Review of Cold In-Place Recycled Asphalt Concrete Projects, HR-392, 1998

Highway Research Project HR-392 was undertaken to evaluate cold in-place asphalt recycled (CIR) projects in the State of Iowa. The research involved assessment of performance levels, investigation of factors that most influence pavement performance and economy, and development of guidelines for CIR project selection. The performance was evaluated in two ways: Pavement Condition Indices (PCI, U.S. Corps of Engineers) were calculated and overall ratings were given on ride and appearance. A regression analysis was extrapolated to predict the future service life of CIR roads. The results were that CIR roads within the State of Iowa, with less than 2000 annual average daily traffic (AADT), have an average predicted service life of fifteen to twenty-six years. Subgrade stability problems can prevent a CIR project from being successfully constructed. A series of Dynamic Cone Penetrometer (DCP) tests were conducted on a CIR project that experienced varying levels of subgrade failure during construction. Based on this case study, and supporting data, it was determined that the DCP test can be used to evaluate subgrades that have insufficient stability for recycling. Overall, CIR roads in Iowa are performing well. It appears that the development of transverse cracking has been retarded and little rutting has occurred. Contracting agencies must pay special attention to the subgrade conditions during project selection. Because of its performance, CIR is a recommended method to be considered for rehabilitating aged low volume (<2000 AADT) asphalt concrete roads in Iowa.

Parallel evolution of facial stripe patterns in the Neolamprologus brichardi/pulcher species complex endemic to Lake Tanganyika.

Colour pattern diversity can be due to random processes or to natural or sexual selection. Consequently, similarities in colour patterns are not always correlated with common ancestry, but may result from convergent evolution under shared selection pressures or drift. Neolamprologus brichardi and Neolamprologus pulcher have been described as two distinct species based on differences in the arrangement of two dark bars on the operculum. Our study uses DNA sequences of the mitochondrial control region to show that relatedness of haplotypes disagrees with species assignment based on head colour pattern. This suggests repeated parallel evolution of particular stripe patterns. The complete lack of shared haplotypes between populations of the same or different phenotypes reflects strong philopatric behaviour, possibly induced by the cooperative breeding mode in which offspring remain in their natal territory and serve as helpers until they disperse to nearby territories or take over a breeding position. Concordant phylogeographic patterns between N. brichardi/N. pulcher populations and other rock-dwelling cichlids suggest that the same colonization routes have been taken by sympatric species and that these routes were affected by lake level fluctuations in the past.

Regional deterministic characterization of fracture networks and its application to GIS-based rock fall risk assessment

The study investigates the possibility to incorporate fracture intensity and block geometry as spatially continuous parameters in GIS-based systems. For this purpose, a deterministic method has been implemented to estimate block size (Bloc3D) and joint frequency (COLTOP). In addition to measuring the block size, the Bloc3D Method provides a 3D representation of the shape of individual blocks. These two methods were applied using field measurements (joint set orientation and spacing) performed over a large field area, in the Swiss Alps. This area is characterized by a complex geology, a number of different rock masses and varying degrees of metamorphism. The spatial variability of the parameters was evaluated with regard to lithology and major faults. A model incorporating these measurements and observations into a GIS system to assess the risk associated with rock falls is proposed. The analysis concludes with a discussion on the feasibility of such an application in regularly and irregularly jointed rock masses, with persistent and impersistent discontinuities.

Urban Governance und nachhaltige Quartiere: Ein Beitrag zur Förderung einer dauerhaft nachhaltigen Stadtentwicklung

Seit den 1990er Jahren werden zunehmend nachhaltige Quartiere realisiert. Dabei besteht häufig eine beachtliche Diskrepanz zwischen den Zielen, die von den beteiligten Akteuren angestrebt werden, deren Umsetzung (Realisierungsphase) und deren Erhalt auf Dauer (Nutzungsphase). Es stellt sich folglich die Frage, auf welche Weise die Projektqualität im Sinne einer nachhaltigen Quartiersentwicklung verbessert werden kann. Diese Projekte sind jedoch enorm komplex aufgrund der großen Interdisziplinarität und Interdependenz ihrer Ziele sowie der vielschichtigen Akteursstrukturen. Sie stellen daher be-sonders hohe Anforderungen an die Projektsteuerung. Das konkrete Ziel dieser Arbeit besteht darin, die Bedeutung einer Prozesssteuerung im Sinne von Urban Governance zur Realisierung und zum Erhalt nachhaltiger Quartiere zu untersuchen. Damit soll einen Beitrag zur Förderung einer nachhalti-gen Stadtentwicklung geleistet werden. Die Arbeit stützt sich auf ein umfassendes theoretisches Fundament zum Thema Governance, wobei die relevanten Elemente für den Kontext nachhaltiger Quartiere herausgearbeitet werden. Die Hypothesen prüfen die Bedeutung der Schlüsselcharakteristika von Urban Governance (Kooperation, Partizipation, Verhandlungen) für die Projektqualität während der Realisierungs- und Nutzungsphase. Eine erste empirische Untersuchung wurde an zwanzig europäischen nachhaltigen Modellquartieren vorgenommen. Stärken und Schwächen aus der Perspektive der Nachhaltigkeit werden analysiert, deren Ursachen identifiziert und Handlungsoptio-nen aufgezeigt. Die Erkenntnisse zeigen die Notwendigkeit einer Verbesserung der Projektsteuerung während der Realisierungs- und der Nutzungsphase. Auf der Grundlage dieser Erkenntnisse wird ein umfassender Ansatz zur empirischen Untersuchung von Urban Governance im Kontext nachhaltiger Quartiere entwickelt. Dieser beruht auf dem akteurzentrierten Institutionalismus und den Merkmalen der Urban Governance. Anhand dieses Ansatzes wird mithilfe von Experteninterviews der Realisierungsprozess des nach-haltigen Quartiers Kronsberg (Hannover) analysiert. Betrachtet werden dabei die beteiligten Akteure und ihre Handlungso-rientierungen, die verwendeten Schlüsselinstrumente sowie aufgetretene Divergenzen zwischen Akteuren und deren Auswirkungen auf die Projekt- und Prozessqualität. Eine Vertiefung relevanter Themenfelder wird anhand der Fallstudie Neu-Oerlikon (Zürich) vorgenommen. Diese empirische Arbeit zeigt, dass eine Prozesssteuerung im Sinne von Urban Governance im Vergleich zu einer klassis-chen hierarchischen Steuerung eine notwendige aber nicht hinreichende Bedingung zur Verbesserung der Projektqualität nachhaltiger Quartiere darstellt. An konkreten Beispielen wird herausgearbeitet, dass der Mehrwert einer solchen Steuerung nur unter bestimmten Voraussetzungen erzielt werden kann: In manchen Situationen ist die Steuerungsform Kooperation und die Interaktionsform Verhandlung in ihrer Wirksamkeit zur Sicherung der Projektqualität begrenzt und hierarchische Interventionen sind notwendig. Nicht ein bestimmtes Steuerungsmodell per se ist geeignet, sondern es kommt auf den Ein-zelfall an: auf die Akteursstruktur, die individuellen und institutionellen Handlungsorientierungen der Akteure und deren Ver-haltensweisen, die Rahmenbedingungen und die Ausgestaltung des Urban Governance-Prozesses. Wenn die Spielregeln dieses Prozesses von den Akteuren nicht wirklich angenommen und gelebt werden, dominieren individuelle und institutio-nelle Akteursinteressen zu Lasten der Projektqualität. Ferner zeigen die Untersuchungen, dass die Partizipation der zukünftigen Quartiersnutzer in der Praxis häufig unzureichend ist. Dies führt zu Einbußen in der Projektqualität. Entscheidend ist auf jeden Fall, dass mindestens ein Akteur, in der Regel die öffentliche Hand, präsent ist, der die Definition anspruchsvoller Nachhaltigkeitsstandards, deren Umsetzung und deren Erhalt sichert sowie die notwendigen Rahmenbedingungen dafür schafft. Diese Arbeit belegt darüber hinaus, dass der Erhalt der Projektqualität während der Nutzungsphase (Faktor Zeit) bisher un-zureichend beachtet und in die Projektplanung einbezogen wird. Gerade dieser Aspekt bestimmt aber, ob das Quartier auch auf Dauer dem Nachhaltigkeitsanspruch gerecht werden kann! Tatsächlich handelt es sich um einen fortlaufenden Prozess, der nicht mit der Einweihung des Quartiers abgeschlossen ist. Vor diesem Hintergrund werden relevante Handlungsfelder beschrieben und die Notwendigkeit der langfristigen Fortsetzung einer Steuerung im Sinne von Urban Governance bzw. der Herausbildung einer Urban Governance-Kultur aufgezeigt. Aus den empirischen Erhebungen werden Erfolgs- und Risikofaktoren für Urban Governance-Prozesse während der Realisierungs- und der Nutzungsphase abgeleitet. Ferner werden bisher vernachlässigte Handlungsfelder (langfristiges Umwelt-management, ökologische Finanzierungsformen, urbane Landwirtschaft, Umweltkommunikation, etc.) eruiert. Die Berücksichtigung dieser Erkenntnisse ist unerlässlich für eine Verbesserung der Projektqualität nachhaltiger Quartiere. ---------------------------------------------- Gouvernance urbaine et quartiers durables: Entre intensions et mise en oeuvre --- Résumé --- Depuis les années 90, la thématique des quartiers durables a gagné en importance, même si leur développement s'est avéré difficile. Le décalage entre les objectifs, leur mise en oeuvre et le projet tel qu'il est vécu par ses habitants est souvent important et nécessite d'être réduit. Un quartier durable est par nature un projet complexe, aux objectifs ambitieux situé à la croisée de multiples champs disciplinaires, mobilisant de nombreux acteurs aux intérêts divergents. De plus, chaque projet, du fait des ses spécificités, requiert un pilotage adapté. L'objectif principal de la recherche vise à analyser la nature du pilotage du processus de conception, de réalisation et d'exploitation des quartiers durables. Ses résultats ont pour ambition de contribuer à optimiser et promouvoir le développement urbain durable. Le fondement théorique de la recherche se base sur le concept de gouvernance urbaine, adapté au contexte particulier de la gouvernance des quartiers durables. La gouvernance urbaine, au sens où nous l'entendons, est un mode de pilotage basé sur la coopération entre les acteurs publics et privés. Les hypothèses centrales du travail testent la portée et les limites des caractéristiques-clefs de la gouvernance urbaine (coopération, participation, négociation), ainsi que l'importance de la notion de pérennité pour la qualité du projet. Dans un premier temps, nous avons analysé vingt quartiers durables modèles européens et identifié leurs atouts et leurs faiblesses en termes de durabilité, ainsi que leurs divers modes de pilotage. Les enseignements tirés de ces exemples révèlent la nécessité d'améliorer le pilotage des projets. Dans un deuxième temps, nous avons élaboré une grille d'analyse fine fondée sur l'approche institutionnelle des acteurs et les caractéristiques-clefs de la gouvernance urbaine. En nous appuyant sur cette grille, nous avons analysé le processus de conception et de réalisation du quartier durable de « Kronsberg » (Hanovre) à l'aide des éléments suivants : les acteurs (avec leurs intérêts et objectifs propres), les instruments d'aménagement du territoire, les modes de pilotage, les zones de divergence et de convergence entre les acteurs, ainsi que leurs impacts sur le processus et le projet. Dans un troisième temps, les hypothèses centrales ont été testées sur le quartier de « Neu-Oerlikon » (Zurich) afin d'approfondir et d'élargir les enseignements tirés de celui de « Kronsberg ». Les résultats des analyses mettent en évidence le fait qu'un pilotage de projet selon le modèle de la gouvernance urbaine est certes une condition nécessaire mais non suffisante pour améliorer la qualité du projet. De plus, la valeur ajoutée de la gouvernance urbaine n'est valable qu'à certaines conditions. En effet, la coopération et la négociation peuvent même, dans certaines situations, réduire la qualité du projet ! Le principal enseignement de la recherche révèle qu'il n'y a pas de mode de pilotage idéal, mais que la qualité d'un projet dépend d'une multitude de facteurs, tels que les constellations d'acteurs, leurs intérêts personnels et institutionnels, les conditions cadres et les « règles du jeu » de la gouvernance urbaine. Si les « règles du jeu » en particulier ne sont pas réellement appropriées par l'ensemble des acteurs, les intérêts et les comportements personnels ou institutionnels prédominent au détriment de la qualité du projet. De même, si la participation des futurs usagers à l'élaboration du projet de quartier durable n'est pas assurée, tant la qualité du projet que sa pérennité en pâtissent. Nous avons également constaté que la présence d'un acteur (en règle générale les autorités publiques) qui veille à la définition d'objectifs ambitieux en matière de développement durable et à leur application constitue un apport essentiel à la qualité du projet. En outre, la recherche met en évidence les carences dans le suivi et le maintien à long terme des qualités de durabilité de la phase d'exploitation des projets de quartiers durables analysés. Dans la phase d'exploitation, le degré de coopération diminue généralement et les modes de fonctionnement et de pilotage sectoriels se mettent en place au détriment de la qualité du projet. Cela confirme la nécessité de poursuivre le processus de pilotage selon le modèle de la gouvernance urbaine au-delà de la phase de réalisation des projets. La recherche précise les enjeux des champs d'action de la phase d'exploitation (domaine encore peu étudié) et démontre la pertinence du mode de pilotage préconisé. Enfin, les analyses permettent d'identifier des facteurs de réussite et de risque susceptibles d'influencer les systèmes de gouvernance urbaine, ainsi que les enjeux des domaines de la durabilité encore négligés (agriculture urbaine, gestion environnementale dans la durée, comportement des usagers, financement équitable, etc.). La prise en compte de ces enseignements est essentielle à l'amélioration de la gestion de futurs projets de quartiers durables. ---------------------------------------------- Urban Governance and Sustainable Neighbourhoods: A Contribution to a Lasting Sustainable Development --- Abstract --- Since the 1990s, sustainable neighbourhoods have become an increasingly important topic. However, their development has proven to be difficult. There is an often considerable gap, which must be reduced, between the initial goals, the way they are implemented and how the project is finally inhabited. A sustainable neighbourhood is inherently a complex project, with ambitious goals that lie at the intersection of multiple disciplines, involving numerous stakeholders with diverging interests. Moreover, each project, due to its specific characteristics, requires an adapted steering. The main goal of this research is to analyse the nature of the steering process during the planning, realisation and use of sustainable neighbourhoods. The results aim to contribute to the promotion of sustainable urban development. The theoretical foundation of this research is based on the concept of urban governance, adapted to the particular context of sustainable neighbourhoods. Urban governance is understood in this work, as a mode of project steering based on the cooperation between public and private stakeholders. The central hypotheses of this work test the importance and the limits of the key characteristics of urban governance (cooperation, participation, negotiation) as well as the importance of continuity for the project quality. To begin with, we surveyed and analysed twenty exemplary European sustainable neighbourhoods and identified their strengths and weaknesses in terms of sustainability, as well as their diverse steering modes. The lessons learned from these examples reveal the need to improve the projects' steering. Secondly we elaborated a detailed framework for analysis founded on stakeholder-centred institutionalism and the key characteristics of urban governance. By systematically applying this framework, we analysed the planning and implementation process of the sustainable neighbourhood "Kronsberg" (Hannover). Our focus was on the following dimensions: the stakeholders (with their particular interests and goals), the instruments of spatial planning, the steering modes, the points of divergence and convergence amongst the stakeholders, as well as their impacts on the process and on the project. The final step was to test the core hypotheses on the neighbourhood "Neu-Oerlikon" (Zürich) in order to broaden the lessons learned from "Kronsberg". The results of the analysis highlight the fact that an urban governance type project steering is certainly a necessary but insufficient condition to improve the project quality. Moreover, the added value of urban governance is only valid under certain conditions. In fact, cooperation and negotiation can even in certain situations reduce the project's quality! The main lesson of this research is that there is not an ideal steering mode, but rather that the quality of the project depends on numerous factors, such as the stakeholder constellation, their individual and institutional interests, the general conditions and the "rules of the game" of urban governance. If these "rules of the game" are not really appropriated by all stakeholders, individual and institutional interests and behaviours predominate at the expense of the project's quality. Likewise, if the future users' participation in the project development is insufficient, both the project's quality and its continuity suffer. We have also observed that the presence of a stakeholder (in general the public authorities) who ensures the definition of ambitious goals in terms of sustainable development and their implementation is crucial for the project's quality. Furthermore, this research highlights the deficiencies in the follow-up and long-term preservation of the sustainability qualities in the neighbourhood projects which we have analysed. In the use phase, the degree of cooperation generally diminishes. Attitudes and project management become more sectorial at the expense of the project's quality. This confirms the need to continue the steering process according to the principles of urban governance beyond the project's implementation phase. This research specifies the challenges that affect the use phase (a still neglected area) and shows the relevance of the recommended steering mode. Finally, the analyses also identify the success and risk factors that may influence urban-governance systems, as well as the challenges of still neglected fields of sustainability (urban agriculture, long-term environmental management, user behaviour, fair funding, etc.). Taking into account these outcomes is essential to improve the management of future sustainable-neighbourhood projects.

FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information.

Place branding : a conceptual and theoretical framework

Within the context of rising competition between territories, identity has become the most important element of recognition, differentiation and commodification in the communicative process within which cities, regions and countries position themselves. Geographical spaces thus compete in terms of this identity, which is then subjected to fierce comparison and competition (Nogué, 1999; Anholt, 2007a). The territorial brand thus entails the reinvention of places through a process of brand construction (branding) based on the promotion of the individual and collective identities of geographical spaces; these identities, in turn, are imbued with the intangible factors associated with their respective territorial identities.

The Learning Affect Monitor (LAM) - A computer-based system integrating quantitative and qualitative assessment of affective states in daily life.

The Learning Affect Monitor (LAM) is a new computer-based assessment system integrating basic dimensional evaluation and discrete description of affective states in daily life, based on an autonomous adapting system. Subjects evaluate their affective states according to a tridimensional space (valence and activation circumplex as well as global intensity) and then qualify it using up to 30 adjective descriptors chosen from a list. The system gradually adapts to the user, enabling the affect descriptors it presents to be increasingly relevant. An initial study with 51 subjects, using a 1 week time-sampling with 8 to 10 randomized signals per day, produced n = 2,813 records with good reliability measures (e.g., response rate of 88.8%, mean split-half reliability of .86), user acceptance, and usability. Multilevel analyses show circadian and hebdomadal patterns, and significant individual and situational variance components of the basic dimension evaluations. Validity analyses indicate sound assignment of qualitative affect descriptors in the bidimensional semantic space according to the circumplex model of basic affect dimensions. The LAM assessment module can be implemented on different platforms (palm, desk, mobile phone) and provides very rapid and meaningful data collection, preserving complex and interindividually comparable information in the domain of emotion and well-being.

Practical considerations for improving the productivity of mass spectrometry-based proteomics.

Mass spectrometry (MS) is currently the most sensitive and selective analytical technique for routine peptide and protein structure analysis. Top-down proteomics is based on tandem mass spectrometry (MS/ MS) of intact proteins, where multiply charged precursor ions are fragmented in the gas phase, typically by electron transfer or electron capture dissociation, to yield sequence-specific fragment ions. This approach is primarily used for the study of protein isoforms, including localization of post-translational modifications and identification of splice variants. Bottom-up proteomics is utilized for routine high-throughput protein identification and quantitation from complex biological samples. The proteins are first enzymatically digested into small (usually less than ca. 3 kDa) peptides, these are identified by MS or MS/MS, usually employing collisional activation techniques. To overcome the limitations of these approaches while combining their benefits, middle-down proteomics has recently emerged. Here, the proteins are digested into long (3-15 kDa) peptides via restricted proteolysis followed by the MS/MS analysis of the obtained digest. With advancements of high-resolution MS and allied techniques, routine implementation of the middle-down approach has been made possible. Herein, we present the liquid chromatography (LC)-MS/MS-based experimental design of our middle-down proteomic workflow coupled with post-LC supercharging.

El consum multipantalla. Estudi sobre l’ús de mitjans tradicionals i nous per part de nens, joves, adults i gent gran a Catalunya

Des de fa una dècada es parla de la convergència digital, que ha propiciat la conjunció de la informàtica amb els mitjans de comunicació i la interconnexió en xarxa. Actualment circulen amb facilitat suports vells i nous cada vegada més flexibles. La conseqüència per als usuaris és que avui disposen d’una varietat àmplia de continguts connectats permanentment en qualsevol lloc i en qualsevol moment, a través de diverses plataformes i amb una convivència rica i complexa. En aquest context, aquest article mostra les conclusions d’un estudi de camp sobre l’ús, el consum i les preferències de suports i de continguts de la comunicació digital per part de grups d’infants, de joves, d’adults i de gent gran a Catalunya.

Cellular immune responses against mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is known to have two main outcomes: latent infection (LTBI) where the pathogen is in a dormant form or active tuberculosis disease (TB), which is, most of the time, highly transmissible. Over one-third of the world's population asymptomatically harbours a latent form of Mtb with a 10% risk of disease reactivation. Efficient vaccine strategies remain unknown and the existing BCG vaccine is believed to protect against only some forms of TB (extra-pulmonary TB in children). Moreover, timely identification of TB remains complex with the actual diagnosis based on clinical observations associated to low efficient tests. Furthermore, current therapies are expensive, heavy and long for patients, and present lesser and lesser efficiency against new drug-resistant strains of Mtb. It is thus important to develop our knowledge on host -Mtb relationship to propose new vaccines, diagnosis tools and medications for the future. This thesis aims at improving our understanding of human immunology in the field of TB. All along this work, the same algorithm has been used and points towards the discovery of new correlates of protection through the comparison of T-cell immune responses in patients with LTBI or TB. We performed a comprehensive analysis of T-cell immune responses to Mtb using polychromatic flow cytometiy to study the functional profile of Μ/ό-specific CD4 Τ cells. We observed a polyfunctional profile in LTBI where CD4 Τ cells mainly co-produced IFN-γ, TNF-α and IL-2. In contrast, in TB, Mtó-specific CD4 Τ cells were mostly single TNF-a positive. Thus, analysis of the cytokine profiles was a strong immunological measure discriminating TB and LTBI. We next analyzed Thl7 cells. Mtò-specific Thl7 cells lacked immediate {i.e. ex vivo) IL-17A effector function in both LTBI and TB individuals. Moreover, they were also absent in bronchoalveolar lavages (BALs). Interestingly, we noticed that Mtb- specific Thl7 cells from LTBI but not from TB subjects acquired the ability to produce IL- 17A following Mtb-specific T-cell expansion. We finally performed a comprehensive characterization of Mfè-specific CD8 Τ cells that were detected in most (60%) TB patients and few (15%) LTBI subjects. We observed differences in the phenotype, the cytotoxicity and the proliferative capacities but not in the cytokine profile of Mtò-specific CD8 Τ cells between LTBI and TB. We concluded that the activity of Mtb infection (i.e. latent versus active) and the clinical presentation were associated to distinct profiles of Mtó-specific CD8 T-cell responses. To conclude, a multiparametric analysis including both CD4 and CD8 T-cell responses to Mtb lead to the development of a significantly improved diagnostic test discriminating between LTBI and TB. All together, these results provide new insights into the interaction between Mtb and the host immune response and expand upon our prior knowledge of tuberculosis. - L'infection par Mycobacterium tuberculosis peut résulter en une infection tuberculeuse latente et asymptomatique ou encore en une forme active et la plupart du temps contagieuse, la tuberculose. Un tiers de la population mondiale serait infectée de manière chronique avec 10 % de risques de développer la maladie durant la vie. Il n'existe actuellement aucun vaccin efficace, le BCG ne conférant qu'une protection partielle contre certaines formes extrapulmonaires de la maladie chez l'enfant. D'autre part, il n'existe pas de méthode diagnostique fiable et rapide, celle-ci se basant dans un premier temps sur l'analyse de la situation clinique des patients. Enfin, les thérapies actuelles sont couteuses et contraignantes pour les patients et tendent à ne plus être efficaces contre les souches émergentes de mycobactérie multi-résistantes. Aussi, il est important de bien comprendre la relation hôte-pathogène de manière à pouvoir proposer de nouveaux outils vaccinaux, diagnostiques et thérapeutiques. Ce manuscrit s'inscrit dans cette direction et vise à améliorer nos connaissances de la réponse immunitaire humaine dans le cadre de la tuberculose. Nous avons suivi un algorithme similaire tout au long des études proposées en comparant les réponses immunes des patients latents à celles des patients actifs, et ce, dans le but de mettre en évidence de potentiels corrélats de protection. Nous avons réalisé par cytométrie en flux une analyse du profil fonctionnel des cellules lymphocytaires CD4 dans la réponse au pathogène. Dans le cas de la tuberculose active, les cellules CD4 sécrètent majoritairement du TNF-α quand, au contraire, elles sécrètent à la fois du TNF-α, de l'IFN-γ et de l'IL-2 (poly-fonctionnalité) dans l'infection latente. Cette observation nous a permis de proposer un nouveau test diagnostique de la maladie active. Nous avons aussi étudié les cellules CD4 Thl7, impliquées dans la réponse immunitaire cellulaire contre les pathogènes extracellulaires et les champignons. Nous avons souligné une variation dans la production d'IL-17 entre infection latente et tuberculose active qui pourrait être impliquée dans la protection de l'individu contre le pathogène. D'autre part, ce manuscrit propose une caractérisation des cellules Τ CD8 dites cytotoxiques dans la tuberculose. Des divergences dans la fréquence des réponses observées, le phénotype mais aussi les capacités prolifératives et cytotoxiques ont pu être mises en évidence entre latence et tuberculose active. Ces observations soulignent le rôle important de ce groupe cellulaire dans l'évolution de la maladie et permettent de proposer une amélioration de l'outil diagnostic précédemment proposé et se basant à la fois sur le profil fonctionnel des cellules Τ CD4 ainsi que sur la présence potentielle d'une réponse CD8 spécifique au pathogène. Ces diverses études réalisées sur les cellules Τ humaines répondant spécifiquement à Mtb nous permettent de faire un pas supplémentaire dans la compréhension de notre réponse immunitaire face à ce pathogène particulièrement dangereux qui continue à l'heure actuelle à tuer chaque année des millions de personnes. - La tuberculose (TB) résulte d'une infection bactérienne par Mycobacterium tuberculosis (Mtb) et existe sous deux formes majeures: une forme latente, lorsque la bactérie est en phase de dormance ainsi qu'une forme active durant laquelle la bactérie se divise activement, entraînant les symptômes de la maladie. La personne infectée devient alors contagieuse dans la plupart des cas. Aujourd'hui des études épidémiologiques assument que plus d'un tiers de la population mondiale serait infectée par la forme latente de la bactérie et que 10% des cas réactiveront donnant lieu à diverses présentations de la maladie. Il n'existe actuellement aucun vaccin réellement efficace chez l'adulte. D'autre part, les traitements antibiotiques utilisés sont très lourds pour les patients et les cliniciens doivent faire face à l'émergence de nouvelles souches bactériennes multi-résistantes non affectées par les thérapies existantes. Les autorités sanitaires sont, d'autre part, confrontées à l'absence d'un outil diagnostique rapide, fiable et efficace. En effet, la méthode de référence reste la culture microbiologique du pathogène qui prend généralement plusieurs semaines, pendant lesquelles le patient pourra contaminer d'autres personnes. En résumé, la lutte contre la tuberculose doit passer par l'élaboration d'un vaccin efficace, de nouvelles thérapies, mais aussi par la mise en place de nouveaux tests diagnostics plus rapides afin d'éviter la dissémination de la maladie. Aussi, la relation hôte-bactérie qui n'est actuellement que peu comprise doit être investiguée. Ce travail de thèse a pour but d'étudier la réponse immunitaire chez l'homme infecté par Mtb et vise plus particulièrement l'étude d'une population clé de cellules immunitaires: les lymphocytes T. L'étude des cellules Τ CD4 nous a permis dans un premier temps de proposer un nouveau test diagnostic de la maladie active. Nous avons aussi analysé plus en détail une population spécifique des cellules Τ CD4 (les cellules Thl7), nous permettant d'associer leur fonction avec un possible état physiologique de protection contre le pathogène. En second lieu nous avons réalisé une caractérisation des cellules Τ CD8, à la fois chez les personnes avec des infections latentes et chez les personnes malades. Nous avons mis en évidence des différences fonctionnelles chez les deux groupes de patients, nous permettant ainsi une meilleure compréhension de l'immunité contre Mtb. Enfin, nous avons combiné les différents profils immunologiques obtenus pour développer un test diagnostic plus performant et sensible que celui proposé antérieurement. Ces diverses études réalisées sur les cellules Τ humaines nous permettent de faire un pas supplémentaire dans la compréhension de la réponse immunitaire face à ce pathogène particulièrement dangereux qui continue à tuer chaque année des millions de personnes.

Predictive analysis and mapping of indoor radon concentrations in a complex environment using kernel estimation: an application to Switzerland.

PURPOSE: The aim of this study was to develop models based on kernel regression and probability estimation in order to predict and map IRC in Switzerland by taking into account all of the following: architectural factors, spatial relationships between the measurements, as well as geological information. METHODS: We looked at about 240,000 IRC measurements carried out in about 150,000 houses. As predictor variables we included: building type, foundation type, year of construction, detector type, geographical coordinates, altitude, temperature and lithology into the kernel estimation models. We developed predictive maps as well as a map of the local probability to exceed 300 Bq/m(3). Additionally, we developed a map of a confidence index in order to estimate the reliability of the probability map. RESULTS: Our models were able to explain 28% of the variations of IRC data. All variables added information to the model. The model estimation revealed a bandwidth for each variable, making it possible to characterize the influence of each variable on the IRC estimation. Furthermore, we assessed the mapping characteristics of kernel estimation overall as well as by municipality. Overall, our model reproduces spatial IRC patterns which were already obtained earlier. On the municipal level, we could show that our model accounts well for IRC trends within municipal boundaries. Finally, we found that different building characteristics result in different IRC maps. Maps corresponding to detached houses with concrete foundations indicate systematically smaller IRC than maps corresponding to farms with earth foundation. CONCLUSIONS: IRC mapping based on kernel estimation is a powerful tool to predict and analyze IRC on a large-scale as well as on a local level. This approach enables to develop tailor-made maps for different architectural elements and measurement conditions and to account at the same time for geological information and spatial relations between IRC measurements.

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.

Examination of Curing Criteria for Cold In-Place Recycling Phase 2: Measuring Temperature, Moisture, Deflection and Distress from CIR Test Section, TR-590, 2009

The previous research performed laboratory experiments to measure the impacts of the curing on the indirect tensile strength of both CIR-foam and CIR-emulsion mixtures. However, a fundamental question was raised during the previous research regarding a relationship between the field moisture content and the laboratory moisture content. Therefore, during this research, both temperature and moisture conditions were measured in the field by embedding the sensors at a midpoint and a bottom of the CIR layer. The main objectives of the research are to: (1) measure the moisture levels throughout a CIR layer and (2) develop a moisture loss index to determine the optimum curing time of CIR layer before HMA overlay. To develop a set of moisture loss indices, the moisture contents and temperatures of CIR-foam and CIR-emulsion layers were monitored for five months. Based on the limited field experiment, the following conclusions are derived: 1. The moisture content of the CIR layer can be monitored accurately using the capacitance type moisture sensor. 2. The moisture loss index for CIR layers is a viable tool in determining the optimum timing for an overlay without measuring actual moisture contents. 3. The modulus back-calculated based on the deflection measured by FWD seemed to be in a good agreement with the stiffness measured by geo-gauge. 4. The geo-gauge should be considered for measuring the stiffness of CIR layer that can be used to determine the timing of an overlay. 5. The stiffness of CIR-foam layer increased as a curing time increased and it seemed to be more influenced by a temperature than moisture content. The developed sets of moisture loss indices based on the field measurements will help pavement engineers determine an optimum timing of an overlay without continually measuring moisture conditions in the field using a nuclear gauge.

Examination of Curing Criteria for Cold In-Place Recycling (Phase 3: Calibration of Moisture Loss Indices and Development of Stiffness Gain Model), TR-609, 2011

In the previous study, moisture loss indices were developed based on the field measurements from one CIR-foam and one CIR-emulsion construction sites. To calibrate these moisture loss indices, additional CIR construction sites were monitored using embedded moisture and temperature sensors. In addition, to determine the optimum timing of an HMA overlay on the CIR layer, the potential of using the stiffness of CIR layer measured by geo-gauge instead of the moisture measurement by a nuclear gauge was explored. Based on the monitoring the moisture and stiffness from seven CIR project sites, the following conclusions are derived: 1. In some cases, the in-situ stiffness remained constant and, in other cases, despite some rainfalls, stiffness of the CIR layers steadily increased during the curing time. 2. The stiffness measured by geo-gauge was affected by a significant amount of rainfall. 3. The moisture indices developed for CIR sites can be used for predicting moisture level in a typical CIR project. The initial moisture content and temperature were the most significant factors in predicting the future moisture content in the CIR layer. 4. The stiffness of a CIR layer is an extremely useful tool for contractors to use for timing their HMA overlay. To determine the optimal timing of an HMA overlay, it is recommended that the moisture loss index should be used in conjunction with the stiffness of the CIR layer.