Protein kinase WNK2 as a tumour suppressor gene in malignant gliomas

Malignant glioblastomas are the most common and lethal adult brain tumours, with patients dying within two years from diagnosis. Little is known about the molecular mechanisms underlying the formation and/or development of these tumours, which present a very invasive phenotype within the brain and are genetically heterogeneous and highly resistant to both chemo- and radio-therapies. Recently, the promoter region of the protein kinase WNK2 gene was found to be hypermethylated in 29 of 31 infiltrative gliomas and about 80% of meningiomas. We have previously described that the experimental depletion of WNK2 expression decreases RhoA activity whilst leading to increased Rac1 activity. Because RhoA/Rac1 activities are important for cell migration and glioblastomas are very invasive tumours, we tested the effects of WNK2 on wound-healing assays in glioma cell lines SW1088 and A172. SW1088 cells express endogenous WNK2 and we observed that wound closure was increased upon experimental depletion of endogenous WNK2. In contrast, A172 cells display complete promoter region methylation and WNK2 re-expression was found to decrease migration. Consistently, we observed an increase in Rac1 activity in SW1088 cells upon WNK2 down-regulation, but lower levels of active Rac1 in A172 cells stably expressing WNK2 cDNA when compared with an equivalent cell line stably transfected with the same empty vector. Our studies indicate that loss of WNK2 expression promotes Rac1 activation and may contribute to the highly invasive phenotype that glioblastomas present. We also observed that, in a panel of glioblastoma cell lines, WNK2 promoter methylation correlates with a marked deregulation in Akt, MEK1/2 and ERK1/2 activities, suggesting WNK2 may also be important for tumour cell survival and cell cycle progression.FC

Crossover and self-averaging in the two-dimensional site-diluted Ising model

Using the newly proposed probability-changing cluster (PCC) Monte Carlo algorithm, we simulate the two-dimensional (2D) site-diluted Ising model. Since we can tune the critical point of each random sample automatically with the PCC algorithm, we succeed in studying the sample-dependent $T_c(L)$ and the sample average of physical quantities at each $T_c(L)$ systematically. Using the finite-size scaling (FSS) analysis for $T_c(L)$, we discuss the importance of corrections to FSS both in the strong-dilution and weak-dilution regions. The critical phenomena of the 2D site-diluted Ising model are shown to be controlled by the pure fixed point. The crossover from the percolation fixed point to the pure Ising fixed point with the system size is explicitly demonstrated by the study of the Binder parameter. We also study the distribution of critical temperature $T_c(L)$. Its variance shows the power-law $L$ dependence, $L^{-n}$, and the estimate of the exponent $n$ is consistent with the prediction of Aharony and Harris [Phys. Rev. Lett. {\bf 77}, 3700 (1996)]. Calculating the relative variance of critical magnetization at the sample-dependent $T_c(L)$, we show that the 2D site-diluted Ising model exhibits weak self-averaging.Comment: 6 pages including 6 eps figures, RevTeX, to appear in Phys. Rev.

Geometric K-Homology of Flat D-Branes

We use the Baum-Douglas construction of K-homology to explicitly describe various aspects of D-branes in Type II superstring theory in the absence of background supergravity form fields. We rigorously derive various stability criteria for states of D-branes and show how standard bound state constructions are naturally realized directly in terms of topological K-cycles. We formulate the mechanism of flux stabilization in terms of the K-homology of non-trivial fibre bundles. Along the way we derive a number of new mathematical results in topological K-homology of independent interest.Comment: 45 pages; v2: References added; v3: Some substantial revision and corrections, main results unchanged but presentation improved, references added; to be published in Communications in Mathematical Physic

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

An overview of jets and outflows in stellar mass black holes

In this book chapter, we will briefly review the current empirical understanding of the relation between accretion state and and outflows in accreting stellar mass black holes. The focus will be on the empirical connections between X-ray states and relativistic (`radio') jets, although we are now also able to draw accretion disc winds into the picture in a systematic way. We will furthermore consider the latest attempts to measure/order jet power, and to compare it to other (potentially) measurable quantities, most importantly black hole spin.Comment: Accepted for publication in Space Science Reviews. Also to appear in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

NEOTECTÔNICA NA BACIA DO ALTO RIO GRANDE: APLICAÇÕES EM SUA PORÇÃO MANTIQUEIRENSE

O trabalho tem por objetivo levar a efeito investigações acerca do quadro neotectônico vigente na bacia do alto Rio Grande em sua porção contida na Serra da Mantiqueira, sul de Minas Gerais. A discussão se pautou nos resultados obtidos por interpretações cartográficas, trabalhos de campo e mensuração dos seguintes índices geomórficos: Fator Assimetria de Bacias de Drenagem, Fator de Simetria Topográfica Transversal, Relação Declividade X Extensão do Curso, perfil longitudinal principais canais

Temporal dynamics of the shrub and herbaceous layer of an area of moist grassland in Alto Paraíso de Goiás, Brazil

Este trabalho avaliou a dinâmica estrutural e fl orística de uma comunidade de espécies herbáceo-arbustivas de uma área de campo limpo úmido em Alto Paraíso de Goiás, o primeiro inventário realizado em 2000 (T0) e o segundo em 2007 (T1). A diversidade de Shannon entre os períodos foi comparada pelo teste-t de Hutcheson e a similaridade fl orística, pelo índice de similaridade de Chao-Sørensen. As relações fl orísticas e a cobertura, entre os períodos e as linhas, foram avaliadas por meio de análises de correspondência retifi cada (DCA). Foram amostradas 98 espécies, 88 no T0 e 67 no T1, sendo 31 exclusivas do T0 e 10 do T1. A diversidade fl orística na comunidade foi elevada nos dois períodos, porém diferente entre esses (t = 7,12; p < 0,001), devido a variação no número e cobertura das espécies. A similaridade entre os dois inventários foi alta (Chao-Sørensen ± IC = 0,841 ± 0,074). A ordenação por DCA indicou relações entre a composição fl orística e a cobertura com o gradiente de umidade e de matéria orgânica no solo identifi cados em T0. Houve modifi cações nas linhas em zonas sazonais, as quais se tornaram mais semelhantes às linhas constantemente saturadas por água. Em um intervalo de sete anos o campo limpo úmido apresentou mudanças na composição fl orística e, principalmente na estrutura devido o aumento da cobertura de espécies perenes, cespitosas e entouceiradas, que foram favorecidas pela maior umidade no solo em resposta à elevação da pluviosidade da região. __________________________________________________________________________________________ ABSTRACTTh is study evaluated the fl oristic and structural dynamics of a community of herbaceous-shrub species in an area of moist grassland in Alto Paraíso de Goiás. Th e fi rst inventory was undertaken in 2000 (T0) and the second in 2007 (T1). Shannon’s diversity between the periods was compared by Hutchesons´s t-test, and the fl oristic similarity by the Chao-Sørensen similarity index. Floristic composition and cover, between periods and lines, were evaluated by detrended correspondence analysis (DCA). We sampled 98 species, 88 at T0 and 67 at T1; 31 were unique to T0 and 10 to T1. Floristic diversity in the community was high in both periods, but diff erent between them (t = 7.12, p <0.001), due to variation in species number and coverage. Similarity between the two surveys was high (Chao-Sørensen CI = ± 0.841 ± 0.074). Th e DCA ordination indicated relationships between the fl oristic composition and cover with a gradient of moisture and organic matter in the soil identifi ed in T0. Th ere were changes in the lines in the seasonal zones, which became more similar in those constantly saturated with water. During an interval of seven years the moist grassland showed changes in fl oristic composition and mainly in structure due to increased cover of the clumped tussock perennial species, which were favored by higher soil moisture due to high rainfall in the region

The Fluorescence Detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics Research Section

Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above $2.5\times 10^{17}$ eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% $C.L.$ for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations.Comment: 28 pages, 11 figure