Metabolic oscillations on the circadian time scale in <i>Drosophila</i> cells lacking clock genes.

Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 h. Current models propose that transcriptional feedback loops are the primary mechanism for the generation of circadian oscillations. Within this framework, &lt;i&gt;Drosophila&lt;/i&gt; S2 cells are regarded as "non-rhythmic" cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that &lt;i&gt;Drosophila&lt;/i&gt; S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products, and in particular metabolic enzymes, are rhythmically expressed in a 24-h cycle. Metabolomics analyses extended these findings and demonstrate that central carbon metabolism and amino acid metabolism are core metabolic pathways driven by protein rhythms. We thus demonstrate that 24-h metabolic oscillations, coupled to gene and protein cycles, take place in nucleated cells without the contribution of any known circadian regulators. These results therefore suggest a reconsideration of existing models of the clockwork in &lt;i&gt;Drosophila&lt;/i&gt; and other eukaryotic systems

Effect of synthetic antioxidants on the oxidative stability of biodiesel

Biodiesels were prepared using base catalyzed methanolysis of sunflower, soybean and canola oils. Rancimat oxidative stability measurements showed that the induction period (IP) for neat canola biodiesel conformed to EN 14214, the European specification for biodiesel (IP > 6 h). Stability was enhanced when 0.5 wt.% of the synthetic antioxidants di-tert-butylhydroquinone (DTBHQ) or poly(1,2-dihydro- 2,2,4-trimethylquinoline) (Orox PK) was added. Soybean-based biodiesel spiked with 0.5 wt.% DTBHQ also reached this specification. Orox PK improved the stability of sunflower biodiesel but the 3 h induction period specified by ASTM D-6751 could not be reached. Curiously, canola biodiesel was destabilized on adding the antioxidant Naugard P (tris(nonylphenyl) phosphite).The Institutional Research Development Programme (IRDP) and the THRIP program of the Department of Trade and Industry and the National Research Foundation of South Africa, Ltd as well as Xyris Technology.http://www.elsevier.com/locate/fuelai201

Neutrino Cooling of Neutron Stars. Medium effects

This review demonstrates that neutrino emission from dense hadronic component in neutron stars is subject of strong modifications due to collective effects in the nuclear matter. With the most important in-medium processes incorporated in the cooling code an overall agreement with available soft X ray data can be easily achieved. With these findings so called "standard" and "non-standard" cooling scenarios are replaced by one general "nuclear medium cooling scenario" which relates slow and rapid neutron star coolings to the star masses (interior densities). In-medium effects take important part also at early hot stage of neutron star evolution decreasing the neutrino opacity for less massive and increasing for more massive neutron stars. A formalism for calculation of neutrino radiation from nuclear matter is presented that treats on equal footing one-nucleon and multiple-nucleon processes as well as reactions with resonance bosons and condensates. Cooling history of neutron stars with quark cores is also discussed.Comment: To be published in "Physics of Neutron Star Interiors", Eds. D. Blaschke, N.K. Glendenning, A. Sedrakian, Springer, Heidelberg (2001

Implicit Stochastic Optimization for deriving reservoir operating rules in semiarid Brazil

Este artigo investiga a aplicação de Otimização Estocástica Implícita (OEI) para determinar regras de operações mensais em um sistema de reservatórios localizado no nordeste semi-árido brasileiro. OEI emprega um modelo de otimização determinística para encontrar alocações ótimas do reservatório sob vários cenários possíveis de afluências e posteriormente constrói as regras a partir da análise deste conjunto de liberações ótimas. As políticas operacionais fornecem a alocação mensal do reservatório condicionada ao armazenamento no início do mês e a afluência prevista para o mês. Além da clássica análise de regressão, este estudo estabelece as regras por meio de uma estratégia de interpolação bidimensional. Após a sua identificação, as regras são aplicadas para operar o sistema sob novas realizações de afluências e mostram habilidade para produzir políticas semelhantes às obtidas a partir de otimização determinística tendo estas mesmas afluências como previsão perfeita.._________________________________________________________________________________________ ABSTRACT: This paper deals with the application of Implicit Stochastic Optimization (ISO) to determine monthly operating rules for a reservoir system located in the semiarid Northeast of Brazil. ISO employs a deterministic optimization model to find optimal reservoir allocations under several possible inflow scenarios and later constructs the rules by analyzing the ensemble of these optimal releases. The operating policies provide the monthly reservoir release conditioned on the storage at the beginning of the month and the inflow predicted for the month. In addition to the classical regression analysis, this study establishes the rules by a two-dimensional interpolation strategy. After the rules are identified, they are applied to operate the system under new inflow realizations and show ability to produce policies similar to those obtained by deterministic optimization taking the same inflows as perfect forecasts

Viral nanomotors for packaging of dsDNA and dsRNA

While capsid proteins are assembled around single-stranded genomic DNA or RNA in rod-shaped viruses, the lengthy double-stranded genome of other viruses is packaged forcefully within a preformed protein shell. This entropically unfavourable DNA or RNA packaging is accomplished by an ATP-driven viral nanomotor, which is mainly composed of two components, the oligomerized channel and the packaging enzymes. This intriguing DNA or RNA packaging process has provoked interest among virologists, bacteriologists, biochemists, biophysicists, chemists, structural biologists and computational scientists alike, especially those interested in nanotechnology, nanomedicine, AAA+ family proteins, energy conversion, cell membrane transport, DNA or RNA replication and antiviral therapy. This review mainly focuses on the motors of double-stranded DNA viruses, but double-stranded RNA viral motors are also discussed due to interesting similarities. The novel and ingenious configuration of these nanomotors has inspired the development of biomimetics for nanodevices. Advances in structural and functional studies have increased our understanding of the molecular basis of biological movement to the point where we can begin thinking about possible applications of the viral DNA packaging motor in nanotechnology and medical applications

Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19

BACKGROUND Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARSCoV-2 vaccination and receipt of other trial medications. RESULTS A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P=0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P=0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P=0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding: Bill & Melinda Gates Foundation