Dissertations / Theses on the topic 'Type and effect systems'

We present a general semantic account of Gifford-style type-and-effect systems. These type systems provide lightweight static analyses annotating program phrases with the sets of possible computational effects they may cause, such as memory access and modification, exception raising, and non-deterministic choice. The analyses are used, for example, to justify the program transformations typically used in optimising compilers, such as code reordering and inlining. Despite their existence for over two decades, there is no prior comprehensive theory of type-and-effect systems accounting for their syntax and semantics, and justifying their use in effect-dependent program transformation. We achieve this generality by recourse to the theory of algebraic effects, a development of Moggi’s monadic theory of computational effects that emphasises the operations causing the effects at hand and their equational theory. The key observation is that annotation effects can be identified with the effect operations. Our first main contribution is the uniform construction of semantic models for typeand- effect analysis by a process we call conservative restriction. Our construction requires an algebraic model of the unannotated programming language and a relevant notion of predicate. It then generates a model for Gifford-style type-and-effect analysis. This uniform construction subsumes existing ad-hoc models for type-and-effect systems, and is applicable in all cases in which the semantics can be given via enriched Lawvere theories. Our second main contribution is a demonstration that our theory accounts for the various aspects of Gifford-style effect systems. We begin with a version of Levy’s Callby- push-value that includes algebraic effects. We add effect annotations, and design a general type-and-effect system for such call-by-push-value variants. The annotated language can be thought of as an intermediate representation used for program optimisation. We relate the unannotated semantics to the conservative restriction semantics, and establish the soundness of program transformations based on this effect analysis. We develop and classify a range of validated transformations, generalising many existing ones and adding some new ones. We also give modularly-checkable sufficient conditions for the validity of these optimisations. In the final part of this thesis, we demonstrate our theory by analysing a simple example language involving global state with multiple regions, exceptions, and nondeterminism. We give decision procedures for the applicability of the various effect-dependent transformations, and establish their soundness and completeness.

Magíster en Ciencias, Mención Computación
Los sistemas de tipos-y-efectos (type-and-effect systems) permiten a los programadores hacer valer invariantes y restricciones sobre los efectos secundarios que se generan durante la evaluación de un programa. Los sistemas de tipos-y-efectos consideran efectos secundarios tales como estado, excepciones y E/S, entre otros. Desafortunadamente, los sistemas de tipos-y-efectos también obligan al programador a introducir anotaciones de efectos, lo que implica un esfuerzo adicional. En la práctica, los sistemas de tipos-y-efectos no son comúnmente usados. Conjeturamos que una de las razones importantes para la limitada adopción de los sistemas de efectos son las dificultades para realizar la transición desde un sistema donde los efectos secundarios son implícitos hacia una disciplina de efectos totalmente estática. Los tipos graduales (Gradual typing) permiten a los programadores combinar la flexibilidad de los lenguajes dinámicamente tipados con las garantías provistas por los sistemas de tipos estáticos. En lenguajes con tipos graduales, las anotaciones de tipos son parte del lenguaje, pero no son obligatorias. Un sistema de tipos gradual utiliza la información disponible para proveer garantías estáticas, rechazando los programas claramente incoherentes, e introduce verificaciones en tiempo de ejecución cuando la información estática no es suficiente para aceptar o rechazar definitivamente un programa. Esta tesis demuestra que las ideas de diseño detrás de los tipos graduales pueden aplicarse a los sistemas de tipos-y-efectos, tanto para aumentar la expresividad de estos sistemas así como para proveer flexibilidad para migrar programas con efectos secundarios impl ́ıcitos e irrestrictos hacia programas con una disciplina de efectos completamente estática. Se adaptaron ideas de tipos graduales para introducir verificación gradual de efectos para sistemas de tipos-y-efectos. La verificación gradual de efectos habilita al programador para decidir dónde y cuándo introducir anotaciones de efectos, agregando verificaciones en tiempo de ejecución cuando las anotaciones estáticas son insuficientes. Para evitar redefinir la verificación gradual de efectos para cada disciplina de tipos-y-efectos, introducimos verificación gradual de efectos para una plataforma genérica de tipos-y-efectos, en la que se puede instanciar cualquier disciplina de efectos monotónica, produciendo un sistema coherente. Presentamos la verificación gradual de efectos basándonos en conceptos de interpretación abstracta para construir la verificación gradual de efectos genérica. Utilizando verificación gradual de efectos genérica, introducimos tipos graduales para sistemas de tipos-y-efectos: un sistema donde las anotaciones de efectos y de tipos no son obligatorias, y donde se introducen verificaciones en tiempo de ejecución y casts cuando la información estática no es suficiente para asegurar la coherencia de un programa. De la manera definida, los tipos graduales para sistemas de tipos-y-efectos permiten migrar desde sistemas carentes de anotaciones de efectos o de tipos hacia una disciplina estática de tipos-y-efectos de manera segura.

Distribution systems are designed to operate in radial mode (the simplest system topology) without any generation on the system, unidirectional power flow from the distribution substation to the customers via main feeder(s) and its(their) laterals within a specified range of operating points. The rapid growth of PV module installations on the distribution systems could not only offset the load but also cause a significant impact on the flow of power (active and reactive), voltage level, and fault currents, therefore; concerns about their potential impacts on the stability and operation of the power system have become one of the important issues and may create barriers to their future expansion. The most likely potential impact of the high PV penetration level is losing the voltage regulation, because it is directly related to the amount of reverse power flow. The main goal of this thesis is to approximate the maximum level of PV penetration which the system can accommodate without any impact on the voltage profile, stability, and operation.

Type error reports provide programmers with a description of type errors which exist in their code. Such descriptions are frequently of poor quality, as they often present just one point in the program, rather than all locations in the code which contribute to that type error. Skalpel is a type error report system for the Standard ML language which tackles this problem, by presenting all and only the locations in the program which contribute to the type error. While the original Skalpel gives substantially better error reports than comparable systems, it has a number of limitations such as a lack of support for language features and poor efficiency. In this research we have made a number of contributions, including a full critique of both the Skalpel core theoretical system and its extensions, support for the remaining features of Standard ML, an analysis and improvements to the efficiency, and an investigation for the first time on Skalpel’s theoretical properties.

Using the 1990, 1994 and 1998 Congressional mid-term elections, this study looks at whether the type of primary system in a person's state has an effect on whether or not that person will vote in the general election. The five types of primary systems (closed, semi-closed, semiopen, open and blanket) are explained as well as traditional factors for likelihood of voting. It is hypothesized that the more closed the primary system, the less likely a person is to vote. Data analysis shows that when significant, living in an open primary state does significantly increase the likelihood that a person will vote. However, primary type was significant in only six of the nine models studied here.

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Two randomised controlled trials were conducted to explore the relationship between the consumption of alcoholic beverages and cardiovascular disease risk factors. Study 1 was primarily designed to test the hypothesis that the cardio-protective effect of light alcohol could be mediated, in part, via improvements in endothelial function. Study 1 was also designed to explore the effect of alcohol on both traditional risk factors for cardiovascular disease, such as changes in lipid profile, haemostatic factors and blood pressure, and novel risk factors such as homocysteine, markers of inflammation and oxidative stress. The experimental design of this study also allowed us to determine whether reducing alcohol intake in these moderate-to-heavy drinkers could improvement insulin sensitivity, a component of the metabolic syndrome. In this group of sixteen healthy middle-aged men with a history of moderate to heavy alcohol intake of seven standard drinks per day, reducing intake down to approximately one standard drink per day for four weeks had no beneficial effects on conduit vessel endothelial function as assessed by post-ischaemic brachial artery flow-mediated dilatation, nor were there any detectable changes in soluble E-selectin, endothelin-1 and von Willebrand Factor, which are considered biomarkers of endothelial activation. As this study did not investigate the effect of alcohol on endothelial function in resistance vessels, it cannot exclude the possibility that alcohol may affect endothelial cells resident in that vascular bed. This study does show and confirm, however, that the relationship between alcohol and risk factors for cardiovascular disease is an extremely complex one. On the one hand it demonstrated that alcohol was potentially harmful, increasing blood pressure, plasma F2-isoprostane (oxidative stress), and homocysteine. On the other hand it showed that increasing alcohol intake led to significant reductions in two (i.e. fibrinogen and IL-6) of five inflammatory markers, in addition to improving the HDL-cholesterol profile of these subjects. Although the effects of alcohol on blood pressure, fibrinogen and HDL-cholesterol are not in themselves new, they support our choice of study design and strengthen the argument in favour of accepting the more novel findings of this study, specifically, the lack of effect on endothelial function and insulin sensitivity, and the harmful effect of alcohol in increasing oxidative stress and homocysteine. Study 2 was primarily designed to test the hypothesis that the consumption of red wine may confer greater cardio-protection than beer via improvements in endothelial function. Simultaneously, the study was also designed to determine whether drinking red wine for 4-weeks would have different effects than beer on either traditional risk factors for cardiovascular disease (i.e. blood pressure and lipid profile) or the more novel risk factors, homocysteine and oxidative stress. Using a randomised controlled cross-over study design, Study 2 provides evidence that the regular daily consumption of 4 standard drinks of either beer or red wine does not alter endothelial function, as measured by post-ischaemic flow-mediated vasodilatation of the brachial artery in healthy middle-aged men, nor was there evidence of any beneficial effect of de-alcoholised red wine on brachial artery response. As compliance with drinking protocol was confirmed with increased serum γ-GT and HDL during red wine and beer periods, and increased 24-hr urinary excretion of 4OMGA during red wine and de-alcoholised red wine periods, we are confident that there was excellent compliance with the beverage treatments. Study 2 also provides the first evidence from a carefully controlled intervention study that both red wine and beer elevate blood pressure to a similar degree, with no detectable difference in the magnitude of either treatment. As with endothelial function, there was also no evidence of any beneficial effect of de-alcoholised red wine on blood pressure. In addition, although post hoc analysis found evidence that alcohol increased both plasma homocysteine and urinary excretion of F2-isoprostane and endothelin-1, there was no apparent protective effect conferred from either red wine or de-alcoholised red wine on these cardiovascular risk markers. The results from this study cannot disprove the hypothesis that red wine is more beneficial for cardiovascular health; however, they suggest that if red wine has properties beyond those of beer to confer protection, they are not via any interactions with the nitric oxide regulatory function of the endothelium in conduit vessels nor are they via moderation of the vasopressor, homocysteine-raising, and oxidative stress effects of alcohol. The interpretation of the findings from both intervention studies and their place in the context of our current understanding of the role that alcoholic beverages play in the development and/or prevention of cardiovascular disease are explored in this thesis.

This thesis deals with the important problem of parallelising sequential code. Despite the importance of parallelism in modern computing, writing parallel software still relies on many low-level and often error-prone approaches. These low-level approaches can lead to serious execution problems such as deadlocks and race conditions. Due to the non-deterministic behaviour of most parallel programs, testing parallel software can be both tedious and time-consuming. A way of providing guarantees of correctness for parallel programs would therefore provide significant benefit. Moreover, even if we ignore the problem of correctness, achieving good speedups is not straightforward, since this generally involves rewriting a program to consider a (possibly large) number of alternative parallelisations. This thesis argues that new languages and frameworks are needed. These language and frameworks must not only support high-level parallel programming constructs, but must also provide predictable cost models for these parallel constructs. Moreover, they need to be built around solid, well-understood theories that ensure that: (a) changes to the source code will not change the functional behaviour of a program, and (b) the speedup obtained by doing the necessary changes is predictable. Algorithmic skeletons are parametric implementations of common patterns of parallelism that provide good abstractions for creating new high-level languages, and also support frameworks for parallel computing that satisfy the correctness and predictability requirements that we require. This thesis presents a new type-based framework, based on the connection between structured parallelism and structured patterns of recursion, that provides parallel structures as type abstractions that can be used to statically parallelise a program. Specifically, this thesis exploits hylomorphisms as a single, unifying construct to represent the functional behaviour of parallel programs, and to perform correct code rewritings between alternative parallel implementations, represented as algorithmic skeletons. This thesis also defines a mechanism for deriving cost models for parallel constructs from a queue-based operational semantics. In this way, we can provide strong static guarantees about the correctness of a parallel program, while simultaneously achieving predictable speedups.

Thesis (PhD)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: Mycobacterium tuberculosis, the causative agent of tuberculosis disease, contains five copies of the ESAT-6 gene cluster, each encoding a dedicated ESX protein secretion system which has been defined as a novel Type-VII secretion system. The ESX have been implicated in virulence and survival of M. tuberculosis, and as such present a promising target for novel treatment interventions. This study has investigated the evolution, regulation, functions and substrates of the ESX secretion systems. The evolutionary history of the ESX secretion systems was established using in silico and phylogenetic analyses of the sequenced mycobacteria, closely related actinomycetes and WXG-FtsK clusters from other bacteria. The ESX-4 gene cluster appears to have evolved with the start of the evolution of the mycomembrane, followed by the duplication of ESX-3, which marks the evolution of the genus Mycobacterium. The ESX-1 duplication occurred next, followed by ESX-2 and ESX-5 which occur only in the slow growing mycobacteria. Five additional ESX gene clusters were newly identified and named ESX-P1 to - P5. These additional ESX clusters occur, or are predicted to occur, on plasmid DNA, and appear to be progenitors of the genomic ESX-1 to -5 gene clusters, possibly indicating a plasmid-mediated mechanism of ESX duplication and evolution. The promoters expressing the M. tuberculosis ESX-1 to ESX-5 secretion systems were investigated using a promoter probe assay, and characterised using in silico analyses. Promoters were identified for ESX-1, -2, -3 and -5. The functions of the mycobacterial ESX secretion systems were investigated using whole proteomic, secretomic and metabolomic analyses of the fast growing, non-pathogenic M. smegmatis, which contains three of the ESX secretion systems, ESX-1, 3, and 4. ESX knockout strains of M. smegmatis were generated and used in comparative analyses with wild-type M. smegmatis. ESX-1 was highly expressed in wild-type M. smegmatis, however no specific pathways showed considerable variation when ESX-1 was deleted. Deletion of ESX-3 resulted in substantial variation to multiple cellular pathways, including amino acid, carbohydrate and fatty acid metabolism and oxidative stress. These and other differences indicate possible perturbed polyamine metabolism in the absence of ESX-3. Although no ESX-4 protein components were detected in wild type M. smegmatis, the ESX-4 knockout displayed substantial proteomic variation. Reduced levels of ESX-3 component proteins in the ESX-4 knockout suggest that ESX-4 influences ESX-3 expression. Other variation linked ESX-4 to cell division and molybdenum metabolism. Secretomic analyses of wild-type and ESX knockout M. smegmatis strains were used to search for novel substrates of the M. smegmatis ESX secretion systems. No prototype ESX substrates were identified in the culture filtrates, however 10 possible substrates of the ESX-1, -3 and -4 secretion systems, containing the general ESX secretion signal, YxxxD/E, were identified. The functions of some of these proteins correlate with the ESX functions identified in the proteomic and metabolomic analyses. This study sets the groundwork for future work in understanding the functional roles and expression patterns of these ESX secretion systems and in using global proteomic and metabolomic analyses to understand cellular changes in response to specific signals or genomic changes.
AFRIKAANSE OPSOMMING: Mycobacterium tuberculosis, die veroorsakende agent van tuberkulose, bevat vyf kopieë van die ESAT-6 geengroep, wat elk 'n toegewyde ESX proteïen sekresiesisteem, omskryf as 'n nuwe Tipe-VII sekresiestelsel, kodeer. Die ESX sekresiesisteme is betrokke by virulensie en oorlewing van M. tuberculosis, en is dus belowende teikens vir nuwe behandelings. Hierdie studie het die evolusie, regulasie, funksies en substrate van die ESX sekresiesisteme ondersoek. Die evolusionêre geskiedenis van die ESX sekresiesisteme is bepaal met behulp van in silico en filogenetiese analises van die volgordebepaalde mikobakterieë, nouverwante actinomisete en WXG-FtsK groepe van ander bakterieë. Die ESX-4 geengroep het saam met die evolusie van die mikomembraan ontwikkel, gevolg deur die duplisering van ESX-3, wat die evolusie van die genus Mycobacterium merk. Die ESX-1 duplisering het volgende plaasgevind, gevolg deur ESX-2 en ESX-5, wat slegs in die stadiggroeiende mikobakterieë voorkom. Vyf addisionele ESX geengroepe is nuut geïdentifiseer in hierdie studie en is ESX-P1 tot -P5 genoem. Hierdie addisionale ESX groepe is op, of word voorspel om op, plasmied DNS voor te kom, en mag voorlopers van die genomiese ESX-1 tot -5 geengroepe wees, wat moontlik dui op 'n plasmied-gemedieërde meganisme van ESX duplisering en evolusie. Die promoters wat verantwoordelik is vir die uitdrukking van die M. tuberculosis ESX-1 tot ESX-5 sekresiesisteme is ondersoek deur middel van 'n promoter aktiwiteitstoets, en gekarakteriseer deur in silico analises. Promoters is geidentifiseer vir ESX-1, -2, -3 en -5. Die funksies van die mikobakteriële ESX sekresiesisteme is ondersoek deur proteomiese, sekretomiese en metabolomiese analises van die vinnig-groeiende, nie-patogeniese mikobakterium M. smegmatis, wat ESX- 1, -3 en -4 sekresiesisteme besit. ESX uitslaanmutante van M. smegmatis is gegenereer en gebruik in die vergelykende analises met die wilde-tipe M. smegmatis. ESX-1 is hoogs uitgedruk in wilde-tipe M. smegmatis, maar geen spesifieke metabolise weë het aansienlike variasie getoon wanneer ESX-1 verwyder is. Delesie van ESX-3 het gelei tot aansienlike variasie in verskeie sellulêre weë, insluitend aminosuur-, koolhidraat- en vetsuur-metabolisme en oksidatiewe stres. Hierdie en ander verskille dui op moontlike versteurde poli-amien metabolisme in die afwesigheid van ESX-3. Hoewel geen ESX-4 proteïenkomponente opgespoor is in wilde-tipe M. smegmatis nie, vertoon die ESX-4 uitslaanmutant aansienlike proteomiese variasie. Laer vlakke van ESX-3 proteïne dui daarop dat ESX-4 die uitdrukking van ESX-3 beinvloed. Baie van die proteomiese variasie kan geassosieer word met verlaagde ESX-3 uitdrukking, maar ander variasie mag ESX-4 koppel met seldeling en molibdeen metabolisme. Sekretomiese analises van wilde-tipe en ESX uitslaanmutant M. smegmatis stamme is gebruik om nuwe substrate van die M. smegmatis ESX sekresiesisteme te identifiseer. Geen prototipe ESX substrate is geïdentifiseer in die kultuurfiltraat, maar 10 moontlike substrate van die ESX-1, -3 en -4 sekresiesisteme, met die algemene ESX sekresiesein, YxxxD/E, is geïdentifiseer. Die funksies van sommige van hierdie proteïene korreleer met die funksies geïdentifiseer in die proteomiese en metabolomiese analises. Hierdie studie stel die grondslag vir toekomstige werk in die begrip van die funksionele rol en uitdrukkingspatrone van die ESX sekresiesisteme en in die gebruik van globale proteomiese en metabolomiese analises om sellulêre veranderinge in reaksie op spesifieke seine of genomiese veranderinge te verstaan.
The National Research Foundation
German Academic Exchange Service (DAAD),
The Harry Crossley Foundation
The Ernst and Ethel Erikson Trust
Stellenbosch University

Programming resource-sensitive systems, such as real-time embedded systems, requires guaranteeing both the functional correctness of computations and also that time and space usage fits within constraints imposed by hardware limits or the environment. Functional programming languages have proved very good at meeting the former logical kind of guarantees but not the latter resource guarantees. This thesis contributes to demonstrate the applicability of functional programming in resource-sensitive systems with an automatic program analysis for obtaining guaranteed upper bounds on dynamic space usage of functional programs. Our analysis is developed for a core subset of Hume, a domain-specific functional language targeting resource-sensitive systems (Hammond et al. 2007), and presented as a type and effect system that builds on previous sized type systems (Hughes et al. 1996, Chin and Khoo 2001) and effect systems for costs (Dornic et al. 1992, Reistad and Giord 1994, Hughes and Pareto 1999). It extends previous approaches by using abstract interpretation techniques to automatically infer linear approximations of the sizes of recursive data types and the stack and heap costs of recursive functions. The correctness of the analysis is formally proved with respect to an operational semantics for the language and an inference algorithm that automatically reconstructs size and cost bounds is presented. A prototype implementation of the analysis and operational semantics has been constructed and used to experimentally assess the quality of the cost bounds with some examples, including implementations of textbook functional programming algorithms and simplified embedded systems.

Includes bibliography.
Filamentous bulking, which causes deterioration in sludge settleability has been shown, in two nation-wide surveys to be a problem of considerable proportions. Poor sludge settleability in the secondary clarifier limits the daily flow and load that can be treated in activated sludge wastewater treatment plants. Controlling sludge settleability to relatively low levels i.e. Diluted Sludge Volume Index (DSVI < 100 rnl/g) by controlling filamentous organism proliferation would allow increased daily flow and loads by up to 100 on existing activated sludge wastewater treatment plants. From the two surveys, Blackbeard et al. (1986,1988) found that mainly six filamentous organisms tended to dominate in activated sludges in N and N&P removal plants i.e. types 0092, 0041, 0675, 1851, 0914 and Microthrix parvicella. Four of these six filaments are classified by Jenkins et al (1984) as low Food/Micro-organism (low F/M) filaments. At the University of Cape Town and in a 4 year research programme (1986 to 1989) Gabb et al (1989a) investigated specific methods to control low F /M filament proliferation. Traditionally the promoted specific bulking control method was inclusion of either an anoxic or aerobic selector at the head of the wastewater treatment plant. Gabb et al (1989a) found that selectors did not control low F/M filament proliferation but that continuous aeration did. They concluded that the presence of anoxic and aerobic zones in a treatment plant was an important factor in low F/M filament proliferation. In 1989 a second research programme was initiated at the University of Cape Town to identify the factors that influence low F/M filament proliferation. Completed research thus far has established inter alia that fully anoxic and fully aerobic conditions successfully control low F/M filament proliferation but that alternating anoxic-aerobic conditions in single reactor intermittent aeration systems promoted proliferation. The research presented in this thesis focuses on the interchange between anoxic and aerobic conditions in nitrogen removal systems and its effect on low F/M filament proliferation.

Physical activity (PA) provides many benefits to adolescents with Type 1 Diabetes (T1D); however, adolescents with T1D tend to have lower fitness and PA levels. One reason adolescents with T1D engage in less PA is due to a fear of hypoglycemia. Most studies examining PA in relation to glycemic control measure PA through self-report, thus introducing bias. The purpose of this study was to objectively monitor PA and glucose in adolescents with T1D to examine the temporal associations between moderate and vigorous intensity physical activity (MVPA) and hypoglycemia. Twenty participants (14 to 19 yr, n=10 females and 10 males) with a T1D diagnosis for at least 1 year were recruited. Participant fitness was evaluated via indirect calorimetry during a maximal treadmill exercise test, and body composition was measured using air displacement plethysmography. An accelerometer (GENEActiv, Activinsights Ltd, Kimbolton, UK) was worn on the wrist continuously for 7 days and the waveform data used to estimate MVPA in min/d. Blood glucose values were simultaneously tracked using continuous glucose monitoring (DexCom SEVEN PLUS, San Diego, CA). After controlling for gender, % body fat (%BF), and fitness, the likelihood of hypoglycemia (¡Ü 70 mg/dl) at nighttime or the next day due to MVPA was examined using logistic regression. Participants were of avg fitness (females: 43.9 ml/kg/min; males: 49.8 ml/kg/min) and fatness (females: 26.2%; males: 19.2%), and 63.2% of participants met the US federal guidelines of accumulating 60 min/d of MVPA. Hypoglycemia was 22% more likely in those who had 30 min/d more MVPA than those with less (95% CI: 1.03, 1.45; p =0.022). The results indicate that participating in MVPA increases the risk of hypoglycemia during the night time and the following day. The relationship is independent of gender, %BF and fitness. While promoting PA as a healthy behavior, it is important to educate adolescents with T1D on prevention of hypoglycemia following PA.

Aeromonas species are ubiquitous water-borne bacteria that are able to cause a variety of diseases in poikilothermics and humans. Aeromonas hydrophila is one of the most pathogenic species, responsible for aeromonad septicaemia in fish, gastroenteritis and wound infections in humans. The T3SS is utilized to inject protein effectors directly into host cells. One of the major genetic regulators of the T3SS in several Gram-negative bacterial species is the AraC-like protein ExsA. Lateral flagella are expressed by bacteria upon contact with host cells or a surface and are required for host cell adherence and biofilm formation. However, no direct link between the T3SS and the lateral flagella system has yet been found in A. hydrophila. Moreover, the genetic regulation of the T3SS that involves the master regulator ExsA has not been determined in A. hydrophila AH-3. The aim of this project is to determine the genetic regulation of the T3SS and the potential interaction between the T3SS and the lateral flagella system in A. hydrophila AH-3. The genes encoding the T3SS regulatory components including exsA, exsD, exsC and exsE were mutated and the activities of the T3SS promoters were measured in exs mutant backgrounds. The interactions between each of the Exs proteins were investigated using BACTH assay and Far-Western Blot. Together, the findings suggested a regulatory cascade that the effector protein ExsE was bound to the chaperone protein ExsC, which sequestered the anti-activator ExsD from inhibiting the T3SS master regulator ExsA via direct protein-protein interactions. The T3SS regulatory components were also shown to affect the expression of the lateral flagella system using swarming assays. The activities of the lateral flagella promoters were shown to be repressed by the absence of ExsD and ExsE, suggesting that the T3SS master regulator ExsA was a negative regulator of the lateral flagella system.

The objective of this Thesis is to investigate the phenomenon of voltage unbalance on electrical wind power systems. A large part of this work is the literature review of all relative work that has been done so far. This serves first as a guideline to define and measure voltage unbalance and second as a tool to spot open research questions that can inspire future work. A case study is then used to investigate the voltage unbalance at a wind farm in Näsudden, Gotland. Using real-time measurements and a simulation of the power system in MATLAB/Simulink, an evaluation of the propagation of the voltage unbalance from the distribution to the turbine level is carried out. The effect that different transformer connection types have on the propagation is studied through simulations. Many assumptions and simplifications had to be made due to several limiting factors during this work, mainly related to time and data restrictions. The main result shows that when Delta – Wye Grounded and Wye – Wye Grounded transformers are used, the unbalance is halved when it passes to the turbine side. On the other hand, when Wye Grounded – Wye Grounded configuration was used, the unbalance was unaffected. The results also include a comparison of the use of different indices to quantify a voltage unbalance.

Hyperglycaemia is a main feature of diabetes, and this pathology is a main complication of pregnancy. Diabetic patients often require tighter glycaemic control in pregnancy, as glucose metabolism changes, and insulin dosages need to be adjusted. Throughout gestation, the placenta is therefore subjected to periods of hyperglycaemic insult. Thus, we wished to study how brief periods of hyperglycaemia affected the feto-placental vasculature, through study of important permeability molecules, pro-permeability VEGFa, anti-permeability VEGFb, and junctional stability molecule VE-cadherin. A 15mM concentration of glucose was chosen because it is a level seen postprandially in diabetic pregnancies. We explored this by explant and perfusion methods. We tested two chorionic villous explants methodologies to validate them for 4h and 24h duration studies, and found that a free-floating methodology which sought to replicate the in utero flow was not appropriate, as this resulted in high basal levels of endothelial VEGF and low junctional VE-cadherin, a feature that we hypothesised to be a wound healing response. Therefore, we chose the stationary explants methodology, with no simulation of flow, for our subsequent experiments. The stationary method, where chorionic villi were incubated with hyperglycaemia (15mM glucose) vs. euglycaemia (5mM glucose) for the two different durations (4h and 24h) revealed that 15mM glucose was affecting junctional stability and the pro-permeability molecule VEGF-A after a 24h hyperglycaemic insult, but that VEGF was not affected by 4h. Given that 4h is a physiologically important timepoint (representing a postprandial glucose peak seen in diabetic pregnancies), we continued with this timepoint in further experiments. Whilst we found no effect of 15mM glucose insult after a 4h incubation on total VEGF expression, we found that the recently discovered anti-permeability VEGFb splice variant was decreased in hyperglycaemia compared to euglycaemic explants. Furthermore, the there was a significant negative correlation between total VEGF and VEGFb levels, indicating that the ratio of the two molecules was changing in diabetic explants compared to normal explants. The diabetic explants showed no further down-regulation of VEGFb on 15mM glucose insult, indicating a tolerance of the diabetic placental vessels to hyperglycaemia. We then investigated whether total VEGF and/or VEGFb were important predictors of vascular dysfunction as measured by an increased in leakage to 76Mr dextran-TRITC tracer in a well established perfusion model. The vascular bed was perfused with 15mM glucose administered to the maternal circuit. After a 3h hyperglycaemic perfusion, we observed high total VEGF, low VEGFb, and a loss of VE-cadherin from the endothelial junctions. These changes corresponded to a mild increase in leakage to 76Mr dextran tracer measured by counting vessels showing 'hotspots' of tracer at perivascular regions (18% of vessels leakage in the hyperglycaemic perfusions vs. 10% leakage in the euglycaemic perfusions). The percentage of vessels exhibiting tracer leakage showed a significant negative correlation with VEGFb (Spearman r value -0.8857) but not total VEGF, indicating that the former may be an important predictor of vascular dysfunction. It would be clinically important to be able to predict placental vascular dysfunction in diabetic pregnancies. Further experiments are needed to see whether the VEGFa/VEGFb ratio can predict vascular leakage under hyperglycaemia and the other main feature of diabetic pregnancies, hyperinsulinaemic insult, and whether the hyperglycaemic insult resulting in the diabetic phenotype is reversible upon euglycaemic conditions being restored. Our studies so far have shown that the diabetic phenotype can be partly replicated, in terms of vascular leakage, with a single 15mM hyperglycaemic insult. Chronic insult may well prove to result in the fully leaky vessels observed in diabetic placentae. VEGFb might be an important predictor of this leakage, and may be clinically used for assessment of risks in diabetic pregnancies.

The type I interferon (IFN) system plays a central role in the etiopathogenesis of many autoimmune diseases, e.g. systemic lupus erythematosus (SLE). Activation of the type I IFN system in SLE is promoted by endogenous nucleic acid-containing immune complexes (ICs) which stimulate plasmacytoid dendritic cells (pDCs). This thesis focuses on the regulation of IFN-α production in pDCs, by interactions with B cells and natural killer (NK) cells, and by genetic factors. In Study I, RNA-IC-stimulated CD56dim NK cells were found to be activated via FcγRIIIa and enhanced the IFN-α production by pDCs. The enhancing effect of the NK cells was mediated via both soluble factors, such as the cytokine MIP-1β, and in a cell-cell contact mediated manner via the adhesion molecule LFA-1. In Study II, B cells enhanced the IFN-α production by pDCs via cell-cell contact or soluble factors, depending on the stimuli. The cell-cell contact-mediated enhancement, when the cells were stimulated with RNA-IC, was abolished by blocking the cell adhesion molecule CD31. B cells stimulated with the oligonucleotide ODN2216 enhanced the IFN-α production via soluble factors. In Study III, gene variants related to autoimmune or inflammatory diseases were analyzed for the association to the IFN-α production by pDCs, alone or in coculture with NK or B cells. Depending on cell combination, 18-86 SNPs (p < 0.001) were associated with the IFN-α production. Several of the SNPs showed novel associations to the type I IFN system, while some loci have been described earlier for their association with SLE, e.g. IL10 and PXK. In Study IV, several B cell populations were affected by cocultivation with pDCs and stimulation with RNA-IC. The frequency of CD24hiCD38hi B cells of regulatory character was increased in the pDC-B cell cocultures. However, RNA-IC-stimulation only induced modest levels of IL-10. A remarkably increased frequency of double negative CD27-IgD- B cells was found in the RNA-IC-stimulated cocultures of pDCs and B cells. In conclusion, the findings in the present thesis reveal novel mechanisms behind the regulation of the type I IFN system which could be important targets in autoimmune diseases with constantly activated pDCs.

Les préoccupations actuelles concernant l'exploitation sécuritaire des centrales nucléaires existantes et la conception d’architectures spéciales envisagées pour la quatrième génération de réacteurs nucléaires se combinent avec l’intérêt plus prononcé pour l'efficacité et la fiabilité de l'équipement d'un système énergétique. Cela fait que dans un souci de meilleure compréhension et optimisation basée sur des moyens modernes de conception assistée par l’ordinateur, l'étude de différentes parties de ces systèmes fait de plus en plus l’objet de recherches approfondies. . Parmi les types proposés pour la quatrième génération de réacteurs nucléaires font partie ceux ayant comme agent de refroidissement les sels fondus, respectivement le sodium fondu. En raison de leurs propriétés physiques, les sels fondus et le sodium liquide ont le potentiel d'être déplacés par les pompes électromagnétiques. Cet ouvrage est à la fois une étude approfondie des phénomènes qui se produisent en raison de l'écoulement du fluide dans le champ électromagnétique d’une pompe électromagnétique - interaction magnétohydrodynamique - et un rapport sur les capacités et les avantages des outils informatiques modernes pour faciliter la conception et l'optimisation des pompes électromagnétiques. Afin d’atteindre l'objectif principal de la thèse, notamment une meilleure compréhension des phénomènes interdépendants spécifique à l’opération des pompes électromagnétiques, deux objectifs secondaires ont été considérés. Le premier objectif concerne la pleine exploitation des modèles électromagnétiques numériques en éléments finis afin d'obtenir autant d'informations que possible sur le comportement des pompes électromagnétiques, dans l’hypothèse où on ne tient pas compte de l'écoulement des fluides. Le deuxième objectif était la construction des modèles numériques qui réunissent l’électromagnétisme et la dynamique des fluides, respectivement des modèles numériques qui regroupent les deux phénomènes caractérisant l’écoulement magnétohydrodynamique dans les canaux des pompes électromagnétiques. Dans l'étude dédiée au pompage électromagnétique de sels fondus, la thèse met en évidence des problèmes spécifiques liés à la génération de forces électromagnétiques dans les fluides faibles conducteurs d'électricité et fournit des résultats sur les applications où le pompage électromagnétique de sels fondus peut être efficace. À l’aide des modèles électromagnétiques nous avons obtenu des informations importantes sur l'influence du nombre de pôles électromagnétiques et de la fréquence d’alimentation sur la caractéristique Pression - Vitesse des pompes annulaires à induction. Ils ont été analysés le phénomène de blindage créé par les parois métalliques - avec des répercussions négatives sur les performances de la pompe, les effets de freinage exercés à l'entrée et à la sortie du canal de la pompe et la relation entre la capacité de surcharge hydrodynamique et la caractéristique Pression - Vitesse des pompes à induction. Une section spéciale a été consacrée à l'analyse de la dépendance de la force électromagnétique du temps et de l’espace et à l’étude de non-uniformitées des quantités de nature électromagnétique en direction azimutale dans les pompes annulaires à induction.Dans le chapitre qui traite de l'interaction magnétohydrodynamique à base de modèles couplés, ils sont proposés deux modèles qui couplent l'électromagnétisme et l’écoulement. Ils sont présentés les avantages des modèles couplés, en matière de la précision des résultats, par rapport aux modèles électromagnétiques. Il est également présenté l'évolution des profils de vitesse, de densité de force et de courant sous l'influence du champ électromagnétique et de l’écoulement de sodium à vitesses différentes. Les contributions de la thèse sont complétées par des observations importantes sur les méthodes de travail et les logiciels utilisés tout au long de l'étude
The actual concerns with respect to safe operation of existing nuclear plants and to designing special architectures envisaged for the fourth generation of nuclear reactors, corroborated with the increasing interest for efficiency and reliability of any equipment belonging to an energetic system, make that more and more research endeavors to be devoted to the study of various parts of these systems for a better understanding and optimization based on modern techniques of computer aided design. Among the types proposed for the fourth generation of nuclear reactors belong those that have as cooling agent molten salts, respectively liquid sodium. Many reactors of previous generations use mechanical pumps of special design for driving the coolants. Molten salts and liquid sodium, thanks to their physical properties, have the potential to be driven using electromagnetic pumps. Although the technology of electromagnetic pumping of electroconductive fluids was developed since the first half of the last century, currently it undergoes a revival due to the reconsideration of its multiple technological and security advantages. This work is both an intimate study of the phenomena that occur as a result of the electroconductive fluids flow in the electromagnetic field of an electromagnetic pump – magnetohydrodynamic interaction - and a report on the capabilities and advantages of modern computational tools to facilitate design and optimization of electromagnetic pumps.To achieve the principal goal of deeper understanding of the interdependent phenomena specific to electromagnetic pumps operation, two auxiliary objectives were considered. The first is related to the full exploitation of electromagnetic finite element models in order to retrieve as much information as possible about electromagnetic pumps behavior in a simplifying hypothesis that does not take into account the fluid dynamics. The second auxiliary objective is to build numerical models that couple the electromagnetism and the fluid dynamics, namely the two interdependent physics that govern the magnetohydrodynamic flow through channels of electromagnetic pumps.In the section dealing with the study of electromagnetic pumping of molten salts, the thesis highlights specific problems related the generation of electromagnetic forces in fluids with low electrical conductivity and provides results with respect to applications where electromagnetic pumping of molten salts can be effective. With the electromagnetic numerical models were obtained important data about the influence of the number of electromagnetic poles and supply frequency on the Pressure – Velocity characteristic of annular linear induction pumps. Were analyzed the shielding effect generated by the metallic walls - with negative repercussions on pumps performances, braking effects exerted at pump inlet and pump outlet and the connection between the overload capacity and Pressure – Velocity characteristic of induction pumps. A special portion was devoted to the analysis of the time and space dependence of the electromagnetic force and to the study of the non-uniformities of electromagnetic quantities in azimuth direction of annular linear induction pumps.In the chapter devoted to the magnetohydrodynamic interaction through coupled models, the thesis proposes two models that couple the electromagnetism and the fluid flow, one realized using multiphysic software and the second by coupling two different softwares. There are presented the advantages of the coupled models with respect to the results accuracy in comparison with electromagnetic models. It is presented the evolution of velocity, force and current densities profiles under the influence of the electromagnetic field and of different sodium mean velocities.The contributions of the thesis are completed with significant observations related to the study methods and software tools used along the study process
Preocupările actuale în legătură cu exploatarea în siguranță a centralelor nucleare existente și în legătură cu proiectarea arhitecturilor speciale de reactoare nucleare pentru generația a patra,coroborate cu interesul tot mai pronunțat pentru eficiența și fiabilitatea oricărui echipament dintr-un sistem energetic, fac ca tot mai multe demersuri de cercetare să se îndrepte spre studiul diverselor subansamble ale acestor sisteme pentru o mai buna înțelegere și optimizare pe baza mijloacelor moderne de proiectare asistată de calculator. Din rândul tipurilor propuse pentru generația a patra de reactoare nucleare fac parte și cele care au ca agent de răcire săruri topite, respectiv sodiu topit. Multe reactoare nucleare de generație anterioară folosesc ca mijloc de antrenare a fluidelor de răcire pompe mecanice de construcție specială. Sărurile topite ăi sodiul lichid, datorită proprietăților fizice,au potențialul de a fi recirculate cu ajutorul pompelor electromagnetice. Deși tehnologia pompării electromagnetice a fluidelor electroconductoare a fost dezvoltată încă din prima parte a secolului trecut, în prezent cunoaște o renaștere datorită reconsiderării multiplelor avantaje tehnologice și de securitate în exploatare. Lucrarea de față este atât un studiu al fenomenelor intime ce au loc ca urmare a curgerii fluidelor electroconductoare în câmpul electromagnetic al pompelor electromagnetice – interacțiune magnetohidrodinamică - cât și un raport despre capabilitățile și avantajele uneltelor moderne de calcul de a înlesni proiectarea și optimizarea pompelor electromagnetice. Pentru a atinge scopul principal al tezei, și anume o înțelegere mai adâncă a fenomenelor interdependente specifice funcționării pompelor electromagnetice, au fost considerate două obiective secundare. Primul obiectiv se referă la exploatarea la maximum a modelelor electromagnetice numerice în element finit cu scopul de a obține cât mai multe informații cu putință despre comportamentul pompelor electromagnetice în ipoteza care nu ia în considerare curgerea fluidelor. Al doilea obiectiv a fost construirea unor modele numerice care cuplează electromagnetismul și curgerea, respectiv, cuplează modelele numerice ale celor două fenomene ce caracterizează curgerea magnetohidrodinamică din canalele pompelor electromagnetice. În partea dedicată studiului pompării electromagnetice a sărurilor topite, teza evidențiază problemele specifice legate de generarea forțelor electromagnetice în fluide slab conductoare electric și oferă rezultate cu privire la aplicațiile unde pomparea electromagnetică a sărurilor topite poate fi eficientă. Cu ajutorul modelelor electromagnetice s-au obținut date importante despre influența numărului de poli electromagnetici și frecvența de alimentare asupra caracteristicii Presiune – Viteză a pompelor electromagnetice inelare de inducție. Au fost analizate fenomenul de ecranare creat de peretii metalici – cu repercursiuni negative asupra performanțelor pompelor, efectele de frânare exercitate la intrarea și la ieșirea din canalul de pompare și legătura dintre capacitatea de suprasarcină hidrodinamică și caracteristica Presiune – Viteză a pompelor de inducție. O secțiune specială a fost consacrată analizei dependenței de timp și a variației de la punct la punct a forței electromagnetice, precum și studiului neuniformităților mărimilor de natură electromagnetic în direcție azimutală în pompele inelare de inducție. În capitolul despre interacțiunea magnetohidrodinamică pe baza modelelor cuplate, se propun două modele ce cuplează electromagnetismul și curgerea fluidelor, unul realizat cu ajutorul unui singur software și al doilea realizat prin cuplarea a două software-uri diferite. Sunt prezentate avantajele modelelor cuplate din punctul de vedere al acurateței rezultatelor în comparație cu modelele electromagnetice …

Serum vitamin D deficiency/insufficiency, Chronic Kidney Disease (CKD) and elevated blood pressure are important health concerns especially among minorities with type 2 diabetes. The effect of vitamin D3 supplementation (cholecalciferol) at 6,000 IU/day (d) vs. 4,000 IU/d on kidney function and cardiovascular disease markers among Hispanics and African Americans with type 2 diabetes and hypovitaminosis D (/ml) was evaluated. Subjects (n=63) were recruited from two clinics in Miami-Dade County, FL. Fasting venous blood and fresh, single-voided first morning urine samples were collected from each participant by a certified phlebotomist and analyzed by Solstas Lab Partners, Davie, FL. Linear mixed models were used to compare the interaction between time and intervention. Least Significant Difference (LSD) comparisons were used to detect significant differences within and between 4,000 IU/d and 6,000 IU/d groups from baseline, 3 and 6 months. In the 4,000 IU/d and 6,000 IU/d groups, a significant increase in serum 25-hydroxy vitamin D [25(OH)D] levels were observed from baseline [(19.9±1.1 ng/mL) and (21.4±1.3 ng/mL)] to 3 months [(36.1±2.2 ng/mL, p3 longer than 6 months may be needed to determine sustained long term effects in kidney and cardiovascular disease markers. Further research could provide more information for translation of these findings into recommendations for individuals with CKD, hypertension and type 2 diabetes. The efficacy of vitamin D3 supplementation as complementary therapy for CKD and blood pressure in minority and other ethnic groups needs further investigation in larger and longer duration randomized controlled trials.

Background The incidence of type 2 diabetes has increased dramatically, particularly among Latinos. While several studies suggest the beneficial effect of lowering glycemic index and glycemic load in patients with type 2 diabetes, no data exists regarding this issue in the Latino population. The purpose of this study was to determine the effect of lowering glycemic index and glycemic load on diabetes control, lipid profiles and anthropometrics among Latinos with type 2 diabetes. Methods Subjects participated in a 12 month randomized clinical trial. The intervention targeted diabetes knowledge, attitudes and behavioral capabilities related to diabetes self management with content including nutrition and physical activity. The nutrition protocol emphasized reduction in glycemic index, fat, salt and portion size and increase in fiber. The control group was given usual care. Measurements included Hba1c, fasting glucose, total cholesterol (TC), low density lipoproteins (LDL) and high density lipoproteins (HDL), HDL:LDL ratio, TC:HDL ratio, waist circumference and BMI and were collected at baseline, 4 and 12-months. Results Two hundred fifty two Latino adults with type 2 diabetes participated in the study. Baseline mean HbA1C was 8.98% (SD=1.87), BMI was 34.76 kg/cm (SD=6.94), age was 56 (SD=11.18) years and 76% were female. Reduction in glycemic index was positively associated with a reduction in logHbA1c (p=0.006), HDL:LDL ratio (p=0.037) and waist circumference (p=0.003) overtime, but not with fasting glucose, TC, LDL and HDL, TC:HDL ratio, body weight or BMI. No significant associations were found between glycemic load and any measures. Conclusion Results suggest that lowering glycemic index may have a positive effect on some markers of diabetes control, lipid profiles and anthropometrics among Latinos with type 2 diabetes, but not others. While statistically significant reductions in GI and GL were noted, the actual reduction was small. Thus, greater reduction in GI and GL may be needed for clinical significance and greater effect on metabolic outcomes. Future research should target populations with higher baseline GI and GL.

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Bachelors
Arts and Sciences
Psychology

Since type B adverse drug reactions tend to be rare and serious, they tend to be treated by tertiary-care specialists; and since they are commonly iatrogenic, the specialists should be concerned to document carefully not only the case per se but also the drug use history, leading to practice data of good research quality. The specialist should also be concerned to submit the data record to a central facility that would supply the probabilities, evidence-based, that a recent drug use by a patient caused the adverse event. Continual and systematic accumulation of these data records at the central facility--using the same logistic and organizational framework for each of different type B events--provides for both the numerator and denominator series for etiologic research. Since the targeted events are quite rare, the catchment population of the "registry" would have to be very large, international in scope, especially if the system is to provide for rapid resolution of crises arising from novel suspicions of type B effects with respect to newly marketed drugs.

This thesis presents a characterization of those categories with weak factorization systems that can interpret the theory of intensional dependent type theory with Σ, Π, and identity types. We use display map categories to serve as models of intensional dependent type theory. If a display map category (C, D) models Σ and identity types, then this structure generates a weak factorization system (L, R). Moreover, we show that if the underlying category C is Cauchy complete, then (C, R) is also a display map category modeling Σ and identity types (as well as Π types if (C, D) models Π types). Thus, our main result is to characterize display map categories (C, R) which model Σ and identity types and where R is part of a weak factorization system (L, R) on the category C. We offer three such characterizations and show that they are all equivalent when C has all finite limits. The first is that the weak factorization system (L, R) has the properties that L is stable under pullback along R and all maps to a terminal object are in R. We call such weak factorization systems type theoretic. The second is that the weak factorization system has what we call an Id-presentation: it can be built from certain categorical structure in the same way that a model of Σ and identity types generates a weak factorization system. The third is that the weak factorization system (L, R) is generated by a Moore relation system. This is a technical tool used to establish the equivalence between the first and second characterizations described. To conclude the thesis, we describe a certain class of convenient categories of topological spaces (a generalization of compactly generated weak Hausdorff spaces). We then construct a Moore relation system within these categories (and also within the topological topos) and thus show that these form display map categories with Σ and identity types (as well as Π types in the topological topos).

S-Net is a declarative coordination language rooted in stream processing with a runtime that automatically distributes the computational units among available resources. It is conceived in response to the change of processor development trend, from making the speed faster to embedding more cores. For performance reasons, the S-Net compiler is responsible for generating some additional information, through type inference, which is used by the runtime to make data delivery decisions. This requires the compiler to be supported by a sound type system which can ensure that the program behaviour meets the expectations of the language designers and the programmers. However, due to S-Net's design principle of ease of use, the S-Net type system was believed to be simple and was only informally documented. As we empirically tested the type inference implementation, we gradually revealed the hidden complexity of the calculus behind the apparently easy-to-use language, which was clearly beyond the capability of the informal type system. We then attempted several formulations of the type system, each addressing more issues we have found, but a complete solution was still missing. S-Net now urgently needs a formal type system with proofs of soundness. We have identified a major issue which has been making it difficult to design a correct type system, that is the type-semantics interdependency. In this thesis, we present a new design of the S-Net semantics and type system with no type-semantics interdependency, in terms of a new language BL-Net, a reduced S-Net which preserves only the type-related behaviour, which has an operational semantics reflecting that of S-Net, and a type system with the soundness and completeness proof. Our contributions also include a bridging solution to fit the new type system into the existing compiler structure.

This thesis concerns types systems for nominal terms, a new syntax, close to informal practice, for representing and reasoning about formal languages that use binders. Nominal techniques allow a rst-order approach to binding in formal languages, providing direct access to both binders and bound variables and a formal axiomatisation of -equivalence. This approach is promising, not least because it has been shown that unication and matching of nominal representations is both decidable and tractable, giving rise to nominal models of computation and programming languages. Nominal terms, a nominal extension of rst-order terms, are now well studied, particularly in the context of equational reasoning. However, type systems for nominal terms have not yet been extensively researched. The development of type systems for nominal terms allows the application of the nominal approach to binding to the areas of specication and verication. Programming languages and environments based upon certifying type systems facilitate formal descriptions of operational semantics and the implementation of ecient compilers. Such features are increasingly important, particularly in critical domains where mathematical certainty is a necessity, such as medicine, telecommunications, transport and defence. This work rst denes three variations on a simple type system for nominal terms in the style of Church's simply typed lambda calculus. An ML-style polymorphic type system is then studied for which a type inference algorithm is provided and implemented. This type system is then applied to equational theories. Two formulations of typed rewriting are presented, one more expressive and one more ecient. Finally, a dependent type system is given for nominal terms extended with atom substitution, with a view to developing a nominal logical framework.

Les protéines synthétisées et sécrétées par les bactéries jouent des rôles importants pour leur survie. Les bactéries à Gram négatif ont développé des voies de sécrétion en tant qu'armes principales pour transporter des facteurs de virulence dans l'environnement extracellulaire ou dans des cellules hôte. L'un de ces systèmes, le T9SS a été principalement étudié chez l'agent pathogène oral Porphyromonas gingivalis et chez la bactérie mobile Flavobacterium johnsoniae. Un autre complexe, le T2SS est le principal déterminant de la virulence de la bactérie Pseudomonas aeruginosa, un agent pathogène de la fibrose kystique. Dans le cadre de ma thèse, j'ai résolu la structure atomique de plusieurs composants centraux du T9SS et du T2SS. Concernant le projet T9SS, j'ai essayé de cristalliser le domaine cytoplasmique de GldL de F. johnsoniae. La co-cristallisation de GldL avec des Nbs a été réalisée sans succès. Néanmoins, les structures cristallines de deux nanobody contre GldL ont été résolues par remplacement moléculaire. De plus, j'ai également travaillé sur la protéine PG1058 de P. gingivalis. J'ai résolu sa structure par diffraction anomale à la longueur d’onde du selenium. Concernant le projet T2SS, je me suis concentré sur la partie N-terminale de XcpQ, une sous-unité de la sécrétine. J'ai résolu la structure cristalline de XcpQN012 seul et en complexe avec le nanobody vhh04 à une résolution de 2,98 Å et de 2,9 Å, respectivement. Enfin, j'ai participé à la détermination structurale de TssK, un composant de plaque de base du système de T6SS et déterminer la structure cristalline d'un nanobody contre le domaine périplasmique de PorM
Proteins synthesized and secreted by bacteria serve many important roles in their survival. In particular, Gram-negative bacteria have evolved secretion pathways as the main weapons for transporting virulence factors into target cells or into the extracellular environment. One of these systems, the type IX secretion system (T9SS) or the Por secretion system, has been studied mainly in the oral pathogen Porphyromonas gingivalis and the gliding bacterium Flavobacterium johnsoniae. Another complex, the type II secretion system (T2SS) is the main determinant of the virulence of Pseudomonas aeruginosa, a cystic fibrosis pathogen. In my PhD thesis, I solved the atomic structure of several core components of both T9SS and T2SS.For the T9SS project, I tried to crystallize the cytoplasmic domain of GldL from F. johnsoniae. The co-crystallization of GldL with Nbs was unsuccessfull. The crystal structures of two nanobodies against GldL were solved by molecular replacement. I also worked on the PG1058 protein of P. gingivalis. I obtained crystals of the selenomethionine-derivatized PG1058 OmpA_C-like domain that diffracted up to 1.55 Å, and solved its structure by single-wavelength anomalous diffraction. For the T2SS project, I focused on the N-terminal part of XcpQ, a subunit of the secretin. I solved the crystal structure of XcpQN012 alone and in complex with nanobody vhh04 at a resolution of 2.98 Å and 2.9 Å, respectively. In addition, I also took part in the structural determination of the base plate component TssK of the T6SS and determined the crystal structure of one nanobody (vhh19) against the periplasmic domain of PorM

Let g = g(\(A\)) be a Kac--Moody Lie algebra with generalized Carlan matrix \(A\). Brundan, Goodwin and independently Kostant developed a theory of root system known as Levi type root system when \(A\) is a Carlan matrix so that g(\(A\)) is a finite dimensional semisimple Lie algebra. This theory replicates much of the structure of usual root systems. In this thesis we build up the theory of Lie algebras to review this. Then we go on to define Levi type roots for the case where \(A\) is of affine type. To describe Levi type root systems we show how these roots are related to the roots of centralizers of nilpotent elements in g. We also determine the normalizers of parabolic subgroups of finite and affine Weyl groups of classical types which can be viewed as the Weyl groups for so called root systems.