Leung Yun Shing Wilson. / "May 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 157-184). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest dissertations and theses, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The increasing commoditization of computers in modern society has exceeded the pace of associated developments in reliability. Although theoretical computer science has advanced greatly in the last thirty years, many of the best techniques have yet to find their way into embedded computers, and their failure can have a great potential for disrupting society. This dissertation presents some approaches to improve computer reliability using software and hardware techniques, and makes the following claims for novelty: innovative development of a toolchain and libraries to support extraction from dependent type checking in a theorem prover; conceptual design and deployment in reconfigurable hardware; an extension of static type-safety to hardware description language and FPGA level; elimination of legacy C code from the target and toolchain; a novel hardware error detection scheme is described and compared with conventional triple modular redundancy. The elimination of any user control of memory management promotes robustness against buffer overruns, and consequently prevents vulnerability to common Trojan techniques. The methodology identifies type punning as a key weakness of commonly encountered embedded languages such as C, in particular the extreme difficulty of determining if an array access is in bounds, or if dynamic memory has been properly allocated and released. A method of eliminating dependence on type-unsafe libraries is presented, in conjunction with code that has optionally been proved correct according to user-defined criteria. An appropriately defined subset of OCaml is chosen with support for the Coq theorem prover in mind, and then evaluated with a custom backend that supports behavioural Verilog, as well as a fixed execution unit and associated control store. Results are presented for this alternative platform for reliable embedded systems development that may be used in future industrial flows. To provide assurance of correct operation, the proven software needs to be executed in an environment where errors are checked and corrected in conjunction with appropriate exception processing in the event of an uncorrectable error. Therefore, the present author’s previously published error detection scheme based on dual-rail logic and self-checking checkers is further developed and compared with traditional N-modular redundancy.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-06-12T17:33:35Z No. of bitstreams: 1 KellySilva.pdf: 1053190 bytes, checksum: 14ae6885897006b813bbfa8df8168e7c (MD5) / Made available in DSpace on 2017-06-12T17:33:35Z (GMT). No. of bitstreams: 1 KellySilva.pdf: 1053190 bytes, checksum: 14ae6885897006b813bbfa8df8168e7c (MD5) Previous issue date: 2016-07-25 / Diabetes Mellitus (DM) is a heterogeneous group of metabolic disorders that have in common hyperglycemia. Diabetics under treatment with insulin therapy must embrace responsibility of the control and management of their condition on a daily basis; in this context the congnitive theory of self efficacy (SE) proposed by Bandura can be considered a decisive factor in achieving behavioral goals of diabtes, resulting in improvements to self-care and glycemic control. The research here presented aimed to analyse the self efficacy to the treatment of patients with diabetes mellitus type 1 and 2 in insulin therapy and its correlaton with sociodemographic and clinical variables. To that end, we conducted and analytical study of cross-sectional, with quantitative approach and sample consisting on 134 patients with DM type 1 and 2 in insulin therapy at University Hospital's Endocrinology Clinic - Unit President Dutra (HUUPD) of São Luís-MA. For data collection, we used two instruments: identification data with open and closed questions related to sociodemographic and clinical variables and the Insulin Management Diabetes Self Efficacy (IMDSES), Brazilian version. The search resulted 3.07 global media, on the scale of self efficacy, the areas that stood out with the highest and lowest average respectively were the general management domain (3.38) and the diet field (2.90). We have found the following significant correlations: marital status (widowed had more SE in the diet), education (the higher the education, the better the SE in the management, control and correction of glycemia), treatment with diet and insulin (higher SE in the diet), absence of dyslipidemia (increased SE to the overall management of diabtes) and age (higher SE for older in the diet). It was concluded that there are factors relates to socioeconomic and clinical features that interfare in self efficacy of patients with Diabetes mellitus type 1 e 2 in insulin therapy, against the desease. / O Diabetes Mellitus (DM) é um grupo heterogêneo de distúrbios metabólicos que apresentam em comum a hiperglicemia, resultado de defeitos na ação da insulina, na secreção de insulina ou em ambas. Os diabéticos que fazem tratamento com insulinoterapia devem assumir a responsabilidade do controle e gestão de sua condição no dia a dia. Nesse contexto, a teoria cognitiva da autoeficácia (AE) proposta por Bandura pode ser considerada um fator decisivo para atingir as metas comportamentais do diabetes, resultando em melhorias para o autocuidado e controle glicêmico. A pesquisa que se apresenta, teve como objetivo analisar a autoeficácia do tratamento dos portadores de diabetes mellitus tipo 1 e 2 em insulinoterapia e a sua correlação com as variáveis sociodemográficas e clínicas. Para tanto, foi realizado um estudo analítico de corte transversal, com abordagem quantitativa e amostra de 134 portadores de DM tipo 1 e 2 em insulinoterapia, atendidos no Ambulatório de Endocrinologia do Hospital Universitário - Unidade Presidente Dutra (HUUPD) de São Luís-MA. Para a coleta de dados, utilizaram-se dois instrumentos: dados de identificação com questões abertas e fechadas referente às variáveis sociodemográficas e clínicas e o Insulin Management Diabetes Self Efficacy (IMDSES), versão brasileira. A pesquisa resultou média global de 3,07 na escala de autoeficácia, os domínios que se destacaram com maior e menor média respectivamente foram o domínio administração geral (3,38) e o domínio dieta (2,90). Encontraram-se as seguintes correlações significativas: estado civil (viúvos tinham maior AE na dieta), escolaridade (quanto maior a escolaridade, melhor a AE na administração, controle e correção da glicemia), tratamento com dieta e insulina (maior AE na dieta), ausência de dislipidemia (maior AE para o manejo geral do diabetes) e idade (maior AE para os mais velhos na dieta). Concluiu-se que existem fatores relacionados às características socioeconômicas e clínicas que interferem na autoeficácia do portador de Diabetes mellitus tipo 1 e 2 em Insulinoterapia, frente à doença.

Aims: Thiazolidinediones have been advocated as second or third line insulin sensitizing agents in the management of type 2 diabetes (T2DM). Their widespread use has been hampered by concerns about their cardiovascular safety, including fluid retention. Metformin is established as first-line glucose-lowering pharmacotherapy in T2DM. It has also been suggested that it may have benefits in alleviating insulin resistance in type 1 diabetes (T1DM). This thesis examined: (i) cardiovascular, renal and metabolic differences between individuals with T2DM ‘tolerant’ or ‘intolerant’ of TZDs; (ii) risk factors for TZD-associated oedema in T2DM; and (iii) the potential for metformin as adjunct therapy in T1DM. Methods: (i) A small clinical study characterising TZD tolerant and intolerant individuals with T2DM; (ii) A population-based epidemiological study of TZD induced oedema in individuals with T2DM in Tayside, Scotland (using incident loop diuretic prescription as a surrogate); (iii) A systematic review and meta-analysis of published studies of adjunct metformin in T1DM. Results (i) During a five-day high sodium diet, two known TZD-intolerant individuals with T2DM had reductions in haematocrit, aldosterone, and diastolic BP and increases in ANP and central and peripheral augmentation indices which were outwith reference ranges derived from nine TZD-tolerant individuals; (ii) Predictors of time to loop diuretic prescription included age, body mass index, systolic BP, haematocrit, ALT and macrovascular disease but rates of this outcome did not differ by therapy: 4.3% (TZDs) vs 4.7% (other agents) [unadjusted OR 0.909 (95% CI 0.690, 1.196); p = 0.493]; (iii) In meta-analysis of nine small studies in T1DM (192.8 patient-years of follow-up), metformin was associated with a reduction in total daily insulin dose (6.6 units/day; p < 0.001) but no studies examined cardiovascular surrogates or outcomes. Conclusions: Hypotheses were generated for several potential biomarkers predictive of TZD-induced oedema but the clinical importance of TZDs as a risk factor for oedema in individuals with T2DM was questioned. As there is some evidence for the safety of metformin as an adjunct therapy in T1DM but little evidence of efficacy, larger studies are warranted.

Le diabète de type 2 (DT2) progresse dans le monde entier de manière alarmante. Les complications sont graves et les traitements sont souvent inefficaces et donnent beaucoup d'effets indésirables. Le resvératrol (RSV) et la curcumine (Cur), des polyphénols naturels, sont connus pour leurs différentes activités pharmacologiques, y compris antidiabétiques. Les objectifs de cette étude ont été d'évaluer les effets de la combinaison de ces deux polyphénols sur l'amélioration de la tolérance au glucose. Nos résultats montrent que chez des souris soumises à un régime riche en graisse (HFD), le RSV améliore la tolérance au glucose alors que la Cur n'a pas d'effet significatif. De manière surprenante, lorsque les deux polyphénols sont administrés simultanément, la Cur inhibe l'effet du RSV sur l'amélioration de la tolérance au glucose. Pour expliquer cet antagonisme, nous avons évalué l'effet de ces polyphénols associés ou pas sur le métagénome. Nos résultats indiquent que la Cur et le RSV normalisent la flore intestinale altérée par le HFD. Lors d'une association de ces polyphénols, la Cur inhibe aussi l'effet du RSV sur la croissance de certaines espèces bactériennes. Ainsi, la Cur bloque l'effet inhibiteur du RSV sur Alistipes putredinis. Nos données indiquent que ces polyphénols sont en général anti-inflammatoires mais leur association peut être synergique in vitro ou bien, à l'opposé, antagoniste in vivo pour l'expression de certaines cytokines. Afin d'évaluer l'effet physiologique de la modification de la flore intestinale par les polyphénols, nous avons étudié le métabolome. Parallèlement au métagénome, chacun des polyphénols améliore le profil métabolomique altéré par le HFD. Cependant, la Cur s'oppose à l'effet du RSV. Les données de ce travail indiquent que la Cur n'est pas associable au RSV pour améliorer la tolérance au glucose. / Each year, the worldwide impact of type 2 diabetes (T2D) increases significantly. The complications are serious and treatments are often ineffective and provide a lot of side effects. Resveratrol (RSV) and curcumin (Cur) are natural polyphenols known for their different pharmacological activities, including anti-diabetic. The objectives of this study were to evaluate the effects of the combination of these polyphenols on glucose tolerance improvement. Our results show that in animals fed with a high fat diet (HFD), RSV improved glucose tolerance while Cur displayed no significant effect. Surprisingly, when both polyphenols were administered simultaneously, Cur inhibited the effect of RSV on glucose tolerance improvement. To explain this antagonism between both polyphenols on glucose tolerance, we have evaluated the effect of these compounds on the metagenome associated or not. Our results indicate that RSV and Cur normalized gut flora altered by HFD. When Cur and RSV were administrated simultaneously, Cur inhibited the effect of RSV on the growth of some bacterial species. Thus, Cur blocked the inhibitory effect of RSV on Alistipes putredinis. Our data indicate that these polyphenols displayed generally anti-inflammatory effects, but their combination may be either synergistic in vitro or antagonistic in vivo on the expression of some cytokines. To evaluate the physiological effect of the gut flora changes induced by polyphenols, we have drawn a parallel between metagenome and metabolome data. Each of the polyphenols improved by itself the metabolomic profile altered by HFD. However, Cur hindered the effect of RSV. In a whole, this study indicates that combination of Cur with RSV is not successful to further enhance the RSV-induced improvement of glucose tolerance.

The main purpose of this thesis is to compare the performance of the score test and the likelihood ratio test by computing type I errors and type II errors when the tests are applied to the geometric distribution and inflated binomial distribution. We first derive test statistics of the score test and the likelihood ratio test for both distributions. We then use the software package R to perform a simulation to study the behavior of the two tests. We derive the R codes to calculate the two types of error for each distribution. We create lots of samples to approximate the likelihood of type I error and type II error by changing the values of parameters. In the first chapter, we discuss the motivation behind the work presented in this thesis. Also, we introduce the definitions used throughout the paper. In the second chapter, we derive test statistics for the likelihood ratio test and the score test for the geometric distribution. For the score test, we consider the score test using both the observed information matrix and the expected information matrix, and obtain the score test statistic zO and zI . Chapter 3 discusses the likelihood ratio test and the score test for the inflated binomial distribution. The main parameter of interest is w, so p is a nuisance parameter in this case. We derive the likelihood ratio test statistics and the score test statistics to test w. In both tests, the nuisance parameter p is estimated using maximum likelihood estimator pˆ. We also consider the score test using both the observed and the expected information matrices. Chapter 4 focuses on the score test in the inflated binomial distribution. We generate data to follow the zero inflated binomial distribution by using the package R. We plot the graph of the ratio of the two score test statistics for the sample data, zI /zO , in terms of different values of n0, the number of zero values in the sample. In chapter 5, we discuss and compare the use of the score test using two types of information matrices. We perform a simulation study to estimate the two types of errors when applying the test to the geometric distribution and the inflated binomial distribution. We plot the percentage of the two errors by fixing different parameters, such as the probability p and the number of trials m. Finally, we conclude by briefly summarizing the results in chapter 6.

Thesis (MSc. (Physics)) --University of Limpopo, 2009 / Calculations were carried out on transition-metal sulphides (TMS) and transitionmetal arsenides (TMA), in both pyrite- and marcasite-type structures, using planewave (PW) pseudopotential methods within density functional theory (DFT) in the local density approximation (LDA). The structural, electronic and optical properties for both pyrite- and marcasite-type structures (naturally occurring and converted) have been investigated. The equilibrium lattice parameters were investigated and are in good agreement with the experimental values. The heats of formation calculations predict that the naturally occurring pyrite- and marcasite-type structures are more stable than the converted ones. In particular, the calculated pyrite-type RuS2 compares well to the experimental value (with energy difference of 0.381 eV/atom). The bulk modulus and elastic properties were calculated. The predicted anisotropic ratio shows that the naturally occurring pyrite- and marcasite-type structures are more stable than the converted ones. Moreover, the electronic density of states and band structure calculations reveal that most compositions shows semiconducting behaviour except for the converted pyritetype structures, i.e OsAs2 and RuAs2 where a metallic behaviour was observed. The electronic charge density and charge density difference show charge accumulation on bonding atoms, predicting the charge gain/ loss and nature of bonding to be covalent/ weak ionic between the atoms. Lastly, optical properties are computed at equilibrium and predict that naturally occurring structures have lower absorption and reflectivity than the converted structures. At different pressures ranging from -10 GPa to 10 GPa, the absorption and reflectivity spectra show a shift from the 0 GPa spectrum for all the structures / National Research Foundation

Cette thèse propose une approche monographique du parcours professionnel de Pierre Guariche, décorateur-créateur d’ensembles-Architecte d'intérieur français. Les «Trente Glorieuses» représentent un tournant décisif chez ce professionnel car elles coïncident avec les débuts de l'industrialisation de la filière ameublement. Le contexte historique et politique explique son engagement dans la création de programmes complets d'objets destinés il meuble les logements standardisés de la Reconstruction. Il comprend que le mobilier de série, fabriqué par des procédés industriels et a des prix raisonnables. peut remédier aux effets de l'insuffisance de la politique de l'Etat français. Afin d'adapter son mobilier «moderne» au plan-type. il s'inspire dl' la production des designers américains et crée des objets rationnels normalisés et innovants sur le plan technique et esthétique. En 1954, il sollicite Michel Mortier et Joseph-André Motte, et crée avec eux l' Atelier de Recherches Plastiques. Ils comprennent tous les trois que les jeunes créateurs doivent se fédérer autour d'un projet commun: la promotion de leurs meubles de série auprès des industriels, Par la suite, chacun reprend son indépendance pour se consacrer à ses travaux respectifs. Les nouvelles orientations professionnelles de Pierre Guariche lui offrent la possibilité de collaborer à des programmes inédits d'architecture intérieure, nés de la politique d'aménagement du territoire. Cette thèse aborde donc le contexte social, politique et économique durant lequel il exerce son activité mais également des faits et des acteurs, ce qui ouvre de futurs champs à explorer dans l'histoire du design français. / This thesis puts forward a monographic approach to the career of Peter Guariche, designer-creator of French interior designer assemblies. The "Glorious thirty" represent a decisive turning point for this professional because they coincide with the beginning of industrialization in the furniture sector. The historical and political context explains his involveruent in the creation of full programs of articles intended to furnish standardized Reconstruction housing. He realizes that the mass production furniture, produced by industrial processes and at reasonable prices, can solve the effects of the failure of the policy of the French state, To adjust his "modem" furniture in the plan-type, it is inspired by the production of Arnerican designers and creates innovative standardized and rational objects on a technical and aesthetical level. ln 1954, he solicits Michel Mortier and Joseph-André Motte and creates with them L'Atelier de Recherches Plastiques. They understand that ail three young designers must unite around a common project: promoting their mass production furniture with manufacturers. Thereafter. each of them takes their independence and takes back their respective work. The ncw professional guidance of Pierre Guariche offers him the opportunity to collaborate on original interior architectural programs. stemming from the land use policy. This thesis deals with the social, political and economic contexts in which he practices, but also the facts and actors. which open up future areas to explore in the history of French design.

The estimation of the Pareto distribution can be computationally expensive and the method is badly biased. In this work, an improved Least Squares derivation is used and the estimation will be less biased. Numerical examples and figures are provided so that one may observe the solution more clearly. Furthermore, by varying the different methods of estimation, a comparing of the estimators of the parameters is given. The improved Least Squares derivation is confidently employed for it is economic and efficient.

Contexte : Le schwannome vestibulaire (SV) est une tumeur bénigne de la gaine du nerf vestibulaire. La plupart des SV présentent une inactivation somatique bi-allèlique du gène suppresseur de tumeur NF2. L’inactivation congénitale du gène NF2 est impliquée dans le développement de la Neurofibromatose de type 2, une maladie génétique autosomique dominante prédisposant au développement de tumeurs multiples du système nerveux central et en particulier de schwannomes vestibulaires bilatéraux. Le traitement des schwannomes vestibulaires repose sur la chirurgie ou la radiothérapie délivrée en conditions stéréotaxiques. La réduction de la dose d’irradiation des schwannomes vestibulaires a permis d’améliorer le pronostic fonctionnel auditif tout en garantissant un taux de réponse satisfaisant. Pourtant de nombreux patients présenteront une surdité neurosensorielle progressive. Afin de poursuivre cette réduction de dose d’irradiation, des modèles biologiques fidèles récapitulant le statut d’inactivation du gène NF2 et la surdité neurosensorielle sont nécessaires à l’élaboration d’une approche préclinique.Problématique : Nous avons proposé de développer des systèmes modèles in-vitro et in-vivo compatibles avec l’étude de la radiosensibilité des schwannomes vestibulaires en combinaison avec des thérapies ciblant les voies de signalisation spécifiquement activées par la perte de fonction NF2.Méthodes : Les lignées cellulaires humaines de schwannomes vestibulaires NF2 (HEI_193, HEI_182), et de cellules de Schwann vestibulaire contrôle (HEI_286) ont été cultivées en essai clonogénique afin de déterminer le nombre d’unité formatrices de colonies à doses croissantes d’inhibiteur mTOR (Rapamycine), PI3K (GDC_0941), mTOR et PI3K (BEZ_235) pour déterminer le 50% d’inhibition de croissance (GI50%) puis en combinaison à doses croissantes de radiation gamma (Co60). La lignée cellulaire murine inactivée pour nf2 (SC4#9) a été utilisée pour réaliser des greffes syngéniques orthotopiques. La croissance des tumeurs a été suivie par IRM et bioluminescence et l’audition déterminée par potentiels évoqués auditifs. L’analyse histologique des cochlées a été réalisée par coloration en hématoxyline et éosine puis par fluorescence après clarification cochléaire. Des volumes complets ont été obtenus par microscopie confocale à balayage laser.Résultats : Les essais clonogéniques réalisés en Agarose ont identifié une radiorésistance relative des lignées humaines de schwannomes mutées pour NF2 par comparaison au contrôle humain non muté. Cette résistance identifiée en réponse à l’exposition à une dose unique d’irradiation gamma peut être contournée par l’inhibition de la voie mTOR au moment de l’irradiation restituant une sensibilité comparable au contrôle humain non muté. Une tendance à un bénéfice de l’association d’une inhibition mTOR à un inhibiteur PI3 kinase a été retrouvée à une dose maximum d’irradiation. Un modèle murin de schwannome vestibulaire qui récapitule la croissance dans l’angle ponto-cérébelleux et la perte d’audition a été développé par injection stéréotaxique dans le paquet acoustico faciale. Le suivi de croissance de ce schwannome a été caractérisé par IRM et bio-luminescence in-vivo. Enfin un protocole de clarification cochléaire a été adapté aux mammifères murins pour permettre l’étude histologique de cochlées intactes compatible avec l’étude de l’otoxicité des schwannomes et/ou de leur traitement .Conclusion : Les modèles décrits dans cette thèse permettent l’évaluation pré-clinique de stratégies thérapeutiques combinant thérapie ciblée et irradiation gamma en dose unique. L’amélioration des connaissances des mécanismes participant à l’ototoxicité des schwannomes et de leur traitement permettra d’améliorer le ciblage moléculaire afin de réduire les effets auditifs secondaires de la radiochirurgie. / Context: Vestibular schwannomas (VS) are benign neoplasm arising from the Schwann cells of the vestibular nerve. Most of sporadic VS carry a bi-allelic inactivation of the tumor suppressor gene NF2. Congenital inactivation of the NF2 gene is linked to the onset of Neurofibromatosis type 2 (NF2), a genetic condition predisposing to the development of multiple benign tumor of the central nervous system with bilateral VS as a hallmark. Treatment of VS is either surgical or by use of radiation therapy delivered in stereotactic condition. A significant dose reduction has led to improving the hearing outcomes while maintaining good tumor control. Meanwhile a significant number of treated patients will develop a progressive sensorineural hearing loss (SNHL). Laboratory models that faithfully recapitulate NF2 gene inactivation and SNHL are needed to pursue the reduction of the dose delivered.Aim: We aimed at developing new models in-vitro and in-vivo for the study of vestibular schwannoma radio sensitivity in combination with selected compounds that selectively target the pathways activated secondary to NF2 loss of function.Methodes: Human vestibular schwannoma cell lines (HEI_193, HEI_182) and control human Schwann cell line (HEI_286) were used in clonogenic assay to determine the number of colony forming unit (CFU) spontaneously and at increasing dosing of mTOR inhibitor (Rapamycin), PI3 kinase inhibitor (GDC_0941), PI3K-mTOR dual inhibitor (BEZ_235) to determine the 50% growth inhibitory threshold (GI50%) then in combination with increasing radiation regimen of gamma radiation emitted by a source of Co60. The mouse cell line inactivated for nf2 (SC4#9) was used to generate orthotropic syngrafts. The growth of the tumor was monitored using MRI and bioluminescence imaging and hearing was tested by recording auditory brainstem responses. Pathology of the cochlea were obtained from paraffin embedded sections and then using fluorescence confocal microscopy of whole mounted transparent cochleae.Results: Soft agar clonogenic assays were used and identified a resistance to radiation therapy in human cell lines of VS inactivated for NF2 when compared to the non-mutated control. This radiation resistance could be overcome by pre-exposure to the mTOR inhibitor Rapamycin allowing a return to the radiosensibility of non-mutated control. There was a tendency toward a beneficial effect when using a dual inhibition of the mTOR and PI3 kinase at a maximum dose of exposure to radiation. A mouse model of VS has been developed by stereotactic seeding of nf2 deficient cell line SC4#9 targeting the cochleo-vestibular nerve complex. It recapitulates the growth in the suitable micro-environment and secondary SNHL. The growth has been characterized using MRI and in-vivo bioluminescence imaging. Hearing loss was confirmed using sequential ABR. Last a protocol for the clarification of whole mounted cochleae has been adapted to species of rodents suitable for the pathological study of ototoxic change secondary to VS and/or its treatment.Conclusion: The models presented in this thesis may be used for the preclinical evaluation of combined therapeutic approaches with single dose gamma radiation. A better understanding of the mechanisms involved in ototoxicity secondary to VS and of its treatment would improve the molecular targeting in order to warrant better auditory outcomes.