The B_s and D_s decay constants in 3 flavor lattice QCD

Capitalizing on recent advances in lattice QCD, we present a calculation of the leptonic decay constants f_{B_s} and f_{D_s} that includes effects of one strange sea quark and two light sea quarks. The discretization errors of improved staggered fermion actions are small enough to simulate with 3 dynamical flavors on lattices with spacings around 0.1 fm using present computer resources. By shedding the quenched approximation and the associated lattice scale ambiguity, lattice QCD greatly increases its predictive power. NRQCD is used to simulate heavy quarks with masses between 1.5 m_c and m_b. We arrive at the following results: f_{B_s} = 260 \pm 7 \pm 26 \pm 8 \pm 5 MeV and f_{D_s} = 290 \pm 20 \pm 29 \pm 29 \pm 6 MeV. The first quoted error is the statistical uncertainty, and the rest estimate the sizes of higher order terms neglected in this calculation. All of these uncertainties are systematically improvable by including another order in the weak coupling expansion, the nonrelativistic expansion, or the Symanzik improvement program.Comment: 4 page

Adenovirus serotype 26 utilises sialic acid bearing glycans as a primary cell entry receptor

Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis (EKC). As non-enveloped, double stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus serotype 26 (HAdV-D26) is both a cause of EKC and other disease, and a promising vaccine vector. HAdV-D26 derived vaccines are under investigation as protective platforms against HIV, Zika, RSV infections and are in Phase-III clinical trials for Ebola. We recently demonstrated that HAdV-D26 does not utilise CD46 or desmoglein 2 as entry receptors, whilst the putative interaction with Coxsackie and Adenovirus Receptor (CAR) is low affinity and unlikely to represent the primary cell receptor. Here, we definitively establish sialic acid as the primary entry receptor utilised by HAdV-D26. We demonstrate removal of cell surface sialic acid inhibits HAdV-D26 infection and provide a high-resolution crystal structure of HAdV-D26 fiber-knob in complex with sialic acid

Real-Time TEM Imaging of the Formation of Crystalline Nanoscale Gaps

We present real-time transmission electron microscopy of nanogap formation by feedback controlled electromigration that reveals a remarkable degree of crystalline order. Crystal facets appear during feedback controlled electromigration indicating a layer-by-layer, highly reproducible electromigration process avoiding thermal runaway and melting. These measurements provide insight into the electromigration induced failure mechanism in sub-20 nm size interconnects, indicating that the current density at failure increases as the width decreases to approximately 1 nm

Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions

Adenovirus based vectors are of increasing importance for wide ranging therapeutic applications. As vaccines, vectors derived from human adenovirus species D serotypes 26 and 48 (HAdV-D26/48) are demonstrating promising efficacy as protective platforms against infectious diseases. Significant clinical progress has been made, yet definitive studies underpinning mechanisms of entry, infection, and receptor usage are currently lacking. Here, we perform structural and biological analysis of the receptor binding fiber-knob protein of HAdV-D26/48, reporting crystal structures, and modelling putative interactions with two previously suggested attachment receptors, CD46 and Coxsackie and Adenovirus Receptor (CAR). We provide evidence of a low affinity interaction with CAR, with modelling suggesting affinity is attenuated through extended, semi-flexible loop structures, providing steric hindrance. Conversely, in silico and in vitro experiments are unable to provide evidence of interaction between HAdV-D26/48 fiber-knob with CD46, or with Desmoglein 2. Our findings provide insight into the cell-virus interactions of HAdV-D26/48, with important implications for the design and engineering of optimised Ad-based therapeutics

Racial Differences in Survival among Hemodialysis Patients after Coronary Artery Bypass Grafting

The aim of this study was to examine racial differences in long-term survival among hemodialysis patients after coronary artery bypass grafting (CABG). To our knowledge this has not been previously addressed in the literature. Black and white hemodialysis patients undergoing first-time, isolated CABG procedures between 1992 and 2011 were compared. Survival probabilities were computed using the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 207 (2%) patients were on hemodialysis at the time of CABG. White (n = 80) hemodialysis patients had significantly decreased 5-year survival compared with black (n = 127) patients (adjusted HR = 1.9, 95% CI = 1.2–2.8). Our finding provides useful outcome information for surgeons, primary care providers, and their patients

Requirements for Thermochemical Data in the Lighting Community

The need for thermochemical data in the lighting industry is reviewed; these data are required not only in the research and development phase but also throughout the product life cycle. This review has lead to: a summary of commercially available integrated thermochemical databanks; a bibliography of thermodynamic databases available in electronic format; a list of collections of thermodynamic data that are highly valuable but not available in electronic format; a bibliography for chemical systems of specific interest to research into high intensity discharge lamps. The bibliographies will be of interest to those involved in molten salts and ionic liquids research as well as to those seeking information on alloys, oxide systems and nuclear materials. A review of the current state of ab initio calculations for the determination of thermochemical parameters is also included

Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications

Oncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα-binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications

Risk-Adjusted Survival after Coronary Artery Bypass Grafting: Implications for Quality Improvement

Mortality represents an important outcome measure following coronary artery bypass grafting. Shorter survival times may reflect poor surgical quality and an increased number of costly postoperative complications. Quality control efforts aimed at increasing survival times may be misleading if not properly adjusted for case-mix severity. This paper demonstrates how to construct and cross-validate efficiency-outcome plots for a specified time (e.g., 6-month and 1-year survival) after coronary artery bypass grafting, accounting for baseline cardiovascular risk factors. The application of this approach to regional centers allows for the localization of risk stratification rather than applying overly broad and non-specific models to their patient populations