1,491 research outputs found

    Uncovering the Mechanism of Aggregation of Human Transthyretin.

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    The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify ÎČ-strands F and H as necessary for TTR aggregation. Based on the crystal structures of these segments, we designed two non-natural peptide inhibitors that block aggregation. This work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy

    Enhancing Financial Literacy among College Athletes

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    College students, including athletes, have limited exposure to financial education prior to enrolling in college (Britt et al., 2015). Athletes juggling two full-time roles as athlete and college student have limited time for financial education and the opportunity to work. Some athletes receive athletic scholarships and some do not, but either way, many athletes must seek additional funding and student loans to pay for college. Huston’s (2010) model demonstrated connections between financial literacy, behaviors, and education to serve as a framework for our study. The purpose of this study was to determine college athletes’ subjective and objective financial literacy, how they applied this knowledge, and their preferred mode(s) of financial education to pilot financial literacy education geared specifically for athletes based on their preferences. Data was collected from two institutions in the same Power 5 conference: monthly spending logs, focus groups, interviews, a financial knowledge survey, and pre- and post-tests flanking a financial literacy module in first-year experience courses and summer bridge. A Money 101 course was piloted over eight weeks, and peer financial counseling was offered. As athletes might gain access to their name, image, and likeness (NIL) for potential income in the near future, financial education is paramount

    Evaluating Tidal Marsh Sustainability in the Face of Sea-Level Rise: A Hybrid Modeling Approach Applied to San Francisco Bay

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    Tidal marshes will be threatened by increasing rates of sea-level rise (SLR) over the next century. Managers seek guidance on whether existing and restored marshes will be resilient under a range of potential future conditions, and on prioritizing marsh restoration and conservation activities.Building upon established models, we developed a hybrid approach that involves a mechanistic treatment of marsh accretion dynamics and incorporates spatial variation at a scale relevant for conservation and restoration decision-making. We applied this model to San Francisco Bay, using best-available elevation data and estimates of sediment supply and organic matter accumulation developed for 15 Bay subregions. Accretion models were run over 100 years for 70 combinations of starting elevation, mineral sediment, organic matter, and SLR assumptions. Results were applied spatially to evaluate eight Bay-wide climate change scenarios.Model results indicated that under a high rate of SLR (1.65 m/century), short-term restoration of diked subtidal baylands to mid marsh elevations (-0.2 m MHHW) could be achieved over the next century with sediment concentrations greater than 200 mg/L. However, suspended sediment concentrations greater than 300 mg/L would be required for 100-year mid marsh sustainability (i.e., no elevation loss). Organic matter accumulation had minimal impacts on this threshold. Bay-wide projections of marsh habitat area varied substantially, depending primarily on SLR and sediment assumptions. Across all scenarios, however, the model projected a shift in the mix of intertidal habitats, with a loss of high marsh and gains in low marsh and mudflats.Results suggest a bleak prognosis for long-term natural tidal marsh sustainability under a high-SLR scenario. To minimize marsh loss, we recommend conserving adjacent uplands for marsh migration, redistributing dredged sediment to raise elevations, and concentrating restoration efforts in sediment-rich areas. To assist land managers, we developed a web-based decision support tool (www.prbo.org/sfbayslr)

    Azide Thermolysis Frameworks: Self‐inflating, Porous, and Lightweight Materials

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    Porous organic materials have received increasing attention due to their potential applications, such as gas storage, gas separation, and catalysis. In this work, we present a series of aromatic, polyazide-containing building blocks that enable the formation of a new class of amorphous porous organic materials. The azide precursors are obtained in moderate to good yields following an easy synthesis procedure. By thermal decomposition, self-inflating porous structures named Azide Thermolysis Frameworks (ATFs) can be obtained. Modified thermogravimetric analysis is used to determine the onset temperature at which the azides decompose and the frameworks are formed. The frameworks are further investigated via infrared (IR) spectroscopy, elemental analysis, scanning electron microscopy (SEM), and gas adsorption measurements. Specific surface areas and pore sizes are determined by nitrogen adsorption measurements at 77 K using the Brunauer–Emmett–Teller method (BET) to give surface areas of up to 677 m2^2/g for the ATF resulting from the thermolysis of TPB-Azide at 450 °C, which can compete with early Covalent Organic Frameworks (COFs). The specific surface area can be tuned by varying the thermolysis temperature

    Performance of distributed PV in the UK: a statistical analysis of over 7000 systems

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    In June 2015, the UK fleet of solar photovoltaic (PV) systems reached 7.8 GWp of capacity, but there are wide gaps in our understanding of the performance of these systems, which has lead to the conservative limit of 10 GWp being imposed on UK PV capacity by the Department of Energy and Climate Change. Here we present the results of a statistical analysis of real world UK PV systems which donate data to the Microgen Database, of which there are over 7000. The mean yearly-integrated Performance Ratio (PR) of domestic scale UK PV is 83% with a standard deviation of 7%. By considering yearly-integrated PR, we have shown that 4.1 % of systems suffered long-term underperformance relative to their nominal efficiencies during 2013. The mean degradation rate for crystalline Siliconbased PV systems in the UK is -0.8 ± 0.1% per year. The state-of-the-art of UK PV, in terms of technology, manufacturing, and installation-standards, is found to have increased by 1% per year between 2002 and 2013

    Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

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    Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and UmeĂ„, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of UmeĂ„ University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

    SARS-CoV-2 Variant of Concern B.1.1.7: Diagnostic Sensitivity of Three Antigen-Detecting Rapid Tests.

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    Funder: Foundation for Innovative New DiagnosticsFunder: World Health OrganizationFunder: Ministry of Science, Research and Culture, State of Baden Wuerttemberg, German

    The Malaria Cell Atlas: single parasite transcriptomes across the complete Plasmodium life cycle

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    Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. We profiled the single-cell transcriptomes of thousands of individual parasites, deriving the first high-resolution transcriptional atlas of the entire life cycle. We then used our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected individuals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a eukaryotic parasite and an open-access reference dataset for the study of malaria parasites
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