371 research outputs found

    AOIPS 3 user's guide. Volume 2: Program descriptions

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    The Atmospheric and Oceanographic Information Processing System (AOIPS) 3 is the version of the AOIPS software as of April 1989. The AOIPS software was developed jointly by the Goddard Space Flight Center and General Sciences Corporation. A detailed description of very AOIPS program is presented. It is intended to serve as a reference for such items as program functionality, program operational instructions, and input/output variable descriptions. Program descriptions are derived from the on-line help information. Each program description is divided into two sections. The functional description section describes the purpose of the program and contains any pertinent operational information. The program description sections lists the program variables as they appear on-line, and describes them in detail

    The characteristics of environmental particulate matter in the urban area of Beijing, China, during the 2008 Olympic Games

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    Atmospheric particulate matter (PM) and street dust samples from the Chaoyang District of eastern Beijing were studied over a period encompassing the 2008 Beijing Olympic Games. PM10 concentration data are combined with trajectory clustering and potential source contribution function (PSCF) methods to identify the principal transport pathways. Sources for high-concentration aerosol events and airflow from the surrounding Hebei Province and Shandong Province to the southeast are found to exert the most significant external influence on Beijing's air quality. China undertook a number of initiatives to improve air quality for the Olympic Games and we show that PM10 concentrations and magnetic susceptibility were significantly lower during the Olympic period compared to the pre-Olympic period confirming that controlling local sources in Beijing and shutting factories in surrounding provinces substantially improved air quality. On short timescales PM10 shows an inverse correlation to relative humidity and hence precipitation which acts to improve air quality. Atmospheric PM and street dust remained high through the Olympic period probably due in part to redistribution of historical sources and implying that the aim of zero pollution is not achievable in the short term. Analysis of the heavy metal content in both PM and street dust identifies consistently high values of Zn, with Pb relatively higher in the PM; a primary source in vehicular emissions therefore seems likely. Copyright (C) 2016 Turkish National Committee for Air Pollution Research and Control. Production and hosting by Elsevier B.V. All rights reserved.West Light Foundation of CAS [XBBS201302]; National Natural Science Foundation of China [40525013]SCI(E)ARTICLE1141-148

    Differential involvement of the microtubule cytoskeleton in insulin receptor substrate 1 (IRS-1) and IRS-2 signaling to AKT determines the response to microtubule disruption in breast carcinoma cells

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    The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor 1 receptor (IGF-1R) and its close family member, the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling. Treatment with drugs that either stabilize or disrupt microtubules reveal that an intact microtubule cytoskeleton contributes to IRS-2- but not IRS-1-mediated activation of AKT by IGF-1. Proximal IGF-1R signaling events, including IRS tyrosine phosphorylation and recruitment of PI3K, are not inhibited by microtubule disruption, indicating that IRS-2 requires the microtubule cytoskeleton at the level of downstream effector activation. IRS-2 colocalization with tubulin is enhanced upon Taxol-mediated microtubule stabilization, which, together with the signaling data, suggests that the microtubule cytoskeleton may facilitate access of IRS-2 to downstream effectors such as AKT. Of clinical relevance is that our data reveal that expression of IRS-2 sensitizes breast carcinoma cells to apoptosis in response to treatment with microtubule-disrupting drugs, identifying IRS-2 as a potential biomarker for the response of breast cancer patients to Vinca alkaloid drug treatment

    Oxygen hole formation controls stability in LiNiO2 cathodes

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    Ni-rich lithium-ion cathode materials achieve both high voltages and capacities but are prone to structural instabilities and oxygen loss. The origin of the instability lies in the pronounced oxidation of O during delithiation: for LiNiO2, NiO2, and the rock salt NiO, density functional theory and dynamical mean-field theory calculations based on maximally localized Wannier functions yield a Ni charge state of ca. +2, with O varying between −2 (NiO), −1.5 (LiNiO2), and −1 (NiO2). Calculated X-ray spectroscopy Ni K and O K-edge spectra agree well with experimental spectra. Using ab initio molecular dynamics simulations, we observe loss of oxygen from the (012) surface of delithiated LiNiO2, two surface O⋅− radicals combining to form a peroxide ion, and the peroxide ion being oxidized to form O2, leaving behind two O vacancies and two O2− ions. Preferential release of 1O2 is dictated via the singlet ground state of the peroxide ion and spin conservation

    Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC)

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    The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). High IRS-2 expression was significantly associated with decreased overall survival in adenocarcinoma (ADC) patients, whereas low IRS-1 cytoplasmic expression showed a trend toward association with decreased overall survival in squamous cell carcinoma (SCC) patients. Tumors with low IRS-1 and high IRS-2 expression were found to be associated with poor outcomes in ADC and SCC, indicating a potential role for IRS-2 in the aggressive behavior of NSCLC. Our results suggest distinct contributions of IRS-1 and IRS-2 to the biology of ADC and SCC that impact disease progression

    The window period of NEUROGENIN3 during human gestation

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    The basic helix-loop-helix transcription factor, NEUROG3, is critical in causing endocrine commitment from a progenitor cell population in the developing pancreas. In human, NEUROG3 has been detected from 8 weeks postconception (wpc). However, the profile of its production and when it ceases to be detected is unknown. In this study we have defined the profile of NEUROG3 detection in the developing pancreas to give insight into when NEUROG3- dependent endocrine commitment is possible in the human fetus. Immunohistochemistry allowed counting of cells with positively stained nuclei from 7 wpc through to term. mRNA was also isolated from sections of human fetal pancreas and NEUROG3 transcription analyzed by quantitative reverse transcription and polymerase chain reaction. NEUROG3 was detected as expected at 8 wpc. The number of NEUROG3-positive cells increased to peak levels between 10 wpc and 14 wpc. It declined at and after 18 wpc such that it was not detected in human fetal pancreas at 35-41 wpc. Analysis of NEUROG3 transcription corroborated this profile by demonstrating very low levels of transcript at 35-41 wpc, more than 10-fold lower than levels at 12-16 wpc. These data define the appearance, peak and subsequent disappearance of the critical transcription factor, NEUROG3, in human fetal pancreas for the first time. By inference, the window for pancreatic endocrine differentiation via NEUROG3 action opens at 8 wpc and closes between 21 and 35 wpc

    Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.

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    To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.This project received support from the UK Medical Research Council (MRC) (R.E.J. was a clinical research training fellow; additional funding from MR/L009986/1 to N.B. and N.A.H.; and MR/J003352/1 to K.P.H.), the Academy of Medical Sciences (supported by Wellcome Trust, MRC, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK) (R.E.J.), the Society for Endocrinology (R.E.J.), the Wellcome Trust (N.A.H. was a senior fellow in clinical science, 088566; additional support from grant 105610/Z/14/Z), and the British Council and JDRF (14BX15NHBG to N.A.H.)

    Antidepressants and youth suicide in New York City, 1999-2002

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41247/1/leon_antidepressants and youth suicide_2006.pd

    Excavations at the site of Vasino, Lautem District, Timor-Leste

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    This chapter explores the archaeology and ethnohistory of one of the distinctive fortified settlements in the eastern part of Timor-Leste. In 2009, a team from The Australian National University (ANU), together with local people, partially excavated the site of Vasino, located close to the north coast of Timor-Leste, above the modern village of Moro-Parlamento (Figure 4.1). The site had been fortified with large stone walls and the aim was to provide more data on when, how and why these fortifications were used in the region. Two related questions guided the research. First, when was the main period of fort construction initiated? Secondly, what were the prevailing environmental and social conditions of those times

    Early human B cell response to Ebola virus in four U.S. survivors of infection

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    The human B cell response to natural filovirus infections early after recovery is poorly understood. Previous serologic studies suggest that some Ebola virus survivors exhibit delayed antibody responses with low magnitude and quality. Here, we sought to study the population of individual memory B cells induced early in convalescence. We isolated monoclonal antibodies (MAbs) from memory B cells from four survivors treated for Ebola virus disease (EVD) 1 or 3 months after discharge from the hospital. At the early time points postrecovery, the frequency of Ebola-specific B cells was low and dominated by clones that were cross-reactive with both Ebola glycoprotein (GP) and with the secreted GP (sGP) form. Of 25 MAbs isolated from four donors, only one exhibited neutralization activity. This neutralizing MAb, designated MAb EBOV237, recognizes an epitope in the glycan cap of the surface glycoprotein. In vivo murine lethal challenge studies showed that EBOV237 conferred protection when given prophylactically at a level similar to that of the ZMapp component MAb 13C6. The results suggest that the human B cell response to EVD 1 to 3 months postdischarge is characterized by a paucity of broad or potent neutralizing clones. However, the neutralizing epitope in the glycan cap recognized by EBOV237 may play a role in the early human antibody response to EVD and should be considered in rational design strategies for new Ebola virus vaccine candidates
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