358 research outputs found

    Colorblind and Multicultural Prejudice Reduction Strategies in High-Conflict Situations

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    We tested colorblind and multicultural prejudice-reduction strategies under conditions of low and high interethnic conflict. Replicating previous work, both strategies reduced prejudice when conflict was low. But when conflict was high, only the colorblind strategy reduced prejudice (Studies 1 and 2). Interestingly, this colorblind response seemed to reflect suppression. When prejudice was assessed more subtly (with implicit measures), colorblind participants demonstrated bias equivalent to multicultural participants (Study 2). And, after a delay, colorblind participants showed a rebound, demonstrating greater prejudice than their multicultural counterparts (Study 3). Similar effects were obtained when ideology was measured rather than manipulated (Study 4). We suggest that conflict challenges the tenets of a colorblind ideology (predicated on the absence of group differences) but not those of a multicultural ideology (which acknowledges difference)

    Peptides identified on monocyte-derived dendritic cells: a marker for clinical immunogenicity to FVIII products

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    The immunogenicity of protein therapeutics is an important safety and efficacy concern during drug development and regulation. Strategies to identify individuals and subpopulations at risk for an undesirable immune response represent an important unmet need. The major histocompatibility complex (MHC)–associated peptide proteomics (MAPPs) assay directly identifies the presence of peptides derived from a specific protein therapeutic on a donor’s MHC class II (MHC-II) proteins. We applied this technique to address several questions related to the use of factor VIII (FVIII) replacement therapy in the treatment of hemophilia A (HA). Although .12 FVIII therapeutics are marketed, most fall into 3 categories: (i) human plasma-derived FVIII (pdFVIII), (ii) full-length (FL)–recombinant FVIII (rFVIII; FL-rFVIII), and (iii) B-domain–deleted rFVIII. Here, we investigated whether there are differences between the FVIII peptides found on the MHC-II proteins of the same individual when incubated with these 3 classes. Based on several observational studies and a prospective, randomized, clinical trial showing that the originally approved rFVIII products may be more immunogenic than the pdFVIII products containing von Willebrand factor (VWF) in molar excess, it has been hypothesized that the pdFVIII molecules yield/ present fewer peptides (ie, potential T-cell epitopes). We have experimentally tested this hypothesis and found that dendritic cells from HA patients and healthy donors present fewer FVIII peptides when administered pdFVIII vs FL-rFVIII, despite both containing the same molar VWF excess. Our results support the hypothesis that synthesis of pdFVIII under physiological conditions could result in reduced heterogeneity and/or subtle differences in structure/conformation which, in turn, may result in reduced FVIII proteolytic processing relative to FL-rFVIII

    Probing scrambling using statistical correlations between randomized measurements

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    We propose and analyze a protocol to study quantum information scrambling using statistical correlations between measurements, which are performed after evolving a quantum system from randomized initial states. We prove that the resulting correlations precisely capture the so-called out-of-time-ordered correlators and can be used to probe chaos in strongly-interacting, many-body systems. Our protocol requires neither reversing time evolution nor auxiliary degrees of freedom, and can be realized in state-of-the-art quantum simulation experiments.Comment: This version v2 (8 pages, 7 figures) includes important new results compared to our original submission. (1) We present a protocol and corresponding mathematical proof to access OTOCs with local operations, and which can be realized in quantum simulation experiments with available technology. (2) We illustrate the realization of the protocols with different examples for Hubbard and spin model

    Antarctic bottom and lower circumpolar deep water circulation in the eastern Indian Ocean

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    Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): C02006, doi:10.1029/2005JC003011.Net northward transport below γn > 28.1 kgm−3 (≈3200 m) into the Perth Basin of between 4.4 and 5.8 Sv is estimated from a year-long current meter mooring array between the Broken and Naturaliste Plateaus. Northward transport of between 2.0 and 2.5 Sv of Antarctic Bottom Water (γn >28.2 kgm−3), that must upwell within the southern region of the Perth Basin, results in an area-averaged diapycnal velocity and diffusivity of w*=2.5− 3.1× 10−6 ms−1 and κ = 13−15×10−4 m2s−1, respectively. Diffusivity estimates for the Perth Basin are several times larger than area averaged mixing estimates for the abyssal subtropical South Atlantic and Pacific Oceans. However, the dissipation of turbulent kinetic energy required to maintain the abyssal mixing in the Perth basin, ε=O(10−9 Wkg−1), is similar to that required in the South Atlantic Ocean. The area-averaged diffusivity in the Perth Basin does not require unreasonable energy dissipation rates as this ocean basin is only weakly stratified. The abyssal diffuvisity of the Perth Basin results from intense mixing at the basin boundary and in the basin interior over rough topography. The complex bathymetry and low abyssal stratification suggests that the Indian Ocean, for a given energy dissipation, may support a larger meridional overturning circulation than other subtropical basins.BMS was supported by funds from the Ocean and Climate Change Institute at the Woods Hole Oceanographic Institution, and The James S. Cole and Cecily C. Selby Endowed Fund and The Penzance Endowed Fund in support of Assistant Scientists. The mooring array was funded by Australia’s CSIRO Marine Research

    Development of an Alcohol Dehydrogenase Biosensor for Ethanol Determination with Toluidine Blue O Covalently Attached to a Cellulose Acetate Modified Electrode

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    In this work, a novel voltammetric ethanol biosensor was constructed using alcohol dehydrogenase (ADH). Firstly, alcohol dehydrogenase was immobilized on the surface of a glassy carbon electrode modified by cellulose acetate (CA) bonded to toluidine blue O (TBO). Secondly, the surface was covered by a glutaraldehyde/bovine serum albumin (BSA) cross-linking procedure to provide a new voltammetric sensor for the ethanol determination. In order to fabricate the biosensor, a new electrode matrix containing insoluble Toluidine Blue O (TBO) was obtained from the process, and enzyme/coenzyme was combined on the biosensor surface. The influence of various experimental conditions was examined for the characterization of the optimum analytical performance. The developed biosensor exhibited sensitive and selective determination of ethanol and showed a linear response between 1 × 10−5 M and 4 × 10−4 M ethanol. A detection limit calculated as three times the signal-to-noise ratio was 5.0 × 10−6 M. At the end of the 20th day, the biosensor still retained 50% of its initial activity

    Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy

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    Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence

    Metaphors in Nanomedicine: The Case of Targeted Drug Delivery

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    International audienceThe promises of nanotechnology have been framed by a variety of metaphors, that not only channel the attention of the public, orient the questions asked by researchers, and convey epistemic choices closely linked to ethical preferences. In particular, the image of the 'therapeutic missile' commonly used to present targeted drug delivery devices emphasizes precision, control, surveillance and efficiency. Such values are highly praised in the current context of crisis of pharmaceutical innovation where military metaphors foster a general mobilization of resources from multiple fields of cutting-edge research. The missile metaphor, reminiscent of Paul Ehrlich's 'magic bullet', has framed the problem in simple terms: how to deliver the right dose in the right place at the right moment? Chemists, physicists and engineers who design multi-functional devices operating in vitro can think in such terms, as long as the devices are not actually operating through the messy environment of the body. A close look at what has been done and what remains to be done suggests that the metaphor of the "therapeutic missile" is neither sufficient, nor even necessary. Recent developments in nanomedicine suggest that therapeutic efficacy cannot be obtained without negotiating with the biological milieu and taking advantage of what it affords. An 'oïkological' approach seems more appropriate, more heuristic and more promising than the popular missile. It is based on the view of organism as an oikos that has to be carefully managed. The dispositions of nanocapsules have to be coupled with the affordances of the environment. As it requires dealing with nanoparticles as relational entities (defined by their potential for interactions) rather than as stable substances (defined by intrinsic properties) this metaphor eventually might well change research priorities in nanotechnology in general

    Countdown to 2030 : tracking progress towards universal coverage for reproductive, maternal, newborn, and child health

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    Building upon the successes of Countdown to 2015, Countdown to 2030 aims to support the monitoring and measurement of women's, children's, and adolescents' health in the 81 countries that account for 95% of maternal and 90% of all child deaths worldwide. To achieve the Sustainable Development Goals by 2030, the rate of decline in prevalence of maternal and child mortality, stillbirths, and stunting among children younger than 5 years of age needs to accelerate considerably compared with progress since 2000. Such accelerations are only possible with a rapid scale-up of effective interventions to all population groups within countries (particularly in countries with the highest mortality and in those affected by conflict), supported by improvements in underlying socioeconomic conditions, including women's empowerment. Three main conclusions emerge from our analysis of intervention coverage, equity, and drivers of reproductive, maternal, newborn, and child health (RMNCH) in the 81 Countdown countries. First, even though strong progress was made in the coverage of many essential RMNCH interventions during the past decade, many countries are still a long way from universal coverage for most essential interventions. Furthermore, a growing body of evidence suggests that available services in many countries are of poor quality, limiting the potential effect on RMNCH outcomes. Second, within-country inequalities in intervention coverage are reducing in most countries (and are now almost non-existent in a few countries), but the pace is too slow. Third, health-sector (eg, weak country health systems) and non-health-sector drivers (eg, conflict settings) are major impediments to delivering high-quality services to all populations. Although more data for RMNCH interventions are available now, major data gaps still preclude the use of evidence to drive decision making and accountability. Countdown to 2030 is investing in improvements in measurement in several areas, such as quality of care and effective coverage, nutrition programmes, adolescent health, early childhood development, and evidence for conflict settings, and is prioritising its regional networks to enhance local analytic capacity and evidence for RMNCH
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