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Cu is a unique metal that catalyzes carbon monoxide/carbon dioxide (CO/CO 2 ) to form high-order hydrocarbons and oxygenates through the CO/CO 2 reduction reaction (CO/CO 2 RR) at decent selectivity and productivity.
The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis. In response to fluctuating blood glucose levels ChREBP activity is regulated mainly by nucleocytoplasmic shuttling of ChREBP. Under high glucose ChREBP binds to importin α and importin β and translocates into the nucleus to initiate transcription. We have previously shown that the nuclear localization signal site (NLS) for ChREBP is bipartite with the NLS extending from Arg158 to Lys190. Here, we report the 2.5 Å crystal structure of the ChREBP-NLS peptide bound to importin α. The structure revealed that the NLS binding is monopartite, with the amino acid residues K171RRI174 from the ChREBP-NLS interacting with ARM2–ARM5 on importin α. We discovered that importin α also binds to the primary binding site of the 14-3-3 proteins with high affinity, which suggests that both importin α and 14-3-3 are each competing with the other for this broad-binding region (residues 117–196) on ChREBP. We screened a small compound library and identified two novel compounds that inhibit the ChREBP-NLS/importin α interaction, nuclear localization, and transcription activities of ChREBP. These candidate molecules support developing inhibitors of ChREBP that may be useful in treatment of obesity and the associated diseases.
Abstract Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1–28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose.
The growing adoption of photovoltaic systems in power distribution networks has yielded numerous advantages, but it has also introduced challenges, particularly in managing overvoltage issues. Uncoordinated photovoltaic integration can lead to voltage rise beyond acceptable levels. Curtailing active power is an effective method for addressing overvoltage issues in power distribution systems. Nevertheless, it is essential to distribute the curtailment fairly among the resources to maintain fairness and achieve a well-balanced utilization of renewable energy. This paper presents a comparative study of different fairness schemes for active power curtailment in photovoltaic integration systems. Three different curtailment methods are selected for demonstration: i) proportional, ii) egalitarian, and iii) financial. The study involves evaluating the curtailment schemes based on their ability to distribute the curtailed power among the photovoltaic systems in a justifiable manner, focusing on their formulation and distributed solution. A detailed performance comparison is carried out to highlight the cost of catering for fairness schemes in photovoltaic curtailment using relevant metrics, where simulations are carried out using a modified IEEE 123-bus test case.
In this work, a new configuration of the modular multilevel converter (MLC) based on the parallel connection of three-level active-neutral-point-clamped (3L-ANPC) cells as well as its improved modulation method is proposed for 1 MHz, 1 MW electric vehicle (EV) megacharger. In the proposed paralleled modular ANPC-MLC, only six high-frequency silicon carbide (SiC) power switches operating at 333 kHz are required to generate 1 MHz switching frequency spectrum. Moreover, the operating voltage of all power devices is halved, the magnitude of the first switching frequency harmonic cluster is decreased by the factor of five, and the load current is equally distributed between the 3L-ANPC legs by employing the proposed improved modulation method. Hence, the modularity, efficiency, and power density of the proposed converter are notably increased, whereas the value of passive components and the overall switching loss are remarkably decreased. In addition, an optimized design of the one 3L-ANPC cell of the proposed paralleled modular ANPC-MLC for 1 MHz, 1MW EV megacharger using Ansys SIwave, Icepak, and Q3D finite element method platforms is presented and analyzed in detail. The provided experimental results of the down-scaled setup verify the feasibility and viability of the proposed configuration as well as its improved switching pattern.
This article presents an open-switch postfault operational technique with enhanced torque–speed region for three-level (3L) active neutral point clamped (ANPC) inverter-driven symmetrical six-phase (SSP) permanent magnet synchronous machines (PMSMs). Maximum torque (MT), minimum loss (ML), and single three-phase (STP) operations are commonly used for the postfault operations of six-phase drives. The maximum possible torque and speed in these operations are generally limited by voltage, current ratings, and the neutral point configuration of the motor. To enhance the postfault torque and speed operating region, the torque and speed limits in different postfault operational techniques are determined based on the voltage, current constraints, and neutral point configuration of the SSP-PMSM. In this work, a unified postfault operation is proposed that increases the postfault operational limits by combining MT, ML, and STP operations and modifying the neutral point configuration of the SSP-PMSM. In addition, a technique is also presented that modifies the pulsewidth modulation technique to enable full torque operation below 0.5 p.u. speed. The proposed postfault operational technique enables full-speed (1 p.u.) operation by operating in STP mode and full torque operation (1 p.u.) below 0.5 p.u. speed. Furthermore, the postfault operational technique is experimentally validated using a Gallium Nitride (GaN) device-based3L-ANPC inverter-driven SSP-PMSM.
The biological bases of longevity are not well understood, and there are limited biomarkers for the prediction of long life. We used a high-throughput, discovery-based proteomics approach to identify serum peptides and proteins that were associated with the attainment of longevity in a longitudinal study of community-dwelling men age ≥65 years. Baseline serum in 1196 men were analyzed using liquid chromatography–ion mobility–mass spectrometry, and lifespan was determined during ~12 years of follow-up. Men who achieved longevity (≥90% expected survival) were compared to those who died earlier. Rigorous statistical methods that controlled for false positivity were utilized to identify 25 proteins that were associated with longevity. All these proteins were in lower abundance in long-lived men and included a variety involved in inflammation or complement activation. Lower levels of longevity-associated proteins were also associated with better health status, but as time to death shortened, levels of these proteins increased. Pathway analyses implicated a number of compounds as important upstream regulators of the proteins and implicated shared networks that underlie the observed associations with longevity. Overall, these results suggest that complex pathways, prominently including inflammation, are linked to the likelihood of attaining longevity. This work may serve to identify novel biomarkers for longevity and to understand the biology underlying lifespan.
Global vegetation and land-surface models embody interdisciplinary scientific understanding of the behaviour of plants and ecosystems, and are indispensable to project the impacts of environmental change on vegetation and the interactions between vegetation and climate. Furthermore, systematic errors and persistently large differences among carbon and water cycle projections by different models highlight the limitations of current process formulations. In this review, focusing on core plant functions in the terrestrial carbon and water cycles, we show how unifying hypotheses derived from eco-evolutionary optimality (EEO) principles can provide novel, parameter-sparse representations of plant and vegetation processes. We present case studies that demonstrate how EEO generates parsimonious representations of core, leaf-level processes that are individually testable and supported by evidence. EEO approaches to photosynthesis and primary production, dark respiration and stomatal behaviour are ripe for implementation in global models. EEO approaches to other important traits, including the leaf economics spectrum and applications of EEO at the community level are active research areas. Independently tested modules emerging from EEO studies could profitably be integrated into modelling frameworks that account for the multiple time scales on which plants and plant communities adjust to environmental change.
Wood-decaying fungi of the class Agaricomycetes (phylum Basidiomycota) are saprotrophs that break down lignocellulose and play an important role in nutrient recycling. They secrete a wide range of extracellular plant cell wall degrading enzymes that break down cellulose, hemicellulose, and lignin, the main building blocks of plant biomass. Although the production of these enzymes is regulated mainly at the transcriptional level, no activating regulators have been identified in any wood-decaying fungus in the class Agaricomycetes. We studied the regulation of cellulase expression in the wood-decaying fungus Schizophyllum commune. Comparative genomics and transcriptomics on two wild isolates revealed a Zn 2 Cys 6 -type transcription factor gene (roc1) that was highly upregulated during growth on cellulose, compared to glucose. It is only conserved in the class Agaricomycetes. A roc1 knockout strain showed an inability to grow on medium with cellulose as sole carbon source, and growth on cellobiose and xylan (other components of wood) was inhibited. Growth on non-wood-related carbon sources was not inhibited. Cellulase gene expression and enzyme activity were reduced in the Δroc1 strain. ChIP-Seq identified 1474 binding sites of the Roc1 transcription factor. Promoters of genes involved in lignocellulose degradation were enriched with these binding sites, especially those of LPMO (lytic polysaccharide monooxygenase) CAZymes, indicating that Roc1 directly regulates these genes. A conserved motif was identified as the binding site of Roc1, which was confirmed by a functional promoter analysis. Together, Roc1 is a key regulator of cellulose degradation and the first identified in wood-decaying fungi in the phylum Basidiomycota.
This dataset contains data files for multiple measurements of sample biogeochemistry and function collected for the Soils SFA Chitin Decomposition project in task 2.2. Samples were generated from soil incubated under different moisture levels, with and without chitin. Each sheet in the file refers to the preprocessed data collected. Sheet 1 "Respiration" measures CO2 production daily for the course of the incubation. Sheet 2 "Biomass" contains the microbial biomass and salt extractable measurements for carbon and nitrogen. Sheet 3 "Chitin" is for HPLC measured chitin from each sample. Sheet 4 "Extracellular Enzyme Assays" records the level of activity for several enzyme assays. Sheet 5 "Enzyme Kinetics" measures degradation of substrate over time for all samples.
Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiated robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo , Mavs -/- mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified defects in type I interferon and interferon responsive gene expression within microglia in Mavs -/- mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis.
In this paper the National Renewable Energy Laboratory (NREL) explores the commercial and industrial (C&I) energy efficiency market in the Dominican Republic, including the market’s current status. During NREL’s engagement with its Dominican counterparts, NREL noted market gaps, identified by both public and private sector market actors, that became the focus of this report. The intent is two-fold. First, to assist potential customers, project financing institutions, and various government agencies understand where the energy efficiency sector stands, in August 2020. Second to help them recognize the scope, scale, and opportunity for energy savings from untapped potential large reductions in energy expenditures. This research identified how savings could be captured through improvements to the enabling environment, technical capacity, and level of activity in the sector. Moreover, it determined that through taking action to catalyze energy efficiency investment, the government could make significant progress towards its self-declared NDC goals, and result in tens of millions of dollars in savings across the Dominican economy for both the private and public sectors.
Microalgal docosahexaenoic acid (DHA) and astaxanthin (AST) may substitute for fish oil and synthetic AST in aquafeeds. This study explored the effects and mechanisms of those substitutions on AST metabolism and redox status of rainbow trout fed plant protein meal (PM)- or fishmeal (FM)-based diets. Two parallel experiments (PM vs. FM) were performed with 612 juvenile rainbow trout for 16 weeks as a 2 × 3 factorial arrangement of treatments with two AST sources (synthetic (SA) vs. microalgal (AA), at 80 mg/kg) and three levels (0, 50, and 100%) of fish oil substitutions with DHA-rich microalgae. The fish oil substitutions exhibit main effects (p < 0.05) and/or interactive effects (p < 0.05) with the source of AST on AST deposition, malondialdehyde and glutathione concentrations, and mRNA levels and activities of major redox enzymes (glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), and superoxide dismutase (SOD)) in the muscle and liver of trout fed both diet series. The AST source produced only differences in tissue AST deposition (p < 0.05) and number of metabolites. In conclusion, the substitutions of fish oil by the DHA-rich microalgae exerted more impacts than those of SA by AA on redox status and functional expression of antioxidant enzymes in the tissues of rainbow trout.
The paper focuses on packaging of dismantled and fragmented reactor components into containers and their transport to their storage and/or disposal facility within the immediate dismantling strategy applied on decommissioning of nuclear power plant (NPP) finally shutdown after standard operation. The main purpose of the paper is to present the process of design, manufacture, testing and use of new transport and storage containers for activated intermediate level waste (ILW) from V1 NPP decommissioning at Jaslovske Bohunice site. Legislation conditions, container selection process, requirements on their design and manufacture, scope of associated licensing documentation and technical procedures applied up to their use on site are described in detail. (authors)
ABSTRACT Dominance of Lactobacillus species in vaginal communities is a hallmark of healthy conditions in the female genital tract. Key nutrients for lactobacilli include sugars produced when glycogen is degraded by α-amylase in the vagina. While α-amylase activity has been demonstrated in vaginal fluids, it is unclear whether α-amylases are produced solely by the host, bacteria in the vagina, or both. We screened cervicovaginal mucus from 23 reproductive-age women, characterized the species composition of vaginal communities, measured vaginal pH, and determined levels of amylase activity, glycogen, and lactic acid. Based on differences in these measured variables, one sample from each of four individual donors was selected for metagenomic and proteomic analyses. Of eight putative bacterial amylases identified in the assembled bacterial metagenomes, we detected four in vaginal fluids. These amylases were produced by various bacteria in different vaginal communities. Moreover, no two communities were the same in terms of which bacteria were producing amylases. Although we detected bacterial amylases in vaginal fluids, there was no clear association between the bacterial species that was dominant in a community and the level of amylase activity. This association was likely masked by the presence of human α-amylase, which was also detected in vaginal fluids. Finally, the levels of amylase activity and glycogen were only weakly associated. Our findings show, for the first time, that multiple amylases from both bacterial and human origins can be present simultaneously in the vagina. This work also suggests that the link between glycogen, amylase, and Lactobacillus in the vagina is complex. IMPORTANCE In this study, we show that multiple bacteria in the vaginal community produce amylases that hydrolyze glycogen into simpler sugars (i.e., maltose and maltotriose). These sugars serve as “common goods” that sustain bacterial populations in vaginal communities. Given the temporal changes that are observed in the human vaginal microbiome, we expect the kinds of bacterial amylases produced will also vary over time. These differences influence the pool of resources that are broadly shared and shape the species composition of the vaginal bacterial community.
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 μg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti–S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273–induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine–induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.
In December 2021, SRR-E sent an ~185 mL sample identified as FPP-3 from a F-Area pump pit sump to SRNL for analysis. The sample was pale yellow in color and contained a small amount of suspended solids visually estimated to be less than 1% by volume. SRNL analysis indicated that the sample contained 4.4 E+05 dpm/mL Cs-137, 6.2 E+05 dpm/mL total beta activity, 9.3 E+02 dpm/mL beta activity following cesium removal, and below detectable levels of alpha activity following cesium removal. In addition, the sample contained 0.015 M free OH- and 947 μg total organic carbon/mL.
In December 2021, SRR-E sent an ~250 mL sample identified as HDB-7 from an H-Area diversion box sump to SRNL for analysis. The sample was clear and colorless and free from any solids. SRNL analysis indicated that the sample contained 2.97E+05 dpm/mL Cs-137, 3.74E+05 dpm/mL total beta activity, 1.04E+03 dpm/mL beta activity following cesium removal, and below detectable levels of alpha activity and alpha activity following cesium removal. In addition, the pH of the sample was 7.32, free hydroxide concentration was 2.09E-07 M, and the density was 0.991 g/mL.