The North House is a proof-of-concept prefabricated solar powered home designed for northern climates, and intended for the research and promotion of high-performance sustainable architecture. Led by faculty at the University of Waterloo, the development and design of the project involved a broad collaboration between faculty and students at the University of Waterloo, with Ryerson University and Simon Fraser University. The North House prototype competed in the U.S. Department of Energy’s Solar Decathlon in October of 2009. This thesis identifies the North House as a component-based building. It illustrates in detail the components of which the house is composed, the sequence by which they are assembled, and the details that allow for the building’s rapid assembly and disassembly. Finally, the thesis explores the possibilities afforded by componentbased architecture including adaptability, off-site fabrication and demountability. Drawing on this, the thesis projects future ways of designing buildings sustainable to both manufacture and operate.

Depression and stimulant drug addiction each result in massive losses of health, productivity and human lives every year. Despite decades of research, current treatment regimes for depression are ineffective in approximately half of all patients. Therapy available to stimulant drug addicts is largely ineffective and moreover, dedicated treatments for drug dependence (including abuse of cocaine) are non-existent. Thus, there is a pressing need to further understanding of the molecular mechanisms underlying these disorders in order to develop novel, targeted therapeutic strategies. Chromatin remodeling, including changes in histone acetylation, has been proposed to play a role in both the etiology and treatment of depression and stimulant abuse. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate numerous cellular processes, including transcription, cell cycle progression and differentiation. Moreover, histone acetylation has been shown to regulate hippocampal neurogenesis, a cellular response associated with the pathogenesis and treatment of depression and stimulant abuse (Hsieh et al., 2004, Yamaguchi et al., 2004, Fischer et al., 2007). Ultimately, such basic cellular processes impact higher order function, namely cognition and emotion. Indeed, recent studies suggest that HDAC activity in selected forebrain regions, including ventral striatum and hippocampus, modulate stimulant- and antidepressantinduced behavior (Kumar et al., 2005, Tsankova et al., 2006a, Fischer et al., 2007). These reports highlight an association between chromatin remodeling and diverse behavioral changes, including changes induced by the pleiotropic HDAC inhibitor, sodium butyrate (SB), (Kumar et al., 2005, Tsankova et al., 2006a, Fischer et al., 2007). However, behavioral, brain-metabolic and molecular effects of SB treatment in the context of rodent models of depression, dopaminergic sensitization and repeated cocaine administration remained unclear. The work described in this thesis illustrates the potential for chromatin modifying drugs in mechanisms underlying the experimental pharmacology of depression and stimulant addiction. Specifically, the data presented here support the view that treatment with the short chain fatty acid, sodium butyrate enhances: (1) antidepressant-like behavioral effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine (2) locomotor sensitization induced by repeated administration of the dopamine D1/D5 receptor agonist SKF82958; and(3) brain metabolic activation upon repeated cocaine administration as evidenced by fMRI in awake rats. Furthermore, this report provides evidence that these treatment paradigms will result in chromatin modification changes associated with active transcription, in addition to increased mRNA levels of plasticity-associated genes, including brain-derived neurotrophic factor (BDNF) at key brain regions implicated in the pathogenesis of depression and stimulant addiction. To date, little is known regarding the underlying mechanisms of action mediating the enhancing effects of sodium butyrate on the various antidepressant- and stimulantrelated paradigms. Our findings underscore the potential of chromatin-modifying drugs to profoundly affect the behavioral response of an animal to antidepressant and stimulant drugs and warrants consideration in the context of developing novel therapeutic strategies.

O presente trabalho descreve o desenvolvimento de um microcomputador de 8 bits. O projeto inclui além dos circuitos básicos, lógica adicional para extender a memória contornando o limite normal de endereçamento. Um disco virtual uma interface em RAM e uma interface para \"Winchester\" foram desenvolvidas para extender a capacidade de armazenamento secundário e a velocidade de execução. Suporte para o coprocessador AM9511 é fornecido para freqüentes cálculos em ponto flutuante. Rotinas para operações básicas de E/,. manipulação da memória e \"Caching\" de disco, foram desenvolvidas para suportar o sistema operacional CP/M. Um monitor residente com montador, desmontador e funções de E/S de alto nível, foi construído para ajudar no desenvolvimento de aplicações dedicadas. / The present works describes the development of an 8 bits microcomputer system. The project includes, besides the basic circuity, additional logic for memory extension behind the regular address limit. A virtual RAM disk and a Winchester interface were developed to extend secondary storage and execution speed. For floating point intensive calculations support for an AM9511 coprocessor is given. Routines for basic I/O operations, memory management and disk \"Caching\" were developed to support the CP/M operating system. A resident monitor with assembly, disassembly and high level I/O functions was constructed to aid the development of dedicated application.

Les travaux présentés dans ce manuscrit portent sur la conception des lignes de désassemblageen contexte incertain. Une ligne de désassemblage consiste en unesuccession de postes de travail où les tâches sont exécutées séquentiellement au niveau de chaque poste. La conception d'un tel système, de revalorisationdes produits en fin de vie, peut être ramenée à un problème d'optimisation combinatoire.Ce dernier cherche à obtenir une configuration permettant d'optimiser certains objectifs enrespectant des contraintes techniques, économiques et écologiques.Dans un premier temps, nous décrivons les activités principales de la revalorisation des produitsen fin de vie, en particulier le désassemblage. Puis, après présentation des travaux de la littératureportant sur la prise en compte des incertitudes des durées opératoires lors de la conception des lignesde production, nous nous focalisons sur l'étude des incertitudes des durées opératoires des tâches de désassemblage.Ainsi, nous présentons trois modélisations principales avec leurs approches de résolution.La première s'intéresse à la minimisation des arrêts de la ligne causés par les incertitudes des durées des opérationsde désassemblage. La deuxième cherche à garantir un niveau opérationnel de la ligne lié à sa cadence de fonctionnement.Le but de la troisième modélisation est l'intégration des problématiques de conception des ligneset de séquencement des tâches de désassemblage. Enfin, les performances des méthodes de résolutionproposées sont présentées en analysant les résultats d'optimisation sur un ensemble d'instances de taille industrielle. / This thesis is dedicated to the problem of disassembly line design in uncertain context. A disassembly linecan be represented as a succession of workstations where tasks are performed sequentially at each workstation.The design of such a product recovery system can be reduced to a combinatorial optimization problem which seeksa line configuration that optimizes certain objectives under technical, economical and environmental constraints.We begin by describing the principal product recovery activities especially disassembly. Then, after a literaturereview on the design of production lines under uncertainty of task processing times, we focus our study on the consideration of the disassembly task time uncertainties. Hence, we present three main models as well as the associatedsolution approaches. The first one is interested in minimizing the line stoppages caused by the task processing timeuncertainties. The second one seeks to guarantee an operational level closely related with the line speed. The goal of thethird model is to integrate the line design and sequencing problems. At last, the performances of the proposed solutionapproaches are presented by analyzing the optimization results on a set of instances of industrial size.

Människans negativa miljöpåverkan har orsakat att jordens temperaturökning har fördubblats på kort tid och vars åtgärd kräver omgående förändringar i samhället. Ett hållbart förhållningssätt är väsentligt för att inte äventyra kommande generationers förutsättningar på jorden. En omställning till en cirkulär ekonomi är nödvändigt för att gynna en hållbar utveckling. Byggsektorns resursanvändning och avfall orsakar en stor andel av samhällets miljöpåverkan och har en betydelsefull roll i den cirkulära övergången. Återbruk av bygg- och rivningsavfall är en viktig del av cirkulära strategier, men som sektorn varit långsamma på att implementera. Kandidatarbetet undersöker möjligheterna att utforma en mindre trävilla med hänsyn på återbruk. Syftet med studien är att framställa en förslagshandling för en trävilla som tar hänsyn på cirkulära strategier som möjliggör återbruk av de ingående komponenterna. Studien baseras på en kvalitativ metod som inledningsvis bestod av en litteraturstudie, därefter hölls workshop med aktörer i byggbranschen för att ta del av deras kunskaper inom ämnesområdet. I konsultation med aktörerna diskuterades möjligheter och svårigheter vid utformning av småhus med hänsyn till återbruksbara byggnadskomponenter. Studiens resultat visar att byggsektorn i största allmänhet är medvetna om de ekologiska fördelarna av cirkulära strategier som att projektera för demontering, men att dessa inte nyttjas i någon större utsträckning. Det beror delvis på byggsektorns okunskap om hur byggnaders utformning påverkar komponenternas möjlighet till återbruk och dels på osäkerheterna kring den ekonomiska lönsamheten. För att öka återbruk i byggsektorn kommer sektorn behöva ekonomiska incitament som nya avgifts- och beskattningsstrukturer. För att främja återbruk av ingående byggkomponenter är det viktigt att tidigt planera för komponenternas åtkomlighet, reparation och demontering. För att förenkla förändringsarbete och underhåll bör byggnaden utformas med stora öppna ytor och med en så stor andel prefabricerade moduler och komponenter. Byggnadens komponenter bör väljas med hänsyn på att de ska vara hållbara och lätta att hantera vid montering och demontering.

Jak3, a member of the Janus family of tyrosine kinases, is essential for signaling via the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These Jak3-dependent cytokines primarily activate STAT5 and are critical for lymphoid generation and differentiation. Using naïve CD4+ T cells from Jak3-deficient mice and wild type CD4+ T cells treated with a pharmacological inhibitor of Jak3, we report that Jak3-dependent cytokine signals are not required for the proliferation of naïve CD4+ T cells. This is illustrated by the similar percentage of divided cells, comparable cell divisions, intact cell cycle progression and unaffected regulation of cell cycle proteins in the absence of Jak3. In contrast to proliferation, differentiation of naïve CD4+ T cells into Th1 effector cells requires Jak3-dependent cytokine signals. In the absence of Jak3, naïve CD4+ T cells proliferate robustly, but produce little IFN-γ after Th1 polarization in vitro. This defect is not due to reduced activation of STAT1 or STAT4, nor to impaired up-regulation of the transcription factor T-bet. Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. These data indicate that while Jak3-dependent signals are dispensable for naïve CD4+ T cell proliferation, Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 differentiation.

Für Brennstoffzellen wird in den kommenden Jahren ein erhebliches Marktwachstum prognostiziert. Aktuell besteht die Notwendigkeit die technischen und wirtschaftlichen Herausforderungen für einen Markthochlauf zu realisieren. Hierzu müssen neue hochratenfähige Fertigungstechnologien entwickelt werden, um die Produktions- und Stückkosten zu senken. Für das Stapeln von Brennstoffzellen-Stacks sollen zukünftig mehrere entwickelte Konzepte für das „Stacking im Fließverfahren“ betrachtet und hinsichtlich ihrer Machbarkeit und Wirtschaftlichkeit überprüft werden. Zusätzlich müssen hochratenfähige Prüfverfahren entwickelt werden, um eine Null-Fehler-Produktion der kostenintensiven Komponenten und Systeme zu gewährleisten. Hierbei sollen u.a. KI-basierte Technologien genutzt werden. Die Abhandlung zeigt den aktuellen Stand der Technik auf dem Gebiet des Stapelns und stellt innovative und zugleich wirtschaftliche technische Lösungsansätze vor, wie die Fertigungsprozesse zukünftig gestaltet werden können und welche technologischen Neuerungen dafür notwendig sein werden. Weiterhin steht die Demontage der Brennstoffzellen unter dem Aspekt einer optimalen Verwertung (Recycling) sowie insbesondere der Nachnutzung (ReUse) im Fokus der Betrachtungen. / Considerable market growth is forecast for fuel cells in the coming years. Currently, there is a need to realise the technical and economic challenges for a market ramp-up. To this end, new high-rate manufacturing technologies must be developed in order to reduce production and unit costs. For the stacking of fuel cell stacks, several developed concepts for 'stacking in a flow process' are to be considered in the future and examined with regard to their feasibility and economic efficiency. In addition, high-rate testing methods must be developed to ensure zero-defect production of the cost-intensive components and systems. Among other things, AI-based technologies are to be used here. The paper shows the current state of the art in the field of stacking and presents innovative and at the same time economical technical solution approaches, how the manufacturing processes can be designed in the future and which technological innovations will be necessary for this. Furthermore, the disassembly of the fuel cells under the aspect of optimal utilisation (recycling) as well as re-utilisation (ReUse) is the focus of the considerations.

In the last years electric vehicles gained importance as a more sustainable alternative to traditional vehicles. The introduction of an electric powertrain leads to lower air-pollution emissions but it also involves the introduction of new materials in the product life cycle, e. g., the rare earths and lithium contained in the motor and in the batteries. Those materials have an environmental impact and they need to be disposed properly. The aim of this thesis is to have a quantitative knowledge of the environmental balance linked to the use of a different powertrain. Furthermore, this study explores how this balance can be modified improving the recycling and the end of life management. Specifically in this thesis, an average electric scooter has been chosen as a case study. The electric scooter is used as object of comparison with a traditional internal-combustion-engine scooter. The choice of a two-wheeled mean of transport is linked to the low level of facilities involved. This report first includes a definition of the case of study; this section also presents a description of the technologies taken into exam. It is also presented the result of interviews with dismantlers to depict the current process of EoL management of a scooter. The central part of thesis deals with different recycling scenarios. With the help of the Material Hygiene mind-set, a qualitative analysis and different recycling scenarios are proposed. The recycling scenarios involve the component of the electric powertrain that are peculiar of the electric vehicle. They mainly are the electric motor and the lithium battery pack. The last part of the analysis encompasses a Life Cycle Assessment of an average electric scooter to give a quantitative meaning to the life cycle comparison and to assess the environmental benefits of the proposed recycling scenarios. To perform the Life Cycle Assessment a software, SimaPro 7.3, is used. This software lets the user insert the bill of materials of the product and it associates to each material its environmental loads according to the database EcoInvent v.2.2. Keywords: electric scooter, lithium battery, permanent magnet, neodymium, Material Hygiene, Design for Disassembly, Life Cycle Assessment, LCA / Negli ultimi anni i veicoli elettrici sono emersi come un ’alternativa sostenibile ai veicoli tradizionali. L’introduzione di un gruppo propulsore elettrico permette emissioni inquinanti più basse ma comporta anche l’introduzione di nuovi materiali nel ciclo di vita del prodotto, e.g., le terre rare e il litio contenuti rispettivamente nel motore e nelle batterie. Questi materiali hanno un impatto ambientale e hanno bisogno di essere trattati correttamente. Lo scopo di questa tesi è di avere una comprensione quantitativa del bilancio dal punto di vista ambientale legato al l’adozione di sistema di propulsione elettrico. Inoltre, è indagato come questo bilanco possa essere influenzato migliorando il ricic laggio e la gestione dell’ultima fase di vita del prodotto. Nello specifico, in questa tesi, uno scooter elettrico è stato scelto come caso di studio. Lo scopo è di comparare questo scooter con uno tradizionale considerando il ciclo di vita del prodotto. Il mezzo di trasporto a due ruote è stato scelto perché considerato più semplice da modellare in quanto privo di componenti non inerenti al trasporto (es. aria condizionata, hi-fi, etc.). Questo report anzitutto include una definizione del caso di studio, questa sezione presenta anche una descrizione delle principali tecnologie coinvolte nel prodotto studiato. In questa parte del lavoro è anche riportato il risultato di interviste a rottamatori di scooter per illustrare l’attuale iter di rottamazione di uno scooter. La parte centrale della tesi tratta i differenti scenari di riciclaggio. Sfruttando la mentalità Material Hygiene vengono proposte un’analisi qualitativa e differenti scenari di rici claggio. Gli scenari di riciclaggio coinvologono il progettista a livelli differenti. Questi scenari riguardano i componenti del sistema di propulsione elettrico. Essi sono principalmente il motore elettrico e le batterie al litio. L’ultima parte dell’analisi riguarda il Life Cycle Assessment di uno scooter elettrico al fine di dare un significato quantitativo al confronto tra i cicli di vita delle due alternative. Inoltre, il life cycle assessment ha lo scopo di verificare e quantificare i benefici di impatto ambientale collegati all’adozione degli scenari di riciclaggio proposti. Per svolgere il Life Cycle Assessment è stato usato un sofware, SimaPro 7.3. Questo software permette all’utente di inserire l’elenco dei materiali di un prodotto e di associare a ciascun materiale il proprio impatto ambientale. Il software ha a disposizione per la modellazione i database di impatto ambientale EcoInvent 2.2. Parole chiave: scooter elettrico, batteria al litio, magnete permanente, neodimio, Material Hygiene, Design for Disassembly, Life Cycle Assessment, LCA

DNA double-strand break (DSB) repair is essential for maintenance of genome stability. However, the compaction of the eukaryotic genome into chromatin creates an inherent barrier to any DNA-mediated event, such as during DNA repair. This demands that there be mechanisms to modify the chromatin structure and thus access DNA. Recent work has implicated a host of chromatin regulators in the DNA damage response and several functional roles have been defined. Yet the mechanisms that control their recruitment to DNA lesions, and their relationship with concurrent histone modifications, remain unclear. We find that efficient DSB recruitment of many yeast chromatin regulators is cell-cycle dependent. Furthering this, we find recruitment of the INO80, SWR-C, NuA4, SWI/SNF, and RSC enzymes is inhibited by the non-homologous end joining machinery, and that their recruitment is controlled by early steps of homologous recombination. Strikingly, we find no significant role for H2A.X phosphorylation (γH2AX) in the recruitment of chromatin regulators, but rather that their recruitment coincides with reduced levels of γH2AX. We go on to determine the chromatin remodeling enzyme Fun30 functions in histone dynamics surround a DSB, but does not significantly affect γH2AX dynamics. Additionally, we describe a conserved functional interaction among the chromatin remodeling enzyme, SWI/SNF, the NuA4 and Gcn5 histone acetyltransferases, and phosphorylation of histone H2A.X. Specifically, we find that the NuA4 and Gcn5 enzymes are both required for the robust recruitment of SWI/SNF to a DSB, which in turn promotes the phosphorylation of H2A.X.

XIST RNA established the precedent for a noncoding RNA that stably associates with and regulates chromatin, however it remains poorly understood how such RNAs structurally associate with the interphase chromosome territory. I demonstrate that transgenic XIST RNA localizes in cis to an autosome as it does to the inactive X chromosome, hence the RNA recognizes a structure common to all chromosomes. I reassess the prevalent thinking in the field that a single protein, Scaffold Attachment Factor-A (SAF-A/hnRNP U), provides a single molecule bridge required to directly tether the RNA to DNA. In an extensive series of experiments in multiple cell types, I examine the effects of SAF-A depletion or different SAF-A mutations on XIST RNA localization, and I force XIST RNA retention at mitosis to examine the effect on SAF-A. I find that SAF-A is not required to localize XIST RNA but is one of multiple proteins involved, some of which frequently become lost or compromised in cancer. I additionally examine SAF-A’s potential role localizing repeat-rich CoT-1 RNA, a class of abundant RNAs that we show tightly and stably localize to euchromatic interphase chromosome territories, but release upon disruption of the nuclear scaffold. Overall, findings suggest that instead of “tethering” chromosomal RNAs to the scaffold, SAF-A is one component of a multi-component matrix/scaffold supporting interphase nuclear architecture. Results indicate that Cot-1 and XIST RNAs form integral components of this scaffold and are required to maintain the chromosomal association of SAF-A, substantially advancing understanding of how chromatin-associated RNAs contribute to nuclear structure.