Limited sampling strategies for estimation of cyclosporine exposure in pediatric hematopoietic stem cell transplant recipients : methodological improvement and introduction of sampling time deviation analysis.

Le suivi thérapeutique est recommandé pour l’ajustement de la dose des agents immunosuppresseurs. La pertinence de l’utilisation de la surface sous la courbe (SSC) comme biomarqueur dans l’exercice du suivi thérapeutique de la cyclosporine (CsA) dans la transplantation des cellules souches hématopoïétiques est soutenue par un nombre croissant d’études. Cependant, pour des raisons intrinsèques à la méthode de calcul de la SSC, son utilisation en milieu clinique n’est pas pratique. Les stratégies d’échantillonnage limitées, basées sur des approches de régression (R-LSS) ou des approches Bayésiennes (B-LSS), représentent des alternatives pratiques pour une estimation satisfaisante de la SSC. Cependant, pour une application efficace de ces méthodologies, leur conception doit accommoder la réalité clinique, notamment en requérant un nombre minimal de concentrations échelonnées sur une courte durée d’échantillonnage. De plus, une attention particulière devrait être accordée à assurer leur développement et validation adéquates. Il est aussi important de mentionner que l’irrégularité dans le temps de la collecte des échantillons sanguins peut avoir un impact non-négligeable sur la performance prédictive des R-LSS. Or, à ce jour, cet impact n’a fait l’objet d’aucune étude. Cette thèse de doctorat se penche sur ces problématiques afin de permettre une estimation précise et pratique de la SSC. Ces études ont été effectuées dans le cadre de l’utilisation de la CsA chez des patients pédiatriques ayant subi une greffe de cellules souches hématopoïétiques. D’abord, des approches de régression multiple ainsi que d’analyse pharmacocinétique de population (Pop-PK) ont été utilisées de façon constructive afin de développer et de valider adéquatement des LSS. Ensuite, plusieurs modèles Pop-PK ont été évalués, tout en gardant à l’esprit leur utilisation prévue dans le contexte de l’estimation de la SSC. Aussi, la performance des B-LSS ciblant différentes versions de SSC a également été étudiée. Enfin, l’impact des écarts entre les temps d’échantillonnage sanguins réels et les temps nominaux planifiés, sur la performance de prédiction des R-LSS a été quantifié en utilisant une approche de simulation qui considère des scénarios diversifiés et réalistes représentant des erreurs potentielles dans la cédule des échantillons sanguins. Ainsi, cette étude a d’abord conduit au développement de R-LSS et B-LSS ayant une performance clinique satisfaisante, et qui sont pratiques puisqu’elles impliquent 4 points d’échantillonnage ou moins obtenus dans les 4 heures post-dose. Une fois l’analyse Pop-PK effectuée, un modèle structural à deux compartiments avec un temps de délai a été retenu. Cependant, le modèle final - notamment avec covariables - n’a pas amélioré la performance des B-LSS comparativement aux modèles structuraux (sans covariables). En outre, nous avons démontré que les B-LSS exhibent une meilleure performance pour la SSC dérivée des concentrations simulées qui excluent les erreurs résiduelles, que nous avons nommée « underlying AUC », comparée à la SSC observée qui est directement calculée à partir des concentrations mesurées. Enfin, nos résultats ont prouvé que l’irrégularité des temps de la collecte des échantillons sanguins a un impact important sur la performance prédictive des R-LSS; cet impact est en fonction du nombre des échantillons requis, mais encore davantage en fonction de la durée du processus d’échantillonnage impliqué. Nous avons aussi mis en évidence que les erreurs d’échantillonnage commises aux moments où la concentration change rapidement sont celles qui affectent le plus le pouvoir prédictif des R-LSS. Plus intéressant, nous avons mis en exergue que même si différentes R-LSS peuvent avoir des performances similaires lorsque basées sur des temps nominaux, leurs tolérances aux erreurs des temps d’échantillonnage peuvent largement différer. En fait, une considération adéquate de l'impact de ces erreurs peut conduire à une sélection et une utilisation plus fiables des R-LSS. Par une investigation approfondie de différents aspects sous-jacents aux stratégies d’échantillonnages limités, cette thèse a pu fournir des améliorations méthodologiques notables, et proposer de nouvelles voies pour assurer leur utilisation de façon fiable et informée, tout en favorisant leur adéquation à la pratique clinique.

Treating delusional disorder : a comparison of cognitive-behavioural therapy and attention placebo control

Objective: Cognitive-behavioural therapy (CBT) has proved effective in treating delusions, both in schizophrenia and delusional disorder (DD). Clinical trials of DD have mostly compared CBT with either treatment as usual, no treatment, or a wait-list control. This current study aimed to assess patients with DD who received CBT, compared with an attention placebo control (APC) group. Method: Twenty-four individuals with DD were randomly allocated into either CBT or APC groups for a 24-week treatment period. Patients were diagnosed on the basis of structured clinical interviews for mental disorders and the Maudsley Assessment of Delusion Schedule (MADS). Results: Completers in both groups (n = 11 for CBT; n = 6 for APC) showed clinical improvement on the MADS dimensions of Strength of Conviction, Insight, Preoccupation, Systematization, Affect Relating to Belief, Belief Maintenance Factors, and Idiosyncrasy of Belief. Conclusion: When compared with APC, CBT produced more impact on the MADS dimensions for Affect Relating to Belief, Strength of Conviction, and Positive Actions on Beliefs.

Evaluation of Reducibility of Trunk Asymmetry in Lateral Bending

The value of the lateral bending test is important in the assessment of spinal curve mobility and prediction of surgical outcome in the treatment of adolescent idiopathic scoliosis (AIS). However, radiographic bending tests are unable to assess the reducibility of trunk asymmetry. This study aims to exploit surface topography measurement in order to evaluate the changes in shape of the trunk (a) between bending and neutral standing positions, and (b) between standing pre- and post-operative visits, in a cohort of adolescents with AIS having undergone surgical correction; and to correlate the differences measured in cases (a) and (b). Our cohort includes 13 patients with right thoracic AIS. Each patient had their 3D trunk surface digitized with a multi-head InSpeck system in standing posture (at the pre-op and post-op visits) and in maximum voluntary right and left bending (at the pre-op visit). We developed a novel trunk shape analysis method which produces a set of inclined trunk cross-sections allowing comparison between different postures. Two asymmetry indices, trunk rotation (TR) and back surface rotation (BSR), were computed in all cases and a statistical analysis was performed. Our correlation study (Pearson test) showed fair correlations in most cases between the changes in side-bending and those post-surgery, with the strongest relationship (p-value < 0.01) when combining the TR measurements from both bendings. These results provide evidence that the bending test can be used to assess trunk asymmetry reducibility. The proposed approach could provide a non-invasive trunk asymmetry reducibility test for routine clinical use in AIS surgery planning.

Dopamine Receptor Gene Expression In Streptozotocin Induced Diabetic Rats And Its Role In Insulin Secretion

Diabetes Mellitus is a metabolic disorder associated with insulin deficiency, which not.only affects the carbohydrate metabolism but also is associated with various central and peripheral complications. Chronic hyperglycemia during diabetes mellitus is a major initiator of diabetic microvascular complications like retinopathy, neuropathy, The central nervous system (CNS) neurotransmitters play an important role in the regulation of glucose homeostasis. These neurotransmitters mediate rapid intracellular communications not only within the central nervous system but also in the peripheral tissues. They exert their function through receptors present in both neuronal and non neuronal cell surface that trigger second messenger signaling pathways. Dopamine is a neurotransmitter that has been implicated in various central neuronal degenerative disorders like Parkinson's disease and behavioral diseases like Schizophrenia. Dopamine is synthesised from tyrosine, stored in vesicles in axon terminals and released when the neuron is depolarised. Dopamine interacts with specific membrane receptors to produce its effect. Dopamine plays an important role both centrally and peripherally. The recent identification of five dopamine receptor subtypes provides a basis for understanding dopamine's central and peripheral actions . Dopamine receptors are classified into two major groups : DA D1 like and DA D2 like. Dopamine D1 like receptors consists of DA D1 and DA D5 receptors . Dopamine D2 like receptors consists of DA D2, DA D3 and DA D4 receptors. Stimulation of the DA D1 receptor gives rise to increased production of cAMP. Dopamine D2 receptors inhibit cAMP production, but activate the inositol phosphate second messenger system . Impairment of central dopamine neurotransmission causes muscle rigidity, hormonal regulation , thought disorder and cocaine addiction. Peripheral dopamine receptors mediate changes in blood flow, glomerular filtration rate, sodium excretion and catecholamine release. The dopamine D2 receptors increased in the corpus striatum and cerebral cortex but decreased in the hypothalamus and brain stem indicating their involvement in regulating insulin secretion. Dopamine D2 receptor which has a stimulatory effecton insulin secretion decreased in the pancreatic islets during diabetes. Our in vitro studies confirmed the stimulatory role of dopamine D2 receptors in stimulation of glucose induced insulin secretion. A detailed study at the molecular level on the mechanisms involved in the role of dopamine in insulin secretion, its functional modification could lead to therapeutic interventions that will have immense clinical importance.

Design and Development of Fiber Optic Sensors for Trace Detection of Certain Environmental Pollutants

In recent years,photonics has emerged as an essential technology related to such diverse fields like laser technology,fiber optics,communication,optical signal processing,computing,entertainment,consumer electronics etc.Availabilities of semiconductor lasers and low loss fibers have also revolutionized the field of sensor technology including telemetry. There exist fiber optic sensors which are sensitive,reliable.light weight and accurate devices which find applications in wide range of areas like biomedicine,aviation,surgery,pollution monitoring etc.,apart from areas in basic sciences.The present thesis deals with the design,fabrication and characterization of a variety of cost effective and sensitive fiber optic sensors for the trace detetction of certain environment pollutants in air and water.The sensor design is carried out using the techniques like evanescent waves,micro bending and long period gratings.

Numerical Investigations on Soil Structure Interaction of Multistorey Frames

Frames are the most widely used structural system for multistorey buildings. A building frame is a three dimensional discrete structure consisting of a number of high rise bays in two directions at right angles to each other in the vertical plane. Multistorey frames are a three dimensional lattice structure which are statically indeterminate. Frames sustain gravity loads and resist lateral forces acting on it. India lies at the north westem end of the Indo-Australian tectonic plate and is identified as an active tectonic area. Under horizontal shaking of the ground, horizontal inertial forces are generated at the floor levels of a multistorey frame. These lateral inertia forces are transferred by the floor slab to the beams, subsequently to the columns and finally to the soil through the foundation system. There are many parameters that affect the response of a structure to ground excitations such as, shape, size and geometry of the structure, type of foundation, soil characteristics etc. The Soil Structure Interaction (SS1) effects refer to the influence of the supporting soil medium on the behavior of the structure when it is subjected to different types of loads. Interaction between the structure and its supporting foundation and soil, which is a complete system, has been modeled with finite elements. Numerical investigations have been carried out on a four bay, twelve storeyed regular multistorey frame considering depth of fixity at ground level, at characteristic depth of pile and at full depth. Soil structure interaction effects have been studied by considering two models for soil viz., discrete and continuum. Linear static analysis has been conducted to study the interaction effects under static load. Free vibration analysis and further shock spectrum analysis has been conducted to study the interaction effects under time dependent loads. The study has been extended to four types of soil viz., laterite, sand, alluvium and layered.The structural responses evaluated in the finite element analysis are bending moment, shear force and axial force for columns, and bending moment and shear force for beams. These responses increase with increase in the founding depth; however these responses show minimal increase beyond the characteristic length of pile. When the soil structure interaction effects are incorporated in the analysis, the aforesaid responses of the frame increases upto the characteristic depth and decreases when the frame has been analysed for the full depth. It has been observed that shock spectrum analysis gives wide variation of responses in the frame compared to linear elastic analysis. Both increase and decrease in responses have been observed in the interior storeys. The good congruence shown by the two finite element models viz., discrete and continuum in linear static analysis has been absent in shock spectrum analysis.

Modification of Linear Low Density Polyethylene for Improved Photo and Biodegradation

LLDPE was blended with poly (vinyl alcohol) and mechanical, thermal, spectroscopic properties and biodegradability were investigated. The biodegradability of LLDPE/PVA blends has been studied in two environments, viz. (1) a culture medium containing Vibrio sp. and (2) a soil environment over a period of 15 weeks. Nanoanatase having photo catalytic activity was synthesized by hydrothermal method using titanium-iso-propoxide. The synthesized TiO2 was characterized by X-Ray diffraction (XRD), BET studies, FTIR studies and scanning electron microscopy (SEM). The crystallite size of titania was calculated to be ≈ 6nm from the XRD results and the surface area was found to be about 310m2/g by BET method. SEM shows that nanoanatase particles prepared by this method are spherical in shape. Linear low density polyethylene films containing polyvinyl alcohol and a pro-oxidant (TiO2 or cobalt stearate with or without vegetable oil) were prepared. The films were then subjected to natural weathering and UV exposure followed by biodegradation in culture medium as well as in soil environment. The degradation was monitored by mechanical property measurements, thermal studies, rate of weight loss, FTIR and SEM studies. Higher weight loss, texture change and greater increments in carbonyl index values were observed in samples containing cobalt stearate and vegetable oil. The present study demonstrates that the combination of LLDPE/PVA blends with (I) nanoanatase/vegetable oil and (ii) cobalt stearate/vegetable oil leads to extensive photodegradation. These samples show substantial degradation when subsequent exposure to Vibrio sp. is made. Thus a combined photodegradation and biodegradation process is a promising step towards obtaining a biodegradable grade of LLDPE.

A Study Of The Strength And Compressibility Characteristics Of Cochin Marine Clays

With the advent of urbanisation and consequent search for more and more habitable land, it was imperative that the large tracts of marine clays, considered inhabitable earlier, had to be reclaimed and developed. These marine clays, wellknown for its high compressibility and poor shear strength, posed numerous problems to the builders and Cochin was no exception. It is only less than a decade since active research work was initiated on marine clays in general and Cochin marine clays in particular. Eventhough some systematic studies are available on compressibility characteristics, attempts to study the shear strength aspects and development of techniques to improve it have been very limited. This work is an investigation on the consolidation and shear strength characteristics of Cochin marine clays including methods to improve the same

Electronic structure and magnetic interactions of the spin-chain compounds Ca2CuO3 and Sr2CuO3

The results are presented of a combined periodic and cluster model approach to the electronic structure and magnetic interactions in the spin-chain compounds Ca2CuO3 and Sr2CuO3. An extended t-J model is presented that includes in-chain and interchain hopping and magnetic interaction processes with parameters extracted from ab initio calculations. For both compounds, the in-chain magnetic interaction is found to be around -240 meV, larger than in any of the other cuprates reported in the literature. The interchain magnetic coupling is found to be weakly antiferromagnetic, -1 meV. The effective in-chain hopping parameters are estimated to be ~650 meV for both compounds, whereas the value of the interchain hopping parameter is 30 meV for Sr2CuO3 and 40 meV for Ca2CuO3, in line with the larger interchain distance in the former compound. These effective parameters are shown to be consistent with expressions recently suggested for the Néel temperature and the magnetic moments, and with relations that emerge from the t-J model Hamiltonian. Next, we investigate the physical nature of the band gap. Periodic calculations indicate that an interpretation in terms of a charge-transfer insulator is the most appropriate one, in contrast to the suggestion of a covalent correlated insulator recently reported in the literature.

CBIR Using Local and Global Properties of Image Sub-blocks

This paper proposes a content based image retrieval (CBIR) system using the local colour and texture features of selected image sub-blocks and global colour and shape features of the image. The image sub-blocks are roughly identified by segmenting the image into partitions of different configuration, finding the edge density in each partition using edge thresholding, morphological dilation and finding the corner density in each partition. The colour and texture features of the identified regions are computed from the histograms of the quantized HSV colour space and Gray Level Co- occurrence Matrix (GLCM) respectively. A combined colour and texture feature vector is computed for each region. The shape features are computed from the Edge Histogram Descriptor (EHD). Euclidean distance measure is used for computing the distance between the features of the query and target image. Experimental results show that the proposed method provides better retrieving result than retrieval using some of the existing methods

Nonlinear Analysis of Shear Dominant Prestressed Concrete Beams using ANSYS

This study reports the details of the finite element analysis of eleven shear critical partially prestressed concrete T-beams having steel fibers over partial or full depth. Prestressed T-beams having a shear span to depth ratio of 2.65 and 1.59 that failed in shear have been analyzed using the ‘ANSYS’ program. The ‘ANSYS’ model accounts for the nonlinearity, such as, bond-slip of longitudinal reinforcement, postcracking tensile stiffness of the concrete, stress transfer across the cracked blocks of the concrete and load sustenance through the bridging action of steel fibers at crack interface. The concrete is modeled using ‘SOLID65’- eight-node brick element, which is capable of simulating the cracking and crushing behavior of brittle materials. The reinforcement such as deformed bars, prestressing wires and steel fibers have been modeled discretely using ‘LINK8’ – 3D spar element. The slip between the reinforcement (rebars, fibers) and the concrete has been modeled using a ‘COMBIN39’- nonlinear spring element connecting the nodes of the ‘LINK8’ element representing the reinforcement and nodes of the ‘SOLID65’ elements representing the concrete. The ‘ANSYS’ model correctly predicted the diagonal tension failure and shear compression failure of prestressed concrete beams observed in the experiment. The capability of the model to capture the critical crack regions, loads and deflections for various types of shear failures in prestressed concrete beam has been illustrated.

Adrenergic and muscarinic receptor subtypes functional regulation during diabetogenesis: Effect of curcumin and vitamin D3 pre-treatment

In the present study, the initial phase was directed to confirm the effects of curcumin and vitamin D3 in preventing or delaying diabetes onset by studying the blood glucose and insulin levels in the pre-treated and diabetic groups. Behavioural studies were conducted to evaluate the cognitive and motor function in experimental rats. The major focus of the study was to understand the cellular and neuronal mechanisms that ensure the prophylactic capability of curcumin and vitamin D3. To elucidate the mechanisms involved in conferring the antidiabetogenesis effect, we examined the DNA and protein profiles using radioactive incorporation studies for DNA synthesis, DNA methylation and protein synthesis. Furthermore the gene expression studies of Akt-1, Pax, Pdx-1, Neuro D1, insulin like growth factor-1 and NF-κB were done to monitor pancreatic beta cell proliferation and differentiation. The antioxidant and antiapoptotic actions of curcumin and vitamin D3 were examined by studying the expression of antioxidant enzymes - SOD and GPx, and apoptotic mediators like Bax, caspase 3, caspase 8 and TNF-α. In order to understand the signalling pathways involved in curcumin and vitamin D3 action, the second messengers, cAMP, cGMP and IP3 were studied along with the expression of vitamin D receptor in the pancreas. The neuronal regulation of pancreatic beta cell maintenance, proliferation and insulin release was studied by assessing the adrenergic and muscarinic receptor functional regulation in the pancreas, brain stem, hippocampus and hypothalamus. The receptor number and binding affinity of total muscarinic, muscarinic M1, muscarinic M3, total adrenergic, α adrenergic and β adrenergic receptor subtypes were studied in pancreas, brain stem and hippocampus of experimental rats. The mRNA expression of muscarinic and adrenergic receptor subtypes were determined using Real Time PCR. Immunohistochemistry studies using confocal microscope were carried out to confirm receptor density and gene expression results. Cell signalling alterations in the pancreas and brain regions associated with diabetogenesis and antidiabetogenesis were assessed by examining the gene expression profiles of vitamin D receptor, CREB, phospholipase C, insulin receptor and GLUT. This study will establish the anti-diabetogenesis activity of curcumin and vitamin D3 pre-treatment and will attempt to understand the cellular, molecular and neuronal control mechanism in the onset of diabetes.Administration of MLD-STZ to curcumin and vitamin D3 pre-treated rats induced only an incidental prediabetic condition. Curcumin and vitamin D3 pretreated groups injected with MLD-STZ exhibited improved circulating insulin levels and behavioural responses when compared to MLD-STZ induced diabetic group. Activation of beta cell compensatory response induces an increase in pancreatic insulin output and beta cell mass expansion in the pre-treated group. Cell signalling proteins that regulate pancreatic beta cell survival, insulin release, proliferation and differentiation showed a significant increase in curcumin and vitamin D3 pre-treated rats. Marked decline in α2 adrenergic receptor function in pancreas helps to relent sympathetic inhibition of insulin release. Neuronal stimulation of hyperglycemia induced beta cell compensatory response is mediated by escalated signalling through β adrenergic, muscarinic M1 and M3 receptors. Pre-treatment mediated functional regulation of adrenergic and cholinergic receptors, key cell signalling proteins and second messengers improves pancreatic glucose sensing, insulin gene expression, insulin secretion, cell survival and beta cell mass expansion in pancreas. Curcumin and vitamin D3 pre-treatment induced modulation of adrenergic and cholinergic signalling in brain stem, hippocampus and hypothalamus promotes insulin secretion, beta cell compensatory response, insulin sensitivity and energy balance to resist diabetogenesis. Pre-treatment improved second messenger levels and the gene expression of intracellular signalling molecules in brain stem, hippocampus and hypothalamus, to retain a functional neuronal response to hyperglycemia. Curcumin and vitamin D3 protect pancreas and brain regions from oxidative stress by their indigenous antioxidant properties and by their ability to stimulate cellular free radical defence system. The present study demonstrates the role of adrenergic and muscarinic receptor subtypes functional regulation in curcumin and vitamin D3 mediated anti-diabetogenesis. This will have immense clinical significance in developing effective strategies to delay or prevent the onset of diabetes.

Political Education in Plural Societies: Using the Anti-Bias Approach to Challenge Oppression in Bombay and Berlin

This study addresses the effectivity of the Anti-Bias approach and training methodology as a pedagogical political strategy to challenge oppression among student groups in the cities of Bombay and Berlin. The Anti-Bias trainings conducted within the framework of this study also become the medium through which the perpetuation of oppressive structures by students within and outside the school is investigated. Empirical data from predominantly qualitative investigations in four secondary schools, two each in Bombay and Berlin, is studied and analysed on the basis of theoretical understandings of prejudice, discrimination and identity. This study builds on insights offered by previous research on prejudices and evaluations of anti-bias and diversity interventions, where the lack of sufficient research and thorough evaluations testing impact has been identified (Levy Paluck, 2006). The theoretical framework suggests that prejudices and discriminatory practices are learnt and performed by individuals over the years by way of pre-existing discourses, and that behaviour and practices can be unlearnt through a multi-step process. It proposes that the discursive practices of students contribute to the constitution of their viable selves and in the constitution of ‘others’. Drawing on this framework, the study demonstrates how student-subjects in Bombay and Berlin perpetuate oppressive discourses by performing their identities and performing identities onto ‘others’. Such performative constitution opens up the agency of the individual, disclosing the shifting and dynamic nature of identities. The Anti-Bias approach is posited as an alternative to oppressive discourses and a vehicle that encourages and assists the agency of individuals. The theoretical framework, which brings together a psychological approach to prejudice, a structural approach to discrimination and a poststructural approach to identity, facilitates the analysis of the perpetuation of dominant discourses by the students, as well as how they negotiate their way through familiar norms and discourses. Group discussions and interviews a year after the respective trainings serve to evaluate the agency of the students and the extent to which the training impacted on their perceptions, attitudes and behavioural practices. The study reveals the recurrence of the themes race, religion, gender and sexuality in the representational practices of the students groups in Berlin and Bombay. It demonstrates how students in this study not only perform, but also negotiate and resist oppressive structures. Of particular importance is the role of the school: When schools offer no spaces for discussion, debate and action on contemporary social issues, learning can neither be put into practice nor take on a positive, transformative form. In such cases, agency and resistance is limited and interventionist actions yield little. This study reports the potential of the Anti-Bias approach and training as a tool of political education and action in education. It demonstrates that a single training can initiate change but sustaining change requires long-term strategies and on-going actions. Taking a poststructural perspective, it makes concrete suggestions to adapt and alter the Anti-Bias approach and the implementation of Anti-Bias trainings.

More women in informatics research and education

Speaker: Lynda Hardman Organiser: Time: 04/02/2015 12:30-13:30 Location: B32/3077 Abstract The challenges of addressing gender inequalities in science, technology, engineering, mathematics and medicine is widely acknowledged. We currently hold a bronze award and ECS is one of many academic units in the University which has gained Athena Swan Charter status. In this seminar, Professor Lynda Hardman, Chair of the Informatics Europe working group "Women in Informatics Research and Education” will be explaining the causes of issued underlying gender inequality and constructive routes to addressing this important agenda. In undertaking to commit to an action plan which is a prerequisite of gaining charter status, the University or academic department agreed to accept and incorporate the Athena Swan six principles listed below: * To address gender inequalities requires commitment and action from everyone, at all levels of the organisation * To tackle the unequal representation of women in science requires changing cultures and attitudes across the organisation * The absence of diversity at management and policy-making levels has broad implications which the organisation will examine * The high loss rate of women in science is an urgent concern which the organisation will address * The system of short-term contracts has particularly negative consequences for the retention and progression of women in science, which the organisation recognises * There are both personal and structural obstacles to women making the transition from PhD into a sustainable academic career in science, which require the active consideration of the organisation. This seminar is designed to provide an opportunity to explore these issues NOTE: Lynda will be basing here talk on some of the work she directed as chair of the "Women in Informatics Research and Education” working group. The purpose of the working group is to actively participate and promote actions that contribute to improve gender balance in Information and Communication Sciences and Technologies. The first concrete result of the working group's activities was the publication of the booklet "More Women in Informatics Research and Education" in 2013. The booklet is a compact source of clear and simple best practices to deans and heads of departments that aim to increase the participation of women as both students and employees in their institutions. Many tips included were also inspired by colleagues already in leading positions who have already implemented actions in their institutions to attract more women and ensure their continued participation in the organization at commensurate ratios with their male colleagues. The booklet is endorsed by the European Commission and features a foreword by Neelie Kroes, Vice-President of the European Commission, responsible for the Digital Agenda.

Modelling, control and supervision for a class of hybrid systems

The aim of this thesis is to narrow the gap between two different control techniques: the continuous control and the discrete event control techniques DES. This gap can be reduced by the study of Hybrid systems, and by interpreting as Hybrid systems the majority of large-scale systems. In particular, when looking deeply into a process, it is often possible to identify interaction between discrete and continuous signals. Hybrid systems are systems that have both continuous, and discrete signals. Continuous signals are generally supposed continuous and differentiable in time, since discrete signals are neither continuous nor differentiable in time due to their abrupt changes in time. Continuous signals often represent the measure of natural physical magnitudes such as temperature, pressure etc. The discrete signals are normally artificial signals, operated by human artefacts as current, voltage, light etc. Typical processes modelled as Hybrid systems are production systems, chemical process, or continuos production when time and continuous measures interacts with the transport, and stock inventory system. Complex systems as manufacturing lines are hybrid in a global sense. They can be decomposed into several subsystems, and their links. Another motivation for the study of Hybrid systems is the tools developed by other research domains. These tools benefit from the use of temporal logic for the analysis of several properties of Hybrid systems model, and use it to design systems and controllers, which satisfies physical or imposed restrictions. This thesis is focused in particular types of systems with discrete and continuous signals in interaction. That can be modelled hard non-linealities, such as hysteresis, jumps in the state, limit cycles, etc. and their possible non-deterministic future behaviour expressed by an interpretable model description. The Hybrid systems treated in this work are systems with several discrete states, always less than thirty states (it can arrive to NP hard problem), and continuous dynamics evolving with expression: with Ki ¡ Rn constant vectors or matrices for X components vector. In several states the continuous evolution can be several of them Ki = 0. In this formulation, the mathematics can express Time invariant linear system. By the use of this expression for a local part, the combination of several local linear models is possible to represent non-linear systems. And with the interaction with discrete events of the system the model can compose non-linear Hybrid systems. Especially multistage processes with high continuous dynamics are well represented by the proposed methodology. Sate vectors with more than two components, as third order models or higher is well approximated by the proposed approximation. Flexible belt transmission, chemical reactions with initial start-up and mobile robots with important friction are several physical systems, which profits from the benefits of proposed methodology (accuracy). The motivation of this thesis is to obtain a solution that can control and drive the Hybrid systems from the origin or starting point to the goal. How to obtain this solution, and which is the best solution in terms of one cost function subject to the physical restrictions and control actions is analysed. Hybrid systems that have several possible states, different ways to drive the system to the goal and different continuous control signals are problems that motivate this research. The requirements of the system on which we work is: a model that can represent the behaviour of the non-linear systems, and that possibilities the prediction of possible future behaviour for the model, in order to apply an supervisor which decides the optimal and secure action to drive the system toward the goal. Specific problems can be determined by the use of this kind of hybrid models are: - The unity of order. - Control the system along a reachable path. - Control the system in a safe path. - Optimise the cost function. - Modularity of control The proposed model solves the specified problems in the switching models problem, the initial condition calculus and the unity of the order models. Continuous and discrete phenomena are represented in Linear hybrid models, defined with defined eighth-tuple parameters to model different types of hybrid phenomena. Applying a transformation over the state vector : for LTI system we obtain from a two-dimensional SS a single parameter, alpha, which still maintains the dynamical information. Combining this parameter with the system output, a complete description of the system is obtained in a form of a graph in polar representation. Using Tagaki-Sugeno type III is a fuzzy model which include linear time invariant LTI models for each local model, the fuzzyfication of different LTI local model gives as a result a non-linear time invariant model. In our case the output and the alpha measure govern the membership function. Hybrid systems control is a huge task, the processes need to be guided from the Starting point to the desired End point, passing a through of different specific states and points in the trajectory. The system can be structured in different levels of abstraction and the control in three layers for the Hybrid systems from planning the process to produce the actions, these are the planning, the process and control layer. In this case the algorithms will be applied to robotics ¡V a domain where improvements are well accepted ¡V it is expected to find a simple repetitive processes for which the extra effort in complexity can be compensated by some cost reductions. It may be also interesting to implement some control optimisation to processes such as fuel injection, DC-DC converters etc. In order to apply the RW theory of discrete event systems on a Hybrid system, we must abstract the continuous signals and to project the events generated for these signals, to obtain new sets of observable and controllable events. Ramadge & Wonham¡¦s theory along with the TCT software give a Controllable Sublanguage of the legal language generated for a Discrete Event System (DES). Continuous abstraction transforms predicates over continuous variables into controllable or uncontrollable events, and modifies the set of uncontrollable, controllable observable and unobservable events. Continuous signals produce into the system virtual events, when this crosses the bound limits. If this event is deterministic, they can be projected. It is necessary to determine the controllability of this event, in order to assign this to the corresponding set, , controllable, uncontrollable, observable and unobservable set of events. Find optimal trajectories in order to minimise some cost function is the goal of the modelling procedure. Mathematical model for the system allows the user to apply mathematical techniques over this expression. These possibilities are, to minimise a specific cost function, to obtain optimal controllers and to approximate a specific trajectory. The combination of the Dynamic Programming with Bellman Principle of optimality, give us the procedure to solve the minimum time trajectory for Hybrid systems. The problem is greater when there exists interaction between adjacent states. In Hybrid systems the problem is to determine the partial set points to be applied at the local models. Optimal controller can be implemented in each local model in order to assure the minimisation of the local costs. The solution of this problem needs to give us the trajectory to follow the system. Trajectory marked by a set of set points to force the system to passing over them. Several ways are possible to drive the system from the Starting point Xi to the End point Xf. Different ways are interesting in: dynamic sense, minimum states, approximation at set points, etc. These ways need to be safe and viable and RchW. And only one of them must to be applied, normally the best, which minimises the proposed cost function. A Reachable Way, this means the controllable way and safe, will be evaluated in order to obtain which one minimises the cost function. Contribution of this work is a complete framework to work with the majority Hybrid systems, the procedures to model, control and supervise are defined and explained and its use is demonstrated. Also explained is the procedure to model the systems to be analysed for automatic verification. Great improvements were obtained by using this methodology in comparison to using other piecewise linear approximations. It is demonstrated in particular cases this methodology can provide best approximation. The most important contribution of this work, is the Alpha approximation for non-linear systems with high dynamics While this kind of process is not typical, but in this case the Alpha approximation is the best linear approximation to use, and give a compact representation.