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NGC 407 is a lenticular galaxy located in the constellation Pisces. It was discovered on September 12, 1784 by William Herschel. It was described by Dreyer as "very faint, very small, southwestern of 2.", the other being NGC 410. | https://en.wikipedia.org/wiki?curid=53091909 |
NGC 409 is an elliptical galaxy located in the constellation Sculptor. It was discovered on November 29, 1837 by John Herschel. It was described by Dreyer as "extremely faint, small, round, very small (faint) star near." | https://en.wikipedia.org/wiki?curid=53091972 |
NGC 410 is an elliptical galaxy located in the constellation Pisces. It was discovered on September 12, 1784 by William Herschel. It was described by Dreyer as "pretty bright, pretty large, northeastern of 2.", the other being NGC 407. | https://en.wikipedia.org/wiki?curid=53094397 |
Carl August Lundström (1844 -1914) was a Finnish entomologist who specialised in Diptera especially Nematocera. He was a Professor in Helsinki. His insect collection is held by the Finnish Museum of Natural History. partial list | https://en.wikipedia.org/wiki?curid=53118394 |
Edward M. Stricker is an American neuroscientist, currently a University Professor at the University of Pittsburgh and formerly Dean at its Honors College. Professor Stricker (born in New York, NY) earned a bachelor's degree from the University of Chicago in 1960, a master's degree in chemistry from that same institution in 1961, and a PhD in psychology from Yale University in 1965. He held faculty positions at McMaster University in Hamilton, Ontario from 1967 to 1971, and at the University of Pittsburgh from 1971 to 1986, before being named University Professor in 1986. His research career spanned four decades and focused on various aspects of homeostasis, most prominently the physiological and behavioral contributions to body fluid balance, and recovery of function following damage to brain catecholamine-containing neurons. For this work he received the research scientist award from the U.S. National Institute of Mental Health (1981-1986) and the distinguished career award from the Society for the Study of Ingestive Behavior (2015). During his academic career, Stricker has served in various administrative roles at the University of Pittsburgh, including director of the behavioral neuroscience program (1983-1986), founding chair of the department of neuroscience (1986-2002), founding director of the center for neuroscience and schizophrenia (1990-1995), co-director of the center for neuroscience (1996-2002), and Dean of the University Honors College (2011-2017) | https://en.wikipedia.org/wiki?curid=53122933 |
Edward M. Stricker His teaching ranged from introductory courses to graduate courses in neuroscience, as well as interdisciplinary honors courses. In recognition of his teaching, the University of Pittsburgh has awarded him the 2001 Tina & David Bellet Teaching Excellence Award and 1992 Chancellor's Distinguished Teaching Award. | https://en.wikipedia.org/wiki?curid=53122933 |
Christian Stenhammar (1783-1866) was a Swedish naturalist interested in lichens and an entomologist who specialised in Diptera.His collection is held by Uppsala University.He was a clergyman. Genera named to honor are "Stenhammara" and "Stenhammarella" Eckhard K. Groll | https://en.wikipedia.org/wiki?curid=53127594 |
NGC 413 is a spiral galaxy of type SB(r)c located in the constellation Cetus. It was discovered in 1886 by Francis Leavenworth. It was described by Dreyer as "extremely faint, pretty small, very little extended." | https://en.wikipedia.org/wiki?curid=53134676 |
NGC 414 is a pair of lenticular galaxies (PGC 4254 and PGC 93079) of types S0 and E/S0, respectively, located in the constellation Pisces. It was discovered on October 22, 1867 by Herman Schultz. It was described by Dreyer as "very faint, small, irregularly round, much brighter middle, II 220 to the northwest.", with II 220 being NGC 410. | https://en.wikipedia.org/wiki?curid=53144610 |
NGC 415 is a spiral galaxy of type SB(rb)b located in the constellation Sculptor. It was discovered on September 1, 1834 by John Herschel. It was described by Dreyer as "very faint, small, round, gradually a little brighter middle." | https://en.wikipedia.org/wiki?curid=53144687 |
Benjamin August Gimmerthal (1779, Zittau- 1848, Riga (then Russian Empire)) was a German entomologist who specialised in Diptera. His collection of Chloropidae is held by the Museum of Systematic Zoology, University of Latvia, Riga. The remaining Diptera and other insects by the Natural History Museum of Latvia (Homepage) partial list | https://en.wikipedia.org/wiki?curid=53155094 |
List of scattering experiments This is a list of scattering experiments. | https://en.wikipedia.org/wiki?curid=53155398 |
Joseph Jean Baptiste Géhin (1816, Remiremont - 1889, Remiremont) was a French naturalist and entomologist who specialised in Coleoptera. He also studied Diptera. He was an apothecary in Metz. His collections of Carabidae were purchased by René Oberthür and are now held by Muséum national d'histoire naturelle in Paris.Géhin described the wheat midge "Sitodiplosis mosellana" and several species of Carabidae. He was a Member of Société entomologique de France and made significant contributions to economic entomology. | https://en.wikipedia.org/wiki?curid=53159112 |
Karl Escherich Karl Leopold Escherich (18 September 1871 – 22 November 1951) was a German entomologist and professor of zoology. Known as a pioneer of applied entomology and expert in termites, he was rector of the University of Munich from 1933 to 1936. Escherich was born in Schwandorf, Bavaria, to parents Hermann N. Escherich and Katharina von Stengel. His older brother Georg Escherich would become a noted forester and politician. He studied medicine in Munich and Würzburg, graduating in 1893. After gaining his postdoctoral qualification in Strasbourg in 1901, he received a professorship at the Department of Forest Zoology in Tharandt in 1907, which had been orphaned since the death of Hinrich Nitsche. In 1914 he joined the Chair of Applied Zoology at the Ludwig-Maximilians-University of Munich, where he succeeded August Pauly. In 1917 he was elected a member of the Academy of Sciences Leopoldina. After a 1911 trip to the United States, he conceived a plan to redesign applied entomology in Germany after the American model. In 1913 he co-founded the German Society for Applied Entomology. was one of the few forestry academics who took part in the early Hitler movement of the inflation period. He joined the Nazi Party in 1921, and participated in the 1923 Munich Putsch. In 1924, he still participated in the election campaign for the "Volkischer Block", but remained remote from the new NSDAP. For his research, received the Goethe Medal for Art and Science | https://en.wikipedia.org/wiki?curid=53159121 |
Karl Escherich To commemorate its founder, the German Society for Applied Entomology awards the Escherich Medal for outstanding achievements in the field of entomology. | https://en.wikipedia.org/wiki?curid=53159121 |
NGC 417 is a lenticular galaxy of type SAB0 located in the constellation Cetus. It was discovered in 1886 by Francis Leavenworth. It was described by Dreyer as "extremely faint, extremely small, round." | https://en.wikipedia.org/wiki?curid=53163163 |
NGC 418 is a barred spiral galaxy of type SB(s)c located in the constellation Sculptor. It was discovered on September 28, 1834 by John Herschel. It was described by Dreyer as "faint, pretty large, round, very gradually a little brighter middle, western of 2.", the other being NGC 423. | https://en.wikipedia.org/wiki?curid=53163190 |
Siamese buffalo The Krabue buffalo (Thai: กระบือ; ("krabue") being the Thai word for "water buffalo") also known as the Siamese buffalo, Thai water buffalo or Thai swamp buffalo is a large breed of water buffalo indigenous to Thailand. | https://en.wikipedia.org/wiki?curid=53166752 |
Johann Jacob Bremi-Wolf (25 May 1791, Dübendorf – 27 February 1857, Zürich) was a Swiss entomologist and "Kunsthandwerker" (art turner) in Zürich. He was deaf due to illness at the age of 11. His entomological herbarium is held by the Museum Wiesbaden. Other parts of his insect collection, especially Diptera are held by the . | https://en.wikipedia.org/wiki?curid=53170285 |
NGC 7640 is a barred spiral galaxy in the constellation of Andromeda. There is evidence that this galaxy has experienced an interaction with another galaxy in the (astronomically) recent past. It is not immediately obvious this is a spiral galaxy from the photograph because it is edge on. | https://en.wikipedia.org/wiki?curid=53177263 |
Color Genomics Color is a population health technology company which provides genetic tests and analysis directly to patients as well as through employers. The product focuses on genes that indicate risk for heart disease, cancer, and that affect medication response. The company was co-founded in 2015 by Elad Gil, Nish Bhat, and Othman Laraki, who now serves as company CEO, in Burlingame, California. A native of Casablanca, Morocco, Laraki came to the US to attend Stanford, where he studied computer science as an undergraduate and graduate student. Following stints at Google and Twitter, Laraki was inspired to examine the link between genetics and disease after his grandmother passed away from breast cancer, his mother was diagnosed with the disease twice, and he learned he was a carrier of a "BRCA2" pathogenic variant. Laraki teamed up with Elad Gil, who has a Ph.D. in Biology from MIT, to examine the technology available for genetic testing and determine how to make it more affordable and accessible. Color is venture-backed and raised its series C round in August 2017. The company’s investors include General Catalyst, Khosla Ventures, Emerson Collective, CRV, Initialized Capital, Laurene Powell Jobs and Bono. Prior to Color’s founding, clinical genetic testing was out of reach for most individuals, unless they had a significant personal or family history of hereditary disease | https://en.wikipedia.org/wiki?curid=53178099 |
Color Genomics Testing used to cost $4,000, insurance had burdensome requirements for coverage, and even if insurance would cover the costs, testing often required multiple in-person visits, preventing people from learning information that could save their lives. Color’s product is a genetic test that costs $249, genetic counseling, and services for physicians. The Color test analyzes 30 genes that highly impact risk for the most common hereditary cancers, 30 genes that impact risk for hereditary heart conditions and 14 genes that impact an individual’s genetic response to medications. Color provides technology, software, and clinical services for population health programs. Their services include: Color has partnered with health systems including NorthShore University Health System, Ochsner Health System, and Jefferson Health. Color also works with companies like Visa, Levi Strauss, Salesforce, Instacart, Nvidia, OpenTable, SAP, Slack, Stripe, and Snap to offer their employees access to Color’s clinical grade genomic services, including physician-ordered genetic tests, board-certified genetic counselors, and clinical pharmacists, enabling employees to better understand their risk for certain hereditary cancers, heart disease, and genes that may impact medication response. Color’s physician-ordered test can be initiated by individuals online, and a sample collection kit is sent in the mail. Individuals provide a saliva sample and return the kit in a pre-paid package | https://en.wikipedia.org/wiki?curid=53178099 |
Color Genomics Color's CLIA-certified and CAP-approved lab analyzes for variants in the breast cancer genes "BRCA1" and "BRCA2", as well as 28 other genes associated with breast, prostate, colon, uterine, stomach, melanoma, pancreatic, and ovarian cancers. The test also identifies variants in 30 genes related to hereditary heart conditions as well as genes that may impact medication response. Genetic counseling with board-certified genetic counselors is available for free to all individuals who use Color. In 2018, Color was selected, alongside the Broad Institute of MIT and Harvard, and the Laboratory for Molecular Medicine (LMM) at Partners HealthCare, to establish one of three genome centers around the country for the National Institutes of Health’s historic "All of Us" Research Program. "All of Us" will sequence one million or more people across the US, with the goal of accelerating health research and enabling individualized prevention, treatment, and care. The program has a focus on recruitment from populations that have been historically underrepresented in clinical science and genomic medicine, in order to build a diverse biomedical data resource that provides a foundation for better insights into the biological, environmental, and behavioral factors that influence health. In 2019, Color was named the sole awardee to deliver all of the genetic counseling for "All of Us" | https://en.wikipedia.org/wiki?curid=53178099 |
Color Genomics As the awardee, Color will customize software and tools to integrate data from all the genome centers, standardize reporting across the program, and ensure all results are returned in a unified way. This is a first year $4.6 million grant as part of a multi-year $25 million project. In collaboration with the Women’s Health Initiative and Dr. Mary-Claire King at the University of Washington, Color provided genetic sequencing for the cohort of 10,000 Fabulous Ladies Over Seventy (FLOSSIES). This is the largest publicly available dataset of genetic variants associated with hereditary cancer in healthy, older individuals. Color Data, a database containing aggregated genetic and clinical information from 50,000 individuals who took a Color test, helps researchers and scientists identify genotype-phenotype correlations and novel variants for functional analysis, as well as enables data-driven drug discovery and development. It is the largest public database of its kind. As a part of the MAGENTA Study, which aims to improve availability of genetic testing for hereditary cancer syndromes to at-risk individuals through the use of an online genetic testing service, Color is working with a Stand Up to Cancer Dream Team that includes physicians, scientists and researchers from the MD Anderson Cancer Center and the University of Washington to provide genetic counseling to high-risk individuals through delivery models such as tele-counseling. In collaboration with Dr | https://en.wikipedia.org/wiki?curid=53178099 |
Color Genomics Laura Esserman at University of California and Sanford Health, Color is providing genetic testing for WISDOM, a 100,000-woman study that is comparing annual screenings with personalized, risk-based breast cancer screenings. As part of the GENtleMEN Study, Color is working with Dr. Heather Cheng at the Fred Hutchinson Cancer Research Center and the University of Washington to provide genetic testing and counseling to men with advanced prostate cancer. Color contributes anonymized variants to ClinVar, a free database managed by the National Center for Biotechnology Information (NCBI) at the National Institutes of Health (NIH) that helps researchers identify links between genes and disease. Color’s research collaborators include: | https://en.wikipedia.org/wiki?curid=53178099 |
Edouard Perris full name Jean-Pierre Omer Anne (1808, Pau- Mont-de-Marsan 1878) was a French explorer and entomologist who specialised in Coleoptera and to a lesser extent Diptera and other orders. He was Chef de division à la préfecture des Landes. Perris was a Member of Société Entomologique de France. His collection is held by excepting Cicindelidae, Carabini und Lebiini which are held by Museum Dax, Landes. partial list (prolific author) | https://en.wikipedia.org/wiki?curid=53178605 |
Patrick Douglas Baird (1912 – 1 January 1984) was a Scottish glaciologist who worked in the Canadian Arctic. He was born the fourth son of Brigadier-General E.W.D. Baird of Caithness, Scotland and was educated at Edinburgh Academy and Corpus Christi College, Cambridge, graduating in Geology. After working for some years as a geologist in Africa he joined the British-Canadian Arctic Expedition of 1936-39, working in Southampton Island, the Melville Peninsula and Baffin Island. In 1939 he crossed Bylot Island and sailed in the Hudson Bay Company ship "Nascopie" to join the Royal Canadian Artillery. During the war he was concerned with paratrooper training in Scotland and with arctic and mountain warfare training back in Canada, rising to the rank of lieutenant-colonel. He achieved a measure of celebrity status in 1945/6 when he successfully led the main party in "Exercise Muskox" on a 3400-mile expedition around the Canadian Arctic from Churchill via Victoria Island and Coppermine to the Peace River. In 1946 he was appointed chief of the Arctic Section of the Canadian Defence Research Board and the following year made Director of the Montreal Office of the Arctic Institute of North America, an organisation established to improve Canadian scientific and technical expertise in the Arctic | https://en.wikipedia.org/wiki?curid=53208278 |
Patrick Douglas Baird During his time there he organised and led two major expeditions to Baffin Island, one in 1950 to the Barnes Ice Cap region and one in 1953 to the Pangnirtung Pass and Penny Highlands area, which carried out the first glaciological investigations in the Canadian Arctic. Baird became an acknowledged authority on mountain glacier research and arctic mountaineering. In 1954 he returned to his native Scotland to work for five years as a senior research fellow in Geography at the University of Aberdeen. Whilst there he started to write his book "The Polar World" which was later published in 1964. In 1959 he returned to Canada as director of the Gault Estate of McGill University, a 2,600-acre property at Mont-St-Hilaire, Quebec, and as supervisor of Northern Field Studies in the Department of Geography. In 1952 he was awarded the Founder's Medal of the Royal Geographical Society for "his explorations in the Canadian Arctic". Other awards included the Bruce Memorial Medal of the Royal Society of Edinburgh and a Queen Elizabeth II Coronation Medal. He died in Ottawa in 1984. He had married twice, to Gillian Margaret Warren, with whom he had a son and three daughters and to Geneva Adair Jackson of Montreal. The Baird Peninsula of Baffin Island is named after him. | https://en.wikipedia.org/wiki?curid=53208278 |
NGC 6801 is a spiral galaxy in the constellation of Cygnus. It was discovered by Lewis A. Swift on August 5, 1886. In May 2011 a Type Ia supernova, 2011df, was detected in NGC 6801. 2015af, a Type II supernova was discovered in August 2015. | https://en.wikipedia.org/wiki?curid=53248722 |
NGC 4707 is an irregular galaxy in the constellation of Canes Venatici. It was discovered by John Herschel on 5 June 1834, and was described by John Louis Emil Dreyer, the compiler of the New General Catalogue, as a "small, stellar" galaxy. has a morphological type of Sm or Im, meaning that it is mostly irregular or has very weak spiral arms. The galaxy was imaged by the Hubble Space Telescope in 2016. The image showed the galaxy had little to no signs of a central bulge or any prominent structures (typical of Magellanic-type spirals). However, the telescope could resolve many stars, as well as several turquoise-colored star forming regions. | https://en.wikipedia.org/wiki?curid=53250541 |
Leaf flushing is the production of a flush of new leaves typically produced simultaneously on all branches of a bare plant or tree. succeeds leaf fall, and is delayed by winter in the temperate zone or by extreme dryness in the tropics but leaf fall and leaf flushing in tropical deciduous forests can overlap, with new leaves produced during the same period when old leaves are shed. Leaf-flushing can be synchronized among trees of a single species or even across species in an area. Studies show that insect herbivory plays a major role in moulding leaf flushing phenology in trees of the seasonal tropics. | https://en.wikipedia.org/wiki?curid=53258862 |
NGC 1222 is an early-type lenticular galaxy located in the constellation of Eridanus. The galaxy was discovered on 5 December 1883 by the French astronomer Édouard Stephan. John Louis Emil Dreyer, the compiler of the New General Catalogue, described it as a "pretty faint, small, round nebula" and noted the presence of a "very faint star" superposed on the galaxy. NGC 1222's morphological type of S0 would suggest that it should have a mostly smooth profile and a very dull appearance. However, the galaxy was imaged by the Hubble Space Telescope in 2016, and the image showed that there were several bright blue star forming regions, as well as dark reddish areas of interstellar dust. is currently interacting with and swallowing two dwarf galaxies that are supplying the gas and dust needed to become a starburst galaxy. | https://en.wikipedia.org/wiki?curid=53261402 |
NGC 5308 is an edge-on lenticular galaxy in the constellation of Ursa Major. It was discovered on 19 March 1790 by William Herschel. It was described by John Louis Emil Dreyer as "bright, pretty large" when he compiled the New General Catalogue. A small, irregular galaxy near has been given the designation LEDA 2802348. was imaged by the Hubble Space Telescope in 2016. The galaxy appears to be a flat, smooth disk, typical of most lenticular galaxies. Many large globular clusters orbit the galaxy; these are visible as tiny dots surrounding the galaxy, and are mostly made of old, aging stars similar to the galaxy itself. SN 1996bk, a type Ia supernova, was discovered in in October 1996. The supernova was 10.5" south and 17.9" west of center of the galaxy, and had an apparent visual magnitude of 15. | https://en.wikipedia.org/wiki?curid=53264021 |
Comet (experiment) COMET (COherent Muon to Electron Transition) is currently a funded experiment in J-PARC, Tokai, Japan. In contrast to the usual muon decay to an electron and neutrino, COMET seeks to look for neutrinoless muon to electron conversion, where the electron flies away with an energy of 104.8 MeV. Muon to electron conversion is not forbidden in the Standard Model but the branching ratio is about formula_1 considering neutrino oscillations. In beyond the Standard Model approaches the muon to electron conversion process can be as high as formula_2 e.g. via the supersymmetric formula_3. COMET will be using a new beamline connecting the J-PARC main ring and the J-PARC Nuclear and particle Physics Experimental Hall (NP hall). The current spokesperson is Kuno Yoshitaka alongside project manager Mihara Satoshi. The collaboration consists of universities coming from 15 countries. | https://en.wikipedia.org/wiki?curid=53281588 |
Oscar Ringdahl (1885–1966) was a Swedish entomologist who specialised in Diptera and Trichoptera. Ringdahl described many new species from Sweden and Lappland. Parts of his personal collection are in the Swedish Museum of Natural History and Lund University Zoology Museum (Lunds Universitet Zoologiska museet), Lund. Partial list:: | https://en.wikipedia.org/wiki?curid=53289070 |
Eric Hessels Eric A. Hessels is a Canadian physicist, currently a Canada Research Chair and Distinguished Research Professor at York University in Toronto, Ontario. In September 2019, Hessels et al. measured the Lamb shift for hydrogen to measure the radius of a proton and demonstrated that it is consistent with the value obtained for muonic hydrogen. This proved that the supposed discrepancy known as the proton radius puzzle did not exist. | https://en.wikipedia.org/wiki?curid=53292802 |
NGC 2357 is a spiral galaxy located in the constellation of Gemini. It was discovered by Édouard Stephan on 6 February 1885. SN 2010bj, a Type II-P supernova, was detected in February 2010, and SN 2015I, a Type Ia supernova was detected in May 2015. | https://en.wikipedia.org/wiki?curid=53293034 |
NGC 3464 is a barred spiral galaxy in the constellation of Hydra, discovered 14 January 1886 by Ormond Stone. Two supernovae were observed in in 2002. SN 2002J, a Type Ic supernova, was detected 21 January, and SN 2002hy, a Type Ib supernova, was detected 12 November. A Type Ia supernova, SN 2015H, was first observed 10 February 2015. | https://en.wikipedia.org/wiki?curid=53294175 |
NGC 420 is a lenticular galaxy of type S0 located in the constellation Pisces. It was discovered on September 12, 1784 by William Herschel. It was described by Dreyer as "faint, pretty small, round, brighter middle." | https://en.wikipedia.org/wiki?curid=53294475 |
Biomedical research in the United States The US carries out 46% of global research and development (R&D) in the life sciences, making it the world leader in medical research. Life sciences accounted for 51% of federal research expenditure in 2011. The National Institutes of Health (NIH) are considered the government's flagship biomedical research funding organization. Between 2004 and 2014, NIH funding remained relatively flat and was not increased to keep pace with inflation. The NIH budget peaked at circa $35 billion per year from 2003 to 2005 and was around $30 billion in 2015. Government efforts to increase allocations to research between 2013 and 2016 were often thwarted by the congressional austerity drive, with Congress withholding approval of the federal government's budget several times. Over this period, the executive's priorities were taken forward largely thanks to collaboration between the government, industry and the non-profit sector. This was particularly true for the health sector which, like climate change, was a priority for the Obama administration. A key policy objective of the Obama administration was to develop more targeted therapies while reducing the time and cost of drug development. Developing a new drug takes well over a decade and has a failure rate of more than 95%. The most expensive failures happen in late phase clinical trials. It is thus vital to pinpoint the right biological targets (genes, proteins and other molecules) early in the process, so as to design more rational drugs and better tailored therapies | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States The 21st Century Cures Act was signed into law on 13 December 2016, a year after the release of the UNESCO Science Report. The report had predicted that, ‘were the bill to pass into law, it would alter the way in which clinical trials are conducted by allowing new and adaptive trial designs that factor in personalized parameters, such as biomarkers and genetics. This provision has proven controversial, with doctors cautioning that overreliance on biomarkers as a measure of efficacy can be misleading, as they may not always reflect improved patient outcomes'. Another government scheme hopes to increase the number of new diagnostics and therapies for patients, while reducing the time and cost of developing these. At the launch of the Accelerating Medicines Partnership in February 2014, NIH director Francis S. Collins stated that 'Currently, we are investing too much money and time in avenues that don't pan out, while patients and their families wait'. Over the five years to 2019, this public−private partnership is developing up to five pilot projects for three common but difficult-to-treat diseases: Alzheimer's disease, type 2 (adult onset) diabetes and the autoimmune disorders of rheumatoid arthritis and lupus. The partnership involves the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), as well as 10 major biopharmaceutical companies and several non-profit organizations like the Alzheimer's Association | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States The industrial partners are Abbvie (US), Biogen (US), Bristol-Myers Squibb (US), GlaxoSmithKline (UK), Johnson & Johnson (US), Lilly (US), Merck (US), Pfizer (US), Sanofi (France) and Takeda (Japan). Laboratories share samples, such as blood or brain tissue from deceased patients, to identify biomarkers. They also participate in NIH clinical trials. One critical component is that industry partners have agreed to make the data and analyses arising from the partnership accessible to the broad biomedical community. They will not use any discoveries to develop their own drug until these findings have been made public. In April 2013, the government announced another public−private partnership, this time to implement its Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. The goal of this project is to leverage genetic, optical and imaging technologies to map individual neurons and complex circuits in the brain, eventually leading to a more complete understanding of this organ's structure and function. By 2015, the BRAIN Initiative had ‘obtained commitments of over US$ 300 million in resources from federal agencies (National Institutes of Health, Food and Drug Administration, National Science Foundation, etc.), industry (National Photonics Initiative, General Electric, Google, GlaxoSmithKline, etc.) and philanthropy (foundations and universities)’. The Precision Medicine Initiative has been another government priority | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States Defined as delivering the right treatment to the right patient at the right time, precision medicine tailors treatments to patients based on their unique physiology, biochemistry and genetics. In his 2016 budget request, the president asked for US$215 million to be shared by the NIH, National Cancer Institute and FDA to fund the Precision Medicine Initiative. In 2013, US pharmaceutical companies spent $40 billion on R&D inside the US and nearly another $11 billion on R&D abroad. Between 2005 and 2010, pharmaceutical and biopharmaceutical companies increased their investment in precision medicine by roughly 75% and a further increase of 53% is projected by 2015. Between 12% and 50% of the products in their drug development pipelines are related to personalized medicine. The federal government and most of the 50 states that make up the United States offer R&D tax credits to particular industries and companies. Congress usually renews a tax credit every few years. According to a survey by the "Wall Street Journal" in 2012, companies do not factor in these credits when making décisions about investing in R&D, since they cannot rely on these credits being renewed. In 2014, six US biopharmaceutical companies figured in the global Top 50 for the volume of expenditure on R&D. The following have figured in the Top 20 for at least ten years: Intel, Microsoft, Johnson & Johnson, Pfizer and IBM | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States Google was included for the first time in 2013 and Amazon in 2014, which is why the online store does not figure in the Top 50 for 2014. Global top 50 companies by R&D volume and intensity, 2014 <nowiki>*</nowiki> R&D intensity is defined as R&D expenditure divided by net sales. <nowiki>**</nowiki> Although incorporated in the Netherlands, Airbus's principal manufacturing facilities are located in France, Germany, Spain and the UK. Source: "UNESCO Science Report: towards 2030" (2015), Table 9.3, based on Hernández "et. al" (2014) "EU R&D Scoreboard: the 2014 EU Industrial R&D Investment Scoreboard". European Commission: Brussels, Table 2.2. The National Venture Capital Association has reported that, in 2014, venture capital investment in the life sciences was at its highest level since 2008: in biotechnology, $6.0 billion was invested in 470 deals and, in life sciences overall, $8.6 billion in 789 deals (including biotechnology and medical devices). Two-thirds (68%) of the investment in biotechnology went to first-time/early-stage development deals and the remainder to the expansion stage of development (14%), seed-stage companies (11%) and late-stage companies (7%). However, it was the software industry which invested in the greatest number of deals overall: 1 799, for an investment of $19.8 billion. Second came internet-specific companies, garnering US$11.9 billion in investment through 1 005 deals. Many of these companies are based in the State of California, which alone concentrates 28% of US research | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States Total investment in venture capital amounted to US$48.3 billion in 2014, for 4 356 deals. This represented ‘an increase of 61% in dollars and a 4% increase in deals over the prior year,’ reported the National Venture Capital Association. The Organisation for Economic Cooperation and Development estimates that venture capital investment in the United States had fully recovered by 2014. In recent years, a number of pharmaceutical companies have made strategic mergers to relocate their headquarters overseas to gain a tax advantage, including Medtronic and Endo International. Pfizer's own attempt to take over the British pharmaceutical company AstraZeneca aborted in 2014 after Pfizer admitted plans to cut research spending in the combined company. One policy concern for the Obama administration has been the steep rise in the price of prescription drugs, in a country where these prices are largely unregulated. From January 2008 to December 2014, the price of commonly used branded drugs increased by a little over 127%, even as the price of commonly prescribed generic drugs decreased by almost 63%. In 2014, spending on prescription drugs hit $374 billion. This increase in spending was fuelled by the costly new drugs on the market for treating hepatitis C ($11 billion), rather than by the millions of newly insured Americans under the Patient Protection and Affordable Care Act of 2010 ($1 billion) | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States About 31% of this spending went on specialty drug therapies to treat inflammatory conditions, multiple sclerosis, oncology, hepatitis C and HIV, etc., and 6.4% on traditional therapies to treat diabetes, high cholesterol, pain, high blood pressure and heart disease, asthma, depression and so on’. Fuelling the 'astronomic' rise in consumer prices for prescription drugs has been a new trend in the US, the acquisition of pharmaceuticals through licensing, purchase, a merger or acquisition. In the first half of 2014, the value of mergers and acquisitions by pharmaceutical companies totalled US$317.4 billion and, in the first quarter of 2015, the drug industry accounted for a little more than 45% of all US mergers and acquisitions. Several pharmaceutical companies have made strategic mergers in recent years to relocate their headquarters overseas to order to gain a tax advantage. Pfizer's own attempt to take over the British pharmaceutical company Astrazeneca aborted in 2014, after Pfizer admitted plans to cut research spending in the combined company. The Biologics Price Competition and Innovation Act was signed into law in March 2010 to encourage the development of generic drug competition as a cost containment measure for high-priced pharmaceuticals. Part of the government's signatory Patient Protection and Affordable Care Act, it has created a pathway for fast-track licensure for biological products that are shown to be ‘biosimilar’ to, or ‘interchangeable’ with, an approved biological product | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States One inspiration for the act was that the patents for many biologic drugs will expire in the next decade. Although the act was passed in 2010, the first biosimilar was only approved in the US by the FDA in 2015: Zarxio, made by Sandoz. Zarxio is a biosimilar of the cancer drug Neupogen, which boosts the patient's white blood cells to ward off infection. In September 2015, a US court ruled that the Neupogen brand manufacturer Amgen could not block Zarxio from being sold in the US. Neupogen costs about US$3 000 per chemotherapy cycle; Zarxio hit the US market on 3 September 2015 at a 15% discount. In Europe, the same drug had been approved as early as 2008 and has been safely marketed there ever since. The lag in development of an approval pathway in the US has been criticized for impeding access to biological therapies. The true cost savings from the use of biosimilars is difficult to assess. A 2014 study by the Rand Institute estimates a range of US$13–66 billion in savings over 2014–2024, depending upon the level of competition and FDA regulatory approval patterns. Unlike generics, biosimilars cannot be approved on the basis of minimal and inexpensive tests to prove bioequivalence. Since biological drugs are complex, heterogeneous products derived from living cells, they can only be shown to be highly similar to the appropriate reference product and therefore require demonstration that there are no clinically meaningful differences in safety and efficacy | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States The extent to which clinical trials are required will largely determine the cost of development. Orphan diseases affect fewer than 200 000 Americans each year. Since the Orphan Drug Act of 1983, over 400 drugs and biologic products for rare diseases have been designated by the Food and Drug Administration (as of 2015), 260 alone in 2013. In 2014, sales of the top 10 orphan drugs in the US amounted to US$18.32 billion; by 2020, orphan drugs sales worldwide are projected to account for 19% (US$28.16 billion) of the total US$176 billion in prescription drug spending. However, orphan drugs cost about 19.1 times more than non-orphan drugs (on an annual basis) in 2014, at an average annual cost per patient of US$137 782. Some are concerned that the incentives given to pharmaceutical companies to develop orphan drugs by the FDA's orphan drug products programme is taking the companies’ attention away from developing drugs that will benefit more of the population. There are more than 6500 medical device companies in the US, more than 80% of which have fewer than 50 employees. According to the US Department of Commerce, the market size of the medical device industry in the US is expected to reach US$133 billion by 2016. Observers foresee the further development and emergence of wearable health monitoring devices, telediagnosis and telemonitoring, robotics, biosensors, three-dimensional (3D) printing, new "in vitro" diagnostic tests and mobile apps that enable users to monitor their health and related behaviour better | https://en.wikipedia.org/wiki?curid=53296445 |
Biomedical research in the United States Until 2010, the United States of America was a net exporter of pharmaceuticals. Since 2011, it has become a net importer of these goods. The United States has lost its world leadership for high-tech goods. Even computing and communications equipment is now assembled in China and other emerging economies, with high-tech value-added components being produced elsewhere. The United States is a post-industrial country. Imports of high-tech products far exceed exports. However, the United States' technologically skilled workforce produces a large volume of patents and can still profit from the license or sale of these patents. Within the United States' scientific industries active in research, 9.1% of products and services are concerned with the licensing of intellectual property rights. When it comes to trade in intellectual property, the United States remains unrivalled. Income from royalties and licensing amounted to $129.2 billion in 2013, the highest in the world. Japan comes a distant second, with receipts of $31.6 billion in 2013. The United States' payments for use of intellectual property amounted to $39.0 billion in 2013, exceeded only by Ireland ($46.4 billion). Health care in the United States Science policy in the United States Science and technology in the United States | https://en.wikipedia.org/wiki?curid=53296445 |
NGC 1741 is a distant pair of interacting galaxies (NGC 1741A and NGC 1741B) in the Eridanus constellation. It was discovered on 6 January 1878 by French astronomer Édouard Stephan. As a result of the collision, the galaxies are in a rapid starbust phase. The galaxies are classed as Wolf–Rayet galaxies due to their high content of rare Wolf–Rayet stars. This pair of spiral galaxies is made up of PGC 16570 (NGC 1741B) and PGC 16574 (NGC 1741A). This pair is part of the Halton Arp catalog as Arp 259 and the Hickson Compact Group as HCG 31A (NGC 1741A) and HCG 31B (NGC 1741B). | https://en.wikipedia.org/wiki?curid=53303491 |
FlowFET A flowFET is a microfluidic component which allows the rate of flow of liquid in a microfluidic channel to be modulated by the electrical potential applied to it. In this way, it behaves as a microfluidic analogue to the field effect transistor, except that in the flowFET the flow of liquid takes the place of the flow of electric current. Indeed, the name of the flowFET is derived from the naming convention of electronic FETs (e.g. MOSFET, FINFET etc.). A flowFET relies on the principal of electro-osmotic flow (EOF). In many liquid-solid interfaces, there is an electrical double layer that develops due to interactions between the two phases. In the case of a microfluidic channel, this results in a charged layer of liquid on the periphery of the fluid column which surrounds the bulk of the liquid. This electric double layer has an associated potential difference known as the zeta potential. When an appropriately-oriented electrical field is applied to this interfacial double layer (i.e. parallel to the channel and in the plane of the electric double layer), the charged liquid ions experience a motive Lorentz force. Since this layer sheaths the fluid column, and since this layer moves, the entire column of liquid will begin to move with a speed formula_1. The velocity of the fluid layer "diffuses" into the bulk of the channel from the periphery towards the centre due to viscous coupling | https://en.wikipedia.org/wiki?curid=53307338 |
FlowFET The speed is related to the strength of the electric field formula_2, the magnitude of the zeta potential formula_3, the permittivity formula_4 and the viscosity formula_5 of the fluid: formula_6 In a FlowFET, the zeta potential between the channel walls and the fluid can be altered by applying an electrical field "perpendicular" to the channel walls. This has the effect of altering the motive force experienced by the mobile liquid atoms in the double layer. This change in the zeta-potential can be used to control both the magnitude and direction of the electro-osmotic flow in the microchannel. The controlling voltage need only be in the range of 50 V for a typical microfluidic channel, since this correlates to a gradient of 1.5 MV/cm due to the channel size. Variation of the dimensions (e.g. insulating layer thickness between the channel wall and gate electrode) due to the manufacturing process can lead to inexact control of the zeta potential. This can be exacerbated in the case of wall contamination, which can alter the channel wall surface's electrical properties adjacent to the gate electrode. This will affect the local flow characteristics, which may be especially important in chemical synthesis systems whose stoichiometry are directly related to the transport rate of reaction precursors and reaction products. There are constraints placed on the fluid that can be manipulated in a FlowFET. Since it relies on EOF, only fluids producing an EOF in response to an applied electric field may be used | https://en.wikipedia.org/wiki?curid=53307338 |
FlowFET While the controlling voltage need only be on the order of 50V, the EOF-producing voltage along the channel axis is larger, on the order of 300V. It is noticed experimentally that electrolysis may occur at the electrode contacts. This water electrolysis can alter the pH in the channel and adversely affect biological cells and biomolecules, while gas bubbles tend to "clog" microfluidic systems. In further analogy with microelectronic systems, the switching time for a flowFET is inversely proportional to its size. Scaling down a flowFET results in a reduction in the amount of time for the flow to equilibrate to a new flow rate following a change in the applied electrical field. It should be noted, however, that the frequency of flowFET is many orders of magnitude slower than with an electronic FET. A sees potential uses in massively parallel microfluidic manipulation, for example in DNA microarrays. Without using a FlowFET, it is necessary to control the rate of EOF by changing the magnitude of the EOF-producing field (i.e. the field parallel to the channel's axis) while leaving the zeta potential unaltered. In this arrangement, however, simultaneous control of EOF in channels connected with each other cannot easily be accomplished. A provides a way of controlling microfluidic flow in a way that uses no moving parts. This is in stark contrast to other solutions including pneumatically-actuated peristaltic pumps such as presented by Wu et al | https://en.wikipedia.org/wiki?curid=53307338 |
FlowFET Fewer moving parts allows less opportunity for mechanical breakdown of a microfluidic device. This may be increasingly relevant as large future iterations of large microelectronic fluidic (MEF) arrays continue to increase in size and complexity. The use of bi-directional electronically-controlled flow has interesting options for particle and bubble cleaning operations. | https://en.wikipedia.org/wiki?curid=53307338 |
NGC 5264 NGC 5264, also known as DDO 242, is an irregular galaxy in the constellation Hydra. It is part of the M83 subgroup of the Centaurus A/M83 Group, located some 15 million light years (4.5 megaparsecs) away. The galaxy was discovered on 30 March 1835 by John Herschel, and it was described as "very faint, pretty large, round, very little brighter middle" by John Louis Emil Dreyer, the compiler of the New General Catalogue. was imaged by the Hubble Space Telescope in 2016. The galaxy is relatively small: it is a dwarf galaxy, a type of galaxy much smaller than normal spiral galaxies and elliptical galaxies. In fact, it is only 11000 light years (3300 parsecs) wide at its widest; our own galaxy, Milky Way, in comparison, is about ten times larger. Dwarf galaxies like these usually have about a billion stars. also is relatively blue-coloured; this is from it interacting with other galaxies, supplying it with gas for star formation. | https://en.wikipedia.org/wiki?curid=53311012 |
Thomas Glanville Taylor (22 November 1804 – 4 May 1848) was an English astronomer who worked extensively at the Madras Observatory and produced the Madras Catalogue of Stars from around 1831 to 1839. He was the son of Thomas Taylor, assistant at the Royal Greenwich Observatory, and his wife Susannah née Glanville, born at Ashburton, Devon. John Pond, the Astronomer Royal, suggested that the young boy choose a career in astronomy and he joined the observatory in 1820. From August 1822 he was in charge of making transit observations, and his ability was noted by Sir Edward Sabine. Taylor then worked on Stephen Groombridge's star catalogue. Taylor was appointed director of the East India Company's observatory at Madras, arriving there on 15 September 1830. He brought with him new equipment including transit telescopes and a mural circle. He worked with four Indian assistants, who took observations when he went to join the Great Trigonometrical Survey. Taylor collaborated with John Caldecott of the Travancore observatory to make observations on the magnetic field, especially the magnetic equator, of the earth around 1837. A Fellow of the Royal Astronomical Society and the Royal Society (elected 10 February 1842) Taylor helped establish an observatory at Doddabetta in Ootacamund. He was suffering from tuberculosis when he went to visit his ailing daughter in England in 1848. She died in April, and he himself died a month later, in Southampton. He was succeeded at the Madras Observatory by William Stephen Jacob (1813-1862) | https://en.wikipedia.org/wiki?curid=53345171 |
Thomas Glanville Taylor Taylor began the publication of the "Madras General Catalogue of Stars" which was praised by Sir George Airy. His catalogues were of importance in navigation and in the Trigonometrical Survey for determining longitude as well as latitude. Taylor married Eliza Baratty, daughter of Colonel Eley, on 4 July 1832. They had three sons and a daughter. | https://en.wikipedia.org/wiki?curid=53345171 |
Lilabati Bhattacharjee (née Ray) was a mineralogist, crystallographer and a physicist. She studied with scientist Satyendra Nath Bose and completed her MSc in Physics from the Rajabazar Science College campus of University of Calcutta in 1951. Mrs Bhattacharjee specialised in the fields of structural crystallography, optical transform methods, computer programming, phase transformations, crystal growth, topography, instrumentation and made important contributions to these fields. She served as a Senior Mineralogist at the Geological Survey of India and later went on to become the Director (Mineral Physics) of the organisation. She was married to Siva Brata Bhattacherjee, and had two children. | https://en.wikipedia.org/wiki?curid=53349635 |
CRISPR-Display (CRISP-Disp) is a modification of the CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats) system for genome editing. The CRISPR/Cas9 system uses a short guide RNA (sgRNA) sequence to direct a "Streptococcus pyogenes" Cas9 nuclease, acting as a programmable DNA binding protein, to cleave DNA at a site of interest. CRISPR-Display, in contrast, uses a nuclease deficient Cas9 (dCas9) and an engineered sgRNA with aptameric accessory RNA domains, ranging from 100bp to 5kb, outside of the normal complementary targeting sequence. The accessory RNA domains can be functional domains, such as long non-coding RNAs (lncRNAs), protein-binding motifs, or epitope tags for immunochemistry. This allows for investigation of the functionality of certain lncRNAs, and targeting of ribonucleoprotein (RNP) complexes to genomic loci. was first published in Nature Methods in July 2015, and developed by David M. Shechner, Ezgi Hacisuleyman, Scott T. Younger and John Rinn at Harvard University and Massachusetts Institute of Technology (MIT), USA. The CRISPR/Cas9 system is based on an adaptive immune system of prokaryotic organisms, and its use for genome editing was first proposed and developed in collaboration between Jennifer Doudna (University of California, Berkeley) and Emmanuelle Charpentier (Max Planck Institute for Infection Biology, Germany). The method, and its application in editing human cells, was published in Science on August 17, 2012 | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display In January 2013, the Feng Zhang lab at the Broad Institute at MIT published another method in Science, having further optimized the sgRNA structure and expression for use in mammalian cells. By the beginning of 2014, almost 2500 studies mentioning CRISPR in their title has been published. Non-coding RNAs (ncRNAs) are RNA transcripts that are not translated into a protein product, but instead exert their function as RNA molecules. They are involved in a range of processes, like post-transcriptional regulation of gene expression, genomic imprinting, and regulating the chromatin state, and thereby the expression, of a given locus. Many ncRNAs have been discovered, but in many cases, their function has yet to be accurately dissected due to technical challenges. ncRNA function is often not affected by introducing point mutations and premature stop codons. ncRNAs are also thought to regulate gene expression, so deletion studies have a hard time distinguishing effects of ncRNA loss from effects of gene misregulation due to the deletion. Studies of ncRNAs have also lacked the throughput necessary for discerning the RNA based functionality. To meet these challenges, the Rinn lab therefore developed a synthetic biology approach, using CRISPR/Cas9 system, with the Cas9 acting as a conduit, to target ncRNA modules to ectopic genomic locations, and investigating the ncRNAs effects on reporter genes and other genomic features at that site. CRISPR-Disp modifies the CRISPR/Cas9 technology by using a catalytically inactive, i | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display e. nuclease deficient, Cas9 mutant (dCas9), and altering the RNA used for targeting Cas9 to a genomic location. Since sgRNAs are usually expressed by RNA polymerase III, which limits the length of the RNA domain that can be inserted, incorporates RNA polymerase II to permit expression of longer transcripts (~80–250 nucleotides) to overcome this limitation. can therefore add larger RNA domains, like natural and lncRNA domains, without affecting dCas9 localization. The sgRNA is engineered with an aptameric accessory RNA domain in the sequence outside of the targeting sequence. In the development of the technique, five model cofactors with different topology constructs were used: TOP1-4 and INT with an accessory domain (P4-P6 domain) at different positions, including the 5’ and 3’ end and internally within the sgRNA. Each domain contained a stem-loop that can be recognized by a PP7 bacteriophage coat protein. The complex was delivered into mammalian cells (HEK293FT cells) by a lentiviral vector. To ensure that the attached RNA module both retains targeting functionality as well as the resulting complex drive transcriptional activation at a specific site of interest, transient reporter gene expression of luciferase and fluorescent protein was measured | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display Two variations of such a transcription activator assay was performed; directly with a dCas9 fused to a transcriptional activator/repressor (VP64, a factor known to enhance gene expression) (Direct activation) or indirectly where the transcriptional activator is fused to an RNA binding protein module on the sgRNA (Bridged activation). Reporter gene activation through direct activation imply the sgRNA variant binds and targets dCas9 efficiently. All the five topologies showed direct activation except TOP3 and TOP4, which showed reduced activity. Bridged activation indicates that the fused RNA accessory domain is intact in mature dCas9 complexes. Bridged activation was observed with TOP1, TOP3 and INT. The results were recapitulated at endogenous loci by targeting minimal sgRNA and selective expanded topologies (TOP1 and INT) to human ASCL1, IL1RN, NTF3 and TTN promoters. Direct and bridged activation were observed by qRT-PCR for each construct proving that CRISP-Disp allows deployment of large RNA domains to genomic loci. The effect of internal (stem-loop) insertion size on dCas9 complex was assessed using INT-like constructs with cassettes of PP7 stem loops with a size range from 25 nt to 247 nt. Each construct induced significant activation in the reporter assays signifying that internal insertion size does not influence the dCas9 complex function. Similarly, the effect of internal insert sequence was also determined through a set of unique sgRNA variants displaying cassettes of 25 random nucleotides | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display Reporter assays and RIP-Seq confirmed that sequence does not govern complex efficacy. The utility of CRISP-Disp was explored with an array of functional RNA domains such as natural protein binding motifs, artificial aptamers and small molecules with varying size. While all the complexes were functional and viable, and successfully deployed the RNA domains at endogenous loci, the efficacy changed with length and expression levels. This suggests that optimization of structure and sequence might be important required before designing the construct. To determine if artificial lncRNA scaffolds can be used with CRISPR-Display, dCas9 complexes were assembled with artificial RNA with a size comparable to lncRNAs. The constructs were expanded to ~650nt size with an additional P4-P6 domain with hairpin loops that can be recognized by another phage coat protein, MS2. These topology constructs were called double TOP0-2 with the two domains either together at 5’ or 3’end or separately at each end. Transient reporter assays followed by confirmation with RNA Immunoprecipitation sequencing (RIP-qPCR) showed that all the three constructs retained both the domains in the complex. This was also tested with natural lncRNA domains by building Pol II-driven TOP1 and INT constructs fused with human lncRNA domains | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display lncRNAs used had lengths between ~90–4800 nt, and included the NoRC-binding pRNA, three enhancer-transcribed RNAs (eRNAs) FALEC, TRERNA1 and ncRNA-a3), "Xist" A-repeat (RepA), and the 4,799-nt transcriptional activator "HOTTIP". While all the constructs showed significant direct activation, it decreased with increasing lncRNA-sgRNA length. These lncRNA domains could regulate the reporters independent of dCas9 with pRNA and RepA repressing the GLuc reporter expression (repressors) and TRERNA1, ncRNA-a3 and HOTTIP inducing activation (activators), but were properly targeted to an ectopic location of interest by using the CRISP-Disp system. Thus, CRISP-Disp enables control of gene expression with deployment of both artificial scaffolds as well as natural lncRNA domains. allows for previously unavailable studies of lncRNA functionality, artificial ncRNA functionalization, recruitment of endogenous and engineered proteins to genomic loci, and locus affinity tagging for cell imaging. allows targeted localization of natural lncRNAs to ectopic sites for investigation of their function. Exposing various ectopic DNA loci to natural lncRNAs can help show the effects of lncRNAs on gene expression and chromatin state, and help dissect the mechanism of such effects | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display One of the major outstanding questions in the study of lncRNAs is whether effects on chromatin state or gene expression adjacent to a lncRNA locus is due to functional, sequence-specific mechanisms of the lncRNA itself, or due simply to the act of transcribing the lncRNA. Localizing lncRNA to ectopic sites with can help separate the function of the RNA itself from the effects of transcribing such RNA species. Before CRISPR-Display, such studies were challenging due to low throughput, and inability to distinguish lncRNA function from other confounding factors like cryptically encoded peptides or functional DNA elements. also allows for targeted use of the wide array of artificial RNAs with specific functionality, such as RNAs for recruitment of endogenous RNA-binding proteins, antibody affinity tagging, and recruitment of tagged fusion proteins. One example of artificial ncRNA functionalization is incorporating RNA domains recognized by specific antibodies to the sgRNA. can target the sgRNA with a particular epitope sequence to various loci, and fluorescently tagged antibodies can be used to image the locus, showing its localization in the nucleus, and possible interactions with other tagged proteins or genomic loci. Endogenous proteins known to bind a specific RNA motif can be recruited to ectopic genomic locations by incorporating the RNA motif into the sgRNA. can also recruit fusion proteins engineered to bind specific RNA sequences | https://en.wikipedia.org/wiki?curid=53354629 |
CRISPR-Display Recruiting these proteins can allow studies of specific proteins’ and protein complexes’ effects on gene regulation and chromatin states, as well as specific regulation of certain genes for investigation of gene function. Due to the modularity of the sgRNA, several different sgRNAs with distinct functional modules can be expressed in each cell at once. The different RNA modules can then work simultaneously and independently, allowing for, for example, regulation of one genomic location whilst imaging the effects of the regulation at another location. The possible applications of will continue to increase with further development and understanding of ncRNA functionalization. It is not unreasonable to think that may one day enable complex synthetic biology systems, with distinct temporal expression of sgRNAs, and networks and circuits of gene regulation by targeting of regulatory proteins. | https://en.wikipedia.org/wiki?curid=53354629 |
Nikolaj Iljitsch Baranov (sometimes Baranoff) (1887, Oryol-1981, London) was a Russian entomologist who specialised in Diptera. His collection of Palearctic Tachinidae is held by the Smithsonian Institution Washington D.C..Baranov described many new species. He worked as an entomologist at the Institute of Hygiene in Zagreb. partial list | https://en.wikipedia.org/wiki?curid=53363170 |
Third-generation sequencing (also known as long-read sequencing) is a class of DNA sequencing methods currently under active development. Third generation sequencing works by reading the nucleotide sequences at the single molecule level, in contrast to existing methods that require breaking long strands of DNA into small segments then inferring nucleotide sequences by amplification and synthesis. Critical challenges exist in the engineering of the necessary molecular instruments for whole genome sequencing to make the technology commercially available. Second-generation sequencing (short-read sequencing), often referred to as Next-generation sequencing (NGS), has dominated the DNA sequencing space since its development. It has dramatically reduced the cost of DNA sequencing by enabling a massively-paralleled approach capable of producing large numbers of reads at exceptionally high coverages throughout the genome. Since eukaryotic genomes contain many repeated sequence (DNA), a major limitation to this class of sequencing methods is the length of reads it produces. Briefly, second generation sequencing works by first amplifying the DNA molecule and then conducting sequencing by synthesis. The collective fluorescent signal resulting from synthesizing a large number of amplified identical DNA strands allows the inference of nucleotide identity. However, due to random errors, DNA synthesis between the amplified DNA strands would become progressively out-of-sync. Quickly, the signal quality deteriorates as the read-length grows | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing In order to preserve read quality, long DNA molecules must be broken up into small segments, resulting in a critical limitation of second generation sequencing technologies. Computational efforts aimed to overcome this challenge often rely on approximative heuristics that may not result in accurate assemblies. By enabling direct sequencing of single DNA molecules, third generation sequencing technologies have the capability to produce substantially longer reads than second generation sequencing. Such an advantage has critical implications for both genome science and the study of biology in general. However, third generation sequencing data have much higher error rates than previous technologies, which can complicate downstream genome assembly and analysis of the resulting data. These technologies are undergoing active development and it is expected that there will be improvements to the high error rates. For applications that are more tolerant to error rates, such as structural variant calling, third generation sequencing has been found to outperform existing methods. Sequencing technologies with a different approach than second-generation platforms were first described as "third-generation" in 2008-2009. There are several companies currently at the heart of third generation sequencing technology development, namely, Pacific Biosciences, Oxford Nanopore Technology, Quantapore (CA-USA), and Stratos (WA-USA). These companies are taking fundamentally different approaches to sequencing single DNA molecules | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing PacBio developed the sequencing platform of single molecule real time sequencing (SMRT), based on the properties of zero-mode waveguides. Signals are in the form of fluorescent light emission from each nucleotide incorporated by a DNA polymerase bound to the bottom of the zL well. Oxford Nanopore’s technology involves passing a DNA molecule through a nanoscale pore structure and then measuring changes in electrical field surrounding the pore; while Quantapore has a different proprietary nanopore approach. Stratos Genomics spaces out the DNA bases with polymeric inserts, ""Xpandomers"", to circumvent the signal to noise challenge of nanopore ssDNA reading. Also notable is Helicos's single molecule fluorescence approach, but the company entered bankruptcy in the fall of 2015. In comparison to the current generation of sequencing technologies, third generation sequencing has the obvious advantage of producing much longer reads. It is expected that these longer read lengths will alleviate numerous computational challenges surrounding genome assembly, transcript reconstruction, and metagenomics among other important areas of modern biology and medicine. It is well known that eukaryotic genomes including primates and humans are complex and have large numbers of long repeated regions. Short reads from second generation sequencing must resort to approximative strategies in order to infer sequences over long ranges for assembly and genetic variant calling | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing Pair end reads have been leveraged by second generation sequencing to combat these limitations. However, exact fragment lengths of pair ends are often unknown and must also be approximated as well. By making long reads lengths possible, third generation sequencing technologies have clear advantages. Epigenetic markers are stable and potentially heritable modifications to the DNA molecule that are not in its sequence. An example is DNA methylation at CpG sites, which has been found to influence gene expression. Histone modifications are another example. The current generation of sequencing technologies rely on laboratory techniques such as ChIP-sequencing for the detection of epigenetic markers. These techniques involve tagging the DNA strand, breaking and filtering fragments that contain markers, followed by sequencing. Third generation sequencing may enable direct detection of these markers due to their distinctive signal from the other four nucleotide bases. Other important advantages of third generation sequencing technologies include portability and sequencing speed. Since minimal sample preprocessing is required in comparison to second generation sequencing, smaller equipments could be designed. Oxford Nanopore Technology has recently commercialized the MinION sequencer. This sequencing machine is roughly the size of a regular USB flash drive and can be used readily by connecting to a laptop | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing In addition, since the sequencing process is not parallelized across regions of the genome, data could be collected and analyzed in real time. These advantages of third generation sequencing may be well-suited in hospital settings where quick and on-site data collection and analysis is demanded. Third generation sequencing, as it currently stands, faces important challenges mainly surrounding accurate identification of nucleotide bases; error rates are still much higher compared to second generation sequencing. This is generally due to instability of the molecular machinery involved. For example, in PacBio’s single molecular and real time sequencing technology, the DNA polymerase molecule becomes increasingly damaged as the sequencing process occurs. Additionally, since the process happens quickly, the signals given off by individual bases may be blurred by signals from neighbouring bases. This poses a new computational challenge for deciphering the signals and consequently inferring the sequence. Methods such as Hidden Markov Models, for example, have been leveraged for this purpose with some success. On average, different individuals of the human population share about 99.9% of their genes. In other words, approximately only one out of every thousand bases would differ between any two person. The high error rates involved with third generation sequencing are inevitably problematic for the purpose of characterizing individual differences that exist between members of the same species | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing Genome assembly is the reconstruction of whole genome DNA sequences. This is generally done with two fundamentally different approaches. When a reference genome is available, as one is in the case of human, newly sequenced reads could simply be aligned to the reference genome in order to characterize its properties. Such reference based assembly is quick and easy but has the disadvantage of “hiding" novel sequences and large copy number variants. In addition, reference genomes do not yet exist for most organisms. "De novo" assembly is the alternative genome assembly approach to reference alignment. It refers to the reconstruction of whole genome sequences entirely from raw sequence reads. This method would be chosen when there is no reference genome, when the species of the given organism is unknown as in metagenomics, or when there exist genetic variants of interest that may not be detected by reference genome alignment. Given the short reads produced by the current generation of sequencing technologies, de novo assembly is a major computational problem. It is normally approached by an iterative process of finding and connecting sequence reads with sensible overlaps. Various computational and statistical techniques, such as de bruijn graphs and overlap layout consensus graphs, have been leveraged to solve this problem. Nonetheless, due to the highly repetitive nature of eukaryotic genomes, accurate and complete reconstruction of genome sequences in de novo assembly remains challenging | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing Pair end reads have been posed as a possible solution, though exact fragment lengths are often unknown and must be approximated. Long read lengths offered by third generation sequencing may alleviate many of the challenges currently faced by de novo genome assemblies. For example, if an entire repetitive region can be sequenced unambiguously in a single read, no computation inference would be required. Computational methods have been proposed to alleviate the issue of high error rates. For example, in one study, it was demonstrated that de novo assembly of a microbial genome using PacBio sequencing alone performed superior to that of second generation sequencing. Third generation sequencing may also be used in conjunction with second generation sequencing. This approach is often referred to as hybrid sequencing. For example, long reads from third generation sequencing may be used to resolve ambiguities that exist in genomes previously assembled using second generation sequencing. On the other hand, short second generation reads have been used to correct errors in that exist in the long third generation reads. In general, this hybrid approach has been shown to improve de novo genome assemblies significantly. DNA methylation (DNAm) – the covalent modification of DNA at CpG sites resulting in attached methyl groups – is the best understood component of epigenetic machinery | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing DNA modifications and resulting gene expression can vary across cell types, temporal development, with genetic ancestry, can change due to environmental stimuli and are heritable. After the discovery of DNAm, researchers have also found its correlation to diseases like cancer and autism. In this disease etiology context DNAm is an important avenue of further research. The current most common methods for examining methylation state require an assay that fragments DNA before standard second generation sequencing on the Illumina platform. As a result of short read length, information regarding the longer patterns of methylation are lost. Third generation sequencing technologies offer the capability for single molecule real-time sequencing of longer reads, and detection of DNA modification without the aforementioned assay. Oxford Nanopore Technologies’ MinION has been used to detect DNAm. As each DNA strand passes through a pore, it produces electrical signals which have been found to be sensitive to epigenetic changes in the nucleotides, and a hidden Markov model (HMM) was used to analyze MinION data to detect 5-methylcytosine (5mC) DNA modification. The model was trained using synthetically methylated "E. coli" DNA and the resulting signals measured by the nanopore technology. Then the trained model was used to detect 5mC in MinION genomic reads from a human cell line which already had a reference methylome | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing The classifier has 82% accuracy in randomly sampled singleton sites, which increases to 95% when more stringent thresholds are applied. Other methods address different types of DNA modifications using the MinION platform. Stoiber et al. examined 4-methylcytosine (4mC) and 6-methyladenine (6mA), along with 5mC, and also created a software to directly visualize the raw MinION data in human-friendly way. Here they found that in "E. coli", which has a known methylome, event windows of 5 base pairs long can be used to divide and statistically analyze the raw MinION electrical signals. A straightforward Mann-Whitney U test can detect modified portions of the "E. coli" sequence, as well as further split the modifications into 4mC, 6mA or 5mC regions. It seems likely that in the future, MinION raw data will be used to detect many different epigenetic marks in DNA. PacBio sequencing has also been used to detect DNA methylation. In this platform the pulse width - the width of a fluorescent light pulse - corresponds to a specific base. In 2010 it was shown that the interpulse distance in control and methylated samples are different, and there is a "signature" pulse width for each methylation type. In 2012 using the PacBio platform the binding sites of DNA methyltransferases were characterized. The detection of N6-methylation in C Elegans was shown in 2015. DNA methylation on "N"-adenine using the PacBio platform in mouse embryonic stem cells was shown in 2016 | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing Other forms of DNA modifications – from heavy metals, oxidation, or UV damage – are also possible avenues of research using Oxford Nanopore and PacBio third generation sequencing. Processing of the raw data – such as normalization to the median signal – was needed on MinION raw data, reducing real-time capability of the technology. Consistency of the electrical signals is still an issue, making it difficult to accurately call a nucleotide. MinION has low throughput; since multiple overlapping reads are hard to obtain, this further leads to accuracy problems of downstream DNA modification detection. Both the hidden Markov model and statistical methods used with MinION raw data require repeated observations of DNA modifications for detection, meaning that individual modified nucleotides need to be consistently present in multiple copies of the genome, e.g. in multiple cells or plasmids in the sample. For the PacBio platform, too, depending on what methylation you expect to find, coverage needs can vary. As of March 2017, other epigenetic factors like histone modifications have not been discoverable using third-generation technologies. Longer patterns of methylation are often lost because smaller contigs still need to be assembled. Transcriptomics is the study of the transcriptome, usually by characterizing the relative abundances of messenger RNA molecules the tissue under study | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing According to the central dogma of molecular biology, genetic information flows from double stranded DNA molecules to single stranded mRNA molecules where they can be readily translated into function protein molecules. By studying the transcriptome, one can gain valuable insight into the regulation of gene expressions. While expression levels as the gene level can be more or less accurately depicted by second generation sequencing, transcript level information is still an important challenge. As a consequence, the role of alternative splicing in molecular biology remains largely elusive. Third generation sequencing technologies hold promising prospects in resolving this issue by enabling sequencing of mRNA molecules at their full lengths. Alternative splicing (AS) is the process by which a single gene may give rise to multiple distinct mRNA transcripts and consequently different protein translations. Some evidence suggests that AS is a ubiquitous phenomenon and may play a key role in determining the phenotypes of organisms, especially in complex eukaryotes; all eukaryotes contain genes consisting of introns that may undergo AS. In particular, it has been estimated that AS occurs in 95% of all human multi-exon genes. AS has undeniable potential to influence myriad biological processes. Advancing knowledge in this area has critical implications for the study of biology in general | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing The current generation of sequencing technologies produce only short reads, putting tremendous limitation on the ability to detect distinct transcripts; short reads must be reverse engineered into original transcripts that could have given rise to the resulting read observations. This task is further complicated by the highly variable expression levels across transcripts, and consequently variable read coverages across the sequence of the gene. In addition, exons may be shared among individual transcripts, rendering unambiguous inferences essentially impossible. Existing computational methods make inferences based on the accumulation of short reads at various sequence locations often by making simplifying assumptions. Cufflinks takes a parsimonious approach, seeking to explain all the reads with the fewest possible number of transcripts. On the other hand, StringTie attempts to simultaneously estimate transcript abundances while assembling the reads. These methods, while reasonable, may not always identify real transcripts. A study published in 2008 surveyed 25 different existing transcript reconstruction protocols. Its evidence suggested that existing methods are generally weak in assembling transcripts, though the ability to detect individual exons are relatively intact. According to the estimates, average sensitivity to detect exons across the 25 protocols is 80% for "Caenorhabditis elegans" genes. In comparison, transcript identification sensitivity decreases to 65% | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing For human, the study reported an exon detection sensitivity averaging to 69% and transcript detection sensitivity had an average of mere 33%. In other words, for human, existing methods are able to identify less than half of all existing transcript. Third generation sequencing technologies have demonstrated promising prospects in solving the problem of transcript detection as well as mRNA abundance estimation at the level of transcripts. While error rates remain high, third generation sequencing technologies have the capability to produce much longer read lengths. Pacific Bioscience has introduced the iso-seq platform, proposing to sequence mRNA molecules at their full lengths. It is anticipated that Oxford Nanopore will put forth similar technologies. The trouble with higher error rates may be alleviated by supplementary high quality short reads. This approach has been previously tested and reported to reduce the error rate by more than 3 folds. Metagenomics is the analysis of genetic material recovered directly from environmental samples. The main advantage for third-generation sequencing technologies in metagenomics is their speed of sequencing in comparison to second generation techniques. Speed of sequencing is important for example in the clinical setting (i.e. pathogen identification), to allow for efficient diagnosis and timely clinical actions. Oxford Nanopore's MinION was used in 2015 for real-time metagenomic detection of pathogens in complex, high-background clinical samples | https://en.wikipedia.org/wiki?curid=53363521 |
Third-generation sequencing The first Ebola virus (EBV) read was sequenced 44 seconds after data acquisition. There was uniform mapping of reads to genome; at least one read mapped to >88% of the genome. The relatively long reads allowed for sequencing of a near-complete viral genome to high accuracy (97–99% identity) directly from a primary clinical sample. A common phylogenetic marker for microbial community diversity studies is the 16S ribosomal RNA gene. Both MinION and PacBio's SMRT platform have been used to sequence this gene. In this context the PacBio error rate was comparable to that of shorter reads from 454 and Illumina's MiSeq sequencing platforms. MinION's high error rate (~10-40%) prevented identification of antimicrobial resistance markers, for which single nucleotide resolution is necessary. For the same reason, eukaryotic pathogens were not identified. Ease of carryover contamination when re-using the same flow cell (standard wash protocols don’t work) is also a concern. Unique barcodes may allow for more multiplexing. Furthermore, performing accurate species identification for bacteria, fungi and parasites is very difficult, as they share a larger portion of the genome, and some only differ by <5%. The per base sequencing cost is still significantly more than that of MiSeq. However, the prospect of supplementing reference databases with full-length sequences from organisms below the limit of detection from the Sanger approach; this could possibly greatly help the identification of organisms in metagenomics. | https://en.wikipedia.org/wiki?curid=53363521 |
SMiLE-Seq Selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq) is a technique developed for the rapid identification of DNA binding specificities and affinities of full length monomeric and dimeric transcription factors in a fast and semi-high-throughput fashion. SMiLE-seq works by loading "in vitro" transcribed and translated “bait” transcription factors into a microfluidic device in combination with DNA molecules. Bound transcription factor-DNA complexes are then isolated from the device, which is followed by sequencing and sequence data analysis to characterize binding motifs. Specialized software is used to determine the DNA binding properties of monomeric or dimeric transcription factors to help predict their "in vivo" DNA binding activity. SMiLE-seq combines three critical functions that makes it unique from existing techniques: (1) the use of capillary pumps to optimize the loading of samples, (2) trapping molecular interactions on the surface of the microfluidic device through immunocapture of target transcription factors, (3) enabling the selection of DNA that is specifically bound to transcription factors from a pool of random DNA sequences. Elucidating the regulatory mechanisms used to govern essential cellular processes is one of the most intensely studied branches of science. Cellular regulatory networks can be incredibly complex, and often involve the coordination of multiple processes that begin with the modulation of gene expression | https://en.wikipedia.org/wiki?curid=53367602 |
SMiLE-Seq The binding of transcription factor molecules to DNA, either alone or in combination with other transcription factors, is used to control gene expression in response to both intra- and extracellular stimuli. Characterizing the binding mechanisms and specificities of transcription factors to specific regions of DNA – and identifying these transcription factors – is a fundamental component of the process of resolving cellular regulatory dynamics. Before the introduction of SMiLE-seq technology, ChIP-seq (chromatin immunoprecipitation sequencing) and HT-SELEX (high throughput systematic evolution of ligands by exponential enrichment) technologies were used to successfully characterize nearly 500 transcription factor-DNA binding interactions. ChIP-seq uses immunoprecipitation to isolate specific transcription factors bound to DNA fragments. Immunoprecipitation is followed by DNA sequencing, which identifies the genomic regions to which transcription factors bind. HT-SELEX, a similar method, uses random, synthetically generated DNA molecules as bait for transcription factors "in vitro". Sequence preferences and binding affinities are characterized based on successful binding interactions between bait molecules and transcription factors. While many unique transcription factor-DNA binding interactions have been characterized using these methods, it is estimated that this described fraction represents fewer than 50% of the transcription factors present in humans | https://en.wikipedia.org/wiki?curid=53367602 |
SMiLE-Seq The development of SMiLE-seq technology has provided an attractive alternative method with the potential to facilitate identification and characterization of previously undescribed transcription factor-DNA binding interactions. SMiLE-seq uses a microfluidic device into which transcription factors, which have been transcribed and translated "in vitro", are loaded. Transcription factor samples (~0.3 ng) are modified by the addition of an enhanced green fluorescent protein (eGFP) tag and combined with both target double-stranded DNA molecules (~8 pmol) tagged with Cyanine Dye5 (Cy5) and a double-stranded competitive DNA model, poly-dIdC, which operates as a negative control to limit spurious binding interactions. When multiple transcription factors are simultaneously analyzed (e.g., when characterization of potential heterodimeric binding interactions is performed), each transcription factor is tagged with a correspondingly unique fluorescent tag. Samples are pumped through the microfluidic device in a passive, twenty-minute process that utilizes capillary action in a series of parallel channels. eGFP-tagged transcription factors are immunocaptured using anchored biotinylated anti-eGFP antibodies. Mechanical depression of a button traps bound transcription factor-DNA complexes, and fluorescent analysis is performed. Fluorescent readouts that identify the presence of multiple fluorescent tags associated with a single antibody indicate heterodimeric binding interactions | https://en.wikipedia.org/wiki?curid=53367602 |
SMiLE-Seq The presence of DNA is confirmed by Cy5 signal detection. A polydimethylsiloxane membrane on the button surface captures successfully bound transcription factor-DNA complexes, while unbound transcription factors and targets are washed away. Following the removal of unbound components, bound DNA molecules are collected, pooled, and amplified. Sequencing is subsequently performed using NextSeq 500 or HiSeq2000 sequencing lanes. Sequence data is used to develop a seed sequence, which is then probed for functional motifs using a uniquely developed hidden Markov model-based software pipeline. The use of microfluidics in SMiLE-seq offers three main advantages when compared to current techniques used to measure protein-DNA interactions (e.g., ChIP-seq, HT-SELEX, and protein binding microarrays). Firstly, it requires fewer transcription factors than other similar techniques (only picograms are required). Secondly, the process is much faster than other techniques (it requires less than an hour, as compared to days). Lastly, SMiLE-seq is not limited by the length of target DNA (a limitation of protein binding microarrays), and is not biased towards stronger affinity protein-DNA interactions (a major limitation of HT-SELEX). Existing technologies have been found to be laborious and technically complex due to improper transcription factor expression or loss of transcription factor-DNA binding properties "in vitro" | https://en.wikipedia.org/wiki?curid=53367602 |
SMiLE-Seq The ability of many transcription factors to bind DNA is dependent on heterodimer formation, and therefore requires the presence of a specific dimer partner for binding. This has been shown to yield incomplete results if transcription factors are individually tested. Heterodimer combinations have been shown to range from 3000 to 25000, and many remain uncharacterized. A technology like SMiLE-seq, which is able to detect these dimeric interactions, is essential to broaden current knowledge and characterization of transcription factor-DNA binding profiles. Additionally, previous technologies have used transcription factor probes in their truncated form, which may reduce their ability to bind and dimerize. SMiLE-seq enables robust identification of DNA binding specificities of full length, previously uncharacterized transcription factors. Furthermore, SMiLE-seq is able to identify transcription factor binding sites over a wide range of binding affinities, which represents a significant limitation of other technologies. In theory SMiLE-seq is not limited to only protein-DNA interactions and may potentially be utilized to study protein-RNA binding properties once the technology has been developed further. The primary limitation of SMiLE-seq is that the technique can only be used to characterize the binding interactions of previously identified transcription factors, as the method requires "in vitro" transcription and translation of the transcription factors prior to their combination with DNA molecules | https://en.wikipedia.org/wiki?curid=53367602 |
SMiLE-Seq Additionally, previous studies have shown that fluorescent protein tags can affect the binding affinity of proteins to their targets. The effect of the specific fluorescent protein tags on binding affinity would have to be investigated to determine whether this would impact specific protein-DNA interactions found using this technology. Further development of SMiLE-seq may involve modifying transcription factor expression conditions to increase the success of analysis. | https://en.wikipedia.org/wiki?curid=53367602 |
Al-Ashraf Umar II al‐Malik al‐Ashraf (Mumahhid al‐Dīn) ʿUmar ibn Yūsuf ibn ʿUmar ibn ʿAlī ibn Rasūl (born c. 1242, died 22 November 1296 in Yemen) was the third Rasulid sultan and a polymath. He is known for writing the first description of the use of a magnetic compass for determining the qibla. Also, his works on astronomy contain important information on earlier sources. In a treatise about astrolabes and sundials, al-Ashraf includes several paragraphs on the construction of a compass bowl (ṭāsa). He then uses the compass to determine the north point, the meridian (khaṭṭ niṣf al-nahār), and the Qibla towards Mecca. This is the first mention of a compass in a medieval Islamic scientific text and its earliest known use as a Qibla indicator, although al-Ashraf did not claim to be the first to use it for this purpose. | https://en.wikipedia.org/wiki?curid=53368843 |
NGC 423 is a lenticular galaxy of type S0/a? located in the constellation Sculptor. It was discovered on November 14, 1835 by John Herschel. It was described by Dreyer as "extremely faint, small, extended, gradually a little brighter middle, eastern of 2.", the other being NGC 418. | https://en.wikipedia.org/wiki?curid=53369366 |
John Goss-Custard Dr John D. Goss-Custard is a British behavioural ecologist; he was one of the first scientists to carry out field work on foraging behaviour making use of optimising models, specifically the optimal diet model. After completing a BSc degree in Zoology at the University of Bristol, he moved to the University of Aberdeen to carry out research for a PhD degree, which he was awarded in 1966. The University of Aberdeen awarded him its DSc degree in 1987. Goss-Custard's PhD was based on the study of foraging in the Common Redshank. Subsequently, he worked at the Centre for Ecology and Hydrology's Furzebrook Research Station at Wareham, Dorset, leading an extensive project on the foraging of overwintering Eurasian Oystercatchers on the estuary of the River Exe. This project led to one of the first uses of agent-based modelling to predict ecological relationships in an extended landscape; the model, developed for the Exe estuary, was subsequently tested successfully on the Wash. This work was surveyed in a book that he edited. Goss-Custard retired from his post at CEH in 2002. Although he did not hold a substantive university post, Goss-Custard held an honorary position at the University of Exeter for many years, and is currently a Visiting Professor at the University of Bournemouth. He co-supervised PhD degrees with colleagues at the University of Exeter and also the University of Oxford. | https://en.wikipedia.org/wiki?curid=53384718 |
Moving the Earth farther away from the sun as the Sun grows hotter during its current hydrogen burning phase has been considered by planetary scientists, including some at Cornell University. Various mechanisms have been proposed to increase the size of the Earth's orbit. The most plausible method would involve redirecting asteroids roughly about 100 km wide via gravity assists around the Earth's orbit and towards Jupiter or Saturn and back in order to gradually move the Earth away from the Sun in order to keep it within the continuously habitable zone. However, this scenario has many practical drawbacks: besides the fact that such a scenario spans vast timescales far longer than human history, it would also put life on Earth at risk, as the repeated encounters could cause the Earth to potentially lose its Moon, therefore severely disrupting Earth's climate and rotation. Additionally, the encounters would require said asteroids to pass extremely dangerously close to Earth, and one slight miscalculation would end up causing the asteroid to hit the Earth instead and potentially sterilizing it, at least down to the level of bacteria, and that the damage done cannot be overemphasized. | https://en.wikipedia.org/wiki?curid=53386033 |
Shu Jie Lam is a Malaysian-Chinese research chemist specialising in biomolecular engineering. She is researching star polymers designed to attack superbugs as antibiotics. | https://en.wikipedia.org/wiki?curid=53391053 |
J. C. Séamus Davis is an Irish physicist who is active in the field of condensed matter physics and who is well-known for low-temperature experiments, e.g. using scanning tunneling microscopy. At present he holds academic positions at Oxford, Cork, and Cornell. Davis was admitted to University College Cork (UCC) in 1978 and studied physics under Frank Fahy, earning a B.Sc. there in 1983. He got a Ph.D. in Physics from the University of California, Berkeley in 1989, became a postdoctoral research associate there in 1990 and joined the faculty in 1993, rising through the ranks to become a full Professor of Physics in 2001. From 1998 to 2003, he was also a Faculty Physicist at Lawrence Berkeley National Laboratory. He then joined Cornell University as a Professor of Physics in 2003, and was appointed J.G. White Distinguished Professor of Physics in 2008. Also in 2007, he became SUPA Distinguished Professor of Physics at the University of St Andrews. He joined Brookhaven National Laboratory in 2007 as a Senior Physicist, and in 2009 was appointed Director of DOE's Center for Emergent Superconductivity, an Energy Frontier Research Center. In 2019 Davis became Professor of Physics at Oxford University, Oxford, UK; Professor of Quantum Physics at University College Cork, IRL and Emeritus Professor of Physics at Cornell University, NY, USA. In April 2020 he was awarded a Royal Society Research Professorship. Research of Davis addresses the macroscopic quantum physics of emergent quantum matter at low temperatures | https://en.wikipedia.org/wiki?curid=53408038 |
J. C. Séamus Davis Active research interests include studies of superconductors, superfluids and supersolids; Kondo, Weyl and Hund metals; magnetic and Kondo topological condensates; and spin & monopole liquids. For these studies, a variety of specialized instrumentation has been developed including scanning tunneling microscopes, quantum interferometers, quantum mechanical oscillators and spin noise spectrometers. Davis has been the recipient of the Outstanding Performance Award of the Berkeley National Lab. (2001), the Science and Technology Award of Brookhaven National Lab. (2013), the Fritz London Memorial Prize (2005) for his research on superfluids, the Kamerlingh-Onnes Memorial Prize (2009) for his research on high temperature superconductivity, and the Science Foundation Ireland Medal of Science (2016). In 2014 he received an Honorary Doctorate (D.Sc.) from National University of Ireland. He is a Fellow of the Institute of Physics (UK), the American Physical Society (USA), the Max Planck Gesellschaft (DE), and a Member of the US National Academy of Sciences. | https://en.wikipedia.org/wiki?curid=53408038 |
Peder Nielsen (1893-1975) was a Danish entomologist who specialised in Diptera especially Nematocera. was a librarian and museologist in Silkeborg. partial list Full list at Craneflies of the World | https://en.wikipedia.org/wiki?curid=53410460 |
NGC 5003 is a spiral galaxy in the constellation Canes Venatici. The celestial object was discovered on April 9, 1787, by the German-British astronomer William Herschel. | https://en.wikipedia.org/wiki?curid=53412666 |
José Luis Sérsic (6 May 1933 – 19 July 1993) was an Argentine astronomer who studied the morphology of galaxies. He is most widely known for the mathematical model of galaxy brightness, the Sersic profile, which bears his name. first published his law in 1963. The asteroid 2691 Sersic is named in his honour. | https://en.wikipedia.org/wiki?curid=53413142 |
Sabine Stanley is a Canadian physicist, currently at Johns Hopkins University in the Zanvyl Krieger School of Arts and Sciences Morton K. Blaustein Department of Earth And Planetary Sciences and was awarded a Bloomberg Distinguished Professorship in 2017. She was previously a Canada Research Chair of Planetary Physics at University of Toronto. She was awarded the William Gilbert Award by the AGU in 2010 and was awarded a Sloan Research Fellowship in 2011. earned a Bachelors of Science in Astronomy and Physics from University of Toronto in 1999. She subsequently earned a Masters in Geophysics in 2003 and a PhD in Geophysics in 2004 from Harvard University. After the awarding of her PhD at Harvard, Dr. was a postdoc working with Maria Zuber from 2004 to 2005 at the Massachusetts Institute of Technology prior to returning to Canada and the University of Toronto. In 2010, Dr Stanley was awarded the William Gilbert Award from the American Geophysical Union for her major theoretical contributions to the study of planetary magnetism and the use of dynamo theory. In 2011, she was amongst the 118 Sloan Foundation fellowship recipients, specifically in Physics and was one of only three Canadian awardees that year. | https://en.wikipedia.org/wiki?curid=53424910 |
Fritz Peus ( 22 April 1904, Siegen- 17 November 1978, Berlin ) full name Friedrich Ferdinand Christian Peus was a German entomologist who specialised in Coleoptera, Diptera and Siphonaptera. From 1923 to 1927 Peus studied zoology, botany and physics at the University of Münster. During the second world war, Peus was engaged as an Army entomologist and employed in malaria research. He had joined the NSDAP party in 1940. Peus was later Director of the Museum für Naturkunde Berlin and Professor for special zoology at the Humboldt University of Berlin and from 1962 up to his retirement in 1969 Professor of applied zoology at the Freie Universität Berlin. partial list | https://en.wikipedia.org/wiki?curid=53425146 |
Ormdl sphingolipid biosynthesis regulator 3 ORMDL sphingolipid biosynthesis regulator 3 is a protein that in humans is encoded by the ORMDL3 gene. This gene is associated with asthma in childhood. Transgenic mice which overexpressing human ORMDL3 have increased levels of IgE. This correlated with increased numbers of macrophages, neutrophils, eosinophils, CD4+ and enhanced Th2 cytokine levels in the lung tissue. Mouse and human ORMDL3 gene encode 153 aa. ORMDL family consists of three members (ORMDL1-3) which are localised in the membrane of endoplasmic reticulum (ER). Human ORMDL1, ORMDL2 and ORMDL3 are localised in chromosomes 2q32, 12q13.2 a 17q21. ORMDL3 plays role in sphingolipid synthesis like negative regulators. It also has a role in regulation of Ca levels in the endoplasmic reticulum. ER is very important for generation, signalisation, functioning and store of intracellular Ca. There are channels, which control the exit of Ca from the ER into the cytoplasm and also pumps (sarco-endoplasmic reticulum Ca ATPase (SERCA)) which return Ca back to the ER. Dysregulation of Ca has the key role in several pathological conditions like dysfunction of SERCA, asthma,and Alzheimer's Mutations in ORMDL3 are associated with inflammatory disease like Crohn's disease, type 1 diabetes, and rheumatiod arthritis. | https://en.wikipedia.org/wiki?curid=53427212 |
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