771 research outputs found

    Paper Session II-B - Solid State Oxygen Sensor Development

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    To anticipate future long-duration mission needs for life support sensors, we explored the feasibility of using thin-film metal-oxide semiconductors. The objective of this task was to develop gas sensors for life support applications which would be suitable for long-duration missions. Metal oxides, such as ZnO, SnO2, and TiO2 have been shown to react with oxygen molecules. Oxygen lowers the metal oxide\u27s electrical resistance. Critical to the performance is the application of the oxide in a thin film on an inert substrate: the thinner the film, the more readily the oxygen penetration and hence the more rapid and sensitive the sensor. Metal oxides are not limited to oxygen detection, rather, oxides offer detection and quantification applications to the complete range of gases of interest, not only for life support systems, but for propellants as well

    In silico discovery of transcription regulatory elements in Plasmodium falciparum

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    <p>Abstract</p> <p>Background</p> <p>With the sequence of the <it>Plasmodium falciparum </it>genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the <it>P. falciparum </it>genome sequence having revealed few <it>cis</it>-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of <it>P. falciparum </it>intergenic regions (~90% AT) presents significant challenges to <it>in silico cis</it>-regulatory element discovery.</p> <p>Results</p> <p>We have developed an algorithm called Gene Enrichment Motif Searching (GEMS) that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich <it>P. falciparum </it>genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from <it>P. falciparum </it>life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative <it>cis</it>-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the <it>Plasmodium </it>literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays were conducted.</p> <p>Conclusion</p> <p>This GEMS analysis demonstrates that <it>in silico </it>regulatory element discovery can be successfully applied to challenging repeat-sequence-rich, base-biased genomes such as that of <it>P. falciparum</it>. The fact that regulatory elements were predicted from a diverse range of functional gene clusters supports the hypothesis that <it>cis</it>-regulatory elements play a role in the transcriptional control of many <it>P. falciparum </it>biological processes. The putative regulatory elements described represent promising candidates for future biological investigation into the underlying transcriptional control mechanisms of gene regulation in malaria parasites.</p

    Full-Shell X-Ray Optics Development at NASA Marshall Space Flight Center

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    NASAs Marshall Space Flight Center (MSFC) maintains an active research program toward the development of high-resolution, lightweight, grazing-incidence x-ray optics to serve the needs of future x-ray astronomy missions such as Lynx. MSFC development efforts include both direct fabrication (diamond turning and deterministic computer-controlled polishing) of mirror shells and replication of mirror shells (from figured, polished mandrels). Both techniques produce full-circumference monolithic (primary + secondary) shells that share the advantages of inherent stability, ease of assembly, and low production cost. However, to achieve high-angular resolution, MSFC is exploring significant technology advances needed to control sources of figure error including fabrication- and coating-induced stresses and mounting-induced distortions

    Impact of sea ice transport on Beaufort Gyre liquid freshwater content

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    The Arctic Ocean’s Beaufort Gyre (BG) is a wind-driven reservoir of relatively fresh seawater, situated beneath time-mean anticyclonic atmospheric circulation, and is covered by mobile pack ice for most of the year. Liquid freshwater accumulation in and expulsion from this gyre is of critical interest due to its potential to affect the Atlantic meridional overturning circulation and due to the importance of freshwater in modulating vertical fluxes of heat, nutrients and carbon in the ocean, and exchanges of heat and moisture with the atmosphere. Here, we investigate the hypothesis that wind-driven sea ice transport into/from the BG region influences the freshwater content of the gyre and its variability. To test this hypothesis, we use the results of a coordinated climate response function experiment with four ice-ocean models, in combination with targeted experiments using a regional setup of the MITgcm, in which we rotate the surface wind forcing vectors (thereby changing the ageostrophic component of these winds). Our results show that, via an effect on the net thermodynamic growth rate, anomalies in sea ice transport into the BG affect liquid freshwater adjustment. Specifically, increased ice import increases freshwater retention in the gyre, whereas ice export decreases freshwater in the gyre. Our results demonstrate that uncertainty in the ageostrophic component of surface winds, and in the dynamic sea ice response to these winds, has important implications for ice thermodynamics and freshwater. This sensitivity may explain some of the observed inter-model spread in simulations of Beaufort Gyre freshwater and its adjustment in response to wind forcing

    Birthing practices of traditional birth attendants in South Asia in the context of training programmes

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    Traditional Birth Attendants (TBA) training has been an important component of public health policy interventions to improve maternal and child health in developing countries since the 1970s. More recently, since the 1990s, the TBA training strategy has been increasingly seen as irrelevant, ineffective or, on the whole, a failure due to evidence that the maternal mortality rate (MMR) in developing countries had not reduced. Although, worldwide data show that, by choice or out of necessity, 47 percent of births in the developing world are assisted by TBAs and/or family members, funding for TBA training has been reduced and moved to providing skilled birth attendants for all births. Any shift in policy needs to be supported by appropriate evidence on TBA roles in providing maternal and infant health care service and effectiveness of the training programmes. This article reviews literature on the characteristics and role of TBAs in South Asia with an emphasis on India. The aim was to assess the contribution of TBAs in providing maternal and infant health care service at different stages of pregnancy and after-delivery and birthing practices adopted in home births. The review of role revealed that apart from TBAs, there are various other people in the community also involved in making decisions about the welfare and health of the birthing mother and new born baby. However, TBAs have changing, localised but nonetheless significant roles in delivery, postnatal and infant care in India. Certain traditional birthing practices such as bathing babies immediately after birth, not weighing babies after birth and not feeding with colostrum are adopted in home births as well as health institutions in India. There is therefore a thin precarious balance between the application of biomedical and traditional knowledge. Customary rituals and perceptions essentially affect practices in home and institutional births and hence training of TBAs need to be implemented in conjunction with community awareness programmes

    Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers

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    PURPOSE: Human papillomavirus (HPV) causes \u3e5% of cancers, but no therapies uniquely target HPV-driven cancers. EXPERIMENTAL DESIGN: We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression. RESULTS: Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein expression correlates with Aurora inhibition-induced apoptosis. Manipulating Rb directly, or by inducing E7 expression, altered cells\u27 sensitivity to Aurora kinase inhibitors. Rb affects expression of the mitotic checkpoint genes MAD2L1 and BUB1B, which we found to be highly expressed in HPV-positive patient tumors. Knockdown of MAD2L1 or BUB1B reduced Aurora kinase inhibition-induced apoptosis, whereas depletion of the MAD2L1 regulator TRIP13 enhanced it. TRIP13 is a potentially druggable AAA-ATPase. Combining Aurora kinase inhibition with TRIP13 depletion led to extensive apoptosis in HPV-positive cancer cells but not in HPV-negative cancer cells. CONCLUSIONS: Our data support a model in which HPV-positive cancer cells maintain a balance of MAD2L1 and TRIP13 to allow mitotic exit and survival in the absence of Rb. Because it does not affect cells with intact Rb function, this novel combination may have a wide therapeutic window, enabling the effective treatment of Rb-deficient cancers

    The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

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    PMCID: PMC3634842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

    IceCube: CubeSat 883-GHz Radiometry for Future Ice Cloud Remote Sensing

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    Ice clouds play a key role in the Earth's radiation budget, mostly through their strong regulation of infrared radiation exchange. Accurate observations of global cloud ice and its distribution have been a challenge from space, and require good instrument sensitivities to both cloud mass and microphysical properties. Despite great advances from recent spaceborne radar and passive sensors, uncertainty of current ice water path (IWP) measurements is still not better than a factor of 2. Submillimeter (submm) wave remote sensing offers great potential for improving cloud ice measurements, with simultaneous retrievals of cloud ice and its microphysical properties. The IceCube project is to enable this cloud ice remote sensing capability in future missions, by raising 874-GHz receiver technology TRL from 5 to 7 in a spaceflight demonstration on 3-U CubeSat in a low Earth orbit (LEO) environment. The NASAs Goddard Space Flight Center (GSFC) is partnering with Virginia Diodes Inc (VDI) on the 874-GHz receiver through its Vector Network Analyzer (VNA) extender module product line, to develop an instrument with precision of 0.2 K over 1-second integration and accuracy of 2.0 K or better. IceCube is scheduled to launch to and subsequent release from the International Space Station (ISS) in mid-2016 for nominal operation of 28 plus days. We will present the updated design of the payload and spacecraft systems, as well as the operation concept. We will also show the simulated 874-GHz radiances from the ISS orbits and cloud scattering signals as expected for the IceCube cloud radiometer

    The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

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    The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses
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