199 research outputs found

    Impact of family in-home quality time on person travel demand

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    This paper introduces the concept of Primary Family Priority Time (PFPT), which represents a high priority household decision to spend time together for in-home activities. PFPT is incorporated into a fully specified and operational activity based (AB) discrete choice model system for Copenhagen, called COMPAS, using the DaySim software platform. Structural tests and estimation results identify two important findings. First, PFPT belongs high in the model hierarchy, and second, strong interactions exist between PFPT and the other day level activity components of the model system. Forecasts are generated for a road pricing and congestion scenario by COMPAS and a comparison version of the model system that excludes PFPT. COMPAS with PFPT exhibits less mode changing and time-of-day shifting in response to pricing and congestion than the comparison version

    The occurrence of Trichophytosis among people and cattle on a farm in Vojvodina, Serbia

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    Dermatophytoses are frequent contagious fungal skin diseases that affect the skin of people and animals. Zoophile dermatophytes pose a significant problem for both human and veterinary medicine, and they are especially present among bovines. In this paper we showed a simultaneous occurrence of trichophytosis among professionally exposed people and bovines on a farm in Vojvodina, Serbia. The tested samples (skin scrapings and hair) originating from people and animals, were positive for Trichophyton verrucosum dermatophyte which was determined by applying a direct microscopic examination of the smears, as well as the isolation and identification of the agents

    Gravitational wave radiometry: Mapping a stochastic gravitational wave background

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    The problem of the detection and mapping of a stochastic gravitational wave background (SGWB), either of cosmological or astrophysical origin, bears a strong semblance to the analysis of CMB anisotropy and polarization. The basic statistic we use is the cross-correlation between the data from a pair of detectors. In order to `point' the pair of detectors at different locations one must suitably delay the signal by the amount it takes for the gravitational waves (GW) to travel to both detectors corresponding to a source direction. Then the raw (observed) sky map of the SGWB is the signal convolved with a beam response function that varies with location in the sky. We first present a thorough analytic understanding of the structure of the beam response function using an analytic approach employing the stationary phase approximation. The true sky map is obtained by numerically deconvolving the beam function in the integral (convolution) equation. We adopt the maximum likelihood framework to estimate the true sky map that has been successfully used in the broadly similar, well-studied CMB map making problem. We numerically implement and demonstrate the method on simulated (unpolarized) SGWB for the radiometer consisting of the LIGO pair of detectors at Hanford and Livingston. We include `realistic' additive Gaussian noise in each data stream based on the LIGO-I noise power spectral density. The extension of the method to multiple baselines and polarized GWB is outlined. In the near future the network of GW detectors, including the Advanced LIGO and Virgo detectors that will be sensitive to sources within a thousand times larger spatial volume, could provide promising data sets for GW radiometry.Comment: 24 pages, 19 figures, pdflatex. Matched version published in Phys. Rev. D - minor change

    Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

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    Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients

    Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models

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    Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols

    New polymorph of InVO4: A high-pressure structure with six-coordinated vanadium

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    This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Inorganic Chemestry, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/ic402043xA new wolframite-type polymorph of InVO4 is identified under compression near 7 GPa by in situ high-pressure (HP) X-ray diffraction (XRD) and Raman spectroscopic investigations on the stable orthorhombic InVO4. The structural transition is accompanied by a large volume collapse (Delta V/V = -14%) and a drastic increase in bulk modulus (from 69 to 168 GPa). Both techniques also show the existence of a third phase coexisting with the low- and high-pressure phases in a limited pressure range close to the transition pressure. XRD studies revealed a highly anisotropic compression in orthorhombic InVO4. In addition, the compressibility becomes nonlinear in the HP polymorph. The volume collapse in the lattice is related to an increase of the polyhedral coordination around the vanadium atoms. The transformation is not fully reversible. The drastic change in the polyhedral arrangement observed at the transition is indicative of a reconstructive phase transformation. The HP phase here found is the only modification of InVO4 reported to date with 6-fold coordinated vanadium atoms. Finally, Raman frequencies and pressure coefficients in the low- and high-pressure phases of InVO4 are reported.This research supported by the Spanish government MINECO under Grant Nos. MAT2010-21270-C04-01/04 and CSD2007-00045. O.G. acknowledges support from Vicerrectorado de Investigacion y Desarrollo of UPV (Grant No. UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11). S.N.A. acknowledges support provided by Universitat de Valencia during his visit to it. B.G.-D. acknowledges the financial support from MINECO through the FPI program.Errandonea, D.; Gomis Hilario, O.; García-Domene, B.; Pellicer Porres, J.; Katari, V.; Achary, SN.; Tyagi, AK.... (2013). New polymorph of InVO4: A high-pressure structure with six-coordinated vanadium. Inorganic Chemistry. 52(21):12790-12798. https://doi.org/10.1021/ic402043xS1279012798522

    Serum markers in interstitial pneumonia with and without Pneumocystis jirovecii colonization: a prospective study

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    <p>Abstract</p> <p>Background</p> <p>In patients with chronic respiratory disease, <it>Pneumocystis jirovecii (P. jirovecii) </it>colonization is observed, and may influence disease progression and systemic inflammation. <it>Pneumocystis </it>pneumonia causes interstitial changes, so making a diagnosis of PCP in patients who have interstitial pneumonia (IP) with <it>P. jirovecii </it>colonization is sometimes difficult based on radiography.</p> <p>Methods</p> <p>This study investigated the prevalence of <it>P. jirovecii </it>colonization in IP patients and assessed pulmonary injury due to <it>P. jirovecii </it>colonization by measurement of serum markers (KL-6, SP-A, SP-D, and (1→3) β-D-glucan (β-D-glucan)) and the peripheral lymphocyte counts, prospectively. A total of 75 patients with idiopathic pulmonary fibrosis (n = 29), collagen vascular-related interstitial pneumonia (n = 19), chronic bronchitis or pneumonia (n = 20), and <it>Pneumocystis </it>pneumonia (n = 7) were enrolled in this prospective study. <it>P. jirovecii </it>DNA was detected in sputum samples, while serum markers and the lymphocyte count were measured in the peripheral blood.</p> <p>Results</p> <p>IP patients (idiopathic pulmonary fibrosis and collagen vascular-related IP) who received oral corticosteroids had a high prevalence of <it>P. jirovecii </it>colonization (23.3%). In IP patients, oral corticosteroid therapy was a significant risk factor for <it>P. jirovecii </it>colonization (<it>P </it>< 0.05). Serum markers did not show differences between IP patients with and without <it>P. jirovecii </it>colonization. The β-D-glucan level and lymphocyte count differed between patients with <it>Pneumocystis </it>pneumonia or <it>P. jirovecii </it>colonization.</p> <p>Conclusion</p> <p>Serum levels of KL-6, SP-A, SP-D, and β-D-glucan were not useful for detecting <it>P. jirovecii </it>colonization in IP patients. However, the serum β-D-glucan level and lymphocyte count were useful for distinguishing <it>P. jirovecii </it>colonization from <it>pneumocystis </it>pneumonia in IP patients.</p

    Mactinin, a fragment of cytoskeletal Îą-actinin, is a novel inducer of heat shock protein (Hsp)-90 mediated monocyte activation

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    <p>Abstract</p> <p>Background</p> <p>Monocytes, their progeny such as dendritic cells and osteoclasts and products including tumor necrosis factor (TNF)-ι, interleukin (IL)-1ι and IL-1β play important roles in cancer, inflammation, immune response and atherosclerosis. We previously showed that mactinin, a degradative fragment of the cytoskeletal protein ι-actinin, is present at sites of monocytic activation in vivo, has chemotactic activity for monocytes and promotes monocyte/macrophage maturation. We therefore sought to determine the mechanism by which mactinin stimulates monocytes.</p> <p>Results</p> <p>Radiolabeled mactinin bound to a heterocomplex on monocytes comprised of at least 3 proteins of molecular weight 88 kD, 79 kD and 68 kD. Affinity purification, mass spectroscopy and Western immunoblotting identified heat shock protein (Hsp)-90 as the 88 kD component of this complex. Hsp90 was responsible for mediating the functional effects of mactinin on monocytes, since Hsp90 inhibitors (geldanamycin and its analogues 17-allylamino-17-demethoxygeldanamycin [17-AAG] and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin [17-DMAG]) almost completely abrogated the stimulatory activity of mactinin on monocytes (production of the pro-inflammatory cytokines IL-1ι, IL-1β and TNF-ι, as well as monocyte chemotaxis).</p> <p>Conclusion</p> <p>Mactinin is a novel inducer of Hsp90 activity on monocytes and may serve to perpetuate and augment monocytic activation, thereby functioning as a "matrikine." Blockage of this function of mactinin may be useful in diseases where monocyte/macrophage activation and/or Hsp90 activity are detrimental.</p
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