Combining multiple classifications of chemical structures using consensus clustering

Consensus clustering involves combining multiple clusterings of the same set of objects to achieve a single clustering that will, hopefully, provide a better picture of the groupings that are present in a dataset. This Letter reports the use of consensus clustering methods on sets of chemical compounds represented by 2D fingerprints. Experiments with DUD, IDAlert, MDDR and MUV data suggests that consensus methods are unlikely to result in significant improvements in clustering effectiveness as compared to the use of a single clustering method. (C) 2012 Elsevier Ltd. All rights reserved

Dispositifs de gouvernance territoriale durable en agriculture Analyse de trois situations en France et au Brésil

La question de la gouvernance est devenue depuis quelques années une préoccupation grandissante des acteurs territoriaux qui cherchent à associer l’ensemble des parties-prenantes à la définition des actions de développement durable. C’est aussi un nouveau champ d’investigation pour les chercheurs qui essaient de comprendre pourquoi et comment les acteurs de terrain passent d’un mode de coordination hiérarchique à un mode plus participatif. Ce passage ne va pas de soi, il nécessite une recomposition. Les acteurs vont soit s’approprier des dispositifs et outils déjà existants et les « bricoler », soit en inventer de nouveaux pour répondre aux enjeux de développement durable. Nous proposons une analyse des comportements d’acteurs agricoles vis-à-vis de dispositifs et outils de gouvernance. Nous illustrons ce travail à partir de trois études de cas. Cette mise en perspective nous amène à conclure que le développement durable, pour qu’il soit mis en œuvre localement, nécessite que les acteurs (ré)définissent ses enjeux et ses objectifs à leur propre niveau d’action.For the last decade, governance issues become of a growing interest for local actors which seek to gather stakeholders around sustainable development actions. Likewise researchers try to understand why and how local actors move from hierarchical modes of co-ordination to a distributed and more participating ones. The shift is not so obvious and involve recombining processes. Local actors have two alternatives: to appropriate existing devices and tools and “tinker” them or to invent new ones to deal with the sustainable development stakes. The paper suggest an analysis of farming actors behaviour facing governance devices and tools, through three case studies. The authors conclude that carrying out sustainable development at the local scale involve local actors planning out its stakes and objectives at the action local level

Dispositifs de gouvernance territoriale durable en agriculture Analyse de trois situations en France et au Brésil

La question de la gouvernance est devenue depuis quelques années une préoccupation grandissante des acteurs territoriaux qui cherchent à associer l’ensemble des parties-prenantes à la définition des actions de développement durable. C’est aussi un nouveau champ d’investigation pour les chercheurs qui essaient de comprendre pourquoi et comment les acteurs de terrain passent d’un mode de coordination hiérarchique à un mode plus participatif. Ce passage ne va pas de soi, il nécessite une recomposition. Les acteurs vont soit s’approprier des dispositifs et outils déjà existants et les « bricoler », soit en inventer de nouveaux pour répondre aux enjeux de développement durable. Nous proposons une analyse des comportements d’acteurs agricoles vis-à-vis de dispositifs et outils de gouvernance. Nous illustrons ce travail à partir de trois études de cas. Cette mise en perspective nous amène à conclure que le développement durable, pour qu’il soit mis en œuvre localement, nécessite que les acteurs (ré)définissent ses enjeux et ses objectifs à leur propre niveau d’action.For the last decade, governance issues become of a growing interest for local actors which seek to gather stakeholders around sustainable development actions. Likewise researchers try to understand why and how local actors move from hierarchical modes of co-ordination to a distributed and more participating ones. The shift is not so obvious and involve recombining processes. Local actors have two alternatives: to appropriate existing devices and tools and “tinker” them or to invent new ones to deal with the sustainable development stakes. The paper suggest an analysis of farming actors behaviour facing governance devices and tools, through three case studies. The authors conclude that carrying out sustainable development at the local scale involve local actors planning out its stakes and objectives at the action local level

Genes Involved in Oxidative Stress Pathways Are Differentially Expressed in Circulating Mononuclear Cells Derived From Obese Insulin-Resistant and Lean Insulin-Sensitive Individuals Following a Single Mixed-Meal Challenge.

Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Reprogramming viral immune evasion for a rational design of next-generation vaccines for RNA viruses

Type I interferons (IFNs-α/β) are antiviral cytokines that constitute the innate immunity of hosts to fight against viral infections. Recent studies, however, have revealed the pleiotropic functions of IFNs, in addition to their antiviral activities, for the priming of activation and maturation of adaptive immunity. In turn, many viruses have developed various strategies to counteract the IFN response and to evade the host immune system for their benefits. The inefficient innate immunity and delayed adaptive response fail to clear of invading viruses and negatively affect the efficacy of vaccines. A better understanding of evasion strategies will provide opportunities to revert the viral IFN antagonism. Furthermore, IFN antagonism-deficient viruses can be generated by reverse genetics technology. Such viruses can potentially serve as next-generation vaccines that can induce effective and broad-spectrum responses for both innate and adaptive immunities for various pathogens. This review describes the recent advances in developing IFN antagonism-deficient viruses, their immune evasion and attenuated phenotypes in natural host animal species, and future potential as veterinary vaccines

Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation.

INTRODUCTION AND OBJECTIVE: Heredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs. RESEARCH DESIGN AND METHODS: In this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation. RESULTS: Postprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation. CONCLUSIONS: Our findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications

Ethnic and gender specific life expectancies of the Singapore population, 1965 to 2009 - Converging, or diverging?

10.1186/1471-2458-13-1012BMC Public Health131

Drawing from Grotowski and Beyond: Kuo Pao Kun’s Discourse on Audiences in Singapore in the 1980s

Much has been researched on Kuo Pao Kun’s multilingualism and multiculturalism. However, as one of one of the most important Asian dramatists, the analysis of Kuo’s discourse on audiences remains largely unexplored. There is a pressing need to understand the ways which theatre practitioners imagine audiences as it points to issues of subjectivity, audience participation and social engagement, especially in a neoliberal society like Singapore where people are often positioned as docile economic subjects. Among the many Asian and Western dramatists Kuo drew inspiration from, Jerzy Grotowski was pivotal. This essay seeks to address this gap by examining how the latter’s ideas was crucial to understanding how Kuo envisioned theatre and audiences alongside his artistic practice