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

The Plasmodium 6--cysteine protein family in sexual and sporozoite stages: targets for malaria vaccine development

Contains fulltext : 93617.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 26 juni 2012Promotor : Sauerwein, R.W.204 p

Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum.

Contains fulltext : 49758schaijk.pdf (publisher's version ) (Closed access)The genome of Plasmodium falciparum contains a small gene family that expresses proteins characterized by the presence of 6-cysteine domains. Most of these proteins are expressed on the surface of the parasite and some are known to play a role in cell-cell interactions. Two members of this family, Pfs48/45 and Pfs230, form a complex localized on the surface of gametes and are recognized as important targets for transmission-blocking vaccines. In this study we report the analysis of an additional member of this family, Pfs47 the closest paralog of Pfs48/45. We demonstrate that Pfs47 is expressed only in female gametocytes and is located on the surface of female gametes following emergence from red blood cells. In contrast to the critical function of P48/45 for male fertility, Pfs47 does not appear crucial for female fertility. Parasites lacking Pfs47 through targeted gene disruption, produce normal numbers of oocysts when included in the blood meal of the mosquito vector. In addition, three monoclonal antibodies against Pfs47 were unable to inhibit oocyst development when present in a blood meal containing wild type parasites. These results show redundancy in protein function for Pfs47 and reduce the support for candidacy of Pfs47 as a transmission-blocking vaccine target

COMPARISON OF DIRECT AND INDIRECT ORTHODONTIC BONDINGTECHNIQUES IN TERMS OF DEMINERALIZATION: AN IN VIVO STUDY

The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of additional members of this family in Plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of P. berghei. This analysis revealed that in addition to P48/45, two members (P230 and P47) also play an essential role in the process of parasite fertilization. Mating studies between parasites lacking P230, P48/45 or P47 demonstrate that P230, like P48/45, is a male fertility factor, consistent with the previous demonstration of a protein complex containing both P48/45 and P230. In contrast, disruption of P47 results in a strong reduction of female fertility, while males remain unaffected. Further analysis revealed that gametes of mutants lacking expression of p48/45 or p230 or p47 are unable to either recognise or attach to each other. Disruption of the paralog of p230, p230p, also specifically expressed in gametocytes, had no observable effect on fertilization. These results indicate that the P. berghei 6-cys family contains a number of proteins that are either male or female specific ligands that play an important role in gamete recognition and/or attachment. The implications of low levels of fertilisation that exist even in the absence of these proteins, indicating alternative pathways of fertilisation, as well as positive selection acting on these proteins, are discussed in the context of targeting these proteins as transmission blocking vaccine candidates

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

BDES2020 - Decorated Shed <Katherine McCourt>

The prodigious rate at which malaria parasites proliferate during asexual blood-stage replication, midgut sporozoite production, and intrahepatic development creates a substantial requirement for essential nutrients, including fatty acids that likely are necessary for parasite membrane formation. Plasmodium parasites obtain fatty acids either by scavenging from the vertebrate host and mosquito vector or by producing fatty acids de novo via the type two fatty acid biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway in Plasmodium falciparum, the species responsible for the most lethal form of human malaria. Using antibodies, we find that the FAS-II enzyme FabI is expressed in mosquito midgut oocysts and sporozoites as well as liver-stage parasites but not during the blood stages. As expected, FabI colocalizes with the apicoplast-targeted acyl carrier protein, indicating that FabI functions in the apicoplast. We further analyze the FAS-II pathway in Plasmodium falciparum by assessing the functional consequences of deleting fabI and fabB/F. Targeted deletion or disruption of these genes in P. falciparum did not affect asexual blood-stage replication or the generation of midgut oocysts; however, subsequent sporozoite development was abolished. We conclude that the P. falciparum FAS-II pathway is essential for sporozoite development within the midgut oocyst. These findings reveal an important distinction from the rodent Plasmodium parasites P. berghei and P. yoelii, where the FAS-II pathway is known to be required for normal parasite progression through the liver stage but is not required for oocyst development in the Anopheles mosquito midgut

Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites

Host-parasite interactio