Le objectif de ma thèse était la caractérisation moléculaire de la P des virus Nipah et Hendra (BL4) du genre Henipavirus. Le génome est encapsidé par la N qui sert de substrat pour la transcription et la réplication. La polymérase est composée par la L e son cofacteur la P. La P est composée d’un domaine N-terminal (PNT) désordonné et un domaine C-terminal (PCT) constitué d’une alternance de régions désordonnés et ordonnés (PMD domaine de multimerization). J'ai étudié PMD, PCT et PNT utilisant le «cross-linking», le CD, le SAXS, la RMN et la modélisation moléculaire. J'ai montré que le PMD du Hendra et Nipah sont un coiled-coil triméreric. La région PCT, est également un trimère en solution. Les protéines P des henipavirus constituent à ce jour le seul exemple de protéines P paramyxovirales ayant une organisation trimérique. En utilisant le SAXS, j'ai obtenu une description de Hendra PNT en tant qu’ensemble conformationnel. J'ai entrepris la caractérisation de la PNT par RMN. J’ai divisée la PNT avec l’approche divide et impera (PNT1,2,3,4). J’ai pu réaliser des expériences permettant l’attribution de PNT1, et j’ai également effectué des mesures de relaxation (R1, R2 et NOE) sur les fragments PNT1, PNT2 et PNT3. Les résultats issus des travaux effectués ont ouvert la voie vers l’obtention d’une description atomistique de la PNT en tant qu'ensemble conformationnel. Ces informations avec les informations structurales que j’ai sur PCT, PMD et XD, devraient conduire à une description atomistique de la P entière en tant qu’ensemble conformationnel. Ces informations structurales détaillées constitueront aussi un socle pour des approches antivirales rationnelles. / The objective of my PhD project was the molecular characterization of the P protein from the Nipah and Hendra viruses (BL4) belonging to the Henipavirus genus. The genome is encapsidated by the N that is the substrate for transcription and replication. The polymerase is made up the L and its cofactor the P. The P protein consists of an intrinsically disordered N-terminal domain (PNT), and a C-terminal domain (PCT) made of alternating disordered and ordered domain (PMD or P multimerization domain). I investigated the PMD, PCT and PNT regions, using cross-linking, AUC, CD, SAXS, NMR and molecular modeling. I showed that Hendra and Nipah PMD are a trimeric coiled-coil in solution. The Henipavirus proteins constitute so far the unique examples of a trimeric organization in paramyxoviral P proteins. The PCT is a trimer as well. Using SAXS, I obtained an ensemble description of PNT. To obtain site-specific information that improve SAXS-based models, I undertook the characterization of Hendra PNT by NMR. The latter was divided using the “divide et impera” approach to get four fragments (PNT1,2,3,4). Experiments for the assignment have been performed for PNT1. R1, R2 and NOE were carried out on PNT1,2,3. Altogether the results laid the basis for achieving an atomic-resolution conformational ensemble description of Hendra PNT. This information, combined with structural information that I collected on PCT, PMD and XD, is expected to lead an atomistic ensemble description of the full-length P, which would represent the first, such a description of a paramyxoviral P protein. This detailed structural information will also constitute an asset for rational antiviral approaches.

La compréhension des interactions intra- et inter-moléculaires à l’échelle atomique représente un enjeu scientifique important. A l’heure actuelle, les techniques de RMN ont déjà prouvé leur efficacité pour l’analyse de ces interactions in vitro, dans les solutions tampons. Toutefois, il a également été montré que la plupart des biomolécules ont une structure et une dynamique différentes in vivo, à l’intérieur des cellules, de celle in vitro. Il est donc crucial d’analyser les biomolécules dans leur milieu naturel, la cellule. Récemment, les progrès dans le domaine de la RMN dans les cellules ont permis de mieux comprendre la dynamique et les interactions des biomolécules présentes dans le milieu cellulaire complexe. Cependant, la biomolécule étudiée étant présente en faibles concentrations, elle possède un faible signal sur le spectre RMN, qu’il est difficile de suivre. De plus, du fait de la forte viscosité du milieu cellulaire, la relaxation rapide de l’aimantation transverse se traduit par un élargissement des raies spectrales. L’utilisation des états de spin à longs temps de vie et de la Polarisation Dynamique Nucléaire suivie par la dissolution de l’échantillon (dissolution-DNP) pourraient permettre de pallier aux problèmes d’élargissement de raies et de sensibilité. L’objectif de ce travail de thèse a été d’explorer les bénéfices des ces avancées récentes de la RMN pour l’étude des petites molécules, peptides et protéines à l’intérieur des cellules. Pour la protéine c-Src, qui appartient à la classe des protéines intrinsèquement désordonnées (IDP), la dynamique de l’ensemble des conformations de l’extrémité N-terminale a été suivie utilisant des états de spin à longs temps de vie LLS. Le signal du noyau de carbone-13 de la molécule de pyruvate a été augmenté utilisant la Polarisation Dynamique Nucléaire (DNP) afin de mieux l’observer dans le milieu cellulaire. Un peptide représentatif pour la partie active d’une autre protéine, IκBα, a été introduit dans des cellules HepG2 par l’électroporation. Les observations faites lors des ces expériences sont discutées dans la perspective de faciliter les études RMN des biomolécules à l’intérieur des cellules. / Most NMR studies are carried out in vitro, but the structure and dynamics of some biomolecules inside cells differ from those in vitro. It thus becomes interesting to analyze biomolecules such as proteins in their natural environment: the cell. Recent progress of in cell NMR allowed to better understand the behaviour of proteins: their dynamics and their interactions with other biomolecules in the cell. But the low concentration of proteins leads to low signal intensity. Moreover, the viscosity of the environment induces faster transverse relaxation, resulting in line broadening for proteins signals. The use of the Long-Lived States and Coherences (LLS and LLC, respectively) as well as dissolution Dynamic Nuclear Polarization (dissolution-DNP) can improve NMR observations in cells. LLS were used to understand and characterize the structure of the N-terminal domain of c-Src, which is intrinsically disordered. To follow the phosphorylation of proteins, a first preliminary study of a 21-aa peptides derived from IKBα electroporated into HepG2 cell lines was carried out.

The continuous evolution of digital technology we enjoy today is the result of ever shrinking, faster and cheaper transistors that make up the ubiquitous integrated circuits of our devices. Over the decades, the industry has gone from purely geometrical scaling to innovative solutions like high-k dielectrics combined with metal gates and FinFETs. A possible future is the use of high mobility materials such as Germanium for the active areas of a transistor instead of Silicon. As a step towards building devices on Ge, we characterize a gate last process with epitaxial deposition of Si0.75Ge0.25 source and drain areas on bulk Si wafers. Devices fabricated are proof-of-concept PMOSFETs and NMOSFETs with channel widths of 10 µm and 40 µm and channel lengths between 0.6 µm and 50 µm. The gate electrode of the fabricated devices is insitu doped polycrystalline Silicon. The devices are electrically characterized through I-V measurements and exhibit a yield of 95%. / Den konstanta utvecklingen av digital teknik som vi åtnjuter idag drivs av den ständiga utvecklingen av transistorer. Dessa blir mer kompakta, snabbare och kostar mindre för varje generation och bygger upp de integrerade kretsar som driver all vår vardagsteknik. Under ett tidsspann på flera decennier har krympningen gått från enbart geometrisk skalning till mer innovativa lösningar. Gate-oxiden har gått från rent kiseldioxid till material med lägre relativ permittivitet vilket möjliggjort en tunnare ekvivalent elektrisk tjocklek än vad som varit möjligt för kiseloxid. FinFet eller så kallade ’tri-gate’ transistorer har ersatt den plana varianten för att öka den ledande arean utan att enheterna sväller ut över substratet. En framtida möjlighet är även att använda material med högre mobilitet för elektroner och hål än kisel där en möjlig kandidat är Germanium. Som ett steg mot målet at bygga Germanium-transistorer tillverkar vi här gate last transistorer med source och drain i in-situ dopad kisel-germanium. Dessa konceptenheter används för att definiera och utveckla tillverkningsprocessen och tillverkas i flera omgångar. Varje skiva innehåller transistorer med en bredd på 40 µm och 10 µm. Kanallängden på transistorerna går mellan 0.6 µm och 50 µm för båda bredderna och av varje enhet finns 101 stycken per kiselskiva (100 mm diameter). Gate-elektroden består i samtliga fall av in-situ dopat poly-kristallint kisel. Enheterna karaktäriseras därefter genom elektriska mätningar och mätdata analyseras och sammanställs. Det visas genom dessa mätningar att ett utfall om över 95% fungerande enheter kan uppnås med processen.

International Development Projects (IDP) are designed to deliver sustained solutions to human life quality threatens. They aim to improve living conditions in emerging countries through initiatives that should provide long-term sustained results. However, the extreme characteristics of IDP contexts challenge traditional project management methodologies. The dynamic nature of stakeholders’ relationships and influence adds additional pressures to the management teams. Higher levels of uncertainty in IDP are faced with non-flexible strategies that compromise the long-term desired results. Not enough participation of relevant stakeholders and beneficiaries limits the impact of development initiatives.   The authors could identify that IDP management is overall an under-investigated field. Specifically, contemporary challenges arisen from unbalanced robust/flexible strategies and low stakeholders participation have undermined the impact success of those projects. Moreover, there is no academic study that constructs on how flexibility could be enhanced in IDP, while maintaining control. Methodologies such as design thinking and agile have elucidated new paths of action for better impact and customer satisfaction in other industries, by enabling flexibility and change management. Despite their huge proven success, these methodologies are still a phenomenon limited to IT and design industries. Therefore, in IDP field there is no framework linking contingency and participatory development theories with flexible methods similar to design thinking and agile methodologies.   In order to bridge this gap the authors will embark in a qualitative study to explore literature and gain insights from actors within the IDP field about the problem at hand. A multiple embedded case study will be conducted with ID academics and practitioners at supervisory and implementation levels from across the world. A possible solution will be designed for IDP management from a different angle to that of traditional management, in order to build up flexibility without compromising project structure. The proposed framework will tackle flexibility and participation issues by integrating design thinking and agile methodologies into IDP.   The theoretical findings suggest that enabling participatory development strategies in the design phase, and expanding the available project knowledge would enhance IDP flexibility.  Likewise, IDP flexibility during the implementation phase is impacted by the quality and relevance of information and methodological tools available, stakeholders’ involvement, as well as the handover process. Therefore, since no previous studies interconnecting those theories to enhanced flexibility could be found in IDP, an expansion of available theoretical knowledge on contingency and participatory development theory in IDP is produced. The authors concluded that design thinking and agile principles may conceptually prove useful to effectively deal with the problems identified, thus project design is more adequate, and collaboration among stakeholders proves effective to deal with uncertainty and complexity. These constructs are explained in the propositions made for the SUITE framework to IDP, which aims to practically contribute to the management field of IDP.

The research focuses on the effectiveness of the integrated development planning (IDP) as a tool to accelerated service delivery: A case study of Aganang Local Municipality. The main problem investigated in the research is that the community of Aganang Local municipality does not have adequate services. The objective of the research is to investigate the integrated development planning process's impact on service delivery, to investigate if the budget is aligned to the IDP and to make possible recommendations on how the IDP could accelerate and improve service delivery. The hypothesis of the research centres on the acceleration of service delivery by implementing the IDP. Change in integration and cooperation in municipalities can be met if the management, process, systems, culture and innovation are improved. Qualitative and quantitative data was used in this research; the primary sources include questionnaires and interviews while the secondary sources include books, journals and reports. The findings revealed that Aganang local municipality has limited capacity in terms of human and financial resources; the municipality should have a retention and succession policy to ensure that the skills in the municipality are retained. The research also revealed that most people in the municipal area are illiterate and have insufficient skills. The study also revealed that the sector departments do not ensure that municipal strategies take cognisance of provincial strategies during the strategic sessions. The study also revealed that the budgets are only done per financial year and not on a Medium Term Expenditure Framework (MTERF) basis (3-year plan) and are not properly aligned to the IDP. The research recommends that municipalities should strengthen the inter-governmental relations to ensure alignment and integration both horizontally and vertically. The research also recommends that the municipality should build capacity and develop skills in the community. The study also recommends adopt the cluster planning and implementation including forward planning to ensure that there is maximum resource allocation and shared functions. The study also recommends that the budget should be on a three-year basis to allow for proper project planning. / Thesis (M.Art. et Scien. (Town and Regional Planning))--North-West University, Potchefstroom Campus, 2008.

Student Number : 0005386G - MSc research report - School of Architecture and Planning - Faculty of Engineering and the Built Environment / The research recognises the IDP as an important post-apartheid planning tool that can potentially lead to integration within the City of Johannesburg. However, for the IDP to attain its mandated goals, an enabling institutional culture of the City and its units need to prevail. The gap/challenge is that the institutional culture of the City and its departments/units are shaped by Joburg 2030, a purely economic strategy that does not embrace the principles needed for attainment of IDP goals. The principles needed for successful formulation and implementation of the IDP are found in equity planning theories and New Institutionalism. These are the principles that do not form part of the Joburg 2030 vision. The solution is for the Joburg 2030 to include the planning principles as already highlighted. This solution will affect departmental practices for the better.

Thesis (MBA.) -- University of Limpopo, 2016 / Integrated Development Plan (IDP) are required for municipalities to function effectively. Local municipalities in South Africa use IDPs as a method to plan for the present and future development in their respective areas.The primary objectives of this study was to assess factors that facilitate or hinder successful implementation of the prioritised programmes or projects in the Integrated Development Plan of the Molemole Local Municipality. The study used qualitative approach to collect data from municipal officials, municipal council and community representatives. The study revealed that the community were not aware of the programmes or projects identified in the IDP and that there is lack of capacity to effectively implement the IDP and, communication between municipal employees and the community is not perceived to be adequate.The study recommends that the municipality should conduct training, improve communication methods and conduct awareness on IDP processes.

Thesis (M.Art. et Scien. (Town and Regional Planning))--North-West University, Potchefstroom Campus, 2008.

International Development Programmes (IDPs) are United Nations‘ (UN) and developedcountries‘ initiatives to develop world‘s least developed countries. IDPs significantly vary fromother mainstream project management topics, as most often they do not have eye for commercialsuccess or are not of simple charity nature of humanitarian perspective aid. Projects under IDPstry to deliver United Nations‘ and rich countries commitment to provide sustainable developmentto developing world in terms of reducing poverty and hunger, improving health and educationsystem, building capacity to face disasters, eliminating gender discrimination, among others.This significant difference and lack of research in this field has left a gap in established projectmanagement methodologies that could be generalised as specifically suitable for IDPs.The knowledge of project selection methodologies has reached to its extreme variety, as itspreads from the simplest model of a checklist to the highest degree mathematical model.Leading researchers in the field have come to conclusion that project selection methods have tomatch the needs of a specific programme or portfolio to serve its purpose. The uniqueness ofIDPs intensified the necessity of choosing projects by understanding the financial and strategicbenefit they can deliver matching their resource requirement. In absence of straight direction inthe research and real life case observations, the practice in project selection in IDPs has not stillbeen an established procedure.To explore this need the authors of this report examined the theoretical framework of projectselection and their compliance with IDPs unique characteristics. Project selection methodsshowed that due to organisations‘ varied need of delivering financial or strategic objectives, theselection models significantly vary. The use of different financial or strategic criteria withdifferent emphasis on them is highlighted in project selection articles. Further analysis wasfocused on project selection stages and possible challenges evolving in the selection process.The researchers tried to explore project selection methods used in IDPs in Bangladesh byanalyzing four different cases. The examination of the project selection process showed that itmainly follows the multi-stage assessment procedure, with project evaluation conducted by theassessment panel, comprised from the functional experts and in some cases stakeholders‘representatives. Further, from the findings it was evident that the primary theoretical suggestionsfor IDPs project selection methods being strategy driven rather than being commercial in natureis true. In all four cases, the researchers have seen the selectors using scoring and ranking modelthat are specifically designed with higher emphasis on the strategic factors, and that try to deliverdevelopment objective rather than contributing to commercial success. In addition, thechallenges in IDP project selection practice are also discussed. Challenges like deliveringdevelopment needs while trying to make the project sustainable in the long run, managing thepowerful influence of different stakeholders in selecting projects, avoiding country politics,among others are making the project selection more difficult. The main contribution of thisresearch has been establishing a primary selection framework from case evidence withsuggestions on appropriate model, set of criteria which can be used and a set of challenges to beaware of. The study is presented as a basis for further research in this field.

The research focuses on the effectiveness of the integrated development planning (IDP) as a tool to accelerated service delivery: A case study of Aganang Local Municipality. The main problem investigated in the research is that the community of Aganang Local municipality does not have adequate services. The objective of the research is to investigate the integrated development planning process's impact on service delivery, to investigate if the budget is aligned to the IDP and to make possible recommendations on how the IDP could accelerate and improve service delivery. The hypothesis of the research centres on the acceleration of service delivery by implementing the IDP. Change in integration and cooperation in municipalities can be met if the management, process, systems, culture and innovation are improved. Qualitative and quantitative data was used in this research; the primary sources include questionnaires and interviews while the secondary sources include books, journals and reports. The findings revealed that Aganang local municipality has limited capacity in terms of human and financial resources; the municipality should have a retention and succession policy to ensure that the skills in the municipality are retained. The research also revealed that most people in the municipal area are illiterate and have insufficient skills. The study also revealed that the sector departments do not ensure that municipal strategies take cognisance of provincial strategies during the strategic sessions. The study also revealed that the budgets are only done per financial year and not on a Medium Term Expenditure Framework (MTERF) basis (3-year plan) and are not properly aligned to the IDP. The research recommends that municipalities should strengthen the inter-governmental relations to ensure alignment and integration both horizontally and vertically. The research also recommends that the municipality should build capacity and develop skills in the community. The study also recommends adopt the cluster planning and implementation including forward planning to ensure that there is maximum resource allocation and shared functions. The study also recommends that the budget should be on a three-year basis to allow for proper project planning. / Thesis (M.Art. et Scien. (Town and Regional Planning))--North-West University, Potchefstroom Campus, 2008.