This research explores two issues when implementing drain-source voltage sensed synchronous rectification (SR) on LLC DC-Transformers (DCXs). Firstly, a current resonance issue caused by the SR controller, and secondly a early turn-off issue from parasitics present in the drain-source sensing path. Two novel methods are proposed to solve the early turn-off issue, and an FPGA based solution is built to validate and fix the resonance issue. Simulations are run to quantify the amount of rectifier power savings possible with the proposed solutions. / Master of Science / This research explores issues and improvements in synchronous rectifiers used in resonant based power conversion circuits. The two issues explored hurt rectifier efficiency, and thus total power conversion circuit efficiency. Implementation issues are identified, simulated, and new solutions are proposed. Simulations are run to quantify the amount of power savings is possible.

Les Glioblastomes (Gb) sont des tumeurs primaires du SNC les plus fréquentes et sont particulièrement agressives car résistantes à la radio/chimiothérapie. Elles présentent généralement une composante solide et infiltrante. Cette dernière étant difficile à éliminer par la chirurgie sera en partie responsable de la récurrence de la tumeur. Une des avancées majeures du domaine est la mise en évidence dans les Gb de sous populations présentant des caractéristiques de précurseurs neuraux. Ces cellules cancéreuses utilisent des réseaux de gènes spécifiques pour maintenir leur prolifération et leur état indifférencié. Une approche possible pour éliminer ces cellules cancéreuses serait de cibler les facteurs de transcription impliqués dans la prolifération ou encore de forcer leur différenciation. Dans ce but, j'ai étudié le rôle de NKX2.2 et NGN2 à partir de 3 cultures primaires multipotentes. Les résultats montrent que l'expression de NKX2.2 dans ces cultures est nécessaire pour la survie, la prolifération et la capacité à former des neurosphères. A l'inverse, la surexpression de NGN2 conduit à une apoptose massive, à un arrêt de la prolifération avec formation de neurones dont certains sont électrophysiologiquement actifs. Une approche différente consisterait à cibler une des protéines impliquées dans la migration pour limiter la composante infiltrante. Des études antérieures ont montrées un rôle clef de DCX dans la migration des jeunes neurones au cours du développement. La forte expression de DCX dans certains Gb m'a conduit à étudier la régulation et le rôle de ce gène. In vitro, les résultats obtenus montrent que DCX est exprimé par une sous population de cellules. La purification des cellules Dcx+ ainsi qu'une étude clonale a permis de montrer qu'elles se comportent comme des progéniteurs multipotents avec une capacité d'autorenouvellement restreinte. Par ailleurs, j'ai montré que les cellules Dcx+ peuvent réverter vers un état Dcx- et que le gène Dcx est régulé par les voies NOTCH et SHH. / Glioblastomas (GB) are the most common primary tumors of the CNS and are particularly resistant to radio/chemotherapy. They generally have a solid and infiltrative component. The latter being difficult to remove by surgery will be partly responsible for tumor recurrence. One of the major advances in the field is highlighted in the Gb of subpopulations with features of neural precursors. Cancer cells use specific gene networks to maintain their proliferation and undifferentiated state. One approach to eliminate these cancer cells would be to target transcription factors involved in the proliferation or to force their differentiation. To this end, I studied the role of NKX2.2 and NGN2 from 3 primary multipotent cultures. The results show that NKX2.2 expression in these cultures is necessary for survival, proliferation and ability to form neurospheres. Conversely, overexpression of NGN2 led to massive apoptosis, proliferation arrest with formation of neurons, some of which are electrophysiologically active. A different approach would be to target proteins involved in migration to limit the invasive component. Previous studies have shown a key role of DCX in the migration of young neurons during development. The strong expression of DCX in some Gb led me to study the regulation and the role of this gene. In vitro, the results show that DCX is expressed by a subpopulation of cells. Purification of Dcx+ cells and clonal study has shown that they behave as multipotent progenitors with limited self-renewal capacity. I also found that Dcx+ cells can revert back to a Dcx- state and that DCX is regulated by SHH and NOTCH pathways.

With lower output voltage (lower than 1V) and higher output current (more than 160A) required in the near future, the voltage regulators for the microprocessors, a kind of special power supplies are facing more and more critical challenges to achieve high efficiency and high power density. 90% plus efficiency for CPU VRs is expected from industry not only for the thermal management, but also for saving on electricity costs, especially for the large data-center systems. At the same time, high power density VRs are also desired due to the increasing power consumption of microprocessors as well as the precious space on CPU motherboard. Current multi-phase Buck VR has its limitation to achieve 90% plus efficiency. With the state of art devices, the single-stage 12V/1.2V 600kHz Buck VR achieves 85% to 86% efficiency at full load condition. In addition, for the future lower output voltage application, the Buck efficiency will drop another 3~4% due to the extreme small duty cycle. From the power density point of view, due to the switching frequency limitation (normally, from 300 kHz to 600 kHz for typical CPU VRs) for acceptable efficiency performance, the multi-phase Buck VR is unable to ensure a small size since it needs bulky output capacitors to meet the challenging transient requirement as well as the output impedance requirement with relatively low bandwidth design. To attain high efficiency and high power density at the same time, in-series two-stage power architecture was proposed. By cutting the single stage into two and utilizing the low voltage devices, the in-series two stages can achieve around 87% efficiency which is similar as single stage with second-stage operating at 1 MHz for less cost. Compared with the in-series one, the other two-stage power architecture is called "Sigma" architecture which is composed by an unregulated converter (DCX) and a regulated buck converter, with a special connection where the inputs are in series while outputs are paralleled. Through this topology, unlike the in-series two-stage where both two stages deliver the full load power, the power will be distributed between unregulated DCX and regulated Buck. If the unregulated DCX can achieve high efficiency, let most power be handled by it and just small power from buck, the Sigma architecture can achieve high efficiency performance based on this concept. The design consideration and process had been investigated by CPES previous graduates. By the designed 1.2V/120A Sigma VR circuit, approaching 90% efficiency was achieved which is around 3~4% efficiency higher than state of the art multi-phase Buck VR. However, it is not the optimal design for best efficiency performance, the improvement methods for higher efficiency is deeply considered and the efficiency potential benefit of this special structure will be clarified in this thesis. Besides the efficiency interest, transient performance of Sigma VR is also a challenging issue needed to be addressed. The state of the art Buck VR needs a bunch of output bulk capacitors to meet the stringent output impedance requirement from Intel and those output bulk capacitors occupy too much space in the motherboard. For Sigma architecture, through the help of the low impedance DCX which can achieve faster current dynamic response, some low voltage bulk capacitors could be replaced by smaller input high voltage capacitors. It is still not clear for us to identify how input capacitor impacts the DCX dynamic current response and how to best choose this impact factor. This thesis will investigate the faster DCX dynamic current performance of Sigma VR, and explain the dynamic impacts from input capacitors, from control design and from DCX impedance Lout. The high voltage capacitors could provide energy through low impedance DCX to deal with the transient load with smaller capacitance, resulting less total cost and footprint with conventional Buck solution. Low impedance DCX is also a desire for achieving fast current response for providing a "non-obstacle" path when energy transferring from input capacitors. The control also has the impact to the DCX current response when the bandwidth is higher than certain frequency. The transient benefit will also be discussed from impedance perspective. In order to improve the efficiency and power density of Sigma VR, several methods are proposed. As a critical component of DCX, the transformer design determines the performance of Sigma VR both to efficiency and power density. By optimizing the transformer design to achieve lower winding loss and smaller leakage inductance, the higher efficiency and faster transient DCX can be obtained. Changing the output capacitors to ceramic ones is helpful when control bandwidth is greater than 100 kHz for both lower cost and smaller footprint. Continually pushing bandwidth can reduce the required output ceramic capacitor number further. In addition, from the study of the loss breakdown, by adjusting the energy ratio of DCX and Buck can achieve higher efficiency based on current device level. What is more, with the same simple concept of adjusting power ratio of DCX and Buck, with the development of devices in the future as well as higher efficiency DCX, Sigma architecture will be more attractive for future's lower output voltage VR application. And it will also be more efficient considering higher than 12V input bus voltage by letting high efficiency DCX handle more power. Utilizing this characteristic, changing the power system delivery architecture from AC input to the microprocessors, the end to end efficiency could be improved. / Master of Science

Made available in DSpace on 2014-12-17T15:28:51Z (GMT). No. of bitstreams: 1 BrunaSL_DISSERT.pdf: 1891001 bytes, checksum: 1d482b920c53ec1f846060dbc2158ebb (MD5) Previous issue date: 2012-08-10 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The cerebral cortex of mammals is histologically organized into different layers of excitatory neurons that have distinct patterns of connections with cortical or subcortical targets. During development, these cortical layers are established through an intricate combination of neuronal specification and migration in a radial pattern known as "insideout": deep-layer neurons are generated prior to upper-layer neurons. In the last few decades, several genes encoding transcription factors involved in the sequential specification of neurons destined to different cortical layers have been identified. However, the influence of early-generated neurons in the specification of subsequent neuronal cohorts remains unclear. To investigate this possible influence, we induced the selective death of cortical neurons from layer V and VI before the generation of layer II, III and IV neurons. Thus, we can evaluate the effects of ablation of early born neurons on the phenotype of late born neurons. Our data shows that one-day after ablation, layer VI neurons expressing the transcription factor TBR1 are newly generated while virtually no neuron expressing TBR1 was generated in the same age in control animals. This suggests that progenitors involved in the generation of neurons destined for superficial layers suffer interference from the selective death of neurons in deep layers, changing their specification. We also observed that while TBR1-positive neurons are located exclusively in deep cortical layers of control animals, many TBR1-positive neurons are misplaced in superficial layers of ablated animals, suggesting that the migration of cortical neurons could be controlled independently of neuronal phenotypes. Furthermore, we observed an increase in layer V neurons expressing CTIP2 and neurons expressing SATB2 and that these cells have changed their distributions. As a conclusion, our data indicate the existence of a mechanism of control exercised by the early-generated neurons in the cerebral cortex on the fate of the progenitors involved in the generation of the following cortical neurons. This mechanism could help to control the number of neurons in different layers and contribute to the establishment of different cortical areas / O c?rtex cerebral de mam?feros encontra-se histologicamente organizado em camadas de neur?nios excitat?rios que, por sua vez, apresentam distintos padr?es de conectividade com alvos corticais ou sub-corticais. Durante o desenvolvimento, estas camadas corticais s?o estabelecidas atrav?s de uma intrincada combina??o entre especifica??o neuronal e migra??o radial num padr?o conhecido como "inside-out" (de dentro para fora). Desta forma, por exemplo, neur?nios infragranulares nas camadas V e VI s?o gerados anteriormente aos neur?nios granulares da camada IV, que por sua vez s?o gerados antes dos supra-granulares das camadas II e III. Na ?ltima d?cada, foram identificados diversos genes codificando fatores de transcri??o envolvidos na especifica??o sequencial de neur?nios destinados ?s diferentes camadas corticais. No entanto, ainda pouco ? sabido sobre a influ?ncia dos neur?nios gerados previamente sobre a especifica??o das coortes neuronais subsequentes. Para investigar esta poss?vel influ?ncia, n?s utilizamos um m?todo de recombina??o g?nica (sistema Cre- Lox) para induzir a morte seletiva de neur?nios das camadas corticais V e VI antes da gera??o dos neur?nios das camadas II, III e IV. Dessa forma, pudemos avaliar os efeitos da abla??o de neur?nios infragranulares sobre o fen?tipo dos neur?nios gerados em seguida. Nossos dados mostraram que, um dia ap?s a abla??o, neur?nios da camada VI expressando o fator de transcri??o TBR1 voltaram a ser gerados enquanto praticamente nenhum neur?nio expressando TBR1 foi gerado na mesma idade em animais controle. Esse dado sugere que os progenitores envolvidos na gera??o de neur?nios destinados ?s camadas superficiais sofrem interfer?ncia da morte seletiva de neur?nios de camadas profundas, mudando sua especifica??o. Uma parte dos neur?nios TBR1 se estabeleceu na camada VI e outra migrou at? as camadas II e III, indicando que o controle dos padr?es migrat?rios pode ser independente dos fen?tipos neuronais. Al?m disso, observamos que na popula??o neuronal total tamb?m ocorreu um aumento na quantidade de neur?nios de camada V expressando CTIP2 e uma altera??o na distribui??o dessas c?lulas. O mesmo foi observado para neur?nios supragranulares expressando SATB2. Em conjunto, nossos dados indicam a exist?ncia de um mecanismo de controle exercido pelos neur?nios gerados inicialmente no c?rtex cerebral sobre o destino dos progenitores envolvidos na gera??o dos demais neur?nios corticais. Tal mecanismo poderia contribuir para o controle do n?mero de neur?nios em diferentes camadas e contribuir para o estabelecimento de diferentes ?reas corticais

Neuronal Nuclei (NeuN) and Doublecortin (DCX) are neuron specific proteins that are used in histological studies of brain structure in a variety of vertebrate taxa.Antibodies against NeuN (anti-NeuN) bind to the Fox-3 protein, an RNA binding protein common in mature neurons. Anti-DCX labels a microtubule-associated protein expressed in actively dividing neural progenitor cells and migrating neurons. The DCX gene encodes a protein that is well conserved across mammalian, avian, and a few reptilian species, therefore anti-DCX staining has been used successfully across a range of vertebrate taxa. Successful neuronal staining using anti-NeuN has been demonstrated in mammals, birds, and the Testudines order (turtles). However, herpetologists who study neurobiology in squamates have had limited success with anti-NeuN and anti-DCX binding to their respective antigens. All commercially available anti-NeuN and anti-DCX antiserums were designed to mammalian antigens, and significant differences in tertiary structure divergence at the epitope where these antibodies bind may explain the failure of anti-NeuN and anti-DCX immunohistochemistry in many squamate species. This study aims to characterize evolutionary differences in gene and protein structure between two species of reptiles (Crotalus oreganus and Sceloporus occidentalis) and mammals. We sequenced the Fox-3 and DCX coding sequences using polymerase chain reaction (PCR) and Sanger sequencing, which allowed us to build phylogenetic trees comparing Fox-3 and DCX deduced protein structures. By identifying structural differences linked to evolutionary variation, new polyclonal antibodies specifically targeting Fox-3 and DCX in reptile brains can be developed to facilitate future investigations of neurogenesis and brain structure in squamate reptiles.

An ever present trend in the power conversion industry is to get higher performance at a lower cost. In a computer server system, the front-end converter, supplying the load subsystems, is typically a multiple output power supply. The power supply unit is custom designed and its output voltages are fully regulated, so it is not very efficient or cost effective. Most of the load systems in this application are supplied by point-of-load converters (POLs). By leaving the output voltage regulation aspect to POLs, the front-end converter does not need to be a fully regulated, multiple output converter. It can be replaced by a dc-dc transformer (DCX), which is a semi-regulated or unregulated, single output dc-dc converter. A DCX can be made using a modular design to simplify expansion of the system capacity. To realize this concept, the DCX block must have a current sharing feature. The current sharing method for a resonant DCX is discussed in this work. To simplify the system architecture, the current sharing method is based on the droop method, which requires no communication between paralleled units. With this method, the current sharing error is inversely proportional to the droop voltage. In traditional DCX implementations, the droop voltage depends on the resistive voltage drops in the power stage, which is not sufficient to achieve the desired current sharing error. The resonant converter has the inherent characteristic that its conversion gain depends on the load current, so the virtual droop resistance can realized by the resonant tank and the droop voltage can be obtained without incurring conduction loss. An LLC resonant converter is investigated for its droop characteristic. The study shows the required droop voltage is achievable at very high switching frequency. To lower the switching frequency, a notch filter is introduced into the LLC resonant tank to increase the sensitivity of the conversion gain versus the operating frequency. The design of the multi-element resonant tank is discussed. Depending soly on the resonant tank, the droop characteristic is largely varied with the component tolerance in the resonant tank. The current sharing error becomes unacceptable. The active droop control is imposed to make the output regulation characteristic insensitive to the component tolerance. The proposed resonant DCX has simpler circuit structure than the fully regulated resonant converter. Finally simulation and experimental results are presented to verify this concept. / Master of Science

L'hétérotopie en bande sous-corticale (SBH) est une malformation caractérisée par la présence d'une bande de neurones ectopiques en regard du cortex normal ou normotopique. La plupart des patients ont une mutation d'un gène encodant une protéine indispensable à la migration des neurones. Les patients présentent une épilepsie pharmacorésistante. La chirurgie ne donne pas de résultats satisfaisants, le foyer épileptogène n'étant jamais clairement délimité. Un modèle de rat reproduisant les caractéristiques observées chez les patients à pu être généré. Même s'il est clair que le cortex normotopique et l'hétérotopie participent aux évènements épileptiformes, leur zone de genèse reste néanmoins inconnue. Le but de cette thèse a été de localiser l'origine de l'activité épileptiforme in vitro sur tranches de cerveau à l'aide d'une technique d'enregistrement multisite.Des activités épileptiformes (ILEs) ont été enregistrées à l'aide d'une technique d'enregistrement extracellulaire multisite à 60 canaux. Un outil d'analyse développé sous Matlab a ensuite permis de caractériser les ILEs et notamment leur origine et étendues spatiales. Après avoir identifié l'importance du cortex normotopique dans la genèse des ILEs, nous en avons supprimé l'excitabilité in vivo. Nous montrons que la surexpression de ces canaux dans les neurones ectopiques n'altère pas la susceptibilité aux crises des animaux concernés alors que la surexpression de ces canaux dans l'hétérotopie et dans le cortex normotopique améliore le phénotype épileptique. Nos résultats suggèrent ainsi un rôle majeur du cortex normotopique dans la genèse des activités épileptiques dans le syndrome du double cortex. / Subcortical Band Heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats.Rats with SBH were generated by knocking‐down the Dcx gene into neocortical progenitors of rat embryos. Origin, spatial extent and laminar profile of bicuculline‐induced interictal‐like activity on neocortical slices were analyzed by using extracellular recordings from 60‐channels microelectrode arrays. Susceptibility to pentylenetetrazole‐induced seizures was assessed by electrocorticography in head‐restrained nonanaesthetized rats. We show that the band heterotopia does not constitute a primary origin for interictal‐like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Further, we report that most interictal‐like discharges originating in the overlying cortex secondarily propagates to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx‐KD rats to display seizures. These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.

Previous research on the relationship between spatial memory and adult hippocampal neurogenesis has been controversial. In the present study, neurogenesis was compared between two natural populations of the same species that differ in their reliance on spatial memory to cache and retrieve stored food. Western red squirrels store food in a single site whereas eastern red squirrels store food in multiple sites. Neurogenesis was assessed using endogenous markers of the number of proliferating cells (Ki-67) and the number of immature neurons (DCX), and neuronal recruitment was determined by measuring the area of the dentate gyrus of the hippocampus. The number of proliferating cells, immature neurons and neuronal recruitment were enhanced in the eastern compared to the western red squirrels, reflecting the food storing strategies used by the squirrels. This suggests that there is a positive correlation between adult hippocampal neurogenesis and spatial learning and memory.

Previous research on the relationship between spatial memory and adult hippocampal neurogenesis has been controversial. In the present study, neurogenesis was compared between two natural populations of the same species that differ in their reliance on spatial memory to cache and retrieve stored food. Western red squirrels store food in a single site whereas eastern red squirrels store food in multiple sites. Neurogenesis was assessed using endogenous markers of the number of proliferating cells (Ki-67) and the number of immature neurons (DCX), and neuronal recruitment was determined by measuring the area of the dentate gyrus of the hippocampus. The number of proliferating cells, immature neurons and neuronal recruitment were enhanced in the eastern compared to the western red squirrels, reflecting the food storing strategies used by the squirrels. This suggests that there is a positive correlation between adult hippocampal neurogenesis and spatial learning and memory.

La migration radiaire est un des processus clefs de la corticogenèse menant à l’établissement d’un cortex en six couches chez les mammifères. La compréhension de ce mécanisme complexe est nécessaire à une meilleure appréhension du développement cortical. Dans ce travail de thèse, j’ai étudié la migration des neurones pyramidaux du cortex sous deux angles distincts. La 1ère partie se place d’un point de vue développemental en appréciant comment le positionnement laminaire résultant d’une migration normale ou anormale affecte la maturation neuronale. La 2nde partie se concentre sur une pathologie migratoire, l’hétérotopie en bande sous-corticale, et les altérations cognitives parfois associées à cette malformation. Pour ces deux projets, la migration neuronale a été altérée chez le rat par knockdown (KD) in utero de la doublecortine (Dcx), un effecteur majeur de la migration. Les neurones positionnés anormalement présentent une orientation incorrecte, un arbre dendritique moins développé, une spinogenère réduite et une altération morpho-fonctionnelle de la synaptogenèse glutamatergique. De plus, notre étude a mis en évidence l’implication de Dcx dans la dendritogenèse et la régulation fine des synapses glutamatergiques in vivo. Enfin, nous avons utilisé les rats Dcx-KD comme modèle d’hétérotopie en bande afin d’étudier comment un déficit de migration neuronale impacte le fonctionnement du cortex. La caractérisation comportementale, réalisée à l’aide d’une large gamme de tests, n’a pas mis en évidence de déficits majeurs des capacités motrices, somatosensorielles ou cognitives chez ces animaux. / Radial migration is one of the key processes leading to the formation of a six-layered cortex in mammals. Understanding this mechanism is necessary to get a better grasp of cortical development. During my PhD, I studied neuronal migration of pyramidal neurons from two different points of views. The 1st part is related to fundamental biology and assesses how laminar misplacement resulting from migration failure influences neuronal maturation. The 2nd one focuses on pathology by investigating a migration disorder, subcortical band heterotopia, and associated cognitive deficits. For both projects, neuronal migration was impaired in rat through in utero knockdown (KD) of doublecortin (Dcx), a major effector of cortical migration. Misplaced neurons display an abnormal orientation, a simplified dendritic arbor, a decreased spinogenesis and morpho-functional alterations of glutamatergic synaptogenesis. Moreover, our study shows that Dcx plays a role in dendritogenesis, in shaping spine morphology and in fine-tuning glutamatergic synaptogenesis. Finally, we used Dcx-KD rats as an animal model of subcortical band heterotopia to assess how migration failure would impact cortical functions. The behavioral characterization carried out through a wide range of tests did not bring to light any major shortcoming regarding motor, somatosensory or cognitive abilities in these animals. Therefore, although Dcx-KD rats display a SBH and develop spontaneous seizures, it does not seem to recapitulate cognitive deficits found in patients.