542 research outputs found

    A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings

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    BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality

    Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae), a parasite of the intertidal bug, Saldula laticollis (Reuter)(Hemiptera: Saldidae) on the Oregon coast

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    This is the publisher’s final pdf. The published article is copyrighted by BioMed Central and can be found at: http://www.biomedcentral.com/.Background: It is rare to find terrestrial nematode lineages parasitizing arthropods inhabiting the intertidal or\ud littoral zone of the oceans. During an ecological study along the Oregon dunes, an allantonematid nematode\ud (Tylenchomorpha: Allantonematidae) was discovered parasitizing the intertidal shore bug, Saldula laticollis (Reuter)\ud (Hemiptera: Saldidae). This shore bug is adapted to an intertidal environment and can survive short periods of\ud submergence during high tides. The present study describes the nematode parasite and discusses aspects of its\ud development, ecology and evolution.\ud Methods: Adults and last instar nymphs of S. laticollis (Hemiptera: Saldidae) were collected from the high intertidal\ud zone among clumps of Juncus L. (Juncaceae) plants at Waldport, Oregon on October 3, 2011. The bugs were\ud dissected in 1% saline solution and the nematodes killed in 1% Ringers solution and immediately fixed in 5%\ud formalin (at 20°C). Third stage juveniles removed from infected hosts were maintained in 1% saline solution until\ud they matured to the adult stage, molted and mated.\ud Results: Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae) is described from last instar nymphs\ud and adults of the intertidal bug, Saldula laticollis on the Oregon coast. The new genus can be distinguished from\ud other genera in the Allantonematidae by a stylet lacking basal knobs in both sexes, an excretory pore located\ud behind the nerve ring, ribbed spicules, a gubernaculum, the absence of a bursa and the elongate-tubular shape of\ud the ovoviviparous parasitic females. Studies of the organogenesis of Halophilanema showed development to third\ud stage juveniles in the uterus of parasitic females. Maturation to the free-living adults and mating occurred in the\ud environment. The incidence of infection of S. laticollis ranged from 0% to 85% depending on the microhabitat in\ud the intertidal zone.\ud Conclusions: Based on the habitat and morphological characters, it is proposed that Halophilanema adapted a\ud parasitic existence fairly recently, evolutionarily speaking. It was probably a free-living intertidal or shore nematode\ud that fed on microorganisms, especially fungi, in the intertidal habitat and became parasitic after saldids entered the\ud environment. Halophilanema represents the first described nematode parasite of an intertidal insect

    Centrifuge modelling of screw piles for offshore wind energy foundations

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    Screw piles (helical piles) can provide a viable, cost-effective and low-noise installation alternative to increasing the size of existing foundation solutions (e.g. monopiles) to meet the demand for the advancement of offshore wind energy into deeper water. Significant upscaling of widely used onshore screw pile geometries will be required to meet the loading conditions of a jacket supported offshore wind turbine. This increase in size will lead to greater installation force and torque. This paper presents preliminary results from centrifuge tests investigating the requirements to install screw piles designed for an offshore wind energy application using specially developed equipment. Results indicate that the equipment is suitable to investigate these screw pile requirements and that significant force is required for such upscaled screw piles, with 19 MN vertical force and 7 MNm torque for the standard design. Optimisation of the screw pile geometry, reduced these forces by 29 and 11% for the vertical and rotational forces respectively

    An update on the Hirsch conjecture

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    The Hirsch conjecture was posed in 1957 in a letter from Warren M. Hirsch to George Dantzig. It states that the graph of a d-dimensional polytope with n facets cannot have diameter greater than n - d. Despite being one of the most fundamental, basic and old problems in polytope theory, what we know is quite scarce. Most notably, no polynomial upper bound is known for the diameters that are conjectured to be linear. In contrast, very few polytopes are known where the bound ndn-d is attained. This paper collects known results and remarks both on the positive and on the negative side of the conjecture. Some proofs are included, but only those that we hope are accessible to a general mathematical audience without introducing too many technicalities.Comment: 28 pages, 6 figures. Many proofs have been taken out from version 2 and put into the appendix arXiv:0912.423

    Intergroup struggles over victimhood in violent conflict: The victim-perpetrator paradigm

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    Most groups in violent, intergroup conflict perceive themselves to be the primary or sole victims of that conflict. This often results in contention over who may claim victim status and complicates a central aim of post-conflict processes, which is to acknowledge and address harms experienced by the victims. Drawing from victimology scholarship and intergroup relations theory, this article proposes the victim-perpetrator paradigm as a framework to analyse how, why and to what end groups in conflict construct and maintain their claims to the moral status of victim. This interdisciplinary paradigm builds on the knowledge that groups utilise the ‘ideal victim’ construction to exemplify their own innocence and blamelessness in contrast to the wickedness of the perpetrator, setting the two categories as separate and mutually exclusive even where experiences of violence have been complex. Additionally, this construction provides for a core intergroup need to achieve positive social identity, which groups may enhance by demonstrating a maximum differentiation between the in-group as victims and those out-groups identified as perpetrators. The paradigm contributes greater knowledge on the social roots of victim contention in conflict, as well as how groups legitimise their violence against out-groups during and after conflict

    On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

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    N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

    ASD: a comprehensive database of allosteric proteins and modulators

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    Allostery is the most direct, rapid and efficient way of regulating protein function, ranging from the control of metabolic mechanisms to signal-transduction pathways. However, an enormous amount of unsystematic allostery information has deterred scientists who could benefit from this field. Here, we present the AlloSteric Database (ASD), the first online database that provides a central resource for the display, search and analysis of structure, function and related annotation for allosteric molecules. Currently, ASD contains 336 allosteric proteins from 101 species and 8095 modulators in three categories (activators, inhibitors and regulators). Proteins are annotated with a detailed description of allostery, biological process and related diseases, and modulators with binding affinity, physicochemical properties and therapeutic area. Integrating the information of allosteric proteins in ASD should allow for the identification of specific allosteric sites of a given subtype among proteins of the same family that can potentially serve as ideal targets for experimental validation. In addition, modulators curated in ASD can be used to investigate potent allosteric targets for the query compound, and also help chemists to implement structure modifications for novel allosteric drug design. Therefore, ASD could be a platform and a starting point for biologists and medicinal chemists for furthering allosteric research. ASD is freely available at http://mdl.shsmu.edu.cn/ASD/
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