Tesis sobre el tema "Spiral array"

The angle of arrival estimation of multiple sources plays a vital role in the field of array signal processing as MIMO systems can be employed at both the transmitter and the receiver end and the system capacity, reliability and throughput can be significantly increased by using array signal processing. Almost all applications require accurate direction of arrival (DOA) estimation to localize the sources of the signals. Another important parameter of localization systems is the array geometry and sensor design which can be application specific and is used to estimate the DOA. In this work, various array geometries and arrival estimation algorithms are studied and then a new scheme for multiple source estimation is proposed and evaluated based on the performance of subspace and non-subspace decomposition methods. The proposed scheme has shown to outperform the conventional Multiple Signal Classification (MUSIC) estimation and Bartlett estimation techniques. The new scheme has a better performance advantage at low and high signal to noise ratio values (SNRs). The research work also studies different array geometries for both single and multiple incident sources and proposes a geometry which is cost effective and efficient for 3, 4, and 5 antenna array elements. This research also considers the shape of the ground plane and its effects on the angle of arrival estimation and in addition it shows how the mutual couplings between the elements effect the overall estimation and how this error can be minimised by using a decoupling matrix. At the end, a novel miniaturised multi element reconfigurable antenna to represent the receiver base station is designed and tested. The antenna radiation patterns in the azimuth angle are almost omni-directional with linear polarisation. The antenna geometry is uniplanar printed logspiral with striplines feeding network and biased components to improve the impedance bandwidth. The antenna provides the benefit of small size, and re-configurability and is very well suited for the asset tracking applications.

In spinal cord injured (SCI) individuals the neural pathway between the brain and the extremities is damaged. However, there is still the capacity to elicit muscle activation despite the absence of any supraspinal input. Recent studies have proposed epidural spinal cord electrical stimulation (ESCS) as a means to facilitate locomotor recovery in SCI humans. In epidural stimulation a number of electrodes are placed in the spine, outside the dura, and stimulus current pulses are used to ‘tune’ the spinal circuitries. Some rat studies have supported this concept, but further testing is required to increase our understanding and optimise the stimulation parameters. Testing protocols are currently limited by the available technology. More specifically, the number of electrodes one can use seriously limits the paradigms that could be investigated. For this reason, electrode arrays, as opposed to the conventional pairs of electrodes, can be used to investigate the effect of ESCS at different sites. The development of epidural electrode arrays for chronic testing in rats is a challenging task due to their small size. The difficulties increase radically when a large number of electrodes need to be independently controlled. It has been well documented in the literature that a large number of connections (wires) is highly undesirable because it either makes the implantation procedure more challenging, or, if the device is successfully placed in the body, it could imperil perfusion, result in infections, tissue damage, or simply cause the device to fail. The development of a flexible epidural electrode array suitable for chronic implantation in rats was the main goal of this work. For the first generation of the system, flexible passive 12-electrode arrays, using silicone rubber and annealed platinum foil, were designed and fabricated—suitable for use with an external stimulator. In vivo evaluation of these devices showed that they failed quickly, 87.5% of the connections after a week inside the spine of a rat. The failure analysis performed highlighted the need to reduce the number of connections to avoid inflammation and improve the mechanical stability of the implants. To overcome the connections ‘bottleneck’ without compromising the number of electrodes (which was necessary for the planned paradigm), our approach was to develop application-specific integrated circuits (ASICs) to be embedded on the arrays, acting as electrode drivers. The ASICs reduce the number of connections to 3, feature a very small silicon footprint (less than 0.36 mm2 core area), consume very low power (up to 114 μW during a full stimulation cycle), and allow for the necessary versatility for the testing with a real-time control system, developed by our collaborators (in the FP7 NEUWalk project). A custom designed ‘hub’, designed by Dr. Clemens Eder, is used to electronically – rather than manually – manage the stimulus parameters and the operation of the ASICs. It can be programmed via a graphical user interface (GUI) or the real-time controller. Moving to the second generation of the system, active (with embedded ASICs) epidural arrays were designed, developed and evaluated. For this version, platinum iridium foil, was preferred, due to its superior mechanical strength. The next part of the work focused on the the different aspects of the fabrication and assembly processes. More specifically, size restrictions related to the implantation site dictated the need to use thinned ASICs. To post-process the already fabricated chips, a method for purely mechanical silicon thinning at individual die level was developed and characterised. For the integration of the ASICs on the arrays an evaluation study was conducted to examine the mechanical reliability of the bonds produced by electrical rivet bonding. Combining all the above, a new fabrication process was developed for the active arrays. Despite the fact that, so far, chronic in vivo testing has not been yet implemented, the produced prototypes were electrically and mechanically evaluated in vitro, and results are satisfactory, as no failed tracks were observed during the chronic tests in the lab. The current setup allows power and data to be transferred to the implant real-time through a connector fixed on the rat’s head, while the animal is on a treadmill or on a runway. This implies that there is no need for a wireless system at this stage. However, more complex experiments where the rats would be able to move freely and interact with other rats unrestricted, developing a behaviour that is closer to their natural, could provide significant new knowledge in the future. Although there are still many things to understand regarding epidural stimulation and its effect before planning an experiment like this, this was kept in mind throughout the whole design and development phases of this system. On this basis, the developed subcomponents are compatible with a system level design of a fully implantable platform to be used in freely moving rats, stimulated for 3 – 4 hours per day. This system comprises the active electrode array, which is the focus of this thesis, together with a miniaturised, battery-powered implantable version of the previously mentioned hub (which is on-going work, and is not presented here).

The dorsal horn of the spinal cord is a complex laminar structure integrating exteroceptive signals from the primary afferent fibers into the central nervous system. The laminae of the spinal cord exhibit specialised roles and distinct processes occur across the axes of the dorsal horn. One of the most common in vivo approaches to recording spinal activity is single unit electrophysiology of cells that are believed to be representative of the subjects perception of stimuli. This approach has produced invaluable data but has not progressed in over half a century and fails to account for the specialised processes that occur in each lamina as well as the considerable cellular heterogeneity within and between laminae. In this thesis the use of linear multi-electrode array technology with 16 electrodes spaced 50 μm apart to have a total range of 750 μm that allows for simultaneous recordings across the laminae is developed and validated for the spinal dorsal horns of adult Sprague-Dawley rats. To do this a series of experiments were performed. The placement of the electrode was first optimised by creating a somatotopic map of evoked activity following hindpaw stimulation. A comprehensive series of electrical stimuli designed to induce differential primary afferent fiber activity were then given to establish how well the array could interpret fiber evoked activity. Mechanical and thermal stimulus paradigms were examined to evaluate the spatial distribution of responses across the dorsal horn; after optimisation the responses were then examined in the contexts of acute and chronic pain models. We found that the results of the unsorted multi-spike activity across the array correlated extremely well with predicted responses from single-unit studies in the existing literature. Fiber specific activation restricted along the dorso-ventral axis was detected as was the encoding of mechanical and thermal stimuli that were both innocuous and nocuous in nature. Comparisons between local field potentials and spike activity showed that multi-spike activity represented spinal processing of incoming signals significantly better. Induction of pain models strengthened the argument for the use of the technique by showing that it is capable of being used in both longitudinal and multi-treatment group studies. The approach produced vastly more data than the single-unit technique it builds upon with few drawbacks.

Une des problématiques qui est souvent associée aux réseaux large bande est l’apparition des lobes de réseaux, liée à la périodicité de l’espacement entre les éléments du réseau. Un autre problème dans les réseaux large bande est la fréquence de fonctionnement de l’élément du réseau. La plus basse fréquence d’opération est généralement liée à la taille de l’élément. Dans cette thèse un réseau d’anneaux concentriques a été développé. Les connections entre les spirales de polarisation opposée diminuent le coefficient de réflexion dans les fréquences basses. La topologie des anneaux concentriques a été optimisée avec des Algorithmes Génétiques pour minimiser le niveau des lobes secondaires relatifs dans les hautes fréquences. L’addition d’une contrainte de taille dans la procédure d’optimisation a assuré que le réseau soit compact. Le réseau optimisé opère entre 1 et 6.9 GHz. Le design a été d’avantage développé avec la technique WAVES avec l’inclusion d’une copie réduite en son centre, ce qu’a permis l’extension de la bande passante jusque 13 GHz. De plus, nous avons proposé un nouveau design pour le réseau de spirales connectés qui consiste en des antennes spirales disposées dans un réseau uniforme avec les bras connectés aux bras des antennes voisines. Les simulations indiquent que le réseau peut avoir une bande passante arbitrairement large selon la finitude du réseau. Un prototype a été construit et mesuré pour valider le concept<br>One of the usual problems associated with wideband arrays is having the highest frequency of operation limited by the appearance of grating lobes, associated with the periodicity in the spacing between elements of the array. Another issue is the working frequency of the element of the array. The lowest frequency of operation is in general related to the size of the element. In this thesis a Concentric Ring Array of Connecting Spirals has been developed. The connections between spirals of opposite polarizations reduces the reflection coefficient at lower frequencies. The concentric rings topology had the radius and relative rotations of each ring optimized using Genetic Algorithms to minimize the RSLL at higher frequencies. The addition of a size constraint in the optimization procedure kept the array compact. The optimized array operates from 1 to 6.9 GHz. The design was then updated using the WAVES technique to include a scaled down copy in its center, extending the bandwidth of the array up to 13 GHz. Moreover, we proposed a new design for the array of connected spirals which consists of arranging spirals in a uniform array and connecting the arms of the neighboring spirals. Simulations indicate that the design can have an arbitrarily large bandwidth depending on the finiteness of the array. A prototype has been built and measured to validate the concept

This project focused on understanding the mechanisms involved in CNS integration. The anatomy and physiology of mammalian olfactory system was investigated in order to develop an organotypic in vitro sensory system to increase our understanding of sensory processing at a neural network level. The olfactory network cultures grown on multielectrode arrays (MEAs) were found to only rarely exhibit electrical activity and it was decided this was an unsuitable preparation for the purposes of this study. The spinal cord was chosen as a secondary sensory system, initially in co-culture with dorsal root ganglia and then alone, with special interest in gap junction function. Gap junctions have received increasing attention as contributors to pattern generation in neuronal ensembles, including the generation or modification of highly coordinated, intense bursting states. The main result section of this study explored the effects of four gap junction blockers (carbenoxolone (CBX), halothane, I-octanol and oleamide) on the spontaneous activity of mouse and rat frontal cortex and spinal cord cultures grown on microelectrode arrays (MEAs). It was our hypothesis that the characteristic coordinated bursting seen in most frontal cortex and in some higher density spinal cord cultures would be influenced via gap junction communication. The four compounds tested generated interesting, and in one case paradoxical effects. Frontal cortex cultures were all inhibited in a dose-dependent manner, which included total cessation of activity by halothane, CBX, I-octanol, or oleamide (at concentrations 250 muM, 100 muM, 20 muM, 20 muM, respectively). All cultures showed spontaneous recovery at lower concentrations and reversibility after culture medium changes at higher concentrations. In addition, measurements of network burst rates and coefficients of variation of burst period indicate that burst coordination among channels was reduced by these compounds. These responses were generally mirrored in the spinal cord, except for CBX, which produced a paradoxical transient intense increase in network spike and burst production. The results of this study show the effect of the gap junction blockers to be not only tissue specific, but also to differ from species to species. It is still unclear whether these differences seen really are through the blockade of gap junctions, or due to the secondary effects of the blockers used. Further studies showed that strychnine (1 muM) prevented this transient activity increase in spinal cord networks, implying that CBX may temporarily block glycine inhibition. Blocking intracellular calcium mobility with thapsigargin (up to 5 muM) did not affect the effects of gap junction blockers used.

Parmi les causes de décès d'origine cardiaque, les troubles du rythme occupent une place majeure, particulièrement les troubles auriculaires. Cette situation alarmante a motivé une recherche intense, mais qui est limitée par la disponibilité de modèles expérimentaux permettant de reproduire les mécanismes cellulaires de déclenchement et d'extensions de ces anomalies. Qu'ils surviennent sur un cœur sain ou pathologique, qu'ils soient bénins ou potentiellement dangereux (risque de mort subite), les troubles du rythme constituent un chapitre important de la cardiologie. Ils posent d'importants problèmes d'ordre diagnostique, pronostique, et thérapeutique. Ils peuvent se produire au niveau atrial (nœud auriculo-ventriculaire, plus tronc du faisceau de HIS avant sa division) ou ventriculaire (après la division du faisceau de HIS en ses deux branches droite et gauche), et ils obéissent à différents mécanismes, au premier rang desquels les réentrées et les hyperautomatismes. Cette thèse s'intéresse à l'étude et la modélisation des troubles du rythme cardiaque à l'échelle cellulaire. Ainsi la problématique de la thèse peut être résumée succinctement par ces quelques mots clés : système non-linéaire, modèles cardiaques, ondes spirales, défibrillation.... Une des questions qui a été soulevée est : comment optimiser le processus de défibrillation pour qu'il soit le moins contraignant pour le patient ? Nous avons commencé par nous intéresser à la défibrillation par stimulation électrique. La stimulation externe peut terminer la fibrillation mais peut aussi éventuellement générer de nouvelles ondes dans le tissu cardiaque. Ce dernier effet de stimulation semble inévitable, si l'énergie de stimulation dépasse certains seuils. Nous nous sommes posé alors une question: comment peut-on terminer la fibrillation en appliquant une stimulation sous le seuil pour éviter d'engendrer d'autres problèmes. Après quelques pistes de réflexion, nous nous sommes orientés vers une stratégie hybride de stimulation qui permet d'atteindre cet objectif. En parallèle de ces travaux, nous avons travaillé aussi sur un système expérimental à base de MEA (Multi Electrodes Array). Ce système nous permet d'acquérir des signaux de cellules cardiaques de rats nouveau-nés en culture in vitro. Etant donné que les données recueillies peuvent être bruitées et erronées, nous avons utilisé des ondelettes pour le débruitage et la méthode de décomposition par les valeurs singulières pour éliminer les mauvais signaux. Comme mentionné précédemment, la stimulation peut provoquer de nouvelles ondes dans le tissu, ceci a été observé expérimentalement sous forme d'ondes spirales. Les prochains travaux serviront à approfondir " la stimulation hybride " au niveau théorique. Ensuite en profitant de notre plateforme MEA, nous allons tester la stratégie de défibrillation par stimulation hybride au niveau expérimental.

Tous les réseaux de neurones immatures génèrent une activité dite « spontanée »qui persiste même en l’absence de toute afférence et est impliquée dans de nombreux processus développementaux. Cette activité apparaît in vitro sous formes de vagues calciques ou électriques pouvant se propager sur de grandes distances et embraser toute la préparation. Toutefois, sa dynamique a été assez peu étudiée jusqu’à présent. En vue de combler quelque peu cette lacune, nous avons utilisé des matrices de microélectrodes (MEA) pour caractériser l’activité rythmique spontanée dans la moelle épinière embryonnaire de souris, sur des préparations aigues et en culture incluant également le tronc cérébral.Les enregistrements MEA produisent des volumes de données très importants qui nécessitent des outils d’analyse performants et adaptés à l’information que l’on souhaite extraire. Nous avons donc développé des méthodes pour la détection, la classification et la cartographie des patrons spatiotemporels d’activité dans les données multicanaux. Notre approche cartographique utilise l’interpolation par splines et est orientée vers la production de cartes multimodales combinant l’activité électrique et des données anatomiques ou biochimiques (marquages). Ces méthodes d’analyse nous ont permis de décrire très précisément l’évolution de l’activité spontanée aux stades précoces (E12.5–E15.5). Nous avons également montré que, à E14.5, l’activité est initiée dans le bulbe, plus précisément dans une région riche en neurones 5-HT, suggérant un nouveau rôle des voies sérotoninergiques descendantes dans la maturation des réseaux spinaux.Enfin, nous avons analysé les mouvements embryonnaires à E14.5 et avons découvert des caractéristiques analogues à la dynamiques spatiotemporelle des activités intraspinales<br>Immature neural networks generate a peculiar type of activity that persists even in the absence of electrical inputs and was termed for this reason “endogenous”or “spontaneous”. This activity is ubiquitous and was found involved in a wide range of developmental events. In vitro, it can be observed as calcium or electrical waves propagating over great distances, often invading the whole preparation,but its dynamics remain poorly described. In order to somewhat fill this gap,we used multielectrode arrays (MEAs) to characterise the spontaneous rhythmic activity in the mouse developing spinal cord, in both acute and cultured isolated hindbrain-spinal cord preparations.To extract relevant information from the massive amounts of data yielded by MEA recordings, adapted analysis tools are needed. Thus, we have developedmethods for the detection, classification and mapping of spatiotemporal patternsof activity in multichannel data. Our mapping approach is based on the thin plates pline interpolation and includes the possibility to combine maps of activity with anatomical or stained data for multimodal imaging.These methods allowed us to analyse in great detail the evolution of spontaneousactivity at early stages (E12.5–E15.5). In addition, we have localised theinitiation site of E14.5 activity in the medulla and shown that it matches a densemidline population of serotoninergic neurons, suggesting a new role for 5-HTpathways in the maturation of spinal networks. Finally, we have recorded andtracked spontaneous limb movements of E14.5 embryos and found that features of motility were consistent with patterns of spinal activity

Ependimomas são tumores gliais raros. Podem ser encontrados em qualquer localização do sistema nervoso central e, apesar de histologia similar, parecem apresentar alterações genômicas distintas. As variáveis clínicas são intercorrelacionadas e, geralmente, incapazes de predizer o curso da doença. O objetivo do presente estudo foi analisar a expressão aumentada de genes e proteínas em ependimomas e correlacionar com dados clínicos dos pacientes. Foram estudados casos de pacientes com ependimoma submetidos à ressecção cirúrgica no Hospital das Clínicas, Universidade de São Paulo, no período entre 1996 e 2011 (33 amostras de tecido congelado para análise de expressão gênica por PCR quantitativo em tempo real e 149 amostras com tecido incluído em parafina, correspondentes a 121 casos devido a recidivas, para análise de proteína por imuno-histoquímica de tissue microarrays). As reações de imuno-histoquímica foram analisadas semiquantitativamente e graduadas com um índice de marcação calculado pelo produto da porcentagem de núcleos marcados pela intensidade de marcação. Oitenta e um casos eram adultos (média de 27,2 anos). Havia 60 casos intracranianos e 61 intramedulares, dos quais 10 eram mixopapilares, 92 grau II e 19 grau III. Ressecção completa foi possível em 62% dos casos e recidiva foi confirmada em 41,1%. Observou-se menor tempo para recidiva em crianças e tumores intracranianos, supratentoriais (p < 0,001 em ambos), histologia anaplásica e ressecções incompletas (p < 0,05 em ambos). Os seguintes genes foram selecionados em dados públicos de SAGE e literatura: ARMC3, CCND1, CHST5, DNALI1, FGFRL1, GNA13, IGF2, MSX1, NOTCH1 e RSPH3. ARMC3, RSHL3, CHST5 e DNALI1 apresentaram maiores níveis de expressão em ependimomas intramedulares (p < 0,05), e FGFRL1, NOTCH1 e CCND1 nos casos supratentoriais (p < 0,01). IGF2 apresentou maiores níveis de expressão em crianças e CHST5 em adultos (p < 0,05 em ambos). Foram observados maiores níveis de expressão de FGFRL1 (p < 0,05), CCND1 e IGF2 (p < 0,01 em ambos) em casos com histologia anaplásica. Nenhum dos genes analisados apresentou impacto no tempo livre de progressão ou na sobrevida. A expressão da proteína codificada por CCND1, ciclina D1, também foi avaliada por imuno-histoquímica, por ser uma proteína com expressão aumentada em diversos tipos de neoplasias e não ter ainda um valor prognóstico bem estabelecido em ependimomas. Houve correlação entre expressão de ciclina D1 a nível de mRNA e da proteína (p < 0,0001). As correlações entre ciclina D1 e histologia anaplásica e localização supratentorial foram confirmadas pela análise proteica (p < 0,0001 em ambos). Adicionalmente, foi também observada maior expressão de ciclina D1 em pacientes mais jovens (p < 0,01). A maior expressão de ciclina D1 em tumores com localização supratentorial foi independente do grau histológico e da idade do paciente. Recidiva foi mais frequente em casos com maiores níveis de expressão de ciclina D1 (p < 0,05), embora uma maior correlação com tempo livre de progressão foi observada apenas em casos com ressecção completa (p < 0,001). Os ependimomas apresentaram expressão gênica diferencial de acordo com idade, localização do tumor e grau histológico nesse estudo. A determinação dos níveis da expressão de ciclina D1 pode ser útil para guiar o seguimento e tratamento dos casos supratentoriais com ressecções completas<br>Ependymomas are rare glial cell-derived tumors. They can be found in any central nervous system localization and despite the histological similarity, they seem to display distinct genomic abnormalities. Clinical variables are intercorrelated and they are usually unable to predict the disease course. We aimed to analyze increased gene and protein expression in ependymomas and to correlate with patients\' clinical data. We studied patients with ependymoma submitted to surgical resections at Hospital das Clinicas, University of São Paulo, from 1996 to 2011 (33 fresh-frozen samples for gene expression analysis by quantitative real-time PCR and 149 formalin-fixed, paraffin-embedded samples, relative to 121 patients due to relapses, for protein analysis by tissue microarray immunohistochemistry). Immunohistochemical reactions were analyzed semi-quantitatively and scored with a labeling index (LI) calculated as the product of the percentage of the positively stained nuclei by the intensity of staining. Eighty-one cases were adults (mean 27.2 years). There were 60 intracranial and 61 spinal cases, of which 10 tumors were myxopapillary, 92 were grade II and 19 were grade III. Gross total resection was achieved in 62% of cases and relapse was confirmed in 41.4% of cases. We observed a shorther time to relapse in children and supratentorial intracranial tumor localization (p<0.001 for both), anaplastic histology and incomplete resections (p<0.05 for both). The following genes were selected based on public SAGE database and literature: ARMC3, CCND1, CHST5, DNALI1, FGFRL1, GNA13, IGF2, MSX1, NOTCH1 and RSPH3. ARMC3, RSHL3, CHST5 and DNALI1 presented higher expression levels in intramedullary ependymomas (p < 0.05) and FGFRL1, NOTCH1 and CCND1 in supratentorial cases (p < 0.01). IGF2 presented higher expression levels in pediatric cases and CHST5 in adults cases (p < 0.05 in both). Higher expression levels of FGFRLI1 (p < 0.05), CCND1 and IGF2 (p < 0.01 for both) were observed in anaplastic histology cases. None of the genes impacted in progression free survival or overall survival of patients. The expression of protein codified by CCND1, cyclin D1, was also evaluated by immunohistochemistry, because its overexpression has been related with several types of neoplasias and its prognostic value has not yet been fully established in ependymomas. There was a correlation of cyclin D1 expression at mRNA and protein levels (p < 0.0001). Correlations between cyclin D1 and anaplastic histology and supratentorial localization were confirmed by protein analyses (p < 0.0001 for both parameters). Additionally, high expression of cyclin D1 was observed in younger patients (p < 0.01). The higher cyclin D1 expression in supratentorial tumor localization was independent of histological grade and age of patient. Relapse was more frequent in cases with higher cyclin D1 expression levels (p < 0.05) although correlation with progression free survival was just observed in gross total resection cases (p < 0.001). Ependymomas presented differential gene expression according to age, tumor localization and histological grade in our study. Determination of cyclin D1 expression levels may be useful to guide follow-up and treatment in supratentorial cases with gross total resection

Recent research demonstrated that besides a role in sex determination and male fertility, the Y chromosome is involved in additional functions including prostate cancer, sex-specific effects on the brain and behaviour, graft-versus-host disease, nociception, aggression and autoimmune diseases. The results presented in this thesis include an analysis of sex-biased genes encoded on the X and Y chromosomes of rodents. Expression data from six different somatic tissues was analyzed and we found that the X chromosome is enriched in female biased genes and depleted of male biased ones. The second study described copy number variation (CNV) patterns in a world-wide collection of human Y chromosome samples. Contrary to expectations, duplications and not deletions were the most frequent variations. We also discovered novel CNV patterns of which some were significantly overrepresented in specific haplogroups. A substantial part of the thesis focuses on analysis of spatial expression of two Y-encoded brain-specific genes, namely PCDH11Y and NLGN4Y. The perhaps most surprising discovery was the observation that X and Y transcripts of both gene pairs are mostly expressed in different cells in human spinal cord and medulla oblongata. Also, we detected spatial expression differences for the PCDH11X gene in spinal cord. The main focus of the spatial investigations was to uncover genetically coded sexual differences in expression during early development of human central nervous system (CNS). Also, investigations of the expression profiles for 13 X and Y homolog gene pairs in human CNS, adult brain, testes and still-born chimpanzee brain samples were included. Contrary to previous studies, we found only three X-encoded genes from the 13 X/Y homologous gene pairs studied that exhibit female-bias. We also describe six novel non-coding RNAs encoded in the human MSY, some of which are polyadenylated and with conserved expression in chimpanzee brain. The description of dimorphic cellular expression patterns of X- and Y-linked genes should boost the interest in the human specific gene PCDH11Y, and draw attention to other Y-encoded genes expressed in the brain during development. This may help to elucidate the role of the Y chromosome in sex differences during early CNS development in humans.<br><p>chinese, finnish, norwegian, schizophrenia, bipolar, bipolar disorder, msy, male specific region Y, PAR1, PAR2, pseudoautosomal, male-biased, female-biased, male biased, female biased, ashkenazi population, structure, variants, YHRD, Elena Jazin, Björn Reinius, Per Ahlberg, brain, hjärna, CNS, central nervous system, IR2, inverted repeat 2, isodicentric, genetics, genetik, padlock, rolling circle, amplification, PCR, sY1191, sY1291, STS, DDX3Y, DAZ, AZFa, AZFb, AZFc, AZF, Repping, haplogroup J, rearrangements, DE-M145, I-M170, E-M96, Q-M242, R-M207, O-M175, G-M201, D-M174, C-M130, NO-M214, N-M231, poland</p>

Chronic pain affects 20 % of the global population, causes suffering, is difficult to treat, and constitutes a large economic burden for society. So far, the characterization of molecular mechanisms of chronic pain-like behaviors in animal models has not translated into effective treatments. In this thesis, consisting of five studies, pain patient biofluids were analyzed with modern proteomic methods to identify biomarker candidates that can be used to improve our understanding of the pathophysiology chronic pain and lead to more effective treatments. Paper I is a proof of concept study, where a multiplex solid phase-proximity ligation assay (SP-PLA) was applied to cerebrospinal fluid (CSF) for the first time. CSF reference protein levels and four biomarker candidates for ALS were presented. The investigated proteins were not altered by spinal cord stimulation (SCS) treatment for neuropathic pain. In Paper II, patient CSF was explored by dimethyl and label-free mass spectrometric (MS) proteomic methods. Twelve proteins, known for their roles in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity, were identified to be associated with SCS treatment of neuropathic pain. In Paper III, proximity extension assay (PEA) was used to analyze levels of 92 proteins in serum from patients one year after painful disc herniation. Patients with residual pain had significantly higher serum levels of 41 inflammatory proteins. In Paper IV, levels of 55 proteins were analyzed by a 100-plex antibody suspension bead array (ASBA) in CSF samples from two neuropathic pain patient cohorts, one cohort of fibromyalgia patients and two control cohorts. CSF protein profiles consisting of levels of apolipoprotein C1, ectonucleotide pyrophosphatase/phosphodiesterase family member 2, angiotensinogen, prostaglandin-H2 D-isomerase, neurexin-1, superoxide dismutases 1 and 3 were found to be associated with neuropathic pain and fibromyalgia. In Paper V, higher CSF levels of five chemokines and LAPTGF-beta-1were detected in two patient cohorts with neuropathic pain compared with healthy controls. In conclusion, we demonstrate that combining MS proteomic and multiplex antibody-based methods for analysis of patient biofluid samples is a viable approach for discovery of biomarker candidates for the pathophysiology and treatment of chronic pain. Several biomarker candidates possibly reflecting systemic inflammation, lipid metabolism, and neuroinflammation in different pain conditions were identified for further investigation.<br>Uppsala Berzelii Technology Centre for Neurodiagnostics

An alternating current electroosmotic micro pumping device has been designed, experimentally tested and theoretically analyzed using an electrohydrodynamic theoretical model applied to a computer simulation model. The device SP-1 is a microelectrode array which uses the principal of AC electroosmosis (EO), ions driven along microelectrode surfaces by coulomb forces produced by tangential electric fields. These ions, when driven, induce a net fluid motion due to viscous drag forces. Three submerged microelectrode wires were deposited on a substrate using microfabrication techniques such that a square spiral geometry was formed. Device SP-1 received asymmetrically applied AC signals creating a travelling wave of potential and resulted in a net fluid flow across the microelectrode array. Microsphere tracer particles were suspended in ethanol to measure the fluid velocity to determine pumping performance and the experimental operating frequency at which maximum fluid velocity is achieved. The experimental results were reviewed and at an AC signal frequency of 125 Hz, device SP-1 was capable of pumping ethanol at a fluid velocity of approximately 270 μm/s. The experimental results were in good agreement with the theoretical predictions produced using the computer simulation model. In addition, the computer simulation model predicted a similar flow profile to those previously predicted and experimentally observed. Overall, novel micropumping device SP-1 was found to produce a net flow comparable to previously tested devices and a computer simulation framework capable of analyzing future micropump design concepts was developed.<br>Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2011-04-01 17:12:02.908

碩士<br>國立高雄海洋科技大學<br>輪機工程研究所<br>92<br>As a result of ever-mounting power-to-weight ratio of a marine diesel engine, the thermal loads of a piston （involving the thermal stress and material temperatures）increased accordingly. To cope with this particular developing trend, heat transfer augmentation for the internal cooling system of piston is essential in order to assure the reliability of piston. This research program examined the heat transfer performances of a spiral cooling passage and an impingement jets array with piston cooling application. The research focused on the influences of reciprocation on the heat transfers in the spiral passage and impingement jets-array. This research implemented an experimental approach that measured the local heat transfer distributions along the spiral flow passage and over the impingement surface at reciprocating frequencies of 0, 0.83, 1.25, 1.67 and 2Hz. The heat transfer results attained from the static and reciprocating tests were compared to unravel the impact of reciprocation on the heat transfer performance. The parametric relationships between the convective heat transfer and inertial, reciprocating and buoyancy forces were subsequently performed with the aim of deriving the designer friendly heat transfer correlations for piston cooling system. Keywords： Reciprocating Spiral Tube, Reciprocating Impinging Jets-Array, Piston Cooling.

The objective of this work is to develop a near-infrared laser device capable of emitting orbital angular momentum (OAM) light. The prototyped device must be suitable for compact, energy-saving optical communication applications. Integrated OAM lasers will revolutionize high-capacity data transmission over any telecommuni- cation network environment, as OAM light can be guided and transmitted through kilometers of optical fibers and propagated in free space and underwater. Several methods for generating OAM light employing various complex monolithic and hybrid integration methods have been demonstrated. In this work, microscale integrated spiral phase plates (SPPs) are chosen to convert the laser beam output into an OAM mode. The concept and design fundamentals of SPPs are discussed, followed by the SPP fabrication process and their implementation in a high-speed communication setup and then integration with a semiconductor laser. SPPs are fabricated by a novel direct laser writing that provides the possibility to rapidly prototype 3D photonic structures via a two-photon polymerization pro- cess. After fabrication, SPPs are used in a fine-tuned free-space optical experimental setup that requires high-precision intercomponent alignment to test the high-speed OAM communication system and analyze the quality of OAM modes, resulting in high-purity OAM signals at data rates up to 1.8 Gbit/s – limited by the avalanche photodetector (APD) frequency response. The fabricated 20-μm-diameter SPPs were the smallest reported in the literature to date for optical characterization. A proof-of-concept monolithic light-emitting array, as a highly integrated OAM laser source, is further proposed for telecommunications and other applications. SPP-integrated 940-nm vertical-cavity surface-emitting laser (VCSEL) array chips that are relatively low-cost, have a small footprint, and are manufacturable in high volumes are developed. SPPs with topological charge modulus values from 1 to 3 are fabricated on the VCSEL arrays, demonstrating OAM modal purities up to ∼65%. The experimentally evaluated data rates in the OAM setup showed consistently sta- ble links up to 2.0 Gbit/s with a bit error ratio of ∼ 1.6 × 10−8 (APD-limited). The challenges of SPP-laser integration are summarized, with the conclusion that the widespread adoption of OAM is limited by the availability of practical integrated solutions for OAM generation and detection.

No<br>A compact-size asymmetrical linearly tapered slot antenna required for portable ultra-wideband (UWB) imaging systems is presented. The total antenna size is reduced compared with the conventional linearly tapered slot antenna by using a triangular slot on the left-hand side of the tapered-shaped radiator, whereas introducing a corrugated pattern of cuts on the right side. The antenna operates over a wide bandwidth extending from 3.1 to 10.6 GHz with a maximum gain of 8.5 dBi. Stable radiation patterns are observed across the operational bandwidth, with cross-polarization levels below 20 dB. The realized antenna structure occupies a volume of 35 x 36 x 0.8 mm3, and possesses the essential time domain fidelity needed for UWB imaging applications. (c) 2012 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2013.

In the last decades, ultrasound imaging systems have become more and more popular thanks to their capability to investigate tissues in safe, cost effective, and non-invasive way. Their role in diagnostic imaging has become fundamental in several medical specialties, thanks also to the introduction of advanced echographic systems fostered by the efforts of several research laboratories around the world. Such efforts are more frequently based on the use of special research scanners, characterized by flexible hardware and programmable software and firmware. These features have been demonstrated ideal for the implementation and test of new methods, such as high frame-rate (HFR) imaging, color flow imaging (CFI), vector Doppler imaging, and 3 D imaging. Especially HFR and 3 D imaging have recently attracted great interest, but they are technically demanding since they involve either the formation of thousands of images per second, or the use of 2-D probes having a large number of elements. Therefore, great challenges must be faced for effective real-time implementation of 3 D and HFR imaging methods. My PhD activity aimed to implement and test advanced 2 D and 3 D ultrasound imaging modalities on an open research scanner called ULA OP 256. In the first part of my work, a new ultrasound imaging modality called Virtual real-time (VRT) was introduced through the modification of the firmware and software of the research scanner ULA-OP 256. With this modality, during a real-time (RT) investigation, the scanner initially acquires and stores in its memory up to 20 s of raw echo data. On user demand, the scanner can be switched to VRT mode: the stored data are re processed by the same resources used in RT but at different (typically lower) rates and, possibly, with different processing algorithms and parameters. In this way, contingent difficulties of image interpretation (especially in presence of rapidly moving phenomena), or possible computational limitations imposed by hardware during continuous RT processing can be overcome. The VRT modality has been demonstrated useful in different applications, for example, to implement a high-PRF version of the Multiline vector Doppler (MLVD) method, and a High- rame-rate CFI method, characterized by enhanced temporal and spatial resolution. The second part of my work included the software upgrade of ULA OP 256; it enabled the use of 2 D probes and the implementation of 3 D scanning methods. The ULA OP 256 can now be coupled to 2 D probes with arbitrary geometries, including matrix and sparse arrays. Furthermore, the scanner is now capable of simultaneously imaging multiple planes with programmable rotational angles. Novel approaches based on a sparse spiral array probe have been implemented and tested for different applications. For example, bi-plane imaging was evaluated for robust flow mediated dilation exams. Real-time 3 D spectral Doppler analysis was also performed. Here, two planes with programmable rotational angles were scanned to produce corresponding B-Mode images, over which multiple Doppler lines could be arbitrarily set to obtain the relative Multigate spectral Doppler (MSD) profiles. Finally, the last part of my work was specifically dedicated to the technical problems involved by HFR 3 D imaging. The management of (several) hundreds of transducer elements of a 2 D probe yields a huge amount of echo data: this makes complex and computationally expensive the processing of data volumes including thousands of lines, especially if performed at HFR. As a case report, the requirements of the main processing stages involved in ULA OP 256 receiver have been thoroughly investigated to detect and, possibly, solve the main bottlenecks. The study has evidenced that the star architecture that digitally interconnects the eight front-end boards of ULA OP 256 may frequently encounter data transfer bandwidth saturation that limits the overall performance in terms of frame/volume rate. A new architecture for data transfer has been proposed and shown effective to reduce the bandwidth requirements and thus, increase the performance of the scanner.

碩士<br>國立臺灣大學<br>電子工程學研究所<br>97<br>The extraordinary light transmission of two-dimensional rectangular metallic meshes is experimentally demonstrated. The results are explained by orthogonally superimposed one-dimensional gratings. For wavelengths that are much larger than the metal strip period, the transmission spectrum of the traditional wire-grid polarizer could be modified by interconnecting wires between the strips. It performs a special filter with a stop band from excited surface current along the additional wires that causes extra resonating modes of the individual structures. The extraordinary transmission of spiral resonators is also experimentally and numerically demonstrated. It is observed that both suface plasmon modes and shape resonance modes will contribute to the enhanced transmission. The shape resonance mode is polarization dependent and will induce giant specific rotatory power. This structure gives rise to a full modulation of polarization states by a single structured metal thin film.

The goal of this study was to create pre-formed neural spheroid networks (NSN) on a polydimethyl siloxane (PDMS) concave microwell array for eventual implantation into the rat brain. Recent studies have shown that stem cells have great potential in treating various neurological insults of the central nervous system, ranging from traumatic brain and spinal cord injury, to neurodegenerative disorders. However, the use of stem cell lines in research are controversial due to the method of obtaining cells, in their formation of teratomas and degeneration into cancer cells, their non-specific differentiation, and lastly in their inability to control the location of neural connections. A novel approach to address this issue utilizes pre-formed neural networks consisting of neural spheroids on polymer scaffolds for the implantation into the rat brain. Yet, it was observed that the cylindrical shape of the wells hindered the transfer process. This study aimed to overcome the lack of neural spheroid network detachment by utilizing concave well structures, using a simple method developed in this laboratory. Primary neurons were isolated from pregnant Sprague Dawley rats at 16 ~ 17 days of gestation. Isolated neurons were cultured in PDMS wells with a concave structure and interconnected by rounded micro channels. It was reported previously that a concave structure enabled an easier and more efficient formation of spheroids, not to mention the ease in extraction of spheroid cells. Various studies have demonstrated the effectiveness of guidance channels in promoting neurite growth. Therefore, micro channels were integrated in the micro array design, and served as a guidance conduit to enhance neurite growth, and by association, spheroid interconnection. The primary neurons formed a spheroid structure after 3 days, upon which they began to sprout new neurites. By day 8, neurite connections peaked. Spheroid diameter underwent an initial decrease then stabilized on day 2. Various well diameters (300~700 um) and channel lengths (1.5 x diameter ~ 3 x diameter) were evaluated, with a 300 um well diameter and 450 um center-to-center channel length found to be optimal. The completed network was assessed for interconnection using calcium imaging and showed coordinated calcium signals between the neural spheroids. The network was then successfully transferred to a collagen matrigel and cultured for a week. The methodology showed an improvement in the transfer of networks, with about a 90% extraction rate. The viability of the NSN on the matrigel was assessed using a Live/Dead assay, and cells were found to have greater than 95% viability. The optimal hydrophilicity was determined for neurite extension and transfer of NSNs onto the matrigel. It was found that an incubation time between 4~6 hours was optimal. Future studies will involve the implantation of the NSN into the rat brain. Additionally, the use of neural progenitor and stem cell lines may provide an autologous source of cells which are immunocompatible with the host. In particular, marrow stromal cells are interesting in that they may also address the ethical concerns. A long term goal is to refine the methodology and apply this research to enable studies in the treatment of patients suffering from spinal cord injury and other neurodegenerative disorders.

No<br>An experimental study of coupling compensation for AOA estimation using compact low profile antenna arrays with element separations of a quarter wavelength has been conducted. Two circular arrays of low profile miniaturised logarithmic spiral antennas deployed on a circular metal plate were used for data acquisition. Using the MUSIC direction-finding algorithm, the AOA estimation errors in receiving mode were observed before and after compensation: the errors were significantly decreased by coupling compensation.<br>The full text is unavailable. The publisher is unable to be contacted.