9,661 research outputs found

    Studies on genetic and epigenetic regulation of gene expression dynamics

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    The information required to build an organism is contained in its genome and the first biochemical process that activates the genetic information stored in DNA is transcription. Cell type specific gene expression shapes cellular functional diversity and dysregulation of transcription is a central tenet of human disease. Therefore, understanding transcriptional regulation is central to understanding biology in health and disease. Transcription is a dynamic process, occurring in discrete bursts of activity that can be characterized by two kinetic parameters; burst frequency describing how often genes burst and burst size describing how many transcripts are generated in each burst. Genes are under strict regulatory control by distinct sequences in the genome as well as epigenetic modifications. To properly study how genetic and epigenetic factors affect transcription, it needs to be treated as the dynamic cellular process it is. In this thesis, I present the development of methods that allow identification of newly induced gene expression over short timescales, as well as inference of kinetic parameters describing how frequently genes burst and how many transcripts each burst give rise to. The work is presented through four papers: In paper I, I describe the development of a novel method for profiling newly transcribed RNA molecules. We use this method to show that therapeutic compounds affecting different epigenetic enzymes elicit distinct, compound specific responses mediated by different sets of transcription factors already after one hour of treatment that can only be detected when measuring newly transcribed RNA. The goal of paper II is to determine how genetic variation shapes transcriptional bursting. To this end, we infer transcriptome-wide burst kinetics parameters from genetically distinct donors and find variation that selectively affects burst sizes and frequencies. Paper III describes a method for inferring transcriptional kinetics transcriptome-wide using single-cell RNA-sequencing. We use this method to describe how the regulation of transcriptional bursting is encoded in the genome. Our findings show that gene specific burst sizes are dependent on core promoter architecture and that enhancers affect burst frequencies. Furthermore, cell type specific differential gene expression is regulated by cell type specific burst frequencies. Lastly, Paper IV shows how transcription shapes cell types. We collect data on cellular morphologies, electrophysiological characteristics, and measure gene expression in the same neurons collected from the mouse motor cortex. Our findings show that cells belonging to the same, distinct transcriptomic families have distinct and non-overlapping morpho-electric characteristics. Within families, there is continuous and correlated variation in all modalities, challenging the notion of cell types as discrete entities

    2023-2024 Boise State University Undergraduate Catalog

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    This catalog is primarily for and directed at students. However, it serves many audiences, such as high school counselors, academic advisors, and the public. In this catalog you will find an overview of Boise State University and information on admission, registration, grades, tuition and fees, financial aid, housing, student services, and other important policies and procedures. However, most of this catalog is devoted to describing the various programs and courses offered at Boise State

    NORMAN AND GRECIAN: A COMPARATIVE ARCHAEOLOGICAL SITE FORMATION ANALYSIS OF TWO STEEL-HULLED GREAT LAKES BULK CARRIERS IN LAKE HURON

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    Thunder Bay National Marine Sanctuary (TBNMS) in Alpena, Michigan contains the remains of approximately 200 shipwrecks. Located within the sanctuary are two vessels, Norman (1890-1895) and Grecian (1891-1906). Both built by Globe Iron Works in the early 1890s, they present an opportunity for a comparative archaeological site formation analysis study. Using historical and archaeological data from Norman and Grecian, several 3D models were created to showcase how they ships transformed as shipwreck sites. Model data is used to communicate the various environmental and anthropogenic factors that have altered these wrecks through time

    Diseño y aplicaciones de sistemas de antenas inteligentes para redes inalámbricas en el contexto de la internet de las cosas

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    [SPA] Esta tesis doctoral se presenta bajo la modalidad de compendio de publicaciones. Las antenas de onda de fuga (LWA) consisten en una estructura de guía de onda que permite la fuga de parte de la potencia a lo largo de la estructura. Por esta razón, la radiación de la antena se produce por la fuga de energía. Para producir una radiación coherente, es necesario controlar esta tasa de radiación a lo largo de la estructura radiante. Así, ajustando con precisión la tasa de radiación, se controla la forma del diagrama de radiación. Las LWAs han sido ampliamente estudiadas por la comunidad científica debido a sus ventajas, tales como, red de alimentación simple, alta directividad y escaneo en frecuencia pasivo. Sin embargo, presentan ciertas desventajas entre las cuales, la más importante a destacar es el efecto de beam-squinting. Éste se produce por la propiedad dispersiva inherente a este tipo de antenas. Además, presentan dificultades a la hora de generar radiación coherente en las direcciones broadside y endfire, aumentando la complejidad del diseńo para la radiación en dichas direcciones. Las LWA han sido relativamente poco utilizadas en aplicaciones prácticas hasta la fecha, a pesar de sus ventajas. Las pocas aplicaciones en las que se han utilizado son los radares de onda continua modulada en frecuencia y los sistemas de enfoque controlado en frecuencia de campo cercano. Esta tesis propone el uso de las LWAs en aplicaciones prácticas aprovechando las ventajas mencionadas anteriormente y teniendo en cuenta los inconvenientes de este tipo de antenas para que su uso no sea limitado. Recientemente, las LWAs han sido propuestas para aplicaciones de localización de bajo coste, ya que permiten el diseńo de estructuras planas con haces directivos. Además, debido al aumento exponencial del uso de la tecnología, es necesario encontrar nuevas tecnologías para una transmisión de datos mayor, más rápida y más eficiente, manteniendo bajos costes de fabricación. Por lo tanto las LWAs pueden ser una solución crucial al mezclar bajos costes de fabricación, alta integrabilidad en diferentes sistemas debido a su tecnología impresa planar y alta directividad al mismo tiempo que se aprovecha su característica dispersiva que proporciona un escaneo pasivo en frecuencia. En este contexto, la principal aportación de esta Tesis consiste en el estudio, análisis, diseńo e integración de LWAs en aplicaciones reales y prácticas. Esta Tesis presenta las siguientes tres contribuciones principales, definidas en los tres bloques principales de este documento: • Estudio y análisis de LWAs para su uso en sistemas de estimación de dirección de llegada basados en técnicas de amplitud de monopulso. Comparar las características y prestaciones de las LWAs junto con las antenas comerciales más utilizadas. Para ello, diseńar y fabricar las HWM-LWAs con el fin de comparar sus prestaciones con las antenas de panel adquiridas comercialmente. Dado que cada aplicación requiere el diseńo de una HWM-LWA nueva y diferente, estudiar y proponer una técnica eficiente de análisis y diseńo de antenas para obtener fácilmente diagramas de radiación monopulso escaneados en frecuencia. • Una vez analizado que las HWM-LWA son una solución factible para su uso en aplicaciones reales de localización debido a sus diversas ventajas. Integrar las HWM-LWAs diseńadas en sistemas digitales para estimación del ángulo de llegada en interiores. Por lo tanto, diseńar, desarrollar, configurar e integrar las LWAs en diferentes sistemas basados en las bandas de frecuencia Wi-Fi ISM de 2,4 GHz y 5 GHz. Finalmente, comparar los resultados de estimación obtenidos con otras soluciones propuestas para corroborar que los LWAs pueden ser utilizados en aplicaciones reales. • Asimismo, debido a su bajo coste de fabricación y a su principal propiedad de escaneo en frecuencia. Ampliar el uso de las LWAs para la localización angular en redes de sensores inalámbricas (WSN) utilizando la banda de frecuencias UHF de 900 MHz. Utilizando así etiquetas RFID pasivas. También estudiar su aplicabilidad en WSNs utilizando etiquetas LoRa activas. Este documento se presenta como una Tesis por compendio, por lo que se presentarán y explicarán brevemente los 4 artículos de revistas que se han publicado durante el programa de doctorado. Además, también se presentarán algunos artículos de conferencias y otros trabajos en revisión para exponer algunas de las investigaciones que no han sido publicadas en revistas hasta la fecha de depósito de tesis. El documento está organizado como se indica a continuación: En la Introducción, se presenta una contextualización del estado del arte y una explicación rigurosa sobre las LWAs y las aplicaciones anteriormente mencionadas. Las dos partes siguientes se vi dedican a presentar y explicar brevemente los trabajos publicados que contribuyen a esta Tesis. En la parte II, se presentan los cuatro artículos que conforman el compendio. Esto es, el análisis de las LWAs para la estimación de la dirección del ángulo de llegada y la integración de las LWAs en sistemas de localización digital usando el protocolo Wi-Fi en el Capítulo 1, la banda de frecuencias ISM UHF 900 MHz se utiliza junto con los HWM-LWAs en el Capítulo 2, luego se implementa en un sistema en tiempo real para la estimación de la dirección de llegada de múltiples tags pasivos en el Capítulo 3 y la integración de LoRa en el Capítulo 4. Finalmente, en la Parte III, se discuten las conclusiones generales y las futuras líneas de investigación. [ENG] This doctoral dissertation has been presented in the form of thesis by publication. Leaky-Wave Antennas (LWA) consist on a waveguide structure which allows the leakage of part of the power along the structure. For this reason, the radiation of the antenna is produced by the leakage of power. In order to produce coherent radiation, it is necessary to control this leakage rate along the radiating structure. Thus, precisely adjusting the leakage rate, the shape of the radiation pattern is controlled. LWAs have been widely studied by the scientific community due to their advantages, such as, simple feeding network, high directivity and passive frequency-scanning performance. However, they present certain disadvantages among which, the most important to highlight is the beam-squinting effect. TThis is due to the inherent dispersion property of this type of antenna. In addition, LWAs present difficulties when generating coherent radiation in broadside and endfire directions, increasing the complexity of the design for radiation in these directions. LWAs have been relatively unused in practical applications to date, despite of their benefits. The few applications in which they have been used are frequency modulated continuous wave radars and near-field frequency controlled focusing systems.This thesis proposes the use of LWAs in practical applications by exploiting the advantages mentioned above while taking into account the drawbacks of this type of antennas so that their use is not limited. Recently, LWAs have been proposed for low-cost localization applications, as they allow the design of planar structures with directive beams. In addition, due to the exponential increase in the use of technology, it is necessary to find new technologies for higher, faster and more efficient data transmission while maintaining low manufacturing costs. Therefore, LWAs can be a crucial solution mixing low manufacturing costs, high integrability in different systems due to their planar printed technology and high directivity while taking advantage of their dispersive characteristic that provides passive frequency scanning. In this context, the main contribution of this Thesis consist of the study, analysis, design and integration of LWAs in real and practical applications. This Thesis presents the following three main contributions, defined in the three main blocks of this document: • Study and analysis of LWAs for its use in direction of arrival estimation systems based on monopulse amplitude techniques. Compare the characteristics and performance of LWAs along with widely used commercial antennas. For this purpose, design and manufacture the HWM-LWAs in order to compare their performance with commercially acquired panel antennas. Since each application requires the design of a new and different HWM-LWA, a main objective of this block is to study and propose an efficient antenna analysis and design technique to facilitate obtaining frequency-scanned monopulse patterns. • Once analyzed that LWAs are a feasible solution for its use in real localization applications due to their several advantages, integrate the designed half-width microstrip (HWM-LWAs) in digital indoor angle-of-arrival estimation systems. Therefore, design, develop, configure and integrate LWAs in different systems based on the Wi-Fi ISM 2.4 GHz and 5 GHz frequency bands. Finally, compare the obtained estimation results with other proposed solutions to corroborate that LWAs can be used in real applications. • Extending the use of antennas for angular localization in sensor networks using the 900 MHz UHF frequency band: the main properties of low manufacturing cost and passive frequency beam scanning can be used in other applications. Thus, the localization estimation of passive RFID tags is studied, as well as their application in Wireless Sensor Networks (WSNs) using active tags with LORA technology. This document is presented as a Thesis by compilation, so the 4 journal articles that have been published during the Ph.D program will be presented and briefly explained. Besides, some conference articles and other work under review will be also presented to expose some of the research that has not been published in journals. The document is organized as outlined hereafter: In Part I, a state-of-the-art contextualization, a rigorous explanation about LWAs and the previous applications mentioned above is presented. The next two parts are dedicated to present and briefly explain the published works included in this Thesis and their main contributions. In Part II the explanation of the four papers which compose the compendium are presented. This is, LWAs analysis for direction of arrival estimation and the integration of LWAs in digital Wi-Fi localization systems in chapter 1, the UHF 900 MHz ISM frequency band is used in conjunction with HWM-LWAs in chapter 2, then, it is implemented in a real time system for direction of arrival estimation of multi RFID tags in chapter 3 and LoRa integration in chapter 4. Finally, in Part III, the overall conclusions and the future research lines are discussed.Esta tesis doctoral se presenta bajo la modalidad de compendio de publicaciones. Está formada por un total de cuatro artículos. Article 1.-: A. Gil-Martinez, M. Poveda-Garcia, J. A. Lopez-Pastor, J. C. Sanchez-Aarnoutse and J. L. Gomez-Tornero, Wi-Fi Direction Finding with Frequency-Scanned Antenna and Channel Hopping Scheme IEEE sensors Journal, , vol. 22, no. 6, pp. 5210-5222, 2022. DOI: 10.1109/JSEN.2021.3122232. Article 2.-: A. Gil-Martinez, M. Poveda-Garcia, D. Cañete-Rebenaque, and J. L. Gomez-Tornero, Frequency-Scanned Monopulse Antenna for RSSI-based Direction Finding of UHF RFID tags IEEE Antennas and Wireless Propagation Letters,, vol. 21, no. 1, pp. 158-162, 2022. DOI: 10.1109/LAWP.2021.3122232. Article 3.-: A. Gil-Martinez, M. Poveda-Garcia, J. Garcia-Fernandez, M. Campo-Valera, D. Cañete-Rebenaque, and J. L. Gomez-Tornero, Direction Finding of RFID tags in UHF Band Using a Passive Beam-Scanning Leaky-Wave Antenna IEEE Journal of Radio Frequency Identi cation, doi: 10.1109/JRFID.2021.3122233. Article 4.-: J. L. Gomez-Tornero, A. Gil-Martinez, M. Poveda-Garcia and D. Cañete-Rebenaque, ARIEL: Passive Beam-Scanning Antenna TeRminal for Iridiscent and E cient LEO Satellite Connectivity in IEEE Antennas and Wireless Propagation Letters, doi: 10.1109/LAWP.2022.3193040.Escuela Internacional de Doctorado de la Universidad Politécnica de CartagenaUniversidad Politécnica de CartagenaPrograma Doctorado en Tecnologías de la Información y las Comunicacione

    It is too hot in here! A performance, energy and heat aware scheduler for Asymmetric multiprocessing processors in embedded systems.

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    Modern architecture present in self-power devices such as mobiles or tablet computers proposes the use of asymmetric processors that allow either energy-efficient or performant computation on the same SoC. For energy efficiency and performance consideration, the asymmetry resides in differences in CPU micro-architecture design and results in diverging raw computing capability. Other components such as the processor memory subsystem also show differences resulting in different memory transaction timing. Moreover, based on a bus-snoop protocol, cache coherency between processors comes with a peculiarity in memory latency depending on the processors operating frequencies. All these differences come with challenging decisions on both application schedulability and processor operating frequencies. In addition, because of the small form factor of such embedded systems, these devices generally cannot afford active cooling systems. Therefore thermal mitigation relies on dynamic software solutions. Current operating systems for embedded systems such as Linux or Android do not consider all these particularities. As such, they often fail to satisfy user expectations of a powerful device with long battery life. To remedy this situation, this thesis proposes a unified approach to deliver high-performance and energy-efficiency computation in each of its flavours, considering the memory subsystem and all computation units available in the system. Performance is maximized even when the device is under heavy thermal constraints. The proposed unified solution is based on accurate models targeting both performance and thermal behaviour and resides at the operating systems kernel level to manage all running applications in a global manner. Particularly, the performance model considers both the computation part and also the memory subsystem of symmetric or asymmetric processors present in embedded devices. The thermal model relies on the accurate physical thermal properties of the device. Using these models, application schedulability and processor frequency scaling decisions to either maximize performance or energy efficiency within a thermal budget are extensively studied. To cover a large range of application behaviour, both models are built and designed using a generative workload that considers fine-grain details of the underlying microarchitecture of the SoC. Therefore, this approach can be derived and applied to multiple devices with little effort. Extended evaluation on real-world benchmarks for high performance and general computing, as well as common applications targeting the mobile and tablet market, show the accuracy and completeness of models used in this unified approach to deliver high performance and energy efficiency under high thermal constraints for embedded devices

    Late-bound code generation

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    Each time a function or method is invoked during the execution of a program, a stream of instructions is issued to some underlying hardware platform. But exactly what underlying hardware, and which instructions, is usually left implicit. However in certain situations it becomes important to control these decisions. For example, particular problems can only be solved in real-time when scheduled on specialised accelerators, such as graphics coprocessors or computing clusters. We introduce a novel operator for hygienically reifying the behaviour of a runtime function instance as a syntactic fragment, in a language which may in general differ from the source function definition. Translation and optimisation are performed by recursively invoked, dynamically dispatched code generators. Side-effecting operations are permitted, and their ordering is preserved. We compare our operator with other techniques for pragmatic control, observing that: the use of our operator supports lifting arbitrary mutable objects, and neither requires rewriting sections of the source program in a multi-level language, nor interferes with the interface to individual software components. Due to its lack of interference at the abstraction level at which software is composed, we believe that our approach poses a significantly lower barrier to practical adoption than current methods. The practical efficacy of our operator is demonstrated by using it to offload the user interface rendering of a smartphone application to an FPGA coprocessor, including both statically and procedurally defined user interface components. The generated pipeline is an application-specific, statically scheduled processor-per-primitive rendering pipeline, suitable for place-and-route style optimisation. To demonstrate the compatibility of our operator with existing languages, we show how it may be defined within the Python programming language. We introduce a transformation for weakening mutable to immutable named bindings, termed let-weakening, to solve the problem of propagating information pertaining to named variables between modular code generating units.Open Acces

    The molecular athlete: exercise physiology from mechanisms to medals

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    Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength, to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial and error" approach with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and inter-individual differences in exercise capacity and performance, with special considerations given to the ageing athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise, and how such adaptations translate from "molecules to medals"

    Innovative Hybrid Approaches for Vehicle Routing Problems

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    This thesis deals with the efficient resolution of Vehicle Routing Problems (VRPs). The first chapter faces the archetype of all VRPs: the Capacitated Vehicle Routing Problem (CVRP). Despite having being introduced more than 60 years ago, it still remains an extremely challenging problem. In this chapter I design a Fast Iterated-Local-Search Localized Optimization algorithm for the CVRP, shortened to FILO. The simplicity of the CVRP definition allowed me to experiment with advanced local search acceleration and pruning techniques that have eventually became the core optimization engine of FILO. FILO experimentally shown to be extremely scalable and able to solve very large scale instances of the CVRP in a fraction of the computing time compared to existing state-of-the-art methods, still obtaining competitive solutions in terms of their quality. The second chapter deals with an extension of the CVRP called the Extended Single Truck and Trailer Vehicle Routing Problem, or simply XSTTRP. The XSTTRP models a broad class of VRPs in which a single vehicle, composed of a truck and a detachable trailer, has to serve a set of customers with accessibility constraints making some of them not reachable by using the entire vehicle. This problem moves towards VRPs including more realistic constraints and it models scenarios such as parcel deliveries in crowded city centers or rural areas, where maneuvering a large vehicle is forbidden or dangerous. The XSTTRP generalizes several well known VRPs such as the Multiple Depot VRP and the Location Routing Problem. For its solution I developed an hybrid metaheuristic which combines a fast heuristic optimization with a polishing phase based on the resolution of a limited set partitioning problem. Finally, the thesis includes a final chapter aimed at guiding the computational evaluation of new approaches to VRPs proposed by the machine learning community
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