Prognostics-based Scheduling to Extend a Distributed Platform Production Horizon under Service Constraint: Model, Complexity and Resolution.

In the field of production scheduling, this paper addresses the problem of optimizing the useful life of a heterogeneous distributed platform composed of identical parallel machines and which has to provide a given production service. Each machine is supposed to be able to provide several throughputs corresponding to different operating conditions. The purpose is to provide a production scheduling that maximizes the production horizon. The use of Prognostics and Health Management (PHM) results in the form of Remaining Useful Life (RUL) allows to adapt the schedule to the wear and tear of machines. This work comes within the scope of Prognostics Decision Making (DM). The key point is to configure the platform, i.e., to select the appropriate profile for each machine during the whole production horizon so as to reach a total throughput based on a customer demand as long as possible. In the homogeneous case, the Longest Remaining Useful Life first algorithm (LRUL) is proposed to find a solution and its optimality is proven. The NP-Completeness of the general case is then shown. A Binary Integer Linear Programming (BILP) model which allows to find optimal solutions for fixed time horizons has been defined. As solving such a BILP is NP-Complete, solutions can however be computed in reasonable time only for small size instances of the problem. Many heuristics are then proposed to cope with large scale decision problems and are compared through simulation results. Exhaustive simulations assess the efficiency of these heuristics. Distance to the theoretical maximal value comes indeed close to 5% for the most efficient ones

Role of the single nucleotide polymorphism rs7903146 of TCF7L2 in inducing nonsense-mediated decay.

Background The single nucleotide polymorphism (SNP) rs7903146 (C/T), located in intron 4 of the transcription factor 7-like 2 gene (TCF7L2), has been associated with an increased risk of developing Type 2 Diabetes, although the molecular mechanism remain elusive. The TCF7L2 gene is alternatively spliced but an association between genotype and splice variants has not been shown convincingly. We hypothesized that a yet unknown extra exon, containing either the C or T genotype of the SNP rs7903146, could introduce a premature stop codon and consequently result in nonsense-mediated decay (NMD). Findings Running the sequences C and T of the SNP region in different servers we found that the two alleles could display differential recognition by splicing factors. The C variant showed the possible inclusion of an unknown exon. This unknown exon contained a stop codon and thus could induce NMD. We then determined that the splicing pattern in isolated mouse islets and MIN6 cells was similar to that in human pancreatic islets. Therefore, we used MIN6 cells to study the splicing of human intron 4: two mini-genes of intron 4 containing either the C/C genotype or the T/T genotype were transfected into MIN6 cells. Our constructs were spliced normally, excluding intron 4, but we did not observe the presence of an extra exon with either construct. Conclusions We found that an extra exon could theoretically exist, although we were not able to capture it in our model. A better model is needed to determine whether a theoretical extra exon can induce NMD

Molecular Targets of Omega 3 and Conjugated Linoleic Fatty Acids – “Micromanaging” Cellular Response

Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and conjugated linoleic acid, as paradigmatic molecules that can be exploited both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids

Differential transcriptional and post-translational transcription factor 7-like regulation among nondiabetic individuals and type 2 diabetic patients.

Human genetic studies have revealed that the T minor allele of single nucleotide polymorphism rs7903146 in the transcription factor 7-like 2 (TCF7L2) gene is strongly associated with an increased risk of diabetes by 30%-40%. Molecular and clinical studies are of great importance for understanding how this unique variation in TCF7L2 influences type 2 diabetes (T2D) onset and progression. At the molecular level, some studies have been performed in diabetic mice and pancreatic islets from healthy human donors. Whereas TCF7L2 mRNA levels are up-regulated in islets, protein levels are down-regulated. We performed studies on TCF7L2 splicing, mRNA expression, and protein levels in immortalized human lymphocytes from nondiabetic individuals and T2D patients carrying the C/C or the at-risk T/T genotype. Our results show differential expression of TCF7L2 splice variants between nondiabetic and T2D patients carrying the at-risk genotype, as well as differences in protein levels. Therefore, we investigated the regulation of splice variants, and our results propose that splicing of exon 4 is under control of the serine-arginine-rich factor transformer 2 β (TRA2B). Finally, we studied the endoplasmic reticulum stress pathways, looking for a posttranslational explanation. We saw a shift in the activation of these pathways between nondiabetic individuals and T2D patients carrying the at-risk genotype. These results suggest that, in human immortalized lymphocytes carrying the at-risk T/T genotype, first the differential expression of TCF7L2 splice variants implies a regulation, at least for exon 4, by TRA2B and second, the differential protein levels between both T/T carriers point to a different activation of endoplasmic reticulum stress pathways

Prognostics-based Scheduling in a Distributed Platform: Model, Complexity and Resolution.

International audienceIn the field of production scheduling, this paper addresses the problem of maximizing the production horizon of a heterogeneous platform composed of identical parallel machines and which has to provide a given production service. Each machine is supposed to be able to provide several throughputs corresponding to different operating conditions.The key point is to select the appropriate profile for each machine during the whole production horizon. The use of Prognostics and Health Management (PHM) results in the form of Remaining Useful Life (RUL) allows to adapt the schedule to the wear and tear of machines. In the homogeneous case, we propose the Longest Remaining Useful Life first algorithm (LRUL) to find a solution and we prove its optimality. The NP-Completeness of the general case is then shown. Many heuristicsare finally proposed to cope with the decision problem and the efficiency of these heuristics. Distance to the theoretical maximal value comes close to 5% for the most efficient ones

Quality Control of HDL: Nutrition and Not Numbers May Determine HDL Functionality

The strong inverse relationship between high density lipoproteins-cholesterol (HDL-C) levels and cardiovascular disease (CVD) has aroused a strong interest in the research of lifestyle and pharmacological agents capable of elevating plasma HDL levels. HDL is essential in reverse cholesterol transport (RCT), thus its anti-atherogenic function. However, torcetrapib, a compound that increases plasma HDL-C levels, was unexpectedly associated with an increased cardiovascular mortality. The findings led to consider that HDL functionality and quality might be more relevant to CVD than the total circulating HDL quantity itself. Adherence to the Mediterranean diet is known to be associated with increased HDL-C and decreased risk of CVD. However, the mechanism by which this happens has been yet poorly investigated and the effect of nutrition on HDL functionality and quality needs further attention

Quality Control of HDL: Nutrition and Not Numbers May Determine HDL Functionality

The strong inverse relationship between high density lipoproteins-cholesterol (HDL-C) levels and cardiovascular disease (CVD) has aroused a strong interest in the research of lifestyle and pharmacological agents capable of elevating plasma HDL levels. HDL is essential in reverse cholesterol transport (RCT), thus its anti-atherogenic function. However, torcetrapib, a compound that increases plasma HDL-C levels, was unexpectedly associated with an increased cardiovascular mortality. The findings led to consider that HDL functionality and quality might be more relevant to CVD than the total circulating HDL quantity itself. Adherence to the Mediterranean diet is known to be associated with increased HDL-C and decreased risk of CVD. However, the mechanism by which this happens has been yet poorly investigated and the effect of nutrition on HDL functionality and quality needs further attention