3,408 research outputs found
Thermal conductivity in the vortex state of d-wave superconductors
We present the results of a microscopic calculation of the longitudinal
thermal conductivity of quasiparticles, , in a 2D d-wave
superconductor in the vortex state. Our approach takes into account both
impurity scattering and a contribution to the thermal transport lifetime due to
the scattering of quasiparticles off of vortices. We compare the results with
the experimental measurements on high-T cuprates and organic
superconductors.Comment: 2 pages, submitted to proceedings of M2S-HTSC-VI (Houston
Genus Two Partition Functions and Renyi Entropies of Large c CFTs
We compute genus two partition functions in two dimensional conformal field
theories at large central charge, focusing on surfaces that give the third
Renyi entropy of two intervals. We compute this for generalized free theories
and for symmetric orbifolds, and compare it to the result in pure gravity. We
find a new phase transition if the theory contains a light operator of
dimension . This means in particular that unlike the second
Renyi entropy, the third one is no longer universal.Comment: 28 pages + Appendice
Sub-AdS Scale Locality in AdS/CFT
We investigate sub-AdS scale locality in a weakly coupled toy model of the
AdS/CFT correspondence. We find that this simple model has the correct
density of states at low and high energies to be dual to Einstein gravity
coupled to matter in AdS. Bulk correlation functions also have the correct
behavior at leading order in the large expansion, but non-local effects
emerge at order . Our analysis leads to the conjecture that any large
CFT that is modular invariant and has the right low-energy density of
states is dual to a gravitational theory with sub-AdS scale locality.Comment: 19 page
Performance of a quality assurance program for assessing dental health in methamphetamine users.
BackgroundSystematic characterization of the dental consequences of methamphetamine (MA) abuse presupposes a rigorous quality assurance (QA) program to ensure the credibility of the data collected and the scientific integrity and validity of the clinical study. In this report we describe and evaluate the performance of a quality assurance program implemented in a large cross-sectional study of the dental consequences of MA use.MethodsA large community sample of MA users was recruited over a 30 month period during 2011-13 and received comprehensive oral examinations and psychosocial assessments by site examiners based at two large community health centers in Los Angeles. National Health and Nutrition Examination Survey (NHANES) protocols for oral health assessments were utilized to characterize dental disease. Using NHANES oral health quality assurance guidelines, examiner reliability statistics such as Cohen's Kappa coefficients and inter-class correlation coefficients were calculated to assess the magnitude of agreement between the site examiners and a reference examiner to ensure conformance and comparability with NHANES practices.ResultsApproximately 9% (n = 49) of the enrolled 574 MA users received a repeat dental caries and periodontal examination conducted by the reference examiner. There was high concordance between the reference examiner and the site examiners for identification of untreated dental disease (Kappa statistic values: 0.57-0.75, percent agreement 83-88%). For identification of untreated caries on at least 5 surfaces of anterior teeth, the Kappas ranged from 0.77 to 0.87, and percent agreement from 94 to 97%. The intra-class coefficients (ICCs) ranged from 0.87 to 89 for attachment loss across all periodontal sites assessed and the ICCs ranged from 0.79 to 0.81 for pocket depth. For overall gingival recession, the ICCs ranged from 0.88 to 0.91. When Kappa was calculated based on the CDC/AAP case definitions for severe periodontitis, inter-examiner reliability for site examiners was low (Kappa 0.27-0.67).ConclusionOverall, the quality assurance program confirmed the procedural adherence of the quality of the data collected on the distribution of dental caries and periodontal disease in MA-users. Examiner concordance was higher for dental caries but lower for specific periodontal assessments
Phosphotyrosine Phosphatases of the AtT-20 Murine Corticotroph Cell Line
Somatostatin (somatotropin release inhibitory factor; SRIF) is a peptide-signaling molecule that activates a family of heterotrimeric guanine nucleotide binding protein (G protein) coupled receptors (sst.-sst-). SRIF receptors control essential intracellular signaling events and, by reducing cyclic nucleotide levels, ion concentrations and protein phosphorylation, ultimately controlling cell proliferation and secretion. In the current study, we investigated the intracellular phosphatase activity present in the AtT-20 cell, as well as whether these enzymes were under direct SRIF receptor control. AtT-20 cells retain many of the properties of anterior pituitary corticotrophs, yet are an established cell line that expresses at least two SRIF receptor subtypes (sst, and sst.). Both SRIF receptor subtypes potently suppress hormonally induced adrenocorticotropic hormone (ACTH) secretion from AtT-20 cells. Since intracellular protein kinase activation plays a crucial role in ACTH release from AtT-20 cells, identifying the corresponding protein phosphatases will provide valuable information on corticotroph function. The novel fluorescent phosphatase substrate, 6,8-difluoro-4-methylumbelliferyl phosphate (DiF MUP) was employed to identify soluble or membrane-associated phosphatase activities. Treatment with a selective tyrosine phosphatase inhibitor (sodium vanadate; Na3 V04) attenuated DiF-MUP phosphatase activity by 75%, suggesting that the dominant activity detected in AtT-20 cells is a tyrosine phosphatase. Na3V04 inhibition was potent as concentration response studies demonstrated an inhibitory concentration for 50% activity nM. (ICso) of 90 A serine/threonine phosphatase inhibitor failed todecrease phosphatase activity, indicating that the dominant phosphatase activity present is due to protein tyrosine phosphatases. Immunoprecipitation studies, in conjunction with sodium dodecyl sulfate polyacrylamide electrophoresis (SDS-P AGE) and immunoblotting identified two intracellular phosphotyrosine phosphatases: Src homology phosphatase- I (SHP-1) and Src homology phosphotyrosine phosphatase-2 (SHP-2). Immunoblotting with phospho specific antisera confirmed the presence of SHP-1 and SHP-2, while also demonstrating that neither enzyme appears to be under SRIF control in AtT-20 cells. Together, these results show that AtT-20 murine corticotrophs contain sodium vanadate sensitive, soluble tyrosine phosphatase activity that is independent of SRIF control
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In search of predictive endophenotypes in addiction: insights from preclinical research.
Drug addiction is widely recognized to afflict some but not all individuals by virtue of underlying risk markers and traits involving multifaceted interactions between polygenic and external factors. Remarkably, only a small proportion of individuals exposed to licit and illicit drugs develop compulsive drug-seeking behavior, maintained in the face of adverse consequences and associated detrimental patterns of drug intake involving extended and repeated bouts of binge intoxication, withdrawal and relapse. As a consequence, research has increasingly endeavored to identify distinctive neurobehavioral mechanisms and endophenotypes that predispose individuals to compulsive drug use. However, research in active drug users is hampered by the difficulty in categorizing putatively causal behavioral traits prior to the initiation of drug use. By contrast, research in experimental animals is often hindered by the validity of approaches used to investigate the neural and psychological mechanisms of compulsive drug-seeking habits in humans. Herein, we survey and discuss the principal findings emanating from preclinical animal research on addiction and highlight how specific behavioral endophenotypes of presumed genetic origin (e.g. trait anxiety, novelty preference and impulsivity) differentially contribute to compulsive forms of drug seeking and taking and, in particular, how these differentiate between different classes of stimulant and non-stimulant drugs of abuse.The authors acknowledge funding support from the UK Medical Research Council (grants G9536855; G0701500; G0802729), the Newton-Cambridge Trust and the Wellcome Trust (grant WT109738MA). The Behavioural and Clinical Neuroscience Institute at Cambridge University is supported by a core award from the Medical Research Council (G1000183) and Wellcome Trust (093875/Z/10/Z).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/gbb.1226
Phosphotyrosine Phosphatases of the AtT-20 Murine Corticotroph Cell Line
Somatostatin (somatotropin release inhibitory factor; SRIF) is a peptide-signaling molecule that activates a family of heterotrimeric guanine nucleotide binding protein (G protein) coupled receptors (sst.-sst-). SRIF receptors control essential intracellular signaling events and, by reducing cyclic nucleotide levels, ion concentrations and protein phosphorylation, ultimately controlling cell proliferation and secretion. In the current study, we investigated the intracellular phosphatase activity present in the AtT-20 cell, as well as whether these enzymes were under direct SRIF receptor control. AtT-20 cells retain many of the properties of anterior pituitary corticotrophs, yet are an established cell line that expresses at least two SRIF receptor subtypes (sst, and sst.). Both SRIF receptor subtypes potently suppress hormonally induced adrenocorticotropic hormone (ACTH) secretion from AtT-20 cells. Since intracellular protein kinase activation plays a crucial role in ACTH release from AtT-20 cells, identifying the corresponding protein phosphatases will provide valuable information on corticotroph function. The novel fluorescent phosphatase substrate, 6,8-difluoro-4-methylumbelliferyl phosphate (DiF MUP) was employed to identify soluble or membrane-associated phosphatase activities. Treatment with a selective tyrosine phosphatase inhibitor (sodium vanadate; Na3 V04) attenuated DiF-MUP phosphatase activity by 75%, suggesting that the dominant activity detected in AtT-20 cells is a tyrosine phosphatase. Na3V04 inhibition was potent as concentration response studies demonstrated an inhibitory concentration for 50% activity nM. (ICso) of 90 A serine/threonine phosphatase inhibitor failed todecrease phosphatase activity, indicating that the dominant phosphatase activity present is due to protein tyrosine phosphatases. Immunoprecipitation studies, in conjunction with sodium dodecyl sulfate polyacrylamide electrophoresis (SDS-P AGE) and immunoblotting identified two intracellular phosphotyrosine phosphatases: Src homology phosphatase- I (SHP-1) and Src homology phosphotyrosine phosphatase-2 (SHP-2). Immunoblotting with phospho specific antisera confirmed the presence of SHP-1 and SHP-2, while also demonstrating that neither enzyme appears to be under SRIF control in AtT-20 cells. Together, these results show that AtT-20 murine corticotrophs contain sodium vanadate sensitive, soluble tyrosine phosphatase activity that is independent of SRIF control
Collaboration in neuroscience: the young PI perspective.
Wellcome Trust, University of Cambridge, CIG, Adelis FoundationThis is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/ejn.1322
Decrease of cocaine, but not heroin, self-administration and relapse by the tyrosine kinase inhibitor masitinib in male Sprague Dawley rats.
RATIONALE: Accumulating evidence shows that cocaine, and also heroin, influence several tyrosine kinases, expressed in neurons and in non-neuronal populations such as microglia, astrocytes and mast-cells. Drug-induced activation of mast cells both triggers inflammatory processes in the brain mediated by the glial cells they activate, and facilitates histamine release which may directly influence the dopamine system. Thus, by triggering the activation and degranulation of mast cells dependent on the tyrosine kinase c-kit and Fyn, the latter being also involved in NMDA-dependent synaptic plasticity, cocaine and heroin may indirectly influence the neural mechanisms that mediate their reinforcing properties. Masitinib, a novel tyrosine kinase inhibitor with high selectivity for c-Kit, Fyn and Lyn, may alter the aberrant consequences of the activation of these tyrosine kinases by cocaine and heroin. OBJECTIVE: We investigated in rats the effect of a chronic oral treatment with masitinib (20 mg/kg) on the reinforcing and motivational properties of self-administered cocaine (250 μg/infusion) and heroin (40 μg/infusion). METHODS: Three different cohorts of rats were trained instrumentally to respond for cocaine, heroin or food under continuous reinforcement. In each group, we assessed the influence of chronic daily treatment with masitinib on the maintenance of instrumental responding and intake and the motivation for the reinforcer. Thus, masitinib and vehicle-treated rats were challenged to adapt to high behavioural demand, to respond under a progressive ratio schedule of reinforcement and to reinstate instrumental responding after extinction and/or abstinence. RESULTS: Masitinib selectively decreased cocaine intake, the motivation for cocaine and the subsequent propensity to respond for cocaine under extinction, while having no effect on instrumental responding for heroin or food. CONCLUSION: The present findings suggest masitinib, a drug with proven efficacy in CNS disorders, could represent a novel treatment for cocaine addiction provided its influence on the reinforcing and incentive properties of the drug is confirmed
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