296 research outputs found

    Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke

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    Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median Π4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals

    Hypoxia mimetic agents for ischemic stroke

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    Every year stroke claims more than 6 million lives worldwide. The majority of them are ischemic stroke. Small molecule-based therapeutics for ischemic stroke has attracted a lot of attention, but none has been shown to be clinically useful so far. Hypoxia-inducible factor-1 (HIF-1) plays a crucial role in the transcriptional adaptation of cells to hypoxia. Small molecule-based hypoxia-mimetic agents either stabilize HIF-1α via HIF-prolyl hydroxylases (PHDs) inhibition or through other mechanisms. In both the cases, these agents have been shown to confer ischemic neuroprotection in vitro and in vivo. The agents which act via PHD inhibition are mainly classified into iron chelators, iron competitors, and 2 oxoglutarate (2OG) analogs. This review discusses HIF structure and key players in the HIF-1 degradation pathway as well as the genes, proteins and chemical molecules that are connected to HIF-1 and how they affect cell survival following ischemic injury. Furthermore, this review gives a summary of studies that used PHD inhibitors and other HIF-1α stabilizers as hypoxia-mimetic agents for the treatment of ischemic injury

    Low-Prandtl-number B\'enard-Marangoni convection in a vertical magnetic field

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    The effect of a homogeneous magnetic field on surface-tension-driven B\'{e}nard convection is studied by means of direct numerical simulations. The flow is computed in a rectangular domain with periodic horizontal boundary conditions and the free-slip condition on the bottom wall using a pseudospectral Fourier-Chebyshev discretization. Deformations of the free surface are neglected. Two- and three-dimensional flows are computed for either vanishing or small Prandtl number, which are typical of liquid metals. The main focus of the paper is on a qualitative comparison of the flow states with the non-magnetic case, and on the effects associated with the possible near-cancellation of the nonlinear and pressure terms in the momentum equations for two-dimensional rolls. In the three-dimensional case, the transition from a stationary hexagonal pattern at the onset of convection to three-dimensional time-dependent convection is explored by a series of simulations at zero Prandtl number.Comment: 26 pages, 9 figure

    Momentum transfer using chirped standing wave fields: Bragg scattering

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    We consider momentum transfer using frequency-chirped standing wave fields. Novel atom-beam splitter and mirror schemes based on Bragg scattering are presented. It is shown that a predetermined number of photon momenta can be transferred to the atoms in a single interaction zone.Comment: 4 pages, 3 figure

    Crime fiction, South Africa : a critical introduction

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    Crime fiction is an emergent category in South African literary studies. This introduction positions South African crime fiction and its scholarship in a global lineage of crime and detective fiction. The survey addresses the question of its literary status as ‘highbrow’ or ‘lowbrow’. It also identifies and describes two distinct sub-genres of South African crime fiction: the crime thriller novel; and the literary detective novel. The argument is that South African crime fiction exhibits a unique capacity for social analysis: a capacity which is being optimised by authors and interrogated by scholar

    Probing Kaluza-Klein Dark Matter with Neutrino Telescopes

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    In models in which all of the Standard Model fields live in extra universal dimensions, the lightest Kaluza-Klein (KK) particle can be stable. Calculations of the one-loop radiative corrections to the masses of the KK modes suggest that the identity of the lightest KK particle (LKP) is mostly the first KK excitation of the hypercharge gauge boson. This LKP is a viable dark matter candidate with an ideal present-day relic abundance if its mass is moderately large, between 600 to 1200 GeV. Such weakly interacting dark matter particles are expected to become gravitationally trapped in large bodies, such as the Sun, and annihilate into neutrinos or other particles that decay into neutrinos. We calculate the annihilation rate, neutrino flux and the resulting event rate in present and future neutrino telescopes. The relatively large mass implies that the neutrino energy spectrum is expected to be well above the energy threshold of AMANDA and IceCube. We find that the event rate in IceCube is between a few to tens of events per year.Comment: 13 pages, 3 figures, LaTeX; typos fixed, version to appear in PR

    Self-consistent model of ultracold atomic collisions and Feshbach resonances in tight harmonic traps

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    We consider the problem of cold atomic collisions in tight traps, where the absolute scattering length may be larger than the trap size. As long as the size of the trap ground state is larger than a characteristic length of the van der Waals potential, the energy eigenvalues can be computed self-consistently from the scattering amplitude for untrapped atoms. By comparing with the exact numerical eigenvalues of the trapping plus interatomic potentials, we verify that our model gives accurate eigenvalues up to milliKelvin energies for single channel s-wave scattering of 23^{23}Na atoms in an isotropic harmonic trap, even when outside the Wigner threshold regime. Our model works also for multi-channel scattering, where the scattering length can be made large due to a magnetically tunable Feshbach resonance.Comment: 7 pages, 4 figures (PostScript), submitted to Physical Review

    Effects of Pore Walls and Randomness on Phase Transitions in Porous Media

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    We study spin models within the mean field approximation to elucidate the topology of the phase diagrams of systems modeling the liquid-vapor transition and the separation of He3^3--He4^4 mixtures in periodic porous media. These topologies are found to be identical to those of the corresponding random field and random anisotropy spin systems with a bimodal distribution of the randomness. Our results suggest that the presence of walls (periodic or otherwise) are a key factor determining the nature of the phase diagram in porous media.Comment: REVTeX, 11 eps figures, to appear in Phys. Rev.

    EFFECT OF CONCURRENT SUBSTANCE USE DISORDER ON THE EFFECTIVENESS OF SINGLE AND COMBINATION ANTIDEPRESSANT MEDICATIONS FOR THE TREATMENT OF MAJOR DEPRESSION: AN EXPLORATORY ANALYSIS OF A SINGLE-BLIND RANDOMIZED TRIAL: Effect of Concurrent Substance Use Disorder

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    The co-occurrence of substance use disorder (SUD) and major depressive disorder (MDD) is common and is often thought to impair response to antidepressant therapy. These patients are often excluded from clinical trials, resulting in a significant knowledge gap regarding optimal pharmacotherapy for the treatment of MDD with concurrent SUD
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