100 research outputs found

    Association of morphological and water factors with irrigated forage cactus yield

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    This study aimed to understand the relationship of morphological characteristics and actual evapotranspiration of forage cactus clones with their productive capacity under different water regimes. The data used in this study were collected between the years 2012 and 2013, in Serra Talhada, State of Pernambuco. The clones Sertânia IPA - IPA, Miúda - MIU and Orelha de Elefante Mexicana - OEM were submitted to three irrigation depths (2.5, 5.0 and 7.5 mm) and three irrigation intervals (7, 14 and 28 days). Cladode and plant morphology, accumulated actual evapotranspiration and yield were obtained at the moment of harvest. Pearson’s correlation matrix was elaborated and, in the sequence, multicollinearity, canonical and path analysis were applied. There was no correlation of yield with the soil water supply and actual evapotranspiration of the clones (p > 0.05). Forage cactus yield was more associated with peculiarities of the morphological characteristics of the clones than with the different soil water supplies or the crop actual evapotranspiration. However, regardless of the water regime and clone, the vigor of the basal cladodes was highly decisive for the expression of the forage cactus productive capacity.Objetivou-se, neste trabalho, compreender a relação de características morfológicas e da evapotranspiração real de clones de palma forrageira com sua capacidade produtiva em diferentes regimes hídricos. Os dados usados nesta pesquisa foram coletados entre os anos de 2012 e 2013, em Serra Talhada, PE. Os clones IPA Sertânia - IPA, Miúda - MIU e Orelha de Elefante Mexicana - OEM foram submetidos a três lâminas (2,5; 5,0; e 7,5 mm) e três intervalos de irrigação (7; 14 e 28 dias). Dados morfológicos dos cladódios e da planta, evapotranspiração real acumulada e desempenho produtivo foram obtidos na ocasião da colheita. A matriz de correlação de Pearson foi elaborada e, em seguida, foram aplicadas análises de multicolinearidade, canônica e de trilha. Não houve correlação da produtividade com o suprimento de água e evapotranspiração real dos clones (p > 0,05). A produtividade da palma esteve mais associada a peculiaridades das características morfológicas dos seus clones do que aos diferentes suprimentos de água no solo ou à evapotranspiração real da cultura. Mas, independente do regime hídrico e do clone, o vigor do cladódio basal foi bastante decisivo para a expressão da capacidade produtiva da palma forrageira irrigada

    Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

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    <p>Abstract</p> <p>Background</p> <p>Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether <it>NOTCH1 </it>mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.</p> <p>Methods</p> <p>T-ALL subtypes, status of <it>SIL-TAL1 </it>fusion, ectopic expression of <it>TLX3</it>, and mutations in <it>FBXW7</it>, <it>KRAS</it>, <it>PTEN </it>and <it>NOTCH1 </it>were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.</p> <p>Results</p> <p>The frequencies of mutations were 43.5% for <it>NOTCH1</it>, while <it>FBXW7</it>, <it>KRAS </it>and <it>PTEN </it>exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of <it>NOTCH1 </it>mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between <it>NOTCH1 </it>mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. <it>SIL-TAL1 </it>was identified as an adverse prognostic factor. <it>NOTCH1 </it>mutation status was not associated with outcome, while the presence of <it>NOTCH1 </it>complex mutations (indels) were associated with a longer overall survival (<it>p </it>= 0.031) than point mutations.</p> <p>Conclusion</p> <p><it>NOTCH1 </it>mutations alone or in combination with <it>FBXW7 </it>did not impact T-ALL prognosis. Nevertheless, complex <it>NOTCH1 </it>mutations appear to have a positive impact on OS and the <it>SIL-TAL1 </it>fusion was validated as a negative prognostic marker in our series of T-ALL.</p

    Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

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    Abstract Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
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