The effects of administration of a nuclear factor kappa-B inhibitor on pulmonary endothelial dysfunction after cardiopulmonary bypass: impact on oxygenation and hemodynamics and development of therapeutic and preventive modalities in a porcine model

Introduction: La circulation extracorporelle (CEC) peut entraîner une dysfonction endothéliale pulmonaire et l’hypertension pulmonaire. Le SN50 agit au niveau de la signalisation cellulaire pour prévenir ces réactions à la CEC et pourrait renverser la dysfonction endothéliale pulmonaire post-CEC sans effets néfastes sur l’hémodynamie. Méthodes: Quatre groups de porcs ont reçu un parmi quatre traîtements avant de subir 90 minutes de CEC et 60 minutes de reperfusion: (1) milrinone nébulisé; (2) sildenafil nébulisé; (3) placebo nébulisé; et (4) SN-50 intraveineux. Un monitoring hémodynamique invasif a été utilisé. La réactivité vasculaire des artères pulmonaires de deuxième ordre a été évaluée face à l’acétylcholine et la bradykinine. Résultats: Le sildénafil produit une augmentation significative de la pression de l’artère pulmonaire (PAP) moyenne à 60 minutes de reperfusion par rapport au début de la chirurgie. Les relaxations dépendantes de l’endothélium face à la bradykinine étaient meilleurs dans les groupes milrinone et SN-50 et surtout dans le groupe sildénafil par rapport au groupe placébo. Le SN-50 produisait de moins bonnes relaxations dépendantes de l’endothélium face à l’acétylcholine que les autres traitements incluant placébo. Conclusion: Le sildénafil prévient mieux la dysfonction endothéliale pulmonaire que les autres traitements. Les bénéfices du SN-50 sont possiblement sous-estimés vu que la dose n’a pas pu être ajustée à la durée de CEC. Le sildenafil inhalé mérite une étude plus importante chez l’humain et le SN-50 dans un model de CEC animal.

A theoretical and experimental dissociation of two models of decision‐making

La prise de décision est un processus computationnel fondamental dans de nombreux aspects du comportement animal. Le modèle le plus souvent rencontré dans les études portant sur la prise de décision est appelé modèle de diffusion. Depuis longtemps, il explique une grande variété de données comportementales et neurophysiologiques dans ce domaine. Cependant, un autre modèle, le modèle d’urgence, explique tout aussi bien ces mêmes données et ce de façon parcimonieuse et davantage encrée sur la théorie. Dans ce travail, nous aborderons tout d’abord les origines et le développement du modèle de diffusion et nous verrons comment il a été établi en tant que cadre de travail pour l’interprétation de la plupart des données expérimentales liées à la prise de décision. Ce faisant, nous relèveront ses points forts afin de le comparer ensuite de manière objective et rigoureuse à des modèles alternatifs. Nous réexaminerons un nombre d’assomptions implicites et explicites faites par ce modèle et nous mettrons alors l’accent sur certains de ses défauts. Cette analyse servira de cadre à notre introduction et notre discussion du modèle d’urgence. Enfin, nous présenterons une expérience dont la méthodologie permet de dissocier les deux modèles, et dont les résultats illustrent les limites empiriques et théoriques du modèle de diffusion et démontrent en revanche clairement la validité du modèle d'urgence. Nous terminerons en discutant l'apport potentiel du modèle d'urgence pour l'étude de certaines pathologies cérébrales, en mettant l'accent sur de nouvelles perspectives de recherche.

Elucidation of the biological roles of Wnt5a signaling in follicle development

La santé folliculaire est déterminée par un nombre de facteurs endocriniens, paracrines et autocrines. Les gonadotrophines hypophysaires sont les principaux moteurs du développement du follicule, mais leurs actions sont modulées localement par les hormones et des facteurs de croissance. Les glycoprotéines de la famille des WNTs représentent une grande famille de molécules impliquées dans différentes voies de signalisation. Ils sont sécrétés dans le but de moduler et coordonner la réponse des follicules aux gonadotrophines, et leurs activités sont indispensables à la fonction ovarienne et à la fertilité féminine. Les WNTs sont généralement classés en fonction de la (des) voie(s) qu’ils activent. Le rôle des membres de la voie canonique WNT et de ses composants tels que CTNNB1, WNT4, WNT2, FZD1 et FZD4 est bien établi au cours du développement du follicule chez les rongeurs. Un rôle similaire des WNTs dans les espèces mono-ovulatoires demeure essentiellement inconnu. De plus, le rôle des WNT non canoniques dans l'ovaire de rongeurs est méconnu. Les objectifs de cette thèse sont (1) d'élucider la régulation hormonale de l'expression de WNT5A et le rôle physiologique de WNT5A dans les cellules de la granulosa bovine in vitro et (2) d'identifier les rôles physiologiques de WNT5A dans l'ovaire de souris par inactivation génique conditionnelle. Chacun de ces objectifs a mené à la publication d’un article à partir des résultats obtenus au cours de cette thèse. Dans le premier article, le rôle de WNT5A dans les cellules de la granulosa bovine a été étudié in vitro. Nous avons constaté que WNT5A est un régulateur négatif de la stéroïdogenèse stimulée par la FSH issue des cellules de la granulosa, et qu'il agit en supprimant l'activité de signalisation des WNTs canoniques tout en induisant la voie de signalisation MAPK8/JUN. le deuxième article, afin d’examiner le rôle de deux WNTs non-canoniques, WNT5A et WNT11, à différents stades de développement folliculaire, nous avons généré des modèles de souris knock-out conditionnels ciblant les cellules de la granulosa pour chacun de ces WNTs. Les résultats obtenus ont permis de mettre en évidence que WNT5A est nécessaire pour assurer la fertilité normale chez la femelle, le développement folliculaire et la stéroïdogenèse ovarienne. Il est aussi un antagoniste de la réponse aux gonadotrophines, agissant par l’intermédiaire de la suppression de la signalisation canonique des WNTs. Chez les souris knock-out pour WNT11, nous ne constatons aucun défaut important dans la fertilité des femelles. L’ensemble de notre travail met en évidence que WNT5A est essentiel pour le développement normal du follicule et qu’il agit pour inhiber la différenciation des cellules de la granulosa. En résumé, nous avons fourni une étude novatrice et approfondie, utilisant plusieurs modèles et techniques pour déterminer les mécanismes par lesquels WNT5A régule le développement des follicules.

A STUDY ON SOFTWARE DEVELOPMENT PROJECT RISK, RISK MANAGEMENT, PROJECT OUTCOMES AND THEIR INTER-RELATIONSHIP

This research was undertaken with an objective of studying software development project risk, risk management, project outcomes and their inter-relationship in the Indian context. Validated instruments were used to measure risk, risk management and project outcome in software development projects undertaken in India. A second order factor model was developed for risk with five first order factors. Risk management was also identified as a second order construct with four first order factors. These structures were validated using confirmatory factor analysis. Variation in risk across categories of select organization / project characteristics was studied through a series of one way ANOVA tests. Regression model was developed for each of the risk factors by linking it to risk management factors and project /organization characteristics. Similarly regression models were developed for the project outcome measures linking them to risk factors. Integrated models linking risk factors, risk management factors and project outcome measures were tested through structural equation modeling. Quality of the software developed was seen to have a positive relationship with risk management and negative relationship with risk. The other outcome variables, namely time overrun and cost over run, had strong positive relationship with risk. Risk management did not have direct effect on overrun variables. Risk was seen to be acting as an intervening variable between risk management and overrun variables.

Development of a Technique for Estimating Rain Parameters from Rain Noise Measurements

The measurement of global precipitation is of great importance in climate modeling since the release of latent heat associated with tropical convection is one of the pricipal driving mechanisms of atmospheric circulation.Knowledge of the larger-scale precipitation field also has important potential applications in the generation of initial conditions for numerical weather prediction models Knowledge of the relationship between rainfall intensity and kinetic energy, and its variations in time and space is important for erosion prediction. Vegetation on earth also greatly depends on the total amount of rainfall as well as the drop size distribution (DSD) in rainfall.While methods using visible,infrared, and microwave radiometer data have been shown to yield useful estimates of precipitation, validation of these products for the open ocean has been hampered by the limited amount of surface rainfall measurements available for accurate assessement, especially for the tropical oceans.Surface rain fall measurements(often called the ground truth)are carried out by rain gauges working on various principles like weighing type,tipping bucket,capacitive type and so on.The acoustic technique is yet another promising method of rain parameter measurement that has many advantages. The basic principle of acoustic method is that the droplets falling in water produce underwater sound with distinct features, using which the rainfall parameters can be computed. The acoustic technique can also be used for developing a low cost and accurate device for automatic measurement of rainfall rate and kinetic energy of rain.especially suitable for telemetry applications. This technique can also be utilized to develop a low cost Disdrometer that finds application in rainfall analysis as well as in calibration of nozzles and sprinklers. This thesis is divided into the following 7 chapters, which describes the methodology adopted, the results obtained and the conclusions arrived at.

Studies Using Computer Simulation Models to Solve Problems Related to Logistics Terminals

This thesis deals with the use of simulation as a problem-solving tool to solve a few logistic system related problems. More specifically it relates to studies on transport terminals. Transport terminals are key elements in the supply chains of industrial systems. One of the problems related to use of simulation is that of the multiplicity of models needed to study different problems. There is a need for development of methodologies related to conceptual modelling which will help reduce the number of models needed. Three different logistic terminal systems Viz. a railway yard, container terminal of apart and airport terminal were selected as cases for this study. The standard methodology for simulation development consisting of system study and data collection, conceptual model design, detailed model design and development, model verification and validation, experimentation, and analysis of results, reporting of finding were carried out. We found that models could be classified into tightly pre-scheduled, moderately pre-scheduled and unscheduled systems. Three types simulation models( called TYPE 1, TYPE 2 and TYPE 3) of various terminal operations were developed in the simulation package Extend. All models were of the type discrete-event simulation. Simulation models were successfully used to help solve strategic, tactical and operational problems related to three important logistic terminals as set in our objectives. From the point of contribution to conceptual modelling we have demonstrated that clubbing problems into operational, tactical and strategic and matching them with tightly pre-scheduled, moderately pre-scheduled and unscheduled systems is a good workable approach which reduces the number of models needed to study different terminal related problems.

Development of Free Space Method for Material Characterisation and GPR Study & A Case Study on Biological Samples

The thesis mainly focuses on material characterization in different environments: freely available samples taken in planar fonn, biological samples available in small quantities and buried objects.Free space method, finds many applications in the fields of industry, medicine and communication. As it is a non-contact method, it can be employed for monitoring the electrical properties of materials moving through a conveyor belt in real time. Also, measurement on such systems at high temperature is possible. NID theory can be applied to the characterization of thin films. Dielectric properties of thin films deposited on any dielectric substrate can be determined. ln chemical industry, the stages of a chemical reaction can be monitored online. Online monitoring will be more efficient as it saves time and avoids risk of sample collection.Dielectric contrast is one of the main factors, which decides the detectability of a system. lt could be noted that the two dielectric objects of same dielectric constant 3.2 (s, of plastic mine) placed in a medium of dielectric constant 2.56 (er of sand) could even be detected employing the time domain analysis of the reflected signal. This type of detection finds strategic importance as it provides solution to the problem of clearance of non-metallic mines. The demining of these mines using the conventional techniques had been proved futile. The studies on the detection of voids and leakage in pipes find many applications.The determined electrical properties of tissues can be used for numerical modeling of cells, microwave imaging, SAR test etc. All these techniques need the accurate determination of dielectric constant. ln the modem world, the use of cellular and other wireless communication systems is booming up. At the same time people are concemed about the hazardous effects of microwaves on living cells. The effect is usually studied on human phantom models. The construction of the models requires the knowledge of the dielectric parameters of the various body tissues. lt is in this context that the present study gains significance. The case study on biological samples shows that the properties of normal and infected body tissues are different. Even though the change in the dielectric properties of infected samples from that of normal one may not be a clear evidence of an ailment, it is an indication of some disorder.ln medical field, the free space method may be adapted for imaging the biological samples. This method can also be used in wireless technology. Evaluation of electrical properties and attenuation of obstacles in the path of RF waves can be done using free waves. An intelligent system for controlling the power output or frequency depending on the feed back values of the attenuation may be developed.The simulation employed in GPR can be extended for the exploration of the effects due to the factors such as the different proportion of water content in the soil, the level and roughness of the soil etc on the reflected signal. This may find applications in geological explorations. ln the detection of mines, a state-of-the art technique for scanning and imaging an active mine field can be developed using GPR. The probing antenna can be attached to a robotic arm capable of three degrees of rotation and the whole detecting system can be housed in a military vehicle. In industry, a system based on the GPR principle can be developed for monitoring liquid or gas through a pipe, as pipe with and without the sample gives different reflection responses. lt may also be implemented for the online monitoring of different stages of extraction and purification of crude petroleum in a plant.Since biological samples show fluctuation in the dielectric nature with time and other physiological conditions, more investigation in this direction should be done. The infected cells at various stages of advancement and the normal cells should be analysed. The results from these comparative studies can be utilized for the detection of the onset of such diseases. Studying the properties of infected tissues at different stages, the threshold of detectability of infected cells can be determined.

Development of solar air heaters & thermal energy storage system for drying applications in food processing industries

In the present work, the author has designed and developed all types of solar air heaters called porous and nonporous collectors. The developed solar air heaters were subjected to different air mass flow rates in order to standardize the flow per unit area of the collector. Much attention was given to investigate the performance of the solar air heaters fitted with baffles. The output obtained from the experiments on pilot models, helped the installation of solar air heating system for industrial drying applications also. Apart from these, various types of solar dryers, for small and medium scale drying applications, were also built up. The feasibility of ‘latent heat thermal energy storage system’ based on Phase Change Material was also undertaken. The application of solar greenhouse for drying industrial effluent was analyzed in the present study and a solar greenhouse was developed. The effectiveness of Computational Fluid Dynamics (CFD) in the field of solar air heaters was also analyzed. The thesis is divided into eight chapters.

Studies on a syntax based approach for translation between structurally different languages and the development of a prototype for Malayalam to English translation

This thesis summarizes the results on the studies on a syntax based approach for translation between Malayalam, one of Dravidian languages and English and also on the development of the major modules in building a prototype machine translation system from Malayalam to English. The development of the system is a pioneering effort in Malayalam language unattempted by previous researchers. The computational models chosen for the system is first of its kind for Malayalam language. An in depth study has been carried out in the design of the computational models and data structures needed for different modules: morphological analyzer , a parser, a syntactic structure transfer module and target language sentence generator required for the prototype system. The generation of list of part of speech tags, chunk tags and the hierarchical dependencies among the chunks required for the translation process also has been done. In the development process, the major goals are: (a) accuracy of translation (b) speed and (c) space. Accuracy-wise, smart tools for handling transfer grammar and translation standards including equivalent words, expressions, phrases and styles in the target language are to be developed. The grammar should be optimized with a view to obtaining a single correct parse and hence a single translated output. Speed-wise, innovative use of corpus analysis, efficient parsing algorithm, design of efficient Data Structure and run-time frequency-based rearrangement of the grammar which substantially reduces the parsing and generation time are required. The space requirement also has to be minimised

Genetic Programming meets Model-Driven Development

Genetic programming is known to provide good solutions for many problems like the evolution of network protocols and distributed algorithms. In such cases it is most likely a hardwired module of a design framework that assists the engineer to optimize specific aspects of the system to be developed. It provides its results in a fixed format through an internal interface. In this paper we show how the utility of genetic programming can be increased remarkably by isolating it as a component and integrating it into the model-driven software development process. Our genetic programming framework produces XMI-encoded UML models that can easily be loaded into widely available modeling tools which in turn posses code generation as well as additional analysis and test capabilities. We use the evolution of a distributed election algorithm as an example to illustrate how genetic programming can be combined with model-driven development. This example clearly illustrates the advantages of our approach – the generation of source code in different programming languages.

Parameter identification of structural dynamic models by inverse statistical analysis

Auf dem Gebiet der Strukturdynamik sind computergestützte Modellvalidierungstechniken inzwischen weit verbreitet. Dabei werden experimentelle Modaldaten, um ein numerisches Modell für weitere Analysen zu korrigieren. Gleichwohl repräsentiert das validierte Modell nur das dynamische Verhalten der getesteten Struktur. In der Realität gibt es wiederum viele Faktoren, die zwangsläufig zu variierenden Ergebnissen von Modaltests führen werden: Sich verändernde Umgebungsbedingungen während eines Tests, leicht unterschiedliche Testaufbauten, ein Test an einer nominell gleichen aber anderen Struktur (z.B. aus der Serienfertigung), etc. Damit eine stochastische Simulation durchgeführt werden kann, muss eine Reihe von Annahmen für die verwendeten Zufallsvariablengetroffen werden. Folglich bedarf es einer inversen Methode, die es ermöglicht ein stochastisches Modell aus experimentellen Modaldaten zu identifizieren. Die Arbeit beschreibt die Entwicklung eines parameter-basierten Ansatzes, um stochastische Simulationsmodelle auf dem Gebiet der Strukturdynamik zu identifizieren. Die entwickelte Methode beruht auf Sensitivitäten erster Ordnung, mit denen Parametermittelwerte und Kovarianzen des numerischen Modells aus stochastischen experimentellen Modaldaten bestimmt werden können.

Development of an ArcGIS extension to model urban climate factors

The possibility to develop automatically running models which can capture some of the most important factors driving the urban climate would be very useful for many planning aspects. With the help of these modulated climate data, the creation of the typically used “Urban Climate Maps” (UCM) will be accelerated and facilitated. This work describes the development of a special ArcGIS software extension, along with two support databases to achieve this functionality. At the present time, lacking comparability between different UCMs and imprecise planning advices going along with the significant technical problems of manually creating conventional maps are central issues. Also inflexibility and static behaviour are reducing the maps’ practicality. From experi-ence, planning processes are formed more productively, namely to implant new planning parameters directly via the existing work surface to map the impact of the data change immediately, if pos-sible. In addition to the direct climate figures, information of other planning areas (like regional characteristics / developments etc.) have to be taken into account to create the UCM as well. Taking all these requirements into consideration, an automated calculation process of urban climate impact parameters will serve to increase the creation of homogenous UCMs efficiently.

A FRAMEWORK FOR ACHIEVING LIFECYCLE VALUE IN AEROSPACE PRODUCT DEVELOPMENT

Creation of lifecycle value - a balance of performance with cost and other attributes - represents a challenge for the development of aerospace products in the twenty-first century. This paper examines the concept of lifecycle value that stems from existing approaches of value management and analysis, lifecycle costing, and systems engineering. To ascertain common characteristics of lifecycle value creation, case studies were done for four aircraft programs: F/A- 18E/F, JAS 39 Gripen, F-16C/D, and B-777. A lifecycle value creation framework is introduced, comprised of three phases: value identification, value proposition, value delivery. Based upon observed practices in the four case studies, six value creation attributes were identified. Capability maturity models for the six attributes and three value creation phases are presented. The resulting framework represents a starting point for programs seeking to create lifecycle value for aerospace products.

Measuring Value in Product Development

“What is value in product development?” is the key question of this paper. The answer is critical to the creation of lean in product development. By knowing how much value is added by product development (PD) activities, decisions can be more rationally made about how to allocate resources, such as time and money. In order to apply the principles of Lean Thinking and remove waste from the product development system, value must be precisely defined. Unfortunately, value is a complex entity that is composed of many dimensions and has thus far eluded definition on a local level. For this reason, research has been initiated on “Measuring Value in Product Development.” This paper serves as an introduction to this research. It presents the current understanding of value in PD, the critical questions involved, and a specific research design to guide the development of a methodology for measuring value. Work in PD value currently focuses on either high-level perspectives on value, or detailed looks at the attributes that value might have locally in the PD process. Models that attempt to capture value in PD are reviewed. These methods, however, do not capture the depth necessary to allow for application. A methodology is needed to evaluate activities on a local level to determine the amount of value they add and their sensitivity with respect to performance, cost, time, and risk. Two conceptual tools are proposed. The first is a conceptual framework for value creation in PD, referred to here as the Value Creation Model. The second tool is the Value-Activity Map, which shows the relationships between specific activities and value attributes. These maps will allow a better understanding of the development of value in PD, will facilitate comparison of value development between separate projects, and will provide the information necessary to adapt process analysis tools (such as DSM) to consider value. The key questions that this research entails are: · What are the primary attributes of lifecycle value within PD? · How can one model the creation of value in a specific PD process? · Can a useful methodology be developed to quantify value in PD processes? · What are the tools necessary for application? · What PD metrics will be integrated with the necessary tools? The research milestones are: · Collection of value attributes and activities (September, 200) · Development of methodology of value-activity association (October, 2000) · Testing and refinement of the methodology (January, 2001) · Tool Development (March, 2001) · Present findings at July INCOSE conference (April, 2001) · Deliver thesis that captures a formalized methodology for defining value in PD (including LEM data sheets) (June, 2001) The research design aims for the development of two primary deliverables: a methodology to guide the incorporation of value, and a product development tool that will allow direct application.

LiDAR data filtering with GRASS GIS for the determination of digital terrain models

In the last years, the use of every type of Digital Elevation Models has iimproved. The LiDAR (Light Detection and Ranging) technology, based on the scansion of the territory b airborne laser telemeters, allows the construction of digital Surface Models (DSM), in an easy way by a simple data interpolation