464 research outputs found

    Neutropenia : an analysis of the risk factors for infection

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    Post-Test Analysis of a 10-Year Sodium Heat Pipe Life Test

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    High-temperature heat pipes are being evaluated for use in energy conversion applications such as fuel cells, gas turbine re-combustors, Stirling cycle heat sources; and with the resurgence of space nuclear power both as reactor heat removal elements and as radiator elements. Long operating life and reliable performance are critical requirements for these applications. Accordingly, long-term materials compatibility is being evaluated through the use of high-temperature life test heat pipes. Thermacore, Inc., has carried out a sodium heat pipe 10-year life test to establish long-term operating reliability. Sodium heat pipes have demonstrated favorable materials compatibility and heat transport characteristics at high operating temperatures in air over long time periods. A representative one-tenth segment Stirling Space Power Converter heat pipe with an Inconel 718 envelope and a stainless steel screen wick has operated for over 87,000 hr (10 years) at nearly 700 C. These life test results have demonstrated the potential for high-temperature heat pipes to serve as reliable energy conversion system components for power applications that require long operating lifetime with high reliability. Detailed design specifications, operating history, and post-test analysis of the heat pipe and sodium working fluid are described. Lessons learned and future life test plans are also discussed

    Glioblastoma Models Reveal the Connection between Adult Glial Progenitors and the Proneural Phenotype

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    Tumor heterogeneity is a major obstacle for finding effective treatment of Glioblastoma (GBM). Based on global expression analysis, GBM can be classified into distinct subtypes: Proneural, Neural, Classical and Mesenchymal. The signatures of these different tumor subtypes may reflect the phenotypes of cells giving rise to them. However, the experimental evidence connecting any specific subtype of GBM to particular cells of origin is lacking. In addition, it is unclear how different genetic alterations interact with cells of origin in determining tumor heterogeneity. This issue cannot be addressed by studying end-stage human tumors.To address this issue, we used retroviruses to deliver transforming genetic lesions to glial progenitors in adult mouse brain. We compared the resulting tumors to human GBM. We found that different initiating genetic lesions gave rise to tumors with different growth rates. However all mouse tumors closely resembled the human Proneural GBM. Comparative analysis of these mouse tumors allowed us to identify a set of genes whose expression in humans with Proneural GBM correlates with survival.This study offers insights into the relationship between adult glial progenitors and Proneural GBM, and allows us to identify molecular alterations that lead to more aggressive tumor growth. In addition, we present a new preclinical model that can be used to test treatments directed at a specific type of GBM in future studies

    An Overview of Long Duration Sodium Heat Pipe Tests

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    High temperature heat pipes are being evaluated for use in energy conversion applications such as fuel cells, gas turbine re-combustors, and Stirling cycle heat sources; with the resurgence of space nuclear power, additional applications include reactor heat removal elements and radiator elements. Long operating life and reliable performance are critical requirements for these applications. Accordingly long-term materials compatibility is being evaluated through the use of high temperature life test heat pipes. Thermacore International, Inc., has carried out several sodium heat pipe life tests to establish long term operating reliability. Four sodium heat pipes have recently demonstrated favorable materials compatibility and heat transport characteristics at high operating temperatures in air over long time periods. A 3l6L stainless steel heat pipe with a sintered porous nickel wick structure and an integral brazed cartridge heater has successfully operated at 650 to 700 C for over 115,000 hours without signs of failure. A second 3l6L stainless steel heat pipe with a specially-designed Inconel 60 I rupture disk and a sintered nickel powder wick has demonstrated over 83,000 hours at 600 to 650 C with similar success. A representative one-tenth segment Stirling Space Power Converter heat pipe with an Inconel 718 envelope and a stainless steel screen wick has operated for over 41 ,000 hours at nearly 700 0c. A hybrid (i.e. gas-fired and solar) heat pipe with a Haynes 230 envelope and a sintered porous nickel wick structure was operated for about 20,000 hours at nearly 700 C without signs of degradation. These life test results collectively have demonstrated the potential for high temperature heat pipes to serve as reliable energy conversion system components for power applications that require long operating lifetime with high reliability, Detailed design specifications, operating hi story, and test results are described for each of these sodium heat pipes. Lessons learned and future life test plans are also discussed

    The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice

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    AbstractBackgroundCerium oxide (CeO2) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles.MethodsAtherosclerosis-prone apolipoprotein E knockout (ApoE−/−) mice were exposed by inhalation to diluted exhaust (1.7mg/m3, 20, 60 or 180min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed.ResultsAddition of CeO2 to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6–8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure.ConclusionsThese results imply that addition of CeO2 nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects

    CODE-2 : moored array and large-scale data report

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    The Coastal Ocean Dynamics Experiment (CODE) was undertaken to identify and study the important dynamical processes which govern the wind-driven motion of coastal water over the continental shelf. The initial effort in this multi-year, multi-institutional research program was to obtain high-quality data sets of all the relevant physical variables needed to construct accurate kinematic and dynamic descriptions of the response of shelf water to strong wind forcing in the 2 to 10 day band. A series of two small-scale, densely- instrumented field experiments of approximately four months duration (called CODE-1 and CODE-2) were designed to explore and to determine the kinematics and momentum and heat balances of the local wind-driven flow over a region of the northern California shelf which is characterized by both relatively simple bottom topography and large wind stress events in both winter and summer. A more lightly instrumented, long -term, large-scale component was designed to help separate the local wind-driven response in the region of the small-scale experiments from motions generated either offshore by the California Current system or in some distant region along the coast, and also to help determine the seasonal cycles of the atmospheric forcing, water structure, and coastal currents over the northern California shelf. The first small-scale experiment (CODE-1) was conducted between April and August, 1981 as a pilot study in "which primary emphasis was placed on characterizing the wind-driven "signal" and the "noise" from which this signal must be extracted. In particular, CODE-1 was designed to identify the key features of the circulation and its variability over the northern California shelf and to determine the important time and length scales of the wind-driven response. The second small-scale experiment (CODE-2) was conducted between April and August, 1982 and was designed to sample more carefully the mesoscale horizonta1 variability observed in CODE-1. This report presents a basic description of the moored array data and some other Eulerian data collected during CODE-2. A brief description of the CODE-2 field program is presented first, followed by a description of the common data analysis procedures used to produce the various data sets presented here. Then basic descriptions of the following data sets are presented: (a) the coastal and moored meteorological measurements, (b) the moored current measurements, (c) array plots of the surface wind stress and near-surface current measurements, (d) the moored temperature and conductivity observations, (e) the bottom pressure measurements, and (f) the wind and adjusted coastal sea level observations obtained as part of the CODE-2 large-scale component.This work has been supported by the National Science Foundation

    Human Brain/Cloud Interface

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    The Internet comprises a decentralized global system that serves humanity’s collective effort to generate, process, and store data, most of which is handled by the rapidly expanding cloud. A stable, secure, real-time system may allow for interfacing the cloud with the human brain. One promising strategy for enabling such a system, denoted here as a “human brain/cloud interface” (“B/CI”), would be based on technologies referred to here as “neuralnanorobotics.” Future neuralnanorobotics technologies are anticipated to facilitate accurate diagnoses and eventual cures for the ∼400 conditions that affect the human brain. Neuralnanorobotics may also enable a B/CI with controlled connectivity between neural activity and external data storage and processing, via the direct monitoring of the brain’s ∼86 × 109 neurons and ∼2 × 1014 synapses. Subsequent to navigating the human vasculature, three species of neuralnanorobots (endoneurobots, gliabots, and synaptobots) could traverse the blood–brain barrier (BBB), enter the brain parenchyma, ingress into individual human brain cells, and autoposition themselves at the axon initial segments of neurons (endoneurobots), within glial cells (gliabots), and in intimate proximity to synapses (synaptobots). They would then wirelessly transmit up to ∼6 × 1016 bits per second of synaptically processed and encoded human–brain electrical information via auxiliary nanorobotic fiber optics (30 cm3) with the capacity to handle up to 1018 bits/sec and provide rapid data transfer to a cloud based supercomputer for real-time brain-state monitoring and data extraction. A neuralnanorobotically enabled human B/CI might serve as a personalized conduit, allowing persons to obtain direct, instantaneous access to virtually any facet of cumulative human knowledge. Other anticipated applications include myriad opportunities to improve education, intelligence, entertainment, traveling, and other interactive experiences. A specialized application might be the capacity to engage in fully immersive experiential/sensory experiences, including what is referred to here as “transparent shadowing” (TS). Through TS, individuals might experience episodic segments of the lives of other willing participants (locally or remote) to, hopefully, encourage and inspire improved understanding and tolerance among all members of the human family

    Elimination of the spin supplementary condition in the effective field theory approach to the post-Newtonian approximation

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    The present paper addresses open questions regarding the handling of the spin supplementary condition within the effective field theory approach to the post-Newtonian approximation. In particular it is shown how the covariant spin supplementary condition can be eliminated at the level of the potential (which is subtle in various respects) and how the dynamics can be cast into a fully reduced Hamiltonian form. Two different methods are used and compared, one based on the well-known Dirac bracket and the other based on an action principle. It is discussed how the latter approach can be used to improve the Feynman rules by formulating them in terms of reduced canonical spin variables.Comment: 42 pages, document changed to match published version, in press; Ann. Phys. (N. Y.) (2012

    Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in the JAK3 gene.

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    High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene was TP53 (97% mutation frequency) followed by BRCA1 (10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, after BRCA1, JAK3 was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-based in vitro functional assay and identified a novel gain-of-function mutation in the kinase domain of JAK3 (p.T1022I). Importantly, p.T1022I JAK3 mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entire JAK3 coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening of CDK12 in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency of JAK3 and CDK12 mutations in a large well characterized cohort. Although p.T1022I JAK3 mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation of CDK12 mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency

    Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in theJAK3gene

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    High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene wasTP53(97% mutation frequency) followed byBRCA1(10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, afterBRCA1,JAK3was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-basedin vitrofunctional assay and identified a novel gain-of-function mutation in the kinase domain ofJAK3(p.T1022I). Importantly, p.T1022IJAK3mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entireJAK3coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening ofCDK12in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency ofJAK3andCDK12mutations in a large well characterized cohort. Although p.T1022IJAK3mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation ofCDK12mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency.ISSN:1932-620
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