Filtering of Defects in Semipolar (11−22) GaN Using 2-Steps Lateral Epitaxial Overgrowth

Good-quality (11−22) semipolar GaN sample was obtained using epitaxial lateral overgrowth. The growth conditions were chosen to enhance the growth rate along the [0001] inclined direction. Thus, the coalescence boundaries stop the propagation of basal stacking faults. The faults filtering and the improvement of the crystalline quality were attested by transmission electron microscopy and low temperature photoluminescence. The temperature dependence of the luminescence polarization under normal incidence was also studied

Prevalence of complaints of arm, neck and shoulder among computer office workers and psychometric evaluation of a risk factor questionnaire

<p>Abstract</p> <p>Background</p> <p>Complaints of Arm Neck and Shoulder (CANS) represent a wide range of complaints, which can differ in severity from mild, periodic symptoms to severe, chronic and debilitating conditions. They are thought to be associated with both physical and psychosocial risk factors. The measurement and identification of the various risk factors for these complaints is an important step towards recognizing (a) high risk subgroups that are relevant in profiling CANS; and (b) also for developing targeted and effective intervention plans for treatment. The purpose of the present study was to investigate the prevalence of CANS in a Dutch population of computer workers and to develop a questionnaire aimed at measuring workplace physical and psychosocial risk factors for the presence of these complaints.</p> <p>Methods</p> <p>To examine potential workplace risk factors for the presence of CANS, the Maastricht Upper Extremity Questionnaire (MUEQ), a structured questionnaire, was developed and tested among 264 computer office workers of a branch office of the national social security institution in the Netherlands. The MUEQ holds 95 items covering demographic characteristics, in addition to seven main domains assessing potential risk factors with regard to (1) work station, (2) posture during work, (3) quality of break time, (4) job demands, (5) job control, and (6) social support. The MUEQ further contained some additional questions about the quality of the work environment and the presence of complaints in the neck, shoulder, upper and lower arm, elbow, hand and wrist. The prevalence rates of CANS in the past year were computed. Further, we investigated the psychometric properties of the MUEQ (i.e. factor structure and reliability).</p> <p>Results</p> <p>The one-year prevalence rate of CANS indicated that 54% of the respondents reported at least one complaint in the arm, neck and/or shoulder. The highest prevalence rates were found for neck and shoulder symptoms (33% and 31% respectively), followed by hand and upper arm complaints (11% to 12%) and elbow, lower arm and wrist complaints (6% to 7%). The psychometric properties of the MUEQ were assessed using exploratory factor analysis which resulted in the identification of 12 factors. The calculation of internal consistency and cross validation provided evidence of reliability and lack of redundancy of items.</p> <p>Conclusion</p> <p>Neck and shoulder complaints are more frequently reported among Dutch computer workers than arm, elbow and hand complaints. The results further indicate that the MUEQ has satisfactory reliability and internal consistency when used to document CANS among computer workers in the Netherlands.</p

Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

<p>Abstract</p> <p>Background</p> <p>Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.</p> <p>Methods</p> <p>In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.</p> <p>Results</p> <p>In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.</p> <p>Conclusion</p> <p>An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00703651.</p

Functional characterization of the trans-membrane domain interactions of the Sec61 protein translocation complex beta-subunit

<p>Abstract</p> <p>Background</p> <p>In eukaryotic cells co- and post-translational protein translocation is mediated by the trimeric Sec61 complex. Currently, the role of the Sec61 complex β-subunit in protein translocation is poorly understood. We have shown previously that in <it>Saccharomyces cerevisiae </it>the trans-membrane domain alone is sufficient for the function of the β-subunit Sbh1p in co-translational protein translocation. In addition, Sbh1p co-purifies not only with the protein translocation channel subunits Sec61p and Sss1p, but also with the reticulon family protein Rtn1p.</p> <p>Results</p> <p>We used random mutagenesis to generate novel Sbh1p mutants in order to functionally map the Sbh1p trans-membrane domain. These mutants were analyzed for their interactions with Sec61p and how they support co-translational protein translocation. The distribution of mutations identifies one side of the Sbh1p trans-membrane domain α-helix that is involved in interactions with Sec61p and that is important for Sbh1p function in protein translocation. At the same time, these mutations do not affect Sbh1p interaction with Rtn1p. Furthermore we show that Sbh1p is found in protein complexes containing not only Rtn1p, but also the two other reticulon-like proteins Rtn2p and Yop1p.</p> <p>Conclusion</p> <p>Our results identify functionally important amino acids in the Sbh1p trans-membrane domain. In addition, our results provide additional support for the involvement of Sec61β in processes unlinked to protein translocation.</p

Pressure-temperature evolution of primordial solar system solids during impact-induced compaction

Prior to becoming chondritic meteorites, primordial solids were a poorly consolidated mix of mm-scale igneous inclusions (chondrules) and high-porosity sub-μm dust (matrix). We used high-resolution numerical simulations to track the effect of impact-induced compaction on these materials. Here we show that impact velocities as low as 1.5 km s−1 were capable of heating the matrix to >1,000 K, with pressure–temperature varying by >10 GPa and >1,000 K over ~100 μm. Chondrules were unaffected, acting as heat-sinks: matrix temperature excursions were brief. As impact-induced compaction was a primary and ubiquitous process, our new understanding of its effects requires that key aspects of the chondrite record be re-evaluated: palaeomagnetism, petrography and variability in shock level across meteorite groups. Our data suggest a lithification mechanism for meteorites, and provide a ‘speed limit’ constraint on major compressive impacts that is inconsistent with recent models of solar system orbital architecture that require an early, rapid phase of main-belt collisional evolution

Mutant INS-Gene Induced Diabetes of Youth: Proinsulin Cysteine Residues Impose Dominant-Negative Inhibition on Wild-Type Proinsulin Transport

Recently, a syndrome of Mutant INS-gene-induced Diabetes of Youth (MIDY, derived from one of 26 distinct mutations) has been identified as a cause of insulin-deficient diabetes, resulting from expression of a misfolded mutant proinsulin protein in the endoplasmic reticulum (ER) of insulin-producing pancreatic beta cells. Genetic deletion of one, two, or even three alleles encoding insulin in mice does not necessarily lead to diabetes. Yet MIDY patients are INS-gene heterozygotes; inheritance of even one MIDY allele, causes diabetes. Although a favored explanation for the onset of diabetes is that insurmountable ER stress and ER stress response from the mutant proinsulin causes a net loss of beta cells, in this report we present three surprising and interlinked discoveries. First, in the presence of MIDY mutants, an increased fraction of wild-type proinsulin becomes recruited into nonnative disulfide-linked protein complexes. Second, regardless of whether MIDY mutations result in the loss, or creation, of an extra unpaired cysteine within proinsulin, Cys residues in the mutant protein are nevertheless essential in causing intracellular entrapment of co-expressed wild-type proinsulin, blocking insulin production. Third, while each of the MIDY mutants induces ER stress and ER stress response; ER stress and ER stress response alone appear insufficient to account for blockade of wild-type proinsulin. While there is general agreement that ultimately, as diabetes progresses, a significant loss of beta cell mass occurs, the early events described herein precede cell death and loss of beta cell mass. We conclude that the molecular pathogenesis of MIDY is initiated by perturbation of the disulfide-coupled folding pathway of wild-type proinsulin

Genome of <i>Leptomonas pyrrhocoris</i>:a high-quality reference for monoxenous trypanosomatids and new insights into evolution of <i>Leishmania</i>

Many high-quality genomes are available for dixenous (two hosts) trypanosomatid species of the genera Trypanosoma, Leishmania, and Phytomonas, but only fragmentary information is available for monoxenous (single-host) trypanosomatids. In trypanosomatids, monoxeny is ancestral to dixeny, thus it is anticipated that the genome sequences of the key monoxenous parasites will be instrumental for both understanding the origin of parasitism and the evolution of dixeny. Here, we present a high-quality genome for Leptomonas pyrrhocoris, which is closely related to the dixenous genus Leishmania. The L. pyrrhocoris genome (30.4 Mbp in 60 scaffolds) encodes 10,148 genes. Using the L. pyrrhocoris genome, we pinpointed genes gained in Leishmania. Among those genes, 20 genes with unknown function had expression patterns in the Leishmania mexicana life cycle suggesting their involvement in virulence. By combining differential expression data for L. mexicana, L. major and Leptomonas seymouri, we have identified several additional proteins potentially involved in virulence, including SpoU methylase and U3 small nucleolar ribonucleoprotein IMP3. The population genetics of L. pyrrhocoris was also addressed by sequencing thirteen strains of different geographic origin, allowing the identification of 1,318 genes under positive selection. This set of genes was significantly enriched in components of the cytoskeleton and the flagellum