Spike-timing dependent plasticity and connectivity in primate sensorimotor cortex

Thesis (Ph.D.)--University of Washington, 2016-06

La supervision du personnel enseignant : une étude comparative Québec-Chine

Méthodologie: Étude menée par questionnaire auprès d’enseignants du primaire, du secondaire et de la formation professionnelle

Optimization of a multielectrode array (MEA)-based approach to study the impact of Aβ on the SH-SY5Y cell line

The human brain stores, integrates, and transmits information recurring to millions of neurons, interconnected by countless synapses. Though neurons communicate through chemical signaling, information is coded and conducted in the form of electrical signals. Neuroelectrophysiology focus on the study of this type of signaling. Both intra and extracellular approaches are used in research, but none holds as much potential in high-throughput screening and drug discovery, as extracellular recordings using multielectrode arrays (MEAs). MEAs measure neuronal activity, both in vitro and in vivo. Their key advantage is the capability to record electrical activity at multiple sites simultaneously. Alzheimer’s disease (AD) is the most common neurodegenerative disease and one of the leading causes of death worldwide. It is characterized by neurofibrillar tangles and aggregates of amyloid-β (Aβ) peptides, which lead to the loss of synapses and ultimately neuronal death. Currently, there is no cure and the drugs available can only delay its progression. In vitro MEA assays enable rapid screening of neuroprotective and neuroharming compounds. Therefore, MEA recordings are of great use in both AD basic and clinical research. The main aim of this thesis was to optimize the formation of SH-SY5Y neuronal networks on MEAs. These can be extremely useful for facilities that do not have access to primary neuronal cultures, but can also save resources and facilitate obtaining faster high-throughput results to those that do. Adhesion-mediating compounds proved to impact cell morphology, viability and exhibition of spontaneous electrical activity. Moreover, SH-SY5Y cells were successfully differentiated and demonstrated acute effects on neuronal function after Aβ addition. This effect on electrical signaling was dependent on Aβ oligomers concentration. The results here presented allow us to conclude that the SH-SY5Y cell line can be successfully differentiated in properly coated MEAs and be used for assessing acute Aβ effects on neuronal signaling.

Real-time analytics on large dynamic graphs

In today's fast-paced and interconnected digital world, the data generated by an increasing number of applications is being modeled as dynamic graphs. The graph structure encodes relationships among data items, while the structural changes to the graphs as well as the continuous stream of information produced by the entities in these graphs make them dynamic in nature. Examples include social networks where users post status updates, images, videos, etc.; phone call networks where nodes may send text messages or place phone calls; road traffic networks where the traffic behavior of the road segments changes constantly, and so on. There is a tremendous value in storing, managing, and analyzing such dynamic graphs and deriving meaningful insights in real-time. However, a majority of the work in graph analytics assumes a static setting, and there is a lack of systematic study of the various dynamic scenarios, the complexity they impose on the analysis tasks, and the challenges in building efficient systems that can support such tasks at a large scale. In this dissertation, I design a unified streaming graph data management framework, and develop prototype systems to support increasingly complex tasks on dynamic graphs. In the first part, I focus on the management and querying of distributed graph data. I develop a hybrid replication policy that monitors the read-write frequencies of the nodes to decide dynamically what data to replicate, and whether to do eager or lazy replication in order to minimize network communication and support low-latency querying. In the second part, I study parallel execution of continuous neighborhood-driven aggregates, where each node aggregates the information generated in its neighborhoods. I build my system around the notion of an aggregation overlay graph, a pre-compiled data structure that enables sharing of partial aggregates across different queries, and also allows partial pre-computation of the aggregates to minimize the query latencies and increase throughput. Finally, I extend the framework to support continuous detection and analysis of activity-based subgraphs, where subgraphs could be specified using both graph structure as well as activity conditions on the nodes. The query specification tasks in my system are expressed using a set of active structural primitives, which allows the query evaluator to use a set of novel optimization techniques, thereby achieving high throughput. Overall, in this dissertation, I define and investigate a set of novel tasks on dynamic graphs, design scalable optimization techniques, build prototype systems, and show the effectiveness of the proposed techniques through extensive evaluation using large-scale real and synthetic datasets.

Henrique Novaes: técnica, território e cidade em uma trajetória profissional: Brasil, primeira metade do século XX

The career of civil engineer Henrique de Novaes, a remarkable figure in the academic, technical and political fields, demonstrates its extensive and relevant work across Brazil in the first half of the twentieth century. It covered from the design of water supply and sewage works, road and rail transport networks, works against drought in the Northeast, hydroelectric and harbor facilities to the urbanization planning and architectural projects, which displays a systematic and multiple production. City and territory conformed to his fields of verification, practical and above all, transformation. The search for understanding of the inclusion of a social actor in this process thus contributes to the specific analysis of the doings of Henrique de Novaes, who graduated at Polytechnic School of Rio de Janeiro in 1906. From a polymorphic activity in different scales, one tries to figure how, through academic education or professional practice, urban history in Brazil can be told or built. The introduction of technological innovations matched the purposes of planning and urban sprawl, as well as met the specifications of regulation and institutionalization of public infrastructure services at the time. The overall plans proposed by the engineer thought of the city as a whole, interconnected to the structural networks. At the same time, the knowledge of a larger physical scale the territory bounces back in the urban in a relationship of reciprocity and completeness. The objective research, therefore, tries to understand the roles played by Henrique de Novaes s works and academic education in the accomplishment of systematic modernization of Brazilian urban space and territory, recovering a little known historical figure by current historiography. It is proposed, as methodological axis, that the study of this professional career configures itself as an essential element for understanding the idea of progress embodied in the technical studies and proposals for improvements and sanitation nationwide in the first half of the twentieth century . The primary sources for the construction of this analysis were technical articles in journals of the period ( Clube de Engenharia , Viação e Revista Brasileira de Engenharia ), and technical reports, government messages, newspaper articles published at the time, autobiographical reports and the engineer s verbal communications with relatives. The work is structured in three chapters: "Biographical traces, academic education and 'technical and political' activities" illustrates the initiation into the technical, public and political environment; Chapter 2, "Technique and territory" outlines his network understanding through sanitation and transport services; Chapter 3 "Technique and City" describes the influence of polytechnics knowledge on the propositions of modernization of cities; Finally, "Final Thoughts: An Evaluation," presents an overview of the affiliations and practice of an engineer in the different scales, and its contribution to the modernization of Brazilian urban and territorial space

Investigation of properties affecting controlled release of macromolecules from PLGA microspheres

Poly(lactide-co-glycolide), or PLGA, microspheres offer a widely-studied biodegradable option for controlled release of therapeutics. An array of fabrication methodologies have been developed to produce these microspheres with the capacity to encapsulate therapeutics of various types; and produce microspheres of a wide range of sizes for different methods of delivery. The encapsulation, stability, and release profiles of therapeutic release based on physical and thermodynamic properties has also been studied and modeled to an extent. Much research has been devoted to tailoring formulations for improved therapeutic encapsulation and stability as well as selective release profiles. Despite the breadth of available research on PLGA microspheres, further analysis of fundamental principles regarding the microsphere degradation, formation, and therapeutic encapsulation is necessary. This work aims to examine additional fundamental principles related to PLGA microsphere formation and degradation from solvent-evaporation of preformed polymer. In particular, mapping the development of the acidic microenvironment inside the microsphere during degradation and erosion is discussed. Also, the effect of macromolecule size and conformation is examined with respect to microsphere diameter and PLGA molecular weight. Lastly, the effects of mechanical shearing and protein exposure to aqueous media during microsphere formation are examined. In an effort to better understand the acidic microenvironment development across the microsphere diameter, pH sensitive dye conjugated to protein that undergoes conformational change at different acidic pH values was encapsulated in PLGA microspheres of diameters ranging from 40 µm to 80 µm, and used in conjunction with fluorescence resonance energy transfer to measure the radial pH change in the microspheres. Qualitative analysis of confocal micrographs was used to correlate fluorescence intensity with pH value, and obtain the radial pH across the center of the microsphere. Therapeutic encapsulation and release from polymeric microspheres is governed by an interconnected variety of factors, including the therapeutic itself. The globular protein bovine serum albumin, and the elongated and significantly smaller enzyme, lysozyme, were encapsulated in PLGA microspheres ranging from 40 µm to 80 µm in diameter. The initial surface morphology upon microsphere formation, release profiles, and microsphere erosion characteristics were explored in an effort to better understand the effect of protein size, conformation, and known PLGA interaction on the formation and degradation of PLGA microspheres and macromolecule release, with respect to PLGA molecular weight and microsphere diameter. In addition to PLGA behavior and macromolecule behavior, the effect of mechanical stresses during fabrication was examined. Two similar solvent extraction techniques were compared for the fabrication of albumin loaded microspheres. In particular, the homogeneity of the microspheres as well as capacity to retain encapsulated albumin were compared. This preliminary study paves the way for a more rigorous treatment of the effect of mechanical forces present in popular microsphere fabrication. Several factors affecting protein release from PLGA microspheres are examined herein. The technique explored for spatial resolution of the pH inside the microsphere proved mildly effective in producing a reliable method of mapping microsphere pH changes. However, notable trends with respect to microsphere size, PLGA molecular weight, and microsphere porosity were observed. Proposed methods of improving spatial resolution of the acidic microenvironment are also provided. With respect to microsphere formation, studies showed that albumin and lysozyme had little effect on the internal homogeneity of the microsphere. Rather, ionic interactions with PLGA played a more significant role in the encapsulation and release of each macromolecule. Studies also showed that higher instances of mechanical stress led to less homogeneous microspheres with lower protein encapsulation. This suggests that perhaps instead of or in addition to modifying the microsphere formation formulation, the fabrication technique itself should be more closely considered in achieving homogeneous microspheres with desired loading.

New challenges for the EU internal security strategy

In recent years, the EU and its member states have experienced a number of changes, as well as challenges, in the areas of politics, economics, security and law. As these areas are interconnected, changes and challenges to any of them have implications for the others, as well as implications for the populations and institutions of the EU or those coming into contact with its international power and influence. This edited collection focuses primarily on security and law, particularly the EU’s internal security strategy. The EU’s Internal Security Strategy, adopted by the Spanish presidency early in 2010, followed the Lisbon Treaty in 2009, building on previous developments within the EU in the Area of Freedom Security and Justice (AFSJ) policy. The focus of the EU Internal Security Strategy is to prevent and combat “serious and organised crime, terrorism and cybercrime, in strengthening the management of our external borders and in building resilience to natural and man-made disasters”. The Internal Security strategy intersects and overlaps with the European Union’s Counter-terrorism strategy, the Strategy for the External Dimension of JHA, and the EU’s Security Strategy. The role of and interaction between these strategies, their supplementing documents, and their implications for crime, victims, the law, political relations, democracy and human rights, form the backdrop against which the chapters in this collection are written. Building on original research by its contributors, this collection comprises work by authors from a wide variety of academic and professional areas and perspectives, as well as different countries, on a variety of areas and issues related to or raised by the EU’s Internal Security Strategy, from intelligence-led policing to human trafficking and port security. This book examines, from a wide variety of disciplinary perspectives including law, geography, politics and practice, both this further refinement of existing internal provisions on cross-border crime, and the increasing external relations of the EU in the AFSJ.

POLYMER-NANOPARTICLE COMPOSITES FOR APPLICATIONS IN FLEXIBLE ELECTRONICS

The aim of this dissertation was to investigate flexible polymer-nanoparticle composites with unique magnetic and electrical properties. Toward this goal, two distinct projects were carried out. The first project explored the magneto-dielectric properties and morphology of flexible polymer-nanoparticle composites that possess high permeability (µ), high permittivity (ε) and minimal dielectric, and magnetic loss (tan δε, tan δµ). The main materials challenges were the synthesis of magnetic nanoparticle fillers displaying high saturation magnetization (Ms), limited coercivity, and their homogeneous dispersion in a polymeric matrix. Nanostructured magnetic fillers including polycrystalline iron core-shell nanoparticles, and constructively assembled superparamagnetic iron oxide nanoparticles were synthesized, and dispersed uniformly in an elastomer matrix to minimize conductive losses. The resulting composites have demonstrated promising permittivity (22.3), permeability (3), and sustained low dielectric (0.1), magnetic (0.4) loss for frequencies below 2 GHz. This study demonstrated nanocomposites with tunable magnetic resonance frequency, which can be used to develop compact and flexible radio frequency devices with high efficiency. The second project focused on fundamental research regarding methods for the design of highly conductive polymer-nanoparticle composites that can maintain high electrical conductivity under tensile strain exceeding 100%. We investigated a simple solution spraying method to fabricate stretchable conductors based on elastomeric block copolymer fibers and silver nanoparticles. Silver nanoparticles were assembled both in and around block copolymer fibers forming interconnected dual nanoparticle networks, resulting in both in-fiber conductive pathways and additional conductive pathways on the outer surface of the fibers. Stretchable composites with conductivity values reaching 9000 S/cm maintained 56% of their initial conductivity after 500 cycles at 100% strain. The developed manufacturing method in this research could pave the way towards direct deposition of flexible electronic devices on any shaped substrate. The electrical and electromechanical properties of these dual silver nanoparticle network composites make them promising materials for the future construction of stretchable circuitry for displays, solar cells, antennas, and strain and tactility sensors.

Aplicação de técnicas de classificação em séries temporais

Hoje, há um interesse crescente pela aprendizagem de uma segunda língua, quer seja por razões profissionais ou pessoais. Esta é uma tendência que se vai afirmando num mundo cada vez mais interconectado. Por outro lado, a democratização das tecnologias computacionais torna possível pensar em desenvolver novas técnicas de ensino de línguas mais automatizadas e personalizadas. Esta dissertação teve como objetivo estudar e implementar um conjunto de técnicas de processamento de sinal e de classificação de séries temporais úteis para o desenvolvimento de metodologias do ensino oral com feedback automático. São apresentados resultados preliminares sobre a prestação destas técnicas, e avaliada a viabilidade deste tipo de abordagem.

PREPARATION OF POLYELECTROLYTE MEMBRANES EMBEDDED WITH ZEOLITE NANOPARTICLES FOR ENHANCED PERFORMANCE IN FORWARD OSMOSIS

Water scarcity is a global issue that has already affected every continent. Membrane technology is considered as one of the most promising candidates for resolving this worsening issue. Among all the membrane processes, the emerging forward osmosis (FO) membrane process is osmotically-driven and has unique advantages compared with other traditional pressure-driven membrane processes. One of the major challenges to advancing the FO membrane process is the lack of a suitable membrane. Polyelectrolyte thin film prepared via layer-by-layer (LbL) technique has demonstrated its excellent performance in many applications including electronics, optics, sensors, etc. Recent studies have revealed the potential of polyelectrolyte thin films in acting as the active separation layer of FO membranes, but significant efforts are still needed to improve the membrane performance and understand the transport mechanisms. This dissertation introduces a novel approach to prepare a zeolite-embedded polyelectrolyte composite membrane for enhanced FO performance. This membrane takes advantages of the versatile LbL process to unprecedentedly incorporate high loading of zeolite nanoparticles, which are anticipated to facilitate water transport due to the uniquely interconnected structure of zeolites. Major topics discussed in this dissertation include: (1) the synthesis and evaluation of the polyelectrolyte-zeolite composite FO membrane, (2) the examination of the fouling resistance to identify its technical limitations, (3) the demonstration of the membrane regenerability as an effective strategy for membrane fouling control, and (4) the investigation of crosslinking effects on the membrane performance to elucidate the transport mechanisms involved in the zeolite-embedded polyelectrolyte membranes. Comparative studies have been made between polyelectrolyte membranes with and without zeolite incorporation. The findings suggest that the zeolite-embedded membrane, although slightly more susceptible to silica scaling, has demonstrated enhanced water flux and separation capability, good resistance to organic fouling, and complete regenerability for fouling control. Additionally, the embedded zeolite nanoparticles are proved to be able to create fast pathways for water transport. Overall, this work provides a novel strategy to create zeolite-polymer composite membranes with enhanced separation performance and unique fouling mitigation properties.

Humankindness: Illness, Animality, and the Limits of the Human in the Victorian Novel

This project posits a link between representations of animals or animality and representations of illness in the Victorian novel, and examines the narrative uses and ideological consequences of such representations. Figurations of animality and illness in Victorian fiction have been examined extensively as distinct phenomena, but examining their connection allows for a more complex view of the role of sympathy in the Victorian novel. The commonplace in novel criticism is that Victorian authors, whether effectively or not, constructed their novels with a view to the expansion of sympathy. This dissertation intervenes in the discussion of the Victorian novel as a vehicle for sympathy by positing that texts and scenes in which representations of illness and animality are conjoined reveal where the novel draws the boundaries of the human, and the often surprising limits it sets on sympathetic feeling. In such moments, textual cues train or direct readerly sympathies in ways that suggest a particular definition of the human, but that direction of sympathy is not always towards an enlarged sympathy, or an enlarged definition of the human. There is an equally (and increasingly) powerful antipathetic impulse in many of these texts, which estranges readerly sympathy from putatively deviant, degenerate, or dangerous groups. These two opposing impulses—the sympathetic and the antipathetic—often coexist in the same novel or even the same scene, creating an ideological and affective friction, and both draw on the same tropes of illness and animality. Examining the intersection of these different discourses—sympathy, illness, and animality-- in these novels reveals the way that major Victorian debates about human nature, evolution and degeneration, and moral responsibility shaped the novels of the era as vehicles for both antipathy and sympathy. Focusing on the novels of the Brontës and Thomas Hardy, this dissertation examines in depth the interconnected ways that representations of animals and animality and representations of illness function in the Victorian novel, as they allow authors to explore or redefine the boundary between the human and the non-human, the boundary between sympathy and antipathy, and the limits of sympathy itself.

Alan Pauls: Poéticas del anacronismo

Alan Pauls (b. 1959) is an Argentine novelist and essayist. His works have barely been studied outside of Latin America; therefore, my work will be one of the first to focus critically and theoretically on his oeuvre and raise awareness of his importance to Contemporary Latin American Literature. The fundamental concept of my thesis is anachronism, which I develop by investigating the ways in which the present and the past are interconnected in the same temporal space. My dissertation has two interconnected parts. In the first, I propose an approach to Pauls’ literary work that emphasizes its engagement with literary and cultural theory. Specifically, I analyze how Pauls’ first novels –El pudor del pornógrafo (1984), El coloquio (1989), Wasabi (1994)– are strongly influenced by various theoretical discourses, especially the work of Roland Barthes. The guiding question of my dissertation’s first part is how one can narrate a fictional text without strictly appropriating narrative devices. Namely, I suggest that Pauls’ conception of literature is inevitably related to critical discourse. In the second part, I study a trilogy that Pauls wrote about the 1970s in Argentina: Historia del llanto (2007), Historia del pelo (2010), and Historia del dinero (2013). Here I focus on how Pauls uses the 1970s to propose a new conceptualization of the “political.” For Pauls, the “political” is not represented in the great events of a particular time but rather in the “effects” that these events produce; these effects are minor, almost imperceptible, and for that reason much more powerful as a literary event mechanism per se. From my point of view, this new conceptualization of the “political” contains in itself a problematic issue: the articulation between personal experience, history, and fiction. In conclusion, this interrelation between theory, politics, history, and fiction defines the path of my dissertation, which would have been just the “starting point” in my personal attempt to reconfigure the map of the Latin American literary contemporaneity.

Demonstrador para rede tempo-real HaRTES

A utilização de sistemas embutidos distribuídos em diversas áreas como a robótica, automação industrial e aviónica tem vindo a generalizar-se no decorrer dos últimos anos. Este tipo de sistemas são compostos por vários nós, geralmente designados por sistemas embutidos. Estes nós encontram-se interligados através de uma infra-estrutura de comunicação de forma a possibilitar a troca de informação entre eles de maneira a concretizar um objetivo comum. Por norma os sistemas embutidos distribuídos apresentam requisitos temporais bastante exigentes. A tecnologia Ethernet e os protocolos de comunicação, com propriedades de tempo real, desenvolvidos para esta não conseguem associar de uma forma eficaz os requisitos temporais das aplicações de tempo real aos requisitos Quality of Service (QoS) dos diferentes tipos de tráfego. O switch Hard Real-Time Ethernet Switching (HaRTES) foi desenvolvido e implementado com o objetivo de solucionar estes problemas devido às suas capacidades como a sincronização de fluxos diferentes e gestão de diferentes tipos de tráfego. Esta dissertação apresenta a adaptação de um sistemas físico de modo a possibilitar a demonstração do correto funcionamento do sistema de comunicação, que será desenvolvido e implementado, utilizando um switch HaRTES como o elemento responsável pela troca de informação na rede entre os nós. O desempenho da arquitetura de rede desenvolvida será também testada e avaliada.

Delito y moral en el Coloquio de los perros

[es] En virtud del pensamiento jurídico de la Edad Moderna los conceptos de delito y pecado estaban interrelacionados. Asimismo, las Novelas ejemplares, entre otras obras literarias, reflejan la ideología imperante y concerniente a la necesaria salvaguarda del orden público y religioso. A la luz del derecho criminal castellano, el principal propósito de este ensayo es el análisis de los comportamientos heterodoxos y de los delitos perpetrados por los personajes del Coloquio de los perros. Algunas prácticas ilícitas contempladas son el robo, el amancebamiento y la brujería. [en]In the Early Modern legal thought the concepts of crime and sin were interconnected. Furthermore Exemplary Novels, amongst other literary works, reflect the prevailing ideology concerning to necessary maintenance of public and religious order. In the light of the Castilian criminal law, the main purpose of this essay is the analysis of the heterodox behaviors and the offences perpetrated by the characters in The dialogue of the dogs. Some narrated crimes are theft, concubinage and sorcery.

Relaciones y capacidades interorganizativas: un enfoque de Supply Chain Management (SCM) en red

El presente trabajo mide, en un contexto colaborativo, un conjunto de mecanismos relacionales interconectados y su incidencia en el performance organizacional. Apoyado en la Visión Relacional (Dyer y Singh, 1998), el trabajo integra mecanismos de las capacidades relacionales y capacidades competitivas en el concepto denominado ¿capacidades interorganizativas¿. Las capacidades interorganizativas se componen de la ¿confianza¿ y los mecanismos ¿combinar recursos complementarios¿, ¿invertir en activos específicos¿, ¿compartir información¿ y ¿solucionar problemas conjuntamente¿. La medición tiene lugar en la Industria Alimentaria (IA) española en un contexto de Supply Chain Management1 en red. Además de mejorar el conocimiento sobre las relaciones interorganizativas, el trabajo también realiza una revisión teórica sobre el sector agroalimentario en general y la IA en particular. Los resultados permiten confirmar, con excepciones, el constructo teórico de las ¿capacidades interorganizativas en un contexto de Supply Chain Management en red¿. Otros resultados obtenidos son los altos niveles de confianza en las relaciones entre socios y una industria que, pese al entorno competitivo y complejo actual, presenta niveles competitivos en términos de flexibilidad, respuesta, calidad y eficiencia. De igual modo, la investigación descubre la implantación de la capacidad de las empresas de la industria para gestionar el conocimiento. En este contexto, los resultados parecen indicar una correcta integración de la cadena de suministros de la IA que confirman la efectiva aplicación de la Supply Chain Management. Otras conclusiones obtenidas son la dependencia que ha tenido y tiene la industria alimentaria española de la distribución, intensificada en parte por la expansión de las marcas del distribuidor (MDDs).