Bruce Rosen

Bruce Rosen is an American physicist and radiologist and a leading expert in the area of functional neuroimaging. His research for the past 30 years has focused on the development and application of physiological and functional nuclear magnetic resonance techniques, as well as new approaches to combine functional magnetic resonance imaging (fMRI) data with information from other modalities such as positron emission tomography (PET), magnetoencephalography (MEG) and noninvasive optical imaging. The techniques his group has developed to measure physiological and metabolic changes associated with brain activation and cerebrovascular insult are used by research centers and hospitals throughout the world.
As Director of the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, he has overseen significant advances including the introduction and development of functional MRI in the early 1990s.
Development of functional MRI.
Rosen is the senior author on two seminal papers in the development of functional MRI. He was one of John (Jack) Belliveau’s thesis advisers when Belliveau – a Harvard graduate student working in the NMR Center (now the Martinos Center) at Massachusetts General Hospital – performed his early experiments using MRI to reveal regional activity in the brain. Using an MR technique he had developed to track blood flow (“dynamic susceptibility contrast”) he imaged the visual cortex of volunteers during periods of both rest and activation. By subtracting one image from the other, he then demonstrated differences in MR signal between the two.
Science recognized the significance of this work as the first demonstration of functional MRI in the human brain. It published Belliveau’s report in November 1991 – with Rosen as the senior author – and featured one of his images on the cover.
The study opened the door to functional imaging the brain with MRI, but because the approach required the use of an intravenous contrast agent it was not suitable for wide application in humans. To address this limitation, Kenneth Kwong, a postdoctoral fellow in the NMR Center, developed a means to measure endogenous signals based on blood oxygenation using gradient echo imaging. He successfully demonstrated the technique in May 1991 and a report of the findings was published in 1992 in the Proceedings of the National Academy of Sciences of the United States of America.
Research Activities.
Rosen leads the activities of several large interdisciplinary and inter-institutional research programs, including the NIH Blueprint-funded Human Connectome Project; the NIH/National Institute of Biomedical Imaging and Bioengineering Biomedical Technology Resource Center, the Center for Functional Neuroimaging Technologies (CFNT); the Biomedical Informatics Research Network (BIRN) Collaborative Tools Support Network; and an NIH/National Center for Complementary and Integrative Health (NCCIH)-funded Center of Excellence for Research on Complementary and Alternative Medicine (e.g., he is, for instance, involved in animal and fMRI research investigating the neurophysiological responses to acupuncture stimulations). He is Principal Investigator/Program Director for two neuroimaging training programs. He has authored more than 300 peer-reviewed articles as well as over 50 book chapters, editorials and reviews.
Education and career.
Rosen graduated from Harvard University in 1977 with an A.B. in Astronomy and Astrophysics. In 1980, he received an M.S. in Physics from Massachusetts Institute of Technology. He went on to earn an M.D. from Hahnemann Medical College in 1982 and a Ph.D. in Medical Physics from MIT in 1984.
He joined the faculty of Harvard Medical School in 1987, when he was also made Director of Clinical NMR in the Department of Radiology at the Massachusetts General Hospital. Today he is Professor of Radiology at Harvard Medical School and Professor of Health Science and Technology at the Harvard-MIT Division of Health Sciences and Technology, as well as Director of the Athinoula A. Martinos Center for Biomedical Imaging at MGH. In 2013, he was named Laurence Lamson Robbins Professor of Radiology at Harvard Medical School.
Awards and recognition.
Rosen is the recipient of numerous awards in recognition of his contributions to the field of functional MRI, including the 2011 Outstanding Researcher award from the Radiological Society of North America (RSNA), and the Rigshospitalet’s International KFJ Award 2011 from the University of Copenhagen/Rigshospitalet. He is a Fellow of the International Society for Magnetic Resonance in Medicine and an ISMRM Gold Medal winner for his contributions to the field of Functional MRI. In addition, he is a Fellow of the American Academy of Arts and Sciences, a Fellow of the American Institute for Medical and Biological Engineering, a member of the Institute of Medicine of the National Academies and a member of the National Academy of Medicine. In 2017 Rosen was elected a Fellow of the National Academy of Inventors.


Bucumolol

Bucumolol is a beta-adrenergic antagonist.


KhAB-500

The KhAB-500 is the provisional naming of a series of World War II-era aerial bombs developed by the Soviet Air Force to deliver chemical weapons.
History and Design.
KhAB-500s were typically filled with yperite (R-5) or phosgene (R-10). It was in diameter and about long. Its loaded weight was about including roughly of chemical agent and a impact-fused burst charge.
Upon detonation, the KhAB-500 R-10 would create a hemispherical cloud of gas with a radius of . In ideal weather conditions, the phosgene cloud could produce serious medical effects up to downwind.
The KhAB-500 was carried by Soviet Union era aircraft.


Stefan Karlsson (professor)

Stefan Karlsson, M.D. Ph.D. (born Iceland, 31 May 1950) is a Professor of Molecular Medicine and Gene Therapy at the Lund Stem Cell Center, in the Department of Laboratory Medicine, Lund University, Sweden. He is recognized for significant contributions to the fields of gene therapy and hematopoietic stem cell biology and in 2009 was awarded the Tobias Prize by The Royal Swedish Academy of Sciences.
Career.
Dr. Karlsson's field of research is the regulation of hematopoietic stem cells and development of stem cell expansion protocols and gene therapy. He performed postdoctoral studies with Professor Arthur W. Nienhuis (1983-1986) at the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH), Bethesda Maryland, where he received a Fogarty International Research Collaboration Award. He served as Chief of the Molecular and Medical Genetics Section, Developmental and Metabolic Neurology Branch (DMNB), National Institute for Neurological Disorders and Stroke (NINDS), NIH, 1988-1996. In 1995 he was recruited as a full professor to Lund University, Sweden, where he founded the Division of Molecular Medicine and Gene Therapy and has been head of this division for twenty years. He is also a founding and current member of the Lund Stem Cell Center, since 2003, and director of the Hemato-Linné Strategic Research Environment (2006-2016) funded through a 10-year Linneus grant from the Swedish Research Council. Dr. Karlsson also holds a consultant physician position at Skåne University Hospital, Sweden.
Research.
Stefan Karlsson is recognized as an important contributor to the field of gene therapy. His early research focused on retroviral vector based gene correction of hematopoietic cells from monogenetic disorders, such as Gaucher’s disease and hemoglobinopathies. The results of these studies led to the first gene therapy clinical trial for the treatment of Gaucher’s disease (1995). He has also developed lentiviral vectors for gene correction of hematopoietic stem cells, and more recently developed preclinical gene therapy models for Gaucher’s disease and Diamond Blackfan anemia. An equal component of his research has been in the field of hematopoietic stem cell biology, where Dr. Karlsson focused on studying the mechanisms of hematopoietic stem cell expansion and maintenance with major contributions to understanding the role of Tgf-beta and more recently Cripto.


Methylbenzylpiperazine

MBZP (1-methyl-4-benzylpiperazine) is a stimulant drug which is a derivative of benzylpiperazine. MBZP has been sold as an ingredient in legal recreational drugs known as "Party pills", initially in New Zealand and subsequently in other countries around the world.
The effects of MBZP are very similar to those of BZP, but the stimulant effect is slightly weaker and it seems to have less of a tendency to cause negative side effects such as headaches and nausea.
Based on the recommendation of the EACD, the New Zealand government has passed legislation which placed BZP, along with the other piperazine derivatives TFMPP, mCPP, pFPP, MeOPP and MBZP, into Class C of the New Zealand Misuse of Drugs Act 1975. A ban was intended to come into effect in New Zealand on December 18, 2007, but the law change did not go through until the following year, and the sale of BZP and the other listed piperazines became illegal in New Zealand as of 1 April 2008. An amnesty for possession and usage of these drugs remained until October 2008, at which point they became completely illegal.
MBZP is classified as a class C drug in the UK.
In Canada MBZP remains unscheduled and uncontrolled as of January, 2015. It is not approved for any medical use but is legally available as a research chemical. MBZP is chemically closely related to the controlled Schedule III substance BZP but the latter's scheduling status shields most of its close derivatives from mandatory analogue laws which in Canada apply only to substances belonging to Schedule I under CDSA regulations, which comprises both explicitly illegal substances as well as legal drugs with the highest potential for abuse and dependence, most of which are listed as US Schedule II in the United States. Unlike the US however, stimulants widely used in the treatment of ADHD and narcolepsy in Canada are classified under Schedule III to avoid impractical administrative complications applied to the dispensing of Schedule I substances, a situation which could prompt some practitioners to abstain from dispensing the most proper treatment in order to avoid legal harassment and time-consuming record-keeping not directly related to patient care. BZP, whose abuse profile compared with ADHD treatment drugs is not documented enough to establish any correlation, nonetheless lacks the potency to qualify for Schedule I but was deemed a serious enough concern for control under Schedule III, allowing Health Canada to suspend its sale, but not that of its less potent derivatives, pending further assessment. MBZP remains uncontrolled in Canada as of 2015.


Deltorphin I

Deltorphin I, also known as [-Ala2]deltorphin I or deltorphin C, is a naturally occurring, exogenous opioid heptapeptide and hence, exorphin, with the amino acid sequence Tyr--Ala-Phe-Asp-Val-Val-Gly-NH2. While not known to be endogenous to humans or other mammals, deltorphin I, along with the other deltorphins and the dermorphins, is produced naturally in the skin of species of "Phyllomedusa", a genus of frogs native to South and Central America. Deltorphin possesses very high affinity and selectivity as an agonist for the δ-opioid receptor, and on account of its unusually high blood-brain-barrier penetration rate, produces centrally-mediated analgesic effects in animals even when administered peripherally.


Biotechnology Journal

The Biotechnology Journal is a peer-reviewed scientific journal covering all aspects of biotechnology.
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2012 impact factor of 3.446.


Emergent BioSolutions

Emergent BioSolutions Inc. is an American multinational specialty biopharmaceutical company headquartered in Gaithersburg, Maryland. It develops vaccines and antibody therapeutics for infectious diseases and opioid overdoses, and it provides medical devices for biodefense purposes. The company's gross revenue in 2018 was $782.4 million; gross income was $438.2 million; earnings before interest, taxes, depreciation, and amortization were $170.5 million.
Among the company's notable products are BioThrax (Anthrax Vaccine Adsorbed), the only anthrax vaccine licensed by the U.S. Food and Drug Administration (FDA) and Narcan (naloxone) for the emergency treatment of opioid overdose. The company also manufactures pharmaceuticals for infectious diseases like cholera and typhoid. During the COVID-19 pandemic, Emergent BioSolutions also produced Johnson & Johnson and AstraZeneca/Oxford vaccines at one of its plants; however, this was marked by contamination and other production issues, and millions of doses of vaccine had to be discarded.
Company history.
Early history.
Emergent BioSolutions was founded on September 5, 1998 by Faud El-Hibri, under the name BioPort, and renamed Emergent BioSolutions in 2004. At the time, the Michigan Department of Public Health, though its Michigan Biologics Products Institute, owned an anthrax vaccine manufacturing facility in Lansing, Michigan. BioPort purchased the facility and the rights to manufacture the vaccine for the U.S. military.
In 2000, operating as Bioport, the company was the subject of Congressional hearings and FDA action (official action indicated (OAI) and voluntary action indicated (VAI)). After the 2001 anthrax attacks that caused the deaths of five Americans and made 17 others ill, Bioport began providing its anthrax vaccine to US biodefense agencies.
Emergent became a publicly traded company in 2006, with its stock trading on the New York Stock Exchange under the symbol EBS.
Mergers, acquisitions and joint ventures.
In June 2012, Emergent, along with Novartis and the Texas A&M University System was selected by the U.S. Department of Health and Human Services as one of the three Centers for Innovation in Advanced Development and Manufacturing. The public-private partnership granted Emergent $163 million over eight years to assist in the development of countermeasures for health, nuclear and radiological epidemics. The purpose is to produce medical countermeasures in the event of a national pandemic. Emergent's facility is located in Maryland and the company expects the site to be operational by the year 2020.
The company purchased Winnipeg, Manitoba's Cangene Corporation in 2013. Cangene's leading product is WinRho, which treats the blood disease immune thrombocytopenic purpura, as well as hemolytic disease of the newborn. Cangene also produces pharmaceuticals that treat Hepatitis B and varicella (chickenpox).
On June 27, 2016, the US Biomedical Advanced Research and Development Authority contracted with Emergent Biosolutions to develop a vaccine for the Zika virus. The contract is spread out over 30 months and is worth around $22 million. The vaccine could reach stage-one clinical trials by early 2017. As of the end of June 2016, 60 countries and territories had reported transmission of the Zika virus from mosquitoes. Emergent could become the first company to develop a vaccine for the virus.
Emergent spun off its biosciences division in August 2016, forming a new company, Aptevo Therapeutics in Seattle, WA.The new company continues its focus on developing treatments for cancer and blood diseases using its technology of dual-ended molecules that assault cancer cells, each end attacking the cancer in a different way. Aptevo had four products available at its inception.
In December 2016, Health Canada approved the purchase of Emergent's new botulism antitoxin called Botulism Antitoxin Heptavalent (BAT). The CDC and Public Health Agency of Canada both identified botulism, a type of food poisoning, as a likely biological threat. Emergent already has a ten-year contract with the Canadian military and national health service to supply BAT that began in 2012. Emergent also provides BAT to the U.S. Strategic National Stockpile. BAT was first licensed in the U.S. in 2013 and is the only botulism antitoxin available in the U.S. for naturally-occurring cases of non-infant botulism.
On March 31, 2017, Emergent signed a modification to its contract with BARDA to "manufacture and store bulk drug substance for its botulism antitoxin, BAT." The contract is valued at approximately $53 million for five years. The contract modification was technical in nature; it allows Emergent to file and deliver the final drug product to the Strategic National Stockpile in the future.
Soligenix Inc. and Emergent agreed to establish a “commercially viable production technology” for the development of RiVax, a potential vaccine aimed to protect against ricin exposure. Currently, there are no treatments for ricin poisoning that have been proven effective. Soligenix is a late-stage biopharmaceutical company that specializes in the development of treatments for rare diseases. A product of castor oil production, the ricin toxin can be a useful biological weapon due to its extreme potency, stability, and accessibility. The National Institute of Allergy and Infectious Diseases funded the development of RiVax costing an estimated $24.7 million. The organization also financially backed the contract between Emergent and Soligenix. Most of the work was conducted in Baltimore, Maryland, at Emergent's manufacturing facility. An expansion of the Baltimore plant, finished in 2017, had $163 million in funding from the U.S. government. In January 2020, Emergent informed Soligenix of manufacturing issues, having provided doses of RiVax that were "out of specification", causing the study to be suspended even after two trial participants had received doses. In April 2020, the Department of Health and Human Services announced that it would not provide further funding for RiVax clinical trials, although the agency did not announce whether this was related to previous issues. In subsequent securities filings, Soligenix stated that it was pursuing $19 million in damages from Emergent in arbitration proceedings.
In 2017, the company purchased the ACAM2000 (smallpox vaccinia) Vaccine, the only FDA-approved (2007)vaccine for active immunization against smallpox for those at a medical high risk of contracting the disease, from Sanofi Pasteur. Two years later, the Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services, has signed a contract with the company worth an estimated US$2.8 billion for the company to provide ACAM2000 over a ten-year period.
In 2018, Emergent acquired Adapt Pharma, the manufacturer of Narcan (naloxone), a widely used nasal spray opioid-overdose antidote, for $735 million. Adapt is headquartered in Dublin, Ireland, and operates from Radnor, PA.
Emergent purchased (also in 2018) the specialty vaccine manufacturer PaxVax, whose product line includes FDA-approved typhoid vaccine Vivotif and cholera vaccine Vaxchora, from its owner, Cerebus Capital Management, a private equity fund. Vaxchora is the only oral vaccine against cholera approved by the FDA in the US. The acquisition also includes rights to vaccines in development. One of these vaccines is being tested as a prophylactic against the acute-respiratory disease adenovirus. Another is focused on the chikungunya virus which is transmitted by mosquitoes. The transaction provides Emergent with a Swiss R&D facility.
Leadership.
Fuad El-Hibri, the founder of the company and former CEO, led the company since its founding as BioPort Inc. until his retirement on April 1, 2012. El-Hibri continues to serve as the executive chairman of Emergent BioSolutions’ board of directors.
Robert G. Kramer Sr. became the company's president and CEO April 1, 2019. Prior to that, he was the president and chief operating officer. He has also served as Chief Operating Officer, Chief Financial Officer and other management positions within the corporation. He received his BA from Clemson University and an MBA from Western Kentucky University. In April 2021, the "Washington Post" reported that Kramer sold $10 million worth of company stock in January and early February 2021 under a November 13, 2020 SEC Rule 10b-5 trading plan, which allows company executives to comply with insider trading laws by setting up predetermined plans to sell company stock. The sale was executed prior to announcements in March about Johnson & Johnson vaccine doses being discarded as well as subsequent ending production of the AstraZeneca vaccine at the Baltimore plant, but the trading plan was set up after the company had experienced COVID-19 vaccine production issues earlier in 2020. On April 19, 2021, the United States House Select Oversight Subcommittee on the Coronavirus Crisis announced an investigation into Emergent BioSolutions, requesting documents and testimony from El-Hibri and Kramer regarding "federal contracts since 2015, all communication with Kadlec as well as information on audits and inspections of its facilities, drug pricing and executive compensation." Later in April, shareholders filed a class action lawsuit against the company, alleging that they were misled by company executives regarding the company's COVID-19 production capacity. Kramer's previous significant sale of company stock under a SEC Rule 10b-5 plan was in April 2016, and several other Emergent executives also sold stock at that time. The share price subsequently fell, and a lawsuit was filed by investors regarding misrepresentation of the size of the U.S. government's order for anthrax vaccine from the company. Emergent denied the allegations, but paid the investors a $6.5 million settlement.
BioThrax.
According to the U.S. National Library of Medicine, BioThrax was first made available in 1970. BioThrax (Anthrax Vaccine Adsorbed), a vaccine licensed by the U.S. Food and Drug Administration. Following a study by scientists from the Centers for Disease Control and Prevention, on December 19, 2008, Emergent received final FDA licensing for use of BioThrax five doses for intramuscular injection. Later in 2009, Emergent received approval from the FDA to extend the shelf life of its anthrax vaccine from three to four years.
BioThrax was approved for distribution in the United States in the US in 2015. BioThrax has received marketing approval in India, Singapore, and Germany. Health Canada, under the agency's Extraordinary Use New Drug Regulations, approved BioThrax for exclusive use against anthrax for an eight-year period. The Regulations provide a dual track for products allowing human usage while gathering clinical data on the effects of that usage. Additionally, the company has applied for approval of BioThrax in France, Poland, United Kingdom, Italy and the Netherlands.
The FDA gave BioThrax an "orphan drug" designation in April 2014. The FDA gives that status to drugs that are used to treat rare diseases. BioThrax is the only anthrax vaccine licensed by the FDA. Another company, VaxGen had received a $877.5 million dollar contract to produce an alternative anthrax vaccine that was reported to "cause fewer side effects", require fewer injections, and have faster effectiveness. Following lobbying from Emergent BioSolutions, VaxGen's contract was cancelled in 2006 due to "poor performance," and development of their anthrax vaccine stopped.
As of April 2014, Emergent has sold over 66 million doses of BioThrax to the U.S. government. Three million U.S. military personnel have received the BioThrax vaccine.
The main buyer of BioThrax is the U.S. Centers for Disease Control and Prevention (CDC). The CDC buys BioThrax for the Strategic National Stockpile (SNS). The government uses the SNS to protect the public in the event of a national emergency like a terrorist attack. As of December 2016, Emergent has a $911 million contract with the CDC for BioThrax. The BioThrax vaccines will go to the SNS. The contract will supply around 29.4 million doses of the vaccine. Additionally, the Biomedical Advanced Research and Development Authority (BARDA) released a notice of intent to purchase around $100 million of BioThrax for the SNS in 2017.
Emergent submitted an application to the FDA for use of a large facility in Lansing, Michigan to produce BioThrax. On June 21, 2016, Emergent announced that it had moved a step forward in the process: the FDA completed the pre-approval phase of its inspection.
The "New York Times" reported in March 2021 that the US government had spent nearly a quarter of a billion dollars annually, nearly half of its budget to maintain the Strategic National Stockpile, to purchase BioThrax from Emergent during the preceding decade. In 2020, the government paid Emergent US$626 million. The report indicated that these purchases depleted funds needed to purchase vaccines and other supplies to respond to COVID-19 or other pandemics, despite prior warnings about the spending.
Narcan.
The early 21st century set in motion the US Opioid Epidemic, "...the most serious and most important public health crisis today,” according to the Mayo Clinic Proceedings. Nasal spray naloxone, trade name “Narcan,” use has increased markedly during the opioid emergency. The epidemic is measured in overdose deaths, and also is seen in a downturn in overall health and the population's sense of well-being. Increased employment of naloxone such as Narcan among first responders and the public as a whole has reduced mortality, but recidivism is high. The US Opioid Epidemic has intensified the need for and continued use of Narcan to save those suffering from overdoses. The number of opioid deaths in the US doubled from 2010 to 2016 to 42,249 according to the FDA.
Narcan is mostly used as a “rescue drug” for individuals suffering from opioid overdose. Narcan, related to morphine, is an opioid antagonist that was originally synthesized and patented by Mozes J. Lewenstein and Jack Fishman in the US in 1961. The drug was patented in the UK by the Japanese company Sankyo (now Daiichi Sankyo). The US FDA approved the drug in treatment of opioid overdose in 1971.
In 2012, concerned about inconsistency of dosage, along with the need for a responder having some specialized training in making the naloxone injection in a tense, highly- charged emergency environment, Phil Skolnick, then director of the Division of Therapeutics & Medical Consequences at the National Institute on Drug Abuse and Roger Crystal, the chief executive officer of Lightlake Therapeutics (now Opiant Pharmaceuticals), teamed to develop an intranasal version of the drug. NIDA then generated a highly concentrated solution of naloxone which Lightlake was able to package in its nasal spray devices. After successful clinical trials, Lightlake entered into a partnership with Adapt Pharma to manufacture the product, Narcan. The FDA approved Narcan nasal spray in November, 2015. Emergent Biosolutions purchased Adapt Pharma in 2018.
In January 2019, the FDA initiated a policy that allows the distribution of naloxone over-the-counter through the use of consumer-friendly labels that Emergent Biosolutions uses in delivering Narcan to consumers. Emergent is required by the FDA to make certain that the product-specific parts of the labels are understood by consumers.
By 2019, seven states - California, Virginia, Arizona, Ohio, Washington, Vermont and Rhode Island – required physicians to provide patients who receive opioid prescriptions (e.g., as a pain killer) to co-prescribe or, at minimum, offer Narcan to high risk patients. Many doctors consider this practice an opportunity to initiate a discussion between health care providers and patients about the dangers and risks of opioid pain medication.
Throughout the US, Narcan and naloxone have been made available OTC in 41 states; exceptions are Delaware, Hawaii, Kansas, Maine, Michigan, Nebraska, Oklahoma, South Dakota and Wyoming. The drug can be found in major retailers like CVS, Walgreens, Walmart and Kroger, as well as independent pharmacies. Many states offer lists of retailers where Narcan can be purchased. Narcan is covered by many health insurance plans.
COVID-19 vaccines and production issues.
Johnson & Johnson and Oxford–AstraZeneca vaccines.
In 2020, the company signed a $135 million deal with Johnson & Johnson to provide and reserve manufacturing capacity for J&J's COVID-19 vaccine candidate for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus which causes COVID-19. Human testing began later that year, and the vaccine received Emergency Use Authorization from the FDA in February 2021.
In June 2020, Cambridge UK-based pharmaceutical developer and manufacturer, AstraZeneca, initiated a $174 million agreement with the company to help develop and produce 300 million doses of the Oxford–AstraZeneca COVID-19 vaccine. AstraZeneca had also signed a previous agreement with Emergent for $87 million (US) naming Emergent a development partner for the vaccine, which was manufactured at the company's Bayview plant in East Baltimore, Maryland.
Production and contamination issues.
Emergent's manufacturing facility in East Baltimore, had previously received $163 million from the US government to make upgrades in order to increase production of vaccines and therapies, including the Johnson & Johnson and AstraZeneca COVID-19 vaccines. However, the plant experienced multiple production issues, and audits in 2020 from several institutions, including internal audits from Emergent, as well as external ones from AstraZeneca, Johnson & Johnson, and U.S. federal government agencies identified issues with deficiencies in employee training, cross-contamination, improper disinfection, and inadequate testing of raw materials. Due to issues with contamination or suspected contamination at the plant between October 2020 and January 2021, 2-3 million doses of AstraZeneca vaccine had to be thrown out, and improper manufacturing of cells in November 2020 caused a batch of Johnson & Johnson vaccine to be thrown out. Later, in March 2021, workers at the Baltimore plant conflated the ingredients of two COVID-19 vaccines, ruining about 15 million doses of Johnson & Johnson's vaccine, and causing them to be discarded. The mix-up, which federal officials attributed to human error, delayed future shipments of the vaccine. The "New York Times" reported on April 5, 2021 that: "Emergent BioSolutions has made about 150 million doses of Covid-19 vaccines at its Baltimore factory. But so far not a single dose has been usable."
As of April 2021, 62 million doses of the Johnson & Johnson vaccine produced at the plant were not discarded but have yet to be distributed, pending assessment for contamination. Consequently, in April 2021, the U.S. Department of Health and Human Services ordered that the plant cease manufacturing of the AstraZeneca vaccine, and that a leadership team from Johnson & Johnson be put in place to run production and manufacturing at the plant, although the workers there are still from Emergent. Amid these issues, the U.S. government added an additional $23 million in funding for the plant for increased production of the Johnson & Johnson vaccine on April 5, 2021.
CEO Robert G. Kramer acknowledged unsanitary conditions, including mold and peeling paint, at the Baltimore plant, before a House subcommittee on May 19, 2021. Mr. Kramer initially testified that contamination of the Johnson & Johnson doses “was identified through our quality control procedures and checks and balances.” But under questioning, he acknowledged that a Johnson & Johnson lab in the Netherlands, not Emergent, had discovered the contaminated doses.
Executive compensation documents made public by the House subcommittee show that the company’s board praised El-Hibri, who cashed in stock shares and options worth more than $42 million in 2020.
International use.
Starting in March 2021, millions of doses of the AstraZeneca vaccine produced at the Baltimore plant, which were in storage and awaiting approval for use in the U.S., were loaned to Canada and Mexico, where that vaccine had been approved for emergency use. At the time the vaccines were loaned, the U.S. government was reportedly unaware at the time of prior production issues at the plant prior to reporting from the "New York Times". AstraZeneca stated that the vaccines distributed had met all "required safety tests and quality control measures"; Canadian and Mexican officials stated that they had reviewed quality and safety documentation provided by the company and that the vaccines were safe for use. In late April 2021, 300,000 doses of the Johnson & Johnson vaccine were sent to Canada. Health Canada delayed the distribution of the vaccine because a substance used in the J&J vaccines was produced at Emergent BioSolutions' Baltimore facility. Similarly, millions of doses of the Johnson and Johnson vaccine produced at the Baltimore plant were distributed to countries in the European Union and South Africa, as well as manufactured vaccine components to South Africa: although doses from one batch were declared safe for administration in the EU, approximately 6-9 million doses were sequestered for further quality testing as of May 2021 due to concerns regarding contamination.
Novavax.
The company also initially teamed with Novavax Inc., a bio-technology company also based in Gaithersburg, MD., in the development and manufacture of the Novavax COVID-19 vaccine. Emergent petitioned the federal government's Biomedical Advanced Research and Development Authority (BARDA) to be chosen for the project, and was selected to produce the vaccine in one of its Maryland facilities. However, following production issues with the Johnson & Johnson and Oxford–AstraZeneca vaccines at its Baltimore plant and to decrease the burden on the plant, Novavax subsequently partnered with a different manufacturer in a new agreement overseen by the U.S. government.
R&D, manufacturing and other products.
RSDL.
One of Emergent's medical countermeasure products is Reactive Skin Decontamination Lotion (RSDL), a lotion that clears and neutralizes chemical warfare agents. The product, used internationally, was tested in a study conducted by the US Army Medical Research Institute of Chemical Defense, where RSDL was found to provide superior protection against soman when decontamination was commenced within three minutes of exposure.
RSDL is made of the chemicals Dekon 139 2,3 butanedione monoxime (DAM). According to the Chemical Hazards Emergency Medical Management office within the United States Department of Health and Human Services, "RSDL is used as a medical device for the decontamination of skin exposed to chemical warfare agents such as sulfur mustard, VX, VR and certain biological toxins." As of September 2017, RSDL is available to the regular public. Previously, it was only available to the military.
The United States Department of Defense in September 2017 awarded the company a contract to supply the RSDL kit (RSDL) to the military. The contract is for five years and is worth $171 million. The RSDL lotion protects people's skin from various chemical warfare agents. The product contains a sponge that is filled with the decontamination lotion in and impermeable packet. When applied to the skin, the lotion reacts with the agent on the skin and quickly neutralizes it so that it becomes non-toxic.
Auto-injector diazepam.
The Medical CBRN (Chemical, Biological, Radiological and Nuclear) Defense Consortium, a DOD initiative within its Joint Program Executive Office for Chemical and Biological Defense has awarded the company US$20 million to develop an auto-injector to administer diazepam. The injection is designed to reverse the effects of nerve agents in military or chemical terrorism situations. The investment supports R&D, manufacturing and negotiating the approval process with the US FDA.
Mt. Sinai Health System collaboration during the COVID-19 pandemic.
The company joined forces with New York City's Mount Sinai Health System and ImmunoTek Bio Centers (New Orleans LA) to research, develop, conduct clinical trials, and manufacture COVID-HIG, hyperimmune globulin, also known as polyclonal antibodies, a concentrated antibody made from plasma acquired from individuals infected with and recovered from COVID-19. The research is designed to determine whether COVID-HIG could protect people at higher risk of exposure and infection (like health care and military personnel) and therefore limit the spread of the infection. The initial study is funded by a $34.6 million (US) grant from the US Dept. of Defense and the Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND).
Public affairs.
Emergent Biosolutions was among many companies giving financial support to delegations at both major party political conventions in the summer of 2016, a practice that "watchdog groups have raised concerns about ... as corporate donors — skittish about Republican nominee Donald J. Trump — have sought new and less overt ways to give money and gain influence".
In October 2018, the company donated two doses of Narcan nasal spray to all 16,568 libraries in the US. Emergent had previously donated 20,000 doses to 4,700 universities in the US in 2017. It later expanded this donation to all US high schools as well. Additionally, the company donated free Narcan kits to 2,700 YMCAs across the US. Narcan and naloxone are offered at major drug retailers like Walgreens and CVS in many states without a prescription.
Emergent Biosolutions PAC donated tens of thousands of dollars in 2020 to both Republicans and Democrats from Joe Biden and Dick Durbin to Andy Harris and Mitch McConnell. The majority of contributions were directed to Democrats (37.6%), but the amount donated favored Republicans (62.4%).


Pyr-T

Pyr-T ("N","N"-tetramethylenetryptamine) is a lesser-known, possible psychedelic drug. Pyr-T was first characterized by S. Mitzal. Toxicity testing was later performed by Hunt and Brimblecombe, and although a lethal dosage was found in rats, a value is not given. In the book "TiHKAL" ("Tryptamines I Have Known and Loved"), neither the dosage nor the duration are reported.
Pyr-T produces few to no effects in humans, but some behavioral changes were observed in animal tests. Very little data exists about the pharmacological properties, metabolism, and toxicity of pyr-T.


Cleveland BioLabs

Cleveland BioLabs, Inc. (NASDAQ: CBLI) is a clinical-stage biotechnology company with a focus on oncology development. It specializes in research and development of products with the potential to treat cancer and protect against death following acute radiation syndrome. The company was founded in 2003 and is headquartered in Buffalo, New York. It has license agreements and collaborations with the Cleveland Clinic, Roswell Park Comprehensive Cancer Center, the Children's Cancer Institute Australia, and the Armed Forces Radiobiology Research Institute.
Since 2012, Yakov Cogan has been the CEO of Cleveland BioLabs.
History.
Cleveland BioLabs was founded in partnership with the Cleveland Clinic in 2003 and moved to the Buffalo Niagara Medical Campus in 2007.
In 2018, the company entered into a joint venture with Buffalo-based Everon Biosciences. The joint venture, Genome Protection Inc., will develop pharmaceuticals that have anti-aging applications, using Cleveland Biolabs' acute radiation exposure drug, Entolimod.
Genome Protection Inc. subsequently received a $10.5 million (US) investment from Israeli businessman and owner of the Premier League’s Chelsea FC, Roman Abramovich.
Financials.
The following table shows key financial figures for the company for 2011, 2012 and 2013 (parenthesis represent negative figures).
Subsidiaries.
Cleveland Biolabs has two majority-owned subsidiaries:


Chlorophyll f

Chlorophyll "f" is a type form of chlorophyll that absorbs further in the red (infrared light) than other chlorophylls. In 2010, it was reported from stromatolites from Western Australia's Shark Bay.
The finding was made by scientists at the University of Sydney led by Professor Min Chen, and is the first discovery of a new form of chlorophyll in 60 years. However, the function of chlorophyll "f" in photosynthetic reactions is uncertain and the ecological distribution of chlorophyll "f" remains unknown. Chlorophyll "f" has been shown to support some of the roles in photosynthetic reactions, in both the energy transfer and in the charge separation processes.
Based on NMR data, optical and mass spectra and density functional theory (DFT) simulation, it is confirmed to have a structure of C55H70O6N4Mg or [2-formyl]-chlorophyll a.


Chlorophyll a

Chlorophyll "a" is a specific form of chlorophyll used in oxygenic photosynthesis. It absorbs most energy from wavelengths of violet-blue and orange-red light, and it is a poor absorber of green and near-green portions of the spectrum. Chlorophyll does not reflect light but chlorophyll-containing tissues appear green because green light, diffusively reflected by structures like cell walls, becomes enriched in the reflected light. This photosynthetic pigment is essential for photosynthesis in eukaryotes, cyanobacteria and prochlorophytes because of its role as primary electron donor in the electron transport chain. Chlorophyll "a" also transfers resonance energy in the antenna complex, ending in the reaction center where specific chlorophylls P680 and P700 are located.
Distribution of chlorophyll "a".
Chlorophyll "a" is essential for most photosynthetic organisms to release chemical energy but is not the only pigment that can be used for photosynthesis. All oxygenic photosynthetic organisms use chlorophyll "a", but differ in accessory pigments like chlorophyll "b". Chlorophyll "a" can also be found in very small quantities in the green sulfur bacteria, an anaerobic photoautotroph. These organisms use bacteriochlorophyll and some chlorophyll "a" but do not produce oxygen. Anoxygenic photosynthesis is the term applied to this process, unlike oxygenic photosynthesis where oxygen is produced during the light reactions of photosynthesis.
Molecular structure.
The molecular structure of chlorophyll "a" consists of a chlorin ring, whose four nitrogen atoms surround a central magnesium atom, and has several other attached side chains and a hydrocarbon tail.
Chlorin ring.
Chlorophyll "a" contains a magnesium ion encased in a large ring structure known as a chlorin. The chlorin ring is a heterocyclic compound derived from pyrrole. Four nitrogen atoms from the chlorin surround and bind the magnesium atom. The magnesium center uniquely defines the structure as a chlorophyll molecule. The porphyrin ring of bacteriochlorophyll is saturated, and lacking alternation of double and single bonds causing variation in absorption of light.
Side chains.
Side chains are attached to the chlorin ring of the various chlorophyll molecules. Different side chains characterize each type of chlorophyll molecule, and alters the absorption spectrum of light.
 For instance, the only difference between chlorophyll "a" and chlorophyll "b" is that chlorophyll "b" has an aldehyde instead of a methyl group at the C-7 position.
Hydrocarbon tail.
Chlorophyll "a" has a long hydrophobic tail, which anchors the molecule to other hydrophobic proteins in the thylakoid membrane of the chloroplast. Once detached from the porphyrin ring, this long hydrocarbon tail becomes the precursor of two biomarkers, pristane and phytane, which are important in the study of geochemistry and the determination of petroleum sources.
Biosynthesis.
The Chlorophyll "a" biosynthetic pathway utilizes a variety of enzymes. In most plants, chlorophyll is derived from glutamate and is synthesised along a branched pathway that is shared with heme and siroheme.
The initial steps incorporate glutamic acid into 5-aminolevulinic acid (ALA); two molecules of ALA are then reduced to porphobilinogen (PBG), and four molecules of PBG are coupled, forming protoporphyrin IX.
Chlorophyll synthase is the enzyme that completes the biosynthesis of chlorophyll "a" by catalysing the reaction
This forms an ester of the carboxylic acid group in chlorophyllide "a" with the 20-carbon diterpene alcohol phytol.
Reactions of photosynthesis.
Absorbance of light.
Light spectrum.
Chlorophyll "a" absorbs light within the violet, blue and red wavelengths while mainly reflecting green. This reflectance gives chlorophyll its green appearance. Accessory photosynthetic pigments broaden the spectrum of light absorbed, increasing the range of wavelengths that can be used in photosynthesis. The addition of chlorophyll "b" next to chlorophyll "a" extends the absorption spectrum. In low light conditions, plants produce a greater ratio of chlorophyll "b" to chlorophyll "a" molecules, increasing photosynthetic yield.
Light gathering.
Absorption of light by photosynthetic pigments converts photons into chemical energy. Light energy radiating onto the chloroplast strikes the pigments in the thylakoid membrane and excites their electrons. Since the chlorophyll "a" molecules only capture certain wavelengths, organisms may use accessory pigments to capture a wider range of light energy shown as the yellow circles. It then transfers captured light from one pigment to the next as resonance energy, passing energy one pigment to the other until reaching the special chlorophyll "a" molecules in the reaction center. These special chlorophyll "a" molecules are located in both photosystem II and photosystem I. They are known as P680 for Photosystem II and P700 for Photosystem I. P680 and P700 are the primary electron donors to the electron transport chain. These two systems are different in their redox potentials for one-electron oxidation. The Em for P700 is approximately 500mV, while the Em for P680 is approximately 1,100-1,200 mV.
Primary electron donation.
Chlorophyll "a" is very important in the energy phase of photosynthesis. Two electrons need to be passed to an electron acceptor for the process of photosynthesis to proceed. Within the reaction centers of both photosystems there are a pair of chlorophyll "a" molecules that pass electrons on to the transport chain through redox reactions.


Cell Biochemistry and Biophysics

Cell Biochemistry and Biophysics is a peer-reviewed scientific journal covering all aspects of the biology of cells, especially their biochemistry and biophysics. It was established in 1979 as "Cell Biophysics" with Nicholas Catsimpoolas as founding editor-in-chief, obtaining its current name in 1996. The journal is published by Springer Science+Business Media and the editor-in-chief is Lawrence J. Berliner (University of Denver).
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2017 impact factor of 1.455.
Peer review problems.
In March 2015 the publisher placed the journal on hold after a pattern of "inappropriate and compromised peer review" was uncovered. "Retraction Watch" noted that the journal had retracted 16 articles in the preceding year that had been generated by the computer program SCIgen, as well as a further paper for plagiarism, although it was not stated whether these cases were related to the suspension.


MRGPRE

Mas-related G-protein coupled receptor member E is a protein that in humans is encoded by the "MRGPRE" gene.


Luke Pyungse Lee

Luke Pyungse Lee (born March 22, 1959) is the Arnold and Barbara Silverman Distinguished Professor of Bioengineering, Biophysics, Electrical Engineering and Computer Science, at University of California, Berkeley. He is founding director of the Biomedical Institute for Global Health Research and Technology (BIGHEART) at the National University of Singapore.
Lee has over 350 peer-reviewed publications and over 40 issued international patents. He is a pioneer in bionanophotonics, plasmonic resonant energy transfer (PRET), rapid photonic PCR, optofluidics, microfluidics for quantitative life sciences, and integrated molecular diagnostics systems. He was elected Fellow of the Royal Society of Chemistry in 2010 and the American Institute of Medical and Biological Engineering in 2012. Lee received the 2009 IEEE William J. Morlock Award in 2009 and the 2010 Ho-Am Prize for his discovery of PRET and the development of quantum nanobiophotonics for optical gene regulations and molecular imaging (photonic RNA switch and gene circuit). His current research interests are quantum electron transfers in living organisms, molecular diagnostics of infectious and neurodegenerative diseases, and "in vitro" neurogenesis, with a focus both on studying fundamental quantum nanobiology and on solving ill-defined problems of global healthcare.
Education & Career.
Luke P. Lee was born the youngest of three boys in the family of a poet father, Sang Ro Lee and a midwife, Bok Soon Ha. After the death of his father, he immigrated to America with his mother and brother in 1976. Lee spent his life in Seoul attending up to 11th grade of high school. After he moved to the US, he attended Wasson high school in Colorado Springs, Colorado for 12th grade. He received a BA in Biophysics from the University of California, Berkeley in 1996 and received his PhD in Applied Science and Technology (Applied Physics: major & Bioengineering: minor) from the University of California, Berkeley in 2000.
In 1999, he became an assistant professor of bioengineering at the University of California, Berkeley. In 2005, he became a full professor and the Lester John and Lynne Dewar Lloyd Distinguished professor of bioengineering and a professor of biophysics at Berkeley. He also served as the Chair Professor in Systems Nanobiology at the Swiss Federal Institute of Technology (ETH, Zürich) from 2006 to 2007. Lee also has a joint appointment in the Department of Electrical Engineering and Computer Science at Berkeley. He has been the co-director of the Berkeley Sensor & Actuator Center since 1999. He became the Arnold and Barbara Silverman Distinguished Professor in 2010 and reappointed again 2015. He was Associate President (International Research and Innovation) and Tan Chin Tuan Centennial Professor at the National University of Singapore from 2016 to 2017.
Prior to his academic career, he had over ten years of extensive R&D and industrial experience in integrated optoelectronics and superconducting electronics. In the late 80s, as a member of technical staff at TRW Inc, he worked on laser holography, quantum-well surface emitting laser, Nb-based Josephson tunnel junctions, and superconducting quantum interference device (SQUID) electronics. In the early 1990s, he worked on high-temperature SQUID magnetometers, Josephson junction devices, and biomagnetic sensors at Conductus Inc.


Rifamycin-B oxidase

In enzymology, a rifamycin-B oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are rifamycin B and O2, whereas its two products are rifamycin O and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on diphenols and related substances as donor with oxygen as acceptor. The systematic name of this enzyme class is rifamycin-B:oxygen oxidoreductase. This enzyme is also called rifamycin B oxidase.


Casamino acid

Casamino acids is a mixture of amino acids and some very small peptides obtained from acid hydrolysis of casein. It is typically used in microbial growth media. It has all the essential amino acids except tryptophan, which is destroyed by digestion with sulfuric or hydrochloric acid.
Casamino acids is similar to tryptone, the latter differing by being an incomplete enzymatic hydrolysis with some oligopeptides present, while casamino acids is predominantly free amino acids.
Uses.
Casamino acids supplies a completely hydrolyzed protein nitrogen source. It contains a small amount of cystine. Tryptophan and vitamins are destroyed by the acid treatment. The remaining amino acids (in varying amounts) are a source of nutrients for various microorganisms. Amino acids are highly soluble and suitable for use in tissue culture. Salt content is typically 30-40%. Casamino acids are either found in the Daptacel brand DTaP vaccine or used in its manufacture.


Patricia H. Clarke

Patricia Hannah Clarke FRS (née Green) (29 July 1919 – 28 January 2010) was a British biochemist.
Education and early life.
Clarke was born in Pontypridd, South Wales, and was educated at Howell's School, Llandaff, from 1930 to 1937, before studying the Natural Sciences Tripos at Girton College, Cambridge, from 1937 to 1940.
Career.
After graduating, she declined a postgraduate post working on aspects of ATP metabolism to contribute to the war effort, taking post at the Armament Research Department of the Ministry of Supply in Swansea to work on explosives. She returned to biochemistry in 1944 when she joined the Wellcome Trust Research Laboratories at Beckenham, Kent. In 1951, she moved to work part-time at the National Collection of Type Cultures of bacteria in the Central Public Health Laboratory at Colindale, London.
Her final move was to the Department of Biochemistry at University College London, as Assistant Lecturer, being appointed Lecturer in 1956, Reader in 1966 and Professor of Microbial Biochemistry in 1973 until her retirement in 1984 – when she was made emeritus professor. During this time she co-wrote the 'Genetics and Biochemistry of Pseudomonas'. Her aim in this paper was to present in one volume the fundamentals, basic methodology, and specific applications of gas-liquid chromatography in microbiology and medicine. In addition to this, some of her most well-recognised papers are: Hydrogen Sulphide Production by Bacteria, An Inducible Amidase Produced by a Strain of Pseudomonas aeruginosa, Biochemical Classification of Proteus and Providence Cultures Butyramide-using Mutants of Pseudomonas aeruginosa 8602 which Produce an Amidase with Altered Substrate Specificity. Her major field of research was bacterial enzymes production and metabolism.
Committee Work.
Clarke was a great supporter of the Biochemical Society and the Society for General Microbiology (SGM) for their roles in education and fostering a scientific community. In 1974, she managed the production of a booklet, "Careers in microbiology", which was published by the SGM to stimulate interest of microbiology in schools. In 1993, the she was one of six female members of the Committee of Women in Science and Technology commissioned by William Waldegrave. The committee's report, "The rising tide", was published by the Cabinet office in 1994. The report drew attention to the areas adversely affecting recruitment and education of women in science; a lack of female role models in education, employers showing bad practice in ensuring opportunities for women and the poor approach to maternity leave.
Personal life.
In 1940, she married Michael Clarke; they had two children in 1947 and 1949. She died at University of Wales Hospital, Cardiff on 28 January 2010, aged 90 years.


Free-flow electrophoresis

Free-flow electrophoresis (FFE), also known as carrier-free electrophoresis, is a matrix-free electrophoretic separation technique. FFE is an analogous technique to capillary electrophoresis, with a comparable resolution, that can used for scientific questions, where semi-preparative and preparative amounts of samples are needed. It is used to quantitatively separate samples according to differences in charge or isoelectric point. Because of the versatility of the technique, a wide range of protocols for the separation of samples like rare metal ions, protein isoforms, multiprotein complexes, peptides, organelles, cells, DNA origami, blood serum and nanoparticles exist. The advantage of FFE is the fast and gentle separation of samples dissolved in a liquid solvent without any need of a matrix, like polyacrylamide in gel electrophoresis. This ensures a very high recovery rate since analytes do not adhere to any carrier or matrix structure. Because of its continuous nature and high volume throughput, this technique allows a fast separation of preparative amounts of samples with a very high resolution. Furthermore, the separations can be conducted under native or denaturing conditions.
History.
FFE was developed in the 1960s by Kurt Hannig at the Max-Planck-Institute in Germany. Until the 1980s, it was a standardized technology for the separation of cells and organelles, and FFE was even tested in space to minimize the sedimentation under zero gravity. As flow cytometry became the standard method for cell sorting, FFE developments focused on the separation of proteins and charged particles. Some groups are also working on miniaturized versions of FFE systems or micro FFEs.
Technique.
The separation chamber consists of a backplate and a front plate. The backplate usually consists of a cooled aluminum block, covered with a plastic covered glass mirror. The front plate is nowadays made of PMMA, in earlier times glass has been used. The distance between the front- and the backplate can be adjusted by spacers and is usually between 0.1 - 0.5 mm. The front plate also contains the inlets for the separation buffers and the sample, the outlets for the fractionation tubes and the platinum wires as electrodes. By applying different buffers over the multiple buffer inlets the operator is able to change pH, salt concentrations or composition and therefore the separation conditions over the width of the chamber.
The separation buffers and the sample are applied by peristaltic pumps, to ensure a laminar flow. A high voltage electric field is applied perpendicular to the laminar flow. Analytes in the laminar flow can be separated by charge density and/or isoelectric point. Because of its highly versatile nature, this technique can make use of different modes of electrophoresis, like for example isotachophoresis, isoelectric focusing or (interval) zone electrophoresis.
At the end of the separation cell, the separated sample is split up at the fractionation tubes and collected in microtiter plates. Afterwards the samples can be characterized by all major techniques like HPLC, LC-MS, mass spectrometry (ESI / MALDI, depending on the protocol used) or electrophoresis (IEF / SDS PAGE, 2D-PAGE).
Applications.
Standard application include the high-resolution separation of protein complexes, membrane proteins, protein and antibody isoforms, cells, subcellular compartments (like organelles, ribosomes) and liposomes. By making use of very flat pH-gradients, generated by ampholytes, it is possible to separate protein isoforms, that vary by less than 0.02 pH units, with a throughput of around 3 mg/h.
It is also possible to add additives to the buffers, to increase the resolution or denature the samples. Typically concentrations of urea up to 8M, 0.1-1% of detergents like: CHAPS, CHAPSO, Digitonin, Dodecyl-ß-D-maltoside, Octyl-ß-D-glucoside, Triton-X-114 (IEF) and DTT up to 50 mM are tolerated.
Key features.


Ablitech, Inc.

Ablitech, Inc. is a biotechnology company founded in Hattiesburg, Mississippi, USA, that specializes in the development and commercialization of platform technologies that heal and protect the human body.
History.
Ablitech was co-founded in 2006 by Dr. Lisa Kemp, Dr. Nick Hammond and Dr. Kenneth Malone on technology licensed from The University of Southern Mississippi.
The formation of Ablitech was a direct result of the National Science Foundation program IGERT – an “interdisciplinary training program, educating U.S. Ph.D. scientists and engineers by building on the foundations of their disciplinary knowledge with interdisciplinary training.”
In 2007, Ablitech received a SBIR Phase I for the development of a bio-transformable drug-eluting coronary stent. Then in 2008 they received another SBIR Phase I for the development of a cancer therapy.
Ablitech received the Mississippi Seed Fund Research and Development investment in 2009 and in 2010. Managed by the Mississippi Technology Alliance, the Mississippi Seed Fund provides high-tech, start-up companies with access to pre-seed financing, early stage risk capital, and product development capital to stimulate and accelerate the development of high-performance, technology-based business ventures in Mississippi.
In 2011, Ablitech received a $2 million grant from the Department of Defense to develop a siRNA based therapy for heterotopic ossification.
Location.
Ablitech is located at the University of Maryland BioPark. The corporation relocated to Baltimore, Maryland in early 2012.
Research.
Ablitech's signature product, VersadelTM, is a nucleic acid platform delivery technology that “provides a non-toxic, biocompatible method for the systemic and local delivery of antisense DNA and siRNA in the body.”


Trolox equivalent antioxidant capacity

The Trolox equivalent antioxidant capacity (TEAC) assay measures the antioxidant capacity of a given substance, as compared to the standard, Trolox. Most commonly, antioxidant capacity is measured using the ABTS Decolorization Assay. Other antioxidant capacity assays which use Trolox as a standard include the diphenylpicrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and ferric reducing ability of plasma (FRAP) assays. The TEAC assay is often used to measure the antioxidant capacity of foods, beverages and nutritional supplements.


ICarbonX

iCarbonX is a company founded by Chinese genomicist Jun Wang, former CEO of Beijing Genomic Institute (BGI), in 2015. iCarbonX combines genomics with other health factors such as metabolites, bacteria and lifestyle choices to create a digitalized form of life.
iCarbonX has raised over $600 million in investment. Tencent Holdings Limited – owner of social-media app WeChat – and Zhongyuan Union Cell & Gene Engineering Corp. invested $200 million in iCarbonX, which made iCarbonX one of only three Chinese healthcare startups with a valuation of more than $1 billion (Unicorn). The company has about 100 employees.
History.
iCarbonX was founded on October 27, 2015. On September 10, 2016 iCarbonX acquired Imagu Vision Technologies, an Israeli AI and image processing company, in order to establish an iCarbonX-Israel R&D center. On January 5, 2017 iCarbonX announced its Digital Life Alliance with seven other companies including SomaLogic, HealthTell, PatientsLikeMe, AOBiome, GALT, Imagu and Robustnique.
On January 5, 2017 iCarbonX released Meum, a digital health management platform. The company name, “iCarbonX,” symbolizes the use of the internet and artificial intelligence to improve life, of which a central element is carbon. The “i” and “X” indicate the company's plans to combine the Internet and artificial intelligence to create something new.


Peptide hormone

Peptide hormones or protein hormones are hormones whose molecules are peptides or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including humans. Most hormones can be classified as either amino acid–based hormones (amine, peptide, or protein) or steroid hormones. The former are water-soluble and act on the surface of target cells via second messengers; the latter, being lipid-soluble, move through the plasma membranes of target cells (both cytoplasmic and nuclear) to act within their nuclei.
Like all peptides and proteins, peptide hormones and protein hormones are synthesized in cells from amino acids according to mRNA transcripts, which are synthesized from DNA templates inside the cell nucleus. Preprohormones, peptide hormone precursors, are then processed in several stages, typically in the endoplasmic reticulum, including removal of the N-terminal signal sequence and sometimes glycosylation, resulting in prohormones. The prohormones are then packaged into membrane-bound secretory vesicles, which can be secreted from the cell by exocytosis in response to specific stimuli (e.g. an increase in Ca2+ and cAMP concentration in cytoplasm).
These prohormones often contain superfluous amino acid residues that were needed to direct folding of the hormone molecule into its active configuration but have no function once the hormone folds. Specific endopeptidases in the cell cleave the prohormone just before it is released into the bloodstream, generating the mature hormone form of the molecule. Mature peptide hormones then travel through the blood to all of the cells of the body, where they interact with specific receptor on the surfaces of their target cells.
Some neurotransmitters are secreted and released in a similar fashion to peptide hormones, and some "neuropeptides" may be used as neurotransmitters in the nervous system in addition to acting as hormones when released into the blood.
When a peptide hormone binds to a receptor on the surface of the cell, a second messenger appears in the cytoplasm, which triggers signal transduction leading to the cellular responses.
Some peptide/protein hormones (angiotensin II, basic fibroblast growth factor-2, parathyroid hormone-related protein) also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.


Charles H. DePuy (chemist)

Charles Herbert DePuy (September 10, 1927 – March 14, 2013) was an American chemist known for his work in gas phase organic ion chemistry.
Early life and education.
Charles H. DePuy was born Detroit, Michigan on September 10, 1927 but did not live there long. His father was an architectural engineer who supervised the construction of post office buildings throughout the southeastern United States and for a time in the US Virgin Islands. In 1942, his father was transferred to Oakland, California to supervise the fortification of government buildings against anticipated attack.
Depuy enrolled at the University of California, Berkeley at age 16, but was drafted and served for 13 months as a hospital laboratory technician. He returned to Berkeley and graduated in 1948.
He enrolled in at Columbia University and began his graduate work in physical organic chemistry with William von Eggers Doering. He moved with Doering to Yale University and received his M.S. degree from Columbia in 1952 and Ph.D. from Yale in 1953. He took a postdoctoral position at the University of California, Los Angeles in the lab of Donald J. Cram.
Academic career.
DePuy joined faculty at Iowa State University and rose quickly to the position of full professor. In 1963, he moved to the University of Colorado, Boulder where he spent the rest of his career.
His research spanned both gas and solution phase physical organic chemistry. He is best known for his development of the flowing afterglow technique for the study of gas phase ion molecule reactions. He developed methods for gas phase hydrogen-deuterium exchange, substitution and elimination reactions, and comparisons of gas and solution phase reaction energetics.
He was the author of “Introduction to Organic Chemistry” (with Douglas Applequist and Kenneth L. Rinehart) and “Exercises in Organic Spectroscopy” with Robert H. Shapiro.
Awards.
DePuy was n National Institutes of Health Senior Postdoctoral Fellow, Alfred Sloan Fellow, and Guggenheim Fellow, Alexander von Humboldt Fellow. He received the Colorado Section of the American Chemical Society Gold Medallion Award, and the American Chemical Society James Flack Norris Award. He was a member of the American Academy of Arts and Sciences and National Academy of Sciences.


L-glutamate oxidase

In enzymology, a L-glutamate oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are L-glutamate, O2, and H2O, whereas its 3 products are 2-oxoglutarate, NH3, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with oxygen as acceptor. The systematic name of this enzyme class is L-glutamate:oxygen oxidoreductase (deaminating). Other names in common use include glutamate (acceptor) dehydrogenase, glutamate oxidase, glutamic acid oxidase, glutamic dehydrogenase (acceptor), and L-glutamic acid oxidase. It employs one cofactor, FAD.


Stallior


William Granville, 3rd Earl of Bath

William Henry Granville, 3rd Earl of Bath (30 January 1692 – 17 May 1711) was an English nobleman.
Origins.
He was the only son of Charles Granville, 2nd Earl of Bath, by his second wife Isabella de Nassau d'Auverquerque, sister of Henry de Nassau d'Auverquerque, 1st Earl of Grantham.
Career.
He was styled Viscount Lansdown from August to September 1701, when he succeeded in the earldom after his father committed suicide, allegedly because of the debts he had inherited.
Death.
Lord Bath died of smallpox in May 1711, aged 19, when the earldom became extinct.


Yfr2

Yfr2 (cYanobacterial functional RNA-2 later published as Cyano-1 RNA motif) is a family of non-coding RNAs. Members of the Yrf2 family have been identified in almost all studied species of cyanobacteria. The family was identified through a bioinformatics screen of published cyanobacterial genomes, having previously been grouped in a family of Yfr2–5.
The cyano-1 RNA motif family is essentially a synonym for Yfr2, although Cyano-1 does not include the terminator sequence and Yfr2 does.
The function of this ncRNA is unknown, though it has been hypothesised that family members interact with RNA targets through kissing complexes using their highly conserved exposed central consensus element (CSE: IUPAC 5′-RKT SGA
AAC WHG GHM ASA M-3′). Earlier studies noted a similarity to quorum sensing ncRNAs in "Vibrio" bacteria.
The family can be divided into two subgroups, one found in marine cyanobacteria (e.g. the "Prochlorococcus" and "Synechococcus" genera) and the other from freshwater cyanobacteria. Both subgroups have lengths of 63–100 nucleotides (with the marine subgroup genes being on average 22nt longer), a conserved 5′ region and the characteristic Yfr2 CSE. Their secondary structures differ, however, with Yfr2 from marine picocyanobacteria having an additional stem loop. The position of Yfr2 genes is generally unconserved, but yfr2a orthologs were identified as being located 3′ to the gene 50S ribosomal subunit gene rplL in almost all marine cyanobacteria studied. In the genus "Prochlorococcus", Yfr2 genes are found adjacent to Yfr10 and a potential interaction between the two ncRNAs has been theorised.
The initial bioinformatics scan which identified yfr2 also identified yfr1, a functional RNA which is upregulated during stress conditions. Yfr families have now been identified up to yfr21.


Epitalon

Epitalon is a synthetic peptide, telomerase activator, and putative anti-aging drug developed by the St. Petersburg Institute of Bioregulation and Gerontology, which was identified as the putative active component of a bovine pineal gland extract known as epithalamin.
Most studies on epitalon and epithalamin have been conducted by the St. Petersburg Institute of Bioregulation and Gerontology, primarily overseen by Vladimir Khavinson, in Russia.
Chemistry.
Epitalon is a tetrapeptide with the amino acid sequence Ala-Glu-Asp-Gly and the molecular formula C14H22N4O9.
Biological effects.
Studies "in vitro".
Epitalon appears to induce telomere elongation via increased telomerase activity in human somatic cells "in vitro", based on a study in human fibroblast cell cultures.
Elongation of telomeres by epitalon was sufficient to surpass the Hayflick limit in a cell culture of human fetal fibroblast cells, extending their proliferative potential from termination at the 34th passage in the control cell population to beyond the 44th passage in the treated cell population, while increasing the lengths of their telomeres to levels comparable to those of cells in the original culture.
Epitalon induces decondensation of heterochromatin near the centromeres in cultured lymphocytes originating from samples taken from humans of ages 76 to 80 years.
Epitalon appears to inhibit the synthesis of the MMP9 protein "in vitro" in aging skin fibroblasts.
Animal studies "in vivo".
An "in vivo" study in aging mice found that epitalon treatment significantly reduced the incidence of chromosomal aberrations, both for wild-type mice and for mice characterized by an accelerated aging phenotype, which is consistent with increases in telomere length.
Another study in aging rats found that epitalon increased the activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase.
Epitalon reduced the number of spontaneous tumors and the number of metastases in mice that did develop spontaneous tumors in an experiment on one-year-old female C3H/He mice, and is speculated to have oncostatic and anti-metastatic properties.
In a study of chickens subjected to neonatal hypophysectomy and subsequent maturation, epitalon promoted the recovery of the morphological structures of the thymus, as well as the structure and function of the thyroid gland.
Epitalon appears to increase the proliferation of lymphocytes in the thymus, putatively increasing production of interferon gamma by T-cells.
Another study in aging rats demonstrated extension of life span for rats subjected to constant illumination or to a natural light regimen typical of northern regions.
Human clinical studies.
In human clinical studies, epitalon and epithalamin both significantly increased telomere lengths in the blood cells of patients of ages 60-65 and 75-80, and their efficacy was comparable to one another.
Epitalon and epithalamin appear to restore melatonin secretion by the pineal gland in both aged monkeys and humans.
A human clinical trial conducted on a sample of retinitis pigmentosa patients found that epitalon produced a positive clinical effect in 90% of cases in the treated group.
In another human clinical trial conducted on a sample of pulmonary tuberculosis patients, epitalon did not appear to correct pre-existing structural aberrations of chromosomes associated with telomere degradation, but did appear to exert a protective effect against the future development of additional chromosomal aberrations.
A human prospective cohort study conducted on a sample of 266 people over age 60 demonstrated that treatment with epithalamin, the pineal gland extract upon which epitalon is based, produced a 1.6–1.8-fold reduction in mortality during the following 6 years, a 2.5-fold reduction in mortality when combined with thymalin, and a 4.1-fold reduction in mortality when combined with thymalin and administered annually instead of only once at study onset.
Another prospective cohort study on a sample of 79 coronary patients spanning in excess of 12 years found improved metrics of physical endurance, circadian rhythm, and carbohydrate and lipid metabolism in the treated group relative to the control group following 3 years of biannual epithalamin treatments, as well as a 50% lower rate of cardiovascular mortality, a 50% lower rate of cardiovascular failure and serious respiratory disease, and a 28% lower rate of overall mortality.


Microbial drug delivery

Microbial drug delivery is an emerging form of drug administration characterized by the use of commensal microbes that have been genetically modified to produce medications for chronic diseases in humans. Only proteinaceous drugs can be produced by microbes, as DNA encodes for protein. Research into microbial drug delivery refers to this route of administration as topical, since the microbes release the drug directly to the surface of affected tissues, namely the gastrointestinal (GI) epithelium. Microbial drug delivery is not currently used as a standard route of drug administration due to its experimental nature. During clinical trials, it has been used to treat forms of inflammatory bowel disease (IBD). The most prominently studied vehicles of microbial drug administration are the bacterial species, "Lactococcus lactis" and "Bacteroides ovatus."
Medical usage.
The usage of recombinant microbes (i.e. microorganisms designed to contain DNA from two or more different species) has applications in treating chronic diseases. In 2006, Braat "et al". implemented microbial drug delivery with "L. lactis" in clinical trials, successfully treating Crohn’s disease (CD), a form of IBD that causes inflammation and ulceration in the intestines. In this study, a recombinant strain of "L. lactis" containing complimentary DNA (cDNA) for the human interleukin-10 (IL-10) gene was used to treat CD with IL-10, an anti-inflammatory cytokine. Patients consumed capsules containing the microbe to populate the intestines and received therapeutic doses of IL-10 directly from the recombinant bacteria. As this route of administration is experimental, it is currently not available as a standard treatment option.
In a 2013 animal study with "B. ovatus" as the vehicle for microbial drug delivery, researcher Zaed Hamady suggested that recombinant strains of "B. ovatus" containing transforming growth factor-beta (TGF-β) and keratinocyte growth factor-2 (KGF-2) are ready for clinical trials.
Mechanism of drug administration.
"L. lactis" mechanism.
The "L. lactis" mechanism of microbial drug delivery described in the 2006 study of Braat "et al." uses a form of recombinant "L. lactis" (LL-Thy12) which has replaced the gene, Thy12, with the gene for human IL-10. Removal of Thy12, which encodes for the production of thymidine, causes "L. lactis" to become dependent on dietary thymidine to maintain live colonies in the gut. The addition of the IL-10 gene allows for the production of human IL-10 to decreases gut inflammation. Secretion of IL-10 from "L. lactis" in the gut is considered to be a topical administration of the drug to the epithelium, permitting healing in local tissues damaged by inflammation. The administration of IL-10 topically avoids systemic effects, such as immunosuppression in non-target tissues. When using LL-Thy12, IL-10 secretion is dependent on the quantity of live LL-Thy12 in the GI tract. As the presence of dietary thymidine increases the quantity of LL-Thy12, the drug production increases proportionately. Reductions in dietary thymidine kill LL-Thy12, decreasing the production of IL-10. There is a delay of approximately 72-hours between a change in thymidine dosage and the production of IL-10. Due to LL-Thy12’s dependence on thymidine, they will die upon exiting the body through defecation.
"B. ovatus" mechanism.
"B. ovatus" has been used in animal studies as a mode of microbial drug delivery due to its xylanase operon. Operons exist in bacteria to control gene expression and are composed of a DNA sequence containing an operator followed by the genes of interest. The operator in the xylanase operon prevents transcription of genes when bound to a repressor protein. The "B. ovatus" xylanase operon only functions in the presence of the starch, xylan, which removes the repressor and enables production of whichever proteins correlate with the genes located after the operator. For microbial drug delivery, the genes after the operator include those inserted as part of the genetic modification. Xylan is non-digestible to human gastric acid or digestive enzymes, so a predictable quantity of dietary xylan will reach the recombinant "B. ovatus" in the gut, hypothetically allowing for a precise quantity of drug to be produced by the recombinant "B. ovatus". In mice, recombinant "B. ovatus" strains containing genes for growth factors TGF-β and KGF-2 within the xylanase operon have successfully treated ulcerative colitis (UC). The secreted drugs from "B. ovatus" are applied topically to the epithelial lining, affecting local tissues rather than acting systemically. Systemic administration of these growth factors could otherwise cause tumors and increased vascularization of tissues. When administered microbially, TGF-β and KGF-2 facilitate tissue repair only in the colon where they are released.
Safety of microbial drug delivery.
Safety is a major factor in the efficacy of microbial drug delivery. Depending on the type of drug being administered, a certain level of control is required for effective and safe treatment of colonic diseases. The "L. lactis" system has a 72-hour delay between ingesting thymidine and activating IL-10 production, while the "B. ovatus" system allows the drug to be produced once xylan reaches the bacteria. Regarding IL-10 secretions in "L. lactis", the delay is acceptable for treatment of IBD, however any drug that requires a precise dosage and timing may necessitate "B. ovatus" for controlling drug output.
The safety of microbial drug delivery is tied to the microbes’ commensal capability and instance of pathogenesis. A highly pathogenic microbe would not be suitable for medical treatment due to an inherent infection risk. "L. lactis" is considered by the Food and Drug Administration (FDA) to be generally recognized as safe (GRAS), as it is commonly found in widely consumed dairy products, suggesting its safety in medical treatment. "B. ovatus" is naturally found in 10% of healthy human colons, demonstrating safety in its compatibility with the human gut microbiota; however, "Bacteroides" species are known in some cases to cause infections, typically resulting from surgery in the GI tract.
Concerns regarding the containment of recombinant microbes in the gut have been addressed through safety mechanisms in both "L. lactis" and "B. ovatus". Containment refers to the inability of microbes to colonize the external environment, where they may have unknown consequences. LL-Thy12 will die upon removal from the body, as they depend on dietary thymidine for survival. "B. ovatus" is naturally an obligate anaerobe, so any recombinant strain is expected to die in the presence of oxygen once removed from the body.


Homotrimer

A homotrimer is a protein which is composed of three identical units of polypeptide.


Gertrud Szabolcsi

Gertrud Szabolcsi (26 January 1923, Oradea, Romania — 28 March 1993, Budapest, Hungary) was a biochemist. Her research centered on the structure and function of enzymes. She was a member of the Hungarian Academy of Sciences. She was First Lady of Hungary as the second wife of Brunó Ferenc Straub, the last Chairman of the Hungarian Presidential Council from 1988 until 1989.
She and her husband received the 41st president of the United States, George H. W. Bush and his wife, Barbara Bush who visited Hungary on 12 July 1989. Her daughter from her first marriage is linguist Anna Szabolcsi.


CDP-archaeol synthase

CDP-archaeol synthase (, "CDP-2,3-di-O-geranylgeranyl-sn-glycerol synthase", "CTP:2,3-GG-GP ether cytidylyltransferase", "CTP:2,3-di-O-geranylgeranyl-sn-glycero-1-phosphate cytidyltransferase") is an enzyme with systematic name "CTP:2,3-bis-O-(geranylgeranyl)-sn-glycero-1-phosphate cytidylyltransferase". This enzyme catalyses the following chemical reaction
This enzyme catalyses one of the steps in the biosynthesis of polar lipids in Archaea.


Acetylcarnosine

"N"-Acetylcarnosine (NAC) is a naturally occurring compound chemically related to the dipeptide carnosine. The NAC molecular structure is identical to carnosine with the exception that it carries an additional acetyl group. The acetylation makes NAC more resistant to degradation by carnosinase, an enzyme that breaks down carnosine to its constituent amino acids, beta-alanine and histidine.
Actions.
Carnosine and metabolic derivatives of carnosine, including NAC, are found in a variety of tissues but particularly muscle tissue. These compounds have varying degrees of activity as free radical scavengers. It has been suggested that NAC is particularly active against lipid peroxidation in the different parts of the lens in the eye. It is an ingredient in eye drops that are marketed as a dietary supplement (not a drug) and have been promoted for the prevention and treatment of cataracts. There is scant evidence on its safety, and no convincing evidence that the compound has any effect on ocular health.
Research.
Most of the clinical research on NAC has been conducted by Mark Babizhayev of the US-based company Innovative Vision Products (IVP), which markets NAC treatments.
During early experiments performed at the Moscow Helmholtz Research Institute for Eye Diseases, it was shown that NAC (1% concentration), was able to pass from the cornea to the aqueous humour after about 15 to 30 minutes. In a 2004 trial of 90 canine eyes with cataracts, NAC was reported to have performed better than placebo in positively affecting lens clarity. An early human study NAC reported that NAC was effective in improving vision in cataract patients and reduced the appearance of cataract.
The Babizhayev group later published a placebo-controlled clinical trial of NAC in 76 human eyes with mild to advanced cataracts and reported similar positive results for NAC. However, a 2007 scientific review of the current literature discussed the limitations of the clinical trial, noting that the study had low statistical power, a high dropout rate and "insufficient baseline measurement to compare the effect of NAC", concluding that "a separate larger trial is needed to justify the benefit of long-term NAC therapy".
Babizhayev and colleagues published a further human clinical trial in 2009. They reported positive results for NAC as well as arguing "only certain formulas designed by IVP... are efficacious in the prevention and treatment of senile cataract for long-term use."
Commentary.
The Royal College of Ophthalmologists remains very skeptical about claims of efficacy in cataract reversal. It issued the following public statement about NAC in August 2008:The evidence for the effectiveness of N-acetyl carnosine eye drops is based on experience on a small number of cases carried out by a Russian research team [Babizhayev]. To date, the research has not been corroborated and the results replicated by others. The long-term effect is unknown. Unfortunately, the evidence to date does not support the 'promising potential' of this drug in cataract reversal. More robust data from well conducted clinical trials on adequate sample sizes will be required to support these claims of efficacy. Furthermore, we do not feel the evidence base for the safety is in any way sufficient to recommend its use in the short term. More research is needed.
In a 2010 book on ocular disease, the current state of this subject is summarized as follows:
Carnosine (β-alanyl--histidine), and its topical prodrug formulation "N"-acetylcarnosine (NAC), is advertised (especially on the internet) to treat a range of ophthalmic disorders associated with oxidative stress, including age-related and diabetic cataracts. No convincing animal studies or masked clinical trials have been reported.
A Cochrane review summarizing research up to June 2016 has concluded that there is "no convincing evidence that NAC reverses cataract, nor prevents progression of cataract". The authors did not include the studies conducted by the Babizhayev group because they were unable to establish that the research used scientific methods appropriate for clinical trials.
References.
Cochrane Database Syst Rev. 2017 Feb 28;2:CD009493. doi: 10.1002/14651858.CD009493.pub2.


Myxosphaera

Myxosphaera is a radiolarian genus in the Collosphaeridae. The genus may contain bioluminescent species. It is a genus of colonial radiolarians (as opposed to solitary).
Species.
The following species are known (incomplete list):


HrrF RNA

HrrF RNA ("Haemophilus" regulatory RNA responsive to iron Fe) is a small non-coding RNA involved in iron homeostasis in "Haemophilus" species. Orthologues exist only among other "Pasteurellacae." Iron- regulated sRNAs JA01- JA04 were identified in related "Aggregatibacte"r. It is an analog to PrrF and RyhB RNAs. HrrF is maximally expressed when iron levels are low. Ferric uptake regulator (Fur) binds upstream of the "hrrF" promoter. HrrF stability is not dependent on the RNA chaperone Hfq. RNA-seq has shown that HrrF targets are mRNAs of genes whose products are involved in molybdate uptake, deoxyribonucleotide synthesis, and amino acid synthesis.


Walter Reed Army Institute of Research

The Walter Reed Army Institute of Research (WRAIR) is the largest biomedical research facility administered by the U.S. Department of Defense (DoD). The institute is centered at the Forest Glen Annex, in the Forest Glen Park part of the unincorporated Silver Spring urban area in Maryland just north of Washington, DC, but it is a subordinate unit of the U.S. Army Medical Research and Development Command (USAMRDC), headquartered at nearby Fort Detrick, Maryland. At Forest Glen, the WRAIR has shared a laboratory and administrative facility — the Sen Daniel K. Inouye Building, also known as Building 503 — with the Naval Medical Research Center since 1999.
The Institute takes its name from Major Walter Reed, MD (1851–1902), the Army physician who, in 1901, led the team that confirmed the theory that yellow fever is transmitted by a particular mosquito species, rather than by direct contact. Today, the WRAIR fosters and performs biomedical research for the DoD and the US Army. It has recently developed two modern "Centers of Excellence" in the fields of military psychiatry/neuroscience and infectious disease research. The Centers focus, respectively, on soldier fitness, brain injury, and sleep management and in the development of vaccines and drugs for prevention and treatment of such diseases as malaria, HIV/AIDS, dengue fever, wound infections, leishmaniasis, enteric diseases and others.
Official mandate.
Basic and applied medical research supporting U.S. military operations is the focus of WRAIR leaders and scientists. Despite the focus on the military, however, the institute has historically also addressed and solved a variety of non-military medical problems prevalent in the United States and the wider world.
Divisions and Subordinate Units of the WRAIR.
Divisions at the Daniel K. Inouye Building.
The Walter Reed Army Institute of Research hosts two Centers of Excellence for Military Psychiatry and Neuroscience and for Infectious Disease Research which are headquartered in Silver Spring, Maryland.
Center for Military Psychiatry and Neuroscience
Center for Infectious Disease Research
Office of Science Education and Strategic Communications:
The WRAIR supports and collaborates on all other Army Educational Research Programs including the Mobile Discovery Center, the Junior Solar Spring, eCybermission, Uninitiates Introduction to Engineering (UNITE), Research & Engineering Apprentice Program (REAP), International Science & Engineering Fair (INTEL-ISEF), Internships Science & Engineering Program (ISEP), Junior Science & Humanities Symposium (JSHS), Women in Science Project (WISP), Career Related Experience in Science & Technology (CREST), Consortium Research Fellows Program (CRFP), and Science, Mathematics and Research for Transformation Defense Scholarshop for Service Program (SMART).
Research Support:
WRAIR Pilot Bioproduction Facility.
The Pilot Bioproduction Facility (PBF) was established in 1958 as the Department of Biologics Research and is now located at the Walter Reed Army Institute of Research. The PBF mission is research, development, production, and testing of vaccines for human use. The PBF at the Forest Glen Annex is a multi-use facility designed and operated for production of vaccines in compliance with the current Good Manufacturing (cGMP) regulations. Compliance with cGMP ensures that products prepared in the facility will be safe, potent, and reproducible.
Since inception, the PBF has specialized in developing vaccines for Department of Defense mission-related disease threats. The PBF follows all federal regulations that apply to biological products and has expertise in the development and production of vaccines for the prevention of a variety of infectious diseases. Projects for public and private partners are accomplished through inter-agency and cooperative agreements.
Vaccines are produced that will protect Soldiers against diseases that they might encounter in areas of deployment. These include vaccines to prevent dengue fever, malaria, meningitis, cholera, shigellosis, hepatitis A, and HIV. The PBF places compliance, cleanliness, and safety as top priorities in the production process of a vaccine. Once the vaccine is tested for safety, potency, and identity, the vaccine is released for use in approved human clinical studies. Several of the PBF's experimental vaccines have progressed on to advanced clinical testing.
History of the WRAIR.
The WRAIR traces its institutional heritage back to the Army Medical School, founded by U.S. Army Surgeon General George Sternberg in 1893, by some reckonings the first school of public health and preventive medicine in the world. (The other institution vying for this distinction is the Johns Hopkins School of Public Health, founded in 1916.) The organization name was officially changed to the Walter Reed Army Institute of Research in 1953.
External links.
"This article contains information that originally came from US Government publications and websites and is in the public domain."


Lacto-2 RNA motif

The lacto-2 RNA motif is an RNA structure that is conserved amongst bacteria within the order Lactobacillales. The motif consists of a stem-loop whose stem is interrupted by many internal loops and bulges. Nucleotide identities in many places are conserved, and one internal loop in particular is highly conserved.
As lacto-2 RNAs are not consistently located in 5′ UTRs, they are presumed to correspond to non-coding RNAs. However, most (80%) of the RNAs are in a position that may correspond to the 5′ UTR, so it is not inconceivable that the RNA has a role as a cis-regulatory element. Many lacto-2 RNAs are present in operons that encode tRNAs and rRNAs, and many are adjacent to genes encoding protein subunits of the ribosome, although they are not necessarily in the same operon as these protein-coding genes. Lacto-2 RNAs also have a weak association with genes involved in nucleotide biosynthesis and transport, including several independent genes within the de-novo purine biosynthesis pathway and some in pyrimidine biosynthesis.


Phosphomevalonic acid

Phosphomevalonic acid is an intermediate in the Mevalonate pathway.


N2a cell

N2a cells (also known as Neuro2a cells) are a fast-growing mouse neuroblastoma cell line.
Differentiation Properties.
Originating from a mouse, the N2a cell line has a neuronal and amoeboid stem cell morphology, allowing it to differentiate in response to environmental factors. The differentiated cells have many properties of neurons, including neurofilaments. The cells, due to passaging since initial collection, can exhibit responses to toxins that differ from those of neuronal cells in a live organism. Synthesizing large amounts of microtubules, N2a cells are susceptible to viruses (such as herpes simplex and poliovirus) that can alter cell morphology and physiology.
Research Applications.
N2a cells have been used to study neurite outgrowth, neurotoxicity, Alzheimer's disease, asymmetric division of mammalian cell lines, adenoviral transduction, and the diagnosing of rabies.


Coproporphyrinogen I

Coproporphyrinogen I is an isomer of coproporphyrinogen III, a metabolic intermediate in the normal biosynthesis of heme. The compound is not normally produced by the human body; its production and accumulation causes a type of porphyria.
The difference between coproporphyrinogen I and III is the arrangements of the four carboxyethyl ("P" groups) and the four methyl groups ("M" groups). The I isomer has the sequence MP-MP-MP-MP, whereas in the III isomer it is MP-MP-MP-PM, with the last two side chains reversed.
Biosynthesys.
Coproporphyrinogen I is not produced in the normal porphyrin biosynthesis pathway. However, if the enzyme uroporphyrinogen-III cosynthaseis missing or inactive, the compound uroporphyrinogen I is produced instead of uroporphyrinogen III. The enzyme uroporphyrinogen III decarboxylase will also act on the I isomer, producing coproporphyrinogen I:
The reaction entails the conversion of the four carboxymethyl (acetic acid) side chains to methyl groups, with release of four molecules of carbon dioxide.
Unlike the III isomer, coproporphyrinogen I (which is cytotoxic) is not further processed by the body, and accumulates. This situation occurs in the pathological condition called congenital erythropoietic porphyria.


Nucleotide sugars metabolism

In nucleotide sugar metabolism a group of biochemicals known as nucleotide sugars act as donors for sugar residues in the glycosylation reactions that produce polysaccharides. They are substrates for glycosyltransferases. The nucleotide sugars are also intermediates in nucleotide sugar interconversions that produce some of the activated sugars needed for glycosylation reactions. Since most glycosylation takes place in the endoplasmic reticulum and golgi apparatus, there are a large family of nucleotide sugar transporters that allow nucleotide sugars to move from the cytoplasm, where they are produced, into the organelles where they are consumed.
Nucleotide sugar metabolism is particularly well-studied in yeast, fungal pathogens, and bacterial pathogens, such as "E. coli" and "Mycobacterium tuberculosis", since these molecules are required for the synthesis of glycoconjugates on the surfaces of these organisms. These glycoconjugates are virulence factors and components of the fungal and bacterial cell wall. These pathways are also studied in plants, but here the enzymes involved are less well understood.


Whitley Professor of Biochemistry

The position of Whitley Professor of Biochemistry at the University of Oxford is one of the permanent chairs of the university, and the first in the field of biochemistry at the university. It is associated with a fellowship at Trinity College, Oxford, and was established with an endowment of £10,000 by Edward Whitley of Trinity College. Benjamin Moore was nominated by Whitley, a former student of Moore, as the first professor. Since its creation, the position has been held by:


Orthopoxvirus inclusion bodies

Orthopoxvirus inclusion bodies are aggregates of stainable protein produced by poxvirus virions in the cell nuclei and/or cytoplasm of epithelial cells in humans. They are important as sites of viral replication.
Morphology.
Morphologically there are two types of Orthopoxvirus inclusion bodies, Type-A inclusion bodies and Guarnieri bodies. Type-A inclusion bodies are found only in certain poxviruses like cowpox. The Guarnieri bodies are found in all poxvirus infections and their presence is diagnostic. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. However, all orthopoxviruses exhibit identical brick-shaped virions by electron microscopy.
Guarnieri bodies are named for Giuseppe Guarnieri, (1856-1918) an Italian physician who first described them.