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HARMAN Professional Delights Indian Content Creators and ‘Prosumers’ With A Range of Exciting New Products




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Hyundai Motor Company and HARMAN International launch the world’s first road noise cancellation system into production

Stamford, Connecticut – February 03, 2020 – HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, has launched the world’s first active road...




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Powerful HARMAN Solutions That Create a Comfortable and Productive At-Home Setup

All around the world, parents, students and professionals alike are adjusting to a new reality that involves strict quarantine, social distancing and work from home measures. Without a doubt, the COVID-19 pandemic has changed the way people lead their...




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Hyper Productivity Bundle_Ignite_dash




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UPDATE 2-Auto production collapses by 99% in Mexico and Brazil due to coronavirus

Auto production in Mexico and Brazil, Latin America's top producers, plunged by an unprecedented 99% in April as a result of the coronavirus crisis, with the two countries building a total of just 5,569 vehicles.




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Pfizer to outsource some drug production, focus on coronavirus vaccine

Pfizer Inc said on Friday it is in talks to shift more of its medicine production to outside contractors as it prepares for large-scale production of an experimental vaccine to prevent COVID-19, should it prove safe and effective.




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UPDATE 1-Pfizer to outsource some drug production, focus on coronavirus vaccine

Pfizer Inc said on Friday it is in talks to shift more of its medicine production to outside contractors as it prepares for large-scale production of an experimental vaccine to prevent COVID-19, should it prove safe and effective.




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BCG vaccine helps fight infections by boosting immune cell production

The BCG tuberculosis vaccine boosts the production of immune cells and this may explain how it protects newborns from dying of sepsis




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2nd U.S. Ice Cream Maker Pulls All Products After Listeria Threat

Title: 2nd U.S. Ice Cream Maker Pulls All Products After Listeria Threat
Category: Health News
Created: 4/24/2015 12:00:00 AM
Last Editorial Review: 4/27/2015 12:00:00 AM




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Don't Drink or Inject Our Product, Lysol Maker Says in Response to Trump Remark

Title: Don't Drink or Inject Our Product, Lysol Maker Says in Response to Trump Remark
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




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As Coronavirus Fears Surge, Keep Cleaning Products Away From Children

Title: As Coronavirus Fears Surge, Keep Cleaning Products Away From Children
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




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Don't Believe All the 'Science' on CBD Products

Title: Don't Believe All the 'Science' on CBD Products
Category: Health News
Created: 3/16/2020 12:00:00 AM
Last Editorial Review: 3/17/2020 12:00:00 AM




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Legal Pot Products Too Potent for Chronic Pain

Title: Legal Pot Products Too Potent for Chronic Pain
Category: Health News
Created: 3/27/2020 12:00:00 AM
Last Editorial Review: 3/27/2020 12:00:00 AM




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Production of Two Excedrin Painkillers Halted

Title: Production of Two Excedrin Painkillers Halted
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/22/2020 12:00:00 AM




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FDA Bans Products That Help Kids Hide Vape Use From Parents

Title: FDA Bans Products That Help Kids Hide Vape Use From Parents
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM




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Injuries a Drain on Employee Productivity

Title: Injuries a Drain on Employee Productivity
Category: Health News
Created: 5/5/2020 12:00:00 AM
Last Editorial Review: 5/5/2020 12:00:00 AM




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The Hypercomplex Genome of an Insect Reproductive Parasite Highlights the Importance of Lateral Gene Transfer in Symbiont Biology

ABSTRACT

Mobile elements—plasmids and phages—are important components of microbial function and evolution via traits that they encode and their capacity to shuttle genetic material between species. We here report the unusually rich array of mobile elements within the genome of Arsenophonus nasoniae, the son-killer symbiont of the parasitic wasp Nasonia vitripennis. This microbe’s genome has the highest prophage complement reported to date, with over 50 genomic regions that represent either intact or degraded phage material. Moreover, the genome is predicted to include 17 extrachromosomal genetic elements, which carry many genes predicted to be important at the microbe-host interface, derived from a diverse assemblage of insect-associated gammaproteobacteria. In our system, this diversity was previously masked by repetitive mobile elements that broke the assembly derived from short reads. These findings suggest that other complex bacterial genomes will be revealed in the era of long-read sequencing.

IMPORTANCE The biology of many bacteria is critically dependent on genes carried on plasmid and phage mobile elements. These elements shuttle between microbial species, thus providing an important source of biological innovation across taxa. It has recently been recognized that mobile elements are also important in symbiotic bacteria, which form long-lasting interactions with their host. In this study, we report a bacterial symbiont genome that carries a highly complex array of these elements. Arsenophonus nasoniae is the son-killer microbe of the parasitic wasp Nasonia vitripennis and exists with the wasp throughout its life cycle. We completed its genome with the aid of recently developed long-read technology. This assembly contained over 50 chromosomal regions of phage origin and 17 extrachromosomal elements within the genome, encoding many important traits at the host-microbe interface. Thus, the biology of this symbiont is enabled by a complex array of mobile elements.




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WRKY13 Enhances Cadmium Tolerance by Promoting D-CYSTEINE DESULFHYDRASE and Hydrogen Sulfide Production

Hydrogen sulfide (H2S), a plant gasotransmitter, functions in the plant response to cadmium (Cd) stress, implying a role for cysteine desulfhydrase in producing H2S in this process. Whether d-CYSTEINE DESULFHYDRASE (DCD) acts in the plant Cd response remains to be identified, and if it does, how DCD is regulated in this process is also unknown. Here, we report that DCD-mediated H2S production enhances plant Cd tolerance in Arabidopsis (Arabidopsis thaliana). When subjected to Cd stress, a dcd mutant accumulated more Cd and reactive oxygen species and showed increased Cd sensitivity, whereas transgenic lines overexpressing DCD had decreased Cd and reactive oxygen species levels and were more tolerant to Cd stress compared with wild-type plants. Furthermore, the expression of DCD was stimulated by Cd stress, and this up-regulation was mediated by a Cd-induced transcription factor, WRKY13, which bound to the DCD promoter. Consistently, the higher Cd sensitivity of the wrky13-3 mutant was rescued by the overexpression of DCD. Together, our results demonstrate that Cd-induced WRKY13 activates DCD expression to increase the production of H2S, leading to higher Cd tolerance in plants.




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Sensory-Directed Genetic and Biochemical Characterization of Volatile Terpene Production in Kiwifruit

Terpene volatiles are found in many important fruit crops, but their relationship to flavor is poorly understood. Here, we demonstrate using sensory descriptive and discriminant analysis that 1,8-cineole contributes a key floral/eucalyptus note to the aroma of ripe 'Hort16A’ kiwifruit (Actinidia chinensis). Two quantitative trait loci (QTLs) for 1,8-cineole production were identified on linkage groups 27 and 29a in a segregating A. chinensis population, with the QTL on LG29a colocating with a complex cluster of putative terpene synthase (TPS)-encoding genes. Transient expression in Nicotiana benthamiana and analysis of recombinant proteins expressed in Escherichia coli showed four genes in the cluster (AcTPS1a–AcTPS1d) encoded functional TPS enzymes, which produced predominantly sabinene, 1,8-cineole, geraniol, and springene, respectively. The terpene profile produced by AcTPS1b closely resembled the terpenes detected in red-fleshed A. chinensis. AcTPS1b expression correlated with 1,8-cineole content in developing/ripening fruit and also showed a positive correlation with 1,8-cineole content in the mapping population, indicating the basis for segregation is an expression QTL. Transient overexpression of AcTPS1b in Actinidia eriantha fruit confirmed this gene produced 1,8-cineole in Actinidia. Structure-function analysis showed AcTPS1a and AcTPS1b are natural variants at key TPS catalytic site residues previously shown to change enzyme specificity in vitro. Together, our results indicate that AcTPS1b is a key gene for production of the signature flavor terpene 1,8-cineole in ripe kiwifruit. Using a sensory-directed strategy for compound identification provides a rational approach for applying marker-aided selection to improving flavor in kiwifruit as well as other fruits.




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Emerging Issues in Male Adolescent Sexual and Reproductive Health Care

Pediatricians are encouraged to address male adolescent sexual and reproductive health on a regular basis, including taking a sexual history, discussing healthy sexuality, performing an appropriate physical examination, providing patient-centered and age-appropriate anticipatory guidance, and administering appropriate vaccinations. These services can be provided to male adolescent patients in a confidential and culturally appropriate manner, can promote healthy sexual relationships and responsibility, can and involve parents in age-appropriate discussions about sexual health.




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E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) Without Respiratory Symptoms

Electronic cigarette or vaping product use–associated lung injury (EVALI) is a newly emerging diagnosis in the United States, yet the incidence has surged greatly in the past year. With the trend of using electronic cigarettes (e-cigarettes) and vaping rising at an alarming rate among teenagers, many are resorting to friends, illicit drug dealers, and other informal sources to obtain their e-cigarettes, which is greatly contributing to the national outbreak of EVALI. The incidence of adolescents presenting with the constellation of respiratory, gastrointestinal, and constitutional symptoms characteristic of EVALI has been widely reported within the nation. We present one such case of an adolescent boy with a 2-year history of daily vaping who presented with nausea, vomiting, weight loss, and fever but lacked the respiratory symptoms that have been reported in the majority of EVALI cases reported thus far. Computed tomography scan of the abdomen and pelvis revealed an incidental finding of lung pathology characteristic of EVALI, prompting further workup and diagnosis of EVALI. In this case, it is demonstrated that the presentation of EVALI can be variable and is still poorly defined. The rising morbidity and mortality from EVALI reveal the importance of considering EVALI in all patients with a history of vaping or e-cigarette use, regardless of the presence or absence of respiratory symptoms.




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E-cigarette Product Characteristics and Subsequent Frequency of Cigarette Smoking

BACKGROUND:

There is a dearth of evidence regarding the association of use of electronic cigarettes (e-cigarettes) with certain product characteristics and adolescent and young adult risk of unhealthy tobacco use patterns (eg, frequency of combustible cigarette smoking), which is needed to inform the regulation of e-cigarettes.

METHODS:

Data were collected via an online survey of participants in the Southern California Children’s Health Study from 2015 to 2016 (baseline) and 2016 to 2017 (follow-up) (N = 1312). We evaluated the association of binary categories of 3 nonmutually exclusive characteristics of the e-cigarette used most frequently with the number of cigarettes smoked in the past 30 days at 1-year follow-up. Product characteristics included device (vape pen and/or modifiable electronic cigarette [mod]), use of nicotine in electronic liquid (e-liquid; yes or no), and use for dripping (directly dripping e-liquid onto the device; yes or no).

RESULTS:

Relative to never e-cigarette users, past-30-day e-cigarette use was associated with greater frequency of past-30-day cigarette smoking at follow-up. Among baseline past-30-day e-cigarette users, participants who used mods (versus vape pens) smoked >6 times as many cigarettes at follow-up (mean: 20.8 vs 1.3 cigarettes; rate ratio = 6.33; 95% confidence interval: 1.64–24.5) after adjustment for sociodemographic characteristics, baseline frequency of cigarette smoking, and number of days of e-cigarette use. After adjustment for device, neither nicotine e-liquid nor dripping were associated with frequency of cigarette smoking.

CONCLUSIONS:

Baseline mod users (versus vape pen users) smoked more cigarettes in the past 30 days at follow-up. Regulation of e-cigarette device type warrants consideration as a strategy to reduce cigarette smoking among adolescents and young adults who vape.




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Glycoprotein 5 Is Cleaved by Cathepsin E during Porcine Reproductive and Respiratory Syndrome Virus Membrane Fusion [Virus-Cell Interactions]

Porcine reproductive and respiratory syndrome (PRRS) is a serious viral disease affecting the global swine industry. Its causative agent, PRRS virus (PRRSV), is an enveloped virus, and therefore membrane fusion between its envelope and host cell target membrane is critical for viral infection. Though much research has focused on PRRSV infection, the detailed mechanisms involved in its membrane fusion remain to be elucidated. In the present study, we performed confocal microscopy in combination with a constitutively active (CA) or dominant negative (DN) mutant, specific inhibitors, and small interfering RNAs (siRNAs), as well as multiple other approaches, to explore PRRSV membrane fusion. We first observed that PRRSV membrane fusion occurred in Rab11-recycling endosomes during early infection using labeled virions and subcellular markers. We further demonstrated that low pH and cathepsin E in Rab11-recycling endosomes are critical for PRRSV membrane fusion. Moreover, PRRSV glycoprotein 5 (GP5) is identified as being cleaved by cathepsin E during this process. Taken together, our findings provide in-depth information regarding PRRSV pathogenesis, which support a novel basis for the development of antiviral drugs and vaccines.

IMPORTANCE PRRS, caused by PRRSV, is an economically critical factor in pig farming worldwide. As PRRSV is a lipid membrane-wrapped virus, merging of the PRRSV envelope with the host cell membrane is indispensable for viral infection. However, there is a lack of knowledge on its membrane fusion. Here, we first explored when and where PRRSV membrane fusion occurs. Furthermore, we determined which host cell factors were involved in the process. Importantly, PRRSV GP5 is shown to be cleaved by cathepsin E during membrane fusion. Our work not only provides information on PRRSV membrane fusion for the first time but also deepens our understanding of the molecular mechanisms of PRRSV infection, which provides a foundation for future applications in the prevention and control of PRRS.




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Trained and Ready, but Not Serving?--Family Physicians Role in Reproductive Health Care




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Wolbachia-infected ant colonies have increased reproductive investment and an accelerated life cycle [RESEARCH ARTICLE]

Rohini Singh and Timothy A. Linksvayer

Wolbachia is a widespread group of maternally-transmitted endosymbiotic bacteria that often manipulates the reproductive strategy and life history of its hosts to favor its own transmission. Wolbachia mediated phenotypic effects are well characterized in solitary hosts, but effects in social hosts are unclear. The invasive pharaoh ant, Monomorium pharaonis, shows natural variation in Wolbachia infection between colonies and can be readily bred under laboratory conditions. We previously showed that Wolbachia-infected pharaoh ant colonies had more queen-biased sex ratios than uninfected colonies, which is expected to favor the spread of maternally-transmitted Wolbachia. Here, we further characterize the effects of Wolbachia on the short- and longer-term reproductive and life history traits of pharaoh ant colonies. First, we characterized the reproductive differences between naturally infected and uninfected colonies at three discrete time points and found that infected colonies had higher reproductive investment (i.e. infected colonies produced more new queens), particularly when existing colony queens were three months old. Next, we compared the long-term growth and reproduction dynamics of infected and uninfected colonies across their whole life cycle. Infected colonies had increased colony-level growth and early colony reproduction, resulting in a shorter colony life cycle, when compared to uninfected colonies.




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Heat dissipation capacity influences reproductive performance in an aerial insectivore [RESEARCH ARTICLE]

Simon Tapper, Joseph J. Nocera, and Gary Burness

Climatic warming is predicted to increase the frequency of extreme weather events, which may reduce an individual's capacity for sustained activity due to thermal limits. We tested whether the risk of overheating may limit parental provisioning of an aerial insectivorous bird in population decline. For many seasonally breeding birds, parents are thought to operate close to an energetic ceiling during the 2-3 week chick-rearing period. The factors determining the ceiling remain unknown, although it may be set by an individual's capacity to dissipate body heat (the heat dissipation limitation hypothesis). Over two breeding seasons we experimentally trimmed the ventral feathers of female tree swallows (Tachycineta bicolor, Vieillot, 1808) to provide a thermal window. We then monitored maternal and paternal provisioning rates, nestling growth rates, and fledging success. We found the effect of our experimental treatment was context-dependent. Females with an enhanced capacity to dissipate heat fed their nestlings at higher rates than controls when conditions were hot, but the reverse was true under cool conditions. Control females and their mates both reduced foraging under hot conditions. In contrast, male partners of trimmed females maintained a constant feeding rate across temperatures, suggesting attempts to match the feeding rate of their partners. On average, nestlings of trimmed females were heavier than controls, but did not have a higher probability of fledging. We suggest that removal of a thermal constraint allowed females to increase provisioning rates, but additionally provided nestlings with a thermal advantage via increased heat transfer during maternal brooding. Our data provide support for the heat dissipation limitation hypothesis and suggest that depending on temperature, heat dissipation capacity can influence reproductive success in aerial insectivores.




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Immunosenescence and its influence on reproduction in a long-lived vertebrate [RESEARCH ARTICLE]

Jessica M. Judson, Dawn M. Reding, and Anne M. Bronikowski

Immunosenescence is a well-known phenomenon in mammal systems, but its relevance in other long-lived vertebrates is less understood. Further, the influence of age and reproductive effort on immune function in long-lived species can be challenging to assess, as long-term data are scarce and it is often difficult to sample the oldest age classes. We used the painted turtle (Chrysemys picta) to test hypotheses of immunosenescence and a trade-off between reproductive output and immune function in a population of a long-lived vertebrate that has been monitored for over 30 years. These long-term data are utilized to employ a unique approach of aging turtles with mark-recapture data and population-specific growth modeling to obtain more accurate estimates of age. We analyzed natural antibodies, lysis ability, and bactericidal competence in 126 individuals from 1 to 33 years of age captured during May and June in 2011. Older turtles exhibited greater natural antibody levels than young individuals across sexes. Young females with large clutches exhibited greater lysis ability, while older females with large clutches had decreased lysis ability, suggesting a trade-off between reproductive output and immune function conditional upon age. However, bactericidal competence increased later in the nesting season for older females. Our study rejects the hypothesis of immunosenescence in a long-lived turtle, despite evidence of actuarial and reproductive senescence in this population. Additionally, we detected mixed evidence for a trade-off between reproduction and immune health.




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Fructose Production and Metabolism in the Kidney

Understanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, inflammation, and fibrosis in the kidney. A recent scientific advance is the discovery that fructose can be endogenously produced from glucose under pathologic conditions, not only in kidney diseases, but also in diabetes, in cardiac hypertrophy, and with dehydration. Why humans have such a deleterious mechanism to produce fructose is unknown, but it may relate to an evolutionary benefit in the past. In this article, we aim to illuminate the roles of fructose as it relates to gluconeogenesis and fructoneogenesis in the kidney.




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Flavin-Containing Monooxygenase 1 Catalyzes the Production of Taurine from Hypotaurine [Articles]

Taurine is one of the most abundant amino acids in mammalian tissues. It is obtained from the diet and by de novo synthesis from cysteic acid or hypotaurine. Despite the discovery in 1954 that the oxygenation of hypotaurine produces taurine, the identification of an enzyme catalyzing this reaction has remained elusive. In large part, this is due to the incorrect assignment, in 1962, of the enzyme as an NAD-dependent hypotaurine dehydrogenase. For more than 55 years, the literature has continued to refer to this enzyme as such. Here we show, both in vivo and in vitro, that the enzyme that oxygenates hypotaurine to produce taurine is flavin-containing monooxygenase (FMO) 1. Metabolite analysis of the urine of Fmo1-null mice by 1H NMR spectroscopy revealed a buildup of hypotaurine and a deficit of taurine in comparison with the concentrations of these compounds in the urine of wild-type mice. In vitro assays confirmed that human FMO1 catalyzes the conversion of hypotaurine to taurine, utilizing either NADPH or NADH as cofactor. FMO1 has a wide substrate range and is best known as a xenobiotic- or drug-metabolizing enzyme. The identification that the endogenous molecule hypotaurine is a substrate for the FMO1-catalyzed production of taurine resolves a long-standing mystery. This finding should help establish the role FMO1 plays in a range of biologic processes in which taurine or its deficiency is implicated, including conjugation of bile acids, neurotransmitter, antioxidant and anti-inflammatory functions, and the pathogenesis of obesity and skeletal muscle disorders.

SIGNIFICANCE STATEMENT

The identity of the enzyme that catalyzes the biosynthesis of taurine from hypotaurine has remained elusive. Here we show, both in vivo and in vitro, that flavin-containing monooxygenase 1 catalyzes the oxygenation of hypotaurine to produce taurine.




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Theophylline Acetaldehyde as the Initial Product in Doxophylline Metabolism in Human Liver [Articles]

Doxophylline (DOXO) and theophylline are widely used as bronchodilators for treating asthma and chronic obstructive pulmonary disease, and DOXO has a better safety profile than theophylline. How DOXO’s metabolism and disposition affect its antiasthmatic efficacy and safety remains to be explored. In this study, the metabolites of DOXO were characterized. A total of nine metabolites of DOXO were identified in vitro using liver microsomes from human and four other animal species. Among them, six metabolites were reported for the first time. The top three metabolites were theophylline acetaldehyde (M1), theophylline-7-acetic acid (M2), and etophylline (M4). A comparative analysis of DOXO metabolism in human using liver microsomes, S9 fraction, and plasma samples demonstrated the following: 1) The metabolism of DOXO began with a cytochrome P450 (P450)–mediated, rate-limiting step at the C ring and produced M1, the most abundant metabolite in human liver microsomes. However, in human plasma, the M1 production was rather low. 2) M1 was further converted to M2 and M4, the end products of DOXO metabolism in vivo, by non-P450 dismutase in the cytosol. This dismutation process also relied on the ratio of NADP+/NADPH in the cell. These findings for the first time elucidated the metabolic sites and routes of DOXO metabolism in human.

SIGNIFICANCE STATEMENT

We systematically characterized doxophylline metabolism using in vitro and in vivo assays. Our findings evolved the understandings of metabolic sites and pathways for methylxanthine derivatives with the aldehyde functional group.




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Monitoring Radioisotope Production and Transport




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DOE Accepting Isotope Production R&D Applications




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Medical Cannabinoid Products in Children and Adolescents




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Advancing Biologics Development Programs with Legacy Cell Lines: Advantages and Limitations of Genetic Testing for Addressing Clonality Concerns Prior to Availability of Late Stage Process and Product Consistency Data

The bioprocessing industry uses recombinant mammalian cell lines to generate therapeutic biologic drugs. To ensure consistent product quality of the therapeutic proteins, it is imperative to have a controlled production process. Regulatory agencies and the biotechnology industry consider cell line "clonal origin" an important aspect of maintaining process control. Demonstration of clonal origin of the cell substrate, or production cell line, has received considerable attention in the past few years, and the industry has improved methods and devised standards to increase the probability and/or assurance of clonal derivation. However, older production cell lines developed before the implementation of these methods, herein referred to as "legacy cell lines," may not meet current regulatory expectations for demonstration of clonal derivation. In this article, the members of the IQ Consortium Working Group on Clonality present our position that the demonstration of process consistency and product comparability of critical quality attributes throughout the development life cycle should be sufficient to approve a license application without additional genetic analysis to support clonal origin, even for legacy cell lines that may not meet current day clonal derivation standards. With this commentary, we discuss advantages and limitations of genetic testing methods to support clonal derivation of legacy cell lines and wish to promote a mutual understanding with the regulatory authorities regarding their optional use during early drug development, subsequent to Investigational New Drug (IND) application and before demonstration of product and process consistency at Biologics License Applications (BLA) submission.




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Control Strategy Approach for a Well-Characterized Vaccine Drug Product

Trumenba (MenB-FHbp; bivalent rLP2086), the first meningococcal serogroup B vaccine approved in the United States and subsequently approved in Europe, Canada, and Australia, is well-characterized. Pfizer devised a control strategy approach by using a simplified control strategy wheel for Trumenba based on International Council for Harmonisation (ICH) Q8 (R2), Q9, Q10, and Q11 guidelines, which provide complementary guidance on pharmaceutical development, quality risk management, quality systems, and development and manufacture of drug substances, respectively. These guidelines ensure product quality using a scientific and risk-based approach. Trumenba contains two factor H binding proteins (FHbps), one from each of the two FHbp subfamilies (A and B), adsorbed onto aluminum phosphate. Trumenba manufacturing processes are complicated by the recombinant protein expression of Subfamily A and B proteins and the nature of the drug product (suspension in syringes); the latter also introduces challenges in controlling product critical quality attributes during the development process. In such complex systems, the control strategy is critical to ensuring consistent desired product quality; it also supports the regulatory requirement of continued improvement through continuous process verification and aids regulatory filing. This article describes Pfizer's approach toward robust control strategy development, built on product and process understanding, and links control strategy to regulatory document sections and flow of controls. Specifically, an approach is presented on product quality attribute criticality determination based on safety and efficacy and on an understanding of process parameter criticality. This was achieved by studying the impact of the approach on product quality attributes to define process parameter and in-process controls. This approach is further explained through Trumenba case studies, highlighting specific quality attributes and the associated controls implemented, and provides a holistic view of controls employed for both drug substance and drug product.




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Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion

OBJECTIVE

Sodium–glucose cotransporter 2 (SGLT2) inhibition causes an increase in endogenous glucose production (EGP). However, the mechanisms are unclear. We studied the effect of SGLT2 inhibitors on EGP in subjects with type 2 diabetes (T2D) and without diabetes (non-DM) in kidney transplant recipients with renal denervation.

RESEARCH DESIGN AND METHODS

Fourteen subjects who received a renal transplant (six with T2D [A1C 7.2 ± 0.1%] and eight non-DM [A1C 5.6 ± 0.1%) underwent measurement of EGP with [3-3H]glucose infusion following dapagliflozin (DAPA) 10 mg or placebo. Plasma glucose, insulin, C-peptide, glucagon, and titrated glucose-specific activity were measured.

RESULTS

Following placebo in T2D, fasting plasma glucose (FPG) (143 ± 14 to 124 ± 10 mg/dL; P = 0.02) and fasting plasma insulin (12 ± 2 to 10 ± 1.1 μU/mL; P < 0.05) decreased; plasma glucagon was unchanged, and EGP declined. After DAPA in T2D, FPG (143 ± 15 to 112 ± 9 mg/dL; P = 0.01) and fasting plasma insulin (14 ± 3 to 11 ± 2 μU/mL; P = 0.02) decreased, and plasma glucagon increased (all P < 0.05 vs. placebo). EGP was unchanged from baseline (2.21 ± 0.19 vs. 1.96 ± 0.14 mg/kg/min) in T2D (P < 0.001 vs. placebo). In non-DM following DAPA, FPG and fasting plasma insulin decreased, and plasma glucagon was unchanged. EGP was unchanged from baseline (1.85 ± 0.10 to 1.78 ± 0.10 mg/kg/min) after DAPA, whereas EGP declined significantly with placebo. When the increase in EGP production following DAPA versus placebo was plotted against the difference in urinary glucose excretion (UGE) for all patients, a strong correlation (r = 0.824; P < 0.001) was observed.

CONCLUSIONS

Renal denervation in patients who received a kidney transplant failed to block the DAPA-mediated stimulation of EGP in both individuals with T2D and non-DM subjects. The DAPA-stimulated rise in EGP is strongly related to the increase in UGE, blunting the decline in FPG.




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Burkholderia cepacia Complex Bacteria: a Feared Contamination Risk in Water-Based Pharmaceutical Products [Reviews]

Burkholderia cepacia (formerly Pseudomonas cepacia) was once thought to be a single bacterial species but has expanded to the Burkholderia cepacia complex (Bcc), comprising 24 closely related opportunistic pathogenic species. These bacteria have a widespread environmental distribution, an extraordinary metabolic versatility, a complex genome with three chromosomes, and a high capacity for rapid mutation and adaptation. Additionally, they present an inherent resistance to antibiotics and antiseptics, as well as the abilities to survive under nutrient-limited conditions and to metabolize the organic matter present in oligotrophic aquatic environments, even using certain antimicrobials as carbon sources. These traits constitute the reason that Bcc bacteria are considered feared contaminants of aqueous pharmaceutical and personal care products and the frequent reason behind nonsterile product recalls. Contamination with Bcc has caused numerous nosocomial outbreaks in health care facilities, presenting a health threat, particularly for patients with cystic fibrosis and chronic granulomatous disease and for immunocompromised individuals. This review addresses the role of Bcc bacteria as a potential public health problem, the mechanisms behind their success as contaminants of pharmaceutical products, particularly in the presence of biocides, the difficulties encountered in their detection, and the preventive measures applied during manufacturing processes to control contamination with these objectionable microorganisms. A summary of Bcc-related outbreaks in different clinical settings, due to contamination of diverse types of pharmaceutical products, is provided.




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SAIGON GARDEN RIVERSIDE VILLAGE THE UNIQUE PRODUCT IN DISTRICT 9, PRICE FROM 21 million VND/M

-Location: Long Binh ward, district 9, HCM city. -Price only from 21 million VND/m2. -The house is in the heart of nature, a peaceful place for yourself. -The unique masterpiece in Saigon. ----- HIGHLIGHTS -Landscape channel leading to each villa. -Tennis court and children's pla...




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AMD Ramping Up CPU Production for Xbox Series X and PlayStation 5

Microsoft and Sony are both hard at working preparing their next generation consoles, the Xbox Series X and PlayStation 5, for launch this holiday season. 

A key factor in getting as many consoles shipped for both companies will be from AMD, who will be providing the latest Zen 2-powered CPU and matching Navi GPU.

AMD is ramping up production as they expect semi-custom revenue to grow in the second quarter and have a big increase in the second half of 2020 as they provide parts for the Xbox Series X and PS5. 

"We expect semi-custom revenue to increase in the second quarter and be heavily weighted towards the second-half of the year, as we ramp production to support the holiday launches of the new PlayStation 5 and Xbox Series X consoles," said AMD CEO Dr. Lisa Su. 

Thanks Tom's Hardware.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443398/amd-ramping-up-cpu-production-for-xbox-series-x-and-playstation-5/




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Robots are taking manufacturing jobs but making firms more productive

Robots are replacing manufacturing workers in France, making companies more productive and reducing employment across the industry




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PTC: Pokemon Go-style tech used to speed up ventilator production



COMPUTER services company PTC is using augmented reality , the enhanced visual technology seen in Pokemon Go smartphone games and Iron Man movies, to produce ventilators in record time for the NHS.




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Early Devonian Fossil Provides Earliest Evidence for Advanced Reproductive Biology in Land Plants

A species of plant that grew about 400 million years ago (Early Devonian period) produced a spectrum of spore sizes, which is an essential innovation necessary for all advanced plant reproductive strategies, including seeds and flowers. The Devonian period is one of the most important time periods for the evolution of land plants. It witnessed [...]




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All product creators can learn something from Jackbox Games’ user experiences

While Jackbox clearly owes a great deal of its current popularity to the shelter-in-place policies, they've also been honing their craft for years. It's worth looking at what makes them work.




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BCG vaccine helps fight infections by boosting immune cell production

The BCG tuberculosis vaccine boosts the production of immune cells and this may explain how it protects newborns from dying of sepsis




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Samsung confirms mass production of 5nm chips soon

Alongside its financial results for Q1






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Sonny Perdue’s predictions about meat production recoveries could be coming true

Meat production this week is up about 3 percent compared with the previous week, according to market reports by SiriusXM’s Rural Radio. That’s still off by as much as a third from a year ago. The numbers are causing some retailers to ration fresh meat purchases or risk selling out their entire supplies. The beef,... Continue Reading




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Highly efficient hydrogen gas production using sunlight, water and hematite

Hydrogen is a possible next generation energy solution, and it can be produced from sunlight and water using photocatalysts. A research group has now developed a strategy that greatly increases the amount of hydrogen produced using hematite photocatalysts. In addition to boosting the high efficiency of what is thought to be the world's highest performing photoanode, this strategy will be applied to artificial photosynthesis and solar water-splitting technologies via university-industry collaborations.




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Tesla has not received 'green light' to resume production: California county health official

Tesla Inc has not been allowed to resume operations at its California vehicle factory as local lockdown measures to curb the spread of the coronavirus remain in effect, a county health official said on Friday.