5,561 research outputs found

    Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy.

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    Macroautophagy is a fundamental and evolutionarily conserved catabolic process that eradicates damaged and aging macromolecules and organelles in eukaryotic cells. Decorin, an archetypical small leucine-rich proteoglycan, initiates a protracted autophagic program downstream of VEGF receptor 2 (VEGFR2) signaling that requires paternally expressed gene 3 (PEG3). We have discovered that PEG3 is an upstream transcriptional regulator of transcription factor EB (TFEB), a master transcription factor of lysosomal biogenesis, for decorin-evoked endothelial cell autophagy. We found a functional requirement of PEG3 for TFEB transcriptional induction and nuclear translocation in human umbilical vein endothelial and PAER2 cells. Mechanistically, inhibiting VEGFR2 or AMP-activated protein kinase (AMPK), a major decorin-activated energy sensor kinase, prevented decorin-evoked TFEB induction and nuclear localization. In conclusion, our findings indicate a non-canonical (nutrient- and energy-independent) mechanism underlying the pro-autophagic bioactivity of decorin via PEG3 and TFEB

    Distribution and Habitat Use of Benthic Fishes in the lower Kanawha River, West Virginia

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    The Kanawha River in West Virginia is a historically diverse system in terms of ichthyofauna although, like many other large rivers, it has been subjected to a suite of anthropomorphic perturbations. These include this system being modified to allow the passage of commercial vessels for industry thus altering flow regimes, increased sedimentation, water depth, and channelization, and decreased interactions with its floodplain. Additionally, the fishes of this system have suffered from deleterious historical water quality issues caused by intensive timber operations, mining, and industrial waste. Post Clean Air Act, Clean Water Act, and Surface Mining Control and Reclamation Act water quality has substantially improved and assessments of pelagic fishes within this system indicate that they have responded positively. However, due to sampling bias with traditional collection techniques, the WVDNR was data deficient on benthic fishes within this nonwadeable system. This study successfully detected seven species that were previously undetected from the Kanawha River proper by implementing benthic otter trawling with the Gerken Siamese Trawl (Innovative Net Systems). In addition to expanding the known distributions of many of West Virginia’s benthic fishes within the Kanawha River proper this study was also able to elucidate associations between several benthic fishes and their habitat use in large rivers, indicating that islands may be providing “islands” of habitat that are important to benthic fishes in this system and that physical habitat is likely more influential to benthic fishes’ habitat use than water quality

    Prosthesis coupling

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    A coupling for use in an apparatus for connecting a prosthesis to the bone of a stump of an amputated limb is described which permits a bio-compatible carbon sleeve forming a part of the prosthesis connector to float so as to prevent disturbing the skin seal around the carbon sleeve. The coupling includes a flexible member interposed between a socket that is inserted within an intermedullary cavity of the bone and the sleeve. A lock pin is carried by the prosthesis and has a stem portion which is adapted to be coaxially disposed and slideably within the tubular female socket for securing the prosthesis to the stump. The skin around the percutaneous carbon sleeve is able to move as a result of the flexing coupling so as to reduce stresses caused by changes in the stump shape and/or movement between the bone and the flesh portion of the stump

    Jets in GRBs

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    In several GRBs afterglows, rapid temporal decay is observed which is inconsistent with spherical (isotropic) blast-wave models. In particular, GRB 980519 had the most rapidly fading of the well-documented GRB afterglows, with t^{-2.05\pm 0.04} in optical as well as in X-rays. We show that such temporal decay is more consistent with the evolution of a jet after it slows down and spreads laterally, for which t^{-p} decay is expected (where p is the index of the electron energy distribution). Such a beaming model would relax the energy requirements on some of the more extreme GRBs by a factor of several hundreds. It is likely that a large fraction of the weak (or no) afterglow observations are also due to the common occurrence of beaming in GRBs, and that their jets have already transitioned to the spreading phase before the first afterglow observations were made. With this interpretation, a universal value of p~2.5 is consistent with all data.Comment: 4 page

    Overview of Orion Crew Module and Launch Abort Vehicle Dynamic Stability

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    With the retirement of the Space Shuttle, NASA is designing a new spacecraft, called Orion, to fly astronauts to low earth orbit and beyond. Characterization of the dynamic stability of the Orion spacecraft is important for the design of the spacecraft and trajectory construction. Dynamic stability affects the stability and control of the Orion Crew Module during re-entry, especially below Mach = 2.0 and including flight under the drogues. The Launch Abort Vehicle is affected by dynamic stability as well, especially during the re-orientation and heatshield forward segments of the flight. The dynamic stability was assessed using the forced oscillation technique, free-to-oscillate, ballistic range, and sub-scale free-flight tests. All of the test techniques demonstrated that in heatshield-forward flight the Crew Module and Launch Abort Vehicle are dynamically unstable in a significant portion of their flight trajectory. This paper will provide a brief overview of the Orion dynamic aero program and a high-level summary of the dynamic stability characteristics of the Orion spacecraft

    TCAD simulation studies of novel geometries for CZT ring-drift detectors

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    In this work, technology computer-aided design (TCAD) simulation results of new CZT ring-drift detector geometries are presented. The physics model was developed and validated against the results from an existing device which had been comprehensively characterised at x-ray wavelengths. The model was then applied to new detector geometries and a systematic study of the parameters influencing charge collection performed. A comparison between one- two- and three-ring circle and semi-rectangular (or squircle) geometries is presented. In was found that charge collection with the squircle ring configuration was systematically better than the circular configuration and extends approximately m further from the collecting anode. In addition, a two-ring geometry device is shown to collect charge m and m further from the anode when compared to one- and three- ring geometries, respectively. Based on these results, we derive an optimum configuration which potentially can be multiplied on larger crystals, offering an increased charge collection volume without compromising energy resolution
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