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Shigella flexneri is a bacterial pathogen which causes dysentery by invading the epithelial cells of the colon. In order to survive and replicate inside the host, S. flexneri requires many genes present on both its chromosome and the large virulence plasmid it carries. This study examines which genes are required for infection of cultured epithelial cells in order to understand which processes are used by S. flexneri during the infection process. This analysis pinpointed genes involved in metabolism, LPS synthesis, protein homeostasis and virulence effector proteins. The role of Elongation factor P (EF-P) in S. flexneri virulence is also investigated in this study. EF-P is a bacterial translation factor that is post-translationally modified with a [Beta]-lysine by the action of PoxA. Here it is shown that both EF-P and PoxA are necessary for virulence of S. flexneri. Loss of either EF-P or PoxA leads to an impaired ability of S. flexneri to invade epithelial cells. Proteomic analysis of efp and poxA deletion mutants revealed decreased levels of several virulence effector proteins, as well as proteins for the biosynthesis of the siderophore aerobactin. Virulence proteins were affected due to decreased levels of the master virulence regulator VirF. Reduction in VirF transcription is likely due to decreased levels of CpxA, which activates virF through the response regulator CpxR. The role of CpxAR in reduced synthesis of VirF and its downstream effectors was confirmed by showing increased invasion when a mutation resulting in constitutively vii activated CpxR was introduced into the efp mutant. Thus, modified EF-P is one of the chromosomal factor necessary for the virulence of this bacterial pathogen. / text

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Children with specific deficits in language do not form a homogeneous group, but present with varied profiles of language skills and deficits. Research in children with language problems has focussed on deficits in the acquisition of lexical forms and syntactic structures of language, but our understanding of children's deficits with the meaning of language remains limited. Sociocognitive abilities are necessary for discovering the meaning of language, and it has been hypothesised that some children with specific deficits in language have sociocognitive difficulties. In this thesis, it is argued that nonverbal imitation, which does not involve the processing of structural aspects of language, may be indicative of sociocognitive difficulties. More specifically, it is argued that types of nonverbal imitation which serve a primarily social Junction are more informative about sociocognitive abilities than types of nonverbal imitation which serve a primarily instrumental function. In line with this reasoning, it has been found that different forms of nonverbal imitation can be separately impaired and associated with different language skills in children with autism spectrum disorder (ASO), who are known to have sociocognitive difficulties. However, there has been very little exploration of nonverbal imitation skills in children with specific deficits in language, and existing studies have predominantly involved school-age children. This study set out to investigate elicited immediate nonverbal imitation as a measure of sociocognitive skills in young typically developing (TO) children and children with specific language delay (SLO), and also to investigate relations between performance on nonverbal imitation and language in the SLD sample. A subsidiary aim was to compare the performance of the TD and SLD samples on verbal imitation. Participants were German-speaking TD (n=60) and SLD (n=45) children aged 2-3 1/2 years, who were divided into three age groups (2;0-2;5, 2;6-2;11, 3;0-3;5 years). A novel battery of tasks measured their attempt and ability to imitate a range of nonverbal (body movements, common instrumental acts on objects, pretend acts) and verbal (words, nonwords, sentences) target acts. It was found that groups with SLD performed significantly below TO groups on some, but importantly not all, nonverbal imitation tasks. Results demonstrated that children with SLD did not have a general difficulty with nonverbal imitation, but a specific difficulty with target acts hypothesised to serve a primarily social function. A comparison of types and rates of nonverbal imitation errors revealed that error patterns in the oldest SLD group resembled those in the youngest TD group, suggesting a delay rather than deviance in some types of nonverbal imitation within the SLD sample. Different relations between performance on nonverbal imitation and language emerged at different ages, pointing towards the possibility that the nature of associations between nonverbal imitation and language might be linked to age and change over time. As expected, results revealed verbal imitation deficits in the SLD sample at all ages. The theoretical and clinical implications of findings are discussed.

This thesis focuses on the subject of varieties for modules for elementary abelian p-groups. Given a homogeneous polynomial over an algebraically closed field of char- acteristic 2 we will give constructions for modules of small dimension having that polynomial as variety. This is similar to an earlier construction given by Jon Carlson but our modules will in general be of considerably smaller dimension. We also investigate the connection between the variety of a module and its Loewy length. We show that working over an algebraically closed field of characteristic 2 with modules of Loewy length 2 allows us to find modules with any hypersurface as their variety. On the other hand we also demonstrate that in odd characteristic p, with modules of Loewy length p, the only possible varieties are finite unions of linear hypersurfaces.

To investigate the underlying structural features of the neuropeptides α-melanotropin (α-MSH) and substance P (SP), which are responsible for their biological actions, the following study was undertaken. By means of side-chain, fragment and conformational restriction analysis, several α-MSH peptides were prepared by solid-phase synthesis and evaluated by the frog and lizard skin bioassays. Using conformational restriction and fragment methods, several SP peptides were synthesized and examined for biological activity on the guinea-pig isolated ileum, rat brain binding and intrathecal injection assay systems. The results with the new α-MSH analogues show that the histidine-6 side-chain is not needed for signal transduction, but is very important for full potency. The tryptophan-9 side-chain is similarly not needed for signal transduction, but is critically important for full potency. The data also indicate that the positions 6 and 9 side-chains are important for full potency because they likely interact with the melanophore receptor, rather than playing a role in conformationally folding the MSH peptide into a pseudocyclic structure. The results also show that the arginine side-chain at position 8 is not particularly important for signal transduction or full potency, but on the lizard skin bioassay this side-chain is implicated in the previously reported prolongation of Nle⁴, D-Phe⁷-α-MSH. The data provided by the SP peptides suggest that the previously postulated pseudocyclic structure of the 5-11 sequence may not be as fundamental to SP activity as heretofore believed. The data suggest that this type of turn conformation may be important for signal transduction, but is apparently not the only requirement for receptor recognition. Finally, the data show that part of the signal transduction message of SP is contained within the 5-8 region of the peptide, but that most of the receptor recognition elements are probably located outside this sequence.

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In my PhD thesis I propose a Bayesian nonparametric estimation method for structural econometric models where the functional parameter of interest describes the economic agent's behavior. The structural parameter is characterized as the solution of a functional equation, or by using more technical words, as the solution of an inverse problem that can be either ill-posed or well-posed. From a Bayesian point of view, the parameter of interest is a random function and the solution to the inference problem is the posterior distribution of this parameter. A regular version of the posterior distribution in functional spaces is characterized. However, the infinite dimension of the considered spaces causes a problem of non continuity of the solution and then a problem of inconsistency, from a frequentist point of view, of the posterior distribution (i.e. problem of ill-posedness). The contribution of this essay is to propose new methods to deal with this problem of ill-posedness. The first one consists in adopting a Tikhonov regularization scheme in the construction of the posterior distribution so that I end up with a new object that I call regularized posterior distribution and that I guess it is solution of the inverse problem. The second approach consists in specifying a prior distribution on the parameter of interest of the g-prior type. Then, I detect a class of models for which the prior distribution is able to correct for the ill-posedness also in infinite dimensional problems. I study asymptotic properties of these proposed solutions and I prove that, under some regularity condition satisfied by the true value of the parameter of interest, they are consistent in a "frequentist" sense. Once I have set the general theory, I apply my bayesian nonparametric methodology to different estimation problems. First, I apply this estimator to deconvolution and to hazard rate, density and regression estimation. Then, I consider the estimation of an Instrumental Regression that is useful in micro-econometrics when we have to deal with problems of endogeneity. Finally, I develop an application in finance: I get the bayesian estimator for the equilibrium asset pricing functional by using the Euler equation defined in the Lucas'(1978) tree-type models.

This thesis contains three essays on microeconometrics, networks and economic development. In the first two essays I focus on developing country settings (Tanzania and Nepal respectively) to study how rural villagers form their social networks, and how the existence of these informal links impacts their welfare. The third essay focuses on the international trade of arms to investigate whether the political orientation of government in power makes any difference to arms export policy.