Holographic non-perturbative corrections to gauge couplings

We give a direct microscopic derivation of the F-theory background that corresponds to four D7 branes of type I' theory by taking into account the D-instanton contributions to the emission of the axio-dilaton field in the directions transverse to the D7's. The couplings of the axio-dilaton to the D-instanton moduli modify its classical source terms which are shown to be proportional to the elements of the D7 brane chiral ring. Solving the bulk field equations with the non-perturbatively corrected sources yields the full F-theory background. This solution represents the gravitational dual of the four-dimensional theory living on a probe D3 brane of type I', namely of the N=2, Sp(1) SYM theory with Nf=4. Our results provide an explicit microscopic derivation of the non-perturbative gravitational dual of this theory. They also explain the recent observation that the exact coupling for this theory can be entirely reconstructed from its perturbative part plus the knowledge of the chiral ring on the D7 branes supporting its flavor degrees of freedom.Comment: Latex, 39 pages, 6 figure

The entropy of black holes: a primer

After recalling the definition of black holes, and reviewing their energetics and their classical thermodynamics, one expounds the conjecture of Bekenstein, attributing an entropy to black holes, and the calculation by Hawking of the semi-classical radiation spectrum of a black hole, involving a thermal (Planckian) factor. One then discusses the attempts to interpret the black-hole entropy as the logarithm of the number of quantum micro-states of a macroscopic black hole, with particular emphasis on results obtained within string theory. After mentioning the (technically cleaner, but conceptually more intricate) case of supersymmetric (BPS) black holes and the corresponding counting of the degeneracy of Dirichlet-brane systems, one discusses in some detail the ``correspondence'' between massive string states and non-supersymmetric Schwarzschild black holes.Comment: 51 pages, 4 figures, talk given at the "Poincare seminar" (Paris, 6 December 2003), to appear in Poincare Seminar 2003 (Birkhauser

Bayesian Multimodel Inference for Geostatistical Regression Models

The problem of simultaneous covariate selection and parameter inference for spatial regression models is considered. Previous research has shown that failure to take spatial correlation into account can influence the outcome of standard model selection methods. A Markov chain Monte Carlo (MCMC) method is investigated for the calculation of parameter estimates and posterior model probabilities for spatial regression models. The method can accommodate normal and non-normal response data and a large number of covariates. Thus the method is very flexible and can be used to fit spatial linear models, spatial linear mixed models, and spatial generalized linear mixed models (GLMMs). The Bayesian MCMC method also allows a priori unequal weighting of covariates, which is not possible with many model selection methods such as Akaike's information criterion (AIC). The proposed method is demonstrated on two data sets. The first is the whiptail lizard data set which has been previously analyzed by other researchers investigating model selection methods. Our results confirmed the previous analysis suggesting that sandy soil and ant abundance were strongly associated with lizard abundance. The second data set concerned pollution tolerant fish abundance in relation to several environmental factors. Results indicate that abundance is positively related to Strahler stream order and a habitat quality index. Abundance is negatively related to percent watershed disturbance

Chemoprevention of Colonic Polyps with Balsalazide: An Exploratory, Double-Blind, Placebo-Controlled Study

A number of agents, including aspirin, nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, folic acid, calcium, and vitamins, have been evaluated for their potential in chemoprevention of sporadic colorectal adenomas or cancer. Preclinical data suggest that 5-aminosalicylates also may have a chemopreventive effect. To investigate chemoprevention of colonic polyps with balsalazide, a 5-aminosalicylate prodrug. In this randomized, double-blind, placebo-controlled study, adults diagnosed with small polyps in the rectosigmoid colon were treated with either balsalazide 3 g/d or placebo for 6 months. Follow-up lower endoscopy was performed, and all polyps were measured and analyzed histologically. The primary endpoint was reduction in mean size of the largest polyp per subject. Among 241 participants screened, 86 were randomized to treatment, with 75 subjects evaluable. Balsalazide 3 g/d (n = 38) did not significantly reduce the mean size of the largest colonic polyp or the number of polyps compared with placebo (n = 37). Although not significant, post-hoc analysis revealed that total adenoma burden per subject, calculated as the sum of the volumes of all adenomas in mm3, increased by 55% in the balsalazide group compared with 95% in the placebo group. Although balsalazide did not have significant chemopreventive effects on established colonic polyps, these results can aid in designing future prospective studies

Inhibition of E2-induced expression of BRCA1 by persistent organochlorines

BACKGROUND: Environmental persistent organochlorines (POCs) biomagnify in the food chain, and the chemicals are suspected of being involved in a broad range of human malignancies. It is speculated that some POCs that can interfere with estrogen receptor-mediated responses are involved in the initiation and progression of human breast cancer. The tumor suppressor gene BRCA1 plays a role in cell-cycle control, in DNA repair, and in genomic stability, and it is often downregulated in sporadic mammary cancers. The aim of the present study was to elucidate whether POCs have the potential to alter the expression of BRCA1. METHODS: Using human breast cancer cell lines MCF-7 and MDA-MB-231, the effect on BRCA1 expression of chemicals belonging to different classes of organochlorine chemicals (the pesticide toxaphene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and three polychlorinated biphenyls [PCB#138, PCB#153 and PCB#180]) was measured by a reporter gene construct carrying 267 bp of the BRCA1 promoter. A twofold concentration range was analyzed in MCF-7, and the results were supported by northern blot analysis of BRCA1 mRNA using the highest concentrations of the chemicals. RESULTS: All three polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin reduced 17β-estradiol (E2)-induced expression as well as basal reporter gene expression in both cell lines, whereas northern blot analysis only revealed a downregulation of E2-induced BRCA1 mRNA expression in MCF-7 cells. Toxaphene, like E2, induced BRCA1 expression in MCF-7. CONCLUSION: The present study shows that some POCs have the capability to alter the expression of the tumor suppressor gene BRCA1 without affecting the cell-cycle control protein p21(Waf/Cip1). Some POCs therefore have the potential to affect breast cancer risk

The significance of tumour microarchitectural features in breast cancer prognosis: a digital image analysis

BACKGROUND: As only a minor portion of the information present in histological sections is accessible by eye, recognition and quantification of complex patterns and relationships among constituents relies on digital image analysis. In this study, our working hypothesis was that, with the application of digital image analysis technology, visually unquantifiable breast cancer microarchitectural features can be rigorously assessed and tested as prognostic parameters for invasive breast carcinoma of no special type. METHODS: Digital image analysis was performed using public domain software (ImageJ) on tissue microarrays from a cohort of 696 patients, and validated with a commercial platform (Visiopharm). Quantified features included elements defining tumour microarchitecture, with emphasis on the extent of tumour-stroma interface. The differential prognostic impact of tumour nest microarchitecture in the four immunohistochemical surrogates for molecular classification was analysed. Prognostic parameters included axillary lymph node status, breast cancer-specific survival, and time to distant metastasis. Associations of each feature with prognostic parameters were assessed using logistic regression and Cox proportional models adjusting for age at diagnosis, grade, and tumour size. RESULTS: An arrangement in numerous small nests was associated with axillary lymph node involvement. The association was stronger in luminal tumours (odds ratio (OR) = 1.39, p = 0.003 for a 1-SD increase in nest number, OR = 0.75, p = 0.006 for mean nest area). Nest number was also associated with survival (hazard ratio (HR) = 1.15, p = 0.027), but total nest perimeter was the parameter most significantly associated with survival in luminal tumours (HR = 1.26, p = 0.005). In the relatively small cohort of triple-negative tumours, mean circularity showed association with time to distant metastasis (HR = 1.71, p = 0.027) and survival (HR = 1.8, p = 0.02). CONCLUSIONS: We propose that tumour arrangement in few large nests indicates a decreased metastatic potential. By contrast, organisation in numerous small nests provides the tumour with increased metastatic potential to regional lymph nodes. An outstretched pattern in small nests bestows tumours with a tendency for decreased breast cancer-specific survival. Although further validation studies are required before the argument for routine quantification of microarchitectural features is established, our approach is consistent with the demand for cost-effective methods for triaging breast cancer patients that are more likely to benefit from chemotherapy

Older employees' declining attitudes over 20 years and across classes

British employers, under increasing competitive pressures, and applying new technology and work organization, have sought to reduce labour costs, resulting in work intensification and precarity. Older employees as a result are exposed to work demands that conflict with expectations of favourable treatment in late career. National survey data for Britain in the years 1992, 2001, 2006 and 2012 demonstrate a decline in overall job attitude among older employees following the changed conditions of the 1990s and across the major recession that began in 2008. To assess whether this decline is unequally distributed, decomposition by socio-economic class is carried out. This shows that older employees in the ‘service class’ of managerial and professional employees are affected at least as much as older employees in intermediate and less-skilled classes, thus underlining the age effect and showing that ‘service-class’ employees are not invulnerable to a changing economic environment

Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons

We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics

Regulation of GSK-3 Activity as A Shared Mechanism in Psychiatric Disorders

Serin/Treonin kinaz ailesinin üyelerinden bir kinaz olarak ilk kez glikojen sentaz’ı inhibe ettiği keşfedilen glikojen sentaz kinaz-3 (GSK-3), günümüzde bilinen 50’den fazla substratı ile birçok hücre içi düzenleyici mekanizmada görev alan geniş etki spektrumlu bir enzim olarak kabul edilmektedir. GSK-3’ün memelilerde GSK-3α ve GSK-3β olmak üzere yapısal olarak yüksek homoloji gösteren iki izoformu bulunmaktadır. Her iki izoform birçok dokuda yaygın dağılım göstermekle beraber, en yüksek oranda beyinde bulunmakta ve genellikle benzer fonksiyonlar göstermektedirler. Diğer protein kinazların aksine GSK-3 uyarılmamış hücrede yapısal olarak aktif yani defosforile halde bulur. Protein kinaz A (PKA), protein kinaz B (PKB;AKT) ve protein kinaz C (PKC) gibi diğer protein kinazlarla fosforilasyona uğrayarak olarak inaktive edilir. Günümüzde artmış GSK-3 aktivitesinin major depresyon, bipolar bozukluk, hiperaktivite bozuklukları gibi hastalıklar ve şizofreni oluşumunda rol oynayabileceğine ilişkin önemli bulgular mevcuttur. Bu nedenle söz konusu psikiyatrik hastalıklarda arttığı gösterilen GSK-3 aktivitesinin azaltılmasının tedavide umut verici bir yaklaşım olabileceği kabul edilebilir. Bu gözden geçirme çalışmasında yukarıda sözü edilen psikiyatrik hastalıkların oluşmasında görev alan GSK-3 aracılı mekanizmalara kısaca değinilerek GSK-3’ün aktivitesinin düzenlenmesinde rol oynadığı gösterilen klinikte kullanılan ilaçlara yer verilmiştir. Anahtar sözcükler: GSK-3, depresyon, bipolar bozukluk, şizofren