10,522 research outputs found

    Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans

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    Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C.elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.X1144sciescopu

    III-nitride Light-emitting Diode with Embedded Photonic Crystals

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    A photonic crystal has been embedded within an InGaN/GaN light-emitting diode structure via epitaxial lateral overgrowth of a p-type GaN capping layer. The photonic crystal is a hexagonal-closed-packed array of nano-pillars patterned by nanosphere lithography; the capping layer planarizes the disconnected pillars to form a current-injection device. Optical properties of the nanostructures and devices are extensively studied through a range of spectroscopy techniques and simulations. Most significantly, the emission wavelengths of embedded photonic crystal light-emitting diodes are nearly invariant of injection currents, attributed to partial suppression of the built-in piezoelectric in the quantum wells. © 2013 AIP Publishing LLC.published_or_final_versio

    Raman and photoluminescence characterization of focused ion beam patterned InGaN/GaN multi-quantum-wells nanopillar array

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    High crystal quality GaN nanopillar arrays containing InGaN/GaN multi-quantum wells (MQWs) have been fabricated by focused ion beam followed by wet etch treatments to remove the ion damage. The first order Raman spectra reveal a well-built additional peak when the diameter of the nanopillars is less than 220 nm. This peak is also observed in the GaN pillars without MQW and is clearly assigned to the surface optical (SO) mode originating from the A 1 phonon in wurtzite GaN. The frequency of this SO mode is found to be sensitive with the diameter and surface roughness of the nanopillars. Temperature-variable photoluminescence measurements show that a broadband emission in the as-grown sample split into the two well-resolved bands for nanopillars and the emission band at the higher energy side quickly thermally quenched. © 2011 American Institute of Physics.published_or_final_versio

    Association of early atherosclerosis with vascular wall shear stress in hypercholesterolemic zebrafish

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    Although atherosclerosis is a multifactorial disease, the role of hemodynamic information has become more important. Low and oscillating wall shear stress (WSS) that changes its direction is associated with the early stage of atherosclerosis. Several in vitro and in vivo models were proposed to reveal the relation between the WSS and the early atherosclerosis. However, these models possess technical limitations in mimicking real physiological conditions and monitoring the developmental course of the early atherosclerosis. In this study, a hypercholesterolaemic zebrafish model is proposed as a novel experimental model to resolve these limitations. Zebrafish larvae are optically transparent, which enables temporal observation of pathological variations under in vivo condition. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro particle image velocimetry (PIV) technique, and spatial distribution of lipid deposition inside the model was quantitatively investigated after feeding high cholesterol diet for 10 days. Lipids were mainly deposited in blood vessel of low WSS. The oscillating WSS was not induced by the blood flows in zebrafish models. The present hypercholesterolaemic zebrafish would be used as a potentially useful model for in vivo study about the effects of low WSS in the early atherosclerosis.1144Ysciescopu

    Potential impact of reactive vaccination in controlling cholera outbreaks: An exploratory analysis using a Zimbabwean experience

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    Background. To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures. Objectives. To explore the potential impact of a hypothetical reactive oral cholera vaccination using the example of the recent large-scale cholera outbreak in Zimbabwe. Methods. This was a retrospective cost-effectiveness analysis calculating the health and economic burden of the cholera outbreak in Zimbabwe with and without reactive vaccination. The primary outcome measure was incremental cost per disability-adjusted life year (DALY) averted. Results. Under the base-case assumptions (assuming 50% coverage among individuals aged ≥2 years), reactive vaccination could have averted 1 320 deaths and 23 650 DALYs. Considering herd immunity, the corresponding values would have been 2 920 deaths and 52 360 DALYs averted. The total vaccination costs would have been ~74millionand 74 million and ~21 million, respectively, with per-dose vaccine price of US5and5 and 1. The incremental costs per DALY averted of reactive vaccination were 2770and2 770 and 370, respectively, for vaccine price set at 5and5 and 1. Assuming herd immunity, the corresponding cost was 980withvaccinepriceof980 with vaccine price of 5, and the programme was cost-saving with a vaccine price of $1. Results were most sensitive to case-fatality rate, per-dose vaccine price, and the size of the outbreak. Conclusions. Reactive vaccination has the potential to be a costeffective measure to contain cholera outbreaks in countries at high risk. However, the feasibility of implementation should be further evaluated, and caution is warranted in extrapolating the findings to different settings in the absence of other in-depth studies

    WiMIR: An Informetric Study on Women Authors in ISMIR

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    Poster session 3: paper no. PS3-29Organized by New York University and Columbia UniversityThe Music Information Retrieval (MIR) community is becoming increasingly aware of a gender imbalance evident in ISMIR participation and publication. This paper reports upon a comprehensive informetric study of the publication, authorship and citation characteristics of female researchers in the context of the ISMIR conferences. All 1,610 papers in the ISMIR proceedings written by 1,910 unique authors from 2000 to 2015 were collected and analyzed. Only 14.1% of all papers were led by female researchers. Temporal analysis shows that the percentage of lead female authors has not improved over the years, but more papers have appeared with female coauthors in very recent years. Topics and citation numbers are also analyzed and compared between female and male authors to identify research emphasis and to measure impact. The results show that the most prolific authors of both genders published similar numbers of ISMIR papers and the citation counts of lead authors in both genders had no significant difference. We also analyzed the collaboration patterns to discover whether gender is related to the number of collaborators. Implications of these findings are discussed and suggestions are proposed on how to continue encouraging and supporting female participation in the MIR field.published_or_final_versio

    Crystallization and preliminary X-ray crystallographic analysis of SEDL

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    SEDL (known also as sedlin) is a 140 amino-acid protein with a putative role in endoplasmic reticulum-to-Golgi transport. Several missense mutations and deletion mutations in the SEDL gene, which result in protein truncation by frame shift, are responsible for spondyloepiphyseal dysplasia tarda, a progressive skeletal disorder. The protein is identical to MIP-2A, which was shown to interact physically with c-myc promotor-binding protein 1 (MBP-1) and relieve the regulatory role of MBP-1 as a general transcription repressor. In order to gain insights into the function of SEDL by structural analysis, the protein was overexpressed and crystallized as a first step. SEDL was overexpressed in Escherichia coli and crystallized using the hanging-drop vapour-diffusion method at 298 K. The crystals belong to the orthorhombic space group C2221, with unit-cell parameters a = 46.69, b = 101.30, c = 66.15 A. The unit cell is likely to contain one molecule of SEDL, with a crystal volume per protein mass (VM) of 2.36 A3 Da-1 and a solvent content of about 47.9% by volume. A native data set to 2.8 A resolution was obtained from a flash-cooled crystal using synchrotron radiation.open1

    Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

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    RE-1 silencing transcription factor (REST) is a transcriptional repressor that regulates gene expression by binding to repressor element 1. However, despite its critical function in physiology, little is known about its interaction proteins. Here we identified 204 REST-interacting proteins using affinity purification and mass spectrometry. The interactome included proteins associated with mRNA processing/splicing, chromatin organization, and transcription. The interactions of these REST-interacting proteins, which included TRIM28, were confirmed by co-immunoprecipitation and immunocytochemistry, respectively. Gene Ontology (GO) analysis revealed that neuronal differentiation-related GO terms were enriched among target genes that were co-regulated by REST and TRIM28, while the level of CTNND2 was increased by the knockdown of REST and TRIM28. Consistently, the level of CTNND2 increased while those of REST and TRIM28 decreased during neuronal differentiation in the primary neurons, suggesting that CTNND2 expression may be coregulated by both. Furthermore, neurite outgrowth was increased by depletion of REST or TRIM28, implying that reduction of both REST and TRIM28 could promote neuronal differentiation via induction of CTNND2 expression. In conclusion, our study of REST reveals novel interacting proteins which could be a valuable resource for investigating unidentified functions of REST and also suggested functional links between REST and TRIM28 during neuronal development.1121Ysciescopu
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