Parallel Processing for VLSI CAD Applications a Tutorial

Coordinated Science Laboratory was formerly known as Control Systems LaboratorySemiconductor Research CorporationAuthor's name appears in front matter as Prithviraj Banerje

A Self Assembled Nanoelectronic Quantum Computer Based on the Rashba Effect in Quantum Dots

Quantum computers promise vastly enhanced computational power and an uncanny ability to solve classically intractable problems. However, few proposals exist for robust, solid state implementation of such computers where the quantum gates are sufficiently miniaturized to have nanometer-scale dimensions. Here I present a new approach whereby a complete computer with nanoscale gates might be self-assembled using chemical synthesis. Specifically, I demonstrate how to self-assemble the fundamental unit of this quantum computer - a 2-qubit universal quantum controlled-NOT gate - based on two exchange coupled multilayered quantum dots. Then I show how these gates can be wired using thiolated conjugated molecules as electrical connectors. A qubit is encoded in the ground state of a quantum dot spin-split by the Rashba interaction. Arbitrary qubit rotations are effected by bringing the spin splitting energy in a target quantum dot in resonance with a global ac magnetic field by applying a potential pulse of appropriate amplitude and duration to the dot. The controlled dynamics of the 2-qubit controlled-NOT operation (XOR) can be realized by exploiting the exchange coupling with the nearest neighboring dot. A complete prescription for initialization of the computer and data input/output operations is presented.Comment: 22 pages, 4 figure

Advanced sensors technology survey

This project assesses the state-of-the-art in advanced or 'smart' sensors technology for NASA Life Sciences research applications with an emphasis on those sensors with potential applications on the space station freedom (SSF). The objectives are: (1) to conduct literature reviews on relevant advanced sensor technology; (2) to interview various scientists and engineers in industry, academia, and government who are knowledgeable on this topic; (3) to provide viewpoints and opinions regarding the potential applications of this technology on the SSF; and (4) to provide summary charts of relevant technologies and centers where these technologies are being developed

Development of adaptive transducer based on biological sensory mechanism

textAn adaptive sensor concept and prototype has been developed based on a sensing element which is analogous to and inspired by the arrangement of outer hair cells and inner hair cells between the basilar membrane and tectorial membrane which form the organ of corti in mammalian cochlea. The bio-inspired design was supported by development of a bond graph model of the electromotility (active response) of outer hair cells. Outer hair cells perform like actuators and simulation results using this model are compared with physiological data found in the literature to verify its characteristic response. Insight gained from the model is used to develop a sensor structure analogous to the organ of corti and designed to measure acceleration. A piezoelectric bimorph was selected as the transducer basis, and a bond graph model of the bimorph in an accelerometer configuration was formulated to aid control design and simulation. There is no published data regarding the type of information transmitted among the inner hair cells, outer hair cells, and brain. Consequently, a controller intended to adjust the adaptation process similar to what might exist in the cochlear system has been developed for the sensor and based on a model referenced adaptive control algorithm. Simulations verify that the algorithm can successfully control and enhance performance of the sensor. Practicability of the design is evaluated by a series of experiments on a prototype. This study focused on using a controller structure that was programmed, implemented, and tested using programmable logic based on FPGA technology. The experiments evaluated how well the adaptive sensor could meet a specified performance requirement. Implementation issues that arise, such as the need for differentiators in the adaptive controller or internal propagation of vibration within the sensor structure, hinder the tuning ability. Nevertheless, the trends indicate that the algorithm can meet the desired performance if certain limitations can be overcome. Finally, recommendations have been made for expansion of the research in such fields as an alternative structure for tuning, sensor networking, and reference sensor configuration.Mechanical Engineerin

Gcn4p and novel upstream activating sequences regulate targets of the unfolded protein response.

Eukaryotic cells respond to accumulation of unfolded proteins in the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR), a signal transduction pathway that communicates between the ER and the nucleus. In yeast, a large set of UPR target genes has been experimentally determined, but the previously characterized unfolded protein response element (UPRE), an upstream activating sequence (UAS) found in the promoter of the UPR target gene KAR2, cannot account for the transcriptional regulation of most genes in this set. To address this puzzle, we analyzed the promoters of UPR target genes computationally, identifying as candidate UASs short sequences that are statistically overrepresented. We tested the most promising of these candidate UASs for biological activity, and identified two novel UPREs, which are necessary and sufficient for UPR activation of promoters. A genetic screen for activators of the novel motifs revealed that the transcription factor Gcn4p plays an essential and previously unrecognized role in the UPR: Gcn4p and its activator Gcn2p are required for induction of a majority of UPR target genes during ER stress. Both Hac1p and Gcn4p bind target gene promoters to stimulate transcriptional induction. Regulation of Gcn4p levels in response to changing physiological conditions may function as an additional means to modulate the UPR. The discovery of a role for Gcn4p in the yeast UPR reveals an additional level of complexity and demonstrates a surprising conservation of the signaling circuit between yeast and metazoan cells

Growing cybernetic ears: transduction and performativity in the analogue and digital what have you

At a time when digital technologies have become ubiquitous in music making, and where the majority of research into music technology happens at the computational ‘cutting edge’, this practice-based PhD explores analogue technologies deemed, in the main, obsolete, anachronistic, or as quaint nostalgic throwbacks, and asks how a combination of technological, historical and practice-based research, focused through commitment to artistic outputs in the domain of music technology, might shed new light on the terms analogue and digital, and on the nature of the analogue-digital relationship. Underlying much contemporary enthusiasm for ‘the digital’ are progress narratives that rely on both a succession logic (old analogue technology gets replaced by new digital technology) and an assumption of isomorphism (the digital technology does all the same things as the replaced technology, though often with ‘enhanced’ affordances). This thesis questions such assumptions along historical, philosophical and practice-based trajectories. Key to these research trajectories is the trans-discipline cybernetics, in particular the second-order cybernetics of Gordon Pask, whose self-designation ‘philosophical mechanic’ indicates the importance he placed on a cyclical, mutually accommodating thinking-designing-making. Pask presented a powerful practical methodology for the examination and creation of dynamical systems in flux, systems that evolve as a result of participant interaction, systems that can be seen to manifest self-organisation. Second-order cybernetics puts the emphasis on processes in interaction rather than positing pre-existing objects (including concepts) in a world ‘out there’. Cybernetics helps us to explore systems whose complexity and interdependence precludes the separation out into constituent parts, systems where control is shared across multiple mutually interacting dimensions, and where the observer is a committed participant whose actions, interests and biases cannot be divorced from the interactions therein. Two other key concepts are: (1) transduction, which relates energy, information, patterns of growth, or other dynamical processes across media or between domains; (2) performativity, an interventional act that brings forth a world. Transduction is essential to an understanding of recording studio processes and practices: the microphone, signal processing and recording itself all rely on transduction. When viewed from a performative perspective, actions such as recording are found to be carried out very differently when the final stage of transduction is discrete (the case with the now ubiquitous digital audio workstation) or continuous (such as recording to tape). This difference is primarily due to the hyper-plasticity of digital audio, a taking of sound ‘out of time’. Rather than seeing this as an evolution of ‘precursor’ analogue technologies, as most accounts have it, this thesis takes the perspective that this is a difference in kind, rather than one of degree, and explores that difference with a particular focus on emergent and intertwined cultural, embodied and technological systems, rather than on end products. The second half of the thesis presents the compositional practice, ranging from experimental work on tape music composition and installation, through a series of modular synthesis live performances, to tape-based recording of pop music. The physical, gestural engagement with the resistant materiality of these technologies emphasises a very different cognitive engagement with processes of composition and production to that which happens with supposed ‘successor’ digital technologies; assumptions of isomorphism, buttressed by skeuomorphic emulation, tend to occlude this cognitive distinction. This thesis is offered as an act of cybernetic musicking – resolutely practical in orientation, with a wide-ranging, trans-disciplinary theoretical framework, and with the emphasis not on things but on ongoing processes in complex interaction with a world in constant becoming

Design and analysis of SRAMs for energy harvesting systems

PhD ThesisAt present, the battery is employed as a power source for wide varieties of microelectronic systems ranging from biomedical implants and sensor net-works to portable devices. However, the battery has several limitations and incurs many challenges for the majority of these systems. For instance, the design considerations of implantable devices concern about the battery from two aspects, the toxic materials it contains and its lifetime since replacing the battery means a surgical operation. Another challenge appears in wire-less sensor networks, where hundreds or thousands of nodes are scattered around the monitored environment and the battery of each node should be maintained and replaced regularly, nonetheless, the batteries in these nodes do not all run out at the same time. Since the introduction of portable systems, the area of low power designs has witnessed extensive research, driven by the industrial needs, towards the aim of extending the lives of batteries. Coincidentally, the continuing innovations in the field of micro-generators made their outputs in the same range of several portable applications. This overlap creates a clear oppor-tunity to develop new generations of electronic systems that can be powered, or at least augmented, by energy harvesters. Such self-powered systems benefit applications where maintaining and replacing batteries are impossi-ble, inconvenient, costly, or hazardous, in addition to decreasing the adverse effects the battery has on the environment. The main goal of this research study is to investigate energy harvesting aware design techniques for computational logic in order to enable the capa- II bility of working under non-deterministic energy sources. As a case study, the research concentrates on a vital part of all computational loads, SRAM, which occupies more than 90% of the chip area according to the ITRS re-ports. Essentially, this research conducted experiments to find out the design met-ric of an SRAM that is the most vulnerable to unpredictable energy sources, which has been confirmed to be the timing. Accordingly, the study proposed a truly self-timed SRAM that is realized based on complete handshaking protocols in the 6T bit-cell regulated by a fully Speed Independent (SI) tim-ing circuitry. The study proved the functionality of the proposed design in real silicon. Finally, the project enhanced other performance metrics of the self-timed SRAM concentrating on the bit-line length and the minimum operational voltage by employing several additional design techniques.Umm Al-Qura University, the Ministry of Higher Education in the Kingdom of Saudi Arabia, and the Saudi Cultural Burea

Multicellular Models Bridging Intracellular Signaling and Gene Transcription to Population Dynamics

Cell signaling and gene transcription occur at faster time scales compared to cellular death, division, and evolution. Bridging these multiscale events in a model is computationally challenging. We introduce a framework for the systematic development of multiscale cell population models. Using message passing interface (MPI) parallelism, the framework creates a population model from a single-cell biochemical network model. It launches parallel simulations on a single-cell model and treats each stand-alone parallel process as a cell object. MPI mediates cell-to-cell and cell-to-environment communications in a server-client fashion. In the framework, model-specific higher level rules link the intracellular molecular events to cellular functions, such as death, division, or phenotype change. Cell death is implemented by terminating a parallel process, while cell division is carried out by creating a new process (daughter cell) from an existing one (mother cell). We first demonstrate these capabilities by creating two simple example models. In one model, we consider a relatively simple scenario where cells can evolve independently. In the other model, we consider interdependency among the cells, where cellular communication determines their collective behavior and evolution under a temporally evolving growth condition. We then demonstrate the framework\u27s capability by simulating a full-scale model of bacterial quorum sensing, where the dynamics of a population of bacterial cells is dictated by the intercellular communications in a time-evolving growth environment

Study of Strategies for Genetic Variant Discrimination and Detection by Optosensing

Tesis por compendio[ES] La medicina actual se dirige hacia un enfoque más personalizado basándose en el diagnóstico molecular del paciente a través del estudio de biomarcadores específicos. Aplicando este principio molecular, el diagnóstico, pronóstico y selección de la terapia se apoyan en la identificación de variaciones específicas del genoma humano, como variaciones de un único nucleótido (SNV). Para detectar estos biomarcadores se dispone de una amplia oferta de tecnologías. Sin embargo, muchos de los métodos en uso presentan limitaciones como un elevado coste, complejidad, tiempos de análisis largos o requieren de personal y equipamiento especializado, lo que imposibilita su incorporación masiva en la mayoría de los sistemas sanitarios. Por tanto, existe la necesidad de investigar y desarrollar soluciones analíticas que aporten información sobre las variantes genéticas y que se puedan implementar en diferentes escenarios del ámbito de la salud con prestaciones competitivas y económicamente viables. El objetivo principal de esta tesis ha sido desarrollar estrategias innovadoras para resolver el reto de la detección múltiple de variantes genéticas que se encuentran en forma minoritaria en muestras biológicas de pacientes, cubriendo las demandas asociadas al entorno clínico. Las tareas de investigación se centraron en la combinación de reacciones de discriminación alélica con amplificación selectiva de DNA y el desarrollo de sistemas ópticos de detección versátiles. Con el fin de atender el amplio abanico de necesidades, en el primer capítulo, se presentan resultados que mejoran las prestaciones analíticas de la reacción en cadena de la polimerasa (PCR) mediante la incorporación de una etapa al termociclado y de un agente bloqueante amplificando selectivamente las variantes minoritarias que fueron monitorizadas mediante fluorescencia a tiempo real. En el segundo capítulo, se logró la discriminación alélica combinando la ligación de oligonucleótidos con la amplificación de la recombinasa polimerasa (RPA), que al operar a temperatura constante permitió una detección tipo point-of-care (POC). La identificación de SNV se llevó a cabo mediante hibridación en formato micromatriz, utilizando la tecnología Blu-Ray como plataforma de ensayo y detección. En el tercer capítulo, se integró la RPA con la reacción de hibridación alelo especifica en cadena (AS-HCR), en formato array para genotipar SNV a partir de DNA genómico en un chip. La lectura de los resultados se realizó mediante un smartphone. En el último capítulo, se presenta la síntesis de un nuevo reactivo bioluminiscente que se aplicó a la monitorización de biomarcadores de DNA a tiempo real y final de la RPA basada en la transferencia de energía de resonancia de bioluminiscencia (BRET), eliminando la necesidad de una fuente de excitación. Todas las estrategias permitieron un reconocimiento especifico de la variante de interés, incluso en muestras que contenían tan solo 20 copias de DNA genómico diana. Se consiguieron resultados sensibles (límite de detección 0.5% variante/total), reproducibles (desviación estándar relativa < 19%), de manera sencilla (3 etapas o menos), rápida (tiempos cortos de 30-200 min) y permitiendo el análisis simultaneo de varios genes. Como prueba de concepto, estas estrategias se aplicaron a la detección e identificación en muestras clínicas de biomarcadores asociados a cáncer colorrectal y enfermedades cardiológicas. Los resultados se validaron por comparación con los métodos de referencia NGS y PCR, comprobándose que se mejoraban los requerimientos técnicos y la relación coste-eficacia. En conclusión, las investigaciones llevadas a cabo posibilitaron desarrollar herramientas de genotipado con propiedades analíticas competitivas y versátiles, aplicables a diferentes escenarios sanitarios, desde hospitales a entornos con pocos recursos. Estos resultados son prometedores al dar respuesta a la demanda de tecnologías alternativas para el diagnóstico molecular personalizado.[CA] La medicina actual es dirigeix cap a un enfocament més personalitzat basant-se en el diagnòstic molecular del pacient a través de l'estudi de biomarcadors específics. Aplicant aquest principi molecular, el diagnòstic, pronòstic i selecció de la teràpia es recolzen en la identificació de variacions específiques del genoma humà, com variacions d'un únic nucleòtid (SNV). Per a detectar aquests biomarcadors, es disposa d'una àmplia oferta de tecnologies. No obstant això, molts dels mètodes en ús presenten limitacions com un elevat cost, complexitat, temps d'anàlisis llargues o requereixen de personal i equipament especialitzat, la qual cosa impossibilita la seua incorporació massiva en la majoria dels sistemes sanitaris. Per tant, existeix la necessitat d'investigar i desenvolupar solucions analítiques que aporten informació sobre les variants genètiques i que es puguen implementar en diferents escenaris de l'àmbit de la salut amb prestacions competitives i econòmicament viables. L'objectiu principal d'aquesta tesi ha sigut desenvolupar estratègies innovadores per a resoldre el repte de la detecció múltiple de variants genètiques que es troben en forma minoritària en mostres biològiques de pacients, cobrint les demandes associades a l'entorn clínic. Les tasques d'investigació es van centrar en la combinació de reaccions de discriminació al·lèlica amb amplificació selectiva de DNA i al desenvolupament de sistemes òptics de detecció versàtils. Amb la finalitat d'atendre l'ampli ventall de necessitats, en el primer capítol, es presenten resultats que milloren les prestacions analítiques de la reacció en cadena de la polimerasa (PCR) mitjançant la incorporació d'una etapa al termociclat i d'un agent bloquejant amplificant selectivament les variants minoritàries que van ser monitoritzades mitjançant fluorescència a temps real. En el segon capítol, es va aconseguir la discriminació al·lèlica combinant el lligament d'oligonucleòtids amb l'amplificació de la recombinasa polimerasa (RPA), que en operar a temperatura constant va permetre una detecció tipus point-of-care (POC). La identificació de SNV es va dur a terme mitjançant hibridació en format micromatriu, utilitzant la tecnologia Blu-Ray com a plataforma d'assaig i detecció. En el tercer capítol, es va integrar la RPA amb la reacció d'hibridació al·lel específica en cadena (AS-HCR), en format matriu per a genotipar SNV a partir de DNA genòmic en un xip. La lectura dels resultats es va realitzar mitjançant un telèfon intel·ligent. En l'últim capítol, es presenta la síntesi d'un nou reactiu bioluminescent que es va aplicar al monitoratge de biomarcadors de DNA a temps real i final de la RPA basada en la transferència d'energia de ressonància de bioluminescència (BRET), eliminant la necessitat d'una font d'excitació. Totes les estratègies van permetre un reconeixement específic de la variant d'interès, fins i tot en mostres que només contenien 20 còpies de DNA genòmic diana. Es van aconseguir resultats sensibles (límit de detecció 0.5% variant/total), reproduïbles (desviació estàndard relativa < 19%), de manera senzilla (3 etapes o menys), ràpida (temps curts de 30-200 min) i permetent l'anàlisi simultània de diversos gens. Com a prova de concepte, aquestes estratègies es van aplicar a la detecció i identificació en mostres clíniques de biomarcadors associats a càncer colorectal i a malalties cardiològiques. Els resultats es van validar per comparació amb els mètodes de referència NGS i PCR, comprovant-se que es milloraven els requeriments tècnics i la relació cost-eficàcia. En conclusió, les investigacions dutes a terme van possibilitar desenvolupar eines de genotipat amb propietats analítiques competitives i versàtils, aplicables a diferents escenaris sanitaris, des d'hospitals a entorns amb pocs recursos. Aquests resultats són prometedors en donar resposta a la demanda de tecnologies alternatives per al diagnòstic molecular personalitzat.[EN] Current medicine is moving towards a more personalized approach based on the patients' molecular diagnosis through the study of specific biomarkers. Diagnosis, prognosis and therapy selection, applying this molecular principle, rely on identifying specific variations in the human genome, such as single nucleotide variations (SNV). A wide range of technologies is available to detect these biomarkers. However, many of the employed methods have limitations such as high cost, complexity, long analysis times, or requiring specialized personnel and equipment, making their massive incorporation in most healthcare systems impossible. Therefore, there is a need to research and develop analytical solutions that provide information on genetic variants that can be implemented in different health scenarios with competitive and economically feasible performances. The main objective of this thesis has been to develop innovative strategies to solve the challenge of multiple detection of genetic variants that are found in a minority amount in patient samples, covering the demands associated with the clinical setting. Research tasks focused on the combination of allelic discrimination reactions with selective DNA amplification and the development of versatile optical detection systems. In order to meet the wide range of needs, in the first chapter, the analytical performances of the polymerase chain reaction (PCR) were improved by incorporating a thermocycling step and a blocking agent to amplify selectively minority variants that were monitored by real-time fluorescence. In the second chapter, allelic discrimination was achieved by combining oligonucleotide ligation with recombinase polymerase amplification (RPA), which operates at a constant temperature, allowing point-of-care (POC) detection. SNV identification was carried out by hybridization in microarray format, using Blu-Ray technology as the assay platform and detector. RPA was integrated with allele-specific hybridization chain reaction (AS-HCR), in an array format to genotype SNV from genomic DNA on a chip in the third chapter. The reading of the results was performed using a smartphone. In the last chapter, a new bioluminescent reagent was synthesized. It was applied to real-time and endpoint DNA biomarker monitoring based on bioluminescence resonance energy transfer (BRET), eliminating the need for an excitation source. All the strategies allowed specific recognition of the target variant, even in samples containing as few as 20 copies of target genomic DNA. Sensitive (limit of detection 0.5% variant/total), reproducible (relative standard deviation < 19%), simple (3 steps or less), fast (short times of 30-200 min) results were achieved, allowing simultaneous analysis of several genes. As proof of concept, these strategies were applied to detect and identify biomarkers associated with colorectal cancer and cardiological diseases in clinical samples. The results were validated by comparison with reference methods such as NGS and PCR, proving that the technical requirements and cost-effectiveness were improved. In conclusion, the developed research made it possible to develop genotyping tools with competitive analytical properties and versatile, applicable to different healthcare scenarios, from hospitals to limited-resource environments. These results are promising since they respond to the demand for alternative technologies for personalized molecular diagnostics.The authors acknowledge the financial support received from the Generalitat Valenciana PROMETEO/2020/094, GRISOLIA/2014/024 PhD Grant and GVA-FPI-2017 PhD grant, the Spanish Ministry of Economy and Competitiveness MINECO projects CTQ2016-75749-R and PID2019-110713RB-I00 and European Regional Development Fund (ERDF).Lázaro Zaragozá, A. (2022). Study of Strategies for Genetic Variant Discrimination and Detection by Optosensing [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/185216TESISCompendi