Discourse Semantics for the Analysis of Change in Language

This paper purports to elaborate and address several issues which lie at the intersection of computational linguistics and psychology. The first issue addressed is that of the interaction between discourse and semantics by virtue of empirical linguistic and psychotherapeutic evidence. This paper then gives a formal account of the knowledge representation and reasoning processes involved in the construction of an XML knowledge base for use in the sematic analysis of psychotherapeutic transcripts. Computational methods for the automatic mark-up and inference of the psychotherapeutic phenomena under investigation are detailed in order to further develop intuitions behind a particular pragmatic theory of language known as the Metamodel. The work presented here ultimately aims to produce a sustainable system for the evaluation of the effectiveness of any given psychotherapeutic technique. The possibility exists for such a system to recognise successful therapeutic mechanisms and further still, to infer new ones, or suggest improvements, or offer novel explanations as to the success or failure of the therapy itself. The work discussed here stems from research in computational linguistics, psychotherapy, and philosophy. The corpus used is a culmination of client transcripts taken before, during, and after therapy. The particular therapeutic technique used here is known as the Metamodel (Bandler and Grinder, 1975). The Metamodel was originally proffered as a method of language analysis suitable for use by practitioners of any psychotherapeutic technique. It theorises that speech utterances are related to a clients deep structure through three primary mechanisms, namely generalisation, deletion, and distortion. Previous hand tagging of our data has proven support for such claims. It is our aim to automate the identification and reasoning process. The issues and processes involved in the automation of such tagging are discussed here. Architectural and philosophical issues relating syntax (or grammar), semantics (Larson and Segal, 1995), and pragmatics (Grice, 1989; Searle, 1969) are raised. Discourse Representation Theory (Kamp, 1981; Asher and Lascarides, 1995) is discussed and used here in order to infer discourse relations.Hosted by the Scholarly Text and Imaging Service (SETIS), the University of Sydney Library, and the Research Institute for Humanities and Social Sciences (RIHSS), the University of Sydney

Development and demise of plasmodium liver stage parasites.The hunt for a genetically attenuated malaria vaccine

Contains fulltext : 112643.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 10 juni 2013Promotor : Sauerwein, R.W. Co-promotor : Janse, C.J

Hybrid modelling for mechanical systems : methodologies and applications

A serial hybrid modeling approach is applied to mechanical systems. Here, hybrid means that models are based on combined structural and empirical approaches. The main system behavior is described by a physical model, while complex internal forces are modeled by black box neural networks. For a special class of systems this methodology is extended and a novel approach is presented modeling the whole system behavior by hierarchical neural networks, that fit the relation between system outputs and internal system variables. Useful information about the nonlinear system can be extracted from the resulting models. The power of hybrid modeling is illustrated with experimental results and some important issues considering the practical implementation are dealt with

Plasmodium liver load following parenteral sporozoite administration in rodents

Item does not contain fulltextOne of the bottlenecks in the development of a whole sporozoite malaria vaccine is the route and method of sporozoite administration. Immunization and challenge of human volunteers by mosquito bites is effective, but cannot be used as a vaccine. Intravenous immunization with sporozoites is effective in rodents and non-human primates, and being studied in humans, but is not yet used for licensed vaccines for infectious diseases. Intradermal and subcutaneous immunization regimens show a strong decrease in protective efficacy, which in rodents, is associated with a decreased degree of parasite liver infection during immunization. The objective of this study was to explore alternative routes of sporozoite administration to increase efficiency of liver infection. Using in vivo imaging, we found that IM injection of sporozoites resulted in a greater parasite liver load compared to ID and SC injection. The use of small inoculation volumes and multiple injections further increased the subsequent liver load. These observations were corroborated in a Plasmodium yoelii model using cryopreserved sporozoites administered ID. Our findings provide a rationale for the design of clinical trials to optimize needle and syringe administration of Plasmodium falciparum sporozoites

Memory-like IFN-gamma response by NK cells following malaria infection reveals the crucial role of T cells in NK cell activation by P. falciparum.

NK cells are rapid IFN-gamma responders to Plasmodium falciparum-infected erythrocytes (PfRBC) in vitro and are involved in controlling early parasitaemia in murine models, yet little is known about their contribution to immune responses following malaria infection in humans. Here, we studied the dynamics of and requirements for in vitro NK responses to PfRBC in malaria-naive volunteers undergoing a single experimental malaria infection under highly controlled circumstances, and in naturally exposed individuals. NK-specific IFN-gamma responses to PfRBC following exposure resembled an immunological recall pattern and were tightly correlated with T-cell responses. However, although PBMC depleted of CD56(+) cells retained 20-55% of their total IFN-gamma response to PfRBC, depletion of CD3(+) cells completely abrogated the ability of remaining PBMC, including NK cells, to produce IFN-gamma. Although NK responses to PfRBC were partially dependent on endogenous IL-2 signaling and could be augmented by exogenous IL-2 in whole PBMC populations, this factor alone was insufficient to rescue NK responses in the absence of T cells. Thus, NK cells make a significant contribution to total IFN-gamma production in response to PfRBC as a consequence of their dependency on (memory) T-cell help, with likely positive implications for malaria vaccine development

Assessing the adequacy of attenuation of genetically modified malaria parasite vaccine candidates.

Item does not contain fulltextThe critical first step in the clinical development of a malaria vaccine, based on live-attenuated Plasmodium falciparum sporozoites, is the guarantee of complete arrest in the liver. We report on an approach for assessing adequacy of attenuation of genetically attenuated sporozoites in vivo using the Plasmodium berghei model of malaria and P. falciparum sporozoites cultured in primary human hepatocytes. We show that two genetically attenuated sporozoite vaccine candidates, Deltap52+p36 and Deltafabb/f, are not adequately attenuated. Sporozoites infection of mice with both P. berghei candidates can result in blood infections. We also provide evidence that P. falciparum sporozoites of the leading vaccine candidate that is similarly attenuated through the deletion of the genes encoding the proteins P52 and P36, can develop into replicating liver stages. Therefore, we propose a minimal set of screening criteria to assess adequacy of sporozoite attenuation necessary before advancing into further clinical development and studies in humans

Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations.

Contains fulltext : 89802.pdf (publisher's version ) (Closed access)BACKGROUND: The full-length (L-) variant of caspase-12 is believed to predispose to sepsis. It has been replaced in the genome of most human populations by the (S-) variant, which leads to premature termination of translation. Strikingly, the L-allele is still widely prevalent in African populations, presumably due to a counterbalancing selective force specific to this continent, for which malaria is a prime candidate. METHODS: We investigated associations between caspase-12 genotype and malarial parameters in three West-African populations, in studies encompassing immunological, clinical and obstetric data. RESULTS: The caspase-12 L-allele was found at frequencies of 11-34%. Plasmodium falciparum-stimulated mononuclear cells from S/L heterozygote donors produced stronger interferon-gamma and interleukin-10 responses than S/S homozygotes (p = 0.011 and p = 0.023 in uninfected and infected donors respectively). Nevertheless, we found no association between caspase-12 genotype and either the presentation of severe malaria or individual clinical parameters in sick children. Amongst pregnant women, the caspase-12 genotype did not influence peripheral or placental malaria infection, or basic obstetric parameters. Interestingly, perinatal mortality was more frequent in children of both S/S and L/L than S/L mothers, independent of placental P. falciparum-infection. CONCLUSION: We find little clinical or epidemiological evidence that malaria has contributed to the persistence of functional caspase-12 in Africa, suggesting either that alternative selective forces are at work or that genetic drift underlies its current global distribution.1 juni 201