1,846 research outputs found
ANĂLISE TERMOMECĂâNICA DE ESTRUTURAS DE AĂO VIA ACOPLAMENTO MCD/MRPR
Quando expostos Ă temperatura elevada, os elementos estruturais tĂȘm sua capacidade resistente comprometida, pois as caracterĂsticas fĂsicas e de resistĂȘncia dos materiais empregados nas estruturas se deterioram com o aumento de temperatura. Nesse contexto, o presente trabalho tem como objetivo apresentar um novo mĂłdulo computacional,denominado aqui CS-ASA/FSA, capaz de realizar a anĂĄlise numĂ©rica de estruturas de aço sujeitas Ă temperaturas elevadas. Esse mĂłdulo utiliza o MĂ©todo dos Elementos Finitos (MEF) e a anĂĄlise inelĂĄstica Ă© baseada no MĂ©todo da RĂłtula PlĂĄstica Refinado (MRPR) acoplado ao MĂ©todo da Compatibilidade de DeformaçÔes (MCD). Esse Ășltimo mĂ©todo foi adotado para avaliar tanto a capacidade resistente da seção transversal, quanto as rigidezes axial e Ă flexĂŁo de estruturas de aço sob elevadas temperaturas. A construção da relação momentocurvatura se torna essencial para tal avaliação. Por fim, os resultados obtidos sĂŁo comparados aos numĂ©ricos e experimentais encontrados na literatura
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DSM-5 latent classes of alcohol users in a population-based sample: Results from the SĂŁo Paulo Megacity Mental Health Survey, Brazil
Background: We aimed to identify different categorical phenotypes based upon the DSM-V criteria of alcohol use disorders (AUD) among alcohol users who had at least one drink per week in the past year (n = 948). Methods: Data are from the SĂŁo Paulo Megacity Mental Health Survey collected in 2005â2007, as part of the World Mental Health Survey Initiative. A latent class analysis of the 11 DSM-5-AUD criteria was performed using Mplus, taking into account complex survey design features. Weighted logistic regression models were used to examine demographic correlates of the DSM-5-AUD latent classes. Results: The best latent-class model was a three-class model. We found a ânon-symptomatic classâ (69.7%), a âuse in larger amounts classâ (23.2%), defined by high probability (>70%) of the âuse in larger amountsâ criterion only, and a âhigh-moderate symptomatic classâ (7.1%), defined by high-moderate probability of all the 11 AUD criteria. Compared to those in the non-symptomatic class, individuals in the âhigh-moderate symptomatic classâ were more likely to have been married, have lower educational attainment and to be unemployed or in non-regular/informal employment. Those on the âuse in larger amounts classâ were more likely to have been married or never married. Conclusion: The two symptomatic classes clearly represented the dimensionality of the new proposed AUD criteria, and could be more specifically targeted by different prevention or treatment strategies. DSM-5-AUD has the advantage of shedding light on risky drinkers included in the âuse in larger amounts classâ, allowing for preventive interventions, which will reach a large number of individuals
Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction
O ciclo glicose-ĂĄcido graxo explica a preferĂȘncia do tecido muscular pelos ĂĄcidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercĂcio de alta intensidade, hĂĄ aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espĂ©cies reativas de oxigĂȘnio (EROs) durante a atividade muscular sugere que o balanço redox intracelular Ă© importante na regulação do metabolismo de lipĂdios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteĂna desacopladora mitocondrial. O efeito oposto Ă© esperado durante a atividade moderada. Assim, as questĂ”es levantadas nesta revisĂŁo sĂŁo: Por que o mĂșsculo esquelĂ©tico utiliza preferencialmente os lipĂdios no estado basal e de atividade moderada? Por que o ciclo glicose-ĂĄcido graxo falha em exercer seus efeitos durante o exercĂcio intenso? Como o mĂșsculo esquelĂ©tico regula o metabolismo de lipĂdios e carboidratos em regime envolvendo o ciclo contração-relaxamento555303313CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTĂFICO E TECNOLĂGICO - CNPQCOORDENAĂĂO DE APERFEIĂOAMENTO DE PESSOAL DE NĂVEL SUPERIOR - CAPESFUNDAĂĂO DE AMPARO Ă PESQUISA DO ESTADO DE SĂO PAULO - FAPESPsem informaçãoThe glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle
Regulation of glucose and fatty acid metabolism in skeletal muscle during contraction
O ciclo glicose-ĂĄcido graxo explica a preferĂȘncia do tecido muscular pelos ĂĄcidos graxos durante atividade moderada de longa duração. Em contraste, durante o exercĂcio de alta intensidade, hĂĄ aumento na disponibilidade e na taxa de oxidação de glicose. A produção de espĂ©cies reativas de oxigĂȘnio (EROs) durante a atividade muscular sugere que o balanço redox intracelular Ă© importante na regulação do metabolismo de lipĂdios/carboidratos. As EROs diminuem a atividade do ciclo de Krebs e aumentam a atividade da proteĂna desacopladora mitocondrial. O efeito oposto Ă© esperado durante a atividade moderada. Assim, as questĂ”es levantadas nesta revisĂŁo sĂŁo: Por que o mĂșsculo esquelĂ©tico utiliza preferencialmente os lipĂdios no estado basal e de atividade moderada? Por que o ciclo glicose-ĂĄcido graxo falha em exercer seus efeitos durante o exercĂcio intenso? Como o mĂșsculo esquelĂ©tico regula o metabolismo de lipĂdios e carboidratos em regime envolvendo o ciclo contração-relaxamento.The glucose-fatty acid cycle explains the preference for fatty acid during moderate and long duration physical exercise. In contrast, there is a high glucose availability and oxidation rate in response to intense physical exercise. The reactive oxygen species (ROS) production during physical exercise suggests that the redox balance is important to regulate of lipids/carbohydrate metabolism. ROS reduces the activity of the Krebs cycle, and increases the activity of mitochondrial uncoupling proteins. The opposite effects happen during moderate physical activity. Thus, some issues is highlighted in the present review: Why does skeletal muscle prefer lipids in the basal and during moderate physical activity? Why does glucose-fatty acid fail to carry out their effects during intense physical exercise? How skeletal muscles regulate the lipids and carbohydrate metabolism during the contraction-relaxation cycle
Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: Effect of catalase overexpression
AbstractThe mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500ÎŒM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with ÎČ-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and ÎČ-oxidation of fatty acids
The BLue Amazon Brain (BLAB): A Modular Architecture of Services about the Brazilian Maritime Territory
We describe the first steps in the development of an artificial agent focused
on the Brazilian maritime territory, a large region within the South Atlantic
also known as the Blue Amazon. The "BLue Amazon Brain" (BLAB) integrates a
number of services aimed at disseminating information about this region and its
importance, functioning as a tool for environmental awareness. The main service
provided by BLAB is a conversational facility that deals with complex questions
about the Blue Amazon, called BLAB-Chat; its central component is a controller
that manages several task-oriented natural language processing modules (e.g.,
question answering and summarizer systems). These modules have access to an
internal data lake as well as to third-party databases. A news reporter
(BLAB-Reporter) and a purposely-developed wiki (BLAB-Wiki) are also part of the
BLAB service architecture. In this paper, we describe our current version of
BLAB's architecture (interface, backend, web services, NLP modules, and
resources) and comment on the challenges we have faced so far, such as the lack
of training data and the scattered state of domain information. Solving these
issues presents a considerable challenge in the development of artificial
intelligence for technical domains
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes
Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) Îł Activators and Pan-PPAR Partial Agonists
Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) Îł to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARÎł ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8âC10) bind the PPARÎł LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARÎł LBD, stronger partial agonists with full length PPARÎł and exhibit full blockade of PPARÎł phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARÎł also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/ÎČ-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARÎł modulators with useful clinical profiles among natural products
The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study
AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4âweeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4âweeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, PÂ =Â 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, Pâ<â0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, PÂ =Â 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, PÂ =Â 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease
Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction
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