Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change.

OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.

iNKT/CD1d-antitumor immunotherapy significantly increases the efficacy of therapeutic CpG/peptide-based cancer vaccine.

BACKGROUND: Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells. METHODS: Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin. RESULTS: The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in this context, CTLs rather than NK cells are essential for the enhanced tumor inhibition. CONCLUSIONS: Altogether, our study in mice demonstrates that αGC/CD1d-antitumor fusion protein greatly increases the efficacy of a therapeutic CpG-based cancer vaccine, first as an adjuvant during T cell priming and second, as a therapeutic agent to redirect immune responses to the tumor site.

Modeling of hybrid systems by piecewise decomposition

Piecewise linear models systems arise as mathematical models of systems in many practical applications, often from linearization for nonlinear systems. There are two main approaches of dealing with these systems according to their continuous or discrete-time aspects. We propose an approach which is based on the state transformation, more particularly the partition of the phase portrait in different regions where each subregion is modeled as a two-dimensional linear time invariant system. Then the Takagi-Sugeno model, which is a combination of local model is calculated. The simulation results show that the Alpha partition is well-suited for dealing with such a system

Sales restriction, quality selection and the mode of competition

A regulator imposing “sales restrictions” on firms competing in oligopolistic markets may enhance quality provision by the firms. Moreover, for most restrictions levels, the impact on quality selection is invariant to the mode of competition

Variétés CR polarisées et G-polarisées, partie I

Polarized and G-polarized CR manifolds are smooth manifolds endowed with a double structure: a real foliation &em&F&/em& (given by the action of a Lie group G in the G-polarized case) and a transverse CR distribution. Polarized means that (E,J) is roughly speaking invariant by&em&F&/em&. Both structures are therefore linked up. The interplay between them gives to polarized CR-manifolds a very rich geometry. In this paper, we study the properties of polarized and G-polarized manifolds, putting special emphasis on their deformations.

Type II and IIIA thumb hypoplasia reconstruction.

Thumb hypoplasia treatment requires considering every component of the maldevelopment. Types II and IIIA hypoplasia share common features such as first web space narrowing, hypoplasia or absence of thenar muscles and metacarpophalangeal joint instability. Many surgical techniques to correct the malformation have been described. We report our surgical strategy that includes modifications of the usual technique that we found useful in reducing morbidity while optimizing the results. A diamond-shape kite flap was used to widen the first web space. Its design allowed primary closure of the donor site using a Dufourmentel flap. The ring finger flexor digitorum superficialis was transferred for opposition transfer, and the same tendon was used to stabilize the metacarpophalangeal joint on its ulnar and/or radial side depending on a uniplanar or more global instability. An omega-shaped K-wire was placed between the first and second metacarpals to maintain a wide opening of the first web space without stressing the reconstructed ulnar collateral ligament of the MCP joint. We report a clinical series of 15 patients (18 thumbs) who had this reconstructive program.

The role of energetic value in dynamic brain response adaptation during repeated food image viewing.

The repeated presentation of simple objects as well as biologically salient objects can cause the adaptation of behavioral and neural responses during the visual categorization of these objects. Mechanisms of response adaptation during repeated food viewing are of particular interest for better understanding food intake beyond energetic needs. Here, we measured visual evoked potentials (VEPs) and conducted neural source estimations to initial and repeated presentations of high-energy and low-energy foods as well as non-food images. The results of our study show that the behavioral and neural responses to food and food-related objects are not uniformly affected by repetition. While the repetition of images displaying low-energy foods and non-food modulated VEPs as well as their underlying neural sources and increased behavioral categorization accuracy, the responses to high-energy images remained largely invariant between initial and repeated encounters. Brain mechanisms when viewing images of high-energy foods thus appear less susceptible to repetition effects than responses to low-energy and non-food images. This finding is likely related to the superior reward value of high-energy foods and might be one reason why in particular high-energetic foods are indulged although potentially leading to detrimental health consequences.

N-dimensional dynamical systems exploiting instabilities in full

We report experimental and numerical results showing how certain N-dimensional dynamical systems are able to exhibit complex time evolutions based on the nonlinear combination of N-1 oscillation modes. The experiments have been done with a family of thermo-optical systems of effective dynamical dimension varying from 1 to 6. The corresponding mathematical model is an N-dimensional vector field based on a scalar-valued nonlinear function of a single variable that is a linear combination of all the dynamic variables. We show how the complex evolutions appear associated with the occurrence of successive Hopf bifurcations in a saddle-node pair of fixed points up to exhaust their instability capabilities in N dimensions. For this reason the observed phenomenon is denoted as the full instability behavior of the dynamical system. The process through which the attractor responsible for the observed time evolution is formed may be rather complex and difficult to characterize. Nevertheless, the well-organized structure of the time signals suggests some generic mechanism of nonlinear mode mixing that we associate with the cluster of invariant sets emerging from the pair of fixed points and with the influence of the neighboring saddle sets on the flow nearby the attractor. The generation of invariant tori is likely during the full instability development and the global process may be considered as a generalized Landau scenario for the emergence of irregular and complex behavior through the nonlinear superposition of oscillatory motions

Esfingolipids i senyal•lització cel.lular: l'(E)-2-hexadecenal com a possible lípid bioactiu

L’esfingosina-1-fosfat (S1P) és un lípid bioactiu amb funcions crucials en la biologia cel•lular. Entre aquestes, la seva activitat mitogènica i citoprotectora són les més estudiades. L’S1P és catabolitzada intracel•lularment mitjançant l’esfingosina-1-fosfat liasa (SGPL1) per generar (E)-2-hexadecenal i fosforiletanolamina. L’objectiu d’aquest projecte és explorar si l’(E)-2-hexadecenal és realment un catabòlit innocu o bé si, pel seu caràcter acceptor de Michael, és capaç de reaccionar amb pèptids o proteïnes específics. Aquesta interacció podria traduïr-se en funcions biològiques determinades, algunes de les quals són possiblement atribuïdes a l’esfingosina-1-fosfat com a tal. Per poder explorar el potencials adductes proteïcs amb l’aldehid, s’han emprat, sobre cèl•lules HeLa que sobreexpressen SGPL1, sondes anàlegs a esfingosina i esfinganina (i els seus derivats fosforil•lats) que presenten una funció azida en la posició omega de la cadena esfingoide. Aquestes, mitjançant química click sense coure, s’han fet reaccionar amb una molècula que presenta un dibenzociclooctí unit a biotina DBCObiotina). Després d’aïllar les proteïnes així biotinilades amb una reïna d’estreptavidina, aquestes es van separar per electroforesi. Les bandes proteïques observades es van extreure del gel i es van digerir amb tripsina, per posteriorment analitzar els pèptids per MALDI-TOF, el que permetria l’identificació de proteïnes a partir de “peptide mass fingerprinting”. Lamentablement, a la fi d’aquest contracte, encara no s’ha pogut identificar cap proteïna que s’uneixi a l’aldehid alliberat per la reacció de l’esfingosina-1- fosfat liasa. No obstant, durant aquest temps s’ha millorat el mètode per detectar aquests adductes proteïcs. Per això, si la recerca continua en aquesta línia, properament es podria saber amb certesa si existeixen o no aquestes interaccions covalents entre determinades proteïnes i l’(E)-2-hexadecenal.

L'intégration de la sexualité en consultation gynécologique : discordances entre les perceptions des femmes et celles des gynécologues.

Dès les années 2000, l'Office Fédéral de la Santé Publique recommande aux médecins de premier recours, dont les gynécologues, d'aborder activement la sexualité en consultation, en raison notamment de l'augmentation des infections sexuellement transmissibles asymptomatiques (1ST). Dans le même sens, comme le montrent nombre d'études, plus de 70% des patientes souhaiteraient être interrogées au sujet de leur sexualité en consultation gynécologique. Or, il semble que peu de médecins intègrent systématiquement des questions de sexualité dans leur anamnèse. La revue de la littérature relève que les recherches réalisées à ce jour ont été menées principalement à l'aide de questionnaire selon une perspective naturaliste, qui étudie la sexualité de manière décontextualisée et qui la conçoit comme un invariant biologique et par conséquent universel. Notre objectif est de saisir en profondeur les perceptions et le vécu des gynécologues et des femmes, face à l'intégration de la sexualité en consultation gynécologique. Nous avons adopté une perspective critique en psychologie de la santé (Santiago-Delefosse & Chamberlain, 2008 ; Murray, 2004a ; Lyons & Chamberlain, 2006) qui permet de privilégier d'une part, l'étude de la signification que les sujets donnent à la sexualité dans leur contexte socio-historique et, d'autre part, une vision de l'être humain comprenant des dimensions corporelles, psychologiques et sociétales (Santiago-Delefosse, 2011). Pour ce faire, nous avons utilisé un dispositif de méthodes mixtes en deux phases. Dans la première phase, nous avons mené 21 entretiens semi directifs avec des gynécologues hommes et femmes. Puis, nous avons réalisé 3 groupes focalisés (N=16) avec des femmes âgées de 23 à 65 ans. La seconde phase a consisté à créer un questionnaire, élaboré à partir des résultats de la première phase, afin d'élargir l'expérience de l'intégration de la sexualité en consultation, à une population plus diversifiée de femmes (N=421). Les données récoltées par le biais de ces trois méthodes nous ont permis d'esquisser un modèle présentant les processus en jeu dans la situation de non intégration de la sexualité en consultation gynécologique. Celui-ci relève non seulement des lacunes dans le cursus universitaire de médecine en matière de sexualité, mais également d'importantes discordances entre les gynécologues et les femmes interviewés concernant le rôle du gynécologue, la perception de l'intime, la perception d'introduire le sujet de la sexualité en consultation, ainsi que de la définition même de la sexualité. Nos résultats ouvrent sur des perspectives pratiques pour la consultation gynécologique, ainsi que sur des pistes pour des recherches futures dans l'étude de la sexualité, selon une perspective plus intégrative. -- Since the 2000's, the Swiss Federal Office of Public Health recommended primary care physicians, including gynaecologists, to actively address sexuality issues in consultation, namely because of the increasing incidence of Sexually Transmitted Infections (STI). In line with this, studies have shown that more than 70% of patients would like to be asked about their sexuality by their gynaecologist. However, physicians do not take systematically sexual histories from their patients. Literature in the field has highlighted that most research has been restricted to using questionnaires following a naturalist theoretical perspective according to which sexual behaviour is defined as biologically invariant, hence, universal. Our objective is to deepen understand perceptions from gynaecologists and women with regard to the integration of sexuality in consultations. A critical health psychology approach allows us to consider on the one hand sexuality as a construct that is inseparable from a given socio-historical context. On the other hand, this approach takes into consideration an embodied, social and psychological definition of human beings. Therefore, we used a mixed methods design that included two main research steps : First, we conducted 21 semi-structured interviews with male and female gynaecologists. In this phase, we also led 3 focus groups made up of 16 women aged from 21 to 65. Second, a survey was implemented (N= 421) based on findings stemming from the first phase. This allowed us to further analyse experiences on the integration of sexuality and to extend findings to a more diversified population of women. The data analysis allowed us to create a model that highlights the processes involved in the non integration of sexuality during gynaecological consultation. It shows a lack of training in sexology within medical programs. Moreover, it emphasises the mismatches on perceptions between gynaecologists and women concerning the gynaecologist's role ; intimacy, the issue of whether introducing sexuality topics, and finally, on the actual definition of sexuality itself. Our findings open new research perspectives for the study of sexuality by proposing a more integrative approach. They also provide practical and clinical perspectives concerning consultations in gynaecology.

Apoplastic polyesters in Arabidopsis surface tissues--a typical suberin and a particular cutin.

Cutinized and suberized cell walls form physiological important plant-environment interfaces as they act as barriers limiting water and nutrient loss and protect from radiation and invasion by pathogens. Due to the lack of protocols for the isolation and analysis of cutin and suberin in Arabidopsis, the model plant for molecular biology, mutants and transgenic plants with a defined altered cutin or suberin composition are unavailable, causing that structure and function of these apoplastic barriers are still poorly understood. Transmission electron microscopy (TEM) revealed that Arabidopsis leaf cuticle thickness ranges from only 22 nm in leaf blades to 45 nm on petioles, causing the difficulty in cuticular membrane isolation. We report the use of polysaccharide hydrolases to isolate Arabidopsis cuticular membranes, suitable for depolymerization and subsequent compositional analysis. Although cutin characteristic omega-hydroxy acids (7%) and mid-chain hydroxylated fatty acids (8%) were detected, the discovery of alpha,omega-diacids (40%) and 2-hydroxy acids (14%) as major depolymerization products reveals a so far novel monomer composition in Arabidopsis cutin, but with chemical analogy to root suberin. Histochemical and TEM analysis revealed that suberin depositions were localized to the cell walls in the endodermis of primary roots and the periderm of mature roots of Arabidopsis. Enzyme digested and solvent extracted root cell walls when subjected to suberin depolymerization conditions released omega-hydroxy acids (43%) and alpha,omega-diacids (24%) as major components together with carboxylic acids (9%), alcohols (6%) and 2-hydroxyacids (0.1%). This similarity to suberin of other species indicates that Arabidopsis roots can serve as a model for suberized tissue in general.

Health Information and the Choice of Fish Species: An Experiment Measuring the Impact of Risk and Benefit Information, April 2006

An experiment was conducted in France to evaluate the impact of health information on consumers’ choice between two different types of fish. Successive messages revealing risks (methylmercury) and benefits (omega-3s) of consuming the fish, along with consumption recommendations, were delivered. Results show a significant difference of reaction according to the order and type of information. The information about risks had a larger marginal impact on change in willingness to pay (WTP) than did the information about benefits. While the results show that detailed messages on risks/benefits, including recommendations for nutrition behavior, matter in the modification of WTP, 40% of respondents did not change their initial choices after the revelation of health information.

n-3 PUFAs modulate T-cell activation via protein kinase C-alpha and -epsilon and the NF-kappaB signaling pathway.

We elucidated the mechanisms of action of two n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in Jurkat T-cells. Both DHA and EPA were principally incorporated into phospholipids in the following order: phosphatidylcholine < phosphatidylethanolamine < phosphatidylinositol/phosphatidylserine. Furthermore, two isoforms of phospholipase A(2) (i.e., calcium-dependent and calcium-independent) were implicated in the release of DHA and EPA, respectively, during activation of these cells. The two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon. The two n-3 PUFAs also inhibited the nuclear translocation of nuclear factor kappaB (NF-kappaB) and the transcription of the interleukin-2 (IL-2) gene in PMA-activated Jurkat T-cells. Together, these results demonstrate that DHA and EPA, being released by two isoforms of phospholipase A(2), modulate IL-2 gene expression by exerting their action on two PKC isoforms and NF-kappaB in Jurkat T-cells.

Medidas de Perda na Avalia ção do Desempenho de Fundos de Investimentos

Uma das medidas de performance mais utilizada e a medida de Sharpe. A sua utiliza c~ao e inadequada quando as rendibilidades n~ao seguem uma distribui c~ao normal, assim originou o aparecimento de uma variedade de medidas alternativas. Em fun c~ao disso, surge ent~ao a quest~ao de saber se essas medidas alternativas produzem rankings signi cativamente diferentes da que se obt em com a medida de Sharpe. Apesar da exist^encia de muitos estudos emp ricos sobre esta problem atica a resposta n~ao e consensual. Neste trabalho fez-se a compara c~ao entre o ranking produzido pela medida de Sharpe e as algumas medidas alternativas, as que se baseiam no Low Partial Moments (Omega, Sortino, Kappa3 e Upside Potential Ratio) e, as que se baseiam no VaR - Value-at-Risk (ERV - Excess Return on VaR, ERMV - Excess Return on Modi ed VaR, ERCV - Excess Return on Conditional VaR e ERV? - Excess Return com VaR hist orico). Utilizando 26 fundos de investimentos norte-americanos, com registo di ario das rendibilidades para o per odo de Janeiro 2000 a Setembro 2009, encontrou-se um elevado coe ciente de correla c~ao de Spearman e de Kendall entre a medida de Sharpe e as alternativas, bem como as alternativas entre si, excepto para Upside Potential Ratio que os coe cientes s~ao relativamente baixos. Os resultados permitem concluir que existe uma medida que proporciona ordena c~oes diferentes.

Medidas de Perda na Avaliacão do Desempenho de Fundos de Investimentos

Uma das medidas de performance mais utilizada e a medida de Sharpe. A sua utilizacão e inadequada quando as rendibilidades não seguem uma distribuicão normal, assim originou o aparecimento de uma variedade de medidas alternativas. Em fun c~ao disso, surge então a questão de saber se essas medidas alternativas produzem rankings signi cativamente diferentes da que se obt em com a medida de Sharpe. Apesar da existencia de muitos estudos emp ricos sobre esta problem atica a resposta não e consensual. Neste trabalho fez-se a comparacão entre o ranking produzido pela medida de Sharpe e as algumas medidas alternativas, as que se baseiam no Low Partial Moments (Omega, Sortino, Kappa3 e Upside Potential Ratio) e, as que se baseiam no VaR - Value-at-Risk (ERV - Excess Return on VaR, ERMV - Excess Return on Modi ed VaR, ERCV - Excess Return on Conditional VaR e ERV? - Excess Return com VaR hist orico). Utilizando 26 fundos de investimentos norte-americanos, com registo di ario das rendibilidades para o per odo de Janeiro 2000 a Setembro 2009, encontrou-se um elevado coe ciente de correla c~ao de Spearman e de Kendall entre a medida de Sharpe e as alternativas, bem como as alternativas entre si, excepto para Upside Potential Ratio que os coe cientes s~ao relativamente baixos. Os resultados permitem concluir que existe uma medida que proporciona ordena c~oes diferentes.