There has been a constant need for low power techniques to achieve high performance at the lowest possible power dissipation. Lots of works have been done to achieve this target. These works have focused on the different aspects of power reduction. One of these aspects of power saving is Dynamic power reduction. This thesis work is focused on this aspect of power saving by reducing the unnecessary transitioning in the circuit. To achieve this, new method called data gating, is proposed here which stops unnecessary toggling in the circuit using different forms of gating mechanisms. This thesis is organized as follows; first chapter is about the low power design of CMOS circuits. That chapter covers the sources of power dissipation in ICs as well as the techniques that have been used to minimize the power consumption. Second chapter talks more about dynamic power consumption. Techniques used for reducing dynamic power consumption through reduction in switching activities are mentioned in that chapter. Also the new technique, Data Gating, to reduce dynamic power is proposed in second chapter. Third chapter talks about simulation setup, tools used for simulation. Results obtained from different simulations are presented in that chapter. Fourth Chapter is about the analysis of simulation results. It also outlines some possible limitations of the proposed method as well as certain points that need to be considered before applying new technique. Fifth and final chapter summarizes the conclusion and possible future work that can be done to enhance the proposed technique, Data Gating. / text

During skeletal muscle stimulation, there is a summation of local events of Ca2+ release from the sarcoplasmic reticulum, known as Ca2+ sparks. Ca2+ sparks originate from groups of skeletal ryanodine receptors (RyR1) that activate and close in synchrony. This synchrony allows for the rapid and massive release of Ca2+ from the sarcoplasmic reticulum to initiate contraction and, more important, would provide a mechanism to terminate Ca2+ release under conditions where independent RyR1 are normally active. RyR1 mutations can result in abnormal intracellular Ca2+ signaling that is associated with numerous skeletal muscle disorders including malignant hyperthermia and central core disease. Therefore, investigating the mechanisms that control RyR1 function can help identify how these mutations cause deleterious Ca2+ handling. Currently, most published research on RyR1s gating utilizes single RyR1 reconstituted into planar lipid bilayers to test isolated RyR1. However, in vivo, arrays of RyR1 function in synchrony. Attempts to reconstitute RyR1s into planar lipid bilayers result in experiments that contain multiple channels, which under specific conditions may gate in synchrony, also known as coupled gating. Coupled RyR1 gating was first reported by A. Marks' laboratory and attributed to FK-506 binding protein 12 (FKBP12) associating with neighboring RyR1s the stabilization of RyR1-RyR1 interactions that promote coupled gating. Previous studies suggested that ATP is required for coupled RyR1 gating; however, the mechanism by which ATP promotes the coordinated activity of RyR1s has not been elucidated and is the focus of this thesis. Therefore, my hypothesis is that the agonist action of ATP and FKBP12 bound to RyR1 are required for coupled RyR1 gating. In addition, new pharmacological tools are required to better understand coupled RyR gating. Thus, an additional goal is to identify pharmacological agents that modulate RyR1s in an innovative manner, i.e., help to uncover novel aspects of RyR1 gating and conduction. This investigation suggests that the adenosine based nucleotides, ATP, ADP and AMP, are agonists of RyR1s and promote coupled RyR1 gating in planar lipid bilayers. However, ADP and AMP were unable to maintain coupled RyR1 gating with physiological levels of Mg2+. This suggests that coupled gating would be impaired when the levels ATP decrease, as in muscle fatigue. When ATP was compared to other nucleotides (GTP, ITP, and TTP), the results suggest that the nucleotide agonist action on RyR1s is dependent on the phosphate groups and amino group on the nucleobase. As ATP is the most efficient nucleotide for coupled gating, I also investigated the indirect action of ATP to act as a kinase substrate or alter the cytoskeletal network. The addition of kinases, phosphatases and cytoskeletal modulators did not produce a significant disruption of coupled RyR1 gating. I also tested the role of addition of exogenous FKBP12 to RyR1s that gated independently or had partial coupling, but coupled gating was never improved. Also, the addition of high doses of rapamycin to remove FKBP12 from coupled RyR1 failed to functionally uncouple the channels. Finally, I attempted to find pharmacological agents that could aid in the understanding of coupled RyR1. Some agents were found to modulate RyR1s; however, I did not find a probe that would affect kinetics/conductance of RyR1s and was suitable for comparing coupled gating in bilayers with Ca2+ sparks in cells. Overall, coupled RyR gating is dependent on the physiological modulators ATP and Mg2+. This thesis represents a step forward in identifying the requirements for coupled RyR1 gating and understanding how RyR1s function in cells. Until an understanding of how these receptors communicate in cells is obtained, how different mutations alter the Ca2+ leak will continue to be quite difficult to study.

Ce travail de recherche est basé sur la technologie Ultra Large Bande (ULB), en particulier pour des applications bas débit (standard IEEE 802.15.4) tels que les réseaux de capteurs, les transmissions WPAN ou encore WBAN. La modélisation et la conception d’un récepteur non cohérent ULB pour les communications radio impulsionnelles ont été réalisées. Un des facteurs les plus importants dans les communications ULB est la sensibilité du récepteur, qui détermine la portée de transmission maximale. Un autre facteur aussi important est la consommation d’énergie qui influence directement la durée de vie de la source d’alimentation (batterie). Dans ce contexte, nous présentons dans le chapitre I une introduction sur la technologie ULB et ses diverses applications. Le chapitre II présente la modélisation au niveau système ainsi que d’une étude comparative des récepteurs non cohérents basés sur la détection d’énergie et la pseudo-Détection d’énergie. Dans le chapitre III sont présentés la méthode de conception et de réalisation d’un récepteur non cohérent ULB dans la bande de 3-5 GHz, ainsi que les résultats de mesure et ses performances en termes de sensibilité et de consommation d’énergie. Finalement, le chapitre IV présente une étude théorique sur les différents modes de fonctionnement du transistor MOS afin de mieux comprendre le fonctionnement de chaque bloc du récepteur. Cela permet de proposer de nouvelles architectures pour la détection d’énergie. Enfin, à partir de ces études nous réalisons l’optimisation du récepteur en termes de sensibilité et de consommation d’énergie. / This research is based on Ultra Wide Band (UWB) technology, in particularly for low-Rate applications such as sensor network, WPAN and WBAN (for the standard IEEE 802.15.4). The model and design of a non coherent receiver for UWB impulse radio communications has been completed. One of the most important factors in the UWB communications is the receiver sensitivity which determines the maximum transmission range. Another important factor is the energy consumption that determines the lifetime of the power source (battery). In this context, we present in Chapter I an introduction to UWB technology and its different applications. Chapter II deals with a modeling at the system level of non-Coherent receivers as well as a comparative study based on the energy detection and pseudo energy detection. In Chapter III is presented the method of design and implementation of a non-Coherent UWB receiver in the band of 3-5 GHz, as well as measurement results and performance in terms of sensitivity and power consumption. Finally, Chapter IV presents a theoretical study on the different modes of operation of the MOS transistor to understand the operation of each block of the receiver. This allows us to show the new architectures for energy detection and perform the optimization of receiver in terms of sensitivity and power consumption.

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Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [114]-128).

Cys-loop receptors are membrane proteins that are key players for the fast synaptic neurotransmission. Their ion transport initiates new nerve signals after activation by small agonist molecules, but this function is also highly sensitive to allosteric modulation by a number of compounds such as anesthetics, alcohol or anti-parasitic agents. For a long time, these modulators were believed to act primarily on the membrane, but the availability of high- resolution structures has made it possible to identify several binding sites in the transmembrane domains of the ion channels. It is known that ligand binding in the extracellular domain causes a conformational earthquake that interacts with the transmembrane domain, which leads to channel opening. The investigations carried out in this thesis aim at understanding the connection between ligand binding and channel opening. I present new models of the mammalian GABAA receptor based on the eukaryotic structure GluCl co-crystallized with an anti-parasitic agent, and show how these models can be used to study receptor-modulator interactions. I also show how removal of the bound modulator leads to gradual closing of the channel in molecular dynamics simulations. In contrast, simulations of the receptor with both the agonist and the modulator remain stable in an open-like conformation. This makes it possible to extract several key interactions, and I propose mechanisms for how the extracellular domain motion is initiated. The rapid increase in the number of cys-loop receptor structures the last few years has further made it possible to use principal component analysis (PCA) to create low-dimensional descriptions of the conformational landscape. By performing PCA on the crystal structure ensemble, I have been able to divide the structures into functional clusters and sample the transitions between them using various sampling methods. The studies presented in this thesis contribute to our understanding of the gating mechanism and the functional clustering of the cys-loop receptor structures, which both are important to design new allosteric modulator drugs that influence the channel function, in particular to treat neurological disorders. / <p>QC 20160518</p>

A series of rapid, high sensitivity capillary electrophoresis (CE) separation systems have been developed for the analysis of biological analytes and systems. A majority of the work has focused on development of novel instrumentation, in which new injection and detection strategies were investigated to improve the sensitivity of fast CE. A novel optical injection interface for capillary zone electrophoresis based upon the photophysical activation of caged dye attached to the target analyte was developed. The primary advantage of this approach is the lower background and background-associated noise resulting from reduced caged-fluorescein emission in conjunction with the high quantum yield of the resulting fluorescein. Improved detection limits were obtained compared to those observed in photobleaching-based optical gating. A primary drawback of photolytic optical gating CE is the lack of available caged-dye analogs with sufficiently fast reaction kinetics for online derivatization. To overcome this limitation, we have developed a chemical derivatization scheme for primary amines that couples the fast kinetic properties of o-phthaldialdehyde (OPA) with the photophysical properties of visible, high quantum yield, fluorescent dyes. The feasibility of this approach was evaluated by using an OPA/fluorescent thiol reaction, which was used to monitor neurotransmitter mixtures and proteins. The utilization of a high power ultraviolet light emitting diode for fluorescence detection in CE separations has been introduced to analyze a range of environmentally and biologically important compounds, including polyaromatic hydrocarbons and biogenic amines, such as neurotransmitters, amino acids and proteins, that have been derivatized with UV-excited fluorogenic labels. To understand cellular chemistry, it is imperative that single cells should be studied. This work was focused on developing CE based method to characterize the cellular uptake of TAT-EGFP. We demonstrated TAT mediated delivery of EGFP protein into HeLa cells and TAT-EGFP loaded single cell was analyzed by CE-LIF to determine the intracellular EGFP content. An application of CE-LIF for the determination of biogenic amine levels in the antennal lobes of the Manduca sexta is also explored and methods were developed to analyze a single antennal lobe dissected from moths. The lobe was digested and contents were labeled with the fluorogenic dye prior to CZE analysis.

Ten to 15% of the population is temperamentally shy and have elevated physiological stress responses to novel social situations. Yet, the neural mechanisms underlying this personality trait are not fully understood (Beaton et al., 2009; Schmidt et al., 1997). Efficiently attending to, acting on, and remembering relevant stimuli and filtering out less important information is critical given the sheer volume of sensory and perceptual stimuli the brain is exposed to. Relevant stimuli that garner attention are remembered and consolidated with existing memories. Stimuli that do not warrant extended attention are ignored or habituated to in a process underpinned by cortical and subcortical inhibitory brain networks that reduce processing load on finite attentional resources (Freedman et al., 1991; Adler et al., 1998). Inefficient filtering of irrelevant stimuli could underpin anxiety in those with temperamental shyness and anxiety (Aron, Aron, & Davies, 2005). We measured the P50 auditory event-related potential (ERP) using a paired auditory click paradigm, as well as self-reported social anxiety and shyness, and salivary cortisol in two groups of healthy young adults selected for being very shy or very gregarious. While shy and gregarious groups demonstrated a similar P50 ERP to sound one (S1), the shy group showed elevated P50 amplitudes in response to the second sound (S2) compared to the gregarious group. Participants categorized as being lower or higher on social anxiety displayed a reverse pattern: those higher in social anxiety had a reduced response to S1 compared to those lower in social anxiety, yet a similar response to S2. Further, higher salivary cortisol predicted smaller differences and larger ratios in the P50 ERP from S1 to S2.