Géopatrimoines des trois Chablais : identification et valorisation des témoins glaciaires

Cette recherche s'intéresse aux témoins glaciaires des Chablais dans quatre de leurs dimensions : géopatrimoine, connaissance objective, inventaire de géosites et valorisation. En 2009, débutait le projet 123 Chablais, pour une durée de quatre ans. Ce projet, élaboré dans le cadre du programme Interreg IV France-Suisse, avait pour but de dynamiser le développement économique local en s'appuyant sur les patrimoines régionaux. Le géopatrimoine, identifié comme une de ces ressources, faisait donc l'objet de plusieurs actions, dont cette recherche. Le premier objectif de ce travail était d'acquérir une vision synthétique des témoins glaciaires locaux et d'en améliorer la connaissance, notamment, leur chronologie. Une série de datations par isotopes cosmogéniques produits in situ a permis de compléter des données disponibles pour deux stades glaciaires bien identifiés: le dernier maximum glaciaire (LGM) et un stade de retrait du glacier du Rhône (le stade de Monthey). Le second objectif était centré sur les processus d'identification et d'inventaire des géosites glaciaires. L'analyse des résultats de l'inventaire a fait apparaître quelques caractéristiques du patrimoine glaciaire chablaisien, discret, diversifié, et comportant deux spécificités exploitables dans le cadre d'une médiation scientifique : son statut de « berceau de la théorie glaciaire » et ses liens étroits avec des activités de la vie quotidienne, en tant que matière première, support de loisir ou facteur de risque. Finalement, cette recherche a débouché sur l'élaboration d'une exposition itinérante sur le patrimoine glaciaire des Chablais.

Identification and functional characterization of a monofunctional peroxisomal enoyl-CoA hydratase 2 that participates in the degradation of even cis-unsaturated fatty acids in Arabidopsis thaliana.

A gene, named AtECH2, has been identified in Arabidopsis thaliana to encode a monofunctional peroxisomal enoyl-CoA hydratase 2. Homologues of AtECH2 are present in several angiosperms belonging to the Monocotyledon and Dicotyledon classes, as well as in a gymnosperm. In vitro enzyme assays demonstrated that AtECH2 catalyzed the reversible conversion of 2E-enoyl-CoA to 3R-hydroxyacyl-CoA. AtECH2 was also demonstrated to have enoyl-CoA hydratase 2 activity in an in vivo assay relying on the synthesis of polyhydroxyalkanoate from the polymerization of 3R-hydroxyacyl-CoA in the peroxisomes of Saccharomyces cerevisiae. AtECH2 contained a peroxisome targeting signal at the C-terminal end, was addressed to the peroxisome in S. cerevisiae, and a fusion protein between AtECH2 and a fluorescent protein was targeted to peroxisomes in onion cells. AtECH2 gene expression was strongest in tissues with high beta-oxidation activity, such as germinating seedlings and senescing leaves. The contribution of AtECH2 to the degradation of unsaturated fatty acids was assessed by analyzing the carbon flux through the beta-oxidation cycle in plants that synthesize peroxisomal polyhydroxyalkanoate and that were over- or underexpressing the AtECH2 gene. These studies revealed that AtECH2 participates in vivo to the conversion of the intermediate 3R-hydroxyacyl-CoA, generated by the metabolism of fatty acids with a cis (Z)-unsaturated bond on an even-numbered carbon, to the 2E-enoyl-CoA for further degradation through the core beta-oxidation cycle.

Dynamic responses of oxygen uptake at the onset and end of moderate and heavy exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in VO2 are found in the literature. Therefore the purpose of this study was to examine VO2 on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT), or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of VO2 during cycling exercise in the heavy-intensity domain.

Dynamic responses of O2 uptake at the onset and end of exercise in trained subjects.

Inconsistencies about dynamic asymmetry between the on- and off-transient responses in .VO2 are found in the literature. Therefore the purpose of this study was to examine .VO2on- and off-transients during moderate- and heavy-intensity cycling exercise in trained subjects. Ten men underwent an initial incremental test for the estimation of ventilatory threshold (VT) and, on different days, two bouts of square-wave exercise at moderate (<VT) and heavy (>VT) intensities. .VO2 kinetics in exercise and recovery were better described by a single exponential model (<VT) or by a double exponential with two time delays (>VT). For moderate exercise, we found a symmetry of .VO2 kinetics between the on- and off-transients (i.e., fundamental component), consistent with a system manifesting linear control dynamics. For heavy exercise, a slow component superimposed on the fundamental phase was expressed in both the exercise and recovery, with similar parameter estimates. But the on-transient values of the time constant were appreciably faster than the associated off-transient, and independent of the work rate imposed (<VT and >VT). Our results do not support a dynamically linear system model of .VO2 during cycling exercise in the heavy-intensity domain.

Evidence evaluation in fingerprint comparison and automated fingerprint identification systems: modeling between finger variability

In the context of the investigation of the use of automated fingerprint identification systems (AFIS) for the evaluation of fingerprint evidence, the current study presents investigations into the variability of scores from an AFIS system when fingermarks from a known donor are compared to fingerprints that are not from the same source. The ultimate goal is to propose a model, based on likelihood ratios, which allows the evaluation of mark-to-print comparisons. In particular, this model, through its use of AFIS technology, benefits from the possibility of using a large amount of data, as well as from an already built-in proximity measure, the AFIS score. More precisely, the numerator of the LR is obtained from scores issued from comparisons between impressions from the same source and showing the same minutia configuration. The denominator of the LR is obtained by extracting scores from comparisons of the questioned mark with a database of non-matching sources. This paper focuses solely on the assignment of the denominator of the LR. We refer to it by the generic term of between-finger variability. The issues addressed in this paper in relation to between-finger variability are the required sample size, the influence of the finger number and general pattern, as well as that of the number of minutiae included and their configuration on a given finger. Results show that reliable estimation of between-finger variability is feasible with 10,000 scores. These scores should come from the appropriate finger number/general pattern combination as defined by the mark. Furthermore, strategies of obtaining between-finger variability when these elements cannot be conclusively seen on the mark (and its position with respect to other marks for finger number) have been presented. These results immediately allow case-by-case estimation of the between-finger variability in an operational setting.

Industrie laitière : de la vache à la fromagerie, identification des tâches générant de fortes quantités de bioaérosols

La France possède le plus grand cheptel bovin d'Europe, dont environ la moitié de vaches laitières (82 000 exploitations de vaches laitières avec 45 vaches en moyenne (RGA 2010, agreste)). La forte densité des animaux, l'utilisation de litière d'origine organique (copeaux de bois, paille), la distribution de fourrage sec (foin, grain) et l'accumulation d'excréments génèrent d'énormes quantités de poussières organiques. De plus, la taille des exploitations a tendance à s'agrandir avec une mise à l'herbe des animaux de moins en moins importante et donc une exposition des travailleurs plus importante à la poussière organique. Cette poussière peut être très riche en endotoxines(1) issues de la membrane cellulaire de certaines bactéries. Les effets sur la santé d'une exposition chronique aux endotoxines sont bien connus et concernent principalement des atteintes du système respiratoire (1-4) ainsi que des atteintessystémiques, avec l'apparition d'un état fébrile, lors d'exposition aiguë à de fortes concentrations. La plupart du temps, les études ayant mesuré l'exposition des fermiers aux endotoxines n'ont pas déterminé précisément quelle(s) tâche(s) spécifique(s) ou quelles caractéristiques de l'élevage étaient associées avec la plus forte exposition. Pourtant, une meilleure identification de ces tâches est essentielle à la mise en place de mesures de prévention ciblée. La première étude présentée a analysé, à l'aide d'outils statistiques performants, les déterminants de l'exposition personnelle à la poussière inhalable et aux endotoxines des travailleurs de fermes de vaches laitières. La seconde étude s'est intéressée à l'exposition aux bioaérosols lors des étapes de maturation du fromage. En effet, celle-ci nécessite l'utilisation délibérée de bactéries et de moisissures spécifiques qui sont facilement aérosolisées. L'exposition des travailleurs à ces microorganismes peut être responsable de maladies respiratoires de type allergique (5-7) dont la maladie des laveurs de fromages.

Identification of tumor-associated antigens by large-scale analysis of genes expressed in human colorectal cancer.

Despite the high prevalence of colon cancer in the world and the great interest in targeted anti-cancer therapy, only few tumor-specific gene products have been identified that could serve as targets for the immunological treatment of colorectal cancers. The aim of our study was therefore to identify frequently expressed colon cancer-specific antigens. We performed a large-scale analysis of genes expressed in normal colon and colon cancer tissues isolated from colorectal cancer patients using massively parallel signal sequencing (MPSS). Candidates were additionally subjected to experimental evaluation by semi-quantitative RT-PCR on a cohort of colorectal cancer patients. From a pool of more than 6000 genes identified unambiguously in the analysis, we found 2124 genes that were selectively expressed in colon cancer tissue and 147 genes that were differentially expressed to a significant degree between normal and cancer cells. Differential expression of many genes was confirmed by RT-PCR on a cohort of patients. Despite the fact that deregulated genes were involved in many different cellular pathways, we found that genes expressed in the extracellular space were significantly over-represented in colorectal cancer. Strikingly, we identified a transcript from a chromosome X-linked member of the human endogenous retrovirus (HERV) H family that was frequently and selectively expressed in colon cancer but not in normal tissues. Our data suggest that this sequence should be considered as a target of immunological interventions against colorectal cancer.

MAGE-A3 and MAGE-A4 specific CD4(+) T cells in head and neck cancer patients: detection of naturally acquired responses and identification of new epitopes.

Frequent expression of cancer testis antigens (CTA) has been consistently observed in head and neck squamous cell carcinomas (HNSCC). For instance, in 52 HNSCC patients, MAGE-A3 and -A4 CTA were expressed in over 75% of tumors, regardless of the sites of primary tumors such as oral cavity or hypopharynx. Yet, T-cell responses against these CTA in tumor-bearing patients have not been investigated in detail. In this study, we assessed the naturally acquired T-cell response against MAGE-A3 and -A4 in nonvaccinated HNSCC patients. Autologous antigen-presenting cells pulsed with overlapping peptide pools were used to detect and isolate MAGE-A3 and MAGE-A4 specific CD4(+) T cells from healthy donors and seven head and neck cancer patients. CD4(+) T-cell clones were characterized by cytokine secretion. We could detect and isolate MAGE-A3 and MAGE-A4 specific CD4(+) T cells from 7/7 cancer patients analyzed. Moreover, we identified six previously described and three new epitopes for MAGE-A3. Among them, the MAGE-A3(111-125) and MAGE-A3(161-175) epitopes were shown to be naturally processed and presented by DC in association with HLA-DP and DR, respectively. All of the detected MAGE-A4 responses were specific for new helper epitopes. These data suggest that naturally acquired CD4(+) T-cell responses against CT antigens often occur in vivo in HNSCC cancer patients and provide a rationale for the development of active immunotherapeutic approaches in this type of tumor.

Identification of biologic markers of the premature rupture of fetal membranes: proteomic approach.

In obstetrics, premature rupture of the membranes (PROM) is a frequent observation which is responsible for many premature deliveries. PROM is also associated with an increased risk of fetal and maternal infections. Early diagnosis is mandatory in order to decrease such complications. Despite that current biological tests allowing the diagnosis of PROM are both sensitive and specific, contamination of the samples by maternal blood can induce false positive results. Therefore, in order to identify new potential markers of PROM (present only in amniotic blood, and absent in maternal blood), proteomic studies were undertaken on samples collected from six women at terms (pairs of maternal plasma and amniotic fluid) as well as on four samples of amniotic fluid collected from other women at the 17(th) week of gestation. All samples (N = 16) were analyzed by two-dimensional (2-D) high-resolution electrophoresis, followed by sensitive silver staining. The gel images were studied using bioinformatic tools. Analyses were focused on regions corresponding to pI between 4.5 and 7 and to molecular masses between 20 and 50 kDa. In this area, 646 +/- 113 spots were detected, and 27 spots appeared to be present on the gels of amniotic fluid, but were absent on those of maternal plasma. Nine out of these 27 spots were also observed on the gels of the four samples of amniotic fluids collected at the 17(th) week of pregnancy. Five of these 9 spots were unambiguously detected on preparative 2-D gels stained by Coomassie blue, and were identified by mass spectrometry analyses. Three spots corresponded to fragments of plasma proteins, and 2 appeared to be fragments of proteins not known to be present in plasma. These 2 proteins were agrin (SWISS-PROT: O00468) and perlecan (SWISS-PROT: P98160). Our results show that proteomics is a valuable approach to identify new potential biological markers for future PROM diagnosis.

Dermatophyte identification in skin and hair samples using a simple and reliable nested polymerase chain reaction assay.

BACKGROUND: Dermatophyte identification in tinea capitis is essential for choosing the appropriate treatment and in tinea infections to identify the possible source. The failure of fungi to grow in cultures frequently occurs, especially in cases of previous antifungal therapy. OBJECTIVES: To develop a rapid polymerase chain reaction (PCR) sequencing assay for dermatophyte identification in tinea capitis and tinea corporis. MATERIAL AND METHODS: Fungal DNA was extracted from hair and skin samples that were confirmed to be positive by direct mycological examination. Dermatophytes were identified by the sequence of a 28S ribosomal DNA subunit amplicon generated by nested PCR. RESULTS: Nested PCR was found to be necessary to obtain amplicons in substantial amounts for dermatophyte identification by sequencing. The results agreed with those of classical mycological identification in 14 of 23, 6 of 10, and 20 of 23 cases of tinea capitis, tinea corporis and tinea pedis, respectively, from which a dermatophyte was obtained in culture. In seven of the 56 cases, another dermatophyte was identified, revealing previous misidentification. A dermatophyte was identified in 12 of 18, three of five, and four of nine cases of tinea capitis, tinea corporis and tinea pedis, respectively, in cases in which no dermatophyte grew in culture. CONCLUSIONS: Although the gold standard dermatophyte identification from clinical samples remains fungal cultures, the assay developed in the present study is especially suitable for tinea capitis. Improved sensitivity for the identification of dermatophyte species was obtained as it is possible to identify the dermatophyte when the fungus fails to grow in cultures.

Identification of peptide ligands to the chemokine receptor CCR5 and their maturation by gene shuffling.

The determination of protein-protein interactions and their role in diverse pathophysiological processes is a promising approach to the identification of molecules of therapeutic potential. This paper describes the identification of peptidic CCR5 receptor ligands as potential drug leads against HIV-1 infection using in vitro evolution based on phage display. A phage-displayed peptide library was used to select for anti-CCR5 peptide. Further in vitro evolution of the peptide by exon shuffling was performed to identify peptides with optimized characteristics for CCR5 receptor. This peptide inhibited HIV coreceptor activity in a cell fusion assay with an IC50 of 5 microM. It did not exhibit either agonistic or antagonistic activity on CCR5 in the concentration range used. To our knowledge, this is a first report that describes the identification of peptide ligands specific to the CCR5 receptor from a phage-displayed library and the maturation of the selected peptide sequence by gene shuffling.

Disease identification based on ambulatory drugs dispensation and in-hospital ICD-10 diagnoses: a comparison.

BACKGROUND: Pharmacy-based case mix measures are an alternative source of information to the relatively scarce outpatient diagnoses data. But most published tools use national drug nomenclatures and offer no head-to-head comparisons between drugs-related and diagnoses-based categories. The objective of the study was to test the accuracy of drugs-based morbidity groups derived from the World Health Organization Anatomical Therapeutic Chemical Classification of drugs by checking them against diagnoses-based groups. METHODS: We compared drugs-based categories with their diagnoses-based analogues using anonymous data on 108,915 individuals insured with one of four companies. They were followed throughout 2005 and 2006 and hospitalized at least once during this period. The agreement between the two approaches was measured by weighted kappa coefficients. The reproducibility of the drugs-based morbidity measure over the 2 years was assessed for all enrollees. RESULTS: Eighty percent used a drug associated with at least one of the 60 morbidity categories derived from drugs dispensation. After accounting for inpatient under-coding, fifteen conditions agreed sufficiently with their diagnoses-based counterparts to be considered alternative strategies to diagnoses. In addition, they exhibited good reproducibility and allowed prevalence estimates in accordance with national estimates. For 22 conditions, drugs-based information identified accurately a subset of the population defined by diagnoses. CONCLUSIONS: Most categories provide insurers with health status information that could be exploited for healthcare expenditure prediction or ambulatory cost control, especially when ambulatory diagnoses are not available. However, due to insufficient concordance with their diagnoses-based analogues, their use for morbidity indicators is limited.

Kinematics and dynamic complexity of postural transitions in frail elderly subjects.

The aim of this study was to propose a methodology allowing a detailed characterization of body sit-to-stand/stand-to-sit postural transition. Parameters characterizing the kinematics of the trunk movement during sit-to-stand (Si-St) postural transition were calculated using one initial sensor system fixed on the trunk and a data logger. Dynamic complexity of these postural transitions was estimated by fractal dimension of acceleration-angular velocity plot. We concluded that this method provides a simple and accurate tool for monitoring frail elderly and to objectively evaluate the efficacy of a rehabilitation program.