Anomaly Free Non-Supersymmetric Large NN Gauge Theories from Orientifolds

We construct anomaly free non-supersymmetric large N gauge theories from orientifolds of Type IIB on C^3/G orbifolds. In particular, massless as well as tachyonic one-loop tadpoles are cancelled in these models. This is achieved by starting with ${\cal N}=1,2$ supersymmetric orientifolds with well defined world-sheet description and including discrete torsion (which breaks supersymmetry) in the orbifold action. In this way we obtain non-trivial non-chiral as well as anomaly free chiral large N gauge theories. We point out certain subtleties arising in the chiral cases. Subject to certain assumptions, these theories are shown to have the property that computation of any M-point correlation function in these theories reduces to the corresponding computation in the parent ${\cal N}=4$ oriented theory. This generalizes the analogous results recently obtained in supersymmetric large N gauge theories from orientifolds, as well as in (non)supersymmetric large N gauge theories without orientifold planes.Comment: 18 pages, revtex, minor misprints corrected, a clarifying footnote added (to appear in Phys. Rev. D

High-Energy Tests of Lorentz Invariance

We develop a perturbative framework with which to discuss departures from exact Lorentz invariance and explore their potentially observable ramifications. Tiny non-invariant terms introduced into the standard model Lagrangian are assumed to be renormalizable (dimension $\le 4$), invariant under $SU(3)\otimes SU(2)\otimes U(1)$ gauge transformations, and rotationally and translationally invariant in a preferred frame. There are a total of 46 independent TCP-even perturbations of this kind, all of which preserve anomaly cancellation. They define the energy-momentum eigenstates and their maximal attainable velocities in the high-energy limit. The effects of these perturbations increase rapidly with energy in the preferred frame, more rapidly than those of TCP-odd perturbations. Our analysis of Lorentz-violating kinematics reveals several striking new phenomena that are relevant both to cosmic-ray physics ({\it e.g.,} by undoing the GZK cutoff) and neutrino physics ({\it e.g.,} by generating novel types of neutrino oscillations). These may lead to new and sensitive high-energy tests of special relativity.Comment: 33 pages, uses harvmac. This 2nd revision corrects two typos, an error in the Appendix, and includes further acknowledgement

Non-Perturbative Superpotentials in F-theory and String Duality

We use open-closed string duality between F-theory on K3xK3 and type II strings on CY manifolds without branes to study non-perturbative superpotentials in generalized flux compactifications. On the F-theory side we obtain the full flux potential including D3-instanton contributions and show that it leads to an explicit and simple realization of the three ingredients of the KKLT model for stringy dS vacua. The D3-instanton contribution is highly non-trivial, can be systematically computed including the determinant factors and demonstrates that a particular flux lifts very effectively zero modes on the instanton. On the closed string side, we propose a generalization of the Gukov-Vafa-Witten superpotential for type II strings on generalized CY manifolds, depending on all moduli multiplets.Comment: 49 pages, harvmac, 1 figure; references & figures adde

Type IIA Moduli Stabilization

We demonstrate that flux compactifications of type IIA string theory can classically stabilize all geometric moduli. For a particular orientifold background, we explicitly construct an infinite family of supersymmetric vacua with all moduli stabilized at arbitrarily large volume, weak coupling, and small negative cosmological constant. We obtain these solutions from both ten-dimensional and four-dimensional perspectives. For more general backgrounds, we study the equations for supersymmetric vacua coming from the effective superpotential and show that all geometric moduli can be stabilized by fluxes. We comment on the resulting picture of statistics on the landscape of vacua.Comment: 48 pages, 2 figures, LaTeX. v2: references added. v3: minor comments & references adde

Characterization of a fluvial aquifer at a range of depths and scales: the Triassic St Bees Sandstone Formation, Cumbria, UK

Fluvial sedimentary successions represent porous media that host groundwater and geothermal resources. Additionally, they overlie crystalline rocks hosting nuclear waste repositories in rift settings. The permeability characteristics of an arenaceous fluvial succession, the Triassic St Bees Sandstone Formation in England (UK), are described, from core-plug to well-test scale up to ~1 km depth. Within such lithified successions, dissolution associated with the circulation of meteoric water results in increased permeability (K~10−1–100 m/day) to depths of at least 150 m below ground level (BGL) in aquifer systems that are subject to rapid groundwater circulation. Thus, contaminant transport is likely to occur at relatively high rates. In a deeper investigation (> 150 m depth), where the aquifer has not been subjected to rapid groundwater circulation, well-test-scale hydraulic conductivity is lower, decreasing from K~10−2 m/day at 150–400 m BGL to 10−3 m/day down-dip at ~1 km BGL, where the pore fluid is hypersaline. Here, pore-scale permeability becomes progressively dominant with increasing lithostatic load. Notably, this work investigates a sandstone aquifer of fluvial origin at investigation depths consistent with highly enthalpy geothermal reservoirs (~0.7–1.1 km). At such depths, intergranular flow dominates in unfaulted areas with only minor contribution by bedding plane fractures. However, extensional faults represent preferential flow pathways, due to presence of high connective open fractures. Therefore, such faults may (1) drive nuclear waste contaminants towards the highly permeable shallow (< 150 m BGL) zone of the aquifer, and (2) influence fluid recovery in geothermal fields

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures. This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival