To understand how the components of a complex system like the biological cell interact and regulate each other, we need to collect data for how the components respond to system perturbations. Such data can then be used to solve the inverse problem of inferring a network that describes how the pieces influence each other. The work in this thesis deals with modelling the cell regulatory system, often represented as a network, with tools and concepts derived from systems biology. The first investigation focuses on network sparsity and algorithmic biases introduced by penalised network inference procedures. Many contemporary network inference methods rely on a sparsity parameter such as the L1 penalty term used in the LASSO. However, a poor choice of the sparsity parameter can give highly incorrect network estimates. In order to avoid such poor choices, we devised a method to optimise the sparsity parameter, which maximises the accuracy of the inferred network. We showed that it is effective on in silico data sets with a reasonable level of informativeness and demonstrated that accurate prediction of network sparsity is key to elucidate the correct network parameters. The second investigation focuses on how knowledge from association networks can be transferred to regulatory network inference procedures. It is common that the quality of expression data is inadequate for reliable gene regulatory network inference. Therefore, we constructed an algorithm to incorporate prior knowledge and demonstrated that it increases the accuracy of network inference when the quality of the data is low. The third investigation aimed to understand the influence of system and data properties on network inference accuracy. L1 regularisation methods commonly produce poor network estimates when the data used for inference is ill-conditioned, even when the signal to noise ratio is so high that all links in the network can be proven to exist for the given significance. In this study we elucidated some general principles for under what conditions we expect strongly degraded accuracy. Moreover, it allowed us to estimate expected accuracy from conditions of simulated data, which was used to predict the performance of inference algorithms on biological data. Finally, we built a software package GeneSPIDER for solving problems encountered during previous investigations. The software package supports highly controllable network and data generation as well as data analysis and exploration in the context of network inference. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.</p><p> </p>

L‐glutamate is associated with several neurological disorders; thus, monitoring fast dynamics of L‐glutamate is of great importance in the field of neuroscience. Electrode miniaturization demanded by many applications leads to reduced surface area and decreased amounts of immobilized enzymes on coated electrodes. As a result, lower signal‐to‐noise ratios are observed for oxidase‐enzyme based sensors. To increase the signal‐to‐noise ratio we have developed a process to fabricate micro‐ and nano‐ structures on the microelectrode surface. Localized surface‐plasmon resonances (SPR) has been extensively used to design label‐free biosensors that can monitor receptor‐ligand interactions. A major challenge with localized SPR sensors is that they remain highly susceptible to interference because they respond to both solution refractive index changes and surface binding of the target analyte. The key concept introduced in the present work is the exploitation of transverse and longitudinal resonance modes of nanorod arrays to differentiate between bulk refractive index changes and surface interactions. The transverse bulk sensitivity of the localized SPR sensor (107 nm/RIU) remains competitive with typical single mode gold nanosphere SPR sensors. The figure of merit for the device’s cross‐sensitivity (1.99) is comparable to that of typical wavelength‐interrogated propagating SPR sensors with self referencing.

Thesis (Ph.D.); Submitted to the University of California, Berkeley, CA (US); 24 Nov 2004. / Published through the Information Bridge: DOE Scientific and Technical Information. "LBNL--56751" McGuire, John Andrew. USDOE Director. Office of Science. Office of Basic Energy Sciences. Materials Science and Engineering Division (US) 11/24/2004. Report is also available in paper and microfiche from NTIS.

abstract: A dual-channel directional digital hearing aid (DHA) front-end using a fully differential difference amplifier (FDDA) based Microphone interface circuit (MIC) for a capacitive Micro Electro Mechanical Systems (MEMS) microphones and an adaptive-power analog font end (AFE) is presented. The Microphone interface circuit based on FDDA converts the capacitance variations into voltage signal, achieves a noise of 32 dB SPL (sound pressure level) and an SNR of 72 dB, additionally it also performs single to differential conversion allowing for fully differential analog signal chain. The analog front-end consists of 40dB VGA and a power scalable continuous time sigma delta ADC, with 68dB SNR dissipating 67u¬W from a 1.2V supply. The ADC implements a self calibrating feedback DAC, for calibrating the 2nd order non-linearity. The VGA and power scalable ADC is fabricated on 0.25 um CMOS TSMC process. The dual channels of the DHA are precisely matched and achieve about 0.5dB gain mismatch, resulting in greater than 5dB directivity index. This will enable a highly integrated and low power DHA / Dissertation/Thesis / Ph.D. Electrical Engineering 2011

The extension from Quantitative Magnetic Resonance Imaging to synthetic imaging has the clear advantage of being able to continually image the patient after the exam. MR techniques such as DWI are commonly used but have some clear disadvantages resulting from the use of echoplanar imaging. It should then be asked whether one imaging technique is objectively better. If one technique is better, the incorporation in clinical settings could produce better diagnostic rates, and save valuable time. In order to quantitatively assess the quality of these techniques, the SNR and CNR values of similar tissues were compared. The pre-analysis discussion concentrating on the spatial resolution and artifacts, supports that synthetic images have an advantage over DWI due to higher resolution and absence of artifacts. The SNR and CNR values were calculated for each patient and image type for the comparison, initially assuming that the synthetic images would have a higher mean SNR and CNR. In most cases the differences between scan types was found to not be statistically significant. In conclusion, this analysis could not support the initial theory that the synthetic images had a higher SNR or CNR. The research shows that they are more likely to be comparable. An investigation of the diagnostic power of the synthetic in comparison to standard DWI would give clinical relevance to these results.

Résumé confidentiel / Résumé confidentiel

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Submitted by Leonardo Cavalcante (leo.ocavalcante@gmail.com) on 2018-04-26T16:07:18Z No. of bitstreams: 1 Arquivototal.pdf: 2172337 bytes, checksum: 610ecfccf9e2afc70327ee3d1dffb901 (MD5) / Made available in DSpace on 2018-04-26T16:07:18Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 2172337 bytes, checksum: 610ecfccf9e2afc70327ee3d1dffb901 (MD5) Previous issue date: 2017-02-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Several species are inserted in the acoustic space due to a long evolutionary process. There is a negative allometric relation between body mass and acoustic frequencies, and this relationship can be optimized through signal-to-noise ratio, signal threshold or efficiency limits according to body size. Additionally, the acoustic competition can cause divergence in the use of the frequency expected by allometry, creating a structured acoustic space. The efficiency of propagation can push the vocalizations of the smaller species to a lower portion of the spectrum. To analyze the vocal allometry, we conducted type II linear regressions (Ranged Major Axis) with acoustic data of New World Parrots (Psittacidae – Arini), New World Doves (8 genera), woodcreepers (Dendrocolaptinae), tinamous (Tinamidae) and thrushes (25 species). To verify the existence of non-random patters in the use of the acoustic space, we used null model with Pianka overlap index. To test whether smaller species use lower frequencies than the expected by allometry, we used Wilcoxon Sign Rank. These were tested with acoustic data from a bird assembly of the Carajás National Forest. We used the dominant frequency (FDOM), the minimum fundamental frequency (FFMIN) and the maximum fundamental frequency (FFMAX). The allometric relation was found in parrots, doves, woodcreepeers and in the fundamental frequencies of tinamous. No structure was found in the use of acoustic frequencies. FDOM and FFMIN differed significantly from those expected by allometry, but both were higher than expected. Sound communication has been shaped by a long process of natural selection, through distinct evolutionary forces, each having a role in the acoustic signal. / A forma com que diversas espécies estão inseridas no espaço acústico é resultado de um longo processo evolutivo. Existe uma relação alométrica negativa entre a massa corporal e as frequências acústicas, podendo esta relação ser otimizada em função da relação sinal-ruído, da intensidade do sinal ou por limites de eficiência de acordo com o tamanho corporal. Adicionalmente, a competição acústica pode gerar divergência no uso da frequência esperada pela alometria fazendo com que ocorra uma estruturação do espaço acústico. Já a eficiência da propagação pode direcionar as vocalizações das espécies menores para a porção grave do espectro. Para analisar a alometria vocal conduzimos regressões lineares do tipo II (Ranged Major Axis) com dados acústicos de psitacídeos neotropicais (Psittacidae - tribo Arini), pombos neotropicais (8 gêneros), dendrocolaptídeos (Dendrocolaptinae), tinamídeos (Tinamidae) e turdídeos (25 espécies). Para verificar a existência de padrões não aleatórios no uso do espaço acústico, utilizamos modelo nulo com o índice de sobreposição de Pianka. Para testar se as espécies menores utilizam frequências mais graves, utilizamos Wilcoxon Sign Rank. Estes foram testados com dados acústicos de uma assembleia de aves da Floresta Nacional de Carajás. Utilizamos a frequência dominante (FDOM), a frequência fundamental mínima (FFMIN) e a frequência fundamental máxima (FFMAX). A relação alométrica foi encontrada em psitacídeos, pombos, dendrocolaptídeos e nas frequências fundamentais de tinamídeos. Não foi encontrada estruturação no uso das frequências acústicas. A FDOM e a FFMIN diferiram significantemente do esperado pela alometria, porém ambas foram mais agudas que o esperado. A comunicação sonora tem sido moldada por um longo processo de seleção natural, através de forças evolutivas distintas, cada uma tendo um papel no sinal acústico.

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Na escola as crianças estão envolvidas em atividades nas quais predomina a fala dos professores e de seus colegas. Deste modo, uma acústica adequada nas salas de aula e uma relação sinal-ruído (S/R) favorável são vitais para todos os alunos. Para melhorar a relação S/R a fim de favorecer o reconhecimento da fala no ruído, várias estratégias são utilizadas, incluindo a indicação dos Sistemas de Frequência Modulada (FM). Diante de indicações de sistemas FM para uso em ambientes educacionais, este estudo teve como objetivo avaliar o impacto do sistema de campo livre digital para as habilidades relacionadas ao desempenho acadêmico de indivíduos com audição periférica normal e para a voz do professor. Participaram 20 crianças com média de idade de oito anos matriculadas no 3º ano do ensino fundamental, divididas igualmente em dois grupos (controle e experimental) e seu professor. O grupo experimental foi exposto ao sistema de campo livre Digimaster 5000 e o professor utilizou o transmissor Inspiro por três meses consecutivos. Os grupos foram avaliados por meio de testes padronizados antes e após três meses de uso do equipamento, assim como a voz do professor. Os instrumentos de pesquisa utilizados para avaliação dos alunos foram os testes Perfil de Habilidades Fonológicas, Teste de Nomeação Automática Rápida (RAN), Teste de Desempenho Escolar (TDE) e Compreensão Leitora. Para avaliação da voz do professor foram aplicados: questionário, escala de desconforto do trato vocal e realizadas as análises perceptivo-auditiva e acústica. Também foram aplicados questionários e colhidos depoimentos sobre a experiência do uso do sistema de campo livre digital por parte dos alunos e do professor. Não houve diferença estatisticamente significante na comparação entre as avaliações e na comparação entre os grupos com relação ao teste Perfil de Habilidades Fonológicas e o RAN. O grupo experimental apresentou resultados estatisticamente significantes no substeste de Leitura do TDE. No teste de compreensão leitora, ambos os grupos apresentaram resultados estatisticamente significantes no tempo de leitura quando comparadas as avaliações. Na avaliação da voz do professor observou-se que na escala do desconforto do trato vocal, houve melhora do sintoma de aperto, sugerindo redução da tensão vocal. A análise perceptivo-auditiva evidenciou melhora na rouquidão e soprosidade após o uso do sistema de campo livre digital tanto na emissão da vogal /a/ quanto na contagem, e na análise acústica também observou melhora na voz. Por meio dos depoimentos e questionários sobre a experiência do uso do sistema de campo livre digital, os alunos relataram ouvir melhor o professor, e o mesmo relatou melhora na escuta e atenção dos alunos para instruções verbais. Conclui-se que o uso do sistema de campo livre digital foi efetivo para melhora no desempenho acadêmico dos alunos no teste padronizado em leitura, na melhora de inteligibilidade da fala do professor relatada pelos alunos e na redução da tensão vocal do professor. O sistema de campo livre digital minimiza o impacto do ruído em sala de aula. / At school, children are involved in activities in which the speech of teachers and classmates prevail. Thus, proper acoustics in the classrooms and a favorable signal-to-noise (S/N) ratio are vital for all students. In order to improve the S/N ratio, so as to promote the recognition of speech in noise, several strategies are used, including the use of Frequency Modulated Systems (FM). Considering the indications for use of FM systems in educational environments, this study aimed to evaluate the benefits of digital soundField system for skills related to academic performance of normal-hearing individuals and teachers voice. This study included 20 children with a mean age of eight, enrolled in the 3rd grade, equally grouped into two groups (control e experimental), and their teacher. The experimental group was exposed to Digimaster 5000 system and the teacher used the Inspiro transmitter for three consecutive months. The groups and the teachers voice were assessed through standardized tests before and after three months of using the equipment. The research tools used to evaluate the students included the Phonological Abilities Profile, Rapid Automatized Naming (RAN), Academic Performance Test (TDE) and Reading Comprehension. To evaluate the teachers voice we applied questionnaire, vocal tract discomfort scale and carried out the auditory-perceptive and acoustic analyses. We also applied specific questionnaires and collected testimonials from students and teacher on their experience of using digital soundField system. There was no statistically significant difference when comparing the evaluations nor when comparing the groups as regards the Phonological Abilities Profile and the RAN. The experimental group showed statistically significant results in the TDE reading subtest. In the reading comprehension test, both groups showed statistically significant results in the reading time. The evaluation of the teachers voice showed that, in the vocal tract discomfort scale, there was an improvement in the tight symptom, suggesting reduced vocal strain. The auditory-perceptive analysis showed improvement in hoarseness and breathiness after using the digital soundField system both in the emission of the /a/ vowel and in the counting, and in the acoustic analysis an improvement in the voice was also noted. Through testimonials and questionnaires on their experience using the digital soundField system in the classroom, the students reported they could better listen to the teacher, and the teacher reported students showed improvement in their listening and attention to verbal instructions. It is concluded that the use of digital SoundField system was effective for improving the academic performance of students in standardized testing in reading, improves speech intelligibility teacher reported by students and reducing teacher vocal strain. The digital SoundField system minimizes the impact of noise in the classroom.