Chronic kidney disease (CKD) is defined as glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 for 3 months and is characterized by progressive loss of renal function. The second leading cause of CKD is hypertension. More than half of CKD patients also suffer from hypertension. Arteries and arterioles adjust to the fluctuations in the systematic blood pressure through a mechanism called autoregulation. In the kidneys, autoregulation protects the delicate glomeruli capillaries from high blood pressure and occurs through myogenic constriction (MC). MC refers to contraction of arterioles in response to an increase in the blood pressure. Chronically hypertensive individuals and animal models have an enhanced MC, leading to minimal renal injury despite their elevated blood pressure. Experimental and clinical evidence point to a role for the MC in the pathogenesis of the CKD, however, the mechanism through which preglomerular arterial MC contributes to CKD has not been fully elucidated. This thesis showed that augmented MC in chronically hypertensive animal models was due to increased thromboxane A2 prostaglandin that was not released from the endothelium (Chapter 2). Nevertheless, inhibiting MC while also reducing the blood pressure prevented salt-induced renal injury even though the blood pressure was still not normalized compared to the normotensive controls (Chapter 3). The resulting improvement in renal structure and function could be attributed to the reduction in the blood pressure, albumin, and uromodulin (UMOD) excretion (Chapter 3). UMOD is a kidney-specific glycoprotein that, based on a genome-wide association study have the strongest association to CKD (Chapter 3). Comparing two CKD hypertensive animal models further revealed that CKD progression was independent of the blood pressure and strongly associated with UMOD excretion levels (Chapter 4). Collectively, the data discussed in this thesis demonstrates potential therapeutic targets in CKD hypertensive animal models. / Dissertation / Doctor of Philosophy (PhD)

Dissertation thesis deals with development and implementation of Business Intelligence (BI) solutions for Small and Medium Sized Enterprises (SME) in the Czech Republic. This thesis represents climax of author's up to now effort that has been put into completing a methodological model for development of this kind of applications for SMEs using self-owned skills and minimum of external resources and costs. This thesis can be divided into five major parts. First part that describes used technologies is divided into two chapters. First chapter describes contemporary state of Business Intelligence concept and it also contains original taxonomy of Business Intelligence solutions. Second chapter describes two Knowledge Discovery in Databases (KDD) techniques that were used for building those BI solutions that are introduced in case studies. Second part describes the area of Czech SMEs, which is an environment where the thesis was written and which it is meant to contribute to. This environment is represented by one chapter that defines the differences of SMEs against large corporations. Furthermore, there are author's reasons why he is personally focusing on this area explained. Third major part introduces the results of survey that was conducted among Czech SMEs with support of Department of Information Technologies of Faculty of Informatics and Statistics of University of Economics in Prague. This survey had three objectives. First one was to map the readiness of Czech SMEs for BI solutions development and deployment. Second was to determine major problems and consequent decisions of Czech SMEs that could be supported by BI solutions and the third objective was to determine top factors preventing SMEs from developing and deploying BI solutions. Fourth part of the thesis is also the core one. In two chapters there is the original Methodology for development and deployment of BI solutions by SMEs described as well as other methodologies that were studied. Original methodology is partly based on famous CRISP-DM methodology. Finally, last part describes particular company that has become a testing ground for author's theories and that supports his research. In further chapters it introduces case-studies of development and deployment of those BI solutions in this company, that were build using contemporary BI and KDD techniques with respect to original methodology. In that sense, these case-studies verified theoretical methodology in real use.

Cette thèse vise à contribuer à la compréhension des cycle de vie d’une opération humanitaire (HOLC). Gestion de la chaîne d'approvisionnement humanitaire (HSCM) dans un contexte de mise en perspective et dans l’objectif de proposer un modèle décisionnel qui s'applique aux phases de HOLC lors d’une situation réelle. Cela inclut la mise en oeuvre du modèle proposé pour concevoir et développer un outil d'aide à la décision afin d'améliorer les performances de la logistique humanitaire tant dans les opérations de secours nationaux qu’internationaux.Cette recherche est divisée en trois phases. La première partie vise à présenter le sens de l'étude ; la zone de recherche prise en compte pour la gestion de la chaîne d'approvisionnement (SCM) doit être clairement définie. La première phase consiste à clarifier et définir le HSCM HL, la gestion de la chaîne d'approvisionnement commerciale (CSCM) et le SCM, ainsi que la relation entre ces différents éléments. La gestion du cycle de vie du projet (PLCM) et les différentes approches sont également présentés. La compréhension de la différence entre la gestion du cycle de vie du projet (PLM) et la PLCM est également nécessaire, cela ne peut être abordé dans la phase de cycle de vie de l'opération humanitaire. De plus, les modèles Multiple-Criteria Decision Making (MCDM) et l’aide à la décision concernant le HL sont analysés pour établir le fossé existant en matière de recherche. Les approches MCDM qui mettent en oeuvre le système d'aide à la décision (DSS) et la manière dont le MAS a été utilisé dans le contexte HSCM sont étudiées.La deuxième phase consiste en la proposition d’un modèle décisionnel fondé sur l’approche MCDM à l'appui de la décision du décideur avant qu'il/elle prenne des mesures. Ce modèle prévoit le classement des alternatives concernant l'entrepôt, le fournisseur et le transport au cours des phases de HOLC. Le modèle décisionnel proposé est réalisée en 3 scénarios. I. La décision en 4phases HOLC – opération de secours internationale de la Croix-Rouge Française (CRF). II. La décision en3phases HOLC – opération nationale dela Croix-Rouge thaïlandaise (TRC). III. La décision au niveau de la phase de réponse HOLC – opération internationale du TRC dans quatre pays. Dans cette phase, le scénario I et II sont réalisés étape par étape au travers de calculs numériques et formules mathématiques. Le scénario III sera présenté dans la troisième phase. Pour établir trois scénarios, les données internes recueillies lors des entretiens avec le chef de la logistique de la Croix-Rouge Française, et le vice-président de la fondation de la Coix-Rouge thaïlandaise, seront utilisées. Les données externes proviennent de chercheurs qui sont des experts dans le domaine HL ou le champ du HSCM, de la littérature, et de sources issues des organismes humanitaires (documents d’ateliers, rapports, informations publiées sur leurs sites officiels).Dans la troisième phase, une application Internet multi-critères (decision support system MCDSS WB) mettant en oeuvre le modèle proposé est élaborée. Afin d'atteindre une décision appropriée en temps réel, le WB-MCDSS est développé sur la base d’un protocole client-serveur et est simple à utiliser. Le dernier mais non le moindre ; une application de validation du modèle est réalisée à l'aide de l'approche de l'analyse de sensibilité. / This thesis aims to contribute to the understanding of HOLC in context of the HSCM and to propose a decision model which applies to the phases of HOLC the decision making regarding a real situation . This include the implementation of the proposed model to design and develop a decision support tool in order to improve the performance of humanitarian logistics in both national and international relief operations.This research is divided into three phases; the first phase is to clarify and define HL among HSCM, commercial supply chain management (CSCM) and SCM and their relationship. Project Life Cycle Management (PLCM) approaches are also presented. The difference between project life cycle management (PLM) and PLCM is also required to distinguish a clear understanding which can be addressed in the phase of humanitarian operation life cycle. Additionally, the literature of Multiple-Criteria Decision Making (MCDM) models and existing decision aid system for HL are analyzed to establish the research gap. The MCDM approaches which implement the decision support system (DSS) and lastly how DSS has been used in the HSCM context.The second phase is to propose a decision model based on MCDM approaches to support the decision of the decision maker before he/she takes action. This model provides the ranking alternatives to warehouse, supplier and transportation over the phases of HOLC. The proposed decision model is conducted in 3 scenarios; I. The decision in 4-phase HOLC, international relief operation of French Red Cross (FRC). II. The decision on 3-phase HOLC, national operation by the Thai Red Cross (TRC). III. The decision on response phase HOLC, international operation by the FRC in four countries. In this phase, the scenario I and II are performed step by step though numerical calculation and mathematical formulas. The scenario III will be presented in the third phase.In the third phase, an application of web-based multi-criteria decision support system (WB-MCDSS) which implement the proposed model is developed. The web-based multi-criteria decision support system is developed based on the integration of analytical hierarchy process (AHP) and TOPSIS approaches. In order to achieve an appropriate decision in a real time response, the WB-MCDSS is developed based on server-client protocol and is simple to operate. Last but not least, a validation application of the model is performed using the sensitivity analysis approach.

A l’avenir, l'agriculture et l'environnement vont pouvoir bénéficier de plus en plus de données hétérogènes collectées par des réseaux de capteurs sans fil (RCSF). Ces données alimentent généralement des outils d’aide à la décision (OAD). Dans cette thèse, nous nous intéressons spécifiquement aux systèmes sensibles et adaptatifs au contexte basés sur un RCSF et un OAD, dédiés au suivi de phénomènes naturels. Nous proposons ainsi une formalisation pour la conception et la mise en œuvre de ces systèmes. Le contexte considéré se compose de données issues du phénomène étudié mais également des capteurs sans fil (leur niveau d’énergie par exemple). Par l’utilisation des ontologies et de techniques de raisonnement, nous visons à maintenir le niveau de qualité de service (QdS) des données collectées (en accord avec le phénomène étudié) tant en préservant le fonctionnement du RCSF. Pour illustrer notre proposition, un cas d'utilisation complexe, l'étude des inondations dans un bassin hydrographique, est considéré. Cette thèse a produit un logiciel de simulation de ces systèmes qui intègre un système de simulation multi-agents (JADE) avec un moteur d’inférence à base de règles (Jess). / In the future, agriculture and environment will rely on more and more heterogeneous data collected by wireless sensor networks (WSN). These data are generally used in decision support systems (DSS). In this dissertation, we focus on adaptive context-aware systems based on WSN and DSS, dedicated to the monitoring of natural phenomena. Thus, a formalization for the design and the deployment of these kinds of systems is proposed. The considered context is established using the data from the studied phenomenon but also from the wireless sensors (e.g., their energy level). By the use of ontologies and reasoning techniques, we aim to maintain the required quality of service (QoS) level of the collected data (according to the studied phenomenon) while preserving the resources of the WSN. To illustrate our proposal, a complex use case, the study of floods in a watershed, is described. During this PhD thesis, a simulator for context-aware systems which integrates a multi-agent system (JADE) and a rule engine (Jess) has been developed.Keywords: ontologies, rule-based inferences, formalization, heterogeneous data, sensors data streams integration, WSN, limited resources, DSS, adaptive context-aware systems, QoS, agriculture, environment.

Inflammatory bowel diseases, (IBD), are a group of chronic disorders of the gastro-intestinal tract, and include Crohn’s disease (CD) and Ulcerative Colitis (UC). The pathogenesis is not known, but involves at least in part a loss of tolerance towards the commensal colonic microbiota. In this thesis, we show in animal models of CD and UC that the colonic mucosal blood flow increased compared to healthy animals. This blood flow increase is due to an up regulation of endothelial nitric oxide synthase (NOS). Further, we show in the UC model that the thickness of the firmly adherent colonic mucus layer increased compared to healthy animals. This increase is due to an up regulation of inducible NOS in the epithelium. Both the blood flow and mucus thickness increase appear to be protective mechanisms.  We demonstrate that the firmly adherent colonic mucus layer acts as a partial barrier towards luminal bacteria. In the UC model, this barrier is destroyed, causing increased bacterial translocation. The adhesion molecule P-selectin was up regulated in the UC model, leading to increased interactions between leukocytes and the endothelium, but also increased interactions between platelets and the endothelium. This indicates that not only leukocytes, but also platelets are involved in colonic inflammation. The addition of the probiotic bacterial strain Lactobacillus reuteri prevented disease by normalizing P-selectin levels and endothelial interactions with leukocytes and platelets. Lactobacillus reuteri also decreased bacterial translocation over the epithelium. In summary, this thesis highlights the importance of colonic barrier functions, and investigates the role of the microbiota in experimental IBD.

The application of environmental performance indicators (EPIs) has received increasing attention by both governments and international organisations as a tool for assessing complex environmental scenarios in national and local decision making processes. However, at the regional scale there is a gap in the application of EPIs, as this has not been well understood and defined due to a limited theoretical foundation and often insufficient data from all participant countries. The regional scale is important because it can incorporate natural ecosystems which often transcend national boundaries. A case study is developed for the Lower Mekong Subregion (LMS), where four riparian Southeast Asian countries (Lao PDR, Thailand, Cambodia, and Viet Nam) share the Lower Mekong River. The research proposes a conceptual framework to identify approaches for developing criteria for acceptable and appropriate EPIs which can be used to support and implement decision making processes by relevant organisations at the regional level. This research evaluates the application of environmental performance indicators using methodologies that assess cross-national quantitative and qualitative data and existing decision support systems. In addition, global and national indicators are examined for application and relation to the regional context. The research finds that the application of EPIs varies according to spatial scale, and is diverse among the four countries. Data availability is also identified as a major problem encountered during the development and selection of EPIs. The study finds that the governance of the existing regional body is ineffective due to differing agendas pursued by each participating country. This is because the current regional body is structured only to facilitate information exchange and cooperation in a limited manner, focusing so far only on water management issues. LMS regional goals need to be set in order to guide the stakeholders in identifying an appropriate set of EPIs. Most importantly, the research is intended to be a catalyst for encouraging the participants to integrate methods and other species of EPIs proposed in this research in their environmental assessment policies.

<p>The internal and external challenges construction companies face such as variability, low productivity, inefficient processes, waste, uncertainties, risks, fragmentation, adversarial contractual relationships, competition, and those resulting from internal and external challenges such as cost overruns and delays negatively affect company performance and profitability. Though research publications abound, these challenges persist, which indicates that the following gaps exist. Lean construction, process improvement, and performance improvement research have been conducted wherein improvement principles, and best practices are used to ameliorate performance issues, but several knowledge gaps exist. Few companies use these improvement principles and best practices. For those companies applying improvements, there is no established link between these improvements and performance/profitability to guide companies. Further, even when companies use improvement principles and best practices, they apply only one or two, whereas an integrated application of these improvement principles and best practices would be more effective. The other gap the author identified is the lack of strategic tools that construction companies can use to improve and manage their profitability. This thesis tried to fill the knowledge gap, at least partially, by developing a two-part excellence model for profitability improvement of construction companies. The excellence model lays out strategies that would enable companies to overcome the challenges and improve their profitability. The excellence model also gives an iterative and recursive continuous improvement model and flowchart to improve the profitability of construction companies. The researcher used high impact principles, guidelines, and concepts from the literature on organizational effectiveness, critical success factors, strategic company profitability growth enablers, process improvement, and process maturity models, performance improvement, and organizational excellence guidelines to develop the two-part excellence model.</p> <p>The author also translated the two-part excellence model into the diagnostic tool and Decision Support System (DSS) by use of process diagrams, fishbone diagrams, root cause analysis, and use of improvement principles, countermeasures and best practices at the most granular (lowest intervention) levels to do away with root causes of poor performance. The author developed the diagnostic tool and Decision Support System (DSS) in Access 2016 to serve as a strategic tool to improve and manage the profitability of construction companies. The researcher used improvement principles, and best practices from scientific and practitioner literature to develop company and project process flow diagrams, and fishbone (cause and effect) diagrams for company, department, employee, interactions and project performance for the profitability improvement, which are the engines of the diagnostic tool and DSS. The diagnostic tool and DSS use continuous improvement cycles iteratively and recursively to improve the profitability of construction companies from the current net profit of 2-3 percent to a higher value.</p>