Achieving acceptable plane wave uniformity throughout an expanded volume is necessary to conduct scattering measurements on a large target in a controlled environment. An expanded volume is large relative to the size of the nearfield array configuration used to produce plane wave uniformity. The optimum set of shading coefficients for a nearfield array may not produce acceptable plane wave uniformity as the volume and frequency domain are expanded for a given array configuration. Choosing the frequency domain as a single frequency for an optimum set of coefficients will produce plane wave uniformity throughout the largest possible volume for a given array configuration. This study determines the acceptability of uniformity results produced by an optimum set of frequency dependent coefficients throughout an expanded volume for two array configurations that comprise a system for measuring bistatic target strength in the nearfield. Minimizing the frequency domain chosen for an optimum set of coefficients will produce plane wave uniformity for the largest possible volume for a given array configuration. This study determines the acceptability of uniformity results produced by an optimum set of frequency dependent coefficients throughout an optimistic volume for two array configurations that comprise a bi-static array.

In this thesis, a Neural Network (NN) based beamforming algorithm is proposed for real time target tracking problem. The algorithm is performed for two applications, linear and cylindrical arrays. The linear array application is implemented with equispaced omnidirectional sources. The influence of the number of antenna elements and the angular seperation between the incoming signals on the performance of the beamformer in the linear array beamformer is studied, and it is observed that the algorithm improves its performance by increasing both two parameters in linear array beamformer. The cylindrical array application is implemented with twelve microstrip patch antenna (MPA) elements. The angular range of interest is divided into twelve sectors. Since three MPA elements are used to form the beam in each sector, the input size of the neural network (NN) is reduced in cylindrical array. According to the reduced size of NN, the training time of the beamformer is decreased. The reduced size of the NN has no degradation in forming the beams to the desired directions. The angular separation between the targets is an important parameter in cylindrical array beamformer.

In some antenna applications, having high directivity while keeping the antenna dimensions small is desired, which can be obtained by use of superdirective arrays. Superdirective arrays have been popular in academic world since a superdirective array provides higher directivity than the uniformly excited antenna array of same length. In this thesis, superdirective arrays are investigated by making high precision numerical computations. Superdirective array element excitations, array factors and directivities are inspected for different number of elements. Superdirective array pattern and directivity features are compared to uniformly excited array pattern and directivities. Superdirective array tolerance is investigated by examination of array element excitation sensitivities. Bandwidth of superdirective arrays is also inspected. Multiple Precision Toolbox is used during numerical computations in Matlab.

Local soil conditions influence the characteristics of earthquake ground shaking and these effects must be taken into account when specifying ground shaking levels for seismic design. These effects are quantified via site response analysis, which involves the propagation of earthquake motions from the base rock through the overlying soil layers to the ground surface. Site response analysis provides surface acceleration-time series, surface acceleration response spectra, and/or spectral amplification factors based on the dynamic response of the local soil conditions. This dissertation investigates and compares the results from different site response methods. Specifically, equivalent-linear time series analysis, equivalent-linear random vibration theory analysis, and nonlinear time series analysis are considered. In the first portion of this study, hypothetical sites and events are used to compare the various site response methods. The use of hypothetical events at hypothetical sites allowed for the seismic evaluation process used in engineering practice to be mimicked. The hypothetical sites were modeled after sites with characteristics that are representative of sites in the Eastern and Western United States. The input motions selected to represent the hypothetical events were developed using the following methods: stochastically-simulated time series, linearly-scaled recorded time series, and spectrally-matched time series. The random vibration theory input motions were defined using: seismological source theory, averaging of the Fourier amplitude spectra computed from scaled time series, and a response spectrum compatible motion. All of the different input motions were then scaled to varying intensity levels and propagated through the sites to evaluate the relative differences between the methods and explain the differences. Data recorded from borehole arrays, which consist of instrumentation at surface and at depth within the soil deposit, are used to evaluate the absolute bias of the site response methods in the second portion of this study. Borehole array data is extremely useful as it captures both the input motion and the surface motion, and can be used to study solely the wave propagation process within the soil deposit. However, comparisons using the borehole data are complicated by the assumed wavefield at the base of the array. In this study, sites are selected based on site conditions and the availability of high intensity input motions. The site characteristics are then developed based on site specific information and data from laboratory soil testing. Comparisons between the observed and computed response are used to first assess the wavefield at the base of the array, and then to evaluate the accuracy of the site response methods. / text

Recently, covering arrays have been the subject of considerable research attention as they hold both theoretical interest and practical importance due to their applications to testing. In this thesis, we perform the first comprehensive study of a generalization of covering arrays called variable strength covering arrays, where we dictate the interactions to be covered in the array by modeling them as facets of an abstract simplicial complex. We outline the necessary background in the theory of hypergraphs, combinatorial testing, and design theory that is relevant to the study of variable strength covering arrays. We then approach questions that arise in variable strength covering arrays in a number of ways. We demonstrate their connections to hypergraph homomorphisms, and explore the properties of a particular family of abstract simplicial complexes, the qualitative independence hypergraphs. These hypergraphs are tightly linked to variable strength covering arrays, and we determine and identify several of their important properties and subhypergraphs. We give a detailed study of constructions for variable strength covering arrays, and provide several operations and divide-and-conquer techniques that can be used in building them. In addition, we give a construction using linear feedback shift registers from primitive polynomials of degree 3 over arbitrary finite fields to find variable strength covering arrays, which we extend to strength-3 covering arrays whose sizes are smaller than many of the best known sizes of covering arrays. We then give an algorithm for creating variable strength covering arrays over arbitrary abstract simplicial complexes, which builds the arrays one row at a time, using a density concept to guarantee that the size of the resultant array is asymptotic in the logarithm of the number of facets in the abstact simplicial complex. This algorithm is of immediate practical importance, as it can be used to create test suites for combinatorial testing. Finally, we use the Lovasz Local Lemma to nonconstructively determine upper bounds on the sizes of arrays for a number of different families of hypergraphs. We lay out a framework that can be used for many hypergraphs, and then discuss possible strategies that can be taken in asymmetric problems.

Modern electronic systems, especially sensor and imaging systems, are beginning to incorporate their own neural network subsystems. In order for these neural systems to learn in real-time they must be implemented using VLSI technology, with as much of the learning processes incorporated on-chip as is possible. The majority of current VLSI implementations literally implement a series of neural processing cells, which can be connected together in an arbitrary fashion. Many do not perform the entire neural learning process on-chip, instead relying on other external systems to carry out part of the computation requirements of the algorithm. The work presented here utilises two dimensional instruction systolic arrays in an attempt to define a general neural architecture which is closer to the biological basis of neural networks - it is the synapses themselves, rather than the neurons, that have dedicated processing units. A unified architecture is described which can be programmed at the microcode level in order to facilitate the processing of multiple neural network types. An essential part of neural network processing is the neuron activation function, which can range from a sequential algorithm to a discrete mathematical expression. The architecture presented can easily carry out the sequential functions, and introduces a fast method of mathematical approximation for the more complex functions. This can be evaluated on-chip, thus implementing the entire neural process within a single system. VHDL circuit descriptions for the chip have been generated, and the systolic processing algorithms and associated microcode instruction set for three different neural paradigms have been designed. A software simulator of the architecture has been written, giving results for several common applications in the field.

This work deals with the further development of a method for Direction of Arrival (DOA) estimation based on the Discrete Fourier Transform (DFT) of the sensor array output. In the existing DFT-based algorithm, relatively high SNR is considered, and it is assumed that a large number of sensors are available. In this study an overview of some of the most commonly used DOA estimation techniques will be presented. Then the performance of the DFT method will be analyzed and compared with the performance of existing techniques. Two main objectives will be studied, firstly the reduction of the number of sensors and secondly the performance of the DFT based technique in the presence of noise. Experimental simulations will be presented to illustrate that in absence of noise, the proposed method is very fast and using just one snapshot is sufficient to accurately estimate DOAs. Also, in presence of noise, the method is still relatively fast and using a small number of snapshots, it can accurately estimate DOAs. The above mentioned properties are the result of taking an average of the peaks of the DFTs, X_n (k), obtained from a sequence of N_s snapshots. With N_s sufficiently large, the average over N_s snapshots approaches expected value. Also, the conditions that should be satisfied to avoid overlapping of main-lobes, and thus loosing the DOA of some signals, in the DFT spectrum are examined. This study further analyzes the performance of the proposed method as well as two other commonly used algorithms, MUSIC and conventional beamformer. An extensive simulation was conducted and different features of the spatial DFT technique, such as accuracy, resolution, sensitivity to noise, effect of multiple snapshots and the number of sensors were evaluated and compared with those of existing techniques. The simulations indicate that in most aspects the proposed spatial DFT algorithm outperforms the other techniques. / Graduate

La déficience intellectuelle (DI) touche 1 à 3% de la population générale avec un excès de sujets de sexe masculin. Cette affection est caractérisée par une extrême hétérogénéité clinique et génétique rendant son élucidation complexe. La révolution technologique des outils permettant l’analyse du génome intervenue depuis les années 2000 avec l’analyse chromosomique sur microréseau et singulièrement depuis 2010 avec les applications du séquençage à haut débit a considérablement facilité l’identification de nouveaux gènes. Nous avons tiré avantage de ce phénomène pour identifier trois affections neurologiques à caractère familial Nous avons procédé selon une méthodologie structurée pour conduire, grâce à la mise en place d’un réseau de collaborations, à la découverte ou à la confirmation de l’existence de nouvelles formes de DI. 1.Séquençage de l'exome couplé à la recherche de variations du nombre de copies 2. Mise à jour d’une altération de séquence génique potentiellement causale retrouvée chez le cas index et chez les autres sujets atteints de la famille 3.Extension des résultats à d’autres familles par la constitution d’une cohorte de réplication 4.Élaboration d’une série d’études fonctionnelles venant conforter l’hypothèse de causalité par la création d’un modèle animal et/ou la réalisation d’études biochimiques spécifiquesL’application de cette méthodologie nous a permis de conduire à terme trois projets : L’individualisation d’une forme syndromique de DI récessive autosomique associée à une malformation du rachis cervical et liée aux mutations bi-alléliques de CDK10. La caractérisation d’une encéphalopathie récessive autosomique létale associée à une hypertonie sévère et à une arthrogrypose distale liée aux mutations bi-alléliques d’ATAD1. L’implication de FRMPD4 dans une nouvelle forme de DI non syndromique liée à l’X / Intellectual disability (ID) impacts 1 to 3% of the general population with an excess of affected males. This condition is characterized by an extreme clinical and genetic heterogeneity making the deciphering of its causes more complex. The technological revolution that took place in the study of the genome over the last two decades has provided a useful tool for identification of new genetic entities. This is particularly true for chromosomal micro-array analysis since early 2000s and for next generation sequencing since 2011. We took advantage of this by identifying the molecular basis of three singular conditions. We applied a structured methodology and created a network of collaborations to define or confirm these new ID syndromes. 1. Whole exome sequencing alongside with array-CGH 2.Identification of a candidate gene sequence alteration in the index case and other affected patients of the family 3.Constitution and study of a replication cohort 4.Biochemical studies and/or animal models in order to support the assumption of causalityBased on this research strategy, we were able to complete the following projects : Discovery of a syndromic form of autosomal recessive ID associated with cervical spine defects due to bi-allelic CDK10 mutations. Identification of an ATAD1-related profound and lethal autosomal recessive encephalopathy with stiffness and distal arthrogryposis. Characterization of a FRMPD4-related X-linked non-syndromic ID

Orientador: Célia Regina Nogueira / Resumo: A Leucemia Mielóide Crônica (LMC) é uma doença malígna, clonal, da célula tronco hematopoética. A descoberta do cromossomo filadélfia e subsequente identificação do gene BCR-ABL, levaram a compreensão da biologia da doença que culminou com o desenvolvimento de drogas alvo-específicas, assim como o de métodos moleculares para o monitoramento da doença. O foco atual das pesquisas em LMC está voltado para o maior entendimento dos mecanismos moleculares e epigenéticos que levam a resistência terapêutica e progressão da doença. Estudos recentes demonstram que a expressão de micro-RNAs específicos modula oncogenes e genes supressores envolvidos no desenvolvimento de neoplasias. Ao encontro a esta tendência, propomos um estudo que procurou identificar o perfil de micro-RNAs dos pacientes bons respondedores aos tratamentos de primeira linha para LMC. Avaliamos o perfil de micro-RNAs, de 41 pacientes com LMC que atingiram resposta citogenética completa (ausência do cromossomo Filadélfia) após o tratamento com inibidor de tirosinaquinase e transplante alogênico de células progenitoras hematopoéticas, por meio do sistema de micro-RNA PCR arrays (TaqMan® Human Micro-RNA Array A e B). Identificamos uma assinatura de micro-RNA distinta entre os grupos tratados, apesar de se encontrarem no mesmo patamar de resposta clínica e citogenética. Palavras-chave: Leucemia Mielóide Crônica, micro-RNA, imatinibe, transplante, qPCR array. / Abstract: Chronic Myeloid Leukemia (CML) is a malignant clonal hematopoietic stem cell disease. The discovery of the Philadelphia chromosome and subsequent identification of the gene BCR-ABL have led to understanding the biology of the disease and the development of target-specific drugs, as well as molecular methods for monitoring the disease. The current focus of research in the CML is facing the greatest understanding of the molecular and epigenetic mechanisms that lead to therapy resistance and disease progression. Recent studies show that the expression of specific micro-RNAs modulates oncogenes and tumor suppressor genes involved in cancer development.We are proposing a new study in the literature that aims to identify the profile of micro-RNAs of patients good responders to first-line treatments for CML.Evaluated the profile of micro-RNAs in 41 CML patients who achieved a complete cytogenetic response (absence of Philadelphia chromosome) after treatment with tyrosine kinase inhibitor and allogeneic bone marrow transplantation, through the micro-RNA- PCR arrays (TaqMan® Human Micro-RNA Array A e B). We identified a distinct micro-RNA signature between the treated groups, despite being on the same level of cytogenetic and clinical response.Key Words: Chronic Myeloid LeuKemia, micro-RNA, imatinib, bone marrow transplantation, qPCR array. / Mestre

Experimentos de Imagens por Ressonância Magnética (IRM) em pequenos animais, assim como em humanos, exigem um conjunto especifico de bobinas de Radiofrequência (RF) para maximizar ambos a homogeneidade de campo durante a transmissão e a Relação Sinal Ruído (RSR) durante a recepção. As geometrias mais comuns de bobinas transmissoras utilizadas em sistemas de humanos são as bobinas tipo gaiola ou Birdcage Coil. Dentre as geometrias de bobinas receptoras, o conceito de bobina tipo Phased Array é amplamente utilizado em aplicações que necessitam de alta RSR em uma grande região de interesse, além de permitirem obter imagens com metodologias de aquisição paralela. Este trabalho descreve o desenvolvimento de um conjunto de bobinas transmissoras e receptoras especificamente projetadas para a aquisição de imagens do cérebro de ratos para o estudo do hipocampo. As geometrias de bobinas transmissoras estudadas foram dois Birdcages com 8 e 16 condutores e a geometria proposta por nós chamada Double Crossed Saddle (DCS Coil). Para a recepção desenvolvemos uma bobina de superfície com dois loops e um Phased Array com dois canais de recepção. Os resultados confirmam que dentre as bobinas transmissoras desenvolvidas a geometria do tipo Birdcage com 16 condutores é a mais homogênea, produzindo campos de RF com alta uniformidade em regiões de interesse de até 80% do diâmetro interno das bobinas. No entanto, o elevado número de capacitores em sua estrutura faz com que a geometria DCS coil, devido à sua simplicidade e reduzido número de capacitores, represente uma alternativa em experimentos onde as condições de carga da amostra possam variar. Dentre as geometrias de receptoras estudadas a bobina de superfície obteve maior desempenho em termos de RSR em comparação com o Phased Array de 2 canais. A comparação dos resultados utilizando bobinas específicas para a transmissão e recepção com uma bobina volumétrica operando como transmissora e receptora simultaneamente comprova a superioridade em termo de RSR dos sistemas que utilizam bobinas dedicadas, sendo confirmados através de imagens in vivo do cérebro de ratos, possibilitando aquisições com mesma resolução e RSR em um tempo reduzido de experimento. / Magnetic Resonance Imaging (MRI) experiments on small animals, as well as in human, require a specific RF coil set in order to maximize the Radiofrequency (RF) field homogeneity during transmission and Signal-to-Noise Ratio (SNR) during reception. The most common geometries of RF transmitter coil used in human systems are the well known Birdcage resonators. Among the receiver coils geometry the concept of NMR Phased Arrays or multi channel coils is widely employed in applications that need a high SNR in a large region of interest (ROI), further allowing parallel imaging acquisition methodologies. The work reported here describes the development of a transmit-only and receive-only RF coil set actively detuned specifically designed to MRI acquisition of rats brain for purposes of neuroscience studies. The transmitter geometries developed were two Birdcages with 8 and 16 rungs and our proposed geometry named Double Crossed Saddle (DCS). For reception we developed one common surface coil made of two turn loops and a 2-channel Phased Array, both actively detuned during reception. The results have confirmed that the 16 rungs Birdcage are superior among other transmit coils in producing homogeneous RF field inside a ROI of 80% of coil´s inner diameter. However, the simplicity and reduced number of capacitors makes the DCS coil a good choice in experiments with different samples and load conditions. Among the receive coils developed, the surface coil showed a better SNR in comparison with the 2-channel Phased array, which has the advantage of producing a large area with high SNR. The SNR of both surface coil and 2-channel array was compared with a transceiver Saddle Crossed coil, available at our lab, specific designed to obtain rat brain images. These results have corroborated that transmit-only and receive-only RF coils have best performance than transceiver volume coils for obtain MRI images of rats brain, allowing image acquisition with same resolution and reduced scan time.