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

Preparation and characterization of starch-poly-epsilon-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications

One limitation associated with the delivery of bioactive agents concerns the short half-life of these molecules when administered intravenously, which results in their loss from the desired site. Incorporation of bioactive agents into depot vehicles provides a means to increase their persistence at the disease site. Major issues are involved in the development of a proper carrier system able to deliver the correct drug, at the desired dose, place and time. In this work, starch-poly-e-caprolactone (SPCL) microparticles were developed for use in drug delivery and tissue engineering (TE) applications. SPCL microparticles were prepared by using an emulsion solvent extraction/evaporation technique, which was demonstrated to be a successful procedure to obtain particles with a spherical shape (particle size between 5 and 900 lm) and exhibiting different surface morphologies. Their chemical structure was confirmed by Fourier transform infrared spectroscopy. To evaluate the potential of the developed microparticles as a drug delivery system, dexamethasone (DEX) was used as model drug. DEX, a well-known component of osteogenic differentiation media, was entrapped into SPCL microparticles at different percentages up to 93%. The encapsulation efficiency was found to be dependent on the polymer concentration and drug-to-polymer ratio. The initial DEX release seems to be governed mainly by diffusion, and it is expected that the remaining DEX will be released when the polymeric matrix starts to degrade. In this work it was demonstrated that SPCL microparticles containing DEX can be successfully prepared and that these microparticular systems seem to be quite promising for controlled release applications, namely as carriers of important differentiation agents in TE.E.R.B. thanks the Marie Curie Host Fellowships for Early Stage Research Training (EST) "Alea Jacta EST" (MEST-CT-2004-008104) for providing her with a PhD Fellowship. This work was partially supported by the European NoE EXPERTISSUES (NMP3-CT-2004-500283)

Clinical And Morphological Evolution Of The Induced Experimental Arthritis In Rattus Novergicus Albinus

The models of experimental arthritis become important in the inquiry of different therapeutical alternatives and briefing of articulate pathogenesis. The possibility of measuring the injury of the articular cartilage makes the experimental model relevantly important, as well as the systemic biological effects that involve the different therapeutics: The radiological and histological aspects of the cartilage were researched in the model of Zynoman-induced arthritis in Rattus novergicus. Rats were submitted to the intra-articular injection (1.0ml) and sacrificed at different times, under anesthesia. The knee joints were surgically removed and processed for coloring in hematoxylin eosin (H&E). The radiographic analyses were carried out through images obtained with dental periapical film. The animals presented serious and gradual synovitis associated to the injury of the cartilage that was evaluated up to 14 days after the stimulation injection. The arthritis model by Zymosan allows the study of the inflammatory alteration of the synovial tissue and of the cartilage. In the presence of Zymosan, the juxtarticular and periarticular tissues develop similar alterations to those found in the autoimmune diseases.2427581Arnett, F.C., Edworthy, S.M., Bloch, D.A., McShane, D.J., Fries, J.F., Cooper, N.S., The American Rheumatism Association 1987 revised criteria for classification of rheumatoid arthritis (1988) Arthritis Rheum, 31, pp. 315-324Brahn, E., Animal models of rheumatoid arthritis: Clues to etiology and treatment (1991) Clin Orthop, 265, pp. 42-53Bernotiene, E., Palmer, G., Talabot-Ayer, D., Quinodoz, I.S., Aubert, M.L., Gabay, C., Delayed resolution of acute inflammation during zymosaninduced in leptin-deficient mice. Arthritis Res (2004) Ther, 6, pp. R256-R263Brandt, K.D., (2000) An Atlas of Osteoarthritis, , Pathernon Publishing, New YorkCossermelli, W., (2000) Terapêutica Em Reumatologia, , São Paulo: Lemos EditorialConsalter, A., Ciconelli, R., Epidemiologia e etiologia da Artrite Reumatóide (2005) Sin Reumatol, 2, pp. 34-38Crilly, A., Genotyping for disease associated HLA DR beta 1 alleles and the need for early joint surgery in rheumatoid arthritis: A quantitative evaluation (1999) Ann Rheum. Dis, 58, pp. 114-117Damas, J., Involvement of platelet-activating factor in the hypotensive response to zymosan in rats (1991) J Lipid Mediat, 3, pp. 333-344Douglas, C.R., (2000) Pato Fisiologia Geral - Mecanismos Da Doença, , São Paulo (SP): Robe EditorialDi Carlo, F.J., Fiore, J.V., In Zymosan Composition (1958) Sci, 127, pp. 756-757Fleiss, J.L., (1981) Statistical Methods For Rates and Proportions, , 2a ed. John Wiley &ampSons Inc. Nova IorqueFrasnelli, M.E., Tarusio, D., TLR2 modulates inflammation in zymosan-induced arthritis in mice (2005) Arthritis Res Ther, 7, pp. 370-379Gegout, P., Gillet, P., Chevrier, D., Guingamp, C., Terlain, B., Netter, P., Characterization of zymosan-induced arthritis in the rat: Effects on joint inflammation and cartilage metabolism (1994) Life Sci, 17, pp. 321-326Hadler, N.M., A Pathogenic Model For erosive synovitis: Lessons from animal arthritides (1976) Arthritis Rheum, 19, pp. 256-266. , Marc-Apr;Imrie, R., Animal Models of Arthritis (1976) Lab Anim Sci, Apr, 26, pp. 345-351Hardin, J.A., Dendritic cells: Potential triggers of autoimmunity and targets for therapy (2005) Ann Rheum Dis, 64, pp. 86-90Keystone, E.C., Schorlemmer, H.U., Pope, C., Allison, A.C., Zymosan induced arthritis: A model of chronic proliferative arthritis following activation of the alternative pathway of complement (1977) Arthritis Rheum, 20, pp. 1397-1401Konno, S., Tsurufuji, S., Analysis of the factor(s) involved in pathogenesis of zymosaninduced inflammation in rats (1985) Japan J Pharmacol, 38, pp. 177-184Laurindo, I.M.M., Ximenes, A.C., Lima, F.A.C., Pinheiro, G.R.C.L.R., Bertolo, M.B., Alencar, P., Xavier, R.M., Radominski, S.C., (2002) Artrite Reumatóide: Diagnóstico E Tratamento, , Projeto Diretrizes Associação Médica Brasileira e Conselho Federal de MedicinaLipski, P.E., Rheumatoid arthritis (1998) Harrison's Principles of Internal Medicine, , New York: McGraw HillLubberts, E., Joosten, L.A., van den, B.L., Adenoviral vector mediated overexpression of IL-4 in the knee joint of mice with collagen- induced arthritis prevents cartilage destruction (1999) J Immunol, 163, pp. 4546-4556Mehling, A., Beissert, S., Dendritic Cells Under Investigation in Autoimmune Disease Critical Reviews (2003) Biochemistry and Molecular Biology, 38, pp. 1-21Moreira, C., Carvalho, M.A.P., (2001) Reumatologia - Diagnóstico E Tratamento, pp. 371-389. , 2a ed. Rio de Janeiro (RJ): Médica e CientíficaNouri, A.M.E., Panayi, G.S., Goodman, S.M., Cytokines and the chronic inflammation of rheumatic disease: I - the presence of interleukin- 1 in synovial fluids (1994) Clin Exp Immunol, 55, pp. 295-302Oliver, S.J., Brahn, E., Combination therapy in rheumatoid arthritis: The animal model perspective (1996) J Rheum, 23 (24 SUPPL), pp. 56-60Rocha, A.C., Aragão, A.G.M., Oliveira, R.C., Pompeu, M.M.L., Vale, M.R., Ribeiro. RA: Periarthritis promotes gait disturbance in zymosan-induced arthritis in rats (1996) Inflamm Res, 48, pp. 485-490Rubin, E., Gorstein, F., Rubin, R., Schwarting, R., Strayer, D., (2006) Patologia. Bases Clinico Patológicas Da Medicina, , Guanabara Koogan 4.a edSAS System For Windows (Statistical Analysis System), , versão 9.1.3 Service Pack 3. 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On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Faixas normais de nutrientes em cana-de-açúcar pelos métodos ChM, DRIS e CND e nível crítico pela distribuição normal reduzida

Existem diversos métodos para a interpretação da diagnose foliar; o nível crítico ou as faixas de suficiência descritas na literatura são os mais utilizados. Porém, o uso de métodos de determinação de faixas normais de nutrientes que contemplam regiões específicas (localidades) aumenta a eficiência da interpretação. O objetivo deste trabalho foi determinar as faixas normais de nutrientes para a cultura da cana-de-açúcar, mediante a utilização dos métodos Chance Matemática (ChM), Sistema Integrado de Diagnose e Recomendação (DRIS) e Diagnose da Composição Nutricional (CND), além do Nível Crítico determinado pelo método de distribuição normal reduzida. O trabalho foi realizado tomando-se como base dados relativos a teores de nutrientes em amostras foliares e de produtividade de lavouras comerciais de cana-de-açúcar, localizadas no município de Campos de Goytacazes, RJ. Com o método da ChM, foram obtidas faixas de suficiência semelhantes aos métodos DRIS e CND, para N, Ca, S e Mn, enquanto para P, K, Mg, Cu e Zn os valores obtidos pela ChM foram superiores. A utilização dos métodos ChM, DRIS e CND, em lavouras comerciais de cana-de-açúcar em geral, possibilitou a obtenção de menor amplitude da faixa normal dos nutrientes, em comparação com os valores alcançados pelos métodos nível crítico e faixa de suficiência