Protein function and dysfunction, and their intimate ties to protein structure, has been a core focus of research for several decades. More recently, research into the lack of structure in proteins has reached fever pitch. Intrinsically disordered proteins (IDPs) are proteins (or protein regions) that exist as collapsed or extended, dynamically mobile conformational ensembles, either at secondary or tertiary level, whilst remaining biologically active. The properties of IDPs can impede their study; they are often inherently unstable, are vastly wide-ranging in molecular weight and often difficult to express in large quantities. Mass spectrometry (MS) has evolved into a tool for the study of dynamic systems such as IDPs due to its large dynamic range, high sensitivity, low sample consumption and its lack of bias towards the folded state of a protein. The addition of ion mobility separation to mass spectrometry analysis (IM-MS) provides insight into the conformations adopted by proteins and their complexes, measuring their rotationally averaged collision cross section which can be compared with coordinates from other biophysical techniques such as X-ray crystallography, NMR and to molecular modelling. The work presented in this thesis uses both MS and IM-MS, along with several other biophysical techniques, to interrogate a number of IDPs which are implicated in cancer. Firstly, variable temperature IM-MS is used to probe several proteins of increasing disorder; structured protein cytochrome c, the tumour suppressor protein p53 and the oncoprotein Murine Double Minute 2 (Mdm2), performing IM-MS measurements at a range of temperature from 200 K to 571 K to elucidate the gas-phase unfolding behaviour of each protein. The interaction between p53 and Mdm2 is a current target for cancer drug therapy. Hence MS and IM-MS, alongside circular dichroism and hydrogen-deuterium exchange are next employed to determine the effect of several known small molecule ligands on the conformations adopted by these disordered domains. The significant structuring of both of these disordered proteins upon binding to their respective ligands can be observed using IM-MS, but is not apparent when using other biophysical techniques, highlighting the ability of IM-MS to capture conformational changes occurring in solution on a short timescale. The regulation of disorder in cells is postulated to be mediated by proline residues. I investigate the impact of proline replacement on the populations of conformers presented by p53 using a range of mutants and then go on to study how these mutations impact upon the binding stoichiometry, affinity and conformational preference of p53 for its interaction partner Mdm2. Finally, the disordered melanoma associated antigen 4 MAGE-A4, and its ability to bind to p53 and block its transcriptional activity is probed using MS and IM-MS.

OLIVEIRA, Adaíla Monteiro de. Análise dos regimes próprios de previdência social dos municípios cearenses à luz do índice de desenvolvimento previdenciário (IDP) - 2006 a 2008. 2011. 67f. Dissertação (mestrado profissional) - Programa de Pós Graduação em Economia, CAEN, Universidade Federal do Ceará, Fortaleza, CE, 2011. / Submitted by Mônica Correia Aquino (monicacorreiaaquino@gmail.com) on 2013-08-27T20:21:14Z No. of bitstreams: 1 2011_dissert_amoliveira.pdf: 616265 bytes, checksum: aadd289a4199311e404ab2b82499db11 (MD5) / Approved for entry into archive by Mônica Correia Aquino(monicacorreiaaquino@gmail.com) on 2013-08-27T20:22:42Z (GMT) No. of bitstreams: 1 2011_dissert_amoliveira.pdf: 616265 bytes, checksum: aadd289a4199311e404ab2b82499db11 (MD5) / Made available in DSpace on 2013-08-27T20:22:43Z (GMT). No. of bitstreams: 1 2011_dissert_amoliveira.pdf: 616265 bytes, checksum: aadd289a4199311e404ab2b82499db11 (MD5) Previous issue date: 2011 / The study aims to analyze comparatively the level of development of the social security to the public sector (RPPSs - Regimes Próprios de Previdência Social) in cities of the State of Ceará – Brazil, from the period of 2006 to 2008, with available data on the Internet. To this end, it was made use of bibliography and data collection. The study dealt with information taken from the Annual Statement of Actuarial Valuations (DRAA – Demonstrativo Anual das Avaliações Atuariais), Social Security Statement and others. After collecting the data, it was performed the calculation of the indicators that construct the Social Security Development Index (IDP – Índice de Desenvolvimento Previdenciário). They are indicators of: 1)incorporated reserves (IRC – Indicador das Reservas Constituídas); 2) impairment of net current revenues (DPI – Dívida Pública Implícita); 3) pension plans maturity (IMP – Indicador de Maturidade Previdenciária); 4) commitment current (ICC – Indicador de Comprometimento Corrente); 5) commitment to personal tax (IFP – Indicador de Comprometimento Fiscal com Pessoal); and 6) legal framework (CRP – Certificado de Regularidade Previdenciária). The results of the study show that recent changes in legislation are allowing the construction and growth of sustainable pension systems, since most of the twenty-nine cities examined showed a change in level of pension plans development in the years 2006 to 2008, and suggests the inclusion of additional cost as another indicator of management of the IDP, whose influence was demonstrated by an econometric model. / Este estudo objetiva analisar, comparativamente, o nível de desenvolvimento previdenciário dos Regimes Próprios de Previdência Social (RPPSs) dos municípios do Estado do Ceará no período de 2006 a 2008 que possuem dados disponíveis na internet. Para esse fim, fez-se uso de pesquisa bibliográfica e coleta de dados. Trata-se de um estudo que envolveu informações do Demonstrativo Anual das Avaliações Atuariais (DRAA), Demonstrativo Previdenciário e outros. Após a coleta dos dados, foi realizado o cálculo dos indicadores que compõem o Índice de Desenvolvimento Previdenciário (IDP). São eles: Reservas Constituídas (IRC), Comprometimento da RCL (DPI), Maturidade Previdenciária (IMP), Comprometimento Corrente (ICC), Comprometimento Fiscal com Pessoal (IFP) e Enquadramento Legal (CRP). Os resultados do estudo mostram que as recentes mudanças ocorridas na legislação estão permitindo a construção e o crescimento de sistemas previdenciários sustentáveis, pois, dos vinte e nove municípios analisados, a maioria apresentou uma evolução no nível de desenvolvimento previdenciário no decorrer dos anos 2006 a 2008, bem como sugere a inclusão do custo suplementar como mais um indicador de gestão do IDP, cuja influência foi demonstrada através de um modelo econométrico.

This study aims to identify barriers to access and participation of adult internally displaced persons (IDPs) within the metropolitan area of Medellin, Colombia, as perceived by a sample of advisors, administrators and educators working with this population. Displacement often presents substantial barriers to education and IDPs fulfilling their human rights. These barriers and their underlying structures are analysed and compared to Cross' (1981) situational, institutional and dispositional categories, as well as corresponding the data to Maslow’s (1943) 5-scale Hierarchy of Needs.  The study found a variety of reasons why IDPs do not participate in education, and complex networks between these, which could be mapped to Maslow’s and Cross’ theoretical models. Lack of resources, cost/ benefit choices (both economically and in terms of time) and family obligations figure as much as poor prior study experience, literacy skills and confidence in one's own abilities. This is not surprising, and agrees with the literature regarding adult education of this population. This study aims to contribute to a complex model of deterrents to participation. A full model could be combined with existing knowledge to form a dynamic model of participation in adult education of the IDP population.

Magister Administrationis - MAdmin / The primary objective of this study is to critically examine the extent to which the Drakenstein municipality has achieved the principles spelt out in legislation and policy documents in relation to the implementation of Integrated Development Planning (IDP). Central to this process is to determine the roles that each of the stakeholders plays In the design, implementation and monitoring of the IDP On investigating the IDP it became evident that there were various shortcomings in the process in which it was prepared. For example, there was a lack of participation with necessary stakeholders, and, as a result of inadequate knowledge on the subject, councillor discussion in general council meetings on issues pertaining to development and especially to the IDP process was inadequate. Also lacking was the necessary administrative capacity, and proper consultation with other spheres of government with regards to the IDP process. The IDP is a key development instrument for Drakenstein municipality and its people and it is essential that proper systems are in place to effectively address the need for development in the region. However, budgetary constraints curtail the capacity of the Municipality to address all its priorities in one given year. Important and significant gaps therefore exist between the IDP and departmental business plans. It is in these gaps where the private sector and community organisations can add to the capacity of the municipality in support of broad community development priorities. Therefore, to address the aforementioned, it was found that departments should institute business plans in order to translate strategic themes into tangible and measurable activities. The IDP should define synergies between the activities of the Council, NGOsjCBOs and the business community (especially the farming sector) where different players are encouraged to explore roles for their organisations towards a better life for all.

Cette thèse se situe à l’interface entre la biologie et la biophysique. Les méthodologies utilisées recouvrent principalement la résonance magnétique nucléaire (RMN), la diffusion des rayons X aux petits angles (SAXS), le dichroïsme circulaire (CD) et la spectroscopie de fluorescence. Une première partie vise à étudier le domaine de liaison à l’ADN (DBD) du récepteur des androgènes (AR) et les déterminants de l’interaction avec l’ADN. Une mutation faux-sens dans le DBD altère la spécificité de reconnaissance de l’ADN du récepteur bien que la structure tridimensionnelle soit identique au DBD sauvage. Les résultats montrent un changement dans la dynamique du récepteur mutant entrainant une déstabilisation de l’homo-dimère.La seconde partie de ma thèse consiste à établir un lien séquence/fonction au niveau du domaine N terminal (NTD) de AR. D’après la littérature, cette région joue un rôle important pour l’activité du récepteur, et elle est également décrite comme étant intrinsèquement désordonnée. Les résultats révèlent que cette région établit des contacts transitoires avec le DBD. Ceci suggère l’existence d'un couplage allostérique entre le DBD et les résidus adjacents sur le NTD.Ce couplage modifie l'ensemble conformationnel accessible au NTD en favorisant une conformation en hélice-α. / My PhD project is at the boundary between biology and biophysic. Methods used include nuclear magnetic resonance (NMR), small ange X-ray scattering (SAXS), circular dichroïsm (CD) and fluorescence spectroscopy. The androgen receptor (AR) DNA binding domain (DBD) and its interaction with DNA was studied in a first part. A mutation in the DBD leads to a modified DNA recognition by the mutant compared to the wild-type. Our results indicate changes in dynamic of the mutant receptor that leads to the homodimer destabilisation.The second part of my project aim to establish a link between sequence and function of the AR N terminal domain (NTD).As described in literature, this region is involved in the activity of the receptor and is also an intrinsically disordered protein (IDP). The results obtained during my thesis indicate that this region is involved in transient contact with the DBD. This suggest an allosteric coupling between the DBD and the neighboring residues on the NTD.This coupling modifies the conformational ensemble accessible to the NTD by stabilizing a α-helix conformation.

Cloud-based applications especially SaaS applications have become essential for startups and various sized businesses. Adapting to these web applications helps to reduce operational costs and further provide flexibility in accessing individual data of the users. On the other hand, usage of these cloud services poses security-related issues such as authentication, authorization, web application security. Additionally, if the on-premises application is moved to the cloud then the traditional Identity solutions will not work, which affects the user authentication. This thesis considers ‘Authentication’ as one of the main security issues to be addressed. Thus, a new federated Identity and Access Management (IAM) system needs to be realized, which can be used for both on-premises and cloud to authenticate users correctly and securely. To meet the described challenges within the cybersecurity domain, this thesis focuses on two aspects of IT Security: 1) SaaS application rely on IAM; 2) IAM for securely authenticating users. This thesis work addresses both these aspects in two parts. First, by developing a SaaS web application that includes an authentication module with the support of the SAML 2.0 standard protocol. Second, the use of open source WSO2 IAM server for authenticating the users securely. To implement a SaaS application, a play framework PAC4j security library is used to support SAML SSO profile for authenticating users. The profile provides functionality for the two scenarios: SAML- Service provider and SAML- Identity Provider. The developed SaaS application acts as a service provider while WSO2 identity server acts as an Identity Provider. The SAML request-response authentication workflow between these providers are verified to prove the correctness and security of user login information. The research presented in this thesis is helpful for startup companies, that are initially looking to minimize application cost that works both on-premises and cloud without compromising on the security of user’s login information.

Made available in DSpace on 2014-06-11T19:22:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-03-30Bitstream added on 2014-06-13T18:08:14Z : No. of bitstreams: 1 demarqui_en_me_prud.pdf: 4998562 bytes, checksum: 5482d66ba7d8db635205618558aeb138 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Este trabalho propõe uma metodologia monoscópica para a determinação automática da altura de edifícios em fotografias aéreas digitais, baseando-se no deslocamento radial dos pontos projetados no plano imagem e na geometria formada no momento de obtenção da fotografia aérea. O conhecimento da altura de edifícios pode ser utilizado para a modelagem da superfície em áreas urbanas, estudos para a instalação de antenas de transmissão de sinais, planejamento de rotas para aeronaves, geração de true-orthophoto etc.. A metodologia emprega um conjunto de etapas para a detecção das bordas dispostas radialmente em relação ao sistema de coordenadas fotogramétrico, sendo que estas bordas representam as arestas laterais dos edifícios registradas na fotografia. Na primeira etapa realiza-se a redução do espaço de busca através da detecção das sombras projetadas pelos edifícios, gerando sub-imagens das áreas no entorno de cada sombra detectada. Na seqüência, é realizada a extração de bordas e conexão dos pixels destas sub-imagens. As bordas são analisadas individualmente para identificar qual par, dentre os pontos que compõem a borda, melhor corresponde aos extremos da aresta lateral do edifício. Os critérios utilizados para a seleção dos pares de pontos são os seguintes: análise do coeficiente linear da equação da reta formada pelo par de pontos; distância entre os pontos; e grau de sobreposição com a borda rotulada. Deste modo, a partir da seleção das arestas laterais, assim como o conhecimento da altura de vôo, são calculadas as alturas destes edifícios. Os resultados alcançados nos testes realizados com imagens reais se mostraram promissores para a identificação das arestas e cálculo da altura de edifícios. / This work proposes an automatic extraction of buildings height in digital images through a monoscopic methodology. Surface modeling of urban areas planning of aircraft routes, true-orthophoto and so on, can be performed by knowing the buildings heights. In photographs taken from an aircraft the buildings edges appear as radial lines due to the relief displacement, which occurs radially from the principal point. The first step of the methodology consists on the sub-images creation with the aim to reduce the search space on image. Thus, its used a shadows extraction procedure, by selecting only those with the biggest area (projected at ground) according to threshold. The edge extraction and pixels connection are performed for each sub-image produced and analyzed individually in order to identify if they belong to a building. The adopted criteria are based on the linear coefficient of straight line, the distance and the overlapping degree with regard to the labeled edge. With the lateral edges selected and the knowledge of the flight height, the buildings heights can be calculated. The experimental results obtained with real images show that the proposed approach is suitable to perform the automatic identification of the buildings height in digital images.

A qualitative research approach was utilised with the goal to explore the views and interpretation of community members concerning the participation in the Integrated Development Plan (IDP) of the City of Johannesburg Municipality. The objectives were to conceptualise the legal and policy framework for the implementation of IDP's in South African municipalities (with reference to community/public participation); explore the nature and extent of community participation in the IDP processes (understanding of the IDP process and its meaning to the community); explore community participation in relation to decision-making in the process of IDP consultation, and make suggestions for advocacy on meaningful community participation to optimise the success of IDP in the City of Johannesburg Municipality. Using applied research made it possible for suggestions of meaningful community participation to optimise the success of IDP in the City of Johannesburg Municipality. A sample of 18 participants was drawn from Region E of which only 10 people participated, focusing on Alexandra as the population. The most suitable research design was a qualitative design with a collective case study. A focus group session was held with each of the two groups of participants. The focus group session with community representatives took place at the AlexSankopano multi-purpose main hall in Alexandra, whilst the session with the representatives of the City of Johannesburg municipality, took place at the boardroom of Region E offices in Sandton. Data collected were analysed using Creswell's data analysis spiral. The findings of the research showed that, although participation in the IDP of the Alexandra community which forms part of Region E of the City of Johannesburg Municipality was acknowledged, it was not meaningful and effective to the community and municipal officials. The above finding seems to suggest that the value of community participation for sustainable development in the community, as well as for nation building has not been realised. / Mini Dissertation (MA)--University of Pretoria, 2016. / Social Work and Criminology / MA / Unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18805号 / 理博第4063号 / 新制||理||1584(附属図書館) / 31756 / 京都大学大学院理学研究科地球惑星科学専攻 / (主査)教授 土`山 明, 准教授 三宅 亮, 准教授 伊藤 正一 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

The random-coil model has been dominant for unfolded proteins since the 1950’s; however, some experiments showed that the unfolded proteins were biased toward specific conformations in conflict with the random-coil model. Recently, residual dipolar couplings (RDCs) and paramagnetic relaxation enhancement (PRE) were applied to obtain a large amount of structural information on unfolded proteins. Typically, these data were interpreted in a framework of random-coil ensembles with a good agreement between experimental data and theoretical predictions. In this thesis, it was tested whether locally organized nonrandom ensembles could describe this agreement equally as well. Using a complete set of RDC and PRE data for denatured ubiquitin, it was revealed that there was no distinguishable difference between random-coil ensembles and ensembles containing 50% native structure. Thus, while it is important to measure as many RDCs or PRE as possible, even the best datasets may be insensitive to local organization in unfolded proteins.