Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways

Fission product release from LWR fuel defected in steam in the temperature range 500 to 1600/sup 0/C

For practical purposes the release of cesium and iodine from LWR fuel rods in the temperature range 500 to 1600/sup 0/C can be considered to originate from three sources: (1) the gap inventory with release by both burst (vented gas) and diffusion; (2) grain boundary with release by tunnel formation; and (3) UO/sub 2/ matrix with release by solid state diffusion. The chemical behavior of released iodine and cesium (at least after contact with steam) is predominantly that of CsI and CsOH. Fission gas release is the sum of the plenum inventory, gas embedded in the fuel and cladding surface layers and that released by tunnel formation, and solid state diffusion from the UO/sub 2/ matrix. A small amount of large particle-sized fuel dust is ejected at time of rupture

Polypyrrole-Fe2O3 nanohybrid materials for electrochemical storage

We report on the synthesis and electrochemical characterization of nanohybrid polypyrrole (PPy) (PPy/Fe2O3) materials for electrochemical storage applications. We have shown that the incorporation of nanoparticles inside the PPy notably increases the charge storage capability in comparison to the “pure” conducting polymer. Incorporation of large anions, i.e., paratoluenesulfonate, allows a further improvement in the capacity. These charge storage modifications have been attributed to the morphology of the composite in which the particle sizes and the specific surface area are modified with the incorporation of nanoparticles. High capacity and stability have been obtained in PC/NEt4BF4 (at 20 mV/s), i.e., 47 mAh/g, with only a 3% charge loss after one thousand cyles. The kinetics of charge–discharge is also improved by the hybrid nanocomposite morphology modifications, which increase the rate of insertion–expulsion of counter anions in the bulk of the film. A room temperature ionic liquid such as imidazolium trifluoromethanesulfonimide seems to be a promising electrolyte because it further increases the capacity up to 53 mAh/g with a high stability during charge–discharge processes

Chloride-Based Additive Engineering for Efficient and Stable Wide-Bandgap Perovskite Solar Cells

Metal halide perovskite based tandem solar cells are promising to achieve power conversion efficiency beyond the theoretical limit of their single-junction counterparts. However, overcoming the significant open-circuit voltage deficit present in wide-bandgap perovskite solar cells remains a major hurdle for realizing efficient and stable perovskite tandem cells. Here, a holistic approach to overcoming challenges in 1.8 eV perovskite solar cells is reported by engineering the perovskite crystallization pathway by means of chloride additives. In conjunction with employing a self-assembled monolayer as the hole-transport layer, an open-circuit voltage of 1.25 V and a power conversion efficiency of 17.0% are achieved. The key role of methylammonium chloride addition is elucidated in facilitating the growth of a chloride-rich intermediate phase that directs crystallization of the desired cubic perovskite phase and induces more effective halide homogenization. The as-formed 1.8 eV perovskite demonstrates suppressed halide segregation and improved optoelectronic properties

Three-dimensional laser micro- and nano-structuring of acrylated poly(ethylene glycol) materials and evaluation of their cytoxicity for tissue engineering applications

The natural cell environment is characterised by complex three-dimensional structures, which contain features at multiple length scales. Many in vitro studies of cell behaviour in three dimensions rely on the availability of artificial scaffolds with controlled three-dimensional topologies. In this paper, we demonstrate fabrication of three-dimensional scaffolds for tissue engineering out of poly(ethylene glycol) diacrylate (PEGda) materials by means of two-photon polymerization (2PP). This laser nanostructuring approach offers unique possibilities for rapid manufacturing of three-dimensional structures with arbitrary geometries. The spatial resolution dependence on the applied irradiation parameters is investigated for two PEGda formulations, which are characterized by molecular weights of 302 and 742. We demonstrate that minimum feature sizes of 200 nm are obtained in both materials. In addition, an extensive study of the cytotoxicity of the material formulations with respect to photoinitiator type and photoinitiator concentration is undertaken. Aqueous extracts from photopolymerized PEGda samples indicate the presence of water-soluble molecules, which are toxic to fibroblasts. It is shown that sample aging in aqueous medium reduces the cytotoxicity of these extracts; this mechanism provides a route for biomedical applications of structures generated by 2PP microfabrication and photopolymerization technologies in general. Finally, a fully biocompatible combination of PEGda and a photoinitiator is identified. Fabrication of reproducible scaffold structures is very important for systematic investigation of cellular processes in three dimensions and for better understanding of in vitro tissue formation. The results of this work suggest that 2PP may be used to polymerize poly(ethylene glycol)-based materials into three-dimensional structures with well-defined geometries that mimic the physical and biological properties of native cell environments

A survey of energy drink consumption patterns among college students

<p>Abstract</p> <p>Background</p> <p>Energy drink consumption has continued to gain in popularity since the 1997 debut of Red Bull, the current leader in the energy drink market. Although energy drinks are targeted to young adult consumers, there has been little research regarding energy drink consumption patterns among college students in the United States. The purpose of this study was to determine energy drink consumption patterns among college students, prevalence and frequency of energy drink use for six situations, namely for insufficient sleep, to increase energy (in general), while studying, driving long periods of time, drinking with alcohol while partying, and to treat a hangover, and prevalence of adverse side effects and energy drink use dose effects among college energy drink users.</p> <p>Methods</p> <p>Based on the responses from a 32 member college student focus group and a field test, a 19 item survey was used to assess energy drink consumption patterns of 496 randomly surveyed college students attending a state university in the Central Atlantic region of the United States.</p> <p>Results</p> <p>Fifty one percent of participants (<it>n </it>= 253) reported consuming greater than one energy drink each month in an average month for the current semester (defined as energy drink user). The majority of users consumed energy drinks for insufficient sleep (67%), to increase energy (65%), and to drink with alcohol while partying (54%). The majority of users consumed one energy drink to treat most situations although using three or more was a common practice to drink with alcohol while partying (49%). Weekly jolt and crash episodes were experienced by 29% of users, 22% reported ever having headaches, and 19% heart palpitations from consuming energy drinks. There was a significant dose effect only for jolt and crash episodes.</p> <p>Conclusion</p> <p>Using energy drinks is a popular practice among college students for a variety of situations. Although for the majority of situations assessed, users consumed one energy drink with a reported frequency of 1 – 4 days per month, many users consumed three or more when combining with alcohol while partying. Further, side effects from consuming energy drinks are fairly common, and a significant dose effect was found with jolt and crash episodes. Future research should identify if college students recognize the amounts of caffeine that are present in the wide variety of caffeine-containing products that they are consuming, the amounts of caffeine that they are consuming in various situations, and the physical side effects associated with caffeine consumption.</p

Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias

The calcium-sensing receptor (CaSR) is a homodimeric G-protein-coupled receptor that signals via intracellular calcium (Ca2+i) mobilisation and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK) to regulate extracellular calcium (Ca2+e) homeostasis. The central importance of the CaSR in Ca2+e homeostasis has been demonstrated by the identification of loss- or gain-of-function CaSR mutations that lead to familial hypocalciuric hypercalcaemia (FHH) or autosomal dominant hypocalcaemia (ADH), respectively. However, the mechanisms determining whether the CaSR signals via Ca2+i or ERK have not been established, and we hypothesised that some CaSR residues, which are the site of both loss- and gain-of-function mutations, may act as molecular switches to direct signalling through these pathways. An analysis of CaSR mutations identified in >300 hypercalcaemic and hypocalcaemic probands revealed five 'disease-switch' residues (Gln27, Asn178, Ser657, Ser820 and Thr828) that are affected by FHH and ADH mutations. Functional expression studies using HEK293 cells showed disease-switch residue mutations to commonly display signalling bias. For example, two FHH-associated mutations (p.Asn178Asp and p.Ser820Ala) impaired Ca2+i signalling without altering ERK phosphorylation. In contrast, an ADH-associated p.Ser657Cys mutation uncoupled signalling by leading to increased Ca2+i mobilization while decreasing ERK phosphorylation. Structural analysis of these five CaSR disease-switch residues together with four reported disease-switch residues revealed these residues to be located at conformationally active regions of the CaSR such as the extracellular dimer interface and transmembrane domain. Thus, our findings indicate that disease-switch residues are located at sites critical for CaSR activation and play a role in mediating signalling bias