eVOC: a controlled vocabulary for unifying gene expression data.

Expression data contribute significantly to the biological value of the sequenced human genome, providing extensive information about gene structure and the pattern of gene expression. ESTs, together with SAGE libraries and microarray experiment information, provide a broad and rich view of the transcriptome. However, it is difficult to perform large-scale expression mining of the data generated by these diverse experimental approaches. Not only is the data stored in disparate locations, but there is frequent ambiguity in the meaning of terms used to describe the source of the material used in the experiment. Untangling semantic differences between the data provided by different resources is therefore largely reliant on the domain knowledge of a human expert. We present here eVOC, a system which associates labelled target cDNAs for microarray experiments, or cDNA libraries and their associated transcripts with controlled terms in a set of hierarchical vocabularies. eVOC consists of four orthogonal controlled vocabularies suitable for describing the domains of human gene expression data including Anatomical System, Cell Type, Pathology and Developmental Stage. We have curated and annotated 7016 cDNA libraries represented in dbEST, as well as 104 SAGE libraries,with expression information,and provide this as an integrated, public resource that allows the linking of transcripts and libraries with expression terms. Both the vocabularies and the vocabulary-annotated libraries can be retrieved from http://www.sanbi.ac.za/evoc/. Several groups are involved in developing this resource with the aim of unifying transcript expression information.

Obesity in Switzerland: a critical assessment of prevalence in children and adults.

The objective was to analyze the situation in Switzerland regarding the prevalence of overweight or obesity in children, adolescents and adults. The data were compared with France, an adjacent much larger country. The results showed that there is a definitive lack of objective information in Switzerland on the prevalence of obesity at different ages. As in other European studies, the fact that many national surveys are classically based on subject interviews (self-reported weights and heights rather than measured values) implies that the overweight/obesity prevalence is largely underestimated in adulthood. For example, in a recent Swiss epidemiological study, the prevalence of obesity (BMI greater than 30 kg/m(2)) averaged 6-7% in young men and women (25-34 y), the prevalence being underestimated by a factor of two to three when body weight was self-reported rather than measured. This phenomenon has already been observed in previous European studies. It is concluded that National Surveys based on telephone interviews generally produce biased obesity prevalence results, although the direction of the changes in prevalence of obesity and its evolution with repeated surveys using strict standardized methodology may be evaluated correctly. Therefore, these surveys should be complemented by large-scale epidemiological studies (based on measured anthropomeric variables rather than declared) covering the different linguistic areas of Switzerland. An epidemiological body weight (BMI) monitoring surveillance system, using a harmonized methodology among European countries, would help to accurately assess differences in obesity prevalence across Europe without methodological bias. It will permit monitoring of the dynamic evolution of obesity prevalence as well as the development of appropriate strategies (taking into account the specificity of each country) for obesity prevention and treatment.

Ecological and historical drivers of diversification in the fly genus Chiastocheta Pokorny.

Coevolution is among the main forces shaping the biodiversity on Earth. In Eurasia, one of the best-known plant-insect interactions showing highly coevolved features involves the fly genus Chiastocheta and its host-plant Trollius. Although this system has been widely studied from an ecological point of view, the phylogenetic relationships and biogeographic history of the flies have remained little investigated. In this integrative study, we aim to test the monophyly of the five Chiastocheta eco-morphological groups, defined by Pellmyr in 1992, by inferring a mitochondrial phylogeny. We further apply a new approach to assess the effect of (i) different molecular substitution rates and (ii) phylogenetic uncertainty on the inference of the spatio-temporal evolution of the group. From a taxonomic point of view, we demonstrate that only two of Pellmyr's groups (rotundiventris and dentifera) are phylogenetically supported, the other species appearing para- or polyphyletic. We also identify the position of C. lophota, which was not included in previous surveys. From a spatio-temporal perspective, we show that the genus arose during the Pliocene in Europe. Our results also indicate that at least four large-scale dispersal events are required to explain the current distribution of Chiastocheta. Moreover, each dispersal to or from Asia is associated with a host-shift and seems to correspond to an increase in speciation rates. Finally, we highlight the correlation between diversification and climatic fluctuations, which indicate that the cycles of global cooling over the last million years had an influence on the radiation of the group.

Resting-State Functional Connectivity Emerges from Structurally and Dynamically Shaped Slow Linear Fluctuations.

Brain fluctuations at rest are not random but are structured in spatial patterns of correlated activity across different brain areas. The question of how resting-state functional connectivity (FC) emerges from the brain's anatomical connections has motivated several experimental and computational studies to understand structure-function relationships. However, the mechanistic origin of resting state is obscured by large-scale models' complexity, and a close structure-function relation is still an open problem. Thus, a realistic but simple enough description of relevant brain dynamics is needed. Here, we derived a dynamic mean field model that consistently summarizes the realistic dynamics of a detailed spiking and conductance-based synaptic large-scale network, in which connectivity is constrained by diffusion imaging data from human subjects. The dynamic mean field approximates the ensemble dynamics, whose temporal evolution is dominated by the longest time scale of the system. With this reduction, we demonstrated that FC emerges as structured linear fluctuations around a stable low firing activity state close to destabilization. Moreover, the model can be further and crucially simplified into a set of motion equations for statistical moments, providing a direct analytical link between anatomical structure, neural network dynamics, and FC. Our study suggests that FC arises from noise propagation and dynamical slowing down of fluctuations in an anatomically constrained dynamical system. Altogether, the reduction from spiking models to statistical moments presented here provides a new framework to explicitly understand the building up of FC through neuronal dynamics underpinned by anatomical connections and to drive hypotheses in task-evoked studies and for clinical applications.

One naive T cell, multiple fates in CD8+ T cell differentiation.

The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR-pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets.

Comparative modular analysis of gene expression in vertebrate development

The focus of my PhD research was the concept of modularity. In the last 15 years, modularity has become a classic term in different fields of biology. On the conceptual level, a module is a set of interacting elements that remain mostly independent from the elements outside of the module. I used modular analysis techniques to study gene expression evolution in vertebrates. In particular, I identified ``natural'' modules of gene expression in mouse and human, and I showed that expression of organ-specific and system-specific genes tends to be conserved between such distance vertebrates as mammals and fishes. Also with a modular approach, I studied patterns of developmental constraints on transcriptome evolution. I showed that none of the two commonly accepted models of the evolution of embryonic development (``evo-devo'') are exclusively valid. In particular, I found that the conservation of the sequences of regulatory regions is highest during mid-development of zebrafish, and thus it supports the ``hourglass model''. In contrast, events of gene duplication and new gene introduction are most rare in early development, which supports the ``early conservation model''. In addition to the biological insights on transcriptome evolution, I have also discussed in detail the advantages of modular approaches in large-scale data analysis. Moreover, I re-analyzed several studies (published in high-ranking journals), and showed that their conclusions do not hold out under a detailed analysis. This demonstrates that complex analysis of high-throughput data requires a co-operation between biologists, bioinformaticians, and statisticians.

Contribution of the Global Regulator Gene gacA to Persistence and Dissemination of Pseudomonas fluorescens Biocontrol Strain CHA0 Introduced into Soil Microcosms.

Structural and regulatory genes involved in the synthesis of antimicrobial metabolites are essential for the biocontrol activity of fluorescent pseudomonads and, in principle, amenable to genetic engineering for strain improvement. An eventual large-scale release of such bacteria raises the question of whether such genes also contribute to the persistence and dissemination of the bacteria in soil ecosystems. Pseudomonas fluorescens wild-type strain CHA0 protects plants against a variety of fungal diseases and produces several antimicrobial metabolites. The regulatory gene gacA globally controls antibiotic production and is crucial for disease suppression in CHA0. This gene also regulates the production of extracellular protease and phospholipase. The contribution of gacA to survival and vertical translocation of CHA0 in soil microcosms of increasing complexity was studied in coinoculation experiments with the wild type and a gacA mutant which lacks antibiotics and some exoenzymes. Both strains were marked with spontaneous resistance to rifampin. In a closed system with sterile soil, strain CHA0 and the gacA mutant multiplied for several weeks, whereas these strains declined exponentially in nonsterile soil of different Swiss origins. The gacA mutant was less persistent in nonrhizosphere raw soil than was the wild type, but no competitive disadvantage when colonizing the rhizosphere and roots of wheat was found in the particular soil type and during the period studied. Vertical translocation was assessed after strains had been applied to undisturbed, long (60-cm) or short (20-cm) soil columns, both planted with wheat. A smaller number of cells of the gacA mutant than of the wild type were detected in the percolated water and in different depths of the soil column. Single-strain inoculation gave similar results in all microcosms tested. We conclude that mutation in a single regulatory gene involved in antibiotic and exoenzyme synthesis can affect the survival of P. fluorescens more profoundly in unplanted soil than in the rhizosphere.

Application of text-mining for updating protein post-translational modification annotation in UniProtKB.

BACKGROUND: The annotation of protein post-translational modifications (PTMs) is an important task of UniProtKB curators and, with continuing improvements in experimental methodology, an ever greater number of articles are being published on this topic. To help curators cope with this growing body of information we have developed a system which extracts information from the scientific literature for the most frequently annotated PTMs in UniProtKB. RESULTS: The procedure uses a pattern-matching and rule-based approach to extract sentences with information on the type and site of modification. A ranked list of protein candidates for the modification is also provided. For PTM extraction, precision varies from 57% to 94%, and recall from 75% to 95%, according to the type of modification. The procedure was used to track new publications on PTMs and to recover potential supporting evidence for phosphorylation sites annotated based on the results of large scale proteomics experiments. CONCLUSIONS: The information retrieval and extraction method we have developed in this study forms the basis of a simple tool for the manual curation of protein post-translational modifications in UniProtKB/Swiss-Prot. Our work demonstrates that even simple text-mining tools can be effectively adapted for database curation tasks, providing that a thorough understanding of the working process and requirements are first obtained. This system can be accessed at http://eagl.unige.ch/PTM/.

Integrated application of geochemical and geophysical methods for hydrogeological impact assessment for tunneling in fractured rock

The interaction of tunneling with groundwater is a problem both from an environmental and an engineering point of view. In fact, tunnel drilling may cause a drawdown of piezometric levels and water inflows into tunnels that may cause problems during excavation of the tunnel. While the influence of tunneling on the regional groundwater systems may be adequately predicted in porous media using analytical solutions, such an approach is difficult to apply in fractured rocks. Numerical solutions are preferable and various conceptual approaches have been proposed to describe and model groundwater flow through fractured rock masses, ranging from equivalent continuum models to discrete fracture network simulation models. However, their application needs many preliminary investigations on the behavior of the groundwater system based on hydrochemical and structural data. To study large scale flow systems in fractured rocks of mountainous terrains, a comprehensive study was conducted in southern Switzerland, using as case studies two infrastructures actually under construction: (i) the Monte Ceneri base railway tunnel (Ticino), and the (ii) San Fedele highway tunnel (Roveredo, Graubiinden). The chosen approach in this study combines the temporal and spatial variation of geochemical and geophysical measurements. About 60 localities from both surface and underlying tunnels were temporarily and spatially monitored during more than one year. At first, the project was focused on the collection of hydrochemical and structural data. A number of springs, selected in the area surrounding the infrastructures, were monitored for discharge, electric conductivity, pH, and temperature. Water samples (springs, tunnel inflows and rains) were taken for isotopic analysis; in particular the stable isotope composition (δ2Η, δ180 values) can reflect the origin of the water, because of spatial (recharge altitude, topography, etc.) and temporal (seasonal) effects on precipitation which in turn strongly influence the isotopic composition of groundwater. Tunnel inflows in the accessible parts of the tunnels were also sampled and, if possible, monitored with time. Noble-gas concentrations and their isotope ratios were used in selected locations to better understand the origin and the circulation of the groundwater. In addition, electrical resistivity and VLF-type electromagnetic surveys were performed to identify water bearing fractures and/or weathered areas that could be intersected at depth during tunnel construction. The main goal of this work was to demonstrate that these hydrogeological data and geophysical methods, combined with structural and hydrogeological information, can be successfully used in order to develop hydrogeological conceptual models of the groundwater flow in regions to be exploited for tunnels. The main results of the project are: (i) to have successfully tested the application of electrical resistivity and VLF-electromagnetic surveys to asses water-bearing zones during tunnel drilling; (ii) to have verified the usefulness of noble gas, major ion and stable isotope compositions as proxies for the detection of faults and to understand the origin of the groundwater and its flow regimes (direct rain water infiltration or groundwater of long residence time); and (iii) to have convincingly tested the combined application of a geochemical and geophysical approach to assess and predict the vulnerability of springs to tunnel drilling. - L'interférence entre eaux souterraines et des tunnels pose des problèmes environnementaux et de génie civile. En fait, la construction d'un tunnel peut faire abaisser le niveau des nappes piézométriques et faire infiltrer de l'eau dans le tunnel et ainsi créer des problème pendant l'excavation. Alors que l'influence de la construction d'un tunnel sur la circulation régionale de l'eau souterraine dans des milieux poreux peut être prédite relativement facilement par des solution analytiques de modèles, ceci devient difficile dans des milieux fissurés. Dans ce cas-là, des solutions numériques sont préférables et plusieurs approches conceptuelles ont été proposées pour décrire et modéliser la circulation d'eau souterraine à travers les roches fissurées, en allant de modèles d'équivalence continue à des modèles de simulation de réseaux de fissures discrètes. Par contre, leur application demande des investigations importantes concernant le comportement du système d'eau souterraine basées sur des données hydrochimiques et structurales. Dans le but d'étudier des grands systèmes de circulation d'eau souterraine dans une région de montagnes, une étude complète a été fait en Suisse italienne, basée sur deux grandes infrastructures actuellement en construction: (i) Le tunnel ferroviaire de base du Monte Ceneri (Tessin) et (ii) le tunnel routière de San Fedele (Roveredo, Grisons). L'approche choisie dans cette étude est la combinaison de variations temporelles et spatiales des mesures géochimiques et géophysiques. Environs 60 localités situées à la surface ainsi que dans les tunnels soujacents ont été suiviès du point de vue temporel et spatial pendant plus de un an. Dans un premier temps le projet se focalisait sur la collecte de données hydrochimiques et structurales. Un certain nombre de sources, sélectionnées dans les environs des infrastructures étudiées ont été suivies pour le débit, la conductivité électrique, le pH et la température. De l'eau (sources, infiltration d'eau de tunnel et pluie) a été échantillonnés pour des analyses isotopiques; ce sont surtout les isotopes stables (δ2Η, δ180) qui peuvent indiquer l'origine d'une eaux, à cause de la dépendance d'effets spatiaux (altitude de recharge, topographie etc.) ainsi que temporels (saisonaux) sur les précipitations météoriques , qui de suite influencent ainsi la composition isotopique de l'eau souterraine. Les infiltrations d'eau dans les tunnels dans les parties accessibles ont également été échantillonnées et si possible suivies au cours du temps. La concentration de gaz nobles et leurs rapports isotopiques ont également été utilisées pour quelques localités pour mieux comprendre l'origine et la circulation de l'eau souterraine. En plus, des campagnes de mesures de la résistivité électrique et électromagnétique de type VLF ont été menées afin d'identifier des zone de fractures ou d'altération qui pourraient interférer avec les tunnels en profondeur pendant la construction. Le but principal de cette étude était de démontrer que ces données hydrogéologiques et géophysiques peuvent être utilisées avec succès pour développer des modèles hydrogéologiques conceptionels de tunnels. Les résultats principaux de ce travail sont : i) d'avoir testé avec succès l'application de méthodes de la tomographie électrique et des campagnes de mesures électromagnétiques de type VLF afin de trouver des zones riches en eau pendant l'excavation d'un tunnel ; ii) d'avoir prouvé l'utilité des gaz nobles, des analyses ioniques et d'isotopes stables pour déterminer l'origine de l'eau infiltrée (de la pluie par le haut ou ascendant de l'eau remontant des profondeurs) et leur flux et pour déterminer la position de failles ; et iii) d'avoir testé d'une manière convainquant l'application combinée de méthodes géochimiques et géophysiques pour juger et prédire la vulnérabilité de sources lors de la construction de tunnels. - L'interazione dei tunnel con il circuito idrico sotterraneo costituisce un problema sia dal punto di vista ambientale che ingegneristico. Lo scavo di un tunnel puô infatti causare abbassamenti dei livelli piezometrici, inoltre le venute d'acqua in galleria sono un notevole problema sia in fase costruttiva che di esercizio. Nel caso di acquiferi in materiale sciolto, l'influenza dello scavo di un tunnel sul circuito idrico sotterraneo, in genere, puô essere adeguatamente predetta attraverso l'applicazione di soluzioni analitiche; al contrario un approccio di questo tipo appare inadeguato nel caso di scavo in roccia. Per gli ammassi rocciosi fratturati sono piuttosto preferibili soluzioni numeriche e, a tal proposito, sono stati proposti diversi approcci concettuali; nella fattispecie l'ammasso roccioso puô essere modellato come un mezzo discreto ο continuo équivalente. Tuttavia, una corretta applicazione di qualsiasi modello numerico richiede necessariamente indagini preliminari sul comportamento del sistema idrico sotterraneo basate su dati idrogeochimici e geologico strutturali. Per approfondire il tema dell'idrogeologia in ammassi rocciosi fratturati tipici di ambienti montani, è stato condotto uno studio multidisciplinare nel sud della Svizzera sfruttando come casi studio due infrastrutture attualmente in costruzione: (i) il tunnel di base del Monte Ceneri (canton Ticino) e (ii) il tunnel autostradale di San Fedele (Roveredo, canton Grigioni). L'approccio di studio scelto ha cercato di integrare misure idrogeochimiche sulla qualité e quantité delle acque e indagini geofisiche. Nella fattispecie sono state campionate le acque in circa 60 punti spazialmente distribuiti sia in superficie che in sotterraneo; laddove possibile il monitoraggio si è temporalmente prolungato per più di un anno. In una prima fase, il progetto di ricerca si è concentrato sull'acquisizione dati. Diverse sorgenti, selezionate nelle aree di possibile influenza attorno allé infrastrutture esaminate, sono state monitorate per quel che concerne i parametri fisico-chimici: portata, conduttività elettrica, pH e temperatura. Campioni d'acqua sono stati prelevati mensilmente su sorgenti, venute d'acqua e precipitazioni, per analisi isotopiche; nella fattispecie, la composizione in isotopi stabili (δ2Η, δ180) tende a riflettere l'origine delle acque, in quanto, variazioni sia spaziali (altitudine di ricarica, topografia, etc.) che temporali (variazioni stagionali) della composizione isotopica delle precipitazioni influenzano anche le acque sotterranee. Laddove possibile, sono state campionate le venute d'acqua in galleria sia puntualmente che al variare del tempo. Le concentrazioni dei gas nobili disciolti nell'acqua e i loro rapporti isotopici sono stati altresi utilizzati in alcuni casi specifici per meglio spiegare l'origine delle acque e le tipologie di circuiti idrici sotterranei. Inoltre, diverse indagini geofisiche di resistività elettrica ed elettromagnetiche a bassissima frequenza (VLF) sono state condotte al fine di individuare le acque sotterranee circolanti attraverso fratture dell'ammasso roccioso. Principale obiettivo di questo lavoro è stato dimostrare come misure idrogeochimiche ed indagini geofisiche possano essere integrate alio scopo di sviluppare opportuni modelli idrogeologici concettuali utili per lo scavo di opere sotterranee. I principali risultati ottenuti al termine di questa ricerca sono stati: (i) aver testato con successo indagini geofisiche (ERT e VLF-EM) per l'individuazione di acque sotterranee circolanti attraverso fratture dell'ammasso roccioso e che possano essere causa di venute d'acqua in galleria durante lo scavo di tunnel; (ii) aver provato l'utilità di analisi su gas nobili, ioni maggiori e isotopi stabili per l'individuazione di faglie e per comprendere l'origine delle acque sotterranee (acque di recente infiltrazione ο provenienti da circolazioni profonde); (iii) aver testato in maniera convincente l'integrazione delle indagini geofisiche e di misure geochimiche per la valutazione della vulnérabilité delle sorgenti durante lo scavo di nuovi tunnel. - "La NLFA (Nouvelle Ligne Ferroviaire à travers les Alpes) axe du Saint-Gothard est le plus important projet de construction de Suisse. En bâtissant la nouvelle ligne du Saint-Gothard, la Suisse réalise un des plus grands projets de protection de l'environnement d'Europe". Cette phrase, qu'on lit comme présentation du projet Alptransit est particulièrement éloquente pour expliquer l'utilité des nouvelles lignes ferroviaires transeuropéens pour le développement durable. Toutefois, comme toutes grandes infrastructures, la construction de nouveaux tunnels ont des impacts inévitables sur l'environnement. En particulier, le possible drainage des eaux souterraines réalisées par le tunnel peut provoquer un abaissement du niveau des nappes piézométriques. De plus, l'écoulement de l'eau à l'intérieur du tunnel, conduit souvent à des problèmes d'ingénierie. Par exemple, d'importantes infiltrations d'eau dans le tunnel peuvent compliquer les phases d'excavation, provoquant un retard dans l'avancement et dans le pire des cas, peuvent mettre en danger la sécurité des travailleurs. Enfin, l'infiltration d'eau peut être un gros problème pendant le fonctionnement du tunnel. Du point de vue de la science, avoir accès à des infrastructures souterraines représente une occasion unique d'obtenir des informations géologiques en profondeur et pour échantillonner des eaux autrement inaccessibles. Dans ce travail, nous avons utilisé une approche pluridisciplinaire qui intègre des mesures d'étude hydrogéochimiques effectués sur les eaux de surface et des investigations géophysiques indirects, tels que la tomographic de résistivité électrique (TRE) et les mesures électromagnétiques de type VLF. L'étude complète a été fait en Suisse italienne, basée sur deux grandes infrastructures actuellement en construction, qui sont le tunnel ferroviaire de base du Monte Ceneri, une partie du susmentionné projet Alptransit, situé entièrement dans le canton Tessin, et le tunnel routière de San Fedele, situé a Roveredo dans le canton des Grisons. Le principal objectif était de montrer comment il était possible d'intégrer les deux approches, géophysiques et géochimiques, afin de répondre à la question de ce que pourraient être les effets possibles dû au drainage causés par les travaux souterrains. L'accès aux galeries ci-dessus a permis une validation adéquate des enquêtes menées confirmant, dans chaque cas, les hypothèses proposées. A cette fin, nous avons fait environ 50 profils géophysiques (28 imageries électrique bidimensionnels et 23 électromagnétiques) dans les zones de possible influence par le tunnel, dans le but d'identifier les fractures et les discontinuités dans lesquelles l'eau souterraine peut circuler. De plus, des eaux ont été échantillonnés dans 60 localités situées la surface ainsi que dans les tunnels subjacents, le suivi mensuelle a duré plus d'un an. Nous avons mesurés tous les principaux paramètres physiques et chimiques: débit, conductivité électrique, pH et température. De plus, des échantillons d'eaux ont été prélevés pour l'analyse mensuelle des isotopes stables de l'hydrogène et de l'oxygène (δ2Η, δ180). Avec ces analyses, ainsi que par la mesure des concentrations des gaz rares dissous dans les eaux et de leurs rapports isotopiques que nous avons effectués dans certains cas spécifiques, il était possible d'expliquer l'origine des différents eaux souterraines, les divers modes de recharge des nappes souterraines, la présence de possible phénomènes de mélange et, en général, de mieux expliquer les circulations d'eaux dans le sous-sol. Le travail, même en constituant qu'une réponse partielle à une question très complexe, a permis d'atteindre certains importants objectifs. D'abord, nous avons testé avec succès l'applicabilité des méthodes géophysiques indirectes (TRE et électromagnétiques de type VLF) pour prédire la présence d'eaux souterraines dans le sous-sol des massifs rocheux. De plus, nous avons démontré l'utilité de l'analyse des gaz rares, des isotopes stables et de l'analyses des ions majeurs pour la détection de failles et pour comprendre l'origine des eaux souterraines (eau de pluie par le haut ou eau remontant des profondeurs). En conclusion, avec cette recherche, on a montré que l'intégration des ces informations (géophysiques et géochimiques) permet le développement de modèles conceptuels appropriés, qui permettant d'expliquer comment l'eau souterraine circule. Ces modèles permettent de prévoir les infiltrations d'eau dans les tunnels et de prédire la vulnérabilité de sources et des autres ressources en eau lors de construction de tunnels.

Optimization of Snow Drifting Mitigation and Control Methods for Iowa Conditions Part II, TR-626, 2015

Blowing and drifting of snow is a major concern for transportation efficiency and road safety in regions where their development is common. One common way to mitigate snow drift on roadways is to install plastic snow fences. Correct design of snow fences is critical for road safety and maintaining the roads open during winter in the US Midwest and other states affected by large snow events during the winter season and to maintain costs related to accumulation of snow on the roads and repair of roads to minimum levels. Of critical importance for road safety is the protection against snow drifting in regions with narrow rights of way, where standard fences cannot be deployed at the recommended distance from the road. Designing snow fences requires sound engineering judgment and a thorough evaluation of the potential for snow blowing and drifting at the construction site. The evaluation includes site-specific design parameters typically obtained with semi-empirical relations characterizing the local transport conditions. Among the critical parameters involved in fence design and assessment of their post-construction efficiency is the quantification of the snow accumulation at fence sites. The present study proposes a joint experimental and numerical approach to monitor snow deposits around snow fences, quantitatively estimate snow deposits in the field, asses the efficiency and improve the design of snow fences. Snow deposit profiles were mapped using GPS based real-time kinematic surveys (RTK) conducted at the monitored field site during and after snow storms. The monitored site allowed testing different snow fence designs under close to identical conditions over four winter seasons. The study also discusses the detailed monitoring system and analysis of weather forecast and meteorological conditions at the monitored sites. A main goal of the present study was to assess the performance of lightweight plastic snow fences with a lower porosity than the typical 50% porosity used in standard designs of such fences. The field data collected during the first winter was used to identify the best design for snow fences with a porosity of 50%. Flow fields obtained from numerical simulations showed that the fence design that worked the best during the first winter induced the formation of an elongated area of small velocity magnitude close to the ground. This information was used to identify other candidates for optimum design of fences with a lower porosity. Two of the designs with a fence porosity of 30% that were found to perform well based on results of numerical simulations were tested in the field during the second winter along with the best performing design for fences with a porosity of 50%. Field data showed that the length of the snow deposit away from the fence was reduced by about 30% for the two proposed lower-porosity (30%) fence designs compared to the best design identified for fences with a porosity of 50%. Moreover, one of the lower-porosity designs tested in the field showed no significant snow deposition within the bottom gap region beneath the fence. Thus, a major outcome of this study is to recommend using plastic snow fences with a porosity of 30%. It is expected that this lower-porosity design will continue to work well for even more severe snow events or for successive snow events occurring during the same winter. The approach advocated in the present study allowed making general recommendations for optimizing the design of lower-porosity plastic snow fences. This approach can be extended to improve the design of other types of snow fences. Some preliminary work for living snow fences is also discussed. Another major contribution of this study is to propose, develop protocols and test a novel technique based on close range photogrammetry (CRP) to quantify the snow deposits trapped snow fences. As image data can be acquired continuously, the time evolution of the volume of snow retained by a snow fence during a storm or during a whole winter season can, in principle, be obtained. Moreover, CRP is a non-intrusive method that eliminates the need to perform man-made measurements during the storms, which are difficult and sometimes dangerous to perform. Presently, there is lots of empiricism in the design of snow fences due to lack of data on fence storage capacity on how snow deposits change with the fence design and snow storm characteristics and in the estimation of the main parameters used by the state DOTs to design snow fences at a given site. The availability of such information from CRP measurements should provide critical data for the evaluation of the performance of a certain snow fence design that is tested by the IDOT. As part of the present study, the novel CRP method is tested at several sites. The present study also discusses some attempts and preliminary work to determine the snow relocation coefficient which is one of the main variables that has to be estimated by IDOT engineers when using the standard snow fence design software (Snow Drift Profiler, Tabler, 2006). Our analysis showed that standard empirical formulas did not produce reasonable values when applied at the Iowa test sites monitored as part of the present study and that simple methods to estimate this variable are not reliable. The present study makes recommendations for the development of a new methodology based on Large Scale Particle Image Velocimetry that can directly measure the snow drift fluxes and the amount of snow relocated by the fence.

Simulated-annealing-based conditional simulation for the local-scale characterization of heterogeneous aquifers

Simulated-annealing-based conditional simulations provide a flexible means of quantitatively integrating diverse types of subsurface data. Although such techniques are being increasingly used in hydrocarbon reservoir characterization studies, their potential in environmental, engineering and hydrological investigations is still largely unexploited. Here, we introduce a novel simulated annealing (SA) algorithm geared towards the integration of high-resolution geophysical and hydrological data which, compared to more conventional approaches, provides significant advancements in the way that large-scale structural information in the geophysical data is accounted for. Model perturbations in the annealing procedure are made by drawing from a probability distribution for the target parameter conditioned to the geophysical data. This is the only place where geophysical information is utilized in our algorithm, which is in marked contrast to other approaches where model perturbations are made through the swapping of values in the simulation grid and agreement with soft data is enforced through a correlation coefficient constraint. Another major feature of our algorithm is the way in which available geostatistical information is utilized. Instead of constraining realizations to match a parametric target covariance model over a wide range of spatial lags, we constrain the realizations only at smaller lags where the available geophysical data cannot provide enough information. Thus we allow the larger-scale subsurface features resolved by the geophysical data to have much more due control on the output realizations. Further, since the only component of the SA objective function required in our approach is a covariance constraint at small lags, our method has improved convergence and computational efficiency over more traditional methods. Here, we present the results of applying our algorithm to the integration of porosity log and tomographic crosshole georadar data to generate stochastic realizations of the local-scale porosity structure. Our procedure is first tested on a synthetic data set, and then applied to data collected at the Boise Hydrogeophysical Research Site.

Iowa's Renewable Energy and Infrastructure Impacts, TR-593, 2010

The federal government is aggressively promoting biofuels as an answer to global climate change and dependence on imported sources of energy. Iowa has quickly become a leader in the bioeconomy and wind energy production, but meeting the United States Department of Energy’s goal having 20% of U.S. transportation fuels come from biologically based sources by 2030 will require a dramatic increase in ethanol and biodiesel production and distribution. At the same time, much of Iowa’s rural transportation infrastructure is near or beyond its original design life. As Iowa’s rural roadway structures, pavements, and unpaved roadways become structurally deficient or functionally obsolete, public sector maintenance and rehabilitation costs rapidly increase. More importantly, costs to move all farm products will rapidly increase if infrastructure components are allowed to fail; longer hauls, slower turnaround times, and smaller loads result. When these results occur on a large scale, Iowa will start to lose its economic competitive edge in the rapidly developing bioeconomy. The primary objective of this study was to document the current physical and fiscal impacts of Iowa’s existing biofuels and wind power industries. A four-county cluster in north-central Iowa and a two-county cluster in southeast Iowa were identified through a local agency survey as having a large number of diverse facilities and were selected for the traffic and physical impact analysis. The research team investigated the large truck traffic patterns on Iowa’s secondary and local roads from 2002 to 2008 and associated those with the pavement condition and county maintenance expenditures. The impacts were quantified to the extent possible and visualized using geographic information system (GIS) tools. In addition, a traffic and fiscal assessment tool was developed to understand the impact of the development of the biofuels on Iowa’s secondary road system. Recommended changes in public policies relating to the local government and to the administration of those policies included standardizing the reporting and format of all county expenditures, conducting regular pavement evaluations on a county’s system, cooperating and communicating with cities (adjacent to a plant site), considering utilization of tax increment financing (TIF) districts as a short-term tool to produce revenues, and considering alternative ways to tax the industry.

Development of pharmaceutical care services in nursing homes: practice and research in a Swiss canton.

OBJECTIVE: The aim of this study was to assess the implementation process and economic impact of a new pharmaceutical care service provided since 2002 by pharmacists in Swiss nursing homes. SETTING: The setting was 42 nursing homes located in the canton of Fribourg, Switzerland under the responsibility of 22 pharmacists. METHOD: We developed different facilitators, such as a monitoring system, a coaching program, and a research project, to help pharmacists change their practice and to improve implementation of this new service. We evaluated the implementation rate of the service delivered in nursing homes. We assessed the economic impact of the service since its start in 2002 using statistical evaluation (Chow test) with retrospective analysis of the annual drug costs per resident over an 8-year period (1998-2005). MAIN OUTCOME MEASURES: The description of the facilitators and their implications in implementation of the service; the economic impact of the service since its start in 2002. RESULTS: In 2005, after a 4-year implementation period supported by the introduction of facilitators of practice change, all 42 nursing homes (2,214 residents) had implemented the pharmaceutical care service. The annual drug costs per resident decreased by about 16.4% between 2002 and 2005; this change proved to be highly significant. The performance of the pharmacists continuously improved using a specific coaching program including an annual expert comparative report, working groups, interdisciplinary continuing education symposia, and individual feedback. This research project also determined priorities to develop practice guidelines to prevent drug-related problems in nursing homes, especially in relation to the use of psychotropic drugs. CONCLUSION: The pharmaceutical care service was fully and successfully implemented in Fribourg's nursing homes within a period of 4 years. These findings highlight the importance of facilitators designed to assist pharmacists in the implementation of practice changes. The economic impact was confirmed on a large scale, and priorities for clinical and pharmacoeconomic research were identified in order to continue to improve the quality of integrated care for the elderly.

Structural, metamorphic and geochronological relations between the Zanskar Shear Zone and the Miyar Shear Zone (NW Indian Himalaya): Evidence for two distinct tectonic structures and implications for the evolution of the High Himalayan Crystalline of Zanskar

The geologic structures and metamorphic zonation of the northwestern Indian Himalaya contrast significantly with those in the central and eastern parts of the range, where the high-grade metamorphic rocks of the High Himalayan Crystalline (HHC) thrust southward over the weakly metamorphosed sediments of the Lesser Himalaya along the Main Central Thrust (MCT). Indeed, the hanging wall of the MCT in the NW Himalaya mainly consists of the greenschist facies metasediments of the Chamba zone, whereas HHC high-grade rocks are exposed more internally in the range as a large-scale dome called the Gianbul dome. This Gianbul dome is bounded by two oppositely directed shear zones, the NE-dipping Zanskar Shear Zone (ZSZ) on the northern flank and the SW-dipping Miyar Shear Zone (MSZ) on the southern limb. Current models for the emplacement of the HHC in NW India as a dome structure differ mainly in terms of the roles played by both the ZSZ and the MSZ during the tectonothermal evolution of the HHC. In both the channel flow model and wedge extrusion model, the ZSZ acts as a backstop normal fault along which the high-grade metamorphic rocks of the HHC of Zanskar are exhumed. In contrast, the recently proposed tectonic wedging model argues that the ZSZ and the MSZ correspond to one single detachment system that operates as a subhorizontal backthrust off of the MCT. Thus, the kinematic evolution of the two shear zones, the ZSZ and the MSZ, and their structural, metamorphic and chronological relations appear to be diagnostic features for discriminating the different models. In this paper, structural, metamorphic and geochronological data demonstrate that the MSZ and the ZSZ experienced two distinct kinematic evolutions. As such, the data presented in this paper rule out the hypothesis that the MSZ and the ZSZ constitute one single detachment system, as postulated by the tectonic wedging model. Structural, metamorphic and geochronological data are used to present an alternative tectonic model for the large-scale doming in the NW Indian Himalaya involving early NE-directed tectonics, weakness in the upper crust, reduced erosion at the orogenic front and rapid exhumation along both the ZSZ and the MSZ.

Implicit methods for qualitative modeling of gene regulatory networks.

Advancements in high-throughput technologies to measure increasingly complex biological phenomena at the genomic level are rapidly changing the face of biological research from the single-gene single-protein experimental approach to studying the behavior of a gene in the context of the entire genome (and proteome). This shift in research methodologies has resulted in a new field of network biology that deals with modeling cellular behavior in terms of network structures such as signaling pathways and gene regulatory networks. In these networks, different biological entities such as genes, proteins, and metabolites interact with each other, giving rise to a dynamical system. Even though there exists a mature field of dynamical systems theory to model such network structures, some technical challenges are unique to biology such as the inability to measure precise kinetic information on gene-gene or gene-protein interactions and the need to model increasingly large networks comprising thousands of nodes. These challenges have renewed interest in developing new computational techniques for modeling complex biological systems. This chapter presents a modeling framework based on Boolean algebra and finite-state machines that are reminiscent of the approach used for digital circuit synthesis and simulation in the field of very-large-scale integration (VLSI). The proposed formalism enables a common mathematical framework to develop computational techniques for modeling different aspects of the regulatory networks such as steady-state behavior, stochasticity, and gene perturbation experiments.