395 research outputs found

    Internal Universes in Models of Homotopy Type Theory

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    We begin by recalling the essentially global character of universes in various models of homotopy type theory, which prevents a straightforward axiomatization of their properties using the internal language of the presheaf toposes from which these model are constructed. We get around this problem by extending the internal language with a modal operator for expressing properties of global elements. In this setting we show how to construct a universe that classifies the Cohen-Coquand-Huber-Mörtberg (CCHM) notion of fibration from their cubical sets model, starting from the assumption that the interval is tiny - a property that the interval in cubical sets does indeed have. This leads to an elementary axiomatization of that and related models of homotopy type theory within what we call crisp type theory

    On the six-dimensional origin of the AGT correspondence

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    We argue that the six-dimensional (2,0) superconformal theory defined on M \times C, with M being a four-manifold and C a Riemann surface, can be twisted in a way that makes it topological on M and holomorphic on C. Assuming the existence of such a twisted theory, we show that its chiral algebra contains a W-algebra when M = R^4, possibly in the presence of a codimension-two defect operator supported on R^2 \times C \subset M \times C. We expect this structure to survive the \Omega-deformation.Comment: References added. 14 page

    Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

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    New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

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    A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

    Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

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    Measurement of Higgs boson production and properties in the WW decay channel with leptonic final states

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    Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

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    C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation

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    Intronic GGGGCC (G4C2) hexanucleotide repeat expansion within the human C9orf72 gene represents the most common cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of repeat-containing C9orf72 RNA results in the production of neurotoxic dipeptide-repeat proteins (DPRs). Here, we developed a high-throughput drug screen for the identification of positive and negative modulators of DPR levels. We found that HSP90 inhibitor geldanamycin and aldosterone antagonist spironolactone reduced DPR levels by promoting protein degradation via the proteasome and autophagy pathways respectively. Surprisingly, cAMP-elevating compounds boosting protein kinase A (PKA) activity increased DPR levels. Inhibition of PKA activity, by both pharmacological and genetic approaches, reduced DPR levels in cells and rescued pathological phenotypes in a Drosophila model of C9ALS/FTD. Moreover, knockdown of PKA-catalytic subunits correlated with reduced translation efficiency of DPRs, while the PKA inhibitor H89 reduced endogenous DPR levels in C9ALS/FTD patient-derived iPSC motor neurons. Together, our results suggest new and druggable pathways modulating DPR levels in C9ALS/FTD

    Study of double parton scattering using W+2-jet events in proton-proton collisions at √s=7 TeV

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    Search for Dark Matter and Supersymmetry with a Compressed Mass Spectrum in the Vector Boson Fusion Topology in Proton-Proton Collisions at root s=8 TeV

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