GEMINGA’S PUZZLING PULSAR WIND NEBULA

postprin

Analytic Solution of Bremsstrahlung TBA

We consider the quark--anti-quark potential on the three sphere or the generalized cusp anomalous dimension in planar N=4 SYM. We concentrate on the vacuum potential in the near BPS limit with $L$ units of R-charge. Equivalently, we study the anomalous dimension of a super-Wilson loop with L local fields inserted at a cusp. The system is described by a recently proposed infinite set of non-linear integral equations of the Thermodynamic Bethe Ansatz (TBA) type. That system of TBA equations is very similar to the one of the spectral problem but simplifies a bit in the near BPS limit. Using techniques based on the Y-system of functional equations we first reduced the infinite system of TBA equations to a Finite set of Nonlinear Integral Equations (FiNLIE). Then we solve the FiNLIE system analytically, obtaining a simple analytic result for the potential! Surprisingly, we find that the system has equivalent descriptions in terms of an effective Baxter equation and in terms of a matrix model. At L=0, our result matches the one obtained before using localization techniques. At all other L's, the result is new. Having a new parameter, L, allows us to take the large L classical limit. We use the matrix model description to solve the classical limit and match the result with a string theory computation. Moreover, we find that the classical string algebraic curve matches the algebraic curve arising from the matrix model.Comment: 50 pages, 5 figures. v2: references added, JHEP versio

Interstellar Turbulence II: Implications and Effects

Interstellar turbulence has implications for the dispersal and mixing of the elements, cloud chemistry, cosmic ray scattering, and radio wave propagation through the ionized medium. This review discusses the observations and theory of these effects. Metallicity fluctuations are summarized, and the theory of turbulent transport of passive tracers is reviewed. Modeling methods, turbulent concentration of dust grains, and the turbulent washout of radial abundance gradients are discussed. Interstellar chemistry is affected by turbulent transport of various species between environments with different physical properties and by turbulent heating in shocks, vortical dissipation regions, and local regions of enhanced ambipolar diffusion. Cosmic rays are scattered and accelerated in turbulent magnetic waves and shocks, and they generate turbulence on the scale of their gyroradii. Radio wave scintillation is an important diagnostic for small scale turbulence in the ionized medium, giving information about the power spectrum and amplitude of fluctuations. The theory of diffraction and refraction is reviewed, as are the main observations and scintillation regions.Comment: 46 pages, 2 figures, submitted to Annual Reviews of Astronomy and Astrophysic

The generalized cusp in ABJ(M) N = 6 Super Chern-Simons theories

We construct a generalized cusped Wilson loop operator in N = 6 super Chern-Simons-matter theories which is locally invariant under half of the supercharges. It depends on two parameters and interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines, representing a natural generalization of the quark-antiquark potential in ABJ(M) theories. For particular choices of the parameters we obtain 1/6 BPS configurations that, mapped on S^2 by a conformal transformation, realize a three-dimensional analogue of the wedge DGRT Wilson loop of N = 4. The cusp couples, in addition to the gauge and scalar fields of the theory, also to the fermions in the bifundamental representation of the U(N)xU(M) gauge group and its expectation value is expressed as the holonomy of a suitable superconnection. We discuss the definition of these observables in terms of traces and the role of the boundary conditions of fermions along the loop. We perform a complete two-loop analysis, obtaining an explicit result for the generalized cusp at the second non-trivial order, from which we read off the interaction potential between heavy 1/2 BPS particles in the ABJ(M) model. Our results open the possibility to explore in the three-dimensional case the connection between localization properties and integrability, recently advocated in D = 4.Comment: 53 pages, 10 figures, added references, this is the version appeared on JHE

Ensemble-Based Computational Approach Discriminates Functional Activity of p53 Cancer and Rescue Mutants

The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain (“cancer mutants”). Activity can be restored by second-site suppressor mutations (“rescue mutants”). This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD), without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC) metric was strongly correlated (r2 = 0.77) with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i) p53 cancer mutants were more flexible than wild-type protein, (ii) second-site rescue mutations decreased the flexibility of cancer mutants, and (iii) negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants

Reaction rates and transport in neutron stars

Understanding signals from neutron stars requires knowledge about the transport inside the star. We review the transport properties and the underlying reaction rates of dense hadronic and quark matter in the crust and the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes, references updated, overview graphic added in the introduction, improvements in Sec IV.A.

Systematics of the cusp anomalous dimension

We study the velocity-dependent cusp anomalous dimension in supersymmetric Yang-Mills theory. In a paper by Correa, Maldacena, Sever, and one of the present authors, a scaling limit was identified in which the ladder diagrams are dominant and are mapped onto a Schrodinger problem. We show how to solve the latter in perturbation theory and provide an algorithm to compute the solution at any loop order. The answer is written in terms of harmonic polylogarithms. Moreover, we give evidence for two curious properties of the result. Firstly, we observe that the result can be written using a subset of harmonic polylogarithms only, at least up to six loops. Secondly, we show that in a light-like limit, only single zeta values appear in the asymptotic expansion, again up to six loops. We then extend the analysis of the scaling limit to systematically include subleading terms. This leads to a Schrodinger-type equation, but with an inhomogeneous term. We show how its solution can be computed in perturbation theory, in a way similar to the leading order case. Finally, we analyze the strong coupling limit of these subleading contributions and compare them to the string theory answer. We find agreement between the two calculations.Comment: 33 pages, 4 figures. Complete LO six-loop result added. Typos corrected. Version accepted for publicatio

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited

Hypoxia-Inducible Factor 1α Determines Gastric Cancer Chemosensitivity via Modulation of p53 and NF-κB

BACKGROUND: Reduced chemosensitivity of solid cancer cells represents a pivotal obstacle in clinical oncology. Hence, the molecular characterization of pathways regulating chemosensitivity is a central prerequisite to improve cancer therapy. The hypoxia-inducible factor HIF-1alpha has been linked to chemosensitivity while the underlying molecular mechanisms remain largely elusive. Therefore, we comprehensively analysed HIF-1alpha's role in determining chemosensitivity focussing on responsible molecular pathways. METHODOLOGY AND PRINCIPAL FINDINGS: RNA interference was applied to inactivate HIF-1alpha or p53 in the human gastric cancer cell lines AGS and MKN28. The chemotherapeutic agents 5-fluorouracil and cisplatin were used and chemosensitivity was assessed by cell proliferation assays as well as determination of cell cycle distribution and apoptosis. Expression of p53 and p53 target proteins was analyzed by western blot. NF-kappaB activity was characterized by means of electrophoretic mobility shift assay. Inactivation of HIF-1alpha in gastric cancer cells resulted in robust elevation of chemosensitivity. Accordingly, HIF-1alpha-competent cells displayed a significant reduction of chemotherapy-induced senescence and apoptosis. Remarkably, this phenotype was completely absent in p53 mutant cells while inactivation of p53 per se did not affect chemosensitivity. HIF-1alpha markedly suppressed chemotherapy-induced activation of p53 and p21 as well as the retinoblastoma protein, eventually resulting in cell cycle arrest. Reduced formation of reactive oxygen species in HIF-1alpha-competent cells was identified as the molecular mechanism of HIF-1alpha-mediated inhibition of p53. Furthermore, loss of HIF-1alpha abrogated, in a p53-dependent manner, chemotherapy-induced DNA-binding of NF-kappaB and expression of anti-apoptotic NF-kappaB target genes. Accordingly, reconstitution of the NF-kappaB subunit p65 reversed the increased chemosensitivity of HIF-1alpha-deficient cells. CONCLUSION AND SIGNIFICANCE: In summary, we identified HIF-1alpha as a potent regulator of p53 and NF-kappaB activity under conditions of genotoxic stress. We conclude that p53 mutations in human tumors hold the potential to confound the efficacy of HIF-1-inhibitors in cancer therapy