362 research outputs found

    Deformation quantisation for unshifted symplectic structures on derived Artin stacks

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    We prove that every 00-shifted symplectic structure on a derived Artin nn-stack admits a curved A∞A_{\infty} deformation quantisation. The classical method of quantising smooth varieties via quantisations of affine space does not apply in this setting, so we develop a new approach. We construct a map from DQ algebroid quantisations of unshifted symplectic structures on a derived Artin nn-stack to power series in de Rham cohomology, depending only on a choice of Drinfeld associator. This gives an equivalence between even power series and certain involutive quantisations, which yield anti-involutive curved A∞A_{\infty} deformations of the dg category of perfect complexes. In particular, there is a canonical quantisation associated to every symplectic structure on such a stack, which agrees for smooth varieties with the Kontsevich--Tamarkin quantisation for even associators.Comment: 27pp.; v2 Propositions 1.23 and 3.10 added; v3 several small additions; v4 several changes following referee's comments, to appear in Select

    Derived coisotropic structures II: stacks and quantization

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    We extend results about nn-shifted coisotropic structures from part I of this work to the setting of derived Artin stacks. We show that an intersection of coisotropic morphisms carries a Poisson structure of shift one less. We also compare non-degenerate shifted coisotropic structures and shifted Lagrangian structures and show that there is a natural equivalence between the two spaces in agreement with the classical result. Finally, we define quantizations of nn-shifted coisotropic structures and show that they exist for n>1n>1.Comment: 45 pages. Contains the second half of arXiv:1608.01482v1 with new material adde

    Semicosimplicial DGLAs in deformation theory

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    We identify Cech cocycles in nonabelian (formal) group cohomology with Maurer-Cartan elements in a suitable L-infinity algebra. Applications to deformation theory are described.Comment: Largely rewritten. Abstract modified. 15 pages, Latex, uses xy-pi

    The Unintended Consequences of a European Neighbourhood Policy without Russia

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    After Russia’s retreat from the European Neighbourhood Policy, the EU’s policy towards its eastern neighbours was split up. The internal unintended consequence of the EU’s choice to leave its policy unaltered was a tension between the objective of privileged relations with ENP countries and a promise to recognise the interests of Russia as an equal partner. Externally, the unintended outcome was that this fostered two opposing strategic environments: a cooperative one for the EaP and a competitive one with Russia. In terms of the management of unintended consequences, the EU has actively sought to reinforce its normative hegemony towards EaP countries, while at the same time mitigating certain negative unintended effects

    Functional Blockade of Small GTPase RAN Inhibits Glioblastoma Cell Viability

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    Glioblastoma, the most common malignant tumor in the brain, lacks effective treatments and is currently incurable. To identify novel drug targets for this deadly cancer, the publicly available results of RNA interference screens from the Project Achilles database were analyzed. Ten candidate genes were identified as survival genes in 15 glioblastoma cell lines. RAN, member RAS oncogene family (RAN) was expressed in glioblastoma at the highest level among all candidates based upon cDNA microarray data. However, Kaplan-Meier survival analysis did not show any correlation between RAN mRNA levels and patient survival. Because RAN is a small GTPase that regulates nuclear transport controlled by karyopherin subunit beta 1 (KPNB1), RAN was further analyzed together with KPNB1. Indeed, GBM patients with high levels of RAN also had more KPNB1 and levels of KPNB1 alone did not relate to patient prognosis. Through a Cox multivariate analysis, GBM patients with high levels of RAN and KPNB1 showed significantly shorter life expectancy when temozolomide and promoter methylation of O6-methylguanine DNA methyltransferase were used as covariates. These results indicate that RAN and KPNB1 together are associated with drug resistance and GBM poor prognosis. Furthermore, the functional blockade of RAN and KPNB1 by importazole remarkably suppressed cell viability and activated apoptosis in GBM cells expressing high levels of RAN, while having a limited effect on astrocytes and GBM cells with undetectable RAN. Together, our results demonstrate that RAN activity is important for GBM survival and the functional blockade of RAN/KPNB1 is an appealing therapeutic approach

    The challenges of renewed independence: The Baltic states since 1991

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    This article offers a comparative assessment of how successfully Estonia, Latvia, and Lithuania have coped with the challenges of renewed independence since 1991, focusing on various aspects of political, economic, and social development. In the post-communist context the Baltic states have clearly outpaced other former Soviet republics and also performed reasonably well in comparison to the countries of Eastern Europe. The convergence of the Baltic experience, which began already in the early 20th century, has continued in the recent past as well, as the three states have adopted a number of similar approaches in domestic politics, the search for security, and economic policy. They also face a number of similar unsolved problems, including considerable political alienation, tensions in relations with Russia, socioeconomic disparity, and demographic challenges. The most important difference in the issues confronting the Baltic states today continues to be the large non-Baltic, mainly Russian presence in Estonia and Latvia, a result of Soviet-era policies. How to effect the meaningful integration of a multiethnic society remains a continuing challenge in these two countries. In contrast, population shifts under Soviet rule never became massive in Lithuania, and ethnic relations are a minor issue there today

    Disruption of the acetate kinase (ack) gene of Clostridium acetobutylicum results in delayed acetate production

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    In microorganisms, the enzyme acetate kinase (AK) catalyses the formation of ATP from ADP by de-phosphorylation of acetyl phosphate into acetic acid. A mutant strain of Clostridium acetobutylicum lacking acetate kinase activity is expected to have reduced acetate and acetone production compared to the wild type. In this work, a C. acetobutylicum mutant strain with a selectively disrupted ack gene, encoding AK, was constructed and genetically and physiologically characterized. The ack− strain showed a reduction in acetate kinase activity of more than 97% compared to the wild type. The fermentation profiles of the ack− and wild-type strain were compared using two different fermentation media, CGM and CM1. The latter contains acetate and has a higher iron and magnesium content than CGM. In general, fermentations by the mutant strain showed a clear shift in the timing of peak acetate production relative to butyrate and had increased acid uptake after the onset of solvent formation. Specifically, in acetate containing CM1 medium, acetate production was reduced by more than 80% compared to the wild type under the same conditions, but both strains produced similar final amounts of solvents. Fermentations in CGM showed similar peak acetate and butyrate levels, but increased acetoin (60%), ethanol (63%) and butanol (16%) production and reduced lactate (−50%) formation by the mutant compared to the wild type. These findings are in agreement with the proposed regulatory function of butyryl phosphate as opposed to acetyl phosphate in the metabolic switch of solventogenic clostridia

    The Authoritarian Past and South European Democracies: an introduction

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    It is the object of the contributors to this volume to compare how Southern European democracies have reacted to past authoritarian regimes. This introduction has three sections. In the first we seek to frame the concepts of authoritarian legacies, transitional justice and the politics of the past as they are applied here. In the second we analyse the forms of transitional justice that were present during the processes of democratisation in Southern Europe, while the third section presents an outline of the volume and of the contributions made by its authors

    Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

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    Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∼40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≥10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands
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