The room temperature phosphine-free synthesis of near-infrared emitting HgSe quantum dots

Luminescent mercury selenide (HgSe) quantum dots have been synthesised by a phosphine-free method using oleic acid as a capping agent. The modification of experimental conditions such as temperature resulted in particles of various sizes (15–100 nm) and morphologies not previously seen in HgSe, with emission tuneable between 1000 nm and 1350 nm

Structure determination of Murine Norovirus NS6 proteases with C-terminal extensions designed to probe protease-substrate interactions

Noroviruses are positive-sense single-stranded RNA viruses. They encode an NS6 protease that cleaves a viral polyprotein at specific sites to produce mature viral proteins. In an earlier study we obtained crystals of murine norovirus (MNV) NS6 protease in which crystal contacts were mediated by specific insertion of the C-terminus of one protein (which contains residues P5-P1 of the NS6-7 cleavage junction) into the peptide binding site of an adjacent molecule, forming an adventitious protease-product complex. We sought to reproduce this crystal form to investigate protease–substrate complexes by extending the C-terminus of NS6 construct to include residues on the C-terminal (P′) side of the cleavage junction. We report the crystallization and crystal structure determination of inactive mutants of murine norovirus NS6 protease with C-terminal extensions of one, two and four residues from the N-terminus of the adjacent NS7 protein (NS6 1′, NS6 2′, NS6 4′). We also determined the structure of a chimeric extended NS6 protease in which the P4-P4′ sequence of the NS6-7 cleavage site was replaced with the corresponding sequence from the NS2-3 cleavage junction (NS6 4′ 2|3).The constructs NS6 1′ and NS6 2′ yielded crystals that diffracted anisotropically. We found that, although the uncorrected data could be phased by molecular replacement, refinement of the structures stalled unless the data were ellipsoidally truncated and corrected with anisotropic B-factors. These corrections significantly improved phasing by molecular replacement and subsequent refinement.The refined structures of all four extended NS6 proteases are very similar in structure to the mature MNV NS6—and in one case reveal additional details of a surface loop. Although the packing arrangement observed showed some similarities to those observed in the adventitious protease-product crystals reported previously, in no case were specific protease–substrate interactions observed

Structural Insights into Differences in Drug-binding Selectivity between Two Forms of Human α1-Acid Glycoprotein Genetic Variants, the A and F1*S Forms

Human α1-acid glycoprotein (hAGP) in serum functions as a carrier of basic drugs. In most individuals, hAGP exists as a mixture of two genetic variants, the F1*S and A variants, which bind drugs with different selectivities. We prepared a mutant of the A variant, C149R, and showed that its drug-binding properties were indistinguishable from those of the wild type. In this study, we determined the crystal structures of this mutant hAGP alone and complexed with disopyramide (DSP), amitriptyline (AMT), and the nonspecific drug chlorpromazine (CPZ). The crystal structures revealed that the drug-binding pocket on the A variant is located within an eight-stranded β-barrel, similar to that found in the F1*S variant and other lipocalin family proteins. However, the binding region of the A variant is narrower than that of the F1*S variant. In the crystal structures of complexes with DSP and AMT, the two aromatic rings of each drug interact with Phe-49 and Phe-112 at the bottom of the binding pocket. Although the structure of CPZ is similar to those of DSP and AMT, its fused aromatic ring system, which is extended in length by the addition of a chlorine atom, appears to dictate an alternative mode of binding, which explains its nonselective binding to the F1*S and A variant hAGPs. Modeling experiments based on the co-crystal structures suggest that, in complexes of DSP, AMT, or CPZ with the F1*S variant, Phe-114 sterically hinders interactions with DSP and AMT, but not CPZ. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Biomechanical Tolerance of Whole Lumbar Spines in Straightened Posture Subjected to Axial Acceleration

Quantification of biomechanical tolerance is necessary for injury prediction and protection of vehicular occupants. This study experimentally quantified lumbar spine axial tolerance during accelerative environments simulating a variety of military and civilian scenarios. Intact human lumbar spines (T12‐L5) were dynamically loaded using a custom‐built drop tower. Twenty‐three specimens were tested at sub‐failure and failure levels consisting of peak axial forces between 2.6 and 7.9 kN and corresponding peak accelerations between 7 and 57 g. Military aircraft ejection and helicopter crashes fall within these high axial acceleration ranges. Testing was stopped following injury detection. Both peak force and acceleration were significant (p \u3c 0.0001) injury predictors. Injury probability curves using parametric survival analysis were created for peak acceleration and peak force. Fifty‐percent probability of injury (95%CI) for force and acceleration were 4.5 (3.9–5.2 kN), and 16 (13–19 g). A majority of injuries affected the L1 spinal level. Peak axial forces and accelerations were greater for specimens that sustained multiple injuries or injuries at L2–L5 spinal levels. In general, force‐based tolerance was consistent with previous shorter‐segment lumbar spine testing (3–5 vertebrae), although studies incorporating isolated vertebral bodies reported higher tolerance attributable to a different injury mechanism involving structural failure of the cortical shell. This study identified novel outcomes with regard to injury patterns, wherein more violent exposures produced more injuries in the caudal lumbar spine. This caudal migration was likely attributable to increased injury tolerance at lower lumbar spinal levels and a faster inertial mass recruitment process for high rate load application. Published 2017. This article is a U.S. Government work and is in the public domain in the USA

Happy to help? A systematic review and meta-analysis of the effects of performing acts of kindness on the well-being of the actor

© 2018 The Authors. Do acts of kindness improve the well-being of the actor? Recent advances in the behavioural sciences have provided a number of explanations of human social, cooperative and altruistic behaviour. These theories predict that people will be ‘happy to help’ family, friends, community members, spouses, and even strangers under some conditions. Here we conduct a systematic review and meta-analysis of the experimental evidence that kindness interventions (for example, performing ‘random acts of kindness’) boost subjective well-being. Our initial search of the literature identified 489 articles; of which 24 (27 studies) met the inclusion criteria (total N = 4045). These 27 studies, some of which included multiple control conditions and dependent measures, yielded 52 effect sizes. Multi-level modeling revealed that the overall effect of kindness on the well-being of the actor is small-to-medium (δ = 0.28). The effect was not moderated by sex, age, type of participant, intervention, control condition or outcome measure. There was no indication of publication bias. We discuss the limitations of the current literature, and recommend that future research test more specific theories of kindness: taking kindness-specific individual differences into account; distinguishing between the effects of kindness to specific categories of people; and considering a wider range of proximal and distal outcomes. Such research will advance our understanding of the causes and consequences of kindness, and help practitioners to maximise the effectiveness of kindness interventions to improve well-being

Thoracoscopic oesophageal atresia/tracheo-oesophageal fistula (OA/TOF) repair is associated with a higher stricture rate: a single institution’s experience

Purpose: Thoracoscopic OA/TOF repair was first described in 1999. Currently, less than 10% of surgeons routinely employ minimally access surgery. Our primary aim was to review our immediate-, early- and long-term outcomes with this technique compared with the open approach. Methods: A retrospective review of all patients undergoing primary OA/TOF (Type C) repair at our institution from 2009 was conducted. Outcome measures included length of surgery, conversion rate from thoracoscopy, early complications such as anastomotic leak and post-operative complications such as anastomotic strictures needing dilatations. Fisher’s exact and Kruskal–Wallis tests were used for statistical analysis. Results: 95 patients in total underwent OA/TOF repair during the study period of which 61 (64%) were completed via an open approach. 34 were attempted thoracoscopically of which 11 (33%) were converted. There was only one clinically significant anastomotic leak in our series that took place in the thoracoscopic group. We identified a significantly higher stricture rate in our thoracoscopic cohort (72%) versus open surgery (43%, P < 0.05). However, the median number of dilations (3) performed was not significantly different between the groups. There was one recurrent fistula in the thoracoscopic converted to open group. Our median follow-up was 60 months across the groups. Conclusion: In our experience, the clinically significant leak rate for both open and thoracoscopic repair as well as recurrent fistula is much lower than has been reported in the literature. We do not routinely perform contrast studies and are, thus, reporting clinically significant leaks only. The use of post-operative neck flexion, ventilation and paralysis is likely to be protective towards a leak. Thoracoscopic OA/TOF repair is associated with a higher stricture rate compared with open surgery; however, these strictures respond to a similar number of dilatations and are no more refractory. Larger, multicentre studies may be useful to investigate these finding further

Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>

Molecular and morphometric variation within and between population samples of the articulate brachiopod &lt;i&gt;Terebratulina&lt;/i&gt; spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation

Probabilistic Inductive Classes of Graphs

Models of complex networks are generally defined as graph stochastic processes in which edges and vertices are added or deleted over time to simulate the evolution of networks. Here, we define a unifying framework - probabilistic inductive classes of graphs - for formalizing and studying evolution of complex networks. Our definition of probabilistic inductive class of graphs (PICG) extends the standard notion of inductive class of graphs (ICG) by imposing a probability space. A PICG is given by: (1) class B of initial graphs, the basis of PICG, (2) class R of generating rules, each with distinguished left element to which the rule is applied to obtain the right element, (3) probability distribution specifying how the initial graph is chosen from class B, (4) probability distribution specifying how the rules from class R are applied, and, finally, (5) probability distribution specifying how the left elements for every rule in class R are chosen. We point out that many of the existing models of growing networks can be cast as PICGs. We present how the well known model of growing networks - the preferential attachment model - can be studied as PICG. As an illustration we present results regarding the size, order, and degree sequence for PICG models of connected and 2-connected graphs.Comment: 15 pages, 6 figure

ASMs and Operational Algorithmic Completeness of Lambda Calculus

We show that lambda calculus is a computation model which can step by step simulate any sequential deterministic algorithm for any computable function over integers or words or any datatype. More formally, given an algorithm above a family of computable functions (taken as primitive tools, i.e., kind of oracle functions for the algorithm), for every constant K big enough, each computation step of the algorithm can be simulated by exactly K successive reductions in a natural extension of lambda calculus with constants for functions in the above considered family. The proof is based on a fixed point technique in lambda calculus and on Gurevich sequential Thesis which allows to identify sequential deterministic algorithms with Abstract State Machines. This extends to algorithms for partial computable functions in such a way that finite computations ending with exceptions are associated to finite reductions leading to terms with a particular very simple feature.Comment: 37 page