173 research outputs found

    Effect of HIV infection and antiretroviral therapy on hepatitis B virus (HBV)-specific T cell responses in patients who have resolved HBV infection

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    Coinfection with hepatitis B virus (HBV) is a common occurrence in human immunodeficiency virus (HIV)–positive patients and an increasing cause of morbidity and mortality. The CD8+ T cell response is critical for long-term control of HBV in patients resolving acute infection. Here, we examine the effect of HIV on HBV-specific CD8+ T cell responses in patients who have resolved HBV infection. A cross-sectional study showed a reduction in HBV-specific CD8+ T cell responses in HIV-positive, HBV-immune patients, compared with those in HIV-negative, HBV-immune patients. A longitudinal study of a subgroup of patients examined whether this attrition could be reversed by effective antiretroviral therapy. The introduction of highly active antiretroviral therapy (HAART) resulted in reconstitution of some HBV-specific CD4+ and CD8+ T cell responses, in association with restoration of CD4+ T cell counts. These data provide a mechanism to account for the observed impairment of control of HBV infection in the setting of HIV infection and support the ability of HAART to reconstitute functionally active T cell responses

    Computational modelling of placental amino acid transfer as an integrated system

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    AbstractPlacental amino acid transfer is essential for fetal development and its impairment is associated with poor fetal growth. Amino acid transfer is mediated by a broad array of specific plasma membrane transporters with overlapping substrate specificity. However, it is not fully understood how these different transporters work together to mediate net flux across the placenta. Therefore the aim of this study was to develop a new computational model to describe how human placental amino acid transfer functions as an integrated system. Amino acid transfer from mother to fetus requires transport across the two plasma membranes of the placental syncytiotrophoblast, each of which contains a distinct complement of transporter proteins. A compartmental modelling approach was combined with a carrier based modelling framework to represent the kinetics of the individual accumulative, exchange and facilitative classes of transporters on each plasma membrane. The model successfully captured the principal features of transplacental transfer. Modelling results clearly demonstrate how modulating transporter activity and conditions such as phenylketonuria, can increase the transfer of certain groups of amino acids, but that this comes at the cost of decreasing the transfer of others, which has implications for developing clinical treatment options in the placenta and other transporting epithelia

    Indestructibility of Vopenka's Principle

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    We show that Vopenka's Principle and Vopenka cardinals are indestructible under reverse Easton forcing iterations of increasingly directed-closed partial orders, without the need for any preparatory forcing. As a consequence, we are able to prove the relative consistency of these large cardinal axioms with a variety of statements known to be independent of ZFC, such as the generalised continuum hypothesis, the existence of a definable well-order of the universe, and the existence of morasses at many cardinals.Comment: 15 pages, submitted to Israel Journal of Mathematic

    The forms of repetition in social and environmental reports: insights from Hume's notion of ?impressions?

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    This paper focuses on the use of repetition, both in narrative and visual forms, in social and environmental reports. It investigates the forms of repetition as a rhetorical device adopted by the preparer of a social and environmental report in helping the process of knowledge acquisition, as outlined by Hume (1739). Drawing from Hume?s (1739) philosophical idea of an ?impression?, and the work of Davison (2014a) we classify repetitions into ?identical?, ?similar? and ?accumulated? forms. It is argued that the rationale for distinguishing between the different forms of repetition can be linked to their different potential or intensity in acting on different stimuli with a view to enhance learning. The empirical element of this study is based on the stand-alone social and environmental reports of a sample of 86 cooperative banks in Northern Italy; the analysis of these reports indicates that repetition is widespread and that cooperative banks use all forms of repetition, albeit to a varying extent within the different reported themes. The paper contributes to the literature by offering an alternative interpretation of repetition using an interdisciplinary perspective and by providing new insights on social and environmental reporting practices in the cooperative banking sector

    Computational modelling of amino acid exchange and facilitated transport in placental membrane vesicles

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    AbstractPlacental amino acid transport is required for fetal development and impaired transport has been associated with poor fetal growth. It is well known that placental amino acid transport is mediated by a broad array of specific membrane transporters with overlapping substrate specificity. However, it is not fully understood how these transporters function, both individually and as an integrated system. We propose that mathematical modelling could help in further elucidating the underlying mechanisms of how these transporters mediate placental amino acid transport.The aim of this work is to model the sodium independent transport of serine, which has been assumed to follow an obligatory exchange mechanism. However, previous amino acid uptake experiments in human placental microvillous plasma membrane vesicles have persistently produced results that are seemingly incompatible with such a mechanism; i.e. transport has been observed under zero-trans conditions, in the absence of internal substrates inside the vesicles to drive exchange. This observation raises two alternative hypotheses; (i) either exchange is not fully obligatory, or (ii) exchange is indeed obligatory, but an unforeseen initial concentration of amino acid substrate is present within the vesicle which could drive exchange.To investigate these possibilities, a mathematical model for tracer uptake was developed based on carrier mediated transport, which can represent either facilitated diffusion or obligatory exchange (also referred to as uniport and antiport mechanisms, respectively). In vitro measurements of serine uptake by placental microvillous membrane vesicles were carried out and the model applied to interpret the results based on the measured apparent Michaelis–Menten parameters Km and Vmax. In addition, based on model predictions, a new time series experiment was implemented to distinguish the hypothesised transporter mechanisms. Analysis of the results indicated the presence of a facilitated transport component, while based on the model no evidence for substantial levels of endogenous amino acids within the vesicle was found

    Chandra X-ray observations of the 3C295 cluster core

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    We examine the properties of the X-ray gas in the central regions of the distant (z=0.46), X-ray luminous cluster of galaxies surrounding the powerful radio source 3C 295, using observations made with the Chandra Observatory. Between radii of 50-500 kpc, the cluster gas is approximately isothermal with an emission-weighted temperature, kT ~5 keV. Within the central 50 kpc radius this value drops to kT ~3.7 keV. The spectral and imaging Chandra data indicate the presence of a cooling flow within the central 50 kpc radius of the cluster, with a mass deposition rate of approximately 280 solar masses per year. We estimate an age for the cooling flow of 1-2 Gyr, which is approximately one thousand times older than the central radio source. We find no evidence in the X-ray spectra or images for significant heating of the X-ray gas by the radio source. We report the detection of an edge-like absorption feature in the spectrum for the central 50 kpc region, which may be due to oxygen-enriched dust grains. The implied mass in metals seen in absorption could have been accumulated by the cooling flow over its lifetime. Combining the results on the X-ray gas density profile with radio measurements of the Faraday rotation measure in 3C295, we estimate the magnetic field strength in the region of the cluster core to be B ~12 \muG.Comment: 27 pages, 16 figs, 5 tables. Accepted for publication in MNRA

    'Education, education, education' : legal, moral and clinical

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    This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

    Model Analysis of Time Reversal Symmetry Test in the Caltech Fe-57 Gamma-Transition Experiment

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    The CALTECH gamma-transition experiment testing time reversal symmetry via the E2/M1 mulipole mixing ratio of the 122 keV gamma-line in Fe-57 has already been performed in 1977. Extending an earlier analysis in terms of an effective one-body potential, this experiment is now analyzed in terms of effective one boson exchange T-odd P-even nucleon nucleon potentials. Within the model space considered for the Fe-57 nucleus no contribution from isovector rho-type exchange is possible. The bound on the coupling strength phi_A from effective short range axial-vector type exchange induced by the experimental bound on sin(eta) leads to phi_A < 10^{-2}.Comment: 5 pages, RevTex 3.

    Cold Gas in Cluster Cores

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    I review the literature's census of the cold gas in clusters of galaxies. Cold gas here is defined as the gas that is cooler than X-ray emitting temperatures (~10^7 K) and is not in stars. I present new Spitzer IRAC and MIPS observations of Abell 2597 (PI: Sparks) that reveal significant amounts of warm dust and star formation at the level of 5 solar masses per year. This rate is inconsistent with the mass cooling rate of 20 +/- 5 solar masses per year inferred from a FUSE [OVI] detection.Comment: 10 pages, conference proceeding

    Effective Cost-Sharing Models in Higher Education: Insights from Low-Income Students in Australian Universities

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    This study examines the global trend in shifting university costs from national governments to individual students and families, with a specific focus on the existing cost-sharing model in Australian higher education. The research examines the manner in which the availability of income-contingent loans (through the Higher Education Contribution Scheme, or HECS) enters into individual cost assessments and evaluative frameworks during the university exploration and search process of low-income Australian youth, and the resulting lessons that might be applied to other national contexts. Semi-structured interviews with 16 participants addressed a broad range of issues related to the development of educational aspirations, and how beliefs and attitudes about cost influenced participants’ understanding and decision-making regarding tertiary enrollment and post-graduate plans. A number of discreet and related themes emerged from analysis of the interviews, including motivations for attending university; pre-university cost considerations; self-assessments of skills, abilities, and personal traits and characteristics; general financial orientation; pre-university experiences and influences; and the role of others including family, peers, teachers and other school staff. The author concludes that the Australian system is worthy of consideration by other nations as a possible mechanism for enhancing access to higher education for individuals who might otherwise not possess the opportunity to participate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42840/1/10734_2004_Article_6373.pd
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