Superloop Equations and Two Dimensional Supergravity

We propose a discrete model whose continuum limit reproduces the string susceptibility and the scaling dimensions of $(2,4m)$-minimal superconformal models coupled to $2D$-supergravity. The basic assumption in our presentation is a set of super-Virasoro constraints imposed on the partition function. We recover the Neveu-Schwarz and Ramond sectors of the theory, and we are also able to evaluate all planar loop correlation functions in the continuum limit. We find evidence to identify the integrable hierarchy of non-linear equations describing the double scaling limit as a supersymmetric generalization of KP studied by Rabin.Comment: 34 page

The Algebra of Non-Local Charges in Non-Linear Sigma Models

We obtain the exact Dirac algebra obeyed by the conserved non-local charges in bosonic non-linear sigma models. Part of the computation is specialized for a symmetry group $O(N)$. As it turns out the algebra corresponds to a cubic deformation of the Kac-Moody algebra. The non-linear terms are computed in closed form. In each Dirac bracket we only find highest order terms (as explained in the paper), defining a saturated algebra. We generalize the results for the presence of a Wess-Zumino term. The algebra is very similar to the previous one, containing now a calculable correction of order one unit lower.Comment: 27 pages + figures available via ftp, Plain TeX, IFUSP/P-106

Transferability Intercomparison: An Opportunity for New Insight on the Global Water Cycle and Energy Budget

A new approach, called transferability intercomparisons, is described for advancing both understanding and modeling of the global water cycle and energy budget. Under this approach, individual regional climate models perform simulations with all modeling parameters and parameterizations held constant over a specific period on several prescribed domains representing different climatic regions. The transferability framework goes beyond previous regional climate model intercomparisons to provide a global method for testing and improving model parameterizations by constraining the simulations within analyzed boundaries for several domains. Transferability intercomparisons expose the limits of our current regional modeling capacity by examining model accuracy on a wide range of climate conditions and realizations. Intercomparison of these individual model experiments provides a means for evaluating strengths and weaknesses of models outside their “home domains” (domain of development and testing). Reference sites that are conducting coordinated measurements under the continental-scale experiments under the Global Energy and Water Cycle Experiment (GEWEX) Hydrometeorology Panel provide data for evaluation of model abilities to simulate specific features of the water and energy cycles. A systematic intercomparison across models and domains more clearly exposes collective biases in the modeling process. By isolating particular regions and processes, regional model transferability intercomparisons can more effectively explore the spatial and temporal heterogeneity of predictability. A general improvement of model ability to simulate diverse climates will provide more confidence that models used for future climate scenarios might be able to simulate conditions on a particular domain that are beyond the range of previously observed climates

AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our fi ndings show how prostate tumors undergo a metabolic reprogramming that refl ects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médica

Impacts of orography on large-scale atmospheric circulation

Some of the largest and most persistent circulation errors in global numerical weather prediction and climate models are attributable to the inadequate representation of the impacts of orography on the atmospheric flow. Existing parametrization approaches attempting to account for unresolved orographic processes, such as turbulent form drag, low-level flow blocking or mountain waves, have been successful to some extent. They capture the basic impacts of the unresolved orography on atmospheric circulation in a qualitatively correct way and have led to significant progress in both numerical weather prediction and climate modelling. These approaches, however, have apparent limitations and inadequacies due to poor observational evidence, insufficient fundamental knowledge and an ambiguous separation between resolved and unresolved orographic scales and between different orographic processes. Numerical weather prediction and climate modelling has advanced to a stage where these inadequacies have become critical and hamper progress by limiting predictive skill on a wide range of spatial and temporal scales. More physically-based approaches are needed to quantify the relative importance of apparently disparate orographic processes and to account for their combined effects in a rational and accurate way in numerical models. We argue that, thanks to recent advances, significant progress can be made by combining theoretical approaches with observations, inverse modelling techniques and high-resolution and idealized numerical simulations

Evolutionary Relationships of Ljungan Virus Variants Circulating in Multi-Host Systems across Europe

The picornavirus named ‘Ljungan virus’ (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission

Evolutionary Relationships of Ljungan Virus Variants Circulating in Multi-Host Systems across Europe

The picornavirus named ‘Ljungan virus’ (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission

Shallow whole-genome sequencing of Aedes japonicus and Aedes koreicus from Italy and an updated picture of their evolution based on mitogenomics and barcoding

Aedes japonicus and Aedes koreicus are two invasive mosquitoes native to East Asia that are quickly establishing in temperate regions of Europe. Both species are vectors of arboviruses, but we currently lack a clear understanding of their evolution. Here, we present new short-read, shallow genome sequencing of A. japonicus and A. koreicus individuals from northern Italy, which we used for downstream phylogenetic and barcode analyses. We explored associated microbial DNA and found high occurrences of Delftia bacteria in both samples, but neither Asaia nor Wolbachia. We then assembled complete mitogenomes and used these data to infer divergence times estimating the split of A. japonicus from A. koreicus in the Oligocene, which was more recent than that previously reported using mitochondrial markers. We recover a younger age for most other nodes within Aedini and other Culicidae. COI barcoding and phylogenetic analyses indicate that A. japonicus yaeyamensis, A. japonicus amamiensis, and the two A. koreicus sampled from Europe should be considered as separate species within a monophyletic species complex. Our studies further clarify the evolution of A. japonicus and A. koreicus, and indicate the need to obtain whole-genome data from putative species in order to disentangle their complex patterns of evolution

AKT1 and MYC induce distinctive metabolic fingerprints in human prostate cancer

Cancer cells may overcome growth factor dependence by deregulating oncogenic and/or tumor-suppressor pathways that affect their metabolism, or by activating metabolic pathways de novo with targeted mutations in critical metabolic enzymes. It is unknown whether human prostate tumors develop a similar metabolic response to different oncogenic drivers or a particular oncogenic event results in its own metabolic reprogramming. Akt and Myc are arguably the most prevalent driving oncogenes in prostate cancer. Mass spectrometry-based metabolite profiling was performed on immortalized human prostate epithelial cells transformed by AKT1 or MYC, transgenic mice driven by the same oncogenes under the control of a prostate-specific promoter, and human prostate specimens characterized for the expression and activation of these oncoproteins. Integrative analysis of these metabolomic datasets revealed that AKT1 activation was associated with accumulation of aerobic glycolysis metabolites, whereas MYC overexpression was associated with dysregulated lipid metabolism. Selected metabolites that differentially accumulated in the MYC-high versus AKT1-high tumors, or in normal versus tumor prostate tissue by untargeted metabolomics, were validated using absolute quantitation assays. Importantly, the AKT1/MYC status was independent of Gleason grade and pathologic staging. Our fi ndings show how prostate tumors undergo a metabolic reprogramming that refl ects their molecular phenotypes, with implications for the development of metabolic diagnostics and targeted therapeutics.Instituto de Investigaciones Bioquímicas de La PlataFacultad de Ciencias Médica

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved