<p align="justify">Aujourd'hui, la gestion des documents est l'un des problèmes les plus importants en informatique. L'objectif de cette thèse est de proposer un système de gestion documentaire basé sur une approche appelée recherche structurée et collaborative. Les caractéristiques essentielles sont :</p> <ul><li><p align="justify">Dès lors que les utilisateurs ont plusieurs centres d'intérêts, ils sont décrits par des profils, un profil correspondant à un centre d'intérêt particulier. C'est la partie structurée du système.</li> </p> <li><p align="justify">Pour construire une description des profils, les utilisateurs jugent des documents en fonction de leur intérêt</li> </p> <li><p align="justify">Le système regroupe les profils similaires pour former un certain nombre de communautés virtuelles</li></p> <li><p align="justify">Une fois les communautés virtuelles définies, des documents jugés comme intéressants par certains utilisateurs d'une communauté peuvent être partagés dans toute la communauté. C'est la partie collaborative du système.</p> </li></ul> <p align="justify">Le système a été validé sur plusieurs corpora de documents en utilisant une méthodologie précise et offre des résultats prometteurs.</p>

本篇論文從認知語意學的角度來探討分類詞的本質，並且結合了Fillmore (1975) 的框架 (frame) 理論和Langacker (1987) 的顯影(profiling) 概念，作為分析的理論基礎，說明語言如何透過分類詞機制來凸顯名詞在認知上的某些語意特徵。本論文所嘗試提出的理論架構最終目的在於解釋所有的分類詞語言，但為提昇語料的可信度，語料來源以台灣華語中的分類詞為主。 研究分析主要建構於名物框架 (N-frame) 的認知基礎上，進而檢視台灣華語中不同類別之名詞藉由不同之分類詞所彰顯的語意特徵 (feature)，同樣重要的是不同的語意特徵在台灣華語分類詞系統中的優先排序。最後我們從其他的分類詞語言中，如閩南語及日語，論證名物框架系及彰顯機制統的普遍性；唯不同的分類詞語言或不同方言中所選擇顯影的語意特徵以及其優先排序都可能有所不同，分類詞系統也因此呈現複雜多樣的面貌。 / On the basis of the theory of Frame, proposed by Fillmore (1975), and the models of profile and base segregation, proposed by Langcker (1987), this thesis aims at a cognitive approach to explain how languages manifest certain cognitive features of a noun by means of classifiers. In addition, the theoretical framework tries to explain all the known classifier languages and to foster a greater accountability and reliability of the data, this study focuses on Taiwan Mandarin. The data analysis is based on the cognitive foundation of an N-frame, whereby it is found that Taiwan Mandarin categorizes nouns by profiling different features of nouns through the use of different classifiers. A hierarchy or ranking of classifier features in Taiwan Mandarin is also provided. Finally, in all known classifier languages, such as Southern Min and Japanese, it is found that the application of the use of an N-frame is consistent and universal in human cognition. The only thing that varies is the profiling system that each language employs and the hierarchy of features it selects. Thus, the use of classifiers manifests varied and complex aspects.

Hepatitis C Virus (HCV) infects 170 million people worldwide. The current treatment regimen, which is combination therapy with pegylated interferon (PegIFN) and Ribavirin (Rib), cures only 50% of the patients infected with the most prevalent HCV genotype. Therefore, there is a pressing need to understand the molecular mechanism of interferon resistance and to develop a prognostic tool to predict who will respond to treatment before initiation of therapy. It has been firmly established that the virus-host interaction plays an important role in determining treatment outcomes. My thesis investigated the host factors that are involved in interferon resistance with an aim to provide insights into the molecular mechanism of IFN resistance. cDNA microarray analysis identified 18 differentially expressed hepatic genes from pretreatment liver tissues of responders (Rs) and non-responders (NRs). Based on the differential expression levels of these 18 genes, a prognostic tool was developed to predict who will respond to therapy, with a positive predicting value (PPV) of 96%. Most of these 18 genes are interferon stimulated genes (ISGs) and they are more highly expressed in NR livers, indicating that preactivation of interferon signaling in the pre-treatment liver tissues contributes to NR. 3 out of the 18 genes are involved in an ubiquitin-like ISG15/USP18 signaling pathway that plays an important role in interferon response. Over-expression of USP18 and ISG15 in the pretreatment liver tissues of NR promotes HCV production and blunts interferon anti-HCV activity. There exists a distinct cell-type specific ISG activation in the pretreatment liver tissues of Rs and NRs. Up-regulation of the two ISGs that I tested (ISG15 and MxA) was found mainly in hepatocytes in NRs while ISG activation was preferentially observed in macrophages in Rs. Taking all these data together, pre-activation of interferon signaling and cell-type specific gene activation in the pretreatment liver tissues of patients infected with HCV are associated with treatment non-response. HCV exploits the host interferon system to favour its persistence by enhanced replication /secretion stimulated by a few ISGs (ISG15, USP18) in response to IFN. The developed prognostic tool can be used to stratify patients for treatment and the novel insights of the molecular mechanism of IFN resistance in HCV patients offer potential drug targets for future development.

Globalisation yields numerous challenges and continuous changes in the economic environment, rapid technological advancements, and an increased emphasis on organisational competitiveness. The existing practice in the Telecommunications company relied on conventional recruitment-on-vacancy and training. In 1997, a customer contact research programme was launched to review the specific competencies underlying the full range of customer contact roles, in order to understand the constructs which would underlie effective assessment of people for the role of sales and marketing. The aim of this research was to evaluate the effectiveness of an assessment battery in a telecommunications company. The assessment battery measures the participants' essential skills, behaviour and performance to bring about critical development action. The Work Profiling System (WPS) and Subject Matter Experts in the Sales Division identified the fifteen competencies. The assessment battery consisted of Ability Tests: Verbal Evaluation (VCC3) and Numerical Evaluation (NCC4), and a personality questionnaire: Customer Contact Styles Questionnaire (CCSQ7.2). The Customer Contact Competency Inventory (CCCI) was electronically administered to the sales representatives' respective managers in 2006, to give objective 360" feedback. The study population (n=97) consisted of sales representatives working in a Telecommunication company. The objectives for this research were to validate the chosen selection battery for the sales representatives, and determine its relation to manager-rated performance. Descriptive and inferential statistics were used to analyse the data. Stepwise multiple regression analyses were carried out to determine whether the independent variables (CCSQ7.2 and Ability Tests) hold any predictive value regarding the dependent variable (CCCI). The results of the regression analyses showed that Verbal Evaluation (VCC3) was a significant predictor of: Convincing, Communicating Orally, Results Driven. Problem Solving and Organisation. Modest (R4) was a significant predictor of Convincing. Participative (R5) was a significant predictor of Problem Solving and Organisation. Overall, it can be stated that there is a significant relationship between the test battery and job performance. The results in this study reflect that correlations between personality, ability and performance were small to moderate. This is lower than expected and what is found in similar international research. This is probably due to the flawed criterion. The results should be used with caution to prevent making a Type I1 error. Recommendations for future research are made. vii / Thesis (M.A. (Industrial Psychology))--North-West University, Potchefstroom Campus, 2007.

Over the past ten years, the development of High Throughput (HT) synthetic chemistry techniques has allowed the rapid preparation of libraries of hundreds to thousands of compounds. These tools are now extensively used for drug and material discovery programmes. The subsequent development of analytical capabilities to carry out qualitative and quantitative assessment of the compounds generated by HT synthesis as well as their HT screening has led to a dramatic broadening of the scope of HT techniques, ranging from image based analysis techniques to mass spectrometry (MS). Based on the latter, a range of solid phase and solution phase analytical constructs was developed to enable the qualitative and quantitative assessment of mixtures of small compounds, using positive electrospray MS as the sole analytical tool. A version of the construct allowed HT reactivity profiling to be carried out on a range of ten carboxylic acids, ten aldehydes and ten isonitriles in the Ugi 4-component condensation reaction. The effect of various parameters such as the concentration of the monomers on the reactivity was investigated. The elaboration of a HT Hammett parameter assessment method was made possible by the development of an electrophilic version of the construct. The value of the Hammett value was afforded by means of combinatorial Hammett plots and values were successfully evaluated in a HT mode for around thirty anilines with substituents in the meta and para position of the aromatic ring. Finally, analytical constructs were used in an attempt to evaluate enzyme reaction kinetics via the labelling of peptides and small drug fragment with coded constructs, to afford affinity determinations between the enzyme (protease) and peptidic or fragment based substrates.

Mutations found in genes encoding human Elongator complex subunits have been linked to neurodevelopmental disorders such as familial dysautonomia (FD), rolandic epilepsy and amyotrophic lateral sclerosis. In addition, loss-of-function mutations in genes encoding Elongator complex subunits cause defects in neurodevelopment and reduced neuronal function in both mice and nematodes. The Elongator complex is a conserved protein complex comprising six subunits (Elp1p-Elp6p) found in eukaryotes. The primary function of this complex in yeast is formation of the 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) side chains found on wobble uridines (U34) in tRNAs. The aim of this thesis is to investigate the physiological consequences of Elongator complex inactivation in humans and in the yeast Saccharomyces cerevisiae. Inactivation of the Elongator complex causes widespread defects in a multitude of different cellular processes in S. cerevisiae. Thus, we investigated metabolic alterations resulting from Elongator complex inactivation. We show that deletion of the S. cerevisiae ELP3 gene leads to widespread metabolic alterations. Moreover, all global metabolic alterations observed in the elp3Δ strain are not restored in the presence of elevated levels of hypomodified tRNAs that normally have the modified nucleoside mcm5s2U. Collectively, we show that modified wobble nucleosides in tRNAs are required for metabolic homeostasis. Elongator mutants display sensitivity to DNA damage agents, but the underlying mechanism explaining this sensitivity remains elusive. We demonstrate that deletion of the S. cerevisiae ELP3 gene results in post-transcriptional reduction of Ixr1p levels. Further, we show that the reduced Ixr1p levels prevent adequate Rnr1p levels upon treatment with DNA damage agents. These findings suggest that reduced Ixr1p levels could in part explain why Elongator mutants are sensitive to DNA damage agents. Depletion of Elongator complex subunits results in loss of wobble uridine modifications in plants, nematodes, mice and yeast. Therefore, we investigated whether patients with the neurodegenerative disease familial dysautonomia (FD), who have lower levels of the ELP1 protein, display reduced amounts of modified wobble uridine nucleosides. We show that tRNA isolated from brain tissue and fibroblast cell lines derived from FD patients have 64–71% of the mcm5s2U nucleoside levels observed in total tRNA from non-FD brain tissue and non-FD fibroblasts. Overall, these results suggest that the cause for the neurodegenerative nature of FD could be translation impairment caused by reduced levels of modified wobble uridine nucleosides in tRNAs. Thus, our results give new insight on the importance of modified wobble uridine nucleosides for neurodevelopment.

A new approach for predicting octanol-water partition coefficients (Log P) of linear perfluorinated compounds, making use of the limited experimental data available, previous observations and the consistent similarities observed between the experimental and calculated (with electronic structure methods and using EPI suite) slopes of the linear plots of Log P values with the number of carbon atoms (N = 2 to 11) is described here. Eight families of linear organic compounds were investigated: carboxylic acids, perfluorinated carboxylic acids, sulfonic acids and perfluorinated sulfonic acids, together with their corresponding conjugate bases. To the best of our knowledge, this work reports the first application of density functional theory methods to the calculation of Log P values of perfluorinated compounds. A second part of the thesis, describes the study of the thermodynamic stability of the PFOA family of 39 structural isomers with the M06-2X, LC-ωPBE, B97D and B3LYP functionals and with the PM6 method. The PM6 results closely resemble the M06-2X results for neutral PFOAs, but greatly disagree regarding anions. The four functionals applied behave similarly from a qualitative point of view, but quantitatively speaking, the LC-ωPBE and B97D results are between the M06-2X and B3LYP stability results. M06-2X ranks highly substituted isomers as more stable than did B3LYP, and ranks less-branched isomers quite low in relative stability compared to B3LYP. Various similarities with a former PFOSs study applying the M06-2X and B3LYP functionals have been identified. The degree of branching within structural isomers cannot always be precisely determined, and is not the only aspect that determines thermodynamic stability; the pattern of substitution seems to also play a significant role. / Graduate

MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression at both the mRNA and protein levels. MiRNAs have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. We investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N =35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain-specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development. Given that miRNAs can bind to their targets with imperfect complementarity, computational prediction of true miRNA:mRNA interactions has been difficult and therefore, functional validation of miRNA:mRNA interactions has been relatively sparse. Thus, it was the goal of this study to demonstrate biological functionality of miRNAs on their targets by evaluating transcriptional and translational levels of gene expression(real-time PCR, western blot) as well as determining miRNA target-site specificity (luciferase reporter gene assays). We investigated two miRNAs, miR-132 and miR-137, both of which have been shown to regulate neuronal function and development, and are believed to be associated with schizophrenia from two distinct avenues of research, miR-132 from expression studies and miR-137 from genetic studies. We demonstrated miR-132 down-regulates NTF3, DISC1, and GRIK5 at the transcript level and down-regulates GRIK5 at the protein level as well. Furthermore, we demonstrated miR-137 down-regulates TCF4, CACNA1C, CDK6, ANK3, and ZNF804A at the transcript level, and down-regulates TCF4, CACNA1C, and CDK6 at the protein level. Going further, we also demonstrated miR-137 binds specifically to target sites in the 3'-UTR of CACNA1C, TCF4, and CDK6, suggesting repression of these genes is directly mediated by miR-137. In total, this study provides strong evidence that miRNA dysregulation may contribute to schizophrenia pathogenesis.

Coccolithophores are single-celled marine phytoplankton, which produce intricate calcium carbonate platelets or ‘coccoliths’. Emiliania huxleyi is the most abundant and widespread coccolithophore, and is one of the most productive calcifying species on earth, playing a key role in global carbon, carbonate and sulphur cycles. Despite much research into coccolithophore biology, the underlying function of their coccoliths is still unknown. The main aim of the research reported in this thesis was to examine the impact of calcification on metabolism in coccolithophores. Calcification is a significant global process, so it is important to discover what effect it has on the metabolism of cells. The major metabolites each have different costs and benefits to the cell, which will vary depending on the habitat and environmental conditions the cell is in. By comparing the metabolite profiles of different strains, including calcifying, non-calcifying, haploid and diploid cells, differences in metabolite composition and potential patterns related to cell type were investigated. Low molecular weight (LMW) metabolites were characterised using a combination of metabolomic techniques. In agreement with previous research, dimethylsulphoniopropionate (DMSP) was the most abundant compound, followed by mannitol and glycine betaine (GBT). Less abundant sugars, polyols and amino acids were also identified. Environmental factors were manipulated to investigate how the principal metabolites were affected by salinity, different light intensities and nutrient (phosphate and nitrate) limitation. The data revealed a striking difference between haploid and diploid cells of the same strain, with the haploid containing lower concentrations of most of the major metabolites. Thus it is proposed that haploid cells have a different osmoregulatory strategy from the diploid cells. A negative correlation was found between DMSP and mannitol, suggesting that mannitol has a dual function, not only as a major storage compound but also as a principal compatible solute. Untargeted metabolite profiling is becoming a popular tool to investigate phenotypes and varying environmental conditions. LC-ESI-QTOF-MS/MS analyses of a wide range of metabolites showed that it is an effective method to identify differences and similarities between E. huxleyi strains grown in different conditions. Strain and growth phase appear to be the more important factors in differentiating metabolite profiles. Surprisingly there were no obvious metabolite profiling differences between calcifying and non-calcifying cells. Untargeted analysis can, however, be used to identify the compounds that did display differences, and which may be important biomarkers, so warrant further investigation. A range of metabolite profiling techniques highlighted important differences between strains, which will hopefully lead onto further research into the metabolome of E. huxleyi, and the unravelling of important metabolic pathways. There has been little research into the LMW metabolites of E. huxleyi, and especially comparisons between strains. Thus the use of metabolomics is a novel way to investigate the difference between cell types and the possible functions of calcification.

Psychological profiling of an offender Psychological profiling is a method of investigation developed in the 70's in the USA. This method is founded on research of behaviour of unknown offender with purpose to make conclusions about his personality. The purpose of my thesis is to find out how psychological profile can help during investigation. I would like to prove that psychological profiling belongs to investigation, that it can help during investigation and that it can bring a new view on case. The source of knowledge about the offender's behaviour and personality is the crime scene or text analyse. The thesis is composed of three chapters, each of them dealing with different aspects of psychological profiling. Chapter One is introductory and is subdivided into two parts. Part one describes history of psychological profiling. Part Two deals with theorethical background of psychological profiling. Chapter Two focuses on practical part of psychological profiling and consists of seven parts. This chapter explains the process of making a psychological profile, differences between mass-murder, serial-killer ad spree killer, characteristics of expert who creates a psychological profile, limits of psychological profile and differences between crimes committed by intimate people and those by unknown...