Eukaryotic cells are characterised by membranes with varied and dynamic compositions and shapes. Consequently, membrane-binding proteins are tuned to recognise and modify these membrane states to perform their functions. To study the curvature sensitivity of proteins, I have developed a single-particle assay using NanoSight technology that tracks the Brownian motion of particles to measure their size. I optimised this system to track fluorescently labelled lipid-binding domains bound to liposomes of different sizes moving freely in solution. The comparison of the size distribution of the total liposomes with the fluorescently labelled population allowed me to determine their curvature preferences. To validate the method I tested proteins from the Bin/Amphiphysin/Rvs (BAR) superfamily, which are inherently curved and have known curvature preferences. My method was capable of recapitulating the behaviour of BAR domains with different curvature preferences. I then expanded the range of targets and showed that this assay is also capable of detecting curvature preferences for a variety of other lipid-binding domain families. As such, I identified AKT PH domain as a new curvature-sensing domain. Finally, using the ENTH domain of Epsin1 that causes vesicle budding, I demonstrated that this method can also be used to study membrane remodelling. Trafficking involves generation and sensing of membrane curvature combined with recognition of specific cargo. Endophilin consists of a curvature-sensitive BAR domain followed by an SH3 (Src-homology 3) domain and has recently been identified in a clathrin-independent endocytosis pathway, FEME (fast endophilin-mediated endocytosis), involved in the uptake of cell surface receptors. Endophilin recognises ligands via its SH3 domain, binding G-protein coupled receptors (GPCRs) directly in their intracellular loop 3 and receptor tyrosine kinase (RTKs) via adaptor proteins. However, a specific recognition motif has not been identified yet. Here, using a combination of biophysical approaches and NMR spectroscopy, I characterised the Endophilin binding motif of ALIX (ALG-2-interacting protein X) adaptor protein and of the GPCR $\alpha$2A adrenergic receptor. Comparison of SH3-peptide models resulted in a putative Endophilin recognition site.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2016-09-15T18:07:44Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissert_CeciliaFonte-BC.pdf: 9067315 bytes, checksum: f386f12e79500bfa9cc202505a477de6 (MD5) / Made available in DSpace on 2016-09-15T18:07:44Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissert_CeciliaFonte-BC.pdf: 9067315 bytes, checksum: f386f12e79500bfa9cc202505a477de6 (MD5) Previous issue date: 2016-01-26 / CNPQ / Nos últimos anos o setor independente de jogos digitais cresceu exponencialmente, recebendo reconhecimento do público, da imprensa e do mercado. Entretanto, a conceituação de games independentes é apresentada na literatura através de um complexo emaranhado de definições que divergem entre si. Esta pesquisa pretende então compreender qual o sentido de independência no contexto de atividades culturais e como ele se traduz no campo de jogos. Para tal, primeiramente será realizado um estudo da cultura independente mais ampla que buscará perceber como se dá sua conceituação, como ela se transforma com o passar dos anos e quais as ideias e práticas que perpetua. Nesse momento, serão observados importantes cenários alternativos (contracultura da déc. de 60 e Punk) assim como a produção de zines, publicações que alimentam as comunidades indies. Esse estudo inicial - que tem o intuito de encontrar as características comuns às manifestações independentes - servirá como base para a análise posterior da produção independente de jogos que tem o objetivo de verificar como os desenvolvedores praticam a independência. A pesquisa indica que o universo de jogos descrito como indie é bastante amplo e heterogêneo, mas que nele, é possível encontrar game designers que compartilham de muitos dos ideais e comportamentos propagados pela cultura independente ao longo do tempo. / In recent years the independent game sector has grown exponentially, gaining recognition from the audience, the press and the market. However, the concept of independent games is presented in the literature through a complex maze of definitions that differ from each other. This research aims to understand then what is the sense behind the independence in cultural activities and how it translates on the game industry. For that, at first, a study about the broad independente culture will be conducted, which will seek to comprehend how its conceptualization is given, how it changes over the years and what ideas and practices are perpetuated by it. At this context, important alternative scenarios will be observed (the counterculture of the sixties and the Punk movement), as well as the production of zines, publications that feed the indie communities. This initial study - which intends to find the common characteristics of the independent manifestations - will serve as a basis for the further analysis of the production of indie games, that will have the purpose of seeing how developers practice independence. This research indicates that the gaming universe described as indie is broad and heterogeneous, but that it carries game designers who share many of the ideals and behaviors spread by the independent culture over time

The generation of random number sequences, that is, of unpredictable sequences free from any structure, has found numerous applications in the field of information technologies. One of the most sensitive applications is cryptography, whose modern practice makes use of secret keys that must indeed be unpredictable for any potential adversary. This type of application demands highly secure randomness generators.This thesis contributes to the device-independent approach to quantum random number generation (DIRNG, for Device-Independent Random Number Generation). Those methods of randomness generation exploit the fundamental unpredictability of the measurement of quantum systems. In particular, the security of device-independent methods does not appeal to a specific model of the device itself, which is treated as a black box. This approach therefore stands in contrast to more traditional methods whose security rests on a precise theoretical model of the device, which may lead to vulnerabilities caused by hardware malfunctions or tampering by an adversary.Our contributions are the following. We first introduce a family of robust self-testing criteria for a class of quantum systems that involve partially entangled qubit pairs. This powerful form of inference allows us to certify that the contents of a quantum black box conforms to one of those systems, on the sole basis of macroscopically observable statistical properties of the black box.That result leads us to introduce and prove the security of a protocol for randomness generation based on such partially entangled black boxes. The advantage of this method resides in its low shared entanglement cost, which allows to reduce the use of quantum resources (both entanglement and quantum communication) compared to existing DIRNG protocols.We also present a protocol for randomness generation based on an original estimation of the black-box correlations. Contrary to existing DIRNG methods, which summarize the accumulated measurement data into a single quantity---the violation of a unique Bell inequality---, our method exploits a complete, multidimensional description of the black-box correlations that allows it to certify more randomness from the same number of measurements. We illustrate our results on a numerical simulation of the protocol using partially entangled states. / La génération de suites de nombres aléatoires, c'est-à-dire de suites imprévisibles et dépourvues de toute structure, trouve de nombreuses applications dans le domaine des technologies de l'information. L'une des plus sensibles est la cryptographie, dont les pratiques modernes font en effet appel à des clés secrètes qui doivent précisément être imprévisibles du point de vue d'adversaires potentiels. Ce type d'application exige des générateurs d'aléa de haute sécurité.Cette thèse s'inscrit dans le cadre de l'approche indépendante des appareils des méthodes quantiques de génération de nombres aléatoires (en anglais, Device-Independent Random Number Generation ou DIRNG). Ces méthodes exploitent la nature fondamentalement imprévisible de la mesure des systèmes quantiques. En particulier, l'appellation "indépendante des appareils" implique que la sécurité de ces méthodes ne fait pas appel à un modèle théorique particulier de l'appareil lui-même, qui est traité comme une boîte noire. Cette approche se distingue donc de méthodes plus traditionnelles dont la sécurité repose sur un modèle théorique précis de l'appareil et peut donc être compromise par un dysfonctionnement matériel ou l'intervention d'un adversaire.Les contributions apportées sont les suivantes. Nous démontrons tout d'abord une famille de critères de "self-testing" robuste pour une classe de systèmes quantiques impliquant des paires de systèmes à deux niveaux (qubits) partiellement intriquées. Cette forme d'inférence particulièrement puissante permet de certifier que le contenu d'une boîte noire quantique est conforme à l'un de ces systèmes, sur base uniquement de propriétés statistiques de la boîte observables macroscopiquement.Ce résultat nous amène à introduire et à prouver la sécurité d'une méthode de génération d'aléa basée sur ces boîtes noires partiellement intriquées. L'intérêt de cette méthode réside dans son faible coût en intrication, qui permet de réduire l'usage de ressources quantiques (intrication ou communication quantique) par rapport aux méthodes de DIRNG existantes.Nous présentons par ailleurs une méthode de génération d'aléa basée sur une estimation statistique originale des corrélations des boîtes noires. Contrairement aux méthodes de DIRNG existantes, qui résument l'ensemble des mesures observées à une seule grandeur (la violation d'une inégalité de Bell unique), notre méthode exploite une description complète (et donc multidimensionnelle) des corrélations des boîtes noires qui lui permet de certifier une plus grande quantité d'aléa pour un même nombre de mesures. Nous illustrons ensuite cette méthode numériquement sur un système de qubits partiellement intriqués. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

It is the purpose of this thesis to point out areas of failure and weaknesses in the Federal independent regulatory commissions, and recommendations for improvement, as seen by Louis J. Hector, James M. Landis, Emmette S. Redford, Bernard Schwartz and the Special Subcommittee on Legislative Oversight. A secondary purpose of the study is to present action taken by Congress and President Kennedy in response to recent criticisms of the commissions. The scope of the thesis is limited to the major problems of policy-making, personnel matters, and efficiency of the major independent regulatory commissions. The material presented in the thesis covers five chapters. Chapter I includes a general introductory statement, the purpose and scope of the study, and the method of organization. Chapter II is a presentation of the criticisms and recommendations of Hector, Redford, and Landis in respect to the problems of policy-making and coordination faced by the independent commissions. Chapter III examines the problems of commission personnel in respect to qualifications, turnover, and ethical conduct. Chapter IV concerns the efficiency of the independent commissions, showing examples of delay and incompetence in the performance of the functions of the CAB, the FPC, and other commissions. Criticisms and recommendations include those of Hector, the Special Subcommittee, and Landis. Chapter V, the conclusion, re-emphasizes the importance of the problems facing the commissions. Attention is given to action taken by Congress and President Kennedy to improve the efficiency of certain commissions. An analysis of the criticisms and recommendations of the sources used is presented.

It is estimated that 65 million people worldwide have epilepsy, and many of them have uncontrollable seizures even with the use of medication. A seizure occurs when the normal electrical activity of the brain is interrupted by sudden and unusually intense bursts of electrical energy, and these bursts can be observed and detected by the use of an electroencephalograph (EEG) machine. This work presents an algorithm that monitors subtle changes in scalp EEG characteristics to predict seizures. The algorithm is built to calibrate itself to every specifc patient based on recorded data, and is computationally effcient enough for future on-line applications. The presented algorithm performs ICA-based artifact filtering and Lasso-based feature selection from a large array of statistical features. Classification is based on a neural network using Bayesian regularized backpropagation.The selected method was able to classify 4 second long preictal segments with an average sensitivity of 99.53% and an average specificity of 99.9% when tested on 15 different patients from the CHB-MIT database.

Endosomal trafficking can influence the composition of the plasma membrane and the ability of cells to polarize their membranes. Here, we examined whether trafficking through clathrin-independent endocytosis (CIE) affects the ability of T cells to form a cell-cell conjugate with antigen-presenting cells (APCs). We show that CIE occurs in both the Jurkat T cell line and primary human T cells. In Jurkat cells, the activities of two guanine nucleotide binding proteins, Arf6 and Rab22 (also known as Rab22a), influence CIE and conjugate formation. Expression of the constitutively active form of Arf6, Arf6Q67L, inhibits CIE and conjugate formation, and results in the accumulation of vacuoles containing lymphocyte function-associated antigen 1 (LFA-1) and CD4, molecules important for T cell interaction with the APC. Moreover, expression of the GTP-binding defective mutant of Rab22, Rab22S19N, inhibits CIE and conjugate formation, suggesting that Rab22 function is required for these activities. Furthermore, Jurkat cells expressing Rab22S19N were impaired in spreading onto coverslips coated with T cell receptor-activating antibodies. These observations support a role for CIE, Arf6 and Rab22 in conjugate formation between T cells and APCs.

D.Ed.

Class of 2005 Abstract / Objectives: To determine if delivery of medications to an independent living facility increases patient adherence. Methods: Retrospective review of patient pharmacy refill records was completed using a data extraction form in order to calculate a number of days deviation from a projected refill date based on days supply. Data on the use of express pay, auto fill, and delivery service and payment type was collected as well as age and gender. Residents of The Fountains independent living facility were eligible to be included in this study if they had complete data in the pharmacy refill records for at least one scheduled maintenance medication taken for a continuous, three-month period. Results: There were 21 subjects in the delivery group and 18 in the pick-up group. Both groups were primarily women (76.2 percent and 61.1 percent respectively). Age was also similar (85.8 and 83.8, p=0.285). The delivery group had significantly more maintenance medications than the pick-up group (mean=2.8, SD=1.1 and mean=1.7, SD=1.1 respectively). Seven of the nine time deviations were greater for the pick-up group than for the delivery group (p= 0.09 for sign test). Implications: It appears that a delivery service can increase adherence, particularly in a population of advanced age.

The increasing demand for electricity, the rising price of energy from conventional sources and limited electricity supply are a global concern. The demand on electricity generation could be alleviated by diversifying the sources from which electricity is obtained to achieve the goals of long-term electricity supply. Diversification implies finding alternative sources of energy such as renewable energy for the production of electricity. The South African electricity system is under increased pressure to provide and maintain electricity supply to its users. Electricity production may be regarded as a key contributor to the social and economic development of South Africa. The challenges are so serious that it will gradually become increasingly difficult to extract sufficient resources to satisfy increasing electricity demand. Growth in the electricity and industrial sectors signifies profound changes in the entire energy industry. The South African power utility Eskom, supplies 94% of South Africa’s electricity but the risk of inadequate supply because of increasing electricity demand is mitigated through the employment of Independent Power Producers (IPPs) which supply to the grid. However, although a limited number of IPP entrepreneurs sell electricity to the Eskom grid, there is no enabling entrepreneurial environment in which they can thrive. There is no positive movement to inaugurate policies and processes. This has created an opportunity for Smart Grid access as a viable option to accommodate IPP entrepreneurs into the grid. Investing in renewable electricity sources may provide feasible alternatives for the electricity industry, it would alleviate pressure on current supply whilst creating an enabling entrepreneurial environment for IPP entrepreneurs and increase entrepreneurial activity. This study investigates a proposed model for an enabling entrepreneurial environment for IPPs in the RE sector that can be utilised to ensure increased entrepreneurial activity within the electricity industry. Establishing such an enabling environment would contribute positively to the alleviation of the electricity demand crisis, result in lower carbon emissions and create a sustainable, more diverse electricity generation mix. This proposed IPP industry model for an enabling entrepreneurial environment is presented to address the problems experienced at the different levels of the electricity industry. The model can be utilised to increase entrepreneurial activity while eradicating major electricity challenges at different levels in the South African electricity industry. The results indicate that that RE, in the form of solar and wind, has the potential to expand the South African electricity industry significantly. Therefore, in order to reform the South African electricity industry, stakeholders need to embrace entrepreneurship as IPP entrepreneurs. This can be done effectively by the incorporation of IPP entrepreneurs into the electricity network. However, an enabling entrepreneurial environment in which to operate must be ensured. In this study, five important variables support the establishment of an enabling entrepreneurial environment for IPP entrepreneurs. These have been identified as; Smart Grids, Entrepreneurship, Renewable electricity environment, SA policy and Stakeholder theory. An important contribution has been made towards Stakeholder Theory. This has proven to be instrumental within the RE sector of the electricity industry in South Africa, as the mentioned role players have a reciprocal role to play. Three surveys were conducted at three levels of the electricity industry, namely, at organisational, legislative and entrepreneurial levels and included Eskom Management, National Energy Regulator (NERSA) Management and Approved and Non-approved IPPs. Both qualitative and quantitative research methods were utilised in this research study. The results indicate that SA Policy is instrumental in assisting stakeholders to facilitate the IPP process and feed the power from RE generation into the network. Most respondents were positive about the role of Smart Grids in future electricity generation and their contribution towards creating an enabling entrepreneurial environment for IPP entrepreneurs. Respondents indicated that by policy decisions, greater emphasis can be placed on the results of climate change and environmental challenges. Emphasis on the incorporation of stakeholders proved imperative to this group (IPPs). The results indicated that stakeholder management is a key factor contributing to the establishment of an enabling entrepreneurial environment. The major contribution of this study is a proposed entrepreneurial model that can improve future sustainability of the electricity supply.

Most descriptions of the rise of the Canadian welfare state emphasize that traditional social welfare institutions were always inadequate and it took the Depression to demonstrate the need for better, more comprehensive arrangements. Beyond the enlightening influence of the Depression, the rise of current welfare state institutions is attributed to the efforts and influences of politicians, unions, social reformers, and intellectuals. This myth about the rise of the welfare state has been so widely accepted that there has been little effort expended in examining pre-welfare state social insurance arrangements. The findings of this case study of the Independent Order of Oddfellows of British Columbia (IOOFBC) sickness insurance indicate that before 1930 there was an extensive formalized system of social insurance. The study also reveals that rather than having demonstrated the inadequacies of the traditional welfare mechanisms, the severe economic conditions of the Depression devastated the existing social insurance arrangements which created the impetus for the rise of the welfare state. Up until 1930, membership in a fraternal organization, like the Independent Order of Oddfellows (IOOF), was one of the most important sources of sickness/health insurance and life insurance throughout the world. Fraternal insurers were able to provide insurance at a lower cost than commercial insurers through their non-profit motive and their use of screening and peer monitoring practices to alleviate problems of adverse selection and moral hazard. Until 1930, 13% of the population in British Columbia had sickness/health insurance coverage through fraternal membership. Critics of fraternal insurance argued that while fraternal insurers may have had low costs, they led a financially precarious existence due to their hazardous pricing practices. An analysis of IOOFBC lodges for the period 1891 to 1950 reveals that this is not a good explanation of the decline of fraternal insurance. Even with the most hazardous of pricing practices, IOOFBC lodges had almost no probability of being bankrupted by high claims. Early in lodge operations, surplus revenues were invested in assets, like the lodge hall, which generated revenues that subsidized lodge operations and benefit payments. Given that fraternal insurers were viable, why was fraternal membership not an important source of insurance coverage after the Depression? An analysis of the memberships of four IOOFBC lodges over the period 1891 to 1980 reveals that the devastation of fraternal memberships in the Depression promoted the growth of alternative (commercial and government) insurance arrangements. In the 1930s, more workers than ever before were without sickness insurance coverage. As the probability of suspension for non-payment of dues tripled, workers would have had little expectation of remaining in a fraternal membership long enough to collect sick benefits that were primarily needed after age 45. Through and after the Depression, IOOFBC lodges abandoned their insurance functions. Lodge memberships had "aged" so much between 1930 and 1945 that the increased lodge benefit liabilities made reforming the IOOFBC's beneficial systems impractical. If changes were not made to the IOOFBC subordinate lodges' dues and benefits, lodges would have had to potentially draw on their assets to meet their inflated obligations. The solution adopted was to abandon sick benefits altogether as members who had always been opposed to the insurance. / Arts, Faculty of / Vancouver School of Economics / Graduate