La déformation visco-plastique de la glace est fortement anisotrope, le plan de glissement préferé étant la plan de base. Le fait que dans un polycristal chaque grain possède sa propre direction de déformation produit des incompatibilités et un champ de contrainte complexe. La déformation à été étudiée expérimentellement en mésurant la dis- tortion des plans cristallins de mono- et polycristaux de glace artificielle. Les expériences ont été réalisées à l'aide d'un faisceau synchrotron. Une nouvelle procédure éxperimental, basée sur les méthodes de l'imagerie en diffraction de Bragg, comme lumière blanche, im- agerie sur la courbe de diffraction et topographie laminaire et ponctuelle, a été dévéloppée. Les désorientations angulaires, les largeurs à mi-hauteur et les intensités intégrées ont été mésurées dans les trois dimensions spatiales de l'échantillon et avec une résolution de 50× 50 × 50µm3. Les algorithmes d'analyse de données ont été écrits pour extraire des données des résultats quantitatifs, et pour calculer les neuf composantes du tenseur de courbure ainsi que la distortion entière des plans cristallins. Les résultats ont permis d'observer les premières étappes de la déformation de la glace. Par example la polygonisation d'un grain à été observée.

The purpose of this study is to evaluate potential travel time impacts of the implementation of exclusive heavy-vehicle lanes on the Interstate Highway 35 (IH 35) corridor, in the Austin metropolitan area. The analysis considers heavy vehicles (trucks) and non-heavy vehicles (cars) as separate system elements and as an integrated system. The study modeled traffic operations on IH 35, during the AM and PM peak hours, under two traffic scenarios, Existing and Inside Truck-Only Lanes using the software VISSIM 5.4. The limits of the study are FM 1431 in Round Rock, on the north, and SH 45 near Buda, on the south. The Existing scenario modeled traffic operations under current IH 35 geometric conditions and traffic control rules, in which trucks are prohibited from the inside lane and cars are allowed in all lanes. The Inside Truck-Only Lanes scenario modeled traffic operations under the assumption that trucks are restricted to the inside lane only and cars are prohibited from the inside lane. Travel times across the study area corridor were measured in the models to compare the performance of the Inside Truck-Only Lanes scenario relative to the Existing scenario. / text

Neurons perform complex computations, communications and precise transmissions of information in the form of action potentials (APs). The high level of heterogeneity and complexity at all levels of organization within a neuron and the functional requirement of highly permeable cell membranes leave neurons exposed to damage when energy levels are insufficient for the active maintenance of ionic gradients. When energy is limiting the ionic gradient across a neuron’s cell membrane risks being dissipated which can have dire consequences. Other researchers have advocated “generalized channel arrest” and/or “spike arrest” as a means of reducing the neuronal permeability allowing neurons to adjust the demands placed on their electrogenic pumps to lower levels of energy supply. I investigated the consequences of hypoxia on the propagation of a train of APs down the length of a fast conducting axon capable of transmitting APs at very high frequencies. Under normoxic conditions I found that APs show conduction velocities and instantaneous frequencies nearly double that of neurons experiencing energy limiting hypoxic conditions. I show that hypoxia affects AP conduction differently for different lengths of axon and for APs of different instantaneous frequencies. Action potentials of high instantaneous frequency in branching lengths of axon within ganglia were delayed more significantly than those in non-branching lengths contained within the connective and fail preferentially in branching axon. I found that octopamine attenuates the effects of hypoxia on AP propagation for the branching length of axon but has no effect on the non-branching length of axon. Additionally, for energetically stable cells, application of the anti-diabetic medication metformin or the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 resulted in a reduced performance similar to that seen in neurons experiencing energetic stress. Furthermore both metformin and ZD7288 affect the shape of individual APs within an AP train as well as the original temporal sequence of the AP train, which encodes behaviourally relevant information. I propose that the reduced performance observed in an energetically compromised cell represents an adaptive mechanism employed by neurons in order to maintain the integrity of their highly heterogeneous and complex organization during periods of reduced energy supply. / Thesis (Master, Biology) -- Queen's University, 2011-10-07 14:41:46.972

Made available in DSpace on 2015-12-06T23:46:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2013 / Este trabalho possui o objetivo de avaliar a usabilidade das interfaces graficas de dois sistemas de Gestão hospitalar. Os sitemas escolhidos foram o PEP/Unifesp e Tasy, por serem produzidos no Brasil e possuir origens distintas. O primeiro e um sistema nao comercializado, pertence e e utilizado na universidade de São Paulo. O segundo e um sistema comercializado pela empresa Philips, onde varias instituicoes de Saúde o utilizam inclusive o Hospital do Rim o qual doi o foco da pesquisa. A avaliacao da usabilidade foi realizada atraves de duas tecnicas documentadas na literatura. A primeira etapa consistiu na avaliacao do tipo diagnostica ou preditiva, onde nao e necessaria a utilizacao de usuarios finais dos sistemas. Essa fase foi realizada pelo autor junto de duas pessoas voluntarias, onde responderam o checklist denominado Ergolist. A segunda avaliacao, do tipo prospectivo, foi realizada com o usuario sendo o proprio avaliador das interfaces. Eles responderam a um questionario. Para as duas tecnicas, foram utilizados criterios ergonomicos desenvolvidos pelos pesquisadores franceses Bastien e Scapin, sao 18 criterios e subcriterios que as interfaces devem possuir para obter boa usabilidade. A amostra foi compostas por 20 medicos, escolhidos de acordo com a disponibilidade dos medicos, ou seja foi uma amostra de conveniencia. Os resultados mostraram que os ambientes apresentaram problemas de adaptabilidade, pois nao possuem flexibilidade em suas interfaces e nao levam em consideracao a experiencia do usuario. Por sua vez, os criterios coerencia e legibilidade obtiveram os melhores resultados para os dois sistemas, confirmando assim que as informacoes presentes na interface sao de facil acesso e que as paginas seguem padroes bem definidos. Alguns criterios utilizados na pesquisa obtiveram resultados diferentes nas avaliacoes. Dessa forma, podemos salientar a necessidade de utilizar varias tecnicas em conjunto para a avaliacao de usabilidade / The main objective of this project is to evaluate the usefulness of the graphicinterfaces of two systems of hospital management. The chosen systems were o PEP/Unifesp e Tasy; because they were developed in Brazil and they have different origins. The first one is a noncommercial system, it belongs and it’s used by the University of São Paulo. The second system is a commercialized system by Philips; many institutions are using it, especially the Hospital do Rim (São Paulo) which is the focus of the research. The evaluation of the usefulness was applied thought two technics documented in literature. The first step was diagnostic or predictive evaluation, which is not necessary the use of the final system users. This step was performed by the author and two volunteers; they answered the checklist named “Ergolist”. The second evaluation, a prospective, was performed by the user as the evaluator of the interfaces. They answered a questionnaire. Both technics, ergonomics criterion were developed by French researchers Bastien and Scapin. There are 18 criteria and sub-criteria that interfaces should have in order to get a good usability. The sample was composed by 20 doctors, randomly chosen by the author. The results showed that the environments presented adaptability issues, due to the inflexibility of the interfaces; it was not taken into consideration the user experience. Therefore the criteria coherence and readability achieved the best results systems, thus confirming that the information in the interface are easy to access and that the pages follow well-defined patterns. Some criteria used in the survey scored differently in evaluations. Thus, it is important to highlight the need to use several techniques together for usability evaluation. / BV UNIFESP: Teses e dissertações

SH3 and multiple ankyrin repeat domains 3 (SHANK3) is a multidomain scaffold protein that is highly augmented in the postsynaptic density (PSD) of excitatory glutamatergic synapses within the central and peripheral nervous systems. SHANK3 links neurotransmitter receptors, ion channels, and other critical membrane proteins to intracellular cytoskeleton and signal transduction pathways. Mutations in SHANK3 are linked with a number neuropsychiatric disorders including autism spectrum disorders (ASDs). Intellectual disability, impaired memory and learning, and epilepsy are some of the deficits commonly associated with ASDs that result from mutations in SHANK3. Interestingly, these symptoms show some clinical overlap with presentations of human neurological disorders involving hyperpolarization-activated cyclin nucleotide-gated (HCN) channels. In fact, it has recently been demonstrated in human neurons that SHANK3 haploinsufficiency causes Ih-channel dysfunction, and that SHANK3 has a physical interaction with HCN channels via its ANKYRIN repeat domain. These insights suggest that SHANK3 may play important roles in HCN channel expression and function, and put forward the idea that HCN channelopathies may actually encourage some of the symptoms observed in patients with SHANK-deficiency related ASDs. In this study, we provide preliminary data that suggests the ANK domain of SHANK3 interacts with COOH portion of HCN1. We also exploited the differences between two mouse models of autism to show that a subset of SHANK3 isoforms may be involved in the proper expression and function of HCN channels. We found that HCN2 expression is significantly decreased in a mouse model lacking all major isoforms of SHANK3 (exons 13-16 deleted; Δ13-16), while HCN2 expression is unaltered in a mouse model only lacking SHANK3a and SHANK3b (exons 4-9 deleted; Δ4-9). Surprisingly, we also found that HCN4 expression is altered in SHANK3Δ13-16, but not SHANK3Δ4-9. Taken together, our results show HCN channelopathy as a major downstream carrier of SHANK3 deficiency.

Der vorliegenden Studie Die dialektische Lebenskunst von Guy Debord, Verworfener & Kulturschatz liegt eine interdisziplinäre Untersuchung des Gesamtwerks jenes französischen Radikalen zugrunde. Debords kohärentes Bestreben hatte darin bestanden, zu einer Leidenschaft der Existenz zurückzufinden, wie sie als Grundlage zur Umwälzung des verarmten Alltagslebens dienen sollte. Zugleich Ehre und Pläsier war es ihm dabei, der „Gesellschaft des Spektakels“ - 1967 in einem strategisch eingesetzten ‚Theoriebuch‘ in Form von Zweckentfremdungen analysiert - zu schaden, wo er nur konnte. Kategorisierungsversuche seiner Tätigkeiten und Umtriebe ‚unterlief‘ der Wahlpariser regelmäßig. Lediglich den Einordnungen als Filmemacher und Enragé stimmte er zu. Interpretationsschwerpunkte liegen auf der Begutachtung von Bildmanifesten und Selbstporträts, wozu seine sieben Filme zählen. Im Rahmen eines an Gerald Raunig und Bazon Brock angelehnten Theoriedesigns, wird sein provokantes Vorgehen in neun Kapiteln (I – IX) als Gesamtkunst-Experiment und Lebenskunstwerk beschrieben. Fundamental ist hierbei das Diktum Brocks, dass ein Totalkunstwerk ein Postulat seiner eigenen Verwirklichung darstellt. Die Gliederung des Stoffes folgt dem romanhaften Werdegang eines Initiators zweier Avantgardeformationen sowie dem Vollzug einer ‚Überwindung‘ der Kunst in deren Reihen. Das Gravitätszentrum aller Aktivitäten und ein Scharnier der Abhandlung ist die klandestine Rolle, welche die Situationistische Internationale bei der Verwirklichung der Mai-Revolte 1968 in Frankreich spielte. / In its character the study Guy Debords Art of Living, Accursed Poet & Cultural Treasury is an interdisciplinary examination of this French radical’s strange and obscure ways. His coherent achievement may be judged as an approach to regain a lost passion of existence in order to revolutionize everyday life. Debord found pleasure and pride in his lifelong ambition to demolish the so-called “Socitey of the Spectacle”, which he analyzed in his infamous book by the same title, first published in 1967. Often quoted since, rarely described as the invention and event it was. Debord defended himself againt categorization. But he agreed on being titulated a filmmaker and enraged person in the tradition of a perverted French Revolution. Following a theory-design, paying references to Gerald Raunig and Bazon Brock, his provocative approach is discussed in nine chapters (I-IX). Baring in mind that – according to Brock – a total work is a postulate of its own realization. The script follows the novel-like progress of a co-founder and lustful destroyer of two avantgarde-troups. All of the group activities are gravitating around what happened in Paris at the heyday of May 68.

No / We address the problem of recognition and growth of ice nuclei in simulation of supercooled bulk water. Bond orientation order parameters based on the spherical harmonics analysis are shown to be ineffective when applied to ice nucleation. Here we present an alternative method which robustly differentiates between hexagonal and cubic ice forms. The method is based on accumulation of the maximum projection of bond orientations onto a set of predetermined vectors, where different terms can contribute with opposite signs with the result that the irrelevant or incompatible molecular arrangements are damped out. We also introduce an effective cluster size by assigning a quality weight to each molecule in an ice-like cluster. We employ our cluster analysis in Monte Carlo simulation of homogeneous ice formation. Replica-exchange umbrella sampling is used for biasing the growth of the largest cluster and calculating the associated free energy barrier. Our results suggest that the ice formation can be seen as a two-stage process. Initially, short tetrahedrally arranged threads and rings are present; these become correlated and form a diffuse ice-genic network. Later, hydrogen bond arrangements within the amorphous ice-like structure gradually settle down and simultaneously `tune-up¿ nearby water molecules. As a result, a well-shaped ice core emerges and spreads throughout the system. The process is very slow and diverse owing to the rough energetic landscape and sluggish molecular motion in supercooled water, while large configurational fluctuations are needed for crystallization to occur. In the small systems studied so far the highly cooperative molecular rearrangements eventually lead to a relatively fast percolation of the forming ice structure through the periodic boundaries, which inevitably affects the simulation results. / EPSRC

Les cannabinoïdes sont une large classe de molécules qui agissent principalement sur les neurones, affectant la sensation de douleur, l'appétit, l'humeur, l'apprentissage et la mémoire. Des récepteurs cannabinoïdes spécifiques (CBR) ont été identifiés dans les neurones et d'autres types de cellules. Cependant, l'activation des CBR ne peut pas modifier directement l'excitabilité électrique des neurones, car les CBR ne génèrent pas de signaux électriques par eux-mêmes. Au lieu de cela, le potentiel membranaire et la signalisation électrique dans toutes les cellules excitables, y compris les neurones, sont générés par des canaux ioniques intégrés dans la membrane cellulaire. Récemment, il a été démontré que le cannabinoïde synthétique WIN55,212-2 affecte la mémoire en activant les récepteurs CB1, entraînant des changements de signalisation qui affectent le courant Ih généré par les canaux cycliques (HCN) activés par l'hyperpolarisation. Cependant, il a également été démontré que les cannabinoïdes régulent directement la fonction de plusieurs canaux ioniques, indépendamment de l'activation du CBR. Nous examinons ici si les cannabinoïdes, le 9-tétrahydrocannabidiol (THC) et le cannabidiol (CBD), que l'on trouve dans le cannabis sativa, peuvent réguler directement les canaux HCN1. En utilisant une pince de tension à deux électrodes (TEVC), sur des ovocytes de Xenopus, qui n'expriment pas de CBR, nous surveillons les changements dans la relation courant-tension, la cinétique de déclenchement et la dépendance à la tension des courants HCN1 dans des concentrations croissantes de cannabinoïdes. Nos données suggèrent que le CBD et le THC modulent directement le courant de HCN1. Étant donné que les cannabinoïdes sont des molécules thérapeutiques prometteuses pour le traitement de plusieurs troubles neurologiques, comprendre quelles cibles ils affectent, le mécanisme de leur régulation et comment ils se lient à des cibles potentielles sont des étapes essentielles de leur utilisation en tant que thérapies efficaces et du développement de cibles plus puissantes et plus efficaces médicaments spécifiques. / Cannabinoids are a broad class of molecules that act primarily on neurons, affecting pain sensation, appetite, mood, learning and memory. Specific cannabinoid receptors (CBRs) have been identified in neurons, and other cell types. However, activating CBRs cannot directly alter electrical excitability in neurons, since CBRs do not generate electrical signals on their own. Instead, membrane potential and electrical signaling in all excitable cells, including neurons, are generated by ion channels embedded in the cell membrane. Recently, it has been shown that the synthetic cannabinoid WIN55,212-2 effects memory by activating CB1 receptors, leading to signaling changes that affect the Ih current generated by hyperpolarization-activated cyclic-nucleotide gated (HCN) channels. However, cannabinoids have also been shown to directly regulate the function of several ion channels, independently of CBR activation. Here we examine whether cannabinoids, 9-tetrahydrocannabidiol (THC) and cannabidiol (CBD), which are found in cannabis sativa, can directly regulate HCN1 channels. Using two-electrode voltage clamp (TEVC), on Xenopus oocytes, which do not express CBRs, we monitor changes in the current-voltage relationship, gating kinetics, and voltage-dependence of HCN1 currents in increasing concentrations of cannabinoids. Our data suggests CBD and THC directly modulate HCN1 current. Since cannabinoids are promising therapeutic molecules for the treatment of several neurological disorders, understanding what targets they affect, the mechanism of their regulation, and how they bind to potential targets are critical steps in their use as effective therapies and the development of more potent and target specific drugs.

Pressure tubes pick up hydrogen while they are in service within CANDU reactors. Sufficiently high hydrogen concentration can lead to hydride precipitation during reactor shutdown/repair at flaws, resulting in the potential for eventual rupture of the pressure tubes by a process called Delayed Hydride Cracking (DHC). The threshold stress intensity factor (KIH) below which the cracks will not grow by delayed hydride cracking of Zr-2.5Nb micro pressure tubes (MPTs) has been determined using a load increasing mode (LIM) method at different temperatures. MPTs have been used to allow easy study of the impact of properties like texture and grain size on DHC. Previous studies on MPTs have focused on creep and effects of stress on hydride orientation; here the use of MPTs for DHC studies is confirmed for the first time. Micro pressure tube samples were hydrided to a target hydrogen content of 100 ppm using an electrolytic method. For DHC testing, 3 mm thick half ring samples were cut out from the tubes using Electrical Discharge Machining (EDM) with a notch at the center. A sharp notch with a root radius of 15 µm was introduced by broaching to facilitate crack initiation. The direct current potential drop method was used to monitor crack growth during the DHC tests. For the temperature range tested the threshold stress intensity factors for the micro pressure tube used were found to be 6.5-10.5 MPa.m1/2 with the value increasing with increasing temperature. The average DHC velocities obtained for the three different test temperatures 180, 230 and 250oC were 2.64, 10.87 and 8.45 x 10-8 m/s, respectively. The DHC data obtained from the MPTs are comparable to the data published in the literature for full sized CANDU pressure tubes. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2009-04-24 12:55:36.917

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