Data integration for the analysis of uncharacterized proteins in Mycobacterium tuberculosis

Includes abstract.Includes bibliographical references (leaves 126-150).Mycobacterium tuberculosis is a bacterial pathogen that causes tuberculosis, a leading cause of human death worldwide from infectious diseases, especially in Africa. Despite enormous advances achieved in recent years in controlling the disease, tuberculosis remains a public health challenge. The contribution of existing drugs is of immense value, but the deadly synergy of the disease with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS) and the emergence of drug resistant strains are threatening to compromise gains in tuberculosis control. In fact, the development of active tuberculosis is the outcome of the delicate balance between bacterial virulence and host resistance, which constitute two distinct and independent components. Significant progress has been made in understanding the evolution of the bacterial pathogen and its interaction with the host. The end point of these efforts is the identification of virulence factors and drug targets within the bacterium in order to develop new drugs and vaccines for the eradication of the disease

Détermination du débit de filtration glomérulaire au cours de la drépanocytose au Sénégal: Schwartz, Cockcroft et Gault, MDRD, CKD-EPI ou JSCCS ?

La détermination du Débit de Filtration Glomérulaire (DFG) est importante chez les drépanocytaires du fait qu’ils constituent un groupe de patients chez lesquels des atteintes rénales sont fréquemment décrites notamment l’hyperfiltration glomérulaire. Dès lors, à une époque où les calculateurs en ligne proposent simultanément différentes formules de détermination du DFG, il serait important d’évaluer au sein d’une population noire africaine drépanocytaire l’équivalence entre ces formules qui ont été développées et validées sur des populations caucasiennes et afro-américaines à DFG normal ou diminué. Ainsi cette étude avait pour but d’évaluer l’interchangeabilité des différentes formules de détermination du DFG en les appliquant à des drépanocytaires. Des enfants et adultes sénégalais drépanocytaires homozygotes ont été alors recrutés et leur DFG calculé. La fréquence de l’hyperfiltration glomérulaire et celle de l’insuffisance rénale ont été calculées à partir des résultats obtenus avec les formules de Schwartz et du CKD-EPI. La concordance des différentes formules a été évaluée avec la méthode Bland-Altman. Au total 56 adultes et 62 enfants ont été inclus dans l’étude. L’insuffisance rénale a été notée chez 1,78% des adultes et 9,68% des enfants ; l’hyperfiltration glomérulaire chez 66,10% des adultes et 25,8% des enfants. Par rapport aux formules de référence (CKD-EPI, Schwartz), tous les biais relevés étaient significativement différents de zéro à l’exception de celui de Cockcroftet Gault qui était statistiquement nul. Les limites de concordance étaient toutes inacceptablement larges par rapport aux limites attendues à l’exception de celles du CKD-EPI sans ajustement sur la race. Ainsi, la formule de Schwartz n’était pas interchangeable avec celle du JSCCS chez les enfants, tout comme celle du CKD-EPI ne l’était pas non plus avec celles du JSCCS, de Cockcroft, du MDRD ou du CKD-EPI sans ajustement sur la race chez les adultes drépanocytaires.   English title: Determination of glomerular filtration rate in sickle cell disease in Senegal: Schwartz, Cockcroft and Gault, MDRD, CKD-EPI or JSCCS? Determination of Glomerular Filtration Rate (GFR) is important in patients living with sickle cell disease (SCD) because they constitute a group of patients where kidney dysfunction is frequently described, in particular glomerular hyperfiltration. Therefore, at a time when online calculators simultaneously propose different formulas to estimate GFR, it would be important to evaluate in a black African population living with SCD the equivalence between these formulas which have been developed and validated on Caucasian and African American populations with normal or decreased GFR. Thus, the aim of this study was to evaluate interchangeability of different GFR formulas in a group of patients living with SCD. Homozygous Senegalese sickle cell children and adults were then recruited and their GFR computed using Schwartz and JSCCS in children, Cockcroft and Gault, CKD-EPI with and without adjustment for ethnicity, MDRD and JSCCS formulas in adults. The frequency of glomerular hyperfiltration and renal failure was computed based on the results generated using Schwartz and CKD-EPI formulas. The agreement between formulas was assessed with BlandAltman method. A total of 56 adults and 62 children were included in this study. Renal failure was observed in 1.78% of adults and 9.68% of children; glomerular hyperfiltration in 66.10% of adults and 25.8% of children. Compared with reference formulas (CKD-EPI, Schwartz), all biases found were significantly different from zero except for Cockcroft and Gault formula bias, which was statistically zero. The limits of agreement were all unacceptably wide compared with the expected limits with the exception of CKD-EPI without adjustment for ethnicity. Thus, Schwartz formula would not be interchangeable with JSCCS formula in children, nor was the CKD-EPI formula interchangeable with the JSCCS, Cockcroft and Gault, MDRD or CKD-EPI without adjustment for ethnicity formulas in adults living with sickle cell anemia

Traffic Engineering using Multipath Routing Approaches

Thesis (MSc (Mathematical Sciences. Computer Science))--University of Stellenbosch, 2007.It is widely recognized that Traffic engineering (TE) mechanisms have to be added to the IP transport functionalities to provide QoS guarantees while ensuring efficient use of network resources. Traffic engineering is a network management technique which routes traffic to where bandwidth is available in the network to achieve QoS agreements between current and future demands and the available network resources. Multi-path routing has been proven to be a more efficient TE mechanism than Shortest Path First (SPF) routing in terms of proffit maximization and resource usage optimization. However the identiffication of set of paths over which traffic is forwarded from source to the destination and the distribution of traffic among these paths are two issues that have been widely addressed by the IP community but remain an open issue for the emerging generation IP networks. Building upon different frameworks, this thesis revisits the issue of multi-path routing to present and evaluate the performance of different traffic splitting mechanisms to achieve QoS routing in Multi-Protocol Label Switching (MPLS) and Wireless Sensor Networks (WSNs). Three main contributions are identified in this thesis. First, we extend an optimization model that used the M/M/1 queueing model on a simple network consisting of a single source-destination pair by using the M/M/s queueing model on a general network consisting of several source-destination pairs. The model solves a multi-path routing problem by defining a Hamiltonian as a function of delay incurred and subjecting this Hamiltonian to Pontryagin's cost minimization to achieve efficient diffusion of traffic over the available parallel paths. Second, we revisit the problem of cost-based optimization in a multi-path setting by using a Game theoretical framework to propose and evaluate the performance of competitive and cooperative multi-path routing schemes and the impact of the routing metric (cost) on the difference between these two schemes. Finally, building upon a previously proposed optimization benchmark, we propose an Energy constrained QoS routing scheme for Wireless Sensor Networks and show through simulation that our scheme outperforms the benchmark scheme

A quantitative approach to analyzing genome reductive evolution using protein-protein interaction networks: A case study ofMycobacterium leprae

The advance in high-throughput sequencing technologies has yielded complete genome sequences of several organisms, including complete bacterial genomes. The growing number of these available sequenced genomes has enabled analyses of their dynamics, as well as the molecular and evolutionary processes which these organisms are under. Comparative genomics of different bacterial genomes have highlighted their genome size and gene content in association with lifestyles and adaptation to various environments and have contributed to enhancing our understanding of the mechanisms of their evolution. Protein-protein functional interactions mediate many essential processes for maintaining the stability of the biological systems under changing environmental conditions. Thus, these interactions play crucial roles in the evolutionary processes of different organisms, especially for obligate intracellular bacteria, proven to generally have reduced genome sizes compared to their nearest free-living relatives. In this study, we used the approach based on the Renormalization Group (RG) analysis technique and the Maximum-Excluded-Mass-Burning (MEMB) model to investigate the evolutionary process of genome reduction in relation to the organization of functional networks of two organisms. Using a Mycobacterium leprae (MLP) network in comparison with a Mycobacterium tuberculosis (MTB) network as a case study, we show that reductive evolution in MLP was as a result of removal of important proteins from neighbours of corresponding orthologous MTB proteins. While each orthologous MTB protein had an increase in number of interacting partners in most instances, the corresponding MLP protein had lost some of them. This work provides a quantitative model for mapping reductive evolution and protein-protein functional interaction network organization in terms of roles played by different proteins in the network structure

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Comparison of disturbances of nephropathy biomarkers between sickle cell anemia patients and controls.

Comparison of disturbances of nephropathy biomarkers between sickle cell anemia patients and controls.</p

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Comparison of means of anthropometric and biochemical parameters between sickle cell anemia patients and unmatched controls and then age- and sex-matched controls.

Comparison of means of anthropometric and biochemical parameters between sickle cell anemia patients and unmatched controls and then age- and sex-matched controls.</p