No / Prolonged hyperglycaemia impairs vascular reactivity and inhibits voltage-activated K+ (Kv) channels. We examined acute effects of altering glucose concentration on the activity and inhibition by endothelin-1 (ET-1) of Kv currents of freshly isolated rat arterial myocytes. Peak Kv currents recorded in glucose-free solution were reversibly reduced within 200 s by increasing extracellular glucose to 4 mm. This inhibitory effect of glucose was abolished by protein kinase C inhibitor peptide (PKC-IP), and Kv currents were further reduced in 10 mm glucose. In current-clamped cells, membrane potentials were more negative in 4 than in 10 mm glucose. In 4 mmd-glucose, 10 nm ET-1 decreased peak Kv current amplitude at +60 mV from 23.5 ± 3.3 to 12.1 ± 3.1 pA pF−1 (n = 6, P < 0.001) and increased the rate of inactivation, decreasing the time constant around fourfold. Inhibition by ET-1 was prevented by PKC-IP. When d-glucose was increased to 10 mm, ET-1 no longer inhibited Kv current (n = 6). Glucose metabolism was required for prevention of ET-1 inhibition of Kv currents, since fructose mimicked the effects of d-glucose, while l-glucose, sucrose or mannitol were without effect. Endothelin receptors were still functional in 10 mmd-glucose, since pinacidil-activated ATP-dependent K+ (KATP) currents were reduced by 10 nm ET-1. This inhibition was nearly abolished by PKC-IP, indicating that endothelin receptors could still activate PKC in 10 mmd-glucose. These results indicate that changes in extracellular glucose concentration within the physiological range can reduce Kv current amplitude and can have major effects on Kv channel modulation by vasoconstrictors.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Gated developments, also known as gated communities, have become a feature of urban living throughout the world and have been the subject of intensive research. Gated developments in South African cities are a ubiquitous feature of the post-apartheid urban landscape with many new housing developments in the form of secure estates or fortified townhouse complexes. Almost all the international literature on gated developments has focused on them as a metropolitan phenomenon. Very few international studies have investigated gated developments in non-metropolitan locales and this topic is unexplored in the South African context. This dissertation addresses this research gap. The study area is the entire non-metropolitan area of the Western Cape province. The politicoadministrative concept of non-metropolitan is used rather than the descriptor rural because the latter implies an area of primary production with no diversification of productive activities. The study area excludes the metropolitan area of Cape Town but includes the rest of the province within which there are settlements of varying sizes having a diverse range of economic activities. It is in these places that gated developments were investigated to cover and discover particular aspects of the hitherto unexplored non-metropolitan gated developments of South Africa. The specific objectives were to place the research in the theoretical and conceptual debates of gated developments; map the occurrence of the phenomenon; and spatially analyse the location and security aspects of the developments at a macro scale. Two towns, Swellendam and Ceres, were selected as case studies as their gated developments present a host of significant features warranting further micro-scale analysis. The spatial and locational analyses yielded other researchable themes specific to certain types of developments, namely retirement gated developments in Oudtshoorn and Swellendam and gated developments outside the urban edge. A comprehensive spatially-linked database of gated developments in the study area was compiled from numerous sources, culminating in a process of groundtruthing that resulted in the collection of data on the physical features of each development. Qualitative data was collected from respondents through interviews, electronic communications and a questionnaire survey. Distribution patterns of gated developments were determined from spatial data and data on physical features was used to calculate security level index values for the gated developments. These data sets enabled spatial and typological comparisons to be made. Qualitative data added a ‘voice’ to the quantitative data and provided insights into social, economic and planning aspects of gated developments. The location of gated developments in the province is largely determined by proximity to metropolitan Cape Town and areas with high occurrences of amenities. The spatio-temporal patterns and typological distinctions of gated developments are influenced by location-specific factors. In some towns the gated developments typify a living space and in others a living and lifestyle space. The security features of gated developments also vary typologically and spatially. Crime data was used to show that the distribution of non-metropolitan gated developments is not necessarily associated with towns with high levels of criminal activity. Security in these developments is not a response to rampant crime, rather a strategy brought into play in case something happens – preparedness in the unlikely event of a breach of security. The gated developments in the two case-study towns are strongly influenced by locationspecific needs, the purposes of residents and the processes of municipalities. Niche market gated developments, as represented in the thematic case studies of retirement gated developments and gated developments outside the urban edge are promoted by pull factors within towns and by the allure of an exclusive rural residential lifestyle of living in areas with high amenity offerings. The latter is linked to the transformation of agricultural land into gated developments, which signals a shift to postproductivist change in the study area. The results of this seminal investigation into non-metropolitan gated developments suggest avenues for further research endeavour. These include the need for greater understanding of the changing nature of social relations between gated and the non-gated inhabitants of non-metropolitan locales; investigation of the potential for increased topophobia within towns; and examinations of the functions of the various stakeholders and role players in establishing non-metropolitan gated developments. / AFRIKAANSE OPSOMMING: Geslote woonbuurte, ook bekend as geslote gemeenskappe, ’n kenmerk van baie stede regoor die wêreld, het die onderwerp van intensiewe navorsing geword. Geslote woonbuurte in Suid-Afrikaanse stede is ‘n alomteenwoordige kenmerk van die post-apartheid stedelike landskap met baie nuwe behuisingsontwikkelings wat as beveiligde landgoede en meenthuiskomplekse gebou word. Die meerderheid van die internasionale literatuur oor geslote woonbuurte beskou hulle as ’n metropolitaanse verskynsel. Baie min internasionale studies het geslote gemeenskappe in niemetropolitaanse lokaliteite ondersoek en dié onderwerp is onverken in die Suid-Afrikaanse konteks. Hierdie proefskrif vul dié navorsingsleemte. Die studiegebied is die hele nie-metropolitaanse gebied van die Wes-Kaap provinsie. Die politiesadministriewe konsep ‘nie-metropolitaans’ word gebruik in plaas van die benaming ‘landelik’ omdat laasgenoemde ’n gebied van primêre produksie met geen diversifisering van ekonomiese aktiwiteite impliseer. Dus, sluit die studiegebied die metropolitaanse gebied van Kaapstad uit, maar sluit die res van die provinsie in waar nedersettings van verskeie grootte en met ’n diverse reeks ekonomiese aktiwiteite voorkom. Dit is in hierdie gebiedens dat geslote woonbuurte ondersoek word met die doel om besondere aspekte van hierdie tot nou toe onverkende nie-metropolitaanse geslote woonbuurte in Suid-Afrika, na vore te bring. Die spesifieke doelwitte is om die navorsing binne die breër teorietiese en konseptuele debatte rondom geslote woonbuurte te plaas; die verspreiding van die verskynsel te karteer; die ligging en die sekuriteitsaspekte van die woonbuurte op makro skaal ruimtelik te ontleed. Ceres en Swellendam word as gevallestudies behandel. Die twee dorpe se geslote woonbuurte ’n menigte beduidende kenmerke van hul geslote woonbuurte vertoon, wat verdere mikro skaalanalise regverdig. Die ruimtelike en liggingsanalises het navorsingwaardige temas oor spesifieke tipes geslote woonbuurte onthul. Die temas sluit geslote aftreewoonbuurte in Oudtshoorn en Swellendam en geslote woonbuurte buitekant dorpsgrense in. ’n Omvattende ruimtelike databasis van geslote woonbuurte binne die studiegebeid is uit verskeie bronne saamgestel en ’n proses van terreinverifiëring het vir die inwin van data oor fisiese kenmerke van elke woonbuurt gesorg. Kwalitatiewe data is by respondente verkry deur middel van onderhoude, elektroniese kommunikasie en ’n vraelys opname. Verspreidingspatrone van die geslote woonbuurte is aan die hand van die ruimtelike data vasgestel en die data oor die fisiese verskynsels is gebruik om ’n sekuriteitsindekswaardes van die geslote woonbuurte te bereken. Die datastelle het ruimtelike en tipologiese vergelykings moontlik gemaak. Kwalitatiewe data het ’n ‘stem’ aan die kwantitiewe data verleen en insig in die sosiale, ekonomiese en beplanningsaspekte van geslote woonbuurte verskaf. Die ligging van geslote woonbuurte in die provinsie is grootliks deur nabyheid aan die Kaapse metropool en gebiede met ’n hoë voorkoms van geriewe beïnvloed. Die ruimtelike- en tydspatrone en tipologiese kenmerke van geslote woonbuurte is deur liggingspesifiekefaktore beïnvloed. In sommige dorpe is die geslote woonbuurte as ’n ‘leefruimte’ gekenmerk, terwyl ander geslote woonbuurte as ‘leefruimte en leefstylruimte’ getipeer word. Die sekuriteitsverskynsels van geslote woonbuurte het ook tipologiese en ruimtelike verskeidenheid getoon. Misdaaddata is gebruik om te toon dat die verspreiding van nie-metropolitaanse geslote woonbuurte nie noodwendig ooreenstem met dorpe met hoë misdaadsyfers nie. Sekuriteit is nie ’n reaksie op buitensporige misdaadsyfers nie, eerder ’n strategie wat in werking tree in geval iets gebeur – paraatheid vir die onwaarskynlike gebeurtenis van ’n sekuriteitskending. Die ontwikkeling van geslote woonbuurte in die gevallestudiedorpe is sterk deur liggingspesifieke behoeftes, die doelstellings van inwoners en prosesse van munisipaliteite beïnvloed. Geslote woonbuurte wat nismarkte bedien, soos dié wat deur die tematiese gevallestudies verteenwoordig is, word bevorder deur sekere aantrekkingsfaktore wat dorpe bied en die bekoring van ’n eksklusiewe landelike residensiële lewensstyl in gebiede met ’n hoë voorkoms van geriewe vir lewensgenieting. Laasgenoemde is gekoppel aan die omskepping van landbougrond vir die bou van geslote woonbuurte wat ’n aanduiding van post-produktivistiese verandering in die studiegebeid is. Dié eerste en gedagteprikkelende ondersoek oor nie-metropoolitaanse geslote woonbuurte opper temas vir verdere navorsing. Dit sluit in ’n verstaan van die moontlike veranderings in sosiale verhoudings tussen die inwoners van geslote en ongeslote nie-metropolitaanse lokaliteite, die moontlikheid van verhoogde topofobie in dorpe; en ondersoeke oor die rol van verskillende insethouers en rolspelers in die ontwikkeling van nie-metropoolitaanse geslote woonbuurte.

Esta tese trata dos ambientes coletivos dos condomínios horizontais e dos loteamentos fechados construídos a partir de 1990 na cidade de Londrina Pr. Busca descobrir quais as necessidades dos usuários (moradores) e, a partir da avaliação de desempenho físico e de satisfação do usuário voltada aos ambientes construídos e de uso coletivo, com ênfase nos aspectos social, funcional, segurança, durabilidade e manutenabilidade, formula procedimentos metodológicos de desempenho de avaliação para dar suporte na definição de programas de necessidades para futuros empreendimentos similares. Propõe um modelo metodológico que encontra suporte no Analytic Hierarchy Process (AHP) para hierarquizar os atributos e as alternativas que influenciam nas decisões de projeto (critérios e subcritérios) e cuja calibragem do modelo se dá por meio da Avaliação Pós-Ocupação (APO), envolvendo os pontos de vista dos moradores, dos administradores ou síndicos, dos autores dos projetos destes empreendimentos, além dos levantamentos in loco realizado pelo pesquisador. / ABSTRACT This thesis deals with collective environments of gated communities and plots which started being built in 1990 in the city of Londrina-PR. It searches for finding out the needs of the users (residents) and, from the evaluation of their physical performance and satisfaction regarding the built and collective environments, with special emphasis on social, functional, safety, durability and maintenance aspects, conceives the methodological procedures of performance evaluation to support the definition of programs of needs for future similar developments. It proposes a methodological model supported by the Analytic Hierarchy Process (AHP) to form as a hierarchy the attributes and the alternatives which have influence on the design decisions (criteria and sub-criteria), whose calibration of the proposed methodological model took place through the Post-Occupancy Evaluation (POE), involving the viewpoints from the residents, the administrators or syndics and architects, besides the surveys in loco carried out by this researcher.

Esta tese trata dos ambientes coletivos dos condomínios horizontais e dos loteamentos fechados construídos a partir de 1990 na cidade de Londrina Pr. Busca descobrir quais as necessidades dos usuários (moradores) e, a partir da avaliação de desempenho físico e de satisfação do usuário voltada aos ambientes construídos e de uso coletivo, com ênfase nos aspectos social, funcional, segurança, durabilidade e manutenabilidade, formula procedimentos metodológicos de desempenho de avaliação para dar suporte na definição de programas de necessidades para futuros empreendimentos similares. Propõe um modelo metodológico que encontra suporte no Analytic Hierarchy Process (AHP) para hierarquizar os atributos e as alternativas que influenciam nas decisões de projeto (critérios e subcritérios) e cuja calibragem do modelo se dá por meio da Avaliação Pós-Ocupação (APO), envolvendo os pontos de vista dos moradores, dos administradores ou síndicos, dos autores dos projetos destes empreendimentos, além dos levantamentos in loco realizado pelo pesquisador. / ABSTRACT This thesis deals with collective environments of gated communities and plots which started being built in 1990 in the city of Londrina-PR. It searches for finding out the needs of the users (residents) and, from the evaluation of their physical performance and satisfaction regarding the built and collective environments, with special emphasis on social, functional, safety, durability and maintenance aspects, conceives the methodological procedures of performance evaluation to support the definition of programs of needs for future similar developments. It proposes a methodological model supported by the Analytic Hierarchy Process (AHP) to form as a hierarchy the attributes and the alternatives which have influence on the design decisions (criteria and sub-criteria), whose calibration of the proposed methodological model took place through the Post-Occupancy Evaluation (POE), involving the viewpoints from the residents, the administrators or syndics and architects, besides the surveys in loco carried out by this researcher.

Yu Wai Ching. / "Architecture Department, Chinese University of Hong Kong, Master of Architecture Programme 2007-2008, design report." / Includes bibliographical references (p. 204-206). / Thesis Statement --- p.5 / Study Method --- p.9 / "Phenomenon, Principle & Appearance" --- p.11 / Study Area --- p.15 / Precedent study --- p.17 / Chapter - --- Chinese character --- p.19 / Chapter - --- Platonic solid --- p.35 / Chapter - --- Crystal --- p.43 / Architectural example study --- p.59 / Chapter - --- Phenomenon - simple but interesting subdivision --- p.61 / Chapter - --- Principle - subdivision --- p.71 / Chapter - --- envelope arrangment --- p.115 / Chapter - --- opening --- p.127 / Chapter - --- space extension --- p.135 / Chapter - --- Reading examples with principles --- p.145 / Testing on site --- p.155 / Site context --- p.157 / Site planning --- p.163 / Testing on village houses --- p.177 / Housing types --- p.179 / Floor units --- p.183 / House unit --- p.189 / Bibliography --- p.203

Achieving appropriate and natural backchanneling behavior in social robots remains a challenge in Human-Robot Interaction (HRI). This thesis addresses this issue by utilizing methods from Safe Reinforcement Learning in particular shielding to improve social robot backchanneling behavior. The aim of the study is to develop and implement a safety shield that guarantees appropriate backchanneling. In order to achieve that, a Recurrent Neural Network (RNN) is trained on a human-human conversational dataset. Two agents are built; one uses a random algorithm to backchannel and another uses shields on top of its algorithm. The two agents are tested using a recorded human audio, and later evaluated in a between-subject user study with 41 participants. The results did not show any statistical significance between the two conditions, for the chosen significance level of α &lt; 0.05. However, we observe that the agent with shield had a better listening behavior, more appropriate backchanneling behavior and missed less backchanneling opportunities than the agent without shields. This could indicate that shields have a positive impact on the robot’s behavior. We discuss potential explanations for why we did not obtain statistical significance and shed light on the potential for further exploration. / Att uppnå lämpligt och naturligt upbbackningsbeteende i sociala robotar är fortfarande en utmaning i Människa-Robot Interaktion (MRI). Den här avhandlingen tar upp detta problem genom att använda metoder från säker förstärkningsinlärning i synnerhet avskärmning för att förbättra sociala robotars upbbackningsbeteende. Syftet med studien är att utveckla och implementera en säkerhetsavskärmning som garanterar lämplig upbbackning. För att uppnå det, tränas ett återkommande neuralt nätverk på en människa-människa konversationsdatamängd. Två agenter byggs; en använder en slumpmässig algoritm för att upbbacka och en annan använder avskärmninng ovanpå sin algoritm. De två agenterna testas med hjälp av ett inspelat mänskligt ljud och utvärderas senare i en användarstudie med 41 deltagare. Resultaten visade inte någon statistisk signifikans mellan de två skicken, för den valda signifikansnivån &lt; 0, 05. Vi observerar dock att agenten med avskärmning hade ett bättre lyssningsbeteende, mer lämplig upbbackningsbeteende och missade mindre upbbacknings-möjligheter än agenten utan avskärmning. Detta kan indikera att avskärmning har en positiv inverkan på robotarnas beteende. Vi diskuterar potentiella förklaringar till varför vi inte fick statistisk signifikans och belyser potentialen för ytterligare utforskning.

Master of Regional and Community Planning / Department of Landscape Architecture/Regional and Community Planning / Larry L. Lawhon / Gated communities are a growing residential phenomenon in the United States with almost ten percent of households living in gated communities in 2005 (Knox, 2008; Census, 2005). In this study “gated communities” are defined, according to Low (2003), as a residential neighborhood with walls and gates surrounding the development, which excludes non-residents access to all interior amenities including residences, open space, and activities. People are seeking life behind a gate for many reasons, but include the search for security, safety, privacy, prestige, exclusivity, control, and community (Blakely & Snyder, 1999). As this style of development is expanding and as all socio-economic groups want to live in gated communities, cities are beginning to realize gated communities affect all members of the community, not just the ones secluded behind the gate (El Nasser, 2002). After reviewing literature, the author found, the generally accepted social implications and consequences resulting from gated communities were identified as social segregation, loss of community, and division; although, there were also positive results for some people living within gated communities. This report, through a case study format, investigated if the social implications of gated communities are considered during the development review process. Rockwood Falls Estates and Meadows is a suburban gated community and the surrounding local governments, Johnson County and Overland Park, were the object of the case study. The author concluded that gated communities have benefits and concerns. Further, the author found that gated communities can be effectively controlled if the local governments have adopted specific policies dealing with gated communities and implement this policy through specific design review procedures.

Enzymes are ubiquitous in biological systems. They catalyze chemical reactions and are involved in many biochemical processes. The enzyme of interest is Pseudomonas aeruginosa D-arginine dehydrogenase (PaDADH). This flavin-dependent enzyme is composed of approximately 375 amino acid residues and has a broad substrate specificity with D-amino acids. A water recognition motif, observed in roughly 1200 non-redundant protein data bank (PDB) structures, was revealed to be embedded near the active site of PaDADH. This motif coincides with the conformational changes of the enzyme’s gated mechanism. Molecular dynamics simulations were carried out to study the gated properties and structural characteristics of PaDADH in solution. Single amino acid mutations were undertaken to further understand the dynamics of the gated mechanism of this enzyme. In addition, pKa,shift analyses were evaluated to probe for the basic catalytic amino acid residue that is suggested to trigger the catalytic mechanism of PaDADH.

Cette thèse porte sur les modèles génératifs en apprentissage automatique. Deux nouveaux modèles basés sur les réseaux de neurones y sont proposés. Le premier modèle possède une représentation interne où une certaine structure a été imposée afin d’ordonner les caractéristiques apprises. Le deuxième modèle parvient à exploiter la structure topologique des données observées, et d’en tenir compte lors de la phase générative. Cette thèse présente également une des premières applications de l’apprentissage automatique au problème de la tractographie du cerveau. Pour ce faire, un réseau de neurones récurrent est appliqué à des données de diffusion afin d’obtenir une représentation des fibres de la matière blanche sous forme de séquences de points en trois dimensions.

Sulfatide is a galactolipid and a major lipid component of the myelin sheath. Its production is catalyzed by the enzyme cerebroside sulfotransferase (CST). To determine the functions of sulfatide, the gene encoding CST was genetically disrupted resulting in mice incapable of sulfatide synthesis. Using these mice, it has been shown in the central nervous system (CNS) that sulfatide is essential for normal myelin synthesis and stability even though the onset of myelination is not impaired. Additionally, proper initial clustering of paranodal proteins and cluster maintenance of nodal proteins is impaired suggesting that paranodal domains are important for long-term node stability. In contrast to the CNS, a requirement for sulfatide in the initiation of myelination, and in initiation of paranodal and nodal clustering or in the long-term maintenance of these clusters in the peripheral nervous system (PNS) has not been analyzed. Therefore, we have employed a combination of electron microscopic, immunocytochemical, and confocal microscopic analyses of the CST KO mice to determine the role of sulfatide in PNS myelination and onset of protein domain formation and maintenance. For these studies we have quantified myelin thickness, paranodal structural integrity, and the number of paranodal and nodal protein clusters in the CST KO and wild type mice at 4 days, 7 days, and 10 months of age. Our findings indicate that myelination onset is not delayed in the absence of sulfatide and that both the node and paranode are grossly normal; however, closer analysis reveals that paranodal junctions are compromised, Schwann cell microvilli are disoriented and the myelin-axon interface along the internodal region is transiently disrupted. In addition, we report that the paranodal myelin protein neurofascin 155 (Nfasc155) shows a transient decrease in initial clustering in the CST null mice at 4 days of age that is restored to WT levels by 7 days of age that is also maintained in the adult mice. Whereas nodal clustering of neuronal voltage-gated sodium channels is initially normal, cluster number is significantly but also transiently reduced by 7 days of age. By 10 months of age, the number of sodium channel clusters is restored to normal levels. In contrast, clustering of neither the paranodal neuronal protein contactin nor the myelin nodal protein gliomedin is altered at any of the ages studied. Together our findings suggest that sulfatide is not essential for PNS myelination or for protein domain formation in contrast to its more vital role in the development and maintenance of the CNS.