972 research outputs found

    Ultradian glucocorticoid exposure directs gene-dependent and tissue-specific mRNA expression patterns in vivo

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    In this paper we report differential decoding of the ultradian corticosterone signal by glucocorticoid target tissues. Pulsatile corticosterone replacement in adrenalectomised rats resulted in different dynamics of Sgk1 mRNA production, with a distinct pulsatile mRNA induction profile observed in the pituitary in contrast to a non-pulsatile induction in the prefrontal cortex (PFC). We further report the first evidence for pulsatile transcriptional repression of a glucocorticoid-target gene in vivo, with pulsatile regulation of Pomc transcription in pituitary. We have explored a potential mechanism for differences in the induction dynamics of the same transcript (Sgk1) between the PFC and pituitary. Glucocorticoid receptor (GR) activation profiles were strikingly different in pituitary and prefrontal cortex, with a significantly greater dynamic range and shorter duration of GR activity detected in the pituitary, consistent with the more pronounced gene pulsing effect observed. In the prefrontal cortex, expression of Gilz mRNA was also non-pulsatile and exhibited a significantly delayed timecourse of increase and decrease when compared to Sgk1, additionally highlighting gene-specific regulatory dynamics during ultradian glucocorticoid treatment

    Diffraction Considerations for Planar Detectors in the Few-Mode Limit

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    Filled arrays of bolometers are currently being employed for use in astronomy from the far-infrared through millimeter parts of the electromagnetic spectrum. Because of the large range of wavelengths for which such detectors are applicable, the number of modes supported by a pixel will vary according to the specific application of a given available technology. We study the dependence of image fidelity and induced polarization on the size of the pixel by employing a formalism in which diffraction due to the pixel boundary is treated by propagating the second-order statistical correlations of the radiation field through a model optical system. We construct polarized beam pattern images of square pixels for various ratios of p/\lambda where p is the pixel size and \lambda is the wavelength of the radiation under consideration. For the limit in which few modes are supported by the pixel (p/\lambda<1), we find that the diffraction due to the pixel edges is non-negligible and hence must be considered along with the telescope diffraction pattern in modeling the ultimate spatial resolution of an imaging system. For the case in which the pixel is over-moded (p/\lambda>1), the geometric limit is approached as expected. This technique gives a quantitative approach to optimize the imaging properties of arrays of planar detectors in the few-mode limit.Comment: 20 pages, 8 figure

    Detector Modeling and CMB Polarimetry Technology Development at GSFC

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    Pixel size limits the resolution in the focal plane. This should be accounted for in optical design. Alternatively, this reduces the effective number of independent detectors. Polarization and scattering are intrinsically related, and both are more severe at low pnambda. Future work: Quantification of the pixel cross-coupling- calculate a theoretical covariance matrix to predict performance of future detector arrays

    Petroleomics by ion mobility mass spectrometry: resolution and characterization of contaminants and additives in crude oils and petrofuels

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    Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ion mobility-mass spectrometry (IM-MS), performed with exceptional resolution and sensitivity in a new uniform-field drift tube ion mobility quadrupole time-of-flight (IM-QTOF) instrument, is shown to provide a useful tool for resolving and characterizing crude oils and their contaminants, as well as petrofuels and their additives. Whereas direct analysis of a crude oil sample contaminated with demulsifiers by the classical ESI(+/-)-FTICR-MS petroleomic approach was unsatisfactory since it responds only with abundance and m/z, and ionization is impaired due to suppression of polar compounds of crude oil by additives likely used in petroleum industry, IM-MS enables mobility separation of ions, particularly of double bond equivalent (DBE) series for a giving CnX class providing separated spectra which are typical obtained either for the crude oil or the contaminants, even suffering of ion suppression or low ionization efficiency. The combination of improved IM resolution and high mass resolving power (40,000@400) of the QTOF instrument provides useful information on class (N, NO, NS, etc.), carbon number (C-n), and unsaturation (DBE) levels for crude oils, allowing one to infer geochemical properties from DBE trends that can be compared with IM-MS data. As demonstrated by results of gasoline samples with additives, the IM-MS system also allows efficient separation and characterization of additives and contaminants in petrofuels.Ion mobility-mass spectrometry (IM-MS), performed with exceptional resolution and sensitivity in a new uniform-field drift tube ion mobility quadrupole time-of-flight (IM-QTOF) instrument, is shown to provide a useful tool for resolving and characterizing71144504463FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2013/19161-4]2013/19161-4sem informaçãosem informaçãoWe would like to thank the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) for the scholarship awarded to J.M.S. (process number 2013/19161-4), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Des

    Soft Templating and Disorder in an Applied 1D Cobalt Coordination Polymer Electrocatalyst

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    Disordered materials with resilient and soft-templated functional units bear the potential to fill the pipeline of robust catalysts for renewable energy storage. However, for novel materials lacking long-range order, the ability to discern local structure with atomic resolution still pushes the boundaries of current analytical and modeling approaches. We introduce a two-pillar strategy to monitor the formation and unravel the structure of the first disordered onedimensional cobalt coordination polymer catalyst, Co-dppeO2. This target material excels through proven high performance in commercial alkaline electrolyzers and organic transformations. We demonstrate that the key architecture behind this activity is the unconventional embedding of hydrated {H2O-Co2(OH)2-OH2} edge-site motifs, nested into a flexible organic matrix of highly oxidized and bridging hydrophobic dppeO2 ligands. Our combination of in situ spectroscopy and computational modeling of X-ray scattering and absorption spectra, backed with complementary experimental techniques, holds the key to understanding the atomic-range structure of important disordered materials

    The Baculovirus Uses a Captured Host Phosphatase to Induce Enhanced Locomotory Activity in Host Caterpillars

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    The baculovirus is a classic example of a parasite that alters the behavior or physiology of its host so that progeny transmission is maximized. Baculoviruses do this by inducing enhanced locomotory activity (ELA) that causes the host caterpillars to climb to the upper foliage of plants. We previously reported that this behavior is not induced in silkworms that are infected with a mutant baculovirus lacking its protein tyrosine phosphatase (ptp) gene, a gene likely captured from an ancestral host. Here we show that the product of the ptp gene, PTP, associates with baculovirus ORF1629 as a virion structural protein, but surprisingly phosphatase activity associated with PTP was not required for the induction of ELA. Interestingly, the ptp knockout baculovirus showed significantly reduced infectivity of larval brain tissues. Collectively, we show that the modern baculovirus uses the host-derived phosphatase to establish adequate infection for ELA as a virion-associated structural protein rather than as an enzyme

    A test of financial incentives to improve warfarin adherence

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    <p>Abstract</p> <p>Background</p> <p>Sub-optimal adherence to warfarin places millions of patients at risk for stroke and bleeding complications each year. Novel methods are needed to improve adherence for warfarin. We conducted two pilot studies to determine whether a lottery-based daily financial incentive is feasible and improves warfarin adherence and anticoagulation control.</p> <p>Methods</p> <p>Volunteers from the University of Pennsylvania Anticoagulation Management Center who had taken warfarin for at least 3 months participated in either a pilot study with a lottery with a daily expected value of 5(N=10)oradailyexpectedvalueof5 (N = 10) or a daily expected value of 3 (N = 10). All subjects received use of an Informedix Med-eMonitor™ System with a daily reminder feature. If subjects opened up their pill compartments appropriately, they were entered into a daily lottery with a 1 in 5 chance of winning 10anda1in100chanceofwinning10 and a 1 in 100 chance of winning 100 (pilot 1) or a 1 in 10 chance of winning 10anda1in100chanceofwinning10 and a 1 in 100 chance of winning 100 (pilot 2). The primary study outcome was proportion of incorrect warfarin doses. The secondary outcome was proportion of INR measurements not within therapeutic range. Within-subject pre-post comparisons were done of INR measurements with comparisons with either historic means or within-subject comparisons of incorrect warfarin doses.</p> <p>Results</p> <p>In the first pilot, the percent of out-of-range INRs decreased from 35.0% to 12.2% during the intervention, before increasing to 42% post-intervention. The mean proportion of incorrect pills taken during the intervention was 2.3% incorrect pills, compared with a historic mean of 22% incorrect pill taking in this clinic population. Among the five subjects who also had MEMS cap adherence data from warfarin use in our prior study, mean incorrect pill taking decreased from 26% pre-pilot to 2.8% in the pilot. In the second pilot, the time out of INR range decreased from 65.0% to 40.4%, with the proportion of mean incorrect pill taking dropping to 1.6%.</p> <p>Conclusion</p> <p>A daily lottery-based financial incentive demonstrated the potential for significant improvements in missed doses of warfarin and time out of INR range. Further testing should be done of this approach to determine its effectiveness and potential application to both warfarin and other chronic medications.</p

    Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

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    BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500
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