Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes

Forensic anthropology at Medico Legal Centre of the Faculty of Medicine of Ribeirão Preto/USP - comparative study of cases from 1999-2009

Forensic Anthropology is an area of knowledge that applies the methods of physical anthropology andarcheology within a legal context. The Medico Legal Centre (CEMEL) of the Faculty of Medicine of RibeirãoPreto of University of São Paulo (FMRP-USP) has a Forensic Anthropology Laboratory (LAF), created in2005 in a partnership project with the University of Sheffield (UK) and financed by the British Foreign andCommonwealth Office Global Opportunities Fund. As part of this project, a protocol for skeletal analysiswas established, supported by an upgraded scientific infrastructure, for application in a socially important context in Brazil. Accumulated cases from 1999 to 2006 were analyzed initially, followed by casesfrom 2007 to 2009. These analyses indicated that many skeletons forwarded to CEMEL were incomplete,making the completion of a biological profile difficult. Despite of this, a statistically significant increasewas detected in the mean number of bones forwarded in the 2007-2009 group (112.83) in comparison tothe 1999-2006 group (79.57). Also, a statistically significant decline in the mean age from 38.34 years inthe 1999-2006 group to 35.65 years in the 2007-2009 group was detected, probably associated withviolent crime. Analysis indicated that in the 1999-2006 group, handedness could not be assigned in themajority of the cases (57.14%), while in the 2007-2009 group assignment was possible in the majority ofthe cases (85.72%), with 57.15% being right-handed and 28.57% left. The improvement in assignmentis explained by the increase in the mean number of bones forwarded per skeleton. For all other examinedanthropological parameters, no statistical difference was detected.  Male,  Caucasian and right- handedskeletons were predominant in both groups. The chance of identifying an individual through anthropological examination increased from 73.81% in 1999-2006 group to 90.47% in 2007-2009. These resultsindicate that improvement in the quality bone recovery from the scene and subsequent anthropologicalanalysis increases the likelihood of individual identification, fulfilling the scientific and social goals offorensic anthropological examination.A Antropologia Forense é uma área de conhecimento que aplica os métodos da antropologia física e daarqueologia em um contexto legal. O Centro de Medicina Legal (CEMEL) da Faculdade de Medicina deRibeirão Preto da Universidade de São Paulo (FMRP-USP) possui um Laboratório de AntropologiaForense (LAF), criado em 2005, em um projeto de parceria com a University of Sheffield (UK) e financiado pelo British Foreign and Commonwealth Office Global Opportunities Fund. Como parte desseprojeto, foi elaborado um protocolo para análise de ossadas com uma estrutura científica atualizadaaplicável ao contexto social brasileiro. Inicialmente foram analisados os casos acumulados de 1999 a2006, seguidos dos casos de 2007 a 2009. Este estudo revelou que a maioria das ossadas encaminhadas ao CEMEL estavam incompletas, o que dificulta a obtenção de um perfil bioantropológico.Apesar disso, um aumento estatisticamente significativo foi detectado no número médio de ossosencaminhados no grupo de 2007-2009 (112,83) em comparação com o grupo de 1999-2006 (79,57).Além disso, foi detectado um declínio estatisticamente significativo na média de idade de 38,34 anos nogrupo de 1999-2006 para 35,65 anos no grupo de 2007-2009, provavelmente associado a crimesviolentos. A análise indicou que na maioria dos casos (57,14%), no grupo de 1999-2006, a lateralidadenão poderia ser atribuída, enquanto que no grupo de 2007-2009 foi possível atribuir a lateralidade namaioria dos casos (85,72%), sendo que 57,15% eram destros e 28,57% canhotos. A melhora na atribui-ção pode ser explicada pelo aumento do número médio de ossos enviados por esqueleto. Para todosos outros parâmetros antropológicos analisados, não foram detectadas diferenças estatisticamentesignificativas. Esqueletos do sexo masculino, caucasianos e destros foram predominantes em ambosos grupos. A chance de identificar um indivíduo através do exame antropológico aumentou de 73,81%em 1999-2006 para 90,47% em 2007-2009. Estes resultados indicam uma melhoria na qualidade dacoleta dos ossos no local de seu encontro, e subseqüente, um aumento da probabilidade de identifica-ção do individuo através da análise antropológica, cumprindo o papel científico e social do exameantropológico forense

The Minimal Model of Nonbaryonic Dark Matter: A Singlet Scalar

We propose the simplest possible renormalizable extension of the Standard Model - the addition of just one singlet scalar field - as a minimalist model for non-baryonic dark matter. Such a model is characterized by only three parameters in addition to those already appearing within the Standard Model: a dimensionless self-coupling and a mass for the new scalar, and a dimensionless coupling, \lambda, to the Higgs field. If the singlet is the dark matter, these parameters are related to one another by the cosmological abundance constraint, implying that the coupling of the singlet to the Higgs field is large, \lambda \sim O(0.1 - 1). Since this parameter also controls couplings to ordinary matter, we obtain predictions for the elastic cross section of the singlet with nuclei. The resulting scattering rates are close to current limits from both direct and indirect searches. The existence of the singlet also has implications for current Higgs searches, as it gives a large contribution to the invisible Higgs width for much of parameter space. These scalars can be strongly self-coupled in the cosmologically interesting sense recently proposed by Spergel and Steinhardt, but only for very low masses (< 1 GeV), which is possible only at the expense of some fine-tuning of parameters.Comment: 26 pages, latex. Minor revisions, few references adde

Linear and non-linear perturbations in dark energy models

I review the linear and second-order perturbation theory in dark energy models with explicit interaction to matter in view of applications to N-body simulations and non-linear phenomena. Several new or generalized results are obtained: the general equations for the linear perturbation growth; an analytical expression for the bias induced by a species-dependent interaction; the Yukawa correction to the gravitational potential due to dark energy interaction; the second-order perturbation equations in coupled dark energy and their Newtonian limit. I also show that a density-dependent effective dark energy mass arises if the dark energy coupling is varying.Comment: 12 pages, submitted to Phys. Rev; v2: added a ref. and corrected a typ

Direct detection of Higgs-portal dark matter at the LHC

We consider the process in which a Higgs particle is produced in association with jets and show that monojet searches at the LHC already provide interesting constraints on the invisible decays of a 125 GeV Higgs boson. Using the existing monojet searches performed by CMS and ATLAS, we show the 95% confidence level limit on the invisible Higgs decay rate is of the order of the total Higgs production rate in the Standard Model. This limit could be significantly improved when more data at higher center of mass energies are collected, provided systematic errors on the Standard Model contribution to the monojet background can be reduced. We also compare these direct constraints on the invisible rate with indirect ones based on measuring the Higgs rates in visible channels. In the context of Higgs portal models of dark matter, we then discuss how the LHC limits on the invisible Higgs branching fraction impose strong constraints on the dark matter scattering cross section on nucleons probed in direct detection experiments.Comment: 6 pages, 3 figures; v2: references added; v3: monojet and Higgs data updated, version published in EPJ

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

Propriedades de ZrO2 (Y2 O3) reciclado proveniente da confecção de próteses dentárias

RESUMO O objetivo deste trabalho foi a recuperação de descartes de ZrO2(Y2O3) oriundos de laboratórios de próteses dentárias, a partir do seu reprocessamento. Os descartes de ZrO2(Y2O3) foram fragmentados, peneirados e calcinados a 900ºC. Pós com tamanho menor que 32&#956;m foram prensados uniaxialmente a 100MPa e sinterizados em temperaturas entre 1400 e 1600ºC-120min. Análise de difração de raios X realizadas nos materiais calcinados indicaram a presença majoritária da fase ZrO2 tetragonal. Os compactos apresentaram densidade a verde próximo a 47% e as amostras sinterizadas tiveram sua densidade relativa variando entre 83,5% e 95%, para temperaturas de sinterização de 1400 e 1600ºC, respectivamente. Os resultados da análise de difração de raios X indicaram a presença da fase ZrO2 tetragonal, com dureza Vickers e tenacidade máxima obtidos para as amostras sinterizadas a 1600ºC, da ordem de 1100 HV e 5,7 MPa.m1/2 respectivamente