Enantiomer discrimination and ion receptors

Highly lipophilic α-, β- and γ- cyclodextrin derivatives were prepared in order to obtain enantiomer selective ionophores for β-aryl ammonium ions and selective ionophores for tetrahedral ammonium ions. The extent of cyclodextrin functionalisation and the homogeneity of the products was investigated by chemical depolymerisation, (^1)H and (^13)C NMR and (+)-FAB-, FD- and ES- mass spectral analysis. For each cyclodextrin, the products of alkylation were found to consist of several constitutional isomers and homologues. These highly lipophilic molecules were incorporated into solvent polymeric membranes and investigated as electrochemical sensors for chiral molecules incorporating an aryl ring. Electrodes using BBPA as the plasticizer were stable and well defined with a limit of detection for ephedrine of -log[c] = 6.5. Interference from serum levels of Na+, K+, Ca2+ and Mg2+ is minimal (-logK(^POT) = 3.9). The electrodes were highly enantioselective in binding ephedrine and closely related homologues. The mechanism of enantiomer discrimination was investigated by several multi-nuclear NMR techniques and the complexation process was investigated by ES-MS. Lipophilic per-O-octylated α-, β- and γ- cyclodextrins exhibit size selectivity and cation discrimination in the binding of +NH4, +NMe4 and +NEt4. Sensors based on per-O-octyl-β-cyclodextrin show excellent sensitivity and good selectivity for +NMe4 over metal cations and may be used for the detection of cationic surfactants. Complexation was studied in situ and competitively by ES-MS as well as by and relaxation time acquisition. The possibility of developing several chiral crown ether and cyclam based ionophores was also investigated

Endogenizing Syndromes

African and African American StudiesGovernmen

A role for glycolipid biosynthesis in severe fever with thrombocytopenia syndrome virus entry

A novel bunyavirus was recently found to cause severe febrile illness with high mortality in agricultural regions of China, Japan, and South Korea. This virus, named severe fever with thrombocytopenia syndrome virus (SFTSV), represents a new group within the Phlebovirus genus of the Bunyaviridae. Little is known about the viral entry requirements beyond showing dependence on dynamin and endosomal acidification. A haploid forward genetic screen was performed to identify host cell requirements for SFTSV entry. The screen identified dependence on glucosylceramide synthase (ugcg), the enzyme responsible for initiating de novo glycosphingolipid biosynthesis. Genetic and pharmacological approaches confirmed that UGCG expression and enzymatic activity were required for efficient SFTSV entry. Furthermore, inhibition of UGCG affected a post-internalization stage of SFTSV entry, leading to the accumulation of virus particles in enlarged cytoplasmic structures, suggesting impaired trafficking and/or fusion of viral and host membranes. These findings specify a role for glucosylceramide in SFTSV entry and provide a novel target for antiviral therapies

Antiplatelet Therapy and Platelet Function Testing

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58558/1/20370_ftp.pd

Assessing movement of the California sea cucumber Parastichopus californicus in response to organically enriched areas typical of aquaculture sites

Funding was provided by Fisheries and Oceans Canada’s Aquaculture Collaborative Research and Development Program, Viking Bay Ventures and the Klahoose Shellfish Limited Partnership.An increasing global demand for sea cucumbers has led to interest in benthic ranching of the California sea cucumber Parastichopus californicus beneath existing aquaculture sites in British Columbia, Canada, where high levels of total organic matter (TOM) are typical. The objective of the present study was to investigate movement of P. californicus in relation to areas of increased organic content to assess the feasibility of sea cucumber ranching beneath existing aquaculture sites. A laboratory experiment using adult sea cucumbers showed that P. californicus changed their foraging behaviour based on available amounts of TOM, moving more randomly in high-TOM (~8.0%) areas and more directly in low-TOM (~1.4%) ones. They also moved more rapidly in areas with high TOM than in those with low TOM. As long as animals were exposed to high TOM, they did not abandon random movement. Because of this behaviour, aquaculture tenures may retain a population of cultured individuals, but could also attract wild individuals from the surrounding area.Publisher PDFPeer reviewe

Towards an Improved High Resolution Global Long-Term Solar Resource Database

This paper presents an overview of an ongoing project to develop and deliver a solar mapping processing system to the National Renewable Energy Laboratory (NREL) using the data sets that are planned for production at the National Climatic Data Center (NCDC). NCDC will be producing a long-term radiance and cloud property data set covering the globe every three hours at an approximate resolution of 10 x 10 km. NASA, the originators of the Surface meteorology and Solar Energy web portal are collaborating with SUNY-Albany to develop the production system and solar algorithms. The initial result will be a global long-term solar resource data set spanning over 25 years. The ultimate goal of the project is to also deliver this data set and production system to NREL for continual production. The project will also assess the impact of providing these new data to several NREL solar decision support tools

Optimisation of a Molecular Dynamics Simulation of Chromosome Condensation

We present optimisations applied to a bespoke bio-physical molecular dynamics simulation designed to investigate chromosome condensation. Our primary focus is on domain-specific algorithmic improvements to determining short-range interaction forces between particles, as certain qualities of the simulation render traditional methods less effective. We implement tuned versions of the code for both traditional CPU architectures and the modern many-core architecture found in the Intel Xeon Phi coprocessor and compare their effectiveness. We achieve speed-ups starting at a factor of 10 over the original code, facilitating more detailed and larger-scale experiments

A rule based quality control method for hourly rainfall data and a 1 km resolution gridded hourly rainfall dataset for Great Britain: CEH-GEAR1hr

High-resolution gridded precipitation products are rare globally, particularly below a daily time-step, yet many hydrological applications require, or can be improved by, a higher temporal resolution of rainfall data. Here, we present a new 1 km resolution gridded hourly rainfall dataset for Great Britain (Gridded estimates of hourly areal rainfall for Great Britain (1990–2014) [CEH-GEAR1hr]) using data from over 1900 quality controlled rainfall gauges, which improves upon the current UK national gridded precipitation datasets at daily time-step. We extend and automate a quality control (QC) procedure to permit the use of hourly data for 1990–2014 and independently validate the QC using daily rainfall data and recorded historic events. Our two-tiered validation approach, at daily and hourly timescales, indicates that spurious extreme values are excluded from the resultant dataset, while legitimate values are preserved. We use a nearest neighbour interpolation scheme to derive gridded hourly rainfall values at 1 km resolution, to temporally disaggregate the CEH-GEAR daily gridded dataset and produce an hourly dataset with consistent daily totals. This provides a unique resource for hydrological applications in Great Britain. The CEH-GEAR1hr dataset, associated metadata and QC information, will be freely available from the Environmental Information Data Centre (EIDC) and hosted alongside the daily and monthly CEH-GEAR product

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid

Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. Objectives:We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations. Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation