844 research outputs found

    Band-gap expansion in the surface-localized electronic structure of MoS2(0002)

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    The electronic band structure of MoS2 single crystals has been investigated using angle-resolved photoelectron spectroscopy and first-principles calculations. The orbital symmetry and k dispersion of these electronic states responsible for the direct and the indirect electronic band gaps have been unambiguously determined. By experimentally probing an increase of the electronic band gap, we conclude that a MoS2 (0002) surface localized state exists just below the valence band maximum at the Gamma point. This electronic state originates from the sulfur planes within the topmost layer. Our comprehensive study addresses the surface electronic structure of MoS2 and the role of van der Waals interlayer interactions.open112625Nsciescopu

    A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

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    Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

    Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport

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    Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis

    Thermal conductivity of refractory glass fibres

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    In the present study, the current international standards and corresponding apparatus for measuring the thermal conductivity of refractory glass fibre products have been reviewed. Refractory glass fibres are normally produced in the form of low-density needled mats. A major issue with thermal conductivity measurements of these materials is lack of reproducibility in the test results due to transformation of the test material during the test. Also needled mats are inherently inhomogeneous, and this poses additional problems. To be able to compare the various methods of thermal conductivity measurement, a refractory reference material was designed which is capable of withstanding maximum test temperatures (1673 K) with minimum transformation. The thermal conductivity of this reference material was then measured using various methods according to the different standards surveyed. In order to compare different materials, samples have been acquired from major refractory glass fibre manufacturers and the results have been compared against the newly introduced reference material. Materials manufactured by melt spinning, melt blowing and sol–gel have been studied, and results compared with literature values

    Understanding dominance: The effect of changing the definition of dominance when using TDS with consumers

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    Temporal dominance of sensations (TDS) is a widely used method to assess dynamic sensory perception. While TDS has been studied more extensively with trained panels, there is growing interest in testing the method with consumers. However, little is known about how consumers interpret the notion of “dominance” to decide which attribute they should select at a given point in time. This study investigated the effect of a changing definition of dominance on TDS results. Consumers, all of who had never undertaken a TDS test before, were recruited in three separate groups where they were briefly trained on TDS where dominance was defined as either: (a) most attention-catching sensation (TDS session), (b) most intense sensation (TIS session), or (c) most changing sensation (TCS session). Results showed that TDS curves were similar between all three sessions, suggesting that consumers’ TDS results are only marginally influenced by the definition of dominance

    Comparison of the pathogenesis of the highly passaged MCMV Smith strain with that of the low passaged MCMV HaNa1 isolate in BALB/c mice upon oronasal inoculation

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    Murine cytomegalovirus (MCMV) Smith strain is widely used in mouse models to study HCMV infections. Due to high serial passages, MCMV Smith has acquired genetic and biological changes. Therefore, a low passaged strain would be more relevant to develop mouse models. Here, the pathogenesis of an infection with MCMV Smith was compared with that of an infection with a low passaged Belgian MCMV isolate HaNa1 in BALB/c adult mice following oronasal inoculation with either a low (10(4) TCID50/mouse) or high (10(6) TCID50/mouse) inoculation dose. Both strains were mainly replicating in nasal mucosa and submandibular glands for one to two months. In nasal mucosa, MCMV was detected earlier and longer (1-49 days post inoculation (dpi)) and reached higher titers with the high inoculation dose compared to the low inoculation dose (14-35 dpi). In submandibular glands, a similar finding was observed (high dose: 7-49 dpi; low dose: 14-42 dpi). In lungs, both strains showed a restricted replication. In spleen, liver and kidneys, only the Smith strain established a productive infection. The infected cells were identified as olfactory neurons and sustentacular cells in olfactory epithelium, macrophages and dendritic cells in NALT, acinar cells in submandibular glands, and macrophages and epithelial cells in lungs for both strains. Antibody analysis demonstrated for both strains that IgG(2a) was the main detectable antibody subclass. Overall, our results show that significant phenotypic differences exist between the two strains. MCMV HaNa1 has been shown to be interesting for use in mouse models in order to get better insights for HCMV infections in immunocompetent humans

    Diagnosis and Treatment of Lupus Nephritis: Survey Results on Four Important Issues

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    Objectives. To investigate the perception of and treatment pattern with regard to the four important issues in the management of lupus nephritis (LN), and to identify which parts of the LN treatment are difficult for physicians to carry out in clinical practice. Methods. Four steps were carried out: pre-survey, LN symposium, post-survey, and meeting after the symposium.The two surveys were conducted with the same contents regarding renal biopsy, induction and maintenance treatment for class III and IV LN, and treatment for class V LN. The results of the first survey and the changes in opinion reflected in the second survey were comparatively analyzed. Results. In the first survey, most of the respondent physicians replied that they would immediately conduct biopsy in the case of significant proteinuria. For the induction treatment of class III and IV LN, most of the respondent physicians selected high-dose cyclophosphamide. Mycophenolate mofetil and steroid combination therapy were selected for the maintenance treatment, and tacrolimus for the treatment of class V LN. There was a controversy in the drug selection, however, especially on the maintenance treatment of class III and IV LN and on the treatment of non-responsive class V LN. Conclusion. Some discrepancies were found in the treatment of LN in the real world. Although no recommendation was made for Korean LN patients in this study, the study results will help physicians select the most reasonable treatment for Korean LN patients based on experts’ experiences and objective evidence

    Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

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    BACKGROUND: BAHD acyltransferases, named after the first four biochemically characterized enzymes of the group, are plant-specific enzymes that catalyze the transfer of coenzyme A-activated donors onto various acceptor molecules. They are responsible for the synthesis in plants of a myriad of secondary metabolites, some of which are beneficial for humans either as therapeutics or as specialty chemicals such as flavors and fragrances. The production of pharmaceutical, nutraceutical and commodity chemicals using engineered microbes is an alternative, green route to energy-intensive chemical syntheses that consume petroleum-based precursors. However, identification of appropriate enzymes and validation of their functional expression in heterologous hosts is a prerequisite for the design and implementation of metabolic pathways in microbes for the synthesis of such target chemicals. RESULTS: For the synthesis of valuable metabolites in the yeast Saccharomyces cerevisiae, we selected BAHD acyltransferases based on their preferred donor and acceptor substrates. In particular, BAHDs that use hydroxycinnamoyl-CoAs and/or benzoyl-CoA as donors were targeted because a large number of molecules beneficial to humans belong to this family of hydroxycinnamate and benzoate conjugates. The selected BAHD coding sequences were synthesized and cloned individually on a vector containing the Arabidopsis gene At4CL5, which encodes a promiscuous 4-coumarate:CoA ligase active on hydroxycinnamates and benzoates. The various S. cerevisiae strains obtained for co-expression of At4CL5 with the different BAHDs effectively produced a wide array of valuable hydroxycinnamate and benzoate conjugates upon addition of adequate combinations of donors and acceptor molecules. In particular, we report here for the first time the production in yeast of rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as chlorogenic acid, and glycerol hydroxycinnamate esters. Similarly, we achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids; and benzoate/caffeate alcohol esters. In some instances, the additional expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed the synthesis of p-coumarate conjugates and eliminated the need to supplement the culture media with 4-hydroxycinnamate. CONCLUSION: We demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates

    2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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