Teaching data-driven control: from linear design to adaptive control with throttle valves

Electric throttle valves represent a challenge for control design, as their dynamics involve strong nonlinearities, characterized by an asymmetric hysteresis. Carrying experiments on multiple valves, a large variability in the characteristics of each valve and erratic steady-state behaviors can also be noticed, impairing classical model-based control strategies. Nevertheless, local data-driven linear models can be obtained and simple proportional-integral (PI) controllers, tuned individually for each valve with the appropriate data set, provide good tracking performance. As these controllers cannot be transposed from one valve to another, a robust strategy and an adaptive controller (using identification in closed-loop and controller re-design) may be necessary to propose a general method. This work aims at promoting control education on a simple yet challenging process, going from frequency analysis and linear design to an adaptive control method implemented with an online recursive algorithm.Comment: 12 page

Унікальне дослідження багатовікового розвитку української культури (рецензія на 5-томне видання «Історія української культури»)

Наприкінці 2013 р. було успішно завершено великий академічний видавничий проект – «Історія української культури» у п’яти томах (дев’яти книгах). Ця подія стала масштабним явищем у науковому і культурному житті сучасної України

Approche expérimentale de l'amorçage de la CSC des aciers inoxydables austénitiques pré-déformés en milieu primaire de REP

National audienceLes aciers inoxydables de type 304L et 316L sont très employés dans le circuit primaire des centrales nucléaires REP du fait de leur bonne résistance à la corrosion généralisée à haute température. Quelques cas de corrosion sous contrainte (CSC) de type intergranulaire ont toutefois été rapportés en milieu primaire nominal. La présente étude vise à développer un modèle semi-empirique de l'amorçage de la CSC intergranulaire des aciers inoxydables 304L et 316L pré-déformés par traction et à améliorer la compréhension du rôle de la pré-déformation sur les mécanismes de la CSC. Des résultats obtenus en parallèle par le CEA sur un autre acier 316L, de composition chimique différente, et pour une autre voie de pré-déformation (laminage) seront également discutés

Rectal cancer with synchronous unresectable metastases: arguments for therapeutic choice

Environ 4 000 patients sont pris en charge chaque année en France pour un cancer du rectum avec des métastases synchrones jugées non résécables en réunion de concertation pluridisciplinaire (RCP). Il n’existe pas de consensus sur la stratégie thérapeutique à proposer et parmi les trois options possibles, les critères de choix restent relativement imprécis. – La chirurgie première est certes le meilleur traitement pour contrôler les symptômes rectaux mais elle n’a pas démontré qu’elle augmentait la survie et la résécabilité secondaire des métastases par rapport aux autres options et comporte un risque de résection incomplète, de complications pouvant retarder ou empêcher la chimiothérapie, de progression accélérée de la maladie métastatique et de mortalité comprise entre 1 et 5 %. – La radio-chimiothérapie première suivie d’une chirurgie permet le contrôle des symptômes rectaux mais retarde la chimiothérapie pour les métastases qui dominent le pronostic ; elle expose aux mêmes risques de complications que la chirurgie première. – La chimiothérapie première nous paraît intéressante en absence de complications locales sévères (occlusion, hémorragie) ; elle est potentiellement efficace sur les métastases à distance qui conditionnent le pronostic et sur la tumeur primitive qui répond souvent de manière similaire ; elle ne fige pas la stratégie et offre la possibilité de l’adapter à chaque évaluation selon la réponse, la tolérance et les possibilités de résection (tumeur primitive et métastases). Dans tous les cas, il est fondamental de discuter ces dossiers au cas par cas en RCP pour adapter la stratégie thérapeutique aux caractéristiques du patient, de la tumeur primitive et de l’extension métastatique, ainsi qu’à la réponse obtenue aux traitements proposés successivement.Rectal cancers with synchronous unresectable metastases are diagnosed in about 4 000 patients. There is yet no consensus on the therapeutic strategy for these cases which must be discussed during multidisciplinary meeting. Three options are available and arguments of choice remain relatively weak. – First-line resection of the primary rectal tumour is indeed the best treatment to control rectal symptoms but it does not seem to improve survival and secondary resectability of metastases when compared to other options; moreover incomplete resection or complications may delay chemotherapy, accelerate the metastastic process and mortality rate ranges from 1 to 5%. – First-line radio-chemotherapy followed by surgery allows for controlling rectal symptoms but delays chemotherapy for metastases dominating the prognosis; it exposes the patients to the same morbidity and mortality as first-line surgery. – First-line chemotherapy is the third valid option in the absence of major rectal symptoms (occlusion, haemorrhage); chemotherapy is potentially efficient on distant metastases bearing a high prognosis impact and on the primary rectal tumour, which often has a similar response. First-line chemotherapy allows for adapting the therapeutic strategy after each evaluation according to the tumour response, side effects and possibility of resection (primary rectal tumour and metastases). In all cases, medical records of such patients should be discussed during a multidisciplinary meeting to adapt the therapeutic strategy to the patient’s characteristics, primary rectal tumor, metastases staging and evolution

Analysis of KLF transcription factor family gene variants in type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The Krüppel-like factor (<it>KLF</it>) family consists of transcription factors that can activate or repress different genes implicated in processes such as differentiation, development, and cell cycle progression. Moreover, several of these proteins have been implicated in glucose homeostasis, making them candidate genes for involvement in type 2 diabetes (T2D).</p> <p>Methods</p> <p>Variants of nine <it>KLF </it>genes were genotyped in T2D cases and controls and analysed in a two-stage study. The first case-control set included 365 T2D patients with a strong family history of T2D and 363 normoglycemic individuals and the second set, 750 T2D patients and 741 normoglycemic individuals, all of French origin. The SNPs of six <it>KLF </it>genes were genotyped by Taqman^®SNP Genotyping Assays. The other three <it>KLF </it>genes (KLF2, -15 and -16) were screened and the identified frequent variants of these genes were analysed in the case-control studies.</p> <p>Results</p> <p>Three of the 28 SNPs showed a trend to be associated with T2D in our first case-control set (P < 0.10). These SNPs, located in the <it>KLF2, KLF4 </it>and <it>KLF5 </it>gene were then analysed in our second replication set, but analysis of this set and the combined analysis of the three variants in all 2,219 individuals did not show an association with T2D in this French population. As the <it>KLF2</it>, -15 and -16 variants were representative for the genetic variability in these genes, we conclude they do not contribute to genetic susceptibility for T2D.</p> <p>Conclusion</p> <p>It is unlikely that variants in different members of the <it>KLF </it>gene family play a major role in T2D in the French population.</p

Glucose-Dependent Regulation of NR2F2 Promoter and Influence of SNP-rs3743462 on Whole Body Insulin Sensitivity

Background: The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that insulin represses NR2F2 gene expression in pancreatic β-cells. The cis-regulatory region of the NR2F2 promoter is unknown and its influence on metabolism in humans is poorly understood. The present study aimed to identify the regulatory regions that control NR2F2 gene transcription and to evaluate the effect of NR2F2 promoter variation on glucose homeostasis in humans. Methodology/Principal Findings: Regulation of the NR2F2 promoter was assessed using gene reporter assays, ChIP and gel shift experiments. The effects of variation at SNP rs3743462 in NR2F2 on quantitative metabolic traits were studied in two European prospective cohorts. We identified a minimal promoter region that down-regulates NR2F2 expression by attenuating HNF4α activation in response to high glucose concentrations. Subjects of the French DESIR population, who carried the rs3743462 T-to-C polymorphism, located in the distal glucose-responsive promoter, displayed lower basal insulin levels and lower HOMA-IR index. The C-allele at rs3743462 was associated with increased NR2F2 binding and decreased NR2F2 gene expression. Conclusions/Significance: The rs3743462 polymorphism affects glucose-responsive NR2F2 promoter regulation and thereby may influence whole-body insulin sensitivity, suggesting a role of NR2F2 in the control of glucose homeostasis in humans. © 2012 Boutant et al

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study

<p>Abstract</p> <p>Background</p> <p>The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC). However, it was reported to have no efficacy in 3^rdor later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin.</p> <p>Methods</p> <p>Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg) in combination with FOLFIRI or simplified FOLFOX4 every 14 days.</p> <p>Results</p> <p>Ten patients (32.2%) had an objective response (1 CR, 9 PR) and 12 (38.8%) were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2^ndor 3^rdline and 25% and 55% in 4^thor later line respectively (p = 0.024 and p = 0.008). Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28) the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS) and overall survival (OS) were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients.</p> <p>Conclusion</p> <p>This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.</p

Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study

<p>Abstract</p> <p>Background</p> <p>Candidate gene and genome-wide association studies have both reproducibly identified several common Single Nucleotide Polymorphisms (SNPs) that confer type 2 diabetes (T2D) risk in European populations. Our aim was to evaluate the contribution to T2D of five of these established T2D-associated loci in the Arabic population from Tunisia.</p> <p>Methods</p> <p>A case-control design comprising 884 type 2 diabetic patients and 513 control subjects living in the East-Center of Tunisia was used to analyze the contribution to T2D of the following SNPs: E23K in <it>KCNJ11/Kir6.2</it>, K121Q in <it>ENPP1</it>, the -30G/A variant in the pancreatic β-cell specific promoter of Glucokinase, rs7903146 in <it>TCF7L2 </it>encoding transcription factor 7-like2, and rs7923837 in <it>HHEX </it>encoding the homeobox, hematopoietically expressed transcription factor.</p> <p>Results</p> <p><it>TCF7L2</it>-rs7903146 T allele increased susceptibility to T2D (OR = 1.25 [1.06–1.47], <it>P </it>= 0.006) in our study population. This risk was 56% higher among subjects carrying the TT genotype in comparison to those carrying the CC genotype (OR = 1.56 [1.13–2.16], <it>P </it>= 0.002). No allelic or genotypic association with T2D was detected for the other studied polymorphisms.</p> <p>Conclusion</p> <p>In the Tunisian population, <it>TCF7L2</it>-rs7903146 T allele confers an increased risk of developing T2D as previously reported in the European population and many other ethnic groups. In contrast, none of the other tested SNPs that influence T2D risk in the European population was associated with T2D in the Tunisian Arabic population. An insufficient power to detect minor allelic contributions or genetic heterogeneity of T2D between different ethnic groups can explain these findings.</p

Statistical distance as a measure of physiological dysregulation is largely robust to variation in its biomarker composition

Physiological dysregulation may underlie aging and many chronic diseases, but is chal-lenging to quantify because of the complexity of the underlying systems. Recently, we de-scribed a measure of physiological dysregulation, DM, that uses statistical distance to assess the degree to which an individual’s biomarker profile is normal versus aberrant. However, the sensitivity of DM to details of the calculation method has not yet been sys-tematically assessed. In particular, the number and choice of biomarkers and the defini-tion of the reference population (RP, the population used to define a “normal” profile) may be important. Here, we address this question by validating the method on 44 common clinical biomarkers from three longitudinal cohort studies and one cross-sectional survey. DMs calculated on different biomarker subsets show that while the signal of physiological dysregulation increases with the number of biomarkers included, the value of additional markers diminishes as more are added and inclusion of 10-15 is generally sufficient. As long as enough markers are included, individual markers have little effect on the final met-ric, and even DMs calculated from mutually exclusive groups of markers correlate with each other at r~0.4-0.5. We also used data subsets to generate thousands of combina-tions of study populations and RPs to address sensitivity to differences in age range, sex, race, data set, sample size, and their interactions. Results were largely consistent (but not identical) regardless of the choice of RP; however, the signal was generally clearer with a younger and healthier RP, and RPs too different from the study population per-formed poorly. Accordingly, biomarker and RP choice are not particularly important in most cases, but caution should be used across very different populations or for fine-scale analyses. Biologically, the lack of sensitivity to marker choice and better performance of younger, healthier RPs confirm an interpretation of DM physiological dysregulation and as an emergent property of a complex system