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For decades electrophysiologists have recorded and characterized the biophysical properties of a rich diversity of neuron types. This diversity of neuron types is critical for generating functionally important patterns of brain activity and implementing neural computations. In this thesis, I developed computational methods towards quantifying neuron diversity and applied these methods for understanding the functional implications of within-type neuron variability and across-type neuron diversity. First, I developed a means for defining the functional role of differences among neurons of the same type. Namely, I adapted statistical neuron models, termed generalized linear models, to precisely capture how the membranes of individual olfactory bulb mitral cells transform afferent stimuli to spiking responses. I then used computational simulations to construct virtual populations of biophysically variable mitral cells to study the functional implications of within-type neuron variability. I demonstrate that an intermediate amount of intrinsic variability enhances coding of noisy afferent stimuli by groups of biophysically variable mitral cells. These results suggest that within-type neuron variability, long considered to be a disadvantageous consequence of biological imprecision, may serve a functional role in the brain. Second, I developed a methodology for quantifying the rich electrophysiological diversity across the majority of the neuron types throughout the mammalian brain. Using semi-automated text-mining, I built a database, Neuro- Electro, of neuron type specific biophysical properties extracted from the primary research literature. This data is available at http://neuroelectro.org, which provides a publicly accessible interface where this information can be viewed. Though the extracted physiological data is highly variable across studies, I demonstrate that knowledge of article-specific experimental conditions can significantly explain the observed variance. By applying simple analyses to the dataset, I find that there exist 5-7 major neuron super-classes which segregate on the basis of known functional roles. Moreover, by integrating the NeuroElectro dataset with brain-wide gene expression data from the Allen Brain Atlas, I show that biophysically-based neuron classes correlate highly with patterns of gene expression among voltage gated ion channels and neurotransmitters. Furthermore, this work lays the conceptual and methodological foundations for substantially enhanced data sharing in neurophysiological investigations in the future.

Many single-agent search algorithms have parameters that need to be tuned. Although settings found by offline tuning will exhibit strong average performance, properly selecting parameter settings for each problem can result in substantially reduced search effort. We consider the use of dovetailing as a way to deal with this issue. This procedure performs search with multiple parameter settings simultaneously. We present results testing the use of dovetailing with the weighted A*, weighted IDA*, weighted RBFS, and BULB algorithms on the sliding tile and pancake puzzle domains. Dovetailing will be shown to significantly improve weighted IDA*, often by several orders of magnitude, and generally enhance weighted RBFS. In the case of weighted A* and BULB, dovetailing will be shown to be an ineffective addition to these algorithms. A trivial parallelization of dovetailing will also be shown to decrease the search time in all considered domains.

abstract: A collection of stories as viewed through the lens of Oulipo methodology. / Dissertation/Thesis / Masters Thesis Creative Writing 2015

O uso da irrigação em cafeeiro é uma tecnologia que vem se consolidando e mostrando-se economicamente viável ao longo dos tempos, trazendo junto com ela a técnica da fertirrigação. Desta forma, o presente estudo teve como objetivo avaliar a influência de formas de aplicação e fontes de fertilizantes sobre a condutividade elétrica e pH da solução do solo, bem como no desenvolvimento e produção do café conilon irrigado por gotejamento. O trabalho foi desenvolvido em São Gabriel da Palha, Espírito Santo, utilizando o clone 12V da variedade INCAPER 8142. O experimento foi delineado em blocos ao acaso (DBC) com seis tratamentos e quatro blocos. Os tratamentos adotados foram: T1 - Controle - adubação nitrogenada e potássica aplicada via solo nas fontes ureia e cloreto de potássio; T2 - Adubação nitrogenada e potássica aplicada via solo nas fontes ureia e cloreto de potássio de liberação controlada; T3 - Adubação nitrogenada e potássica aplicada via fertirrigação nas fontes ureia e cloreto de potássio; T4 - Adubação nitrogenada e potássica aplicada via fertirrigação nas fontes nitrato de amônio e sulfato de potássio; T5 - Adubação nitrogenada e potássica aplicada via fertirrigação nas fontes nitrato de amônio e nitrato de potássio; T6 - Adubação nitrogenada e potássica aplicada via solo nas fontes ureia e cloreto de potássio de liberação controlada no período de outubro a março (período chuvoso) e adubação nitrogenada e potássica aplicada via fertirrigação, nas fontes nitrato de amônio e sulfato de potássio no período de abril a setembro (período seco). Foi monitorado o pH e condutividade elétrica da solução do solo, avaliações biométricas das plantas tais como altura, comprimento do primeiro ramo plagiotrópico e número de nós no primeiro ramo plagiotrópico, além da produção por planta e estimativa de produtividade. Os tratamentos T1 e T3 que utilizaram ureia e cloreto de potássio e o T4 - nitrato de amônio e sulfato de potássio disponibilizaram maiores quantidade de nitrogênio na forma amoniacal, causando maior acidificação do bulbo. Em contrapartida os tratamentos T2, T5 e T6 apresentaram menor acidificação, com diferença estatística significativa na variação do pH nas duas profundidades analisadas a partir de 18 meses da aplicação dos tratamentos. Nos tratamentos T2 e T6 observou-se menor salinidade inicial na avaliação aos 90 dias após o plantio através da leitura da condutividade elétrica da solução do solo. Para as avaliações biométricas, os tratamentos T2, T4, T5 e T6 diferiram estatisticamente dos tratamentos T1 e T3, influenciando positivamente à altura de plantas, comprimento e número de nós no primeiro ramo plagiotrópico. / Fertigation is a widespread technology in coffee cultivation; however, with the insertion of new fertilizers technologies, new studies are required. This study aims to evaluate the influence of application types and fertilizers sources on the electrical conductivity and pH of the soil solution in the wet bulb as well its influence in the development and production of drip irrigated conilon coffee. The study was conducted in São Gabriel da Palha, Espírito Santo (Brazil), using 12V clone variety INCAPER 8142. The experiment was designed in randomized blocks (DBC) with six treatments and four blocks. The adopted treatments were: T1 - Control / nitrogen and potassium fertilization applied via soil: urea and potassium chloride; T2 - Nitrogen and potassium fertilization applied via soil : urea and potassium chloride with release controlled; T3 - Nitrogen and potassium fertilization applied by fertigation: urea and potassium chloride; T4 - Nitrogen and potassium fertilization applied by fertigation: ammonium nitrate and potassium sulfate; T5 - Nitrogen and potassium fertilization applied by fertigation: ammonium nitrate and potassium nitrate; T6 - Nitrogen and potassium fertilization applied via soil: urea and potassium chloride with controlled release in the period from October to March (rainy season) and nitrogen and potassium fertilization applied by fertigation, ammonium nitrate and potassium sulphate in the period from April to September (dry season). The biometric evaluations of the plants were: height, length of the first branch and number of nodes in the first plagiotrophycal in addition to production per plant and productivity estimate. T1 and T3 treatments using immediate solubility of urea and T4 - ammonium nitrate have provided large amount of nitrogen in the ammonium form, causing increased acidification in the bulb. In contrast the T2, T5 and T6 treatments had lower acidification, with statistically significant differences in the pH variation in two depths analyzed from 18 months of treatment application. In treatments T2 and T6 it was observed lower initial salinity in the evaluation at 90 days after planting through the EC reading. To biometric assessments, treatments T2, T4, T5 and T6 differ statistically from T1 and T3, influencing plant height, length and number of nodes in the first plagiotrophycal.

Introdução: Existem evidências clínicas de que os movimentos do mecanismo velofaríngeo (MVF) podem ser aumentados com o uso do obturador faríngeo a ponto de o mesmo ser descartado ou até que se consiga diminuir ao máximo o gap velofaríngeo. O aumento do movimento das paredes faríngeas torna o individuo um melhor candidato para correção cirúrgica da disfunção velofaríngea (DVF). Este aumento na atividade das paredes faríngeas, no entanto, não é um achado universal com o uso do obturador, principalmente para aqueles pacientes que apresentam articulações compensatórias ou que apresentam velofaringe hipodinâmica. Objetivo: O presente estudo tem por objetivo avaliar o movimento das estruturas do MVF durante a fala, em pacientes que apresentam insuficiência velofaríngea (IVF) e que fazem uso de obturador faríngeo. A avaliação foi realizada antes (C1) e após pelo menos seis meses de uso do mesmo (C2). Material e Método: A casuística foi constituída de 25 pacientes, com fissura de palato e/ou de lábio e palato (8 mulheres e 17 homens), com idades variando entre 20 e 47 anos (média= 36 anos). Todos os pacientes apresentavam IVF após a cirurgia de palato e utilizavam obturador faríngeo havia pelo menos 6 meses. Para a avaliação do MVF com e sem o obturador faríngeo, todos pacientes haviam sido submetidos à avaliação nasoendoscópica durante fala. As 50 video-gravações dos exames de nasoendoscopia (25 na condição C1 e 25 na condição C2) foram editadas em um DVD e avaliadas por três fonoaudiólogas experientes, designadas juízas, quanto aos seguintes aspectos: movimento do véu palatino, movimento das paredes laterais da faringe, tamanho e tipo do gap velofaríngeo e anel de Passavant. Para a avaliação foi utilizado o protocolo proposto por Golding-Kushner et al (1990), especialmente adaptado para este estudo. Resultados: Neste estudo o grau de concordância intra-juízas foi de 82% para a juíza A, e 62% para as juízas B e C, para todos os aspectos do MVF avaliados. Já o grau de concordância inter-juízas variou de 49 a 88%, com média de 69%. Apesar de não terem sido encontradas diferenças estatisticamente significantes entre as condições C1 e C2, observamos que 17 (68%) dos 25 pacientes avaliados apresentaram diferenças na atividade muscular em pelo menos um dos 11 aspectos estudados. Conclusão: Os achados deste estudo demonstraram mudanças na atividade velofaríngea sugerindo que o uso do obturador faríngeo no tratamento da DVF pode ser útil tanto no processo de diagnóstico (para identificação do potencial de mudança no funcionamento velofaríngeo e na fala) quanto durante o tratamento da IVF (otimizando os resultados cirúrgicos). / Introduction: There are clinical evidence that movements of velopharyngeal mechanism can be increased with the use of speech bulbs to the point of elimination of the bulbo or until the maximum reduction of the velopharyngeal gap is achieved. An increase in the movements of pharyngeal wall turns the individual to a better candidate for surgical correction of velopharyngeal dysfunction (VPD). An increase in the activity of pharyngeal walls, however, is not an universal finding for all individual with speech bulbs, particularly for those Who use compensatory articulation or that present hypodynamic velopharynx.Objective: The present study has the objective of evaluate movement of the velopharyngeal structures during speech in patients with velopharyngeal insufficiency using speech bulbs. The evaluation was done before (C1) and at least 6 months after use of the bulb (C2).Material and Methods: The sample included 25 patients with cleft palate and/or cleft lip and palate (8 males and 17 females), with ages varying between 20 and 47 years (mean=36 years). All patients presented with velopharyngeal insufficiency and were using speech bulbs for at least 6 months. For the evaluation of the velopharyngeal mechanism with and without the speech bulb, all patients were submitted to nasoendoscopic evaluation during production of speech. All 50 video-recordings (25 in the C1 condition and 25 in the C2 condition) were edited into a DVD and evaluated by three experienced speech-language pathologists who judged the samples regarding the following aspects: movement of velum, movement of pharyngeal walls, type and size of velopharyngeal gap and Passavants Pad. For this study was used the protocol proposed by Golding-Kushner et al (1990), specially adapted for this evaluation.Results: In this study intra-judge agreement of 82% was found for judge A, and 62% for judges B and C, when all aspects rated were considered. Inter-judge agreement varied between 49% and 88% with a mean of 69%. Even though a significant difference was not found between the pré and pot speech bulb conditions, 17 (68%) subjects presented with differences in velopharyngeal activity in at least on of the 11 aspects studied. Conclusion: The findings of this study demonstrated changes in the velopharyngeal activity suggesting that the use of speech bulbs during treatment of VPD can help the diagnostic process (in the identification of the potential for changes of velopharyngeal functioning and of speech) and also can help in the treatment (by optimizing surgical results).

A hipernasalidade é uma alteração da ressonância de fala que surge quando há um acoplamento indesejável entre as cavidades oral e nasal durante a fala, geralmente, decorrente de uma disfunção do mecanismo velofaríngeo. A relação entre tamanho da abertura velofaríngea e a hipernasalidade de fala ainda não é um fenômeno bem compreendido. Em particular, pouco se sabe sobre o perfil acústico das vogais em diferentes condições de abertura velofaríngea. O objetivo deste estudo é descrever o perfil espectrográfico e nasométrico da vogal [a] e sua contraparte nasal [ã] durante a produção de fala em condições de abertura velofaríngea diferentes, porém de tamanho controlado. Este estudo foi conduzido por meio da análise acústica e perceptivo-auditiva da fala de um único sujeito com fissura pós-forame incompleta, usuário de uma prótese de palato obturadora, onde o controle do tamanho da abertura velofaríngea foi feito por meio de orifícios de 10 \'MM POT.2\', 20 \'MM POT.2\' e 30 \'MM POT.2\', criados experimentalmente no bulbo de réplicas da prótese deste sujeito. Dois pares mínimos de vogal oral versus vogal nasal inseridos em frase-veículo foram usados como corpus para coleta das amostras de fala, totalizando um número de 136 amostras analisadas neste estudo. O controle do tamanho da abertura velofaríngea (tamanho do gap) mostrou-se uma variável importante na definição do perfil acústico da fala hipernasal, embora não tenha havido linearidade entre os tamanhos de abertura velofaríngea e o grau de nasalância, nem com valores formânticos ou de duração. / Hypernasality is a resonance disorder due to the coupling between the oral and nasal cavities, usually associated to velopharyngeal dysfunction. The relationship between size of velopharyngeal opening and speech hypernasality is not a well understood phenomenon. Particularly, little is known between the acoustic profiles of vowels under differents conditions of velopharyngeal opening. The objective of this study is to describe the acoustic profile of the vowel [a] and its counterpart [ã], during speech production under different, but controlled, sizes of velopharyngeal opening. This study involved the acoustic and auditory-perceptual analysis of the speech of a single subject with incomplete operated cleft palate and a remaining velopharyngeal insufficiency treated with a speech bulb. The subjects speech appliance was duplicated allowing for the introduction of openings of controlled sizes in the bulb (10 \'MM POT.2\', 20 \'MM POT.2\' e 30 \'MM POT.2\'). Two minimal-pair words with the vowel [a] and two with the vowel [ã] produced within a phrase were used as speech corpus leading to a total of 136 speech samples analyzed in this study. Controlling size of velopharyngeal opening was important in the definition of the acoustic profile og hypernasal speech, however, the results of this study did not indicate a linear relation between size of velopharyngeal opening and nasalance scores not with formant or duration measures.

Precursores neurais originados na zona subventricular (ZSV) de algumas espécies animais possuem uma rota de migração neuronal destinada ao bulbo olfatório principal (BOP), onde os neuroblastos migrantes se diferenciam em interneurônios. Esta corrente migratória é mantida na idade adulta. A compreensão de como se organiza na idade fetal é essencial para a compreensão geral e estabelecimento de novas terapias celulares. O objetivo deste estudo é caracterizar a composição celular e organização morfológica da ZSV e da corrente rostral migratória (CRM) em encéfalos de fetos caninos. A ZSV, CRM e BOP foram obtidos de fetos caninos de aproximadamente 57 dias de idade gestacional. O tecido foi analisado através de coloração de Nissl, método de imunohistoquímica de dupla marcação com duplacortina (DCX), fator de transcrição SOX2, proteína glial fibrilar ácida (GFAP), calbindina (CALB), calretinina (CALR) e tirosina-hidroxilase (TH). Foram feitas a análise relativa da expressão da imunorreatividade e análise quantitativa de colocalização celular, além do método de microscopia eletrônica de transmissão. Os resultados mostram que a ZSV dorsal possui células imunorreativas (ir) para o DCX ao longo da parede ventricular, dispostas tangencialmente e fileiras de células SOX2-ir foram encontradas na mesma orientação. A imunorreatividade de GFAP foi mais forte na ZSV dorsal e as células possuem fibras dirigidas tangencialmente adjacentes ao ventrículo lateral e fibras orientadas radialmente em direção ao córtex. A CRM de feto de cão tem início na ZSV anterior e segue caudalmente ao redor da cabeça do núcleo caudado e desce na vertical até se curvar rostralmente em direção ao BOP onde termina na camada de células granulares (CCG). A CRM tem aparência homogênea e densa e possui células positivas para o DCX nas porções iniciais e para SOX2 e GFAP por toda a extensão. Não houve células positivas para CALB, CALR e TH em nenhuma região da ZSV e CRM. No BOP, os resultados mostraram que a camada glomerular (CG) possui células imunorreativas a CALR, TH, SOX2 e GFAP. Na camada plexiforme externa (CPE) houve células imunorreativas a CALB, CALR, SOX2 e GFAP e na CCG, houve células imunorreativas a CALR, SOX2 e GFAP. Na análise de colocalização, foram encontrados na CG neurônios CALR que colocalizam com células SOX2 e uma baixa colocalização de neurônios TH e células SOX2. Na CPE, foi observado um baixo número de colocalização de neurônios CALR e CALB e na CCG, as células SOX2 colocalizam com os neurônios CALR. As conclusões mostram que o feto de cão possui uma CRM em direção BOP, com imunorreatividade celular para DCX, SOX2 e GFAP na ZSV e CRM e para CALB, CALR, TH, SOX2 e GFAP nas principais camadas do BOP / Neural precursors originated in the subventricular zone (SVZ) of some animal species have a migration route destined for main olfactory bulb (MOB), where migrants neuroblasts differentiate into olfactory interneurons. This migratory stream is maintained in adulthood. Understanding how it is organized in fetal age is essential for general understanding and establishment of new cell therapies. The aim of this study is characterize the cellular composition and morphological organization of the SVZ and rostral migratory stream (RMS) of brains of canine fetuses. The SVZ, RMS and MOB was obtained from canine fetuses of the approximately 57 gestacional days-old. The tissue was analyzed by Nissl staining and by immunohistochemical methods for double labelling with doublecortin (DCX), transcription factor SOX2, glial fibrillary acid protein (GFAP), calbindin (CALB), calretinin (CALR) and tyrosinehydroxylase (TH). Semiquantitative analysis of immunoreactivity and quantitative analysis of colocalization were realized, besides ultrastructural analysis by electron microscopy. The results show that in dorsal SVZ, DCX immunoreactive cells were found along the ventricular wall, arranged tangentially and lines of SOX2 cells were also found in the same orientation. The GFAP immunostaining is stronger in dorsal SVZ with tangentially directed fibers near the lateral ventricle and radially oriented fibers toward the cortex. The RMS of dog fetus begins at anterior SVZ and follows caudally around the head of the caudate nucleus and vertically descends to bend rostrally into the MOB, where it ends in the granular cell layer (GCL).The RMS have SOX2 positive cells on entire length, showing a homogeneous appearance and high cell density. There is no positive CALB cells or CALR in any region of the SVZ and RMS. The results of the MOB show that the glomerular layer (GL) there were cells immunoreactive to CALR, TH, SOX2 and GFAP. In the external plexiforme layer (EPL) there were immunoreactive cells for CALR, CALB, SOX2 and GFAP and, the GCL, the prevalence is higher for CALR neurons, SOX2-ir and GFAP-ir cells. In colocalization analysis, they were found a some CALR positive neurons in GL that colabeled with SOX2 cells and a low colocalization of TH neurons and SOX2 cells. In EPL, was observed a low colocalization number of CALR and CALB neurons and in GCL, SOX2 cells colabeled with CALR neurons. The conclusions show that the dog fetus has a RMS directed to the MOB, with cellular immunoreactivity for DCX, SOX2 and GFAP in the ZSV and RMS and cellular immunoreactivity for SOX2 CALB, CALR, TH and GFAP in main olfactory bulb layers

Les cellules periglomerulaires du bulbe olfactif conforment une population hétérogène avec des propriétés moléculaires, synaptiques, morphologiques et biophysiques diverses toujours étudiés de façon indépendante. Toutefois, cette diversité suggère que des groupes différents des cellules periglomerulaires pourraient avoir des rôles différents. Dans la première partie de ma thèse je cherche à associer, pour la première fois, différents marqueurs de la diversité des neurones periglomerulaires de façon à aider à comprendre les potentielles implications fonctionnelles que les cellules periglomerulaires pourraient avoir dans le traitement de l’information olfactive. Les cellules periglomerulaires reçoivent des courants inhibiteurs postsynaptiques mais les circuits responsables de cette inhibition restent méconnus. À l’aide des enregistrements électrophysiologiques dans des tranches aiguës horizontales de bulbe olfactif de souris et des techniques d’optogénétique je montre que des projections centrifuges GABAergiques en provenance du télencéphale basal modulent fortement l’inhibition des cellules periglomerulaires de type 2 ainsi que des cellules granulaires et des cellules à axone courtes. / In the olfactory bulb periglomerular cells form a heterogeneous population with diverse molecular, synaptic, morphological and biophysical properties that have always been considered independently and never explored together. However, such diversity suggests different functional implications. On the first part of this thesis, I aim to associate, for the first time, different markers of periglomerular diversity together to put in perspective the functional implications that differebt subgroups of these cells could exert in odor processing. Periglomerular cells receive inhibitory postsynaptic currents but the circuits mediating this inhibition remain poorly understood. Using a combination of patch-clamp recordings in mouse horizontal olfactory bulb slices and optogenetics I demonstrate that centrifugal GABAergic projections from the basal forebrain strongly mediate inhibition of type 2 periglomerular cells but also granule cells and deep short axon cells.

Les projections corticales de retour conduisent l'information vers des relais de traitement de l'information plus précoces. Elles sont essentielles pour la perception sensorielle. En ce qui concerne l'olfaction, l'information sensorielle est constituée d'une multitude de molécules odorantes, et c'est ce mélange complexe qui pénètre dans la cavité nasale. En fonction du contexte, c'est une partie ou une autre de cet ensemble de molécules qui va être importante d'un point de vue comportemental. Les signaux corticaux de retour permettraient de focaliser son attention sur les odeurs pertinentes de l'environnement. Au cours de mon doctorat, j'ai étudié le rôle de la signalisation inhibitrice GABAergique dans ces retours corticaux vers le bulbe olfactif, le premier relais de l'information olfactive. La première partie de mon travail a mis en évidence une modulation métabotropique GABAergique du retour cortical excitateur. Nos expériences caractérisent ensuite l'effet produit par cette modulation sur le bulbe olfactif. Nous avons ainsi démontré que la signalisation GABAergique au niveau de retours corticaux change de manière profonde la réponse du bulbe olfactif aux stimuli olfactifs. Dans un deuxième temps, j'ai trouvé que le cortex olfactif envoie non seulement des projections de retour excitatrices, mais aussi des retours inhibiteurs. Des expériences précisent ensuite la localisation de ce retour GABAergique, ainsi que son impact sur le bulbe olfactif. Nous avons notamment observé qu'en manipulant l'activité de ces fibres GABAergiques, nous pouvions modifier le comportement olfactif. / Cortical feedback conducts information towards earlier relays of information processing. It is instrumental for sensory perception. In the olfactory system, odorants are never experienced in isolation by the nose, and they might be meaningful to the animal or not depending on the context. Feedback inputs onto early processing stages are poised to permit selective attention to the relevant odorants in the olfactory scene. During my thesis work, I focused on understanding the key role that inhibitory GABAergic signaling plays in the cortical feedback to the olfactory bulb in mice.The first part of my work started with the discovery of excitatory transmission between cortical feedback inputs and the olfactory bulb is modulated by metabotropic receptors for GABA. Next, the impact of this regulation on the olfactory bulb network was investigated. We found that GABAergic signaling at cortical feedback axons profoundly changes the response of the olfactory bulb output cells to odor stimulation. In the second part of my thesis, I found that the cortical projections to the olfactory bulb not only comprises of excitatory components, but also inhibitory components. The precise origin of this GABAergic feedback was then determined and its impact on the olfactory bulb network is currently assessed. In particular, we observed that manipulating the activity of this GABAergic feedback perturbs olfactory behavior.