4,696 research outputs found

    Anticoagulation in Atrial Fibrillation Patients

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    Atrial fibrillation (AF) is the most common arrhythmia and may cause thromboembolic events, typically stroke. Advances in pharmacological approaches to anticoagulation and groundbreaking large randomized controlled trials of non-vitamin K antagonist oral anticoagulants (NOACs) have changed the paradigm of anticoagulation therapy. Furthermore, observational studies support the efficacy and safety of NOAC. Few studies address the differences among NOACs, but prescriptions should be based on a thorough understanding of their pharmacological differences, including interactions, side effects, reversibility, and practical approach. In a subset of patients with AF, warfarin may still be the preferable option. Consequently, an individualized approach to oral anticoagulation is crucial

    Anti-malarial activity of geldanamycin derivatives in mice infected with Plasmodium yoelii

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    Background Geldanamycin (GA), a benzoquinone ansamycin antibiotic has been shown in vitro to possess anti-plasmodial activity. Pharmacological activity of this drug is attributed to its ability to inhibit PfHSP90. The parasite growth arrest has been shown to be due to drug-induced blockage of the transition from ring to trophozoite stage. To further evaluate the consequences of this pharmacodyamic feature, the anti-malarial activity of GA analogs with enhanced drug properties in a Plasmodium-infected animal model have been evaluated for their capacity to induce clearance of the parasite. In the process, a hypothesis was subsequently tested regarding the susceptibility of the cured animals to malaria reflected in an attenuated parasite load that may be evoked by a protective immune response in the host. Methods Six weeks old Swiss mice were infected with a lethal Plasmodium yoelii (17XL) strain. On appearance of clinical symptoms of malaria, these animals were treated with two different GA derivatives and the parasite load was monitored over 15-16 days. Drug-treated animals cured of the parasite were then re-challenged with a lethal dose of P. yoelii 17XL. Serum samples from GA cured mice that were re-challenged with P. yoelii 17XL were examined for the presence of antibodies against the parasite proteins using western blot analysis. Results Treatment of P. yoelii 17XL infected mice with GA derivatives showed slow recovery from clinical symptoms of the disease. Blood smears from drug treated mice indicated a dominance of ring stage parasites when compared to controls. Although, P. yoelii preferentially invades normocytes (mature rbcs), in drug-treated animals there was an increased invasion of reticulocytes. Cured animals exhibited robust protection against subsequent infection and serum samples from these animals showed antibodies against a vast majority of parasite proteins. Conclusions Treatment with GA derivatives blocked the transition from ring to trophozoite stage presumably by the inhibition of HSP90 associated functions. Persistence of parasite in ring stage leads to robust humoral immune response as well as a shift in invasion specificity from normocytes to reticulocyte. It is likely that the treatment with the water-soluble GA derivative creates an attenuated state (less virulent with altered invasion specificity) that persists in the host system, allowing it to mount a robust immune response

    Chaotic memristor

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    We suggest and experimentally demonstrate a chaotic memory resistor (memristor). The core of our approach is to use a resistive system whose equations of motion for its internal state variables are similar to those describing a particle in a multi-well potential. Using a memristor emulator, the chaotic memristor is realized and its chaotic properties are measured. A Poincar\'{e} plot showing chaos is presented for a simple nonautonomous circuit involving only a voltage source directly connected in series to a memristor and a standard resistor. We also explore theoretically some details of this system, plotting the attractor and calculating Lyapunov exponents. The multi-well potential used resembles that of many nanoscale memristive devices, suggesting the possibility of chaotic dynamics in other existing memristive systems.Comment: Applied Physics A (in press

    Saints, heroes, sages, and villains

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    This essay explores the question of how to be good. My starting point is a thesis about moral worth that I’ve defended in the past: roughly, that an action is morally worthy if and only it is performed for the reasons why it is right. While I think that account gets at one important sense of moral goodness, I argue here that it fails to capture several ways of being worthy of admiration on moral grounds. Moral goodness is more multi-faceted. My title is intended to capture that multi-facetedness: the essay examines saintliness, heroism, and sagacity. The variety of our common-sense moral ideals underscores the inadequacy of any one account of moral admirableness, and I hope to illuminate the distinct roles these ideals play in our everyday understanding of goodness. Along the way, I give an account of what makes actions heroic, of whether such actions are supererogatory, and of what, if anything, is wrong with moral deference. At the close of the essay, I begin to explore the flipside of these ideals: villainy

    Coverage, Continuity and Visual Cortical Architecture

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    The primary visual cortex of many mammals contains a continuous representation of visual space, with a roughly repetitive aperiodic map of orientation preferences superimposed. It was recently found that orientation preference maps (OPMs) obey statistical laws which are apparently invariant among species widely separated in eutherian evolution. Here, we examine whether one of the most prominent models for the optimization of cortical maps, the elastic net (EN) model, can reproduce this common design. The EN model generates representations which optimally trade of stimulus space coverage and map continuity. While this model has been used in numerous studies, no analytical results about the precise layout of the predicted OPMs have been obtained so far. We present a mathematical approach to analytically calculate the cortical representations predicted by the EN model for the joint mapping of stimulus position and orientation. We find that in all previously studied regimes, predicted OPM layouts are perfectly periodic. An unbiased search through the EN parameter space identifies a novel regime of aperiodic OPMs with pinwheel densities lower than found in experiments. In an extreme limit, aperiodic OPMs quantitatively resembling experimental observations emerge. Stabilization of these layouts results from strong nonlocal interactions rather than from a coverage-continuity-compromise. Our results demonstrate that optimization models for stimulus representations dominated by nonlocal suppressive interactions are in principle capable of correctly predicting the common OPM design. They question that visual cortical feature representations can be explained by a coverage-continuity-compromise.Comment: 100 pages, including an Appendix, 21 + 7 figure
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