Machine learning for geospatial data : algorithms, software tools and case studies

Résumé Cette thèse est consacrée à l'analyse, la modélisation et la visualisation de données environnementales à référence spatiale à l'aide d'algorithmes d'apprentissage automatique (Machine Learning). L'apprentissage automatique peut être considéré au sens large comme une sous-catégorie de l'intelligence artificielle qui concerne particulièrement le développement de techniques et d'algorithmes permettant à une machine d'apprendre à partir de données. Dans cette thèse, les algorithmes d'apprentissage automatique sont adaptés pour être appliqués à des données environnementales et à la prédiction spatiale. Pourquoi l'apprentissage automatique ? Parce que la majorité des algorithmes d'apprentissage automatiques sont universels, adaptatifs, non-linéaires, robustes et efficaces pour la modélisation. Ils peuvent résoudre des problèmes de classification, de régression et de modélisation de densité de probabilités dans des espaces à haute dimension, composés de variables informatives spatialisées (« géo-features ») en plus des coordonnées géographiques. De plus, ils sont idéaux pour être implémentés en tant qu'outils d'aide à la décision pour des questions environnementales allant de la reconnaissance de pattern à la modélisation et la prédiction en passant par la cartographie automatique. Leur efficacité est comparable au modèles géostatistiques dans l'espace des coordonnées géographiques, mais ils sont indispensables pour des données à hautes dimensions incluant des géo-features. Les algorithmes d'apprentissage automatique les plus importants et les plus populaires sont présentés théoriquement et implémentés sous forme de logiciels pour les sciences environnementales. Les principaux algorithmes décrits sont le Perceptron multicouches (MultiLayer Perceptron, MLP) - l'algorithme le plus connu dans l'intelligence artificielle, le réseau de neurones de régression généralisée (General Regression Neural Networks, GRNN), le réseau de neurones probabiliste (Probabilistic Neural Networks, PNN), les cartes auto-organisées (SelfOrganized Maps, SOM), les modèles à mixture Gaussiennes (Gaussian Mixture Models, GMM), les réseaux à fonctions de base radiales (Radial Basis Functions Networks, RBF) et les réseaux à mixture de densité (Mixture Density Networks, MDN). Cette gamme d'algorithmes permet de couvrir des tâches variées telle que la classification, la régression ou l'estimation de densité de probabilité. L'analyse exploratoire des données (Exploratory Data Analysis, EDA) est le premier pas de toute analyse de données. Dans cette thèse les concepts d'analyse exploratoire de données spatiales (Exploratory Spatial Data Analysis, ESDA) sont traités selon l'approche traditionnelle de la géostatistique avec la variographie expérimentale et selon les principes de l'apprentissage automatique. La variographie expérimentale, qui étudie les relations entre pairs de points, est un outil de base pour l'analyse géostatistique de corrélations spatiales anisotropiques qui permet de détecter la présence de patterns spatiaux descriptible par une statistique. L'approche de l'apprentissage automatique pour l'ESDA est présentée à travers l'application de la méthode des k plus proches voisins qui est très simple et possède d'excellentes qualités d'interprétation et de visualisation. Une part importante de la thèse traite de sujets d'actualité comme la cartographie automatique de données spatiales. Le réseau de neurones de régression généralisée est proposé pour résoudre cette tâche efficacement. Les performances du GRNN sont démontrées par des données de Comparaison d'Interpolation Spatiale (SIC) de 2004 pour lesquelles le GRNN bat significativement toutes les autres méthodes, particulièrement lors de situations d'urgence. La thèse est composée de quatre chapitres : théorie, applications, outils logiciels et des exemples guidés. Une partie importante du travail consiste en une collection de logiciels : Machine Learning Office. Cette collection de logiciels a été développée durant les 15 dernières années et a été utilisée pour l'enseignement de nombreux cours, dont des workshops internationaux en Chine, France, Italie, Irlande et Suisse ainsi que dans des projets de recherche fondamentaux et appliqués. Les cas d'études considérés couvrent un vaste spectre de problèmes géoenvironnementaux réels à basse et haute dimensionnalité, tels que la pollution de l'air, du sol et de l'eau par des produits radioactifs et des métaux lourds, la classification de types de sols et d'unités hydrogéologiques, la cartographie des incertitudes pour l'aide à la décision et l'estimation de risques naturels (glissements de terrain, avalanches). Des outils complémentaires pour l'analyse exploratoire des données et la visualisation ont également été développés en prenant soin de créer une interface conviviale et facile à l'utilisation. Machine Learning for geospatial data: algorithms, software tools and case studies Abstract The thesis is devoted to the analysis, modeling and visualisation of spatial environmental data using machine learning algorithms. In a broad sense machine learning can be considered as a subfield of artificial intelligence. It mainly concerns with the development of techniques and algorithms that allow computers to learn from data. In this thesis machine learning algorithms are adapted to learn from spatial environmental data and to make spatial predictions. Why machine learning? In few words most of machine learning algorithms are universal, adaptive, nonlinear, robust and efficient modeling tools. They can find solutions for the classification, regression, and probability density modeling problems in high-dimensional geo-feature spaces, composed of geographical space and additional relevant spatially referenced features. They are well-suited to be implemented as predictive engines in decision support systems, for the purposes of environmental data mining including pattern recognition, modeling and predictions as well as automatic data mapping. They have competitive efficiency to the geostatistical models in low dimensional geographical spaces but are indispensable in high-dimensional geo-feature spaces. The most important and popular machine learning algorithms and models interesting for geo- and environmental sciences are presented in details: from theoretical description of the concepts to the software implementation. The main algorithms and models considered are the following: multi-layer perceptron (a workhorse of machine learning), general regression neural networks, probabilistic neural networks, self-organising (Kohonen) maps, Gaussian mixture models, radial basis functions networks, mixture density networks. This set of models covers machine learning tasks such as classification, regression, and density estimation. Exploratory data analysis (EDA) is initial and very important part of data analysis. In this thesis the concepts of exploratory spatial data analysis (ESDA) is considered using both traditional geostatistical approach such as_experimental variography and machine learning. Experimental variography is a basic tool for geostatistical analysis of anisotropic spatial correlations which helps to understand the presence of spatial patterns, at least described by two-point statistics. A machine learning approach for ESDA is presented by applying the k-nearest neighbors (k-NN) method which is simple and has very good interpretation and visualization properties. Important part of the thesis deals with a hot topic of nowadays, namely, an automatic mapping of geospatial data. General regression neural networks (GRNN) is proposed as efficient model to solve this task. Performance of the GRNN model is demonstrated on Spatial Interpolation Comparison (SIC) 2004 data where GRNN model significantly outperformed all other approaches, especially in case of emergency conditions. The thesis consists of four chapters and has the following structure: theory, applications, software tools, and how-to-do-it examples. An important part of the work is a collection of software tools - Machine Learning Office. Machine Learning Office tools were developed during last 15 years and was used both for many teaching courses, including international workshops in China, France, Italy, Ireland, Switzerland and for realizing fundamental and applied research projects. Case studies considered cover wide spectrum of the real-life low and high-dimensional geo- and environmental problems, such as air, soil and water pollution by radionuclides and heavy metals, soil types and hydro-geological units classification, decision-oriented mapping with uncertainties, natural hazards (landslides, avalanches) assessments and susceptibility mapping. Complementary tools useful for the exploratory data analysis and visualisation were developed as well. The software is user friendly and easy to use.

Certified Budget Report FY 2016, June 4, 2015

The Certified Budget Report is prepared annually by each community college. Each college has specific steps that it follows in order to prepare this report and to submit it to the controlling county auditor by March 15 of each year. In January, the valuation reports are available from the county auditors to use as a basis for tax revenue estimates. In preparing the Certified Budget Report, historical year numbers are verified, current year numbers are re-estimated, and the next fiscal year numbers are estimated. Once the Certified Budget Report is prepared, it is filed with the community college board. After filing with the community college board, a public hearing is set. The date for the public hearing must be published no sooner than 20 days before the hearing and no later than 10 days before the hearing. At that public hearing, any comments from the public are heard and the board votes to accept the budget. If adopted by the board, the budget is filed with the controlling county auditor.

On the connectivity of the escaping set for complex exponential Misiurewicz parameters

Let $ E_{\lambda}(z)=\lambda {\rm exp}(z), \lambda\in \mathbb{C}$, be the complex exponential family. For all functions in the family there is a unique asymptotic value at 0 (and no critical values). For a fixed $ \lambda$, the set of points in $ \mathbb{C}$ with orbit tending to infinity is called the escaping set. We prove that the escaping set of $ E_{\lambda}$ with $ \lambda$ Misiurewicz (that is, a parameter for which the orbit of the singular value is strictly preperiodic) is a connected set.

Can the impact of bed closure in intensive care units be reliably monitored?

OBJECTIVE: To assess the properties of various indicators aimed at monitoring the impact on the activity and patient outcome of a bed closure in a surgical intensive care unit (ICU). DESIGN: Comparison before and after the intervention. SETTING: A surgical ICU at a university hospital. PATIENTS: All patients admitted to the unit over two periods of 10 months. INTERVENTION: Closure of one bed out of 17. MEASUREMENTS AND RESULTS: Activity and outcome indicators in the ICU and the structures upstream from it (emergency department, operative theater, recovery room) and downstream from it (intermediate care units). After the bed closure, the monthly medians of admitted patients and ICU hospital days increased from 107 (interquartile range 94-112) to 113 (106-121, P=0.07) and from 360 (325-443) to 395 (345-436, P=0.48), respectively, along with the linear trend observed in our institution. All indicators of workload, patient severity, and outcome remained stable except for SAPS II score, emergency admissions, and ICU readmissions, which increased not only transiently but also on a mid-term basis (10 months), indicating that the process of patient care delivery was no longer predictable. CONCLUSIONS: Health care systems, including ICUs, are extraordinary flexible, and can adapt to multiple external constraints without altering commonly used activity and outcome indicators. It is therefore necessary to set up multiple indicators to be able to reliably monitor the impact of external interventions and intervene rapidly when the system is no longer under control.

Set reformulacions per a una dramatúrgia interactiva

La hibridació de les noves tecnologies amb la posada en escena, en obres i espais de representació, està obrint noves formes d'aproximació al fet dramatúrgic. Així s'ha esdevingut en la història del teatre sobre l'escriptura, l'escenografia o l'acció actoral. El que aquí volem tractar és com les tecnologies interactives poden representar un altre d'aquests moments d'inflexió. Aquest article parteix de l'experiència obtinguda en la direcció, juntament amb Montse Figueras, de la instal·lació Prometzeus presentada a la sala Muncunill de Terrassa el 2004. Una aproximació amateur en l’experimentació de noves dramatúrgies que feia ús de tecnologies audiovisuals interactives. Volem presentar una primera reflexió sobre la qüestió i exposar set d'aquestes possibles reformulacions. Set punts on les tecnologies interactives reformulen el llenguatge teatral.

An assurance-based model to holistically assess the information security posture

EXECUTIVE SUMMARY : Evaluating Information Security Posture within an organization is becoming a very complex task. Currently, the evaluation and assessment of Information Security are commonly performed using frameworks, methodologies and standards which often consider the various aspects of security independently. Unfortunately this is ineffective because it does not take into consideration the necessity of having a global and systemic multidimensional approach to Information Security evaluation. At the same time the overall security level is globally considered to be only as strong as its weakest link. This thesis proposes a model aiming to holistically assess all dimensions of security in order to minimize the likelihood that a given threat will exploit the weakest link. A formalized structure taking into account all security elements is presented; this is based on a methodological evaluation framework in which Information Security is evaluated from a global perspective. This dissertation is divided into three parts. Part One: Information Security Evaluation issues consists of four chapters. Chapter 1 is an introduction to the purpose of this research purpose and the Model that will be proposed. In this chapter we raise some questions with respect to "traditional evaluation methods" as well as identifying the principal elements to be addressed in this direction. Then we introduce the baseline attributes of our model and set out the expected result of evaluations according to our model. Chapter 2 is focused on the definition of Information Security to be used as a reference point for our evaluation model. The inherent concepts of the contents of a holistic and baseline Information Security Program are defined. Based on this, the most common roots-of-trust in Information Security are identified. Chapter 3 focuses on an analysis of the difference and the relationship between the concepts of Information Risk and Security Management. Comparing these two concepts allows us to identify the most relevant elements to be included within our evaluation model, while clearing situating these two notions within a defined framework is of the utmost importance for the results that will be obtained from the evaluation process. Chapter 4 sets out our evaluation model and the way it addresses issues relating to the evaluation of Information Security. Within this Chapter the underlying concepts of assurance and trust are discussed. Based on these two concepts, the structure of the model is developed in order to provide an assurance related platform as well as three evaluation attributes: "assurance structure", "quality issues", and "requirements achievement". Issues relating to each of these evaluation attributes are analysed with reference to sources such as methodologies, standards and published research papers. Then the operation of the model is discussed. Assurance levels, quality levels and maturity levels are defined in order to perform the evaluation according to the model. Part Two: Implementation of the Information Security Assurance Assessment Model (ISAAM) according to the Information Security Domains consists of four chapters. This is the section where our evaluation model is put into a welldefined context with respect to the four pre-defined Information Security dimensions: the Organizational dimension, Functional dimension, Human dimension, and Legal dimension. Each Information Security dimension is discussed in a separate chapter. For each dimension, the following two-phase evaluation path is followed. The first phase concerns the identification of the elements which will constitute the basis of the evaluation: ? Identification of the key elements within the dimension; ? Identification of the Focus Areas for each dimension, consisting of the security issues identified for each dimension; ? Identification of the Specific Factors for each dimension, consisting of the security measures or control addressing the security issues identified for each dimension. The second phase concerns the evaluation of each Information Security dimension by: ? The implementation of the evaluation model, based on the elements identified for each dimension within the first phase, by identifying the security tasks, processes, procedures, and actions that should have been performed by the organization to reach the desired level of protection; ? The maturity model for each dimension as a basis for reliance on security. For each dimension we propose a generic maturity model that could be used by every organization in order to define its own security requirements. Part three of this dissertation contains the Final Remarks, Supporting Resources and Annexes. With reference to the objectives of our thesis, the Final Remarks briefly analyse whether these objectives were achieved and suggest directions for future related research. Supporting resources comprise the bibliographic resources that were used to elaborate and justify our approach. Annexes include all the relevant topics identified within the literature to illustrate certain aspects of our approach. Our Information Security evaluation model is based on and integrates different Information Security best practices, standards, methodologies and research expertise which can be combined in order to define an reliable categorization of Information Security. After the definition of terms and requirements, an evaluation process should be performed in order to obtain evidence that the Information Security within the organization in question is adequately managed. We have specifically integrated into our model the most useful elements of these sources of information in order to provide a generic model able to be implemented in all kinds of organizations. The value added by our evaluation model is that it is easy to implement and operate and answers concrete needs in terms of reliance upon an efficient and dynamic evaluation tool through a coherent evaluation system. On that basis, our model could be implemented internally within organizations, allowing them to govern better their Information Security. RÉSUMÉ : Contexte général de la thèse L'évaluation de la sécurité en général, et plus particulièrement, celle de la sécurité de l'information, est devenue pour les organisations non seulement une mission cruciale à réaliser, mais aussi de plus en plus complexe. A l'heure actuelle, cette évaluation se base principalement sur des méthodologies, des bonnes pratiques, des normes ou des standards qui appréhendent séparément les différents aspects qui composent la sécurité de l'information. Nous pensons que cette manière d'évaluer la sécurité est inefficiente, car elle ne tient pas compte de l'interaction des différentes dimensions et composantes de la sécurité entre elles, bien qu'il soit admis depuis longtemps que le niveau de sécurité globale d'une organisation est toujours celui du maillon le plus faible de la chaîne sécuritaire. Nous avons identifié le besoin d'une approche globale, intégrée, systémique et multidimensionnelle de l'évaluation de la sécurité de l'information. En effet, et c'est le point de départ de notre thèse, nous démontrons que seule une prise en compte globale de la sécurité permettra de répondre aux exigences de sécurité optimale ainsi qu'aux besoins de protection spécifiques d'une organisation. Ainsi, notre thèse propose un nouveau paradigme d'évaluation de la sécurité afin de satisfaire aux besoins d'efficacité et d'efficience d'une organisation donnée. Nous proposons alors un modèle qui vise à évaluer d'une manière holistique toutes les dimensions de la sécurité, afin de minimiser la probabilité qu'une menace potentielle puisse exploiter des vulnérabilités et engendrer des dommages directs ou indirects. Ce modèle se base sur une structure formalisée qui prend en compte tous les éléments d'un système ou programme de sécurité. Ainsi, nous proposons un cadre méthodologique d'évaluation qui considère la sécurité de l'information à partir d'une perspective globale. Structure de la thèse et thèmes abordés Notre document est structuré en trois parties. La première intitulée : « La problématique de l'évaluation de la sécurité de l'information » est composée de quatre chapitres. Le chapitre 1 introduit l'objet de la recherche ainsi que les concepts de base du modèle d'évaluation proposé. La maniéré traditionnelle de l'évaluation de la sécurité fait l'objet d'une analyse critique pour identifier les éléments principaux et invariants à prendre en compte dans notre approche holistique. Les éléments de base de notre modèle d'évaluation ainsi que son fonctionnement attendu sont ensuite présentés pour pouvoir tracer les résultats attendus de ce modèle. Le chapitre 2 se focalise sur la définition de la notion de Sécurité de l'Information. Il ne s'agit pas d'une redéfinition de la notion de la sécurité, mais d'une mise en perspectives des dimensions, critères, indicateurs à utiliser comme base de référence, afin de déterminer l'objet de l'évaluation qui sera utilisé tout au long de notre travail. Les concepts inhérents de ce qui constitue le caractère holistique de la sécurité ainsi que les éléments constitutifs d'un niveau de référence de sécurité sont définis en conséquence. Ceci permet d'identifier ceux que nous avons dénommés « les racines de confiance ». Le chapitre 3 présente et analyse la différence et les relations qui existent entre les processus de la Gestion des Risques et de la Gestion de la Sécurité, afin d'identifier les éléments constitutifs du cadre de protection à inclure dans notre modèle d'évaluation. Le chapitre 4 est consacré à la présentation de notre modèle d'évaluation Information Security Assurance Assessment Model (ISAAM) et la manière dont il répond aux exigences de l'évaluation telle que nous les avons préalablement présentées. Dans ce chapitre les concepts sous-jacents relatifs aux notions d'assurance et de confiance sont analysés. En se basant sur ces deux concepts, la structure du modèle d'évaluation est développée pour obtenir une plateforme qui offre un certain niveau de garantie en s'appuyant sur trois attributs d'évaluation, à savoir : « la structure de confiance », « la qualité du processus », et « la réalisation des exigences et des objectifs ». Les problématiques liées à chacun de ces attributs d'évaluation sont analysées en se basant sur l'état de l'art de la recherche et de la littérature, sur les différentes méthodes existantes ainsi que sur les normes et les standards les plus courants dans le domaine de la sécurité. Sur cette base, trois différents niveaux d'évaluation sont construits, à savoir : le niveau d'assurance, le niveau de qualité et le niveau de maturité qui constituent la base de l'évaluation de l'état global de la sécurité d'une organisation. La deuxième partie: « L'application du Modèle d'évaluation de l'assurance de la sécurité de l'information par domaine de sécurité » est elle aussi composée de quatre chapitres. Le modèle d'évaluation déjà construit et analysé est, dans cette partie, mis dans un contexte spécifique selon les quatre dimensions prédéfinies de sécurité qui sont: la dimension Organisationnelle, la dimension Fonctionnelle, la dimension Humaine, et la dimension Légale. Chacune de ces dimensions et son évaluation spécifique fait l'objet d'un chapitre distinct. Pour chacune des dimensions, une évaluation en deux phases est construite comme suit. La première phase concerne l'identification des éléments qui constituent la base de l'évaluation: ? Identification des éléments clés de l'évaluation ; ? Identification des « Focus Area » pour chaque dimension qui représentent les problématiques se trouvant dans la dimension ; ? Identification des « Specific Factors » pour chaque Focus Area qui représentent les mesures de sécurité et de contrôle qui contribuent à résoudre ou à diminuer les impacts des risques. La deuxième phase concerne l'évaluation de chaque dimension précédemment présentées. Elle est constituée d'une part, de l'implémentation du modèle général d'évaluation à la dimension concernée en : ? Se basant sur les éléments spécifiés lors de la première phase ; ? Identifiant les taches sécuritaires spécifiques, les processus, les procédures qui auraient dû être effectués pour atteindre le niveau de protection souhaité. D'autre part, l'évaluation de chaque dimension est complétée par la proposition d'un modèle de maturité spécifique à chaque dimension, qui est à considérer comme une base de référence pour le niveau global de sécurité. Pour chaque dimension nous proposons un modèle de maturité générique qui peut être utilisé par chaque organisation, afin de spécifier ses propres exigences en matière de sécurité. Cela constitue une innovation dans le domaine de l'évaluation, que nous justifions pour chaque dimension et dont nous mettons systématiquement en avant la plus value apportée. La troisième partie de notre document est relative à la validation globale de notre proposition et contient en guise de conclusion, une mise en perspective critique de notre travail et des remarques finales. Cette dernière partie est complétée par une bibliographie et des annexes. Notre modèle d'évaluation de la sécurité intègre et se base sur de nombreuses sources d'expertise, telles que les bonnes pratiques, les normes, les standards, les méthodes et l'expertise de la recherche scientifique du domaine. Notre proposition constructive répond à un véritable problème non encore résolu, auquel doivent faire face toutes les organisations, indépendamment de la taille et du profil. Cela permettrait à ces dernières de spécifier leurs exigences particulières en matière du niveau de sécurité à satisfaire, d'instancier un processus d'évaluation spécifique à leurs besoins afin qu'elles puissent s'assurer que leur sécurité de l'information soit gérée d'une manière appropriée, offrant ainsi un certain niveau de confiance dans le degré de protection fourni. Nous avons intégré dans notre modèle le meilleur du savoir faire, de l'expérience et de l'expertise disponible actuellement au niveau international, dans le but de fournir un modèle d'évaluation simple, générique et applicable à un grand nombre d'organisations publiques ou privées. La valeur ajoutée de notre modèle d'évaluation réside précisément dans le fait qu'il est suffisamment générique et facile à implémenter tout en apportant des réponses sur les besoins concrets des organisations. Ainsi notre proposition constitue un outil d'évaluation fiable, efficient et dynamique découlant d'une approche d'évaluation cohérente. De ce fait, notre système d'évaluation peut être implémenté à l'interne par l'entreprise elle-même, sans recourir à des ressources supplémentaires et lui donne également ainsi la possibilité de mieux gouverner sa sécurité de l'information.

Overlap Between Common Genetic Polymorphisms Underpinning Kidney Traits and Cardiovascular Disease Phenotypes: The CKDGen Consortium.

BACKGROUND: Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits. STUDY DESIGN: We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests). SETTING & PARTICIPANTS: Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium. PREDICTOR: We used 19 kidney SNPs and 64 vascular SNPs. OUTCOMES & MEASUREMENTS: Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria. RESULTS: In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)). LIMITATIONS: The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations. CONCLUSIONS: Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.

Structural analysis, clay mineralogy and K-Ar dating of fault gouges from Centovalli Line (Central Alps) for reconstruction of their recent activity

Between the cities of Domodossola and Locarno, the complex ``Centovalli Line'' tectonic zone of the Central Alps outlines deformation phases over a long period of time (probably starting similar to 30 Ma ago) and under variable P-T conditions. The last deformation phases developed gouge-bearing faults with a general E-W trend that crosscuts the roots of the Alpine Canavese zone and the Finero ultramafic body. Kinematic indicators show that the general motion was mainly dextral associated with back thrusting towards the S. The <2 mu m clay fractions of fault gouges from Centovalli Line consist mainly of illite, smectite and chlorite with varied illite-smectite, chlorite-smectite and chlorite-serpentine mixed-layers. Constrained with the illite crystallinity index, the thermal conditions induced by the tectonic activity show a gradual trend from anchizonal to diagenetic conditions. The <2 and <0.2 mu M clay fractions, and hydrothermal K-feldspar separates all provide K-Ar ages between 14.2 +/- 2.9 Ma and roughly 0 Ma, with major episodes at about 12,8, 6 and close to 0 Ma These ages set the recurrent tectonic activity and the associated fluid circulations between Upper Miocene and Recent. On the basis of the K-Ar ages and with a thermal gradient of 25-30 degrees C/km, the studied fault zones were located at a depth of 4-7 km. If they were active until now as observed in field, the exhumation was approximately 2.5-3.0 km for the last 12 Ma with a mean velocity of 0.4 mm/y. Comparison with available models on the recent Alpine evolution shows that the tectonic activity in the area relates to a continuum of the back-thrusting movements of the Canavese Line, and/or to several late-extensional phases of the Rhone-Simplon line. The Centovalli-Val Vigezzo zone therefore represents a major tectonic zone of the Central-Western Alps resulting from different interacting tectonic events. (C) 2011 Elsevier B.V. All rights reserved.

Iowa Roads and Streets Functional Classification Manual, 1975

This manual provides a set of procedural rules and regulations for use in functionally classifying all roads and streets in Iowa according to the character of service they are intended to provide. Functional classification is a requirement of the 1973 Code of Iowa (Chapter 306) as amended by Senate File 1062 enacted by the 2nd session of the 65th General Assembly of Iowa. Functional classification is defined as the grouping of roads and streets into systems according to the character of service they will be expected to provide, and the assignment of jurisdiction over each class to the governmental unit having primary interest in each type of service. Stated objectives of the legislation are: "Functional classification will serve the legislator by providing an equitable basis for determination of proper source of tax support and providing for the assignment of financial resources to the governmental unit having responsibility for each class of service. Functional classification promotes the ability of the administrator to effectively prepare and carry out long range programs which reflect the transportation needs of the public." All roads and streets in legal existence will be classified. Instructions are also included in this manual for a continuous reporting to the Highway Commission of changes in classification and/or jurisdiction resulting from new construction, corporation line changes, relocations, and deletions. This continuous updating of records is absolutely essential for modern day transportation planning as it is the only possible way to monitor the status of existing road systems, and consequently determine adequacy and needs with accuracy.

Early Iron Age Pottery: A Quantitative Approach. Proceedings of the International Round Table organized by the Swiss School of Archaeology in Greece (Athens, Novembre 28-30, 2008).

Quantitative approaches in ceramology are gaining ground in excavation reports, archaeological publications and thematic studies. Hence, a wide variety of methods are being used depending on the researchers' theoretical premise, the type of material which is examined, the context of discovery and the questions that are addressed. The round table that took place in Athens on November 2008 was intended to offer the participants the opportunity to present a selection of case studies on the basis of which methodological approaches were discussed. The aim was to define a set of guidelines for quantification that would prove to be of use to all researchers. Contents: 1) Introduction (Samuel Verdan); 2) Isthmia and beyond. How can quantification help the analysis of EIA sanctuary deposits? (Catherine Morgan); 3) Approaching aspects of cult practice and ethnicity in Early Iron Age Ephesos using quantitative analysis of a Protogeometric deposit from the Artemision (Michael Kerschner); 4) Development of a ceramic cultic assemblage: Analyzing pottery from Late Helladic IIIC through Late Geometric Kalapodi (Ivonne Kaiser, Laura-Concetta Rizzotto, Sara Strack); 5) 'Erfahrungsbericht' of application of different quantitative methods at Kalapodi (Sara Strack); 6) The Early Iron Age sanctuary at Olympia: counting sherds from the Pelopion excavations (1987-1996) (Birgitta Eder); 7) L'aire du pilier des Rhodiens à Delphes: Essai de quantification du mobilier (Jean-Marc Luce); 8) A new approach in ceramic statistical analyses: Pit 13 on Xeropolis at Lefkandi (David A. Mitchell, Irene S. Lemos); 9) Households and workshops at Early Iron Age Oropos: A quantitative approach of the fine, wheel-made pottery (Vicky Vlachou); 10) Counting sherds at Sindos: Pottery consumption and construction of identities in the Iron Age (Stefanos Gimatzidis); 11) Analyse quantitative du mobilier céramique des fouilles de Xombourgo à Ténos et le cas des supports de caisson (Jean-Sébastien Gros); 12) Defining a typology of pottery from Gortyn: The material from a pottery workshop pit, (Emanuela Santaniello); 13) Quantification of ceramics from Early Iron Age tombs (Antonis Kotsonas); 14) Quantitative analysis of the pottery from the Early Iron Age necropolis of Tsikalario on Naxos (Xenia Charalambidou); 15) Finding the Early Iron Age in field survey: Two case studies from Boeotia and Magnesia (Vladimir Stissi); 16) Pottery quantification: Some guidelines (Samuel Verdan).

A note on the Lorenz-maximal allocations in the imputation set

In this note we introduce the Lorenz stable set and provide an axiomatic characterization in terms of constrained egalitarianism and projection consistency. On the domain of all coalitional games, we find that this solution connects the weak constrained egalitarian solution (Dutta and Ray, 1989) with their strong counterpart (Dutta and Ray, 1991)

Ultrastructural analysis of neuronal plasticity in the adult mouse

ABSTRACT Adult neuronal plasticity is a term that corresponds to a set of biological mechanisms allowing a neuronal circuit to respond and adapt to modifications of the received inputs. Mystacial whiskers of the mouse are the starting point of a major sensory pathway that provides the animal with information from its immediate environment. Through whisking, information is gathered that allows the animal to orientate itself and to recognize objects. This sensory system is crucial for nocturnal behaviour during which vision is not of much use. Sensory information of the whiskers are sent via brainstem and thalamus to the primary somatosensory area (S1) of the cerebral cortex in a strictly topological manner. Cell bodies in the layer N of S 1 are arranged in ring forming structures called barrels. As such, each barrel corresponds to the cortical representation in layer IV of a single whisker follicle. This histological feature allows to identify with uttermost precision the part of the cortex devoted to a given whisker and to study modifications induced by different experimental conditions. The condition used in the studies of my thesis is the passive stimulation of one whisker in the adult mouse for a period of 24 hours. It is performed by glueing a piece of metal on one whisker and placing the awake animal in a cage surrounded by an electromagnetic coil that generates magnetic field burst inducing whisker movement at a given frequency during 24 hours. I analysed the ultrastructure of the barrel corresponding the stimulated whisker using serial sections electron microscopy and computer-based three-dimensional reconstructions; analysis of neighbouring, unstimulated barrels as well as those from unstimulated mice served as control. The following elements were structurally analyzed: the spiny dendrites, the axons of excitatory as well as inhibitory cells, their connections via synapses and the astrocytic processes. The density of synapses and spines is upregulated in a barrel corresponding to a stimulated whisker. This upregulation is absent in the BDNF heterozygote mice, indicating that a certain level of activity-dependent released BDNF is required for synaptogenesis in the adult cerebral cortex. Synpaptogenesis is correlated with a modification of the astrocytes that place themselves in closer vicinity of the excitatory synapses on spines. Biochemical analysis revealed that the astrocytes upregulate the expression of transporters by which they internalise glutamate, the neurotransmitter responsible for the excitatory response of cortical neurons. In the final part of my thesis, I show that synaptogenesis in the stimulated barrel is due to the increase in the size of excitatory axonal boutons that become more frequently multisynaptic, whereas the inhibitory axons do not change their morphology but form more synapses with spines apposed to them. Taken together, my thesis demonstrates that all the cellular elements present in the neuronal tissue of the adult brain contribute to activity-dependent cortical plasticity and form part of a mechanism by which the animal responds to a modified sensory experience. Throughout life, the neuronal circuit keeps the faculty to adapt its function. These adaptations are partially transitory but some aspects remain and could be the structural basis of a memory trace in the cortical circuit. RESUME La plasticité neuronale chez l'adulte désigne un ensemble de mécanismes biologiques qui permettent aux circuits neuronaux de répondre et de s'adapter aux modifications des stimulations reçues. Les vibrisses des souris sont un système crucial fournissant des informations sensorielles au sujet de l'environnement de l'animal. L'information sensorielle collectée par les vibrisses est envoyée via le tronc cérébral et le thalamus à l'aire sensorielle primaire (S 1) du cortex cérébral en respectant strictement la somatotopie. Les corps cellulaires dans la couche IV de S 1 sont organisés en anneaux délimitant des structures nommées tonneaux. Chaque tonneau reçoit l'information d'une seule vibrisse et l'arrangement des tonneaux dans le cortex correspond à l'arrangement des vibrisses sur le museau de la souris. Cette particularité histologique permet de sélectionner avec certitude la partie du cortex dévolue à une vibrisse et de l'étudier dans diverses conditions. Le paradigme expérimental utilisé dans cette thèse est la stimulation passive d'une seule vibrisse durant 24 heures. Pour ce faire, un petit morceau de métal est collé sur une vibrisse et la souris est placée dans une cage entourée d'une bobine électromagnétique générant un champ qui fait vibrer le morceau de métal durant 24 heures. Nous analysons l'ultrastructure du cortex cérébral à l'aide de la microscopie électronique et des coupes sériées permettant la reconstruction tridimensionnelle à l'aide de logiciels informatiques. Nous observons les modifications des structures présentes : les dendrites épineuses, les axones des cellules excitatrices et inhibitrices, leurs connections par des synapses et les astrocytes. Le nombre de synapses et d'épines est augmenté dans un tonneau correspondant à une vibrisse stimulée 24 heures. Basé sur cela, nous montrons dans ces travaux que cette réponse n'est pas observée dans des souris hétérozygotes BDNF+/-. Cette neurotrophine sécrétée en fonction de l'activité neuronale est donc nécessaire pour la synaptogenèse. La synaptogenèse est accompagnée d'une modification des astrocytes qui se rapprochent des synapses excitatrices au niveau des épines dendritiques. Ils expriment également plus de transporteurs chargés d'internaliser le glutamate, le neurotransmetteur responsable de la réponse excitatrice des neurones. Nous montrons aussi que les axones excitateurs deviennent plus larges et forment plus de boutons multi-synaptiques à la suite de la stimulation tandis que les axones inhibiteurs ne changent pas de morphologie mais forment plus de synapses avec des épines apposées à leur membrane. Tous les éléments analysés dans le cerveau adulte ont maintenu la capacité de réagir aux modifications de l'activité neuronale et répondent aux modifications de l'activité permettant une constante adaptation à de nouveaux environnements durant la vie. Les circuits neuronaux gardent la capacité de créer de nouvelles synapses. Ces adaptations peuvent être des réponses transitoires aux stimuli mais peuvent aussi laisser une trace mnésique dans les circuits.

Inferring the mode of origin of polyploid species from next-generation sequence data.

Many eukaryote organisms are polyploid. However, despite their importance, evolutionary inference of polyploid origins and modes of inheritance has been limited by a need for analyses of allele segregation at multiple loci using crosses. The increasing availability of sequence data for nonmodel species now allows the application of established approaches for the analysis of genomic data in polyploids. Here, we ask whether approximate Bayesian computation (ABC), applied to realistic traditional and next-generation sequence data, allows correct inference of the evolutionary and demographic history of polyploids. Using simulations, we evaluate the robustness of evolutionary inference by ABC for tetraploid species as a function of the number of individuals and loci sampled, and the presence or absence of an outgroup. We find that ABC adequately retrieves the recent evolutionary history of polyploid species on the basis of both old and new sequencing technologies. The application of ABC to sequence data from diploid and polyploid species of the plant genus Capsella confirms its utility. Our analysis strongly supports an allopolyploid origin of C. bursa-pastoris about 80 000 years ago. This conclusion runs contrary to previous findings based on the same data set but using an alternative approach and is in agreement with recent findings based on whole-genome sequencing. Our results indicate that ABC is a promising and powerful method for revealing the evolution of polyploid species, without the need to attribute alleles to a homeologous chromosome pair. The approach can readily be extended to more complex scenarios involving higher ploidy levels.

Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid related disorders

Genetic variants influence the risk to develop certain diseases or give rise to differences in drug response. Recent progresses in cost-effective, high-throughput genome-wide techniques, such as microarrays measuring Single Nucleotide Polymorphisms (SNPs), have facilitated genotyping of large clinical and population cohorts. Combining the massive genotypic data with measurements of phenotypic traits allows for the determination of genetic differences that explain, at least in part, the phenotypic variations within a population. So far, models combining the most significant variants can only explain a small fraction of the variance, indicating the limitations of current models. In particular, researchers have only begun to address the possibility of interactions between genotypes and the environment. Elucidating the contributions of such interactions is a difficult task because of the large number of genetic as well as possible environmental factors.In this thesis, I worked on several projects within this context. My first and main project was the identification of possible SNP-environment interactions, where the phenotypes were serum lipid levels of patients from the Swiss HIV Cohort Study (SHCS) treated with antiretroviral therapy. Here the genotypes consisted of a limited set of SNPs in candidate genes relevant for lipid transport and metabolism. The environmental variables were the specific combinations of drugs given to each patient over the treatment period. My work explored bioinformatic and statistical approaches to relate patients' lipid responses to these SNPs, drugs and, importantly, their interactions. The goal of this project was to improve our understanding and to explore the possibility of predicting dyslipidemia, a well-known adverse drug reaction of antiretroviral therapy. Specifically, I quantified how much of the variance in lipid profiles could be explained by the host genetic variants, the administered drugs and SNP-drug interactions and assessed the predictive power of these features on lipid responses. Using cross-validation stratified by patients, we could not validate our hypothesis that models that select a subset of SNP-drug interactions in a principled way have better predictive power than the control models using "random" subsets. Nevertheless, all models tested containing SNP and/or drug terms, exhibited significant predictive power (as compared to a random predictor) and explained a sizable proportion of variance, in the patient stratified cross-validation context. Importantly, the model containing stepwise selected SNP terms showed higher capacity to predict triglyceride levels than a model containing randomly selected SNPs. Dyslipidemia is a complex trait for which many factors remain to be discovered, thus missing from the data, and possibly explaining the limitations of our analysis. In particular, the interactions of drugs with SNPs selected from the set of candidate genes likely have small effect sizes which we were unable to detect in a sample of the present size (<800 patients).In the second part of my thesis, I performed genome-wide association studies within the Cohorte Lausannoise (CoLaus). I have been involved in several international projects to identify SNPs that are associated with various traits, such as serum calcium, body mass index, two-hour glucose levels, as well as metabolic syndrome and its components. These phenotypes are all related to major human health issues, such as cardiovascular disease. I applied statistical methods to detect new variants associated with these phenotypes, contributing to the identification of new genetic loci that may lead to new insights into the genetic basis of these traits. This kind of research will lead to a better understanding of the mechanisms underlying these pathologies, a better evaluation of disease risk, the identification of new therapeutic leads and may ultimately lead to the realization of "personalized" medicine.