Search results for "TFA"
showing 10 items of 58 documents
Matrix metalloproteinase-12 cleaved fragment of titin as a predictor of functional capacity in patients with heart failure and preserved ejection fra…
2020
Serum levels of matrix metalloproteinase-12 cleaved fragment of titin (TIM), a novel circulatory biomarker specific for cardiac titin degradation, has emerged as a potential biomarker in cardiovascular diseases. In this work, we aimed to evaluate the association between TIM and maximal functional capacity assessed by the percentage of predicted peak exercise oxygen uptake (pp-peakVO2) in patients with heart failure and preserved ejection fraction (HFpEF). Design. In this post-hoc study, we included 46 stable symptomatic (New York Heart Association II-III) HFpEF patients enrolled in the TRAINING-HF study (NCT02638961). pp-peak-VO2 was calculated from baseline values. Baseline circulating lev…
Conflict resolution in the multi-stakeholder stepped spillway design under uncertainty by machine learning techniques
2021
Abstract The optimal spillway design is of great significance since these structures can reduce erosion downstream of the dams. This study proposes a risk-based optimization framework for a stepped spillway to achieve an economical design scenario with the minimum loss in hydraulic performance. Accordingly, the stepped spillway was simulated in the FLOW-3D® model, and the validated model was repeatedly performed for various geometric states. The results were used to form a Multilayer Perceptron artificial neural network (MLP-ANN) surrogate model. Then, a risk-based optimization model was formed by coupling the MLP-ANN and NSGA-II. The concept of conditional value at risk (CVaR) was utilized…
A Conditional Value–at–Risk Model for Insurance Products with Guarantee
2009
We propose a model to select the optimal portfolio which underlies insurance policies with a guarantee. The objective function is defined in order to minimise the conditional value at-risk (CVaR) of the distribution of the losses with respect to a target return. We add operational and regulatory constraints to make the model as flexible as possible when used for real applications. We show that the integration of the asset and liability side yields superior performances with respect to naive fixed-mix portfolios and asset based strategies. We validate the model on out-of-sample scenarios and provide insights on policy design.
Mitochondrial DNA Replication in Health and Disease
2011
Mitochondria are dynamic, semi-autonomous organelles that play a diverse role in cellular physiopathology, being involved in bioenergetics, ROS generation/signaling and redox balance, β-oxidation of free fatty acids, Ca2+ homeostasis, thermogenesis, and essential anabolic pathways (fatty acids, cholesterol, urea, haem and bile acids). They contain their own, mitochondrial DNA (mtDNA) which is one of the main points in favor of the hypothesis of the endosymbiotic origin of these organelles (Lang et al., 1999). The human mitochondrial genome, a 16.5 kb circular DNA consisting of a heavy and a light chain, contains 37 genes, 13 of which encode proteins involved in the mitochondrial electron tr…
Mitochondrial involvement in non-alcoholic steatohepatitis
2007
Non-alcoholic steatohepatitis (NASH) is an increasing recognized condition that may progress to end-stage liver disease. There are consistent evidences that mitochondrial dysfunction plays a central role in NASH whatever its origin. Mitochondria are the key controller of fatty acids removal and this is part of an intensive gene program that modifies hepatocytes to counteract the excessive fat storage. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of ROS that in turn trigger lipid peroxidation, cytokines release and cell death. In this review we briefly recall the role of mitochondria in fat…
Astrocytes Protect Neurons from Aβ1-42 Peptide-Induced Neurotoxicity Increasing TFAM and PGC-1 and Decreasing PPAR-γ and SIRT-1
2015
One of the earliest neuropathological events in Alzheimer's disease is accumulation of astrocytes at sites of Aβ1-42 depositions. Our results indicate that Aβ1-42 toxic peptide increases lipid peroxidation, apoptosis and cell death in neurons but not in astrocytes in primary culture. Aβ1-42-induced deleterious neuronal effects are not present when neurons and astrocytes are mixed cultured. Stimulation of astrocytes with toxic Aβ1-42 peptide increased p-65 and decreased IκB resulting in inflammatory process. In astrocytes Aβ1-42 decreases protein expressions of sirtuin 1 (SIRT-1) and peroxisome proliferator-activated receptor γ (PPAR-γ) and over-expresses peroxisome proliferator-activated re…
Pharmacogenetics of treatments for pancreatic cancer
2019
Introduction: Despite clinical efforts, pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The scarcity of effective therapies can be reflected by the lack of reliable biomarkers to adapt anticancer drugs prescription to tumors’ and patients’ features. Areas covered: Pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best matches individual and tumor genetic profile, but it has not yet led to gains in outcome. This review describes PDAC pharmacogenetics findings, critically reappraising studies on polymorphisms and -omics profiles correlated to response to gemcitabine, FOLFIRINOX, and nab-paclitaxel combinations, as well as l…
Hedging foreign exchange rate risk: Multi-currency diversification
2016
Abstract This article proposes a multi-currency cross-hedging strategy that minimizes the exchange risk. The use of derivatives in small and medium-sized enterprises (SMEs) is not common but, despite its complexity, can be interesting for those with international activities. In particular, the reduction in the exchange risk borne through the use of natural multi-currency cross-hedging is measured, considering Conditional Value-at-Risk (CVaR) and Value-at-Risk (VaR) for measuring market risk instead of the variance. CVaR is minimized using linear programmes, while a multiobjective genetic algorithm is designed for minimizing VaR, considering two scenarios for each currency. The results obtai…
The BIOSAFEPAPER project for in vitro toxicity assessments: preparation, detailed chemical characterisation and testing of extracts from paper and bo…
2008
International audience; Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-foo…
Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches.
2014
Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria. Cells respond to different physiologic, metabolic, and pathologic changes by regulating this organelle with high morphological and functional adaptability. A considerable number of proteins, transcription factors, upstream regulatory proteins and secondary mechanisms are involved in MB and the stabilization of new mitochondrial DNA. These MB activators and regulators, including the main participating proteins (e.g. PGC-1α and mtTFA), are candidates for therapeutic intervention in diverse diseases, like neurodegenerative disorders, metabolic syndrome, sarcopenia, cardiac pathophysiolo…