283 research outputs found
Deformation quantisation for unshifted symplectic structures on derived Artin stacks
We prove that every -shifted symplectic structure on a derived Artin
-stack admits a curved 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 -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
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
Semicosimplicial DGLAs in deformation theory
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
Derived coisotropic structures II: stacks and quantization
We extend results about -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
-shifted coisotropic structures and show that they exist for .Comment: 45 pages. Contains the second half of arXiv:1608.01482v1 with new
material adde
The Unintended Consequences of a European Neighbourhood Policy without Russia
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
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
Disruption of the acetate kinase (ack) gene of Clostridium acetobutylicum results in delayed acetate production
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
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
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.
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
Communism and the Meaning of Social Memory: Towards a Critical-Interpretive Approach
This article was published in the journal, Integrative Psychological and Behavioral Science [© Springer Verlag] and the definitive version is available at: http://dx.doi.org/10.1007/s12124-012-9207-xUsing a case study of representations of communism in Romania, the paper offers a sketch of a critical-interpretive approach for exploring and engaging with the social memory of communism. When one considers the various contemporary appraisals, responses to and positions towards the communist period one identifies and one is obliged to deal with a series of personal and collective moral/political quandaries. In their attempt to bring about historical justice, political elites create a world that conforms more to their needs and desires than to the diversity of meanings of communism, experiences and dilemmas of lay people. This paper argues that one needs to study formal aspects of social memory as well as "lived", often conflicting, attitudinal and mnemonic stances and interpretive frameworks. One needs to strive to find the meaning of the social memory of communism in the sometimes contradictory, paradoxical attitudes and meanings that members of society communicate, endorse and debate. Many of the ethical quandaries and dilemmas of collective memory and recent history can be better understood by describing the discursive and sociocultural processes of meaning-making and meaning-interpretation carried out by members of a polity
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