Active transport

In cellular biology, active transport is the movement of molecules across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellular energy to achieve this movement. There are two types of active transport: primary active transport that uses adenosine triphosphate (ATP), and secondary active transport that uses an electrochemical gradient.
Active cellular transportation (ACT).
Unlike passive transport, which uses the kinetic energy and natural entropy of molecules moving down a gradient, active transport uses cellular energy to move them against a gradient, polar repulsion, or other resistance. Active transport is usually associated with accumulating high concentrations of molecules that the cell needs, such as ions, glucose and amino acids. Examples of active transport include the uptake of glucose in the intestines in humans and the uptake of mineral ions into root hair cells of plants.
History.
In 1848, the German physiologist Emil du Bois-Reymond suggested the possibility of active transport of substances across membranes.
Rosenberg (1948) formulated the concept of active transport based on energetic considerations, but later it would be redefined.
In 1997, Jens Christian Skou, a Danish physician received the Nobel Prize in Chemistry for his research regarding the sodium-potassium pump.
One category of cotransporters that is especially prominent in research regarding diabetes treatment is sodium-glucose cotransporters. These transporters were discovered by scientists at the National Health Institute. These scientists had noticed a discrepancy in the absorption of glucose at different points in the kidney tubule of a rat. The gene was then discovered for intestinal glucose transport protein and linked to these membrane sodium glucose cotransport systems. The first of these membrane transport proteins was named SGLT1 followed by the discovery of SGLT2. Robert Krane also played a prominent role in this field.
Background.
Specialized transmembrane proteins recognize the substance and allow it to move across the membrane when it otherwise would not, either because the phospholipid bilayer of the membrane is impermeable to the substance moved or because the substance is moved against the direction of its concentration gradient. There are two forms of active transport, primary active transport and secondary active transport. In primary active transport, the proteins involved are pumps that normally use chemical energy in the form of ATP. Secondary active transport, however, makes use of potential energy, which is usually derived through exploitation of an electrochemical gradient. The energy created from one ion moving down its electrochemical gradient is used to power the transport of another ion moving against its electrochemical gradient. This involves pore-forming proteins that form channels across the cell membrane. The difference between passive transport and active transport is that the active transport requires energy, and moves substances against their respective concentration gradient, whereas passive transport requires no cellular energy and moves substances in the direction of their respective concentration gradient.
In an antiporter, one substrate is transported in one direction across the membrane while another is cotransported in the opposite direction. In a symporter, two substrates are transported in the same direction across the membrane. Antiport and symport processes are associated with secondary active transport, meaning that one of the two substances is transported against its concentration gradient, utilizing the energy derived from the transport of another ion (mostly Na, K or H ions) down its concentration gradient.
If substrate molecules are moving from areas of lower concentration to areas of higher concentration (i.e., in the opposite direction as, or "against" the concentration gradient), specific transmembrane carrier proteins are required. These proteins have receptors that bind to specific molecules (e.g., glucose) and transport them across the cell membrane. Because energy is required in this process, it is known as 'active' transport. Examples of active transport include the transportation of sodium out of the cell and potassium into the cell by the sodium-potassium pump. Active transport often takes place in the internal lining of the small intestine.
Plants need to absorb mineral salts from the soil or other sources, but these salts exist in very dilute solution. Active transport enables these cells to take up salts from this dilute solution against the direction of the concentration gradient. For example, chloride (Cl−) and nitrate (NO3−) ions exist in the cytosol of plant cells, and need to be transported into the vacuole. While the vacuole has channels for these ions, transportation of them is against the concentration gradient, and thus movement of these ions is driven by hydrogen pumps, or proton pumps.
Primary active transport.
Primary active transport, also called direct active transport, directly uses metabolic energy to transport molecules across a membrane. Substances that are transported across the cell membrane by primary active transport include metal ions, such as Na+, K+, Mg2+, and Ca2+. These charged particles require ion pumps or ion channels to cross membranes and distribute through the body.
Most of the enzymes that perform this type of transport are transmembrane ATPases. A primary ATPase universal to all animal life is the sodium-potassium pump, which helps to maintain the cell potential. The sodium-potassium pump maintains the membrane potential by moving three Na+ ions out of the cell for every two K+ ions moved into the cell. Other sources of energy for primary active transport are redox energy and photon energy (light). An example of primary active transport using redox energy is the mitochondrial electron transport chain that uses the reduction energy of NADH to move protons across the inner mitochondrial membrane against their concentration gradient. An example of primary active transport using light energy are the proteins involved in photosynthesis that use the energy of photons to create a proton gradient across the thylakoid membrane and also to create reduction power in the form of NADPH.
Model of active transport.
ATP hydrolysis is used to transport hydrogen ions against the electrochemical gradient (from low to high hydrogen ion concentration). Phosphorylation of the carrier protein and the binding of a hydrogen ion induce a conformational (shape) change that drives the hydrogen ions to transport against the electrochemical gradient. Hydrolysis of the bound phosphate group and release of hydrogen ion then restores the carrier to its original conformation.
Types of primary active transporters.
Adenosine triphosphate-binding cassette transporters (ABC transporters) comprise a large and diverse protein family, often functioning as ATP-driven pumps. Usually, there are several domains involved in the overall transporter protein's structure, including two nucleotide-binding domains that constitute the ATP-binding motif and two hydrophobic transmembrane domains that create the "pore" component. In broad terms, ABC transporters are involved in the import or export of molecules across a cell membrane; yet within the protein family there is an extensive range of function.
In plants, ABC transporters are often found within cell and organelle membranes, such as the mitochondria, chloroplast, and plasma membrane. There is evidence to support that plant ABC transporters play a direct role in pathogen response, phytohormone transport, and detoxification. Furthermore, certain plant ABC transporters may function in actively exporting volatile compounds and antimicrobial metabolites.
In petunia flowers ("Petunia hybrida"), the ABC transporter PhABCG1 is involved in the active transport of volatile organic compounds. PhABCG1 is expressed in the petals of open flowers. In general, volatile compounds may promote the attraction of seed-dispersal organisms and pollinators, as well as aid in defense, signaling, allelopathy, and protection. To study the protein PhABCG1, transgenic petunia RNA interference lines were created with decreased "PhABCG1" expression levels. In these transgenic lines, a decrease in emission of volatile compounds was observed. Thus, PhABCG1 is likely involved in the export of volatile compounds. Subsequent experiments involved incubating control and transgenic lines that expressed "PhABCG1" to test for transport activity involving different substrates. Ultimately, PhABCG1 is responsible for the protein-mediated transport of volatile organic compounds, such as benezyl alcohol and methylbenzoate, across the plasma membrane.
Additionally in plants, ABC transporters may be involved in the transport of cellular metabolites. Pleiotropic Drug Resistance ABC transporters are hypothesized to be involved in stress response and export antimicrobial metabolites. One example of this type of ABC transporter is the protein NtPDR1. This unique ABC transporter is found in "Nicotiana tabacum" BY2 cells and is expressed in the presence of microbial elicitors. NtPDR1 is localized in the root epidermis and aerial trichomes of the plant. Experiments using antibodies specifically targeting NtPDR1 followed by Western blotting allowed for this determination of localization. Furthermore, it is likely that the protein NtPDR1 actively transports out antimicrobial diterpene molecules, which are toxic to the cell at high levels.
Secondary active transport.
In secondary active transport, also known as "coupled transport" or "cotransport", energy is used to transport molecules across a membrane; however, in contrast to primary active transport, there is no direct coupling of ATP. Instead, it relies upon the electrochemical potential difference created by pumping ions in/out of the cell. Permitting one ion or molecule to move down an electrochemical gradient, but possibly against the concentration gradient where it is more concentrated to that where it is less concentrated, increases entropy and can serve as a source of energy for metabolism (e.g. in ATP synthase). The energy derived from the pumping of protons across a cell membrane is frequently used as the energy source in secondary active transport. In humans, sodium (Na+) is a commonly cotransported ion across the plasma membrane, whose electrochemical gradient is then used to power the active transport of a second ion or molecule against its gradient. In bacteria and small yeast cells, a commonly cotransported ion is hydrogen. Hydrogen pumps are also used to create an electrochemical gradient to carry out processes within cells such as in the electron transport chain, an important function of cellular respiration that happens in the mitochondrion of the cell.
In August 1960, in Prague, Robert K. Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption. Crane's discovery of cotransport was the first ever proposal of flux coupling in biology.
Cotransporters can be classified as symporters and antiporters depending on whether the substances move in the same or opposite directions.
Antiporter.
In an antiporter two species of ion or other solutes are pumped in opposite directions across a membrane. One of these species is allowed to flow from high to low concentration which yields the entropic energy to drive the transport of the other solute from a low concentration region to a high one.
An example is the sodium-calcium exchanger or antiporter, which allows three sodium ions into the cell to transport one calcium out. This antiporter mechanism is important within the membranes of cardiac muscle cells in order to keep the calcium concentration in the cytoplasm low. Many cells also possess calcium ATPases, which can operate at lower intracellular concentrations of calcium and sets the normal or resting concentration of this important second messenger. But the ATPase exports calcium ions more slowly: only 30 per second versus 2000 per second by the exchanger. The exchanger comes into service when the calcium concentration rises steeply or "spikes" and enables rapid recovery. This shows that a single type of ion can be transported by several enzymes, which need not be active all the time (constitutively), but may exist to meet specific, intermittent needs.
Symporter.
A symporter uses the downhill movement of one solute species from high to low concentration to move another molecule uphill from low concentration to high concentration (against its concentration gradient). Both molecules are transported in the same direction.
An example is the glucose symporter SGLT1, which co-transports one glucose (or galactose) molecule into the cell for every two sodium ions it imports into the cell. This symporter is located in the small intestines, heart, and brain. It is also located in the S3 segment of the proximal tubule in each nephron in the kidneys. Its mechanism is exploited in glucose rehydration therapy This mechanism uses the absorption of sugar through the walls of the intestine to pull water in along with it. Defects in SGLT2 prevent effective reabsorption of glucose, causing familial renal glucosuria.
Bulk transport.
Endocytosis and exocytosis are both forms of bulk transport that move materials into and out of cells, respectively, via vesicles. In the case of endocytosis, the cellular membrane folds around the desired materials outside the cell. The ingested particle becomes trapped within a pouch, known as a vesicle, inside the cytoplasm. Often enzymes from lysosomes are then used to digest the molecules absorbed by this process. Substances that enter the cell via signal mediated electrolysis include proteins, hormones and growth and stabilization factors. Viruses enter cells through a form of endocytosis that involves their outer membrane fusing with the membrane of the cell. This forces the viral DNA into the host cell.
Biologists distinguish two main types of endocytosis: pinocytosis and phagocytosis.
Exocytosis involves the removal of substances through the fusion of the outer cell membrane and a vesicle membrane. An example of exocytosis would be the transmission of neurotransmitters across a synapse between brain cells.


George I (Miskito)

George I was king of the Miskito from 1755 to 1776. He was brother of King Edward and son of Jeremy II and was chosen king because Edward's eldest son was still too young to rule.
Divisions.
According to a report on the country written in 1773 by Brian Edwards, his lands were divided into two population groups, the "Samboes" (Miskito Sambu) who were mixed indigenous and African, and "pure Indians" (Miskito Tawira); and was further divided into four domains: the domains of the king and the general in the north and west, inhabited by "Samboes" and the domains of the governor and admiral inhabited by "pure Indians." British settlers first reported this fourfold division in 1766 and it is possible that George created or consolidated it.
Population.
Edwards also observed that in 1770, George's kingdom had a population that he estimated numbered between 7,000 and 10,000 fighting men, which at a ratio of four civilians to one fighter would make 28,000 and 40,000 people. In addition to Miskitos, the population included 1,400 British inhabitants, of which 136 where white, 112 of mixed race and about 600 slaves, mostly concentrated around the British settlement of Black River, but other concentrations were at Cabo Gracias a Dios and at Bluefields.
Political Developments during his Reign.
One of the tensions within the Miskito domain was that between the Zambu and Tawira, since the Zambus controlled the north and west (primarily in modern-day Honduras) and were vigorously pushing their authority southward into Tawira domains (which lay mostly in today's Nicaragua). This pattern was resisted by Dilson, who was the Admiral and thus controlled the extreme southern parts of the Miskito domain. In June 1769 the Zambu Admiral, Israel Sella, warned the king that Dilson's brother, Jaspar Hall along with two "Mosquito men" named John Chord and Vizer visited the Spanish at Cartago and received gifts as a part of a plan to displace the English from the shore. Spanish officials declared that Dilson was the "governor of the Miskito nation." Dilson also involved Briton, the Governor, who also controlled a Tawira population, in his cause.
At the same time, Tempest, the Zambu General traveled to England attempt to persuade the king of England to separate the administration of the English living in Central America from Jamaica, a move which led George to believe he was plotting his overthrow. The threat was sufficient that George sought aid from both Dilson and Briton, but only Briton agreed to assist him.
George also gave many generous land grants to Englishmen to establish plantations. He gave many around Black River, their largest settlement, but also gave them around Bluefields, which was in land ruled by the Tawira Admiral, a definite move to establish his authority throughout the Miskito Kingdom. Among these grants were ones given to Dr Charles Irwin, who sought the assistance of Olaudah Equiano to recruit slaves in 1776. In exchange, the Tawira Admiral, Dilson II continued negotiations with the Spanish.
The Miskito Kingdom and the American Revolution.
Perhaps as a result of the earlier negotiations undertaken by Tempest, George visited Jamaica in 1774 to place his kingdom under the "sovereignty of his Majesty" the king of England, and received gifts in exchange. He is said to have sent the king of England a barrel of soil from the Miskito Kingdom and promised to supply 5,000 fighters to the English suppress any revolt that might break out in North America.
Death.
George died during a smallpox epidemic in 1777, and was succeeded by his son George II Frederic.


HopC RNA motif

The "hopC" RNA motif is a predicted cis-regulatory element identified by a bioinformatic screen for conserved RNA secondary structures. "hopC" RNAs are exclusively found within bacteria classified within the genus "Helicobacter", some of which are human pathogens that infect the stomach and can cause ulcers.
"hopC" RNAs are found upstream of an operon of two genes called "hopC" and "hopB" (also called "alpa" and "alpB"). Experiments on the start of transcription for the "hopCB" operon indicate that "hopC" RNAs lie within the 5' untranslated region of this operon. The "hopCB" operon is induced to higher levels of expression in response to low pH. This fits in with data that HopCB is involved in binding to human epithelial cells, which is presumably something that the bacteria do during infection of the low-pH environment of the stomach.
Previous work suggested that a repeat of 13 thymidine nucleotides might be involved in regulating the abundance of the "hopCB" operon. However, this 13-nucleotide region lies upstream of the transcription start site, and is therefore independent of "hopC" motif RNAs.


Charlotte Cavendish, Marchioness of Hartington

Charlotte Elizabeth Cavendish, Marchioness of Hartington, Baroness Clifford (born Lady Charlotte Boyle; 27 October 1731 – 8 December 1754) was the daughter of Richard Boyle, 3rd Earl of Burlington and Lady Dorothy Savile. From 1748 until her death she was married to William Cavendish, Marquess of Hartington, later the 4th Duke of Devonshire and Prime Minister of Great Britain.
Family and early life.
Lady Charlotte Elizabeth Boyle was the only surviving daughter of Richard Boyle, 3rd Earl of Burlington and Lady Dorothy Savile. Her mother was the daughter of William Savile, 2nd Marquess of Halifax.
Personal life.
On 28 March 1748, she married William Cavendish, then the Marquess of Hartington, who later became the 4th Duke of Devonshire and the Prime Minister of Great Britain. The advantageous union had been arranged since childhood and was happy. The marriage helped him rise politically. They had four children: William, Dorothy, Richard, and George.
Baroness Clifford of Londesborough.
Charlotte inherited great wealth upon the death of her father in 1754. As the heir of her father, she succeeded to the title of Baroness Clifford of Londesborough "suo jure". Through her marriage, the Cavendish family, with the main title of "Duke of Devonshire", inherited the 3rd Earl of Burlington's estates (the title went to the Orrery Boyles). These estates included: Burlington House, Piccadilly, London (now the Royal Academy of Arts); Chiswick House, London; Londesborough Hall, Yorkshire; Bolton Abbey, Yorkshire; Lismore Castle, County Waterford, Ireland. Charlotte was her father's sole remaining heir.
The Marchioness of Hartington died on 8 December 1754 at Uppingham, Rutland from smallpox. The next year her husband William succeeded his father as Duke of Devonshire.
Issue.
Charlotte and her husband William had four children:


Hayaatun Sillem

Hayaatun Sillem (née Is’harc) is the chief executive officer (CEO) of the Royal Academy of Engineering.
Education.
Sillem attended Godolphin and Latymer School. She earned a master's degree in biochemistry from the University of Oxford in 1998. She completed a PhD funded by Cancer Research UK at University College London in 2002 investigating the JAK-STAT signaling pathway supervised by Ian M. Kerr.
Career.
Sillem joined the Royal Academy of Engineering in 2002 as an Engineering Policy Advisor. She joined the Department for International Development 2005. In 2004 she became a Committee Specialist to the Science and Technology Select Committee, and later as a Specialist Adviser to the House of Commons Science & Technology Committee.
In 2006, Sillem joined Royal Academy of Engineering as Head of International Activities. She led the Academy's partnership with Africa. In this role she published "Engineering Change: Towards a sustainable future in the developing world". She went on to publish "Engineers for Africa: Identifying engineering capacity needs in Sub-Saharan Africa," a summary report. The report identified the capacity needs of engineering that are felt across Sub-Saharan Africa, and developed approaches to meeting these needs.
Sillem was appointed to Director of Programmes and Fellowship in 2011. She is interested in how science and engineering can help with humanitarian admin, and how engineering can drive international development. She published "Investing in Innovation" in 2015. In May 2016, Sillem was appointed Director of Strategy and Deputy Chief Executive of the Royal Academy of Engineering. In March 2017 she was appointed a Fellow of the Institution of Engineering and Technology. She spoke at the launch of Angela Saini's book in June 2017.
Sillem co-founded the Royal Academy of Engineering enterprise hub. She hosted the 10th Young Arab Women Leaders STEM conference in London in December 2017. She was appointed CEO of the Royal Academy of Engineering in January 2018. She is a champion of the Government's Year of Engineering, looking to increase diversity amongst the UK's engineering workforce through the campaign "This is Engineering".
In 2019, Sillem was 31st in "Computer Weekly"'s 50 'Most Influential Women in UK Tech' shortlist.
She is a trustee of the London Transport Museum. She is a judge for St Andrews Prize for the Environment. She has written for "The Huffington Post".
Awards and honours.
Sillem was appointed Commander of the Order of the British Empire (CBE) in the 2020 New Year Honours for services to international engineering. In 2021, Sillem received an Engineering and Physical Sciences Suffrage Science award.


Iron(II) cyanide

Iron(II) cyanide is an inorganic compound with the empirical formula Fe(CN)2. It may have a Fe2[Fe(CN)6] structure.
Production.
Iron(II) cyanide can be produced by dissolving ammonium ferrocyanide at 320 °C.
3 (NH4)4Fe(CN)6 → Fe2Fe(CN)6 + 12 NH4CN
Reaction.
Iron(II) cyanide can react with potassium hydroxide solvent to produce iron(II) hydroxide and potassium ferrocyanide.
Fe2Fe(CN)6 + 4 KOH → 2 Fe(OH)2 + K4Fe(CN)6


Fatty-acid peroxidase

In enzymology, a fatty-acid peroxidase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are palmitate and H2O2, whereas its 3 products are pentadecanal, CO2, and H2O.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a peroxide as acceptor (peroxidases). The systematic name of this enzyme class is hexadecanoate:hydrogen-peroxide oxidoreductase. This enzyme is also called long chain fatty acid peroxidase.


Ferric reducing ability of plasma

Ferric reducing ability of plasma (FRAP, also "Ferric ion reducing antioxidant power") is an antioxidant capacity assay that uses Trolox as a standard. The FRAP assay was first performed by Iris Benzie and J. J. Strain of the Human Nutrition Research Group at the University of Ulster, Coleraine. The method is based on the formation of O-Phenanthroline-Fe(2+) complex and its disruption in the presence of
chelating agents. This assay is often used to measure the antioxidant capacity of foods, beverages and nutritional supplements containing polyphenols.
Experimental procedure.
A reaction mixture
containing 1 ml of 0.05% O -Phenanthroline in methanol, 2 ml ferric chloride (200 M) and 2 ml of various
concentrations ranging from 10 to 1000 g
was incubated at room temperature for 10
min and the absorbance of the same was
measured at 510 nm. EDTA was used as a classical metal chelator. The experiment was
performed in triplicates. The ferric reducing activity of date seed extract was estimated
based on the method of Benzie and Strain (1999). The FRAP
reagent was prepared by mixing 50 ml of acetate buffer (0.3 M)
at pH 3.6, 5 ml of tripyridyltriazine (TPTZ) solution 10 mM
prepared in HCl (40 mM) and 5 ml of ferric chloride solution
(FeCl3) (20 mM). 2 ml of the freshly prepared FRAP reagent
was added to 10 lL of the extract. Then the absorbance was
measured at 593 nm against the blank after 10 min at room
temperature. The standard curve was constructed using Trolox.
The result was expressed as Trolox equivalent in
mg/100 g of dry weight (DW) date seed.


Michiei Oto

Michiei Oto is a molecular biologist and an expert on the application of biotechnology to genetic testing.
He was the first to propose gene literacy education.
Oto was born in Japan. He received a bachelor's degree in biochemistry from Chiba University in 1980 and a Ph.D. from the School of Medicine at Tokyo Medical and Dental University. He is the department director of biotechnology at Tokyo Technical College and a visiting Lecturer at Tokyo University of Agriculture and Technology, Maebashi Institute of Technology and Kogakuin University.


Netsmart Technologies

Netsmart Technologies is an American company that develops and sells health information technology, including for electronic health records and health information exchanges, for organizations and entities in the behavioral health, human services, and post-acute care (which consists of home care and hospice and senior living) markets.
Netsmart was founded in 1992 although its technology origins go back to 1968 with the founding of Creative Socio-Medics, which it acquired in 1994. Netsmart has since grown via many other acquisitions. It is headquartered in Overland Park, Kansas.
Origins.
Netsmart Technologies was originally known as Medical Services Corporation. Created in September 1992, this was a holding company which did business under a subsidiary called Carte Medical Corporation. In October 1993, Medical Services Corp. merged its subsidiary into itself and became directly known as Carte Medical. In June 1994, Carte Medical acquired Creative Socio-Medics (CSM).
Creative Socio-Medics had been founded by Gerald O. Koop and John F. Phillips in 1968. It had then been acquired in 1973 by Advanced Computer Techniques (ACT), a New York City-based software company that specialized in language compilers but also engaged in information technology consulting and hosted service bureaus. CSM specialized in delivering software products and hardware and software services in the human services field, specifically for behavioral health providers such as psychiatric hospitals and mental health clinics. In 1989, CSM had stopped sharing physical facilities with the rest of ACT and relocated to Islip, New York on Long Island. CSM had tended to be profitable some years but not other years and was rarely in solid financial shape. By the early 1990s, ACT's other businesses had been closed down and it was motivated to sell CSM as well.
In June 1995, Carte Medical Corporation's name was changed to CSMC Corporation, and in February
1996, the name was finally changed to Netsmart Technologies, Inc. Creative Socio-Medics became the company's operations arm that it did business through.
Public company.
James L. Conway, who had previously been an executive for a credit subsidiary of ITT Corporation, became president of Netsmart Technologies in January 1996 and its CEO in April 1998. Several former ACT and CSM executives still held executive or board positions with Netsmart, including Koop and Phillips as well as Chief Financial Officer Anthony F. Grisanti and Chairman of the Board Edward D. Bright. Another former executive, Oscar H. Schachter, did legal work for them.
In August 1996, Netsmart Technologies staged an initial public offering and became a public company. The company was traded on NASDAQ under the symbol NTST.
Around 1999, the company began a period of rapid growth, with revenues increasing almost fivefold over the next six years, with both acquisitions and organic growth being responsible. It was especially strong in contracts with the different states. By the end of 2002, the company had 145 employees. Leading up to 2003, the business of Creative Socio-Medics benefited from the phase-in that year of Title II of the Health Insurance Portability and Accountability Act (HIPAA), which required the establishment of national standards for transactions involving electronic health records. The Avatar software suite from Creative Socio-Medics generally cost from $250,000 to $1 million at that time and covered patient tracking, medical records management, and scheduling and billing for both inpatient and outpatient services.
In 2003, the company moved from Islip to Great River, New York. By 2004, it had been profitable for five straight years and 23 quarters in a row.
By 2005, Netsmart was the largest information technology provider within the behavioral health care sector, with revenues of around $50 million. That year it acquired its biggest competitor, CMHC Systems of Ohio, which was especially strong in community mental health centers, for $18 million. Conway remained CEO of the merged entity. At this point the Creative Socio-Medics and CMHC names were retired and the company operated solely as Netsmart. By the end of 2005 its profitability streak had reached 30 quarters in a row.
Private equity buyout.
The purchase of CMHC in turn attracted the interest of private equity firms. In 2006, Netsmart agreed to be bought out by two such firms, Bessemer Venture Partners and Insight Venture Partners, for $115 million.
Shareholders then sued the company on the grounds that Netsmart's board of directors had not looked hard enough for a strategic buyer. The acquisition was held up for a while in early 2007 when Judge Leo E. Strine, Jr. of the Delaware Court of Chancery barred the sale until management better explained its decision to sell the company to these two particular firms. This was done and the sale went through. The case, "In Re: Netsmart Technologies, Inc. Shareholders Litigation", became influential in delineating the responsibilities of management when agreeing to a private equity buyout.
In 2010, Genstar Capital, another private equity firm, acquired Netsmart Technologies from Bessemer Venture Partners and Insight Venture Partners. New management came in 2011 in the form of CEO Michael G. Valentine and COO Thomas Herzog, both of whom had previously been senior executives at the health care information technology company Cerner in the Kansas City metropolitan area. Conway went into retirement. As a consequence of the management change, Netsmart Technologies relocated its headquarters in that year to Overland Park, Kansas. Many of the company's management functions have moved there, while many development, sales, and legal functions remain in the office in Great River. They constructed a "Solutionarium" with an IMAX-like experience in the headquarters facility to foster collaboration with their customers.
By 2011, there were some 18,000 clients using Netsmart Technologies products or services. The company had 600 employees and revenues of $110 million. Netsmart continued to engage in acquisitions and form alliances, including some in 2012 towards offering cloud services and data mining for behavioral health providers.
In March 2016, Netsmart was bought by a joint venture of GI Partners and Allscripts for $950 million.
In October 2016, Netsmart acquired HealthMEDX, based in Ozark, Missouri, developers of a long-term care electronic health record product.
In May 2020, the company acquired McBee, a 250-employee health care consulting firm based in Wayne, Pennsylvania.
In June 2020, Netsmart acquired Quality In Real Time (QIRT), a health care IT company based in New York.


Crossover interference

Crossover interference is the term used to refer to the non-random placement of crossovers with respect to each other during meiosis. The term is attributed to Hermann Joseph Muller, who observed that one crossover "interferes with the coincident occurrence of another crossing over in the same pair of chromosomes, and I have accordingly termed this phenomenon ‘interference’."
Meiotic crossovers (COs) appear to be regulated to ensure that COs on the same chromosome are distributed far apart (crossover interference). In the nematode worm "Caenorhabditis elegans", meiotic double-strand breaks (DSBs) outnumber COs. Thus not all DSBs are repaired by a recombination process(es) leading to COs. The RTEL-1 protein is required to prevent excess meiotic COs. In "rtel-1" mutants meiotic CO recombination is significantly increased and crossover interference appears to be absent. RTEL1 likely acts by promoting synthesis-dependent strand annealing which results in non-crossover (NCO) recombinants instead of COs (see diagram). Normally, about half of all DSBs are converted into NCOs. RTEL-1 appears to enforce meiotic crossover interference by directing the repair of some DSBs towards NCOs rather than COs.
In humans, recombination rate increases with maternal age. Furthermore, placement of female recombination events appears to become increasingly deregulated with maternal age, with a larger fraction of events occurring within closer proximity to each other than would be expected under simple models of crossover interference.
High negative interference.
Bacteriophage T4.
High negative interference (HNI), in contrast to positive interference, refers to the association of recombination events ordinarily measured over short genomic distances, usually within a gene. Over such short distances there is a positive correlation (negative interference) of recombinational events. As studied in bacteriophage T4 this correlation is greater the shorter the interval between the sites used for detection. HNI is due to multiple exchanges within a short region of the genome during an individual mating event. What is counted as a “single exchange” in a genetic cross involving only distant markers may in reality be a complex event that is distributed over a finite region of the genome. Switching between template DNA strands during DNA synthesis (see Figure, SDSA pathway), referred to as copy-choice recombination, was proposed to explain the positive correlation of recombination events within the gene. HNI appears to require fairly precise base complementarity in the regions of the parental genomes where the associated recombination events occur.
HIV.
Each human immunodeficiency virus (HIV) particle contains two single-stranded positive sense RNA genomes. After infection of a host cell, a DNA copy of the genome is formed by reverse transcription of the RNA genomes. Reverse transcription is accompanied by template switching between the two RNA genome copies (copy-choice recombination). From 5 to 14 recombination events per genome occur at each replication cycle. This recombination exhibits HNI. HNI is apparently caused by correlated template switches during minus-strand DNA synthesis. Template switching recombination appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes.


Ion semiconductor sequencing

Ion semiconductor sequencing is a method of DNA sequencing based on the detection of hydrogen ions that are released during the polymerization of DNA. This is a method of "sequencing by synthesis", during which a complementary strand is built based on the sequence of a template strand.
A microwell containing a template DNA strand to be sequenced is flooded with a single species of deoxyribonucleotide triphosphate (dNTP). If the introduced dNTP is complementary to the leading template nucleotide, it is incorporated into the growing complementary strand. This causes the release of a hydrogen ion that triggers an ISFET ion sensor, which indicates that a reaction has occurred. If homopolymer repeats are present in the template sequence, multiple dNTP molecules will be incorporated in a single cycle. This leads to a corresponding number of released hydrogens and a proportionally higher electronic signal.
This technology differs from other sequencing-by-synthesis technologies in that no modified nucleotides or optics are used. Ion semiconductor sequencing may also be referred to as Ion Torrent sequencing, pH-mediated sequencing, silicon sequencing, or semiconductor sequencing.
Technology development history.
The technology was licensed from DNA Electronics Ltd, developed by Ion Torrent Systems Inc. and was released in February 2010. Ion Torrent have marketed their machine as a rapid, compact and economical sequencer that can be utilized in a large number of laboratories as a bench top machine. Roche's 454 Life Sciences is partnering with DNA Electronics on the development of a long-read, high-density semiconductor sequencing platform using this technology.
Technology.
Sequencing chemistry.
In nature, the incorporation of a deoxyribonucleoside triphosphate (dNTP) into a growing DNA strand involves the formation of a covalent bond and the release of pyrophosphate and a positively charged hydrogen ion. A dNTP will only be incorporated if it is complementary to the leading unpaired template nucleotide. Ion semiconductor sequencing exploits these facts by determining if a hydrogen ion is released upon providing a single species of dNTP to the reaction.
Microwells on a semiconductor chip that each contain many copies of one single-stranded template DNA molecule to be sequenced and DNA polymerase are sequentially flooded with unmodified A, C, G or T dNTP. If an introduced dNTP is complementary to the next unpaired nucleotide on the template strand it is incorporated into the growing complementary strand by the DNA polymerase. If the introduced dNTP is not complementary there is no incorporation and no biochemical reaction. The hydrogen ion that is released in the reaction changes the pH of the solution, which is detected by an ISFET. The unattached dNTP molecules are washed out before the next cycle when a different dNTP species is introduced.
Signal detection.
Beneath the layer of microwells is an ion sensitive layer, below which is an ISFET ion sensor. All layers are contained within a CMOS semiconductor chip, similar to that used in the electronics industry.
Each chip contains an array of microwells with corresponding ISFET detectors.
Each released hydrogen ion then triggers the ISFET ion sensor. The series of electrical pulses transmitted from the chip to a computer is translated into a DNA sequence, with no intermediate signal conversion required. Because nucleotide incorporation events are measured directly by electronics, the use of labeled nucleotides and optical measurements are avoided. Signal processing and DNA assembly can then be carried out in software.
Sequencing characteristics.
The per base accuracy achieved in house by Ion Torrent on the Ion Torrent Ion semiconductor sequencer as of February 2011 was 99.6% based on 50 base reads, with 100 Mb per run. The read-length as of February 2011 was 100 base pairs. The accuracy for homopolymer repeats of 5 repeats in length was 98%. Later releases show a read length of 400 base pairs These figures have not yet been independently verified outside of the company.
Strengths.
The major benefits of ion semiconductor sequencing are rapid sequencing speed and low upfront and operating costs. This has been enabled by the avoidance of modified nucleotides and optical measurements.
Because the system records natural polymerase-mediated nucleotide incorporation events, sequencing can occur in real-time. In reality, the sequencing rate is limited by the cycling of substrate nucleotides through the system. Ion Torrent Systems Inc., the developer of the technology, claims that each incorporation measurement takes 4 seconds and each run takes about one hour, during which 100-200 nucleotides are sequenced. If the semiconductor chips are improved (as predicted by Moore’s law), the number of reads per chip (and therefore per run) should increase.
The cost of acquiring a pH-mediated sequencer from Ion Torrent Systems Inc. at time of launch was priced at around $50,000 USD, excluding sample preparation equipment and a server for data analysis. The cost per run is also significantly lower than that of alternative automated sequencing methods, at roughly $1,000.
Limitations.
If homopolymer repeats of the same nucleotide (e.g. ) are present on the template strand (strand to be sequenced) then multiple introduced nucleotides are incorporated and more hydrogen ions are released in a single cycle. This results in a greater pH change and a proportionally greater electronic signal. This is a limitation of the system in that it is difficult to enumerate long repeats. This limitation is shared by other techniques that detect single nucleotide additions such as pyrosequencing. Signals generated from a high repeat number are difficult to differentiate from repeats of a similar but different number; "e.g.", homorepeats of length 7 are difficult to differentiate from those of length 8.
Another limitation of this system is the short read length compared to other sequencing methods such as Sanger sequencing or pyrosequencing. Longer read lengths are beneficial for "de novo" genome assembly. Ion Torrent semiconductor sequencers produce an average read length of approximately 400 nucleotides per read.
The throughput is currently lower than that of other high-throughput sequencing technologies, although the developers hope to change this by increasing the density of the chip.
Application.
The developers of Ion Torrent semiconductor sequencing have marketed it as a rapid, compact and economical sequencer that can be utilized in a large number of laboratories as a bench top machine. The company hopes that their system will take sequencing outside of specialized centers and into the reach of hospitals and smaller laboratories. A January 2011 New York Times article, "Taking DNA Sequencing to the Masses", underlines these ambitions.
Due to the ability of alternative sequencing methods to achieve a greater read length (and therefore being more suited to whole genome analysis) this technology may be best suited to small scale applications such as microbial genome sequencing, microbial transcriptome sequencing, targeted sequencing, amplicon sequencing, or for quality testing of sequencing libraries.


Apricus Biosciences

Apricus Biosciences, Inc. is a San Diego based biopharmaceutical company advancing innovative medicines in urology and rheumatology.
Apricus Biosciences' first product, Vitaros®, has been approved in Europe and Canada for the treatment of erectile dysfunction Other compounds in development include: low testosterone, rheumatology, sexual dysfunction, pain,
History.
Until September 10, 2010, when it formally changed its name, Apricus Biosciences, Inc. () had been operating in the pharmaceutical industry since 1995 under the name NexMed, Inc. NASDAQ:NEXM. On November 15, 2010, Apricus Bio received Canadian approval for its topical ED treatment Vitaros and it announced European approval on June 10, 2013.
Location.
Apricus Biosciences is headquartered in San Diego, CA. The company, and its subsidiaries, has approximately 35 employees.
Products.
Vitaros® - is a rapid-onset (generally 5–15 minutes) topical cream for the treatment of erectile dysfunction. It contains Prostaglandin E1 as the active ingredient and the Company's proprietary permeation enhancer (NexACT®) which facilitates the delivery of the drug into the blood stream. The current formulation of Vitaros requires refrigeration and is delivered via a small individual dispenser. Vitaros has been approved for patient use in Canada and Europe and to date (January 24, 2015) has been launched by marketing partners in the United Kingdom (Takeda), Germany (Sandoz), Sweden (Sandoz) and Belgium (Sandoz). Six additional European territories are expected to launch Vitaros during 2015.
Apricus has developed a room temperature formulation of Vitaros which is housed and delivered in a small, custom developed, disposable dispenser or "room temperature device" (RTD). Initial production of Vitaros RTD has commenced in order to generate the required stability data required for marketing approval. The Company continues to expect its commercial partners to launch the Vitaros RTD in 2016.
In November 2007 Apricus Biosciences sold the rights for the refrigerated formulation of Vitaros in the US to Warner Chilcott.
Fispemifene is a new chemical entity initially being pursued for the treatment of low testosterone (secondary hypogonadism) in males. Apricus plans to begin a Phase 2b clinical trial with fispemifene in this indication in the first half of 2015, with top-line data expected to be reported by the end of 2015. Apricus in-licensed the U.S. rights to fispemifene from Forendo Pharma in Q4 2014. Since then, it has transferred the regulatory filings from Forendo, developed a Phase 2b clinical trial protocol, held a scientific advisory board meeting with experts in the field to refine its development strategy, initiated the manufacturing process for the drug, and begun the clinical trial site selection process.
RayVa™ is a topical cream for the treatment of Raynaud's phenomenon, a circulatory disorder affecting the hands and feet. Patient enrollment commenced in December 2014 for a 45-patient Phase 2a clinical trial for RayVa which is expected to be completed and results announced in the second quarter in 2015. RayVa has the potential to be the only FDA approved treatment for this debilitating condition. RayVA contains Prostaglandin E1 as the active ingredient and Apricus' permeation enhancer (NexACT) which facilitates the delivery of the drug into the blood stream.
Femprox® is a topical cream for the treatment of female sexual interest / arousal disorder. It contains Prostaglandin E1 as the active ingredient and a permeation enhancer (NexACT) which facilitates the delivery of the drug into the blood stream.
NexACT Technology.
NexACT® is a proprietary water-soluble small molecule permeation enhancer which temporarily changes the permeation dynamics of the lipid bi-layer and transiently loosens the tight junctions between the cells so that active drug molecules can be rapidly absorbed into systemic circulation. The NexACT technology is used in both Vitaros and RayVA. It can also improve the solubility of compounds resulting in enhanced drug permeation.
Leadership.
Richard Pascoe - CEO Mr. Pascoe joined Apricus in March 2013 following the merger of Somaxon Pharmaceuticals with Pernix. At Somaxon Mr. Pascoe was the Chief Executive Officer since August 2008 and was responsible for the FDA approval of Somaxon’s lead drug Silenor®. Prior to Somaxon, Mr. Pascoe was with ARIAD Pharmaceuticals, Inc., a specialty pharmaceutical company where he was most recently Senior Vice President and Chief Operating Officer.
Prior to joining ARIAD in 2005, Mr. Pascoe held a series of senior management roles at King Pharmaceuticals, Inc., a specialty pharmaceutical company, including Senior Vice President positions in both marketing and sales, as well as Vice President positions in both international sales and marketing and hospital sales. Prior to King, Mr. Pascoe was in the commercial groups at Medco Research, Inc. (which was acquired by King), COR Therapeutics, Inc., B. Braun Interventional and The BOC Group. Mr. Pascoe is a member of the board of directors of KemPharm, Inc., Cohera Medical, Inc., and the Corporate Directors Forum (CDF).
Mr. Pascoe served as a Commissioned Officer with the U.S. Army 24th Infantry Division, following his graduation from the United States Military Academy at West Point where he received a B.S degree in Leadership.
Brian Dorsey - SVP, Chief Development Officer Mr. Dorsey has served in the Pharmaceutical and Biotechnology industries for over 20 years where he has provided high-level drug development, regulatory and QC/QA leadership of pharmaceutical candidates from early development to FDA approval. He has held various senior management roles with pharmaceutical companies, most recently at Pernix Therapeutics as Senior Vice President Pharmaceutical Development. Prior to this, Mr. Dorsey held managerial positions of increasing responsibility at Somaxon Pharmaceuticals, Baxter Bioscience and Pfizer Global Research and Development.
Mr. Dorsey received his Master of Science in Executive Leadership and his B.A. in Chemistry from the University of San Diego.
Barbara Troupin, MD, MBA - SVP, Chief Medical Officer Dr. Troupin has held various senior management roles with VIVUS, Inc. in the areas of Medical Affairs and Clinical Development since 2006. In these roles, Dr. Troupin was the clinician lead for the Phase 3 program for Qsymia, as well as the lead contributor for all medical review of the Qsymia New Drug Application and was the lead medical presenter at the successful Qsymia FDA Advisory Committee Meeting. Prior to this, Dr. Troupin held Medical Director positions at the Profil Institute for Clinical Research and Radiant Research, both contract research organizations.
Dr. Troupin received her M.D. from the University of Pennsylvania School of Medicine and her M.B.A. from the Wharton School of Business.


Psychrobacter aquaticus

Psychrobacter aquaticus is a Gram-negative, psychrophilic, halotolerant, nonmotile bacterium of the genus "Psychrobacter" which was isolated from the McMurdo Dry Valley region of Antarctica.


Para-Methoxyphenylpiperazine

"para"-Methoxyphenylpiperazine (MeOPP, pMPP, 4-MPP; Paraperazine) is a piperazine derivative with stimulant effects which has been sold as an ingredient in "Party pills", initially in New Zealand and subsequently in other countries around the world.
Pharmacology.
MeOPP is anecdotally said to induce significantly less anxiety than similar piperazines, and is usually taken at doses between 120–200 mg. It does not produce prominent stimulant effects, but is instead said to be relaxing, however it is often mixed with stimulant piperazine derivatives such as benzylpiperazine (BZP) for a combined effect.
MeOPP has been found "in vitro" to inhibit the reuptake and induce the release of the monoamine neurotransmitters. This is a mechanism of action shared with drugs of abuse such as amphetamines, and MeOPP produces somewhat similar effects although it is much less potent and is thought to have relatively insignificant abuse potential. Piperazine derivatives such as trifluoromethylphenylpiperazine (TFMPP) have also been shown to exert a major part of their mechanism of action as nonselective serotonin receptor agonists, and MeOPP has also been demonstrated to act in this way.
Legal status.
New Zealand.
Based on the recommendation of the EACD, the New Zealand government has passed legislation which placed BZP, along with a number of other piperazine derivatives into Class C of the New Zealand Misuse of Drugs Act 1975. A ban was intended to come into effect in New Zealand on December 18, 2007, but the law change did not go through until the following year, and the sale of BZP and the other listed piperazines became illegal in New Zealand as of 1 April 2008. An amnesty for possession and usage of these drugs remained until October 2008, at which point they became completely illegal.
United States.
MeOPP is not scheduled at the federal level in the United States.
Florida.
"Methoxyphenylpiperazine" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida.


BioAmber

BioAmber Inc. was a Delaware (USA) registered Canadian sustainable chemicals company that was headquartered in Montreal, Quebec, Canada. It's proprietary technology platform combined industrial biotechnology and chemical catalysis to convert renewable feedstock into building block chemicals for use in a wide variety of everyday products including plastics, resins, food additives and personal care products. BioAmber was listed on the New York Stock Exchange between May 2013 and February 2018, under the symbol BIOA. It was also listed on the Toronto Stock Exchange under the same symbol. Bioamber officially ceased operations in August 2018', all directors of the company resigned & PriceWaterhouseCoopers proceeded forward in court authorized control of the company's fate. BioAmber no longer has any offices or facilities in Canada or the United States after completion of a CCAA Insolvency / USA Chapter 15 foreign arrangement, in which the company was liquidated & all major assets were sold off. On November 22nd, 2019 FINRA, (https://www.finra.org/about) the USA Financial Regulatory Authority officially suspended the company's CUSIP registration thus finalizing the outcome for Bioamber & delisting it from all tradeable stock exchanges.
History.
BioAmber was established in 2008 as a result of a spin-off from New York-based Diversified Natural Products (DNP). The company was originally named DNP Green Technology and was based in Princeton, New Jersey. Prior to the spin-off, DNP had established a joint venture with France-based Agro-Industrie Recherches et Développements (ARD) to develop and commercialize bio-based succinic acid. In 2010, DNP Green Technology acquired 100 percent of the joint venture from ARD and changed its corporate name to BioAmber.
After the Company was spun off from DNP, it was privately financed in 2009' by a group of institutional investors led by Sofinnova Partners, Mitsui & Co., Samsung Ventures and the Cliffton Group. In 2011 and 2012, Naxos Capital Partners and Lanxess became investors in the Company, which raised a total of $87 million over three rounds of financing between 2009 and 2012. In May 2013, BioAmber completed its initial public offering on the New York Stock Exchange under the symbol BIOA, raising $80 million in gross proceeds and issuing warrants for an additional $44 million in common stock.
Companies' Creditors Arrangement Act (CCAA).
On May 4, 2018, BioAmber filed for bankruptcy protection under Chapter 11 in the US and entered into CCAA protection in Canada, with the intent of restructuring the company. After failure to secure additional financing could not be negotiated, the proceedings moved to a US Chapter 15 bankruptcy and CCAA liquidation of the company. The court monitor overseeing the case was PriceWaterhouseCoopers.
On October 22, 2018 under the CCAA / USA Chapter 15, a transaction occurred for substantially all of BioAmber's assets between BioAmber and LCY Biosciences "LCYB", the designated purchaser in the joint venture formed between Visolis and LCY Chemical Corp. In a turn of events, LCY Chemical Corp was itself acquired by KKR in a $1.56 billion acquisition which saw LCY itself taken "private". The KKR / LCY transaction closed at the end of January 2019. According to a letter of intent, "Letter of Intent for Investment in BioAmber Inc." submitted by Deepak Dugar, the President of Visolis, LCY Biosciences intends to own and continue to operate the bio-based succinic acid plant at Sarnia with the addition of viable alternative products added.
Technology.
BioAmber produced bio-based succinic acid by fermenting sugars. The company used a proprietary yeast that it has exclusively licensed from Cargill. Cargill originally identified a yeast strain that has the ability to ferment at a low pH. Cargill modified that strain for the production of lactic acid and has been using that new yeast strain at commercial scale since 2009. BioAmber collaborated with Cargill to develop from the original strain a new one that could ferment at a low pH and tolerate high concentrations of succinic acid, giving it a distinct advantage over other microorganisms producing succinic acid via fermentation. BioAmber had designed its former commercial plant in Sarnia for the production of bio-based succinic acid to operate with its yeast technology.
BioAmber had a license from Johnson Matthey Davy Technologies a catalyst technology that converts bio-based succinic acid into bio-based 1,4-butanediol (BDO). The technology involves the vapor phase hydrogenation of succinic acid ester into BDO and tetrahydrofuran (THF). JM Davy is reportedly the global leader in BDO and THF technology, with 14 licenses deployed representing approximately 800,000 tons per year of installed BDO and THF capacity, or 25% of worldwide capacity. Their technology produced BDO/THF from maleic anhydride, a petrochemical. The first step in that route converts MA to succinic acid; thus succinic is an alternative feedstock. JM Davy has adjusted its process and tested BioAmber's bio-succinic acid so it can substitute maleic anhydride without impacting performance, process economics or product quality.
Sustainability.
The use of fermentation to produce building block chemicals offers the prospect of an improved carbon footprint and lower energy intensity than the petrochemical route to the same chemicals.
Manufacturing.
BioAmber produced bio-based succinic acid from January 2010 to December 2014 at a large demonstration plant owned and operated by the Company's former joint venture partner, ARD. The demonstration plant operated at the 350,000 liter fermenter scale, which at the time was one of the largest scale fermentations among start-up companies in the field of bio-based chemicals. BioAmber claim to have gained extensive experience from operating this plant for five years and incorporated the learning and improvements into the design of its commercial plant in Sarnia, Canada.<ref name="BioAmber S-1/A"></ref>
BioAmber established a joint venture with Mitsui & Co. to build and operate a bio-succinic acid plant in Sarnia, Ontario with a manufacturing capacity of per year, with BioAmber owning 60% of the venture. The facility began construction in August 2013 and began commercial operations in November 2015. The cost of construction was US$141 million and it created 60 full-time jobs. It is the world's largest bio-based succinic acid plant.
BioAmber's Integrated Management Systems in Sarnia were ISO 9001:2008 registered, ISO 14001:2004 registered, BS OHSAS 18001:2007 registered, and FSSC 22000 registered within four months of operational start-up.
Markets.
Succinic acid is a platform chemical that can be used in a broad range of markets, from high value niche applications such as personal care products and food
additives, to large volume applications such as bioplastics, pigments, plasticizers, polyurethanes, resins and coatings. In 2004, the United States Department of Energy (USDOE) published a report on "Top Value-Added Chemicals from Biomass," identifying the top opportunities for the production of chemicals from biomass. The study prioritized twelve chemicals, from a group of over 300 possible building blocks that could be most effectively manufactured from sugars. Bio-succinic acid was recognized as one of the renewable building block chemicals with the greatest technical feasibility and commercial potential.
Historically, the high cost of producing succinic acid from petroleum feedstock limited its use to a narrow range of applications such as pharmaceuticals and food ingredients. As a result, based on 2011 estimates, the market for petroleum-based succinic acid was approximately 51,000 metric tons per year, representing a market size of approximately $350 million. However, market research firms and consultants predict that manufacturing bio-succinic acid will make succinic acid economically feasible for use in greater volumes across a spectrum of new applications. A study published in September 2013 by Transparency Market Research projects that the global market for succinic acid will grow at a CAGR of 19.4% between 2012 and 2018. A study published in August 2012 by Roland Berger Strategy Consultants projects that the succinic acid market will grow at a compounded annual growth rate of between 25% and 30% through 2020, when the global market size is expected to be between 500,000 and 700,000 metric tons.
The major uses of 1,4 BDO are in the production of THF and polybutylene terephthalate, or PBT. THF is used to produce spandex fibers and other performance polymers, resins, solvents and printing inks for plastics. PBT is an engineering-grade thermoplastic that combines excellent mechanical and electrical properties with robust chemical resistance. The automotive and electronics industries heavily rely on PBT to produce connectors, insulators, wheel covers, gearshift knobs and reinforcing beams.
References.
(1)SEC 8K resignation of BioAmber Board Of Directors *
(2)PWC Insolvency Trustee reports *
(3)PWC Monitor Report with unsealed documents + Asset list *


Hydroxytertatolol

Hydroxytertatolol is a beta blocker. It is a derivative of tertatolol.


Heinz Gibian

Heinz Rudolf Gibian (30 March 1916 – 13 May 1995) was a German biochemist, who was noted for his research on steroid hormones.
He was a senior researcher at the drug research department of Schering AG and was later a member of the company's senior management. He was also an honorary Professor of biochemistry at the Free University of Berlin.
Gibian was born in Munich. He earned his Doktoringenieur degree at the Technical University of Munich, where he was a student of the Nobel laureate Hans Fischer. He was also a board member of the Society for Biochemistry and Molecular Biology. He died in Berlin, aged 79.


Sir Thomas Isham, 3rd Baronet

Sir Thomas Isham, 3rd Baronet of Lamport (15 March 1656/57 – 26 July 1681) is known for a diary he wrote from 1671 to 1673 of his observations as a teenage member of the English aristocracy.
Life.
Thomas Isham II, the eldest son and second child of Sir Justinian Isham I and his wife Vere Leigh, was born on 15 March 1656/57 in Northamptonshire. When his father died on 2 March 1675, Thomas succeeded at 19 years of age to the baronetcy of Lamport, Northamptonshire. He matriculated at Christ Church, Oxford that June, three months after becoming baronet, but he would have only been able to spend a few months at most in his studies, as he embarked in October of the following year on a tour of Europe with his cousin and tutor the Reverend Zacchaeus Isham. Though it was not uncommon for the young English gentry of the time to tour the continent for several months as part of their education, Sir Thomas and Zacchaeus stayed a full two and a half years, a large part of their time spent in Italy collecting art works.
Returning to Lamport, Sir Thomas contracted to marry Mary van de Bempde, the daughter of a Dutch merchant, but he died of smallpox in London on 26 July 1681 before his marriage could take place. He was buried several days later on 9 August in Lamport, and succeeded in the baronetcy by his younger brother Sir Justinian Isham, who became the 4th baronet.
Diary.
Sir Thomas is remembered mainly for a diary that he wrote in Latin from 1671 to 1673 at the command of his father. It is made up largely of one-sentence entries, with occasional longer anecdotes of local newsworthy events, as relayed to the boy by visitors. His diary is noteworthy in that it provides a glimpse of the everyday life of a teenage member of the English gentry, as played out in a country estate. His diary first became widely available in 1875 when it was first published, but the most readily available edition is a 1971 publication of a translation by Norman Marlow with annotations by the 12th baronet Sir Gyles Isham.
A portrait of Sir Thomas Isham painted about 1675 by Sir Peter Lely, about the time Thomas became baronet, hangs at Lamport Hall, and there is a reduced copy of Lely's work by Mary Beale.


Hannah Steinberg

Hannah Steinberg (16 March 1926 - 11 December 2019) was a pioneer of experimental psychopharmacology, the study of the interaction of drugs on the human mind.
Early life.
Steinberg was born in Vienna to the lawyer Michael Steinberg and his wife Marie (nee Wein). They arranged for her to leave Vienna in 1938 and she was one of the first Jewish children to travel on the Kindertransport. and arrived in London where she was educated at Putney High School and Queen Anne's School, Caversham. After studying for a Certificate in Commerce at Reading University and then at Denton Secretarial College she changed course. After beginning a degree in French at University College London, she then converted to Psychology and graduated with a first in 1948.
Career.
Her curiosity about science led her to work with Frank Winton in the pharmacology department at UCL, where she completing a PhD exploring the effects of nitrous oxide on task completion. She discovered that small amounts interfered with completing complex tasks but that it also improved memory recall. She continued to work at UCL for the rest of her career, in 1962 becoming the first Reader of Psychopharmacology in the world and in 1970, the first Professor of Psychopharmacology. Her research focused on the effects of drug combinations, which she discovered could not be predicted from the actions of the drugs alone. She also explored how the drug efficacy could be impacted by the emotional state of the drug taker. From this her interests grew to encompass drug-taking behaviours and addiction. Many of her test subjects were students and she also tested on staff, including J. B. S. Haldane, but she never tested drugs on humans that she had not tested on herself. She also worked closely with Elizabeth Sykes, her long-term colleague and partner, to investigate benefits of exercise for wellbeing and creativity the potential my harmful exercise addiction.
Other work.
Steinberg was a founding member of the British Association of Psychopharmacology and the International College of Neuropyschopharmacology. She also founded the Academic Women's Achievement Group at UCL; the minutes from 1979 to 1986 are held at the National Archives.


InDevR

InDevR is a biotechnology company in Boulder, Colorado, that develops advanced life science instrumentation and assays for analysis of viruses and other microorganisms, as well as protein detection and characterization, with product focus on Virus Quantification and pathogen detection/identification.
History.
The company was founded in 2003 by Kathy L. Rowlen, Laura R. Kuck, and John W. Birks as an LLC. The origin of the name derived from its early stage goals of Instrument Development and Research. The company converted to a corporation in 2005 with a shift toward product sales and customer support.
In 2005, InDevR purchased majority ownership of 2B Technologies, a leader in the field of analytical instruments for atmospheric and environmental measurements. An ISO 9001:2000-certified manufacturer, 2B Technologies has produced and sold over 2,000 ozone monitors and related instruments.
InDevR is a recipient of the government-sponsored Small Business Innovation Research program. The company received a Phase I grant in 2006 to develop a revolutionary instrument for Virus Quantification from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Based on demonstration of feasibility in Phase I, InDevR received a Phase II grant in 2008. Both of these grants led directly to the creation of several high-tech jobs that continue to date as InDevR translated the funding for research and development into the commercially available Virus Counter product line.
In 2012, InDevR spun off the Virus Counter Instrument to ViroCyt, LCC. The focus of InDevR's efforts will now be on the development and commercialization of their low-density microarray technology, which can be used to improve the analysis of viruses and other microorganisms as well as detecting and characterizing proteins.
Products.
ampliPHOX.
ampliPHOX Colorimetric Detection Technology was created as a research tool for the analysis of low-density microarrays by providing rapid, cost effective colorimetric detection with minimal user input. Rather than a fluorescent label traditionally used in microarray applications, ampliPHOX Colorimetric Detection Technology utilizes a photoinitiator that, when activated by light, generates signal amplification through polymerization of an organic monomer. The detection technology is easy to use and can be completed within minutes when applied to low-density microarrays. The ampliPHOX Reader is used to activate photopolymerization on low-density microarrays, to image the resulting pattern of visual spots, and automatically interpret the image – providing the user with immediate results.
In addition to the ampliPHOX Colorimetric Detection Technology, InDevR also supplies Custom Low Density Microarrays specifically designed to work with the ampliPHOX platform. The Custom Microarrays can include up to 850 unique probes per array. Research at the USDA has utilized ampliPHOX to profile Shiga toxin-producing Escherichia coli by identifying the O-antigen gene clusters and virulence genes.
FluChip.
The FluChip was invented by a joint team of scientists at the University of Colorado at Boulder and the Centers for Disease Control and Prevention (Atlanta) in an NIAID-supported effort led by then-Professor Kathy Rowlen. InDevR licensed the intellectual property from the University of Colorado and CDC in 2009. Identification of influenza viruses using the FluChip is one application InDevR is targeting in their development of a fully automated molecular diagnostics platform.
VaxArray.
VaxArray is a multiplexed immunoassay for quantifying influenza hemagglutinin (HA) protein. The assay is based on a “universal” panel of subtype‐specific monoclonal antibodies printed in an array format. This technology enables vaccine researchers and manufacturers to track HA concentration from crude extracts through finished product.
Vidia.
The Vidia™ Microarray Imaging System from InDevR delivers quantitative fluorescence results for multiplexed microarray assays.


Sinobioway Group

Sinobioway Group Co., Ltd. was one of the university-owned enterprises of Peking University (the other were Founder Group, Jade Bird Software and Peking University Science Park). The company currently majority (60%) owned by a Peking University professor and other employee of Peking University. The pinyin of the Chinese short name was Wèimíng Jítuán, literally Anonymous Group (or Unnamed Group). However, Sinobioway was not related to other Weiming Group, such as Weiming (Fujian) Investment Group.
Sinobioway Group was incorporated on 19 October 1992. The group now involved in pharmaceutical, agriculture, environment management and other industries.
Equity investments.
Sinobioway Group is the largest shareholder of Sinobioway Medicine () for 26.38% (as at 30 June 2016). Sinobioway Medicine was involved in the delisting of Sinovac Biotech. Sinobioway Medicine, full name "Shandong Sinobioway Medicine Co., Ltd." (formerly known as Wanchang Science & Technology), acquired "Sinobioway Medicine Co., Ltd." as part of a backdoor listing in 2015.
Sinobioway Group also owned 60% stake of an intermediate holding company () which was the largest shareholder of PKU Hi-tech (, now known as CAU Technology) for 37.94% shares. In 2005 the stake in the intermediate company were under auction by court ruling, in order to refurbish the debt of Sinobioway Group. It was acquired by a subsidiary of China Agricultural University.
Shareholders.
Sinobioway Group is 60% owned by an intermediate holding company Hainan Tiandao Investment () that was owned 83.38% by Pan Aihua (), a Peking University professor and chairman of the group; Yang Xiaomin (), the president for 8.80% stake, Luo Deshun (), the vice-president (and former staff of PKU in student affairs) for 3.94% stake and Zhao Furong (), the vice-president (and former auditor of PKU) for 3.88% stake. Another vice-president of the group, Wang Jun (), did not own any stake in the company. However, according to the National Enterprise Credit Information Publicity System, the stake of Sinobioway Group were pledged in full or in part several times by the intermediate holding and Zhao Furong, in October 2012 (by Zhao personally), December 2014, June 2015, November 2015 and December 2016, to Chengdu Haizhen Investment (twice, ), Guoyuan Trust (), Shenzhen Central Yunnan Commercial Factoring () and 1314 Fund ().
The second largest shareholder of Sinobioway Group was the Peking University for 40% stake.
In the past Zhao Furong owned 30% personally as the joint-second largest shareholder of Sinobioway Group (behind the Peking University which owned 40%) in 2005.


Cinitapride

Cinitapride (trade names Cintapro, Pemix) is a gastroprokinetic agent and antiemetic agent of the benzamide class which is marketed in India, Mexico, Pakistan and Spain. It acts as an agonist of the 5-HT1 and 5-HT4 receptors and as an antagonist of the 5-HT2 receptors.
Uses.
It is indicated for the treatment of gastrointestinal disorders associated with motility disturbances such as gastroesophageal reflux disease, non-ulcer dyspepsia and delayed gastric emptying. It may be also used in the management of nausea and vomiting.


Carlo Montemagno

Carlo Montemagno (August 7, 1956 – October 11, 2018) was an American engineer and expert in nanotechnology and biomedical engineering, focusing on futuristic technologies to create interdisciplinary solutions for the grand challenges in health, energy and the environment. He has been considered as one of the pioneers of bionanotechnology. Some of his fundamental contributions include the development of biomolecular motors for powering inorganic nanodevices while at Cornell and muscle-driven self-assembled nanodevices while at UCLA.
Academic career.
Montemagno received his bachelor's degree in Agricultural and Biological Engineering from Cornell University in New York, his master's degree in Petroleum and Natural Gas Engineering from Pennsylvania State University, and his doctoral degree in Civil Engineering and Geological Sciences from the University of Notre Dame in Indiana.
Montemagno died in office while serving as the Chancellor of Southern Illinois University Carbondale. Right before moving to SIU, he directed the interdisciplinary Ingenuity Lab at the University of Alberta in Edmonton, Canada. He also served as the Director of the Biomaterials Program for the Canadian Research Council's National Institute for Nanotechnology as well as a Strategic Research Chair in Intelligent Nanosystems for the National Research Council. Before joining the University of Alberta, he was the Founding Dean of the College of Engineering and Applied Sciences at the University of Cincinnati.
His previous academic appointments include being the Founding Chair of the Department of Bioengineering and Biomedical Engineering, Co-Director of the NASA Center for Cell Mimetic Space Exploration, and Associate Director of the California Nanosystems Institute at the University of California, Los Angeles, the Director of the Biomedical Engineering Graduate Program at Cornell University and the Group Leader in Environmental Physics at the Argonne National Laboratory in Chicago. He also served in the U. S. Navy Civil Engineer Corps for nine years, leaving with the rank of lieutenant.
Awards and honors.
Throughout his career, Montemagno received many awards for his scientific innovations, including the Feynman Prize in Nanotechnology (for creating single molecule biological motors with nano-scale silicon devices), the Earth Award Grand Prize (for cell-free artificial photosynthesis with over 95% efficiency) and the CNBC Business Top 10 Green Innovators award (for Aquaporin Membrane water purification and desalination technology). He was named a Bill & Melinda Gates Grand Challenge Winner for his development of an oral vaccine delivery system that increased vaccine stability. He was a Fellow for the American Institute for Medical and Biomedical Engineering, the American Academy for Nanomedicine and the NASA Institute for Advanced Concepts.
Personal life.
Carlo Montemagno was born in 1956 to Gasper Patrick and Jacqueline Ann (Graham) Montemagno in Bronx, NY. He married Pamela Ann LaCava in 1976, and they remained married until his death. He was an avid reader and collector of books and an aerobatic and commercial pilot. He also enjoyed dog sports, falconry, ice climbing, science fiction, war movies and disco. Montemagno died in 2018 in St. Louis due to complications arising from cancer.


Hairy RNA localisation element (HLE)

The hairy localisation element (HLE) is an RNA element found in the 3' UTR of the hairy gene. HLE contains two stem-loops. HLE is essential for the mediation of apical localisation and the two stem-loop structures act to allow the recognition of hairy mRNA by the localisation machinery. HLE is found in "Drosophila" species.


Methyltransferase/kinase WbdD

Methyltransferase/kinase WbdD and "WbdD" is a bifunctional enzyme that regulates the length of the LPS O-antigen polysaccharide chain. Stops the polymerization of the chain by phosphorylating and then methylating the phosphate on the terminal sugar. This terminal modification is essential for export of the O-antigen across the inner membrane. WbdD is also required for correct localization of the WbdA mannosyltransferase.
This protein is involved in the pathway LPS O-antigen biosynthesis, which is part of Bacterial outer membrane biogenesis.
Catalytic activities:
S-adenosyl-L-methionine + 3-O-phospho-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3))(n)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-alpha-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol = S-adenosyl-L-homocysteine + 3-O-methylphospho-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3))(n)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-alpha-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol.
ATP + alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3))(n)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-alpha-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol = ADP + 3-O-phospho-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-(alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3))(n)-alpha-D-Man-(1->3)-alpha-D-Man-(1->3)-alpha-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol.


Macroscelides micus

Macroscelides micus (common name Etendeka round-eared sengi or Etendeka round-eared elephant shrew) is a species of elephant shrew in the family Macroscelididae. It is only found in gravel plains in the Etendeka formation of north-west Namibia. Measuring about long and weighing less than an ounce (28 grams), the species is the smallest in the elephant shrew family.
Description.
"Macroscelides micus" is the smallest known elephant shrew. Its body shape resembles that of a long-nosed mouse. However, as a member of the superorder Afrotheria, it is actually more closely related to elephants and manatees than mice. It has pink skin and red fur which helps it camouflage itself against the volcanic rocks of its environment. It weighs less than one ounce (28 grams) and is long, including the tail, when fully grown. "M. micus" has long, thin legs relative to its body.
"M. micus" does not burrow, instead sleeping in bushes. It uses its long nose to hunt for ground insects. Some elephant shrew species are known to be monogamous and mate for life. It is unknown if this is the case for "M. micus". The young of "M. micus", which are often born as twins, are capable of running from birth.
Discovery and identification.
"Macroscelides micus" was first spotted as an unusual sample (collected in 2006) among a collection of elephant shrews stored at the California Academy of Sciences, its red fur distinguishing it from other specimens. Genetic testing suggested it was a distinct species, but additional evidence was needed to confirm the finding. Dumbacher "et al." traveled to the Namib Desert nine times over a number of years where they set traps baited with peanut butter, oats, and Marmite. A total of 21 elephant shrew specimens were obtained, 15 of which belonged to the new species.
In 2014, Dumbacher "et al." formally described "M. micus" as a new species. The specific name comes from the Greek "mikros", meaning small. The "Etendeka" in the common name is the native word for the mountain range where "M. micus" lives. The scientific team speculated the species had not previously been identified because it has a small range in a remote area that is hard to reach.
Related species.
"Macroscelides micus" is sympatric with "Macroscelides flavicaudatus", but remains physically and genetically distinguishable from it. The study which first identified "M. micus" did not find evidence of gene flow or interbreeding between the populations. Additionally, the species live in different habitats. "M. micus" is found among the gravel at the bases of hills and mountains in low-lying areas of the Etendeka geological formation; "M. flavicaudatus" is found among sedimentary deposits in the Awahab Outliers and river valleys.
"M. micus" does not overlap "Macroscelides proboscideus" geographically. A maximum likelihood analysis of four genes by computational phylogenetics indicated that "M. proboscideus" and "M. flavicaudatus" are sister species, with "M. micus" being less closely related.
The authors also explained several limitations and confusions involving an enigmatic report of "Macroscelides melanotis" (Ogleby 1838), whose type specimen was not available for destructive DNA testing and had an "unnatural" appearance. Recommending "M. melanotis" be treated as a "nomen dubium", they expressed doubt that the described characteristics were consistent with "M. micus": "The reported pale, reddish brown chest color is not visible on the specimen, nor is the dunnish white abdomen or throat."


Bluebird bio

bluebird bio, Inc., based in Cambridge, Massachusetts, is a biotechnology company that develops gene therapies for severe genetic disorders and cancer.
The company's only - in the European Union (EU) - approved drug is betibeglogene autotemcel (Zynteglo), which treats transfusion-dependent beta thalassemia (TDT), a rare genetic blood disorder, and has been approved for use by the European Medicines Agency. The company has been criticized for the $1.8 million cost of the drug, which is the second most expensive drug in the world.
The company is developing LentiGlobin gene therapy for the treatment of sickle cell disease and cerebral adrenoleukodystrophy. It is also developing T cell product candidates to treat acute myeloid leukemia, Merkel-cell carcinoma, diffuse large B-cell lymphoma, and MAGEA4 solid tumors.
History.
The company was founded as Genetix Pharmaceuticals in April 1992 by MIT faculty members Philippe Leboulch and Irving London.
In 2001, Walter Ogier was appointed Chief Executive Officer of Genetix Pharmaceuticals, and the company was focused on the development of LentiglobinTM for the treatment of sickle cell disease and thalassemia major (beta-thalassemia), the two most globally prevalent severe human genetic diseases.
In September 2010, preliminary results of clinical trials of LentiglobinTM at Hospital Necker in Paris France were published in the journal Nature by Drs. Marina Cavazzano-Calvo and Philippe Leboulch, scientific founder of Genetix Pharmaceuticals / bluebird bio. Stable (21 months) transfusion independence had been successfully achieved by a patient with severe beta-thalassemia who had been treated with Lentiglobin 2 years earlier. This represented the first-ever long term correction of a major human genetic disease by gene therapy. Nature 467, 318–322 (2010)
Also in September 2010, the company was renamed bluebird bio and Nick Leschly was named chief executive officer.
In June 2013, the company became a public company via an initial public offering, raising $116 million.
In June 2014, the company acquired Precision Genome Engineering Inc. for up to $156 million.
In November 2017, Celgene, now Bristol-Myers Squibb (BMS), announced a collaboration with bluebird bio regarding bb2121 Anti-BCMA CAR-T Cell Therapy. In May 2020 the FDA issued a refusal to file letter to BMS and bluebird bio's marketing application seeking approval of idecabtagene vicleucel (ide-cel) for patients with heavily pre-treated relapsed and refractory multiple myeloma. In September 2020, the FDA accepted bluebird’s marketing application for ide-cel in and established a PDUFA goal date of March 27, 2021. US approval of ide-cel by March 31, 2021 is one of the required remaining milestones of the contingent value rights (CVR) issued upon the close of Bristol Myers Squibb's purchase of Celgene in 2019. Ide-cel is a BCMA-directed genetically modified autologous CAR-T-cell immunotherapy.
In August 2018, the company announced a collaboration with Regeneron Pharmaceuticals to discover, develop and commercialize new cell therapies for cancer.


4-NEMD

4-NEMD is a potent sedative drug which acts as a selective alpha-2 adrenergic agonist. It is closely related to dexmedetomidine but is several times more potent. Like other alpha-2 agonists, it produces sedative and muscle relaxant effects but without producing respiratory depression. It is not currently used in medicine but has been researched as the basis for a potential new generation of alpha-2 agonist drugs, which may have selectivity for the different subtypes of the alpha-2 receptor. It has two isomers, with the (S) isomer being the more potent, as with medetomidine. 4-NEMD was also investigated by the United States military as an anaesthetic agent, most likely for use in surgery but possibly also for use as a non-lethal incapacitating agent, although this has not been officially confirmed.