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Waterborne resins see article Electrophoretic deposition The resins used for electrodeposition are usually epoxy, acrylic or phenolic resin types. They are formulated with functional groups which when neutralised form ionic groups on the polymer backbone. These confer water solubility on the polymer. They are available as anodic versions which deposit on the cathode of an electrochemical cell or cathodic which deposit on the cathode. Cathodic electrodeposition resins dominate and they have revolutionised corrosion protection in the automotive industry. They are applied as OEM (Original Equipment Manufacture) rather than as a refinishing system. Cathodic resins contain amines on the polymer backbone which are neutralised by acids groups such as acetic acid to give a stable aqueous dispersion. When an electric current is passed through a car body that is dipped in a bath containing a paint based on a cathodic electrodeposition resin, the hydroxyl ions formed near the cathode deposit the paint on the car body. The electric current needed for this is determined by the number of ionic centres. Dispersions of waterborne resins for electrocoating usually contain some co-solvents such as butyl glycol and isopropanol and are usually very low in solids content i.e. 15%. They usually have molecular weights in the region of 3–4000. Paints based on them tend to have PVCs of less than 10 i.e. a very high binder to pigment ratio. Many resins are available waterborne but can be hybrids or blends | https://en.wikipedia.org/wiki?curid=63417066 |
Waterborne resins An example would be polyurethane dispersions blended or hybridized with acrylic resins. Waterborne epoxy resins may be modified with acrylate and then further modified with side chains having many fluorine atoms on them. see main article Water Water is in some ways an unusual chemical. It is a very powerful and universal solvent. Most liquids reduce in volume on freezing, but water expands. It occurs naturally on earth in all three states of solid (ice), liquid (water) and gas(water vapour and steam). At 273.16 K or 0.16 °C (known as the triple point) it can coexist in all three states simultaneously. It has a very low molecular weight of 18 and yet a relatively high boiling point of 100 C. This is due to inter molecular forces and in particular hydrogen bonding. The surface tension is also high at 72 dynes/cm (mN/metre) which affects its ability to wet certain surfaces. It evaporates (latent heat of evaporation 2260 kJ per kg) very slowly in comparison to some solvents and hardly at all when the relative humidity is very high. It has a very high specific heat capacity (4.184 kJ/kg/K ) and that is why it is used in central heating systems in the United Kingdom and Europe. These factors have to be borne in mind when formulating waterborne resins and other water based systems such as adhesives and coatings | https://en.wikipedia.org/wiki?curid=63417066 |
Waterborne resins find use in industrial coatings, UV coatings, floor coatings, hygiene coatings, wood coatings, adhesives, concrete coatings, automotive coatings, clear coatings and anticorrosive applications including waterborne epoxy based anticorrosive primers They are also used in the design and manufacture of medical devices such as the polyurethane dressing, a liquid bandage based on polyurethane dispersion.. Over the years they have also been used in polymer modified cements and repair mortars | https://en.wikipedia.org/wiki?curid=63417066 |
Caesium cyanide (chemical formula: CsCN) is the caesium salt of hydrogen cyanide. It is a white solid, easily soluble in water, with a smell reminiscent of bitter almonds, and with crystals similar in appearance to sugar. has chemical properties similar to potassium cyanide and it is a very toxic chemical. Hydrogen cyanide reacts with caesium hydroxide giving caesium cyanide and water: | https://en.wikipedia.org/wiki?curid=63425559 |
Guanine tetrad In molecular biology, a guanine tetrad (also known as a G-tetrad or G-quartet) is a structure composed of four guanine bases in a square planar array. They most prominently contribute to the structure of G-quadruplexes, where their hydrogen bonding stabilizes the structure. Usually, there are at least two guanine tetrads in a G-quadruplex, and they often feature Hoogsteen-style hydrogen bonding. Guanine tetrads are formed by sequences rich in guanine, such as GGGGC. They may also play a role in the dimerization of non-endogenous RNAs to facilitate the replication of some viruses. Guanine tetrads dimerize through their 5' ends since it is more energetically favorable in terms of free energy. They can be stabilized by central cations, such as lithium, sodium, potassium, rubidium, or cesium. However, they still form a variety of different structures. Guanine tetrads are not always stable, but the sugar-phosphate backbone of DNA can assist in stability of the guanine tetrads themselves. Guanine tetrads are more stable when stacked, as intermolecular forces between each layers help stabilize them. Guanine tetrads can also influence recombination, replication, and transcription. For instance, guanine tetrads are found in the promoter region of the Myc family of oncogenes. They also function in immunoglobulin class switching and may play a role in the genome of HIV. Guanine tetrads appear frequently in the telomeric regions of DNA. | https://en.wikipedia.org/wiki?curid=63426903 |
COVID-19 drug development COVID‑19 drug development is the research process to develop a preventative vaccine or therapeutic prescription drug that would alleviate the severity of 2019-20 coronavirus disease (COVID‑19). Internationally during April 2020, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing 115 vaccine candidates and 249 potential therapies for COVID‑19 disease in various stages of preclinical or clinical research. By late April, some 330 clinical trials were in progress worldwide to evaluate potential therapies against COVID-19. The World Health Organization (WHO), European Medicines Agency (EMA), US Food and Drug Administration (FDA), and the Chinese government and drug manufacturers were coordinating with academic and industry researchers to speed development of vaccines, antiviral drugs, and post-infection therapies. The International Clinical Trials Registry Platform of the WHO recorded 536 clinical studies to develop post-infection therapies for COVID‑19 infections, with numerous established antiviral compounds for treating other infections under clinical research to be repurposed. In March, the WHO initiated the "SOLIDARITY Trial" in 10 countries, enrolling thousands of people infected with COVID‑19 to assess treatment effects of four existing antiviral compounds with the most promise of efficacy | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development A dynamic, systematic review was established in April 2020 to track the progress of registered clinical trials for COVID‑19 vaccine and therapeutic drug candidates. Vaccine and drug development is a multistep process, typically requiring more than five years to assure safety and efficacy of the new compound. In February 2020, the WHO said it did not expect a vaccine against SARS-CoV-2 – the causative virus for COVID‑19 – to become available in less than 18 months, and conservative estimates of time needed to prove a safe, effective vaccine is about 12 months (early 2021). Several national regulatory agencies, such as EMA and FDA, approved procedures to expedite clinical testing. By April, four potential post-infection therapies – favipiravir, remdesivir, lopinavir and hydroxychloroquine (or chloroquine) – were in the final stage of human testing – Phase III-IV clinical trials – and five vaccine candidates had entered the second stage of human safety, dosing, and efficacy evaluation, Phase II. Drug development is the process of bringing a new infectious disease vaccine or therapeutic drug to the market once a lead compound has been identified through the process of drug discovery. It includes laboratory research on microorganisms and animals, filing for regulatory status, such as via the FDA, for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development The entire process – from concept through preclinical testing in the laboratory to clinical trial development, including Phase I-III trials – to approved vaccine or drug typically takes more than a decade. Development of a COVID‑19 vaccine or therapeutic antiviral drug begins with matching a chemical concept to the potential prophylactic mechanism of the future vaccine or antiviral activity in vivo. New chemical entities (NCEs, also known as "new molecular entities" or NMEs) are compounds that emerge from the process of drug discovery to specify a vaccine or antiviral therapeutic candidate having promise for activity against a biological target related to COVID‑19 disease. At the beginning of vaccine or drug development, little is known about the safety, toxicity, pharmacokinetics, and metabolism of the NCE in humans. It is the function and obligation of drug development to assess all of these parameters prior to human clinical trials to prove safety and efficacy. A further major objective of drug development is to recommend the dose and schedule for the first use in a human clinical trial ("first-in-human" [FIH] or First Human Dose [FHD], previously also known as "first-in-man" [FIM]). In addition, drug development must establish the physicochemical properties of the NCE: its chemical makeup, stability, and solubility. Manufacturers must optimize the process they use to make the chemical so they can scale up from a medicinal chemist producing milligrams, to manufacturing on the kilogram and ton scale | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development They further examine the product for suitability to package as capsules, tablets, aerosol, intramuscular injectable, subcutaneous injectable, or intravenous formulations. Together, these processes are known in preclinical and clinical development as "chemistry, manufacturing, and control" (CMC). Many aspects of drug development focus on satisfying the regulatory requirements of drug licensing authorities. These generally constitute tests designed to determine the major toxicities of a novel compound prior to first use in humans. It is a regulatory requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the body that might be affected by the drug (e.g., the skin if the new vaccine is to be delivered by skin injection). Increasingly, these tests are made using "in vitro" methods (e.g., with isolated cells), but many tests can only be made by using experimental animals to demonstrate the complex interplay of metabolism and drug exposure on toxicity. The information is gathered from this preclinical testing, as well as information on CMC, and submitted to regulatory authorities (in the US, to the FDA), as an Investigational New Drug (IND) or Biologics License Application application for a vaccine | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development If the IND is approved, development moves to the clinical phase, and the progress of performance in humans – if a vaccine under development in the United States – is monitored by the FDA in a "vaccine approval process." Over 2018–20, new initiatives to stimulate vaccine and antiviral drug development included partnerships between governmental organizations and industry, such as the European Innovative Medicines Initiative, the US "Critical Path Initiative" to enhance innovation of drug development, and the "Breakthrough Therapy" designation to expedite development and regulatory review of promising candidate drugs. To accelerate refinement of diagnostics for detecting COVID‑19 infection, a global diagnostic pipeline tracker was formed. During March 2020, the Coalition for Epidemic Preparedness Innovations (CEPI) initiated an international COVID‑19 vaccine development fund, with the goal to raise for vaccine research and development, and committed to investments of in vaccine development across several countries. The Canadian government announced in funding for 96 research projects on medical countermeasures against COVID‑19, including numerous vaccine candidates at Canadian universities, with plans to establish a "vaccine bank" of new vaccines for implementation if another coronavirus outbreak occurs. The Bill & Melinda Gates Foundation invested 150 million in April for development of COVID-19 vaccines, diagnostics, and therapeutics | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development In March 2020, the United States Department of Energy, National Science Foundation, NASA, industry, and nine universities pooled resources to access supercomputers from IBM, combined with cloud computing resources from Hewlett Packard Enterprise, Amazon, Microsoft, and Google, for drug discovery. The COVID‑19 High Performance Computing Consortium is also being used to forecast disease spread, model possible vaccines, and screen thousands of chemical compounds to design a COVID‑19 vaccine or therapy. The C3.ai Digital Transformation Institute, an additional consortium of Microsoft, six universities (including the Massachusetts Institute of Technology, a member of the first consortium), and the National Center for Supercomputer Applications in Illinois, working under the auspices of C3.ai, an artificial intelligence software company, are pooling supercomputer resources toward drug discovery, medical protocol development and public health strategy improvement, as well as awarding large grants to researchers who propose to use AI to carry out similar tasks by May. In March 2020, the distributed computing project Folding@home launched a program to assist drug developers, initially simulating protein targets from SARS-CoV-2 virus and the related SARS-CoV virus, which has been studied previously | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development Clinical trial programs involve three, multiple-year stages toward product approval, and a fourth, post-approval stage for ongoing safety monitoring of the vaccine or drug therapy: The process of defining characteristics of the drug does not stop once an NCE is advanced into human clinical trials. In addition to the tests required to move a novel vaccine or antiviral drug into the clinic for the first time, manufacturers must ensure that any long-term or chronic toxicities are well-defined, including effects on systems not previously monitored (fertility, reproduction, immune system, among others). If a vaccine candidate or antiviral compound emerges from these tests with an acceptable toxicity and safety profile, and the manufacturer can further show it has the desired effect in clinical trials, then the NCE portfolio of evidence can be submitted for marketing approval in the various countries where the manufacturer plans to sell it. In the United States, this process is called a "new drug application" or NDA. A clinical trial design in progress may be modified as an "adaptive design" if accumulating data in the trial provide early insights about positive or negative efficacy of the treatment. The global Solidarity and European Discovery trials of hospitalized people with severe COVID‑19 infection apply adaptive design to rapidly alter trial parameters as results from the four experimental therapeutic strategies emerge | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development Adaptive designs within ongoing Phase II-III clinical trials on candidate therapeutics may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, and coordinating design changes for a specific trial across its international locations. Most novel drug candidates (NCEs) fail during drug development, either because they have unacceptable toxicity or because they simply do not prove efficacy on the targeted disease, as shown in Phase II-III clinical trials. Critical reviews of drug development programs indicate that Phase II-III clinical trials fail due mainly to unknown toxic side effects (50% failure of Phase II cardiology trials), and because of inadequate financing, trial design weaknesses, or poor trial execution. A study covering clinical research in the 1980-90s found that only 21.5% of drug candidates that started Phase I trials were eventually approved for marketing. During 2006–15, the success rate of obtaining approval from Phase I to successful Phase III trials was under 10% on average, and 16.2% specifically for vaccines. The high failure rates associated with pharmaceutical development are referred to as an "attrition rate", requiring decisions during the early stages of drug development to "kill" projects early to avoid costly failures. One 2010 study assessed both capitalized and out-of-pocket costs for bringing a single new drug to market as about US$1.8 billion and $870 million, respectively | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development A median cost estimate of 2015-16 trials for development of 10 anti-cancer drugs was $648 million. In 2017, the median cost of a pivotal trial across all clinical indications was $19 million. The average cost (2013 dollars) of each stage of clinical research was US$25 million for a Phase I safety study, $59 million for a Phase II randomized controlled efficacy study, and $255 million for a pivotal Phase III trial to demonstrate its equivalence or superiority to an existing approved drug, possibly as high as $345 million. The average cost of conducting a 2015-16 pivotal Phase III trial on an infectious disease drug candidate was $22 million. The full cost of bringing a new drug (i.e., new chemical entity) to market – from discovery through clinical trials to approval – is complex and controversial. In a 2016 review of 106 drug candidates assessed through clinical trials, the total capital expenditure for a manufacturer having a drug approved through successful Phase III trials was $2.6 billion (in 2013 dollars), an amount increasing at an annual rate of 8.5%. Over 2003-13 for companies that approved 8-13 drugs, the cost per drug could rise to as high as $5.5 billion, due mainly to international geographic expansion for marketing and ongoing costs for Phase IV trials for continuous safety surveillance. Alternatives to conventional drug development have the objective for universities, governments, and the pharmaceutical industry to collaborate and optimize resources | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development According to two organizations tracking clinical trial progress on potential therapeutic drugs for COVID‑19 infections, 29 Phase II-IV efficacy trials were concluded in March or scheduled to provide results in April from hospitals in China – which experienced the first outbreak of COVID‑19 in late 2019. Seven trials were evaluating repurposed drugs already approved to treat malaria, including four studies on hydroxychloroquine or chloroquine phosphate. Repurposed antiviral drugs make up most of the Chinese research, with 9 Phase III trials on remdesivir across several countries due to report by the end of April. Other potential therapeutic candidates under pivotal clinical trials concluding in March-April are vasodilators, corticosteroids, immune therapies, lipoic acid, bevacizumab, and recombinant angiotensin-converting enzyme 2, among others. The COVID‑19 Clinical Research Coalition has goals to 1) facilitate rapid reviews of clinical trial proposals by ethics committees and national regulatory agencies, 2) fast-track approvals for the candidate therapeutic compounds, 3) ensure standardised and rapid analysis of emerging efficacy and safety data, and 4) facilitate sharing of clinical trial outcomes before publication. A dynamic review of clinical development for COVID‑19 vaccine and drug candidates was in place, as of April | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development By March 2020, the international Coalition for Epidemic Preparedness Innovations (CEPI) committed to research investments of US$100 million across several countries, and issued an urgent call to raise and rapidly invest $2 billion for vaccine development. Led by the Bill and Melinda Gates Foundation with partners investing million and coordinating with the World Health Organization, the COVID‑19 Therapeutics Accelerator began in March, facilitating drug development researchers to rapidly identify, assess, develop, and scale up potential treatments. The COVID‑19 Clinical Research Coalition formed to coordinate and expedite results from international clinical trials on the most promising post-infection treatments. In early 2020, numerous established antiviral compounds for treating other infections were being repurposed or developed in new clinical research efforts to alleviate the illness of COVID‑19. Pivotal Phase III trials assess whether a candidate drug has efficacy specifically against a disease, and – in the case of people hospitalized with severe COVID‑19 infections – test for an effective dose level of the repurposed or new drug candidate to improve the illness (primarily pneumonia) from COVID‑19 infection. For an already-approved drug (such as hydroxychloroquine for malaria), Phase III-IV trials determine in hundreds to thousands of COVID‑19-infected people the possible extended use of an already-approved drug for treating COVID‑19 infection | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development As of early April 2020, 103 candidate therapeutics were in preclinical or a stage of Phase I-IV development, with trial results for 29 drug candidates expected during April. In March, the World Health Organization (WHO) launched the coordinated "Solidarity Trial" in 10 countries on five continents to rapidly assess in thousands of COVID‑19 infected people the potential efficacy of existing antiviral and anti-inflammatory agents not yet evaluated specifically for COVID‑19 illness. By late April, hospitals in over 100 countries were involved in the trial. The individual or combined drugs being studied are 1) lopinavir–ritonavir combined, 2) lopinavir–ritonavir combined with interferon-beta, 3) remdesivir or 4) (hydroxy)chloroquine in separate trials and hospital sites internationally. With about 15% of people infected by COVID‑19 having severe illness, and hospitals being overwhelmed during the pandemic, WHO recognized a rapid clinical need to test and repurpose these drugs as agents already approved for other diseases and recognized as safe. The Solidarity project is designed to give rapid insights to key clinical questions: Enrolling people with COVID‑19 infection is simplified by using data entries, including informed consent, on a WHO website. After the trial staff determines the drugs available at the hospital, the WHO website randomizes the hospitalized subject to one of the trial drugs or to the hospital standard of care for treating COVID‑19 | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development The trial physician records and submits follow-up information about the subject status and treatment, completing data input via the WHO Solidarity website. The design of the Solidarity trial is not double-blind – which is normally the standard in a high-quality clinical trial – but WHO needed speed with quality for the trial across many hospitals and countries. A global safety monitoring board of WHO physicians examine interim results to assist decisions on safety and effectiveness of the trial drugs, and alter the trial design or recommend an effective therapy. A similar web-based study to Solidarity, called "Discovery", was initiated in March across seven countries by INSERM (Paris, France). The Solidarity trial seeks to implement coordination across hundreds of hospital sites in different countries – including those with poorly-developed infrastructure for clinical trials – yet needs to be conducted rapidly. According to John-Arne Røttingen, chief executive of the Research Council of Norway and chairman of the Solidarity trial international steering committee, the trial would be considered effective if therapies are determined to "reduce the proportion of patients that need ventilators by, say, 20%, that could have a huge impact on our national health-care systems." During March, funding for the Solidarity trial reached million from 203,000 individuals, organizations and governments, with 45 countries involved in financing or trial management | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development During April, the British "Recovery Trial" was launched initially in 132 hospitals across the UK, expanding to become the world's largest COVID‑19 clinical study involving 5400 infected people under treatment at 165 UK hospitals, as of 17 April. The trial is examining different potential therapies for severe COVID‑19 infection: lopinavir/ritonavir, low-dose dexamethasone (an anti-inflammatory steroid), hydroxychloroquine, and azithromycin (a common antibiotic). Numerous candidate drugs under study as "supportive" treatments to relieve discomfort during illness, such as NSAIDs or bronchodilators, are not included in the table below. Others in early-stage Phase II trials or numerous treatment candidates in Phase I trials, are also excluded. Drug candidates in Phase I-II trials have a low rate of success (under 12%) to pass through all trial phases to gain eventual approval. Once having reached Phase III trials, therapeutic candidates for diseases related to COVID‑19 infection – infectious and respiratory diseases – have a success rate of about 72%. Chloroquine is an anti-malarial medication that is also used against some auto-immune diseases. Hydroxychloroquine is more commonly available than chloroquine in the United States. Although several countries use chloroquine or hydroxychloroquine for treatment of persons hospitalized with COVID‑19, as of March 2020 the drug has not been formally approved through clinical trials in the United States | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development Chloroquine has been recommended by Chinese, South Korean and Italian health authorities for the treatment of COVID‑19, although these agencies and the US CDC noted contraindications for people with heart disease or diabetes. In the United States, the experimental treatment is authorized only for emergency use for patients who are hospitalized but are not able to receive treatment in a clinical trial. In February 2020, both drugs were shown to effectively reduce COVID‑19 illness, but a further study concluded that hydroxychloroquine was more potent than chloroquine and had a more tolerable safety profile. Preliminary results from a trial indicated that chloroquine is effective and safe in COVID‑19 pneumonia, "improving lung imaging findings, promoting a virus-negative conversion, and shortening the disease course." On 18 March, the WHO announced that chloroquine and the related hydroxychloroquine would be among the four drugs studied as part of the Solidarity clinical trial. Hydroxychloroquine and chloroquine have numerous, potentially serious, side effects, such as retinopathy, hypoglycemia, or life-threatening arrhythmia and cardiomyopathy. Both drugs have extensive interactions with prescription drugs, affecting the therapeutic dose and disease mitigation. Some people have allergic reactions to these drugs | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development On 12 April, a preliminary clinical trial conducted at a hospital in Brazil was stopped when several people given high doses of chloroquine for COVID‑19 infection developed irregular heart rates, causing 11 deaths. The NIH recommends against the use of a combination of hydroxychloroquine and azithromycin because of the resulting increased risk of sudden cardiac death. Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir was "clearly effective". Of 35 patients in Shenzhen tested negative in a median of 4 days, while the length of illness was 11 days in the 45 patients who did not receive it. In a study conducted in Wuhan on 240 patients with pneumonia half were given favipiravir and half received umifenovir. The researchers found that patients recovered from coughs and fevers faster when treated with favipiravir, but that there was no change in how many patients in each group progressed to more advanced stages of illness that required treatment with a ventilator. On 22 March 2020, Italy approved the drug for experimental use against COVID‑19 and began conducting trials in the three regions most affected by the disease. The Italian Pharmaceutical Agency reminded the public that the existing evidence in support of the drug is scant and preliminary. A nucleotide analog, remdesivir is an antiviral drug candidate originally developed to treat Ebola virus disease. It is specifically an adenosine analog which inserts into viral RNA chains, causing premature breaking of the chains | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development It is being studied as a possible post-infection treatment for COVID-19. As of April 2020, there were nine Phase III trials on remdesivir across several countries. On 29 April 2020, the US National Institute of Allergy and Infectious Diseases (NIAID) announced interim results of a trial assessing 1,063 participants hospitalized with severe COVID-19, showing that remdesivir provided a 31% faster time to recovery from COVID-19 infection and improved symptoms in 11 days compared to placebo-treated people who required 15 days. Dr. Anthony Fauci, director of the NIAID stated, "the data shows remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery." In a clinical trial conducted in China over February-March 2020 and reported on 29 April, remdesivir was not effective in reducing the time for improvement from COVID-19 infections or deaths, and caused various adverse effects in the remdesivir-treated participants, requiring the investigators to terminate the trial. On 1 May 2020, the U.S. Food and Drug Administration granted Gilead Emergency Use Authorization of remdesivir to be distributed and used by licensed health care providers to treat adults and children hospitalized with severe COVID‐19. Severe COVID‐19 is defined as patients with an oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO), a heart‐lung bypass machine | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development Distribution of remdesivir under the EUA will be controlled by the U.S. government for use consistent with the terms and conditions of the EUA. Gilead will supply remdesivir to authorized distributors, or directly to a U.S. government agency, who will distribute to hospitals and other healthcare facilities as directed by the U.S. Government, in collaboration with state and local government authorities, as needed. Possible side effects of remdesivir are: The most common adverse effects in people treated with remdesivir were respiratory failure and blood biomarkers of organ impairment, including low albumin, low potassium, low count of red blood cells, low count of thrombocytes, and elevated bilirubin (jaundice). Other reported adverse effects include gastrointestinal distress, elevated transaminase levels in the blood (liver enzymes), infusion site reactions, and electrocardiogram abnormalities. Drug repositioning (also called drug repurposing) – the investigation of existing drugs for new therapeutic purposes – is one line of scientific research followed to develop safe and effective COVID‑19 treatments. Several existing antiviral medications, previously developed or used as treatments for Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV/AIDS, and malaria, are being researched as COVID‑19 treatments, with some moving into clinical trials | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development During the COVID‑19 outbreak, drug repurposing is the clinical research process of rapidly screening and defining the safety and efficacy of existing drugs already approved for other diseases to be used for people with COVID‑19 infection. In the usual drug development process, confirmation of repurposing for new disease treatment would take many years of clinical research – including pivotal Phase III clinical trials – on the candidate drug to assure its safety and efficacy specifically for treating COVID‑19 infection. In the emergency of a growing COVID‑19 pandemic, the drug repurposing process was being accelerated during March 2020 to treat people hospitalized with COVID‑19. Clinical trials using repurposed, generally safe, existing drugs for hospitalized COVID‑19 people may take less time and have lower overall costs to obtain endpoints proving safety (absence of serious side effects) and post-infection efficacy, and can rapidly access existing drug supply chains for manufacturing and worldwide distribution. In an international effort to capture these advantages, the WHO began in mid-March 2020 expedited international Phase II-III trials on four promising treatment options – the SOLIDARITY trial – with numerous other drugs having potential for repurposing in different disease treatment strategies, such as anti-inflammatory, corticosteroid, antibody, immune, and growth factor therapies, among others, being advanced into Phase II or III trials during 2020 | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development In March, the United States Centers for Disease Control and Prevention (CDC) issued a physician advisory concerning remdesivir for people hospitalized with pneumonia caused by COVID‑19: "While clinical trials are critical to establish the safety and efficacy of this drug, clinicians without access to a clinical trial may request remdesivir for compassionate use through the manufacturer for patients with clinical pneumonia." Phase I trials test primarily for safety and preliminary dosing in a few dozen healthy subjects, while Phase II trials – following success in Phase I – evaluate therapeutic efficacy against the COVID-19 disease at ascending dose levels (efficacy based on biomarkers), while closely evaluating possible adverse effects of the candidate therapy (or combined therapies), typically in hundreds of people. A trial design for Phase II studies of possible COVID-19 drugs is randomized, placebo-controlled, and conducted at multiple sites, while determining more precise, effective doses and monitoring for adverse effects. The success rate for Phase II trials to advance to Phase III (for all diseases) is about 31%, and for infectious diseases specifically, about 43%. Depending on its duration (longer more expensive) – typically a period of several months to two years – an average-length Phase II trial costs million (2013 dollars, including preclinical and Phase I costs). Successful completion of a Phase II trial does not reliably forecast that a candidate drug will be successful in Phase III research | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development Phase III trials for COVID-19 involve hospitalized participants, and test effectiveness of the treatment to prevent the disease, while monitoring for adverse effects at the optimal dose, such as in the multinational Solidarity trial. According to two sources reporting early-stage clinical trials on potential COVID-19 post-infection therapies, there were some 36 Phase II trials underway or planned to start in April 2020. According to one source (as of late April 2020), diverse categories of preclinical or early-stage clinical research for developing COVID‑19 therapeutic candidates were: In March 2020, the main protease of the SARS-CoV-2 virus was identified as a target for post-infection drugs. This enzyme is essential to the host cell to reproduce the ribonucleic acid of the virus. To find the enzyme, scientists used the genome published by Chinese researchers in January 2020 to isolate the main protease. Protease inhibitors approved for treating human immunodeficiency viruses (HIV) – lopinavir and ritonavir – have preliminary evidence of activity against the coronaviruses, SARS and MERS. As a potential combination therapy, they are used together in two Phase III arms of the 2020 global Solidarity project on COVID‑19. A preliminary study in China of combined lopinavir and ritonavir found no effect in people hospitalized for COVID‑19 | https://en.wikipedia.org/wiki?curid=63435931 |
COVID-19 drug development The term "preclinical research" is defined by laboratory studies in vitro and in vivo, indicating a beginning stage for development of a preventative vaccine, antiviral or other post-infection therapies, such as experiments to determine effective doses and toxicity in animals, before a candidate compound is advanced for safety and efficacy evaluation in humans. To complete the preclinical stage of drug development – then be tested for safety and efficacy in an adequate number of people infected with COVID‑19 (hundreds to thousands in different countries) – is a process likely to require 1–2 years for COVID‑19 therapies, according to several reports in early 2020. Despite these efforts, the success rate for drug candidates to reach eventual regulatory approval through the entire drug development process for treating infectious diseases is only 19%. | https://en.wikipedia.org/wiki?curid=63435931 |
List of gene therapies This page contains a list of commercially available gene therapies. | https://en.wikipedia.org/wiki?curid=63455108 |
Shvab–Zeldovich formulation The is an approach to remove the chemical-source terms from the conservation equations for energy and chemical species by linear combinations of independent variables, when the conservation equations are expressed in a common form. Expressing conservation equations in common form often limits the range of applicability of the formulation. The method was first introduced by V. A. Shvab in 1948 and by Yakov Zeldovich in 1949. For simplicity, assume combustion takes place in a single global irreversible reaction formula_1 where formula_2 is the ith chemical species of the total formula_3 species and formula_4 and formula_5 are the stoichiometric coefficients of the reactants and products, respectively. Then, it can be shown that the rate of moles produced per unit volume of any species formula_6 is constant and given by formula_7 where formula_8 is the mass of species i produced or consumed per unit volume and formula_9 is the molecular weight of species i. The main approximation involved in Shvab-Zeldovich formulation is that all binary diffusion coefficients formula_10 of all pairs of special are equal and equal to the thermal diffusion. In other words, Lewis number of all species are constant and equal to one. This puts a limitation on the range of applicability of the formulation since in reality, except for methane, ethylene, oxygen and some other reactants, Lewis numbers vary significantly from unity | https://en.wikipedia.org/wiki?curid=63465236 |
Shvab–Zeldovich formulation The steady, low Mach number conservation equations for the species and energy in terms of the rescaled independent variables are given by formula_11 where formula_12 is the mass fraction of species i, formula_13 is the specific heat at constant pressure of the mixture, formula_14 is the temperature and formula_15 is the formation enthalpy of species i, reduce to formula_16 where formula_17 is the gas density and formula_18 is the flow velocity. The formula_19 nonlinear equations can be replaced with formula_3 linear equations and one nonlinear equation. Suppose the nonlinear equation corresponds to formula_21 so that formula_22 then by defining the linear combinations formula_23 and formula_24, the governing equations reduce to formula_25 where the nonlinear reaction term disappears. | https://en.wikipedia.org/wiki?curid=63465236 |
Wheal Maid (also Wheal Maiden) is a former mine in the Camborne-Redruth-St Day Mining District, 1.5km east of St Day. Between 1800 and 1840, profits are said to have been up to £200,000. In 1852, the mine was almalgamated with Poldice Mine and Carharrack Mine and worked as St Day United mine. Throughout the 1970s and 1980s, the mine site was turned into large lagoons and used as a tip for two other nearby mines: Mount Wellington and Wheal Jane. The site was bought from Carnon Enterprises by Gwennap District Council for a price of £1 in 2002. An investigation by the Environment Agency that concluded in 2007 found that soil near the mine had high levels of arsenic, copper and zinc contamination and by 2012, it was deemed too hazardous for human activity. The mine gains attention during dry spells when the lagoons dry up and leaving brightly coloured stains on the pit banks and bed. In 2014, a 72-year-old man from Falmouth died at the site after what was initially thought to be a cycling accident. It was later found that the man had been murdered. A 34-year-old was found guilty and sentenced to life and to serve at least 28 years | https://en.wikipedia.org/wiki?curid=63475215 |
Timeline of crystallography This is a timeline of crystallography. | https://en.wikipedia.org/wiki?curid=63481723 |
Taiwan Typhoon and Flood Research Institute The (TTFRI) is a research institute which is part of the National Applied Research Laboratories of Taiwan. The was inaugurated in 2011 in the city of Taichung. Lee Cheng-shang was the inaugural Director. TTFRI is a coordinator of research into quantitative precipitation forecasting. TTFRI has worked with the Central Weather Bureau to develop a radar assimilation system which has increased the accuracy of the six hour rainfall forecast by twenty percent. In 2018 TTFRI began a project to improve the flood management of Cayo District in Belize in partnership with the Belizean Government which is one of Taiwan's few remaining official diplomatic allies. In 2015 TTFRI acquired a set of UAVs from Australia for use their typhoon research program. Early attempts to acquire UAVs in 2005 were scrapped due to stricter air traffic controls imposed as a result of global terrorism. | https://en.wikipedia.org/wiki?curid=63488346 |
Potassium selenide (KSe) is an inorganic compound formed from selenium and potassium. It can be produced by the reaction of selenium and potassium. If the two are combined in liquid ammonia, the purity is higher. has a cubic, antifluorite crystal structure. | https://en.wikipedia.org/wiki?curid=63488665 |
Arginine finger In molecular biology, an arginine finger is an amino acid residue of some enzymes. Arginine fingers are often found in the protein superfamily of AAA+ ATPases, GTPases, and dUTPases, where they assist in the catalysis of the gamma phosphate or gamma and beta phosphates from ATP or GTP, which creates a release of energy which can be used to perform cellular work. Thus, they are essential for many forms of life, and are highly conserved. Arginine fingers function through non-covalent interactions. They may also assist in dimerization, and while they are found in a wide variety of enzymes, they are not ubiquitous. Generally, the role of the arginine finger in catalysis is to function in transition state stabilization to allow water to perform a nucleophilic attack to cleave off a number of phosphate groups. However, there are exceptions, and arginine fingers can assist in other roles. Additionally, arginine fingers may be attached to different subunits or other proteins in a multiprotein complex. Arginine fingers sometimes interact with guanidinium during their role in catalysis. Arginine fingers often work with other features in their assistance of catalysis. For example, in some trimeric dUTPases, such as those of "M. tuberculosis", arginine fingers at the 64th and 140th residue can work with magnesium to cleave dUTP into dUMP and a pyrophosphate | https://en.wikipedia.org/wiki?curid=63491308 |
Arginine finger The underlying mechanism of action for this is a nucleophilic attack; the positively charged magnesium ion () pulls on an oxygen of the beta and gamma phosphates to allow water to hydrolyze the bond between the beta and alpha phosphates. The arginine fingers help stabilize the transition state. Arginine fingers often interact with other motifs such as the Walker motifs and to perform catalysis more efficiently. Arginine fingers are also present in Ras GTPases, where they help cleave GTP to turn Ras off. Ras is a GTPase which functions in signal transduction to regulate cell growth and division. In addition to being positively charged, which helps arginine fingers function as a catalyst, the arginine finger in Ras displaces solvent molecules and creates an optional charge distribution. Like those of dUPTases, the arginine fingers of Ras GTPases are assisted by a magnesium ion. Furthermore, multiple arginine finger residues can all point towards the same point, thus focusing their effect. Mutations affecting the arginine fingers of Ras lead to trouble catalyzing GTP by factors of around two to five orders of magnitude. Thus, as Ras is an oncogene and is activated and deactivated by the hydrolysis of GTP, mutations in Ras's arginine finger residues can lead to cancer. Glutamate also plays a role near arginine fingers and is stabilized by the arginines' backbone chain carboxyl groups, which are known as knuckles. In heterotrimeric G proteins, catalysis of GTP can be assisted by aluminum tetrafluoride () and RGS4 | https://en.wikipedia.org/wiki?curid=63491308 |
Arginine finger Heterotrimeric G proteins are larger three-part proteins serve in signal transduction of many pathways. The catalytic mechanism for GTP hydrolysis in heterotrimeric G proteins consists of an active state where catalysis is likely to occur and an inactive state where catalysis is unlikely. In the active state, stabilizes the transition state and points the arginine finger residue towards GTP. This causes increased charge density on the beta phosphate of GTP and planarization of the gamma phosphate, which creates an opening and reduces steric hindrance for water to hydrolyze the phosphoanhydride beta-gamma bond. This is because the gamma phosphate's bond to the beta phosphate bends, exposing its connection and allowing the subsequent nucleophilic substitution reaction initiated by water. The complex formed with RGS4 assists in this process by creating strain on the bond between the gamma and beta phosphates and assisting in distributing more charge onto the beta phosphate. ATP synthase consists of a F and F subunit. The F subunit contains alpha and beta subunits of its own which can assist in the formation of ATP, or hydrolyze it to serve as a proton pump. Though most catalytic actions happen on the beta subunits, the alpha subunits each contain an arginine finger. The role of the arginine finger in ATP synthase is akin to the function of the arginine finger residues of G proteins; to help split ATP | https://en.wikipedia.org/wiki?curid=63491308 |
Arginine finger For example, if the arginine of the arginine finger is substituted by lysine, possibly due to a missense mutation, the αR364K mutant results. In the αR364K mutant, the ability of ATP synthase to hydrolyze ATP is decreased around a thousandfold compared to the wild type. A RecQ helicase is one of a family of helicases that helps reduce sister chromatid exchange during meiosis to lower mutation rates. RecQ helicases are found in many organisms, ranging from "E. coli" to humans. One of these helicases, the Bloom syndrome protein, contains an arginine finger which assists in its hydrolysis of ATP. In humans, the arginine finger of the Bloom syndrome protein is Arg982. The RecQ helicase, along with most proteins containing arginine fingers, is inhibited by sodium orthovanadate, which interferes with the arginien finger residue. | https://en.wikipedia.org/wiki?curid=63491308 |
Calconcarboxylic acid (IUPAC name 3-hydroxy-4-[(2-hydroxy-4-sulfonaphthalen-1-yl)diazenyl]naphthalene-2-carboxylic acid; commonly called Patton and Reeder's Indicator) is an azo dye (chemical formula CHCHOHCH) which is used as an indicator for complexometric titrations of calcium with ethylenediaminetetraacetic acid (EDTA) in the presence of magnesium. Structurally, it is similar to eriochrome blue black R, which is obtained from calconcarboxylic acid by decarboxylation and reaction with sodium hydroxide. Calconcarboxlic acid is soluble in water and a variety of other solvents, including water, sodium hydroxide, ethanol and methanol. It has a violet colour in dissolved form in ethanol. The melting point of calconcarboxylic acid is at approximately 300 °C, where it undergoes thermal decomposition. Though the determination of calcium and magnesium by complexometric titration with standard solutions of disodium dihydrogen tetraacetate, utilising Eriochrome Black T as indicator is widely accepted and quite adequately understood, it, like other complexometric titration methods, suffers from the limitations of having an indistinct end point (where a photometric titrator is needed to provide acceptable accuracy) and/or having to separate the metals before titration can occur. was thus adopted as a superior alternative due to its ability to give a good and visual end point and its rapid performance even with the presence of magnesium | https://en.wikipedia.org/wiki?curid=63498286 |
Calconcarboxylic acid As described by Patton & Reeder (1956), calconcarboxylic acid can be synthesised by coupling diazotized 1-amino-2-naphthol-4-sulfonic acid with 2-hydroxy-3-napthoic acid. As mentioned previously, calconcarboxylic acid (or Patton-Reeder Indicator) is used for the determination of calcium ion concentration by complexometric titration. The method uses EDTA (ethylenediaminetetraacetic acid) to form a complex with calcium (Ca) ions. The Patton-Reeder Indicator (hereafter PR) is used as the indicator. PR alone is a dye with blue colour, but when it forms a complex with the suspended calcium ions, it undergoes a colour change from blue to pink/red. However, it must be noted that the metal ion-PR complex has less stability than the metal ion-EDTA complex. Hence, when a Ca-PR complex comes into contact with EDTA, the Ca2+ ions react with EDTA to form a stronger, more stable complex with it (Ca-EDTA). For the complexometric titration, the indicator is first added to the titrant containing the calcium ions to form the calcium ion-indicator complex (Ca-PR) with a pink/red colour. This is then titrated against a standard solution of EDTA. The endpoint can be observed when the indicator produces a sharp, stable colour change from wine red to pure blue, which occurs at pH values between 12 and 14, this indicates the end point of the titration, as the Ca-PR complexes have been completely replaced by the Ca-EDTA complexes and hence the PR indicator reverts to its blue colour | https://en.wikipedia.org/wiki?curid=63498286 |
Calconcarboxylic acid The reaction can be given by: The Patton-Reeder Indicator is often used here in the form of a triturate. It also must be noted that this method of complexometric titration is dependent on the pH of the solution being sufficiently high to ensure that magnesium ions precipitate as magnesium hydroxide before the PR indicator is added to prevent interference with the results, as if magnesium were present, the EDTA would also form complexes with it. Concentrated sodium hydroxide or Potassium hydroxide is usually added to the solution to this end. The accuracy of this method may also be affected by the presence of metal ions such as copper, iron, cobalt, zinc or manganese in sufficiently high concentrations. | https://en.wikipedia.org/wiki?curid=63498286 |
C12-15 pareth-12 is the INCI name for an emulsifier and surfactant commonly used in cosmetics formulations. It is a polyethylene glycol ether formed by combining synthetic C–C fatty alcohols with 12 moles of ethylene oxide. | https://en.wikipedia.org/wiki?curid=63499308 |
Henry A. Bent (December 21, 1926–January 3, 2015) was a professor of physical chemistry who studied molecular orbitals to develop atomic hybridization and valence bond theories. Bent's rule, which predicts the orbital hybridization of an central atom as a function of the electronegativities of the substituents attached to it, is named for him. He made major contributions to the analysis of the entropy component of thermodynamic free energy in relation to the second law of thermodynamics and whether various chemical processes are spontaneous. Bent was also interested in the periodic laws of the elements and promoted the left-step alternative periodic table (based on orbital-filling rules). | https://en.wikipedia.org/wiki?curid=63514630 |
Nitensidine D is a toxic alkaloid natural product that was isolated from the leaves of the South American legume Pterogyne nitens.. It is also hypothesized to be a possible intermediate in the still unknown, seemingly monoterpene based, terrestrial biosynthetic pathway for tetrodotoxin. | https://en.wikipedia.org/wiki?curid=63530577 |
Dysprosium(III) fluoride is an inorganic compound of dysprosium with a chemical formula DyF. It can be produced by mixing dysprosium(III) chloride or dysprosium(III) carbonate into 40% hydrofluoric acid. | https://en.wikipedia.org/wiki?curid=63554061 |
METRNL Meteorin-like/Meteorin-Beta (Metrnl) is a small (~27kDa) secreted protein encoded by a gene called meteorin-like (METRNL). is highly expressed in mucosal tissues, skin and activated macrophages. Metrnl has also been described to be a hormone A screen of human skin-associated diseases showed significant over-expression of in psoriasis, prurigo nodularis, actinic keratosis and atopic dermatitis. is also up-regulated in synovial membranes of human rheumatoid arthritis. Metrnl participates in the control of inflammatory responses and is a critical regulator of muscle regeneration. | https://en.wikipedia.org/wiki?curid=63556051 |
Olga Bogdanova Olga Konstantinovna Bogdanova (Russian: Ольга Константиновна Богда́нова; 29 June n.s., 1896 — March 1982) was a Soviet chemist, a specialist in organic catalysis. In the 1920s Bogdanova worked in a laboratory at a synthetic rubber factory. From the early 1930s she worked at the N. D. Zelinsky Institute of Organic Chemistry of the Academy of Sciences of the Soviet Union (now: Russian Academy of Sciences). Bordanova was a student and, for many years, a colleague of Academicians N. D. Zelinsky and A. A. Balandin. Bogdanova held a Ph.D. in Chemistry, and she was a senior research associate. She was buried in the Vagankovo Cemetery. | https://en.wikipedia.org/wiki?curid=63563827 |
Marine Chemistry (journal) Marine Chemistry is an international peer-reviewed scientific journal for publications in the field of chemistry in the marine environment. The journal is currently published by Elsevier. Its editor-in-chief is T.S. Bianchi. According to the Journal Citation Reports, Marine Chemistry had a 2018 impact factor of 2.713. | https://en.wikipedia.org/wiki?curid=63586322 |
Archaeal translation is the process by which messenger RNA is translated into proteins in archaea. Not much is known on this subject, but on the protein level it seems to resemble eukaryotic translation. Most of the initiation, elongation, and termination factors in archaea have homologs in eukaryotes. Shine-Dalgarno sequences only are found in a minority of genes for many phyla, with many leaderless mRNAs probably initiated by scanning. The process of ABCE1 ATPase-based recycling is also shared with eukaryotes. Being a prokaryote without a nucleus, archaea do perform transcription and translation at the same time like bacteria do. | https://en.wikipedia.org/wiki?curid=63589365 |
Archaeal transcription is the process in which a segment of archeaeal DNA is copied into a newly synthesized strand of RNA using the sole Pol II-like RNA polymerase (RNAP). The process occurs in three main steps: initiation, elongation, and termination; and the end result is a strand of RNA that is complementary to a single strand of DNA. A number of transcription factors govern this process with homologs in both bacteria and eukaryotes, with the core machinery more similar to eukaryotic transcription. Because archaea lack a membrane-enclosed nucleus like bacteria do, transcription and translation can happen at the same time on a newly-generated piece of mRNA. Operons are widespread in archaea. Initiation in archaea is governed by TATA-binding protein (TBP), factor B (TFB), and factor E (TFE) that are homologous to eukaryotic TBP, TFIIB, and TFIIE respectively. These factors recognize the promoter core sequence (TATA box, B recognition element) upstream of the coding region and recruits the RNAP to form a closed transcription preinitiation complex (PIC). The PIC is turned into an open state with the local DNA helix "melting" to load the template strand of DNA. The RNAP undergoes "abortive initiation": it makes and releases many short (2-15nt) segments before generating a transcript of significant length. This continues until it moves past the promoter (promoter escape), loosening TBP's grasp on the DNA, and swapping TFE out for elongation factors Spt4/5. How this escape happens exactly remains to be studied | https://en.wikipedia.org/wiki?curid=63589689 |
Archaeal transcription After getting out of the promoter region, the RNAP moves into the elongation state, where it keeps growing the new RNA strand in a processive process. Double stranded DNA that enters from the front of the enzyme is unzipped to avail the template strand for RNA synthesis. For every DNA base pair separated by the advancing polymerase, one hybrid RNA:DNA base pair is immediately formed. DNA strands and nascent RNA chain exit from separate channels; the two DNA strands reunite at the trailing end of the transcription bubble while the single strand RNA emerges alone. A number of elongation factors help with the rate and processivity of the RNAP. Factors of the Spt4/Spt5 family (bacterial homolog of Spt5 is called "NusG") stimulate transcription by binding to the RNAP clamp on one side of the DNA channel and to the gate loop on the other. The resultant DSIF locks the clamp into a closed state to prevent the elongation complex (EC) from dissociating. Spt5 also has a NGN domain that helps the two strands separate. A KOW domain probably hooks the RNAP up to a ribosome so that translation and transcription happen together. Some archaea have a Elf1 homolog that might also act as an elongation factor. The RNAP occasionally stops and starts moving backwards when it encounters a roadblock or some difficult sequences. When this happens, the EC gets stuck because the reactive 3' edge of the RNA is out of the active site | https://en.wikipedia.org/wiki?curid=63589689 |
Archaeal transcription The transcript cleavage factor TFS (a TFIIS homolog) helps resolve this issue by generating a cut so that a new 3' end is available in the active site. Some archaeon have up to 4 paralogs of TFS with divergent functions. Not much is known about archaeal termination. Euryarchaeal RNAPs seem to terminate on their on when poly-U stretches appear. | https://en.wikipedia.org/wiki?curid=63589689 |
Ferulic acid decarboxylase Ferulic acid decarboxylases (Fdc) are decarboxylase enzymes capable of the reversible decarboxylation of aromatic carboxylic acids such as ferulic acid and cinnamic acid. Fdc's are fungal homolouges of the "E.coli" UbiD enzyme which is involved in ubiquinone biosynthesis. This places Fdc within the wider UbiD enzyme family, representing a distinct clade within the family Presence of "fdc1" and the associated "pad1" genes (Pad1 homolougous to UbiX in "E.coli") were shown to be required for the decarboxylation of phenylacrylic acids in "Saccharomyces cerevisiae". In 2015 the cofactor prFMN was discovered in the active site of Fdc1 from "Aspergillus niger" (AnFdc) by crystallography, prior to this genetic studies had lead to the assumption that both UbiD and UbiX encoded isofunctional decarboxylases. In actuality UbiX/Pad were found to be flavin preyltransferases supplying the prFMN cofactor to UbiD/Fdc where it is utilised for the reversible decarboxylation of alpha-beta unsaturated carboxylic acid substrates. Since the discovery of prFMN AnFDC has become the most well understood representative of the UbiD enzyme family In the same paper in which the structure of prFMN was deduced in the active site of AnFdc1 there was a proposal for the mechanism by which Fdc1 decarboxylates α,β-unsaturated carboxylic acids. Not all UbiD enzymes decarboxylate acrylic acid substrates and other mechanisms may be at play for alternative substrates | https://en.wikipedia.org/wiki?curid=63592402 |
Ferulic acid decarboxylase In the case of AnFdc1 it was noted that prFMN displays an azomethine ylide characteristic C4a-N5+=C1’(Figure 1). This is a well-known 1,3-dipole in organic chemistry, positioned in the enzyme active site near to the α,β-unsaturated carboxylic acid substrate which contains a 1,3-dipolarophile. Thus, it was proposed that a 1,3-dipolar cycloaddition mechanism was responsible for the enzymatic decarboxylation. This was confirmed in a later paper The mechanism proposed in for 1,3-dipolar cycloaddition by Fdc1 is as follows (intermediates represented in Figure 1): A study went on to present evidence for the 1,3-dipolar cycloaddition, due to suspected turnover of cinnamic acid a crystal structure of AnFdc1 in complex with α-fluorocinnamic acid revealed the substrate Cα and Cβ carbons are located directly above the prFMN C1’ and C4a respectively (shown as Sub in Figure 1 - with cinnamic acid as opposed to α-fluorocinnamic acid). Cinnamic acid was confirmed to bind in a similar manner using inactive AnFdc1 crystals containing FMN. The AnFdc1 E282Q mutant crystallised with cinnamic acid revealed a structure corresponding to the Int2 species, this was taken to mean that progression through the 1,3-dipolarcycloadition cycle was halted as E282 is unable to donate a proton to the alkene moiety. In order to observe the Int1 and Int3 structures alkyne analogues were used. Like alkenes these compounds can also act as dipolarophiles but cycloaddition would yield a cycloadduct containing a double bond | https://en.wikipedia.org/wiki?curid=63592402 |
Ferulic acid decarboxylase An inactive AnFdc1 enzyme (with prFMN bound) co-crystallised with the phenylpropiolic acid revealed binding in a similar manner to the α-fluorocinnamic acid AnFdc1 and cinnamic acid AnFdc1 with FMN bound (Inhib). An active AnFdc1 enzyme co-crystallised with phenylpropiolic acid revealed clear density for a 3-pyrroline cycloadduct (Int3’) between the alkyene and prFMN. Int3’ represents a structure post decarboxylation, so it was assumed that over the time it took for crystallisation (~24h) the decarboxylation had occurred. Using a rapid soaking procedure, a different cycloadduct was observed that retained the carboxyl moiety (Int1’). | https://en.wikipedia.org/wiki?curid=63592402 |
National Federation of Chemical Industries The (, FNIC) is a trade union representing workers in the chemical industry in France. The union was founded in 1907 as the Oil and Gas Workers' Federation, as an affiliate of the General Confederation of Labour (CGT). In 1909, it was renamed as the Federation of Chemical Products. In 1921, it suffered a major split, with left-wingers forming the United Federation of Chemical Industries, but they rejoined in 1935, with their general secretary, Eduoard Finck, becoming secretary of the merged union. By 1994, the union's membership had fallen 22,156. It has since stabilised, and was 24,814 in 2019. | https://en.wikipedia.org/wiki?curid=63592865 |
Alison R. Fout is an American inorganic chemist at the University of Illinois at Urbana-Champaign where she holds the rank of associate professor. She has contributed to the discovery of new catalysts with NHC ligands. She discovered a family of catalysts that reduce oxyanions such as nitrate, perchlorate to nitric oxide and chloride, respectively. As an independent investigator, she received the following recognition: She also was recognized from scientific journals. In 2016, she received recognition as New Talent Americas from Dalton Transactions. That same year, the American Chemical Society awarded her as an Emerging Investigator in Bioinorganic Chemistry. In 2019 she received the Thieme Chemistry Journals Award. In 2017 she presented the Dalton Lectures at the University of California, Berkeley. At the 2018 Metals in Biology Gordon Conference, she received the Ed Stiefel Young Investigator Award. | https://en.wikipedia.org/wiki?curid=63602368 |
H3K36me is an epigenetic modification to the DNA packaging protein Histone H3, specifically, the mono-methylation at the 36th lysine residue of the histone H3 protein. There are diverse modifications at H3K36, such as phosphorylation, methylation, acetylation, and ubiquitylation, which have many important biological processes. The methylation of H3K36 has particularly had effects in transcriptional repression, alternative splicing, dosage compensation, DNA replication and repair, DNA methylation, and the transmission of the memory of gene expression from parents to offspring during development. H3K36me2 indicates dimethylation of lysine 36 on histone H3 protein subunit: This diagram shows the progressive methylation of a lysine residue. The mono-methylation denotes the methylation present in H3K36me1. Lysine methylation is the addition of a methyl group to the lysine of histone proteins. This occurs via histone lysine methyltransferase (HMTase) that utilize "S"-adenosylmethionine to specifically place the methyl group on histone Lys or Arg residues. So far, there have only been eight specific mammalian enzymes discovered that can methylate H3K36 in vitro and/or in vivo, all of which have identical catalytic SET domains but, different preferences for Lys36 residues in different methylation states. The genomic DNA of eukaryotic cells is wrapped around special protein molecules known as histones. The complexes formed by the looping of the DNA are known as chromatin | https://en.wikipedia.org/wiki?curid=63611863 |
H3K36me The basic structural unit of chromatin is the nucleosome, which consists of the core octamer of histones (H2A, H2B, H3, and H4) as well as a linker histone and about 180 base pairs of DNA wrapped around it. These core histones are rich in lysine and arginine residues. The carboxyl (C) terminal end of these histones contribute to histone-histone interactions, as well as histone-DNA interactions. The amino (N) terminal charged tails are the site of the post-translational modifications, such as the one seen in H3K36me3. The post-translational modification of histone tails by either histone-modifying complexes or chromatin remodeling complexes is interpreted by the cell and leads to the complex, combinatorial transcriptional output. It is thought that a histone code dictates the expression of genes by a complex interaction between the histones in a particular region. The current understanding and interpretation of histones come from two large scale projects: ENCODE and the Epigenomic roadmap. The purpose of the epigenomic study was to investigate epigenetic changes across the entire genome. This led to chromatin states which define genomic regions by grouping the interactions of different proteins and/or histone modifications together. Chromatin states were investigated in Drosophila cells by looking at the binding location of proteins in the genome. The use of ChIP-sequencing revealed regions in the genome characterized by different banding | https://en.wikipedia.org/wiki?curid=63611863 |
H3K36me Different developmental stages were profiled in Drosophila as well, an emphasis was placed on histone modification relevance. A look into the data obtained led to the definition of chromatin states based on histone modifications. Certain modifications were mapped and enrichment was seen to localize in certain genomic regions. Five core histone modifications were found with each respective one being linked to various cell functions. The human genome was annotated with chromatin states. These annotated states can be used as new ways to annotate a genome independently of the underlying genome sequence. This independence from the DNA sequence enforces the epigenetic nature of histone modifications. Chromatin states are also useful in identifying regulatory elements that have no defined sequence, such as enhancers. This additional level of annotation allows for a deeper understanding of cell-specific gene regulation. The histone mark can be detected in a variety of ways: | https://en.wikipedia.org/wiki?curid=63611863 |
Ethyl 3-bromopropionate is the organobromine compound with the formula BrCHCHCOCH. It is a colorless liquid and an alkylating agent. It is prepared by the esterification of 3-bromopropionic acid. Alternatively, it can be prepared by hydrobromination of ethyl acrylate, a reaction that proceeds in an anti-Markovnikov sense. | https://en.wikipedia.org/wiki?curid=63614556 |
Penning-Malmberg trap The is an electromagnetic device used to confine large numbers of charged particles of a single sign of charge. Much interest in Penning-Malmberg (PM) traps arises from the fact that if the density of particles is large and the temperature low, the gas will become a single-component plasma . While confinement of electrically neutral plasmas is generally difficult, single-species plasmas (an example of a non-neutral plasma ) can be confined for long times in PM traps. They are the method of choice to study a variety of plasma phenomena. They are also widely used to confine antiparticles such as positrons (i.e., anti-electrons) and antiprotons for use in studies of the properties of antimatter and interactions of antiparticles with matter . A schematic design of a PM trap is shown in Fig. 1 , . Charged particles of a single sign of charge are confined in a vacuum inside an electrode structure consisting of a stack of hollow, metal cylinders. A uniform axial magnetic field formula_1 is applied to inhibit positron motion radially, and voltages are imposed on the end electrodes to prevent particle loss in the magnetic field direction. This is similar to the arrangement in a Penning trap, but with an extended confinement electrode to trap large numbers of particles (e.g., formula_2). Such traps are renowned for their good confinement properties. This is due to the fact that, for a sufficiently strong magnetic field, the canonical angular momentum formula_3 of the charge cloud (i.e | https://en.wikipedia.org/wiki?curid=63621945 |
Penning-Malmberg trap , including angular momentum due to the magnetic field B) in the direction formula_4 of the field is approximately formula_5 (1) where formula_6 is the radial position of the formula_7th particle, formula_8 is the total number of particles, and formula_9 is the cyclotron frequency, with particle mass m and charge e. If the system has no magnetic or electrostatic asymmetries in the plane perpendicular to formula_1, there are no torques on the plasma; thus formula_3 is constant, and the plasma cannot expand. As discussed below, these plasmas do expand due to magnetic and/or electrostatic asymmetries thought to be due to imperfections in trap construction. The PM traps are typically filled using sources of low energy charged particles. In the case of electrons, this can be done using a hot filament or electron gun . For positrons, a sealed radioisotope source and “moderator” (the latter used to slow the positrons to electron-volt energies) can be used . Techniques have been developed to measure the plasma length, radius, temperature, and density in the trap, and to excite plasma waves and oscillations . It is frequently useful to compress plasmas radially to increase the plasma density and/or to combat asymmetry-induced transport . This can be accomplished by applying a torque on the plasma using rotating electric fields [the so-called “rotating wall” (RW) technique] , or in the case of ion plasmas, using laser light . Very long confinement times (e.g., hours or days) can be achieved using these techniques | https://en.wikipedia.org/wiki?curid=63621945 |
Penning-Malmberg trap Particle cooling is frequently necessary to maintain good confinement (e.g., to mitigate the heating from RW torques). This can be accomplished in a number of ways, such as using inelastic collisions with molecular gases , or in the case of ions, using lasers . In the case of electrons or positrons, if the magnetic field is sufficiently strong, the particles will cool by cyclotron radiation . The confinement and properties of single species plasmas in (what are now known as) PM traps was first studied by John Malmberg and John DeGrassie . Confinement was shown to be excellent as compared to that for neutral plasmas. It was also shown that, while good, confinement is not perfect and there are particle losses. Penning-Malmberg traps have been used to study a variety of transport mechanisms. Figure 2 shows an early study of confinement in a PM trap as a function of a background pressure of He gas. At higher pressures, transport is due to electron-atom collisions, while at lower pressures, there is a pressure-independent particle loss mechanism. The latter (“anomalous transport”) mechanism has been shown to be due to inadvertent magnetic and electrostatic asymmetries and the effects of trapped particles [5]. There is evidence that confinement in PM traps is improved if the main confinement electrode (blue in Fig. 1) is replaced by a series of coaxial cylinders biased to create a smoothly varying potential well (a “multi-ring PM trap”) | https://en.wikipedia.org/wiki?curid=63621945 |
Penning-Malmberg trap One fruitful area of research arises from the fact that plasmas in PM traps can be used to model the dynamics of inviscid two-dimensional fluid flows . PM traps are also the device of choice to accumulate and store anti-particles such as positrons and antiprotons . One has been able to create positron and antiproton plasmas and to study electron-beam positron plasma dynamics . Pure ion plasmas can be laser-cooled into crystalline states . Cryogenic pure-ion plasmas are used to study quantum entanglement . The PM traps also provide an excellent source for cold positron beams. They have been used to study with precision positronium (Ps) atoms (the bound state of a positron and an electron, lifetime ≤ 0.1 μs) and to create and study the positronium molecule (Psformula_12, formula_13) . Recently PM-trap-based positron beams have been used to produce practical Ps-atom beams . Antihydrogen is the bound state of an antiproton and a positron and the simplest antiatom. Nested PM traps (one for antiprotons and another for positrons) have been central to the successful efforts to create, trap and to compare the properties of antihydrogen with those of hydrogen . The antiparticle plasmas (and electron plasmas used to cool the antiprotons) are carefully tuned with an array of recently developed techniques to optimize the production antihydrogen atoms . These neutral antiatoms are then confined in a minimum-magnetic-field trap . | https://en.wikipedia.org/wiki?curid=63621945 |
NAD+ Five-prime cap In molecular biology, the NAD+ five-prime cap (NAD+ 5’ cap) refers to a molecule of nicotinamide adenine dinucleotide (NAD+), a nucleoside-containing metabolite, covalently bonded the 5’ end of cellular mRNA. While the more common methylated guanosine (m7G) cap is added to RNA by a capping complex that associates with RNA polymerase II (RNAP II), the NAD cap is added during transcriptional initiation by the RNA polymerase itself, acting as a non-canonical initiating nucleotide (NCIN). As such, while m7G capping can only occur in organisms possessing specialized capping complexes, because NAD capping is performed by RNAP itself, it is hypothesized to occur in most, if not all, organisms. The NAD+ 5’ cap has been observed in bacteria, contrary to the long-held belief that prokaryotes lacked 5’-capped RNA, as well as on the 5’ cap of eukaryotic mRNA, in place of the m7G cap. This modification also potentially allows for selective degradation of RNA within prokaryotes as different pathways are involved in the degradation of NAD+-capped and uncapped 5′-triphosphate-RNAs. In eukaryotic cells, while the more commonly observed m7G cap promotes the stability of the mRNA and supports translation, the NAD+ cap targets the RNA transcript for decay, facilitated by the non-canonical decapping enzyme, DXO. Considering the centrality of NAD in redox chemistry and post-translational protein modification, its attachment to RNA represents potentially undiscovered pathways in RNA metabolism and regulation | https://en.wikipedia.org/wiki?curid=63623716 |
NAD+ Five-prime cap In prokaryotes, the 5’ NAD+ modification is established by bacterial RNAP during transcription initiation and has been shown to display functions analogous to those of the eukaryotic 5’ cap. In-vitro transcribed NAD-modified RNA was shown to be more resistant to RNase E, the main enzyme in the decay pathway of "E. coli". NAD-modification further was shown to decelerate RNA processing by RNA pyrophosphohydrolase (RppH), which is known to trigger RNase-E-mediated decay through the conversion of 5′-triphosphate-RNA to 5′-monophosphate-RNA. Nudc, a nudix phosphohydrolase, can decap NAD-RNA through hydrolyzing NAD(H) into NMN(H) and AMP, causing RNase-E-mediated decay, but is inactive against 5′-triphosphate-RNA. This 5’ modification allows for the selective initiation of degradation for a subset of RNAs as the NAD-capped RNAs are stabilized in the presence of RppH, but are decapped by Nudc, while the 5′-triphosphate-RNAs are susceptible to RppH but not Nudc. Next generation sequencing (NGS) of the NAD-RNA conjugates in "E. coli" revealed an abundance of a specific group of small regulatory RNAs (sRNAs) which are known to be involved in stress response systems, as well as enzymes involved in cellular metabolism. The small number of RNA transcripts with a NAD cap might allow the cell to selectively degrade these RNAs separate from other pathways | https://en.wikipedia.org/wiki?curid=63623716 |
NAD+ Five-prime cap Considering that the stress responses are known to affect NAD+ concentration, this finding further supports the possibility of undiscovered pathways linking the energetic state of a cell to mRNA turnover. NAD capping has also been suggested to recruit specific proteins to the 5’ end of the RNA as NAD is one of the most common protein ligands. NAD-binding pockets are well characterized in many proteins and could help the localization of the RNA to an enzyme or receptor. Many NAD-utilizing metabolic enzymes can also bind to RNA, presenting the possibility of unknown ribonucleoprotein complexes. NAD+ 5’ capped RNA have been found in yeast, humans, and Arabidopsis thaliana. In eukaryotes, the NAD+ cap is removed by non-canonical decapping enzymes from the DXO family. DeNADing by DXO results in a 5’ end monophosphate RNA distinct from NudC which results in NMN plus 5′ monophosphate RNA. Importantly, DXO is ~6 fold more efficient at decapping NAD+ compared to m7G, suggesting that it selectively degrades NAD-capped RNA rather than the more common m7G cap, similar to NudC. The m7G cap has been shown to promote translation through recruitment of the initiation complex onto the mRNA. However, the NAD+-cap does not provide a similar function as NAD+-capped and polyadenylated mRNA displayed similar levels of translation "in vitro" to uncapped mRNA | https://en.wikipedia.org/wiki?curid=63623716 |
NAD+ Five-prime cap Additionally, the 5’ NAD+ cap further promotes decay of the RNA it is attached to, NAD+-capped and polyadenylated mRNA were demonstrated "in vitro" to be less stable than mRNAs lacking a 5’ cap, suggesting that the NAD+ modification is actively facilitating DXO-mediated RNA decay. While the relationship between RNA-binding proteins, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and NAD+ concentration is established, the NAD+ cap has been hypothesized to represent a direct link between RNA expression levels and cellular metabolism. It is known that energy stresses such as glucose deprivation and caloric restriction influence NAD+ concentrations and can possibly impact NAD+ capping. Additionally, as low-nutrient conditions can affect mRNA stability, and seeing as NAD+ caps promote mRNA decay, it is possible that the energetic state of a cell could affect NAD+-capping and thus mRNA turnover. Certain findings, such as the higher abundance of NAD+-capped transcripts in stationary-phase bacteria as well as yeast grown on synthetic media, point toward this possibility. | https://en.wikipedia.org/wiki?curid=63623716 |
Organopolonium chemistry describes the synthesis and properties of chemical compounds containing a carbon to polonium chemical bond. As polonium is a highly radioactive element (its most commonly used isotope, Po, has a half-life of about 138 days), organopolonium chemistry is mostly unexplored, and what is known is mostly confined to tracer-level studies due to self-destruction and charring of the compounds by the energetic alpha decay of polonium. Moreover, the C–Po bond is even weaker than the C–Te and C–Se bonds; compounds with those bonds tend to decompose over time to form elemental tellurium and selenium respectively. Identification of such compounds has mostly been accomplished using chromatography, with analogous tellurium compounds as references, as classical chemical methods cannot be applied. Their production is often accomplished by the beta decay of Bi-containing organobismuth compounds. Some compounds have been claimed but not securely identified. Relatively well-characterised derivatives are mostly restricted to dialkyl and diaryl polonides (RPo), triarylpolonium halides (ArPoX), and diarylpolonium dihalides (ArPoX). Polonium also forms soluble compounds with some chelating agents, such as 2,3-butanediol and thiourea. | https://en.wikipedia.org/wiki?curid=63633407 |
Hyper–Rayleigh scattering Optical Activity ( ), is a nonlinear optical physical effect whereby chiral scatterers (such as nanoparticles or molecules) convert light (or other electromagnetic radiation) to higher frequencies via harmonic generation processes, in a way that the intensity of generated light depends on the chirality of the scatterers. "Hyper–Rayleigh scattering" is a nonlinear optical counterpart to Rayleigh scattering. "Optical activity" refers to any changes in light properties (such as intensity or polarization) that are due to chirality. The effect was theoretically predicted in 1979, in a mathematical description of hyper Raman scattering optical activity. Within this theoretical model, upon setting the initial and final frequencies of light to the same value, the mathematics describe the Hyper Rayleigh Scattering Optical Activity. The theory was well in advance of its time, and the effect remained elusive for 40 years. Its author David L. Andrews referred to it as the "Impossible Theory". However, in January 2019, an experimental demonstration was reported by Ventsislav K. Valev and his team. The team investigated the hyper Rayleigh scattering (at the second harmonic generation frequency) from chiral nanohelices made of silver. Valev and his team observed that the intensity of the hyper Rayleigh scattering light depended on the direction of circularly polarized light and that this dependence reversed with the chirality of the nanohelices | https://en.wikipedia.org/wiki?curid=63634457 |
Hyper–Rayleigh scattering Valev's work unambiguously established that the effect is physically possible, opening the way for nonlinear chiroptical investigations of a variety of chiral light-scattering materials. Hyper Rayleigh Scattering Optical Activity (HRS OA) is arguably the most fundamental nonlinear chiral optical (chiroptical) effect; since other nonlinear chiroptical effects have additional requirements, which make them conceptually more involved, i.e. less fundamental. HRS OA is a scattering effect and therefore it does not require the frequency conversion process to be coherent; contrary to other nonlinear chiroptical effects, such as Second Harmonic Generation Circular Dichroism or Second Harmonic Generation Optical Rotation. Moreover, HRS OA is a parametric process (optics): the initial and final quantum mechanical states of the excited electron are the same. Because the excitation proceeds via virtual states, there is no restriction on the frequency of incident light. By contrast, other nonlinear scattering effects, such as two-photon circular dichroism and hyper-Raman are non-parametric - they require real energy states that restrict the frequencies at which these effects can be observed. Soon after the first demonstration of Hyper Rayleigh Scattering Optical Activity in metal nanoparticles, the effect was also reported in organic molecules, specifically aromatic oligoamide foldamers. | https://en.wikipedia.org/wiki?curid=63634457 |
CCR4-Not Carbon Catabolite Repression—Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression. The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase. The complex is present both in the nucleus where it regulates transcription and in the cytoplasm where it associates with translating ribosomes and RNA processing bodies. The human complex is composed of structural (non-catalytic) subunits and those that have exonuclease and E3 ligase activity. Some but not all of the human subunits are conserved in budding yeast. Molecular weight of human subunits from Uniprot. | https://en.wikipedia.org/wiki?curid=63668273 |
Chao-Jun Li is a professor of chemistry at McGill University, Montréal. He works on organic transformation applied to Green chemistry, including C-H activation, reactions in water and photochemistry. Li was born in 1963, and got his BSc from Zhengzhou university (1979-1983), and completed his MSc. in organic synthesis at the Chinese Academy of Sciences (1985-1988) with Prof. T.H. Chan. He then moved to McGill University (Montréal, Québec) to do his PhD (1989-1992) with Prof. Chan again, along with Prof. David Harpp, and went on a NSERC-funded postdoc with Prof. Barry Trost at Stanford University in the United States (1992-1994). Li started as an Assistant Professor at Tulane University in 1994, at attained the title of Professor of Chemistry in 2000. He then moved in 2003 to McGill University, where he obtained a Canada Research Chair (Tier I) in Green Chemistry. He has also been the Director of NSERC CREATE for Green Chemistry (2012-2018), the Director of CFI Infrastructure for Green Chemistry and Green Chemicals (2008-2018) and has been the Co-Director of the Center for Green Chemistry and Catalysis since 2009. Li's research encompasses various aspects of green chemistry applied to organic chemistry: organometallics, catalysis (thermal and light-based). Most notably, he is known for using water as a reaction media for various chemical reactions (hydrogenation, Grignard coupling,) Li originated the concepts of Aldehyde-Alkyne-Amine Coupling (A3_coupling_reaction)and the Cross-Dehydrogenative Coupling (CDC Reaction) | https://en.wikipedia.org/wiki?curid=63668520 |
Chao-Jun Li His work on GaN nanowires as photocatalysts for the conversion of methane into benzene was covered by Phys.org in 2015, leaving propects for hydrogen storage. Subsequently, his team showed that they were also able to convert methanol into ethanol. He also made breakthroughs in using hydrazones as nucleophiles in cross-coupling, and on the direct amination of phenol derivatives. Reactions in water: A3 coupling reaction Cross-Dehydrogenative Coupling GaN photocatalysts Hydrazones as coupling agents: | https://en.wikipedia.org/wiki?curid=63668520 |
Okubo-Weiss parameter The Okubo-Weiss parameter, normally represented as 'W', is a measure of the relative importance of deformation and rotation, which is calculated as the sum of the squares of normal and shear strain minus the relative vorticity. This is widely applicable in fluid properties particularly in identifying and addressing the oceanic eddies. For a horizontally non-divergent flow in the ocean, the equation to calculate W is in the form W=s² +s² -ω². Eddies in which vorticity dominates strain are marked by negative W. Normally, in the analysis in a global perspective, closed contours of W =-2×10 s were considered as eddies. Sea surface height (SSH) either wholly negative or wholly positive within such contours indicates cyclonic or anticyclonic polarity respectively. The centre of the eddy is defined to be the maximum or minimum SSH area within the W contour and the eddy diameter is defined as that of the circle with area equal to that enclosed by the W contour. The method may track noise-induced artifacts as eddies in certain cases, to avoid this, the W field is smoothed with half power filter cutoffs, for example of 1.5°×1.5° and only cases for which the W contour of at least 0.25° pixels or equivalent to an area about 50km² can be considered. | https://en.wikipedia.org/wiki?curid=63676220 |
Spoof surface plasmon Spoof surface plasmons, also known as spoof surface plasmon polaritons, are surface electromagnetic waves in microwave and terahertz regimes that propagate along planar interfaces with sign-changing permittivities. Spoof surface plasmons are a type of surface plasmon polariton, which ordinarily propagate along metal and dielectric interfaces in infrared and visible frequencies. Since surface plasmon polaritons cannot exist naturally in microwave and terahertz frequencies due to dispersion properties of metals, spoof surface plasmons necessitate the use of artificially-engineered metamaterials. Spoof surface plasmons share the natural properties of surface plasmon polaritons, such as dispersion characteristics and subwavelength field confinement. They were first theorized by John Pendry et al. Surface plasmon polaritons (SPP) result from the coupling of delocalized electron oscillations ("surface plasmon") to electromagnetic waves ("polariton"). SPPs propagate along the interface between a positive- and a negative-permittivity material. These waves decay perpendicularly from the interface ("evanescent field") | https://en.wikipedia.org/wiki?curid=63677270 |
Spoof surface plasmon For a plasmonic medium that is stratified along the z-direction in Cartesian coordinates, dispersion relation for SPPs can be obtained from solving Maxwell's equations: where Per this relation, SPPs have shorter wavelengths than light in free space for a frequency band below surface plasmon frequency; this property, as well as subwavelength confinement, enables new applications in subwavelength optics and systems beyond the diffraction-limit. Nevertheless, for lower frequency bands such as microwave and terahertz, surface plasmon polariton modes are not supported; metals function approximately as perfect electrical conductors with imaginary dielectric functions in this regime. Per the effective medium approach, metal surfaces with subwavelength structural elements can mimic the plasma behaviour, resulting in artificial surface plasmon polariton excitations with similar dispersion behaviour. The use of subwavelength structures to induce low-frequency plasmonic excitations was first theorized by John Pendry et al. in 1996; Pendry proposed that a periodic lattice of thin metallic wires with a radius of 1 μm could be used to support surface-bound modes, with a plasma cut-off frequency of 8.2 GHz. In 2004, Pendry et al. extended the approach to metal surfaces that are perforated by holes, terming the artificial SPP excitations as "spoof surface plasmons." In 2006, terahertz pulse propagation in planar metallic structures with holes were shown via FDTD simulations. Martin-Cano et al | https://en.wikipedia.org/wiki?curid=63677270 |
Spoof surface plasmon has realized the spatial and temporal modulation of guided terahertz modes via metallic parallelepiped structures, which they termed as "domino plasmons." Designer spoof plasmonic structures were also tailored to improve the performance of terahertz quantum cascade lasers in 2010. Spoof surface plasmons were proposed as a possible solution for decreasing the crosstalk in microwave integrated circuits, transmission lines and waveguides. In 2013, Ma et al. demonstrated a matched conversion from coplanar waveguide with a characteristic impedance of 50Ω to a spoof-plasmonic structure. In 2014, integration of commercial low-noise amplifier with spoof plasmonic structures was realized; the system reportedly worked from 6 to 20 GHz with a gain around 20 dB. Kianinejad et al. also reported the design of a slow-wave spoof-plasmonic transmission line; conversion from quasi-TEM microstrip modes to TM spoof plasmon modes were also demonstrated. Khanikaev et al. reported nonreciprocal spoof surface plasmon modes in structured conductor embedded in an asymmetric magneto-optical medium, which results in one-way transmission. Pan et al. observed the rejection of certain spoof plasmon modes with an introduction of electrically resonant metamaterial particles to the spoof plasmonic strip. Localized spoof surface plasmons were also demonstrated for metallic disks in microwave frequencies. | https://en.wikipedia.org/wiki?curid=63677270 |
List of CBRN warfare forces Several countries around the world maintain military units that are specifically trained to cope with CBRN (Chemical, Biological, Radiological, Nuclear) threats. Beside this specialized units, most modern armed forces undergo generalized basic CBRN self-defense training for all their personnel. Atomic-Biological-Chemical Defense Company ("Čete Atomsko-Biološko-Hemijske Odbrane") Army Navy Army Air Force Islamic Revolutionary Guard Corps Inter-services Army Air Force Army Army Reserve Army National Guard Marines | https://en.wikipedia.org/wiki?curid=63681020 |
Ring and Ball Apparatus is used to determine the softening point of Bitumen, waxes, LDPE, HDPE/PP blend granules, rosin and solid hydrocarbon resins. The apparatus was first designed way back in the 1910s while ASTM adopted a test method in 1916. This instrument is ideally used for materials having softening point in the range of 30⁰C to 157⁰C. The solid sample is taken in a petri dish and melted by heating it on a standard hot plate. The bubble free liquefied sample is poured from the petri dish and cast into the ring. The cast sample in the ring is kept undisturbed for one hour to solidify. Excess material is removed with hot knife. The ring is set with the ball on top with ball guides on the grooved plate within the heating bath. As the temperature rises, the balls begin to sink through the rings carrying a portion of the softened sample with it. The temperature at which the steel balls touch the bottom plate determines the softening point in degree centigrade. | https://en.wikipedia.org/wiki?curid=63682456 |
Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) is a naturally occurring para-benzoquinone isolated from dried berries of "Embelia ribes" plants. has a wide spectrum of biological activities, including antioxidant, antitumor, anti-inflammatory, analgesic, anthelmintic, antifertility and antimicrobial. Several studies have reported antidiabetic activity of embelin treatment significantly decreased paraquat‐induced lung injury through suppressing oxidative stress, inflammatory cascade (inflammatory cytokines release), and MAPK/NF‐κB signaling pathway in paraquat‐intoxicated rats selectively inhibits 5-LOX and microsomal prostaglandin E2 synthase-1 | https://en.wikipedia.org/wiki?curid=63687736 |
Thermogravitational cycle A thermogravitational cycle is a reversible thermodynamic cycle using the gravitational works of weight and buoyancy to respectively compress and expand a working fluid. Consider a column filled with a transporting medium and a balloon filled with a working fluid. Due to the hydrostatic pressure of the transporting medium, the pressure inside the column increases along the "z" axis (see figure). Initially, the balloon is inflated by the working fluid at temperature "T" and pressure "P" and located on top of the column. A thermogravitational cycle is decomposed into four ideal steps: For a thermogravitational cycle to occur, the balloon has to be denser than the transporting medium during 1→2 step and less dense during 3→4 step. If these conditions are not naturally satisfied by the working fluid, a weight can be attached to the balloon to increase its effective mass density. An experimental device working according to thermogravitational cycle principle was developed in a laboratory of the University of Bordeaux and patented in France. Such thermogravitational electric generator is based on inflation and deflation cycles of an elastic bag made of nitrile elastomer cut from a glove finger. The bag is filled with a volatile working fluid that has low chemical affinity for the elastomer such as perfluorohexane (CF). It is attached to a strong NdFeB spherical magnet that acts both as a weight and for transducing the mechanical energy into voltage | https://en.wikipedia.org/wiki?curid=63687901 |
Thermogravitational cycle The glass cylinder is filled with water acting as transporting fluid. It is heated at the bottom by a hot circulating water-jacket, and cooled down at the top by a cold water bath. Due to its low boiling point temperature (56°C), the perfluorohexane drop contained in the bag vaporizes and inflates the balloon. Once its density is lower than the water density, the balloon raises according to Archimedes’ principle. Cooled down at the column top, the balloon deflates partially until its gets effectively denser than water and starts to fall down. As seen from the videos, the cyclic motion has a period of several seconds. These oscillations can last for several hours and their duration is limited only by leaks of the working fluid through the rubbery membrane. Each time the magnet goes through the coil produces a variation in the magnetic flux. An electromotive force is created and detected through an oscilloscope. It has been estimated that the average power of this machine is 7 μW and its efficiency is 4.8 x 10. Although these values are very small, this experiment brings a proof of principle of renewable energy device for harvesting electricity from a weak waste heat source without need of other external energy supply, e.g. for a compressor in a regular heat engine. The experiment was successfully reproduced by undergraduate students in preparatory classes of the Lycée Hoche in Versailles. Several other applications based on the thermogravitational cycles could be found in the literature | https://en.wikipedia.org/wiki?curid=63687901 |
Thermogravitational cycle For example: The efficiency "η" of a thermogravitational cycle depends on the thermodynamic processes the working fluid goes through during each step of the cycle. Below some examples: | https://en.wikipedia.org/wiki?curid=63687901 |
Transposed Paternò−Büchi reaction The transposed Paternò−Büchi reaction involves a ππ* excited state of alkene reacting with a ground state carbonyl functionality. This is reversal of the traditional Paternò−Büchi reaction where an excited carbonyl group reacts with a ground state alkene. This strategy was first reported by Sivaguru and co-workers with reaction of enamides. | https://en.wikipedia.org/wiki?curid=63690875 |
Aza Paternò−Büchi reaction involves an ππ* excited state of alkene reacting with a ground state imine. This strategy was developed by the laboratory Sivaguru and co-workers to overcome the shortcomings involving direct excitation of imines. Traditionally addition of excited imines to carbon-carbon double bonds involves making the imines as part of a carbocycle. | https://en.wikipedia.org/wiki?curid=63690941 |
Bulky cyclopentadienyl ligands In the area of organometallic chemistry, a bulky cyclopentadienyl ligand is jargon for a ligand of the type CHR where R is larger than n-alkyl and n = 3 or 4. Representative examples are the tetraisopropyl derivative CH(Pr) and the tris tert-butyl derivative 1,2,4-CH("tert"-Bu). These ligands are so large that their complexes behave differently from the pentamethylcyclopentadienyl analogues. Because they cannot closely approach the metal, these bulky ligands stabilize high spin complexes, e.g. (CH("tert"-Bu))FeI. These large ligands stabilize highly unsaturated derivatives such as (CH("tert"-Bu))FeN. The ("tert"-butyl)cyclopentadiene is prepared by alkylation of cyclopentadiene with "tert"-butyl bromide in the presence of sodium hydride and dibenzo-18-crown-6. The intermediate in this synthesis is di-tert-butylcyclopentadiene. This compound is conveniently prepared by alkylation of cyclobutadiene with tert-butyl bromide under phase-transfer conditions. Illustrative of the unusual complexes made possible with these bulky ligands is molecular iron nitrido complex ((t-Bu)CH)FeN. In contrast to (CMe)IrCl, ((t-Bu)CH)IrCl is monomeric. | https://en.wikipedia.org/wiki?curid=63698532 |
Joyce Jacobson Kaufman (21 June 1929 - 26 August 2016) was an American chemist known for advancing the science of quantum chemistry and for clinical research on anaesthetics. Born to an immigrant family in the Bronx and educated at Johns Hopkins University, she worked at the Sorbonne and at Martin Marietta before returning to Johns Hopkins. She was elected as a fellow of the American Institute of Chemists in 1965, and of the American Physical Society in 1966. Her other accolades include the 1973 Garvan Medical Award of the American Chemical Society and the Legion of Honour in 1969. | https://en.wikipedia.org/wiki?curid=63706861 |
Yuancheng Group Yuancheng Group, also known as Wuhan Yuancheng Technology Development Co., Ltd., is a Chinese chemical manufacturing company headquartered in Wuhan, China. The company is a notable supplier of precursors for the manufacturing of illicit drugs, such as Methamphetamine and Fentanyl. Yuancheng has approximately 700 employees and 30 locations across China. Yuancheng is designated as a New and High Technology Enterprise and therefore receives additional incentives from the Chinese government. The 2019–20 coronavirus pandemic lockdown in China restricted the supply of precursors and resulted in price increases of street drugs in the USA. The supply shortages resulted in price increases and shortages in illegal drugs that were been noticed on the street of the UK. US law enforcement also told the NY Post that Mexican drug cartels were having difficulty in obtaining precursors. | https://en.wikipedia.org/wiki?curid=63714872 |
Armando J. Parodi (born March 16, 1942) is an Argentinean glycobiologist. He did his initial education at the School of Sciences of the University of Buenos Aires. His PhD work was done under Luis Federico Leloir, a recipient of the Nobel Prize in Chemistry for his work involving the finding of sugar nucleotides and how they play a role in the making of oligosaccharides and polysaccharides. He also pursued postdoc work at the Pasteur Institute in Paris, France and Duke University in Durham, NC, USA. Although his father was a physician who worked more in academia than in a clinic, the lack of strong science teachers in secondary school led him to become more interested in politics. However, when he graduated high school, Parodi attended the School of Sciences at the University of Buenos Aires. The reason for this, was his interest in Chemistry that developed as a result of having a Chemistry teacher in secondary school that excited him about the subject. Due to the restructuring of the Higher Education system as a result of Juan Peron’s dictatorship, many of his professors were younger and recent graduates of post-doctoral programs in the US and Europe. During his final year at the University of Buenos Aires, his father suggested that he should pursue his PhD at the Fundacion Instituto Leloir, and so he enrolled in the Biochemistry course there. While working under Luis. F. Leloir, Parodi saw that Leloir was able to synthesize particulate glycogen "de novo" and that influenced the direction of his future research | https://en.wikipedia.org/wiki?curid=63726772 |
Armando J. Parodi Parodi also completed a 2 year postdoctoral fellowship at the Pasteur Institute in Paris, France. While working under Luis F. Leloir, Parodi’s research was involved with the synthesis of particulate glycogen "de novo" using UDP-Glc and rat livers for glycogen synthase. In 1970, he joined Leloir and Nicolas Behrens in their research that was involved with the incubation of dolichol-P-Glc using liver microsomes to transfer glucose to a dolichol-P-P-linked glycan known as Glc3Man9GlcNAc2-P-P-dolichol. After completing his fellowship in Paris, and returning to Buenos Aires, between the years of 1975 and 1978, he conducted research involved with demonstrating the presence of a dolichol-P-dependent pathway of N-glycosylation in yeast. However, a paper in 1980 that stated the lack of free or sugar-bound dolichol-P in trypanosomatid protozoa meant that the pathway he discovered was not in the organism. This lead him to do his own research with trypanosomatids and using C Glucose he found that the synthesis of dolichol-P-P-glycans in protozoa was possible but glucose was lacking in the formed glycans. Further research into glycans in trypanosomes, specifically Trypanosoma cruzi, was conducted by Parodi. Using short pulses of C, three protein glycans were produced and they were known as GlcManGlcNAc, GlcManGlcNAc, and GlcManGlcNAc. These were then replaced by ManGlcNAc, ManGlcNAc, ManGlcNAc, and ManGlcNAc in the mature versions of the glycoproteins | https://en.wikipedia.org/wiki?curid=63726772 |
Armando J. Parodi This led to the conclusion that the transfer of a glucose to the ManGlcNAc was the only way that GlcManGlcNAc could have been made. Parodi also looked into how glucosylation/deglucosylation in the ER’s lumen were involved with the correct folding of N-linked glycoproteins. His research led him to find that misfolding allowed for conformations that would allow for glycoproteins to act as glucose acceptors. He was able to find this using UDP-Glc: glycoprotein GT that worked as ways of sensing the various conformations of the glycoproteins. The sensitive of GT was very helpful as it was able to detect formations that were undetectable via other methods. This work was crucial in discovering how protein folding was controlled. By looking at how GT encouraged proper folding, the enzyme was found as a stress protein and there was increased synthesis of it during periods of stress for the ER. Recent work by Parodi has looked at how Glucosidase I removes glucose from Glc3Man9GlcNAc2. He has looked at how glycosylation MOGS-CDG leads to Glucosidase 1 encoding gene mutations. Absence of this GI has been linked to death in certain yeasts, specifically, "Schizosaccharomyces pombe." Parodi and his team wanted to look at this mutation and understand what was causing the defects in these Δ"gls1-S" cells. | https://en.wikipedia.org/wiki?curid=63726772 |
Vengeance and Retribution are Mine Vengeance and Retribution are Mine: Community, the Holocaust, and Abba Kovner's Avengers () is a book by Israeli historian Dina Porat on Nakam, a small group of Holocaust survivors led by Abba Kovner which sought violent revenge against Germans. She chose the title to express her belief that humans should leave revenge for God. It was first published in 2019 by Pardes Publishing / Haifa University Press in Hebrew, and is the first scholarly book on Nakam. | https://en.wikipedia.org/wiki?curid=63727097 |
Toxic Terror (book) Toxic Terror: Assessing Terrorist Use of Chemical and Biological Weapons (2000) is a MIT Press book edited by Jonathan B. Tucker which has twelve chapters by different authors discussing use of chemical and biological weapons by terrorists from 1946 to 1998. Only three groups caused "mass casualties" and only one attack (the 1995 Tokyo subway sarin attack) approached terrorism. The book therefore shows that the groups were not able to achieve much damage with these unconventional weapons, contrary to warnings of an extreme threat. | https://en.wikipedia.org/wiki?curid=63729856 |
Compact Cassette tape types and formulations Audio compact cassettes use magnetic tape of three major types which differ in fundamental magnetic properties, the level of bias applied during recording, and the optimal time constant of replay equalization. Specifications of each type were set in 1979 by the International Electrotechnical Commission (IEC). By this time, Type I (IEC I, 'ferric' or 'normal' tapes) included pure gamma ferric oxide formulations, Type II (IEC II, or 'chrome' tapes) included ferricobalt and chromium dioxide formulations, and Type IV (IEC IV, or 'metal' tapes) included metal particle tapes - the best performing, but also the most expensive. In the 1980s the lines between three types blurred. Panasonic developed evaporated metal tapes that could be made to match any of the three IEC types. Metal particle tapes migrated to Type II and Type I, ferricobalt formulations migrated to Type I. By the end of the decade performance of the best Type I ferricobalt tapes ('superferrics') approached that of Type IV tapes; performance of entry-level Type I tapes gradually improved until the very end of compact cassette production. Double-layer Type III (IEC III, ferrichrome or ferrochrome) tape formulations, advanced by Sony and BASF in the 1970s, never gained substantial market presence. 'Type 0' was a non-standard designation for early compact cassettes that did not conform to IEC specification; in the XXI century it is infomally used to denote any low quality or counterfeit cassette | https://en.wikipedia.org/wiki?curid=63742889 |
Compact Cassette tape types and formulations Magnetic recording relies on the use of hard ferrimagnetics or ferromagnetics - materials that require strong external magnetic fields to be magnetized, and that retain substantial residual magnetization after the magnetizing field is removed. Two fundamental magnetic properties, relevant for audio recording, are: A useful figure of merit of tape technology is the squareness ratio of the hysteresis curve. It is an indicator of tape uniformity and its linearity in analogue recording. Increase of the ratio defers the onset of compression and distortion, and allows fuller utilization of the tape's dynamic range within the limits of remanence. Squareness ratio of basic ferric tapes rarely exceeds 0.75; squareness ratio of the best tapes exceeds 0.9. Manufacturers of bulk tape provided extremely detailed technical descriptions of their product, with numerous charts and dozens of numeric parameters. From the end user viewpoint, the most important electroacoustic properties of the tape are: Frequency range, per se, is usually unimportant. At low recording levels (-20 dB referred to nominal level) all quality tapes can reliably reproduce frequencies from to , which is sufficient for high fidelity audio. However, at high recording levels treble output is further limited by saturation. At Dolby recording level the upper frequency limit shrinks to a value between for a typical chromium dioxide tape, and for metal tapes; in case of chromium dioxide, this is partially offset by very low hiss levels | https://en.wikipedia.org/wiki?curid=63742889 |
Compact Cassette tape types and formulations In practice, high-level frequency range is not as important as the smoothness of midrange and treble frequency response. The original specification for Compact Cassette was set by Philips in 1962–1963. Of the three then available tape formulations that matched Philips requirements, the BASF PES-18 tape became the original reference. Other chemical companies followed with tapes of varying quality, often incompatible with BASF reference. By 1970 a new, improved generation of tapes firmly established itself on the market, and became the de facto reference for aligning tape recorders - thus the compatibility issue worsened even further. In 1971 it was tackled by the Deutsches Institut für Normung (DIN), which set the standard for chromium dioxide tapes; in 1978 the International Electrotechnical Commission (IEC) enacted the comprehensive standard on cassette tapes; one year later the IEC mandated the use of notches for automatic tape type recognition. Since then, the four cassette tape types were known as IEC I, IEC II, IEC III and IEC IV. The numerals follow historic sequence in which these types were commercialized, and do not imply their relative quality or intended purpose. An integral part of the IEC standard is the set of four IEC reference tapes. Type I and Type II references were manufactured by BASF, Type III reference by Sony, Type IV reference by TDK | https://en.wikipedia.org/wiki?curid=63742889 |
Compact Cassette tape types and formulations Unlike consumer tapes, which were manufactured continuously over years, each reference tape was made in a single production batch by the IEC-approved factory. These batches were made large enough to fill the need of the industry for many years. A second run was impossible, because the chemists were unable to replicate the reference with proper precision. From time to time, the IEC revised the set of references; the final revision took place in April 1994. The choice of reference tapes, and the IEC role in general has been debated. Meinrad Liebert, designer of Studer and Revox cassette decks, criticized the IEC for failing to enforce the standards and lagging behind the constantly changing market. Liebert wrote that while the market clearly branched into distinct, incompatible "premium" and "budget" subtypes, the IEC tried in vain to select an elusive "market average"; meanwhile, the industry moved forward, disregarding outdated references. This, according to Liebert, explained sudden demand for built-in tape calibration tools that were almost unheard-of in the 1970s. From the end user viewpoint, the IEC standard defined two principal properties of each type: Type I, or IEC I, ferric or 'normal' cassettes were historically the first, the most common and the least expensive; they dominated the prerecorded cassette market. Magnetic layer of a ferric tape consists of around 30% synthetic binder and 70% magnetic powder - acicular (oblong, needle-like) particles of gamma ferric oxide (γ-FeO), with a length of to | https://en.wikipedia.org/wiki?curid=63742889 |
Compact Cassette tape types and formulations Each particle of such size contains a single magnetic domain. The powder was and still is manufactured in bulk by chemical companies specializing in mineral pigments for the paint industry. Ferric magnetic layers have brown colour, its shade and intensity depending mostly on the size of particles. Type I tapes must be recorded with 'normal' (low) bias flux and replayed with time constant. Over time, ferric oxide technology developed continuously, with new, superior generations emerging around every five year. Cassettes of various periods and price points can be sorted into three distinct groups: basic coarse-grained tapes; advanced fine-grained, or microferric, tapes; and highest-grade ferricobalt tapes, having ferric oxide particles encapsulated in a thin layer of cobalt-iron compound. Remanence and squareness of the three groups substantially differ, while coercivity remains almost unchanged at around ( for the IEC reference tape approved in 1979). Quality Type I cassettes have higher midrange MOL than most Type II tapes, slow and gentle MOL roll-off at low frequencies, but less treble headroom than Type II. In practice that means that ferrics lose to chromes and metals at high frequencies, but often win in the bass department, and are a good medium for recording bass-heavy music. Entry-level ferric formulations are made of pure, unmodified, coarse-grained ferric oxide | https://en.wikipedia.org/wiki?curid=63742889 |
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