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There is an increasing number of patients failing second line highly active antiretroviral therapy (AZT, DDI and LPV/r) in South Africa, where HIV-1 subtype C predominates. Mutations at gag cleavage sites (CS) have been found to correlate with resistance mutations in protease (PR). Therefore, it is important to collect data on subtype C protease and gag sequences from patients as these mutations may affect the efficacy of protease inhibitor (PI) containing drug regimens. In this study, 30 subtype-C infected second-line failures were genotyped using the ViroSeqTM resistance genotyping kit and the gag region from these isolates were then characterised. These sequences were then compared to 30 HIV-1 subtype C infected first-line failures (PI-naïve) and subtype B, C and group M naïve sequences that were downloaded from the Los Alamos Sequence Database. Amino acid diversity at the CS was measured using Mega version 4.0. To investigate the effect of CS mutations on replication capacity, a mutation was introduced by site-directed mutagenesis (Stratagene’s QuikChange Site-Directed Mutagenesis kit). Of the 30 second-line failures that we genotyped, only 16 had resistance mutations in PR and 23 in gag. The most frequent major PI mutations were: I54V/L, M46I, V82A, and I84V and in gag CS were V390L/I and A431V. Interestingly the A431V mutation significantly correlated with protease mutations M46I/L, I54V and V82A. The virus carrying the A431V mutation in vitro was found to have a lower replication capacity compared to the wild type. These findings emphasize the need for further investigation of gag mutations and their contribution to the evolution of HIV resistance to PIs. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2010.

Didelio meistriškumo krepšininkų ugdymo krūvių išdėstymo racionalumas rengimo makrocikle ir jų įtaka jėgos greitumo rodiklių kaitai išlieka aktualia šiai dienai tyrimo problema. / The rationality of arrangement of educational loads of highly skilled basketball players during preparation macrocycle and their influence on the variation of indices of speed power remains the relevant research problem nowadays.

Sportas svarbus socialinis fenomenas, kuris daro didelę įtaką pagrindinėms visuomenės gyvenimo sferoms: žmonių tarpusavio santykiams, darbinei veiklai, visuomeniniams santykiams, taip pat formuoja madą, etines vertybes, žmonių gyvenimo būdą. K. Kardelis ir F. Motiejūnas (1995), N. B. Stambulova (1999), J. Taylor ir B. C. Ogilvie (2001) ir daugelis kiltų autorių bandė nustatyti lemiamus sportinės karjeros ir jos nutraukimo probleminius periodus. Sportininko karjera yra daug trumpesnė nei kitos profesinės karjeros, nes daugelis sportininkų baigia savo profesinę veiklą savanoriškai arba priversti įvairių aplinkybių, nesulaukę keturiasdešimties metų. Tyrėjai teigia, kad ryškiausias ir daugiausia nerimo sportininkui keliantis sportinės karjeros etapas yra jos pabaiga (Taylor ir Ogilvie, 2001). Tyrimo objektas – didelio meistriškumo sportininkų karjeros pereigos projektavimo galimybės. Tyrimo hipotezė – didelio meistriškumo sportininkų karjeros pereigos kokybė tiesiogiai priklauso nuo atleto individualaus pasirengimo ir racionalaus suvokimo, kad nuoseklus karjeros projektavimas yra būtinas visais jos raidos etapais. Šio darbo tikslas yra ištirti didelio meistriškumo sportininkų karjeros ypatumus bei numatyti jos pereigos projektavimo galimybes. Tyrimo metodai: literatūros šaltinių analizė ir apibendrinimas; interviu metodas; statistinė tyrimo duomenų analizė. Tirtų didelio meistriškumo sportininkų karjeros nutraukimo priežastys: senyvas kaip sportininko amžius, traumos bei... [toliau žr. visą tekstą] / Sport is an important social phenomena, which has an influence on the main society life spheres: relationship between people, working activities, public relations, also form a fashion, ethnic values, people’s lifestyle. K. Kardelis and F. Motiejunas (1995), N. B. Stambulova (1999), J. Taylor and B. C. Ogilvie (2001_ and many other authors tried to determine decisive problematic periods of sporting career and its termination. An athlete’s career is shorter than other professional careers, because many athletes finish their professional activity voluntarily or forced by various circumstances, before reaching 40 years. The researchers claim that the most notable athletic career stage which mainly causes anxiety to the athlete is its termination (Taylor and Ogilvie, 2001). The research object is the designing career transition opportunities of highly skilled athletes. The research hypothesis – the career transition quality of the highly skilled athletes depends directly on athlete’s individual preparation and rational perception, that the consistent career designing is necessary for all development stages. The aim of the research is to analyze the highly skilled athlete’s career peculiarities, also to predict designing possibilities of its transition. The research methods: analysis of literature sources and summary; interview method; statistical research data analysis. The career termination causes of the researched highly skilled athletes: elderly for an athlete’s age... [to full text]

This thesis is a reapproachment of diverse design concepts, brought to bear upon the computer system engineering problem of identification and control of highly constrained multiprocessing (HCM) computer machines. It contributes to the area of meta/general systems methodology, and brings a new insight into the design formalisms, and results afforded by bringing together various design concepts that can be used for the construction of highly constrained computer system architectures. A unique point of view is taken by assuming the process of identification and control of HCM computer systems to be the process generated by the Activity Structures Methodology (ASM). The research in ASM has emerged from the Neuroscience research, aiming at providing the techniques for combining the diverse knowledge sources that capture the 'deep knowledge' of this application field in an effective formal and computer representable form. To apply the ASM design guidelines in the realm of the distributed computer system design, we provide new design definitions for the identification and control of such machines in terms of realisations. These realisation definitions characterise the various classes of the identification and control problem. The classes covered consist of: 1. the identification of the designer activities, 2. the identification and control of the machine's distributed structures of behaviour, 3. the identification and control of the conversational environment activities (i.e. the randomised/ adaptive activities and interactions of both the user and the machine environments), 4. the identification and control of the substrata needed for the realisation of the machine, and 5. the identification of the admissible design data, both user-oriented and machineoriented, that can force the conversational environment to act in a self-regulating manner. All extent results are considered in this context, allowing the development of both necessary conditions for machine identification in terms of their distributed behaviours as well as the substrata structures of the unknown machine and sufficient conditions in terms of experiments on the unknown machine to achieve the self-regulation behaviour. We provide a detailed description of the design and implementation of the support software tool which can be used for aiding the process of constructing effective, HCM computer systems, based on various classes of identification and control. The design data of a highly constrained system, the NUKE, are used to verify the tool logic as well as the various identification and control procedures. Possible extensions as well as future work implied by the results are considered.

Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.

An algorithm for extracting event information from a Coulomb Explosion Imaging (CEI) position sensitive detector (PSD) is developed and compared with previously employed schemes. The PSD is calibrated using a newly designed grid overlay and validates the quality of the described algorithm. Precision calculations are performed to determine how best the CEI apparatus at The University of Waterloo can be improved. An algorithm for optimizing coincidence measurements of polyatomic molecules in CEI experiments is developed. Predictions of improved efficiency based on this algorithm are performed and compared with experiments using a triatomic molecule. Analysis of an OCS targeted CEI experiment using highly charged Argon ions to initiate ionization is performed. The resulting measurements are presented using a variety of visualization tools to reveal asynchronous and sequential fragmentation channels of OCS3+.

In this dissertation, we develop multiscale finite element methods and uncertainty quantification technique for Richards' equation, a mathematical model to describe fluid flow in unsaturated porous media. Both coarse-level and fine-level numerical computation techniques are presented. To develop an accurate coarse-scale numerical method, we need to construct an effective multiscale map that is able to capture the multiscale features of the large-scale solution without resolving the small scale details. With a careful choice of the coarse spaces for multiscale finite element methods, we can significantly reduce errors. We introduce several methods to construct coarse spaces for multiscale finite element methods. A coarse space based on local spectral problems is also presented. The construction of coarse spaces begins with an initial choice of multiscale basis functions supported in coarse regions. These basis functions are complemented using weighted local spectral eigenfunctions. These newly constructed basis functions can capture the small scale features of the solution within a coarse-grid block and give us an accurate coarse-scale solution. However, it is expensive to compute the local basis functions for each parameter value for a nonlinear equation. To overcome this difficulty, local reduced basis method is discussed, which provides smaller dimension spaces with which to compute the basis functions. Robust solution techniques for Richards' equation at a fine scale are discussed. We construct iterative solvers for Richards' equation, whose number of iterations is independent of the contrast. We employ two-level domain decomposition pre-conditioners to solve linear systems arising in approximation of problems with high contrast. We show that, by using the local spectral coarse space for the preconditioners, the number of iterations for these solvers is independent of the physical properties of the media. Several numerical experiments are given to support the theoretical results. Last, we present numerical methods for uncertainty quantification applications for Richards' equation. Numerical methods combined with stochastic solution techniques are proposed to sample conductivities of porous media given in integrated data. Our proposed algorithm is based on upscaling techniques and the Markov chain Monte Carlo method. Sampling results are presented to prove the efficiency and accuracy of our algorithm.

With the rapid and ongoing developments in telecommunication and electronic warfare technology, faster and more flexible systems are in demand. Wideband signal processing is thus needed to implement such systems. Microwave photonics has been introduced as a tool for achieving such ultra broadband signal processing. Instantaneous Frequency Measurement (IFM) receivers play an important role in electronic warfare. They have been developed as a means of obtaining a rapid indication of the presence of a threat and to roughly identify the frequency of the threat signals. They also have the advantages of low-cost, compactness and moderate to good sorting capability in an interference-free environment. The main limitation of the traditional RF IFM receivers is constrained bandwidth. Microwave Photonic IFMs have been considered, but the main disadvantages of photonic realization of the recent IFM receiver is cost. This work aims to propose and demonstrate low-cost photonic IFM receivers with a broad frequency measurement range. The proposed methods are based on the use of photonic mixing to down-convert the RF modulated optical signals to DC. In a RADAR warning receiver, usually a bank of IFMs is required. Increasing the numbers of IFMs requires an increase in the number of photo-detectors. Thus if low-frequency, low-cost detectors can be used, then the net system cost will be reduced significantly. The concept is proven and the issues arising are analyzed. In the proof of concept system, measurement of the RF frequency required advance knowledge of the RF power. Secondly, the use of co-axial RF cables as delay elements limited the bandwidth and increased bulk. Using a photonic hybrid approach to achieve orthogonal measurements was demonstrated as a means of dentifying both RF frequency and power simultaneously and independently. Employing all optical mixing removed the need for co-axial RF cables delays using non-linear optical devices such as Semiconductor Optical Amplifier (SOA) and Highly Non-Linear Fiber (HLNF). The last investigation is to improve the sensitivity of the implemented IFM system. The sensitivity of the implemented system is characterized first and a lock-in technique is employed to improve the sensitivity of the system. The final system achieves a sensitivity of -41 dBm which is comparable with the traditional RF IFM receivers.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.