Mycena inclinata

Mycena inclinata, commonly known as the clustered bonnet or the oak-stump bonnet cap, is a species of mushroom in the family Mycenaceae. The doubtfully edible mushroom has a reddish-brown bell-shaped cap up to in diameter. The thin stem is up to tall, whitish to yellow-brown at the top but progressively becoming reddish-brown towards the base in maturity, where they are covered by a yellowish mycelium that can be up to a third of the length of the stem. The gills are pale brown to pinkish, and the spore print is white. It is a widespread saprobic fungus, and has been found in Europe, North Africa, Asia, Australasia, and North America, where it grows in small groups or tufts on fallen logs and stumps, especially of oak. British mycologist E.J.H. Corner has described two varieties of the mushroom from Borneo. Lookalike species with which "M. inclinata" may be confused include "M. galericulata" and "M. maculata".
Taxonomy, phylogeny, and naming.
First described as "Agaricus inclinatus" by Swedish mycologist Elias Magnus Fries in 1838, it was assigned its current name in 1872 by Lucien Quélet. "Mycena galericulata" var. "calopus" (named by Karsten in 1879), and its basionym "Agaricus galericulatus" var. "calopus" (named by Fries in 1873), are synonyms.
In a molecular study of the large subunit ribosomal DNA sequences of mycorrhizal fungi of the orchid "Gastrodia confusa", "M. inclinata" was found to be closely related to "M. aurantiomarginata", "M. crocata", and "M. leaiana".
The specific epithet "inclinata" means "bent in". The mushroom is commonly known as the "clustered bonnet" or the "oak-stump bonnet cap".
Description.
The cap is light reddish-brown, with a diameter typically ranging from . Initially conic to bell-shaped to convex, it flattens during maturity, developing visible surface grooves corresponding to the gills underneath the cap. The margin of the cap has minute but distinct scallops. The surface is moist and smooth, and hygrophanous. The cap frequently develops splits in the margin, or cracks in the disc (the central part of the cap). The flesh of the cap is thick in the center but thin elsewhere, grayish to whitish, fragile, and with a slightly mealy odor and taste. The gills have a decurrent attachment to the stem (that is, running down the length of the stem) and are a pale brownish color with tinges of red. They are broad (between 3 and 6 mm), and have a close to subdistant spacing, with about 26–35 gills reaching the stem. The fragile stem is long by thick and yellow to yellow-brown, becoming reddish-brown to orange-brown in the bottom half in maturity. The lower portion of young stems is covered with white flecks. Roughly equal in thickness at the top and bottom, the base of the stem is covered by a yellowish mycelium that can be up to a third of the length of the stem. The edibility of the mushroom is "doubtful" and consumption "best avoided", although it is considered nonpoisonous.
Microscopic characteristics.
The spores are 7–9 by 5–6.5 μm, broadly ellipsoid, smooth, and strongly amyloid (it turns black when treated with Melzer's reagent). The basidia (spore-bearing cells) are four-spored. The pleurocystidia (cystidia on the gill face) are not differentiated. The cheilocystidia (cystidia on the gill edge) are embedded in the gill edge and very inconspicuous, club-shaped, 26–36 by 5–10 μm, and have tips that are covered with contorted projections that can be slender or thick. The flesh of the gills is homogeneous, and pale yellowish to dirty brown when stained in iodine. The flesh of the cap has a distinct pellicle, a well-differentiated hypoderm (a region of tissue immediately under the pellicle), and a filamentous tramal body (gill tissue); it is pale yellowish to sordid brownish in iodine stain.
Varieties.
E.J.H. Corner defined the varieties "M. inclinata" var. "kinabaluensis" and var. "subglobospora" in his 1994 publication on Agaric mushrooms of Malesia, a biogeographical region straddling the boundary of the Indomalayan and Australasian realms. The variety "kinabaluensis" (named after its type locality, Kinabalu) has a cap margin that is not scalloped, little or no odor, and cheilocystidia with shorter processes. It was found growing on the dead wood of "Lithocarpus havilandii", a stone oak tree in the beech family. Variety "subglobospora", found in Sabah, has spores that are almost spherical.
Similar species.
"Mycena maculata" bears some resemblance to "M. inclinata", but is only associated with decaying hardwood logs and stumps, and is found in eastern North America, and sometimes on oak on the West Coast. In age, it develops reddish spots on the gills that are not seen in "M. inclinata". "M. inclinata" is often confused with the edible "M. galericulata", a common species that is variable in cap color, size and shape. "M. galericulata" typically has a bluntly conical cap that is dull gray-brown, and white to grayish veins that have numerous cross-veins. "M. polygramma" has a ridged stem that is bluish-gray.
Habitat and distribution.
"Mycena inclinata" is a saprobic fungus, deriving its nutrients from decomposing organic matter found in plant litter such as leaves, twigs, bark and branches. It accomplishes this by producing enzymes capable of breaking down the three major biochemical components of plant cell walls found in litter: cellulose, hemicellulose and lignin.
The fruit bodies of "Mycena inclinata" grow in dense groups or clusters on decaying hardwood logs and stumps (especially oak and chestnut) during the spring and autumn. The fungus forms a white, woolly mycelium on the surface of decomposing oak leaves. Occasionally, it can be found growing on a living tree. In eastern North America, it is abundant in the area bounded by Nova Scotia, Ontario, Manitoba, Missouri, North Carolina, and New York. It has been found in Oregon, but the species appears to be generally rare along the Pacific Coast. The range of the fungus also includes Europe, the Canary Islands, North Africa, East Siberia, Japan, Malesia, Turkey, and New Zealand.
Chemistry.
In a study of the trace metal concentrations of various mushrooms species found in Ordu (Turkey), "M. inclinata" was found to have comparatively high levels of iron (628 mg per kg) and nickel (21.6 mg/kg), measured on a dry weight basis. Laboratory studies have shown that the fungus is resistant to aluminum. The fungus has been investigated for its ability to decolorize synthetic dyes that are used in the textile, plastics, biomedical and foodstuff industries. The dyes are not readily biodegradable, and when discharged into the environment are persistent and many are toxic.


L-erythro-3,5-diaminohexanoate dehydrogenase

In enzymology, a L-erythro-3,5-diaminohexanoate dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are L-erythro-3,5-diaminohexanoate, H2O, and NAD+, whereas its 4 products are (S)-5-amino-3-oxohexanoate, NH3, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-erythro-3,5-diaminohexanoate:NAD+ oxidoreductase (deaminating). This enzyme is also called L-3,5-diaminohexanoate dehydrogenase. This enzyme participates in lysine degradation.


5-(Nonyloxy)tryptamine

5-(Nonyloxy)tryptamine is a tryptamine derivative which acts as a selective agonist at the 5-HT1B receptor. Increasing the O-alkoxy chain length in this series gives generally increasing potency and selectivity for 5-HT1B, with highest activity found for the nonyloxy derivative, having a 5-HT1B binding affinity of 1.0 nM, and around 300-fold selectivity over the related 5-HT1A receptor.


Genus plc

Genus plc is a British-based business selling elite genetics and other products manufactured using biotechnology to cattle and pig farmers. It is headquartered in Basingstoke and is a constituent of the FTSE 250 Index.
History.
The business has its origins in the former Breeding & Production Division of the Milk Marketing Board which was established in 1933 and broken up in 1994. In 1999 Genus acquired ABS Global, a company founded by J.R. Prentice in the US as the "American Breeders Service" in 1941 selling the semen of cattle. In 2005 Genus acquired, through the takeover of Sygen International plc, PIC, a company founded by six pork producers in the UK as the "Pig Improvement Company" in 1962.
Operations.
The Company has three divisions:


Plasmodium helical interspersed subtelomeric protein

The "Plasmodium" helical interspersed subtelomeric proteins (PHIST) or ring-infected erythrocyte surface antigens (RESA) are a family of protein domains found in the malaria-causing "Plasmodium" species. It was initially identified as a short four-helical conserved region in the single-domain export proteins, but the identification of this part associated with a DnaJ domain in "P. falciparum" RESA (named after the ring stage of the parasite) has led to its reclassification as the RESA N-terminal domain. This domain has been classified into three subfamilies, PHISTa, PHISTb, and PHISTc.
The PHIST proteins are exported to the cytoplasm of the infected erythrocyte. The human malaria parasites "P. falciparum" and "P. vivax" have shown a lineage-specific expansion of proteins with this domain. Of the two PHIST genes in the mouse parasite "P. berghei", only one is required for infection. The PHIST domain folds into three long helices (forming a bundle) and two smaller N-terminal helices, and is monomeric in solution. It binds PfEMP1 ATS C-terminus and plays a role in "knob" formation.
RESA.
The full RESA protein in "P. falciparum" also contains a few other domains, namely the DnaJ domain and the DnaJ-associated X domain. A part of the X-domain, RESA/P13830663-670, appears to bind and reinforce spectrin cytoskeleton so that each erythrocyte only hosts one parasite.
"P. falciparum" isolate 3D7 encodes three RESA-family proteins, RESA-1 (P13830//PF3D7_0102200), RESA-2 (M91672.1//PF3D7_1149500), RESA-3 (/PF3D7_1149200). RESA-2 is usually considered a transcribed pseudogene due to a premature stop codon. However, a missense mutation T1526G or T1526C in RESA-2 that removes this stop codon is commly found. It is associated with increased severity of disease.


Azobilirubin

Azobilirubin is a coloured compound formed by the condensation of diazotized sulfanilic acid with bilirubin in the van den Bergh reaction. The quantity of bilirubin in patients with jaundice can be determined by the formation of azobilirubin in the presence of methanol.
The Van den Bergh chemical reaction which is used to measure bilirubin levels, couples bilirubin with diazotized sulfanilic acid. This reaction produced azo pigments, or azobilirubin. The presence of azobilirubin is best indicated by the emergence of a pink-purple color. The intensity of the color will also indicate how much bilirubin is in the blood. Color markers and indicators can be changed. Adding alkaline tartrate can make the purple azobilirubin into a blue azobilirubin. If we have high levels of bilirubin in the blood, the Van den Bergh chemical reaction is used to determine if the bilirubin is conjugated or unconjugated.
Azobilirubin can also be used to determine how much conjugated bilirubin is the blood compared to that of unconjugated bilirubin. This process is done by using both forms of bilirubin alongside a diazo reagent and a caffeine-benzoate reagent. Conjugated bilirubin with the azo reagent will react, whilst the unconjugated bilirubin will not react with the azo reagent.


CsrC RNA family

The 245 nucleotide sRNA of "Escherichia coli", CsrC, was discovered using a genetic screen for factors that regulate glycogen biosynthesis. CsrC RNA binds multiple copies of CsrA, a protein that post-transcriptionally regulates central carbon flux, biofilm formation and motility in E. coli. CsrC antagonises the regulatory effects of CsrA, presumably by sequestering this protein. The discovery of CsrC is intriguing, in that a similar sRNA, CsrB, performs essentially the same function. Both sRNAs possess similar imperfect repeat sequences (18 in CsrB, nine in CsrC), primarily localised in the loops of predicted hairpins, which may serve as CsrA binding elements. Transcription of csrC increases as the culture approaches the stationary phase of growth and is indirectly activated by CsrA via the response regulator UvrY [1]. This RNA was also discovered in "E. coli" during a large scale screen [2]. The gene called SraK, was highly abundant in stationary phase, but low levels could be detected in exponentially growing cells as well [2].


Mount Everest webcam

The Mount Everest webcam was a camera located on Kala Patthar, a mountain in the Nepalese Himalaya, at an altitude of . The webcam captured video footage of the summit of Mount Everest and was the highest webcam in the world. It was installed by Italian scientists as part of the Everest Share 2011 research project by the Nepalese Ev-K2-CNR team, which was intended to gather information regarding climate change by working together with the Everest weather station. As of 2019, the camera is no longer operating.
Features.
The camera was an M12-type model made by the German-based company Mobotix. The M12-type camera is powered by solar cells and operated from 6am to 6pm local time (UTC +5:45). It was capable of operating at temperatures as low as and broadcast its live, high-definition video worldwide via the Internet.
Operation.
The captured video was transmitted wirelessly to the Ev-K2-CNR Pyramid Laboratory/Observatory, located on the slopes of Mount Everest at an altitude of . The live video was analyzed in the observatory, then sent to Italy for further processing.
Last images were given as of 09.11.2015.
Location.
Kala Patthar was chosen as the location for the webcam because of its excellent view of the summit of Mount Everest, including both the north and south-west faces as well as the west ridge.
Highest webcam.
As of May 17, 2011, it is the highest webcam in the world. When installed, it surpassed the previous record holder, at Capanna Regina Margherita Monte Rosa, Italy, at an altitude of .


Richard M. Myers

Richard M. Myers (born March 24, 1954) is an American geneticist and biochemist known for his work on the Human Genome Project (HGP). The National Human Genome Research Institute says the HGP “[gave] the world a resource of detailed information about the structure, organization and function of the complete set of human genes.”  Myers' genome center, in collaboration with the Joint Genome Institute, contributed more than 10 percent of the data in the project.
Myers is President and Science Director of the HudsonAlpha Institute for Biotechnology, a non-profit research institute.  He was previously the chair of the department of genetics at Stanford University and director of the Stanford Human Genome Center.
His research focuses on the human genome with the goal of understanding how allelic variation and gene expression changes contribute to human traits, including diseases, behaviors and other phenotypes.
Early life and education.
Myers was born in Selma, Alabama in 1954 and moved to Tuscaloosa, Alabama at age 10. He attended college at the University of Alabama where he earned his bachelor's degree in biochemistry. He then went to graduate school at the University of California at Berkeley, earning his Ph.D.  in 1982 in the laboratory of Dr. Robert Tjian. After that, Myers spent almost four years as a postdoctoral fellow in the lab of Dr. Tom Maniatis at Harvard University, where he studied human gene regulation. Some new technologies he developed in Maniatis's lab exposed him to the field of human genetics, and much of his work since then has involved developing and using genomics and genetic tools to understand basic human biology and disease.
Origins of the Human Genome Project.
On behalf of Maniatis, Myers attended a conference sponsored by the U.S. Department of Energy and the International Commission for Protection Against Environmental Mutagens and Carcinogens. 19 researchers, including Myers, met at an Alta, Utah ski resort In December 1984 with a challenge in mind. The group explored how scientists might determine whether the atomic bombs dropped on Hiroshima and Nagasaki during World War II increased the rate of mutations in the sperm or eggs of survivors. Scientists believed the high doses of radiation could have increased the germline mutation rate, but they would need methods to measure mutations in the children of survivors. Those methods would allow them to compare the number of mutations in offspring compared to exposed survivors of the bomb blasts.
Myers recalls a conference attendee saying, “The rate is so low that we would have to sequence the entire human genome to know the answer.”  Not long after, the Department of Energy proposed the basis for the Human Genome Project, which began in earnest in 1990.
Early Genetic Research.
In 1985, Myers set up a lab at the University of California in San Francisco. His team sought to understand globin gene expression, studying both cis- and trans-acting components that regulate transcription of the gene.  His team also worked on finding the mutated gene present in people with Huntington disease.  Myers teamed up with Dr. David Cox, a medical geneticist with a Ph.D. in yeast and human genetics.  Their laboratories worked together for 15 years, on multiple technologies for gene hunting, including radiation hybrid mapping, a method that uses high-energy x-rays to fragment human chromosomes that were recovered in somatic cell hybrids and then used to determine the locations of DNA markers in the human genome.  In 1990 they established a human genome center, which they moved to Stanford University in early 1993.  The pair continued working on inherited human diseases. They found the genes for an inherited form of childhood progressive epilepsy (EPM1), a gene important for a key step in development of the cerebellum (the “weaver” gene), and others. Over the course of those years, the Myers lab created and worked with mouse models for Huntington disease and EPM1.
Human Genome Project Contributions.
Cox and Myers in their work at the Stanford Human Genome Center collaborated with the Joint Genome Institute (JGI) in Walnut Creek to sequence the first human genome. That collaboration led to maps of the entire genome, which played a key role in piecing the entire sequence together for the Human Genome Project (HGP). The Stanford group generated genome-wide maps as well as finishing of sequences of three human chromosomes, and their collaboration with JGI contributed 11% of the finished human genome.
The HudsonAlpha Institute for Biotechnology.
Biotech visionaries Jim Hudson and Lonnie McMillian founded the HudsonAlpha Institute for Biotechnology in 2008, recruiting Myers to lead the Institute as president and science director.
The Myers Lab at HudsonAlpha studies the human genome, with a focus on allelic variation and how gene expression changes contribute to human traits, including disease. His group utilizes a number of high-throughput genomic methods, including DNA sequencing, genotyping, chromatin immunoprecipitation, mRNA expression profiling, transcriptional promoter and DNA methylation measurements. The lab also uses computational and statistical tools for identifying, characterizing and understanding how functional elements of the genome work together at the molecular level. Researchers in the Myers Lab use these and other state-of-the-art methods to explore how genomes are involved in brain disorders, ALS, cancer, children born with developmental disorders, autoimmune diseases and other traits.


HutP

HutP (Histidine utilizing Protein) is one of the anti-terminator proteins of "Bacillus subtilis", which is responsible for regulating the expression of the hut structural genes of this organism in response to changes in the intracellular levels of L-histidine and divalent metal ions. In the hut operon, HutP is located just downstream from the promoter, while the five other subsequent structural genes, hutH, hutU, hutI, hutG and hutM, are positioned far downstream from the promoter. In the presence of L-histidine and divalent metal ions, HutP binds to the nascent hut mRNA leader transcript. This allows the anti-terminator to form, thereby preventing the formation of the terminator and permitting transcriptional read-through into the hut structural genes. In the absence of L-histidine and divalent metal ions or both, HutP does not bind to the hut mRNA, thus allowing the formation of a stem loop terminator structure within the nucleotide sequence located between the hutP and structural genes.
HutP is a 16.2 kDa protein consisting of 148 amino acid residues. HutP also exists in five other "Bacillus" species, including "B. anthracis", "B. cereus", "B. halodurans", "B. thuringiensis", and "Geobacillus kautophilus", with 60% sequence identity. Thirumananseri Kumarevel solved the crystal structure of the HutP protein in the apo-form, binary complex (complexed with divalent metal ions or L-histidine), ternary complex (HutP-metal ions-L-histidine) and quaternary complexes (HutP-L-histidine-metal ions-RNA) and elegantly revealed the snapshots of metal-ion mediated anti-termination mechanism for the first time.
References.
1. T. S. Kumarevel, H. Mizuno, P. K. R. Kumar, Structural basis of HutP-mediated anti-termination and roles of the Mg2+ ion and L-histidine ligand, Nature 434 (2005) 183-191.
2. T. S. Kumarevel, Z. Fujimoto, P. Karthe, M. Oda, H. Mizuno, P. K. R. Kumar, Crystal structure of activated HutP; an RNA binding protein that regulates transcription of the hut operon in Bacillus subtilis, Structure 12 (2004) 1269-1280.
3. T. S. Kumarevel, H. Mizuno, P. K. R. Kumar, Allosteric activation of HutP protein, that regulates transcription of hut operon in Bacillus subtilis, mediated by various analogs of histidine, Nucleic Acids Res suppl. 3 (2003) 199-200.
4. M. Oda, N. Kobayashi, A. Ito, Y. Kurusu, K. Taira, cis-acting regulatory sequences for antitermination in the transcript of the Bacillus subtilis hut operon and histidine-dependent binding of HutP to the transcript containing the regulatory sequences, Mol. Microbiol. 35 (2000) 1244-1254.
5. T. S. Kumarevel, H. Mizuno, P. K. R. Kumar, Characterization of the metal ion binding site in the anti-terminator protein, HutP, of Bacillus subtilis, Nucleic Acids Res. 33 (2005) 5494-5502.
6. T. S. Kumarevel, S. C. B. Gopinath, S. Nishikawa, H. Mizuno, P. K. R. Kumar, Identification of important chemical groups of the hut mRNA for HutP interactions that regulate the hut operon in Bacillus subtilis, Nucleic Acids Res. 32, (2004) 3904-3912.


Jonathan Dickinson (New Jersey minister)

Jonathan Dickinson (April 22, 1688 – October 7, 1747) was a Congregational, later Presbyterian, minister, a leader in the Great Awakening of the 1730s and 1740s, and a co-founder and first president of the College of New Jersey, which later became Princeton University.
Biography.
Born in Hatfield, Massachusetts on April 22, 1688, Dickinson studied theology at the Collegiate School of Connecticut, which later changed its name to Yale College, graduating in 1706. In 1709 Dickinson was ordained minister of the Congregational church in Elizabethtown, New Jersey.
Dickinson became concerned about the attempts of the established Church of England to suppress dissenters in New Jersey. Seeing a need for more coordination among dissenting churches, in 1717 Dickinson persuaded his congregation to join the Presbytery of Philadelphia, Pennsylvania. He became an active and influential participant in the affairs of the Presbyterians, and was twice elected moderator of the Synod of Philadelphia. As a former Congregationalist, Dickinson was part of the "New England" faction of Presbyterians who opposed the strict doctrinal requirements favored by the "Scots-Irish" faction. Dickinson was a strong supporter of Presbyterianism, earning a reputation as a leading defender of Calvinism in America. His book "Familiar Letters to a Gentleman, upon a Variety of Seasonable and Important Subjects in Religion" was reprinted a number of times in America and elsewhere.
The Great Awakening that started in the 1730s profoundly changed religion in the American colonies. The Presbyterians were divided into "New Sides" and "Old Sides", supporters and opponents, respectively, of the great revival meetings and the fervent preaching that accompanied them. Dickinson was a moderate "New Sider", supporting the revivals while opposing their more violent excess. His pulpit oratory was centered on "temperance and harmony" and "devoid of antagonizing divisions, but which at the same time was appealing and innovative". In 1738, Dickinson joined with other "New Siders" to form the Presbytery of New York. When the Presbytery of New Brunswick was expelled from the Synod of Philadelphia over its support for the more extreme "New Siders" in 1741, Dickinson and others tried to negotiate a reconciliation. In 1745 the Presbytery of New York withdrew from the Synod of Philadelphia and joined with the Presbytery of New Brunswick to form the Synod of New York. Dickinson was elected the first moderator of the new synod. In general, Dickinson "longed for an experimental and vital religion but not at the expense of social and religious order".
Founding of Princeton University.
Dickinson had long been interested in starting a new college to serve the middle colonies. When he saw that the existing colleges in New England were hostile to the "New Siders", he returned to the project of establishing a college. Dickinson and three other pastors (Ebenezer Pemberton of the Old South Church, grandfather of Ebenezer Pemberton (1746-1835), Aaron Burr, Sr., and John Pierson) enlisted the support of three laymen (William Smith, Peter Van Brugh Livingston, and William Peartree Smith). Led by Dickinson, this group of seven applied to Governor Lewis Morris for a charter. However, the governor rejected their application because he was an Anglican who opposed the Great Awakening. Following the death of Morris, they re-applied to Acting Governor John Hamilton, who granted a charter on October 22, 1746. Because Hamilton was only an acting Governor, the validity of the charter was questioned, and a second charter was then issued by the subsequent Governor Jonathan Belcher.
The first trustees, including five Log College adherents enlisted by Dickinson and Pemberton, announced Dickinson's appointment as the first President of Princeton University in April 1747. Classes began the fourth week in May in the parsonage of Dickinson's church in Elizabethtown, with a student body of eight or ten members. Less than five months later, on October 7, 1747, Jonathan Dickinson died suddenly, due to complications related to smallpox.


Monodehydroascorbate reductase (NADH)

In enzymology, a monodehydroascorbate reductase (MDAR) () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are NADH, H+, and monodehydroascorbate, whereas its two products are NAD+ and ascorbate.
This enzyme belongs to the family of oxidoreductases, specifically those acting on NADH or NADPH, with a quinone or similar compound as an acceptor. The systematic name of this enzyme class is NADH: monodehydroascorbate oxidoreductase. Other names in common use include NADH: semidehydroascorbic acid oxidoreductase, MDHA, semidehydroascorbate reductase, AFR, AFR-reductase, ascorbic free radical reductase, ascorbate free radical reductase, SOR, MDAsA reductase (NADPH), SDA reductase, NADH: ascorbate radical oxidoreductase, NADH-semidehydroascorbate oxidoreductase, ascorbate free-radical reductase, NADH: AFR oxidoreductase, and monodehydroascorbate reductase (NADH2). This enzyme participates in ascorbate and aldarate metabolism.
In plants, the monodehydroascorbate reductase (MDAR) is an enzymatic component of the glutathione-ascorbate cycle that is one of the major antioxidant systems of plant cells for the protection against the damages produced by reactive oxygen species (ROS). The MDAR activity has been described in several cell compartments, such as chloroplasts, cytosol, mitochondria, glyoxysomes, and leaf peroxisomes.


Aphthovirus internal ribosome entry site (IRES)

This family represents the internal ribosome entry site (IRES) of the "Picornaviruses". IRES elements allow cap and end-independent translation of mRNA in the host cell. The IRES achieves this by mediating the internal initiation of translation by recruiting a ribosomal 43S pre-initiation complex directly to the initiation codon and eliminates the requirement for the eukaryotic initiation factor eIF4F.


Biotech Consortium India Limited

Biotech Consortium India Limited (BCIL), New Delhi was incorporated as public limited company in 1990 under The Companies Act, 1956. The consortium is promoted by the Department of Biotechnology, Government of India and financed by the All India Financial Institutions and some corporate sectors. BCIL's major functions include the development and transfer of technology for the commercialisation of biotechnology products, project consultancy, biosafety awareness and human resource development.
BCIL has been successfully managing several Flagship schemes and Programmes of the Department of Biotechnology, Government of India. Most notable include:
1. Biotechnology Industry Partnership Programme
2. Biotechnology Industrial Training Programme
3. Small Business Innovation Research Initiative


Arye Rosen

Arye Rosen is Academy Professor of Biomedical and Electrical Engineering in the School of Biomedical Engineering, Science and Health Systems at Drexel University in Philadelphia, PA and associate vice president at Rowan University and a member of the National Academy of Engineering.
Education.
Rosen got his B.S. degree Electrical Engineering from Howard University and his M.S. degree in Engineering from Johns Hopkins University. Later, he was awarded his M.Sc. in Physiology from Thomas Jefferson University and his Ph.D. Electrical Engineering from Drexel University.
Career.
Rosen's career spent over thirty-six years with the RCA/David Sarnoff Research Center, where he was awarded the rank of Distinguished Member of Technical Staff. His work there centered on the research and development of microwave devices and circuits, microwave optical interaction and high-power semiconductor lasers. For the past forty-five years he has also been engaged in medical research into the use of laser, acoustic and microwave energies for therapeutic medical devices.
Dr. Rosen has worked in the Division of Cardiology at Jefferson Medical College since 1969 where he also holds the title of Associate in Medicine and he holds over 60 U.S. patents in the fields of engineering and medicine.
Personal.
Dr. Arye Rosen has one son, Dr. Harel D. Rosen, a neonatologist and a graduate of Jefferson Medical College, whom he has collaborated with in the founding of the Medical Technology Center for Infants and Children at St. Peter's University Hospital. They also collaborated on engineering a solar-powered blanket used to treat jaundice in developing nations.


Cyanobacterial RNA thermometer

The first cyanobacterial RNA thermometer (RNAT) Hsp17 was found in the 5'UTR of "Synechocystis" heat shock "hsp17" mRNA. Further study demonstrated that cyanobacteria commonly use RNATs to control the translation of their heat shock genes. HspA is a homolog of Hsp17 in thermophilic "Thermosynechococcus elongatus". Two more thermometers were found in the 5'UTRs of mesophilic cyanobacteria "A. variabilis" and "Nostoc" "sp". The first RNAT called avashort was shown to regulate translation by masking the AUG translation start site. The second RNAT called avalong, as it has an extended initial hairpin, might involve tertiary interactions and has similarities to the ROSE element.


Type IV secretion system

The bacterial type IV secretion system, also known as the type IV secretion system or the T4SS, is a secretion protein complex found in gram negative bacteria, gram positive bacteria, and archaea. It is able to transport proteins and DNA across the cell membrane. The type IV secretion system is just one of many bacterial secretion systems. Type IV secretion systems are related to conjugation machinery which generally involve a single-step secretion system and the use of a pilus. Type IV secretion systems are used for conjugation, DNA exchange with the extracellular space, and for delivering proteins to target cells. The type IV secretion system is divided into type IVA and type IVB based on genetic ancestry.
Notable instances of the type IV secretion system include the plasmid insertion into plants of "Agrobacterium tumefaciens", the toxin delivery methods of "Bordetella pertussis" (whooping cough) and "Legionella pneumophila" (Legionnaires' disease), and the F sex pilus.
Function.
The type IV secretion system is a protein complex found in prokaryotes used to transport DNA, proteins, or effector molecules from the cytoplasm to the extracellular space beyond the cell. The type IV secretion system is related to prokaryotic conjugation machinery. Type IV secretion systems are a highly versatile group, present in Gram positive bacteria, Gram negative bacteria, and archaea. They usually involve a single step which utilizes a pilus, though exceptions exist.
Type IV secretion systems are highly diverse, with a variety of functions and types due to different evolutionary paths. Primarily, type IV secretion systems are grouped based on structural and genetic similarity and are only distantly related to each other. Type IVA systems are similar to the VirB/D4 system of "Agrobacterium tumefaciens." Type IVB systems are similar to the Dot/Icm systems found in intracellular pathogens such as "Legionella pneumophila." The “other” type systems resemble neither IVA or IVB. Types are genetically distinct and use separate sets of proteins, however, proteins between the sets have strong homologies to each other, which leads them to function similarly.
Type IV secretion systems are also classified by function into three main types. Conjugative systems: used for DNA transfer via cell to cell contact (a process called conjugation); DNA release and uptake systems: used to exchange DNA with the extracellular environment (a process called transformation); and effector systems: used to transfer proteins to target cells. Conjugative as well as DNA release and uptake systems play an important role in horizontal gene transfer, which allows prokaryotes to adapt to their environment, such as, developing antibiotic resistance. Effector systems allow for the interaction between microbes and larger organisms. The effector systems are used as a toxin delivery method by many human pathogens such as, "Helicobacter pylori" (stomach ulcers), whooping cough, and Legionnaires' disease.
Structure.
Currently, only the structure of type IVA secretion systems, which occur in gram-negative bacteria, is well described. It is composed of 12 protein subunits, VirB1 - VirB11 and VirD4, analogies of which exist in all type IVA systems. The Type 4 secretion system’s components can be separated into 3 groups: the translocation channel scaffold, the ATPases, and the pilus.
The translocation channel scaffold is the portion of the machinery that creates the channel between extracellular space and the cytoplasm through the inner and outer membranes, and contains VirB6 - VirB10. The core complex of the scaffold is composed of 14 copies of VirB7, VirB9, and VirB10 which form a cylindrical channel that spans both membranes and connects the cytoplasm to the extracellular space.
A single protein, VirB10 is integral in both the inner and outer membranes. It inserts into the outer membrane using an α-helical barrel structure which helps form a channel between the two membranes. There is an opening on the cytoplasmic end of the channel which is followed by a large chamber and a second opening. The second opening requires a conformational change to allow substrate passage from the cytoplasm into the channel. Either VirB6 or VirB8 is believed to form the inner membrane pore, as they are integral proteins on the inner membrane and have direct contact with the substrate.
The ATPases consist of VirB4, VirB11, and VirD4, which drive the substrate motion through the channel and provide the system with energy. VirB11 belongs to a class of transmembrane transporters called “traffic ATPases”. VirB4 is not well characterized.
The pilus is composed of VirB2 and VirB5, with VirB2 being the major component. In "A. tumefaciens", the pilus is 8-12 nm in diameter, and less than one µm in length. F pili, another commonly examined type of pilus, are much longer with a length of 2-20 µm.
Mechanism.
Due to the wide variety of type IV secretion systems in both origin and function, it is difficult to state much mechanistically about the group as a whole.
In general, after DNA is packaged in a conjugative system it is recruited by ATPase analogues to the VirD4 coupling protein, then translocated through the pilus. In "A. tumefaciens" specifically, the DNA passes through a characterized chain of enzymes before reaching the pilus. The DNA is recruited by VirD4, then VirB11, then to the intermembrane proteins (VirB6, and VirB8), moved to VirB9, and finally sent to the pilus (VirB2).


MiR-324-5p

miR-324-5p is a microRNA that functions in cell growth, apoptosis, cancer, epilepsy, neuronal differentiation, psychiatric conditions, cardiac disease pathology, and more. As a microRNA, it regulates gene expression through targeting mRNAs. Additionally, miR-324-5p it is both an intracellular miRNA, meaning it is commonly found within the microenvironment of the cell, and one of several circulating miRNAs found throughout the body. Its presence throughout the body both within and external to cells may contribute to miR-324-5p's wide array of functions and role in numerous disease pathologies – especially cancer – in various organ systems.
History.
miR-324-5p first appeared in literature in a paper published by John Kim et. al. in early 2004 that identified 32 entirely new miRNAs from cultured rat cortical neurons using miRNA cloning and RNA analysis. The miRNA quickly gained traction in scientific literature, appearing in articles about the evolutionary conservation of microRNAs, HIV, cancer, and other topics within a few years. Today, the functions and roles of miR-324-5p are still not yet fully characterized.
Structure and targets.
miR-324-5p is a reverse strand miRNA, meaning it is produced from the 5' end of the associated RNA, and spans from position 7,223,342 to 7,223,364 on chromosome 17. Its sequence is CGCAUCCCCUAGGGCAUUGGUG.
miRNA forms following cleavage of pre-miRNA at the hairpin loop by the enzyme dicer within the cytosol. Interestingly, both strands of miR-324's pre-miRNA hairpin loop structure, miR-324-5p and miR-324-3p, become active miRNAs with distinct targets and functions. miR-324-5p has between 166 and 469 predicted targets, including regulators of cell growth, proliferation, survival, cytoskeletal structure, ATP transport, and ion channels. Though miR-324-5p is found on chromosome 17, its targets span across all chromosomes.
Functions.
Cell growth and survival.
miR-324-5p likely regulates cell growth and survival through interaction with multiple pathways. Published research demonstrates that this miRNA interacts with the Hedgehog (HH) signaling pathway via interactions with HH transcription factor Gli1 and HH protein receptor Smo, often contributing to tumorigenesis. miR-324-5p's activating interaction with the protein NfkB also regulates numerous components of cell survival, including cell cycle control, enzyme synthesis, and cell adhesion. In addition, miR-324-5p regulates components of the MAPK pathway, influencing cell growth, proliferation, and survival. Specifically, miR-324-5p downregulates RAF and ERK and is necessary for normal levels of cell growth. Reduced expression leads to increased cell growth and proliferation, and overexpression limits growth, leading to its role in oncogenesis.
Cancer.
Both up and downregulation of miR-324-5p is shown to contribute to various types of cancer.
miR-324-5p plays a role in inflammation and tumorigenesis in colorectal cancer through regulation of CUEDC2, which regulates inflammation via interaction with NF-kB signaling. miR-324-5p can inhibit glioma proliferation, suppress hepatocellular carcinoma and nasopharyngeal carcinoma cell invasion, and regulate growth and pathology in multiple myeloma. Additionally, chromosome 17 deletions, which include deletion of miR-324-5p, are present in 10% of multiple myeloma patients and are associated with poorer prognosis.
In contrast, overexpression of miR-324-5p in gastric cancer cells reduces cell death and promotes growth and proliferation. miR-324-5p has also been shown to reduce the viability of gastric cancer cells via downregulation of TSPAN8, and miR-324-5p expression increased apoptosis in these same gastric cancer cells.
Epilepsy.
Seizures are characterized by high levels of synchronized neuronal activity. One important regulator of neuronal activity is the hyperpolarizing A-type current mediated by potassium channel KV4.2. miR-324-5p downregulates KV4.2, exacerbating conditions that lead to seizure onset, and downregulation of miR-324-5p in mouse models of epilepsy is seizure-suppressive.
Changes in miRNA expression are seen in epileptogenesis and in other disease pathologies. In epilepsy, miR-324-5p expression has been shown to increase and decrease at different timepoints and loci.
Importantly, miR-324-5p has increased association with the RISC complex following seizure in mice, indicating more suppressive activity.
Overall, this suggests that miR-324-5p plays a role in epileptogenesis via targeting of potassium channel KV4.2.
Cardiac disease.
miR-324-5p contributes to cardiac disease pathophysiology and cardiomyocite death through translational inhibition of Mtfr1, leading to reduced mitochondrial fission, apoptosis, and myocardial infarction.
Psychiatric conditions.
MiRNA expression profiles are altered in psychiatric conditions, including depression, anxiety, and PTSD. It has been demonstrated that miR-324-5p expression is altered in the brains of suicide victims with depression and in the amygdala, the fear center of the brain, in PTSD. MiRNAs are an underexplored potential biomarker and target for treatment for psychiatric disease.
Future research and potential in medicine.
miRNA-324-5p is a relatively new and understudied microRNA. It is an important regulator in several diseases, and its effects span across the body from neuronal dysregulation in seizure to hepatocellular carcinoma and cardiac disease. Because microRNAs have numerous targets, they are capable of regulating multiple pathways and circuits, an ability that may be useful in the treatment of complex disorders like epilepsy in which many subsystems are dysregulated. However, the wide-ranging functions of miRNAs may be limiting as well. microRNA expression modulation could lead to unanticipated physiological effects and not provide adequate specificity.


EMDT

2-Ethyl-5-methoxy-"N","N"-dimethyltryptamine (EMDT) is a tryptamine derivative which is used in scientific research. It acts as a selective 5-HT6 receptor agonist, with a Ki of 16 nM, and was one of the first selective agonists developed for this receptor. EMDT inhibits both short- and long-term memory formation in animal studies, and this effect can be reversed by the selective 5-HT6 antagonist SB-399,885. Additionally, it is active in the tail suspension test, suggesting that it could be an effective antidepressant.


Journal of Tissue Engineering

The Journal of Tissue Engineering is a peer-reviewed open-access medical journal that covers research on tissue engineering. Its editors-in-chief are Hae-Won Kim (Dankook University) and Jonathan Knowles (UCL Eastman Dental Institute). It was established in 2010 and is published by Sage Publications.
Abstracting and indexing.
"The Journal of Tissue Engineering" is abstracted and indexed in:


Mycena noctilucens

Mycena noctilucens is a species of agaric fungus in the family Mycenaceae. The species was first described scientifically by E.J.H. Corner in 1954. Found in Malaysia and the Pacific islands, the mycelium of the fungus is bioluminescent.


Lignostilbene alphabeta-dioxygenase

In enzymology, a lignostilbene alphabeta-dioxygenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 1,2-bis(4-hydroxy-3-methoxyphenyl)ethylene and O2, whereas its product is vanillin.
This enzyme belongs to the family of oxidoreductases, specifically those acting on single donors with O2 as oxidant and incorporation of two atoms of oxygen into the substrate (oxygenases). The oxygen incorporated need not be derived from O2. The systematic name of this enzyme class is 1,2-bis(4-hydroxy-3-methoxyphenyl)ethylene:oxygen oxidoreductase (alphabeta-bond-cleaving). It employs one cofactor, iron.


Exelixis

Exelixis, Inc. is a genomics-based drug discovery company located in Alameda, California, and the producer of Cometriq, a treatment approved by the U.S. Food and Drug Administration (FDA) for medullary thyroid cancer with clinical activity in several other types of metastatic cancer.
History.
Exelixis was founded in 1994; the scientific founders were Spyridon Artavanis–Tsakonas, at Yale at that time, and Corey Goodman and Gerry Rubin who were then at the University of California, Berkeley. George Scangos joined the company as CEO in 1996. The business plan was to use model organisms (fruit flies, nematodes, and zebrafish) and functional genomics to identify pathways and biological targets that could be exploited in the fields of agriculture and medicine. It eventually set up a subsidiary, Exelixis Plant Sciences, for the agricultural work.
By 2000 it had left the radical exploratory phase behind and became focused on drug discovery and had a chemical library of 4 million compounds. The company went public that year, after withdrawing its offering the week before; it raised $118 million in a down market.
In 2002 the company signed a broad alliance with GSK to discover new drugs in the fields of cancer, inflammatory diseases, and vascular conditions; GSK paid it $30 million in cash, bought $14 million in stock at twice the market rate, and committed to providing Exelixis with $90 million in research funding; it also offered loan financing of up to $85 million.
By 2002 the company had limited its internal efforts to cancer, and had settled its strategy on discovering and developing drugs that could inhibit targeted small sets of tyrosine kinases that are needed for cancer formation, growth, and metastasis. The sets of TKs had been identified by means of its prior functional genomics work. This approach was controversial at the time; most companies try to selectively target just one protein in their discovery efforts.
In 2006 Exelixis partnered with Daiichi Sankyo on compounds that targeted mineralocorticoid receptors; esaxerenone was part of this collaboration. In 2007, the company partnered its MEK inhibitor program with Genentech; cobimetinib (at that time XL-518) was part of this collaboration. Exelixis had filed an IND on XL-518 prior to the partnership, committed to funding and running the Phase I trial, and retained rights to co-market it in the US.
In 2008 the company partnered its lead cancer drug candidate, XL-184 (which would become called cabozantinib) and another cancer candidate, XL-281, with Bristol Myers Squibb; BMS returned the rights to XL-184 to Exelixis in 2010 and returned the rights to other drug candidate in 2011.
In 2010 Scangos departed as CEO to take over at Biogen and the company appointed Michael M. Morrissey as President and CEO; Morrissey had joined the company in 2000 as Vice President of Discovery Research. At that time the company had eight drugs in clinical trials.
Exelixis' first drug approval came in 2012, when cabozantinib was approved for medullary thyroid cancer, an orphan indication. It was approved in Europe in 2014.
Exelixis invested heavily in exploring cabozantinib in other cancers, betting the future of the company on the drug. In 2014 the drug failed a Phase III trial in prostate cancer, and the company laid off 70% of its employees.
In 2015 Genentech and Exelixis won FDA approval for cobimetinib for certain forms of melanoma.
In March 2016 Exelixis licensed to Ipsen worldwide rights (outside the US, Canada, and Japan) to market cabozantinib.
In April 2016 the FDA granted approval for marketing the tablet formulation as a second line treatment for kidney cancer and the same was approved in Europe in October of that year.
In December 2017, the FDA granted approval for the use of cabozantinib for first line treatment of kidney cancer and in May 2018 approval for first-line treatment was approved in Europe.


Nuclear run-on

A nuclear run-on assay is conducted to identify the genes that are being transcribed at a certain time point. Approximately one million cell nuclei are isolated and incubated with labeled nucleotides, and genes in the process of being transcribed are detected by hybridization of extracted RNA to gene specific probes on a blot. Garcia-Martinez et al. (2004) developed a protocol for the yeast "S. cerevisiae" (Genomic run-on, GRO) that allows for the calculation of transcription rates (TRs) for all yeast genes to estimate mRNA stabilities for all yeast mRNAs.
Alternative microarray methods have recently been developed, mainly PolII RIP-chip: RNA immunoprecipitation of RNA polymerase II with phosphorylated C-terminal domain directed antibodies and hybridization on a microarray slide or chip (the word chip in the name stems from "ChIP-chip" where a special Affymetrix GeneChip was required). A comparison of methods based on run-on and ChIP-chip has been made in yeast (Pelechano et al., 2009). A general correspondence of both methods has been detected but GRO is more sensitive and quantitative. It has to be considered that run-on only detects elongating RNA polymerases whereas ChIP-chip detects all present RNA polymerases, including backtracked ones.
Attachment of new RNA polymerase to genes is prevented by inclusion of sarkosyl. Therefore only genes that already have an RNA polymerase will produce labeled transcripts. RNA transcripts that were synthesized before the addition of the label will not be detected as they will lack the label. These run on transcripts can also be detected by purifying labeled transcripts by using antibodies that detect the label and hybridizing these isolated transcripts with gene expression arrays or by next generation sequencing (GRO-Seq).
Run on assays have been largely supplanted with Global Run on assays that use next generation DNA sequencing as a readout platform. These assays are known as GRO-Seq and provide an incredibly detailed view of genes engaged in transcription with quantitative levels of expression. Array based methods for analyzing Global run on (GRO) assays are being replaced with Next Generation Sequencing which eliminates the design of probes against gene sequences. Sequencing will catalog all transcripts produced even if they are not reported in databases. GRO-seq involves the labeling of newly synthesized transcripts with bromouridine (BrU). Cells or nuclei are incubated with BrUTP in the presence of sarkosyl, which prevents the attachment of RNA polymerase to the DNA. Therefore only RNA polymerase that are already on the DNA before the addition of sarkosyl will produce new transcripts that will be labeled with BrU. The labeled transcripts are captured with anti-BrU antibody labeled beads, converted to cDNAs and then sequenced by Next Generation DNA sequencing. The sequencing reads are then aligned to the genome and number of reads per transcript provide an accurate estimate of the number of transcripts synthesized.


IOMAI

IOMAI was a Biotech company founded in 1997 by Gregory Glenn M.D. of the Walter Reed Army Institute of Research and Dean Lewis, a World Bank employee. The company was the first to develop the concept of transcutaneous immunization, delivery of vaccines to the skin using a patch or similar method. This provided a means to stimulate robust immune responses safely as the skin patch-based immunization targeted Langerhans cells in the skin. The patch technology underwent extensive evaluation in the context of a traveler's diarrhea vaccine which entered Phase 3 pivotal trials in 2009. IOMAI was acquired by Intercell in 2008 and the technology was the subject of a development license to GSK in 2009. Dr. Glenn pioneered needle free delivery to the skin and spawned general interest in skin-targeting vaccine technologies, including intradermal delivery and the use of the heat labile toxin as an adjuvant and the adjuvant patch.


Hydroxylamine reductase (NADH)

In enzymology, a hydroxylamine reductase (NADH) () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are NH3, NAD+, and H2O, whereas its 3 products are hydroxylamine, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is ammonium:NAD+ oxidoreductase. Other names in common use include hydroxylamine reductase, ammonium dehydrogenase, NADH-hydroxylamine reductase, N-hydroxy amine reductase, hydroxylamine reductase (NADH2), and NADH2:hydroxylamine oxidoreductase. This enzyme participates in nitrogen metabolism.


Nature Biotechnology

Nature Biotechnology is a peer reviewed scientific journal published monthly by the Nature Research. The chief editor is Andrew Marshall who is part of an in-house team of editors. The focus of the journal is biotechnology including research results and the commercial business sector of this field. Coverage includes the related biological, biomedical, agricultural and environmental sciences. Also of interest are the commercial, political, legal, and societal influences that affect this field.
The journal continues serial publication under the title "Bio/Technology", which had a publication period of 1983 to 1996.
Abstracting and indexing.
This journal is indexed in


MGM-5 Corporal

The MGM-5 Corporal missile was a nuclear-armed tactical surface-to-surface missile. It was the first guided weapon authorized by the United States to carry a nuclear warhead. A guided tactical ballistic missile, the Corporal could deliver either a nuclear fission, high-explosive, fragmentation or chemical warhead up to a range of .
It was developed by the United States Army in partnership with Caltech's pioneering Jet Propulsion Laboratory, and initially produced by Douglas Aircraft Company. As development continued production shifted to Firestone Tire and Rubber Company (airframe) and Gilfillan Brothers Inc. (guidance). The Corporal was designed as a tactical nuclear missile for use in the event of Cold War hostilities in Western Europe. The first U.S. Army Corporal battalion was deployed in Europe in 1955. Eight Corporal battalions were deployed in Europe and remained in the field until 1964, when the system was replaced by the solid-fueled MGM-29 Sergeant missile system. The Corporal was the third in a series of JPL rockets for the US Army whose names correspond to the progression in Army enlisted ranks, starting with Private before ultimately leading to the MGM-29 Sergeant.
Design and development.
The U.S. Army Ordnance California Institute Technology (ORDCIT) program that eventually produced the Corporal ballistic missile began in June 1944 with a contract to the Guggenheim Aeronautical Laboratories California Institute of Technology (GALCIT) to develop a ballistic guided missile. As the technology to build such a weapon did not exist in the United States it had to be created. GALCIT, later transformed into the Jet Propulsion Laboratory (JPL), began incremental efforts starting with a solid-fuel rocket program called Private. It progressed to a liquid-fuel unguided rocket called WAC Corporal, with a research missile variant (Corporal E) also under development. In late 1949 the Army desired to accelerate the Corporal program to create a military weapon by turning the Corporal E into a crash program. The resultant Corporal ballistic missile was developed by JPL and first flew in its weapon version at White Sands Missile Range, New Mexico, on August 7, 1952. The Corporal crash program involved utilizing as much existing equipment as it could including the WW II SCR-584 radar.
Corporal used a liquid-fueled rocket burning red fuming nitric acid (RFNA) and aniline; the exact mixture of fuel and oxidizer changed over the Corporal service period. From round 11 of the test program it became RFNA as oxidizer and a fuel consisting of 80% aniline with 20% furfuryl alcohol. As the Corporal was a crash program and constantly under development after 1958 to reduce decomposition of the RFNA and improve performance, the propellants were changed to IRFNA (inhibited red fuming nitric acid), 14% NO2, 2.5% H2O, 0.6% HF and 82.9% HNO3 oxidizer, with 46.5% aniline, 46.5% furfuryl alcohol and 7% hydrazine as fuel. this required elaborate and time-consuming preparation immediately before launch, making its tactical responsiveness questionable.
Guidance for the Corporal consisted of a complex system of internal and ground guidance. During the initial launch phase, inertial guidance kept the missile in a vertical position and pre-set guidance steered it during its launch. The ground guidance system was a modified World War II SCR-584 radar which tracked the missile's position, as well as its slant range. This information was sent to an analog computer which calculated the trajectory and any necessary correction to hit the target. A Doppler radar was used to accurately measure the missile's velocity, and this information was also used in the trajectory calculation. The Doppler radar was also used to send the final range correction and warhead arming command after the missile re-entered the atmosphere. Transponder beacons were used in the missile to provide a return signal for tracking at maximum range. The vulnerability of the Corporal system was of concern from the beginning of the weapon program. Electronic anticountermeasures were addressed over the length of the program and would have been greatly improved in Corporal III. Though a variety of warheads from high explosive and fragmentation to chemical had been developed the warhead which the missile was equipped was the W-7 (Mk.7).
A Corporal battalion was composed of 250 men requiring 35 vehicles to deploy and took nine hours to set up the missile to fire once the launch position had been reached. Corporal missile battalions in Europe were highly mobile, considering the large number of support vehicles and personnel required to support the transportation, checkout, and launch of this liquid-fueled nuclear-tipped (or conventional HE or chemical) missile. In Germany, frequent unannounced 'Alerts' were performed—necessitating assembling all personnel and moving vehicles and missiles to a pre-assigned assembly point. From there the battalion would move to a launch site—usually somewhere in a remote forest—set up the missile on its launcher and go through a detailed checkout of the various systems. This was not a trivial operation as these electronic systems were largely vacuum tubes. A mock firing would be performed and the entire battalion would be gone as soon as possible in order to not be a target of counter-battery fire. The deployment in the field during an Alert was amazingly swift due to the highly trained crews.
For what was the first nuclear armed missile the Corporal I was significantly unreliable and inaccurate. The continuing development of the Corporal weapon system led rapidly to the development of the Corporal II. This was initiated while the Corporal I was still under development. Though Corporal I was deemed operable many shortcomings in both the missile and ground equipment tactical usability had become obvious during development. Engineer-User trials had shown that the primary reason for mechanical and electrical causes arose because the systems of the Corporal I were too delicate. Problems detected in the E-U trials were addressed in the Corporal II. The Type II Corporal was subsequently improved in the Corporal IIa and IIb (M2A1) versions. The first Corporal II prototype was flown on October 8, 1953. The first complete Type II system was delivered in February 1955, The Type II Corporal greatly improved the accuracy and reliability of the missile system. When compared to other early missiles the final production Corporal II was reasonably accurate. Still the aggregate accuracy of all Type IIs with a CPE (Circular Probable Error) of 350 meters which was still short of the desired 300 meters. The role of JPL was greatly reduced in 1955–56.
The deficiencies of the Corporal II led to the design and development of Corporal III. The objectives of Corporal III were to produce a much improved weapon system with improved reliability, ground support equipment, and especially ground guidance equipment, to provide the Army with a fully developed weapon. Only small changes to the Corporal IIb missile would be required. In 1956 all research and development work on the Corporal II had been completed. A study at Redstone Arsenal noted that the MGM-29 Sergeant missile system would become available for service in 1963 and that Corporal III equipment should only be procured for additional Corporal units. Though a Type III Corporal was flown in 1957 it was too late for the eternally developing Corporal system. On May 23, 1957 all work on the Corporal III was ended to conserve fund for Sergeant following defense budget cuts. In 1963 the solid-fueled Sergeant missiles with self contained inertial guidance systems which was jamming proof, and which took only an hour from occupying the site to launch of the missile, started replacing the Corporal IIb in Europe. By June 1964 the Corporal system was history in American service. In June 1966 the last Corporal unit, the 27th Guided Weapons Regiment Royal Artillery, retired its Corporals.
Introduction to service.
The first three Corporal battalions were activated in March 1952 with an Engineer-User launch program beginning in January 1953. In the same year the Corporal II system was sold to the United Kingdom. The extremely ambitious original goal of the Corporal program was to have 16 battalions of missiles deployed by July 1954. Two batteries of Corporal I had been organized and equipped by July 1954. The 259th Corporal Battalion deployed to Europe in February 1955. It was followed by other units and by 1960 there were six battalions in Germany, two in Italy and four in the United States. Live-fire training for Germany-based US forces took place at Fort Bliss but later the British Royal Artillery Guided Weapons Range on the Scottish island of South Uist in the Outer Hebrides was used. Missiles were fired toward designated target coordinates in the Atlantic Ocean. Radar on Hirta (the main island of the St Kilda archipelago of Scotland) identified missile landing points. Frequently, Soviet spy ship 'fishing trawlers' would intrude into the target area. The UK adoption of the Corporal resulted in the islet of Rockall being incorporated into the United Kingdom in 1955, the last addition to the UK, to prevent its use by Soviet observers: the UK Minister of Defence Harold Macmillan was concerned that were they do to so, the Soviets might discover how to jam Corporal guidance and tracking radio signals.
Toys.
A version of the Corporal was made as a die-cast toy by manufacturers such as Corgi and Dinky. The Corgi Corporal, marketed to children as "the rocket you can launch", was timed to coincide with the British test firing in 1959.
A 1/40 scale plastic model kit of the Corporal missile with its mobile transporter was produced in the late 1950s and was reissued by Revell-Monogram in 2009.
A 1/48 scale plastic model kit of the Corporal missile with its launcher was produced in 1959 by Hawk and was reissued in 1969 in a glow in the dark version.


Witton Isolation Hospital

Witton Isolation Hospital was a facility for the treatment and quarantine of smallpox victims and their contacts in Birmingham, England, from 1894 to 1966.
History.
Operation.
Built in 1894, Witton Isolation Hospital was initially in a semi-rural district but by the 1930s the site was surrounded by the newly built Kingstanding and Perry Common social housing developments. It occupied the site now enclosed by College Road, Brackenbury Road and Plumstead Road.
Witton Isolation Hospital was used sporadically during the 20th century including the outbreak of smallpox that occurred in the city in 1962. The last cases quarantined there were during January and February 1966, following an outbreak that originated at the University of Birmingham Medical School. Witton Isolation Hospital was eventually superseded by the UK's first National Isolation Hospital, established at nearby Catherine-de-Barnes in 1966.
On 4 May 1966, the last patient was discharged.
During its life as a first-line smallpox hospital Witton had a resident caretaker, but on 2 May 1966 the caretaker resigned. His departure left the facility of ten buildings unguarded, except for the ten feet high perimeter wall. In the middle of 1966, local children broke in, causing some vandalism.
Disposal.
Burning of the building.
After the incident involving children breaking into Witton Isolation Hospital in mid-1966, Birmingham's Chief Medical Officer, Ernest Millar, was contacted by a local resident who had regularly seen the children from the top seats of a double-decker bus.
Dr Millar eventually ordered the facility to be destroyed by fire and on 3 May 1967 – chosen because the wind was blowing from the south, away from the city centre – the buildings were set ablaze by firemen of the Birmingham Fire and Ambulance Service, under the supervision of William Nicholls, Deputy Chief Medical Officer, and George Merrill, Deputy Chief Fire Officer, accompanied by representatives of the news media. All personnel involved in the operation had to wear protective clothing and be inoculated. Four tons of flammable material, including kerosene, waste oil and aluminium powder accelerants, were needed to burn the buildings, which were then empty. All windows were kept open to assist the fire spreading. A virologist from the UK government microbiology laboratories at Porton Down (then part of the Ministry of Defence), was asked to conduct tests to assess the efficiency of the conflagration.
Political aftermath.
The affair was discussed in Parliament. Harold Gurden, Member of Parliament for the Selly Oak constituency in Birmingham, asked the Parliamentary Secretary to the Ministry of Health, Julian Snow, how such a danger could have occurred in "a densely populated area", why the local residents had not been informed, whether the facility was going to be replaced and what evidence there was of the destruction of any remaining sources of smallpox virus by the fire.
In his reply, Julian Snow said:
Later history of the site.
In October 1967 an application to redevelop the site for housing was made to the Birmingham City Council, which was approved by the Council in February 1968.


Papuamide

Papuamides A and B are depsipeptides which appear to protect T cells from HIV. They were isolated from the sponge Theonella, and are part of a larger group of structurally similar depsipeptides—also isolated from sponges—including neamphamide A, callipeltin A, and mirabamides A-D.


Bifidus factor

A bifidus factor (bifidogenic factor) is a compound that specifically enhances the growth of bifidobacteria in either a product or in the intestines of humans and/or animals. Several products have been marketed as bifidogenic factors, such as several prebiotics and methyl-N-acetyl D-glucosamine in human milk.
Background.
Originally, fructose-based carbohydrates inulin and fructooligosaccharides, showed a strong selective stimulation of bifidobacteria so a ‘prebiotic effect’ was considered the same as a ‘bifidogenic effect.
Breast milk.
Human breast milk contains unique and highly diverse human milk oligosaccharides. These oligosaccharides are considered to be a "Bifidus Factor" because they form highly desired intestinal bacteria; it is for this reason that baby formula contains added oligosaccharides in order to help build a child's immune system. Studies showed that infants, who were bottled fed, lacked intestinal colonization of bifidobacteria. This lack of bacteria made the babies susceptible to other infectious bacteria and ailments. The infants who were breast fed had higher concentration of the bacteria and their vulnerability too infections was significantly lower. Breast milk had high amounts of oligosaccharides. As, a result, oligosaccharides were added to milk formula. This method worked and the colonization of bifidobacteria leveled. This suggested that the oligosaccharides found in human milk were candidates for the bifidus factor.
Composition and function.
The bifidus factor might be lacto-N-biose I [LNB], which is a derivative of mucin sugars. However, the exact structure and mechanism behind the bifidus factor remains unknown.
The bacteria would break down lactic acid and acetic acid. The environment of the intestine would become acidic, preventing the growth of any harmful pathogens. The function of LBN is unknown and it is possible that oligosaccharides with terminals of Galβ1-3GlcNAc are the bifidus factors.
Bifidobacteria might suppress infections in infants and children.


Ecopipam

Ecopipam (development codes SCH-39166, EBS-101, and PSYRX-101) is an experimental drug that acts as a selective dopamine D1/D5 receptor antagonist, with little affinity for either dopamine D2-like or 5-HT2 receptors.
Clinical trials.
Based on its profile in animal models, ecopipam was first studied as a treatment for schizophrenia but showed no efficacy. Side effects including sedation, restlessness, vomiting, and anxiety were generally rated mild. There were no reports of Parkinsonian-like extrapyramidal symptoms typically seen with D2 antagonists.
Human clinical studies also showed that ecopipam was an effective antagonist of the acute euphoric effects of cocaine. However, the effect did not persist following repeated administration.
Researchers have postulated that dopamine via D1 receptors in the mesolimbic system is involved with rewarded behaviors and pleasure. One such behavior is eating, and ecopipam has been shown in a large clinical study to be an effective treatment for obesity. However, reports of mild-to-moderate, reversible anxiety and depression made it unsuitable for commercialization as an anti-obesity drug, and its development was stopped for that indication.
As of 2021, Emalex Bioscineces is investigating its potential use for central nervous system disorders. Open-label studies have found ecopipam to reduce gambling behaviors in subjects with pathological gambling and to decrease the motor and vocal tics in adults with Tourette syndrome. A subsequent double-blind placebo-controlled study in pediatric subjects confirmed ecopipam's ability to ameliorate the motor and vocal symptoms seen in patients with Tourette's syndrome. Ecopipam is currently in a phase 2/3 clinical trial for the treatment of Tourette's syndrome in children ages 7 to 17.
Ecopipam is additionally under development for the treatment of Lesch–Nyhan syndrome (phase 3) and restless legs syndrome (phase 1/2).
Chemistry.
Chemically, ecopipam is a synthetic benzazepine derivative. It can be synthesized from a simple tetralin derivative:


Cytochrome c nitrite reductase

Cytochrome "c" nitrite reductase (ccNiR) () is a bacterial enzyme that catalyzes the six electron reduction of nitrite to ammonia; an important step in the biological nitrogen cycle. The enzyme catalyses the second step in the two step conversion of nitrate to ammonia, which allows certain bacteria to use nitrite as a terminal electron acceptor, rather than oxygen, during anaerobic conditions. During this process, ccNiR draws electrons from the quinol pool, which are ultimately provided by a dehydrogenase such as formate dehydrogenase or hydrogenase. These dehydrogenases are responsible for generating a proton motive force.
Cytochrome "c" Nitrite Reductase is a homodimer which contains five c-type heme cofactors per monomer. Four of the heme centers are bis-histidine ligated and presumably serve to shuttle electrons to the active site. The active site heme, however, is uniquely ligated by a single lysine residue.
This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with a cytochrome as acceptor. The systematic name of this enzyme class is ammonia:ferricytochrome-c oxidoreductase.


Hear the Silence

Hear the Silence is a 2003 semi-fictional TV drama based around the discredited idea of a potential link between the MMR vaccine and autism. By then, a contentious issue, the supposed connection originated in a paper by Andrew Wakefield published in 1998. The film debuted on 15 December 2003 at 9 pm on the British network Five. Produced on a budget of £1 million, it stars Hugh Bonneville as Wakefield and Juliet Stevenson as Christine Shields, a fictional mother who discovers the possible MMR-autism link when her son is diagnosed as autistic.
Synopsis.
Christine Shields (Stevenson), who works in a senior capacity for a bank, begins informing a series of doctors that her son appeared to develop autism soon after he received the MMR vaccine, but she receives no sympathy from them, her boss, or even her husband. However, this all changes when she meets Dr. Wakefield (Bonneville), who shares her opinion of the MMR vaccine causing her son's autism. Shields is highly relieved at finding someone who believes her.
At the press conference at which Wakefield announces his research findings, mysterious figures are shown already plotting. Fictional government officials want to achieve Wakefield's "demise", which they intend to bring about by portraying his research as flawed. Although never demonstrated as being based on fact, the film depicts Wakefield being targeted by the government: his phone is tapped and his files are stolen.
Cast.
(in credits order)
Reception.
"Hear the Silence", according to unofficial overnight figures, attracted 1.2 million viewers on its first screening with a 6 percent audience share; Channel Five's films debuting at 9 pm often gained audiences of more than 2 million viewers at the time. Mark Lawson in "The Guardian" wrote that Tim Fywell's direction "ensures that the piece, from its shivery beginnings onwards, has a flu-like hold on the viewer" and is "a fine piece of drama". "The Times" science writer Anjana Ahuja believed there were reasons to praise the drama as it contained a "powerful portrayal of autism, parental frustration and marital strains", despite its serious flaws. It was "deceitful, unbalanced and irresponsible", according to Mark Henderson in "The Times", but also "slick, gripping and professional" and Juliet Stevenson gave an "outstanding" performance.
Otherwise the film was received negatively, with critics arguing that it portrayed the purported MMR-autism link in a mistakenly sympathetic light as scientific evidence supporting the connection was lacking. It was said to idealize Wakefield and vilify the physicians who dismissed the vaccine-autism link by depicting them as "blatant caricatures" ("British Medical Journal"). Jon Joseph in "The Times" wrote "there are definitely no shades of grey" with Wakefield's assertions treated as if they are "a law of nature, like gravity". Of the supposed plot presumed to originate with the drug companies as a means to discredit Wakefield, Ben Goldacre wrote in "The Guardian" of its utter implausibility as the patent on the MMR vaccine had lapsed, it was now generic and no longer highly profitable.
Goldacre wrote that while the film was "moving and convincing" as a drama, it was factually inaccurate: "The only things that the writers of "Hear the Silence" get wrong, to be fair, are the science and the story." In addition, David Aaronovitch wrote that while the film begins by saying that it is a "dramatised account of the work of Dr Andrew Wakefield and his colleagues at the Royal Free Hospital in the late 1990s," the statement is not accurate. Aaronovitch commented: "Wakefield's own history is distorted, as are the opinions of his colleagues. No scientist is permitted to put a contrary case to that of the hero, though the vast majority of them believe he is wrong". Many years later, after Wakefield's paper had been discredited Aaronovitch described the drama as being "a piece of the purest propaganda".
An open letter from 11 leading British doctors working in paediatrics condemned the film, calling it "distorted" and "entirely unbalanced." One of the letter's signatories, Great Ormond Street Hospital paediatrician David Elliman, also called the film "overly sentimental" and "potentially dangerous".
Aftermath.
The discussion programme about the MMR-autism link following the film was a requirement of the broadcasting regulator's impartiality rules. Multiple doctors opposing Wakefield were invited to participate, but boycotted it on the grounds that they considered the film misleading. One of these doctors (David Salisbury, director of the British National Immunization Program) justified his decision to do so by saying that if he and his public health colleagues had appeared as the broadcasters had requested, "We felt we'd be giving respectability to a program that was not respectable." David Henderson in "The Times" thought the eventual discussion was "unreasonably weighted in Wakefield’s favour" and "no antidote to the two hours of emotional blackmail that preceded it". One of the participants in the programme, Anjana Ahuja, felt those questioning his research were in the minority and she regretted the decision of those doctors who had declined to appear. Ahuja described the discussion, hosted by Kirsty Young, as being "ill tempered".
In 2008, responding to the criticism she had received at the time of the broadcast, Stevenson commented in a "Daily Telegraph" interview: "Perhaps it was naive of me to think you could put out a film like that" and "I thought it was generating an interesting debate and that it gave a voice to those who needed a voice - parents who were told they didn't know anything."


Nocardioides alpinus

Nocardioides alpinus is a gram-positive, rod-shaped, psychrophilic and non-motile bacterium from the genus "Nocardioides" that has been isolated from cryoconite of an alpine glacier in the Ötztal Alps in Austria.


ASM-N-5 Gorgon V

The ASM-N-5 Gorgon V was an unpowered air-to-surface missile, developed by the Glenn L. Martin Company during the early 1950s for use by the United States Navy as a chemical weapon delivery vehicle. Developed from the earlier PTV-N-2 Gorgon IV test vehicle, the program was cancelled without any Gorgon Vs seeing service.
Design and development.
The Gorgon V project was begun in 1950 to develop an air-to-surface missile capable of dispersing chemical warfare agents over a combat area. Designing of the missile was contracted to the Glenn L. Martin Company, which used the company's earlier PTV-N-2 Gorgon IV ramjet test missile as a basis for the weapon's design. The Gorgon V was to be a long slender missile, with swept wings and conventional tail. The Gorgon IV's ramjet engine, slung beneath the missile's tail, was replaced in the Gorgon V with a X14A aerosol generator, developed by the Edo Aircraft Corporation.
Operational use of the Gorgon V was intended to be based on two missiles being carried by a launching aircraft. These would be released at an altitude of . The Gorgon V would be piloted by autopilot in a high-subsonic dive. Upon reaching an altitude of or less, as measured by a radar altimeter, the aerosol generator would be activated, dispersing chemical agent over an area of up to by .
Development of the Gorgon V continued throughout the Korean War. In 1953 it was projected that the weapon would be ready for operational service by 1955. Later that year, the Gorgon V was cancelled by the US Navy. It is unknown if any prototypes were constructed before the termination of the project.


Rory A. Cooper

Rory A. Cooper is an American bioengineer who currently serves as FISA/PVA Distinguished Professor, Past Chair, in the Department of Rehabilitation Science and Technology and professor of bioengineering, physical medicine and rehabilitation, and orthopedic surgery at the University of Pittsburgh. He is also assistant vice chancellor for research for STEM and Health Sciences Collaboration. He holds an adjunct faculty position at the Robotics Institute of Carnegie Mellon University, and is an invited professor at Xi'an Jiaotong University in Xi'an, China.
He is the founder and director of the Human Engineering Research Laboratories.
Early life.
In December 1972, Cooper became an Eagle Scout (Boy Scouts of America). He was profiled in the Winter 2019 issue of Eagles' Call magazine.
Cooper enlisted in the United States Army in 1976 and was assigned to the 3rd Ordnance Battalion, 32nd Air Defense Artillery Command with U.S. Army Europe and was later attached to the 5th Signal Command, USAREUR, and the U.S. Military Community Activity Worms, 21st Support Command.
While stationed in Germany in 1980, he was hit by a bus while riding a bicycle. As a result, he became paralyzed from the waist down.
Cooper received a B.S. degree in electrical engineering from California Polytechnic State University, San Luis Obispo in 1985 and an electrical engineering M.Eng. from Cal Poly in 1986. He received the Ph.D. degree in electrical and computer engineering with a concentration in bioengineering from University of California at Santa Barbara in 1989.
Career.
From 1989 to 1994, Cooper was an assistant professor in bioengineering at Sacramento State University. In 1994, Cooper became an associate professor at the Department of Rehabilitation Science and Technology in the School of Health and Rehabilitation Sciences at the University of Pittsburgh (obtaining full professorship in 1998). Also in 1994, he founded the Human Engineering Research Laboratories, which includes the VA Center for Wheelchairs and Associated Rehabilitation Engineering. He served as chair of the Department of Rehabilitation Science and Technology at the University of Pittsburgh from 1997 to 2018.
He is also a senior research career scientist with the United States Department of Veterans Affairs.
Cooper has published almost 300 peer-reviewed journal articles. He is the author of "Rehabilitation Engineering Applied to Mobility and Manipulation" and "Wheelchair Selection and Configuration" and co-edited "An Introduction to Rehabilitation Engineering", "Care of the Combat Amputee", "Warrior Transition Leader: Medical Rehabilitation Handbook"., and "Promoting Successful Reintegration".
Cooper has been a National Academies of Sciences Distinctive Voices Lecturer, ACC Distinguished Lecturer, Smithsonian Institution American Disabilities Act 25th Anniversary Festival Speaker, Young Lecturer at the Royal Military College of Canada, and inaugural American Association for the Advancement of Science-Lemelson Foundation Invention Ambassador. He has also been elected to Eta Kappa Nu, Tau Beta Pi, and Sigma Xi honorary societies. Cooper is a former president of RESNA, and a member of the IEEE-EMBS Medical Device Standards Committee. Additionally, he has been a member of the U.S. Centers for Medicare and Medicaid Services – Medicare Advisory Committee, U.S. Secretary of Veterans Affairs Prosthetics and Special Disability Programs Advisory Committee, chair of the National Advisory Board on Medical Rehabilitation Research, National Institute of Child Health & Human Development, U.S. Department of Defense Health Board Subcommittee on Amputation and Orthopedics, board of directors of Easter Seals, National Academy of Medicine Committee on Assistive Products and Devices, and National Academy of Sciences Keck Foundation Initiative on Human Health Span Steering Committee.
He is the director of the Paralyzed Veterans of America Research Foundation, and currently serves as a member of the Honorary Board of Advisors of the Student Veterans of America, chair of the honorary board of advisors of the Disabled Veterans National Foundation, National Science Foundation Advisory Committee for Education and Human Resources, Command Council of the Staff Sergeant Donnie D. Dixon Center for Military and Veterans Community Services, and World Health Organization GATE Committee.
In 2014, Secretary of the Army John M. McHugh appointed Cooper a civilian aide to the Secretary of the Army.
Inventions and patents.
Cooper holds 25 patents in wheelchair technology. He is the inventor of many advanced mobility devices and assistive technologies. Among these are MEBot, a stair-climbing wheelchair; PneuChair, a wheelchair powered entirely by compressed air; and Virtual Seating Coach, a smartphone app to control power wheelchair seating systems.
The July 26, 2010 issue of "Popular Science" profiled Cooper, and a photo of him with a robotic wheelchair he invented was the issue's centerfold. Cooper and his inventions were also the cover story of the May 2017 issue of "New Mobility". Additionally, Cooper was featured as the cover story of the September 2019 issue of "Inventors Digest."
Cooper is an advocate for diversity within the invention community and in 2020 spoke to the U.S. Congress about American inventors' lack of diversity.
Athletics.
At the 1988 Paralympic Games in Seoul, South Korea, Cooper received a bronze medal in the 4x400-meter wheelchair relay.
Cooper was on the steering committee for the 1996 Paralympic Scientific Congress held in Atlanta, GA, and was the Sports Scientist for the 2008 U.S. Paralympic Team in Beijing, China. He also received the 2013 International Paralympic Scientific Achievement Award. He volunteered his expertise as a member of the US Paralympic staff in 1992, 1996, and 2008.
Cooper served as the chair of the Local Organizing Committee for the National Veterans Wheelchair Games held in Pittsburgh, Pennsylvania in 1998 and 2011.
Cooper has been a competitor in the National Veterans Wheelchair Game since 1983 winning over 200 medals in total in such sports a slalom, track, swimming, table-tennis, and hand-cycle.
At the 32nd National Veterans Wheelchair Games concluded on June 30, 2012, Richmond, Virginia, Cooper earned 5 gold medals in swimming.
Cooper is an accomplished handcyclist and competes annually in the Pittsburgh Marathon.
Recognition and awards.
Cooper is an elected Fellow of the National Academy of Inventors, the American Association for the Advancement of Science, the Rehabilitation Engineering and Assistive Technology Society of North America, the Institute of Electrical and Electronics Engineers, the American Institute for Medical and Biological Engineering, and the Biomedical Engineering Society.
Cooper has received many honors; among the most recent are a 2017 Fellowship in the American Association for the Advancement of Science for engineering, recipient of one of the 2017 Samuel J. Heyman Service to America Medals, recognition as a "Health Hero" in Oprah Magazine, and the 2016 Marlin Mickle Outstanding Innovator Award.
Other awards Cooper has received include the Secretary of Defense Meritorious Civilian Service Medal, National Guard Bureau Minute Man Award, AAAS Mentor Award, Joseph F. Engelberger Award, AIMBE Advocacy Award, Herny Viscardi Achievement Award, U.S. Army Distinguished Civilian Service Medal, U.S. Department of Veterans Affairs Diversity and Inclusion Excellence Award, Olin E. Teague Award, membership in the Pennsylvania Military and Veteran Hall of Fame, Order of Military Medical Merit, Order of Mercury, Order of Saint Maurice, Chapel of Four Chaplains Legion of Honor, DaVinci Lifetime Achievement Award, and the inaugural class of the Spinal Cord Injury Hall of Fame.
In 2009, Cooper was featured on a special edition Cheerios cereal box to celebrate his accomplishments.
In appreciation of his work and accomplishments, the Pittsburgh City Council proclaimed June 17, 2014, as "Dr. Rory A. Cooper Day."
In 2019, the United States Patent and Trademark Office added Cooper to the Inventor Collectible Card Series.
Cooper, on his handcycle, appeared in the center of the October/November 2020 issue of AARP Magazine.


Columbamine oxidase

In enzymology, a columbamine oxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are columbamine and O2, whereas its two products are berberine and H2O.
This enzyme belongs to the family of oxidoreductases, specifically those acting on X-H and Y-H to form an X-Y bond with oxygen as acceptor. The systematic name of this enzyme class is columbamine:oxygen oxidoreductase (cyclizing). This enzyme is also called berberine synthase. This enzyme participates in alkaloid biosynthesis i. It employs one cofactor, iron.


Katherine Jones (academic)

Katherine A. Jones is a professor of regulatory biology and the Edwin K. Hunter Chair at the Salk Institute for Biological Studies. She uses proteomics to study transcription elongation and molecular biology to understand protein coordination. Jones identified elongation factors, a class of proteins which are important in viral gene expression.
Early life and education.
Jones earned her PhD in biochemistry at the University of California, Riverside. She was made a Pew Scholar in 1987. Her Pew Foundation fellowship allowed her to study the transcription mechanisms that are responsible for rapid induction in mammalian genes. Jones showed how the RNA polymerase II transcription factor Sp1 binds to DNA and activates RNA.
Research and career.
Jones is a professor of regulatory biology and Edwin K. Hunter Chair at the Salk Institute for Biological Studies. Jones holds an adjunct position at University of California, San Diego. She has worked extensively on understanding the Human Immunodeficiency Virus (HIV). She investigated several proteins that interact with HIV-Tat (Tat). Tat is a protein created by HIV, which has been described as an "engine for HIV replication". Jones identified several proteins (including Cyclin T1, CycT1, and SSu72) that are required for HIV gene expression. SSu72 is a phosphatase that binds to Tat and speeds up the transcription process that replicates the virus. Unfortunately, CycT1 is needed for normal cell function, so is not an ideal target for antivirals.
Jones looks to create small molecule inhibitors that restrict these proteins. She identified that the small molecule JIB-04 is particularly effective in destroying Tat. She used DIFFpop to identify the protein targets of JIB-04. DIFFpop revealed that JIB-04 decreases the levels of Tat because it binds together two enzymes in the host cell, SHMT2 and BRCC36, which subsequently enable the cells to destroy Tat. At present JIB-04 is too toxic to primary T-cells, but Jones and colleagues are working on investigations of other small molecules that can still inhibit Tat expression.
Jones demonstrated that in colon cancer, the mutated adenomatous polyposis coli (APC) regulates the expression of genes which control cancer growth. She demonstrated that APC cannot turn off growth control genes as it cannot bind to a protein that presents metastasis. She has gone on to show that transcription elongation is involved with the differentiation of stem cells. It is well known that wnt and activin pathways are needed for stem cell growth, but it was unclear how they work together. Jones showed how they work together to activate transcription. She also demonstrated that activation of the wnt signaling pathway can result in colon cancer. During their investigations of embryonic stem cells, Jones identified a third pathway, YAP, which slows the activin pathway and stops stem cells from specialising. She used CRISPR-cas9 to remove the genes that make the YAP protein, reducing the number of steps to convert embryonic stem cells into functional heart cells.
She has also studied the CDK12 gene, which is mutated in 3 - 5% of prostate, ovarian and breast cancers. The majority of cancers that contain a mutated CDK12 gene are not responsive to immunotherapy, so creating inhibitors of CDK12 could make cancers more treatable. When CDK12 is inhibited cells cannot repair DNA and the cells are more likely to die during chemotherapy.
In 2017 Jones filed a lawsuit against the Salk Institute for Biological Studies for gender discrimination, citing that their work had not been recognised their labs were small and they received less funding. She claimed that imagery of women faculty members was used in Salk Institute promotional material to secure funding from donors. Jones settled her case in August 2018.