Randomness has proved to be a powerful tool in all of computation. It is pervasive in areas such as networking, machine learning, computer graphics, optimization, computational number theory and is "necessary" for cryptography. Though randomized algorithms and protocols assume access to "truly" random bits, in practice, they rely on the output of "imperfect" sources of randomness such as pseudo-random number generators or physical sources. Hence, from a theoretical standpoint, it becomes important to view randomness as a resource and to study the following fundamental questions pertaining to it: Extraction: How do we generate "high quality" random bits from "imperfect" sources? Randomization: How do we use randomness to obtain efficient algorithms? Derandomization: How (and when) can we "remove" our dependence on random bits? In this thesis, we consider important problems in these three prominent and diverse areas pertaining to randomness. In randomness extraction, we present extractors for "oblivious bit fixing sources". In (a non-traditional use of) randomization, we have obtained results in machine learning (learning juntas) and proved hardness of lattice problems. While in derandomization, we present a deterministic algorithm for a fundamental problem called "identity testing". In this thesis we also initiate a complexity theoretic study of Hilbert's 17th problem. Here identity testing is used in an interesting manner. A common theme in this work has been the use of tools from areas such as number theory in a variety of ways, and often the techniques themselves are quite interesting.

In this thesis work, importance of radome structures for antenna systems is emphasized. Structural and electromagnetic requirements of various types of radome structures are analyzed and specific properties are given. Electromagnetic scattering analysis of sandwich type radome seams has been done. Total antenna system far electromagnetic field expression, which is the combination of original antenna far electromagnetic field and the scattered electromagnetic field of the framework of the sandwich radome structure has been found and simulated. To enhance electromagnetic transparency of sandwich type radomes two sandwich radome design methods are proposed which are expressed as Geometrical Randomization and Tuning the Seams. Electromagnetic scattering level minimizations advanced by these design methods are presented with related simulations.

In this work, we investigate the general structure and the concepts behind the contemporary electronic voting schemes, with special emphasis on voter verifiable preferential voting, homomorphic tallying and voter privacy. We firstly propose a modification in the Single Transferable Voting (STV) method to be applied to large scale elections with electoral barriers. Our proposal prevents the loss of votes and distributes them securely to the second or higher choices of their voters. This method is most suitably used in e-voting with the voter verifiable &ldquo / Pr&ecirc / t &agrave / Voter: All-In-One&rdquo / scheme that utilizes mix-networks for anonymity. We present a case study considering 2007 Turkish Parliamentary Elections to demonstrate the effect of preferential voting on the election systems that have electoral barriers. After the mathematical formulation of the election procedure, we calculate the wasted votes in 2007 elections and present simulation results for 69 election regions (that have no independent parliament members) by using a combination of &ldquo / modified STV and d&rsquo / Hondt&rdquo / methods, according to four different, politically unbiased scenarios on the distribution of secondary vote choices. Additionally, we modify the &ldquo / Pr&ecirc / t &agrave / Voter: All-In-One&rdquo / scheme by proposing three security enhancing modifications in its ballot construction phase: 1) ballot serial number, 2) digital signature of the first clerk in the mix-net, 3) different random numbers for each row of the ballot. Finally, we demonstrate the potential of multiplicative homomorphic algorithms like RSA for homomorphic tallying. The idea is based on the association of each candidate on the electronic ballot with a prime number, and unique prime factorization of the general vote product. We propose novel randomization methods for homomorphic RSA tallying, and discuss the performance and complexity of the scheme with such randomizations. Our suggestion for an auditable and verifiable e-voting scheme that employs homomorphic RSA tallying with proper randomization has advantages over El Gamal and Paillier tallying, such as having the least encryption complexity and strong anonymity resistant to unlimited computational power.

Le neurofeedback (NF) suscite actuellement un vif intérêt dans la prise en charge du trouble déficitaire de l’attention avec hyperactivité (TDAH) chez l’enfant. Proposée comme méthode alternative à la médication par de nombreux cliniciens, notamment aux États-Unis, le NF est une intervention non-invasive de type électrophysiologique qui repose sur l’apprentissage par conditionnement opérant de l’autorégulation d’ondes cérébrales déviantes. Les études empiriques qui étayent cette pratique font toutefois l’objet de virulentes critiques de la part de spécialistes dans le domaine du TDAH en raison de résultats systématiquement positifs mais non spécifiques, auxquels s’ajoutent de nombreuses lacunes méthodologiques. Les travaux de cette thèse visent à appliquer une méthodologie stricte de type essai clinique contrôlé avec assignation aléatoire afin d’isoler les effets particuliers du NF, en appliquant un protocole d’entraînement propre au déficit primaire sous-tendant le TDAH, soit l’inhibition motrice, dans le but d’évaluer la spécificité de cette intervention. Dans un premier temps, les connaissances relatives à la nosologie du TDAH, à ses principaux traitements, au NF et aux capacités d’inhibition chez l’enfant ayant un TDAH sont présentées (Chapitre 1). Ensuite, les études réalisées dans le cadre de cette thèse sont exposées. Dans l’étude initiale, la spécificité du NF est évaluée sur les capacités d’inhibition grâce à des mesures subjectives, soit des questionnaires de comportements complétés par les parents, ainsi que des mesures objectives, à savoir des tâches neuropsychologiques (Chapitre 2). Afin de préciser davantage les conséquences d’un entraînement à l’autorégulation d’ondes cérébrales, l’étude subséquente s’est intéressée à l’impact neurophysiologiques de l’amélioration des capacités d’inhibition, par le biais d’une étude en potentiels évoqués employant une tâche de performance continue de type Stop-signal (Chapitre 3). Les principaux résultats reflètent un recrutement sous optimal, avec une puissance statistique insuffisante pour réaliser des statistiques quantitatives de groupe. Néanmoins, l’appréciation des données selon une approche d’étude de cas multiples permet de mettre en évidence la présence d’une réponse placebo sur les capacités d’inhibition suite à un entraînement en NF. Finalement, les implications de la taille de l’échantillon, ainsi que les limites et les critiques de ces études sont discutées au Chapitre 4. / In recent years, there has been a lively interest in the use of neurofeedback (NF) as an alternative treatment to pharmacotherapy in pediatric Attention-deficit hyperactivity disorder (ADHD). NF is defined as an operant conditioning procedure whereby an individual learns to self-regulate electrical brain activity. Yet, empirical studies supporting its practice are harshly criticized in the field of ADHD research due to systematic unspecific positive results associated to numerous methodological flaws. Studies presented in this dissertation aim at applying a randomized placebo-controlled clinical trial to the investigation of NF specific effects. In order to further establish treatment specificity, we trained the participants using a NF protocol characteristic to motor-inhibition functioning since it has repeatedly been described as the core deficit in ADHD. The fist part of this thesis comprises a brief review of knowledge concerning ADHD, principal treatments offered for this disorder, NF research in pediatric ADHD and inhibition abilities in these children (Chapter 1). Following are the two studies conducted as part of this dissertation. In the initial study, effects of NF training are investigated on inhibition capacities by means of behavior rating scales and neuropsychological tests (Chapter 2). With the aim of further defining the consequence of training to self-regulate ones brain activity, the subsequent study looks at the neurophysiologic impact of improving inhibition capacities with an event-related potential study using a Stop-signal continuous performance task (Chapter 3). The principal results reveal a non optimal recruitment, with insufficient statistical power, thus precluding quantitative group statistics. Nevertheless, appreciating the data from a multiple case study perspective enables to suggest that a placebo response could be at play following NF training, such as measured by improvements on inhibition capacities. Finally, the implications of such a small sample size, limits and critics of these studies are discussed in Chapter 4.

Made available in DSpace on 2014-12-17T15:16:19Z (GMT). No. of bitstreams: 1 RenataND_DISSERT.pdf: 2023307 bytes, checksum: 3532f146ca9aaaba6df3b1c47898e143 (MD5) Previous issue date: 2013-12-13 / Asthma treatment aims to achieve and maintain the control of the disease for prolonged periods. Inspiratory muscle training (IMT) may be an alternative in the care of patients with asthma, and it is used as a complementary therapy to the pharmacological treatment. Thus, the aim of this study was to investigate the effects of a domiciliary program of IMT on the electromyographic activity of the respiratory muscles in adults with asthma. This is a clinical trial in which ten adults with asthma and ten healthy adults were randomized into two groups (control and training). The electrical activity of inspiratory muscles (sternocleidomastoid (ECM) and diaphragm) was obtained by a surface electromyography. Furthermore, we assessed lung function (spirometry), maximal inspiratory pressure - MIP - (manometer). The functional capacity was evaluated by six minute walk test. Participants were assessed before and after the IMT protocol of 6 weeks with POWERbreathe? device. The training and the control groups underwent IMT with 50% and 15 % of MIP, respectively. The sample data were analyzed using SPSS 20.0, attributing significance of 5 %. Were used t test, ANOVA one way and Pearson correlation. It was observed an increase in MIP, after IMT, in both training groups and in healthy sham group (P < 0.05), which was accompanied by a significant increase in ECM activity during MIP in healthy training group (1488 %) and in asthma training group (ATG) (1186.4%). The ATG also showed a significant increase in diaphragm activity in basal respiration (48.5%). Functional capacity increased significantly in the asthma sham group (26.5 m) and in the asthma training group (45.2 m). These findings suggest that IMT promoted clinical improvements in all groups, especially the ATG, which makes it an important complementary treatment for patients with asthma / O tratamento da asma visa obter e manter o controle da doen?a por per?odos prolongados. O Treinamento Muscular Inspirat?rio (TMI) pode ser uma alternativa na assist?ncia ao paciente asm?tico, sendo utilizado como tratamento complementar ao farmacol?gico Assim, o objetivo deste estudo foi investigar os efeitos de um programa domiciliar de TMI sobre a atividade eletromiogr?fica dos m?sculos respirat?rios em adultos asm?ticos. Trata-se de um ensaio cl?nico em que dez adultos asm?ticos e dez saud?veis foram randomizados em dois grupos (sham e treinamento). A atividade el?trica dos m?sculos inspirat?rios (esternocleidomast?ideo (ECM) e diafragma) foi obtida pela eletromiografia de superf?cie. Al?m disso, foram avaliados a fun??o pulmonar, press?o inspirat?ria m?xima (PIm?x) e capacidade funcional. Os participantes foram avaliados antes e ap?s um protocolo de TMI de 6 semanas. Os grupos treinamento e sham realizaram o TMI com 50% e 15% da PIm?x, respectivamente. Observou-se aumento da PIm?x, ap?s o TMI, nos grupos treinamento e no saud?veis sham (P< 0,05), que foi acompanhado pelo aumento significativo da atividade do ECM durante a PIm?x no grupo treinamento saud?veis (1488%) e no grupo treinamento asm?tico (GTA) (1186,4%). O GTA tamb?m apresentou um aumento significativo da atividade do diafragma na respira??o basal (48,5%). A capacidade funcional aumentou significativamente no grupo sham asm?ticos (26,5m) e no grupo treinamento asm?tico (45,2m). Esses achados sugerem que o TMI promoveu melhoras cl?nicas em todos os grupos, com destaque para o GTA, sendo um op??o n?o farmacol?gica importante para indiv?duos asm?ticos

The power side-channel attack, which allows an attacker to derive secret information from power traces, continues to be a major vulnerability in many critical systems. Numerous countermeasures have been proposed since its discovery as a serious vulnerability, including both hardware and software implementations. Each countermeasure has its own drawback, with some of the highly effective countermeasures incurring large overhead in area and power. In addition, many countermeasures are quite invasive to the design process, requiring modification of the design and therefore additional validation and testing to ensure its accuracy. Less invasive countermeasures that do not require directly modifying the system do exist but often offer less protection. This thesis analyzes two non-invasive countermeasures and examines ways to maximize the protection offered by them while incurring the least amount of overhead. These two countermeasures are called clock phase noise (CPN) and voltage noise (VN), and are placed on the same FPGA as an AES encryption module that we are trying to protect. We test these designs against a highly effective algorithm called correlation power analysis (CPA) and a preprocessing technique called the sliding window attack (SW). We found that the combined effects of the two countermeasures was greater than the impact of either countermeasure when used independently, and published a paper in the 2019 IEEE 30th International Conference on Application-specific Systems, Architectures and Processors (ASAP) on our findings. We found that our best combined countermeasure protected about 76% of the maximum amount of traces that a well-known but invasive competitor, wave dynamic differential logic (WDDL), could with only about 41% of the area and 78% of the power. However, the sliding window attack significantly reduced the amount of protection our combined countermeasure could offer to only 11% of that offered by WDDL. Since then, we updated our methodology and made some adjustments to VN and CPN. Our CPN countermeasure greatly improved, and therefore so did our combined countermeasure, which on average protected up to about 90% of the maximum amount of traces that WDDL could with only about 43% of the area and about 60% of the power. This is remarkable because these results are after the sliding window attack, meaning that our post-proposal countermeasures protect almost as well as WDDL while requiring only about half of the resources.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: The hazard ratio (HR), representing the quantified estimate of treatment effect in survival analysis, measures the instantaneous relative difference of failure risk between two groups. The HR is typically assumed to be independent of time; however, this assumption is usually violated in practice. If the proportionality assumption holds, HR can be validly with the popular Cox proportional hazards model. When not proportional, the Wilcoxon-Gehan has been proposed to test the hypothesis of no difference. These have been recently generalized to evaluate differences in survival time for more than zero survival differences (the “net survival benefit”). Method: In this thesis, an attempt is made to illustrate the properties of generalized Wilcoxon Gehan tests as proposed by Buyse (2009). We use the concept of net survival benefit to re-analyze the trial by the Gastrointestinal Tumor Study Group (1982) by comparing chemotherapy versus combined chemotherapy and radiation in the treatment of locally unresectable gastric cancer. Survival times in days, for the 45 patients were recorded in each treatment arm. In that trial, a delayed treatment effect was observed, thus the HR is non-proportional. To provide a flexible assessment of the treatment effect, the net survival benefit was computed using datasets simulated under typical scenarios of proportional hazards, such as delayed treatment effect. Results: The generalized Wilcoxon statistic U, favored not adding radiation to chemotherapy, but only for survival up to 12 months. At Δ=0, U (0) = 491. In the simulated data sets, the confidence interval under the null hypothesis U (0) is (-152, 388). The test statistic 491 is outside this interval indicating radiation treatment might be beneficial. At U(12) = 219, it is inside the confidence interval of no treatment effect (-154,268) indicating the benefit of Chemo only is gone after 12 months. Conclusions: The net survival benefit measured via Buyse’s generalized Wilcoxon statistic is a measure of treatment effect that is meaningful whether or not hazards are proportional. The associated statistical test is more powerful than the standard log-rank test when a delayed treatment effect is anticipated.

Steroid hormones act as important regulators of physiological processes including gene expression. They provide possible mechanistic explanations of observed sex-dimorphisms in obesity and coronary artery disease (CAD). Here, we aim to unravel causal relationships between steroid hormones, obesity, and CAD in a sex-specific manner. In genome-wide meta-analyses of four steroid hormone levels and one hormone ratio, we identified 17 genome-wide significant loci of which 11 were novel. Among loci, seven were female-specific, four male-specific, and one was sex-related (stronger effects in females). As one of the loci was the human leukocyte antigen (HLA) region, we analyzed HLA allele counts and found four HLA subtypes linked to 17-OH-progesterone (17-OHP), including HLA-B*14*02. Using Mendelian randomization approaches with four additional hormones as exposure, we detected causal effects of dehydroepiandrosterone sulfate (DHEA-S) and 17-OHP on body mass index (BMI) and waist-to-hip ratio (WHR). The DHEA-S effect was stronger in males. Additionally, we observed the causal effects of testosterone, estradiol, and their ratio on WHR. By mediation analysis, we found a direct sex-unspecific effect of 17-OHP on CAD while the other four hormone effects on CAD were mediated by BMI or WHR. In conclusion, we identified the sex-specific causal networks of steroid hormones, obesity-related traits, and CAD.

Peripheral blood biomarkers can inform clinical care and drug development. Establishing causality between biomarker and disease is often critical for such applications, but epidemiological studies are limited due to biases from confounding and reverse causation. Mendelian randomization analysis leverages random inheritance of genetic variants at conception to mimic properties of randomized studies and estimate unconfounded effects between biomarker and disease, or vice-versa. This thesis demonstrates the utility of Mendelian randomization as a complementary tool to elucidate observational studies, predict drug safety and repurposing opportunities, and improve diagnostic biomarkers for cardiometabolic diseases. First, we characterized the hypothesized relationship between lipoprotein(a) and atrial fibrillation. We demonstrated both observed and genetically predicted lipoprotein(a) levels were associated with higher risk of atrial fibrillation across multiple independent cohorts. Importantly, risk was partly mediated independent of atherosclerotic cardiovascular disease, a known consequence of elevated lipoprotein(a) and itself a risk factor for atrial fibrillation. Next, we explored the lifelong effects of endogenous testosterone across a comprehensive set of 461 health outcomes in 161,268 males from the UK Biobank cohort. Using Mendelian randomization analysis, we found higher testosterone had beneficial effects on body composition and bone mineral density but adverse effects on prostate cancer, androgenic alopecia, spinal stenosis, and hypertension. Finally, we applied Mendelian randomization with the intention of discovering biomarkers caused by disease, which are expected to represent markers of early disease. As a proof-of-concept, we applied this framework to identify biomarkers associated with genetic predisposition to kidney function among 238 biomarkers measured in the ORIGIN trial. We discovered reduced kidney function caused increased trefoil factor 3 and showed its addition to models with known risk factors improved discrimination of incident early-stage chronic kidney disease. Taken together, Mendelian randomization identified biomarkers that warrant further study, with promising implications for screening, prevention, and treatment of different cardiometabolic diseases. / Thesis / Doctor of Philosophy (PhD) / Biological markers associated with disease can inform novel therapeutics or diagnostics but distinguishing causation from correlation is challenging. Mendelian randomization – a technique that leverages random inheritance of genetic variation to infer causality – was used to examine the role of biomarkers in cardiometabolic diseases. First, we implicated lipoprotein(a) as a risk factor for atrial fibrillation that acts independent of atherosclerotic cardiovascular disease. Second, we comprehensively characterized the lifelong effects of testosterone on health outcomes in males, where we found evidence of both beneficial and adverse effects on disease. Finally, we discovered trefoil factor 3 as a diagnostic marker for early-stage chronic kidney disease. Altogether, this thesis demonstrated different applications of Mendelian randomization that showcase its utility as a complementary tool to reveal causal biomarkers, and served to identify biomarkers for cardiometabolic diseases that merit further studies to evaluate their potential benefit on patient care.

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