63 research outputs found

    Discovery of Novel Hypermethylated Genes in Prostate Cancer Using Genomic CpG Island Microarrays

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    BACKGROUND: Promoter and 5' end methylation regulation of tumour suppressor genes is a common feature of many cancers. Such occurrences often lead to the silencing of these key genes and thus they may contribute to the development of cancer, including prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to identify methylation changes in prostate cancer, we performed a genome-wide analysis of DNA methylation using Agilent human CpG island arrays. Using computational and gene-specific validation approaches we have identified a large number of potential epigenetic biomarkers of prostate cancer. Further validation of candidate genes on a separate cohort of low and high grade prostate cancers by quantitative MethyLight analysis has allowed us to confirm DNA hypermethylation of HOXD3 and BMP7, two genes that may play a role in the development of high grade tumours. We also show that promoter hypermethylation is responsible for downregulated expression of these genes in the DU-145 PCa cell line. CONCLUSIONS/SIGNIFICANCE: This study identifies novel epigenetic biomarkers of prostate cancer and prostate cancer progression, and provides a global assessment of DNA methylation in prostate cancer

    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

    Liver transplantation: indication and survival

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    O sucesso dos transplantes de fígado certamente seria comprometido se a avaliação pré-operatória dos pacientes não fosse realizada de forma adequada. Isto se justifica devido ao reconhecimento de que o sucesso da cirurgia depende, em princípio, do diagnóstico da doença de base, da determinação de sua extensão e do grau de repercussão sistêmica. No final das décadas de setenta a noventa os progressos da hepatologia na identificação das hepatites virais e no manejo da ascite e da síndrome hepatorrenal melhoraram sobremaneira a expectativa de vida do doente portador de doença hepática crônica. Mas, sem dúvida o transplante ortotópico do fígado (TOF) foi o espetacular avanço da hepatologia moderna. Atualmente o transplante é um tratamento eficaz das hepatopatias crônicas, e o índice de sobrevivência global aos 3 anos é ao redor de 80%. É, portanto, uma alternativa de tratamento indicada nos casos terminais, onde a mortalidade com tratamentos conservadores pode atingir até 70% ao final de 12 meses. Neste artigo, os autores comentam aspectos do TOF, relacionados à indicação e a sobrevida. _________________________________________________________________________________________ ABSTRACT: The success of liver transplantation would be certainly compromised if the pre-operative evaluation was not adequately performed. The success of the liver transplantation depends on the diagnosis of the underlying hepatic disease, the determination of its extension and the degree of systemic repercussion. In the last 30 years, the progress in hepatology, the identification of viral hepatitis and the better management of ascitis and hepatorenal syndrome have increased the life expectancy of patients with chronic liver failure. Undoubtedly, orthotopic liver transplantation represents a great advance in modern hepatology. Nowadays, liver transplantation represents a valid therapeutic option for chronic liver diseases with (and presents) a mean survival rate of about 80% in 3 years. Thus, it is an indicated treatment in situations where the conservative treatment (would) could lead to a (incur) mortality rate as high as 70% in one year. In this article the authors comment (on) various aspects of Orthotopic Liver Transplantation related to indications and survival rates

    Colors of Radio Galaxies at High Redshifts

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    Making direct democracy work: A rational-actor perspective on the graphe paranomon in ancient Athens

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    The specific way the Athenians set up their democracy presents both theoretical and empirical challenges. Decisions were taken by majority vote in the Assembly. To keep politicians in line, the Athenians first used ostracism, which however was replaced by the graphe paranomon around 415 BCE. The latter provided that anybody who had made a proposal in the Assembly could be accused of having made an unconstitutional suggestion, bringing a potentially severe penalty if found guilty. We know of 35 such cases between 403 and 322. During the fourth century the notion of illegality was extended to a mere question of political undesirability. Henceforth any decision by the Assembly could be overturned by the courts, but if the accuser failed to get at least 20% of the jury votes, he was punished instead. While these rules can be seen as a safeguard against bad decisions, they also provided the Athenian politicians with important information about the relative strength of their political support. This effect has not been analysed before, and it may help explain the relative stability of political life in classical Athens. Furthermore this analysis also contributes to our understanding of a curious but often overlooked fact, namely that the decrees of the Athenian Assembly to a great extent concerned honorary rewards, and the use of the graphe paranomon in turn was largely focussed on the honorary decrees
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