5 things to do today to keep your data private However, it’s hard not to be aware of the constant threats that hammer on our digital doors. The joy of the Internet is that we’re all connected to each other, making it easy to share information and commerce. But there’s also a dark side: Just as in the “real” world, the Net is full of evildoers who want to take advantage of the less-than-vigilant among us. Don’t be one of them. On Data Privacy Day, take some time to secure your virtual borders. Here are five things you can do right now that will give you peace of mind and make it little harder for the jerks who want to steal your data, your identity and your cash. • Change your passwords – This is the first thing you should do, and it’s the most effective – so long as your passwords are strong and effective. Change the passwords on all the accounts associated with your personal information, and make each one different. A strong password has a mix of letters, numbers and symbols, and ideally it should be a pass phrase, rather than a single word. If you’re having a hard time coming up with a tough password, there are sites that will make them for you. Try the PC Tools Password Generator – it’s owned by Symantec, so it’s trustworthy – which helps you build a strong, hard-to-crack password. • Adjust your social media privacy settings – Social networks such as Twitter, Facebook and LinkedIn all let you control what information you reveal and to whom. Facebook in particular has fairly powerful privacy settings, but most people don’t change them, either out of inertia or because they’re too intimidating. You can find Facebook’s privacy controls here. Pay particular attention to who can see the items you post – the default is Public, which means everyone can see them – and “Limit the audience for posts you’ve shared with friends of friends or Public”. The latter is confusing, but basically Facebook has reset old posts so only your Friends can see them, even if you originally set them to Public or Friends of Friends. You can also use Facebook’s activity log to review all your items, change individual settings and even delete some you now wish you hadn’t posted. • Get your credit report – Did you know you have the right to get a free copy of your credit report once a year? The three national credit reporting companies – Equifax, Experian and TransUnion – are required to give them to you as part of the Fair Credit Reporting Act. By examining your report, you may be able to catch attempts at identify theft, or even unauthorized credit accounts that have been opened in your name. Fortunately, you don’t have to go through the hassle of contacting each one of the reporting agencies individually. The three have cooperated to streamline the process. AnnualCreditReport.com lets you request reports from all of them. If you’re old-school, you can call 1-877-322-8228. You can find more information at this Federal Trade Commission website. • Update your antivirus software – Time and again, when I hear from people whose PCs are infected with malware, it’s because they let their security software subscription lapse. Paid products like Norton and McAfee do continue to run on your PC even if you don’t pay the annual subscription fee, but they lose their ability to protect against any new threats. And since new viruses, Trojans and spyware are being developed all the time, not keeping your security software up to date instantly puts you at risk. • Update your software – Cyberscum often rely on flaws in software to put spyware and other evil code on your computer. One of the best ways to prevent this is to make sure you operating system and the apps that run on it are up to date. Both Windows and Mac OS X update automatically by default, though users can override that. A word of advice: Don’t. Many of those updates have security fixes and not installing them puts you at risk. Because operating system updates run automatically, the bad guys are turning to flaws in the software that runs on the OSes. You may recall the serious flaw in Java that had even the Department of Homeland Security urging swift action. Because of this, it’s just as important to keep your applications updated. Today, launch each one of the apps you use most often and have it check for updates. Some applications – particularly common plug-ins for browsers, such as Flash – check automatically. When you see a popup from an application that wants to update, don’t delay – let it run ASAP. The data you save may be your own.	{ "pile_set_name": "Pile-CC" }
Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202. Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity. In the patients responding to EHT 0202, a pre-treatment (baseline) transcriptomic signature showed activation of pathways related to AD, CNS disorders, diabetes, inflammation, and autoimmunity, while a post-treatment signature indicated reduced activation of these pathways with induced metabolic and transcription stimulation. This pilot study demonstrates the utility of blood transcriptomic signatures used as biomarkers for predicting patient response or monitoring efficacy, for an administered therapeutic drug in a complex disease such as AD. For EHT 0202 or other AD drugs, such biomarkers may help to improve strategies to better identify appropriate patient populations for treatment, understand the drug mechanism of efficacy, and/or clarify the inherent subjectivity in most clinical endpoints used in this disease.	{ "pile_set_name": "PubMed Abstracts" }
Social justice and intercountry adoptions: the role of the U.S. social work community. Using social justice as the conceptual foundation, the authors present the structural barriers to socially just intercountry adoptions (ICAs) that can exploit and oppress vulnerable children and families participating in ICAs. They argue that such practices threaten the integrity of social work practice in that arena and the survival of ICA as a placement option. Government structures, disparity of power between countries and families on both sides, perceptions regarding poverty, cultural incompetence, misconceptions about orphans and orphanages, lack of knowledge about the impact of institution-based care, and the profit motive are driving forces behind the growing shadow of unethical ICAs. The U.S. social work community has a large role and responsibility in addressing these concerns as the United States receives the most children adopted through ICAs of all receiving countries. In addition to the centrality of social justice as a core value of the profession, the responsibility to carry out ethical and socially just ICA has recently increased as a matter of law, under the implementation legislation to the Hague Convention on Intercountry Adoption. While acknowledging that these issues are complex, authors provide suggestions for corrective policy and practice measures.	{ "pile_set_name": "PubMed Abstracts" }
Occurrence of toxigenic Aspergillus spp. and aflatoxins in selected food commodities of Asian origin sourced in the West of Scotland. The occurrence of Aspergillus moulds and aflatoxins in 12 commercially-available dried foods of Asian origin were examined. All food samples, except green beans and three types of dried fruit, contained multiple genera of moulds of which Aspergillus (55%) was the most frequently detected. Penicillium (15%), Rhizopus (11%), Mucor (3%), Monascus (1%), Eurotium (1%) and unidentified (14%) were also observed. The occurrence of aflatoxigenic moulds, however, did not correspond with the occurrence of aflatoxins in foods. Aflatoxigenic Aspergillus spp. (39 isolates) were recovered from long grain rice, fragrant rice, peanuts, black beans and black pepper. The predominant Aspergillus species was A. parasiticus (61%) while Aspergillus oryzae (3%), Aspergillus utus (5%), Aspergillus niger (5%), Aspergillus ochraceus (3%) and unidentified (23%) were also observed. Long grain rice, fragrant rice, peanuts, black beans and black pepper were positive for Aspergillus but contained undetectable aflatoxins. In contrast, Jasmine brown rice and crushed chilli contained 14.7 and 11.4μg/kg of total aflatoxins, respectively, in the absence of Aspergillus so aflatoxigenic Aspergillus was present at some stage of food production. The results from this study emphasise the need for stricter control measures in reducing occurrence of aflatoxins in foods for export and domestic use.	{ "pile_set_name": "PubMed Abstracts" }
Rarely a week passes without reports that Labour rebels are planning a split of some kind. The latest story, in the Daily Telegraph, suggested that rather than creating a new party (an option that has never been on the cards), MPs intend to form an alternative parliamentary grouping. This would involve electing their own leader and seeking designation as the official opposition. The idea has been discussed in Labour circles ever since Joe Haines, Harold Wilson’s former press secretary, called in January in the New Statesman for the parliamentary party to unilaterally declare independence. But it is not a course that MPs intend to pursue, even if, as most expect, Jeremy Corbyn is re-elected. Labour backbenchers Toby Perkins and Wes Streeting told the NS they knew of "no one" who was advocating the idea, while Jamie Reed said he thought the story was a "put-up job". He added: "McDonnell and Corbyn have no regard for the party. Never have had, never will. They are ones angling for a split. The 81 per cent of Labour MPs who know what we need to do to have a chance of winning in 2020 have no intention of going anywhere." Three senior rebels described reports of a split as “bollocks”. Another said: "Nobody can track down likely source of the Telegraph piece, so it may just be a lone voice. I don’t think it’s a runner." MPs said that further leadership challenges were likely before anyone gave serious consideration to a split. But one added: "If, however, the hard left pursued deselections then those ejected from their own party would most likely feel compelled into a separate party option, which really would be a disastrous split. Unless that’s what McDonnell meant by ‘so be it’." The shadow chancellor is alleged by leadership candidate Owen Smith to have "shrugged his shoulders and said 'If that’s what it takes'" when privately challenged on whether he was prepared to split Labour (a claim described by McDonnell as "complete rubbish"). Corbyn’s opponents believe that some MPs will follow shadow Home Office minister Sarah Champion and return to the frontbench if he wins the contest. But most of the 172 who backed the no confidence motion have no intention of doing so. “We’ve crossed the Rubicon, there’s no going back,” said Streeting. “This is irreparable while Jeremy remains leader.” The SNP is currently bidding to be made the official opposition on the grounds that Corbyn has the support of just 40 MPs, while it has 54. But the rebels believe the Speaker will not award the nationalists this designation since they, unlike Labour, do not even have the potential to form a full frontbench team. Catherine Haddon of the Institute for Government told the NS: "The only argument here would be if the 81 per cent of MPs who voted against Corbyn seemed likely to refuse the whip or to refuse to serve in a Corbyn government were one likely. If that happened the argument does change. But we are not there yet." Both Corbyn supporters and their opponents have sought parliamentary advice on which side would have the right to use the Labour name in the event of a breakaway. The expectation, based on the Registration of Politicial Parties Act, is that the leader would retain ownership. MPs acknowledge the possibility of a future split, but the option is not being pursued at any significant level. Though most rebels expect Corbyn to be re-elected, they hope to narrow his margin of victory and to win among full party members. This, they say, would deny the leader the right to boast of an "overwhelming" mandate. But without a dramatic change in Labour's selectorate, many now believe that it is only through a general election that the party's internal struggle will be resolved.	{ "pile_set_name": "OpenWebText2" }
Q: VB.NET [Cross-thread operation not valid: Control 'txtIncomingText' accessed from a thread........] I'm a beginner in VB.NET, please bear with me. I've downloaded a multiclient TCP-IP Socket Server-Client application in VB.NET. The Server listens pretty well, but the Client encounters below exception: "Cross-thread operation not valid: Control 'txtIncomingText' accessed from a thread other than the thread it was created on." I'll be greateful if you guys could help me with corrected version of the code. Thank you. ' ------- CLIENT CODE ------- Imports System.Windows.Forms Imports System.Collections.Generic Imports System.ComponentModel Imports System.Data Imports System.Drawing Imports System.Linq Imports System.Net Imports System.Net.Sockets Imports System.Text Imports System.Threading Public Class frmClient Inherits Form Private Sub frmClient_Load(sender As System.Object, e As System.EventArgs) Handles MyBase.Load End Sub Private _clientSocket As New Socket(AddressFamily.InterNetwork, SocketType.Stream, ProtocolType.Tcp) Public Sub New() InitializeComponent() End Sub Private receivedBuf As Byte() = New Byte(1023) {} Private thr As Thread Private Sub ReceiveData(ar As IAsyncResult) Dim socket As Socket = DirectCast(ar.AsyncState, Socket) Dim received As Integer = socket.EndReceive(ar) Dim dataBuf As Byte() = New Byte(received - 1) {} Array.Copy(receivedBuf, dataBuf, received) ' These two lines encounter an error ->>>>> txtIncomingText.Text = (Encoding.ASCII.GetString(dataBuf)) rbChat.Text = "\nServer: " + txtIncomingText.Text _clientSocket.BeginReceive(receivedBuf, 0, receivedBuf.Length, SocketFlags.None, New AsyncCallback(AddressOf ReceiveData), _clientSocket) End Sub Private Sub SendLoop() While True 'Console.WriteLine("Enter a request: "); 'string req = Console.ReadLine(); 'byte[] buffer = Encoding.ASCII.GetBytes(req); '_clientSocket.Send(buffer); Dim receivedBuf As Byte() = New Byte(1023) {} Dim rev As Integer = _clientSocket.Receive(receivedBuf) If rev <> 0 Then Dim data As Byte() = New Byte(rev - 1) {} Array.Copy(receivedBuf, data, rev) lbStt.Text = ("Received: " + Encoding.ASCII.GetString(data)) rbChat.AppendText(vbLf & "Server: " + Encoding.ASCII.GetString(data)) Else _clientSocket.Close() End If End While End Sub Private Sub LoopConnect() Dim attempts As Integer = 0 While Not _clientSocket.Connected Try attempts += 1 _clientSocket.Connect(IPAddress.Loopback, 420) Catch generatedExceptionName As SocketException 'Console.Clear(); lbStt.Text = ("Connection attempts: " + attempts.ToString()) End Try End While lbStt.Text = ("Connected!") End Sub Private Sub btnSend_Click(sender As System.Object, e As System.EventArgs) Handles btnSend.Click If _clientSocket.Connected Then Dim buffer As Byte() = Encoding.ASCII.GetBytes(txtText.Text) _clientSocket.Send(buffer) rbChat.AppendText("Client: " + txtText.Text) End If End Sub Private Sub btnConnect_Click(sender As System.Object, e As System.EventArgs) Handles btnConnect.Click LoopConnect() ' SendLoop(); _clientSocket.BeginReceive(receivedBuf, 0, receivedBuf.Length, SocketFlags.None, New AsyncCallback(AddressOf ReceiveData), _clientSocket) Dim buffer As Byte() = Encoding.ASCII.GetBytes("@@" + txtName.Text) _clientSocket.Send(buffer) End Sub End Class A: Well, you should invoke the calls on the control's thread. This is a quick and dirty solution Dim message = Encoding.ASCII.GetString(dataBuf) txtIncomingText.Invoke(Sub() txtIncomingText.Text = message) rbChat.Invoke(Sub() rbChat.Text = Environment.NewLine & "Server: " & message) But you should check if invocation is required first. See https://msdn.microsoft.com/en-us/library/ms171728(v=vs.110).aspx Also, "\n" is not how you make a new line in vb.net (did you copy this code from c#?). And + is not how you concatenate strings in vb.net (see above parenthesis).	{ "pile_set_name": "StackExchange" }
Takeuchi H, Savitzky AH, Ding L, et al. Evolution of nuchal glands, unusual defensive organs of Asian natricine snakes (Serpentes: Colubridae), inferred from a molecular phylogeny. Ecol Evol. 2018;8:10219--10232. 10.1002/ece3.4497 1. INTRODUCTION {#ece34497-sec-0001} =============== In the 20th Century, many biologists were focused on commonalities among taxa, as represented by studies using model organisms (Alberts et al., [2008](#ece34497-bib-0001){ref-type="ref"}). On the other hand, appreciating the diversity of life and its evolutionary origins has been another essential pursuit in biology (Rosenzweig, [1995](#ece34497-bib-0037){ref-type="ref"}; Whittaker, [1972](#ece34497-bib-0051){ref-type="ref"}). Because evolution of novel phenotypic characters, such as wings of birds and mammary glands of mammals, can facilitate the diversification of a lineage (Wagner & Lynch, [2010](#ece34497-bib-0049){ref-type="ref"}), investigation of the evolutionary history of such novel characters can provide basic information that clarifies the processes underlying species diversification. Snakes (Serpentes) comprise a distinct monophyletic taxon within the Squamata (Pyron, Burbrink, & Wiens, [2013](#ece34497-bib-0033){ref-type="ref"}), including over 3,500 species that are distributed on all continents except Antarctica (Wallach, Williams, & Boundy, [2014](#ece34497-bib-0050){ref-type="ref"}). In spite of their seemingly uniform appearance, snakes exhibit prominent morphological and ecological diversity (Greene, [1997](#ece34497-bib-0011){ref-type="ref"}; Lillywhite, [2014](#ece34497-bib-0021){ref-type="ref"}) and have often evolved novel organs that serve particular ecological functions. A well‐known example of a novel defensive structure is the rattle of rattlesnakes, which is used to warn potential predators of the snakes' venomous bite (Greene, [1997](#ece34497-bib-0011){ref-type="ref"}). The rattle evolved once in the ancestor of extant rattlesnakes (Castoe & Parkinson, [2006](#ece34497-bib-0005){ref-type="ref"}; Greene, [1997](#ece34497-bib-0011){ref-type="ref"}), and it has been lost secondarily in some island populations, where selection for defense is reduced in the absence of mammalian predators (Martins, Arnaud, & Murillo‐Quero, [2008](#ece34497-bib-0024){ref-type="ref"}; Rowe, Farrell, & May, [2002](#ece34497-bib-0038){ref-type="ref"}). The nuchal gland system is another example of a novel defensive structure that has evolved in snakes (Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}). Nuchal glands were originally described in a Japanese natricine snake, Rhabdophis tigrinus (Figure [1](#ece34497-fig-0001){ref-type="fig"}; Nakamura, [1935](#ece34497-bib-0031){ref-type="ref"}). The organs, which superficially resemble secretory structures, are embedded in the dermal layer of the dorsal skin of the neck. The nuchal glands of R. tigrinus contain cardiotonic steroid toxins known as bufadienolides (Hutchinson et al., [2007](#ece34497-bib-0019){ref-type="ref"}), which are sequestered from toads consumed as prey and can be redeployed as a defensive mechanism (Hutchinson et al., [2007](#ece34497-bib-0019){ref-type="ref"}). The glands of some other species also contain bufadienolides (Mori et al., unpublished). Ontogenetically, the nuchal glands are of mesodermal origin (Fukada, [1958](#ece34497-bib-0010){ref-type="ref"}; Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}), which is different from any other skin glands of terrestrial vertebrates, all of which arise from ectoderm (Savitzky et al., [2012](#ece34497-bib-0039){ref-type="ref"}). The glands lack a secretory epithelium and consist of a homogeneous population of fluid‐filled cells surrounding a dense aggregation of capillaries. There is no central lumen or duct, and the glands simply rupture through the skin to expel their fluid contents when the snake is under predatory attack (Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}). ![The snake, Rhabdophis tigrinus, in a defensive posture is directing the nuchal glands (NG) toward a perceived threat](ECE3-8-10219-g001){#ece34497-fig-0001} Nuchal glands and the structurally similar nucho‐dorsal glands (which extend the full length of the body; Smith, [1938](#ece34497-bib-0041){ref-type="ref"}) are currently known in 17 species of Asian Natricinae (Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}; Mori, Jono, Ding, et al., [2016](#ece34497-bib-0028){ref-type="ref"}). Hereafter, we refer to all such structures as nuchal glands, for simplicity. No other animals have been reported to possess organs similar in their structural details to the nuchal glands. The 17 species that possess such glands belong to three nominal genera, Balanophis,Macropisthodon, and Rhabdophis. Interestingly, Macropisthodon and Rhabdophis also include species that do not have nuchal glands (Table [1](#ece34497-tbl-0001){ref-type="table"}). This distribution might indicate the occurrence of (a) multiple independent origins of these unusual organs, (b) their secondary loss, and/or (c) improper generic assignment of some species. ###### A species list for the three nominal genera, Balanophis,Macropisthodon, and Rhabdophis Species Glands Source -------------------------------- -------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- *Balanophis ceylonensis* P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *Macropisthodon flaviceps* A/P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *M. plumbicolor* P Mori, Jono, Takeuchi, Ding et al. ([2016](#ece34497-bib-0030){ref-type="ref"}) and Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) M. rhodomelas P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *M. rudis* A Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) and Takeuchi and Mori ([2012](#ece34497-bib-0045){ref-type="ref"}) *Rhabdophis adleri* P Mori, Jono, Ding et al. ([2016](#ece34497-bib-0028){ref-type="ref"}) R. akraios U Doria, Petri, Bellati, Tiso and Pistarino ([2013](#ece34497-bib-0006){ref-type="ref"}) R. angelii U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) R. auriculatus U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) R. barbouri U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) *R. callichromus* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) R. chrysargoides U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) *R. chrysargos* A Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. conspicillatus* A Mori, Jono, Takeuchi and Das ([2016](#ece34497-bib-0029){ref-type="ref"}) *R. formosanus* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Takeuchi, Ota, Oh and Hikida ([2012](#ece34497-bib-0046){ref-type="ref"}) *R. guandongensis* U Zhu, Wang, Takeuchi and Zhao ([2014](#ece34497-bib-0053){ref-type="ref"}) *R. himalayanus* P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. lateralis* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Takeuchi et al. ([2012](#ece34497-bib-0046){ref-type="ref"}) *R. leonardi* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) R. lineatus U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) *R. murudensis* A/P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}), Smith ([1938](#ece34497-bib-0041){ref-type="ref"}), and Steubing and Lian ([2002](#ece34497-bib-0044){ref-type="ref"}) *R. nigrocinctus* P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. nuchalis* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}), Mori, Jono, Takeuchi, Ding et al. ([2016](#ece34497-bib-0030){ref-type="ref"}), and Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. pentasupralabialis* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Mori, Jono, Takeuchi, Ding et al. ([2016](#ece34497-bib-0030){ref-type="ref"}) R. spilogaster A Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. subminiatus* P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. swinhonis* A/P Mao and Chang ([1999](#ece34497-bib-0023){ref-type="ref"}) and Hsiang, Li and Yang (2009) *R. tigrinus* P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Nakamura ([1935](#ece34497-bib-0031){ref-type="ref"}) Species included in the analyses of this study are shown by bold. P, A, and U indicate present, absent, and unknown, respectively. Our study strongly suggests that Balanophis and Macropisthodon, except M. rudis, belong to Rhabdophis. John Wiley & Sons, Ltd To infer the evolutionary history of the nuchal glands, we investigated the molecular phylogenetic relationships among Eurasian natricine species, including all but one of the species that have hitherto been reported to possess such glands (Table [1](#ece34497-tbl-0001){ref-type="table"}). Our phylogeny is based on partial sequences of the oocyte maturation factor Mos (Cmos) gene, the recombination‐activating gene 1 (RAG1), and the mitochondrial cytochrome b (MT‐CYB) gene, for a total of 2.7 kbp. Several recent phylogenetic studies of snakes have either focused on or included a number of Asian natricine species (Figueroa, Mckelvy, Grismer, Bell, & Lailvaux, [2016](#ece34497-bib-0009){ref-type="ref"}; Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"}; Pyron, Kandambi et al., [2013](#ece34497-bib-0034){ref-type="ref"}). However, no previous study has addressed the evolution of the nuchal glands. Furthermore, our sampling of species and populations of Macropisthodon and Rhabdophis is much greater than that of previous studies. Specifically, our main purpose was to answer three questions: (a) Have the nuchal glands originated only once, or have they arisen multiple times independently among natricine snakes? (b) Do the species of Macropisthodon and Rhabdophis that lack such glands represent the secondary loss of those structures? (c) Are any of the species lacking nuchal glands incorrectly assigned to Macropisthodon or Rhabdophis? 2. MATERIALS AND METHODS {#ece34497-sec-0002} ======================== A total of 122 sequences of natricine snakes and three sequences of outgroup taxa were used for phylogenetic analyses (Appendix [1](#ece34497-app-0001){ref-type="app"}). Of those, 54 sequences were obtained from GenBank. Because our preliminary analysis suggested that the sequence data for Rhabdophis adleri registered in GenBank were incorrectly identified, we did not use the GenBank data for that species. The other 68 sequences were obtained by the following methods. In each sample, total DNA was extracted from liver, skeletal muscle, or tail tips, which had been preserved in 99.5% ethanol or in freezers, using the DNeasy Tissue Kit (Qiagen). The Cmos, RAG1, and MT‐CYB regions were amplified with a PCR System GeneAmp 2700 Thermal Cycler (Applied Biosystems), using an Ex Taq Polymerase Kit (Takara Bio Inc.) and primers S77/S78 for Cmos (Lawson, Slowinski, Crother, & Burbrink, [2005](#ece34497-bib-0020){ref-type="ref"}), R13/R18 for RAG1 (Groth & Barrowchlough, [1999](#ece34497-bib-0012){ref-type="ref"}), and L14910/H16064 for MT‐CYB (Burbrink, Lawson, & Slowinski, [2000](#ece34497-bib-0004){ref-type="ref"}). The thermocycling schedule for the polymerase chain reaction (PCR) was identical to that described by these previous studies. Before sequencing, unincorporated primers were removed from the PCR products using polyethylene glycol precipitation. Cycle sequencing reactions were performed with the Big Dye Terminator Cycle Sequence Ready Reaction Kit, version 3.1 (Applied Biosystems), using the same primers as for PCR. The samples purified by ethanol precipitation were sequenced with a 3130xl Genetic Analyzer (Applied Biosystems). All fragments were sequenced for both forward and reverse sense. We assembled them using the GAP 4 program (Staden, [1996](#ece34497-bib-0042){ref-type="ref"}). Using CLUSTAL X (Thompson, Gibson, Plewniak, Jeanmougin, & Higgins, [1997](#ece34497-bib-0048){ref-type="ref"}), 125 sequences were aligned. Identical sequences from different specimens were treated as single units so that 114 sequences were recognized. To infer the phylogeny, we employed Maximum Likelihood (ML) using combined sequences (Cmos + RAG1 + MT‐CYB) and Bayesian inference (BI) using the sequence of mitochondrial DNA (MT‐CYB). For both data sets, the most appropriate pattern of sequence evolution was selected by applying the Bayesian Information Criterion (BIC; Schwarz, [1978](#ece34497-bib-0040){ref-type="ref"}), using MEGA5 (Tamura et al., [2011](#ece34497-bib-0047){ref-type="ref"}). We set the rate categories of discrete gamma rate heterogeneity as eight for ML and BI. Reliability of the ML tree was assessed by calculating bootstrap probability (BP; Felsenstein, [1985](#ece34497-bib-0008){ref-type="ref"}), with 1,000 replications. The BI tree was constructed using BEAST version 1.8 (Drummond & Rambaut, [2007](#ece34497-bib-0007){ref-type="ref"}), employing a single Markov chain Monte Carlo (MCMC) run for 50 million generations, sampled every 1,000 generations, and excluding the first 5 million generations as burn‐in. Convergence of the chains to the stationary distribution was checked by visual inspection, using TRACER version 1.6 (Rambaut, Suchard, Xie, & Drummond, [2007](#ece34497-bib-0036){ref-type="ref"}). To estimate divergence times, we employed Bayesian relaxed‐clock dating, using BEAST version 1.8. Because no fossils of Balanophis,Macropisthodon, or Rhabdophis are known, we set the following calibration points: 30 Mya (SD = 0.115) at the crown of natricine snakes, 22 Mya (SD = 0.15) at the crown of the genus Natrix, and 16 Mya (SD = 0.15) at the crown of the genus Thamnophis (Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}). 3. RESULTS {#ece34497-sec-0003} ========== The final alignment of three gene fragments consisted of 2,767 aligned base pairs. Of those, 787--1,149 bp were from MT‐CYB (114 taxa), 259--689 bp were from Cmos (86 taxa), and 855--929 bp were from RAG1 (21 taxa). The most appropriate model under the BIC was the GTR + G + I model for the data sets of both the ML and BI trees. The ML and BI trees were almost identical in topology. The ML tree (−In L = −35078.3994) is shown in Figure [2](#ece34497-fig-0002){ref-type="fig"}. A consensus tree from the ML and BI analyses is shown in Figure [3](#ece34497-fig-0003){ref-type="fig"}, along with the BP values from ML and the posterior probability (PP) value from BI at each node (shown only for BP ≥ 70% in ML and PP ≥ 0.90 in BI). The main difference between the ML and BI trees is the status of Rhabdophis chrysargos. Unlike the ML tree, the Bl tree supported monophyly of R. chrysargos + R. conspicillatus + 3 species of Xenochrophis (Figure [3](#ece34497-fig-0003){ref-type="fig"}a). ![Maximum likelihood tree (−In L = −35078.3994) based on the combined sequence data of the MT‐CYB, Cmos, and RAG1 genes under GTR + G + I. Bootstrap probabilities are provided at each node. Numerals following scientific names indicate individual codes (see Appendix [1](#ece34497-app-0001){ref-type="app"}). Status of nuchal or nucho‐dorsal glands of our three focal genera (Rhabdophis, Macropisthodon, and Balanophis) is indicated by blue (present), red (absent), purple (present/absent), and green (unknown; see also Table [1](#ece34497-tbl-0001){ref-type="table"}). The photographs have been digitally modified for clarity. Photograph of Balanophis ceylonensis by Udaya Chanaka](ECE3-8-10219-g002){#ece34497-fig-0002} ![Consensus tree based on ML and Bl trees. Bootstrap probabilities (BP) from the maximum likelihood tree (left) and posterior probabilities (PP) from Bayesian inference (right) are shown at each node (shown only BP ≥ 70% and PP ≥ 0.90). (a) All Natricinae included in our analysis. Species of our three focal genera (Rhabdophis,Macropisthodon, and Balanophis) are indicated in bold. (b) Phylogenetic relationships among the nuchal gland clade. For the three focal genera, P, A, and U after the OTU indicate present, absent, or unknown condition, respectively, of nuchal or nucho‐dorsal glands (see also Table [1](#ece34497-tbl-0001){ref-type="table"})](ECE3-8-10219-g003){#ece34497-fig-0003} Monophyly of Natricinae was strongly supported by the PP value. Within this subfamily, monophyly of the New World taxa (the Thamnophiini), and the Old World taxa Natrix,Sinonatrix,Hebius, and Amphiesma +* Xenochrophis + Atretium + Rhabdophis* + Macropisth odon (except M. rudis) + Balanophis clades were highly supported. Of the latter clade, a subclade of Rhabdophis (except R. chrysargos and R. conspicillatus) + Macropisthodon (except M. rudis) + Balanophis was separated from the remainder with strong support (Figure [2](#ece34497-fig-0002){ref-type="fig"}b). The average estimated divergence time of this subclade was 19.18 Mya (16.28--22.16 in 95% credible ranges). Hereafter, we refer to this subclade as the nuchal gland clade (NGC). Within this clade, Macropisthodon plumbicolor first diverged from the other species. The latter include Rhabdophis subminiatus, R. murudensis + Macropisthodon flaviceps,R. himalayanus +* Balanophis ceylonensis, R. tigrinus* + R. lateralis + R. formosanus, and a large group including R. adleri + R. callichromus + R. nigrocinctus + R. swinhonis + R. guangdongensis + R. nuchalis + R. leonardi + R. pentasupralabialis (with \>90% support in BP and/or 0.9 in PP). The latter clade comprises two subclades: R. adleri + R. callichromus + R. nigrocinctus and R. swinhonis + R. guangdongensis + R. nuchalis + R. leonardi + R. pentasupralabialis. Several nominal species exhibit substantial population structuring. Rhabdophis subminiatus exhibits strong differentiation between Laos/Vietnam and Thailand samples, and R. nuchalis consists of a number of population segments and is paraphyletic with respect to both R. leonardi and R. pentasupralabialis. 4. DISCUSSION {#ece34497-sec-0004} ============= Although differing in some details, recent molecular phylogenetic analyses of the Natricinae (Figueroa et al., [2016](#ece34497-bib-0009){ref-type="ref"}; Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"}; Pyron, Burbrink et al., [2013](#ece34497-bib-0033){ref-type="ref"}; Pyron, Kandambi et al., [2013](#ece34497-bib-0034){ref-type="ref"}), including ours, agree on the general pattern of relationships among the major lineages. A basal dichotomy separates the subfamily into two major clades. One includes the entire North American natricine fauna (the Thamnophiini) and its sister group, the Eurasian genus Natrix. Those two, in turn, are sister to a clade containing the Asian genera Opisthotropis and Sinonatrix. A clade containing two endemic Sri Lankan genera, Aspidura and Haplocerus, is variously recovered as sister to this North American--Eurasian clade (Pyron, Burbrink et al., [2013](#ece34497-bib-0033){ref-type="ref"}; Pyron, Kandambi et al., [2013](#ece34497-bib-0034){ref-type="ref"}) or as the most basal branch of the natricine clade (our study, but with weak support). The other major clade of natricines is almost entirely Asian, the sole exception being a monophyletic group of three African genera (Afronatrix, Natriciteres, and Lycognathophis, the latter not included in our analysis). The African clade is variously recovered as sister to, or embedded within, the much larger Asian radiation. The relationships among the Asian taxa display varying topologies among recent analyses, as taxon sampling within this group has improved. Consistent with other recent studies (Guo et al., [2014](#ece34497-bib-0017){ref-type="ref"}), we recover a monophyletic genus Hebius, distant from Amphiesma stolatum, as well as a polyphyletic Xenochrophis, some related to Atretium and others close to Rhabdophis and Macropisthodon. These results engender confidence in our analysis of the relationships within the NGC. 4.1. Evolution of the nuchal glands {#ece34497-sec-0005} ----------------------------------- Our results show that all species that possess nuchal glands belong to a single, strongly supported clade (NGC). Therefore, based on the principle of parsimony, we infer that the common ancestor of this clade possessed nuchal glands. We find no evidence of multiple, independent origins of the glands. Thus, interspecific differences in the distribution and morphology of the glands, such as the occurrence of nucho‐dorsal glands along the entire length of the body in M. plumbicolor and several species of Rhabdophis (Mori, Jono, Ding et al., [2016](#ece34497-bib-0028){ref-type="ref"}; Mori, Jono, Takeuchi, & Das, [2016](#ece34497-bib-0029){ref-type="ref"}; Smith, [1938](#ece34497-bib-0041){ref-type="ref"}) and the presence of elongate, nonsacculated glands accompanied by scaleless areas of skin in M. rhodomelas (not included in our analysis), M. flaviceps, and B. ceylonensis (Smith, [1938](#ece34497-bib-0041){ref-type="ref"}), are considered to represent alternative morphologies that arose after a single evolutionary origin of the nuchal gland system. Further study of the morphological details is needed to clarify the process of glandular diversification within this clade. Among species currently included in Rhabdophis and Macropisthodon,R. chrysargos,R. conspicillatus, and M. rudis have been reported to lack nuchal glands (Table [1](#ece34497-tbl-0001){ref-type="table"}; Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}; Mori, Jono, Takeuchi, & Das, [2016](#ece34497-bib-0029){ref-type="ref"}). Macropisthodon rudis is only distantly related to the NGC (see below), and R. conspicillatus and R. chrysargos also belong to clades outside the NGC. Thus, the absence of the nuchal glands in these species does not constitute secondary loss. Rather, it appears that they have simply retained the ancestral condition of the absence of integumentary defensive glands. Rhabdophis swinhonis has been reported to lack nuchal glands (Table [1](#ece34497-tbl-0001){ref-type="table"}; Mao & Chang, [1999](#ece34497-bib-0023){ref-type="ref"}). However, in contrast to R. conspicill atus and R. chrysargos, our analysis shows that this species occupies a position within the NGC. This strongly suggests that R. swinhonis has secondarily lost the nuchal glands. However, Hsiang, Li, and Yang ([2009](#ece34497-bib-0018){ref-type="ref"}) noted the presence of nuchal glands in this species. If both observations are correct, there are two possible interpretations: either the occurrence of intraspecific variation or the presence of two distinct but cryptic species. Whichever is true, the deeply nested position of R. swinhonis within the NGC implies the recent or ongoing secondary loss of the glands in at least some populations. Intraspecific variation in the presence of the nuchal glands also has been described in R. murudensis and M. flaviceps (Table [1](#ece34497-tbl-0001){ref-type="table"}; Smith, [1938](#ece34497-bib-0041){ref-type="ref"}; Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}). In our analysis, both species are recovered within the NGC. Therefore, as with R. swinhonis, the nuchal glands of R. murudensis and M. flaviceps, if accurately described in the literature, might be in a transitional stage of secondary loss or these nominal species may contain closely related cryptic species. We estimate that the common ancestor of the NGC arose 19.18 Mya. This is only slightly later than the date of 23--24 Mya shown by Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, Figure [2](#ece34497-fig-0002){ref-type="fig"}) for the origin of Rhabdophis, suggesting that nuchal glands arose at or soon after the origin of this genus. 4.2. Taxonomy {#ece34497-sec-0006} ------------- Our analysis requires a reevaluation of the taxonomic status of the genera Balanophis and Macropisthodon. The validity of the monotypic genus Balanophis (Smith, [1938](#ece34497-bib-0041){ref-type="ref"}) has been controversial. Malnate ([1960](#ece34497-bib-0022){ref-type="ref"}) recognized the species as Rhabdophis ceylonensis, and McDowell ([1961](#ece34497-bib-0025){ref-type="ref"}) supported his position. Figueroa et al. ([2016](#ece34497-bib-0009){ref-type="ref"}) found the species nested within Rhabdophis, as sister to R. himalayanus, and despite stating in the text (p. 21) that they declined to synonymize the genera, they recognized the species as R. ceylonensis in their figure 7a. Our analysis also strongly supports a sister relationship between B. ceylonensis and R. himalayanus, and thus, we formally propose that Balanophis be synonymized with Rhabdophis. Our analysis includes three of the four currently recognized species of Macropisthodon (Wallach et al., [2014](#ece34497-bib-0050){ref-type="ref"}), no two of which are recovered as each other\'s closest relative. When the genus was described by Boulenger ([1893](#ece34497-bib-0003){ref-type="ref"}), most other natricine snakes were treated as members of the genus Tropidonotus. Stejneger ([1907](#ece34497-bib-0043){ref-type="ref"}) placed Tropidonotus in the genus Natrix, where it remained until Malnate ([1960](#ece34497-bib-0022){ref-type="ref"}) divided Natrix sensu lato into six genera, resurrecting Rhabdophis Fitzinger, 1843. Malnate suggested that Macropisthodon might later prove not to be distinct from Rhabdophis, but the overreliance on characters of the maxillary dentition had precluded its earlier inclusion in Natrix and presumably influenced Malnate\'s decision to retain the genus. In our analysis, the type species of Macropisthodon,M. flaviceps, is strongly supported as sister to R. murudensis. Figueroa et al. ([2016](#ece34497-bib-0009){ref-type="ref"}) show the fourth species, M. rhodomelas, nested well within Rhabdophis. Therefore, we synonymize Macropisthodon with Rhabdophis. Thus, it is presently reasonable to include all species belonging to the NGC within Rhabdophis, the type species of which is R. subminiatus. However, partitioning of this morphologically diverse clade should be considered in the future. The divergent position of Macropisthodon rudis, which lacks nuchal glands and is recovered as distant from the NGC, supports the resurrection of the monotypic genus Pseudoagkistrodon (Van Denburgh 1909), as suggested by Wallach et al. ([2014](#ece34497-bib-0050){ref-type="ref"}). Although recent studies have differed in the exact placement of this species (Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"}), no analysis with sufficient taxon sampling of Asian natricines has placed it close to Rhabdophis. The taxonomic status of "R". conspicillatus and "R". chrysargos, which lie just outside the NGC, remains to be determined. Our analysis suggests that Rhabdophis contains several undescribed species. Substantial genetic divergence occurs within R. nigrocinctus, R. swinhonis, R. nuchalis, and especially R. subminiatus. A comprehensive analysis of this complex subclade, including both morphological and molecular studies, will be necessary before this group can be reliably partitioned. 5. CONCLUSIONS {#ece34497-sec-0007} ============== Our analysis indicates that the nuchal and nucho‐dorsal glands, as a group, have evolved only once among Asian natricine snakes. The absence of the nuchal glands in some nominally congeneric species, such as M. rudis, R. conspicillatus, and R. chrysargos, reflects old classifications based on phenetic analysis of morphological characters. All of those species lie outside the single clade that possesses the defensive glands. However, a few species within the nuchal gland clade (M. flaviceps, R. murudensis, and R. swinhonis) may represent a transitional stage in the secondary loss of the glands. Clarification of the developmental origin of these unique organs is likely to provide insight into how these neomorphic structures have arisen, diversified, and may subsequently be disappearing in a few species. The nuchal glands are fruitful subjects for investigating the evolution of novel biological systems that involve the complex interplay of morphology, physiology, ecology, and behavior. AUTHOR CONTRIBUTIONS {#ece34497-sec-0009} ==================== Hirohiko Takeuchi designed and performed research, analyzed data, and wrote the paper. Alan H. Savitzky designed research and wrote the paper. Li Ding designed and performed research in China. Anslem de Silva performed research in Sri Lanka. Indraneil Das performed research in Malaysia. Tao Thien Nguyen performed research in Vietnam. Tein‐Shun Tsai performed research in Taiwan. Teppei Jono performed research in China and analyzed data in Japan. Guang‐Xiang Zhu performed research in China. Dharshani Mahaulpatha performed research in Sri Lanka. Yezhong Tang designed and performed research in China. Akira Mori designed and performed research and wrote the paper. DATA ACCESSIBILITY {#ece34497-sec-0010} ================== DDBJ accessions [LC325298](LC325298)--[LC325357](LC325357), [LC325746](LC325746)--[LC325803](LC325803), and [LC326011](LC326011)--[LC326031](LC326031) (DNA sequences). We thank K. Kurita and T. Okamono for further instruction in phylogenetic analyses and Y. Kojima for assistance with executing phylogenetic analyses. We are indebted to H. Ota and N. Kuraishi for providing tissue samples, D.‐E. Lin, C. Li, Y.‐W. Yeh, and C.‐A. Tu for assistance in collecting tissue samples, Q. Chen for field assistance, U. Chanaka for providing a photograph, and the Vice Chancellor and Dean, University of Sri Jayewardenepura for allowing the maintenance of live snakes and for providing laboratory facilities. We are grateful to the Council of Agriculture, Executive Yuan, Taiwan for permits to collect snakes in Taiwan and for the export permit to Kyoto University (Permit No. AGF4X104070012); and to the Department of Wildlife Conservation, Sri Lanka for permits to collect snakes in Sri Lanka and for the export permit to Kyoto University. This study was supported by grants from the Japan--China Joint Research Project (2014--2016) between the Japan Society for the Promotion of Science (JSPS) and National Natural Science Foundation of China (NSFC, 31411140033) and from JSPS Scientific Researches C (26440213) and B (17H03719). This research was partially supported by project grant DTDLXH.19/15 and BSTMV.08/16‐19 to NTT, by the Niche Research Grant Scheme from the Ministry of Higher Education, Government of Malaysia (NRGS/1087/2013(01); IA010200‐0708‐0007) to ID, by a grant from National Natural Science Foundation of China (NSFC, 31401959) to GSZ, and by grants from NSFC (Fund for Young International Scientists: 31450110454), Chinese Academy of Sciences Fellowship for Young International Scientists (Y5C3051100), and JSPS (16J06675) to TJ. This study was also supported in part by the Global COE Program A06 to Kyoto University from MEXT and by funding provided to AHS by Utah State University. 1.1. Accession numbers and their localities (countries) for all DNA sequence data used in the phylogenetic analyses in this study. Individuals with an asterisk indicate identical sequences within the species, and thus have the same accession number. Names (and No.) in the species column correspond to those shown in Figure [1](#ece34497-fig-0001){ref-type="fig"} {#ece34497-sec-0011} =========================================================================================================================================================================================================================================================================================================================================================================== SpeciesIndividual No.CountryAccession no. of GenBankReferencesCyt.bC‐mosRag‐1Afronatrix anoscopusROM19842Liberia[AF420073](AF420073)[AF471123](AF471123)[EU402832](EU402832)Lawson et al., [2005](#ece34497-bib-0020){ref-type="ref"}, de Queiroz, Lawson, and Lemos‐Espinal [2002](#ece34497-bib-0035){ref-type="ref"}, and Wiens et al. ([2008](#ece34497-bib-0052){ref-type="ref"})Amphiesma stolatum\_1HT0548China[LC325319](LC325319)[LC325765](LC325765)--This studyAmphiesma stolatum\_2HT0798Sri Lanka[LC325347](LC325347)[LC325793](LC325793)[LC326030](LC326030)This studyAmphiesma stolatum\_3GP2213China[KJ685693](KJ685693)[KJ685643](KJ685643)[KJ685585](KJ685585)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})Aspidura guentheriRAP0437Sri Lanka[KC347472](KC347472)[KC347380](KC347380)[KC347418](KC347418)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})Atretium schistosum\_1HT0799Sri Lanka[LC325348](LC325348)[LC325794](LC325794)--This studyAtretium schistosum\_2--Sri Lanka[KC347487](KC347487)[KC347383](KC347383)[KC347421](KC347421)Pyron Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})Atretium yunnanensisGP842China[JQ678448](JQ678448)[JQ281787](JQ281787)[KJ685602](KJ685602)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})Balanophis ceylonensis\_1HT0785Sri Lanka[LC325339](LC325339)[LC325785](LC325785)[LC326026](LC326026)This studyBalanophis ceylonensis\\_2HT0786Sri Lanka[LC325339](LC325339)----This studyBalanophis ceylonensis\_3HT0787Sri Lanka[LC325340](LC325340)[LC325786](LC325786)--This studyHaplocercus ceylonensisRS145Sri Lanka[KC347478](KC347478)[KC347401](KC347401)[KC347438](KC347438)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})Hebius atemporaleHT0550China[LC325320](LC325320)[LC325766](LC325766)--This studyHebius craspedogasterHT0801China[LC325350](LC325350)[LC325796](LC325796)--This studyHebius ishigakiensisHT0800Japan[LC325349](LC325349)[LC325795](LC325795)--This studyHebius khasienseHT0679Vietnam[LC325327](LC325327)[LC325773](LC325773)--This studyHebius octolineatusHT0586China[LC325321](LC325321)[LC325767](LC325767)--This studyHebius pryeriHT0340Japan[LC325312](LC325312)[LC325758](LC325758)--This studyHebius vibakari\_1HT0274Japan[LC325309](LC325309)[LC325755](LC325755)--This studyHebius vibakari\_2HT0277Japan[LC325310](LC325310)[LC325756](LC325756)--This studyMacropisthodon flavicepsHT0809Malaysia[LC325355](LC325355)[LC325801](LC325801)--This studyMacropisthodon plumbicolor\_1HT0782Sri Lanka[LC325336](LC325336)[LC325782](LC325782)[LC326025](LC326025)This studyMacropisthodon plumbicolor\_2HT0783Sri Lanka[LC325337](LC325337)[LC325783](LC325783)--This studyMacropisthodon plumbicolor\_3HT0784Sri Lanka[LC325338](LC325338)[LC325784](LC325784)--This studyMacropisthodon rudis\_1HT0339China[LC325311](LC325311)[LC325757](LC325757)[LC326016](LC326016)This studyMacropisthodon rudis\_2GP1266China[JQ687452](JQ687452)[JQ687434](JQ687434)[KJ685566](KJ685566)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})Natriciteres olivacea--Congo[AF471058](AF471058)[AF471146](AF471146)--Lawson et al. ([2005](#ece34497-bib-0020){ref-type="ref"})Natrix maura\_1--Spain[AY866530](AY866530)----Guicking, Lawson, Joger and Wink ([2006](#ece34497-bib-0015){ref-type="ref"})Natrix maura\_2--Tunisia[AY487682](AY487682)----Guicking, Joger and Wink ([2008](#ece34497-bib-0013){ref-type="ref"})Natrix maura\_3--Italy[AY487683](AY487683)----Guicking et al. ([2008](#ece34497-bib-0013){ref-type="ref"})Natrix natrix\_1--Spain[AY866536](AY866536)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})Natrix natrix\_2--France[AY866537](AY866537)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})Natrix tessellata\_1--Iran[AY487574](AY487574)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})Natrix tessellata\_2--Iran[AY487575](AY487575)----Guicking, Joger and Wink ([2009](#ece34497-bib-0014){ref-type="ref"})Natrix tessellata\_3--Bulgaria[AY866533](AY866533)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})Nerodia cyclopion--USA[AF402909](AF402909)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Nerodia erythrogaster--USA[AF402912](AF402912)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Nerodia fasciata--USA[AF402910](AF402910)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Nerodia floridana--USA[AF402911](AF402911)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Nerodia rhombifer--USA[AF402915](AF402915)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Nerodia sipedon--USA[AF402913](AF402913)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Nerodia taxispilota--USA[AF402914](AF402914)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Opisthotropis cheniGP383China[GQ281779](GQ281779)[JQ687441](JQ687441)[KJ685595](KJ685595)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})Opisthotropis guangxiensisGP746China[GQ281776](GQ281776)[JQ687447](JQ687447)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})Opisthotropis lateralisGP646China[GQ281782](GQ281782)[JQ687445](JQ687445)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})Opisthotropis latouchiiGP647China[GQ281783](GQ281783)[JQ687446](JQ687446)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})Opisthotropis typicaHT0794Malaysia[LC325343](LC325343)[LC325789](LC325789)[LC326028](LC326028)This studyPseudoxenodon macrops* (Out group)\_1HT0646China[LC325323](LC325323)[LC325769](LC325769)--This studyPseudoxenodon macrops (Out group)\_2HT0802Malaysia[LC325351](LC325351)[LC325797](LC325797)--This studyRegina grahami--USA[AF402918](AF402918)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Regina rigida\_1--USA[AF402919](AF402919)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Regina rigida\_2CAS:HERP:165994USA[AF471052](AF471052)[AF471120](AF471120)--Lawson et al. ([2005](#ece34497-bib-0020){ref-type="ref"})Regina septemvittata--USA[AF402917](AF402917)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Rhabdophis adleri\_1HT0831China[LC325356](LC325356)[LC325802](LC325802)--This studyRhabdophis adleri\_2HT0832China[LC325357](LC325357)[LC325803](LC325803)--This studyRhabdophis callichromus\_1HT0654Vietnam[LC325324](LC325324)[LC325770](LC325770)--This studyRhabdophis callichromus\_2HT0674Vietnam[LC325325](LC325325)[LC325771](LC325771)[LC326020](LC326020)This studyRhabdophis chrysargosHT0342Malaysia[LC325313](LC325313)[LC325759](LC325759)[LC326017](LC326017)This studyRhabdophis conspicilatusHT0791Malaysia[LC325342](LC325342)[LC325788](LC325788)[LC326027](LC326027)This studyRhabdophis formosanus\_1HT0033Taiwan[LC325304](LC325304)[LC325750](LC325750)--This studyRhabdophis formosanus\\_2HT0031Taiwan[LC325304](LC325304)----This studyRhabdophis formosanus\*\_3HT0030Taiwan[LC325304](LC325304)----This studyRhabdophis guangdongensisSYSr000018China[KF800930](KF800930)[KF800920](KF800920)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})Rhabdophis himalayanus\_1HT0847China[LC325299](LC325299)[LC325746](LC325746)[LC326011](LC326011)This studyRhabdophis himalayanus\\_2HT0848China[LC325299](LC325299)----This studyRhabdophis himalayanus\\_3HT0849China[LC325299](LC325299)----This studyRhabdophis himalayanus\_4CAS224420Myanmar[KF800929](KF800929)[KF800919](KF800919)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})Rhabdophis lateralis\_1HT0855China[LC325302](LC325302)----This studyRhabdophis lateralis\_2GP613China[JQ687444](JQ687444)[GQ281785](GQ281785)[KJ685600](KJ685600)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})Rhabdophis leonardi\_1HT0851China[LC325300](LC325300)[LC325747](LC325747)[LC326012](LC326012)This studyRhabdophis leonardi\\_2HT0852China[LC325300](LC325300)----This studyRhabdophis leonardi\\_3HT0853China[LC325300](LC325300)----This studyRhabdophis leonardi\_4RDQ200905367China[KF800932](KF800932)[KF800922](KF800922)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})Rhabdophis murudensisHT0788Malaysia[LC325341](LC325341)[LC325787](LC325787)--This studyRhabdophis nigrocinctus\_1HT0253Thailand[LC325307](LC325307)[LC325753](LC325753)[LC326015](LC326015)This studyRhabdophis nigrocinctus\_2HT0343Thailand[LC325314](LC325314)[LC325760](LC325760)--This studyRhabdophis nigrocinctus\_3HT0845China[LC325298](LC325298)----This studyRhabdophis nuchalis\_1HT0701China[LC325333](LC325333)[LC325779](LC325779)[LC326022](LC326022)This studyRhabdophis nuchalis\_2HT0803China[LC325352](LC325352)[LC325798](LC325798)--This studyRhabdophis nuchalis\_3HT0807China[LC325353](LC325353)[LC325799](LC325799)[LC326031](LC326031)This studyRhabdophis nuchalis\_4HT0854China[LC325301](LC325301)[LC325748](LC325748)--This studyRhabdophis nuchalis\_5SICAU090001China[KF800925](KF800925)[KF800935](KF800935)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})Rhabdophis pentasupralabialis\_1HT0699China[LC325331](LC325331)[LC325777](LC325777)--This studyRhabdophis pentasupralabialis\_2HT0700China[LC325332](LC325332)[LC325778](LC325778)[LC326021](LC326021)This studyRhabdophis pentasupralabialis\_3HT0808China[LC325354](LC325354)[LC325800](LC325800)--This studyRhabdophis subminiatus\_1HT0267Laos[LC325308](LC325308)[LC325754](LC325754)--This studyRhabdophis subminiatus\_2HT0344Thailand[LC325315](LC325315)[LC325761](LC325761)--This studyRhabdophis subminiatus\_3HT0345Thailand[LC325316](LC325316)[LC325762](LC325762)--This studyRhabdophis subminiatus\_4HT0680Vietnam[LC325328](LC325328)[LC325774](LC325774)--This studyRhabdophis swinhonis\_1HT0021Taiwan[LC325303](LC325303)[LC325749](LC325749)--This studyRhabdophis swinhonis\_2HT0717Taiwan[LC325334](LC325334)[LC325780](LC325780)[LC326023](LC326023)This studyRhabdophis swinhonis\\_3HT0716Taiwan[LC325334](LC325334)----This studyRhabdophis swinhonis\\_4HT0718Taiwan[LC325334](LC325334)----This studyRhabdophis swinhonis\\_5HT0719Taiwan[LC325334](LC325334)----This studyRhabdophis tigrinus\_1HT0098Japan[LC325305](LC325305)[LC325751](LC325751)[LC326013](LC326013)This studyRhabdophis tigrinus\_2HT0177Japan[LC325306](LC325306)[LC325752](LC325752)[LC326014](LC326014)This studySibynophis subpunctatus (Out group)RAP0491Sri Lanka[KC347471](KC347471)[KC347411](KC347411)[KC347449](KC347449)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})Sinonatrix aequifasciata\_1HT0678Vietnam[LC325326](LC325326)[LC325772](LC325772)--This studySinonatrix aequifasciata\_2HT0681Vietnam[LC325329](LC325329)[LC325775](LC325775)--This studySinonatrix aequifasciata\_3GP357China[JQ687430](JQ687430)[JQ687440](JQ687440)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})Sinonatrix annularisGP889China[JQ687431](JQ687431)[JQ687449](JQ687449)[KJ685604](KJ685604)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"})Sinonatrix percarinataGP956China[JQ687433](JQ687433)[JQ687451](JQ687451)[KJ685607](KJ685607)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"})Storeria dekayiCAS:HERP:196039USA[AF471050](AF471050)[AF471154](AF471154)--Lawson et al. ([2005](#ece34497-bib-0020){ref-type="ref"})Thamnophis butleri--USA[AF402923](AF402923)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis couchii--USA[AF402936](AF402936)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis cyrtopsis--USA[AF402924](AF402924)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis elegans--USA[AF402925](AF402925)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis godmani--Mexico[AF420135](AF420135)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis marcianus--USA[AF402926](AF402926)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis ordinoides--USA[AF402927](AF402927)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis proximus----[AF402928](AF402928)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis radix--USA[AF402934](AF402934)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis sirtalis\_1----[AF402929](AF402929)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Thamnophis sirtalis\_2----[AF402930](AF402930)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})Trachischium monticolaGP1487China[JQ687428](JQ687428)[JQ687435](JQ687435)[KJ685570](KJ685570)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"})Xenochrophis asperrimus\_1HT0797Sri Lanka[LC325346](LC325346)[LC325792](LC325792)--This studyXenochrophis asperrimus\_2--Sri Lanka[KC347480](KC347480)[KC347414](KC347414)[KC347451](KC347451)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})Xenochrophis flavipunctatusHT0682Vietnam[LC325330](LC325330)[LC325776](LC325776)--This studyXenochrophis maculatusHT0720Malaysia[LC325335](LC325335)[LC325781](LC325781)[LC326024](LC326024)This studyXenochrophis piscator\_1HT0347Thailand[LC325317](LC325317)[LC325763](LC325763)[LC326018](LC326018)This studyXenochrophis piscator\_2HT0371Vietnam[LC325318](LC325318)[LC325764](LC325764)--This studyXenochrophis piscator\_3HT0796Sri Lanka[LC325345](LC325345)[LC325791](LC325791)--This studyXenochrophis trianguligerusHT0795Malaysia[LC325344](LC325344)[LC325790](LC325790)[LC326029](LC326029)This studyXenochrophis vittatus\_1HT0615Indonesia[LC325322](LC325322)[LC325768](LC325768)[LC326019](LC326019)This studyXenochrophis vittatus\*\_2HT0527Indonesia[LC325322](LC325322)----This study	{ "pile_set_name": "PubMed Central" }
"Hey." "Ohh!" "You scared me." "Sorry." "I hit a wall." "Whoa, oh." "Give me a second." "Well, our time's almost up, anyway." "Here, let me just show you a couple of cool-down stretches." "Next time." "You hired me as your personal trainer, right?" "Right." "And here's your training lesson for today." "Next time needs to be now time." "It's just..." "I got some errands to run." "I'll see you Saturday." "Hey!" " Yeah." " Terry." "Pain is not gain." "Got it?" "I got it." "♪ I'm talkin' behind your back ♪" "♪ you better be payin' attention ♪" "♪ there's a war goin' on" "♪ rollin' up my short sleeves" "♪ ...almost everything I ever had ♪" "♪ and you make me so mad" "♪ I'm lookin' at..." "What do you mean, he's not going?" "Every kid loves trick-or-treating." "Henry's scared." "One of his little buddies told him Halloween was the only time when all the real monsters come out because they can blend in." "Never thought about that." "Good monster strategy." "You did tell him it wasn't true, right?" "Of course I did." "But he's convinced." "Childhood fears are resistant to adult logic." "Sometimes you just have to wait it out." "For how long?" "Well, if he's 23 and this still worries you, you got a problem." "Well, see, the thing is, I think I am partly to blame." "How?" "Well, the other night will and I were up late, we were having some wine, talking about some of the cases we've worked on, and at one point, I said I felt like there was no end" "to all the monsters walking around, and..." "Henry sneaked into the room to listen to the grownups." "Yeah." "We need a cone of silence for our house." "Those of you who like a good mystery, please unleash your inner Agatha Christie, 'cause this one's a real humdinger." "Gary Ellard, Barry Deaver, Paul Hicks, Terry Rodgers." "Over the course of the last month and a half, these 4 men have gotten in their cars in La Grande, Oregon, and drove into the never-to-be-seen-agains-ville, poof, gone." "The latest victim Terry Rodgers disappeared 24 hours ago." "Forensic evidence point us anywhere?" "Uh, point would imply there is evidence, and there is no evidence, at least for the first 3 victims." "No forensics, no witnesses, no ransom demands." "Maybe these guys just voluntarily decided to hit the road." "4 sudden disappearances in a community this small-- this isn't about seeking green pastures." "Based on last known sightings, we're dealing with a sizeable geographic area." "He's efficient and well organized." "It's not easy to make 4 people vanish and stay vanished." "It has been done before, though." "Political kidnappings frequently require holding multiple adults simultaneously." "Or they're already dead." "Nothing says "can't be found"" "like a shallow grave in the middle of nowhere." "Assuming they are alive, how is the unsub controlling them?" "And for what purpose?" "The time between abductions is shortening with each victim." "Wheels up in 30." "♪ Criminal Minds 8x05 ♪ The Good Earth Original Air Date on October 31, 2012" "== sync, corrected by elderman ==" "♪" ""I became insane, with long intervals of horrible sanity."" "Edgar Allan Poe." "Garcia, anything on the last victim, Terry Rodgers?" "Only that he's unemployed and lives in a cabin in the woods." "But primitive, like no flush toilet primitive." "That doesn't fit the victimology of the other 3." "Ellard coaches track and field at a local college," "Deaver's a small business owner, and Hicks is an attorney." "All married with young families." "Another difference-- the first 3 victims were all born and raised in La Grande." "Terry Rodgers only moved to town a couple of months ago." "Do you know where from, Garcia?" "Rhode Island." "Though there's a 5-month gap between Terry being in Rhode Island and then arriving in Oregon." "Where he was and what he was doing is a big fat blank." "It says here that vomit was found in the vicinity of his abduction." "Mm." "Thank you for reminding me of that disgusting detail, Dreamy D." "Yes, that vomit has been collected and is being analyzed as we speak, and I'm very grateful that I have this job and someone has that one that's not me." "Rodgers is the obvious anomaly of the 4, but there's no apparent overlap between any of the victims." "Almost like the unsub was selecting his targets at random." "Blake, you and Morgan go talk to the families of the victims." "See if there's something that links them that's not on paper." "Dave and I will go to the abduction site." "Reid, you and JJ go to Terry Rodgers' cabin." "He's the one we know least about." "Maybe he made himself obscure for a reason." "Sheriff, I'm Agent Hotchner." "This is Agent Rossi." "Sheriff Colwin." "I am glad to have your help." "The best we can reconstruct it, victim's car veered off the road at a low rate of speed, plowed through the fence, and ended up in the field." "He managed to get about 20 feet away before throwing up." "The photo showed a second set of tracks." "Were you able to pull a tread pattern?" "We're checking on it right now." "Maybe our guy got sick and had to pull over." "Or he was forced off the road." "Either way, the unsub was following him." "Mrs. Deaver, did your husband give any indication at all that something might be wrong the night he disappeared?" "No, not at all." "Barry was supposed to coach our son's little league game that night." "So he wasn't depressed, preoccupied?" "Nothing." "It was a day like any other day." "This is what happens to other people." "You see it on the news, you know." "Give it, what, 30 seconds of your time?" "Shake your head, go back to whatever stupid thing you were doing." "Washing dishes or putting away laundry." "You never think it's going to happen to you." "Go ahead, you're on speaker, Garcia." "Sir, I just got the full lab report for the... you know, the regur-- for the puke, and there's no toxins or bacterial infections." "However, Terry Rodgers did have elevated levels of Melatonin in his system." "And I'm sending you the full lab report..." "Now, on your phones." "Elevated?" "His Melatonin levels are off the chart." "Is that significant?" "It's a sedative." "An amount this large would induce extreme drowsiness." "Do you think he might have overdosed my accident?" "No, no, this was no accident." "The victim was drugged." "Sheriff, the police report said there were groceries in Rodgers' car." "Do you know if he ate anything out of the bags?" "He didn't." "We compared the supermarket receipt to what was in the bags." "Nothing missing." "So, how did Rodgers unknowingly ingest such a massive dose of Melatonin?" "You know, aside from the outhouse, this cabin isn't so primitive." "Ok." "Economics, philosophy, political theory." "It isn't exactly breezy, take to the beach reading." "I would, but I don't really like the beach." "Why is that?" "Sandy food, pink skin, limited and unengaging topography, but mostly the drug-resistant bacteria spread by sea gull feces." "Sorry I asked." "You know, there's a lot of material here about global warming, overcrowding." "The evils of technology." "There's no phone, no TV." "I wonder what this guy does for fun." "I think maybe I just found the answer." "Tread marks were inconclusive." "Probably from a pickup truck, though." "What's that?" "The likely routes our 4 victims to on the day they disappeared." "Gary Ellard-- apartment, DMV, was a no-show for his morning class at Eastern Oregon University." "Barry Deaver--home, gas station, never made it to his karate group." "Paul Hicks--home, daughter's preschool, doctor's appointment." "He was supposed to meet a client over here but never showed." "And we already know about Terry Rodgers." "And all this tells you what?" "It's more about what it doesn't tell us." "None of the lines intersect." "I just had a chat with Terry Rodgers' personal trainer." "She said he never talked about his private life." "He's shelling out for a personal trainer?" "This is a guy with no indoor plumbing." "She said he was dedicated." "Not in great shape, but dedicated." "Hey." "You're talking to the room, P.G." "Mm." "If by P.G. You mean parental guidance strongly advised," "I say P.A., prudent advice." "Ok, here's what's happened." "I checked all the employees and vendors and delivery people who work at the supermarket where Terry Rodgers bought his groceries, and there were no red flags." "Also, Barry Deaver, the second victim," "I found his car." " Where?" " Impounded." "It was abandoned 3 weeks ago on Fish Hatchery Road, picked up by Gus' Towing Service, where it has been collecting dust and racking up storage fees ever since." "Where's Fish Hatchery Road?" "Off the beaten track, like Terry Rodgers." "Looks like the unsub's hunting grounds are rural and remote." "Well, to have ended up there," "Barry Deaver must have gone on a diagonal, north first, and then headed west towards his karate class." "So, did you learn anything?" "Yeah." "Spence here does not like the beach." "I don't." "Terry Rodgers definitely wanted to live off the grid." "A small generator for minimal electrical needs." "No phone, no TV, no radio." "And lots of material about the evils of technology, living healthy off the land, that sort of thing." "Sounds like the unabomber." "We did find a small stash of marijuana hidden away." "Did you find any evidence that a baby lived there or visited there?" "Uh, no, why?" "I just got the list of things that he bought at the supermarket." "4 jars of baby food." "A body matching Rodgers' description was found in a river 10 miles out of town." "Easy." "Easy." "Right there." "A fisherman found him washed up on a bank." "Well, other than the ligature marks on the wrists and ankles, there's no signs of violence or torture." "A lot of care was taken with the killing and disposing of the body." "Sedation and drowning." "We may have to dramatically reassess who the unsub is." "What do you mean?" "We might be looking for a woman." "Mommy?" "Lexy!" "I told you to never come out here by yourself." "I know, but I'm hungry." "Stay away from the barn." "There's a lot of dangerous equipment in there." "You could hurt yourself." "Go back to the house and stay there." "I'll be in to fix you something." "But I mean it-- stay there." "Ok." "There's got to be something else that links these victims." "They were all athletic." "Ellard teaches track and field." "Deaver has a martial arts studio." "Paul Hicks had tendonitis from playing competitive tennis." "But Rodgers' trainer said that he was out of shape." "Did the medical examiner determine Rodgers' time of death?" "3 hours from when he was found at the river." "So the unsub kept Rodgers alive for the entire day before drowning him." "Go ahead, Garcia." "Ok." "I've got something." "That's really bugging me." "I can't figure out what Terry Rodgers was doing those missing 5 months." "I mean, you can't sit on a park bench in this country and not leave a paper trail." "But you figured it out." "No." "This is me venting." "What I did figure out was what Terry Rodgers was doing in Rhode island before he went awol." "Check it." "He was married, divorced, married again, currently way behind on child support payments to wife number two, and that's all I know." "If you'll excuse me, I have more digging to do." "Owes child support." "Could explain why Rodgers vanished for 5 months." "And why he lived off the grid." "Hard to find." "And that's what links him to the other victims." "They all fathered children." "We believe the unsub that we're looking for is a woman, who is highly organized, she's thorough, and she's patient." "Based on the complexity and the sophistication of the abductions, we think she is most likely between the ages of 30 and 40." "She's familiar with the rural area surrounding La Grande." "Either a native or someone who's lived there for a while." "We think she's keeping her victims in isolation in the countryside, which means she has access to land or a structure that is remote, hidden, and private." "She's abducting exceptionally health conscious men, ideal specimens, if you will." "Specimens." "For what?" "Possible breeding." "Ability to father children is something we think she's looking for in her victims." "They're all age appropriate, and they are all fathers." "But why kill the last victim?" "She may have seen him as being flawed." "He was the least physically fit of the 4, and he neglected to pay child support." "Making him undesirable." "The victims may be surrogates for a man that she wants but she cannot have." "Because she killed the last victim, we have to consider the possibility that the unsub is engaged in some sort of elimination process." "Preselecting a handful of prime candidates and then whittling them down one by one until she has her ideal breeding partner." "And if this is the case, the the killing's just begun." "Mommy, what's the matter?" "We got a frequent flier." "Which one?" "The tomato lady." "I don't believe this." "Emma." "Dr. Gourse." "Thank God you're here." "Those other doctors don't understand my history." "Yeah, I thought we talked about this last time." "Yeah, we did." "But the scleroderma came back." "Look." "There's nothing on your arm." "But it's right there." "You treated me after my husband died." "It's the same thing." "Yeah, your scleroderma was treated successfully." "You are fine now." "But this could be a mutation." "Things mutate." "What about Stevens-Johnson syndrome?" "Stevens-Johnson is extremely rare." "And you'd have severe blistering all over your face." "Emma, we talked before about how a delusion" "I'm not crazy." "Emma, listen to me." "There may be other issues that are going on with you." "Did you contact the therapist that I recommended?" "I guess that's no." "I'm still waiting on the full M.E. report on Terry Rodgers." "They say they want to retest some of the findings." "Did they say why?" "No." "I recognize that scowl, Aaron." "What are you thinking?" "Something Garcia said earlier about not being able to sit on a park bench in this country without leaving a paper trail." "And..." "So what if Rodgers wasn't in the country for those 5 months?" "It wouldn't be the first time someone crossed borders to get away from troubles." "Guys, there's something interesting about this grocery list." "What?" "Look at the items he bought in bulk." "Garlic, green tea, vitamin D, ginger." "All of these items are specifically known to boost the immune system." "What if Terry Rodgers was seriously ill?" "What about the baby food?" "A side effect of radiation treatment is sores inside the mouth." "In fact, doctors advise you to eat the way an infant would eat." "Chemotherapy?" "The marijuana in the cabin could have been medicinal." "I'll have Garcia check medical facilities outside the country." "And, Reid, you and JJ go to the medical examiner and have them look specifically for a pre-existing condition with Rodgers." "Hotch." "You were right." "Back in June, Rodgers checked himself into an experimental clinic in Mexico." "Cancer." "That's why the unsub disposed of him so quickly." "It was Hodgkin's lymphoma." "Did you find any sedatives in his system?" "The question is, what sedatives didn't we find?" "Melatonin, Valerian, marijuana, hops, catnip, kava-kava..." "Bone meal and kelp." "In the victim's stomach, along with some materials that we're retesting." "Take a look at the bottom." "Sawdust residue caked in the nostrils?" "Not just any sawdust." "Pure pinewood pellet sawdust." "It's usually imported from China." "Was it a 0.5% mixture?" "I don't know." "All I know is, it's not your everyday spread-on-the-floor sawdust." "Yeah." "That was Reid." "They found a half dozen natural sedatives in Rodgers' system." "I don't get it." "The unsub's drugging victims and trusting that they'll conk out at the right place at the right time." "Why not use a pharmaceutical drug?" "Or poison?" "Which would be quicker and a lot more reliable." "Natural holistic elements must be important to her." "She may have health issues of her own." "Go ahead, Garcia." "I just hit the trifecta, but with two things instead of 3." "What is that, a bifecta?" "Exacta." "What do you got?" "Well, that-- anyway, two missing vehicles not missing anymore." "Paul Hicks' car was found by some utility workers an hour ago." "It had rolled off into a ravine." "And Gary Ellard's car was picked up on a speeding violation in Coeur d'Alene, Idaho." "Idaho?" "Stolen by some local kids 10 days ago in La Grande." "Car was just sitting by the side of the road, keys in the ignition." "They made a typically sound teenage decision, decided to take it on a cross-state joyride." "Garcia, I need to know the exact spot where the vehicles were originally found." "On it." "All right, based on what we just got, this is the revised best guess on the victims' routes the days they were abducted." "Two intersect here, the other two here." "And this is where Terry Rodgers bought his groceries." "It looks like Paul Hicks might have gone there after his doctor's appointment." "Now, what was at the intersection where Deaver and Ellard crossed?" "That's a shopping center with a dozen or so businesses." "We're getting a list right now." "One of our deputies sighted an abandoned car on the outskirts of town." "There was a second set of tire tracks behind it that matched those found at Terry Rodgers' abduction site." "Vehicle's registered to Cheryl Winslow, 4801 Davenport Avenue." "These are all from a baby shower." "We contacted her husband." "She's due in 3 weeks." "If this is our unsub, taking a pregnant woman would be a huge shift in victimology." "We profiled she was abducting the men as breeders." "But why take someone else's baby if you're planning on having your own?" "Maybe she can't have one or she lost one." "Ok, so this-- this isn't about fertility, but the experience these men would bring as fathers." "Could she be building a family?" "Ohh..." "Oh, please." "Oh, please." "What are you doing?" "!" "Keep still." "Oh, my God!" "Prep and get her to O.R. 3." "Doctor, is she gonna make it?" "There's been massive blood loss." "She was given a C-section with a serrated-edge knife, then crudely stitched back up." "We found her and the baby in our parking lot." " How's the baby?" " The child is fine." "It's her I'm worried about." "Excuse me." "Touch-and-go for a while, but she's going to make it." "Thank God." "It was a crude stitch-up job, but functional." "Probably what saved her life." "Whoever did this had some practice somewhere." "You think there'd be any way we could talk to her?" "It's very important." "I'm sorry, but the next 24 hours are critical." " She's heavily sedated." " I understand." "Her husband's here." "Excuse me." "Our unsub removed the baby, then returned mother and child to a hospital." "Baby wasn't due for 3 more weeks." "If the unsub's trying to put together the perfect family, maybe a premature infant isn't good enough." "Let's hope not." "That means she'll go out looking for a healthier baby now." "Mommy?" "Mommy?" "Lexy, get down from there!" "That was Hotch." "The doctor told him the placenta was scraped completely out of the victim's uterus." "Every bit of it." "You know, the placenta does carry special significance in many cultures." "In ancient Egypt, it had its own hieroglyph." "And the Ibo tribe in Nigeria considered it to be the child's dead twin." "Well, that would be helpful, if our unsub was an ancient Egyptian or Ibo tribeswoman, but..." "I can hear the high-pitched whine from your I.Q. all the way over here." "What is it?" "It could be placentophagy." "What?" "Consuming it." "In the wild, it's common for animals to eat their own afterbirth." "It's super rich in nutrients." "Whoa, whoa, whoa, wait." "So the unsub might have harvested this last victim... for food?" "Here." "No!" "No..." "No, please, mommy." "I promise I won't go to the barn again." "I promise." "This is not punishment." "I'm trying to keep you healthy." "No!" "No!" "Ohh!" "What's wrong with you?" "!" "Do you have any idea what I did to get that for us?" "Uhh!" "It's ruined." "I'm sorry." "Oh, I'm sorry I yelled at you." "But..." "Mommy?" "It's about food." "Herbal sedatives, gruel, and now the placenta." "Ugh." "And FYI, there's no record of anyone in La Grande buying that weird kind of sawdust the M.E. found." "I'll widen the search." "We still need to figure out how this unsub was able to drug all these men." "The southeast intersect doesn't get us much." "Laundromat, video rental store." "The other intersect is the supermarket, but none of the employees recognized Paul Hicks." "He never shopped there." "Garcia, what day of the week were each of the victims abducted?" "Let me see." "Gary Ellard on a Monday, Barry Deaver on a Saturday," "Terry Rodgers and Paul Hicks both on a Thursday." "Is there anything special that happens in the vicinity of the market on Thursdays?" "Uh...wow, you've done this before, haven't you?" "Yeah." "There's a farmers market across the street from the supermarket every Thursday morning." "And where is it today?" "Pendleton, about 40 miles north on Interstate 84." "I'm sending Blake and Morgan." "Enjoying your Melatonin bar?" "Job's making you paranoid, Blake." "Well, apparently a lot of people work this market." "It's not like everybody else knows everybody else." "I'm gonna get a list of vendors and launch Garcia anyway." "You can see how it happened, though." "And Terry Rodgers got his groceries, made his way back to his car..." "Grabbed a power drink on his way home." "He drank it... and then he tossed it." "Now the Melatonin's in his system with no evidence of where it came from." "Hey, what do you got?" "Full toxicology report." "And?" "Unlike any tox panel I've ever seen before." "They found gypsum?" "Yeah." "Gypsum's rich in sulphur, a vital plant nutrient." "She's feeding her captives soil additives?" "Seed meals, too." "Look, cotton, flax." "Come on." "It's animal feed." "Why would you treat a human being like livestock?" "People raise cattle to eat." "The unsub might be using the placenta as food, but nothing in the profile suggested cannibalism." "I mean...unless the sawdust they found in Terry Rodgers' nose..." "What about it?" "When livestock die, animal carcasses turn into a useful soil amendment through the aerobic biodegration process." " Like compost." " Exactly." "You need to add a substrate high in carbon to balance the nitrogen, and one of the most efficient substrates on earth is pure sawdust." "She's using her victims as human fertilizer." "How are you feeling, honey?" "Mm..." "This won't hurt you." "I made it all from roots and herbs." "All it does is help you take a little nap." "And when you wake up, you'll be the beautiful little girl that you are." "Ok, put your arms around me now." "How are we doing with the farmers market background search?" "Not good." "Turns out that people who grow organic rutabagas are loosey-goosey about punching in a time clock." "Sheriff, if we expand the search of the second intersection by a few square blocks, would we find any markets or restaurants?" "There's a health food co-op 3 blocks away." "The soil will heal you." "Sheriff, the surgeon who operated on Cheryl Winslow said that whoever did the C-section might have done one before." "If she did, we never heard about it." "Nothing like this has ever happened in La Grande." "Well, we can keep looking, expand the search radius to nearby towns." "What about farms?" "My grandparents had a farm in Pennsylvania." "Once my grandmother had to deliver a calf by C-section to a cow that was in distress." "Go ahead, Garcia." "I have got something." "Emma Kerrigan." "She runs a small juice and vegetable stand at the farmers market, and she works part-time giving out free samples at the health food co-op." "I'm sending you her picture now." "That sounds like our unsub." "Where does she live?" "Piping Rock Farms west of town, with 100 acres, belonged to her husband's family." "Wait, she has a husband?" "Had." "Died in a car accident a year and a half ago, leaving her and a 10-year-old daughter." "Let's go." "I've got more info on Emma Kerrigan." "30 E.R. visits in the past 6 months." "Big-time hypochondriac." "A co-worker says she didn't eat anything unless she grew it herself." "To be fair, she did have an actual skin disease a couple years ago-- scleroderma." "Garcia, did the E.R. visits coincide with the death of the husband?" "No." "She was sick with the scleroderma when he died." "Cleared up a few months later." "The E.R. visits didn't kick in until the following year." "Please..." "Clear." "Clear!" "Clear." "What's that?" "Garcia, what happened to Emma Kerrigan's husband's body after he died?" "Uh, cremated." "And what happened to the ashes?" "Obit says they were planning on spreading his ashes in the family garden throughout the 4 seasons." "Renewal, cycle of life, rejuvenation, that kind of thing." "Garcia, you got a map of the farm?" "Place this size, we need to narrow the search." "I got the satellite image." "There's two groups of buildings." "And then there's a small square patch next to a barn that could be a private garden." "All right, let's go." "Hotch." "Back garden." "Emma Kerrigan, FBI." "Put your hands where I can see them." "Emma, put that knife down." "No." "My daughter needs this." "Look at her." "Put it down so we can get her the help she needs." "My daughter will be dead by then." "I believe you, Emma." "I can see how sick she is." "I talked to your doctor." "Dr. Gourse?" "You talked to Dr. Gourse?" "Yes." "He said Lexy is too sick for this to work." "This man's blood won't do anything." "But it has to." "It's all I have left." "No." "No." "What can cure Lexy is what cured you." "Uh..." "Funeral homes are required by law to keep a portion of the remains of those that they cremate." "These are your husband's ashes." "Only these will make your daughter well." "Those are his?" "It's a miracle." "It's a miracle." "Not bad, Blake." "Not bad at all." "Took a chance." "I mean, I saw her fireplace there..." "Alfred Austin said," ""Show me your garden and I shall tell you what you are."" "I assume you're not trick-or-treating either?" "Ah, none of my treats seem to want to call me back, Rossi." "Then I'll buy you dinner." "I'm in." "Uh, excuse me, everybody." "I have an announcement to make." "As I'm sure some of you were aware," "Henry was a little nervous about going trick-or-treating this year." "But he's decided to go anyway." "Great." "What changed his mind?" "The BAU did." "I told him that he should go out on Halloween and try to figure out which monsters are real and which ones are not." "So he wants to be a profiler." "Ah." "He wants to be his favorite profiler." "Wow!" "Yeah!" "Oh, wow!" "You look great, Henry." "Put this on here." "Oh, he's official." "Yeah." "Tell him." "E equals MC squared!" "Oh, there it is!" "Ohh!" "The monsters don't stand a chance." "Oh, I know." "Shall we go get you some candy?" "Come on." "Whoo-hoo." "Watch your back, pretty boy." "== sync, corrected by elderman =="	{ "pile_set_name": "OpenSubtitles" }
When Dr. Lionel Carmant returned to the Montreal Children’s Hospital earlier this week to give a speech for Black History Month, it was a homecoming of sorts. It is where the pediatric neurologist completed part of his training in the 1990s. “Coming back here today, it really hits home - and the house has been quite improved over the years,” he said with a laugh, as he stood in front of the crowd gathered in the P.K. Subban Atrium. Carmant has since moved on to another “house”: Quebec's National Assembly. He’s now the CAQ government’s junior health minister, one of 125 men and women elected last fall. Up until the October 1, 2018 general election, there were just five black MNAs in the entire history of the National Assembly. Now, there are five black MNAs in the legislature at the same time. It’s a sign of the changing times in Quebec politics, and for Liberal MNA and former deputy premier Dominique Anglade, it’s a welcome change. “It's always important to get a good representation of what society generally is, and that's why this year - both in terms of black people, and in terms of women as well - we see progress. So that makes me happy and more positive about the future,” said Anglade. Being elected was a surreal experience for CAQ MNA Christopher Skeete, the son of a French-Canadian mother and a Trinidadian father. “For me, growing up, the idea of having a black president of the United States would have been something I never would have thought I would see in my lifetime, let alone myself getting elected to the National Assembly,” he said, adding that he is particularly proud of the fact there are two black ministers in the current government. “I think we're making great strides. So the message I would say to youth is, "Stop thinking about it. Just go. Just push those barriers," Skeete said. Nadine Girault, of Haitian origin, is also a first-time MNA and the minister of international relations and la Francophonie. She says the black community’s response to her budding political career has been overwhelmingly positive. “It really feels for them like we can take our place and there's room for us, so it's very rewarding. It's a privilege,” said Girault. Now that she has a seat at the table, she’s hoping others will follow in her footsteps. “I think it's on two sides. We have to do more to attract, yes, but black people also have to get involved,” she said. “There were very nice, young black women as candidates, and I look forward to seeing them come back in the next election – because they all said that they're coming back (…) I'm sure that with time, and from one election to the other, we're going to see more and more black people.” Liberal MNA and former Montreal city council speaker Frantz Benjamin said he feels a responsibility to spread knowledge about the historical black presence in Quebec, including the stories of slaves in New France. “The story of Marie-Joseph Angelique, it is not only my story. It is the story of all of Quebec society,” said Benjamin. “Now it is our duty as a member of the National Assembly - but especially the duty of the government - to make sure that at the educational level, more has to be done.” To mark Black History Month this year, the Quebec government announced it will rename a bridge on Highway 50 in the Outaouais in honour of Jean Alfred, Quebec’s first black MNA. Alfred was elected under the Parti Quebecois banner in 1976, when the party came to power for the first time under Rene Levesque. Follow @MJohnsonCTV	{ "pile_set_name": "OpenWebText2" }
Psychoneuroimmunology and AIDS. Although PNI is a relatively new field, basic research has demonstrated the interconnectedness of immune and neurological systems, alerting nurses to the need to conduct multisystem assessments and provide holistic nursing care to persons with AIDS. Although the burden of research does not support the notion that the mind can cure AIDS, preliminary studies suggest that under certain circumstances the psychogenic and physiological conditions of the host alter rates of progression of HIV infection. Nursing research is needed to determine circumstances under which immunomodulating events alter disease progression in this population.	{ "pile_set_name": "PubMed Abstracts" }
The present invention is in the pharmaceutical area, and in particular relates to pharmaceutical compositions containing 5'-diphosphohexose and 5'-diphosphohexosamine derivatives of nucleosides. Acquired immunodeficiency syndrome ("AIDS") was recognized as early as 1979. The number of cases reported to the Centers for Disease Control (CDC) has increased dramatically each year since then, and in 1982 the CDC declared AIDS a new epidemic. Infection with the AIDS virus is highly variable. Initially, the virus replicates abundantly, with virus present in the central nervous system and the cells of the immune system. This is frequently accompanied by fevers, rashes, flulike symptoms and neurological complaints. These symptoms generally disappear within a few weeks, as the amount of virus in the circulation drops. However, virus is still present in the immune cells, the cells of the nervous system, cells of the intestine and bone marrow cells. The victim typically dies two to ten years after the initial asymptomatic period, following a protracted and painful illness. Human immunodeficiency virus, a retrovirus, is the etiological agent of AIDS, as well as of a variety of related disorders, such as AIDS Related Complex (ARC). HIV infection begins when a virion or virus-infected cell binds to susceptible cells and fuses with them, injecting the core protein and viral RNA into the cell. The RNA is transcribed to viral DNA. The double stranded DNA migrates to the nucleus and is integrated into the cell's DNA. The viral DNA can remain dormant for an indefinite period of time, or the genes can replicate and be translated into viral proteins. The viral proteins are assembled into new virions that bud from the cell, spreading the disease. HIV preferentially infects the T4 lymphocytes, immune cells important in helping to suppress infection by other agents, thereby impairing proper functioning of the immune system. As a result of impaired immunity caused by the destruction of helper T-cells by the HIV, the host becomes susceptible to opportunistic infections, various types of cancer such as Kaposi's sarcoma, and other disorders associated with reduced functioning of the immune system. A variety of approaches have been developed to treat AIDS infections, including inhibiting the binding of the virus to host cells with dextran sulfate or soluble CD4 (a glycoprotein found on the surface of cells of the immune system which the HIV binds to when infecting the cells), administration of anti-idiotypic antibodies (an antibody to the antibody against CD4), blockage of viral protein synthesis by compounds such as phosphorothioate, and inhibition of protein glycosylation by compounds such as 2-deoxy-D-glucose. However, these approaches are still in early experimental phases, and have not been approved for clinical treatment. AIDS and ARC chemotherapy have been recently reviewed by Schinazi, Strategies and Targets for Anti-Human Immunodeficiency Virus Type 1 Therapy, "Aids in Children, Adolescents, and Heterosexual Adults: An Interdisciplinary Approach to Prevention," Elsvier, N.Y. 1988); E. D. Clercq, J. Med. Chem. 29, 1561-1569 (1986); H. Mitsuya, S. Broder, Nature 325, 773-778 (1987); and R. Yarchoan, et al., "AIDS Therapies" The Science of AIDS Scientific American (W. H. Freeman and Co. N.Y. 1989). A number of nucleosides have been found to have anti-HIV activity, including 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxycytidine (DDC), 2',3'-dideoxyadenosine (DDA), 3'-azido-2',3'-dideoxyuridine (AzddU), 2',3'-didehydro-2',3'-dieoxycytidine, 3'-deoxy-2',3'-didehydrothymidine, 3'-azido-5-ethyl-2',3'-dideoxyuridine (AzddEU), 3'-azido-5-methyl-2',3'-dideoxycytidine (AzddMeC), 9-(2,3-Dideoxy-2-halo-.beta.-D-arabinofuranosyl)-N.sup.6 -methyladenine (2'-halo-D.sub.2 MeA), and N.sup.6 -methyl-D-glycero-2',3'-dideoxyfuranosyladenosine (D.sub.2 MeA). The present application is a continuation-in-part of applications directed to AzddU. It is generally accepted that the active form of nucleosides such as AZT, AzddU, AzddMeC, D.sub.2 MeA, and DDC is the triphosphorylated derivative. Triphosphorylated deoxynucleosides appear to inhibit the replication of HIV by limiting the production of viral DNA by at least two mechanisms: competitive inhibition of reverse transcriptase and chain termination of viral DNA due to the missing 3'-hydroxyl group. The therapeutic effectiveness of all of the known active nucleosides depends on how easily the nucleoside can enter cells and undergo phosphorylation by cellular enzymes. The efficiency of this process varies considerably among nucleosides, and can severely limit the usefulness of the compounds. For example, nucleoside triphosphates without modification, are not useful clinically, since they cannot pass through the cell membrane, even though the triphosphate may have greater antiviral activity. Nucleosides are also converted by intracellular enzymes into less active metabolites. If the conversion rate to less active compounds is faster than the rate of triphosphorylation of the nucleoside, the pharmaceutical effectiveness of the nucleoside is diminished. For example, it is known that DDA in the triphosphate form is a potent HIV inhibitor in vitro, but in vivo the enzyme adenosine deaminase rapidly converts DDA to the less active DDI (2',3'-dideoxyinosine) before DDA can be phosphorylated. DDI-5'-monophosphate must then be converted to DDA-5'-monophosphate by cellular enzymes to restore the activity of the compound. The therapeutic effectiveness of a drug is the determining factor in the dosage required for therapy. Nucleosides that pass through the cell membrane with difficulty or which are metabolized into less active or inactive forms in the cell must be administered in higher dosages. Unfortunately, most nucleosides are toxic to healthy uninfected cells at high dosage levels. AZT has been studied extensively in humans for treatment of HIV infections. However, bone marrow toxicity and other side effects limit its long term usefulness. For example, Richman, et al., have shown that because of AZT-associated hematological abnormalities, twenty-one percent of patients undergoing AZT therapy required multiple blood transfusions during the six month treatment period. Bone marrow depression may be due to the accumulation of phosphorylated AZT within cells, which may result in a substantial depression of thymidine 5'-triphosphate pools. Another drawback of AZT is its short half life in humans (about 1.1 hour) and its elimination in urine as 3'-azido-3'-deoxy-5'-glucuronylthymidine, a metabolite with no substantial antiviral activity. Many nucleoside derivatives have been developed that have anticancer, anti-bacterial, and anti-fungal activity. Effective therapy with these nucleosides, as with the anti-HIV nucleosides, is significantly affected by the ability of the nucleoside to pass through the cell membrane and diffuse to the active site before the compound is converted to an inactive form or eliminated. Nucleoside diphosphate sugars are used in vivo for the synthesis of oligosaccharides, polysaccharides, glycolipids, glycoproteins, and components of bacterial cell membranes. Certain nucleoside derivatives have been found to block the glycosylation of proteins. However, most, if not all, known nucleoside glycosylation inhibitors show little selectivity and have low activity against viral infections. Camarasa, et al., J. Med. Chem., 28, 40 (1985) reported that uridine 5'-diphosphate glucose analogues, 5'-O-[[[[(2",3",4",6"-tetra-O-benzyl- and 2",3",4",6"-tetra-O-benzoyl-.alpha.-D-glucopyranosyl)oxyl]carbonyl]ami no]sulfonyl]-2',3'-isopropylideneuridine (P-536), a UDP-glucose analog, and the corresponding deisopropylidenated derivatives, show in vitro antiviral activity against herpes simplex virus type 1. Alarcon, et al., in Antimicrobial Agents and Chemotherapy 1257, (1988) reported that P-536 has broad antiviral activity, including activity against adenovirus type 5, vaccinia virus, and poliovirus type 1. The compound was demonstrated to inhibit protein glycosylation if added at a time when late viral proteins were being synthesized, and to inhibit the synthesis of nucleic acids and phosphorylation of nucleosides. Alcina, et al., Antimicrobial Agents and Chemotherapy, 1412 (1988), later demonstrated that the same compound has activity against the flagellated protozoan Trypanosoma cruzi. In light of the state of the art, it is clear that there is a strong need for biologically active nucleoside derivatives that can pass through a cell membrane and reach the active site prior to conversion to inactive metabolites or elimination. It is therefore an object of the present invention to provide nucleoside derivatives that have enhanced antiviral, antibacterial, antifungal or anticancer activity. It is a further object of the present invention to provide nucleoside derivatives that can easily pass through a cell membrane in the proper chemical form to perform a desired biological function, or a chemical form. It is a still further object of the present invention to provide a method to enhance the cellular levels of nucleosides.	{ "pile_set_name": "USPTO Backgrounds" }
coldplayticketschile Contact Details Description Country Songs Alphabet- Vince Gill What causes ear ringing tinnitus? Individuals automatically relate this to old age and loss of listening to and this is not correct. What is even worse is the assumption it can\'t be treated. Even though there are remedies for it. Basketball enthusiasts should attend a game at the Philips Arena and witness the Atlanta Hawks (NBA), the Atlanta Thrashers and the Atlanta Dream (WNBA) groups in actions. It is also a well-liked location for Concerts and occasions. These holiday rentals variety from studio flats to homes that can accommodate 10 or much more individuals. They are highly price-effective for couples touring with other couples, or households of 3 or much more. In fact, vacation rentals can decrease your lodging costs significantly, when in contrast to a hotel. Most also have a totally equipped kitchen, so you can put together a food or two daily. 7) Visit the Savannah Convention & Visitors\' Bureau on Martin Luther King Blvd . You\'ll discover numerous totally free brochures, maps and guidance from reps there about the most inexpensive ways to enjoy the sites. Nationally acknowledged for its drag strip and oval track, Beech Bend is a first course auto racing facility and amusement park. Home to Inventory Car Racing, Fun Racing, and NHRA Drag Racing, the park also hosts national automotive occasions all through the yr. The other side of the park offers amusement rides, picnic locations, a campground, and a drinking water park. Open from March-November. J.E. Wallace was the individual that created the Iowa State Honest\'s initial butter cow sculpture in 1911. He was succeeded by Earl Frank Dutt of Illinois and then the butter cow sculpting was done by Norma \"Duffy\" Lyon of Toledo, Iowa. She was the initial lady to sculpt a cow made out of butter for the Iowa Condition Honest. In 2006, Sarah Pratt grew to become the fourth individual to sculpt butter for the Des Moines Iowa State Fair and is still with them today. Want a split from the tours and sightseeing? Settle down by the tranquil Lake Clara Meer and the calming woods of Piedmont park. It is 180 acres of greenery and park area and adjoins the Atlanta Botanical Garden - an additional www.Coldplaytourtickets.org great place to go to for nature enthusiasts. With more than 30 acres of gardens, forest, wild flower trails and the ten,000 sq.-foot Fuqua Orchid Middle - you will love to get lost in the wild and invest the day roaming about in the wild elegance of it all.	{ "pile_set_name": "Pile-CC" }
---------------------- Forwarded by Vince J Kaminski/HOU/ECT on 07/19/2000 06:41 PM --------------------------- From: Paula Corey@ENRON COMMUNICATIONS on 07/17/2000 08:13 AM To: Richard Weeks/Enron Communications@Enron Communications, Daniel Despres/Enron Communications@Enron Communications, Walter Sonksen/Enron Communications@Enron Communications, Vince J Kaminski/HOU/ECT@ECT cc: Subject: FW: DAVE BARRY Thoughts for the day ... ----- Forwarded by Paula Corey/Enron Communications on 07/17/00 08:16 AM ----- Ed.Sweeney@phh.com 07/17/00 07:56 AM To: Paula Corey/Enron Communications@Enron Communications, CIrons3308@aol.com, jsweeney@paperhub.com, lyn.ure@juno.com cc: Subject: FW: DAVE BARRY Subject: THINGS THAT IT TOOK ME 50 YEARS TO LEARN, by DAVE BARRY Never under any circumstances take a sleeping pill and a laxative on the same night. If you had to identify, in one word, the reason why the human race has not achieved, and never will achieve, its full potential, that word would be "meetings". There is a very fine line between "hobby" and "mental illness." People who want to share their religious views with you almost never want you to share yours with them. And when God, who created the entire universe with all of its glories, decides to deliver a message to humanity, He WILL NOT use, as His messenger, a person on cable TV with a bad hairstyle. You should not confuse your career with your life. No matter what happens ... somebody will find a way to take it too seriously. When trouble arises & things look bad, there is always individual who perceives a solution & is willing to take command. Very often, that person is crazy. Nobody cares if you can't dance well. Just get up and dance. A person who is nice to you, but rude to the waiter, is not a nice person. Never lick a steak knife. Take out the fortune before you eat the cookie. "The one thing that unites all human beings, regardless of age, gender, religion, economic status or ethnic background, is that, deep down inside, we ALL believe that we are above average drivers. You should never say anything to a woman that evenremotely suggests that you think she's pregnant unless you can see an actual baby emerging from her at that moment. Your friends love you anyway. - att1.unk	{ "pile_set_name": "Enron Emails" }
Muscle ATP loss and lactate accumulation at different work intensities in the exercising Thoroughbred horse. The effect of 2 min treadmill exercise, at speeds of 6-12 m.s-1 on an incline of 5 degrees, upon muscle adenine nucleotide loss and lactate accumulation was studied in six Thoroughbred horses. Minimal change occurred in the adenosine triphosphate (ATP) content of the middle gluteal muscle at speeds of 10 m.s-1 or less, but significant loss (up to 47%) had occurred in all horses by 12 m.s-1. The decline in ATP significantly correlated with the accumulation of muscle lactate, beginning shortly after the accumulation of 40 mmol.kg-1 dry muscle lactate. Decline in muscle ATP was mirrored closely by the appearance of ammonia, and to a lesser extent, hypoxanthine and uric acid in plasma. The results suggest that peak accumulation of any of these, or simply the concentration at a specified recovery time, may be used as a measure of ATP loss in the musculature as a whole. This was not so in the case of xanthine, which may also be formed from the degradation of guanidine nucleotides. An In-In plot of plasma ammonia against treadmill speed indicated a break point in accumulation between 8 and 9 m.s-1. The kinetics of ammonia accumulation with speed differed from those of lactate.	{ "pile_set_name": "PubMed Abstracts" }
Myoclonic status epilepticus: video presentation. A young woman with juvenile myoclonic epilepsy had recurrent attacks of myoclonic status epilepticus related to a long history of limited compliance and irregular sleep. The diagnosis of this clinical pattern is based mainly on clinical description. A home video captured an attack.	{ "pile_set_name": "PubMed Abstracts" }
2004 (28) Archives It may sound a little puzzling at first, but in Orchard CMS, more than one theme can be active at any given time. The reason for that is that we have an extensibility point that allows a module (or a theme) to participate in the choice of the theme to use, for each request. The motivation for building the theme engine this way was to enable developers to switch themes based on arbitrary criteria, such as user preferences or the user agent (if you want to serve a mobile theme for phones for example). The choice is made between the active themes, which is why there is a difference between the default theme and the active themes. We do have tutorials on the Orchard site, but we can't cover all topics, and recently I've found myself more and more responding to forum questions by pointing people to an existing module that was solving a similar problem to the one the question was about. A CMS like Orchard is, by definition, designed to store content. What differentiates content from other kinds of data is rather subtle. The way I would describe it is by saying that if you would put each instance of a kind of data on its own web page, if it would make sense to add comments to it, or tags, or ratings, then it is content and you can store it in Orchard using all the convenient composition options that it offers. Otherwise, it probably isn't and you can store it using somewhat simpler means that I will now describe.	{ "pile_set_name": "Pile-CC" }
Dr. Howell founded Village Pediatrics in 1998 after serving 3 years as a military pediatrician in a large group. He is a graduate of the University of Arizona College of Medicine and completed his residency at Fitzsimmons Army Medical Center in Aurora, Colorado. He also completed 2 years fellowship training in Child Behavior and Development at Boston University. He enjoys family, friends, church life, outdoor activities and sports. Crystal L. Rainville, MD Dr. Rainville received her undergraduate degree from Tufts University and her Medical Doctorate from the University of Massachusetts Medical School. She completed her pediatrics residency at Boston's Floating Hospital for Children where she received numerous awards and served as chief resident. A life-long southern Massachusetts resident, Dr. Rainville is looking forward to continuing her family-focused approach to children's health. Yarelis Matos, PsyD Dr. Matos graduated in 1996 from the University of Massachusetts with a Bachelor of Arts and Sciences degree in Psychology. She went on to complete her Masters of Science in Psychology in 1998 and received her Doctor of Psychology in 2000 from the Carlos Albizu University in Miami, Florida. Dr. Matos has extensive experience working with children from 5 to 17 years of age, and also with children of families with multi-cultural and diverse backgrounds. Her clinical training has focused on adolescents with learning, behavioral and emotional difficulties. Charlotte Rydberg, PNP Charlotte graduated from Immanuel Hospital School of Nursing in Omaha, Nebraska. She completed her Pediatrics Nurse Practitioner certification at Northeastern University in Boston, and has a degree in Psychology from Barat College in Lake Forest, Illinois. Charlotte enjoys traveling with her family, skiing, outdoor activities, baking and singing in her church choir. Mary Catherine Finn, PNP Mary Catherine is a graduate of Cornell University School of Nursing in New York. She received a Master's degree in Pediatric Nursing from Boston College and became certified as a Pediatric Nurse Practitioner. She enjoys playing tennis, skiing, reading, and spending time with friends. Christine Lattuada, PNP Christine received her undergraduate degree from Skidmore College in New York. She obtained her Masters of Science in Nursing from Northeastern University.	{ "pile_set_name": "Pile-CC" }
Q: Mediawiki: how to allow users to edit their User pages (but not other pages) Is there a permission in Mediawiki that allows a user with username A-User to create and edit pages A-User, A-User/A-new-page etc but not to edit other pages? A: Not by default. You can find the list of permissions here, and the permissions each user group on a wiki has at Special:ListGroupRights. There is editmyusercss/editmyuserjs which allows users to edit user subpages ending in .css/.js, but probably even that requires the normal edit right. It would be pretty simple to write an extension granting that right, though. See UserPageEditProtection for a similar example (which does the opposite: instead of granting the right to edit own subpages, it takes away the right to edit others' subpages). You could make it do what you want by tweaking the return values in the userCan hook a bit.	{ "pile_set_name": "StackExchange" }
Q: Gallerific .selected Element I'm having a problem with the selected element in Galleriffic. When an image is selected it is not highlighting the correct thumb, it's highlighting the previous one. Edited to remove a soon to be dead link of the website. JS: <script type="text/javascript"> jQuery(document).ready(function($) { // We only want these styles applied when javascript is enabled $('div.navigation').css({'width' : '100%', 'clear' : 'both'}); $('div.content').css('display', 'block'); // Initially set opacity on thumbs and add // additional styling for hover effect on thumbs var onMouseOutOpacity = .7; $('#thumbs ul.thumbs li').opacityrollover({ mouseOutOpacity: onMouseOutOpacity, mouseOverOpacity: 1.0, fadeSpeed: 'fast', exemptionSelector: '.selected' }); // Initialize Advanced Galleriffic Gallery var gallery = $('#thumbs').galleriffic({ delay: 2500, preloadAhead: 10, enableTopPager: true, enableBottomPager: true, maxPagesToShow: 7, imageContainerSel: '#slideshow', controlsContainerSel: '#controls', captionContainerSel: '#caption', loadingContainerSel: '#loading', renderSSControls: false, renderNavControls: false, playLinkText: 'Play Slideshow', pauseLinkText: 'Pause Slideshow', prevLinkText: '&lsaquo; Previous Photo', nextLinkText: 'Next Photo &rsaquo;', nextPageLinkText: 'Next &rsaquo;', prevPageLinkText: '&lsaquo; Prev', enableHistory: false, autoStart: false, syncTransitions: true, defaultTransitionDuration: 900, onSlideChange: function(prevIndex, nextIndex) { // 'this' refers to the gallery, which is an extension of $('#thumbs') this.find('ul.thumbs').children() .eq(prevIndex).fadeTo('fast', onMouseOutOpacity).end() .eq(nextIndex).fadeTo('fast', 1.0); }, onPageTransitionOut: function(callback) { this.fadeTo('fast', 0.0, callback); }, onPageTransitionIn: function() { this.fadeTo('fast', 1.0); } }); }); </script> CSS div.slideshow a.advance-link { display: block; width: 820px; height: 388px; /* This should be set to be at least the height of the largest image in the slideshow / line-height: 0px; / This should be set to be at least the height of the largest image in the slideshow / text-align: center; } div.slideshow a.advance-link:hover, div.slideshow a.advance-link:active, div.slideshow a.advance-link:visited { text-decoration: none; } div.download { float: right; } div.image-title { font-weight: bold; font-size: 1.4em; } div.image-desc { } div.navigation { / The navigation style is set using jQuery so that the javascript specific styles won't be applied unless javascript is enabled. */ text-align: left; } ul.thumbs { clear: both; margin: 0; padding: 0; background-color: #FFF; } ul.thumbs li { display:inline; margin-right: 10px; padding: 0; list-style: none; } a.thumb { display:inline-block; text-decoration: none; } ul.thumbs li.selected a.thumb { color: #0C3 } a.thumb:focus { outline: none; text-decoration: none; } ul.thumbs img { border: none; display: block; } div.pagination { clear: both; } div.navigation div.top { padding-top: 10px; margin-top: 10px; text-align: center; background-color: #fff; } div.navigation div.bottom { text-align: center; } div.pagination a, div.pagination span.current, div.pagination span.ellipsis { display: block; float: left; } div.pagination a:hover { background-color: #eee; text-decoration: none; } div.pagination span.current { font-weight: bold; background-color: #000; border-color: #000; color: #fff; } div.pagination span.ellipsis { border: none; } A: There was an indexing problem, the was considered like an index which was causing it to start off at the wrong place. Solved it! :)	{ "pile_set_name": "StackExchange" }
Q: Keeping XML in Memory between Webservice Calls First, I don't want to use a database or a local file. Is it possible to store variables in memory so they don't have to be created each time the webservice is called? The problem is that FullCompanyListCreateXML(); takes about 1 Minute to create the XDocument. So is there any way to prevent that the xml variable is dropped after the webservice call is finished? [WebMethod(CacheDuration = 120)] public String FullCooperationListChunkGet(int part, int chunksize) { StringBuilder output_xml = new StringBuilder(); XDocument xml = FullCompanyListCreateXML(); IEnumerable<XElement> xml_query = xml.Root.Elements("Cooperation").Skip(part * chunksize).Take(chunksize); foreach (XElement x in xml_query) { output_xml.Append(x.ToString()); } output_xml.Insert(0, "<Cooperations>"); output_xml.Append("</Cooperations>"); return output_xml.ToString().Zip(); } Thanks, Henrik A: 2 ways: 1) You can add a global.asax class to the web service which will get created when the web application is first started, and will persist for as long as the worker process keeps it in memory. Override the 2) create a static class to hold the values See this blog entry, or this post on the topic of adding the global.asax class to web services. You can create things when the session starts, or when the application starts by overriding the Session_Start or Application_Start methods	{ "pile_set_name": "StackExchange" }
Q: Set limits for add content in text file with PHP I need to create a list of last logged members in my website, but i don't wanna user MySQL. i did some search in stackoverflow and Google and wrote this code: ////////////CHECK LIMIT $storage = "engine/data/write.txt"; $readz = file_get_contents($storage); $listz = explode('\|\|\|',$readz); $counter = count( $listz ); if($counter > "3"){ $stop = "1"; }else{ $stop = "0"; } if($stop == "0"){ ///REMOVE MEMBER IF AVAILABLE if ( preg_match("<!-- UserID: {$member_id} -->", $readz)){ $content = file_get_contents($storage); $content = str_replace("<!-- UserID: {$member_id} -->".$user."\|\|\|", '', $content); file_put_contents($storage, $content); } //ADD MEMBER AGAIN if ( !preg_match("<!-- UserID: {$member_id} -->", $readz)){ $beonline_file = fopen($storage, "a+"); fwrite($beonline_file, "<!-- UserID: {$member_id} -->".$user."\|\|\|"); fclose($beonline_file); } } Problem is i can't set limit! how i can edit this code to set limit to add only 20 users in text file? A: Maybe you can do this? if ( !preg_match("<!-- UserID: {$member_id} -->", $readz)){ $nlistz = explode('\|\|\|',$readz); if(count( $nlistz ) == 20){ array_shift($nlistz); $newlistz = implode("\|\|\|",$nlistz); $beonline_file = fopen($storage, "w+"); fwrite($beonline_file, $newlistz."\|\|\|<!-- UserID: {$member_id} -->".$user."\|\|\|"); fclose($beonline_file); }else{ $beonline_file = fopen($storage, "a+"); fwrite($beonline_file, "<!-- UserID: {$member_id} -->".$user."\|\|\|"); fclose($beonline_file); } }	{ "pile_set_name": "StackExchange" }
Q: Value not showing for input field using one way binding angular2 Objective: Get a collection of values based on the dropdown selection and place them in hidden input fields to be included in my model; The relative html: <select class="selectFoo" (change)="onSelect($event.target.value)" name="FooName" ngModel> <option selected="selected">--Select--</option> <option ngFor="let foo of foos" [value]="foo.ID">{{foo.Name}} </option> </select> <input type="hidden" [value]="fooAddress" name="FooAddress" ngModel/> In the code above I called a function named OnSelect to get the data about the selected foo. The foos are populated using a webservice call. Here is the snippet from my ts file. import { Component, OnInit } from '@angular/core'; import { Foo } from './model'; import { DataService } from './data.service'; @Component({ moduleId: module.id, selector: 'add-on', templateUrl: './app.component.html' }) export class AppComponent implements OnInit { foos : Foo[]; selectedFoo: Foo; fooAddress: string; onSelect(fooID){ this.selectedFoo = null; for(var i = 0; i < this.foos.length; i++) { console.log(this.foos[i].ID); if(this.foos[i].ID == fooID){ this.selectedFoo = this.foos[i]; this.fooAddress = this.selectedFoo.Address.toString(); } } } } I originally tried one way binding my value to the selectedFoo but I was getting an error indicating my Address value wasn't defined. I noticed I could set the value equal to selectedFoo and it didn't error. So i created a new variable that was set to the fooAddress based on the selected foo. I get no value even though while stepping through the code I see it has a value. How can I get my value to populate so I can use it in my model? Let me know if I need to provide anything else. Thanks! A: If I am correctly understanding what you are after then something like this would work: <select name="FooName" [(ngModel)]="selectedFoo"> <option>--Select--</option> <option ngFor="let foo of foos" [ngValue]="foo" >{{foo.Name}}</option> </select> <input type="hidden" [value]="selectedFoo?.Address" name="FooAddress" /> //Assuming your 'foo' items are e.g. { ID: 1, Name: 'Hello', Address: '123 Hello St'} Here you can bind the Address property of the selectedFoo directly to your hidden input field, rather than needing to handle the (change) event.	{ "pile_set_name": "StackExchange" }

Barbara Ingram School for the Arts Barbara Ingram School for the Arts is a magnet high school that opened its doors for gifted art students in August 2009. Currently there are eight different majors: Theatre, Musical Theatre, Technical Theatre, Vocal Music, Instrumental Music, Dance, Creative Writing, and Visual Arts. The Literary Arts program was added at the start of the 2011-2012 school year. The school building is located adjacent to the Maryland Theatre in the arts and entertainment district of downtown Hagerstown, Washington County, Maryland, United States. Despite being a public school, applications and auditions are part of a process needed in order to be accepted and then enrolled. Barbara Ingram School is also unique in that it will accept students not only from all of Washington County but also from proximate Maryland counties and areas in nearby Pennsylvania and West Virginia. Rob Hovermale is the current Principal. There are no sports teams originating from the school. BISFA is named for late Barbara Ingram, a Hagerstown native and former public school art teacher. Performances and exhibitions All-School Musicals 2009-2010 The first all school musical was Thoroughly Modern Millie and received rave reviews. 2010-2011 The all school musical The Phantom of the Opera was performed during the 2010 to 2011 school year. Barbara Ingram School for the Arts was one of the first high schools to perform this musical. Not only was the performance well received, it is also considered a milestone in the revival of downtown Hagerstown. 2011-2012 The 2012 all school musical was Disney's Beauty and The Beast and ran for two weekends at the Maryland Theatre. 2012-2013 The 2013 Barbara Ingram was Legally Blonde and received some of the highest praise for acting. It was the final musical for the first full graduating class. 2013-2014 In August 2013, Barbara Ingram announced that its fifth all-school musical will be the classic The Wizard of Oz. It was performed in April 2014. 2014-2015 In April 2015, Shrek the Musical was performed by students from all departments. 2015-2016 In April 2016, Barbara Ingram performed "The little Mermaid" as their 7th all school musical. 2016-2017 In April 2017, Barbara Ingram presented "Seussical" at the Maryland Theater as their 8th musical. 2017-2018 In April 2018, Barbara Ingram presented “Hairspray” at the Maryland Theater as their 9th musical. 2018-2019 In April 2019, Barbara Ingram presented "Mamma Mia!" at the Maryland Theater as their 10th musical. Additional Performances In the summer of 2010 thirty-seven vocalists traveled to New York City to perform in Eric Whitacre's Paradise Lost: Shadows and Wings at Carnegie Hall. The dance department has also traveled to perform at the Orange Bowl. In 2010, the choral ensemble had the opportunity to sing as the backup choir for Todd Rundgren's fall tour. The Barbara Ingram Music Theatre Ensemble, the "Phantasmics", performed at Downtown Disney in Orlando Florida in the summer of 2011 and in Disney and Universal theme parks in 2012. There are many performances year-round at the school, including the yearly Holiday Spectacular, in which all disciplines participate. Performances have occurred in The Maryland Theatre, in the downstairs "Black Box" of the main building, and at other locations around the community. Mascot The Barbara Ingram school mascot is 'The Phantom,' alluding to the alleged ghost that haunts the lower level of the building. The school colors are purple, black and silver. Notable Alumni Nathaniel Philp, Former Volunteer Firefighter, Former Assistant Manager of Moe's Southwest Grill (Hagerstown) References External links Official site Washington County Public Schools: Barbara Ingram School for the Arts Category:Public high schools in Maryland Category:Public schools in Washington County, Maryland Category:Buildings and structures in Hagerstown, Maryland Category:Magnet schools in Maryland Category:Performing arts in Maryland Category:2009 establishments in Maryland Category:Educational institutions established in 2009

{ "pile_set_name": "Wikipedia (en)" }

Lolita, the whale, has been living at the Miami Seaquarium since her capture off the northern Pacific Coast in 1970. © Flickr / Ross Cobb The tank measures 80 x 60 feet wide and 20 feet deep. People for the Ethical Treatment of Animals (PETA), the Animal Legal Defense Fund and other groups had sued the US Department of Agriculture in 2012, claiming the tank Lolita lives in violates the Animal Welfare Act and that regulators have been "rubber-stamping" an aquarium’s license to keep her. "Lolita is being held in the smallest orca tank in America, she has no shelter from the hot sun in Miami, she has no company of a single other orca. And all of those violate the basic standards of the Animal Welfare Act," PETA attorney Delcianna Winders said. The tank measures 80 x 60 feet wide and 20 feet deep. The Judge dismissed the lawsuit in March 2014, on the terms that the agency is allowed to reissue licenses without re-inspecting facilities. Activists argue now that the US District Court should have looked into the animal rights abuses before approving the USDA’s license renewal. "It’s absurd to give out licenses where you know there are blatant violations going on and that undermines the purpose of the animal welfare act," said Winders. But Seaquarium and USDA lawyers beg to differ. Renewing the license only required an annual application, an annual report from the aquarium and a $100 fee, said Assistant US Attorney Anthony Erickson-Pogorzelski. In another attempt to free Lolita, the federal government agreed to list her as an endangered species in February, which would allow for her release into the wild. However, seaquarium officials are skeptical, fearing she would see the fate of Keiko, the orca in the 1993 movie "Free Willy." Keiko was released into the waters off Iceland in 2002 but died a year later after being rejected by wild orcas.

{ "pile_set_name": "OpenWebText2" }

Subungual melanoma--case report and literature review. Subungual melanoma is an infrequent malignant tumor which, despite its visibility and easy accessibility, is often misdiagnosed and thus inappropriately treated. This delay in recognition often results in a worsened prognosis. All persistent nail lesions which do not respond to conservative treatment, whether pigmented or not, should undergo excisional biopsy and pathologic examination. A case of subungual melanoma is presented to illustrate the typical presentation and clinical characteristics.

{ "pile_set_name": "PubMed Abstracts" }

(a) Field of the Invention The present invention relates to a channel state feedback method by quantizing time domain channel coefficients. (b) Description of the Related Art In a multiple-user multiple-antenna communication system, communication between a plurality of terminals and base stations is simultaneously performed at the same time and same frequency through a spatially identified signal. In this instance, a terminal must not be interfered with by a signal transmitted to another user during communication through a single receiving antenna. For this, a base station performs an appropriate beamforming process based on channel information with the terminal. In detail, one part of information to be known by the base station in the multiple-user multiple-antenna communication system is channel information with the terminal to be simultaneously communicated by the base station. In the frequency division duplex (FDD) system, the terminal measures channel information between the base station and the terminal and transmits a measured channel coefficient (a channel value) to the base station so that the base station knows the channel information. Considering the existing multiple-user multiple-antenna communication system, the terminal transmits a quantized direction of a channel vector for the base station and the terminal and a corresponding signal-to-noise ratio (SNR) value to the base station. Here, the channel vector indicates a channel state between the base station and the terminal. The channel state is expressed as a channel vector assuming that the base station has a plurality of transmitting antennas and the terminal has a single receiving antenna. The base station selects a plurality of appropriate terminals from among many terminals in consideration of the channel state, and transmits data to the selected terminals. In this instance, what is to be considered when the terminals are selected is selection of the terminals having less interference between the quantized directions of the channel vectors of the selected terminals and having a great SNR. The orthogonal frequency division multiplexing (OFDM) system is widely used for transmitting signals in the current communication system. However, the above-noted scheme is difficult to apply to the OFDM system because it is proposed for a single-carrier system. This is because channel state transmission in the frequency domain from the terminal to the base station is not performed by all subcarriers, but several subcarriers are sampled by considering the limited feedback resource and the channel state is then transmitted on the sampled subcarrier in the OFDM system. The base station uses the channel state on the sampled subcarrier, and performs an interpolation process for checking state information of the subcarrier receiving no channel state value to know the channel state on the subcarrier. However, the above-noted existing method transmits not the channel vector but the quantized value of the channel vector direction to the base station. Therefore, it is difficult to know directions of other subcarriers by using the quantized direction of the channel vector on a specific sampled subcarrier. The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.

{ "pile_set_name": "USPTO Backgrounds" }

When you subscribe we will use the information you provide to send you these newsletters. Sometimes they’ll include recommendations for other related newsletters or services we offer. OurPrivacy Noticeexplains more about how we use your data, and your rights. You can unsubscribe at any time. Read More Related Articles Restrictions not imposed While at the secure facility on Merseyside, Arnold gradually improved and was moved to the lower-security Edenfield Centre in Prestwich, Manchester, in late 2011. Dr Andrew Haddock, a forensic psychiatrist who was involved in Arnold’s care three years prior to the murder, recommended in January 2013 that should Arnold leave care it should be under special legal orders requiring supervision to prevent a relapse. The court heard when Arnold was eventually released a specialist tribunal chose not to impose such a restriction, called a Community Treatment Order. While the details of that hearing were not discussed, Arnold’s treatment history - including that offered through what is now the Greater Manchester Mental Health NHS Foundation Trust - is under the scope of Coroner Kevin McLoughlin’s investigation. Read More Related Articles Double tragedy Earlier in the day Maureen Lound, Mr Lound’s mum, called for Arnold’s past care - and his involvement with the police and courts, to come under scrutiny. She said: “I bear no malice towards Arnold, he was a very sick man and was moved within days of his arrest to Ashworth special hospital, where he remained until his conviction. “I do not blame Arnold for Will’s death. Unfortunately Arnold did not receive the care and treatment he needed to live safely in the community. A man like Arnold should not have been allowed to roam the streets unsupervised.” Ms Lound also paid tribute to her daughter, Gini, who tragically took her own life just months after her brother’s died. Read More Related Articles Mistakes followed by murder Jurors were told Arnold, homeless when he killed Mr Lound on February 7, 2016, was on the streets despite breaching bail conditions. He was bailed by magistrates following a theft charge in December 2015. He failed to reside at a specific address but was then arrested over shoplifting allegations and breach of bail the following month. William Lound Despite an application by Greater Manchester Police for him to be remanded in custody, magistrates re-bailed him with stricter conditions. He failed to comply with them but an “administrative error” by the force meant the bail condition was not registered. This meant officers were not aware of the further breach and no effort to arrest Arnold over it was made. Ms Lound said she believed an arrest would have presented magistrates with another opportunity to remand him - therefore taking him off the streets before he murdered her son.

{ "pile_set_name": "Pile-CC" }

The ethics of using AOL search data Can researchers ethically use the search data that AOL released last week? Like one of the forest fires that each summer consumes a major chunk of California real estate, the AOL data release scandal has quickly exploded from a campfire into an inferno. Giving the search history of 650,000 users to researchers seemed like a good idea when Abdur Chowdhury first posted it, but the move quickly claimed Dr. Chowdhury's job, as well as that of a supervisor. Maureen Govern, the company's CTO, also resigned the same day. Now the flames of controversy have spread into academia, where researchers desperately want to use the new data set but feel caught in an ethical dilemma. Given that AOL has already pulled the data, and given that it can be used to uniquely identify some individuals, should researchers refuse to use the data for their work? Jon Kleinberg, a computer science professor at Cornell, told the New York Times that he won't touch the hundreds of megabytes of search query data. "Now it's sitting there, in cold storage," he said. "The number of things it reveals about individual people seems much too much. In general, you don't want to do research on tainted data." It would be much easier for the researchers to turn down this forbidden fruit if apples grew on every tree. But when it comes to quality search data, options are limited unless you work for one of the major search engines (or are with the government). For researchers who have been stuck with the same search data for almost 10 years, the new information comes like rain to a Dust Bowl farmer. Jeffrey Seglin, author of a syndicated ethics column called "The Right Thing" (and a book by the same name), tells Ars that, in his view, the ethical obligation "here falls upon the companies that are releasing the data. If these companies have made a commitment to keep individual behavior private, then they have an obligation to make sure that the data they release can't be manipulated to discover the identities of the users." When it comes to research, though, Seglin has no problem with people who want to use the data for their own projects—provided they do not cross one important boundary. "If researchers are using the data to identify individual users, I believe they've crossed an ethical line," Seglin says. But if they don't try to match up the data with actual people, he believes that they are (ethically) in the clear. One unfortunate side effect of the entire AOL debacle is that search engines will now be more wary about releasing data— and they were already stingy to begin with. On the other hand, when they do release data in the future, search engines will certainly pay far more attention to the privacy implications of what they're doing.

{ "pile_set_name": "Pile-CC" }

NEW YORK — "The Daily Show" is unveiling the Donald J. Trump Presidential Twitter Library this weekend. "He is a damn fine twitterer," "Daily Show" host Trevor Noah said. The pop-up exhibit will be at 3 West 57th Street in Manhattan, not far from Trump Tower, Comedy Central announced. It will feature some of the president's better known one-shots, organized around such categories as "SAD! A Retrospective" and "The Commander-In-Tweet." The "Daily Show" will highlight Trump's insults and contradictions and allow "verified survivors" to remember being on the receiving end of his social media outbursts. "I think it's a chance for us to really understand the way in which our commander in chief communicates," said show correspondent Jordan Klepper. The twitter library also features an interactive Trump nickname generator. There's a locked vault jokingly marked as 'Trump's Tax Returns.' But the true highlights are all in 140 characters or less. Daily Show Correspondent Hasan Minhaj's favorite tweet is Trump's well known Cinco de Mayo tweet featuring the taco bowl at Trump Tower. He calls it the Mona Lisa tweet. "It's both pandering to minorities while also plugging his business," Minhaj said. Favorites could change as President Trump is a frequent tweeter. A siren will sound in the library every time Trump tweets. "Whenever he does tweet, a siren will go off bing bing bing bong bing, letting everyone know in the building that he is tweeting, so to either run outside and call loved ones or run underneath a table," Minhaj said. The exhibit runs Friday through Sunday, and will be open from 11 a.m. to 7 p.m. Admission is free.

{ "pile_set_name": "OpenWebText2" }

Introduction {#s1} ============ Chinese herbal medicines (CHMs) were the main treatment method used in ancient times by the Chinese to combat disease. As early as the Qin and Han Dynasty (around 221 BCE to 220 CE), *Sheng Nong\'s Herbal Classic* recorded 365 medicines. By the time of the Ming Dynasty (1368--1644), the number of CHMs listed in the book of *Compendium of Materia Medica* had increased to 1892. Most herbal medicines in such publications have been used constantly throughout medical history and are still applied in practice today. For example, according to *Sheng Nong\'s Herbal Classic, Coptis chinensis* Franch. was found to relieve abdominal pain and diarrhea and this herb is still widely used in China for the treatment of diarrhea or dysentery. Further, *Panax notoginseng* (Burk.) F. H. Chen, a traditional herb was initially used to stop bleeding, promote blood circulation and ease pain, was recorded in the *Compendium of Materia Medica*. It is now commonly used in cases of trauma and cardiovascular, and cerebrovascular diseases. A recent meta-analysis further demonstrated that several *P. notoginseng* preparations are beneficial for patients with unstable angina pectoris (Song et al., [@B121]). Despite the positive effects of CHMs, little is known about their effective constituents, bioactive ingredients, and mechanisms of action. Therefore, in addition to the clinical applications mentioned in classic texts, understanding the specific active ingredients and clarifying the mechanisms of action of these compounds would facilitate the improved application of CHMs. The discovery of the drug artemisinin best illustrates the importance of CHM to the world (Tu, [@B133]), inspiring the notion that, through study of their bioactive ingredients, CHMs can help people around the world to conquer life-threatening diseases. Non-coding RNA molecules (ncRNAs), which mainly comprise miRNA, lncRNA, and circRNA, do not encode proteins; however, as the most abundant class of RNA (at least 90%) (Sana et al., [@B113]), ncRNAs have important functions in gene regulation and are involved in pathological processes contributing to many diseases (Batista and Chang, [@B4]; Memczak et al., [@B97]; Zhang et al., [@B177]), particularly cancer, and cardiovascular and nervous system diseases. Moreover, circRNA and lncRNA act as competitive endogenous RNAs (ceRNA), which are natural miRNA sponges that influence miRNA-induced gene silencing via miRNA response elements (Tay et al., [@B127]). Thus, complex regulatory networks exist, comprising circRNA, lncRNA, miRNA, and target genes. Unraveling of this complexity has laid the foundation for a comprehensive understanding of the pathology and treatment of diseases influenced by gene regulatory networks, rather than only core disease-related genes (Boyle et al., [@B9]). Excitingly, recent studies (Feng et al., [@B30]; Tian F. et al., [@B128]; Zhou Y. et al., [@B196]) have revealed that some miRNA, lncRNA, circRNA, and ceRNA crosstalk can be regulated by bioactive ingredients from CHMs, which often have multiple targets ([Table 1](#T1){ref-type="table"}). By influencing regulatory mechanisms, including pro-apoptosis (Feng et al., [@B30]), anti-proliferation and anti-migration (Liu T. et al., [@B83]), anti-inflammation (Fan et al., [@B28]), anti-atherosclerosis (Han et al., [@B42]), anti-infection (Liu et al., [@B79]), anti-senescence (Zhang J. et al., [@B178]), and suppression of structural remodeling (Liu L. et al., [@B81]), these ingredients exert protective functions in cancer, cardiovascular disease, nervous system disease, inflammatory bowel disease, asthma, infectious diseases, and senescence-related diseases. ###### Detailed information on bioactive ingredients targeting ncRNAs. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ **No**. **Name of ingredient** **Original plant** **ncRNA target** **Gene/protein/pathway** **Disease** --------- ------------------------------------------ ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------ ---------------------------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- 1 Berberine *Coptis chinensis* Franch., *Berberis soulieana* Schneid, *Berberis poiretii* Schneid., *Berberis vernae* Schneid, *Berberis wilsoniae* Hemsl., and *Platycladus orientalis* (Linn.) Franco. miR-99a\~125b (Feng et al., [@B30])\ RAC1, NFκB1, MYC, JUN, and CCND1 (Feng et al., [@B30])\ Multiple myeloma (Luo et al., [@B89]; Feng et al., [@B30]; Yin et al., [@B166]) miR-21 (Luo et al., [@B89])\ IL6/STAT3, PDCD4 (Luo et al., [@B89])\ miR-19a/92a (Yin et al., [@B166]) P53 signaling pathway (Luo et al., [@B89])\ P53, ERB, and MAPK signaling pathways (Feng et al., [@B30]) miR-23a (Wang N. et al., [@B141]) NEK6, P53, P21, GADD45α (Wang N. et al., [@B141]) Hepatocellular carcinoma (Wang N. et al., [@B141]) miR-152\ DNMT1, DNMT3A, DNMT3B, CDK4\ Colorectal cancer (Su et al., [@B123]; Huang et al., [@B48]) miR-429\ (Su et al., [@B123]; Huang et al., [@B48])\ miR-29a (Huang et al., [@B48])\ Pin1-β-catenin-cyclin D1 signaling pathway (Su et al., [@B123]) miR-296-5p (Su et al., [@B123]) miR-34a\ CDK4, CyclinD1, CyclinE, CDK2 (Yang L. H. et al., [@B159]) Melanoma (Yang L. H. et al., [@B159]) miR-154\ miR-26a\ miR-124 (Yang L. H. et al., [@B159]) miR-93 (Chen et al., [@B17]) miR-93/PTEN/AKT signaling pathway (Chen et al., [@B17]) Ovarian cancer (Chen et al., [@B17]) miR-203 (You et al., [@B167]) BCL-w (You et al., [@B167]) Gastric cancer (You et al., [@B167]) miR-27a miR-27b (Wu et al., [@B154]) PPAR-γ (Wu et al., [@B154]) Obesity (Wu et al., [@B154]) lncRNA MRAK052686 (Yuan et al., [@B172]) NRF2 (Yuan et al., [@B172]) Steatotic liver (Yuan et al., [@B172]; Li C. H. et al., [@B69]) miR-373 (Li C. H. et al., [@B69]) EGR1, AKT1\ AKT-mTOR-S6K signaling pathway (Li C. H. et al., [@B69]) miR-29a-3p (Mao et al., [@B94]) IRS1 (Mao et al., [@B94]) Insulin resistance (Mao et al., [@B94]) 2 Artesunate *Artemisia annua* L. lncRNA UCA1\ lncRNA UCA1/miR-184/BCL-2 axis (Zhou S. et al., [@B194]) Prostate cancer (Zhou S. et al., [@B194]) miR-184 (Zhou S. et al., [@B194]) 3 Triptolide/ Triptonide *Tripterygium wilfordii* Hook. f miR-21 (Li et al., [@B74]) Caspase-3 and 9, PTEN (Li et al., [@B74]) Non-small cell lung cancer (Li et al., [@B74]) 227 miRNAs (Reno et al., [@B109]) Focal adhesion kinase (Reno et al., [@B109]) Lung cancer (Reno et al., [@B109]) miR-17-92\ c-MYC, BIM, PTEN, and P21 (Li S. G. et al., [@B71]) Hepatocellular carcinoma (Li S. G. et al., [@B71]) miR-106b-25 (Li S. G. et al., [@B71]) lncRNA THOR (Wang et al., [@B143]) IGF2BP1, Myc, IGF2, and Gli1 (Wang et al., [@B143]) Nasopharyngeal carcinoma (Wang et al., [@B143]) 4 Ailanthone *Ailanthus altissima* (Mill.) Swingle miR-21 (Yang P. et al., [@B160]) caspase 3, caspase 9, Beclin-1, LC3-II, p62, and cyclin D1\ Vestibular schwannomas (Yang P. et al., [@B160]) Ras/Raf/MEK/ERK and mTOR pathways (Yang P. et al., [@B160]) 5 Cordycepin/Soya-cerebroside *Cordyceps militaris* miR-21 (Yang et al., [@B157]) PTEN, Akt (Yang et al., [@B157]) Renal cell carcinoma (Yang et al., [@B157]) miR-432 (Liu S. C. et al., [@B82]) MCP-1\ \ AMPK and AKT signaling pathways (Liu S. C. et al., [@B82]) Osteoarthritis\ (Liu S. C. et al., [@B82]) 6 Tubeimoside I *Bolbostemma paniculatum* (Maxim) Franquet miR-126-5p (Shi et al., [@B118]) VEGF-A/VEGFR-2/ERK signaling pathway (Shi et al., [@B118]) Non-small cell lung cancer (Shi et al., [@B118]) 7 Oridonin *Rabdosia rubescens* (Hemsl.) Hara 105 miRNAs (Gui et al., [@B37]) / Laryngeal cancer (Gui et al., [@B37]) 8 Curcumin *Curcuma longa* L. miR-208 (Guo H. et al., [@B38]) CDKN1A (Guo H. et al., [@B38]) Prostate cancer (Guo H. et al., [@B38]; Cao et al., [@B11]; Liu W. L. et al., [@B84]; Zhang et al., [@B176]) miR-145\ CCND1, CDK4, OCT4, CD44, and CD133 (Liu W. L. et al., [@B84]) lncRNA-ROR (Liu W. L. et al., [@B84]) miR-770-5p\ DLK1-DIO3 (Zhang et al., [@B176]) miR-1247 (Zhang et al., [@B176]) miR-143 (Cao et al., [@B11]) PGK1, FOXD3 (Cao et al., [@B11]) miR-98 (Liu W. L. et al., [@B84]) LIN28A, MMP 2, MMP9 (Liu W. L. et al., [@B84]) Lung cancer (Tang et al., [@B126]; Liu W. L. et al., [@B84]) miR-186\* (Tang et al., [@B126]) / miR-203 (Saini et al., [@B112]) AKT2, SRC (Saini et al., [@B112]) Bladder cancer (Saini et al., [@B112]) miR-33b (Sun et al., [@B124]) XIAP (Sun et al., [@B124]) Gastric cancer (Sun et al., [@B124]) miR-192-5p (Jin et al., [@B57]) PI3K/AKT signaling pathway (Jin et al., [@B57]) Non-small cell lung cancer (Jin et al., [@B57]) miR-7 (Ma et al., [@B92]) SET8 (Ma et al., [@B92]) Pancreatic cancer (Ma et al., [@B92]) miR-30c (Lu et al., [@B87]) MTA1 (Lu et al., [@B87]) Paclitaxel-resistant non-small-cell lung cancer (Lu et al., [@B87]) miR-29b-1-5p (Zhou S. et al., [@B194]) PPARG, RRM2, SRSF1, EPAS1, MAPK, mTOR, PI3K-AKT, AMPK, TNF\ Adriamycin-resistant breast cancer (Zhou S. et al., [@B194]) RAS signaling pathways (Zhou S. et al., [@B194]) lncRNA AK294004 (Wang Q. et al., [@B142]) Cyclin D1(Wang Q. et al., [@B142]) Radioresistant nasopharyngeal carcinoma (Wang N. et al., [@B141]) miR-146a (Wu et al., [@B152])\ NF-κB signaling (Wu et al., [@B152])P38 (Li et al., [@B73]) Glioblastoma (Wu et al., [@B152]; Li et al., [@B73]) miR-378 (Li et al., [@B73]) miR-34a (Guo et al., [@B39]) BCL-2, BMI-1 (Guo et al., [@B39]) Breast cancer (Guo et al., [@B39]; Zhou et al., [@B195]) miR-29b-1-5p\ DDIT4, EPAS1, VEGFA, RPS14, and DCDC2 (Zhou et al., [@B195]) miR-29b-3p\ miR-6068\ miR-6790-5p\ miR-4417 (Zhou et al., [@B195]) miR-122\ FGF2, MMP2, VEGF, HGF, TF, FVII (Zhang S. et al., [@B184]) Hepatocellular Carcinoma (Guo Y. et al., [@B40]; Liu W. L. et al., [@B84]) miR-221 (Zhang S. et al., [@B184]) lncRNA AK125910 (Guo Y. et al., [@B40]) miR-155 (Ma F. et al., [@B91]) TNF-α, IL-6\ LPS-induced inflammatory response (Ma F. et al., [@B91]) PI3K/AKT pathway (Ma F. et al., [@B91]) miR-17-5p (Tian L. et al., [@B129]) WNT signaling pathway effector TCF7l2 (Tian L. et al., [@B129]) Adipogenic differentiation (Tian L. et al., [@B129]) 9 Shikonin *Lithospermum erythrorhizon* Sieb. et Zucc. miR-106b (Huang and Hu, [@B47]) miR-106b/PTEN/AKT/mTOR signaling pathway (Huang and Hu, [@B47]) Endometrioid endometrial cancer (Huang and Hu, [@B47]) miR-128 (Wei et al., [@B148]) BAX (Wei et al., [@B148]) Breast cancer (Wei et al., [@B148]) miR-143 (Liu et al., [@B80]) BAG3 (Liu et al., [@B80]) Glioblastoma (Liu et al., [@B80]) 10 Paeoniflorin *Paeonia lactiflora* Pall. miR-16 (Li W. et al., [@B72]) MMP-9 (Li W. et al., [@B72]) Glioma (Li W. et al., [@B72]) 11 Honokiol *Magnolia grandiflora* miR-34a (Avtanski et al., [@B3]) STAT3\ Breast tumor (Avtanski et al., [@B3]) WNT1-MTA1-β-catenin signaling (Avtanski et al., [@B3]) 12 Schisandrin B *Schisandra sphenanthera* Rehd. et Wils. miR-150\ miR-150/ lncRNA BCYRN1/ cell proliferation axis (Zhang X. Y. et al., [@B185]) Asthma (Lu et al., [@B85]) lncRNA BCYRN1 (Zhang X. Y. et al., [@B185]) 13 Resveratrol Grapes, blueberries, *Morus alba* L.,\ lncRNA MALAT1 (Ji et al., [@B52]) c-MYC, MMP-7\ Colorectal cancer (Ji et al., [@B52]; Karimi Dermani et al., [@B60]) *Polygonum cuspidatum* Sieb. et Zucc. and *Rubus idaeus* L. WNT/β-catenin signaling (Ji et al., [@B52]) miR-200c (Karimi Dermani et al., [@B60]) Vimentin, ZEB-1, E-cadherin (Karimi Dermani et al., [@B60]) miR-221 (Wu and Cui, [@B151]) NF-κB, TFG (Wu and Cui, [@B151]) Melanoma (Wu and Cui, [@B151]) miR-21\ P53, PTEN, EGFR, STAT3, COX-2, NF-κB\ Glioma (Wang G. et al., [@B136]) miR-30a-5p\ PI3K/AKT/mTOR pathway (Wang G. et al., [@B136]) miR-19 (Wang G. et al., [@B136]) miR-155 (Ma C. et al., [@B90]) TNF-α, IL-6, MAPKs, STAT1/STAT3, and SOCS1 (Ma C. et al., [@B90]) LPS-induced inflammatory response (Ma C. et al., [@B90]) miR-663\ JUNB, JUND, activator protein-1 (Tili et al., [@B130]) Malignancies (Tili et al., [@B130]) miR-155 (Tili et al., [@B130]) miR-96 (Bian et al., [@B6]) BAX (Bian et al., [@B6]) Hypoxia/ischemia-induced brain injury (Bian et al., [@B6]) miR-13\ CREB, BDNF (Zhao et al., [@B190]) Alzheimer\'s disease (Zhao et al., [@B190]) miR-124 (Zhao et al., [@B190]) 14 Soybean Isoflavones *Glycine max* (Linn.) Merr. miR-29a\ TRIM68, PGK-1 (Li et al., [@B75]) Prostate cancer (Li et al., [@B75]) miR-1256 (Li et al., [@B75]) 15 Matrine *Sophora flavescens Ait* miR-19b-3p (Wei et al., [@B149]) PTEN (Wei et al., [@B149]) Melanoma (Wei et al., [@B149]) 16 Corylin *Psoralea corylifolia* Linn lncRNA GAS5 (Chen et al., [@B14]) / Hepatocellular carcinoma (Chen et al., [@B14]) 17 Tanshinone IIA/Magnesium lithospermate B *Salvia miltiorrhiza* Bge. miR-155\ TLR4, MyD88, GM-CSF, sICAM-1, CXCL-1, MIP-1α, TNF-α, IL-1β, COX-2\ LPS-induced inflammation (Fan et al., [@B28]) miR-147\ TLR4-NF-κB pathway (Fan et al., [@B28]) miR-184\ miR-29b\ miR-34c (Fan et al., [@B28]) miR-146b\ CRP, ox-LDL, IL-1β, IL-6, IL-12, TNF-α, CCL-2, CD40, and MMP-2 (Xuan et al., [@B156]) Atherosclerosis (Xuan et al., [@B156]) miR-155 (Xuan et al., [@B156]) miR-133 (Zhang et al., [@B180]) MAPK ERK1/2 (Zhang et al., [@B180]) Hypoxia (Zhang et al., [@B180]) miR-1 (Shan et al., [@B116]; Zhang et al., [@B187]) SRF, Kir2.1 (Shan et al., [@B116]) Arrhythmias post-AMI (Shan et al., [@B116]) Cx43, SRF, MEF2,\ Myocardial infarction (Zhang et al., [@B187]) P38 MAPK signal pathway (Zhang et al., [@B187]) miR-107 (Yang et al., [@B164]) GLT-1, glutamate (Yang et al., [@B164]) Cerebral I/R injury (Yang et al., [@B164]) 18 Baicalin *Scutellaria baicalensis* Georgi miR-191a (Wang L. et al., [@B140]) ZO-1 (Wang L. et al., [@B140]) Inflammatory bowel disease (Wang L. et al., [@B140]) miR-294 (Wang J. et al., [@B146]) c-jun and c-fos (Wang J. et al., [@B146]) Inhibition of proliferation (Wang J. et al., [@B138]) 19 Cinnamaldehyde *Cinnamomum cassia* Presl. miR-21\ TNF-α, IL-1β, IL-6, AKT, mTOR, COX2 (Qu et al., [@B107]) Ulcerative colitis (Qu et al., [@B107]) miR-155 (Qu et al., [@B107]) has-circ-0043256, miR-1252 (Tian F. et al., [@B128]) has-circ-0043256/miR-1252/ITCH axis\ Non-small cell lung cancer (Tian F. et al., [@B128]) WNT/β-catenin pathway (Tian F. et al., [@B128]) 20 Geniposide *Gardenia jasminoides Ellis* miR-145 (Su et al., [@B122]) IL-6, TNF-α, MCP-1,\ Inflammation in cardiomyocyte (Su et al., [@B122]) MEK/ERK pathway (Su et al., [@B122]) 21 Carvacrol/ Thymol *Origanum vulgare* L. or wild bergamot miR-155\ TLR2, TLR4, SOCS1, SHIP1 (Khosravi and Erle, [@B61]) Asthma (Khosravi and Erle, [@B61]) miR-146a\ miR-21 (Khosravi and Erle, [@B61]) 22 3-acetyl-11-keto-β-boswellic acid *Boswellia serrata* miR-155 (Sayed et al., [@B114]) P-IκB-α, carbonyl protein, SOCS-1 (Sayed et al., [@B114]) Neuroinflammation (Sayed et al., [@B114]) 23 Sinapic acid *Sinapis alba* L. LncRNA MALAT1 (Han et al., [@B42]) ET-1, IL-1β, ASC, NRLP3, Caspase-1 (Han et al., [@B42]) Diabetic atherosclerosis (Han et al., [@B42]) 24 Polydatin *Polygonum cuspidatum* Sieb. et Zucc. miR-214 (Zhou et al., [@B192]) Blood glucose, ALT, AST, TC, TG, LDL-C, HDL-C, MDA, SOD (Zhou et al., [@B192]) Atherosclerosis with liver dysfunction (Zhou et al., [@B192]) 25 Ampelopsin *Ampelopsis grossedentata* miR-21 (Yang D. et al., [@B158]) eNOS, DDAH1, NO, and ADMA (Yang D. et al., [@B158]) Endothelial dysfunction (Yang D. et al., [@B158]) miR-34a (Kou et al., [@B64]) SIRT1-mTOR signal pathways (Kou et al., [@B64]) Neurodegenerative diseases (Kou et al., [@B64]) 26 Icariine *Epimedium brevicornu* Maxim. miR-34c (Liu et al., [@B79]) RUNX2, JNKs, and p38,\ Bacteria-induced bone loss diseases (Liu et al., [@B79]) NF-kB pathways (Liu et al., [@B79]) miR-21 (Li J. et al., [@B70]) PTEN, RECK, Caspase-3, and BCL-2 (Li J. et al., [@B70]) Ovarian cancer (Li J. et al., [@B70]) 27 Ginsenosides *Panax ginseng* C. A. Mey. miR-15b (Chan et al., [@B13]) IP-10 (Chan et al., [@B13]) H9N2/G1 infection (Chan et al., [@B13]) 28 Salidroside *Rhodiola rosea* L let-7c\ p53, transcription factor CREB\ Senescence (Zhang J. et al., [@B178]) let-7e\ \ miR-3620\ \ miR-411\ \ miR-24-2-5p\ \ miR-485-3p (Zhang J. et al., [@B178]) AKT/mTOR signaling (Zhang J. et al., [@B178]) 29 Phlorizin *Acanthopanax senticosus* (Rupr. et Maxim.) Harms miR-135b (Choi et al., [@B24]) p63, PCNA, integrin α6, integrin β1, and type IV collagen (Choi et al., [@B24]) Skin aging (Choi et al., [@B24]) 30 Osthole *Cnidium monnieri* (L.) Cuss. miR-107 (Xiao et al., [@B155]) Aβ, BACE1, and LDH (Xiao et al., [@B155]) Alzheimer\'s disease (Xiao et al., [@B155]) 31 Panax Notoginseng Saponins *Panax notoginseng* (Burk.) F. H. Chen. miR-29c (Liu L. et al., [@B81]) Collagen (Col) 1a1, Col1a2, Col3a1, Col5a1, FBN1, TGFβ1 (Liu L. et al., [@B81]) Myocardial injury and fibrosis (Liu L. et al., [@B81]) miR-146b-5p (Wang J. et al., [@B146]) / Oxidative damage (Wang J. et al., [@B146]) miR-34a (Lai et al., [@B66]) miR-34a/SIRT1/p53 pathway (Lai et al., [@B66]) Senescence (Lai et al., [@B66]) miR-18a (Yang Q. et al., [@B162]) CD34, VWF (Yang Q. et al., [@B162]) Tumor complicated with myocardial ischemia (Yang Q. et al., [@B162]) miR-222 (Yang Q. et al., [@B161]) p27 and PTEN\ Lewis lung carcinoma (Yang Q. et al., [@B161]) Met/miR-222 axis (Yang Q. et al., [@B161]) 32 Tetrandrine *Stephania tetrandra* S. Moore. miR-27b\ VEGFC, BCL2L12, COL4A3, FGFR2 (Ning et al., [@B103]) Hypertrophic scar (Ning et al., [@B103]) miR-125b (Ning et al., [@B103]) 33 Leonurine *Leonurus artemisia* (Laur.) S. Y. Hu F. miR-1 (Lu et al., [@B86]) ANP, ET-1, p38 MAPK, p-p38 MAPK, myocyte enhancer factor 2, β-myosin heavy chain, and α-myosin heavy chain protein (Lu et al., [@B86]) Cardiomyocyte hypertrophy (Lu et al., [@B86]) 34 Calycosin/\ *Astragalus membranaceus* (Fisch.) Bunge. miR-375 (Wang Y. et al., [@B145]) ER-α and Bcl-2 and RASD1 (Wang Y. et al., [@B145]) Cerebral I/R injury (Wang Y. et al., [@B145]) Astragaloside IV/Total flavonoids lncRNA EWSAT1 (Kong et al., [@B63]) / Nasopharyngeal carcinoma (Kong et al., [@B63]) miR-34a (Zhang C. et al., [@B174]) LDHA, MCT1, MCT4, HIF-1α, CD147, TIGAR and p53 (Zhang C. et al., [@B174]) Gastric carcinoma (Zhang C. et al., [@B174]) miR-378\ / Viral myocarditis (Wan et al., [@B134]) miR-378\* (Wan et al., [@B134]) 35 Paeonol *Paeonia suffruticosa* Andr. and *Cynanchum paniculatum* (Bunge) Kitagawa miR-1 (Zhang and Xiong, [@B179]) / Ischemic arrhythmia (Zhang and Xiong, [@B179]) 36 Salvianolic acid A *Salvia miltiorrhiza* Bge. miR-101 (Yu D. S. et al., [@B168]) tight junction proteins, HO-1, p-caveolin-1, ZO-1, occluding, Nrf2, and Cul3 (Yu D. S. et al., [@B168]) Spinal cord injury (Yu D. S. et al., [@B168]) miR-3686\ MDR1 (Chen et al., [@B15]) Lung cancer (Chen et al., [@B15]) miR-4708-3p\ miR-3667-5p\ miR-4738-3p (Chen et al., [@B15]) 37 Andrographolide *Andrographis paniculata* (Burm. f.) Nees miR-222-3p\ signaling pathways of miRNAs in cancer, MPAKs, and focal adhesion (Lu et al., [@B85]) Hepatoma tumor (Lu et al., [@B85]) miR-106b-5p\ miR-30b-5p\ miR-23a-5p (Lu et al., [@B85]) 38 Puerarin *Radix Puerariae Lobatae* miR-22 (Wang L. et al., [@B139]) caveolin-3, amphiphysin-2, and junctophinlin-2 (Wang L. et al., [@B139]) Cardiovascular diseases (Wang L. et al., [@B139]) ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Methodology {#s2} =========== The bioactive ingredients of CHMs and their interactions with ncRNA targets are the subject of intensive and rapidly expanding research. In this study, we undertook a comprehensive review of this research. The PubMed database was searched using the terms: "(ncRNA) AND herbal medicine", "(((miRNA) OR lncRNA) OR circRNA) AND herbal medicine," "(((miRNA) OR lncRNA) OR circRNA) AND active ingredient," "(((miRNA) OR lncRNA) OR circRNA) AND Chinese herb," "(((miRNA) OR lncRNA) OR circRNA) AND natural agent," "(((miRNA) OR lncRNA) OR circRNA) AND natural compound," or "(((miRNA) OR lncRNA) OR circRNA) AND traditional Chinese medicine." In addition, the China National Knowledge Infrastructure (CNKI) was also searched with terms as follows: "FT = 'Chinese herbal medicine' AND SU = 'ncRNA' NOT (TI = 'Review' OR TI = ' Progress\' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Chinese herbal medicine' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = ' Progress\' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Active ingredient' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Natural compound' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," "FT = \'Natural ingredient' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," "FT = 'Traditional Chinese medicine extract' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')," or "FT = 'Traditional Chinese medicine' AND (SU = 'lncRNA' OR SU = 'miRNA' OR SU = 'circRNA') NOT (TI = 'Review' OR TI = 'Progress' OR TI = 'Overview' OR TI = 'Current situation')." "FT" means full text; "SU" means subject; "TI" means title. Articles included in "Guide to Core Journals of China," "Chinese Science Citation Database" and "Chemical Abstracts" simultaneously, were selected to ensure high quality of literature. According to the above searching method, English and Chinese original articles related to bioactive ingredients of CHMs and any ncRNA (miRNA, lncRNA, or circRNA) were selected manually. Pro-apoptosis Effects of CHMs {#s3} ============================= Apoptosis is programmed cell death, which is a normal physiological process of cells. Imbalance of apoptosis is closely associated with various diseases, particularly cancer. Proteins that inhibit apoptosis are over-expressed in various cancers, and are considered to be related to tumorigenesis and chemotherapy resistance (Mohamed et al., [@B100]); therefore, the induction of apoptosis is a promising method for cancer management (Fulda and Vucic, [@B31]). Recently, several bioactive ingredients of CHMs have been reported to promote apoptosis by targeting miRNA, lncRNA, or ceRNA crosstalk, indicating their potential as complementary therapies for cancer. Berberine --------- Berberine \[BBR, 9,10-Dimethoxy-2,3-(methylenedioxy)-7,8,13,13a-Tetrahydroberbinium; [Chem. 1](#T2){ref-type="table"}\] is an isoquinoline alkaloid extracted from the roots of several species including: *Coptis chinensis* Franch., *Berberis soulieana* Schneid., *Berberis poiretii* Schneid., *Berberis vernae* Schneid., *Berberis wilsoniae* Hemsl., and *Platycladus orientalis* (Linn.) Franco. These herbs are considered to have antipyretic and detoxification effects, based on the theory of traditional Chinese medicine (TCM), and were mainly used to treat diseases of the digestive and urinary systems, such as diarrhea, ulcer, jaundice, and urinary infection, as well as dermatological diseases, including eczema. Newly reported researches (Luo et al., [@B89]; Chai et al., [@B12]) have found the anti-cancer activity of two extracts from *Coptis chinensis* Franch. one of which is BBR. It\'s indicated that BBR affects apoptotic pathways in various cancers through regulation of multiple miRNAs. For example, BBR exerts significantly protective effects in multiple myeloma (MM) through targeting several miRNAs. BBR down-regulates the expression of miR-99a\~125b, miR-17\~92, miR-106\~25 (Feng et al., [@B30]), and miR-21 (Luo et al., [@B89]), thereby influencing the P53, ERB, and MAPK signaling pathways, leading to acceleration of apoptosis and growth inhibition. Moreover, BBR suppresses MM cell viability through down-regulating miR-19a/92a expression (Yin et al., [@B166]). Further, BBR can up regulate miR-23a in hepatocellular carcinoma (HCC) (Wang N. et al., [@B141]), as well as miR-152, miR-429, and miR-29a in colorectal cancer (Huang et al., [@B48]) in a P53-dependent manner. By inducing NEK6 inhibition and transcriptional activation of the P53-associated tumor suppressor genes, P21 and GADD45α, BBR induces cell death, G2/M cell cycle arrest, and tumor growth suppression in HCC cells; in contrast, miR-23a inhibition can attenuate these BBR-mediated functions (Wang N. et al., [@B141]). Besides, BBR also regulates cell cycle and inhibits cell proliferation in melanoma A375 cells through promoting miR-34a, miR-154, miR-26a, and miR-124 expression, as well as suppressing target genes CDK4, CyclinD1, CyclinE, and CDK2 (Yang L. H. et al., [@B159]). Additionally, BBR can enhance cellular sensitivity to chemotherapeutic drugs, helping to address the problem of drug resistance. In ovarian and gastric cancers, BBR can enhance cisplatin sensitivity by regulating the expression of miR-93 (Chen et al., [@B17]) and miR-203 (You et al., [@B167]), respectively, thus inducing apoptosis. Furthermore, there is evidence that BBR can function together with other compound. It has a synergistic antiproliferative effect on colorectal cancer when combined with NVP-AUY922. The potential mechanism underlying this phenomenon was reported to be suppression of CDK4 and induction of miR-296-5p-mediated inhibition of Pin1-β-catenin-cyclin D1 signaling, resulting in cell growth arrest (Su et al., [@B123]). Interestingly, BBR also has protective effects against obesity, steatotic liver and insulin resistance. It inhibits cell viability, cell differentiation, and triglyceride content in a dose- and time-dependent manner, through marked induction of miR-27a and miR-27b; while miR-27a and miR-27b inhibitors can counteract this repressive function of BBR (Wu et al., [@B154]). Steatotic liver results from disordered lipid metabolism, where lncRNA MRAK052686, NRF2 (Yuan et al., [@B172]), and miR-373 (Li C. H. et al., [@B69]) are down-regulated. BBR can reverse the abnormal expression of these genes in steatotic liver, thereby inhibiting the AKT-mTOR-S6K signaling pathway and preventing the development of hepatic steatosis (Li C. H. et al., [@B69]). In addition, through downregulating miR-29a-3p in insulin resistant HepG2 cells, BBR can increase the mRNA and protein expression of IRS1, leading to regulation of the insulin receptor signaling pathway protein (Mao et al., [@B94]). Based on the above results, it is clear that BBR possesses different pharmacological effects via targeting miRNAs. Particularly, it shows obvious advantages for treatment of MM and digestive cancers, mainly through its activities in promotion of apoptosis and inhibition of cell growth. More importantly, its direct anticancer properties are strongly associated with P53 signaling. Therefore, BBR presents as promise for potential future use in cancer treatment. Artesunate ---------- Artesunate (ART, dihydroartemisinin-12-alpha-succinate; [Chem. 2](#T2){ref-type="table"}) is a sesquiterpene lactone extracted from the leafy portions of the Chinese herb, *Artemisia annua* L. It\'s the semisynthetic derivative of artemisinin which is widely known to be a natural antimalarial medicine (Tu, [@B133]). Recently, the function of ART in cancer therapy, by targeting lncRNA and promoting cell apoptosis, was newly identified. The lncRNA, UCA1, is up-regulated in prostate cancer tissues and positively correlated with poor prognosis (Zhou Y. et al., [@B196]). ART significantly decreased the expression of lncRNA UCA1, thereby regulating the downstream miR-184/BCL-2 axis, inducing apoptosis, and inhibiting metastatic ability. Furthermore, these protective effects could be reversed by overexpression of lncRNA UCA1, indicating that it is a target of ART (Zhou Y. et al., [@B196]). Hence, ART exhibits anticancer properties through regulating the ceRNA crosstalk of the lncRNA UCA1/miR-184/BCL-2 axis in prostate cancer. Nevertheless, additional evidence to support these findings is lacking and the stability of this regulatory network requires validation. Triptolide/Triptonide --------------------- Triptolide (TP, (3bs,4as,5as,6r,6ar,7as,7bs,8as,8bs)-6-hydroxy-6a-isopropyl-8b-methyl-3b,4,4a,6,6a,7a,7b,8b,9,10-decahydrotrisoxireno\[6,7:8a,9:4b,5\]phenanthro\[1,2-c\]furan-1(3h)-one; [Chem. 3](#T2){ref-type="table"}) and Triptonide (TN,(3bS,4aS,5aS,6aS,7aS,7bS,8aS,8bS)-6a-isopropyl-8b-methyl-3b,4,4a,7a,7b,8b,9,10-octahydrotrisoxireno\[6,7:8a,9:4b,5\]phenanthro\[1,2-c\]furan-1,6(3H,6aH)-dione; [Chem. 4](#T2){ref-type="table"}) are both diterpene lactone components originated from *Tripterygium wilfordii* Hook. f. (TwHf) that has traditionally been used for treatment of rheumatoid arthritis (RA). A recent study has revealed that TwHf exerts its anti-rheumatic effects through regulation of miR-146a, which is over-expressed in patients with RA and negatively correlated with prognosis. TwHf treatment could significantly decrease miR-146a expression. Moreover, miR-146a could be used as a predictor of patient clinical response to TwHf (Chen Z. Z. et al., [@B21]). Researches about TP and TN broaden the traditional application and generate new pharmacological effect for cancer treatment. TP has been found to exert anticancer activities in lung cancer. It can induce apoptosis and suppress proliferation through inhibiting miR-21 and increasing expression of phosphatase and tensin homolog (PTEN) protein in non-small cell lung cancer. Moreover, miR-21 upregulation could reverse the effect of TP on cell viability and PTEN (Li et al., [@B74]). Furthermore, TP treatment is also reported to regulate 227 miRNAs and markedly decrease the migration, invasion, and metastasis of lung cancer cells (Reno et al., [@B109]). In addition, TP can promote apoptosis and suppress cell proliferation in hepatocellular carcinoma, potentially via inhibition of miR-17-92 and miR-106b-25, in a c-MYC-dependent manner, leading to an increase of BIM, PTEN, and P21 levels (Li S. G. et al., [@B71]). However, TN shows significant therapeutic advantages in human nasopharyngeal carcinoma (NPC). It promotes NPC apoptosis and cell cycle arrest, as well as inhibition of cell migration and invasion, without toxicity to nasopharyngeal epithelial cells. This anti-cancer activity is attributed to suppression of lncRNA THOR, followed by downregulation of IGF2BP1 mRNA targets involving Myc, IGF2, and Gli1. Furthermore, lncRNA THOR knockout enhances the protection of TN on NPC; while lncRNA THOR overexpression reverses TN-induced treatment in cells. *In vivo*, TN administration also obviously impedes subcutaneous NPC xenograft growth in mice. Similarly, lncRNA THOR knockout inhibits xenograft growth (Wang et al., [@B143]). Therefore, TP and TN are attractive candidate chemotherapeutic agents against the above cancers. With regard to TP, PTEN is an important target; while TN possesses anti-cancer activity *in vitro* and *in vivo* through regulating lncRNA THOR/IGF2BP1 signaling. Nevertheless, as the extracts from TwHf with general toxicity (Chen et al., [@B16]; Luo et al., [@B88]), the effectiveness and safety of TP and TN require additional confirmation. Ailanthone ---------- Ailanthone (AIL, Picrasa-3,13(21)-diene-2,16-dione, 11,20-epoxy-1,11,12-trihydroxy-, (1-beta,11-beta,12-alpha)-; [Chem. 5](#T2){ref-type="table"}) is a water-soluble quassinoid extracted from the root bark of *Ailanthus altissima* (Mill.) Swingle. Traditionally, the root bark was used for improvement of itching, bleeding and diarrhea in TCM theory. However, AIL has been newly found to possess anti-tumor activity in different tumors (Chen Y. et al., [@B20]; Peng et al., [@B105]; Yang P. et al., [@B160]). Among those, inhibitory effect of human vestibular schwannomas (VSs) induced by AIL is correlated with miRNA. A research has demonstrated that AIL cleaves caspase 3 and caspase 9, promotes Beclin-1, LC3-II accumulation, and decreases p62, cyclin D1 expression, thus increasing apoptotic cell rate. The upstream mechanism may be suppression of miR-21, and the Ras/Raf/MEK/ERK and mTOR pathways, leading to apoptosis and autophagy in AIL-treated cells. In addition, miR-21 overexpression can attenuate the regulation of AIL on Ras/Raf/MEK/ERK and mTOR pathways, as well as apoptosis and autophagy, indicating miR-21 can be the treatment target of AIL in VSs (Yang P. et al., [@B160]). Cordycepin ---------- Cordycepin (COR, 9-(beta-D-3′-Deoxyribofuranosyl)adenine; [Chem. 6](#T2){ref-type="table"}) is the main bioactive ingredient of *Cordyceps militaris*, a precious CHM. The medicinal herb has immunity-strengthening effect, and has been already used as a health care product in clinical practice. Modern researches broaden the application of COR in various cancers (Wang et al., [@B135]; Liang et al., [@B77]; Yu X. et al., [@B170]). Specifically, treatment of COR for renal cell carcinoma (RCC) is attributed to regulation of miR-21 and PTEN phosphatase. It\'s indicated that COR down-regulates miR-21 expression and Akt phosphorylation, yet promotes PTEN phosphatase in RCC Caki-1 cells, resulting in induction of apoptotic cell death and suppression of cell migration. Furthermore, miR-21 mimic or PTEN siRNA can markedly abolish the above effects induced by COR (Yang et al., [@B157]). Therefore, it\'s confirmed that COR possesses pro-apoptosis and anti-migration function through regulating miR-21/PTEN axis. In addition, soya-cerebroside ([Chem 7](#T2){ref-type="table"}), another extracts from *Cordyceps militaris* is demonstrated to be anti-inflammatory for osteoarthritis (OA). It suppresses AMPK and AKT signaling pathways, and then promotes miR-432 expression in OA synovial fibroblasts, leading to inhibition of monocyte chemoattractant protein-1 (MCP-1), monocyte migration and infiltration, as well as cartilage degradation (Liu S. C. et al., [@B82]). As a result, soya-cerebroside exerts protective effect for OA partially via regulating miR-432, MCP-1, AMPK and AKT pathways; while in this study a clear functional relationships among those factors are not reported. Tubeimoside I ------------- TubeimosideI (TBMSI, nosyl\]-β-D-glucopyranosyl\]oxy\]-2,23-dihydroxy-,28-(O-β-D-xylopyranosyl-(1 → 3)-O-6-deoxy-α-L-mannopyranosyl-(1 → 2)-α-L-arabinopyranosyl)ester, intramol. ester, \[2β,3β(S),4α\]- Tubeimoside TUBEIMOSIDE A(P); [Chem. 8](#T2){ref-type="table"}) is the main triterpenoid saponin originated from *Bolbostemma paniculatum* (Maxim) Franquet. which has detoxification and detumescent activities. Recent studies have revealed the pharmacological action of TBMS1 as a potential anti-cancer agent (Wang et al., [@B144]; Gu et al., [@B36]). A research demonstrated that TBMS1 can promote apoptosis, and attenuate migration, invasion of non-small cell lung cancer cells. The underlying mechanism is attributed to upregulation of miR-126-5p, followed by inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. MiR-126-5p inhibitor can reverse the downregulated VEGF-A and VEGFR-2 induced by TBMS1 treatment; moreover, both miR-126-5p inhibitor, and VEGF-A, VEGFR-2 overexpression upregulate the mRNA expression and phosphorylation of MEK1 and ERK. Significantly, apoptosis, migration and invasion of TBMS1-treated cells can be reversed by either miR-126-5p inhibitor or ERK activator (Shi et al., [@B118]). From the above results, it can be concluded that miR-126-5p/VEGF-A/VEGFR-2/ERK signaling is the protective pathway of TBMS1 for cancer therapy. Oridonin -------- Oridonin (ORI, (14R)-7-alpha,20-Epoxy-1-alpha,6-beta,7,14-tetrahydroxykaur-16-en-15-one, [Chem. 9](#T2){ref-type="table"}) is a ent-kaurane diterpenoid compound mainly originated from *Rabdosia rubescens* (Hemsl.) Hara. Traditionally, the herb was convinced to have the effect of detoxification, circulation promotion and pain relief in China. Currently, ORI is illustrated to participate in the treatment of several tumors via different regulatory pathways. It\'s reported that human laryngeal cancer cell is accelerated to apoptosis after ORI treatment through inhibiting EGFR signaling. Similarly, EGFR suppression increased ORI-induced apoptosis by the promotion of oxidative stress, and activation of intrinsic and extrinsic apoptotic pathways (Kang et al., [@B59]). Moreover, 105 miRNAs are involved in the regulation of ORI-treated pancreatic cancer (Gui et al., [@B37]). Therefore, it\'s possible that miRNAs involve in the anti-cancer activity of ORI; however, whether EGFR is the downstream target of miRNAs deserves more researches. Anti-proliferation and Anti-migration Effects of CHMs {#s4} ===================================================== Abnormal cell proliferation is involved in the pathogenesis of many diseases. In particular, the proliferation and invasion of cancer cells are primary contributors to poor patient outcomes (Gao et al., [@B33]). In addition, asthma is also associated with the cell proliferation and migration in airway smooth muscle (Zhao et al., [@B189]). Hence, suppression of cell proliferation and migration are critical methods for treatment of these diseases. Excitingly, some bioactive ingredients of CHMs have been found to inhibit the proliferation and migration of both cancer and asthma cells through targeting miRNA, lncRNA, or ceRNA crosstalk. Curcumin -------- Curcumin (CUR, (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione; [Chem. 10](#T2){ref-type="table"}) is a phenolic compound extracted from *Curcuma longa* L., which was traditionally used as painkiller in rheumatism and other bone and joint diseases. Recent studies have found that CUR can also act as an anticancer agent, via miRNA and lncRNA targets. CUR inhibits miR-208 and activates expression of the cell cycle suppressor, CDKN1A, resulting in dose-dependent suppression of prostate cancer cell proliferation (Guo H. et al., [@B38]). Further, CUR can significantly increase miR-143 and decrease PGK1 expression, while ectopic expression of FOXD3 can enhance the regulatory effect of CUR on miR-143, thereby inhibiting the proliferation and migration of prostate cancer cells (Cao et al., [@B11]). Further studies reveal that CUR also acts on human prostate cancer stem cells (HuPCaSC). CUR treatment increases the expression of miR-145 and decreases levels of lncRNA-ROR, the cell cycle proteins CCND1, CDK4, and the stem cell markers OCT4, CD44, and CD133. The tumorigenicity of these cells is thereby significantly reduced through inhibition of their proliferation, invasion, and cell cycle arrest (Liu T. et al., [@B83]). Moreover, expression levels of miR-770-5p and miR-1247 in the DLK1--DIO3 imprinted gene cluster were significantly up-regulated, leading to suppression of HuPCaSC proliferation and invasion *in vitro* (Zhang et al., [@B177]). CUR also promotes the expression of miR-98 in lung cancer, thus inhibiting cell growth and migration (Liu W. L. et al., [@B84]). By reducing miR-186^\*^ expression, it induces apoptosis and decreases cell viability in lung cancer cells as well (Tang et al., [@B126]). Furthermore, CUR inhibits both proliferation and accelerates apoptosis in bladder, gastric, non-small cell lung, pancreatic cancers, and hepatic carcinoma via the up-regulation of miR-203 (Saini et al., [@B112]), miR-33b (Sun et al., [@B124]), miR-192-5p (Jin et al., [@B57]), miR-7 (Ma et al., [@B92]), and lncRNA AK125910 (Guo Y. et al., [@B40]), respectively. CUR has also been reported to increase the sensitivity of non-small-cell lung cancer (Lu et al., [@B87]), breast cancer (Zhou S. et al., [@B194]), and nasopharyngeal carcinoma (Wang Q. et al., [@B142]) to chemotherapy drugs by targeting ncRNAs including miR-30c, miR-29b-1-5p, and lncRNA AK294004, respectively, along with their downstream genes. Moreover, CUR can exert synergistic effects in combination with other compounds, to suppress cell proliferation and invasion and induce apoptosis in glioblastoma (Wu et al., [@B152]), breast cancer (Guo et al., [@B39]), and hepatocellular carcinoma (Zhang S. et al., [@B184]). In glioblastoma, miR-378 was found to promote the anticancer effect of CUR by regulating p38 expression, demonstrating the mutual interaction of miRNA and CUR (Li et al., [@B73]). Furthermore, CUR is reported to exert anti-inflammatory effects (Ma F. et al., [@B91]) and to inhibit adipogenic differentiation (Tian L. et al., [@B129]). Notably, as liposome technology is a good method for targeting drug delivery system that can solve the solubility problems of poorly soluble drugs (Allen and Cullis, [@B2]). A research has used this technology to produce CUR-loaded liposome, increasing solubility and oral bioavailability of CUR, as well as reducing first pass effect of hepar. This drug combination can also promote sensitivity of breast cancer cells to chemotherapy, through regulating different miRNAs of miR-29b-1-5p, miR-29b-3p, miR-6068, miR-6790-5p, and miR-4417, as well as their target genes involving DDIT4, EPAS1, VEGFA, RPS14, and DCDC2 (Zhou et al., [@B195]). These data demonstrate that CUR can suppress cell proliferation, growth, and metastasis in various cancers by targeting ncRNAs. In particular, CUR has obvious advantages for the treatment of prostate cancer through its regulation of cancer and cancer stem cells. Moreover, the synergistic effects of CUR with other chemotherapies provide new alternative strategies to address drug resistance. Excitingly, structural improvement of CUR not only ensures its anti-cancer effect, but also promotes the bioavailability. Shikonin -------- Shikonin (SHK, 5,8-dihydroxy-2-((1R)-1-hydroxy-4-methyl-3-penten-1-yl)-1,4-naphthalen-edione; [Chem. 11](#T2){ref-type="table"}) is a naphthoquinone derivative compound. SHK is extracted from the root of the natural herbal medicine, *Lithospermum erythrorhizon* Sieb. et Zucc. This plant was generally used to treat rash, pox, measles, and urticaria in TCM. Modern studies have discovered broader applications for this compound in cancer, by revealing its anti-proliferation function, which is reported to be associated with targeting of miRNAs. SHK can inhibit proliferation and promote apoptosis by modulating the miR-106b/PTEN/AKT/mTOR signaling pathway in endometrioid endometrial cancer (Huang and Hu, [@B47]). Moreover, SHK inhibits the proliferation of breast cancer cells through down-regulation of tumor-derived exosomal miR-128 (Wei et al., [@B148]). In addition, the anticancer activity of SHK in glioblastoma is enhanced by miR-143 by reducing the expression of the anti-apoptosis regulator, BAG3, which is a functional target of miR-143 (Liu et al., [@B80]). Overall, the regulatory relationships between SHK and miRNAs are mutual. SHK could target miR-106b and miR-128 in endometrioid endometrial cancer and breast cancer to prevent cell proliferation. Further, miR-143 expression influences the anticancer activity of SHK in glioblastoma. Finally, the results reviewed above demonstrate that the anti-proliferation activity of SHK in cancers can be attributed to its interactions with miRNAs. Paeoniflorin ------------ Paeoniflorin\[PF,5b-((Benzoyloxy)methyl)tetrahydro-5-hydroxy-2-methyl-2,5-methano-lH-3,4-dioxacyclobuta(cd)pentalen-1a(2H)-yl-beta-D-glucopyranoside; [Chem. 12](#T2){ref-type="table"}\] is the main active ingredient of *Paeonia lactiflora* Pall., which was commonly used to regulate blood circulation and relieve pain in TCM theory. Recent investigations have revealed roles for PF in vasodilation (Goto et al., [@B35]), anti-inflammation (Chen et al., [@B19]; Hu et al., [@B45]), microcirculation improvement (Zhou et al., [@B193]), anti-oxidation (Chen et al., [@B18]), and anti-cancer (Wang et al., [@B137]) activities. Specifically, PF exhibits protective activity in glioma via suppression of cell proliferation and promotion of apoptosis. The potential underlying mechanism may involve upregulation of miR-16 and downregulation of matrix metalloproteinase-9 (MMP-9), which are differentially expressed in glioma tissues and cells compared with healthy controls (Li W. et al., [@B72]). This result lays the foundation for treatment of cancer using PF; however, supporting evidence is insufficient and more investigations are needed. Honokiol -------- Honokiol (HNK, 5,3′-Diallyl-2,4′-dihydroxybiphenyl; [Chem. 13](#T2){ref-type="table"}) is a bioactive polyphenol isolated from *Magnolia grandiflora*. Although the flower was traditionally valued as ornamental, it contains the phenolic ingredient, HNK, which has been shown to have antimicrobial activity (Clark et al., [@B25]). A recent study discovered that HNK has anti-tumor activity; it can markedly inhibit the growth, invasion, and migration of breast cancer cells, and breast-tumor-xenograft growth induced by leptin. HNK promotes the expression of miR-34a, and inhibits WNT1-MTA1-β-catenin signaling, through suppression of STAT3 phosphorylation and recruitment of STAT3 to the promoter of miR-34a (Avtanski et al., [@B3]). Hence, HNK has demonstrated a protective effect on breast cancer in a diet-induced-obese mouse model with high leptin levels and could serve as a new endocrine therapy drug for patients with obesity-related breast cancer accompanied by negative estrogen and progesterone receptors; however, the research described above was limited to animal experiments, and further evidence in humans is required, thus clinical trials are warranted to further investigate HNK. Schisandrin B ------------- SchisandrinB (SchB, 7-dimethyl-ethoxy-stereoisomer;benzo(3,4)cycloocta(1,2-f)(1,3)benzodioxole,5,6,7,8-tetrahydro-1,2,3,13-tetram; [Chem. 14](#T2){ref-type="table"}) is a type of lignan, extracted from *Schisandra sphenanthera* Rehd. et Wils. The original fruit was commonly used to relieve symptoms of cough, gasp, abnormal sweating, nocturnal emission, thirst, and palpitations, under TCM theory. Although it was widely used to treat various diseases in ancient China, its specific target and underlying mechanism of action were unclear. A recent study of Sch B provided information about the involvement of ncRNA. Sch B may increase the expression of miR-150 and subsequently reduce levels of the lncRNA BCYRN1 in airway smooth muscle cells (ASMCs) of asthmatic rats. By regulating these two ncRNAs, Sch B suppresses the proliferation, viability, and migration of ASMCs; therefore, the study generated evidence that partially explains the mechanism underlying the activity of Sch B against asthma (Zhang X. Y. et al., [@B185]). Moreover, Sch B can mediate ceRNA crosstalk between miR-150 and lncRNA BCYRN1, further establishing an miR-150/lncRNA BCYRN1/cell proliferation axis; however, as a new regulatory mechanism influencing asthma, the stability of the ceRNA crosstalk requires further investigation. Resveratrol ----------- Resveratrol (RES, 3,4′,5-trihydroxystilbene; [Chem. 15](#T2){ref-type="table"}) is a natural phenol stilbenoid that is mainly found in food, including the skin of grapes and blueberries, and several CHMs, including *Morus alba* L., *Polygonum cuspidatum* Sieb. et Zucc., and *Rubus idaeus* L. It is considered to protect individuals from cardiovascular diseases, as well as dietary and metabolic diseases (Bradamante et al., [@B10]; Baur et al., [@B5]; Lagouge et al., [@B65]). Recently, its anticancer properties have also been evaluated by researchers and RES has been used as a dietary supplement (Garvin et al., [@B34]; Kalra et al., [@B58]; Roy et al., [@B111]). RES can down-regulate the lncRNA, MALAT1, and up-regulate miR-200c, as well as inhibiting WNT/β-catenin signaling, leading to suppression of cell invasion, metastasis, and migration in colorectal cancer (Ji et al., [@B52]; Karimi Dermani et al., [@B60]). Moreover, by significantly decreasing oncogenic miR-221 and regulating NF-κB and TFG, RES exerts inhibitory effects on melanoma cells, both *in vitro* and *in vivo* (Wu and Cui, [@B151]). In glioma, RES inhibits cell proliferation, arrests the cell cycle in S phase, and induces apoptosis *in vitro*, through down-regulation of miR-21, miR-30a-5p, and miR-19, as well as regulating their targets, including P53, PTEN, EGFR, STAT3, COX-2, NF-κB, and the PI3K/AKT/mTOR pathway (Wang G. et al., [@B136]). RES also has anti-inflammatory effects. It can reduce expression of miR-155 and promote that of its target gene, suppressor of cytokine signaling 1 (SOCS1), leading to subsequent inhibition of the inflammatory factors, TNF-α, IL-6, MAPKs, and STAT1/STAT3 (Ma C. et al., [@B90]). Interestingly, by increasing miR-663 expression, RES down-regulates miR-155, thus acting as both an anti-inflammatory and an anticancer agent (Tili et al., [@B130]). Furthermore, RES exhibits neuroprotective effects. It promotes miR-96 and inhibits its target gene, BAX, resulting in prevention of oxygen/glucose deprivation/re-oxygenation-induced apoptosis and brain damage, while this protective function can be reversed by miR-96 inhibitor (Bian et al., [@B6]). In Alzheimer\'s disease, RES also improves long-term memory formation and induction of long-term potentiation of hippocampus CA1 neurons, through down-regulation of miR-134 and miR-124, and up-regulation of CREB and BDNF (Zhao et al., [@B190]). Therefore, RES is a potential therapeutic agent against cancers, cerebral ischemia, Alzheimer\'s disease, and other inflammatory conditions. Soybean Isoflavones ------------------- Soybean isoflavones (SIF, 3-phenyl-4h-1-benzopyran-4-one; [Chem. 16](#T2){ref-type="table"}) are extracted from *Glycine max* (Linn.) Merr. They act as phytoestrogens in mammals and have been used as dietary supplements. SIF are associated with breast cancer (Douglas et al., [@B27]; Takagi et al., [@B125]). Recently, they have also been demonstrated to suppress cell growth and invasion in prostate cancer. A potential mechanism underlying the anti-prostate cancer activity of SIF is its promotion of miR-29a and miR-1256, leading to down-regulation of TRIM68 and PGK-1 by inhibiting methylation of the miR-29a and miR-1256 promoters (Li et al., [@B75]). Nevertheless, as a controversial ingredient with weak estrogen-like properties, the influence of SIF on hormone-receptor-positive cancers has caused widespread concern. Therefore, research is needed to determine the effectiveness and safety of SIF in the context of different cancers. Matrine ------- Matrine (MAT, (7aS,13aR,13bR,13cS)-Dodecahydro-1H,5H,10H-dipyrido\[2,1-f:3′,2′,1′-ij\](Memczak et al., [@B97]; Song et al., [@B121])naphthyridin-10-one; [Chem. 17](#T2){ref-type="table"}) is the main alkaloid extract from *Sophora flavescens Ait* which was commonly used for diseases of dysentery, eczema and jaundice in China. Modern pharmacological research shows that MAT has protective activity in melanoma, as evidenced by inhibition of proliferation and invasion, and promotion of apoptosis in melanoma cell lines. By downregulating miR-19b-3p expression, MAT increases the protein and mRNA expression of PTEN, a direct target of miR-19b-3p. Similarly, miR-19b-3p downregulation can imitate the effect of MAT; while PTEN silencing reverses the protection induced by MAT (Wei et al., [@B149]). As a result, MAT can exert anti-cancer activity in melanoma via regulating miR-19b-3p/PTEN axis. Corylin ------- Corylin (CL, 3-(2,2-dimethylchromen-6-yl)-7-hydroxychromen-4-one; [Chem. 18](#T2){ref-type="table"}) is the flavonoid compound extracted from *Psoralea corylifolia* Linn. In TCM practice, *Psoralea corylifolia* Linn. was often used for degenerative bone and joint diseases. Newly reported studies have revealed its application in inflammation (Kim et al., [@B62]; Hung et al., [@B51]) and cancer (Chen et al., [@B14]). The anti-cancer activity induced by CL is related to upregulation of tumor suppressor lncRNA GAS5 and its downstream anticancer pathways activation. As a result, the proliferation, migration, and invasiveness, as well as epithelial-mesenchymal transition are all inhibited in hepatocellular carcinoma cells. Moreover, lncRNA GAS5 silencing can attenuate the above inhibitory effect of CL. In an animal experiment, CL is observed to obviously retard tumor growth as well, with no significant physiological toxicity (Chen et al., [@B14]). Taken together, lncRNA GAS5 may act as the treatment target of CL in hepatocellular carcinoma; however, specific downstream gene of lncRNA GAS5 still needs further study. Anti-inflammatory Effects of CHMs {#s5} ================================= Inflammation is a common pathological process involved in many diseases, including coronary heart disease, inflammatory bowel disease, myocarditis, asthma, and neuroinflammatory disorder (Harrington, [@B43]; Robinson et al., [@B110]; Mahajan et al., [@B93]); however, both non-steroidal anti-inflammatory drugs and immunosuppressive agents have clear side effects (Shah and Gecys, [@B115]; Ahmad et al., [@B1]). Consequently, safe and effective anti-inflammatory drugs for the treatment of the basic pathologies underlying the above diseases are still needed. Several bioactive ingredients of CHMs are reported to target miRNA or ceRNA crosstalk, thereby exerting anti-inflammatory effects. Tanshinone IIA -------------- Tanshinone IIA (Tan IIA, Phenanthro \[1, 2-b\]furan-10, 11-dione, 6, 7, 8, 9-tetrahydro-1, 6, 6-trimethyl; [Chem. 19](#T2){ref-type="table"}) is a lipophilic diterpenoid extracted from the root of *Salvia miltiorrhiza* Bge. Under TCM theory, the original herb is considered to promote blood circulation. Recent studies have illustrated that Tan IIA has cardioprotective activity (Shang et al., [@B117]; Feng et al., [@B29]) and injection of sodium Tan IIA sulfonate has been widely used as an adjunctive therapy for cardiovascular diseases in China (Yu M. L. et al., [@B169]). A potential mechanism underlying its inhibition of inflammation (Pan et al., [@B104]; Cheng et al., [@B22]), and an upstream regulator, is miRNA. Tan IIA can reduce the expression levels of cytokines, chemokines, and acute-phase proteins, including TLR4, MyD88, GM-CSF, sICAM-1, CXCl-1, and MIP-1α. Moreover, it significantly inhibits the mRNA expression levels of IL-1β, TNF-α, and COX-2, thereby suppressing lipopolysaccharides (LPS) -induced activation of the TLR4-NF-κB pathway. Furthermore, expression of miR-155, miR-147, miR-184, miR-29b, and miR-34c is also reduced by Tan IIA, and these may be upstream regulators in anti-inflammation processes (Fan et al., [@B28]). In addition, by down-regulation of miR-146b and miR-155, Tan IIA significantly reduces the levels of inflammatory factors, including CRP, ox-LDL, IL-1β, IL-6, IL-12, TNF-α, CCL-2, CD40, and MMP-2, thereby exerting protective functions in atherosclerosis induced by *Porphyromonas gingivalis* (Xuan et al., [@B156]). Another study indicated that Tan IIA can also inhibit apoptosis caused by hypoxia. Through increasing miR-133 expression and activating the stress-induced protein kinase, MAPK ERK1/2, Tan IIA enhances resistance to hypoxic exposure in neonatal cardiomyocytes (Zhang et al., [@B180]). Treatment with Tan IIA has also been illustrated to reverse the abnormal expression of miR-1, SRF, and MEF2, and participates in suppression of the p38 MAPK signaling pathway, restoring declined I(K1) current density and Kir2.1 and Cx43 protein levels, thus lowering the incidence of arrhythmogenesis and mortality after myocardial infarction, and improving cardiac function (Shan et al., [@B116]; Zhang et al., [@B187]). These results provide a partial explanation for the anti-inflammatory and anti-hypoxia activity of Tan IIA via miRNAs in cardiovascular diseases; in particular, miR-155 may be a specific target of Tan IIA in inflammation. Additionally, an aqueous extract from *Salvia miltiorrhiza* Bge., named magnesium lithospermate B (MLB, magnesium (2R)-3-(3,4-dihydroxyphenyl)-2-\[(E)-3-\[(2S,3S)-2-(3,4-dihydroxyphenyl)-3-\[(2R)-3-(3,4-dihydroxyphenyl)-1-oxido-1-oxopropan-2-yl\]oxycarbonyl-7-hydroxy-2,3-dihydro-1-benzofuran-4-yl\]prop-2-enoyl\]oxypropanoate; [Chem. 20](#T2){ref-type="table"}), has neuroprotective effect in ischemia/reperfusion (I/R) injury. I/R injury can lead to miR-107 upregulation, glutamate transporter 1 (GLT-1) suppression and glutamate accumulation, increasing neurological deficit score, infarct volume and cellular apoptosis (Yang Z. B. et al., [@B165]). MLB treatment improves I/R-induced cerebral injury through reversing the abnormal expressions of miR-107, GLT-1 and glutamate (Yang et al., [@B164]). The above results may help to throw light on the underlying mechanisms of Tan IIA and MLB for the treatment of cardiovascular and cerebrovascular diseases from the perspective of miRNA; however, it should be noted that the pharmacological action of *Salvia miltiorrhiza* Bge. is not limited to ncRNAs (Zhu et al., [@B197]). Baicalin -------- Baicalin (BA, 7-D-glucuronic acid-5,6-dihydroxy-flavone; [Chem. 21](#T2){ref-type="table"}) is a flavone glycoside extracted from *Scutellaria baicalensis* Georgi, which was commonly applied for the treatment of respiratory and digestive diseases in CHM. The traditional treatment effects may be related to regulation of inflammatory responses. TNF-α stimulation promotes the expression of miR-191a, causing downregulation of ZO-1 mRNA and protein. BA pretreatment could reverse the effects of ZO-1 and miR-191a expression induced by TNF-α, leading to improved viability and migration of rat small intestine epithelial cells. Furthermore, knockdown of miR-191a expression significantly increased BAL-induced ZO-1 protein expression, thereby enhancing the protective effect of BA on cell motility (Wang L. et al., [@B140]). These data suggest that miR-191a may be an upstream target of BA in the treatment of inflammatory bowel disease; moreover, the therapeutic effects of BA can also be influenced by miR-191a. Also, another research illustrates the proliferative inhibition of mouse embryonic stem cells induced by baicalin. Baicalin suppresses the expression of miR-294, c-jun and c-fos; while miR-294 overexpression could significantly reverse the above effect of baicalin, indicating miR-294 may be the treatment target (Wang J. et al., [@B138]). Therefore, BA exerts anti-inflammatory and anti-proliferative effects by targeting miRNAs and emerges as a potential treatment agent for digestive disease. Further, as BA remains one of the most frequently used medicines for the treatment of cough and phlegm, the activity of BA in respiratory disease warrants similar studies. Cinnamaldehyde -------------- Cinnamaldehyde (CA, 3-phenylprop-2-enaldehyde; [Chem. 22](#T2){ref-type="table"}) is a conjugated aromatic aldehyde extracted from the bark of the Chinese herb, *Cinnamomum cassia* Presl. According to TCM theory, the traditional plant can enhance the function of "yang qi" (a substance with excitatory function in TCM) and is often used to relieve symptoms of weakness. Recent studies have broadened the application of this preparation to the treatment of cerebrovascular diseases, ulcerative colitis, and cancer (Zhao et al., [@B188]; Tian F. et al., [@B128]; Qu et al., [@B107]), where it acts by exerting anti-inflammatory or ncRNA regulatory functions. CA improves symptoms of weight loss, disease activity index, and infiltration of inflammatory cells, by decreasing the levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, as well as the NLRP3 inflammasome, miR-21, and miR-155, in both colon tissue and macrophages. Moreover, levels of reactive oxygen species were also reduced, along with the phosphorylation of AKT, mTOR, and COX2 proteins. Further experiments revealed similar suppression of IL-1β and IL-6 in response to miR-21 or miR-155 inhibitors, demonstrating that these inflammatory factors are positively regulated by miR-21 or miR-155 (Qu et al., [@B107]). As a result, CA suppresses the miR-21/miR-155/IL-1β/IL-6 axis to exert its protective function in ulcerative colitis. CA also has anti-cancer activity through regulation of ceRNA crosstalk and can suppress cell proliferation and induce apoptosis in non-small cell lung cancer. Through upregulation of has-circ-0043256 and ITCH expression, CA inhibits the WNT/β-catenin pathway, while this function can be partially abolished by miR-1252, indicating that miR-1252 may participate in has-circ-0043256-related regulation. Moreover, has-circ-0043256 knockdown can reverse the effects of CA on cells (Tian F. et al., [@B128]). Consequently, has-circ-0043256/miR-1252/ITCH crosstalk may contribute to the anticancer activity of CA. Geniposide ---------- Geniposide (GEN, methyl (1S,4aS,7aS)-7-(hydroxymethyl)-1-\[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl\]oxy-1,4a,5,7a-tetrahydrocyclopenta\[c\]pyran-4-carboxylate; [Chem. 23](#T2){ref-type="table"}) is derived from *Gardenia jasminoides Ellis*, a traditional antipyretic and detoxifying CHM. A recent research reported GEN has effects of anti-inflammatory and cardiomyocyte protection in LPS-injured H9c2 cells. It up-regulates miR-145 expression, inhibits pro-inflammatory factors of IL-6, TNF-α, and MCP-1, and then suppresses the MEK/ERK pathway, thus promoting cell viability and inhibiting apoptosis. Moreover, miR-145 inhibitor could reverse the above protective function induced by GEN pretreatment (Su et al., [@B122]). Therefore, GEN becomes a potential therapeutic agent for myocarditis in practice by targeting miR-145 and anti-inflammation in cardiomyocyte. Carvacrol/Thymol ---------------- Carvacrol (Car, 5-Isopropyl-2-methylphenol; [Chem 24](#T2){ref-type="table"}) and Thymol (Thy, 2-Isopropyl-5-methylphenol; [Chem. 25](#T2){ref-type="table"}) are isolated from the essential oil of *Origanum vulgare* L. or wild bergamot. They are isomers and belong to monoterpenoid phenol. Traditionally, *Origanum vulgare* L. was applied for the treatment of cold and heatstroke. Bergamot can relieve pain and vomit under TCM theory. A research further expanded the applicable scope of these herbs by studying the two bioactive ingredients. Car/Thy can suppress the allergic inflammation in asthma by regulating miRNAs and inflammatory factors. In chitin-induced model, expression levels of miR-155, miR-146a and miR-21, promotor of pro-inflammatory cytokines, are upregulated. Furthermore, SOCS1 and SHIP1, targets of miR-155 and negative regulators of TLR-mediated inflammation, are demonstrated to be inhibited by chitin. However, Car/Thy treatment can reverse the abnormal expressions of TLR2, TLR4, SOCS1, SHIP1, and miR-155, miR-146a, miR-21 (Khosravi and Erle, [@B61]). These results preliminarily establish the relationships between anti-inflammation effect of Car/Thy and miRNAs; but the specific target and corresponding regulatory network are not reported regrettably. Boswellic Acids --------------- Boswellic acids are extracted from oleo-gum-resin of *Boswellia serrata*, a traditional CHM with promoting blood circulation and pain relief function. Boswellic acids contain different ingredients, among which 3-acetyl-11-keto-β-boswellic acid (AKBA, (3R,4R,6aR,6bS,8aR,11R,12S,14bS)-3-acetyloxy-4,6a,6b,8a,11,12,14b-heptamethyl-14-oxo-1,2,3,4a,5,6,7,8,9,10,11,12,12a,14a-tetradecahydropicene-4-carboxylic acid; [Chem. 26](#T2){ref-type="table"}) possesses the most potent anti-inflammatory activity (Siddiqui, [@B120]; Sayed et al., [@B114]). AKBA can attenuate the behavioral dysfunction in LPS-induced neuroinflammation, similarly with that effect of dexamethasone. Moreover, AKBA lowers expression of miR-155, P-IκB-α, and carbonyl protein, and increases contents of normal cytokine and SOCS-1, resulting in effects of anti-apoptotic and anti-amyloidogenic (Sayed et al., [@B114]). Therefore, regulation of miR-155 and downstream protein helps to reveal the possible mechanism underneath AKBA\'s positive role in neuroinflammatory disorders; however, the specific target deserves more verification. Anti-atherosclerosis Effects of CHMs {#s6} ==================================== Atherosclerosis is the basic pathology underlying coronary artery disease, cerebral infarction, and other vascular diseases (Pothineni et al., [@B106]; Li Q. et al., [@B76]). Medicines with anti-atherosclerosis activities are therefore highly significant for the prevention and treatment of these diseases. Statins are currently the main drugs used against atherosclerosis; however, when taken for long periods of time, they risk impairing liver function and causing muscle lysis, particularly in elderly patients (Guyton, [@B41]; Ramakumari et al., [@B108]). Therefore, better drugs with relatively few side effects are needed and CHMs represent a good resource in this context. Recent studies have identified three bioactive ingredients of CHMs as regulators of atherosclerosis through targeting miRNA or lncRNA. Sinapic Acid ------------ Sinapic Acid (SA, 3,5-dimethoxy-4-hydroxycinnamic acid; [Chem. 27](#T2){ref-type="table"}) is the bioactive ingredient isolated from seeds of the Chinese herb, *Sinapis alba* L. The seeds were commonly used to treat cough, phlegm, limb numbness, and chronic abscess. A recent study reported protective effects of SA in atherosclerosis, which helped to partially explain the original application of the seed to treat limb numbness. The lncRNA MALAT1 is significantly up-regulated in rats with diabetic atherosclerosis and low-dose SA treatment can suppress this abnormal expression. Subsequently, pyroptotic death of bone marrow derived macrophages is inhibited, accompanied by decreased expression of ET-1 and IL-1β, and the pyroptotic proteins, ASC, NRLP3, and Caspase-1 (Han et al., [@B42]). Hence, SA exerts anti-inflammatory activity and prevents pyroptosis, thus exerting anti-atherosclerosis effects, through targeting lncRNA MALAT1; however, the efficacy and safety of SA as a potential treatment agent require verification by additional studies. Polydatin --------- Polydatin (PLD, 3,4,5-trihydroxystilbene-3-beta-monoglucoside; [Chem. 28](#T2){ref-type="table"}), also known as Piceid, is the bioactive ingredient from *Polygonum cuspidatum* Sieb. et Zucc. This herb was traditionally used for the treatment of jaundice and cough. However, PLD has also been found to exert protective effects against cardiac hypertrophy (Zhang et al., [@B181]), insulin resistance, and hepatic steatosis (Zhang et al., [@B182]). Further, a recent study has revealed the underlying regulatory action of PLD in atherosclerosis with liver dysfunction. The findings indicated that PLD treatment can markedly lower increased blood glucose, serum ALT, AST, TC, TG, and LDL-C in mice with high-fat diet. Simultaneously, changes in HDL-C, MDA, SOD, and miR-214 were also improved in liver tissue (Zhou et al., [@B192]). This study indicates that PLD can be therapeutically effective in complex diseases by regulating various factors. In addition, PLD shows great potential as a complement to treatment for statin-induced liver damage via its anti-atherosclerosis and liver protection properties; however, the above study only reported the expression levels of various factors induced by PLD, rather than systematically studying the relationships between miR-214 and its target genes. Therefore, further in-depth investigations are required in the future. Ampelopsin ---------- Ampelopsin \[(2r,3r)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chroman-4-one; [Chem. 29](#T2){ref-type="table"}\], alsocalled dihydromyricetin (DHM), is the main flavonoid compound from *Ampelopsis grossedentata*. The original herb has effects of detoxification, anti-inflammatory and analgesic, commonly used as a dietary supplement. DHM is now demonstrated to impede atherosclerotic process by regulating endothelial dysfunction (Yang D. et al., [@B158]), and exert anti-aging effect against neurodegenerative diseases (Kou et al., [@B64]). It inhibits miR-21 expression and then improves endothelial dysfunction induced by TNF-α, accompanied by suppression of abnormal expression of eNOS, DDAH1, NO, and ADMA, as well as improvement of tube formation and migration. Furthermore, miR-21 blockade can produce similar effects with DHM treatment; while miR-21 overexpression abolishes the above protection. Additionally, improvement of endothelial dysfunction can be reversed by a non-specific NOS inhibitor, indicating DHM ameliorates vascular endothelial function and inhibits atherosclerosis by targeting miR-21-mediated DDAH1/ADMA/NO signal pathway (Yang D. et al., [@B158]). Another study reveals that miR-34a is upregulated in D-gal-induced brain aging rats; while DHM management can inhibit the abnormal expression. Moreover, DHM suppresses apoptosis and ameliorates impaired autophagy of neurons in D-gal-injured hippocampus tissue, by up-regulating SIRT1 and down-regulating mTOR signal pathways (Kou et al., [@B64]). Therefore, DHM possesses anti-aging effect partially through regulating miR-34a-mediated SIRT1-mTOR signal pathway, showing important role for the treatment of neurodegenerative diseases. From the above results, it can be seen that DHM exerts not only anti-atherosclerosis effect, but also anti-aging function by targeting miRNAs and downstream signaling pathways. Anti-infection Effects of CHMs {#s7} ============================== Antibiotics and antiviral drugs are basic treatments for infectious diseases; however, a deteriorating situation caused by antibiotic abuse, drug-resistance, and viral mutations is shifting the focus of research attention to other therapeutic and complementary drugs for treatment of these conditions (Miyoshi et al., [@B99]; Jiang et al., [@B55]). To date, two bioactive ingredients of CHMs have been found to contribute to the treatment of infection through regulation of miRNAs. These substances can protect the human body from pathological damage, although they do not directly induce pathogen resistance. Icariine -------- Icariine \[ICA, 2-(4′-methoxyphenyl)-3-rhamnosido-5-hydroxyl-7-glucosido-8-(3′-methyl-2-butylenyl)-4-chromanone; [Chem. 30](#T2){ref-type="table"}\] is the main bioactive flavonoid glucoside extracted from *Epimedium brevicornu* Maxim. Under TCM, this herb was considered to nourish "yang qi" and generally applied for treatment of osteoarticular and reproductive diseases. ICA can suppress osteoclast bone resorption and bone loss, indicating great potential for use as a treatment agent for both aseptic loosening and bacteria-induced bone loss (Zhang et al., [@B186]; Liu et al., [@B79]). Specifically, ICA can restore LPS-induced bone loss, without obvious cytotoxicity. This product can down-regulate expression of the osteogenic inhibitor, miR-34c, while it up-regulates levels of the key transcription factor, RUNX2, thereby inducing osteogenic differentiation and mineral nodule formation. Moreover, miR-34c overexpression can reverse these effects of ICA. Additionally, ICA markedly suppresses LPS-induced activation of JNK, p38, and NF-kB pathways, leading to therapeutic effects in diseases causing bacteria-induced bone loss, such as osteomyelitis and septic arthritis (Liu et al., [@B79]). Interestingly, ICA also exhibits anticancer activity in ovarian cancer via down-regulation of miR-21 expression. This subsequently induces PTEN, RECK, and Caspase-3 activity, while BCL-2 protein expression is inhibited, leading to suppression of cell proliferation and increased apoptosis (Li J. et al., [@B70]). Based on these findings, miR-34c appears to facilitate the mechanisms underlying the role of ICA in infectious bone loss. Furthermore, the identification of miR-21 suggests a potential new application of ICA in cancer therapy. Therefore, there is promise that additional currently unknown functions of this medicinal herb could be determined by studying ncRNA and related regulatory networks. Ginsenosides ------------ Ginsenosides (GS,(3S,5R,8R,9R,10R,14R,17S)-17-(2-hydroxy-6-methylhept-5-en-2-yl)-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta\[a\]phenanthren-3-ol; [Chem. 31](#T2){ref-type="table"}), also referred to as panaxosides, are a class of natural steroid glycosides and triterpene saponins. These products include various active components, such as ginsenoside Re, Rg, Rh, Rb, and Rc. GS are mainly isolated from *Panax ginseng* C. A. Mey., a valuable herb with nourishing effects and a long history of use in ancient China. At present, GS products are not only used to promote health, but also for their activity as immune regulators in many diseases (Jiang Z. et al., [@B56]; Shin et al., [@B119]; Yu X. et al., [@B171]). GS exert a cytoprotective effect, thereby promoting cell viability on avian influenza H9N2/G1 infection. During this process, the expression of miR-15b was up-regulated, while production of IP-10 was markedly inhibited. Furthermore, cytometry and TUNEL analyses indicated that ginsenoside Re prevents apoptosis and DNA damage in human endothelial cells caused by H9N2/G1 (Chan et al., [@B13]). These results are inconsistent with the traditional concept that GS is only suitable for treatment of sub-optimal health status or chronic diseases and greatly expand the potential for application of GS for treatment of acute infectious diseases in the future. Anti-senescence Effects of CHMs {#s8} =============================== Cell senescence is the irreversible state in which cells undergo cycle arrest responding to various factors (Watanabe et al., [@B147]). It participates in biological processes involving embryonic development, wound healing and aging, closely relating to organismal aging and diseases, and thus arousing widespread concerns in researchers (Watanabe et al., [@B147]; de Magalhães and Passos, [@B26]). Currently, several bioactive ingredients of CHMs have been found to act positive roles in anti-senescence. Salidroside ----------- Salidroside \[SAL, 2-(4-Hydroxyphenyl)ethyl beta-D-glucopyranoside; [Chem. 32](#T2){ref-type="table"}\] is the main bioactive extract from *Rhodiola rosea* L. with effects of nourishing "yang qi" and promoting blood circulation under TCM theory. Modern pharmacological study further revealed that the medicinal herb not only exerts anti-fatigue ability, but also improves resistance to hypoxia (Li et al., [@B68]). Moreover, SAL has been supported to possess anti-senescence activity. The potential mechanism is related to regulation of multiple miRNAs expression. Through upregulating let-7c, let-7e, miR-3620, and decreasing expression of miR-411, miR-24-2-5p and miR-485-3p in the aging cells, SAL participates in several pathways involving p53, transcription factor CREB and AKT/mTOR signaling (Zhang J. et al., [@B178]). As is known that both let-7 and mTOR are aging-related (Marasa et al., [@B95]; Wu et al., [@B153]), and the former factor can directly inhibit the expression of the latter (Marcais et al., [@B96]). Therefore, it\'s possible that SAL possesses anti-senescence effect by regulating let-7 and mTOR; however, the predicted regulatory relationship requires more validation in the future. Phlorizin --------- Phlorizin (PZ, Phloretin-2′-O-beta-glucoside; [Chem. 33](#T2){ref-type="table"}) is the main active ingredient of *Acanthopanax senticosus* (Rupr. et Maxim.) Harms which is a traditional CHM with functions.of nourishing and enhancing strength. PZ is convinced to exert effects of anti-fatigue, learning improvement and immune-enhancing (Huang et al., [@B49]). Researches further reported that PZ can act as a promising agent for skin aging (Zhai et al., [@B173]; Choi et al., [@B24]). By promoting epidermal cell proliferation and self-renewal, PZ thickens epidermis to maintain skin structure and resistance to aging. Moreover, PZ increases expression of p63 and proliferating cell nuclear antigen (PCNA), as well as integrin α6, integrin β1 and type IV collagen. Particularly, the mRNA of type IV collagen is also increased and possibly regulated by downregulation of miR-135b (Choi et al., [@B24]). As a result, miR-135b/type IV collagen axis may be the underlying regulatory mechanism of anti-senescence induced by PZ. Osthole ------- Osthole (Ost, 7-methoxy-8-(3-methyl-2-butenyl)-2H-1-benzopyran-2-one; [Chem. 34](#T2){ref-type="table"}) is mainly extracted from *Cnidium monnieri* (L.) Cuss. which was commonly used for nourishing "yang qi" and relieving itching in TCM practice. Current pharmacological researches newly revealed that Ost can improve memory, delay senescence and resist cell damage in Alzheimer\'s disease (AD) (Hu et al., [@B46]; Zheng et al., [@B191]). As it\'s clear that beta-amyloid peptide (Aβ) is the critical pathology of AD, inhibition of Aβ deposition thereby becomes an important treatment strategy for the disease (Wilcock et al., [@B150]). Ost was reported to enhance cyclic AMP response element-binding protein (CREB) phosphorylation and then inhibit Aβ cytotoxicity on neural cells (Hu et al., [@B46]). Further mechanism study indicates that it upregulates miR-107, and then promotes cells viability of neuron, resulting in suppression of the protein expression of Aβ and BACE1, as well as LDH (Xiao et al., [@B155]). Therefore, Ost exertes obvious neuroprotective effect through targeting miR-107 and impeding Aβ deposition, presenting as a potential treatment agent for neurogenic aging and neurodegenerative disease. Inhibitory Effects of CHMs on Structural Remodeling {#s9} =================================================== Structural remodeling is an important factor that can impede the normal functions of tissues and organs. It is also the main pathological change during the late stages of various diseases, making poor prognosis and difficult treatment (Bijkerk et al., [@B7]; Bittencourt et al., [@B8]; Zhuang et al., [@B198]). Encouragingly, three CHM ingredients have been demonstrated to exert protective effects on this pathological change through regulation of miRNAs. Panax Notoginseng Saponins -------------------------- Panax notoginseng saponins (PNS, notoginsenoside-fe, 98%; [Chem. 35](#T2){ref-type="table"}) are a chemical mixture extracted from the root of *Panax notoginseng* (Burk.) F. H. Chen. According to TCM theory, the traditional herb can simultaneously promote blood circulation and prevent bleeding; therefore, it was commonly used to treat coronary artery disease, stroke, gastrointestinal bleeding, irregular menstruation, and bruises. Currently, several PNS preparations, including xuesaitong injections and xuesetong capsules, are widely used to treat cardiovascular diseases (Song et al., [@B121]). The improvement in cardiac prognosis caused by PNS has been attributed to its regulation of miRNAs and suppression of structural remodeling. PNS was reported to increase expression of the anti-fibrotic factor, miR-29c, which is clearly reduced in mice with isoproterenol-induced myocardial fibrogenesis, leading to downregulation of its target genes: collagen (Col) 1a1, Col1a2, Col3a1, Col5a1, Fbn1, and TGFβ1, thus exerting protective effects against myocardial injury and fibrosis (Liu L. et al., [@B81]). In addition, PNS has obvious resistance to H~2~O~2~-induced oxidative damage, showing anti-apoptosis activity in vascular endothelial cells (VECs) by suppressing miR-146b-5p expression (Wang J. et al., [@B146]). Moreover, notoginsenoside R1, one main component of PNS, can delay the process of senescence in VECs by regulating miR-34a/SIRT1/p53 pathway (Lai et al., [@B66]). As a result, through repairing VECs damages, PNS inhibits vascular pathological process. PNS also has an active role in tumors complicated by myocardial ischemia where paradoxical treatment strategy existed. PNS and its major components, Rg1, Rb1, and R1, are implicated in tissue-specific regulation of angiogenesis, and can inhibit tumor growth, as well as attenuating myocardial ischemia. The potential underlying mechanism may be the down-regulation of miR-18a and vascular markers (CD34 and vWF) in tumor, with simultaneous up-regulation of these factors in heart (Yang Q. et al., [@B162]). Notably, by modulating Met/miR-222 axis, and then increasing target genes of tumor suppressor p27 and PTEN expression, PNS selectively inhibits the survival of lewis lung carcinoma cells and attenuates tumor growth in mice (Yang Q. et al., [@B161]). Based on the above results, PNS appears to exert its cardioprotective function by preventing fibrosis, improving vascular endothelium, and promoting angiogenesis in the heart. Simultaneously, considering the cardioprotection and anti-tumor effects through targeting miRNAs, PNS is especially suitable for patients with heart disease and tumor. Tetrandrine ----------- Tetrandrine (TET, 6,6′,7,12-tetramethoxy-2,2′-dimethyl-1 beta-berbaman; [Chem. 36](#T2){ref-type="table"}) is a bisbenzylisoquinoline alkaloid extracted from *Stephania tetrandra* S. Moore. The medicinal plant was often used for treatment of rheumatism and edema under the theories of TCM. Notably, the source plant should not be confused with *Radix Aristolochiae Fangchi* which causes nephrotoxicity, despite their similar Chinese names. A recent study identified a new pharmacological effect of TET in treatment of anti-hypertrophic scarring. The underlying mechanism was suggested to be repression of DNA and collagen synthesis in scar-derived fibroblasts (Liu et al., [@B78]). Furthermore, by upregulating miR-27b and downregulating miR-125b, TET influenced the expression of putative targets, including VEGFC, BCL2L12, COL4A3, and FGFR2, predicted to contribute to several scar and wound healing-related signaling pathways (Ning et al., [@B103]). Consequently, TET has therapeutic potential for the inhibition of skin tissue hyperplasia after wounding or surgery. Leonurine --------- Leonurine (LEO, 4-Guanidino-n-butyl syringate; [Chem. 37](#T2){ref-type="table"}) is the alkaloid compound from *Leonurus artemisia* (Laur.) S. Y. Hu F, which was commonly used for gynecological diseases in TCM. Newly reported results have indicated the cardioprotective effect by studying LEO activity, namely anti-atherosclerosis (Jiang T. et al., [@B54]), anti-oxidation (Gao et al., [@B32]) and resistant to cardiomyocyte hypertrophy (Lu et al., [@B86]). LEO treatment can significantly reduce the surface area of hypertrophic cardiomyocytes, decrease the content of atrial natriuretic peptide (ANP), endothelin-1 (ET-1), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated p38 MAPK (p-p38 MAPK), myocyte enhancer factor 2 and β-myosin heavy chain. Moreover, it also up-regulates the expression levels of α-myosin heavy chain protein and miR-1. Thus, by upregulating miR-1 expression and then inhibiting the activation of p38MAPK signaling pathway, LEO may inhibit AngII-induced cardiomyocyte hypertrophy and structural remodeling (Lu et al., [@B86]). Other Effects of CHMs {#s10} ===================== Bioactive ingredients of CHMs can exert various protective effects through targeting different miRNA, lncRNA, or circRNA. Besides the above mentioned mechanisms, some ingredients also play positive roles in anti-I/R injury, anti-arrhythmia, recovery of blood-spinal cord barrier, and promotion of cardiac differentiation by targeting lncRNA and miRNA. Calycosin/Astragaloside IV -------------------------- Calycosin (CAL, 7,3′-dihydroxy-4′-methoxyisoflavone; [Chem. 38](#T2){ref-type="table"}) is a natural phytoestrogen derived from *Astragalus membranaceus* (Fisch.) Bunge. which can nourish "yang qi" and was commonly used for cardiovascular and cerebrovascular diseases in TCM practice. It\'s indicated that the neuroprotection effect of CAL is related to miRNA. CAL markedly improves the infarcted volume, brain water content, and neurological deficit in cerebral I/R injury rats, by upregulating miR-375, ER-α and Bcl-2, and inhibiting RASD1 expression (Wang Y. et al., [@B145]). Regrettably, a systematic mechanism of miR-375 and those downstream targets has not been revealed in this study. Moreover, CAL also possesses positive role in anti-cancer, enriching the pharmacological effect and application of *Astragalus membranaceus* extracts (Tseng et al., [@B131]; Kong et al., [@B63]). It\'s demonstrated that CAL significantly impedes lncRNA EWSAT1 expression in nasopharyngeal carcinoma (NPC), followed by influenced downstream factors and pathways, leading to inhibitory growth. Furthermore, lncRNA EWSAT1 overexpression can reverse CAL-induced effect, indicating lncRNA EWSAT1 act as the specific target of CAL promisingly (Kong et al., [@B63]). Additionally, Astragaloside IV (ASIV, 3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosylcycloastragenol; [Chem. 39](#T2){ref-type="table"}), another bioactive compound of *Astragalus membranaceus* (Fisch.) Bunge., can ameliorate precancerous lesions of gastric carcinoma (PLGC) markedly. It lowers mRNA and protein expressions of LDHA, MCT1, MCT4, HIF-1α, and CD147, as well as increasing TIGAR and p53 content. Furthermore, ASIV treatment promotes miR-34a expression. As a result, ASIV improves abnormal glycolysis and dysplasia possibly via regulation of miR-34a/LDHA pathway (Zhang C. et al., [@B174]). Interestingly, the total flavonoids of *Astragalus membranaceus* (Fisch.) Bunge. (TFA) can improve heart function damaged by viral myocarditis. By upregulating the expression of miR-378 and miR-378^\*^ in cardiomyocytes infected with coxsackie B3 virus, TFA may inhibit cardiac hypertrophy and improve prognosis (Nagalingam et al., [@B102]; Wan et al., [@B134]). Therefore, it can be speculated that the heart protection of TFA is attributed to inhibition of myocardial pathology by regulating miR-378 and miR-378^\*^. From the above results, it can been seen that although CAL, ASIV and TFA are extracted from the same herb, they have different targets and are applicable for distinct diseases, demonstrating the study necessity of identified ingredients and targets from CHMs. Paeonol ------- Paeonol (PAE, 2′-Hydroxy-4′-methoxyacetophenone; [Chem. 40](#T2){ref-type="table"}) is the main bioactive ingredient of *Paeonia suffruticosa* Andr. and *Cynanchum paniculatum* (Bunge) Kitagawa. The two herbs promoted blood circulation and could be used for cardiovascular diseases in TCM practice. Further pharmacological research shows PAE significantly reduces the incidence of ischemic arrhythmia in rats, including lowered frequency of ventricular premature beat, ventricular tachycardia and ventricular fibrillation. Moreover, it markedly decreases infarct size of myocardium. The potential treatment target is miR-1 which is inhibited by PAE in cardiomyocytes (Zhang and Xiong, [@B179]). Nevertheless, the above study only reveals the possible regulatory relationship between PAE and miR-1, which needs more verification and further identifies the downstream target gene of miRNA. Salvianolic Acid A ------------------ Salvianolic acid A (Sal A, (R)-3-(3,4-Dihydroxyphenyl)-2-(((E)-3-(2-((E)-3,4-dihydroxystyryl)-3,4-dihydroxyphenyl) acryloyl)oxy)propanoic acid; [Chem. 41](#T2){ref-type="table"}) is derived from water-soluble phenolic compound of *Salvia miltiorrhiza* Bge. It has protective effects of anti-IR injury (Jiang et al., [@B53]; Yang et al., [@B163]), recovery of neurological function (Yu D. S. et al., [@B168]) and anti-cancer activities (Chen et al., [@B15]; Lu et al., [@B85]), the latter two pharmacological actions of which are attributed to miRNA regulation. It\'s reported that Sal A significantly increases expression of tight junction proteins and HO-1, and decreases p-caveolin-1 and apoptosis-related proteins, resulting in recovery of blood-spinal cord barrier integrity after spinal cord injury (SCI). Furthermore, HO-1 inhibitor can attenuate the regulation of ZO-1, occluding, and p-caveolin-1 by Sal A. The underlying target and mechanism may be upregulation of miR-101 which promotes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1. Conversely, miR-101 inhibitor accelerates the permeability of rat brain microvascular endothelial cells, and the protein of Cul3 by targeting its mRNA. As a result, Sal A improves neurological function after SCI through targeting miR-101/Cul3/Nrf2/HO-1 signaling pathway (Yu D. S. et al., [@B168]). Another study indicated that Sal A can also down-regulate the expression of multidrug resistance gene MDR1 in lung cancer, thereby emerging as a new treatment agent for lung cancer resistance. The potential mechanism may be related to up-regulation of 4 miRNA expressions including miR-3686, miR-4708-3p, miR-3667-5p, and miR-4738-3p (Chen et al., [@B15]). This study attempts to find the upstream target of Sal A against MDR1 from perspective of post-transcriptional regulation; but current result cannot directly confirm the regulatory correlation between the 4 miRNAs and MDR1. Thus, more and deeper experiments are urgently needed in the future. Andrographolide --------------- Andrographolide (Andro, 17-hydro-9-dehydro-andrographolide; [Chem. 42](#T2){ref-type="table"}) is a diterpenoid lactone compound derived from *Andrographis paniculata* (Burm. f.) Nees, a natural anti-bacterial and anti-viral CHM. A recent study further demonstrates that Andro can inhibit hepatoma tumor growth. It promotes the expression of 22 miRNAs, but declines that of other 10 miRNAs in a xenograft mouse tumor model *in vivo*. Among those upregulated miRNAs, miR-222-3p, miR-106b-5p, miR-30b-5p, and miR-23a-5p are confirmed in cell experiments *in vitro*. Functional analysis reveals that those miRNAs are mainly involved in signaling pathways of miRNAs in cancer, MPAKs and focal adhesion. Moreover, 24 target genes involved in the above signaling pathways are illustrated to be consistent with miRNAs expression (Lu et al., [@B85]). As a result, Andro prevents hepatoma tumor growth partially through regulating miRNA profile; whereas the specific target and underlying mechanism still need deeper study. Puerarin -------- Puerarin (PUE, 7,4\'-Dihydroxy-8-C-glucosylisoflavone; [Chem. 43](#T2){ref-type="table"}) is the main active ingredient extracted from *Radix Puerariae Lobatae* which improved symptoms of fever, neck stiffness, thirst and diarrhea in ancient China. Modern researches reveal the cardiovascular protection of PUE for myocardial infarction (Zhang et al., [@B183]) and arrhythmia (Zhang et al., [@B175]). The active effects may be attributed to promotion of cardiac differentiation (Cheng et al., [@B23]; Wang L. et al., [@B139]). PUE upregulates expression of caveolin-3, amphiphysin-2 and junctophinlin-2, and then ameliorates myofibril array and sarcomeres formation, accompanied by increased t-tubules development in the embryonic stem cell-derived cardiomyocytes. Moreover, PUE suppresses the upstream regulatory factor of caveolin-3, namely miR-22, indicating miR-22/caveolin-3 axis may be the underlying mechanism of cardiomyogenesis induced by PUE (Wang L. et al., [@B139]). Conclusion {#s11} ========== CHM has long been a powerful weapon used by Chinese people to combat disease. Over thousands of years, practitioners of CHM have accumulated a wealth of knowledge which is used to prevent and cure diseases. The theoretical concepts of TCM act as the basis for scientific research into CHM today, including identification of the bioactive ingredients and underlying mechanisms of CHMs that could be of benefit internationally---a gift from the Chinese people to the world (Tu, [@B132], [@B133]). Chinese pharmacologist, Youyou Tu, and her team discovered the highly effective and low-toxicity bioactive ingredient "artemisinin" from *Artemisia annua* L. (also referred to as "qinghao" in Chinese), inspired by, "*A Handbook of Prescriptions for Emergencies"* (written around 317--420 CE), thus making an outstanding contributions to the global treatment of malaria (Tu, [@B133]). Consequently, we became convinced that study of the bioactive ingredients of CHMs is an effective way to reveal their potential mechanisms of action and further broaden their clinical application. By conducting the above comprehensive review, we found that bioactive ingredients of CHMs can play positive roles in treatment of cancer, cardiovascular, nervous system, respiratory, digestive, infectious, and senescence-related diseases. Through targeting various miRNAs, lncRNAs, circRNAs, or ceRNA crosstalk, these ingredients exert protective effects, including pro-apoptosis, anti-proliferation and anti-migration, anti-inflammation, anti-atherosclerosis, anti-infection, anti-senescence, and anti-structural remodeling. Some miRNAs, including miR-21, miR-34a, miR-34c, miR-155, miR-29a, miR-203, miR-27b, miR-184, and miR-143, contributed to the treatment mechanisms of more than one bioactive ingredient of CHMs. In particular, miR-21 was identified as targeted and regulated by BBR (Luo et al., [@B89]), TP (Li et al., [@B74]), RES (Wang G. et al., [@B136]), CA (Qu et al., [@B107]), ICA (Li J. et al., [@B70]), AIL (Yang P. et al., [@B160]), Car/Thy (Khosravi and Erle, [@B61]), DHM (Yang D. et al., [@B158]), and COR (Yang et al., [@B157]), especially in its anti-cancer activities, indicating that this miRNA is stably targetable and responsive to the pharmacological effects of various CHMs. Moreover, miR-155 was associated with inflammatory responses and could be inhibited by CUR, RES, Tan IIA, CA, Car/Thy and AKBA, in inflammatory-related diseases (Tili et al., [@B130]; Fan et al., [@B28]; Khosravi and Erle, [@B61]; Ma F. et al., [@B91]; Xuan et al., [@B156]; Qu et al., [@B107]; Sayed et al., [@B114]). Thus, it is highly likely that miR-155 could represent a new treatment target for anti-inflammation. In addition, three complex ceRNA crosstalk networks were discovered to function in the therapeutic mechanisms of ART, Sch B, and CA. Specifically, ART regulates the lncRNA UCA1/miR-184/BCL-2 axis, to inhibit prostate cancer (Zhou S. et al., [@B194]), while the has-circ-0043256/miR-1252/ITCH axis was involved in the treatment of non-small cell lung cancer by CA (Tian F. et al., [@B128]). The miR-150/ lncRNA BCYRN1 axis was targeted by Sch B treatment, leading to suppression of cell proliferation in asthma (Zhang X. Y. et al., [@B185]). All of these complex networks provide foundations for in-depth understanding and broader application of CHMs in the near future. The interactions between bioactive ingredients of CHMs with ncRNA targets are the subject of intensive and rapidly expanding research. This has helped to reveal the treatment mechanisms underlying the activities of CHMs and offers promising complementary and alternative treatments for diseases, based on scientific research. Although some previous reviews have revealed the increasing importance of bioactive ingredients (Huang et al., [@B50]; Lelli et al., [@B67]) or CHMs (Hong et al., [@B44]) in the treatment of diseases by targeting ncRNA. However, most of them mainly focused on one kind of ncRNA (particularly miRNA), or are limited to a specific disease (mostly cancer) (Mohammadi et al., [@B101]; Mirzaei et al., [@B98]); rather than overall and comprehensive ncRNA targets, ceRNA crosstalk and corresponding mechanisms. As a result, we consider it\'s necessary to make a systematic review about the treatment mechanisms of bioactive ingredients from CHMs by targeting miRNA, lncRNA, and circRNA. From our review, it can be seen that studies are currently in initial and exploratory phases, and several critical problems remain. First, various individual ncRNA molecules are targets of CHM bioactive ingredients; however, recent results are far from sufficient to allow understanding of the complex regulatory interactions between circRNA, lncRNA, miRNA, and mRNA in the treatment of diseases. Second, the metabolism of drugs in single cell lines and animals may differ from that in the human body; therefore, results based on basic research require further verification in clinical trials. Third, each CHM generally contains numerous ingredients and a TCM clinical prescription often consists of several CHMs; therefore, multiple targets and ceRNA crosstalk must occur and the study of classic TCM formulae will further complicate the picture. In conclusion, ncRNAs are potential targets of CHMs and understanding of ceRNA crosstalk has helped to reveal the complex mechanisms underlying multi-target and multi-level regulation of bioactive ingredients from CHMs. Therefore, CHM ingredients represent new and promising choices for future alternative disease treatments. Author Contributions {#s12} ==================== JW and JL designed the study. YD, HC, and JG conducted searches and extracted the data. YL and YD analyzed the data. YD wrote the manuscript. Conflict of Interest Statement ------------------------------ The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. **Funding.** This study was supported by the National Natural Science Foundation of China (No. 81673847; No. 81473561). ###### Chem. 1--43 Chemical formulae of bioactive ingredients from CHMs. ------------------------------------- -------------------------------------------- ![](fphar-10-00515-i0001.jpg)\ ![](fphar-10-00515-i0002.jpg)\ *Chem. 1 Berberine* *Chem. 2 Artesunate* ![](fphar-10-00515-i0003.jpg)\ ![](fphar-10-00515-i0004.jpg)\ *Chem. 3 Triptolide* *Chem. 4 Triptonide* ![](fphar-10-00515-i0005.jpg)\ ![](fphar-10-00515-i0006.jpg)\ *Chem. 5 Ailanthone* *Chem. 6 Cordycepin* ![](fphar-10-00515-i0007.jpg)\ ![](fphar-10-00515-i0008.jpg)\ *Chem. 7 Soya-cerebroside* *Chem. 8 Tubeimoside I* ![](fphar-10-00515-i0009.jpg)\ ![](fphar-10-00515-i0010.jpg)\ Chem. 9 Oridonin Chem. 10 Curcumin ![](fphar-10-00515-i0011.jpg)\ ![](fphar-10-00515-i0012.jpg)\ Chem. 11 Shikonin Chem. 12 Paeoniflorin ![](fphar-10-00515-i0013.jpg)\ ![](fphar-10-00515-i0014.jpg)\ Chem. 13 Honokiol Chem. 14 Schiscandrin B ![](fphar-10-00515-i0015.jpg)\ ![](fphar-10-00515-i0016.jpg)\ Chem. 15 Resveratrol Chem. 16 Soybean isoflavones ![](fphar-10-00515-i0017.jpg)\ ![](fphar-10-00515-i0018.jpg)\ Chem. 17 Matrine Chem. 18 Corylin ![](fphar-10-00515-i0019.jpg)\ ![](fphar-10-00515-i0020.jpg)\ Chem. 19 Tanshinones UA Chem. 20 Magnesium lithospermate B ![](fphar-10-00515-i0021.jpg)\ ![](fphar-10-00515-i0022.jpg)\ Chem. 21 Baicalin Chem. 22 Cinnamaldehyde ![](fphar-10-00515-i0023.jpg)\ ![](fphar-10-00515-i0024.jpg)\ Chem. 23 Geniposide Chem. 24 Carvacrol ![](fphar-10-00515-i0025.jpg)\ ![](fphar-10-00515-i0026.jpg)\ Chem. 25 Thymol Chem. 26 3-acetyl-11-keto-a-boswellic acid ![](fphar-10-00515-i0027.jpg)\ ![](fphar-10-00515-i0028.jpg)\ Chem. 27 Sinapic acid Chem. 28 Polydatin ![](fphar-10-00515-i0029.jpg)\ ![](fphar-10-00515-i0030.jpg)\ Chem. 29 Ampelopsin Chem. 30 Icariine ![](fphar-10-00515-i0031.jpg)\ ![](fphar-10-00515-i0032.jpg)\ Chem. 31 Ginsenosides Chem. 32 Salidroside ![](fphar-10-00515-i0033.jpg)\ ![](fphar-10-00515-i0034.jpg)\ Chem. 33 Phlorizin Chem. 34 Osthole ![](fphar-10-00515-i0035.jpg)\ ![](fphar-10-00515-i0036.jpg)\ Chem. 35 Panax Notoginseng Saponins Chem. 36 Tetrandrine ![](fphar-10-00515-i0037.jpg)\ ![](fphar-10-00515-i0038.jpg)\ Chem. 37 Leonurine Chem. 38 Calycosin ![](fphar-10-00515-i0039.jpg)\ ![](fphar-10-00515-i0040.jpg)\ Chem. 39 Astragaloside IV Chem. 40 Paeonol ![](fphar-10-00515-i0041.jpg)\ ![](fphar-10-00515-i0042.jpg)\ Chem. 41 Salvianolic acid A Chem. 42 Andrographolide ![](fphar-10-00515-i0043.jpg)\ Chem. 43 Puerarin ------------------------------------- -------------------------------------------- [^1]: Edited by: Chandravanu Dash, Meharry Medical College, United States [^2]: Reviewed by: Zijian Zhang, Texas Tech University Health Sciences Center El Paso, United States; Yong Xu, First Hospital of Shanxi Medical University, China [^3]: This article was submitted to Pharmacogenetics and Pharmacogenomics, a section of the journal Frontiers in Pharmacology [^4]: †These authors have contributed equally to this work

{ "pile_set_name": "PubMed Central" }

SS Joplin Victory The SS Joplin Victory was the 12th Victory ship built during World War II under the Emergency Shipbuilding program. She was launched by the California Shipbuilding Company on April 25, 1944 and completed on June 15, 1944. The ship's United States Maritime Commission designation was VC2-S-AP3, hull number 12 (V-12). The 10,500-ton Victory ships were designed to replace the earlier Liberty Ships. Liberty ships were designed to be used just for World War II. Victory ships were designed to last longer and serve the US Navy after the war. The Victory ship differed from a Liberty ship in that they were: faster, longer and wider, taller, had a thinner stack set farther toward the superstructure and had a long raised forecastle. SS Joplin Victory was christened on April 26, 1944 and launched at the yards of the California Shipbuilding Corporation. The launching of The SS Joplin Victory splashed into the water of Wilmington, Los Angeles. World War II SS Joplin Victory served in the Pacific Ocean in World War II as part of the Pacific war. SS Joplin Victory Naval Armed Guard crews earned "Battle Stars" in World War II for the assault occupation of Okinawa. Ward incident SS Joplin Victory was part of a foreign relations project between the United States and China called the Ward incident, a diplomatic incident. In 1949 she streamed in to China port city of Port of Tianjin, called Taku Bar at the time, to remove US citizens at Mukden. She steamed in with the Lakeland Victory. SS Joplin Victory was in port from Dec. 5 to 7, 1949. The two ships removed the US diplomatic staff in China. US Consul General Angus Ward and nineteen other American citizens has spent time in a Communist Chinese jail. On February 3, 1949 she arrived in San Francisco with Shanghai refugees. Korean War SS Joplin Victory served as merchant marine naval ship supplying goods for the Korean War. She help move the 140th Medium Tank Battalion. About 75 percent of the personnel taken to Korea for the Korean War came by the merchant marine ships. The SS Joplin Victory transported goods, mail, food and other supplies. About 90 percent of the cargo was moved by merchant marine naval to the Korean war zone. SS Joplin Victory made trips between 18 November 1950 and 23 December 1952 helping American forces engaged against Communist aggression in South Korea. On Nov. 19, 1952 she was blown by high winds and broke loose from the Oakland Estuary pier, in Oakland, California. She ran into the side of a transport ship, the USN Navy's SS Neshoba. James River She was laid up at Astoria, Oregon in 1952 and later transferred to the James River in Virginia as part of the National Defense Reserve Fleet for years. In 1994 she was scrapped in Alang, India. See also List of Victory ships Liberty ship Type C1 ship Type C2 ship Type C3 ship References Sources Sawyer, L.A. and W.H. Mitchell. Victory ships and tankers: The history of the ‘Victory’ type cargo ships and of the tankers built in the United States of America during World War II, Cornell Maritime Press, 1974, 0-87033-182-5. United States Maritime Commission: Victory Cargo Ships Category:Victory ships Category:Ships built in Los Angeles Category:United States Merchant Marine Category:1944 ships Category:World War II merchant ships of the United States

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Q: Linear Interploation using two arrays I have the following arrays: List_CD = [2410.412434205376, 2287.6750893063017, 2199.2602314650626, 2124.4647889960825, 2084.5846633116403, 2031.9053600816167, 1996.2844020790524, 1957.1098650203032, 1938.4110044030583, 1900.0783178367647, 1877.6396548046785, 1868.2902104714337, 1844.9165996383219, 1816.8682911816766] List_Dose = [10.0, 12.0, 14.0, 16.0, 18.0, 20.0, 22.0, 24.0, 26.0, 28.0, 30.0, 32.0, 34.0, 36.0] what I am trying to do is to do a simple interpolation using: dsize = numpy.interp(2000., List_CD, List_Dose) the result that expect is between 20.0 and 22.0 but I keep getting a value of 10.0 Can anyone help here please? A: xp : 1-D sequence of floats The x-coordinates of the data points, must be increasing. Your List_CD is not increasing. You can sort it in the following way: d = dict(zip(List_CD, List_Dose)) xp = sorted(d) yp = [d[x] for x in xp] numpy.interp(2000., xp, yp) # returns 21.791381359216665 or: order = numpy.argsort(List_CD) numpy.interp(2000., np.array(List_CD)[order], np.array(List_Dose)[order])

{ "pile_set_name": "StackExchange" }

G Man Breaking the Ninth Commandment G Man has been saying that I have said that you can believe in a supernatural deity or God and still be an atheist…which is completely absurd. He recently was on the Drunken Peasants again lying about what I have never said, even though just a few days prior I made it very clear that you can not believe in a God and rationally consider yourself to be an atheist. LIKE, SHARE, and SUBSCRIBE 🙂 (and leave a comment!)

{ "pile_set_name": "Pile-CC" }

---------------------- Forwarded by Judy Hernandez/HOU/ECT on 11/22/2000 08:51 AM --------------------------- Daily-Blessings <dailyblessings.10@lists.postmastergeneral.com> on 11/21/2000 10:47:07 PM To: judy.hernandez@enron.com cc: Subject: Daily Blessing 11/22/00 Daily Blessing http://www.daily-blessings.com/bless147.htm Intelligence http://www.daily-blessings.com/humor54.htm FORGET PC PHONE. GET REAL LONG DISTANCE AT NO COST bigredwire is the first and only company to offer REAL long distance at no cost Switch your long distance to bigredwire and get REAL long distance at zero cost to you. Up to 100 complimentary minutes everyday when you zap your online bill. If you don't zap, pay only 5 cents a minute without fees. Switch now! find out how at http://www.daily-blessings.com/cjbigredwire.htm Hundred's of you have taken advantage of the free download available for the Work From Home folks. If you haven't checked it out yet...you should!! http://www.daily-blessings.com/cjworkfromhome.htm <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> * To remove yourself from this mailing list, point your browser to: http://inbound.postmastergeneral.com/remove?dailyblessings:10 * Enter your email address (judy.hernandez@enron.com) in the field provided and click "Unsubscribe". The mailing list ID is "dailyblessings:10". OR... * Reply to this message with the word "remove" in the subject line. This message was sent to address judy.hernandez@enron.com X-PMG-Recipient: judy.hernandez@enron.com <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>> <<<>>>

{ "pile_set_name": "Enron Emails" }

Social Anhedonia and Romantic Relationship Processes. Social anhedonia is a deficiency in the capacity to experience pleasure from social interactions. This study examined the implications of social anhedonia for romantic relationship functioning, including the association of social anhedonia with sentiments toward romantic partners that are central to relationship functioning (satisfaction, commitment, regard for the partner, and care for the partner's welfare) and analogous perceptions of the partner's sentiments. Data were collected from 281 participants who were involved in romantic relationships. Social anhedonia predicted less satisfaction, regard, and care, and these effects were independent of attachment insecurity and self-esteem. In addition, social anhedonia had an indirect negative effect on commitment via attachment avoidance. Social anhedonia also predicted more negative perceptions of the partner's sentiments. Results suggest that social anhedonia may undermine the functioning of romantic relationships by reducing positive sentiments toward partners and security in the partner's sentiments toward the self.

{ "pile_set_name": "PubMed Abstracts" }

Michael Arndt to Write Screenplay for Star Wars: Episode VII - jwallaceparker http://starwars.com/news/michael-arndt-to-write-screenplay-for-star-wars-episode-vii.html ====== lazugod ...you posted this eleven times. ~~~ dfc Twelve times. I flagged 11 of them.

{ "pile_set_name": "HackerNews" }

Adobe Digital Imaging How-Tos: Essential Techniques for Photoshop CS5, Lightroom 3, and Camera Raw 6 is a concise, current, and affordablefull-color guide to the key techniques for working with digital images. Choose the How-Tos guide when you want to learn the features and functions that provide immediate results. In Photoshop Lightroom 3 Advanced Techniques, photographer Chris Orwig shows how to master the subtleties of Lightroom 3 and maximize its efficiency. The course begins with an in-depth exploration of Lightroom catalogs to keep track of photos, collections, keywords, stacks, and more. Along the way, Chris shows how to integrate Bridge and Photoshop in the Lightroom workflow and shares advanced techniques, including image editing with the adjustment brush, automating actions, using plug-ins and extensions, exporting to email or an FTP server, and more. Exercise files are included with the course. Serious digital photographers, amateur or pro, who seek the fastest, easiest, most comprehensive way to learn Adobe Photoshop Lightroom 3 choose Adobe Photoshop Lightroom 3 Classroom in a Book from the Adobe Creative Team at Adobe Press.

{ "pile_set_name": "Pile-CC" }

A knifeman barricaded himself in a room with a pregnant woman at a refugee centre in Hamburg before being dramatically arrested, it has emerged. Armed police were called amid reports a man with a weapon had stormed into the facility in Hammerbrook area of the German city this morning. He is understood to have been holding a pregnant woman - believed to be his partner - hostage at the centre and was holed-up in a room. A gunman has barricaded himself in refugee centre in the German city of Hamburg, it has been reported (file picture) Footage online shows elite German officers with assault rifles storming into the building this morning at about 10.30am local time. A pregnant woman in a yellow top was seen being led away from the building a short time later. According to Bild, the man was overpowered by police and was seen on a stretcher being taken to an ambulance. Hamburg police said the man had wounded himself during the operation, but the nature of his injuries is not yet known. The police force had earlier taken to Twitter to say a major police operation was underway in the Hammerbook area. Local media reported that the man was a refugee who had been living in another state within Germany. It is not yet known why he barricaded himself in the building.

{ "pile_set_name": "OpenWebText2" }

49er & 49er FX World Championships The 49er World Championships are international sailing regattas in the 49er and 49er FX classes organized by the International Sailing Federation. It was first held in 1997. In 2013, the 49er FX class was added to the programme. The 49er is an Olympic class since 2000. The 49er FX is anan Olympics class since 2016. Editions All-time medal table 49er 49er FX Medalists 49er Open 49er Men's 49er FX Women's 49er Youth 49er FX Youth Multiple medallists 49er 49er FX See also ISAF Sailing World Championships International Sailing Federation References External links International 49er Class Association Sailing competitions Category:Recurring sporting events established in 1997

{ "pile_set_name": "Wikipedia (en)" }

Wearable UV Sensor Based on Carbon Nanotube-Coated Cotton Thread. A fabric-compatible UV sensor is presented using a cellulose-based thread coated with single-wall carbon nanotube ink. Two-terminal resistive responses of the thread were measured upon exposure to UV, and the effects of intensity, wavelength, and on/off cycling were studied. The sensor was tested in the field under direct sunlight, demonstrating practical usability for a wearable/flexible UV sensor system. The results here confirm the potential for an inexpensive wearable sensor in contrast to the conventional rigid and bulky solid-state detectors.

{ "pile_set_name": "PubMed Abstracts" }

4G Wimax Jammer 50 Meters,High Power 4G Block,4G LTE Blocker 60 Meters,Product Description This high quality signal jamming blocker will fit in the palm of your hand, or comfortably in your pocket. Our best seller has no external antennas to break, is loaded with great...

{ "pile_set_name": "Pile-CC" }

Abnormal glucose metabolism in patients treated with antipsychotics. Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical antipsychotics, although the question is still debated because of the presence of many confounding factors. A close relationship between drug-induced weight gain and risk of diabetes has been reported, emphasizing the role of insulin resistance. However, some cases of diabetes developed independently of weight gain, rather rapidly and possibly progressing to ketoacidosis, thus arguing for a severe impairment of insulin secretion. Another debated question is whether diabetes risk is a class action or a differential action. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. Interestingly, reversibility of drug-related diabetes has been reported with aripiprazole. The choice of atypical antipsychotic medication for a specific patient depends on many factors, but the likelihood of developing diabetes should become an important consideration. When prescribing an atypical antipsychotic, a commitment to careful baseline screening and follow-up monitoring is essential in order to mitigate the risk of developing diabetes and associated complications.

{ "pile_set_name": "PubMed Abstracts" }

It has been reported that Girls’ Generation member Taeyeon is in the middle of gearing up for a new solo album. Aiming for a release in the first half of the year, she is currently gathering songs to be included in the album. If all goes according to plan, Taeyeon will be the very first member of Girls’ Generation to make her debut as a solo artist. Taeyeon has already received much recognition from the public for her vocal abilities with a number of solo songs through drama OSTs, such as “If,” “Can You Hear Me,” and more. It is said that the Girls’ Generation member is joining the list of idols from SM Entertainment to take on a solo debut following SHINee’s Taemin, Super Junior’s Kyuhyun, SHINee’s Jonghyun, as well as f(x)’s Amber, who is expected to release a solo album next month. Are you excited to see Taeyeon debut as a solo artist in the near future? Source (1)

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Q: recursively traverse multidimensional dictionary and export to csv I've have a complex multidimensional dictionary that I want to export some of the the key value pairs to a csv file as a running log file. I've tried the various help with exporting to cvs functions and hacked away at most of the code example in stackoverflow on traversing multidimensional dictionaries but have failed to arrive at a solution. This problem is also unique in that it has only some key values I want to export. Here is the dictionary: cpu_stats = {'time_stamp': {'hour': 22, 'month': 5, 'second': 43, 'year': 2014, 'day': 29, 'minute': 31}, 'cpus': [[{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 39}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000}]]} I need to format the values in time_stamp into a yyyy-mm-dd hh:mm:ss and store it as the first cell of the row. I then need the values in 'cpus' for CPU_INDEX, CPU_TEMPERATURE, and CPU_FAN_SPEED in the same row as the time stamp. The csv file should look like this: time_stamp, cpu_index, cpu_temperature, cpu_fan_speed 2014-05-29, 1, 38, 12000 One example I've been hacking away on is: def walk_dict(seq, level=0): """Recursively traverse a multidimensional dictionary and print all keys and values. """ items = seq.items() items.sort() for v in items: if isinstance(v[1], dict): # Print the key before make a recursive call print "%s%s" % (" " * level, v[0]) nextlevel = level + 1 walk_dict(v[1], nextlevel) else: print "%s%s %s" % (" " * level, v[0], v[1]) I get the following output walk_dict(cpu_stats) cpus [[{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 38}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000}]] time_stamp day 29 hour 22 minute 17 month 5 second 19 year 2014 I have also been hacking away at this function as well hoping I can store the date information into variables that can then be formatted into a single string. Unfortuatly it has recursive calls which loose the local variables on subsequent calls. Using global was futile. def parseDictionary(obj, nested_level=0, output=sys.stdout): spacing = ' ' if type(obj) == dict: print >> output, '%s{' % ((nested_level) * spacing) for k, v in obj.items(): if hasattr(v, '__iter__'): # 1st level, prints time and cpus print >> output, '%s:' % (k) parseDictionary(v, nested_level + 1, output) else: # here is the work if k == "hour": hour = v elif k == "month": month = v elif k == "second": second = v elif k == "year": year = v elif k == "day": day = v elif k == "minute": minute = v print >> output, '%s %s' % (k, v) print >> output, '%s}' % (nested_level * spacing) elif type(obj) == list: print >> output, '%s[' % ((nested_level) * spacing) for v in obj: if hasattr(v, '__iter__'): parseDictionary(v, nested_level + 1, output) else: print >> output, '%s%s' % ((nested_level + 1) * spacing, v) print >> output, '%s]' % ((nested_level) * spacing) else: print >> output, '%s%s' % (nested_level * spacing, obj) if __name__ == "__main__": global year global month global day global hour global minute global second cpu_stats = {'time_stamp': {'hour': 22, 'month': 5, 'second': 43, 'year': 2014, 'day': 29, 'minute': 31}, 'cpus': [[{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 39}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000}]]} parseDictionary(cpu_stats) print '%s-%s-%s %s:%s:%s' % (year, month, day, hour, minute, second) output: { time_stamp: { hour 22 month 5 second 27 year 2014 day 29 minute 57 cpus: [ [ { metric_type CPU_INDEX value 1 { metric_type CPU_TEMPERATURE value 39 { metric_type CPU_FAN_SPEED value 12000 ] ] Traceback (most recent call last): File "./cpu.py", line 135, in <module> print '%s-%s-%s %s:%s:%s' % (year, month, day, hour, minute, second) NameError: global name 'year' is not defined Thanks, I appreciate any help in pointing me in the right direction as I'm currently at a loss. A: I agree with @desired login, however assuming you have no control of the incoming data and had to work with what you showed in your questions... You could just traverse it like so: cpu_stats = {'time_stamp': {'hour': 22, 'month': 5, 'second': 43, 'year': 2014, 'day': 29, 'minute': 31}, 'cpus': [ [{'metric_type': 'CPU_INDEX', 'value': 1}, {'metric_type': 'CPU_TEMPERATURE', 'value': 39}, {'metric_type': 'CPU_FAN_SPEED', 'value': 12000} ] ] } timestamp = '' for stats in cpu_stats.keys(): if stats == 'time_stamp': timestamp = '{year}-{month}-{day}'.format(**cpu_stats[stats]) if stats == 'cpus': for cpu in cpu_stats[stats]: cpu_index = '' cpu_temperature = '' cpu_fan_speed = '' for metric in cpu: if metric['metric_type'] == 'CPU_INDEX': cpu_index = str(metric['value']) elif metric['metric_type'] == 'CPU_TEMPERATURE': cpu_temperature = str(metric['value']) elif metric['metric_type'] == 'CPU_FAN_SPEED': cpu_fan_speed = str(metric['value']) print ','.join([timestamp, cpu_index, cpu_temperature, cpu_fan_speed])

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Inflatable Harley Quinn Bat - Suicide Squad 3 1/2in x 30in Plastic Prop | SKU: 687576 Price: $9.99 Knock your Suicide Squad costume out of the park with this Inflatable Harley Quinn Bat. Printed to look like the bat she carries in Suicide Squad, this inflatable bat reads "Good Night". Swing it around as you get into some mischief in your Suicide Squad Harley Quinn costume.

{ "pile_set_name": "Pile-CC" }

The use of halogen lamps in light fixtures provides many advantages over the use of flourescent and incandescent lamps. Halogen light sources provide, among other benefits, pure white light, instant start-up with no flickering, and are operational at any temperature including sub freezing temperatures. However, halogen light fixtures typically employ one or more lamps having a wattage that is often 100 watts or greater. This use of high wattage lamps increases the heat generated in and around the fixture. Thus, there is a need for light fixtures that allow and provide for the efficient dissipation of the heat generated by the lamp or lamps contained therein. Not only will the dissipation of heat prevent the fixture itself from becoming dangerously hot, it also assists in protecting the fixture's internal components from heat damage as well. In addition, because of the high temperatures created by a halogen lamp, the possibility exists that objects located near the lamp may unintentionally combust. Consequently, there is a need for a fixture design that prevents objects or structures such as walls and the like from coming into close contact with the light generated by the fixture in order to reduce the risk of inadvertent combustion.

{ "pile_set_name": "USPTO Backgrounds" }

HELSINKI – Nordic governments are primed to raise suspected GPS jamming of military exercises and communications with Russia. Finland and Norway intend to launch diplomatic discussions with Moscow over suspected GPS signal-jamming by Russia’s military over recent weeks that impacted areas in northern Norway where NATO-led Trident Juncture maneuvers were being conducted. Norway’s defense intelligence agency said it tracked the source of the signal-jamming to a Russian military base on the nearby, heavily fortified Kola Peninsula. Finland’s military intelligence said Norway’s analysis mirrors its own investigations and evaluations. Scrambled GPS signals were first detected during NATO’s large-scale Trident Juncture exercises in Norway at the end of October. Defense and civil aviation chiefs in Finland and Norway warned that the GPS jamming posed a serious risk to both military and commercial aircraft using the affected airspace in the High North. Finland’s Ministry of Foreign Affairs (MFA) has presented the national parliament’s Committee on Foreign Affairs (CFA) a preliminary report on the jamming. The MFA is expected to furnish the panel with a more conclusive report by the end of November. NATO general: Europe not moving fast enough on military mobility Are there changes that NATO nations can easily make to ease the logistics challenge in Europe? The GPS signal-jamming issue is being discussed with the Russian Federation “through diplomatic channels”, said Sari Rautio, director of the MFA’s unit for security policy and crisis management. Russia will almost certainly deny any involvement in jamming military exercises, said Matti Vanhanen, the CFA’s chairman. × Fear of missing out? Sign up for the Early Bird Brief, the defense industry's most comprehensive news and information, straight to your inbox. Thanks for signing up. By giving us your email, you are opting in to the Early Bird Brief. "There is every reason to trust Norway and its intelligence. It’s unlikely that Norway will publicly disclose the methods behind its assessment. As no technical evidence will be offered in the public domain, we may end up in a situation where Russia just denies it. We need to tell Russia that we do not accept disturbances of this kind in our airspace," Vanhanen said. Initial diplomatic contacts between Nordic governments and Moscow has produced a flat denial that Russia was behind the GPS signal-jamming. "There is a tendency to blame Russia for all sins in general. As a rule, these allegations are found to have no basis in actual fact," said Dmitry Peskov, the senior press spokesman to Russian President Vladimir Putin. Norway’s civil aviation authorities opened an investigation into possible GPS signal-jamming in the High North at the end of October when several commercial aircraft reported loss of satellite navigation while flying over the Troms and Finnmark regions in the north of the country. Warnings and confusion preceded Norwegian frigate disaster: here’s what we know The disaster has far-reaching consequences for the Norwegian Navy, which now faces the loss of one of its premier warfighting assets. National aviation authorities in Finland and Norway subsequently issued a so-called notice to airmen (NOTAM) due to widespread disturbances in GPS signals in the airspace of both countries’ northern regions. In Norway, the NOTAM related to the northern airports of Kirkenes and Vadsø which are located close to the border with Russia and the Kola Peninsula. The investigation by Norway into suspected GPS signal-jamming by Russia covered the period between Oct. 16 and Nov. 7. NATO’s Trident Juncture exercises started, following months of field preparation work, on Oct. 25 and finished on Nov. 7. Norway also conducted investigations into suspected jamming of satellite navigation systems by Russia linked to the Zapad-2017 drill. These large-scale military exercises by Russia were held on and around the Kola Peninsula during September and October 2017.

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The integration of song environment by catecholaminergic systems innervating the auditory telencephalon of adult female European starlings. Mate choice is among the most consequential decisions a sexually reproducing organism can make. In many songbird species, females make mate-choice decisions based, in part, on variation between males in songs that reflect their quality. Importantly, females may adjust their choice relative to the prevalence of high quality songs. In European starlings (Sturnus vulgaris), females prefer males that primarily sing long songs over those that primarily sing short songs, and sensitivity of the auditory telencephalon to song length depends on the prevalence of long songs in the environment. Several lines of evidence suggest a role for noradrenergic innervation of the auditory telencephalon in mediating this neuro- and behavioral plasticity. To simulate variation in quality of the song environment, we exposed adult female starlings to 1 week of either long or short songs and then quantified several monoamines and their metabolites in the caudomedial mesopallium and caudomedial nidopallium (NCM) using high performance liquid chromatography. We also used immunocytochemistry to assess these areas for immunoreactive dopamine-beta-hydroxylase (DBH-ir), the enzyme that synthesizes norepinephrine. We found that long songs elevated levels of the principal norepinephrine metabolite, the principal dopamine metabolite, and the probability of DBH-ir in the NCM compared to short songs. Song environment did not appear to influence norepinephrine or dopamine levels. Thus, the quality of the song environment regulates the local secretion of catecholamines, particularly norepinephrine, in the female auditory telencephalon. This may form a basis for plasticity in forebrain sensitivity and mate-choice behavior based on the prevalence of high-quality males.

{ "pile_set_name": "PubMed Abstracts" }

Arthur Covington Arthur Edwin Covington (21 September 1913 – 17 March 2001) was a Canadian physicist who made the first radio astronomy measurements in Canada. Through these he made the valuable discovery that sunspots generate large amounts of microwaves at the 10.7 cm wavelength, offering a simple all-weather method to measure and predict sunspot activity, and their associated effects on communications. The sunspot detection program has run continuously to this day. Early life and education Covington was born in Regina and grew up in Vancouver. He showed an early interest in astronomy, and had built a refractor telescope after meeting members of the local chapter of the Royal Astronomical Society of Canada. He was also interested in amateur radio and operated station VE3CC for a time. He started his career as a radio operator on ships operated by the Canadian National Railways. He put himself through school and eventually earned a bachelor's degree from the University of British Columbia in 1938, and obtained his master's degree from the same institution in 1940 after building an electron microscope. He then moved to University of California in Berkeley where he received his doctoral degree in nuclear physics in 1942. He was still at Berkeley when he was invited to join the National Research Council (NRC) in Ottawa in 1942 as a radar technician, working at the NRC's Radio Field Station. Solar observations Immediately after the war Covington became interested in radio astronomy, and built a small telescope out of the electronic parts from a surplus SCR-268 radar combined with parts from another receiver originally built to test silicon crystal radio parts for radar applications. These electronics were attached to the 4 ft (1.2 m) parabolic dish from a Type III gun-laying radar. The system operated at a frequency of 2800 MHz, or a wavelength of 10.7 cm. Initially the instrument was pointed in the direction of various celestial objects, including Jupiter, the Milky Way, aurora borealis, and the Sun, but it proved too insensitive to pick up any source other than the Sun. So a solar study program was started. As time passed, Covington and his colleagues realized that the Sun's emission at 10.7 cm wavelength was varying, which was unexpected. Thinking at that time was that the solar emission at centimeter wavelengths would be simply black body emission from a ball of hot gas. Covington became convinced that the effect was due to sunspots, as the flux appeared to vary with the number of visible spots. The resolution of the device, about seven degrees, made it impossible to "pick out" a spot on the sun's surface for study, making a demonstration of the claim difficult. An opportunity to directly measure this possibility presented itself on November 23, 1946 when a partial solar eclipse passed over the Ottawa area, and Covington was able to conclusively demonstrate that the microwave emissions dropped off precipitously when the Moon covered a particularly large sunspot. This also demonstrated that magnetic fields were instrumental in sunspot activity. It was entirely by accident that the original instrument operated on frequencies suitable to detection of the 10.7 cm signal, and it had never been intended for "production" use. As the importance of the sunspot measurements became obvious, plans were made to continue these observations over a longer time period. As the Radio Field Station was still actively being used for radar development, and causing heavy interference as a result, a new location was selected about five miles (8 km) away at Goth Hill. Here they measured the whole-disk flux and averaged the measurements to produce three highly accurate measurements a day. He then set about designing an instrument that could directly resolve portions of the sun's disk. The new telescope consisted of a 150 ft (46 m) long section of 3 by 1½ inch metal waveguide cut with slots in locations to create a simple interferometer with a fan-shaped area of sensitivity. The amount of flux gathered was improved by placing the waveguide in metal trough, and the direction of aim could be changed slightly by rotating the waveguide inside the trough, but in general terms it was used to take measurements as the sun passed through its "beam". The new telescope started operation in 1951, allowing them to directly measure the flux from the Sun's corona and the temperature of the regions above sunspots (about 1,500,000 °C). The Goth Hill observatory also included a number of other instruments for a variety of measurements. ARO Increasing radar and radio use in the Ottawa area presented interference problems, and Covington turned his attention to finding a more suitable "radio quiet" location for the program. This led to the creation of the Algonquin Radio Observatory (ARO) in Algonquin Park, about 150 km northwest of Ottawa but relatively easy to access on major highways. A new 6 ft (1.8 m) parabolic dish solar flux telescope was built in 1960, operating in parallel before taking over duties from the Goth Hill instrument in 1962. In 1964 an identical instrument was installed at the Dominion Radio Astrophysical Observatory (DRAO) in British Columbia. This was followed by a more powerful version of the waveguide instrument, this time focused by a series of thirty-two 10 ft (3 m) dishes arranged over a 700 ft (215 m) waveguide, which opened in 1966. The ARO was greatly expanded in 1966 with the opening of the 150 ft (46 m) deep-space telescope. This was a major research site through the 1960s and 70s, although limitations in its design made it see less use in the 1980s. For some time this instrument was joined by a smaller 18 m telescope originally located at the David Dunlap Observatory outside Toronto, operated by the University of Toronto. The original solar observatories remained in use until 1990 when funding drawdowns at the NRC forced the closure of the entire Algonquin site. In 1991 the 1.8 m dish was moved to the DRAO as a backup instrument. Covington's work led to other solar-related discoveries. Observations in 1969 led to the realization that certain types of major sunspot breakouts were preceded by a particular type of radio signal, which allowed advanced prediction of upcoming solar storms. As other teams also started studying the solar flux they noticed that the different teams all came to different conclusions about the total flux, due to differences in the instruments and other effects. Covington worked on an effort to correlate these measurements and solve a single flux number, which was published in 1972. He also played a role in the construction of the Indian River Observatory, an amateur built 200 m interferometer. Retirement Covington remained director of the ARO until he retired in 1978. He died in 2001 in Kingston, Ontario, at the age of 88. One of the buildings at the Dominion Radio Astrophysical Observatory was named in his honour in 2003. He had many hobbies including a fondness for rare books, many of which have been donated to Queen's University in the Riche-Covington collection. Notes The exact location of "Goth Hill" is not known, as this term does not appear on modern maps. According to the City of Ottawa Archives, it is likely located on a plot of land south of the downtown Ottawa area, a plot formerly owned by Robert Goth that appears in the Beldon Atlas, 1878. The terms "hill" and "ridge" were commonly applied to otherwise nondescript land throughout the Gloucester Township area. The Goth plot lies off the eastern end of runway 25 of the Ottawa Macdonald-Cartier International Airport, west of CFS Leitrim. This location fits with all of the known references, which describe it as being "five miles south of Ottawa in South Gloucester". References Category:1913 births Category:2001 deaths Category:Canadian physicists

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Q: Can the javascript .bind go up multiple levels? I have a piano Keyboard object in JavaScript and JQuery, like so: function Keyboard(name, size, xPos, yPos, octaves) { this.name = name; this.size = size; this.setDimensions = function (){}; this.highlightKeyboard = function (){}; ... etc. } It's got a bunch of methods to set dimensions, generate the keyboard using divs for the keys, generate major and minor scales referencing the classes of the divs, etc. I wrote 4 methods to highlight a major scale when I press a certain key, a minor scale when I press a different key, major and minor triads with two other keys. They all worked, but after writing them I realized all 4 methods use a lot of the same code so I've been trying to consolidate by bringing out most of the code into separate methods in the main Keyboard object so I can call them repeatedly. The problem I'm having now that I'm consolidating is getting the $(document).keypress objects to play nice with the external code. What I want is something like this (partial code sample—I left out all the code to generate the keyboard and everything else that wasn't relevant because it seems to be working OK other than this one issue): function Keyboard(name, size, xPos, yPos, octaves) { this.getMajorTonic = (function(userNote) { // code to determine myTonic return myTonic; }); this.setMajScale = function(myTonic) { var scale = []; // code to determine scale[]; return scale; }; this.setScaleClasses = function(scale) { // code to determine scale_classes[] return scale_classes; }; this.highlightKeyboard = function (scale, scale_classes){}; // code to add highlighted classes to my divs based // on the values in scale and scale_classes }; this.findMajorScales = function(userNote); var myTonic = this.getMajorTonic(userNote); var scale = this.setMajScale(myTonic); var scale_classes = this.setScaleClasses(scale); var highlightKeyboard = this.highlightKeyboard; $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard(scale, scale_classes) } }); }; } var keys = new Keyboard("piano", 1, 0, 0, 2); keys.findMajorScales("E"); The desired effect is that when I load the page, it generates a blank keyboard, but when I press the "m" key, it highlights the E Major scale using the this.highlightKeyboard method. So I want to pass the this.findMajorScales method a this.highlightKeyboard method with no arguments, and then have the arguments filled in and the method executed when the "m" key is pressed. Most everything works, including the ($document).keypress object—it executes other code, just not the this.highlightKeyboard method with the right arguments. How do I accomplish this? Does .bind have something to do with it? I can't really figure out if it's applicable here or if I need to do something else. Thanks so much! Jake A: So I want to pass the this.findMajorScales method a this.highlightKeyboard method with no arguments, and then have the arguments filled in and the method executed when the "m" key is pressed. You are listening for M fine, so the only problem you have is invoking highlightKeyboard in the correct context. Consider var foo = {bar: function () {return this}), bar = foo.bar; What will foo.bar() return? (foo) What will bar() return? (window or null or throws an error, etc) You have a lot of options There are several ways around this, you've already mentioned Function.prototype.bind and it may be conceptually easier for you to use Function.prototype.call, Function.prototype.apply or even passing the this variable through using another identifier instead. In either case, the default this in the handler will no longer be an instanceof Keyboard as the event is coming from document Using Function.prototype.bind you have a few options var highlightKeyboard = this.highlightKeyboard.bind(this); $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard(scale, scale_classes); } }); // or binding args ahead of time too var highlightKeyboard = this.highlightKeyboard.bind(this, scale, scale_classes); $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard(); } }); // or binding the handler $(document).keypress(function (event) { if (event.which === 109) { this.highlightKeyboard(scale, scale_classes); } }.bind(this)); Using Function.prototype.call or .apply, requires ref to this var highlightKeyboard = this.highlightKeyboard; var me = this; $(document).keypress(function (event) { if (event.which === 109) { highlightKeyboard.call(me, scale, scale_classes); } }); Just using a ref to this var me = this; $(document).keypress(function (event) { if (event.which === 109) { me.highlightKeyboard(scale, scale_classes); } }); Finally, one more solution is to write a function which generates what you want, this is very similar to what .bind is doing but is supported in environments that don't support .bind (read: legacy) $(document).keypress(function (me) { // this function generates the inside one return function (event) { // this is the function used as the handler if (event.which === 109) { me.highlightKeyboard(scale, scale_classes); } }; }(this)); // passing in `this` as param `me`

{ "pile_set_name": "StackExchange" }

Q: image map software for coordinates using magic wand Quick question... there are lots of ways to create an image map (old school, I know!) for a web page, but I have a requirement for one. I want to have an interactive map showing UK counties. I have the map, I have "mapspinner" (also dreamweaver) to do the polymap... but, I was wondering if there was a way to use a magic wand to get the area's coordinates? I have tried using photoshop export to illustrator paths, but the file doesn't contain any coords (as expected really!). Does anyone know a way to do this? (I see that fireworks might do it, but I don't have that software) thanks in advance. A: GIMP can do this. See http://docs.gimp.org/en/plug-in-imagemap.html for a tutorial of exactly the task you are trying to accomplish.

{ "pile_set_name": "StackExchange" }

Instant Payment - 10:36 Papierüberweisung: Mühsam, langsam, teuer Bild: dpa Im Hochfrequenzhandel an den Börsen geht es um Mikrosekunden. Eine schlichte Überweisung aber braucht noch immer einen Tag oder länger. Das soll sich bald ändern. Bitte melden Sie sich an, um diesen Artikel auf Ihrem Merkzettel zu speichern. Viele Bankkunden könnten vom kommenden Jahr an Geldbeträge innerhalb von wenigen Sekunden auf ein anderes Konto überweisen. Für die neue Echtzeitüberweisung (Instant Payments) werde ab November europaweit ein einheitlicher Rechtsrahmen gelten, sagte der Hauptgeschäftsführer des Bundesverbandes deutscher Banken (BdB), Michael Kemmer. „Im ersten Quartal 2018 wird es die ersten Anbieter geben.“ Allerdings dämpft Kemmer die Erwartungen: „Es wird sicher noch eine Zeit lang dauern, bis sie sich durchgesetzt hat“, merkte der Verbandsvertreter an. Denn für die Kreditinstitute gebe es keine Verpflichtung, an „Instant Payments“ teilzunehmen. Gebrauchtwagen sofort bezahlt Beim Instant Payment soll der Überweisungsbetrag dem Empfänger innerhalb von zehn Sekunden auf dem Konto des Empfängers gutgeschrieben sein. Der Auftrag erfolgt per Online-Banking oder mit einer Smartphone-App. Bislang werden Überweisungen in der Regel am folgenden Bankarbeitstag gutgeschrieben. „Die Überweisung in Sekunden könnte ein Ersatz für Bargeldzahlungen werden“, sagte Kemmer. „Das wird vieles erleichtern“, etwa Probleme beim Warenkauf vermeiden, die dadurch entstehen, dass das Geld dem Verkäufer erst mit einem Tag Verzögerung gutgeschrieben wird. Ein gutes Beispiel hierfür sei der Autoverkauf privat zu privat. Die Bankenbranche reagiert mit dem System auch auf eine Reihe von Angeboten von Online-Bezahldiensten wie Paypal. „Zurzeit wechseln Payment-Dienstleister für hohe Summen den Besitzer, weil hier ein ertragreiches Geschäftsfeld erwartet wird“, erklärte Kemmer. „In Deutschland finden sie jedoch einen extrem harten Wettbewerb vor. Das macht es für die Banken schwierig, solche hohen Investitionen wieder hereinzuwirtschaften.“ Bezahlen mit der Girocard sei neben der Lastschrift das beliebteste bargeldlose Verfahren im Handel. Noch nicht im großen Stil durchgesetzt habe sich in Deutschland das kontaktlose Bezahlen mit Karte oder mit einem Smartphone plus App. „Hier gibt es verschiedene Anbieter, die sich auf dem Markt versuchen. Entscheidend ist, was sich in der Fläche durchsetzen wird“, sagte Kemmer. Mehr zum Thema Beim kontaktlosen Bezahlen muss die Plastikkarte im Abstand von weniger als vier Zentimeter an das Terminal des Händlers gehalten werden. Ohne Eingabe einer Geheimnummer ist der Betrag, der dann vom Girokonto abgebucht wird, in der Regel pro Vorgang auf 25 Euro begrenzt. Aus Sicherheitsgründen kann nur wenige Male hintereinander ohne Geheimzahl bezahlt werden. Es gibt auch ein Tageslimit, das von Bank zu Bank unterschiedlich hoch ist.

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This guy built a replica of a McLaren F1 that actually looks decent, complete with a Top Gear influenced "Hammond seat". Top Gear Fanatic Builds Replica Of £5,000,000 Supercar From Scrap Barcroft Cars - The Home Of Amazing Car Stories Online SUBSCRIBE: http://bit.ly/1sHvkD5 A Top Gear fa...More New 1,000 bhp electric supercar from Spain hits 0-62 in just 3.4 seconds and a top speed of 186 mph! Meet the VOLAR-e.. 1.000 hp and 1,500 Nm Fastest Electric Supercar in the World Spanish engineering firm Applus+Idiada has developed an electric supercar known as Volar-E. Presentation of the most p...More

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Q: Force a browser's visibility setting to true I'm trying to set up some specs against a real (not headless) browser but some of the javascript on the target page only runs if the browser is visible (it doesn't need to be the active app). I've been perusing the W3C Page Visibility API docs and [MDN's] too but I can't see a way to manipulate the setting while running Watir. I know there's the option of running the spec on a headless machine but while I'm developing the specs it'd be handy to not have to switch back and forth between browser and terminal to avoid timeouts and failures. I've had a look for Chrome switches that might help and found this very helpful list but it doesn't appear to have the magic bullet either. I've also tried browser.execute_script('document.hidden = false'); but that had no effect. Any help or insight would be much appreciated. A: It's possible to force this status with a Javascript injection via execute_script. To simulate a visible document: Object.defineProperty(document, 'visibilityState', {value: 'visible', writable: true}); Object.defineProperty(document, 'hidden', {value: false, writable: true}); document.dispatchEvent(new Event("visibilitychange")); To simulate an hidden document: Object.defineProperty(document, 'visibilityState', {value: 'hidden', writable: true}); Object.defineProperty(document, 'hidden', {value: true, writable: true}); document.dispatchEvent(new Event("visibilitychange")); Note that you'll have to run it again if the page is reloaded.

{ "pile_set_name": "StackExchange" }

Q: Trying to get a count of labels used in Gmail using Gmail API I am trying to go one level deeper with the demo code that utilises labels to extract the count of each label used within my inbox. e.g label1 = 5, label2 =10 etc and with a date. Any suggestions? Demo code: function listLabels() { var response = Gmail.Users.Labels.list('me'); if (response.labels.length == 0) { Logger.log('No labels found.'); } else { Logger.log('Labels:'); for (var i = 0; i < response.labels.length; i++) { var label = response.labels[i]; Logger.log('- %s', label.name); } } } A: Using the Users.messages:list function call from the GMail API should get you your results. The trick here is to pass label.id to the labelIds argument as a list function listLabels() { var response = Gmail.Users.Labels.list('me'); if (response.labels.length == 0) { Logger.log('No labels found.'); } else { Logger.log('Labels:'); for (var i = 0; i < response.labels.length; i++) { var label = response.labels[i]; // Use the label name to get the messages that match this label var label_messages = Gmail.Users.Messages.list('me', {'labelIds': [label.id]}); Logger.log('%s = %s', label.name, label_messages.resultSizeEstimate); } } }

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The internet revolution BuzzFeed UK editor Luke Lewis speaks to Grace Marsh about launching in the UK, British humour and what makes the site so successful Tuesday 30 September 2014 How did you get involved in BuzzFeed? BuzzFeed launched in the UK in March 2013. It had been established in the US and actually goes back all the way to 2006. They really started ramping it up, and it started becoming more of a big deal really in 2011/12. So that’s when I became a huge fan of what they were doing so I contacted them and kind of figured that they might want to launch in the UK. So I said if you do, if you’re thinking about it, then you should consider me. And actually I was kind of right in that position because they were thinking about launching, they just hadn’t really got round to it yet. So yeah, that happened in early 2013. What was it like when you first started? Initially, it was very much kind of experimental, there was only three of us, we were sharing an office which was another company’s, you know, it was quite low key. The audience was there, and since then we’ve been building it up so the UK editorial team is about 30 people now. In terms of consumers, now we have 15 million unique users in the UK and globally 150 million per month. What makes BuzzFeed UK different from BuzzFeed US? The main thing that distinguishes BuzzFeed in the UK from in the US is our focus on humour. So if you look at all the most viral, most widely shared articles that we’ve ever done in the UK, they’re mostly funny. That’s not really true in the US; humour is a pretty big part of what they do, but it’s not like the number one priority. How have you adapted content for a UK audience? Around about the time that we launched, things that were doing very well in the US was cute animal stuff, chill, uplift articles were very popular—a really huge article around that time was ‘photos that will restore your faith in humanity’. That kind of thing was really popular in the US and we kind of experimented with that in the UK, but it didn’t work that well. But when we focused more specifically on humour, self-deprecating humour and regional identity is another one – those things worked incredibly well so we really focused on those. What do you think makes people enjoy reading things like ‘ten reasons why you’re from the north’? There is a slight element of mockery invovled, especially self-mockery, that’s an important thing. When we’re writing about a certain niche, or a certain regional identity, you want people who are part of that identity to share it themselves, so if it’s really nasty, sort of slagging off Geordies for example, then they wouldn’t share it, but if it’s sort of gently mocking in a way that they can agree with, then it works. Because you know that’s just the great British thing. Self-depreciating humour is a really big part of our identity. What makes regional identity so important? The reason that identity is really powerful I think is that British media traditionally has kind of ignored the regions beyond London. And so we were really keen to not do that on BuzzFeed. In fact we want to embrace that more actually. We’re gonna sort of ramp up the amount of regional stuff that we’re doing. How do the British public respond to articles about cute cats and Kim Kardashian? Humour is extremely important to us, then there’s also the whole news side of BuzzFeed and celebrity stuff; it’s always popular but it tends not to be shared that well. Those kind of things, Kim Kardashian, there’s a lot of entertainment value. They do quite well from the homepage and people do like to read it, but then people won’t necessarily share it. It’s part of the mix, but not necessarily our main focus. How popular is sport on BuzzFeed? It’s the same with sport as with celebrity stuff; we kind of dipped our toe in the water with sport, but it’s an area that is very, very well served in the British media, by the newspapers and we’ve not quite found a route into that. Maybe in the future, but at the moment, sport is now something we’re really focused on. Is it BuzzFeed’s unique, easy to read format that makes it so successful? Yes, absolutely. We’re thinking about impact and accessibility. For a couple of hundred years, the format of a news story has not really changed very much. It’s about 500 words of copy, with one picture at the top. Especially news online, there’s not been much kind of innovation; they’re really just taken from newspapers. They’re just repurposed, with one picture and 500 words of copy and often it’s just rewritten from the wire. What makes BuzzFeed different? We do like to think about how we like to present news stories and getting away from that classic structure of a newspaper which is often like an inverted pyramid. Newspaper journalists will try to cram as many details as they can into the first few sentences and then the story gets less and less relevant. How do you achieve this? We kind of flip it on its head and we make it more conversational, a bit more chronological. News journalists will often just start at the beginning – this is the person, this is his name, this is how old he is. And then you kind of start telling it like a story, as if you were in conversation with a friend. So I think that’s what makes our news stories a little bit less artificial and a little bit more conversational, which I think is why they work well on Facebook. Is Facebook the most popular sharing platform? It definitely is yeah, but that just reflects the fact that it’s the biggest social media platform by far. The second biggest one is Pinterest and the third is Twitter. To be honest, Twitter is slightly bigger in the UK but globally Pinterest drives significantly more interest than Twitter because it’s huge in the US. How can students get themselves noticed on the internet? You can kind of make the mistake of trying to be on every platform. I’m not personally on Pinterest; it drives a lot on interest on BuzzFeed but I’m not sure it’s a great way of selling yourself. Facebook is kind of underrated as a way of promoting yourself. I’ve always had a public facebook profile and posted lots of links there, and have now built up a bit of a following. I think sometimes people neglect Facebook and focus on Twitter. Why is the more light-hearted content so popular on BuzzFeed? It just reflects the reality of how people consume content nowadays. I think the organising principal of the web now is the kind of activity stream, especially the Facebook newsfeed. If you look at your newsfeed right now, I’m sure there’s news stories and serious stuff about what’s going on in the world, but there’s also stuff about your friends and family, throwaway entertaining stuff as well. And I think that’s just how people live their lives. So it makes sense that BuzzFeed should reflect that. So you’ve got the serious and the light-hearted, entertaining co-exisiting very closely and I think that’s just a natural reflection of life really. I think that’s great. It’s great writing about universities because all it takes is for one person to put it on Facebook and people in their year share it, then it starts to spread to people that once went to that university and it ends up as being tens of thousands of people and that’s brilliant, that’s what BuzzFeed is all about really.

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Q: How to use HoC with React Native I have an listing app where users can add items for multiple categories, when they want to add new record, there are 3 related screens with this particular feature. All of those screens have <Header/> component, so i thought HoC would be nice here so that i can reuse it across 3 screens. However, i could not accomplish it. Here is what i tried so far: This is my HoC class import React, { Component } from 'react'; import { View, StyleSheet, Text, StatusBar } from 'react-native'; import Header from '../components/Header'; const NewAd = (WrappedComponent) => { class NewAdHoc extends Component { handleBackPress = () => { this.props.navigation.navigate('Home'); StatusBar.setBarStyle('dark-content', true); } render() { const {contentText, children} = this.props return ( <View style={styles.container}> <Header headerText={'Yeni ilan ekle'} onPress={this.handleBackPress} /> <View style={styles.contentContainer}> <Text style={styles.contentHeader}>{contentText}</Text> <WrappedComponent/> </View> </View> ); } } return NewAdHoc; } this is my screen: class NewAdScreen extends Component { render() { const Content = () => { return ( <View style={styles.flatListContainer}> <ListViewItem /> </View> ); } return ( NewAdHoc(Content) ) } } after that i am getting error TypeError: (0 , _NewAdHoc.NewAdHoc) is not a function(…) and i have no idea how can i fix it because this is my first time using hocs on a react-native app. I have looked why this error is popping and they suggest import components in this way: import {NewAdHoc} from '../hocs/NewAdHoc'; but even this is not solved it. any help will be appreciated, thanks. A: The main purpose of a HOC is to encapsulate and reuse stateful logic across components. Since you are just reusing some jsx and injecting nothing in WrappedComponent you should be using a regular component here: const NewAd = ({ contentText, children }) => { handleBackPress = () => { this.props.navigation.navigate('Home'); StatusBar.setBarStyle('dark-content', true); } return ( <View style={styles.container}> <Header headerText={'Yeni ilan ekle'} onPress={this.handleBackPress} /> <View style={styles.contentContainer}> <Text style={styles.contentHeader}>{contentText}</Text> {children} </View> </View> ); } And use it like this return( <> <NewAd> <Screen1 /> </NewAd> <NewAd> <Screen2 /> </NewAd> <NewAd> <Screen3 /> </NewAd> </> )

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The present invention relates to real-time navigation and more specifically to utilizing non-GPS information to update navigation information in real-time. Navigation devices exist today that utilize GPS information to track the location of the navigation device and thus the device's user. Existing navigation devices typically store a cartographic map of data indicative of a roadway network for a geographic area and offer various applications and features to support the user's navigation through the geographic area. One exemplary application is to provide the user with audio instructions to direct the user between source and destination locations within the roadway network. Various routing parameters exist upon which the route through the roadway network may be based, such as time, distance and the like. However, the data stored in the navigation device that is indicative of the roadway network is static in that the data is representative of the status of the roadway network only as of the last time that the navigation device was uploaded with a new cartographic map of the roadway network. The cartographic map reflects limited non-periodic or non-reoccurring information regarding the status of the roadway network. For example, while the cartographic map may store data identifying road segments that typically exhibit slow travel times (e.g. due to numerous traffic lights, rough road conditions and the like), the data is unable to identify for non-reoccurring, one time events that impact travel over the roadway network. Examples of non-reoccurring events are traffic accidents, icy road conditions, flooded roads, construction, weather conditions, temporary traffic back-ups and the like. Heretofore, travelers generally obtained information regarding these non-reoccurring events through the automobile's FM/AM radio that played various types of content, such as entertainment-related content, traffic-related content and the like. To obtain travel-related content, drivers tuned to a weather channel or traffic channel to hear local travel conditions. No system exists that is able to utilize real-time travel-related content to update navigation information and provide updated navigation information to the user. A need remains for improved navigation devices, modular electronic devices and methods for use thereof that are better suited to inform users of real-time travel-related conditions and to utilize such real-time travel-related conditions to update navigation information.

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Sabres to hold part of training camp in Rochester 'The Sabres will hold daily on-ice workouts at the ESL Sports Centre from September 15th through September 20th. All workouts will be free and open to the public. "This is a great opportunity for our fans in Rochester to come see the team first hand," Regier said. "It will give them a preview of our team and should build some excitement for our preseason game versus Chicago and our regular season game against New Jersey in November."'

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{ "type": "bundle", "id": "bundle--4ec75f30-2415-4ef5-81d0-c7443b8c9f9d", "spec_version": "2.0", "objects": [ { "id": "relationship--6d102ef8-c831-413d-b2cb-392517638b0b", "created_by_ref": "identity--c78cb6e5-0c4b-4611-8297-d1b8b55e40b5", "description": "[Zebrocy](https://attack.mitre.org/software/S0251) uses HTTP for C2.(Citation: Palo Alto Sofacy 06-2018)(Citation: Unit42 Cannon Nov 2018)(Citation: ESET Zebrocy Nov 2018)(Citation: Unit42 Sofacy Dec 2018)(Citation: ESET Zebrocy May 2019)(Citation: Accenture SNAKEMACKEREL Nov 2018)", "object_marking_refs": [ "marking-definition--fa42a846-8d90-4e51-bc29-71d5b4802168" ], "external_references": [ { "url": "https://researchcenter.paloaltonetworks.com/2018/06/unit42-sofacy-groups-parallel-attacks/", "description": "Lee, B., Falcone, R. (2018, June 06). Sofacy Group\u2019s Parallel Attacks. Retrieved June 18, 2018.", "source_name": "Palo Alto Sofacy 06-2018" }, { "source_name": "Unit42 Cannon Nov 2018", "url": "https://researchcenter.paloaltonetworks.com/2018/11/unit42-sofacy-continues-global-attacks-wheels-new-cannon-trojan/", "description": "Falcone, R., Lee, B. (2018, November 20). Sofacy Continues Global Attacks and Wheels Out New \u2018Cannon\u2019 Trojan. Retrieved November 26, 2018." }, { "source_name": "ESET Zebrocy Nov 2018", "url": "https://www.welivesecurity.com/2018/11/20/sednit-whats-going-zebrocy/", "description": "ESET. (2018, November 20). Sednit: What\u2019s going on with Zebrocy?. Retrieved February 12, 2019." }, { "description": "Lee, B., Falcone, R. (2018, December 12). Dear Joohn: The Sofacy Group\u2019s Global Campaign. Retrieved April 19, 2019.", "url": "https://unit42.paloaltonetworks.com/dear-joohn-sofacy-groups-global-campaign/", "source_name": "Unit42 Sofacy Dec 2018" }, { "source_name": "ESET Zebrocy May 2019", "url": "https://www.welivesecurity.com/2019/05/22/journey-zebrocy-land/", "description": "ESET Research. (2019, May 22). A journey to Zebrocy land. Retrieved June 20, 2019." }, { "description": "Accenture Security. (2018, November 29). SNAKEMACKEREL. Retrieved April 15, 2019.", "url": "https://www.accenture.com/t20181129T203820Z__w__/us-en/_acnmedia/PDF-90/Accenture-snakemackerel-delivers-zekapab-malware.pdf#zoom=50", "source_name": "Accenture SNAKEMACKEREL Nov 2018" } ], "source_ref": "malware--a4f57468-fbd5-49e4-8476-52088220b92d", "relationship_type": "uses", "target_ref": "attack-pattern--df8b2a25-8bdf-4856-953c-a04372b1c161", "type": "relationship", "modified": "2020-03-17T02:54:27.611Z", "created": "2018-10-17T00:14:20.652Z" } ] }

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Q: IE reading inherited font size from computed style (currentStyle) is incorrect I've put a little test case together here: http://jsfiddle.net/D4sLk/2/ Basically I have the following font sizes set: * (everything): 12px container: 20px test element: inherit The DOM hierarchy is: container > test element. In IE9, the font size is reported as 12px using testEl.currentStyle.fontSize but is displayed as 20px. In Chrome and FF it seems fine. Are there any workarounds to this issue? Or have I done something really stupid? A: Try using font-size: 1em instead of using inherit. The reason for this is because I've found that inherit seems to have issues in IE. It rendered fine when I looked in IE9, however for some reason testEl.currentStyle.fontSize and $(testEl).css('font-size') both returned 12px as well. I've read that to use font-size: inherit in IE8, you would need to specify a !DOCTYPE, however it should be fine in IE9 (http://www.w3schools.com/cssref/pr_font_font-size.asp). For some reason, testEl.currentStyle.fontSize and $(testEl).css('font-size') are not picking up the correct values in IE9. When you set the font-size to 1em, you are sizing it up to 100% of the parent font-size, which in this case results to 20px. From http://www.w3schools.com/cssref/css_units.asp: 1em is equal to the current font size. 2em means 2 times the size of the current font. E.g., if an element is displayed with a font of 12 pt, then '2em' is 24 pt. The 'em' is a very useful unit in CSS, since it can adapt automatically to the font that the reader uses As a result, computedStyle.fontSize and $(testEl).css('font-size'), should both return 20px. Hope this helps!

{ "pile_set_name": "StackExchange" }

194 U.S. 458 (1904) MATTER OF CHRISTENSEN ENGINEERING COMPANY. No. 15, Original. Supreme Court of United States. Submitted April 25, 1904. Decided May 31, 1904. IN THE SUPREME COURT OF THE UNITED STATES. *459 Mr. W.A. Jenner for petitioner. Mr. Frederic H. Betts for respondent. MR. CHIEF JUSTICE FULLER, after making the foregoing statement, delivered the opinion of the court. The examination in Bessette v. W.B. Conkey Company, 194 U.S. 324, just decided, of the right of review in contempt cases precludes the necessity of extended discussion. In that case Bessette was not a party to the suit, and the controversy had been settled by a final decree, from which, so far as appeared, no appeal had been taken. He was found guilty of contempt of court, and a fine of $250 imposed, payable to the United States, with costs. In this case the Christensen Engineering Company was a party. The contempt was disobedience of a preliminary injunction and the judgment in contempt was intermediate the preliminary injunction and the decree making it permanent. The fine was payable, one-half to the United States, and the other half to the complainant. The distinction between a proceeding in which a fine is imposed by way of compensation to the party injured by the disobedience, and where it is by way of punishment for an act done in contempt of the power and authority of the court, is pointed out in Bessette's case, and disclosed by some of the cases referred to in the opinion. In New Orleans v. Steamship Company, 20 Wall. 387, the act in contempt was by one not then a party to the suit. No order was entered against him until the final decree in the case, *460 and then he was punished for the act of disobedience, purely as an act of a criminal nature, and without compensation to the plaintiff in whose favor the injunction was originally ordered. No review under the then existing law was allowable. In Hayes v. Fischer, 102 U.S. 121, the contempt proceeding was remedial and compensatory, and the entire amount of the fine was ordered paid to the plaintiff in reimbursement. It was held that, if the remedial feature was alone to be considered, and the proceeding regarded as a part of the suit, it could not be brought to this court by writ of error, but could only be corrected on appeal from the final decree; if to be regarded as a criminal action, then it was one of which this court had no jurisdiction, either by writ of error or appeal. In Ex parte Debs et al., 159 U.S. 251, there was nothing of a remedial or compensatory nature. No fine was imposed, but only a sentence of imprisonment. This court had no jurisdiction of a writ of error in such a case. And see O'Neal v. United States, 190 U.S. 36. In Worden v. Searls, 121 U.S. 14, the proceeding was remedial and compensatory, in that for violations of a preliminary injunction the defendants were ordered to pay the plaintiff $250 "as a fine for said violation," by one order, and, by another order, to pay a fine of $1,182 to the clerk, to be paid over by him to the plaintiff for "damages and costs," the $1,182 being made up of $682 profits made by the infringement, and $500 expenses of plaintiff in the contempt proceedings. These interlocutory orders were reviewed by this court on appeal from the final decree, and as that decree was reversed, the orders were also set aside, this being done "without prejudice to the power and right of the Circuit Court to punish the contempt referred to in those orders, by a proper proceeding." It was also said "that, though the proceedings were nominally those of contempt, they were really proceedings to award damages to the plaintiff, and to reimburse to him his expenses." These authorities show that when an order imposing a fine for violation of an injunction is substantially one to reimburse *461 the party injured by the disobedience, although called one in a contempt proceeding, it is to be regarded as merely an interlocutory order, and to be reviewed only on appeal from the final decree. In the present case, the fine payable to the United States was clearly punitive and in vindication of the authority of the court, and, we think, as such it dominates the proceeding and fixes its character. Considered in that aspect, the writ of error was justified, and the Circuit Court of Appeals should have taken jurisdiction. Petitioner entitled to mandamus.

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DeLane Matthews DeLane Matthews (born August 7, 1961) is an American actress. She is best known for her role as Beth Barry in the CBS television sitcom Dave's World from 1993 to 1997. Life and career DeLane Matthews was raised in northern Florida. She moved to Manhattan after being hired to join the Kennedy Center/Juilliard School Acting Company. Acting in theater productions, she appeared Off-Broadway in City Boys at the Jewish Rep, and Pieces of Eight at The Public Theater. She also performed in The Cradle Will Rock, The Merry Wives of Windsor, and Pericles, and toured in The Bat, Grease, The Invaders and I Oughta Be in Pictures. Television Following daytime television work in The Guiding Light in New York City, Matthews transitioned into primetime television on the Peter Boyle ABC comedy series Joe Bash (1986), playing the part of the streetwalker Lorna. It was cancelled after six episodes. In 1988, she went to star opposite Scott Bakula in the CBS sitcom Eisenhower and Lutz. She later starred on the NBC sitcom FM (1989-1990) with Robert Hays and Patricia Richardson, and in 1992 landed a leading role on the ABC sitcom Laurie Hill. In 1993, Matthews landed a female leading role opposite Harry Anderson in the CBS sitcom Dave's World; the series ran to 1997. Matthews guest-starred in a number of television series, include Murphy Brown, Quantum Leap, From the Earth to the Moon, Diagnosis: Murder, Strong Medicine, Cold Case, Nip/Tuck, Castle and well as recurred on The Shield and Saving Grace. In 2001, she joined the cast of ABC soap opera General Hospital playing Janine Matthews. She was regular cast member from October 29, 2001 to June 5, 2003. References External links Category:American television actresses Category:American people of Irish descent Category:Florida State University alumni Category:Actresses from Florida Category:1961 births Category:Living people Category:20th-century American actresses Category:21st-century American actresses Category:People from Rockledge, Florida Category:Power family

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Subscribe to Nintendo Life on If you're a fan of in-game cross-promotion, it might be worth checking out Le Cartel's new game, Heave Ho. It's designed for up to four people and simply requires players to reach a goal without falling to their death. As Heave Ho is published by Devolver Digital, it will include a number of indie game cameos. You'll be able to select avatars based on games such as Enter the Gungeon, Hotline Miami, GRIS, The Messenger, Gato Roboto, My Friend Pedro and many more. See the full line-up below: Pre-order now on Nintendo Switch and PC, available tomorrow!pic.twitter.com/g65z7bcIiM Lose a bunch of friends but gain a new one with My Friend Pedro joining Heave Ho!Pre-order now on Nintendo Switch and PC, available tomorrow! https://t.co/HGm5pdZ4bE @deadtoast_com August 28, 2019 Pre-order now on Nintendo Switch and PC, available Thursday!pic.twitter.com/Mku5RGEZBF Enter the Gungeon is armed to the teeth but Heave Ho is mostly arms and teeth!Pre-order now on Nintendo Switch and PC, available Thursday! https://t.co/HGm5pdHsN4 @DodgeRollGames August 27, 2019 Pre-order now on Nintendo Switch and PC, available Thursday!pic.twitter.com/K5xWmhzMFh Gris faces a whole different kind of grief in Heave Ho!Pre-order now on Nintendo Switch and PC, available Thursday! https://t.co/HGm5pdZ4bE @nomadastudiobcn August 26, 2019 Pre-order now on Nintendo Switch and PC, available August 29! pic.twitter.com/1a676eIOvN "Yes that shoud work." Katana ZERO knows a little something about trying and trying until you get it just perfect!Pre-order now on Nintendo Switch and PC, available August 29! @katana_zero https://t.co/HGm5pdZ4bE August 24, 2019 Pre-order now on Nintendo Switch and PC, available August 29!pic.twitter.com/SKxQx8fHL3 Meow-ve over and provide a helping hand before we love all nine lives - Gato Roboto is making an appearance in Heave Ho!Pre-order now on Nintendo Switch and PC, available August 29! https://t.co/HGm5pdZ4bE August 23, 2019 Pre-order now on Nintendo Switch and PC, available August 29!@devolverdigital pic.twitter.com/IelstWITRo "Do you like dropping other people?" Hotline Miami joins the effort in Heave Ho!Pre-order now on Nintendo Switch and PC, available August 29! https://t.co/HGm5pdZ4bE @HotlineMiami August 21, 2019 Pre-order now on Nintendo Switch and PC, available August 29!pic.twitter.com/jDXyPO8wAS Piku proves that you don't need arms to be a hero in Heave Ho! We're overjoyed to have @PikunikuGame make an appearance in Heave Ho!Pre-order now on Nintendo Switch and PC, available August 29! https://t.co/2Id3evqa05 August 20, 2019 Our review for Heave Ho will go live soon, until then, why not view the trailer at the top of the page to get a better idea of what you can expect. It really does look like it could be a lot of fun with a group of friends or your family members. Will you be downloading this game later today? Leave a comment down below.

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A comparison of four methods of variance component estimation for heritability of embryonic mortality in turkeys. A comparison of four methods for variance component estimation to compute heritability of embryonic mortality in the early (Days 1 to 10) and late (Days 21 to 28) incubation period, was performed using Henderson's Method 3, maximum likelihood (ML), restricted maximum likelihood (REML), and minimum variance quadratic unbiased estimator (MIVQUE). Incubation records from Wrolstad Medium White turkeys divergently selected for semen ejaculate volume were the source of data for the present study. Negative sire components of variance were obtained for early mortality by both Henderson's Method 3 and the MIVQUE procedure. Estimates of the sire variance component for the late mortality period were lower (P less than .05) for ML than those obtained using Henderson's Method 3, REML, and MIVQUE. It was concluded that likelihood procedures (ML and REML) are superior for estimating variance components and genetic parameters from unbalanced data.

{ "pile_set_name": "PubMed Abstracts" }

Q: Trouble posting a JavaScript object with an array of Key Value Pairs to Web Api I have an object (mockup below) I've populated client-side with JavaScript and I need to post it to my server. There's a corresponding type of object defined in a class server-side that I'm expecting to receive. When I attempt to post the object, everything posts fine except for a single property. This property is defined server-side as a List<KeyValuePair<Guid,Bar>>. The Bar doesn't seem to be the issue, as I can post that just fine. Client-side, I've attempted to reformat the corresponding property on the JavaScript object in a few ways (as an array of object pairs, as literal properties on the object, etc.), but it's always an empty list when it arrives at the server. I'm guessing this is a syntax issue, but I'm having trouble figuring out what the proper syntax is, and I'm seeing a lot of conflicting examples online. I'm hoping someone can speak from experience as to how this should be posted. //C# Class MockUp public class Foo { public Guid FooId {get;set;} public string Description {get;set;} public bool Inactive {get;set;} public List<KeyValuePair<Guid,Bar>> FooBar {get;set;} //This comes over as null regardless of how I arrange the object client-side. } //TypeScript Class MockUp class Foo { fooId: string; description: string; inactive: boolean; fooBar: Array<KeyValuePair>; } class KeyValuePair { key: string; value: Bar } class Bar { //...Implementation here mathces Bar on the server } A: Will work if you create a dto for foobar public class FooDto { public Guid FooId {get;set;} public string Description {get;set;} public bool Inactive {get;set;} public List<FooBarDto> FooBar {get;set;} } public class FooBarDto { public Guid Key {get;set;} public Bar Value {get;set;} } The reason why KeyValuePair will not work in this case is because the properties in KeyValuePair are read only, take a look here at the msdn docs you can see that the Key and Value proerties only have getters

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World Online Campaigns Aim to Help Kai the Hitchhiker Beat Murder Rap The never-dull story of Kai the Hitchhiker took a dark turn last week when the viral hero was unexpectedly arrested on murder charges. Since then, a small handful of online campaigns have tried to drum up support for the man who famously referred to himself as "homefree" — not homeless — and set him back on his untethered way. Kai, less frequently known by his given name of Caleb McGillvary, was arrested at a Philadelphia bus terminal last Thursday. He is charged with killing a 73-year-old lawyer named Joseph Galfy, Jr., in Galfy's home in Clark, N.J. Police found Galfy's body in his house last Monday after he and McGillvary met in New York City. The cause of death was determined as blunt force trauma. McGillvary skyrocketed to viral Internet fame in February after using a hatchet to save a utility worker and female bystander. McGillvary had hitched a ride through Fresno, Calif., with a man named Jett Simmons McBride, who referred to himself as Jesus. After pulling into a gas station, McBride allegedly ran his car into a African American Pacific Gas and Electric worker, pinning him to his truck. He then proceeded to get out of his car and beat the 37-year-old worker. At this point, McGillvary found a hatchet in the car and used it to save the worker. A local TV interview shot at the scene quickly became an online sensation. McGillvary found brief national fame, appearing on Jimmy Kimmel Live, where the talk show host presented him with a new surfboard for his act of valor. Shortly thereafter, McGillvary began corresponding with a Georgia man named Terry Ratliff via Facebook and email, according to Ratliff. Ratliff, who made a YouTube remix of McGillvary's local TV interview, said they mostly talked about music and made plans to produce an original song. Ratliff said he was shocked to learn of the murder charge against McGillvary this month. It inspired him to start a GoFundMe campaign with the lofty goal of raising $3 million for McGillvary — the amount prosecutors set for bail upon his arrest. Ratliff realizes that number is likely a pipe dream, but said any money raised will go toward helping McGillvary's legal defense. "I've spoken to some lawyers that might be willing to help, or might take his case pro bono," Ratliff told Mashable. "A public defender would be the worst thing for him, someone with 50 or 100 clients and no time to really work on his case." So far, Ratliff's GoFundMe campaign has raised just over $1,200 online in a week. Similar efforts by others have met similarly meager success. Much of the sympathy for McGillvary stems from a Facebook post he wrote a day after Galfy's alleged murder, but before the story became national news. In the post, which includes graphic language but little detail, McGillvary intimates that he'd been drugged and sexually assaulted. It finishes with a question: "What would you do?" In interviews following his initial rise to fame, McGillvary said that he'd been abused as a kid as well. “You look in his eyes,” Miller, who started the Change.org petition, told NJ.com, “and you can see he’s a good kid.” For all his support, meanwhile, Ratliff acknowledges that he doesn't truly know McGillvary, with whom he'd corresponded extensively before the arrest but never met in person. "Personally, he always seemed alright to me," Ratliff told Mashable. "He seemed like a happy person who wasn't angry at anything. He seemed like a cool guy but, I mean, you never really know what anyone is capable of." What's Hot More in World What's New What's Rising What's Hot Mashable is a leading global media company that informs, inspires and entertains the digital generation. Mashable is redefining storytelling by documenting and shaping the digital revolution in a new voice, new formats and cutting-edge technologies to a uniquely dedicated audience of 42 million monthly unique visitors and 24 million social followers.

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Pharmaceutics Professor Mandip Sachdeva from the Florida A&M University (FAMU) has led a research project to 3D print a cornea in what is reportedly the first example of high throughput printing of human cells, particularly in America. The project was undertaken in two research laboratories in the Dyson Pharmacy Building on the FAMU campus using the Cellink Bio X bio printer. Sachdeva, research assistant Paul Dinh, and Shallu Kutlehria, a graduate assistant in the College of Pharmacy and Pharmaceutical Sciences, will be submitting a white paper detailing the project later this month for journal publication. Potentially, the results of the project could lead to advancements in the medical field for applications related to the cornea, like transplants and treatments. Sachdeva tells Speaking to the Tallahassee Democrat, Sachdeva explained the significance of this breakthrough: “High throughput cornea printing means that we can print multiple corneas in a matter of minutes using a specially designed scaffold by our laboratory.” “This will save time, and hence, will increase efficiency.” Towards 3D printed corneal transplants Sachdeva has been teaching at FAMU for 26 years, and in his time has been awarded $25 million in research funding. The most recent research for 3D bioprinted corneas follows a 2017 grant from the National Science Foundation. Alongside two FAMU-FSU College of Engineering professors, Sachdeva was awarded the grant to research applications for bioprinting, aerospace materials and energy. After initially focusing on materials/devices for biological applications, this research led to ocular research and the 3D printing of corneas. The project began around the beginning of 2018, and centered on replicating the collagen matrix of real cornea with 3D printing by using stromal cells or keratocytes. These cells help develop and maintain normal corneal structure and transparency, as well as helping to repair tissue after injury. “The starting point was, we have to have print the cornea,” Sachdeva added. “A lot of things went into it. When you print the cornea, the bio-ink is very important. You have to formulate a bio-ink to use for the cornea that simulates the human characteristics.” Potential applications for the tissues include cornea transplants, a long-term goal of the project, and creating an in-vitro model for research and drug screening drug. Currently, the team is developing a prototype of a blinking eye model utilizing the 3D printed cornea, which is an upgrade of a basic in-vitro model. The first 3D printed cornea As the potential impact of artificial ocular tissues is realized several efforts in 3D bioprinted corneas have emerged in recent years. Since 2017 the Instituto de Investigación Biomédica del Hospital La Paz (IdiPAZ) in Madrid, Spain, has been working toward the goal of 3D printing viable human corneas by the year 2020. Pandorum Technologies Pvt., a Bangalore-based biotechnology company, has also used 3D bioprinted cornea tissue to promote the scarless healing of wounds in the eye. In 2018, scientists at Newcastle University (NCL) successfully 3D printed human corneas for the first time. Che Connon, Professor of Tissue Engineering at Newcastle University, and his research team created a printable bioink solution from donor stem cells, alginate, and collagen. This was used to successfully 3D print a cornea in under ten minutes. Sachdeva explains the difference between the research project at FAMU to the NCL study, however, “They printed one cornea. [Dinh] said it takes so much time, if you want to print six corneas, or 12 corneas, how do we do that?” “My team developed a high throughput printing system where in about 10 minutes, you can print about six corneas.” Subscribe to the 3D Printing Industry newsletter for the latest 3D bioprinting research. Stay connected by following us on Twitter and liking us on Facebook. Looking for a career in additive manufacturing? Visit 3D Printing Jobs for a selection of roles in the industry. Featured image shows Florida A&M University biology student Paul Dinh holding a 3D printed cornea on the tip of his finger. Photo via Tori Schneider/Tallahassee Democrat.

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Poly(4-vinylpyridinium)hydrogen sulfate: a novel and efficient catalyst for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes under conventional heating and ultrasound irradiation. A simple and convenient procedure for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes is described through a one-pot condensation of 2-naphthol with aryl aldehydes in the presence of poly(4-vinylpyridinium)hydrogen sulfate as an efficient, cheap, readily synthesized and eco-friendly catalyst in a solvent free media using conventional heating and ultrasound irradiation.

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The New Mind Control: How the Internet Flips Elections and Alters Our Thoughts - Jerry2 https://aeon.co/essays/how-the-internet-flips-elections-and-alters-our-thoughts ====== dc2 "Google and its top executives donated more than $800,000 to President Barack Obama and just $37,000 to his opponent, Mitt Romney." Did you just Alter My Thoughts? How much of that $837,000 was Google versus its top executives (based on their personal preferences)?

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Take a trip back in time to when Tallinn was a wealthy city in the Hanseatic league - one which has miraculously preserved its medieval aura right up to the present day! We take you on a stroll along the winding cobblestone streets of the Old Town, recounting legends and stories of medieval life, stopping off for food-tasting along the way – marzipan in the oldest continuously operating pharmacy in Europe; starters at the medieval eatery The Third Dragon; a feast at the Waggehus restaurant; and dessert at the medieval restaurant Olde Hansa, in the setting of an historical rich merchant's home.

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Oh god farking dammit. This new line of proposed Bruce Crow laws in the south aren't enough, right-wing shiatheads here are trying to further influence an already unhinged country into going full-on Nazi in regard to gays? You know who else made it a crime to not report gay people? THE NAZIS. THAT'S NOT EVEN THE JOKE. That dude sounds almost resonable. If scientists tells him that being gay isn't a lifestyle choice, then he won't sign the law. Obviously his own scientists have told him it is a choice, but he seems inclined not to believe that, probably due to diplomatic preasure. Its like he he's going "hold on, all this stuff you told me was bullshiat, people are born like that?". To a lot of homophobic people, the choice part doesn't matter. I mean, it's not like Hitler killed the gays because he thought they were like that just to piss him off. spawn73:That dude sounds almost resonable. If scientists tells him that being gay isn't a lifestyle choice, then he won't sign the law. Obviously his own scientists have told him it is a choice, but he seems inclined not to believe that, probably due to diplomatic preasure. Its like he he's going "hold on, all this stuff you told me was bullshiat, people are born like that?". To a lot of homophobic people, the choice part doesn't matter. I mean, it's not like Hitler killed the gays because he thought they were like that just to piss him off. I think it's more a thing of:He's scared of US cutting their foreign aid and he's looking for an out. Satanic_Hamster:spawn73: That dude sounds almost resonable. If scientists tells him that being gay isn't a lifestyle choice, then he won't sign the law. Obviously his own scientists have told him it is a choice, but he seems inclined not to believe that, probably due to diplomatic preasure. Its like he he's going "hold on, all this stuff you told me was bullshiat, people are born like that?". To a lot of homophobic people, the choice part doesn't matter. I mean, it's not like Hitler killed the gays because he thought they were like that just to piss him off. I think it's more a thing of:He's scared of US cutting their foreign aid and he's looking for an out. Bloody William:The law would also make it a crime not to report gay people. Oh god farking dammit. This new line of proposed Bruce Crow laws in the south aren't enough, right-wing shiatheads here are trying to further influence an already unhinged country into going full-on Nazi in regard to gays? You know who else made it a crime to not report gay people? THE NAZIS. THAT'S NOT EVEN THE JOKE. Well the thing is everyone in a country like that should be scared of laws like that, even the homophobes. It seems unlikely Uganda's court system is infallible, so if someone doesn't like them and decides to report them as gay, are they so sure they could prove they aren't to a jury probably full of people like themselves? Alphax:markfara: Alphax: FirstNationalBastard: Will they eat da poopoo for lunch? I'm sure it was American conservatives who told that guy to say that. Yes. They had an awesomely advanced civilization until the conservatives got involved. Or something. /Not the least bit conservative.//But, you know, come on, here. . . . I've heard the American conservatives were telling the same stories about gay people in the 1950's. So, yeah, pack up the old 'textbooks' and mail them overseas.. and they say the same shiat again. No argument here. My point is that the conservatives didn't jump into some advanced, well-developed culture and make it all anti-gay. They're exploiting a market-niche, absolutely, but they didn't create it. And it would most likely still exist if they hadn't gotten involved. Ever notice how when the Fark Islamophobes are comparing Muslims to Christians, the Christians they use as examples of comparison are not these third world Christians, whose economic and educational circumstances are actually similar to those of most Muslims? Always nice, safe, tame Christians from America?That's because it would be a valid comparison, and Christians wouldn't come out looking any better.

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Springlands, Queensland Springlands is a rural locality in the Whitsunday Region, Queensland, Australia. In the , Springlands had a population of 45 people. Geography The suburb completely surrounds the town of Collinsville. The Collinsville coal mine is located in the suburb. The majority of the western and southern boundary is aligned with the Bowen River. Sonoma State Forest covers 8,800 hectares in the north east of Springlands. Heritage listings Springlands has a number of heritage-listed sites, including: Strathmore Road: Strathmore Homestead References Category:Whitsunday Region Category:Springlands, Queensland Category:Localities in Queensland

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1. Field of the Invention The present invention relates in general to a monitor, and more particularly, to a monitor improved in tilting structure of the monitor against a base member, and improved in combining structure of the base member and an inclined plane. 2. Description of the Related Art As shown in FIG. 1, a conventional monitor includes a base member 201 laid on a horizontal plane, a monitor main body 202 to display a picture thereon, and a link member 210 to link the base member 201 with the main body 202. A lower part of the link member 210 is rotatably combined to the base member 201 by a pair of fixing brackets 204 and 206, and an upper part of the link member 210 is fixed with the main body 202. Thus, along a direction of an arrow “A” in FIG. 1, the link member 210 is vertically rotated against the base member 201, but the main body 202 cannot be tilted against the link member 210. Therefore, with the conventional monitor, it is inconvenient to adjust an angle of the main body 202 as necessary. Contrary to the monitor shown in FIG. 1, it is possible that the upper part of the link member 210 is rotatably combined to the main body 202, and the lower part of the link member 210 is fixed with the base member 201. Accordingly, the angle of the main body 202 is more efficiently adjusted. As computer systems rapidly spread, demand of various monitor capabilities are also being rapidly increased. In relation to the increased demand of the monitor, there has been provided an arm stand to support the monitor, which is manufactured separately from the monitor and combined to the monitor, to thereby meet a user's preference. A combining structure of the monitor and the arm stand has been regulated by VESA (VIDEO ELECTRONIC STANDARD ASSOCIATION). However, in the conventional monitor, because the base member 210 must be laid on the horizontal plane, it is impossible to install the monitor onto an inclined plane such as a wall, the arm stand, etc. Because the main body 202 is not folded to the base member 201, the monitor is packed in a state as shown in FIG. 1, or in a state that the link member 210 is folded to the base member, which is not shown. Thus, a packing volume of the monitor cannot be decreased, thereby increasing costs to keep and carry the monitor. Furthermore, if regulations regarding the angle adjustment of the main body 202 are different in various nations, it is difficult to adaptively meet regulation requirements for the angle adjustment.

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DayZ Standalone SNViolent – 3v3 NW Airfield – Score.. 3-0 Quite a long siege at the NW Airfield. Apologies for some trash talk.. It wasn't me! If you like the video don't forget to press that subscribe button... DayZ Standalone SNViolent – Hacking Piece of S*** I'm not one to usually shout the H word, but what do you think? Keep it legit, brothers. If you like the video don't forget to press that subscribe bu... DayZ Standalone SNViolent – You know what to do with that big fat butt… A random guy we met lightened up our night. Bit creepy. If you like the video don't forget to press that subscribe button. Also, all my gameplay i... DayZ Standalone SNViolent – Guardian Angels – Electro Overwatch Sitting on a rooftop helping out some new spawns get some gear! If you like the video don't forget to press that subscribe button. Also, all my gamepl... Welcome to my channel guys and girls. All my games are streamed through Twitch so drop by and see what i’m playing today! http://www.twitch.tv/snviolent If you like the video don’t forget to press that subscribe button. You can also follow me on twitter for updates on streaming and more YouTube videos. This website is not affiliated with or authorized by Bohemia Interactive a.s. Bohemia Interactive and DAYZ and all associated logos and designs are trademarks or registered trademarks of Bohemia Interactive a.s. DAYZ is created by Dean Hall.

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Nebraska Supreme Court Online Library www.nebraska.gov/apps-courts-epub/ 10/11/2019 01:06 AM CDT - 933 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 State of Nebraska on behalf of K aaden S., a minor child, appellee, v. Jeffery T., appellant, and M andy S., appellee. ___ N.W.2d ___ Filed August 30, 2019. No. S-17-1210. 1. Paternity: Appeal and Error. In a filiation proceeding, questions con- cerning child custody determinations are reviewed on appeal de novo on the record to determine whether there has been an abuse of discretion by the trial court, whose judgment will be upheld in the absence of an abuse of discretion. 2. Judges: Words and Phrases. A judicial abuse of discretion exists if the reasons or rulings of a trial judge are clearly untenable, unfairly depriv- ing a litigant of a substantial right and denying just results in matters submitted for disposition. 3. Evidence: Appeal and Error. In a de novo review, when the evidence is in conflict, the appellate court considers, and may give weight to, the fact that the trial court heard and observed the witnesses and accepted one version of the facts rather than another. 4. Child Custody: Visitation. The Parenting Act does not require any particular parenting time schedule to accompany an award of either sole or joint physical custody, and there exists a broad continuum of possible parenting time schedules that can be in a child’s best interests. 5. Child Custody: Visitation: Words and Phrases. An alternating week- on-week-off parenting time schedule requires the child to spend roughly the same amount of time at each parent’s residence and allows both parents to exert continuous blocks of parenting time for significant periods of time, and thus meets the statutory definition of joint physi- cal custody. 6. Child Custody: Visitation. Where a parenting plan effectively estab- lishes a joint physical custody arrangement, courts will so construe it, regardless of how prior decrees or court orders have characterized the arrangement. - 934 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 7. Divorce: Child Custody. The Parenting Act authorizes a trial court to award joint custody in dissolution actions if the court specifically finds, after a hearing in open court, that joint physical custody or joint legal custody, or both, is in the best interests of the minor child regardless of any parental agreement or consent. 8. Courts: Appeal and Error. The doctrine of stare decisis requires that appellate courts adhere to their previous decisions unless the reasons therefor have ceased to exist, are clearly erroneous, or are manifestly wrong and mischievous or unless more harm than good will result from doing so. The doctrine is entitled to great weight, but it does not require courts to blindly perpetuate a prior interpretation of the law if it was clearly incorrect. 9. Child Custody: Judges. A blanket rule disfavoring joint physical cus- tody is inconsistent with the Parenting Act and unnecessarily constrains the discretion of trial judges in some of the most important and difficult decisions they are called upon to make. 10. Child Custody. Joint physical custody is neither favored nor disfavored under Nebraska law. In fact, no custody or parenting time arrangement is either favored or disfavored as a matter of law. 11. ____. When determining the best interests of the child in deciding cus- tody, a court must consider, at a minimum, (1) the relationship of the minor child to each parent prior to the commencement of the action; (2) the desires and wishes of a sufficiently mature child, if based on sound reasoning; (3) the general health, welfare, and social behavior of the child; (4) credible evidence of abuse inflicted on any family or household member; and (5) credible evidence of child abuse or neglect or domestic intimate partner abuse. 12. Visitation. The Parenting Act provides that the best interests of a child require a parenting plan that provides for a child’s safety, emo- tional growth, health, stability, physical care, and regular school attend ance, and which promotes a child’s continued contact with his or her families and parents who have shown the ability to act in the child’s best interests. 13. ____. When determining the allocation of parenting time that is in a child’s best interests, a trial court should consider the parties’ ability to communicate on issues such as transportation, homework, discipline, medical and dental appointments, and extracurricular activities. Other relevant considerations include stability in the child’s routine, mini- malization of contact and conflict between the parents, and the general nature and health of the individual child. The fact that one parent might interfere with the other’s relationship with the child is also a factor to consider, but is not a determinative factor. - 935 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 14. Child Support: Rules of the Supreme Court. The Nebraska Child Support Guidelines require child support orders to address how the par- ents will provide for the child’s health insurance. 15. ____: ____. Neb. Ct. R. § 4-215(B) of the Nebraska Child Support Guidelines estimates $480 as an ordinary amount of nonreimbursed medical expenses, and that figure is then subsumed within the amount of child support that is ordered. Any nonreimbursed expenses exceeding $480 are prorated between the parties. 16. ____: ____. Child support payments should generally be set according to the child support guidelines. Petition for further review from the Court of Appeals, Pirtle, R iedmann, and Welch, Judges, on appeal thereto from the District Court for Jefferson County, R icky A. Schreiner, Judge. Judgment of Court of Appeals affirmed in part as modi- fied, and in part reversed and remanded with directions. Ronald R. Brackle for appellant. Angelica W. McClure, of Kotik & McClure Law, for appel- lee Mandy S. Heavican, C.J., Miller-Lerman, Cassel, Stacy, Funke, Papik, and Freudenberg, JJ. Stacy, J. In this paternity action, the district court awarded primary legal and physical custody of a minor child to the father and awarded the mother nearly equal parenting time. Child support was calculated using a joint custody worksheet, and the father was ordered to pay monthly support. The father appealed, assigning multiple errors, including that the award of nearly equal parenting time was, in effect, an award of joint physical custody and was an abuse of discretion. The Nebraska Court of Appeals agreed, and it reversed and remanded with directions to modify the mother’s parenting time so it was “consistent with an award of primary physical custody” to the father.1 In 1 State on behalf of Kaaden S. v. Jeffery T., 26 Neb. App. 421, 430, 920 N.W.2d 39, 48 (2018). - 936 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 doing so, the Court of Appeals relied on Nebraska precedent holding that joint physical custody is disfavored and should be reserved for rare cases.2 We granted the mother’s petition for further review to reexamine that precedent.3 We now hold that a blanket rule disfavoring joint physical custody is inconsistent with the Parenting Act,4 which requires that all determinations of custody and parenting time be based on factors affecting the best interests of the child. We thus disapprove of our prior rule disfavoring joint physical custody, and we clarify that Nebraska law neither favors nor disfa- vors any particular custody arrangement and instead requires all such determinations to be based on the best interests of the child. When the custody and parenting time in the instant case are reviewed under this standard, we find no abuse of discretion. We thus reverse the Court of Appeals’ determination to the contrary and remand the matter with directions to affirm the judgment of the district court as it regards custody, parenting time, and child support. I. FACTS Kaaden S. was born to Mandy S. and Jeffery T. in June 2014. The parents did not have a dating relationship either before or after conception. Mandy notified Jeffery of her pregnancy, and Jeffery was at the hospital on the day Kaaden was born. In February 2015, the State filed a paternity action against Jeffery in the district court for Jefferson County, including Mandy as a third-party defendant. Jeffery’s answer admitted paternity, and he filed a cross-claim against Mandy seeking 2 State on behalf of Kaaden S., supra note 1, citing Erin W. v. Charissa W., 297 Neb. 143, 897 N.W.2d 858 (2017). 3 See, e.g., Erin W., supra note 2; Zahl v. Zahl, 273 Neb. 1043, 736 N.W.2d 365 (2007); Trimble v. Trimble, 218 Neb. 118, 352 N.W.2d 599 (1984); Aguilar v. Schulte, 22 Neb. App. 80, 848 N.W.2d 644 (2014). 4 Neb. Rev. Stat. §§ 43-2920 to 43-2943 (Reissue 2016 & Cum. Supp. 2018). - 937 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 joint legal and physical custody of Kaaden and asking that Kaaden’s surname be changed. Mandy’s responsive pleading admitted Jeffery was Kaaden’s father and requested sole legal and physical custody of Kaaden. Genetic testing later con- firmed Jeffery was Kaaden’s biological father. In July 2015, the district court entered an order finding Jeffery was Kaaden’s father, but reserved the issues of custody, parenting time, and child support pending further hearing. Approximately 1 year later, when Kaaden was nearly 2 years old, the district court entered an order establishing temporary child support and parenting time. The temporary order allowed Jeffery supervised, nonovernight visits for 60 days and then progressed to give Jeffery parenting time every other weekend and on Wednesday evenings. Mandy did not comply with the temporary order and con- sistently refused to allow Jeffery overnight parenting time with Kaaden. Jeffery sought to have Mandy held in contempt of court for failing to comply with the temporary order, and the contempt matter was set to be taken up at the time of trial. Generally, as Jeffery’s parenting time with Kaaden increased, the quality of the interaction between Mandy and Jeffery decreased. In November 2016, Jeffery made an audio recording of a particularly contentious interaction with Mandy that occurred during an exchange of Kaaden. In the record- ing, Mandy can be heard yelling at Jeffery and belittling his attempts to build a relationship with Kaaden. During this interaction, Mandy pepper-sprayed Jeffery in the face and then called police to report she had been assaulted. Jeffery played the recording for the officers, and no arrest was made. After this incident, it became even more difficult for Mandy and Jeffery to communicate. Exchanges for parenting time occurred at the sheriff’s office, but remained contentious. The parties twice attempted to mediate the issues of custody, parenting time, and child support, but both times, Mandy refused to sit in the same room with Jeffery and no agreement was reached. - 938 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 1. Trial In May 2017, trial was held on the issues of custody and parenting time, child support, and contempt of the temporary order. Jeffery, whose pleadings originally had requested joint custody, sought primary physical custody of Kaaden at trial. He testified that if awarded primary custody, he would support Mandy and Kaaden’s relationship and adhere to any parenting time order imposed. He also asked that Kaaden’s surname be changed to his surname. Mandy testified that she did not think joint custody would work because she and Jeffery did not communicate well, though she thought that would improve once the litigation was concluded. She asked to be awarded sole legal and physical custody of Kaaden and proposed that Jeffery have parenting time every other weekend. She requested continued child sup- port and opposed changing Kaaden’s surname. Mandy admitted she had not adhered to the parenting plan under the temporary order, but she testified that Kaaden was scared and did not want to have visits with Jeffery. She said that around the time that Jeffery’s parenting time was to increase under the tempo- rary order, Kaaden began exhibiting behavioral problems, so she took him to see a counselor. Kaaden’s counselor testified at trial. She initially diagnosed Kaaden with “separation trauma and extreme anxiety,” but testified he showed significant growth over the 5 months she worked with him. The counselor had no concerns about Mandy as a custodial parent, but offered the opinion that it was best for Kaaden that contact between Mandy and Jeffery be limited. According to the counselor, Mandy had “significant unresolved issues” toward Jeffery, and she recommended Mandy partici- pate in treatment to address it. The counselor had no opinion on the feasibility of joint custody, but did have a recommenda- tion regarding future parenting time. She recommended that after a transition period, Jeffery’s parenting time should be “week on, week off . . . until [Kaaden] reaches middle school grade age.” - 939 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 Before trial, the court appointed an attorney to serve as the guardian ad litem (GAL) for Kaaden. The GAL attended trial but did not testify. Instead, she was ordered by the court to sub- mit a recommendation and written report, which was received into evidence after trial. No party objected to this procedure before the trial court. The GAL’s report detailed that she had met with both par- ties and their counsel, visited Kaaden at both parties’ homes, observed exchanges of Kaaden during parenting time, and interviewed more than a dozen people including a nationally recognized expert in the area of parental alienation, members of Mandy’s family, and friends and acquaintances of Jeffery. The GAL described the case as “one of the most difficult cases [she had] worked on in 20 years of being appointed as a [GAL].” Her report stated she was “completely confident in making the recommendation that Kaaden’s primary physical custody be awarded to . . . Jeffery.” The GAL believed that Mandy’s “loathing” of Jeffery was harmful to Kaaden and that Mandy’s pattern of “parental alienation” was unlikely to change. The GAL expressed the opinion that “it would be in Kaaden’s best interests to be in a parent’s custody [who] is going to make a good faith effort to work with the other parent and not sabotage Kaaden’s relationship with that parent.” (a) Custody and Parenting Time The trial court’s order summarized the evidence adduced at trial and generally found that both parents were fit and had formed a good relationship with Kaaden. But the court noted: The complicating factor in this matter is the lack of a relationship between the parents, both prior to Kaaden’s conception and continuing, and the obvious resentment Mandy has towards Jeff[er]y and the situation in which she now finds herself. Mandy testified that she believes Kaaden needs his father in his life and does not believe that Jeffery abuses Kaaden in any fashion, although she . . . appears to do everything she can to limit or monitor Jeff[er]y and Kaaden’s relationship. The record reflects - 940 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 that she has done everything in her power to prevent Jeff[er]y from being a father to Kaaden by contesting and litigating every attempt he has made to do so. Mandy’s testimony at trial indicated that while she wanted to be a mother at some point in her life she did not envi- sion it happening in this fashion nor was this part of her plan. That said, it’s obvious she loves Kaaden. Her anger towards Jeff[er]y, unfortunately, clouds her judg- ment regarding what is in Kaaden’s best interests at times, especially when it comes to allowing Jeffery to be involved in his life. Mandy and Jeff[er]y both provide safe and appropriate homes for Kaaden where he enjoys a healthy diet, has a bed to sleep in, and toys and activities to keep him occu- pied and engaged. .... The court has addressed the parties, on the record, dur- ing the pendency of this matter. Each time I addressed them I tried to remind them that Kaaden’s interests are best served by having both of his parents involved in his life, and tried to encourage Mandy to see past her hurt, fear, and anger and allow Kaaden to have his father in his life. Unfortunately, the report from [the GAL] indicates those words went in one ear and out the other because nothing has changed with her behavior. It appears she is still putting more value on her hate and anger than she is on Kaaden’s ability to have a father actively engaged in his life and the benefits of that relationship. For the reasons stated above, as well as the firm belief that doing so best ensures compliance with the order of custody so that Kaaden can enjoy the full benefits of having both parents involved in his life to the greatest degree possible, the court finds that it is in Kaaden’s best interests that primary legal and primary physical custody be awarded to . . . Jeff[er]y . . . subject to liberal parenting time with . . . Mandy . . . . - 941 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 The decree awarded Jeffery “primary legal and primary physical care, custody and control” of Kaaden, pursuant to a court-created parenting plan. The parenting plan described the custody award as follows: The father shall have sole legal and physical custody of the minor child and, as such, shall have the legal respon- sibility and authority to make final decisions concerning the parenting functions necessary to raising the child. . . . The principal place of residence (physical custody) of the child shall be with the father, (custodial parent) subject to the terms of this Plan. The court-created parenting plan provided that after a brief transition period, Mandy and Jeffery would have parenting time in alternating 1-week blocks. Exchanges were to occur each Friday at 6 p.m. at the sheriff’s office. The plan addressed holidays and gave each parent 2 uninterrupted weeks of sum- mer parenting time. (b) Child Support and Nonreimbursed Health Care Costs The court used worksheet 3 of the Nebraska Child Support Guidelines, the joint custody worksheet, to calculate child sup- port, and the completed worksheet was attached to the decree. In allocating the number of overnights for each parent (line 5 on the worksheet), the court attributed 182 days to Mandy and 183 days to Jeffery. Jeffery was ordered to pay child sup- port of $93 per month and to provide health insurance for Kaaden. He was also ordered to pay the first $480 of Kaaden’s nonreimbursed reasonable and necessary health care expenses each year, and Mandy was ordered to pay 50 percent of such expenses in excess of $480. (c) Name Change, Contempt, and Attorney Fees Jeffery’s request to change Kaaden’s surname was denied. The court found Mandy in willful contempt for failing to comply with the terms of the temporary order and imposed a - 942 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 sanction of $50, but did not impose a purge plan. Finally, the court declined to award attorney fees and ordered the parties to pay their own fees and costs. 2. Court of A ppeals Jeffery appealed, assigning that the district court erred in (1) ordering equal parenting time, (2) calculating child sup- port using the joint custody worksheet, (3) ordering him to pay the first $480 in nonreimbursed health care expenses, (4) refusing to change Kaaden’s surname, (5) imposing a nominal fine for Mandy’s contempt, and (6) denying his request for attorney fees. The Court of Appeals found no merit to the arguments regarding the name change or attorney fees. But it agreed with Jeffery that the district court erred in its determinations regard- ing parenting time, child support, nonreimbursed health care expenses, and contempt. We summarize the court’s reason- ing below. (a) Custody and Parenting Time Before the Court of Appeals, Jeffery claimed the district court’s parenting plan was “essentially a Joint Physical Custody Plan,”5 which he argued was an abuse of discretion. The Court of Appeals agreed. It acknowledged that the district court had awarded primary physical custody to Jeffery, but it concluded that by giving Mandy nearly equal parenting time, the district court effectively imposed “the standard joint physical custody arrangement.”6 In considering whether such an arrangement was an abuse of discretion, the Court of Appeals relied on this court’s precedent which holds: Joint physical custody should be reserved for those cases where, in the judgment of the trial court, the parents are of such maturity that the arrangement will not operate to 5 Brief for appellant at 22. 6 State on behalf of Kaaden S., supra note 1, 26 Neb. App. at 431, 920 N.W.2d at 49. - 943 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 allow the child to manipulate the parents or confuse the child’s sense of direction, and will provide a stable atmos phere for the child to adjust, rather than perpetuating tur- moil or custodial wars.7 The Court of Appeals found that Mandy and Jeffery had “vir- tually no ability to communicate with each other regarding Kaaden”8 and concluded it was an abuse of discretion to estab- lish a parenting time schedule that amounted to joint physi- cal custody. It thus affirmed the award of primary legal and physical custody to Jeffery, but reversed the parenting plan and remanded the matter to the district court to implement a parent- ing time schedule “consistent with an award of primary physi- cal custody to Jeffery.”9 It did not indicate what the parameters of such a plan must be. (b) Child Support and Medical Expenses Because the matter was being remanded to reduce Mandy’s parenting time, the Court of Appeals also found the trial court’s use of the joint custody worksheet to calculate child support was in error. It therefore reversed the child support award and remanded the matter for recalculation “using the appropriate worksheet.”10 The Court of Appeals also reversed the provision in the decree requiring Jeffery to pay the first $480 of Kaaden’s nonreimbursed health care expenses. It rea- soned that children’s health care expenses are specifically included in the child support guidelines amount of up to $480 per child per year11 and that consequently, any nonreimbursed health care costs up to $480 were subsumed within the amount of child support ordered.12 It directed the trial court, upon 7 Id., citing Erin W., supra note 2. 8 Id. at 433, 920 N.W.2d at 50. 9 Id. at 430, 920 N.W.2d at 48. 10 Id. at 433, 920 N.W.2d at 50. 11 See Neb. Ct. R. § 4-215(B) (rev. 2011). 12 See, id.; State on behalf of Martinez v. Martinez-Ibarra, 281 Neb. 547, 797 N.W.2d 222 (2011). - 944 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 recalculating child support to reflect Mandy’s reduced parent- ing time, to then allocate nonreimbursed health care costs in excess of $480 accordingly. (c) Name Change, Contempt, and Attorney Fees Although not directly relevant to this petition for further review, we note that the Court of Appeals affirmed the dis- trict court’s refusal to change Kaaden’s surname, affirmed the district court’s denial of Jeffery’s request for attorney fees, and found that the district court committed plain error with respect to the unconditional sanction imposed for Mandy’s contempt. Our opinion on further review does not affect those findings. We granted Mandy’s petition for further review. II. ASSIGNMENTS OF ERROR On further review, Mandy assigns, restated, that the Court of Appeals erred in (1) reversing the parenting plan and remand- ing the matter with instructions to reduce Mandy’s parenting time, (2) finding the record did not support joint physical custody when the district court created a parenting plan that gave Mandy “de facto”13 joint physical custody, and (3) revers- ing the child support calculation and the requirement that Jeffery pay the first $480 of Kaaden’s nonreimbursed health care expenses. III. STANDARD OF REVIEW [1,2] In a filiation proceeding, questions concerning child custody determinations are reviewed on appeal de novo on the record to determine whether there has been an abuse of discretion by the trial court, whose judgment will be upheld in the absence of an abuse of discretion.14 A judicial abuse of discretion exists if the reasons or rulings of a trial judge 13 Brief for appellee Mandy S. in support of petition for further review at 2. 14 Cesar C. v. Alicia L., 281 Neb. 979, 800 N.W.2d 249 (2011). - 945 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 are clearly untenable, unfairly depriving a litigant of a sub- stantial right and denying just results in matters submitted for disposition.15 [3] In such de novo review, when the evidence is in con- flict, the appellate court considers, and may give weight to, the fact that the trial court heard and observed the witnesses and accepted one version of the facts rather than another.16 IV. ANALYSIS In her first two assignments of error, Mandy argues the Court of Appeals erred in reversing the parenting time schedule and remanding the matter with directions to reduce her parent- ing time. After reexamining our jurisprudence, we agree. As noted, the district court awarded Jeffery “primary” legal and physical custody of Kaaden and imposed a parenting plan that gave Mandy nearly equal parenting time. The Court of Appeals relied on its own precedent17 and precedent from this court18 to conclude that an award of nearly equal parenting time amounted to an award of de facto joint physical custody. It found such a custody arrangement was an abuse of discre- tion, relying on the legal proposition that joint physical cus- tody is disfavored and should be reserved for rare cases.19 We granted further review to reexamine that proposition. Before doing so, we set out the legal framework that governs child custody determinations in Nebraska. 1. Legal Custody Under the Parenting Act adopted by the Nebraska Legislature, the concept of child custody encompasses both “legal custody and physical custody.”20 “Legal custody” focuses entirely on 15 Leners v. Leners, 302 Neb. 904, 925 N.W.2d 704 (2019). 16 Cesar C., supra note 14. 17 Hill v. Hill, 20 Neb. App. 528, 827 N.W.2d 304 (2013). 18 Elsome v. Elsome, 257 Neb. 889, 601 N.W.2d 537 (1999). 19 See, Erin W., supra note 2; Aguilar, supra note 3. 20 § 43-2922(7). - 946 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 decisionmaking authority and is defined as “the authority and responsibility for making fundamental decisions regard- ing the child’s welfare, including choices regarding education and health.”21 Here, Jeffery was awarded Kaaden’s legal custody, and no party disputes that award. As such, Jeffery has the final say on fundamental decisions regarding Kaaden’s welfare, such as where he attends school, his religious upbringing, and how his health and medical needs are met.22 Because Kaaden’s legal custody is not at issue in this appeal, we focus our analysis on the issues of physical custody and parenting time. 2. Physical Custody and Parenting Time “Physical custody” is defined by the Parenting Act as “authority and responsibility regarding the child’s place of residence and the exertion of continuous parenting time for significant periods of time.”23 As such, although the Parenting Act does not speak in terms of “sole” or “primary” physical custody, it contemplates that an award of physical custody will determine the child’s primary residence and identify the parent who will exert “significant” and “continuous” parenting time over the child.24 “Joint physical custody” as defined by the Parenting Act means “mutual authority and responsibility of the parents regarding the child’s place of residence and the exertion of continuous blocks of parenting time by both parents over the child for significant periods of time.”25 The Parenting Act does not further define either “significant periods of time” or “con- tinuous blocks,” but it does define “parenting time.”26 21 § 43-2922(13). 22 See id. 23 § 43-2922(20). 24 See id. 25 § 43-2922(12). 26 See id. - 947 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 “Parenting time” is defined under the Parenting Act as “communication or time spent between the child and parent.”27 And the Parenting Act makes clear that regardless of the physi- cal custody arrangement, when parents are exercising parenting time, they are performing “[p]arenting functions.”28 Parenting functions are defined to include maintaining a safe, stable, consistent, and nurturing relationship with the child; attending to the child’s ongoing developmental needs, including feed- ing, clothing, grooming, emotional stability, and appropriate conflict resolution skills; attending to adequate education for the child; assisting the child in maintaining a safe, positive, and appropriate relationship with each parent and other family members; minimizing the child’s exposure to harmful parental conflict; assisting the child in developing skills to maintain safe, positive, and appropriate interpersonal relationships; and exercising support for social, academic, athletic, or other spe- cial interests.29 [4] The Parenting Act does not require any particular par- enting time schedule to accompany an award of either sole or joint physical custody, and there exists a broad continuum of possible parenting time schedules that can be in a child’s best interests. Nebraska has a number of appellate cases in which the parties disagreed over whether a particular custody and parenting time arrangement was properly characterized as sole physical custody with liberal parenting time or as joint physi- cal custody.30 But in this case, that analysis is not difficult, and both parties concede the court effectively imposed a joint physical custody arrangement. We agree. [5] The district court awarded the parents nearly equal par- enting time in the form of an alternating week-on-week-off 27 § 43-2922(19). 28 § 43-2922(17). 29 Id. 30 See, e.g., Dooling v. Dooling, ante p. 494, ___ N.W.2d ___ (2019); Donald v. Donald, 296 Neb. 123, 892 N.W.2d 100 (2017); McDonald v. McDonald, 21 Neb. App. 535, 840 N.W.2d 573 (2013); Hill, supra note 17. - 948 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 schedule. Such a schedule requires Kaaden to spend roughly the same amount of time at each parent’s residence and allows both parents to exert continuous blocks of parenting time for significant periods of time, and thus meets the statutory defini- tion of joint physical custody.31 [6] Where a parenting plan effectively establishes a joint physical custody arrangement, courts will so construe it, regardless of how prior decrees or court orders have charac- terized the arrangement.32 In several cases, we have looked past the labels used by the trial court when describing the physical custody arrangement and have focused instead on the actual terms of the parenting plan adopted by the court.33 Such cases illustrate that it is the trial court’s allocation of parent- ing time that drives the physical custody label, not the other way around. We therefore agree with the parties and the Court of Appeals that regardless of the label used in the decree and parenting plan to describe physical custody, the trial court here effec- tively imposed a joint physical custody arrangement by creat- ing a week-on-week-off parenting time schedule.34 For the sake of clarity, we modify the language of the decree and parenting plan to reflect this holding. We turn next to the question whether, by effectively impos- ing a joint physical custody arrangement, the trial court abused its discretion. The Court of Appeals concluded it did, citing our 31 Becher v. Becher, 299 Neb. 206, 908 N.W.2d 12 (2018) (parenting plan establishing every-other-week parenting time schedule with equal time over summer break meets statutory definition of joint physical custody regardless of label used by trial court). 32 See, id.; Elsome, supra note 18. 33 See, e.g., Dooling, supra note 30, ante at 517, ___ N.W.2d at ___ (“the label that a court uses is not controlling and . . . the classification of a custody arrangement is ultimately dictated by parenting time”); Becher, supra note 31, 299 Neb. at 225, 908 N.W.2d at 29 (“the labels make little difference” when parenting plan sets forth parent’s rights and responsibilities). 34 See id. - 949 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 cases that generally disfavor joint physical custody arrange- ments, especially when there is evidence the parents have diffi- culty communicating.35 The time has come to reexamine those cases, and we turn to that discussion now. 3. Trimble v. Trimble One of the first times this court addressed the concept of joint physical custody was in Trimble v. Trimble,36 decided in 1984. In that case, the trial court awarded physical custody of two young children to the mother, finding she had “spent a great deal more of her time with the children, has the more pre- dictable work and leisure schedule, and was more concerned with the children’s education.”37 On appeal, the father argued it was error not to award joint physical custody. Trimble noted that “in a given case joint custody might very well act to preserve the parent-child bond for both parents and thus avoid the severance of either of the attachments.”38 But without citation or further explanation, Trimble opined: We believe, however, that such arrangements must be reserved for the most rare of cases, i.e., where in the judg- ment of the trial court the parents are of such maturity that the arrangement will not operate to allow the child to manipulate the parents or confuse the child’s sense of direction. A collateral question exists as to why those most ideal of parents, who would satisfactorily cope with the conflicts inherent in a joint child custody arrange- ment, came to be divorced in the first instance. . . . We are not prepared to reject the concept of joint custody, but are not prepared to state that it should be a regular tool in the remedies of the district courts.39 35 See, e.g., Erin W., supra note 2; Zahl, supra note 3; Trimble, supra note 3; Aguilar, supra note 3. 36 Trimble, supra note 3. 37 Id. at 119, 352 N.W.2d at 600. 38 Id. at 119, 352 N.W.2d at 600-01. 39 Id. at 120, 352 N.W.2d at 601. - 950 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 Trimble was decided at a time when Nebraska law did not distinguish between legal and physical custody, so many of our opinions applying Trimble described a blanket rule that “joint custody” is disfavored and must be reserved for the rar- est of cases.40 More recently, articulation of the Trimble rule has focused on joint physical custody; in Zahl v. Zahl,41 we described the rule this way: [J]oint physical custody must be reserved for those cases where, in the judgment of the trial court, the parents are of such maturity that the arrangement will not operate to allow the child to manipulate the parents or confuse the child’s sense of direction, and will provide a stable atmos phere for the child to adjust, rather than perpetuating tur- moil or custodial wars. Trimble and Zahl use different phrasing but stand for the same blanket proposition—that joint custody arrangements are generally disfavored and should be reserved for rare or spe- cial cases. 4. R evisiting Trimble [7] Recently, in Leners v. Leners,42 we cited the rule dis- favoring joint custody but cautioned that it should not be viewed as a “hard-and-fast rule.” We emphasized that the Parenting Act authorizes a trial court to award joint custody 40 See, e.g., Ensrud v. Ensrud, 230 Neb. 720, 727, 433 N.W.2d 192, 197 (1988) (“[t]his court has frequently and consistently expressed disapproval of joint custody as a purported solution for the difficulty confronted by a court in determining a question concerning child custody”); Wilson v. Wilson, 224 Neb. 589, 590, 399 N.W.2d 802, 803 (1987) (“[w]e have . . . stated explicitly that joint custody is not favored and must be reserved for only the rarest of cases”); Korf v. Korf, 221 Neb. 484, 486, 378 N.W.2d 173, 174 (1985) (“[a]n award of joint custody of minor children is not favored. Such an award must be reserved for the most rare of cases”). 41 Zahl, supra note 3, 273 Neb. at 1053, 736 N.W.2d at 373. Accord, Erin W., supra note 2; Schmeidler v. Schmeidler, 25 Neb. App. 802, 912 N.W.2d 278 (2018); Hill, supra note 17. 42 Leners, supra note 15, 302 Neb. at 913, 925 N.W.2d at 712. - 951 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 in dissolution actions “‘if the court specifically finds, after a hearing in open court, that joint physical custody or joint legal custody, or both, is in the best interests of the minor child regardless of any parental agreement or consent.’”43 In Leners, we affirmed an award of joint legal and physi- cal custody, finding it was in the child’s best interests, despite evidence the parents had a contentious relationship. In doing so, we analyzed the parents’ relationship as one of many fac- tors bearing on the child’s best interests. We noted that both parents were fit and that the child had a good relationship with each. We ultimately concluded that by establishing a parent- ing plan that afforded roughly equal parenting time, the trial court had fashioned a schedule that maximized the child’s time with both parents, accommodated the father’s unusual work schedule, and minimized the number of transitions and the need for communication and coordination between the parents. We found this plan served the child’s best interests. Leners did not expressly disapprove of the Trimble rule,44 but our analysis highlighted tension between the best interests analysis required under the Parenting Act and a blanket rule that disfavors joint custody and reserves it only for rare cases. We are persuaded the time has come to expressly reexam- ine the proposition that joint custody arrangements are disfa- vored and “reserved” for rare or special cases.45 The Wyoming Supreme Court recently engaged in a similar reevaluation of its judicial rule disfavoring joint custody. In Bruegman v. Bruegman,46 Wyoming acknowledged that its longstanding rule had been to disfavor joint custody “‘“absent good reason”’” based on the rationale that “‘“stability in a child’s environment is of utmost importance to the child’s 43 Id. at 913-14, 925 N.W.2d at 712, quoting Neb. Rev. Stat. § 42-364(3)(b) (Cum. Supp. 2018). 44 See Trimble, supra note 3. 45 See id. at 120, 352 N.W.2d at 601. 46 Bruegman v. Bruegman, 417 P.3d 157 (Wyo. 2018). - 952 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 well-being”’”47 and out of concern that joint custody could be successful only when “‘“the parents are able to communicate and agree on the matters relevant to the children’s welfare.”’”48 In evaluating whether it should change its rule disfavoring joint custody, the Wyoming court did not analyze the evolv- ing social science on parenting and child development, nor did it discuss arguments advanced for or against joint custody. Instead, it found that its blanket rule disfavoring joint custody was inconsistent with Wyoming statutes that require child cus- tody to be determined based on the best interests of the child. It noted that courts in Iowa49 and Maryland50 had previously criticized application of a blanket rule disfavoring joint physi- cal custody, reasoning that the question whether joint physical custody is appropriate should be based on the individual cir- cumstances of each case and not on general presumptions that may or may not be applicable.51 Wyoming ultimately rejected its precedent disfavoring joint custody and held instead that the fundamental consideration governing all child custody deter- minations is the best interests of the child. Citing the proposi- tion that “‘“joint custody, in any of its multiple forms, is but another option available to the trial judge,”’”52 the Wyoming court concluded that “shared custody should be considered on an equal footing with other forms of custody.”53 47 Id. at 162. 48 Id. 49 In re Marriage of Hansen, 733 N.W.2d 683, 695 (Iowa 2007) (concluding “the joint physical care issue must be examined in each case on the unique facts and not subject to cursory rejection based on a nearly irrebuttable presumption found in our prior cases”). 50 Taylor v. Taylor, 306 Md. 290, 302, 508 A.2d 964, 970 (1986) (reexamining rule that joint physical custody is “an arrangement ‘to be avoided, whenever possible, as an evil fruitful in the destruction of discipline, in the creation of distrust, and in the production of mental distress in the child’”). 51 Bruegman, supra note 46. 52 Id. at 163. Accord Taylor, supra note 50. 53 Id. at 164. - 953 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 5. Joint Custody No Longer Disfavored [8] The doctrine of stare decisis requires that we adhere to our previous decisions unless the reasons therefor have ceased to exist, are clearly erroneous, or are manifestly wrong and mischievous or unless more harm than good will result from doing so.54 The doctrine is entitled to great weight, but it does not require us to blindly perpetuate a prior interpretation of the law if we conclude it was clearly incorrect.55 We can conceive of no principled justification for continu- ing to apply a blanket rule that disfavors joint legal or physi- cal custody, especially when the rule is based on generalized concerns regarding parental maturity and possible behavioral consequences to a child from spending substantial amounts of time with each parent. Such concerns may well be valid in any given case and in that event should be considered in light of all the other factors and circumstances in arriving at a custody and parenting time arrangement that serves the best interests of the child at issue. But a blanket rule disfavoring joint legal or physical custody is difficult to reconcile with the Parenting Act, under which the best interests of the child are the polestar of all child custody and parenting time determinations.56 We see nothing in the Parenting Act that either favors or disfavors any particular custody or parenting time arrange- ment. The Parenting Act simply requires that all custody and parenting time arrangements be determined based on the best interests of the child.57 The Parenting Act “presumes the criti- cal importance of the parent-child relationship in the welfare and development of the child and that the relationship between the child and each parent should be equally considered unless it is contrary to the best interests of the child.”58 The Parenting 54 Davis v. State, 297 Neb. 955, 902 N.W.2d 165 (2017). 55 See id. 56 See §§ 43-2921 to 43-2923. See, also, § 42-364(2) (Reissue 2016). 57 § 43-2923(6). 58 § 43-2921 (emphasis supplied). - 954 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 Act also states that the best interests of the child require, among other things, “appropriate, continuing quality contact” between the child and parents who have shown the ability to act in the child’s best interests.59 The Parenting Act neither expresses nor suggests a default position favoring or disfavor- ing any particular custody arrangement, even one agreed to by the parents,60 and instead requires that all such determinations be based on the best interests of the child.61 We note that, in dissolution actions where the parents have not agreed to joint custody, § 42-364(3) requires that before joint custody may be ordered, there must be a hearing in open court and an express finding that joint custody is in the child’s best interests.62 But we do not understand the provisions of § 42-364(3) to indicate the Legislature either favors or disfa- vors joint custody. All cases governed by the Parenting Act 63 require a judicial determination, whether expressly stated or not, that the custody and parenting time arrangement ordered by the court is in the child’s best interests.64 And a hearing on the record is routinely held to facilitate that judicial determina- tion, whether the parents are submitting an agreed-upon parent- ing plan for approval65 or have contested the issues of custody and parenting time such that a trial is necessary. [9] We conclude that a blanket rule disfavoring joint cus- tody is inconsistent with the Parenting Act and unnecessarily 59 See § 43-2923(3). 60 See § 43-2923(4). 61 §§ 43-2923(6) and 43-2935(1). 62 See, also, State ex rel. Amanda M. v. Justin T., 279 Neb. 273, 280, 777 N.W.2d 565, 571 (2010) (in paternity case, it is preferable to make express finding that order of joint custody is in best interests of child, but it is “not error under the Parenting Act in a paternity case to fail to make a specific finding of best interests”). 63 See § 43-2924. 64 See §§ 43-2921, 43-2923(4) and (6), and 43-2935. See, also, Dooling, supra note 30. 65 See §§ 43-2923(4) and 43-2935. - 955 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 constrains the discretion of trial judges in some of the most important and difficult decisions they are called upon to make. To ensure that custody and parenting time determina- tions are focused on the best interests of the child, trial judges must be able to base their determinations on actual, not pre- sumed, facts. [10] Because a blanket rule disfavoring joint custody limits judicial discretion and may constrain the best interests of the child analysis required by the Parenting Act, we now disap- prove of the Trimble rule and hold that joint custody is nei- ther favored nor disfavored under Nebraska law.66 In fact, we emphasize that no custody or parenting time arrangement is either favored or disfavored as a matter of law, and we disap- prove of prior cases suggesting otherwise. Our holding today necessarily calls into question some of our reasoning in other cases, to the extent such reasoning was premised on the rule disfavoring joint custody.67 But today’s holding does not alter the fact that whether parents come to court having agreed to a joint custody arrangement, or dis- puting the issues of custody and parenting time, the court is required to independently determine that any parenting plan being ordered is in the child’s best interests and must reject or modify parenting plans that are not in the child’s best inter- ests or which do not meet the requirements of the Parenting Act.68 And today’s holding does not change in any respect the various factors courts should consider when deciding what sort of custody and parenting time arrangement is in a child’s best interests;69 it merely eliminates the need to also consider a blanket rule premised on generalized concerns of parental 66 See Trimble, supra note 3. 67 See, e.g., State ex rel. Amanda M., supra note 62 (noting that factual inquiry for awarding joint physical custody is substantially different from that required for making sole custody determination); Zahl, supra note 3. See, also, Aguilar, supra note 3; Hill, supra note 17. 68 See §§ 43-2921, 43-2923(4) and (6), and 43-2935. 69 See §§ 42-364(2), 43-2921, and 43-2923. - 956 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 maturity, manipulative behavior by the child, and perpetuat- ing turmoil and instability. Of course when such concerns are supported by the evidence, they will still be factors for the court to consider, along with all the other factors bearing on the child’s best interests. We discuss those factors next. 6. Equal Parenting Time Was Not A buse of Discretion We turn now to the primary question on further review: whether the district court abused its discretion in creating a parenting plan that gave Mandy and Jeffery nearly equal parenting time, effectively imposing a joint physical custody arrangement. We address that question in light of the evidence adduced regarding Kaaden’s best interests and disregarding our prior case law to the extent it disfavored joint physi- cal custody. (a) Best Interests [11] When determining the best interests of the child in deciding custody, a court must consider, at a minimum, (1) the relationship of the minor child to each parent prior to the commencement of the action; (2) the desires and wishes of a sufficiently mature child, if based on sound reasoning; (3) the general health, welfare, and social behavior of the child; (4) credible evidence of abuse inflicted on any fam- ily or household member; and (5) credible evidence of child abuse or neglect or domestic intimate partner abuse.70 In this case, the trial court analyzed the evidence in light of each of these factors. [12] The Parenting Act also provides that the best inter- ests of a child require a parenting plan that provides for a child’s safety, emotional growth, health, stability, physical care, and regular school attendance71 and which promotes a child’s 70 § 43-2923(6). See, also, Gress v. Gress, 271 Neb. 122, 710 N.W.2d 318 (2006) (reciting rule before amendments to § 43-2923(6)). 71 § 43-2923(1). - 957 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 continued contact with his or her families and parents who have shown the ability to act in the child’s best interests.72 [13] In addition to considering these statutory factors, our case law instructs that when making determinations as to the allocation of parenting time that is in a child’s best interests, a trial court should also consider the parties’ ability to commu- nicate on issues such as transportation, homework, discipline, medical and dental appointments, and extracurricular activi- ties.73 Other relevant considerations include stability in the child’s routine, minimalization of contact and conflict between the parents, and the general nature and health of the individual child.74 The fact that one parent might interfere with the other’s relationship with the child is also a factor to consider, but is not a determinative factor.75 By reciting these factors, we do not suggest that each will be relevant in every case; nor do we imply that a court is prohib- ited from considering other factors not mentioned. No single factor is determinative, and different factors may weigh more heavily in the court’s analysis depending on the evidence pre- sented in each case. The one constant is that “[i]n any proceed- ing involving a child, the best interests of the child shall be the standard by which the court adjudicates and establishes . . . any custody, parenting time, visitation, or other access determina- tions as well as resolution of conflicts affecting each child.”76 (b) Kaaden’s Best Interests Here, the district court, after observing the parties and considering the evidence in light of the factors set out above, 72 § 43-2923(3). 73 See, generally, Coffey v. Coffey, 11 Neb. App. 788, 661 N.W.2d 327 (2003). 74 See State on behalf of Maddox S. v. Matthew E., 23 Neb. App. 500, 873 N.W.2d 208 (2016). 75 Kamal v. Imroz, 277 Neb. 116, 759 N.W.2d 914 (2009); Maska v. Maska, 274 Neb. 629, 742 N.W.2d 492 (2007). 76 § 43-2921. - 958 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 expressly found that an alternating week-on-week-off parent- ing time schedule was in Kaaden’s best interests. This was the parenting time schedule recommended by Kaaden’s counselor, and it is consistent with the court’s express factual findings that both parents are fit and provide a safe and appropriate home environment for Kaaden. Moreover, nearly equal parenting time furthered the court’s stated goal of allowing Kaaden to “enjoy the full benefits of having both parents involved in his life to the greatest degree possible.” In arguing that the award of nearly equal parenting time was an abuse of discretion, Jeffery focuses almost exclusively on evidence of Mandy’s animosity toward him and their dif- ficulty communicating. In our de novo review, we neither ignore nor minimize evidence that the parties have difficulty communicating effectively regarding Kaaden’s welfare, or that Mandy has significant unresolved anger toward Jeffery and actively interfered with his parenting time while the case was pending before the district court. But when all of the evidence is considered in light of Kaaden’s best interests, we cannot find the parenting time awarded here was an abuse of discretion. The trial court was appropriately concerned about Mandy’s interference with Jeffery’s parenting time and her unresolved anger toward him, and it addressed those concerns by award- ing Jeffery sole legal custody. This minimized the need for the parties to confer regularly because Jeffery has the sole author- ity and responsibility to make fundamental decisions regarding Kaaden’s welfare, including choices regarding his education and health. The trial court also explained that placing primary legal custody with Jeffery was the best way to ensure compli- ance with the parenting plan. And despite the tense relationship between Mandy and Jeffery, the record fully supports the trial court’s findings that both Mandy and Jeffery are fit and proper parents who love Kaaden and that both provide him safe and stable homes. The evidence shows both parents have developed a nurturing, - 959 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 positive bond with Kaaden, and it fully supports the trial court’s conclusion that it is in Kaaden’s best interests to have both parents involved in his life to the greatest degree possible. The trial court’s alternating week-on-week-off parenting schedule served to maximize Kaaden’s time with both parents and was directly supported by the testimony of his treating counselor. At the same time, the parenting schedule minimized the need for direct interaction between the parents by limiting exchanges of Kaaden to one time per week at a neutral site. An abuse of discretion occurs when a trial court bases its decision on reasons that are untenable or unreasonable or if its action is clearly against justice or conscience, reason, and evi- dence.77 Here, the trial court made detailed and specific factual findings which were fully supported by the record, and it pro- vided a carefully reasoned explanation for why it considered the custody and parenting time arrangement to be in Kaaden’s best interests. The trial court’s goal was not to find a custody and parent- ing time schedule the parents thought was fair, but to find one that was actually in Kaaden’s best interests. That required the court to create a parenting plan for a child who has a positive and nurturing relationship with both his parents, but whose parents do not have a good relationship with each other. On this record, we find no abuse of discretion in developing a par- enting plan that gave Jeffery sole legal custody and effectively imposed a joint physical custody arrangement with a week-on- week-off parenting time schedule. 7. Nonreimbursed Medical Expenses [14] The Nebraska Child Support Guidelines require child support orders to address how the parents will provide for the child’s health insurance.78 Here, Jeffery was ordered to pro- vide health insurance for Kaaden, and no party challenges that on appeal. 77 Randy S. v. Nicolette G., 302 Neb. 465, 924 N.W.2d 48 (2019). 78 § 4-215. - 960 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 The district court also ordered Jeffery to pay the first $480 of Kaaden’s nonreimbursed reasonable and necessary health care expenses per year, and it ordered Mandy to pay 50 per- cent of such expenses in excess of $480. We understand this language to have effectively allocated responsibility for non- reimbursed health care expenses equally between Mandy and Jeffery. No party contends otherwise, and no party challenges the court’s allocation of expenses in excess of $480. Instead, the parties focus on whether the trial court erred in ordering Jeffery to pay the first $480 of Kaaden’s nonreimbursed health care expenses. We limit our analysis accordingly. Before the Court of Appeals, Jeffery argued it was error to order him to pay the first $480 of nonreimbursed health care expenses. The Court of Appeals agreed, reasoning that the first $480 of nonreimbursed health care expenses was “subsumed within the amount of child support that is ordered.”79 The Court of Appeals thus reversed that portion of the decree. On further review, Mandy argues the Court of Appeals improperly reversed on this issue. We conclude the Court of Appeals cor- rectly interpreted the child support guidelines. [15] Nonreimbursed health care expenses are governed by § 4-215(B) of the child support guidelines, which states, in part, “Children’s health care expenses are specifically included in the guidelines amount of up to $480 per child per year.” As we have explained, “the guidelines estimate $480 as an ordi- nary amount of such nonreimbursed medical expenses, and that figure is then subsumed within the amount of child support that is ordered. Any nonreimbursed expenses exceeding $480 are [then] prorated between the parties.”80 The guidelines do not require the trial court to expressly identify any party as being responsible for the first $480 of nonreimbursed health care expenses, but they do require a 79 State on behalf of Kaaden S., supra note 1, 26 Neb. App. at 434, 920 N.W.2d at 50. 80 State on behalf of Martinez, supra note 12, 281 Neb. at 552, 797 N.W.2d at 222. - 961 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 court to allocate nonreimbursed health care expenses in excess of $480 per year “to the obligor parent as determined by the court.”81 Such allocation “shall not exceed the proportion of the obligor’s parental contribution (worksheet 1, line 6).”82 The guidelines’ reference to an “obligor” refers to the party ordered to pay child support. We therefore agree with the Court of Appeals that under the child support guidelines, the trial court erred in making Jeffery, who is the obligor under its child support calculation, responsi- ble for paying the first $480 of Kaaden’s nonreimbursed health care expenses, when such amounts are already subsumed in the monthly child support payment. The trial court may have had a sound reason for wanting Jeffery to pay such costs, but no explanation was provided in the decree, so we have no basis upon which to review a deviation from the guidelines.83 We affirm the Court of Appeals’ reversal of that portion of the decree requiring Jeffery to pay the first $480 of Kaaden’s non- reimbursed health care costs. 8. Child Support Because the Court of Appeals found the parenting time schedule was an abuse of discretion and remanded the matter to reduce Mandy’s parenting time, it also concluded the trial court erred in using worksheet 3, the joint custody worksheet, to calculate child support. It thus reversed the child support award and remanded the matter for recalculation “using the appropriate worksheet.”84 Mandy assigns this as error. She argues the trial court’s use of worksheet 3 to calculate support was appropriate given the 81 § 4-215(B). 82 Id. 83 See, generally, Neb. Ct. R. § 4-203 (rev. 2011) (child support guidelines shall be applied as rebuttable presumption, and deviations should be supported by specific findings). 84 State on behalf of Kaaden S., supra note 1, 26 Neb. App. at 433, 920 N.W.2d at 50. - 962 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 amount of parenting time she was awarded,85 and she seeks affirmance of the child support as ordered by the district court. No party challenges any other aspect of the child support award, so we confine our analysis to whether it was error to use worksheet 3. [16] Child support payments should generally be set accord- ing to the child support guidelines.86 Section 4-212 of the guidelines explains when, and how, worksheet 3 is to be utilized: When a specific provision for joint physical custody is ordered and each party’s parenting time exceeds 142 days per year, it is a rebuttable presumption that support shall be calculated using worksheet 3. When a specific provi- sion for joint physical custody is ordered and one party’s parenting time is 109 to 142 days per year, the use of worksheet 3 to calculate support is at the discretion of the court. . . . For purposes of these guidelines, a “day” shall be generally defined as including an overnight period. Here, the award of nearly equal parenting time effectively created a joint physical custody arrangement, and we have modified the decree and parenting plan to so describe it. Moreover, under the parenting plan, Mandy’s parenting time far exceeds the rebuttable presumption of 142 overnights per year referenced in § 4-212, and Jeffery has presented no evi- dence or argument that would rebut the presumptive use of worksheet 3. As such, we find no abuse of discretion in the trial court’s decision to use worksheet 3 to calculate child sup- port. We reverse the Court of Appeals’ holding to the contrary, and remand the matter with directions to affirm the district court’s child support award. V. CONCLUSION For the foregoing reasons, we modify the language of the decree and the parenting plan to reflect an award of joint 85 See Neb. Ct. R. § 4-212 (rev. 2011). 86 See Hotz v. Hotz, 301 Neb. 102, 917 N.W.2d 467 (2018). - 963 - Nebraska Supreme Court A dvance Sheets 303 Nebraska R eports STATE ON BEHALF OF KAADEN S. v. JEFFERY T. Cite as 303 Neb. 933 physical custody. We find no abuse of discretion in the custody and parenting time arrangement ordered by the district court, and we reverse the Court of Appeals’ decision to the contrary and remand the matter with directions to affirm that award as modified. We find no abuse of discretion in using worksheet 3 to calculate child support, and we reverse that aspect of the Court of Appeals’ decision as well and remand the matter with directions to affirm the child support award. In all other respects, we affirm the decision of the Court of Appeals. A ffirmed in part as modified, and in part reversed and remanded with directions.

{ "pile_set_name": "FreeLaw" }

Many organizations wish to gain better control over their print environment because printing is a significant source of expenses, and one that is often difficult to manage. These costs come from a variety of printing practices, including the use of inkjets (which are relatively cheap to buy, but relatively expensive to run), inappropriate use of color (e.g., for draft documents, emails, personal files, etc.), and inappropriate use of devices (e.g., large runs sent to small workgroup printers rather than high volume reprographics centers). A number of products in the market allow organizations to track the type of printing that occurs (such as Lexmark Markvision™, HP WebJetAdmin, Xerox® CenterWare™ Web and Pharos Blueprint®). Using this information, organizations can begin to phase out devices with a poor fit with respect to system usage requirements. However, changing user behavior is difficult when users are able to directly access printers on the network. Some existing approaches (e.g., Pharos® Uniprint®, EnvisionWare® LP:TOne, Equitrac® XYZ) can prevent users from accessing printers directly, and instead force them to print via these products' print servers—enabling the system administrator to set appropriate print policies. All of these products have a potential disadvantage, namely that they require changes to the organization print environment, such as through installing components on the workstation, changing the print destination, installing software on the print server, and/or changing the print server queue configuration. Such products may also require the customer to make changes to the printer itself to remove the capability of users to print directly thereto.

{ "pile_set_name": "USPTO Backgrounds" }

HT Motorsports HT Motorsports was an American truck racing team from Martinsville, Virginia, owned by trucking company owner Jim Harris. It fielded entries for the nine years in the Camping World Truck Series before suspending operations early in 2010. Truck No. 24 history This team debuted at a test session at Homestead-Miami Speedway as the No. 92 with Terry Cook driving. He started fifteenth and finished 20th. The No. 24 originally was intended to be the No. 11 Toyota for Red Horse Racing but driver David Starr and Zachry Holdings parted ways with the team in December. This team became the No. 24 for 2009 and Starr had fourteen top-ten finishes. Zachry and Starr left the team after the 2009 season for Randy Moss Motorsports. Truck No. 25 history HT Motorsports made its NASCAR debut at New Hampshire International Speedway in 2001 as the No. 92 Learnframe Dodge. It made four starts that season with Stacy Compton and finished in the top ten in each race. The team then ran at Martinsville Speedway in 2002 as the No. 17 Duck Head Footwear Dodge Ram driven by Darrell Waltrip. He qualified eighteenth but finished thirty-eighth. Waltrip returned at Indianapolis Raceway Park with Tide sponsorship, and finished sixth. Stacy Compton would drive three additional races that season, posting a best finish of eighth at Richmond. In 2003, HT switched to the No. 59 and hired Robert Pressley to drive. Driving with associate sponsorship from Melling Engine Parts, Pressley finished in the top-five four times and finished thirteenth in points. Randy LaJoie ran the first two races of 2004, followed by rookie Mark McFarland. McFarland finished sixth at Mansfield Motorsports Speedway before being cycled out by LaJoie, who had an eighth-place finish at Gateway. Andy Houston drove for three races, but did not finish higher than 14th. Sammy Sanders, Bobby Hamilton, Jr., and Scott Lynch finished out the year in the 59. Pressley returned to HT in 2005, but had only three top-ten finishes and finished 20th in the standings. He was released and replaced by Mike Wallace at the beginning of 2006, but wrecked out of the two races in which he drove for the team. Steve Park became the team's new driver, as the team switched to Ford. Despite a tenth-place finish at Mansfield, he was released after ten races and replaced by Chad Chaffin. After a slow start, the team switched to Toyota and Chaffin finished eighth at Talladega Superspeedway. Terry Cook was named the driver of the 59 for 2007, and had two top-tens and finished fourteenth in points. He was released at the end of the season for Whelen Modified driver Donny Lia, who raced the last race of the season. For 2008, Ted Musgrave will move to the No. 59 team, bringing along his ASE sponsorship. In August 2008 ASE announced they will be leaving NASCAR. After 18 races in season, and a wreck in the 1st practice at Las Vegas Motor Speedway, Musgrave & HT Motorsports parted ways. Stacy Compton replaced him later in the day. Joey Logano made his truck series debut at Talladega starting sixth but crashing early. Terry Cook, recently released from Wyler Racing, drove the No. 59 for the rest of the '08 season. The team switched to the No. 25 for 2009 with Cook returning. He had nine top-tens but was replaced in the final two races by Mike Bliss. References External links Official Website Category:American auto racing teams Category:Companies based in Virginia Category:Defunct NASCAR teams Category:Auto racing teams established in 2001 Category:Sports clubs disestablished in 2010

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package cn.neural.common; import lombok.Getter; import java.util.concurrent.*; /** * A specialized <em>semaphore</em> implementation that provides a number of permits in a given time frame. * <p> * TimedSemaphore sem = new TimedSemaphore(1, TimeUnit.SECOND, 10); * * @author lry */ @Getter public class TimedSemaphore { /** * Constant for a value representing no limit. * If the limit is set to a value less or equal this constant, * the {@code TimedSemaphore} will be effectively switched off. */ public static final int NO_LIMIT = 0; /** * Constant for the thread pool size for the executor. */ private static final int THREAD_POOL_SIZE = 1; /** * The executor service for managing the timer thread. */ private final ScheduledExecutorService executorService; /** * Stores the period for this timed semaphore. */ private final long period; private final TimeUnit unit; /** * A flag whether the executor service was created by this object. */ private final boolean ownExecutor; /** * A future object representing the timer task. */ private ScheduledFuture<?> task; /** * Stores the total number of invocations of the acquire() method. */ private long totalAcquireCount; /** * The counter for the periods. This counter is increased every time a period ends. */ private long periodCount; private int limit; /** * The current counter. */ private int acquireCount; /** * The number of invocations of acquire() in the last period. */ private int lastCallsPerPeriod; /** * A flag whether shutdown() was called. */ private boolean shutdown; public TimedSemaphore(long timePeriod, TimeUnit timeUnit, int limit) { this(null, timePeriod, timeUnit, limit); } public TimedSemaphore(ScheduledExecutorService service, long timePeriod, TimeUnit timeUnit, int limit) { if (timePeriod < 1) { throw new IllegalArgumentException("Time period must be greater than 0!"); } this.period = timePeriod; this.unit = timeUnit; if (service != null) { this.executorService = service; this.ownExecutor = false; } else { ScheduledThreadPoolExecutor timerExecutor = new ScheduledThreadPoolExecutor(THREAD_POOL_SIZE, r -> { Thread t = new Thread(r); t.setDaemon(true); t.setName("MANAGING_TIMER_THREAD"); return t; }); timerExecutor.setContinueExistingPeriodicTasksAfterShutdownPolicy(false); timerExecutor.setExecuteExistingDelayedTasksAfterShutdownPolicy(false); this.executorService = timerExecutor; this.ownExecutor = true; } setLimit(limit); } /** * Returns the limit enforced by this semaphore. The limit determines how * many invocations of {@link #acquire()} are allowed within the monitored period. * * @return the limit */ public final synchronized int getLimit() { return limit; } /** * Sets the limit. This is the number of times the {@link #acquire()} method * can be called within the time period specified. If this limit is reached, * further invocations of {@link #acquire()} will block. Setting the limit * to a value <= {@link #NO_LIMIT} will cause the limit to be disabled, * i.e. an arbitrary number of{@link #acquire()} invocations is allowed in the time period. * * @param limit the limit */ public final synchronized void setLimit(final int limit) { this.limit = limit; } /** * Initializes a shutdown. After that the object cannot be used any more. * This method can be invoked an arbitrary number of times. All invocations * after the first one do not have any effect. */ public synchronized void shutdown() { if (!shutdown) { if (ownExecutor) { // if the executor was created by this instance, it has to be shutdown getExecutorService().shutdownNow(); } if (task != null) { task.cancel(false); } shutdown = true; } } /** * Tests whether the {@link #shutdown()} method has been called on this object. * <p> * If this method returns <b>true</b>, this instance cannot be used any longer. * * @return a flag whether a shutdown has been performed */ public synchronized boolean isShutdown() { return shutdown; } /** * Acquires a permit from this semaphore. This method will block if * the limit for the current period has already been reached. If * {@link #shutdown()} has already been invoked, calling this method will * cause an exception. The very first call of this method starts the timer * task which monitors the time period set for this {@code TimedSemaphore}. * From now on the semaphore is active. * * @throws InterruptedException if the thread gets interrupted * @throws IllegalStateException if this semaphore is already shut down */ public synchronized void acquire() throws InterruptedException { prepareAcquire(); boolean canPass; do { canPass = acquirePermit(); if (!canPass) { wait(); } } while (!canPass); } /** * Tries to acquire a permit from this semaphore. If the limit of this semaphore has * not yet been reached, a permit is acquired, and this method returns * <strong>true</strong>. Otherwise, this method returns immediately with the result * <strong>false</strong>. * * @return <strong>true</strong> if a permit could be acquired; <strong>false</strong> otherwise * @throws IllegalStateException if this semaphore is already shut down */ public synchronized boolean tryAcquire() { prepareAcquire(); return acquirePermit(); } /** * Returns the number of (successful) acquire invocations during the last * period. This is the number of times the {@link #acquire()} method was * called without blocking. This can be useful for testing or debugging * purposes or to determine a meaningful threshold value. If a limit is set, * the value returned by this method won't be greater than this limit. * * @return the number of non-blocking invocations of the {@link #acquire()} method */ public synchronized int getLastAcquiresPerPeriod() { return lastCallsPerPeriod; } /** * Returns the number of invocations of the {@link #acquire()} method for * the current period. This may be useful for testing or debugging purposes. * * @return the current number of {@link #acquire()} invocations */ public synchronized int getAcquireCount() { return acquireCount; } /** * Returns the number of calls to the {@link #acquire()} method that can * still be performed in the current period without blocking. This method * can give an indication whether it is safe to call the {@link #acquire()} * method without risking to be suspended. However, there is no guarantee * that a subsequent call to {@link #acquire()} actually is not-blocking * because in the mean time other threads may have invoked the semaphore. * * @return the current number of available {@link #acquire()} calls in the * current period */ public synchronized int getAvailablePermits() { return getLimit() - getAcquireCount(); } /** * Returns the average number of successful (i.e. non-blocking) * {@link #acquire()} invocations for the entire life-time of this {@code * TimedSemaphore}. This method can be used for instance for statistical * calculations. * * @return the average number of {@link #acquire()} invocations per time * unit */ public synchronized double getAverageCallsPerPeriod() { return periodCount == 0 ? 0 : (double) totalAcquireCount / (double) periodCount; } /** * Starts the timer. This method is called when {@link #acquire()} is called * for the first time. It schedules a task to be executed at fixed rate to * monitor the time period specified. * * @return a future object representing the task scheduled */ protected ScheduledFuture<?> startTimer() { return getExecutorService().scheduleAtFixedRate(this::endOfPeriod, getPeriod(), getPeriod(), getUnit()); } /** * The current time period is finished. This method is called by the timer * used internally to monitor the time period. It resets the counter and * releases the threads waiting for this barrier. */ private synchronized void endOfPeriod() { lastCallsPerPeriod = acquireCount; totalAcquireCount += acquireCount; periodCount++; acquireCount = 0; notifyAll(); } /** * Prepares an acquire operation. * <p> * Checks for the current state and starts the internal timer if necessary. */ private void prepareAcquire() { if (isShutdown()) { throw new IllegalStateException("TimedSemaphore is shut down!"); } if (task == null) { task = startTimer(); } } /** * Internal helper method for acquiring a permit. * * @return a flag whether a permit could be acquired */ private boolean acquirePermit() { if (getLimit() <= NO_LIMIT || acquireCount < getLimit()) { acquireCount++; return true; } return false; } }

{ "pile_set_name": "Github" }

For an amazing selection of original sculptures, statues, prints and DVDs be sure to check out ShiflettBrothers.com. On September 6, 2011, Fabulous Films, with distribution from Shout! Factory, will unleash AIRWOLF: The Movie on DVD for the first time in the U.S. and Canada. Written and directed by Donald P. Bellisario and starring Jan-Michael Vincent, Ernest Borgnine and Alex Cord, AIRWOLF: The Movie boasts full-throttle action, daring high-speed aerial stunts and captivating storylines mixed with international espionage and intrigue. A futuristic high action adventure about a billion dollar helicopter (named Airwolf) equipped with a twin-turbine drum rotor system capable of propelling it to 300 knots, plus 14 firepower options. When the helicopter is purloined by Libyan mercenaries, project director of the CIA (Alex Cord) enlists the help of Vietnam veteran Stringfellow Hawke (Jan-Michael Vincent) and his father’s best friend Dominic Santini (Ernest Borgnine) in an attempt to recover it. The deadly mission takes them to the Middle East where they must battle the enemy to repossess the deadliest aerial weapon ever made.

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[Current prenatal care with reference to state of the art knowledge]. Every physician taking care of pregnant women believes to be well acquainted with the state-of-the-art requirements. However, changes imposed by the new Swiss health insurance legislation (KVG) and by the pressure of Evidence Based Medicine brought these into a new scope. In Switzerland there is no general agreement on optimal pregnancy-care. We propose a care-standard, based on rational and efficient clinical, laboratory and sonographic checks, which allow a timely diagnosis of pregnancy-at-risk. Targeted laboratory investigations as well as the anti-D-immunoprophylaxis, and screening for diabetes mellitus efficiently help to avoid long-term sequelae for mother and child. Screening for toxoplasmosis, HIV, and hepatitis B are compulsory. A vaginal pH below 4.5 prevents premature birth. Diagnosis and treatment of vaginal chlamydial and candida infection are also very important in this respect. The number of sonographies to be performed during pregnancy is a highly political issue, and we have to comply with our dirigistic governmental regulations. However, sonography including search for increased nuchal translucency done early in pregnancy is a key procedure for quality assurance. Supplementation of folic acid started before conception, almost entirely prevents neural tube defects. Hence women need appropriate advice before conception. A new information brochure is available for future parents in Switzerland, and makes all former self-made guidelines unnecessary. UNICEF declared 1998 as the year of safe motherhood. Worldwide still too many women die from pregnancy and delivery. Care for normal pregnancy, and not only for at-risk-pregnancy will therefore continue to make sense.

{ "pile_set_name": "PubMed Abstracts" }

Article content continued Black Friday The symbolism of announcing the drastic measures on a Friday night wasn’t lost on many Venezuelans. In 1983, President Luis Herrera Campins devalued the bolivar for the first time in 22 years after oil prices crashed. The day became to be known locally as “Black Friday.” When in 1989 Venezuela raised gasoline costs, lifted foreign-exchange controls and let the currency plunge, prices soared 21 per cent in one month alone, leading to riots known as the “Caracazo” that killed hundreds and eventually paved the way for Chavez’s rise to power. Military Alliance It’s not clear how the shock measures announced by Maduro will sit with one of his key allies: the military. Top ranking generals have been handed the keys to ministries, the state-run oil company and the lucrative business of food imports. Myriad exchange rates created juicy arbitrage opportunities that enriched many close associates of the state. “Clearly this will hit Maduro’s popularity, but power is being sustained with bullets and not with votes,” Naim said. “As long as the military continues to have access to lucrative businesses it will continue to grant support to the government.” The opposition, a fragmented group of parties whose leaders are either in hiding or in jail, called for protests against the measures Tuesday. Several labour unions also called for a 24-hour national strike. In Caracas this weekend, many small shops were closed while people flocked to supermarkets and gasoline stations to stock up. Online banking services will be suspended for 24 hours starting at 6 p.m. local time in anticipation of the redenomination. Many private companies, already dealing with hyperinflation, years of brain drain, price controls and threats of seizure, now must deal with even faster inflation and mandatory wage hikes. It’s also possible that the exodus of Venezuelans to other countries will increase, even as Ecuador and Peru announced entry restrictions and tensions flared along the border with Brazil. “People are leaving because of a feeling of despair, and the desperation will now increase,” Naim said. Bloomberg.com

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Q: @InitBinder in spring boot not working with @RequestBody If I use @InitBinder without limiting it,it is working fine with @RequestBody to validate my objects. @InitBinder private void initBinder(WebDataBinder binder) { binder.setValidator(validator); } @RequestMapping(method=RequestMethod.POST) public CustomerQuickRegisterEntity saveNewCustomer(@Valid @RequestBody CustomerQuickRegisterEntity customerEntity,BindingResult result) { if(result.hasErrors()) { return new CustomerQuickRegisterEntity(); } return customerQuickRegisterRepository.save(customerEntity); } But problem is that when i limit it to just one object by doing it as @InitBinder("customerEntity") it is not validating the object. So I have searched through stackoverflow and found that @InitBinding only works with objects annotated with @ModelAttribute. Then my question is that it is working fine with @RequestBody when I use it as @InitBinder but does not work well when I use it as @InitBinder("customerEntity") ...why is it so? Is there any other way to validate Objects(Not properties of object Individually) associated with @RequestBody A: This is an old question, but I've managed to get the @InitBinder annotation to bind my custom Validator to a @Valid @RequestBody parameter like this: @InitBinder private void bindMyCustomValidator(WebDataBinder binder) { if ("entityList".equals(binder.getObjectName())) { binder.addValidators(new MyCustomValidator()); } } If you try to filter the bound argument by setting the value of the annotation, then it won't work for a @RequestBody argument. So here I check the object name instead. My method parameter is actually called entities, but Spring had decided to call it entityList. I had to debug it to discover this. A: From the docs, Default is to apply to all command/form attributes and all request parameters processed by the annotated handler class. Specifying model attribute names or request parameter names here restricts the init-binder method to those specific attributes/parameters, with different init-binder methods typically applying to different groups of attributes or parameters. Please have a look here

{ "pile_set_name": "StackExchange" }

Distinguishing medullary carcinoma of the breast from high-grade hormone receptor-negative invasive ductal carcinoma: an immunohistochemical approach. Medullary carcinomas (MCs) represent a rare breast cancer subtype associated with a rather favourable prognosis compared with invasive ductal carcinomas (IDCs). Due to histopathological overlap, MCs are frequently misclassified as high-grade IDCs, potentially leading to overtreatment of MCs. Our aim was to establish novel diagnostic markers distinguishing MCs from hormone receptor-negative high-grade IDCs. Sixty-one MCs and 133 hormone receptor-negative IDCs were analysed in a comparative immunohistochemical study. Applied markers included a comprehensive panel of cytokeratins (CKs), vimentin, smooth muscle actin (SMA), p63, p53, cell adhesion molecules [N-CAM (CD56), syndecan-1 (CD138), E-cadherin and P-cadherin] and development associated transcription factors (AP-2 alpha, AP-2 gamma). A significantly higher proportion of IDCs displayed increased expression of CK7, AP-2 alpha and HER2 in contrast to MCs (CK7: 91% of IDCs versus 77% of MCs; AP-2 alpha: 77% versus 57%; and HER2: 26% versus 7%, each P < 0.01). Vice versa, MCs were slightly more frequently positive for SMA and vimentin (P > 0.05). Hormone receptor-negative high-grade IDCs are significantly associated with luminal differentiation, Her2 and AP-2 alpha overexpression, whereas MCs tend to display myoepithelial features. Markers analysed in this study are of diagnostic value regarding the differential diagnosis of MCs.

{ "pile_set_name": "PubMed Abstracts" }

The standard way of assigning file permissions on Unix systems is so tied into how people think of Unix that many of us seem to forget that this scheme was expanded many years ago to accomodate more than just file owners, groups, and everyone else. The setfacl (set file access control lists) and getfacl (get file access control list) commands were designed to allow more than the traditional limited assignment of privileges. While not disturing the customary owner-group-other permissions, you could, for example, give another account holder the same permissions as the owner or allow more than one group to have special access while not giving that access to just everyone. Everything comes at some cost, however, and to use the setfacl and getfacl commands, a file system has to be mounted with a special option that allows these commands and the underlying expansion of priviledges to be used. After all, there is overhead associated with keeping track of the extra permissions, so you have to opt in by adding an option to the file system in the /etc/fstab file -- the acl option. If you don't, anyone trying to use these commands will likely be confronted with an "operation not supported" error. You may also have to check whether your kernel provides support for this feature. To mount a file system with the acl option, you will need to use a command like this: # mount -t ext4 -o acl /dev/hdb3 /data In the /etc/fstab, this same operation might look like this: /dev/hdb3 /data ext4 defaults,acl 0 1 Indications that the extended permissions are in use are rather subtle. You'll just see a + sign at the end of the normal permissions field. For example: -rw-r-----+ 1 smitten admins 22088 Oct 26 recipe That little + at the end of -rw-r-----+ tells you that there are more permissions than the rw-r----- permissions string is letting on. And, if you want to know more, you just have to use the getfacl command to display the complete permissions for the file. For a file with only standard permissions, you will see something like this: $ getfacl beerlist # file: beerlist # owner: smitten # group: admins user::rw- group::r-- other::--- This shows us what we normally see in a long listing, but in a different format. For a file with the extended permissions, on the other hand, the getfacl command might show you any additional permissions that have been set -- like this: $ getfacl beerlist # file: beerlist # owner: smitten # group: admins user::rw- user:tsmiley:rw- group::r-- mask::rw- other::--- Notice that we now see another user (tsmiley) with read and write permissions and a new field -- the "mask" field that sets default permissions for the file. You can set extended permissions using the setfacl command. Here are some examples where we give a user read, write and execute or add write permission. setfacl -m u:tsmiley:rwx /data/example setfacl -m u:tsmiley:+w /data/example The -m stands for modify. The "u" in u: stands for user. You can assign permissions to groups as well as to individuals. You would assign a group permissions with a "g" as in the examples shown below. setfacl -m g:devt:rwx /data/testcase setfacl -R -m g:devt:+x testcases/ setfacl -m d:g:admins:rwx /data/scripts In the third line in this example, the d: before the g: makes the new settings (rwx) the default for this directory. When files or direcxtories are created under the /data/scripts directory, the admins group will have rwx permission to them as well. After setting a default, you can expect to see these values when you use the getfacl command in the form of an additional line that looks like this: default:group::rwx One of the other complexities that you are likely to run into is the idea of the effective mask setting. If the mask is more restrictive than the permissions that you grant, the mask will take precedence. In the example below, the mask is r-- and reduces the privileges given to the groups to r--. $ getfacl /data/jumping.jar # file: /data/jumping.jar # owner: dbender # group: users user::rw- group::rwx #effective:r-- group:devt:rwx #effective:r-- mask::r-- other::r-- To remove extended permissions for a file or folder, you can use one of these commands. Remove all ACLs from a file: setfacl -b /data/example Remove the default ACL: setfacl -k testcases The mask setting is interesting. It will be set up whenever permissions beyond those of owner, group, and other are used. As you'd read in the man page for the setfacl command, the mask is the union of all permissions from the owning group, named user and group settings. It can limit the permissions that are available but you can change the mask with a command like this: $ setfacl -m mask:rw- /data/example Note that mask can be spelled (mask:) out or abbreviated to m (m:). Generally, it will be set to whatever permissions are intended for the expected collections of users and groups. You can also override this setting when you assign permissions by requesting that no mask be used with the -n or --no-mask setting. The traditional Unix permissions are easy to think about, but can be seriously confining when you need more flexibility in defining what various users or groups on your servers should be able to do. The newer ACL commands give you a lot more leeway in determining who gets what permissions. You just have to work a little harder to be sure they're right.

{ "pile_set_name": "OpenWebText2" }

If you would like to get rich in your line of work, it would be best to be an entrepreneur or a salesperson who consistently goes beyond the targets set for you. To dabble in the world of e-sports, well, only a select few will be able to make a good living out of it, and afterwards as well when they have retired. Still, if you would like to give those restless thumbs and fingers of yours a go, how about checking out the Mortal Kombat eSports tournament that boasts of a $500,000 prize pool? Advertising Half a million in cold, hard cash, now that is certainly pretty difficult to turn down, don’t you think so? Warner Bros. would be the one behind this prize money as they launch the massive Mortal Kombat X eSports program later next month April, with the prize pot being a mouth watering $500,000. This particular venture will also include the third season of ESL Mortal Kombat X Pro League, which will see the cream of the crop from around the world go up against one another this April 3rd. As for the top sixteen players, they will then stand a chance to compete in front of a live audience when June 12 rolls around, while the final eight finalists will be able to duke it out for a slice of the $200,000 from the prize pot. This is because Warner Bros. will host tournaments throughout North America, Europe, the Russian Commonwealth and Latin America at the same time. Filed in . Read more about Mortal Kombat. Source: eventhubs

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Accidental swallowing of a gold cast crown during orthodontic tooth separation. Accidental swallowing of a gold cast crown that became loose after separation with brass wire for orthodontic band placement, is reported. The intervention to remove the ingested crown subsequent to its location in the GI tract on immediate radiographic examination of chest and abdomen included endoscopic examination. Since the crown had past distal to the duodenum it was decided to keep a watch on its movement by daily radiographic examination. The crown passed with excreta on the 5th day uneventfully. Literature on ingestion of foreign bodies of dental origin is reviewed. Possible emergencies and their management is discussed.

{ "pile_set_name": "PubMed Abstracts" }

Manny Pacquiao Gabriel Bouys / AFP / Getty Manny Pacquiao was considered a savior by two groups of people this year: Filipinos and boxing aficionados. For his countrymen, the diminutive (5 ft. 6 in. and change) pugilist once again proved that their archipelago could produce more than tales of violence, poverty and natural disaster that there was some undefined quality that could produce a fighter of such speed, resiliency and charisma as to be a living legend. For boxing fans, Pacquiao defied physics, rising through six weight classes to win seven world titles and galvanizing the sport like no other boxer in years. His two bouts this year were among the most dramatic in the sport: his second-round knockout of Ricky Hatton and his terrifying demolition of the rock-solid Miguel Cotto over 11 rounds. His visceral charm or his bloody attraction will continue into next year with his expected multimillion-dollar, hugely lucrative matchup against Floyd Mayweather Jr., the only fighter remaining who can claim to be his equal.

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Oskar Roehler Oskar Roehler (born 21 January 1959) is a German film director, screenwriter and journalist. He was born in Starnberg as the son of writer Gisela Elsner and the writer Klaus Roehler. Since the mid-1980s he has been working as a screenwriter, for, among others, Niklaus Schilling, Christoph Schlingensief and Mark Schlichter. Since the early 1990s he has also been working as a film director. For his film No Place to Go he won the Deutscher Filmpreis. His 2010 film Jew Suss: Rise and Fall was nominated for the Golden Bear at the 60th Berlin International Film Festival. Partial filmography Gentleman (1995) Silvester Countdown (1997) Gierig (1999) No Place to Go (2000) Suck My Dick (2001) Beloved Sister (2002) Angst (2003) Agnes and His Brothers (2004) The Elementary Particles (2006) Lulu and Jimi (2009) Jew Suss: Rise and Fall (2010) Sources of Life (2013) Punk Berlin 1982 (2015) Subs (2017) References External links Category:1959 births Category:German film directors Category:German-language film directors Category:Living people Category:People from Starnberg

{ "pile_set_name": "Wikipedia (en)" }

Whitman MS in Entrepreneurship Experience The 30-credit-hour Whitman MS in Entrepreneurship program provides a rigorous immersion into the nature of entrepreneurship and the entrepreneurial process. Combining core content with a strong commitment to experiential learning, the program is targeted to students with a passion for entrepreneurship in start-ups and larger, more established companies, and in the for-profit, non-profit, and public sector contexts. Established in 1992, Whitman's program in Entrepreneurship and Emerging Enterprises (EEE) is today one of the most comprehensive and respected in the country. Syracuse University has adopted a campus-wide initiative on entrepreneurship, where entrepreneurship is being integrated into multiple schools and courses across campus. The EEE program has earned recognition as a top-tier program in ratings by U.S. News & World Report, Bloomberg BusinessWeek, and Entrepreneur magazine/Princeton Review.

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Enhancement of association rates by nonspecific binding to DNA and cell membranes. A comprehensive analytic theory is developed for the kinetics of reversible association with specific sites on DNA and receptors on cell membranes in the presence of nonspecific binding to the target surfaces. Nonspecific binding is treated as a short-range attractive potential, which is more fundamental and realistic than the surface sliding model. The presence of a surface potential around the target enhances the rate of specific association and for reversible reactions leads to deviations from single exponential relaxation.

{ "pile_set_name": "PubMed Abstracts" }

Q: How to split a page in six equally sized sectors? I'd like to split an A4 page into six equally sized sectors. I want that page to be in landscape. Each sector has a body of text and a caption. I don't really have an idea where to start. I know I can split a page in to columns, but I need like six minipages, all equally arranged on one paper. The only idea I could come up with, is to use a0poster and then size it down for print. I think however, this is overkill; isn't there a better way to do that? I'm preferably using XeLaTeX, if that is of any importance. A: You can use six minipages; I defined a \Block command using a minipage of the desired width and length with two arguments: the text and the caption (make the necessary formatting adjustments). I added some frames just for visualization purposes (and they will produce some overfull boxes); please delete the lines marked with %delete: \documentclass{article} \usepackage[landscape]{geometry} \newcommand\Block[2]{% \setlength\fboxsep{0pt}\setlength\fboxrule{0.1pt}% delete \fbox{% delete \begin{minipage}[c][.5\textheight][t]{0.333333\textwidth} #1\par #2 \end{minipage}% }% delete } \begin{document} \noindent \Block{text}{caption}% \Block{text}{caption}% \Block{text}{caption}% \par\nointerlineskip\noindent \Block{text}{caption}% \Block{text}{caption}% \Block{text}{caption} \end{document} To meet the requirements in the comment: \documentclass{article} \usepackage[margin=3cm,centering,landscape]{geometry} \newcommand\Block[2]{% \setlength\fboxsep{0pt}\setlength\fboxrule{0.1pt}% delete \fbox{% delete \begin{minipage}[c][\dimexpr.5\textheight-2pt\relax][c]{\dimexpr0.3333333\textwidth-3pt\relax} \centering #1\par #2 \end{minipage}% }% delete } \begin{document} \thispagestyle{empty}% optional: suppress page numbering \noindent \Block{text}{caption}\hfill% \Block{text}{caption}\hfill% \Block{text}{caption}% \vfill \noindent\Block{text}{caption}\hfill% \Block{text}{caption}\hfill% \Block{text}{caption} \end{document} Using some of the options for the geometry package, the text area layout can be modified at will. A: Here's a solution using the pdfpages package. It consists of two steps: First you produce a document with a small paper size, and then you produce another document that combines these small pages onto one A4 landscape page. This is your actual document, where you put all of your text etc. You might have to adapt the margins, page numbers, etc. to your needs. % This file is called sixpages-doc.tex \documentclass{article} \usepackage[paperwidth=9.9cm,paperheight=10.5cm]{geometry} % paperwidth is A4/3, paperheight is A4/2 \usepackage{lipsum}% just for filler text \begin{document} \lipsum[1-6] \end{document} This is the document that puts the six pages on one page: \documentclass{article} \usepackage[landscape,a4paper]{geometry} \usepackage{pdfpages} \begin{document} \includepdf[pages=-,nup=3x2]{sixpages-doc.pdf} % pages=- means all pages % nup "Puts multiple logical pages onto each sheet of paper. The syntax of % this option is: nup=⟨xnup⟩x⟨ynup⟩." (from the manual) % If you want this layout: % 1 3 5 % 2 4 6 % use the option "column". \end{document} This is the output of the second document: A: I know that you want to use minipages. But here is a version using \parbox. You can't have certain things like footnotes here. This answer is given just to complete the list. We ride on Gonzalo's code (thanks @Gonzalo) and modify a bit: \documentclass{article} \usepackage[landscape]{geometry} \newcommand\Block[2]{% \setlength\fboxsep{0pt}\setlength\fboxrule{0.1pt}% delete \fbox{% delete \parbox[c][.5\textheight][t]{0.3\textwidth} {#1\par #2} % }% delete } \begin{document} \noindent \Block{text}{caption}\hfill \Block{text}{caption}\hfill \Block{text}{caption}% \vfill\noindent \Block{text}{caption}\hfill \Block{text}{caption}\hfill \Block{text}{caption} \end{document}

{ "pile_set_name": "StackExchange" }

Von Ronen Steinke, Berlin Das Bundesverteidigungsministerium hat die geplante unehrenhafte Entlassung des Whistleblowers Patrick J. vorerst gestoppt. Das geht aus einem Schreiben des Personalamts der Bundeswehr hervor, das die Süddeutsche Zeitung einsehen konnte. Demnach setze man "den Vollzug" der Entlassung "bis auf Weiteres aus". Der 30 Jahre alte Unteroffizier Patrick J. hatte so viele vertrauliche Hinweise auf rechte Umtriebe abgegeben wie noch kein Bundeswehrsoldat zuvor. In den vergangenen Monaten hatte er auf eigene Initiative ein Dossier mit rechtsradikalen oder vermeintlich rechtsradikalen Äußerungen von mehr als einhundert seiner Kameraden angelegt und dem Geheimdienst der Truppe, dem Militärischen Abschirmdienst (MAD), übergeben. Interne Ermittlungen nur in neun Fällen Nach SZ-Informationen haben nur die wenigsten der Hinweise von Patrick J. bisher bundeswehrinterne Ermittlungen ausgelöst. Viele Vorwürfe waren aus Sicht des MAD zu dünn. In neun Fällen allerdings ist der MAD durch die Mitteilungen von Patrick J. tatsächlich zu Ermittlungen veranlasst worden. Zum Beispiel hatte der Whistleblower dokumentiert, wie sich ein Stabsunteroffizier im Internet mit Rechtsextremisten vernetzte, die das KZ Auschwitz mit Legosteinen nachbauten. Bei einem Oberstabsgefreiten entdeckte er Facebook-Kontakte zu sogenannten Reichsbürgern. Im Netz schrieb dieser Bundeswehrsoldat: "Wir sind eh alle Staatenlos." Das Personalamt der Bundeswehr wollte Patrick J. ursprünglich mit der Begründung entlassen, es fehle ihm an der "charakterlichen Eignung". Zahlreiche seiner Vorwürfe gegen Kameraden seien "übertrieben und haltlos". Auch hätten sich inzwischen Kameraden ihrerseits über Patrick J. beschwert, weshalb er wegen "Missbrauchs der Befehlsbefugnis" zu einer Geldstrafe von 1500 Euro verurteilt worden sei. Patrick J. hat allerdings gegen das Urteil Rechtsmittel eingelegt. Das Bundesverteidigungsministerium, dessen Staatssekretär Gerd Hoofe (CDU) sich in der vergangenen Woche mit Patrick J. getroffen hatte, wollte sich auf SZ-Anfrage nicht zu dem Fall äußern. Hoofe verwies auf den Datenschutz.

{ "pile_set_name": "OpenWebText2" }

Zeta Pavonis Zeta Pavonis, Latinized from ζ Pavonis, is an orange-hued star in the southern constellation Pavo. Its apparent magnitude is 4.01, which is bright enough to be faintly visible to the naked eye. The annual parallax shift of this star is 14.93 mas as seen from Earth, which provides a distance estimate of approximately away from the Sun. It is moving closer to the Sun with a radial velocity of −16.30. Based upon its motion through space, this star appears to be a member of the Hyades Supercluster. This is an evolved K-type giant star with a stellar classification of K0 III, which indicates it has exhausted the supply of hydrogen at its core. The measured angular diameter of this star, after correction for limb darkening, is . At the estimated distance of this star, this yields a physical size of about 19 times the radius of the Sun. The star is radiating 155 times the Sun's luminosity. Zeta Pavonis has a companion, probably optical, of apparent magnitude 12.0 at about 55.6" separation. References Category:K-type giants Category:Hyades Stream Category:Pavo (constellation) Pavonis, Zeta Category:Durchmusterung objects 171759 091792 6982

{ "pile_set_name": "Wikipedia (en)" }

Corynebacterium ulcerans, an emerging human pathogen. While formerly known infections of Corynebacterium ulcerans are rare and mainly associated with contact to infected cattle, C. ulcerans has become an emerging pathogen today. In Western Europe, cases of respiratory diphtheria caused by C. ulcerans have been reported more often than infections by Corynebacterium diphtheria, while systemic infections are also increasingly reported. Little is known about factors that contribute to host colonization and virulence of this zoonotic pathogen. Research in this field has received new impetus by the publication of several C. ulcerans genome sequences in the past years. This review gives a comprehensive overview of the basic knowledge of C. ulcerans, as well as the recent advances made in the analysis of putative virulence factors.

{ "pile_set_name": "PubMed Abstracts" }

Luo Xiangang Luo Xiangang (; born December 1970) is a Chinese engineer specializing in photoelectric technology. He is an academician of the Chinese Academy of Engineering currently serves as director of the Institute of Optics and Electronics, Chinese Academy of Sciences. Biography Luo was born in Cangxi County, Sichuan, in December 1970. He attended Qinglin Village School. He elementary studied at Baiqiao Town Middle School and secondary studied at Chengjiao High School. In 1989 he graduated from Mianyang Teachers' College. He holds a bachelor's degree from Sichuan Normal University, and master's and doctor's degrees from the Institute of Optics and Electronics, Chinese Academy of Sciences. He was a postdoctoral fellow at the Institute of Physical and Chemical Research between May 2001 and May 2002. He was also a research scientist at the institute from May 2001 to January 2005. He joined the Institute of Optics and Electronics, Chinese Academy of Sciences in December 2004. Honours and awards 2008 National Science Fund for Distinguished Young Scholars 2014 Fellow of the International Academy of Photonics and Laser Engineering (IAPLE) 2016 State Technological Invention Award (First Class) 2018 Fellow of the Chinese Optical Society (COS) 2019 Fellow of The Optical Society (OSA) 2019 Fellow of SPIE November 22, 2019 Member of the Chinese Academy of Engineering (CAE) References External links Luo Xiangang on the Institute of Optics and Electronics, Chinese Academy of Sciences Category:1970 births Category:Living people Category:People from Cangxi County Category:Engineers from Sichuan Category:Sichuan Normal University alumni Category:Members of the Chinese Academy of Engineering Category:Fellows of the Optical Society Category:Fellows of SPIE

{ "pile_set_name": "Wikipedia (en)" }

//===- llvm/TableGen/Error.h - tblgen error handling helpers ----*- C++ -*-===// // // The LLVM Compiler Infrastructure // // This file is distributed under the University of Illinois Open Source // License. See LICENSE.TXT for details. // //===----------------------------------------------------------------------===// // // This file contains error handling helper routines to pretty-print diagnostic // messages from tblgen. // //===----------------------------------------------------------------------===// #ifndef LLVM_TABLEGEN_ERROR_H #define LLVM_TABLEGEN_ERROR_H #include "llvm/Support/SourceMgr.h" namespace llvm { void PrintWarning(ArrayRef<SMLoc> WarningLoc, const Twine &Msg); void PrintWarning(const char *Loc, const Twine &Msg); void PrintWarning(const Twine &Msg); void PrintError(ArrayRef<SMLoc> ErrorLoc, const Twine &Msg); void PrintError(const char *Loc, const Twine &Msg); void PrintError(const Twine &Msg); LLVM_ATTRIBUTE_NORETURN void PrintFatalError(const Twine &Msg); LLVM_ATTRIBUTE_NORETURN void PrintFatalError(ArrayRef<SMLoc> ErrorLoc, const Twine &Msg); extern SourceMgr SrcMgr; extern unsigned ErrorsPrinted; } // end namespace "llvm" #endif

{ "pile_set_name": "Github" }

Aceruloplasminemia, an inherited disorder of iron metabolism. Ceruloplasmin, a multi-copper ferroxidase that affects the distribution of tissue iron, has antioxidant effects through the oxidation of ferrous iron to ferric iron. Aceruloplasminemia is an inherited disorder of iron metabolism due to the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. It is characterized by iron accumulation in the brain as well as visceral organs. Clinically, the disease consists of the triad of retinal degeneration, diabetes mellitus, and neurological disease, which include ataxia, involuntary movements, and dementia. These symptoms reflect the sites of iron deposition. The unique involvement of the central nervous system distinguishes aceruloplasminemia from other inherited and acquired iron storage disorders. Twenty-one mutations in the ceruloplasmin gene have been reported in 24 families worldwide. In Japan, the incidence was estimated to be approximately one per 2,000,000 in the case of non-consanguineous marriages. Excess iron functions as a potent catalyst of biologic oxidation. Previously we showed that an increased iron concentration is associated with increased levels of lipid peroxidation in the serum, cerebrospinal fluid, and erythrocyte membranes. The levels of malondialdehyde and 4-hydroxynonenals, indicators of lipid peroxidation, were also elevated in the basal ganglia and cerebral cortex. Positron emission tomography showed diminished brain metabolism of glucose and oxygen. Enzyme activities in the mitochondrial respiratory chain of the basal ganglia were reduced to approximate 45% and 42%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals causes neuronal cell damage through lipid peroxidation and mitochondrial dysfunction in aceruloplasminemia brains.

{ "pile_set_name": "PubMed Abstracts" }

Influence of protein restriction on lymphoid cell populations characterized by the binding of peanut agglutinin. Cells binding peanut agglutinin (PNA) were studied in the thymus, spleen, and mesenteric lymph nodes from mice placed in the post weaning period on protein-restricted diets containing 8% (R8%) and 4% (R4%) casein. The proportion of PNA+ thymocytes and the absolute number of total and PNA+ cells in the thymus were significantly diminished in R8% and R4% mice. Larger proportion of PNA+ thymocytes showed weaker fluorescence in R8% and R4% than in normally fed (N) animals. Recovery of PNA+ thymocytes was observed in R8% but not in R4% mice at 8 weeks. The number of total and PNA+ cells was significantly diminished although the proportion of PNA+ cells was not modified in the peripheral lymphoid organs of R8% and R4% mice. Results indicate that protein restriction preferentially affected the immature cortical PNA+ cells in the thymus whereas cell depletion in the peripheral lymphoid organs occurred at the expense of both the PNA+ and PNA- subpopulations.

{ "pile_set_name": "PubMed Abstracts" }

--- abstract: 'For second countable locally compact Hausdorff groupoids, the property of possessing a Haar system is preserved by equivalence.' address: | Department of Mathematics\ Dartmouth College\ Hanover, NH 03755\ USA author: - 'Dana P. Williams' date: 15 January 2015 title: Haar Systems on Equivalent Groupoids --- [^1] Introduction {#sec:introduction} ============ Beginning with the publication of Renault’s seminal paper [@ren:groupoid], locally compact groupoids have been an especially important way to construct operator algebras. Just as with the time honored group [$\mathcs$]{}-algebra construction, this is done by turning $C_{c}(G)$ into a convolution algebra and then completing. In the group case, there is always a (left) Haar measure on $G$ which allows us to form the convolution product. In the groupoid case, the natural convolution formula requires a family of measures $\lambda^{u}$ with support $G^{u}=\set{x\in G:r(x)=u}$ for each $u\in{G^{(0)}}$. We want the family to be left-invariant in that $x\cdot \lambda^{s(x)} = \lambda^{r(x)}$ where $x\cdot \lambda^{s(x)}(E)=\lambda^{s(x)}(x^{-1}E)$. In order that the convolution formula return a continuous function, we need the continuity condition that $$u\mapsto \int_{G}f(x)\,d\lambda^{u}(x)$$ be continuous for all $f\in C_{c}(G)$ (the necessity is the main result in [@sed:pams86]). Such a family ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$ is called a (continuous) *Haar system* for $G$. An annoying gap in the theory is that there is no theorem guaranteeing Haar systems exist. The only significant positive existence result I am aware of is that if ${G^{(0)}}$ is open in $G$ and the range map is open (and hence the source map as well), then the family consisting of counting measures is always a Haar system. Groupoids with ${G^{(0)}}$ open and for which the range map is open are called *étale*. (It is also true that Lie Groupoids necessarily have Haar systems [@pat:groupoids99]\*[Theorem 2.3.1]{}, but this result is crucially dependent on the manifold structure and hence not in the spirit of this note.) It is also well known that if $G$ is any locally compact groupoid with a Haar system, then its range and source maps must be open. (This is a consequence of Remark \[rem-haar-r-sys\] and Lemma \[lem-pi-sys-open\].) Thus if a locally compact groupoid has a range map which is not open, then it can’t possess a Haar system. Such groupoids do exist; for example, see [@sed:pams86]\*[§3]{}. However, to the best of my knowledge, there is no example of a locally compact groupoid with open range and source maps which does not possess a Haar system. I have yet to find an expert willing to conjecture (even off the record) that all such groupoids need have Haar systems, but the question remains open. The purpose of this note is to provide some additional examples where Haar systems must exist. The main result being that if $G$ and $H$ are equivalent second countable locally compact groupoids (as defined in [@mrw:jot87] for example), and if $G$ has a Haar system, then so does $H$. Since equivalence is such a powerful tool, this result gives the existence of Haar systems on a great number of interesting groupoids. For example, every transitive groupoid with open range and source maps has a Haar system (Proposition \[prop-trans\]). The proof given here depends on several significant results from the literature. The first is that if $\pi:Y\to X$ is a continuous, open surjection with $Y$ second countable, then there is a family of Radon measures ${\{\beta^{x}\}}$ on $Y$ such that $\operatorname*{supp}\beta^{x}=\pi^{-1}(x)$ and $$x\mapsto \int_{Y} f(y)\,d\beta^{x}(y)$$ is continuous for all $f\in C_{c}(Y)$. (This result is due to Blanchard who makes use of a Theorem of Michael’s [@mic:am56].) The second is the characterization in [@kmrw:ajm98]\*[Proposition 5.2]{} of when the imprimitivity groupoid of free and proper $G$-space has a Haar system. The third is the concept of a Bruhat section or cut-off function. These are used in [@bou:integrationII04]\*[Chapter 7]{} to construct invariant measures. They also appear prominently in [@ren:xx14]\*[Lemma 25]{} and [@tu:doc04]\*[§6]{}. Since Blanchard’s result requires separability, we can only consider second countable groupoids here. I would like to thank Marius Ionescu, Paul Muhly, Erik van Erp, Aidan Sims, and especially Jean Renault for helpful comments and discussions. The Theorem {#sec:main-theorem} =========== \[thm-main\] Suppose that $G$ is a second countable, locally compact Hausdorff groupoid with a Haar system ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$. If $H$ is a second countable, locally compact groupoid which is equivalent to $G$, then $H$ has a Haar system. As in [@ren:jot87]\*[p. 69]{} or [@anaren:amenable00]\*[Definition 1.1.1]{}, if $\pi:Y\to X$ is a continuous map between locally compact spaces $Y$ and $X$, then a *$\pi$-system* is a family of (positive) Radon measures $\set{\beta^{x}:x\in X}$ on $Y$ such that $\operatorname*{supp}\beta^{x}\subset \pi^{-1}(x)$ and for every $f\in C_{c}(Y)$, the function $$x\mapsto \int_{Y}f(y)\,d\beta^{x}(y)$$ is continuous. We say that $\beta$ is *full* if $\operatorname*{supp}\beta^{x}=\pi^{-1}(x)$ for all $x\in X$. If $Y$ and $X$ are both (left) $G$-spaces and $\pi$ is equivariant, then we say $\beta$ is *equivariant* if $\gamma\cdot \beta^{x} = \beta^{\gamma\cdot x}$ where $\gamma\cdot \beta^{x}(E)=\beta^{x}(\gamma^{-1}\cdot E)$ for all $(\gamma,x)\in G*X=\set{(\gamma,x):s(\gamma)=r(x)}$. Alternatively, $$\int_{Y}f(\gamma\cdot y)\,d\beta^{x}(y)=\int_{Y} f(y)\,d\beta^{\gamma\cdot x}(y)$$ for all $f\in C_{c}(Y)$ and $(\gamma,x)\in G*X$. \[rem-haar-r-sys\] It is useful to keep in mind that a Haar system on $G$ is a full, equivariant $r$-system on $G$ for the range map $r:G\to{G^{(0)}}$. In many cases, such as [@kmrw:ajm98]\*[§5]{}, $\pi$-systems are reserved for continuous *and open* maps $\pi:Y\to X$. In the case of full systems, the next lemma implies that there is no loss in generality. (This part of the result does not require second countability.) Conversely, if $Y$ is second countable $\pi$ is an open surjection, then Blanchard has proved that full $\pi$ systems must exist. Blanchard’s result will be crucial in the proof of the main result. \[lem-pi-sys-open\] Suppose that $\pi:Y\to X$ is a continuous surjection between second countable locally compact Hausdorff spaces. Then $\pi$ is open if and only if it admits a full $\pi$ system. Suppose that $\beta$ is a full $\pi$ system. To show that $\pi$ is open, we appeal to the usual lifting argument as in [@wil:crossed]\*[Proposition 1.15]{}. Thus we assume that $x_{i}\to \pi(y)$ is a convergent net. It will suffice to produce a subnet ${\{x_{j}\}}_{j\in J}$ and elements $y_{j}\in \pi^{-1}(x_{j})$ such that $y_{j}\to y$. To this end, let $$J=\set{(i,V):\text{$V$ is an open neighborhood of $y$ and $\pi^{-1}(x_{i})\cap V\not=\emptyset$}}.$$ We need to see that $J$ is directed in the expected way: $(i,V)\ge (j,U)$ if $i\ge j$ and $V\subset U$. So let $(k,V)$ and $(j, U)$ be in $J$. Let $f\in C_{c}^{+}(G)$ be such that $f(y)=1$ and $\operatorname*{supp}f\subset V\cap U$. Then $$\beta(f)(x_{i})=\int_{Y} f(y)\,d\beta^{x_{i}}(y) \to \int_{Y} f(y) \, \beta^{\pi(y)}(y)=\beta(f)(\pi(y)).$$ The latter is nonzero since $\beta^{\pi(y)}$ has full support. Hence there is a $k\ge i$ and $k\ge j$ such that $$\int_{Y}f(y)\,d\beta^{x_{i}}(y)\not=0.$$ It follows that $(i,U\cap V)\in J$. Thus if we let $x_{(i,V)}=x_{i}$, then ${\{x_{(i,V)}\}}_{(i,V)\in J}$ is a subnet. If we let $y_{(i,V)}$ be any element of $\pi^{-1}(x_{i})\cap V$, then $y_{(i,V)}\to y$. This suffices. The converse is much more subtle, and is due to Blanchard [@bla:bsmf96]\*[Proposition 3.9]{}. We also need what is sometimes called a *Bruhat section* or *cut-off* function for $\pi$. The construction is modeled after Lemma 1 in Appendix I for [@bou:integrationII04]\*[Chapter 7]{}. Recall that a subset $A\subset Y$ is called $\pi$-compact if $A\cap \pi^{-1}(K)$ is compact whenever $K$ is compact in $X$. We write $C_{c,\pi}(Y)$ for the set of continuous functions on $Y$ with $\pi$-compact support. \[lem-phi-exists\] Let $\pi:Y\to X$ be a continuous open surjection between second countable locally compact Hausdorff spaces. Then there is a $\phi\in C_{c,\pi}^{+}(Y)$ such that $\pi\bigl(\set{y\in Y:\phi(y)>0} \bigr) = X$. Let $\mathscr V=\set{V_{i}}$ be a countable, locally finite cover of $X$ by pre-compact open sets $V_{i}$. Let ${\{\alpha_{i}\}}$ be a partition of unity on $X$ subordinate to $\mathscr V$. Let $\phi_{i}\in C_{c}^{+}(Y)$ be such that $\pi\bigl(\set{y\in Y:\phi_{i}>0}\bigr) \supset V_{i}$. Then we can define $$\phi(y) =\sum_{i} \phi_{i}(y) \alpha_{i}\bigl(\pi(y)\bigr).$$ Since $\mathscr V$ is locally finite, the above sum is finite in a neighborhood of any $y\in Y$. Hence $\phi$ is well-defined and continuous. Local finiteness also implies that every compact subset of $X$ meets at most finitely many $V_{i}$. Since ${\{\alpha_{i}\}}$ is subordinate to $\mathscr V$, it follows that $\phi$ has $\pi$-compact support. If $x\in X$, then there is an $i$ such that $\alpha_{i}(x)>0$. Then there is a $y$ such that $\phi_{i}(y)>0$ and $\pi(y)=x$. Hence the result. Let $Z$ be a $(G,H)$-equivalence. Then the opposite module, ${Z^{\text{op}}}$, is a $(H,G)$ equivalence. Therefore, in view of [@kmrw:ajm98]\*[Proposition 5.2]{}, it will suffice to produce a full $G$-equivariant $s_{{Z^{\text{op}}}}$-system for the structure map $s_{{Z^{\text{op}}}}:{Z^{\text{op}}}\to{G^{(0)}}$. Equivalently, we need a full equivariant $r_{Z}$-system for the map $r_{Z}:Z\to{G^{(0)}}$.[^2] Hence the main Theorem is a consequence of Proposition \[prop-jean-proper-map\] below. The following proposition is even more that what is called for in the proof of Theorem \[thm-main\]: it shows that every proper $G$-space has a full equivariant $r$-system for the moment map whether the action is free or not. It should be noted that pairs $(X,\alpha)$ where $X$ is a proper $G$-space and $\alpha$ and equivariant $r$-system play an important role in the constructions in [@ren:jot87] and [@holren:xx14]. This makes the assertion that such $\alpha$’s always exist even more interesting. \[prop-jean-proper-map\] Let $G$ be a locally compact Hausdorff groupoid with a Haar system ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$. Suppose that $Z$ is a proper $G$-space. Then there is a full equivariant $r_{Z}$-system ${\{\nu^{u}\}}_{u\in{G^{(0)}}}$ for the moment map $r_{Z}:Z\to{G^{(0)}}$. Blanchard’s Lemma \[lem-pi-sys-open\] implies that there is a full $r_{Z}$-system $\beta={\{\beta^{u}\}}_{u\in{G^{(0)}}}$. The idea of the proof is to use the Haar system on $G$ to average this system to create and equivariant system. The technicalities are provided by the next lemma. Notice that since $G$ acts properly, the orbit map $q:Z\to G\backslash Z$ is a continuous open surjection between locally compact Hausdorff spaces. \[lem-phi-fcns\] Let $G$, $Z$, $\lambda$ and $\beta$ be as above. 1. If $F\in C_{c}(G\times Z)$, then $$\Phi(F)(g,u)=\int_{Z} F(g,z)\,d\beta^{u}(z)$$ defines an element of $C_{c}(G\times{G^{(0)}})$. 2. If $f\in C_{c}(Z)$ and $\phi\in C_{c,q}(Z)$, then $$\Psi_{\phi}(f)(g)=\int_{Z} f(g\cdot z)\phi(z) \,d\beta^{s(g)}(z)$$ defines an element of $C_{c}(G)$. \(a) This is straightforward if $F(g,z)=f(g)\phi(z)$ with $f\in C_{c}(G)$ and $\phi\in C_{c}(Z)$. But we can approximate $F$ in the inductive limit topology with sums of such functions. \(b) Let $L=\operatorname*{supp}\phi\cap q^{-1}\bigl(q(\operatorname*{supp}f)\bigr)$. By assumption on $\phi$, $L$ is compact. Since $G$ acts properly on $Z$, the set $$P(\operatorname*{supp}f,L)=\set{g\in G:g\cdot L\cap \operatorname*{supp}f\not=\emptyset}$$ is compact. It follows that $$F(g,z)=f(g\cdot z)\phi(z)$$ defines an element of $C_{c}(G\times Z)$. Then $$\Psi_{\phi}(f)(g)=\Phi(F)(g,s(g)).$$ The assertion follows. Using Lemma \[lem-phi-exists\], we fix $\phi\in C_{c,q}^{+}(Z)$ such that $q\bigl(\set{z:\phi(z)>0} \bigr)=G\backslash Z$. Then we define a Radon measure on $C_{c}(Z)$ by $$\label{eq:1} \nu^{u}(f)=\int_{G}\int_{Z} f(g\cdot z)\phi(z)\,d\beta^{s(g)}(z) \,d\lambda^{u}(g) =\int_{G}\Psi_{\phi}(f)(g) \,d\lambda^{u}(g).$$ Since $\lambda$ is a Haar system and $\Psi_{\phi}(f)\in C_{c}(G)$, we see immediately that $$u\mapsto \nu^{u}(f)$$ is continuous. Clearly, $\operatorname*{supp}\nu^{u}\subset r_{Z}^{-1}(u)$. Suppose $r_{Z}(w)=u$ and $f\in C_{c}^{+}(Z)$ is such that $f(w)>0$. Then there is a $z'\in\set{z:\phi(z)>0}$ such that $q(z')=q(w)$. Hence there is a $g\in G$ such that $g\cdot z'=w$. Note that $r_{Z}(z')=s(g)$ and $r(g)=r_{Z}(g\cdot z)=r_{Z}(w)=u$. Since $\beta^{s(g)}$ has full support and since everything in sight is continuous and non-negative, $$\Psi_{\phi}(g) =\int_{Z} f(g\cdot z)\phi(z)\,\beta^{s(g)}(z)>0.$$ Hence $\nu^{u}(f)>0$ and we have $$\operatorname*{supp}\nu^{u} = r_{Z}^{-1}(u).$$ Hence to complete the proof of the theorem, we just need to establish equivariance. But $$\begin{aligned} \int_{Z} f(g'\cdot z)\,d\nu^{s(g')}(z) &= \int_{G}\int_{Z} f(g'g\cdot z)\phi(z)\,d\beta^{s(g)}(z)\,d\lambda^{s(g')}(g) \\ &= \int_{G}\Psi_{\phi}(f)(g'g)\,d\lambda^{s(g')}(g) \\ \intertext{which, since $\lambda$ is a Haar system on $G$, is} &= \int_{G}\Psi_{\phi}(g) \,d\lambda^{r(g')}(g) \\ &=\int_{G}\int_{Z} f(g\cdot z)\phi(z)\,d\beta^{s(g)}(z) \,d\lambda^{r(g')}(g) \\ \intertext{which, since $g'\cdot s(g')=r(g')$, is} &=\int_{Z}f(z)\,d\nu^{g'\cdot s(g')}(z).\end{aligned}$$ This completes the proof. Proposition \[prop-jean-proper-map\] is interesting even for a group action. The result itself is no doubt known to experts, but is amusing none-the-less. \[cor-jean-group\] Suppose that $G$ is a locally compact group acting properly on a space $X$. Then $X$ has at least one invariant measure with full support. Examples and Comments {#sec:exampl-comm-future} ===================== As pointed out in the introduction, any étale groupoid $G$ has a Haar system. As a consequence of Theorem \[thm-main\], any second countable groupoid equivalent to $G$ has a Haar system (provided $G$ is second countable). In this section, I want to look at some additional examples. In some cases it is possible and enlightening to describe the Haar system in finer detail. Proper Principal Groupoids {#sec:prop-princ-group} -------------------------- Recall that $G$ is called principal if the natural action of $G$ on ${G^{(0)}}$ given by $x\cdot s(x)=r(x)$ is free. We call $G$ proper if this action is proper in that $(x,s(x))\mapsto (r(x),s(x))$ is proper from $G\times {G^{(0)}}\to{G^{(0)}}\times{G^{(0)}}$. If $G$ is a proper principal groupoid with open range and source maps, then the orbit space $G\backslash {G^{(0)}}$ is locally compact Hausdorff, and it is straightforward to check that ${G^{(0)}}$ implements an equivalence between $G$ and the orbit space $G\backslash {G^{(0)}}$. Since the orbit space clearly has a Haar system, the following is a simple corollary of Theorem \[thm-main\]. \[prop-proper-prin\] Every second countable proper principle groupoid with open range and source maps has a Haar system. \[rem-blanchard\] If $G$ is a second countable proper principle groupoid with open range and source maps, then the orbit map $q:{G^{(0)}}\to G\backslash {G^{(0)}}$ sending $u$ to $\dot u$ is continuous and open. Hence Blanchard’s Lemma \[lem-pi-sys-open\] implies there is a full $q$-system ${\{\beta^{\dot u}\}}_{\dot u\in G\backslash {G^{(0)}}}$. It is not hard to check that $\lambda^{u}=\delta_{u}\times \beta^{\dot u}$ is a Haar system for $$G_{q}:=\set{(u,v)\in{G^{(0)}}\times{G^{(0)}}:\dot u = \dot v}.$$ Since $x\mapsto (r(x),s(x))$ is a groupoid isomorphism of $G$ and $G_{q}$, we get an elementary description for a Haar system on $G$. While there certainly exist groupoids that fail to have open range and source maps — and hence cannot have Haar systems — most of these examples are far from proper and principal. In fact the examples I’ve seen are all group bundles which are as a far from principal as possible. This poses an interesting question. Must a second countable, locally compact, proper principal groupoid have open range and source maps? Transitive Groupoids {#sec:transitive-groupoids} -------------------- Recall that a groupoid is called *transitive* if the natural action of $G$ on ${G^{(0)}}$ given by $x\cdot s(x):=r(x)$ is transitive. If $G$ is transitive and has open range and source maps, then $G$ is equivalent to any of its stability groups $H=G_{v}^{v}=\set{x\in G:r(x)=u=s(x)}$ for $v\in{G^{(0)}}$; the equivalence is given by $G_{v}$ with the obvious left $G$-action and right $H$ action. Second countability is required to see that the restriction of the range map to $G_{v}$ onto ${G^{(0)}}$ is open.[^3] Since locally compact groups always have a Haar measure, the following is an immediate consequence of Theorem \[thm-main\]. (Similar assertions can be found in [@sed:pria76].) \[prop-trans\] If $G$ is a second countable, locally compact transitive groupoid with open range and source maps, then $G$ has a Haar system. As before, I don’t know the answer to the following. Must a second countable, locally compact, transitive groupoid have open range and source maps? Blowing Up the Unit Space {#sec:blowing-up-unit} ------------------------- While there are myriad ways groupoid equivalences arise in applications, one standard technique deserves special mention (see [@txlg:acens12] for example). Suppose that $G$ is a second countable locally compact groupoid with a Haar system (or at least open range and source maps). Let $f:Z\to {G^{(0)}}$ be a continuous and open map. Then we can form the groupoid $$\label{eq:2} G[Z]=\set{(z,g,w)\in Z\times G\times Z: \text{$f(z)=r(g)$ and $s(g)=f(w)$}} .$$ (The operations are as expected: $(z',g',z)(z,g,w)=(z',g'g,w)$ and $(z,g,w)^{-1} = (w,g^{-1},z)$.) The idea being that we use $f$ to “blow-up” the unit space of $G$ to all of $Z$. If $\phi:G[Z]\to G$ is the homormorphism $(z,g,w)\mapsto g$, then we get a $(G[Z],G)$-equivalence given by “the graph of $\phi$” (see [@kmrw:ajm98]\*[§6]{}): $$W = \set{(z,g)\in Z\times G:f(z)=r(g)}.$$ The left $G[Z]$-action is given by $(z,g,w)\cdot (w,g')=(z,gg')$ and the right $G$-action by $(w,g')\cdot g = (w,g'g)$. The openness of the range map for $G$ are required to see that the structure map $r_{W}:W\to Z$ is open, while the openness of $f$ is required to see that $s_{W}:W\to {G^{(0)}}$ is open. Assuming $G$ has a Haar system and $Z$ is second countable, Theorem \[thm-main\] implies $G[Z]$ has a Haar system. However in this case we can do a bit better and write down a tidy formula for the Haar system on the blow-up. We still require Blanchard’s Lemma \[lem-pi-sys-open\] that there is a full $f$-system for any continuous open map $f:Z\to {G^{(0)}}$ (provided that $Z$ is second countable). \[prop-blow-up-haar\] Suppose that $G$ is a locally compact Hausdorff groupoid with a Haar system ${\{\lambda^{u}\}}_{u\in{G^{(0)}}}$, and that $Z$ is second countable. Let $f:Z\to{G^{(0)}}$ be a continuous open map, and let $$G[Z]=\set{(w,g,z)\in Z\times G\times Z: \text{$f(w)=r(g)$ and $s(g)=f(z)$}}$$ be the “blow-up” of $G$ by $f$. If ${\{\beta^{u}\}}_{u\in{G^{(0)}}}$ is a full $f$-system, then we get a Haar system ${\{\kappa^{z}\}}_{z\in Z}$ on $G[Z]$ given by $$\kappa^{z}(f)=\int_{G}\int_{Z} f(z,g,w)\,d\beta^{s(g)}(w)\,d\lambda^{f(z)}(g).$$ The proof is relatively straightforward. Imprimitivity Groupoids {#sec:impr-group} ----------------------- If $X$ is a free and proper right $G$-space, then assuming $G$ has open range and source maps, we can form the imprimitivity groupoid $G^{Z}$ as in [@muhwil:plms395]\*[pp. 119+]{}. Specifically we let $G^{Z}$ be the quotient of $X*_{s}X=\set{(x,y)\in X\times X:s(x)=s(y)}$ by the diagonal right $G$-action. Then $G^{Z}$ is a groupoid with respect to the operations $[x,y][y,z]=[x,z]$ and $[x,y]^{-1}=[y,z]$. Furthermore $X$ implements an equivalence between $G^{Z}$ and $G$. Again we can apply Theorem \[thm-main\]. \[prop-imprimitivity\] Suppose that $G$ is a second countable, locally compact Hausdorff groupoid with a Haar system. Let $X$ be a free and proper right $G$-space. Then the imprimitivity groupoid $G^{Z}$ has a Haar system. \[rem-kmrw\] In [@kmrw:ajm98]\*[§§9-10]{}, we associated a group $\operatorname{Ext}(G,\T)$ to any second countable, locally compact Hausdorff groupoid $G$. In [@kmrw:ajm98]\*[Theorem 10.1]{} we showed that $\operatorname{Ext}(G,\T)$ was naturally isomorphic to the Brauer group $\operatorname{Br}(G)$. The definition of $\operatorname{Ext}(G,\T)$ required we consider the space $\mathcal{P}(G)$ of all free and proper right $G$-spaces $X$ *such that $G^{X}$ has a Haar system*. In view of Proposition \[prop-imprimitivity\], $\mathcal{P}(G)$ becomes simply the collection of all free and proper right $G$-spaces. \#1 [^1]: This work was supported in part by a grant from the Simons Foundation. [^2]: The gymnastics with the opposite space is just to accommodate a preference for left-actions. This has the advantage of making closer contact with the literature on $\pi$-systems. [^3]: Proving the openness of $r\restr{G_{v}}$ is nontrivial. It follows from [@ram:jfa90]\*[Theorem 2.1]{} or Theorems 2.2A and 2.2B in [@mrw:jot87]. The assertion and equivalence fail without the second countability assumption as observed in [@mrw:jot87]\*[Example 2.2]{}. It should be noted that in both [@ram:jfa90] and [@mrw:jot87] openness of the range and source maps on a topological groupoid is a standing assumption.

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5 things to do today to keep your data private However, it’s hard not to be aware of the constant threats that hammer on our digital doors. The joy of the Internet is that we’re all connected to each other, making it easy to share information and commerce. But there’s also a dark side: Just as in the “real” world, the Net is full of evildoers who want to take advantage of the less-than-vigilant among us. Don’t be one of them. On Data Privacy Day, take some time to secure your virtual borders. Here are five things you can do right now that will give you peace of mind and make it little harder for the jerks who want to steal your data, your identity and your cash. • Change your passwords – This is the first thing you should do, and it’s the most effective – so long as your passwords are strong and effective. Change the passwords on all the accounts associated with your personal information, and make each one different. A strong password has a mix of letters, numbers and symbols, and ideally it should be a pass phrase, rather than a single word. If you’re having a hard time coming up with a tough password, there are sites that will make them for you. Try the PC Tools Password Generator – it’s owned by Symantec, so it’s trustworthy – which helps you build a strong, hard-to-crack password. • Adjust your social media privacy settings – Social networks such as Twitter, Facebook and LinkedIn all let you control what information you reveal and to whom. Facebook in particular has fairly powerful privacy settings, but most people don’t change them, either out of inertia or because they’re too intimidating. You can find Facebook’s privacy controls here. Pay particular attention to who can see the items you post – the default is Public, which means everyone can see them – and “Limit the audience for posts you’ve shared with friends of friends or Public”. The latter is confusing, but basically Facebook has reset old posts so only your Friends can see them, even if you originally set them to Public or Friends of Friends. You can also use Facebook’s activity log to review all your items, change individual settings and even delete some you now wish you hadn’t posted. • Get your credit report – Did you know you have the right to get a free copy of your credit report once a year? The three national credit reporting companies – Equifax, Experian and TransUnion – are required to give them to you as part of the Fair Credit Reporting Act. By examining your report, you may be able to catch attempts at identify theft, or even unauthorized credit accounts that have been opened in your name. Fortunately, you don’t have to go through the hassle of contacting each one of the reporting agencies individually. The three have cooperated to streamline the process. AnnualCreditReport.com lets you request reports from all of them. If you’re old-school, you can call 1-877-322-8228. You can find more information at this Federal Trade Commission website. • Update your antivirus software – Time and again, when I hear from people whose PCs are infected with malware, it’s because they let their security software subscription lapse. Paid products like Norton and McAfee do continue to run on your PC even if you don’t pay the annual subscription fee, but they lose their ability to protect against any new threats. And since new viruses, Trojans and spyware are being developed all the time, not keeping your security software up to date instantly puts you at risk. • Update your software – Cyberscum often rely on flaws in software to put spyware and other evil code on your computer. One of the best ways to prevent this is to make sure you operating system and the apps that run on it are up to date. Both Windows and Mac OS X update automatically by default, though users can override that. A word of advice: Don’t. Many of those updates have security fixes and not installing them puts you at risk. Because operating system updates run automatically, the bad guys are turning to flaws in the software that runs on the OSes. You may recall the serious flaw in Java that had even the Department of Homeland Security urging swift action. Because of this, it’s just as important to keep your applications updated. Today, launch each one of the apps you use most often and have it check for updates. Some applications – particularly common plug-ins for browsers, such as Flash – check automatically. When you see a popup from an application that wants to update, don’t delay – let it run ASAP. The data you save may be your own.

{ "pile_set_name": "Pile-CC" }

Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202. Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity. In the patients responding to EHT 0202, a pre-treatment (baseline) transcriptomic signature showed activation of pathways related to AD, CNS disorders, diabetes, inflammation, and autoimmunity, while a post-treatment signature indicated reduced activation of these pathways with induced metabolic and transcription stimulation. This pilot study demonstrates the utility of blood transcriptomic signatures used as biomarkers for predicting patient response or monitoring efficacy, for an administered therapeutic drug in a complex disease such as AD. For EHT 0202 or other AD drugs, such biomarkers may help to improve strategies to better identify appropriate patient populations for treatment, understand the drug mechanism of efficacy, and/or clarify the inherent subjectivity in most clinical endpoints used in this disease.

{ "pile_set_name": "PubMed Abstracts" }

Social justice and intercountry adoptions: the role of the U.S. social work community. Using social justice as the conceptual foundation, the authors present the structural barriers to socially just intercountry adoptions (ICAs) that can exploit and oppress vulnerable children and families participating in ICAs. They argue that such practices threaten the integrity of social work practice in that arena and the survival of ICA as a placement option. Government structures, disparity of power between countries and families on both sides, perceptions regarding poverty, cultural incompetence, misconceptions about orphans and orphanages, lack of knowledge about the impact of institution-based care, and the profit motive are driving forces behind the growing shadow of unethical ICAs. The U.S. social work community has a large role and responsibility in addressing these concerns as the United States receives the most children adopted through ICAs of all receiving countries. In addition to the centrality of social justice as a core value of the profession, the responsibility to carry out ethical and socially just ICA has recently increased as a matter of law, under the implementation legislation to the Hague Convention on Intercountry Adoption. While acknowledging that these issues are complex, authors provide suggestions for corrective policy and practice measures.

{ "pile_set_name": "PubMed Abstracts" }

Occurrence of toxigenic Aspergillus spp. and aflatoxins in selected food commodities of Asian origin sourced in the West of Scotland. The occurrence of Aspergillus moulds and aflatoxins in 12 commercially-available dried foods of Asian origin were examined. All food samples, except green beans and three types of dried fruit, contained multiple genera of moulds of which Aspergillus (55%) was the most frequently detected. Penicillium (15%), Rhizopus (11%), Mucor (3%), Monascus (1%), Eurotium (1%) and unidentified (14%) were also observed. The occurrence of aflatoxigenic moulds, however, did not correspond with the occurrence of aflatoxins in foods. Aflatoxigenic Aspergillus spp. (39 isolates) were recovered from long grain rice, fragrant rice, peanuts, black beans and black pepper. The predominant Aspergillus species was A. parasiticus (61%) while Aspergillus oryzae (3%), Aspergillus utus (5%), Aspergillus niger (5%), Aspergillus ochraceus (3%) and unidentified (23%) were also observed. Long grain rice, fragrant rice, peanuts, black beans and black pepper were positive for Aspergillus but contained undetectable aflatoxins. In contrast, Jasmine brown rice and crushed chilli contained 14.7 and 11.4μg/kg of total aflatoxins, respectively, in the absence of Aspergillus so aflatoxigenic Aspergillus was present at some stage of food production. The results from this study emphasise the need for stricter control measures in reducing occurrence of aflatoxins in foods for export and domestic use.

{ "pile_set_name": "PubMed Abstracts" }

Rarely a week passes without reports that Labour rebels are planning a split of some kind. The latest story, in the Daily Telegraph, suggested that rather than creating a new party (an option that has never been on the cards), MPs intend to form an alternative parliamentary grouping. This would involve electing their own leader and seeking designation as the official opposition. The idea has been discussed in Labour circles ever since Joe Haines, Harold Wilson’s former press secretary, called in January in the New Statesman for the parliamentary party to unilaterally declare independence. But it is not a course that MPs intend to pursue, even if, as most expect, Jeremy Corbyn is re-elected. Labour backbenchers Toby Perkins and Wes Streeting told the NS they knew of "no one" who was advocating the idea, while Jamie Reed said he thought the story was a "put-up job". He added: "McDonnell and Corbyn have no regard for the party. Never have had, never will. They are ones angling for a split. The 81 per cent of Labour MPs who know what we need to do to have a chance of winning in 2020 have no intention of going anywhere." Three senior rebels described reports of a split as “bollocks”. Another said: "Nobody can track down likely source of the Telegraph piece, so it may just be a lone voice. I don’t think it’s a runner." MPs said that further leadership challenges were likely before anyone gave serious consideration to a split. But one added: "If, however, the hard left pursued deselections then those ejected from their own party would most likely feel compelled into a separate party option, which really would be a disastrous split. Unless that’s what McDonnell meant by ‘so be it’." The shadow chancellor is alleged by leadership candidate Owen Smith to have "shrugged his shoulders and said 'If that’s what it takes'" when privately challenged on whether he was prepared to split Labour (a claim described by McDonnell as "complete rubbish"). Corbyn’s opponents believe that some MPs will follow shadow Home Office minister Sarah Champion and return to the frontbench if he wins the contest. But most of the 172 who backed the no confidence motion have no intention of doing so. “We’ve crossed the Rubicon, there’s no going back,” said Streeting. “This is irreparable while Jeremy remains leader.” The SNP is currently bidding to be made the official opposition on the grounds that Corbyn has the support of just 40 MPs, while it has 54. But the rebels believe the Speaker will not award the nationalists this designation since they, unlike Labour, do not even have the potential to form a full frontbench team. Catherine Haddon of the Institute for Government told the NS: "The only argument here would be if the 81 per cent of MPs who voted against Corbyn seemed likely to refuse the whip or to refuse to serve in a Corbyn government were one likely. If that happened the argument does change. But we are not there yet." Both Corbyn supporters and their opponents have sought parliamentary advice on which side would have the right to use the Labour name in the event of a breakaway. The expectation, based on the Registration of Politicial Parties Act, is that the leader would retain ownership. MPs acknowledge the possibility of a future split, but the option is not being pursued at any significant level. Though most rebels expect Corbyn to be re-elected, they hope to narrow his margin of victory and to win among full party members. This, they say, would deny the leader the right to boast of an "overwhelming" mandate. But without a dramatic change in Labour's selectorate, many now believe that it is only through a general election that the party's internal struggle will be resolved.

{ "pile_set_name": "OpenWebText2" }

Q: VB.NET [Cross-thread operation not valid: Control 'txtIncomingText' accessed from a thread........] I'm a beginner in VB.NET, please bear with me. I've downloaded a multiclient TCP-IP Socket Server-Client application in VB.NET. The Server listens pretty well, but the Client encounters below exception: "Cross-thread operation not valid: Control 'txtIncomingText' accessed from a thread other than the thread it was created on." I'll be greateful if you guys could help me with corrected version of the code. Thank you. ' ------- CLIENT CODE ------- Imports System.Windows.Forms Imports System.Collections.Generic Imports System.ComponentModel Imports System.Data Imports System.Drawing Imports System.Linq Imports System.Net Imports System.Net.Sockets Imports System.Text Imports System.Threading Public Class frmClient Inherits Form Private Sub frmClient_Load(sender As System.Object, e As System.EventArgs) Handles MyBase.Load End Sub Private _clientSocket As New Socket(AddressFamily.InterNetwork, SocketType.Stream, ProtocolType.Tcp) Public Sub New() InitializeComponent() End Sub Private receivedBuf As Byte() = New Byte(1023) {} Private thr As Thread Private Sub ReceiveData(ar As IAsyncResult) Dim socket As Socket = DirectCast(ar.AsyncState, Socket) Dim received As Integer = socket.EndReceive(ar) Dim dataBuf As Byte() = New Byte(received - 1) {} Array.Copy(receivedBuf, dataBuf, received) ' These two lines encounter an error ->>>>> txtIncomingText.Text = (Encoding.ASCII.GetString(dataBuf)) rbChat.Text = "\nServer: " + txtIncomingText.Text _clientSocket.BeginReceive(receivedBuf, 0, receivedBuf.Length, SocketFlags.None, New AsyncCallback(AddressOf ReceiveData), _clientSocket) End Sub Private Sub SendLoop() While True 'Console.WriteLine("Enter a request: "); 'string req = Console.ReadLine(); 'byte[] buffer = Encoding.ASCII.GetBytes(req); '_clientSocket.Send(buffer); Dim receivedBuf As Byte() = New Byte(1023) {} Dim rev As Integer = _clientSocket.Receive(receivedBuf) If rev <> 0 Then Dim data As Byte() = New Byte(rev - 1) {} Array.Copy(receivedBuf, data, rev) lbStt.Text = ("Received: " + Encoding.ASCII.GetString(data)) rbChat.AppendText(vbLf & "Server: " + Encoding.ASCII.GetString(data)) Else _clientSocket.Close() End If End While End Sub Private Sub LoopConnect() Dim attempts As Integer = 0 While Not _clientSocket.Connected Try attempts += 1 _clientSocket.Connect(IPAddress.Loopback, 420) Catch generatedExceptionName As SocketException 'Console.Clear(); lbStt.Text = ("Connection attempts: " + attempts.ToString()) End Try End While lbStt.Text = ("Connected!") End Sub Private Sub btnSend_Click(sender As System.Object, e As System.EventArgs) Handles btnSend.Click If _clientSocket.Connected Then Dim buffer As Byte() = Encoding.ASCII.GetBytes(txtText.Text) _clientSocket.Send(buffer) rbChat.AppendText("Client: " + txtText.Text) End If End Sub Private Sub btnConnect_Click(sender As System.Object, e As System.EventArgs) Handles btnConnect.Click LoopConnect() ' SendLoop(); _clientSocket.BeginReceive(receivedBuf, 0, receivedBuf.Length, SocketFlags.None, New AsyncCallback(AddressOf ReceiveData), _clientSocket) Dim buffer As Byte() = Encoding.ASCII.GetBytes("@@" + txtName.Text) _clientSocket.Send(buffer) End Sub End Class A: Well, you should invoke the calls on the control's thread. This is a quick and dirty solution Dim message = Encoding.ASCII.GetString(dataBuf) txtIncomingText.Invoke(Sub() txtIncomingText.Text = message) rbChat.Invoke(Sub() rbChat.Text = Environment.NewLine & "Server: " & message) But you should check if invocation is required first. See https://msdn.microsoft.com/en-us/library/ms171728(v=vs.110).aspx Also, "\n" is not how you make a new line in vb.net (did you copy this code from c#?). And + is not how you concatenate strings in vb.net (see above parenthesis).

{ "pile_set_name": "StackExchange" }

Takeuchi H, Savitzky AH, Ding L, et al. Evolution of nuchal glands, unusual defensive organs of Asian natricine snakes (Serpentes: Colubridae), inferred from a molecular phylogeny. Ecol Evol. 2018;8:10219--10232. 10.1002/ece3.4497 1. INTRODUCTION {#ece34497-sec-0001} =============== In the 20th Century, many biologists were focused on commonalities among taxa, as represented by studies using model organisms (Alberts et al., [2008](#ece34497-bib-0001){ref-type="ref"}). On the other hand, appreciating the diversity of life and its evolutionary origins has been another essential pursuit in biology (Rosenzweig, [1995](#ece34497-bib-0037){ref-type="ref"}; Whittaker, [1972](#ece34497-bib-0051){ref-type="ref"}). Because evolution of novel phenotypic characters, such as wings of birds and mammary glands of mammals, can facilitate the diversification of a lineage (Wagner & Lynch, [2010](#ece34497-bib-0049){ref-type="ref"}), investigation of the evolutionary history of such novel characters can provide basic information that clarifies the processes underlying species diversification. Snakes (Serpentes) comprise a distinct monophyletic taxon within the Squamata (Pyron, Burbrink, & Wiens, [2013](#ece34497-bib-0033){ref-type="ref"}), including over 3,500 species that are distributed on all continents except Antarctica (Wallach, Williams, & Boundy, [2014](#ece34497-bib-0050){ref-type="ref"}). In spite of their seemingly uniform appearance, snakes exhibit prominent morphological and ecological diversity (Greene, [1997](#ece34497-bib-0011){ref-type="ref"}; Lillywhite, [2014](#ece34497-bib-0021){ref-type="ref"}) and have often evolved novel organs that serve particular ecological functions. A well‐known example of a novel defensive structure is the rattle of rattlesnakes, which is used to warn potential predators of the snakes' venomous bite (Greene, [1997](#ece34497-bib-0011){ref-type="ref"}). The rattle evolved once in the ancestor of extant rattlesnakes (Castoe & Parkinson, [2006](#ece34497-bib-0005){ref-type="ref"}; Greene, [1997](#ece34497-bib-0011){ref-type="ref"}), and it has been lost secondarily in some island populations, where selection for defense is reduced in the absence of mammalian predators (Martins, Arnaud, & Murillo‐Quero, [2008](#ece34497-bib-0024){ref-type="ref"}; Rowe, Farrell, & May, [2002](#ece34497-bib-0038){ref-type="ref"}). The nuchal gland system is another example of a novel defensive structure that has evolved in snakes (Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}). Nuchal glands were originally described in a Japanese natricine snake, *Rhabdophis tigrinus* (Figure [1](#ece34497-fig-0001){ref-type="fig"}; Nakamura, [1935](#ece34497-bib-0031){ref-type="ref"}). The organs, which superficially resemble secretory structures, are embedded in the dermal layer of the dorsal skin of the neck. The nuchal glands of *R. tigrinus* contain cardiotonic steroid toxins known as bufadienolides (Hutchinson et al., [2007](#ece34497-bib-0019){ref-type="ref"}), which are sequestered from toads consumed as prey and can be redeployed as a defensive mechanism (Hutchinson et al., [2007](#ece34497-bib-0019){ref-type="ref"}). The glands of some other species also contain bufadienolides (Mori et al., unpublished). Ontogenetically, the nuchal glands are of mesodermal origin (Fukada, [1958](#ece34497-bib-0010){ref-type="ref"}; Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}), which is different from any other skin glands of terrestrial vertebrates, all of which arise from ectoderm (Savitzky et al., [2012](#ece34497-bib-0039){ref-type="ref"}). The glands lack a secretory epithelium and consist of a homogeneous population of fluid‐filled cells surrounding a dense aggregation of capillaries. There is no central lumen or duct, and the glands simply rupture through the skin to expel their fluid contents when the snake is under predatory attack (Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}). ![The snake, *Rhabdophis tigrinus*, in a defensive posture is directing the nuchal glands (NG) toward a perceived threat](ECE3-8-10219-g001){#ece34497-fig-0001} Nuchal glands and the structurally similar nucho‐dorsal glands (which extend the full length of the body; Smith, [1938](#ece34497-bib-0041){ref-type="ref"}) are currently known in 17 species of Asian Natricinae (Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}; Mori, Jono, Ding, et al., [2016](#ece34497-bib-0028){ref-type="ref"}). Hereafter, we refer to all such structures as nuchal glands, for simplicity. No other animals have been reported to possess organs similar in their structural details to the nuchal glands. The 17 species that possess such glands belong to three nominal genera, *Balanophis*,*Macropisthodon*, and *Rhabdophis*. Interestingly, *Macropisthodon* and *Rhabdophis* also include species that do not have nuchal glands (Table [1](#ece34497-tbl-0001){ref-type="table"}). This distribution might indicate the occurrence of (a) multiple independent origins of these unusual organs, (b) their secondary loss, and/or (c) improper generic assignment of some species. ###### A species list for the three nominal genera, *Balanophis*,*Macropisthodon*, and *Rhabdophis* Species Glands Source -------------------------------- -------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ***Balanophis ceylonensis*** P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***Macropisthodon flaviceps*** A/P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***M. plumbicolor*** P Mori, Jono, Takeuchi, Ding et al. ([2016](#ece34497-bib-0030){ref-type="ref"}) and Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *M. rhodomelas* P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***M. rudis*** A Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) and Takeuchi and Mori ([2012](#ece34497-bib-0045){ref-type="ref"}) ***Rhabdophis adleri*** P Mori, Jono, Ding et al. ([2016](#ece34497-bib-0028){ref-type="ref"}) *R. akraios* U Doria, Petri, Bellati, Tiso and Pistarino ([2013](#ece34497-bib-0006){ref-type="ref"}) *R. angelii* U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) *R. auriculatus* U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) *R. barbouri* U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) ***R. callichromus*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) *R. chrysargoides* U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) ***R. chrysargos*** A Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***R. conspicillatus*** A Mori, Jono, Takeuchi and Das ([2016](#ece34497-bib-0029){ref-type="ref"}) ***R. formosanus*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Takeuchi, Ota, Oh and Hikida ([2012](#ece34497-bib-0046){ref-type="ref"}) ***R. guandongensis*** U Zhu, Wang, Takeuchi and Zhao ([2014](#ece34497-bib-0053){ref-type="ref"}) ***R. himalayanus*** P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***R. lateralis*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Takeuchi et al. ([2012](#ece34497-bib-0046){ref-type="ref"}) ***R. leonardi*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) *R. lineatus* U Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) ***R. murudensis*** A/P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}), Smith ([1938](#ece34497-bib-0041){ref-type="ref"}), and Steubing and Lian ([2002](#ece34497-bib-0044){ref-type="ref"}) ***R. nigrocinctus*** P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***R. nuchalis*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}), Mori, Jono, Takeuchi, Ding et al. ([2016](#ece34497-bib-0030){ref-type="ref"}), and Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***R. pentasupralabialis*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Mori, Jono, Takeuchi, Ding et al. ([2016](#ece34497-bib-0030){ref-type="ref"}) *R. spilogaster* A Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***R. subminiatus*** P Smith ([1938](#ece34497-bib-0041){ref-type="ref"}) ***R. swinhonis*** A/P Mao and Chang ([1999](#ece34497-bib-0023){ref-type="ref"}) and Hsiang, Li and Yang (2009) ***R. tigrinus*** P Mori et al. ([2012](#ece34497-bib-0027){ref-type="ref"}) and Nakamura ([1935](#ece34497-bib-0031){ref-type="ref"}) Species included in the analyses of this study are shown by bold. P, A, and U indicate present, absent, and unknown, respectively. Our study strongly suggests that *Balanophis* and *Macropisthodon,* except *M. rudis,* belong to *Rhabdophis*. John Wiley & Sons, Ltd To infer the evolutionary history of the nuchal glands, we investigated the molecular phylogenetic relationships among Eurasian natricine species, including all but one of the species that have hitherto been reported to possess such glands (Table [1](#ece34497-tbl-0001){ref-type="table"}). Our phylogeny is based on partial sequences of the oocyte maturation factor Mos (Cmos) gene, the recombination‐activating gene 1 (RAG1), and the mitochondrial cytochrome b (MT‐CYB) gene, for a total of 2.7 kbp. Several recent phylogenetic studies of snakes have either focused on or included a number of Asian natricine species (Figueroa, Mckelvy, Grismer, Bell, & Lailvaux, [2016](#ece34497-bib-0009){ref-type="ref"}; Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"}; Pyron, Kandambi et al., [2013](#ece34497-bib-0034){ref-type="ref"}). However, no previous study has addressed the evolution of the nuchal glands. Furthermore, our sampling of species and populations of *Macropisthodon* and *Rhabdophis* is much greater than that of previous studies. Specifically, our main purpose was to answer three questions: (a) Have the nuchal glands originated only once, or have they arisen multiple times independently among natricine snakes? (b) Do the species of *Macropisthodon* and *Rhabdophis* that lack such glands represent the secondary loss of those structures? (c) Are any of the species lacking nuchal glands incorrectly assigned to *Macropisthodon* or *Rhabdophis*? 2. MATERIALS AND METHODS {#ece34497-sec-0002} ======================== A total of 122 sequences of natricine snakes and three sequences of outgroup taxa were used for phylogenetic analyses (Appendix [1](#ece34497-app-0001){ref-type="app"}). Of those, 54 sequences were obtained from GenBank. Because our preliminary analysis suggested that the sequence data for *Rhabdophis adleri* registered in GenBank were incorrectly identified, we did not use the GenBank data for that species. The other 68 sequences were obtained by the following methods. In each sample, total DNA was extracted from liver, skeletal muscle, or tail tips, which had been preserved in 99.5% ethanol or in freezers, using the DNeasy Tissue Kit (Qiagen). The Cmos, RAG1, and MT‐CYB regions were amplified with a PCR System GeneAmp 2700 Thermal Cycler (Applied Biosystems), using an Ex Taq Polymerase Kit (Takara Bio Inc.) and primers S77/S78 for Cmos (Lawson, Slowinski, Crother, & Burbrink, [2005](#ece34497-bib-0020){ref-type="ref"}), R13/R18 for RAG1 (Groth & Barrowchlough, [1999](#ece34497-bib-0012){ref-type="ref"}), and L14910/H16064 for MT‐CYB (Burbrink, Lawson, & Slowinski, [2000](#ece34497-bib-0004){ref-type="ref"}). The thermocycling schedule for the polymerase chain reaction (PCR) was identical to that described by these previous studies. Before sequencing, unincorporated primers were removed from the PCR products using polyethylene glycol precipitation. Cycle sequencing reactions were performed with the Big Dye Terminator Cycle Sequence Ready Reaction Kit, version 3.1 (Applied Biosystems), using the same primers as for PCR. The samples purified by ethanol precipitation were sequenced with a 3130xl Genetic Analyzer (Applied Biosystems). All fragments were sequenced for both forward and reverse sense. We assembled them using the GAP 4 program (Staden, [1996](#ece34497-bib-0042){ref-type="ref"}). Using CLUSTAL X (Thompson, Gibson, Plewniak, Jeanmougin, & Higgins, [1997](#ece34497-bib-0048){ref-type="ref"}), 125 sequences were aligned. Identical sequences from different specimens were treated as single units so that 114 sequences were recognized. To infer the phylogeny, we employed Maximum Likelihood (ML) using combined sequences (Cmos + RAG1 + MT‐CYB) and Bayesian inference (BI) using the sequence of mitochondrial DNA (MT‐CYB). For both data sets, the most appropriate pattern of sequence evolution was selected by applying the Bayesian Information Criterion (BIC; Schwarz, [1978](#ece34497-bib-0040){ref-type="ref"}), using MEGA5 (Tamura et al., [2011](#ece34497-bib-0047){ref-type="ref"}). We set the rate categories of discrete gamma rate heterogeneity as eight for ML and BI. Reliability of the ML tree was assessed by calculating bootstrap probability (BP; Felsenstein, [1985](#ece34497-bib-0008){ref-type="ref"}), with 1,000 replications. The BI tree was constructed using BEAST version 1.8 (Drummond & Rambaut, [2007](#ece34497-bib-0007){ref-type="ref"}), employing a single Markov chain Monte Carlo (MCMC) run for 50 million generations, sampled every 1,000 generations, and excluding the first 5 million generations as burn‐in. Convergence of the chains to the stationary distribution was checked by visual inspection, using TRACER version 1.6 (Rambaut, Suchard, Xie, & Drummond, [2007](#ece34497-bib-0036){ref-type="ref"}). To estimate divergence times, we employed Bayesian relaxed‐clock dating, using BEAST version 1.8. Because no fossils of *Balanophis*,*Macropisthodon*, or *Rhabdophis* are known, we set the following calibration points: 30 Mya (*SD* = 0.115) at the crown of natricine snakes, 22 Mya (*SD* = 0.15) at the crown of the genus *Natrix*, and 16 Mya (*SD* = 0.15) at the crown of the genus *Thamnophis* (Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}). 3. RESULTS {#ece34497-sec-0003} ========== The final alignment of three gene fragments consisted of 2,767 aligned base pairs. Of those, 787--1,149 bp were from MT‐CYB (114 taxa), 259--689 bp were from Cmos (86 taxa), and 855--929 bp were from RAG1 (21 taxa). The most appropriate model under the BIC was the GTR + G + I model for the data sets of both the ML and BI trees. The ML and BI trees were almost identical in topology. The ML tree (−In *L* = −35078.3994) is shown in Figure [2](#ece34497-fig-0002){ref-type="fig"}. A consensus tree from the ML and BI analyses is shown in Figure [3](#ece34497-fig-0003){ref-type="fig"}, along with the BP values from ML and the posterior probability (PP) value from BI at each node (shown only for BP ≥ 70% in ML and PP ≥ 0.90 in BI). The main difference between the ML and BI trees is the status of *Rhabdophis chrysargos*. Unlike the ML tree, the Bl tree supported monophyly of *R. chrysargos* + *R. conspicillatus* + 3 species of *Xenochrophis* (Figure [3](#ece34497-fig-0003){ref-type="fig"}a). ![Maximum likelihood tree (−In *L* = −35078.3994) based on the combined sequence data of the MT‐CYB, Cmos, and RAG1 genes under GTR + G + I. Bootstrap probabilities are provided at each node. Numerals following scientific names indicate individual codes (see Appendix [1](#ece34497-app-0001){ref-type="app"}). Status of nuchal or nucho‐dorsal glands of our three focal genera (*Rhabdophis, Macropisthodon, and Balanophis*) is indicated by blue (present), red (absent), purple (present/absent), and green (unknown; see also Table [1](#ece34497-tbl-0001){ref-type="table"}). The photographs have been digitally modified for clarity. Photograph of *Balanophis ceylonensis* by Udaya Chanaka](ECE3-8-10219-g002){#ece34497-fig-0002} ![Consensus tree based on ML and Bl trees. Bootstrap probabilities (BP) from the maximum likelihood tree (left) and posterior probabilities (PP) from Bayesian inference (right) are shown at each node (shown only BP ≥ 70% and PP ≥ 0.90). (a) All Natricinae included in our analysis. Species of our three focal genera (*Rhabdophis*,*Macropisthodon*, and *Balanophis*) are indicated in bold. (b) Phylogenetic relationships among the nuchal gland clade. For the three focal genera, P, A, and U after the OTU indicate present, absent, or unknown condition, respectively, of nuchal or nucho‐dorsal glands (see also Table [1](#ece34497-tbl-0001){ref-type="table"})](ECE3-8-10219-g003){#ece34497-fig-0003} Monophyly of Natricinae was strongly supported by the PP value. Within this subfamily, monophyly of the New World taxa (the Thamnophiini), and the Old World taxa *Natrix*,*Sinonatrix*,*Hebius*, and *Amphiesma *+* Xenochrophis *+* Atretium *+* Rhabdophis* + *Macropisth odon* (except *M. rudis*) + *Balanophis* clades were highly supported. Of the latter clade, a subclade of *Rhabdophis* (except *R. chrysargos* and *R. conspicillatus*) + *Macropisthodon* (except *M. rudis*) + *Balanophis* was separated from the remainder with strong support (Figure [2](#ece34497-fig-0002){ref-type="fig"}b). The average estimated divergence time of this subclade was 19.18 Mya (16.28--22.16 in 95% credible ranges). Hereafter, we refer to this subclade as the nuchal gland clade (NGC). Within this clade, *Macropisthodon plumbicolor* first diverged from the other species. The latter include *Rhabdophis subminiatus, R. murudensis* + *Macropisthodon flaviceps*,*R. himalayanus *+* Balanophis ceylonensis, R. tigrinus* + *R. lateralis* + *R. formosanus*, and a large group including *R. adleri* + *R. callichromus + R. nigrocinctus + R. swinhonis* + *R. guangdongensis* + *R. nuchalis* + *R. leonardi* + *R. pentasupralabialis* (with \>90% support in BP and/or 0.9 in PP). The latter clade comprises two subclades: *R. adleri* + *R. callichromus + R. nigrocinctus* and *R. swinhonis* + *R. guangdongensis* + *R. nuchalis* + *R. leonardi* + *R. pentasupralabialis*. Several nominal species exhibit substantial population structuring. *Rhabdophis subminiatus* exhibits strong differentiation between Laos/Vietnam and Thailand samples, and *R. nuchalis* consists of a number of population segments and is paraphyletic with respect to both *R. leonardi* and *R. pentasupralabialis*. 4. DISCUSSION {#ece34497-sec-0004} ============= Although differing in some details, recent molecular phylogenetic analyses of the Natricinae (Figueroa et al., [2016](#ece34497-bib-0009){ref-type="ref"}; Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"}; Pyron, Burbrink et al., [2013](#ece34497-bib-0033){ref-type="ref"}; Pyron, Kandambi et al., [2013](#ece34497-bib-0034){ref-type="ref"}), including ours, agree on the general pattern of relationships among the major lineages. A basal dichotomy separates the subfamily into two major clades. One includes the entire North American natricine fauna (the Thamnophiini) and its sister group, the Eurasian genus *Natrix*. Those two, in turn, are sister to a clade containing the Asian genera *Opisthotropis* and *Sinonatrix*. A clade containing two endemic Sri Lankan genera, *Aspidura* and *Haplocerus*, is variously recovered as sister to this North American--Eurasian clade (Pyron, Burbrink et al., [2013](#ece34497-bib-0033){ref-type="ref"}; Pyron, Kandambi et al., [2013](#ece34497-bib-0034){ref-type="ref"}) or as the most basal branch of the natricine clade (our study, but with weak support). The other major clade of natricines is almost entirely Asian, the sole exception being a monophyletic group of three African genera (*Afronatrix, Natriciteres,* and *Lycognathophis*, the latter not included in our analysis). The African clade is variously recovered as sister to, or embedded within, the much larger Asian radiation. The relationships among the Asian taxa display varying topologies among recent analyses, as taxon sampling within this group has improved. Consistent with other recent studies (Guo et al., [2014](#ece34497-bib-0017){ref-type="ref"}), we recover a monophyletic genus *Hebius*, distant from *Amphiesma stolatum*, as well as a polyphyletic *Xenochrophis*, some related to *Atretium* and others close to *Rhabdophis* and *Macropisthodon*. These results engender confidence in our analysis of the relationships within the NGC. 4.1. Evolution of the nuchal glands {#ece34497-sec-0005} ----------------------------------- Our results show that all species that possess nuchal glands belong to a single, strongly supported clade (NGC). Therefore, based on the principle of parsimony, we infer that the common ancestor of this clade possessed nuchal glands. We find no evidence of multiple, independent origins of the glands. Thus, interspecific differences in the distribution and morphology of the glands, such as the occurrence of nucho‐dorsal glands along the entire length of the body in *M. plumbicolor* and several species of *Rhabdophis* (Mori, Jono, Ding et al., [2016](#ece34497-bib-0028){ref-type="ref"}; Mori, Jono, Takeuchi, & Das, [2016](#ece34497-bib-0029){ref-type="ref"}; Smith, [1938](#ece34497-bib-0041){ref-type="ref"}) and the presence of elongate, nonsacculated glands accompanied by scaleless areas of skin in *M. rhodomelas* (not included in our analysis), *M. flaviceps*, and *B. ceylonensis* (Smith, [1938](#ece34497-bib-0041){ref-type="ref"}), are considered to represent alternative morphologies that arose after a single evolutionary origin of the nuchal gland system. Further study of the morphological details is needed to clarify the process of glandular diversification within this clade. Among species currently included in *Rhabdophis* and *Macropisthodon*,*R. chrysargos*,*R. conspicillatus*, and *M. rudis* have been reported to lack nuchal glands (Table [1](#ece34497-tbl-0001){ref-type="table"}; Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}; Mori, Jono, Takeuchi, & Das, [2016](#ece34497-bib-0029){ref-type="ref"}). *Macropisthodon rudis* is only distantly related to the NGC (see below), and *R. conspicillatus* and *R. chrysargos* also belong to clades outside the NGC. Thus, the absence of the nuchal glands in these species does not constitute secondary loss. Rather, it appears that they have simply retained the ancestral condition of the absence of integumentary defensive glands. *Rhabdophis swinhonis* has been reported to lack nuchal glands (Table [1](#ece34497-tbl-0001){ref-type="table"}; Mao & Chang, [1999](#ece34497-bib-0023){ref-type="ref"}). However, in contrast to *R. conspicill atus* and *R. chrysargos*, our analysis shows that this species occupies a position within the NGC. This strongly suggests that *R. swinhonis* has secondarily lost the nuchal glands. However, Hsiang, Li, and Yang ([2009](#ece34497-bib-0018){ref-type="ref"}) noted the presence of nuchal glands in this species. If both observations are correct, there are two possible interpretations: either the occurrence of intraspecific variation or the presence of two distinct but cryptic species. Whichever is true, the deeply nested position of *R. swinhonis* within the NGC implies the recent or ongoing secondary loss of the glands in at least some populations. Intraspecific variation in the presence of the nuchal glands also has been described in *R. murudensis* and *M. flaviceps* (Table [1](#ece34497-tbl-0001){ref-type="table"}; Smith, [1938](#ece34497-bib-0041){ref-type="ref"}; Mori et al., [2012](#ece34497-bib-0027){ref-type="ref"}). In our analysis, both species are recovered within the NGC. Therefore, as with *R. swinhonis*, the nuchal glands of *R. murudensis* and *M. flaviceps*, if accurately described in the literature, might be in a transitional stage of secondary loss or these nominal species may contain closely related cryptic species. We estimate that the common ancestor of the NGC arose 19.18 Mya. This is only slightly later than the date of 23--24 Mya shown by Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, Figure [2](#ece34497-fig-0002){ref-type="fig"}) for the origin of *Rhabdophis*, suggesting that nuchal glands arose at or soon after the origin of this genus. 4.2. Taxonomy {#ece34497-sec-0006} ------------- Our analysis requires a reevaluation of the taxonomic status of the genera *Balanophis* and *Macropisthodon*. The validity of the monotypic genus *Balanophis* (Smith, [1938](#ece34497-bib-0041){ref-type="ref"}) has been controversial. Malnate ([1960](#ece34497-bib-0022){ref-type="ref"}) recognized the species as *Rhabdophis ceylonensis*, and McDowell ([1961](#ece34497-bib-0025){ref-type="ref"}) supported his position. Figueroa et al. ([2016](#ece34497-bib-0009){ref-type="ref"}) found the species nested within *Rhabdophis*, as sister to *R. himalayanus*, and despite stating in the text (p. 21) that they declined to synonymize the genera, they recognized the species as *R. ceylonensis* in their figure 7a. Our analysis also strongly supports a sister relationship between *B. ceylonensis* and *R. himalayanus*, and thus, we formally propose that *Balanophis* be synonymized with *Rhabdophis*. Our analysis includes three of the four currently recognized species of *Macropisthodon* (Wallach et al., [2014](#ece34497-bib-0050){ref-type="ref"}), no two of which are recovered as each other\'s closest relative. When the genus was described by Boulenger ([1893](#ece34497-bib-0003){ref-type="ref"}), most other natricine snakes were treated as members of the genus *Tropidonotus*. Stejneger ([1907](#ece34497-bib-0043){ref-type="ref"}) placed *Tropidonotus* in the genus *Natrix*, where it remained until Malnate ([1960](#ece34497-bib-0022){ref-type="ref"}) divided *Natrix* sensu lato into six genera, resurrecting *Rhabdophis* Fitzinger, 1843. Malnate suggested that *Macropisthodon* might later prove not to be distinct from *Rhabdophis*, but the overreliance on characters of the maxillary dentition had precluded its earlier inclusion in *Natrix* and presumably influenced Malnate\'s decision to retain the genus. In our analysis, the type species of *Macropisthodon*,*M. flaviceps*, is strongly supported as sister to *R. murudensis*. Figueroa et al. ([2016](#ece34497-bib-0009){ref-type="ref"}) show the fourth species, *M. rhodomelas*, nested well within *Rhabdophis*. Therefore, we synonymize *Macropisthodon* with *Rhabdophis*. Thus, it is presently reasonable to include all species belonging to the NGC within *Rhabdophis*, the type species of which is *R. subminiatus*. However, partitioning of this morphologically diverse clade should be considered in the future. The divergent position of *Macropisthodon rudis*, which lacks nuchal glands and is recovered as distant from the NGC, supports the resurrection of the monotypic genus *Pseudoagkistrodon* (Van Denburgh 1909), as suggested by Wallach et al. ([2014](#ece34497-bib-0050){ref-type="ref"}). Although recent studies have differed in the exact placement of this species (Guo et al., [2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"}), no analysis with sufficient taxon sampling of Asian natricines has placed it close to *Rhabdophis*. The taxonomic status of "*R". conspicillatus* and *"R". chrysargos*, which lie just outside the NGC, remains to be determined. Our analysis suggests that *Rhabdophis* contains several undescribed species. Substantial genetic divergence occurs within *R. nigrocinctus, R. swinhonis, R. nuchalis*, and especially *R. subminiatus*. A comprehensive analysis of this complex subclade, including both morphological and molecular studies, will be necessary before this group can be reliably partitioned. 5. CONCLUSIONS {#ece34497-sec-0007} ============== Our analysis indicates that the nuchal and nucho‐dorsal glands, as a group, have evolved only once among Asian natricine snakes. The absence of the nuchal glands in some nominally congeneric species, such as *M. rudis, R. conspicillatus,* and *R. chrysargos*, reflects old classifications based on phenetic analysis of morphological characters. All of those species lie outside the single clade that possesses the defensive glands. However, a few species within the nuchal gland clade (*M. flaviceps, R. murudensis,* and *R. swinhonis*) may represent a transitional stage in the secondary loss of the glands. Clarification of the developmental origin of these unique organs is likely to provide insight into how these neomorphic structures have arisen, diversified, and may subsequently be disappearing in a few species. The nuchal glands are fruitful subjects for investigating the evolution of novel biological systems that involve the complex interplay of morphology, physiology, ecology, and behavior. AUTHOR CONTRIBUTIONS {#ece34497-sec-0009} ==================== Hirohiko Takeuchi designed and performed research, analyzed data, and wrote the paper. Alan H. Savitzky designed research and wrote the paper. Li Ding designed and performed research in China. Anslem de Silva performed research in Sri Lanka. Indraneil Das performed research in Malaysia. Tao Thien Nguyen performed research in Vietnam. Tein‐Shun Tsai performed research in Taiwan. Teppei Jono performed research in China and analyzed data in Japan. Guang‐Xiang Zhu performed research in China. Dharshani Mahaulpatha performed research in Sri Lanka. Yezhong Tang designed and performed research in China. Akira Mori designed and performed research and wrote the paper. DATA ACCESSIBILITY {#ece34497-sec-0010} ================== DDBJ accessions [LC325298](LC325298)--[LC325357](LC325357), [LC325746](LC325746)--[LC325803](LC325803), and [LC326011](LC326011)--[LC326031](LC326031) (DNA sequences). We thank K. Kurita and T. Okamono for further instruction in phylogenetic analyses and Y. Kojima for assistance with executing phylogenetic analyses. We are indebted to H. Ota and N. Kuraishi for providing tissue samples, D.‐E. Lin, C. Li, Y.‐W. Yeh, and C.‐A. Tu for assistance in collecting tissue samples*,* Q. Chen for field assistance, U. Chanaka for providing a photograph, and the Vice Chancellor and Dean, University of Sri Jayewardenepura for allowing the maintenance of live snakes and for providing laboratory facilities. We are grateful to the Council of Agriculture, Executive Yuan, Taiwan for permits to collect snakes in Taiwan and for the export permit to Kyoto University (Permit No. AGF4X104070012); and to the Department of Wildlife Conservation, Sri Lanka for permits to collect snakes in Sri Lanka and for the export permit to Kyoto University. This study was supported by grants from the Japan--China Joint Research Project (2014--2016) between the Japan Society for the Promotion of Science (JSPS) and National Natural Science Foundation of China (NSFC, 31411140033) and from JSPS Scientific Researches C (26440213) and B (17H03719). This research was partially supported by project grant DTDLXH.19/15 and BSTMV.08/16‐19 to NTT, by the Niche Research Grant Scheme from the Ministry of Higher Education, Government of Malaysia (NRGS/1087/2013(01); IA010200‐0708‐0007) to ID, by a grant from National Natural Science Foundation of China (NSFC, 31401959) to GSZ, and by grants from NSFC (Fund for Young International Scientists: 31450110454), Chinese Academy of Sciences Fellowship for Young International Scientists (Y5C3051100), and JSPS (16J06675) to TJ. This study was also supported in part by the Global COE Program A06 to Kyoto University from MEXT and by funding provided to AHS by Utah State University. 1.1. Accession numbers and their localities (countries) for all DNA sequence data used in the phylogenetic analyses in this study. Individuals with an asterisk indicate identical sequences within the species, and thus have the same accession number. Names (and No.) in the species column correspond to those shown in Figure [1](#ece34497-fig-0001){ref-type="fig"} {#ece34497-sec-0011} =========================================================================================================================================================================================================================================================================================================================================================================== SpeciesIndividual No.CountryAccession no. of GenBankReferencesCyt.bC‐mosRag‐1*Afronatrix anoscopus*ROM19842Liberia[AF420073](AF420073)[AF471123](AF471123)[EU402832](EU402832)Lawson et al., [2005](#ece34497-bib-0020){ref-type="ref"}, de Queiroz, Lawson, and Lemos‐Espinal [2002](#ece34497-bib-0035){ref-type="ref"}, and Wiens et al. ([2008](#ece34497-bib-0052){ref-type="ref"})*Amphiesma stolatum*\_1HT0548China[LC325319](LC325319)[LC325765](LC325765)--This study*Amphiesma stolatum*\_2HT0798Sri Lanka[LC325347](LC325347)[LC325793](LC325793)[LC326030](LC326030)This study*Amphiesma stolatum*\_3GP2213China[KJ685693](KJ685693)[KJ685643](KJ685643)[KJ685585](KJ685585)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})*Aspidura guentheri*RAP0437Sri Lanka[KC347472](KC347472)[KC347380](KC347380)[KC347418](KC347418)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})*Atretium schistosum*\_1HT0799Sri Lanka[LC325348](LC325348)[LC325794](LC325794)--This study*Atretium schistosum*\_2--Sri Lanka[KC347487](KC347487)[KC347383](KC347383)[KC347421](KC347421)Pyron Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})*Atretium yunnanensis*GP842China[JQ678448](JQ678448)[JQ281787](JQ281787)[KJ685602](KJ685602)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})*Balanophis ceylonensis*\_1HT0785Sri Lanka[LC325339](LC325339)[LC325785](LC325785)[LC326026](LC326026)This study*Balanophis ceylonensis*\*\_2HT0786Sri Lanka[LC325339](LC325339)----This study*Balanophis ceylonensis*\_3HT0787Sri Lanka[LC325340](LC325340)[LC325786](LC325786)--This study*Haplocercus ceylonensis*RS145Sri Lanka[KC347478](KC347478)[KC347401](KC347401)[KC347438](KC347438)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})*Hebius atemporale*HT0550China[LC325320](LC325320)[LC325766](LC325766)--This study*Hebius craspedogaster*HT0801China[LC325350](LC325350)[LC325796](LC325796)--This study*Hebius ishigakiensis*HT0800Japan[LC325349](LC325349)[LC325795](LC325795)--This study*Hebius khasiense*HT0679Vietnam[LC325327](LC325327)[LC325773](LC325773)--This study*Hebius octolineatus*HT0586China[LC325321](LC325321)[LC325767](LC325767)--This study*Hebius pryeri*HT0340Japan[LC325312](LC325312)[LC325758](LC325758)--This study*Hebius vibakari*\_1HT0274Japan[LC325309](LC325309)[LC325755](LC325755)--This study*Hebius vibakari*\_2HT0277Japan[LC325310](LC325310)[LC325756](LC325756)--This study*Macropisthodon flaviceps*HT0809Malaysia[LC325355](LC325355)[LC325801](LC325801)--This study*Macropisthodon plumbicolor*\_1HT0782Sri Lanka[LC325336](LC325336)[LC325782](LC325782)[LC326025](LC326025)This study*Macropisthodon plumbicolor*\_2HT0783Sri Lanka[LC325337](LC325337)[LC325783](LC325783)--This study*Macropisthodon plumbicolor*\_3HT0784Sri Lanka[LC325338](LC325338)[LC325784](LC325784)--This study*Macropisthodon rudis*\_1HT0339China[LC325311](LC325311)[LC325757](LC325757)[LC326016](LC326016)This study*Macropisthodon rudis*\_2GP1266China[JQ687452](JQ687452)[JQ687434](JQ687434)[KJ685566](KJ685566)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})*Natriciteres olivacea*--Congo[AF471058](AF471058)[AF471146](AF471146)--Lawson et al. ([2005](#ece34497-bib-0020){ref-type="ref"})*Natrix maura*\_1--Spain[AY866530](AY866530)----Guicking, Lawson, Joger and Wink ([2006](#ece34497-bib-0015){ref-type="ref"})*Natrix maura*\_2--Tunisia[AY487682](AY487682)----Guicking, Joger and Wink ([2008](#ece34497-bib-0013){ref-type="ref"})*Natrix maura*\_3--Italy[AY487683](AY487683)----Guicking et al. ([2008](#ece34497-bib-0013){ref-type="ref"})*Natrix natrix*\_1--Spain[AY866536](AY866536)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})*Natrix natrix*\_2--France[AY866537](AY866537)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})*Natrix tessellata*\_1--Iran[AY487574](AY487574)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})*Natrix tessellata*\_2--Iran[AY487575](AY487575)----Guicking, Joger and Wink ([2009](#ece34497-bib-0014){ref-type="ref"})*Natrix tessellata*\_3--Bulgaria[AY866533](AY866533)----Guicking et al. ([2006](#ece34497-bib-0015){ref-type="ref"})*Nerodia cyclopion*--USA[AF402909](AF402909)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Nerodia erythrogaster*--USA[AF402912](AF402912)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Nerodia fasciata*--USA[AF402910](AF402910)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Nerodia floridana*--USA[AF402911](AF402911)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Nerodia rhombifer*--USA[AF402915](AF402915)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Nerodia sipedon*--USA[AF402913](AF402913)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Nerodia taxispilota*--USA[AF402914](AF402914)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Opisthotropis cheni*GP383China[GQ281779](GQ281779)[JQ687441](JQ687441)[KJ685595](KJ685595)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})*Opisthotropis guangxiensis*GP746China[GQ281776](GQ281776)[JQ687447](JQ687447)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})*Opisthotropis lateralis*GP646China[GQ281782](GQ281782)[JQ687445](JQ687445)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})*Opisthotropis latouchii*GP647China[GQ281783](GQ281783)[JQ687446](JQ687446)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})*Opisthotropis typica*HT0794Malaysia[LC325343](LC325343)[LC325789](LC325789)[LC326028](LC326028)This study*Pseudoxenodon macrops* (Out group)\_1HT0646China[LC325323](LC325323)[LC325769](LC325769)--This study*Pseudoxenodon macrops* (Out group)\_2HT0802Malaysia[LC325351](LC325351)[LC325797](LC325797)--This study*Regina grahami*--USA[AF402918](AF402918)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Regina rigida*\_1--USA[AF402919](AF402919)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Regina rigida*\_2CAS:HERP:165994USA[AF471052](AF471052)[AF471120](AF471120)--Lawson et al. ([2005](#ece34497-bib-0020){ref-type="ref"})*Regina septemvittata*--USA[AF402917](AF402917)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Rhabdophis adleri*\_1HT0831China[LC325356](LC325356)[LC325802](LC325802)--This study*Rhabdophis adleri*\_2HT0832China[LC325357](LC325357)[LC325803](LC325803)--This study*Rhabdophis callichromus*\_1HT0654Vietnam[LC325324](LC325324)[LC325770](LC325770)--This study*Rhabdophis callichromus*\_2HT0674Vietnam[LC325325](LC325325)[LC325771](LC325771)[LC326020](LC326020)This study*Rhabdophis chrysargos*HT0342Malaysia[LC325313](LC325313)[LC325759](LC325759)[LC326017](LC326017)This study*Rhabdophis conspicilatus*HT0791Malaysia[LC325342](LC325342)[LC325788](LC325788)[LC326027](LC326027)This study*Rhabdophis formosanus*\_1HT0033Taiwan[LC325304](LC325304)[LC325750](LC325750)--This study*Rhabdophis formosanus*\*\_2HT0031Taiwan[LC325304](LC325304)----This study*Rhabdophis formosanus\**\_3HT0030Taiwan[LC325304](LC325304)----This study*Rhabdophis guangdongensis*SYSr000018China[KF800930](KF800930)[KF800920](KF800920)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})*Rhabdophis himalayanus*\_1HT0847China[LC325299](LC325299)[LC325746](LC325746)[LC326011](LC326011)This study*Rhabdophis himalayanus*\*\_2HT0848China[LC325299](LC325299)----This study*Rhabdophis himalayanus*\*\_3HT0849China[LC325299](LC325299)----This study*Rhabdophis himalayanus*\_4CAS224420Myanmar[KF800929](KF800929)[KF800919](KF800919)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})*Rhabdophis lateralis*\_1HT0855China[LC325302](LC325302)----This study*Rhabdophis lateralis*\_2GP613China[JQ687444](JQ687444)[GQ281785](GQ281785)[KJ685600](KJ685600)Guo et al. ([2014](#ece34497-bib-0017){ref-type="ref"})*Rhabdophis leonardi*\_1HT0851China[LC325300](LC325300)[LC325747](LC325747)[LC326012](LC326012)This study*Rhabdophis leonardi\*\_*2HT0852China[LC325300](LC325300)----This study*Rhabdophis leonardi\*\_*3HT0853China[LC325300](LC325300)----This study*Rhabdophis leonardi*\_4RDQ200905367China[KF800932](KF800932)[KF800922](KF800922)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})*Rhabdophis murudensis*HT0788Malaysia[LC325341](LC325341)[LC325787](LC325787)--This study*Rhabdophis nigrocinctus*\_1HT0253Thailand[LC325307](LC325307)[LC325753](LC325753)[LC326015](LC326015)This study*Rhabdophis nigrocinctus*\_2HT0343Thailand[LC325314](LC325314)[LC325760](LC325760)--This study*Rhabdophis nigrocinctus*\_3HT0845China[LC325298](LC325298)----This study*Rhabdophis nuchalis*\_1HT0701China[LC325333](LC325333)[LC325779](LC325779)[LC326022](LC326022)This study*Rhabdophis nuchalis*\_2HT0803China[LC325352](LC325352)[LC325798](LC325798)--This study*Rhabdophis nuchalis*\_3HT0807China[LC325353](LC325353)[LC325799](LC325799)[LC326031](LC326031)This study*Rhabdophis nuchalis*\_4HT0854China[LC325301](LC325301)[LC325748](LC325748)--This study*Rhabdophis nuchalis*\_5SICAU090001China[KF800925](KF800925)[KF800935](KF800935)--Zhu et al. ([2014](#ece34497-bib-0053){ref-type="ref"})*Rhabdophis pentasupralabialis*\_1HT0699China[LC325331](LC325331)[LC325777](LC325777)--This study*Rhabdophis pentasupralabialis*\_2HT0700China[LC325332](LC325332)[LC325778](LC325778)[LC326021](LC326021)This study*Rhabdophis pentasupralabialis*\_3HT0808China[LC325354](LC325354)[LC325800](LC325800)--This study*Rhabdophis subminiatus*\_1HT0267Laos[LC325308](LC325308)[LC325754](LC325754)--This study*Rhabdophis subminiatus*\_2HT0344Thailand[LC325315](LC325315)[LC325761](LC325761)--This study*Rhabdophis subminiatus*\_3HT0345Thailand[LC325316](LC325316)[LC325762](LC325762)--This study*Rhabdophis subminiatus*\_4HT0680Vietnam[LC325328](LC325328)[LC325774](LC325774)--This study*Rhabdophis swinhonis*\_1HT0021Taiwan[LC325303](LC325303)[LC325749](LC325749)--This study*Rhabdophis swinhonis*\_2HT0717Taiwan[LC325334](LC325334)[LC325780](LC325780)[LC326023](LC326023)This study*Rhabdophis swinhonis*\*\_3HT0716Taiwan[LC325334](LC325334)----This study*Rhabdophis swinhonis*\*\_4HT0718Taiwan[LC325334](LC325334)----This study*Rhabdophis swinhonis*\*\_5HT0719Taiwan[LC325334](LC325334)----This study*Rhabdophis tigrinus*\_1HT0098Japan[LC325305](LC325305)[LC325751](LC325751)[LC326013](LC326013)This study*Rhabdophis tigrinus*\_2HT0177Japan[LC325306](LC325306)[LC325752](LC325752)[LC326014](LC326014)This study*Sibynophis subpunctatus* (Out group)RAP0491Sri Lanka[KC347471](KC347471)[KC347411](KC347411)[KC347449](KC347449)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})*Sinonatrix aequifasciata*\_1HT0678Vietnam[LC325326](LC325326)[LC325772](LC325772)--This study*Sinonatrix aequifasciata*\_2HT0681Vietnam[LC325329](LC325329)[LC325775](LC325775)--This study*Sinonatrix aequifasciata*\_3GP357China[JQ687430](JQ687430)[JQ687440](JQ687440)--Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"})*Sinonatrix annularis*GP889China[JQ687431](JQ687431)[JQ687449](JQ687449)[KJ685604](KJ685604)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"})*Sinonatrix percarinata*GP956China[JQ687433](JQ687433)[JQ687451](JQ687451)[KJ685607](KJ685607)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"})*Storeria dekayi*CAS:HERP:196039USA[AF471050](AF471050)[AF471154](AF471154)--Lawson et al. ([2005](#ece34497-bib-0020){ref-type="ref"})*Thamnophis butleri*--USA[AF402923](AF402923)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis couchii*--USA[AF402936](AF402936)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis cyrtopsis*--USA[AF402924](AF402924)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis elegans*--USA[AF402925](AF402925)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis godmani*--Mexico[AF420135](AF420135)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis marcianus*--USA[AF402926](AF402926)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis ordinoides*--USA[AF402927](AF402927)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis proximus*----[AF402928](AF402928)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis radix*--USA[AF402934](AF402934)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis sirtalis*\_1----[AF402929](AF402929)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Thamnophis sirtalis*\_2----[AF402930](AF402930)----Alfaro and Arnold ([2001](#ece34497-bib-0002){ref-type="ref"})*Trachischium monticola*GP1487China[JQ687428](JQ687428)[JQ687435](JQ687435)[KJ685570](KJ685570)Guo et al. ([2012](#ece34497-bib-0016){ref-type="ref"}, [2014](#ece34497-bib-0017){ref-type="ref"})*Xenochrophis asperrimus*\_1HT0797Sri Lanka[LC325346](LC325346)[LC325792](LC325792)--This study*Xenochrophis asperrimus*\_2--Sri Lanka[KC347480](KC347480)[KC347414](KC347414)[KC347451](KC347451)Pyron, Kandambi et al. ([2013](#ece34497-bib-0034){ref-type="ref"})*Xenochrophis flavipunctatus*HT0682Vietnam[LC325330](LC325330)[LC325776](LC325776)--This study*Xenochrophis maculatus*HT0720Malaysia[LC325335](LC325335)[LC325781](LC325781)[LC326024](LC326024)This study*Xenochrophis piscator*\_1HT0347Thailand[LC325317](LC325317)[LC325763](LC325763)[LC326018](LC326018)This study*Xenochrophis piscator*\_2HT0371Vietnam[LC325318](LC325318)[LC325764](LC325764)--This study*Xenochrophis piscator*\_3HT0796Sri Lanka[LC325345](LC325345)[LC325791](LC325791)--This study*Xenochrophis trianguligerus*HT0795Malaysia[LC325344](LC325344)[LC325790](LC325790)[LC326029](LC326029)This study*Xenochrophis vittatus*\_1HT0615Indonesia[LC325322](LC325322)[LC325768](LC325768)[LC326019](LC326019)This study*Xenochrophis vittatus\**\_2HT0527Indonesia[LC325322](LC325322)----This study

{ "pile_set_name": "PubMed Central" }

"Hey." "Ohh!" "You scared me." "Sorry." "I hit a wall." "Whoa, oh." "Give me a second." "Well, our time's almost up, anyway." "Here, let me just show you a couple of cool-down stretches." "Next time." "You hired me as your personal trainer, right?" "Right." "And here's your training lesson for today." "Next time needs to be now time." "It's just..." "I got some errands to run." "I'll see you Saturday." "Hey!" " Yeah." " Terry." "Pain is not gain." "Got it?" "I got it." "♪ I'm talkin' behind your back ♪" "♪ you better be payin' attention ♪" "♪ there's a war goin' on" "♪ rollin' up my short sleeves" "♪ ...almost everything I ever had ♪" "♪ and you make me so mad" "♪ I'm lookin' at..." "What do you mean, he's not going?" "Every kid loves trick-or-treating." "Henry's scared." "One of his little buddies told him Halloween was the only time when all the real monsters come out because they can blend in." "Never thought about that." "Good monster strategy." "You did tell him it wasn't true, right?" "Of course I did." "But he's convinced." "Childhood fears are resistant to adult logic." "Sometimes you just have to wait it out." "For how long?" "Well, if he's 23 and this still worries you, you got a problem." "Well, see, the thing is, I think I am partly to blame." "How?" "Well, the other night will and I were up late, we were having some wine, talking about some of the cases we've worked on, and at one point, I said I felt like there was no end" "to all the monsters walking around, and..." "Henry sneaked into the room to listen to the grownups." "Yeah." "We need a cone of silence for our house." "Those of you who like a good mystery, please unleash your inner Agatha Christie, 'cause this one's a real humdinger." "Gary Ellard, Barry Deaver, Paul Hicks, Terry Rodgers." "Over the course of the last month and a half, these 4 men have gotten in their cars in La Grande, Oregon, and drove into the never-to-be-seen-agains-ville, poof, gone." "The latest victim Terry Rodgers disappeared 24 hours ago." "Forensic evidence point us anywhere?" "Uh, point would imply there is evidence, and there is no evidence, at least for the first 3 victims." "No forensics, no witnesses, no ransom demands." "Maybe these guys just voluntarily decided to hit the road." "4 sudden disappearances in a community this small-- this isn't about seeking green pastures." "Based on last known sightings, we're dealing with a sizeable geographic area." "He's efficient and well organized." "It's not easy to make 4 people vanish and stay vanished." "It has been done before, though." "Political kidnappings frequently require holding multiple adults simultaneously." "Or they're already dead." "Nothing says "can't be found"" "like a shallow grave in the middle of nowhere." "Assuming they are alive, how is the unsub controlling them?" "And for what purpose?" "The time between abductions is shortening with each victim." "Wheels up in 30." "♪ Criminal Minds 8x05 ♪ The Good Earth Original Air Date on October 31, 2012" "== sync, corrected by elderman ==" "♪" ""I became insane, with long intervals of horrible sanity."" "Edgar Allan Poe." "Garcia, anything on the last victim, Terry Rodgers?" "Only that he's unemployed and lives in a cabin in the woods." "But primitive, like no flush toilet primitive." "That doesn't fit the victimology of the other 3." "Ellard coaches track and field at a local college," "Deaver's a small business owner, and Hicks is an attorney." "All married with young families." "Another difference-- the first 3 victims were all born and raised in La Grande." "Terry Rodgers only moved to town a couple of months ago." "Do you know where from, Garcia?" "Rhode Island." "Though there's a 5-month gap between Terry being in Rhode Island and then arriving in Oregon." "Where he was and what he was doing is a big fat blank." "It says here that vomit was found in the vicinity of his abduction." "Mm." "Thank you for reminding me of that disgusting detail, Dreamy D." "Yes, that vomit has been collected and is being analyzed as we speak, and I'm very grateful that I have this job and someone has that one that's not me." "Rodgers is the obvious anomaly of the 4, but there's no apparent overlap between any of the victims." "Almost like the unsub was selecting his targets at random." "Blake, you and Morgan go talk to the families of the victims." "See if there's something that links them that's not on paper." "Dave and I will go to the abduction site." "Reid, you and JJ go to Terry Rodgers' cabin." "He's the one we know least about." "Maybe he made himself obscure for a reason." "Sheriff, I'm Agent Hotchner." "This is Agent Rossi." "Sheriff Colwin." "I am glad to have your help." "The best we can reconstruct it, victim's car veered off the road at a low rate of speed, plowed through the fence, and ended up in the field." "He managed to get about 20 feet away before throwing up." "The photo showed a second set of tracks." "Were you able to pull a tread pattern?" "We're checking on it right now." "Maybe our guy got sick and had to pull over." "Or he was forced off the road." "Either way, the unsub was following him." "Mrs. Deaver, did your husband give any indication at all that something might be wrong the night he disappeared?" "No, not at all." "Barry was supposed to coach our son's little league game that night." "So he wasn't depressed, preoccupied?" "Nothing." "It was a day like any other day." "This is what happens to other people." "You see it on the news, you know." "Give it, what, 30 seconds of your time?" "Shake your head, go back to whatever stupid thing you were doing." "Washing dishes or putting away laundry." "You never think it's going to happen to you." "Go ahead, you're on speaker, Garcia." "Sir, I just got the full lab report for the... you know, the regur-- for the puke, and there's no toxins or bacterial infections." "However, Terry Rodgers did have elevated levels of Melatonin in his system." "And I'm sending you the full lab report..." "Now, on your phones." "Elevated?" "His Melatonin levels are off the chart." "Is that significant?" "It's a sedative." "An amount this large would induce extreme drowsiness." "Do you think he might have overdosed my accident?" "No, no, this was no accident." "The victim was drugged." "Sheriff, the police report said there were groceries in Rodgers' car." "Do you know if he ate anything out of the bags?" "He didn't." "We compared the supermarket receipt to what was in the bags." "Nothing missing." "So, how did Rodgers unknowingly ingest such a massive dose of Melatonin?" "You know, aside from the outhouse, this cabin isn't so primitive." "Ok." "Economics, philosophy, political theory." "It isn't exactly breezy, take to the beach reading." "I would, but I don't really like the beach." "Why is that?" "Sandy food, pink skin, limited and unengaging topography, but mostly the drug-resistant bacteria spread by sea gull feces." "Sorry I asked." "You know, there's a lot of material here about global warming, overcrowding." "The evils of technology." "There's no phone, no TV." "I wonder what this guy does for fun." "I think maybe I just found the answer." "Tread marks were inconclusive." "Probably from a pickup truck, though." "What's that?" "The likely routes our 4 victims to on the day they disappeared." "Gary Ellard-- apartment, DMV, was a no-show for his morning class at Eastern Oregon University." "Barry Deaver--home, gas station, never made it to his karate group." "Paul Hicks--home, daughter's preschool, doctor's appointment." "He was supposed to meet a client over here but never showed." "And we already know about Terry Rodgers." "And all this tells you what?" "It's more about what it doesn't tell us." "None of the lines intersect." "I just had a chat with Terry Rodgers' personal trainer." "She said he never talked about his private life." "He's shelling out for a personal trainer?" "This is a guy with no indoor plumbing." "She said he was dedicated." "Not in great shape, but dedicated." "Hey." "You're talking to the room, P.G." "Mm." "If by P.G. You mean parental guidance strongly advised," "I say P.A., prudent advice." "Ok, here's what's happened." "I checked all the employees and vendors and delivery people who work at the supermarket where Terry Rodgers bought his groceries, and there were no red flags." "Also, Barry Deaver, the second victim," "I found his car." " Where?" " Impounded." "It was abandoned 3 weeks ago on Fish Hatchery Road, picked up by Gus' Towing Service, where it has been collecting dust and racking up storage fees ever since." "Where's Fish Hatchery Road?" "Off the beaten track, like Terry Rodgers." "Looks like the unsub's hunting grounds are rural and remote." "Well, to have ended up there," "Barry Deaver must have gone on a diagonal, north first, and then headed west towards his karate class." "So, did you learn anything?" "Yeah." "Spence here does not like the beach." "I don't." "Terry Rodgers definitely wanted to live off the grid." "A small generator for minimal electrical needs." "No phone, no TV, no radio." "And lots of material about the evils of technology, living healthy off the land, that sort of thing." "Sounds like the unabomber." "We did find a small stash of marijuana hidden away." "Did you find any evidence that a baby lived there or visited there?" "Uh, no, why?" "I just got the list of things that he bought at the supermarket." "4 jars of baby food." "A body matching Rodgers' description was found in a river 10 miles out of town." "Easy." "Easy." "Right there." "A fisherman found him washed up on a bank." "Well, other than the ligature marks on the wrists and ankles, there's no signs of violence or torture." "A lot of care was taken with the killing and disposing of the body." "Sedation and drowning." "We may have to dramatically reassess who the unsub is." "What do you mean?" "We might be looking for a woman." "Mommy?" "Lexy!" "I told you to never come out here by yourself." "I know, but I'm hungry." "Stay away from the barn." "There's a lot of dangerous equipment in there." "You could hurt yourself." "Go back to the house and stay there." "I'll be in to fix you something." "But I mean it-- stay there." "Ok." "There's got to be something else that links these victims." "They were all athletic." "Ellard teaches track and field." "Deaver has a martial arts studio." "Paul Hicks had tendonitis from playing competitive tennis." "But Rodgers' trainer said that he was out of shape." "Did the medical examiner determine Rodgers' time of death?" "3 hours from when he was found at the river." "So the unsub kept Rodgers alive for the entire day before drowning him." "Go ahead, Garcia." "Ok." "I've got something." "That's really bugging me." "I can't figure out what Terry Rodgers was doing those missing 5 months." "I mean, you can't sit on a park bench in this country and not leave a paper trail." "But you figured it out." "No." "This is me venting." "What I did figure out was what Terry Rodgers was doing in Rhode island before he went awol." "Check it." "He was married, divorced, married again, currently way behind on child support payments to wife number two, and that's all I know." "If you'll excuse me, I have more digging to do." "Owes child support." "Could explain why Rodgers vanished for 5 months." "And why he lived off the grid." "Hard to find." "And that's what links him to the other victims." "They all fathered children." "We believe the unsub that we're looking for is a woman, who is highly organized, she's thorough, and she's patient." "Based on the complexity and the sophistication of the abductions, we think she is most likely between the ages of 30 and 40." "She's familiar with the rural area surrounding La Grande." "Either a native or someone who's lived there for a while." "We think she's keeping her victims in isolation in the countryside, which means she has access to land or a structure that is remote, hidden, and private." "She's abducting exceptionally health conscious men, ideal specimens, if you will." "Specimens." "For what?" "Possible breeding." "Ability to father children is something we think she's looking for in her victims." "They're all age appropriate, and they are all fathers." "But why kill the last victim?" "She may have seen him as being flawed." "He was the least physically fit of the 4, and he neglected to pay child support." "Making him undesirable." "The victims may be surrogates for a man that she wants but she cannot have." "Because she killed the last victim, we have to consider the possibility that the unsub is engaged in some sort of elimination process." "Preselecting a handful of prime candidates and then whittling them down one by one until she has her ideal breeding partner." "And if this is the case, the the killing's just begun." "Mommy, what's the matter?" "We got a frequent flier." "Which one?" "The tomato lady." "I don't believe this." "Emma." "Dr. Gourse." "Thank God you're here." "Those other doctors don't understand my history." "Yeah, I thought we talked about this last time." "Yeah, we did." "But the scleroderma came back." "Look." "There's nothing on your arm." "But it's right there." "You treated me after my husband died." "It's the same thing." "Yeah, your scleroderma was treated successfully." "You are fine now." "But this could be a mutation." "Things mutate." "What about Stevens-Johnson syndrome?" "Stevens-Johnson is extremely rare." "And you'd have severe blistering all over your face." "Emma, we talked before about how a delusion" "I'm not crazy." "Emma, listen to me." "There may be other issues that are going on with you." "Did you contact the therapist that I recommended?" "I guess that's no." "I'm still waiting on the full M.E. report on Terry Rodgers." "They say they want to retest some of the findings." "Did they say why?" "No." "I recognize that scowl, Aaron." "What are you thinking?" "Something Garcia said earlier about not being able to sit on a park bench in this country without leaving a paper trail." "And..." "So what if Rodgers wasn't in the country for those 5 months?" "It wouldn't be the first time someone crossed borders to get away from troubles." "Guys, there's something interesting about this grocery list." "What?" "Look at the items he bought in bulk." "Garlic, green tea, vitamin D, ginger." "All of these items are specifically known to boost the immune system." "What if Terry Rodgers was seriously ill?" "What about the baby food?" "A side effect of radiation treatment is sores inside the mouth." "In fact, doctors advise you to eat the way an infant would eat." "Chemotherapy?" "The marijuana in the cabin could have been medicinal." "I'll have Garcia check medical facilities outside the country." "And, Reid, you and JJ go to the medical examiner and have them look specifically for a pre-existing condition with Rodgers." "Hotch." "You were right." "Back in June, Rodgers checked himself into an experimental clinic in Mexico." "Cancer." "That's why the unsub disposed of him so quickly." "It was Hodgkin's lymphoma." "Did you find any sedatives in his system?" "The question is, what sedatives didn't we find?" "Melatonin, Valerian, marijuana, hops, catnip, kava-kava..." "Bone meal and kelp." "In the victim's stomach, along with some materials that we're retesting." "Take a look at the bottom." "Sawdust residue caked in the nostrils?" "Not just any sawdust." "Pure pinewood pellet sawdust." "It's usually imported from China." "Was it a 0.5% mixture?" "I don't know." "All I know is, it's not your everyday spread-on-the-floor sawdust." "Yeah." "That was Reid." "They found a half dozen natural sedatives in Rodgers' system." "I don't get it." "The unsub's drugging victims and trusting that they'll conk out at the right place at the right time." "Why not use a pharmaceutical drug?" "Or poison?" "Which would be quicker and a lot more reliable." "Natural holistic elements must be important to her." "She may have health issues of her own." "Go ahead, Garcia." "I just hit the trifecta, but with two things instead of 3." "What is that, a bifecta?" "Exacta." "What do you got?" "Well, that-- anyway, two missing vehicles not missing anymore." "Paul Hicks' car was found by some utility workers an hour ago." "It had rolled off into a ravine." "And Gary Ellard's car was picked up on a speeding violation in Coeur d'Alene, Idaho." "Idaho?" "Stolen by some local kids 10 days ago in La Grande." "Car was just sitting by the side of the road, keys in the ignition." "They made a typically sound teenage decision, decided to take it on a cross-state joyride." "Garcia, I need to know the exact spot where the vehicles were originally found." "On it." "All right, based on what we just got, this is the revised best guess on the victims' routes the days they were abducted." "Two intersect here, the other two here." "And this is where Terry Rodgers bought his groceries." "It looks like Paul Hicks might have gone there after his doctor's appointment." "Now, what was at the intersection where Deaver and Ellard crossed?" "That's a shopping center with a dozen or so businesses." "We're getting a list right now." "One of our deputies sighted an abandoned car on the outskirts of town." "There was a second set of tire tracks behind it that matched those found at Terry Rodgers' abduction site." "Vehicle's registered to Cheryl Winslow, 4801 Davenport Avenue." "These are all from a baby shower." "We contacted her husband." "She's due in 3 weeks." "If this is our unsub, taking a pregnant woman would be a huge shift in victimology." "We profiled she was abducting the men as breeders." "But why take someone else's baby if you're planning on having your own?" "Maybe she can't have one or she lost one." "Ok, so this-- this isn't about fertility, but the experience these men would bring as fathers." "Could she be building a family?" "Ohh..." "Oh, please." "Oh, please." "What are you doing?" "!" "Keep still." "Oh, my God!" "Prep and get her to O.R. 3." "Doctor, is she gonna make it?" "There's been massive blood loss." "She was given a C-section with a serrated-edge knife, then crudely stitched back up." "We found her and the baby in our parking lot." " How's the baby?" " The child is fine." "It's her I'm worried about." "Excuse me." "Touch-and-go for a while, but she's going to make it." "Thank God." "It was a crude stitch-up job, but functional." "Probably what saved her life." "Whoever did this had some practice somewhere." "You think there'd be any way we could talk to her?" "It's very important." "I'm sorry, but the next 24 hours are critical." " She's heavily sedated." " I understand." "Her husband's here." "Excuse me." "Our unsub removed the baby, then returned mother and child to a hospital." "Baby wasn't due for 3 more weeks." "If the unsub's trying to put together the perfect family, maybe a premature infant isn't good enough." "Let's hope not." "That means she'll go out looking for a healthier baby now." "Mommy?" "Mommy?" "Lexy, get down from there!" "That was Hotch." "The doctor told him the placenta was scraped completely out of the victim's uterus." "Every bit of it." "You know, the placenta does carry special significance in many cultures." "In ancient Egypt, it had its own hieroglyph." "And the Ibo tribe in Nigeria considered it to be the child's dead twin." "Well, that would be helpful, if our unsub was an ancient Egyptian or Ibo tribeswoman, but..." "I can hear the high-pitched whine from your I.Q. all the way over here." "What is it?" "It could be placentophagy." "What?" "Consuming it." "In the wild, it's common for animals to eat their own afterbirth." "It's super rich in nutrients." "Whoa, whoa, whoa, wait." "So the unsub might have harvested this last victim... for food?" "Here." "No!" "No..." "No, please, mommy." "I promise I won't go to the barn again." "I promise." "This is not punishment." "I'm trying to keep you healthy." "No!" "No!" "Ohh!" "What's wrong with you?" "!" "Do you have any idea what I did to get that for us?" "Uhh!" "It's ruined." "I'm sorry." "Oh, I'm sorry I yelled at you." "But..." "Mommy?" "It's about food." "Herbal sedatives, gruel, and now the placenta." "Ugh." "And FYI, there's no record of anyone in La Grande buying that weird kind of sawdust the M.E. found." "I'll widen the search." "We still need to figure out how this unsub was able to drug all these men." "The southeast intersect doesn't get us much." "Laundromat, video rental store." "The other intersect is the supermarket, but none of the employees recognized Paul Hicks." "He never shopped there." "Garcia, what day of the week were each of the victims abducted?" "Let me see." "Gary Ellard on a Monday, Barry Deaver on a Saturday," "Terry Rodgers and Paul Hicks both on a Thursday." "Is there anything special that happens in the vicinity of the market on Thursdays?" "Uh...wow, you've done this before, haven't you?" "Yeah." "There's a farmers market across the street from the supermarket every Thursday morning." "And where is it today?" "Pendleton, about 40 miles north on Interstate 84." "I'm sending Blake and Morgan." "Enjoying your Melatonin bar?" "Job's making you paranoid, Blake." "Well, apparently a lot of people work this market." "It's not like everybody else knows everybody else." "I'm gonna get a list of vendors and launch Garcia anyway." "You can see how it happened, though." "And Terry Rodgers got his groceries, made his way back to his car..." "Grabbed a power drink on his way home." "He drank it... and then he tossed it." "Now the Melatonin's in his system with no evidence of where it came from." "Hey, what do you got?" "Full toxicology report." "And?" "Unlike any tox panel I've ever seen before." "They found gypsum?" "Yeah." "Gypsum's rich in sulphur, a vital plant nutrient." "She's feeding her captives soil additives?" "Seed meals, too." "Look, cotton, flax." "Come on." "It's animal feed." "Why would you treat a human being like livestock?" "People raise cattle to eat." "The unsub might be using the placenta as food, but nothing in the profile suggested cannibalism." "I mean...unless the sawdust they found in Terry Rodgers' nose..." "What about it?" "When livestock die, animal carcasses turn into a useful soil amendment through the aerobic biodegration process." " Like compost." " Exactly." "You need to add a substrate high in carbon to balance the nitrogen, and one of the most efficient substrates on earth is pure sawdust." "She's using her victims as human fertilizer." "How are you feeling, honey?" "Mm..." "This won't hurt you." "I made it all from roots and herbs." "All it does is help you take a little nap." "And when you wake up, you'll be the beautiful little girl that you are." "Ok, put your arms around me now." "How are we doing with the farmers market background search?" "Not good." "Turns out that people who grow organic rutabagas are loosey-goosey about punching in a time clock." "Sheriff, if we expand the search of the second intersection by a few square blocks, would we find any markets or restaurants?" "There's a health food co-op 3 blocks away." "The soil will heal you." "Sheriff, the surgeon who operated on Cheryl Winslow said that whoever did the C-section might have done one before." "If she did, we never heard about it." "Nothing like this has ever happened in La Grande." "Well, we can keep looking, expand the search radius to nearby towns." "What about farms?" "My grandparents had a farm in Pennsylvania." "Once my grandmother had to deliver a calf by C-section to a cow that was in distress." "Go ahead, Garcia." "I have got something." "Emma Kerrigan." "She runs a small juice and vegetable stand at the farmers market, and she works part-time giving out free samples at the health food co-op." "I'm sending you her picture now." "That sounds like our unsub." "Where does she live?" "Piping Rock Farms west of town, with 100 acres, belonged to her husband's family." "Wait, she has a husband?" "Had." "Died in a car accident a year and a half ago, leaving her and a 10-year-old daughter." "Let's go." "I've got more info on Emma Kerrigan." "30 E.R. visits in the past 6 months." "Big-time hypochondriac." "A co-worker says she didn't eat anything unless she grew it herself." "To be fair, she did have an actual skin disease a couple years ago-- scleroderma." "Garcia, did the E.R. visits coincide with the death of the husband?" "No." "She was sick with the scleroderma when he died." "Cleared up a few months later." "The E.R. visits didn't kick in until the following year." "Please..." "Clear." "Clear!" "Clear." "What's that?" "Garcia, what happened to Emma Kerrigan's husband's body after he died?" "Uh, cremated." "And what happened to the ashes?" "Obit says they were planning on spreading his ashes in the family garden throughout the 4 seasons." "Renewal, cycle of life, rejuvenation, that kind of thing." "Garcia, you got a map of the farm?" "Place this size, we need to narrow the search." "I got the satellite image." "There's two groups of buildings." "And then there's a small square patch next to a barn that could be a private garden." "All right, let's go." "Hotch." "Back garden." "Emma Kerrigan, FBI." "Put your hands where I can see them." "Emma, put that knife down." "No." "My daughter needs this." "Look at her." "Put it down so we can get her the help she needs." "My daughter will be dead by then." "I believe you, Emma." "I can see how sick she is." "I talked to your doctor." "Dr. Gourse?" "You talked to Dr. Gourse?" "Yes." "He said Lexy is too sick for this to work." "This man's blood won't do anything." "But it has to." "It's all I have left." "No." "No." "What can cure Lexy is what cured you." "Uh..." "Funeral homes are required by law to keep a portion of the remains of those that they cremate." "These are your husband's ashes." "Only these will make your daughter well." "Those are his?" "It's a miracle." "It's a miracle." "Not bad, Blake." "Not bad at all." "Took a chance." "I mean, I saw her fireplace there..." "Alfred Austin said," ""Show me your garden and I shall tell you what you are."" "I assume you're not trick-or-treating either?" "Ah, none of my treats seem to want to call me back, Rossi." "Then I'll buy you dinner." "I'm in." "Uh, excuse me, everybody." "I have an announcement to make." "As I'm sure some of you were aware," "Henry was a little nervous about going trick-or-treating this year." "But he's decided to go anyway." "Great." "What changed his mind?" "The BAU did." "I told him that he should go out on Halloween and try to figure out which monsters are real and which ones are not." "So he wants to be a profiler." "Ah." "He wants to be his favorite profiler." "Wow!" "Yeah!" "Oh, wow!" "You look great, Henry." "Put this on here." "Oh, he's official." "Yeah." "Tell him." "E equals MC squared!" "Oh, there it is!" "Ohh!" "The monsters don't stand a chance." "Oh, I know." "Shall we go get you some candy?" "Come on." "Whoo-hoo." "Watch your back, pretty boy." "== sync, corrected by elderman =="

{ "pile_set_name": "OpenSubtitles" }

When Dr. Lionel Carmant returned to the Montreal Children’s Hospital earlier this week to give a speech for Black History Month, it was a homecoming of sorts. It is where the pediatric neurologist completed part of his training in the 1990s. “Coming back here today, it really hits home - and the house has been quite improved over the years,” he said with a laugh, as he stood in front of the crowd gathered in the P.K. Subban Atrium. Carmant has since moved on to another “house”: Quebec's National Assembly. He’s now the CAQ government’s junior health minister, one of 125 men and women elected last fall. Up until the October 1, 2018 general election, there were just five black MNAs in the entire history of the National Assembly. Now, there are five black MNAs in the legislature at the same time. It’s a sign of the changing times in Quebec politics, and for Liberal MNA and former deputy premier Dominique Anglade, it’s a welcome change. “It's always important to get a good representation of what society generally is, and that's why this year - both in terms of black people, and in terms of women as well - we see progress. So that makes me happy and more positive about the future,” said Anglade. Being elected was a surreal experience for CAQ MNA Christopher Skeete, the son of a French-Canadian mother and a Trinidadian father. “For me, growing up, the idea of having a black president of the United States would have been something I never would have thought I would see in my lifetime, let alone myself getting elected to the National Assembly,” he said, adding that he is particularly proud of the fact there are two black ministers in the current government. “I think we're making great strides. So the message I would say to youth is, "Stop thinking about it. Just go. Just push those barriers," Skeete said. Nadine Girault, of Haitian origin, is also a first-time MNA and the minister of international relations and la Francophonie. She says the black community’s response to her budding political career has been overwhelmingly positive. “It really feels for them like we can take our place and there's room for us, so it's very rewarding. It's a privilege,” said Girault. Now that she has a seat at the table, she’s hoping others will follow in her footsteps. “I think it's on two sides. We have to do more to attract, yes, but black people also have to get involved,” she said. “There were very nice, young black women as candidates, and I look forward to seeing them come back in the next election – because they all said that they're coming back (…) I'm sure that with time, and from one election to the other, we're going to see more and more black people.” Liberal MNA and former Montreal city council speaker Frantz Benjamin said he feels a responsibility to spread knowledge about the historical black presence in Quebec, including the stories of slaves in New France. “The story of Marie-Joseph Angelique, it is not only my story. It is the story of all of Quebec society,” said Benjamin. “Now it is our duty as a member of the National Assembly - but especially the duty of the government - to make sure that at the educational level, more has to be done.” To mark Black History Month this year, the Quebec government announced it will rename a bridge on Highway 50 in the Outaouais in honour of Jean Alfred, Quebec’s first black MNA. Alfred was elected under the Parti Quebecois banner in 1976, when the party came to power for the first time under Rene Levesque. Follow @MJohnsonCTV

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Psychoneuroimmunology and AIDS. Although PNI is a relatively new field, basic research has demonstrated the interconnectedness of immune and neurological systems, alerting nurses to the need to conduct multisystem assessments and provide holistic nursing care to persons with AIDS. Although the burden of research does not support the notion that the mind can cure AIDS, preliminary studies suggest that under certain circumstances the psychogenic and physiological conditions of the host alter rates of progression of HIV infection. Nursing research is needed to determine circumstances under which immunomodulating events alter disease progression in this population.

{ "pile_set_name": "PubMed Abstracts" }

The present invention is in the pharmaceutical area, and in particular relates to pharmaceutical compositions containing 5'-diphosphohexose and 5'-diphosphohexosamine derivatives of nucleosides. Acquired immunodeficiency syndrome ("AIDS") was recognized as early as 1979. The number of cases reported to the Centers for Disease Control (CDC) has increased dramatically each year since then, and in 1982 the CDC declared AIDS a new epidemic. Infection with the AIDS virus is highly variable. Initially, the virus replicates abundantly, with virus present in the central nervous system and the cells of the immune system. This is frequently accompanied by fevers, rashes, flulike symptoms and neurological complaints. These symptoms generally disappear within a few weeks, as the amount of virus in the circulation drops. However, virus is still present in the immune cells, the cells of the nervous system, cells of the intestine and bone marrow cells. The victim typically dies two to ten years after the initial asymptomatic period, following a protracted and painful illness. Human immunodeficiency virus, a retrovirus, is the etiological agent of AIDS, as well as of a variety of related disorders, such as AIDS Related Complex (ARC). HIV infection begins when a virion or virus-infected cell binds to susceptible cells and fuses with them, injecting the core protein and viral RNA into the cell. The RNA is transcribed to viral DNA. The double stranded DNA migrates to the nucleus and is integrated into the cell's DNA. The viral DNA can remain dormant for an indefinite period of time, or the genes can replicate and be translated into viral proteins. The viral proteins are assembled into new virions that bud from the cell, spreading the disease. HIV preferentially infects the T4 lymphocytes, immune cells important in helping to suppress infection by other agents, thereby impairing proper functioning of the immune system. As a result of impaired immunity caused by the destruction of helper T-cells by the HIV, the host becomes susceptible to opportunistic infections, various types of cancer such as Kaposi's sarcoma, and other disorders associated with reduced functioning of the immune system. A variety of approaches have been developed to treat AIDS infections, including inhibiting the binding of the virus to host cells with dextran sulfate or soluble CD4 (a glycoprotein found on the surface of cells of the immune system which the HIV binds to when infecting the cells), administration of anti-idiotypic antibodies (an antibody to the antibody against CD4), blockage of viral protein synthesis by compounds such as phosphorothioate, and inhibition of protein glycosylation by compounds such as 2-deoxy-D-glucose. However, these approaches are still in early experimental phases, and have not been approved for clinical treatment. AIDS and ARC chemotherapy have been recently reviewed by Schinazi, Strategies and Targets for Anti-Human Immunodeficiency Virus Type 1 Therapy, "Aids in Children, Adolescents, and Heterosexual Adults: An Interdisciplinary Approach to Prevention," Elsvier, N.Y. 1988); E. D. Clercq, J. Med. Chem. 29, 1561-1569 (1986); H. Mitsuya, S. Broder, Nature 325, 773-778 (1987); and R. Yarchoan, et al., "AIDS Therapies" The Science of AIDS Scientific American (W. H. Freeman and Co. N.Y. 1989). A number of nucleosides have been found to have anti-HIV activity, including 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxycytidine (DDC), 2',3'-dideoxyadenosine (DDA), 3'-azido-2',3'-dideoxyuridine (AzddU), 2',3'-didehydro-2',3'-dieoxycytidine, 3'-deoxy-2',3'-didehydrothymidine, 3'-azido-5-ethyl-2',3'-dideoxyuridine (AzddEU), 3'-azido-5-methyl-2',3'-dideoxycytidine (AzddMeC), 9-(2,3-Dideoxy-2-halo-.beta.-D-arabinofuranosyl)-N.sup.6 -methyladenine (2'-halo-D.sub.2 MeA), and N.sup.6 -methyl-D-glycero-2',3'-dideoxyfuranosyladenosine (D.sub.2 MeA). The present application is a continuation-in-part of applications directed to AzddU. It is generally accepted that the active form of nucleosides such as AZT, AzddU, AzddMeC, D.sub.2 MeA, and DDC is the triphosphorylated derivative. Triphosphorylated deoxynucleosides appear to inhibit the replication of HIV by limiting the production of viral DNA by at least two mechanisms: competitive inhibition of reverse transcriptase and chain termination of viral DNA due to the missing 3'-hydroxyl group. The therapeutic effectiveness of all of the known active nucleosides depends on how easily the nucleoside can enter cells and undergo phosphorylation by cellular enzymes. The efficiency of this process varies considerably among nucleosides, and can severely limit the usefulness of the compounds. For example, nucleoside triphosphates without modification, are not useful clinically, since they cannot pass through the cell membrane, even though the triphosphate may have greater antiviral activity. Nucleosides are also converted by intracellular enzymes into less active metabolites. If the conversion rate to less active compounds is faster than the rate of triphosphorylation of the nucleoside, the pharmaceutical effectiveness of the nucleoside is diminished. For example, it is known that DDA in the triphosphate form is a potent HIV inhibitor in vitro, but in vivo the enzyme adenosine deaminase rapidly converts DDA to the less active DDI (2',3'-dideoxyinosine) before DDA can be phosphorylated. DDI-5'-monophosphate must then be converted to DDA-5'-monophosphate by cellular enzymes to restore the activity of the compound. The therapeutic effectiveness of a drug is the determining factor in the dosage required for therapy. Nucleosides that pass through the cell membrane with difficulty or which are metabolized into less active or inactive forms in the cell must be administered in higher dosages. Unfortunately, most nucleosides are toxic to healthy uninfected cells at high dosage levels. AZT has been studied extensively in humans for treatment of HIV infections. However, bone marrow toxicity and other side effects limit its long term usefulness. For example, Richman, et al., have shown that because of AZT-associated hematological abnormalities, twenty-one percent of patients undergoing AZT therapy required multiple blood transfusions during the six month treatment period. Bone marrow depression may be due to the accumulation of phosphorylated AZT within cells, which may result in a substantial depression of thymidine 5'-triphosphate pools. Another drawback of AZT is its short half life in humans (about 1.1 hour) and its elimination in urine as 3'-azido-3'-deoxy-5'-glucuronylthymidine, a metabolite with no substantial antiviral activity. Many nucleoside derivatives have been developed that have anticancer, anti-bacterial, and anti-fungal activity. Effective therapy with these nucleosides, as with the anti-HIV nucleosides, is significantly affected by the ability of the nucleoside to pass through the cell membrane and diffuse to the active site before the compound is converted to an inactive form or eliminated. Nucleoside diphosphate sugars are used in vivo for the synthesis of oligosaccharides, polysaccharides, glycolipids, glycoproteins, and components of bacterial cell membranes. Certain nucleoside derivatives have been found to block the glycosylation of proteins. However, most, if not all, known nucleoside glycosylation inhibitors show little selectivity and have low activity against viral infections. Camarasa, et al., J. Med. Chem., 28, 40 (1985) reported that uridine 5'-diphosphate glucose analogues, 5'-O-[[[[(2",3",4",6"-tetra-O-benzyl- and 2",3",4",6"-tetra-O-benzoyl-.alpha.-D-glucopyranosyl)oxyl]carbonyl]ami no]sulfonyl]-2',3'-isopropylideneuridine (P-536), a UDP-glucose analog, and the corresponding deisopropylidenated derivatives, show in vitro antiviral activity against herpes simplex virus type 1. Alarcon, et al., in Antimicrobial Agents and Chemotherapy 1257, (1988) reported that P-536 has broad antiviral activity, including activity against adenovirus type 5, vaccinia virus, and poliovirus type 1. The compound was demonstrated to inhibit protein glycosylation if added at a time when late viral proteins were being synthesized, and to inhibit the synthesis of nucleic acids and phosphorylation of nucleosides. Alcina, et al., Antimicrobial Agents and Chemotherapy, 1412 (1988), later demonstrated that the same compound has activity against the flagellated protozoan Trypanosoma cruzi. In light of the state of the art, it is clear that there is a strong need for biologically active nucleoside derivatives that can pass through a cell membrane and reach the active site prior to conversion to inactive metabolites or elimination. It is therefore an object of the present invention to provide nucleoside derivatives that have enhanced antiviral, antibacterial, antifungal or anticancer activity. It is a further object of the present invention to provide nucleoside derivatives that can easily pass through a cell membrane in the proper chemical form to perform a desired biological function, or a chemical form. It is a still further object of the present invention to provide a method to enhance the cellular levels of nucleosides.

{ "pile_set_name": "USPTO Backgrounds" }

coldplayticketschile Contact Details Description Country Songs Alphabet- Vince Gill What causes ear ringing tinnitus? Individuals automatically relate this to old age and loss of listening to and this is not correct. What is even worse is the assumption it can\'t be treated. Even though there are remedies for it. Basketball enthusiasts should attend a game at the Philips Arena and witness the Atlanta Hawks (NBA), the Atlanta Thrashers and the Atlanta Dream (WNBA) groups in actions. It is also a well-liked location for Concerts and occasions. These holiday rentals variety from studio flats to homes that can accommodate 10 or much more individuals. They are highly price-effective for couples touring with other couples, or households of 3 or much more. In fact, vacation rentals can decrease your lodging costs significantly, when in contrast to a hotel. Most also have a totally equipped kitchen, so you can put together a food or two daily. 7) Visit the Savannah Convention & Visitors\' Bureau on Martin Luther King Blvd . You\'ll discover numerous totally free brochures, maps and guidance from reps there about the most inexpensive ways to enjoy the sites. Nationally acknowledged for its drag strip and oval track, Beech Bend is a first course auto racing facility and amusement park. Home to Inventory Car Racing, Fun Racing, and NHRA Drag Racing, the park also hosts national automotive occasions all through the yr. The other side of the park offers amusement rides, picnic locations, a campground, and a drinking water park. Open from March-November. J.E. Wallace was the individual that created the Iowa State Honest\'s initial butter cow sculpture in 1911. He was succeeded by Earl Frank Dutt of Illinois and then the butter cow sculpting was done by Norma \"Duffy\" Lyon of Toledo, Iowa. She was the initial lady to sculpt a cow made out of butter for the Iowa Condition Honest. In 2006, Sarah Pratt grew to become the fourth individual to sculpt butter for the Des Moines Iowa State Fair and is still with them today. Want a split from the tours and sightseeing? Settle down by the tranquil Lake Clara Meer and the calming woods of Piedmont park. It is 180 acres of greenery and park area and adjoins the Atlanta Botanical Garden - an additional www.Coldplaytourtickets.org great place to go to for nature enthusiasts. With more than 30 acres of gardens, forest, wild flower trails and the ten,000 sq.-foot Fuqua Orchid Middle - you will love to get lost in the wild and invest the day roaming about in the wild elegance of it all.

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---------------------- Forwarded by Vince J Kaminski/HOU/ECT on 07/19/2000 06:41 PM --------------------------- From: Paula Corey@ENRON COMMUNICATIONS on 07/17/2000 08:13 AM To: Richard Weeks/Enron Communications@Enron Communications, Daniel Despres/Enron Communications@Enron Communications, Walter Sonksen/Enron Communications@Enron Communications, Vince J Kaminski/HOU/ECT@ECT cc: Subject: FW: DAVE BARRY Thoughts for the day ... ----- Forwarded by Paula Corey/Enron Communications on 07/17/00 08:16 AM ----- Ed.Sweeney@phh.com 07/17/00 07:56 AM To: Paula Corey/Enron Communications@Enron Communications, CIrons3308@aol.com, jsweeney@paperhub.com, lyn.ure@juno.com cc: Subject: FW: DAVE BARRY Subject: THINGS THAT IT TOOK ME 50 YEARS TO LEARN, by DAVE BARRY Never under any circumstances take a sleeping pill and a laxative on the same night. If you had to identify, in one word, the reason why the human race has not achieved, and never will achieve, its full potential, that word would be "meetings". There is a very fine line between "hobby" and "mental illness." People who want to share their religious views with you almost never want you to share yours with them. And when God, who created the entire universe with all of its glories, decides to deliver a message to humanity, He WILL NOT use, as His messenger, a person on cable TV with a bad hairstyle. You should not confuse your career with your life. No matter what happens ... somebody will find a way to take it too seriously. When trouble arises & things look bad, there is always individual who perceives a solution & is willing to take command. Very often, that person is crazy. Nobody cares if you can't dance well. Just get up and dance. A person who is nice to you, but rude to the waiter, is not a nice person. Never lick a steak knife. Take out the fortune before you eat the cookie. "The one thing that unites all human beings, regardless of age, gender, religion, economic status or ethnic background, is that, deep down inside, we ALL believe that we are above average drivers. You should never say anything to a woman that evenremotely suggests that you think she's pregnant unless you can see an actual baby emerging from her at that moment. Your friends love you anyway. - att1.unk

{ "pile_set_name": "Enron Emails" }

Muscle ATP loss and lactate accumulation at different work intensities in the exercising Thoroughbred horse. The effect of 2 min treadmill exercise, at speeds of 6-12 m.s-1 on an incline of 5 degrees, upon muscle adenine nucleotide loss and lactate accumulation was studied in six Thoroughbred horses. Minimal change occurred in the adenosine triphosphate (ATP) content of the middle gluteal muscle at speeds of 10 m.s-1 or less, but significant loss (up to 47%) had occurred in all horses by 12 m.s-1. The decline in ATP significantly correlated with the accumulation of muscle lactate, beginning shortly after the accumulation of 40 mmol.kg-1 dry muscle lactate. Decline in muscle ATP was mirrored closely by the appearance of ammonia, and to a lesser extent, hypoxanthine and uric acid in plasma. The results suggest that peak accumulation of any of these, or simply the concentration at a specified recovery time, may be used as a measure of ATP loss in the musculature as a whole. This was not so in the case of xanthine, which may also be formed from the degradation of guanidine nucleotides. An In-In plot of plasma ammonia against treadmill speed indicated a break point in accumulation between 8 and 9 m.s-1. The kinetics of ammonia accumulation with speed differed from those of lactate.

{ "pile_set_name": "PubMed Abstracts" }

Myoclonic status epilepticus: video presentation. A young woman with juvenile myoclonic epilepsy had recurrent attacks of myoclonic status epilepticus related to a long history of limited compliance and irregular sleep. The diagnosis of this clinical pattern is based mainly on clinical description. A home video captured an attack.

{ "pile_set_name": "PubMed Abstracts" }

2004 (28) Archives It may sound a little puzzling at first, but in Orchard CMS, more than one theme can be active at any given time. The reason for that is that we have an extensibility point that allows a module (or a theme) to participate in the choice of the theme to use, for each request. The motivation for building the theme engine this way was to enable developers to switch themes based on arbitrary criteria, such as user preferences or the user agent (if you want to serve a mobile theme for phones for example). The choice is made between the active themes, which is why there is a difference between the default theme and the active themes. We do have tutorials on the Orchard site, but we can't cover all topics, and recently I've found myself more and more responding to forum questions by pointing people to an existing module that was solving a similar problem to the one the question was about. A CMS like Orchard is, by definition, designed to store content. What differentiates content from other kinds of data is rather subtle. The way I would describe it is by saying that if you would put each instance of a kind of data on its own web page, if it would make sense to add comments to it, or tags, or ratings, then it is content and you can store it in Orchard using all the convenient composition options that it offers. Otherwise, it probably isn't and you can store it using somewhat simpler means that I will now describe.

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Dr. Howell founded Village Pediatrics in 1998 after serving 3 years as a military pediatrician in a large group. He is a graduate of the University of Arizona College of Medicine and completed his residency at Fitzsimmons Army Medical Center in Aurora, Colorado. He also completed 2 years fellowship training in Child Behavior and Development at Boston University. He enjoys family, friends, church life, outdoor activities and sports. Crystal L. Rainville, MD Dr. Rainville received her undergraduate degree from Tufts University and her Medical Doctorate from the University of Massachusetts Medical School. She completed her pediatrics residency at Boston's Floating Hospital for Children where she received numerous awards and served as chief resident. A life-long southern Massachusetts resident, Dr. Rainville is looking forward to continuing her family-focused approach to children's health. Yarelis Matos, PsyD Dr. Matos graduated in 1996 from the University of Massachusetts with a Bachelor of Arts and Sciences degree in Psychology. She went on to complete her Masters of Science in Psychology in 1998 and received her Doctor of Psychology in 2000 from the Carlos Albizu University in Miami, Florida. Dr. Matos has extensive experience working with children from 5 to 17 years of age, and also with children of families with multi-cultural and diverse backgrounds. Her clinical training has focused on adolescents with learning, behavioral and emotional difficulties. Charlotte Rydberg, PNP Charlotte graduated from Immanuel Hospital School of Nursing in Omaha, Nebraska. She completed her Pediatrics Nurse Practitioner certification at Northeastern University in Boston, and has a degree in Psychology from Barat College in Lake Forest, Illinois. Charlotte enjoys traveling with her family, skiing, outdoor activities, baking and singing in her church choir. Mary Catherine Finn, PNP Mary Catherine is a graduate of Cornell University School of Nursing in New York. She received a Master's degree in Pediatric Nursing from Boston College and became certified as a Pediatric Nurse Practitioner. She enjoys playing tennis, skiing, reading, and spending time with friends. Christine Lattuada, PNP Christine received her undergraduate degree from Skidmore College in New York. She obtained her Masters of Science in Nursing from Northeastern University.

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Q: Mediawiki: how to allow users to edit their User pages (but not other pages) Is there a permission in Mediawiki that allows a user with username A-User to create and edit pages A-User, A-User/A-new-page etc but not to edit other pages? A: Not by default. You can find the list of permissions here, and the permissions each user group on a wiki has at Special:ListGroupRights. There is editmyusercss/editmyuserjs which allows users to edit user subpages ending in .css/.js, but probably even that requires the normal edit right. It would be pretty simple to write an extension granting that right, though. See UserPageEditProtection for a similar example (which does the opposite: instead of granting the right to edit own subpages, it takes away the right to edit others' subpages). You could make it do what you want by tweaking the return values in the userCan hook a bit.

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Q: Gallerific .selected Element I'm having a problem with the selected element in Galleriffic. When an image is selected it is not highlighting the correct thumb, it's highlighting the previous one. Edited to remove a soon to be dead link of the website. JS: <script type="text/javascript"> jQuery(document).ready(function($) { // We only want these styles applied when javascript is enabled $('div.navigation').css({'width' : '100%', 'clear' : 'both'}); $('div.content').css('display', 'block'); // Initially set opacity on thumbs and add // additional styling for hover effect on thumbs var onMouseOutOpacity = .7; $('#thumbs ul.thumbs li').opacityrollover({ mouseOutOpacity: onMouseOutOpacity, mouseOverOpacity: 1.0, fadeSpeed: 'fast', exemptionSelector: '.selected' }); // Initialize Advanced Galleriffic Gallery var gallery = $('#thumbs').galleriffic({ delay: 2500, preloadAhead: 10, enableTopPager: true, enableBottomPager: true, maxPagesToShow: 7, imageContainerSel: '#slideshow', controlsContainerSel: '#controls', captionContainerSel: '#caption', loadingContainerSel: '#loading', renderSSControls: false, renderNavControls: false, playLinkText: 'Play Slideshow', pauseLinkText: 'Pause Slideshow', prevLinkText: '&lsaquo; Previous Photo', nextLinkText: 'Next Photo &rsaquo;', nextPageLinkText: 'Next &rsaquo;', prevPageLinkText: '&lsaquo; Prev', enableHistory: false, autoStart: false, syncTransitions: true, defaultTransitionDuration: 900, onSlideChange: function(prevIndex, nextIndex) { // 'this' refers to the gallery, which is an extension of $('#thumbs') this.find('ul.thumbs').children() .eq(prevIndex).fadeTo('fast', onMouseOutOpacity).end() .eq(nextIndex).fadeTo('fast', 1.0); }, onPageTransitionOut: function(callback) { this.fadeTo('fast', 0.0, callback); }, onPageTransitionIn: function() { this.fadeTo('fast', 1.0); } }); }); </script> CSS div.slideshow a.advance-link { display: block; width: 820px; height: 388px; /* This should be set to be at least the height of the largest image in the slideshow */ line-height: 0px; /* This should be set to be at least the height of the largest image in the slideshow */ text-align: center; } div.slideshow a.advance-link:hover, div.slideshow a.advance-link:active, div.slideshow a.advance-link:visited { text-decoration: none; } div.download { float: right; } div.image-title { font-weight: bold; font-size: 1.4em; } div.image-desc { } div.navigation { /* The navigation style is set using jQuery so that the javascript specific styles won't be applied unless javascript is enabled. */ text-align: left; } ul.thumbs { clear: both; margin: 0; padding: 0; background-color: #FFF; } ul.thumbs li { display:inline; margin-right: 10px; padding: 0; list-style: none; } a.thumb { display:inline-block; text-decoration: none; } ul.thumbs li.selected a.thumb { color: #0C3 } a.thumb:focus { outline: none; text-decoration: none; } ul.thumbs img { border: none; display: block; } div.pagination { clear: both; } div.navigation div.top { padding-top: 10px; margin-top: 10px; text-align: center; background-color: #fff; } div.navigation div.bottom { text-align: center; } div.pagination a, div.pagination span.current, div.pagination span.ellipsis { display: block; float: left; } div.pagination a:hover { background-color: #eee; text-decoration: none; } div.pagination span.current { font-weight: bold; background-color: #000; border-color: #000; color: #fff; } div.pagination span.ellipsis { border: none; } A: There was an indexing problem, the was considered like an index which was causing it to start off at the wrong place. Solved it! :)

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Q: Keeping XML in Memory between Webservice Calls First, I don't want to use a database or a local file. Is it possible to store variables in memory so they don't have to be created each time the webservice is called? The problem is that FullCompanyListCreateXML(); takes about 1 Minute to create the XDocument. So is there any way to prevent that the xml variable is dropped after the webservice call is finished? [WebMethod(CacheDuration = 120)] public String FullCooperationListChunkGet(int part, int chunksize) { StringBuilder output_xml = new StringBuilder(); XDocument xml = FullCompanyListCreateXML(); IEnumerable<XElement> xml_query = xml.Root.Elements("Cooperation").Skip(part * chunksize).Take(chunksize); foreach (XElement x in xml_query) { output_xml.Append(x.ToString()); } output_xml.Insert(0, "<Cooperations>"); output_xml.Append("</Cooperations>"); return output_xml.ToString().Zip(); } Thanks, Henrik A: 2 ways: 1) You can add a global.asax class to the web service which will get created when the web application is first started, and will persist for as long as the worker process keeps it in memory. Override the 2) create a static class to hold the values See this blog entry, or this post on the topic of adding the global.asax class to web services. You can create things when the session starts, or when the application starts by overriding the Session_Start or Application_Start methods

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Q: Set limits for add content in text file with PHP I need to create a list of last logged members in my website, but i don't wanna user MySQL. i did some search in stackoverflow and Google and wrote this code: ////////////CHECK LIMIT $storage = "engine/data/write.txt"; $readz = file_get_contents($storage); $listz = explode('|||',$readz); $counter = count( $listz ); if($counter > "3"){ $stop = "1"; }else{ $stop = "0"; } if($stop == "0"){ ///REMOVE MEMBER IF AVAILABLE if ( preg_match("", $readz)){ $content = file_get_contents($storage); $content = str_replace("".$user."|||", '', $content); file_put_contents($storage, $content); } //ADD MEMBER AGAIN if ( !preg_match("", $readz)){ $beonline_file = fopen($storage, "a+"); fwrite($beonline_file, "".$user."|||"); fclose($beonline_file); } } Problem is i can't set limit! how i can edit this code to set limit to add only 20 users in text file? A: Maybe you can do this? if ( !preg_match("", $readz)){ $nlistz = explode('|||',$readz); if(count( $nlistz ) == 20){ array_shift($nlistz); $newlistz = implode("|||",$nlistz); $beonline_file = fopen($storage, "w+"); fwrite($beonline_file, $newlistz."|||".$user."|||"); fclose($beonline_file); }else{ $beonline_file = fopen($storage, "a+"); fwrite($beonline_file, "".$user."|||"); fclose($beonline_file); } }

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Q: Value not showing for input field using one way binding angular2 Objective: Get a collection of values based on the dropdown selection and place them in hidden input fields to be included in my model; The relative html: <select class="selectFoo" (change)="onSelect($event.target.value)" name="FooName" ngModel> <option selected="selected">--Select--</option> <option *ngFor="let foo of foos" [value]="foo.ID">{{foo.Name}} </option> </select> <input type="hidden" [value]="fooAddress" name="FooAddress" ngModel/> In the code above I called a function named OnSelect to get the data about the selected foo. The foos are populated using a webservice call. Here is the snippet from my ts file. import { Component, OnInit } from '@angular/core'; import { Foo } from './model'; import { DataService } from './data.service'; @Component({ moduleId: module.id, selector: 'add-on', templateUrl: './app.component.html' }) export class AppComponent implements OnInit { foos : Foo[]; selectedFoo: Foo; fooAddress: string; onSelect(fooID){ this.selectedFoo = null; for(var i = 0; i < this.foos.length; i++) { console.log(this.foos[i].ID); if(this.foos[i].ID == fooID){ this.selectedFoo = this.foos[i]; this.fooAddress = this.selectedFoo.Address.toString(); } } } } I originally tried one way binding my value to the selectedFoo but I was getting an error indicating my Address value wasn't defined. I noticed I could set the value equal to selectedFoo and it didn't error. So i created a new variable that was set to the fooAddress based on the selected foo. I get no value even though while stepping through the code I see it has a value. How can I get my value to populate so I can use it in my model? Let me know if I need to provide anything else. Thanks! A: If I am correctly understanding what you are after then something like this would work: <select name="FooName" [(ngModel)]="selectedFoo"> <option>--Select--</option> <option *ngFor="let foo of foos" [ngValue]="foo" >{{foo.Name}}</option> </select> <input type="hidden" [value]="selectedFoo?.Address" name="FooAddress" /> //Assuming your 'foo' items are e.g. { ID: 1, Name: 'Hello', Address: '123 Hello St'} Here you can bind the Address property of the selectedFoo directly to your hidden input field, rather than needing to handle the (change) event.

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