4,201 research outputs found

    Amoxicillin and amoxicillin/clavulanate reduce ethanol intake and increase GLT-1 expression as well as AKT phosphorylation in mesocorticolimbic regions.

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    Studies have shown that administration of the β-lactam antibiotic, ceftriaxone (CEF) attenuates ethanol consumption and cocaine seeking behavior as well as preventing ethanol-induced downregulation of glutamate transporter 1 (GLT-1) expression in central reward brain regions. However, it is not known if these effects are compound-specific. Therefore, the present study examined the effects of two other β-lactam antibiotics, amoxicillin (AMOX) and amoxicillin/clavulanate (Augmentin, AUG), on ethanol drinking, as well as GLT-1 and phosphorylated-AKT (pAKT) levels in the nucleus accumbens (Acb) and medial prefrontal cortex (mPFC) of alcohol-preferring (P) rats. P rats were exposed to free-choice of ethanol (15% and 30%) for five weeks and were given five consecutive daily i.p. injections of saline vehicle, 100 mg/kg AMOX or 100 mg/kg AUG. Both compounds significantly decreased ethanol intake and significantly increased GLT-1 expression in the Acb. AUG also increased GLT-1 expression in the mPFC. Results for changes in pAKT levels matched those for GLT-1, indicating that β-lactam antibiotic-induced reductions in ethanol intake are negatively associated with increases in GLT-1 and pAKT levels within two critical brains regions mediating drug reward and reinforcement. These findings add to a growing literature that pharmacological increases in GLT-1 expression are associated with decreases in ethanol intake and suggest that one mechanism mediating this effect may be increased phosphorylation of AKT. Thus, GLT-1 and pAKT may serve as molecular targets for the treatment of alcohol and drug abuse/dependence

    Targeting Glutamate Uptake To Treat Alcohol Use Disorders

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    Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence

    Consistency, Amplitudes and Probabilities in Quantum Theory

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    Quantum theory is formulated as the only consistent way to manipulate probability amplitudes. The crucial ingredient is a consistency constraint: if there are two different ways to compute an amplitude the two answers must agree. This constraint is expressed in the form of functional equations the solution of which leads to the usual sum and product rules for amplitudes. A consequence is that the Schrodinger equation must be linear: non-linear variants of quantum mechanics are inconsistent. The physical interpretation of the theory is given in terms of a single natural rule. This rule, which does not itself involve probabilities, is used to obtain a proof of Born's statistical postulate. Thus, consistency leads to indeterminism. PACS: 03.65.Bz, 03.65.Ca.Comment: 23 pages, 3 figures (old version did not include the figures

    Thermal simulation of magnetization reversals for size-distributed assemblies of core-shell exchange biased nanoparticles

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    A temperature dependent coherent magnetization reversal model is proposed for size-distributed assemblies of ferromagnetic nanoparticles and ferromagnetic-antiferromagnetic core-shell nanoparticles. The nanoparticles are assumed to be of uniaxial anisotropy and all aligned along their easy axis. The thermal dependence is included by considering thermal fluctuations, implemented via the N\'eel-Arrhenius theory. Thermal and angular dependence of magnetization reversal loops, coercive field and exchange-bias field are obtained, showing that F-AF size-distributed exchange-coupled nanoparticles exhibit temperature-dependent asymmetric magnetization reversal. Also, non-monotonic evolutions of He and Hc with T are demonstrated. The angular dependence of Hc with T exhibits a complex behavior, with the presence of an apex, whose position and amplitude are strongly T dependent. The angular dependence of He with T exhibits complex behaviors, which depends on the AF anisotropy and exchange coupling. The resulting angular behavior demonstrates the key role of the size distribution and temperature in the magnetic response of nanoparticles.Comment: Revised arguments in Introduction and last sectio

    Bayesian Probabilities and the Histories Algebra

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    We attempt a justification of a generalisation of the consistent histories programme using a notion of probability that is valid for all complete sets of history propositions. This consists of introducing Cox's axioms of probability theory and showing that our candidate notion of probability obeys them. We also give a generalisation of Bayes' theorem and comment upon how Bayesianism should be useful for the quantum gravity/cosmology programmes.Comment: 10 pages, accepted by Int. J. Theo. Phys. Feb 200

    Magnetic properties of exchange biased and of unbiased oxide/permalloy thin layers: a ferromagnetic resonance and Brillouin scattering study

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    Microstrip ferromagnetic resonance and Brillouin scattering are used to provide a comparative determination of the magnetic parameters of thin permalloy layers interfaced with a non-magnetic (Al2O3) or with an antiferromagnetic oxide (NiO). It is shown that the perpendicular anisotropy is monitored by an interfacial surface energy term which is practically independent of the nature of the interface. In the investigated interval of thicknesses (5-25 nm) the saturation magnetisation does not significantly differ from the reported one in bulk permalloy. In-plane uniaxial anisotropy and exchange-bias anisotropy are also derived from this study of the dynamic magnetic excitations and compared to our independent evaluations using conventional magnetometryComment: 7 pages, 6 figures, submited to Journal of Physics: Condensed Matte

    Peri-adolescent drinking of ethanol and/or nicotine modulates astroglial glutamate transporters and metabotropic glutamate receptor-1 in female alcohol-preferring rats

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    Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicates that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression. In this study, peri-adolescent female alcohol preferring (P) rats were given binge-like access to water, sucrose (SUC), SUC-NIC, EtOH, or EtOH-NIC for four weeks. The present study determined the effects of these reinforcers on GLT-1, xCT, GLAST, and mGluR1 expression in the nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC). GLT-1 and xCT expression were decreased in the NAc following both SUC-NIC and EtOH-NIC. In addition, only xCT expression was downregulated in the HIP in both of these latter groups. Also, glutathione peroxidase (GPx) activity in the HIP was reduced following SUC, SUC-NIC, EtOH, and EtOH-NIC consumption. Similar to previous work, GLAST expression was not altered in any brain region by any of the reinforcers. However, mGluR1 expression was increased in the NAc in the SUC-NIC, EtOH, and EtOH-NIC groups. These results indicate that peri-adolescent binge-like drinking of EtOH or SUC with or without NIC may exert differential effects on astroglial glutamate transporters and receptors. Our data further parallel some of the previous findings observed in adult rats

    Improving the Representation and Conversion of Mathematical Formulae by Considering their Textual Context

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    Mathematical formulae represent complex semantic information in a concise form. Especially in Science, Technology, Engineering, and Mathematics, mathematical formulae are crucial to communicate information, e.g., in scientific papers, and to perform computations using computer algebra systems. Enabling computers to access the information encoded in mathematical formulae requires machine-readable formats that can represent both the presentation and content, i.e., the semantics, of formulae. Exchanging such information between systems additionally requires conversion methods for mathematical representation formats. We analyze how the semantic enrichment of formulae improves the format conversion process and show that considering the textual context of formulae reduces the error rate of such conversions. Our main contributions are: (1) providing an openly available benchmark dataset for the mathematical format conversion task consisting of a newly created test collection, an extensive, manually curated gold standard and task-specific evaluation metrics; (2) performing a quantitative evaluation of state-of-the-art tools for mathematical format conversions; (3) presenting a new approach that considers the textual context of formulae to reduce the error rate for mathematical format conversions. Our benchmark dataset facilitates future research on mathematical format conversions as well as research on many problems in mathematical information retrieval. Because we annotated and linked all components of formulae, e.g., identifiers, operators and other entities, to Wikidata entries, the gold standard can, for instance, be used to train methods for formula concept discovery and recognition. Such methods can then be applied to improve mathematical information retrieval systems, e.g., for semantic formula search, recommendation of mathematical content, or detection of mathematical plagiarism.Comment: 10 pages, 4 figure
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