Genome-wide Association Studies (GWAS) is the study used to associate common variants and phenotypes and has uncovered thousands of disease-associated variants. However, there is limited research on the contribution of a rare variant. The UK Biobank (UKB) contains detailed medical records and genetic information for nearly 500,000 individuals and offers a great opportunity for genetic association studies on rare variants. Here we focused on the role of rare protein-coding variants on UKB phenotypes. We selected three diseases for analysis: breast cancer, hypothyroidism and type II diabetes. We defined criteria for qualifying variants and pruned the control group to reduce interference signals from similar phenotypes. We identified the most known biomarkers for those diseases, such as BRCA1 and BRCA2 gene for breast cancer, TG and TSHR gene for hypothyroidism and GCK for type II diabetes. This result supports the model validity and clarifies the contribution of rare variants to diseases. Moreover, we also tried the geneset based collapsing method to aggregate information across genes to strengthen the signal from rare variants and build a diagnosis model that only relies on the genetic information. Our model could achieve great performance with an AUC of more than 20% improvement for type II diabetes and breast cancer and more than 90% accuracy for hypothyroidism.

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Les critères de sureté qui régissent le développement de coeurs de réacteurs dequatrième génération implique l’usage d’outils de calcul neutronique performants. Unepremière partie de la thèse reprend toutes les étapes de modélisation neutronique desréacteurs rapides actuellement d’usage dans le code de référence ECCO. La capacité desmodèles à décrire le phénomène d’autoprotection, à représenter les fuites neutroniques auniveau d’un réseau d’assemblages combustibles et à générer des sections macroscopiquesreprésentatives est appréciée sur le domaine des réacteurs rapides innovants respectant lescritères de quatrième génération. La deuxième partie de ce mémoire se consacre à lamodélisation des coeurs rapides avec réflecteur acier. Ces derniers nécessitent ledéveloppement de méthodes avancées de condensation et d’homogénéisation. Plusieursméthodes sont proposées et confrontées sur un problème de modélisation typique : le coeurZONA2B du réacteur maquette MASURCA. / Due to safety rules running on fourth generation reactors’ core development,neutronics simulation tools have to be as accurate as never before. First part of this reportenumerates every step of fast reactor’s neutronics simulation implemented in currentreference code: ECCO. Considering the field of fast reactors that meet criteria of fourthgeneration, ability of models to describe self-shielding phenomenon, to simulate neutronsleakage in a lattice of fuel assemblies and to produce representative macroscopic sections isevaluated. The second part of this thesis is dedicated to the simulation of fast reactors’ corewith steel reflector. These require the development of advanced methods of condensationand homogenization. Several methods are proposed and compared on a typical case: theZONA2B core of MASURCA reactor.

Type-2 fuzzy inferencing for generalised, discretised type-2 fuzzy sets has been impeded by the computational complexity of the defuzzification stage of the fuzzy inferencing system. Indeed this stage is so complex computationally that it has come to be known as the defuzzification bottleneck. The computational complexity derives from the enormous number of embedded sets that have to be individually processed in order to effect defuzzification. Two new approaches to type-2 defuzzification are presented, the sampling method and the Greenfield-Chiclana Collapsing Defuzzifier. The sampling method and its variant, elite sampling, are techniques for the defuzzification of generalised type-2 fuzzy sets. In these methods a relatively small sample of the totality of embedded sets is randomly selected and processed. The small sample size drastically reduces the computational complexity of the defuzzification process, so that it may be speedily accomplished. The Greenfield-Chiclana Collapsing Defuzzifier relies upon the concept of the representative embedded set, which is an embedded set having the same defuzzified value as the type-2 fuzzy set that is to be defuzzified. By a process termed collapsing the type-2 fuzzy set is converted into a type-1 fuzzy set which, as an approximation to the representative embedded set, is known as the representative embedded set approximation. This type-1 fuzzy set is easily defuzzified to give the defuzzified value of the original type-2 fuzzy set. By this method the computational complexity of type-2 defuzzification is reduced enormously, since the representative embedded set approximation replaces the entire collection of embedded sets. The strategy was conceived as a generalised method, but so far only the interval version has been derived mathematically. The grid method of discretisation for type-2 fuzzy sets is also introduced in this thesis. Work on the defuzzification of type-2 fuzzy sets began around the turn of the millennium. Since that time a number of investigators have contributed methods in this area. These different approaches are surveyed, and the major methods implemented in code prior to their experimental evaluation. In these comparative experiments the grid method of defuzzification is employed. The experimental results show beyond doubt that the collapsing method performs the best of the interval alternatives. However, though the sampling method performs well experimentally, the results do not demonstrate it to be the best performing generalised technique.

Thesis (MScEng (Civil Engineering))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Large areas of the earth’s surface are covered by soils that are susceptible to large decreases in bulk volume when they become saturated. These soils are termed collapsing soils and are very common in parts of the USA, Asia, South America and Southern Africa. This study is concerned with the occurrence of these collapsible soils in the residual granites of the Stellenbosch area. The study was undertaken as relatively little is known about the collapse phenomenon in the problematic weathered granites of the Western Cape. The majority of research thus far has been carried out on the deep residual soils formed on basement-granite in the Transvaal areas, whereas little attention has been paid to the Cape granites. The aim of the study was achieved through the experimental work which included double oedometer testing, indicator analyses and shear strength testing. Double oedometer tests were performed to quantify the potential collapse settlement of the soils from the demarcated study area. To provide a better understanding of the collapse behaviour of the soils, indicator analysis, which included Atterberg limits and particle size distributions, were performed. Direct shear tests were further carried out on saturated and natural moisture content specimens to establish the effect of collapsibility on shear strength and whether substantial additional settlement of the saturated soils would occur during shear. It was found that collapsible soils are prevalent in the demarcated study area as the majority of soils showed a potential collapse settlement of 1% or more. Collapse exceeding 5% were calculated in a few instances proving some soils to be highly collapsible. The double oedometer and indicator analysis results were used in an attempt to obtain a relationship between collapse settlement and a combination of easily determined properties such as dry density (void ratio), moisture content and grading, but no meaningful conclusions have emerged. The shear strength tests indicated that a clear correlation does not exist between collapsibility and shear strength. It was further established that a relationship between collapse settlement determined during the double oedometer testing and the volume change during shear strength testing cannot be assumed. It can thus be concluded that soils can be very unpredictable and further research on the collapse phenomenon is indicated. / AFRIKAANSE OPSOMMING: Groot dele van die aarde se oppervlakte is bedek deur grondtipes wat geneig is tot ‘n afname in volume as dit deurweek word. Hierdie gronde word swigversakkende gronde genoem en dit word algemeen teëgekom in dele van die VSA, Asië, Suid-Amerika en Suider-Afrika. In hierdie studie word die voorkoms van swigversakkende gronde in die residuele graniet in die Stellenbosch area ondersoek. Die studie is onderneem aangesien relatief min i.v.m. die swigversakking-verskynsel in die problematiese verweerde graniet van die Weskaap bekend is. Die meeste van die navorsing sover is onderneem op die diep residuele gronde wat gevorm is op die Argaïese graniet in die Transvaal gebied, en betreklik min aandag is geskenk aan die Kaapse graniet. Tydens die studie is eksperimente wat dubbele oedometer toetse, indikator analises, en skuifsterkte toetse insluit, uitgevoer. Dubbele oedometer toetse is uitgevoer om die potensiële swigversakking van die grond in die afgebakende studiegebied te kwantifiseer. In ‘n poging om die swigversakking-verskynsel van die grond beter te verstaan, is indikator analises wat Atterberg grense en partikel grootte verspreiding insluit, uitgevoer. Direkte skuiftoetse is ook uitgevoer op deurweekte grondmonsters en op monsters wat natuurlike vog bevat, om sodoende die effek van swigversakking op skuifsterkte vas te stel en om uit te vind of aansienlike addisionele sakking van die deurweekte gronde tydens skuif plaasvind. Daar is gevind dat swigversakkende gronde die oorheersende grondtipe in die afgebakende studiegebied is waar meeste van die gronde ‘n potensiële swigversakking van meer as 1% toon. ‘n Swigversakking van meer as 5% is in ‘n paar gevalle bereken, wat bewys dat sommige grondtipes hoogs versakkend is. Die resultate van die dubbele oedometer en indikator analises is gebruik in ‘n poging om te bewys dat daar ‘n verhouding bestaan tussen swigversakking en ‘n kombinasie van kenmerke wat maklik vasgestel kan word soos droë digdheid (ruimte verhouding), voginhoud en gradering, maar daar kon nie tot ‘n sinvolle slotsom gekom word nie. Die skuifsterkte toetse toon dat daar nie ‘n duidelike korrelasie bestaan tussen swigversakking en skuifsterkte nie. Daar is verder vasgestel dat dit nie moontlik is om te aanvaar dat daar ‘n verhouding bestaan tussen swigversakking soos vasgestel tydens die dubbele oedometer toetsing, en die verandering in volume tydens skuifsterkte toetsing nie. Daar is dus tot die slotsom gekom dat grond baie onvoorspelbaar kan wees en dat verdere navorsing na die swigversakking-verskynsel nodig is.

In recent years, with only small fractions of modern processors now accessible in a single cycle, computer architects constantly fight against propagation issues across the die. Unfortunately this trend continues to shift inward, and now the even most internal features of the pipeline are designed around communication, not computation. To address the inward creep of this constraint, this work focuses on the characterization of communication within the pipeline itself, architectural techniques to avoid it when possible, and layout co-design for early detection of problems. I present work in creating a novel detection tool for common case operand movement which can rapidly characterize an applications dataflow patterns. The results produced are suitable for exploitation as a small number of patterns can describe a significant portion of modern applications. Work on dynamic dependence collapsing takes the observations from the pattern results and shows how certain groups of operations can be dynamically grouped, avoiding unnecessary communication between individual instructions. This technique also amplifies the efficiency of pipeline data structures such as the reorder buffer, increasing both IPC and frequency. I also identify the same sets of collapsible instructions at compile time, producing the same benefits with minimal hardware complexity. This technique is also done in a backward compatible manner as the groups are exposed by simple reordering of the binarys instructions. I present aggressive pipelining approaches for these resources which avoids the critical timing often presumed necessary in aggressive superscalar processors. As these structures are designed for the worst case, pipelining them can produce greater frequency benefit than IPC loss. I also use the observation that the dynamic issue order for instructions in aggressive superscalar processors is predictable. Thus, a hardware mechanism is introduced for caching the wakeup order for groups of instructions efficiently. These wakeup vectors are then used to speculatively schedule instructions, avoiding the dynamic scheduling when it is not necessary. Finally, I present a novel approach to fast and high-quality chip layout. By allowing architects to quickly evaluate what if scenarios during early high-level design, chip designs are less likely to encounter implementation problems later in the process.

Most research on stock prices is based on the present value model or the more general consumption-based model. When applied to real economic data, both of them are found unable to account for both the stock price level and its volatility. Three essays here attempt to both build a more realistic model, and to check whether there is still room for bubbles in explaining fluctuations in stock prices. In the second chapter, several innovations are simultaneously incorporated into the traditional present value model in order to produce more accurate model-based fundamental prices. These innovations comprise replacing with broad dividends the more narrow traditional dividends that are more commonly used, a nonlinear artificial neural network (ANN) forecasting procedure for these broad dividends instead of the more common linear forecasting models for narrow traditional dividends, and a stochastic discount rate in place of the constant discount rate. Empirical results show that the model described above predicts fundamental prices better, compared with alternative models using linear forecasting process, narrow dividends, or a constant discount factor. Nonetheless, actual prices are still largely detached from fundamental prices. The bubble-like deviations are found to coincide with business cycles. The third chapter examines possible cointegration of stock prices with fundamentals and non-fundamentals. The output gap is introduced to form the non-fundamental part of stock prices. I use a trivariate Vector Autoregression (TVAR) model and a single equation model to run cointegration tests between these three variables. Neither of the cointegration tests shows strong evidence of explosive behavior in the DJIA and S&P 500 data. Then, I applied a sup augmented Dickey-Fuller test to check for the existence of periodically collapsing bubbles in stock prices. Such bubbles are found in S&P data during the late 1990s. Employing econometric tests from the third chapter, I continue in the fourth chapter to examine whether bubbles exist in stock prices of conventional economic sectors on the New York Stock Exchange. The ‘old economy’ as a whole is not found to have bubbles. But, periodically collapsing bubbles are found in Material and Telecommunication Services sectors, and the Real Estate industry group.

Hyperacute renal failure is rarely the initial presentation of systemic lupus erythematosus (SLE). Pregnancy can predispose untreated lupus nephritis to acute renal failure. Collapsing glomerulopathy (CG) type of renal failure is not a new clinicopathological entity. There have been documented cases prior to 1979. It is thought that detection bias coupled with the predilection for HIV has caused this form of glomerulopathy to be incorrectly named or diagnosed as 'malignant focal segmental glomerulosclerosis (FSGS)'. This is a case of CG described in lupus nephritis. We present a case of untreated lupus in a female in whom pregnancy triggered the exacerbation of lupus nephritis that presented as collapsing glomerulopathy.

Estimates of fuel management data for the equilibrium operation of a specific CANDU reactor have been obtained by simulating a period of the reactor's history using the Fuel Management Design Program (FMDP). The collapsing procedure in FMDP has been tested and improved. This procedure prepares a coarse mesh model of the reactor core from a detailed fine mesh calculation. The program calculates a set of coarse mesh parameters which, when used in the flux calculation, will regenerate exactly the same eigenvalue and flux distribution as the fine mesh model. These parameters can then be used with the coarse mesh, to calculate flux distributions for a series of perturbations from the reference calculation used in collapsing. Several coarse mesh models were generated and studied. It was found that coarse mesh calculations with collapsed parameters result in large savings in computing costs compared to the same calculations with fine mesh, but with very little loss in accuracy. / Thesis / Master of Engineering (ME)

We study the application of Bose-Einstein condensates (BECs) to simulations of phenomena across a number of disciplines in physics, using theoretical and computational methods. ¶ Collapsing condensates as created by E. Donley et al. [Nature 415, 39 (2002)] exhibit potentially useful parallels to an inflationary universe. To enable the exploitation of this analogy, we check if current quantum field theories describe collapsing condensates quantitatively, by targeting the discrepancy between experimental and theoretical values for the time to collapse. To this end, we couple the lowest order quantum field correlation functions to the condensate wavefunction, and solve the resulting Hartree-Fock-Bogoliubov equations numerically. Complementarily, we perform stochastic truncated Wigner simulations of the collapse. Both methods also allow us to study finite temperature effects. ¶ We find with neither method that quantum corrections lead to a faster collapse than is predicted by Gross-Pitaevskii theory. We conclude that the discrepancy between the experimental and theoretical values of the collapse time cannot be explained by Gaussian quantum fluctuations or finite temperature effects. Further studies are thus required before the full analogue cosmology potential of collapsing condensates can be utilised. ¶ As the next project, we find experimental parameter regimes in which stable three-dimensional Skyrmions can exist in a condensate. We show that their stability in a harmonic trap depends critically on scattering lengths, atom numbers, trap rotation and trap anisotropy. In particular, for the Rb87 |F=1,m_f=-1>, |F=2,m_f=1> hyperfine states, stability is sensitive to the scattering lengths at the 2% level. We find stable Skyrmions with slightly more than 2*10^6 atoms, which can be stabilised against drifting out of the trap by laser pinning. ¶ As a stepping stone towards Skyrmions, we propose a method for the stabilisation of a stack of parallel vortex rings in a Bose-Einstein condensate. The method makes use of a ``hollow'' laser beam containing an optical vortex, which realises an optical tunnel for the condensate. Using realistic experimental parameters, we demonstrate numerically that our method can stabilise up to 9 vortex rings. ¶ Finally, we focus on analogue gravity, further exploiting the analogy between flowing condensates and general relativistic curved space time. We compare several realistic setups, investigating their suitability for the observation of analogue Hawking radiation. We link our proposal of stable ring flows to analogue gravity, by studying supersonic flows in the optical tunnel. We show that long-living immobile condensate solitons generated in the tunnel exhibit sonic horizons, and discuss whether these could be employed to study extreme cases in analogue gravity. ¶ Beyond these, our survey indicates that for conventional analogue Hawking radiation, simple outflow from a condensate reservoir, in effectively one dimension, has the best properties. We show with three dimensional simulations that stable sonic horizons exist under realistic conditions. However, we highlight that three-body losses impose limitations on the achievable analogue Hawking temperatures. These limitations vary between the atomic species and favour light atoms. ¶ Our results indicate that Bose-Einstein condensates will soon be useful for interdisciplinary studies by analogy, but also show that the experiments will be challenging.