Recently, there has been increasing focus toward the development of small molecules designed to target a specific sequences of double stranded DNA for therapeutic purposes1. Minor groove binding compounds have been shown to be capable of selectivity target GC sites in AT tract DNA2. In this research, binding selectivity was investigated using absorption, fluorescence and circular dichroic properties of selected DB minor groove binders in the presence of two unique DNA sequences. Further insight was gained by comparing the electrostatic potential maps and optimized structures of the compounds of interest. Using the results presented, potential selective minor groove binders can be selected for further investigation and kinetic studies.

Nanomatériaux de silice peuvent être facilement fabriqués, façonné et fonctionnalisés comme plates-formes pour le greffage des nanoparticules pour des applications biomédicales et optiques. Ici, nous utilisons une méthodologie basée sur un modèle de préparer une collection variée de hélicoïdale nanoparticules d'or (PNB) superstructures ayant impartialité contrôlable et mesures structurelles en utilisant PNB que les blocs de construction, et les nanohelices de silice que le modèle. Le matériaux présentent synthétisé bien définir Agencement chiral de PNB suivant l'hélicité de nanohelices de silice, montrant des signaux plasmoniques de dichorism circulaire (CD). D'autres observations ont prouvé ce plasmon CD vient de l'arrangement chiral de PNB et cet effet est très taille, l'échelle et dépend du pH. Nous nous attendons à ce que cette stratégie d'assemblage va découvrir une meilleure vue sur les métamatériaux et de susciter la vue vers "bottom-up" des approches en nanosciences. / Silica nanomaterials can be easily fabricated, fashioned and functionalized as platforms for grafting of nanoparticles for biomedical and optical applications. Herein, we utilize a template-based methodology to prepare a diverse collection of helical gold nanoparticle (GNPs) superstructures having controllable handedness and structural metrics by using GNPs as the building blocks, and the silica nanohelices as the template. The synthesized materials exhibit well-defined chiral arrangement of GNPs following the helicity of silica nanohelices, showing plasmonic circular dichorism (CD) signals. Further observations proved this plasmon CD comes from the chiral arrangement of GNPs and this effect is highly size, scale and pH dependent. We expect that this assembly strategy will discover a better view towards metamaterials and spark the view towards “bottom-up” approaches in nanoscience.

Les accélération de faisceaux de forte puissance et le bombardement d'une cible de spallation permettent d'atteindre les flux requis pour application aux réacteurs sous-critiques pilotés par un accélérateur de particules (ADSR).Parmi les methodes d'acceleration, on trouve les accélérateurs circulaires, en particuler les FFAG et les cyclotrons. Le travail de cette these porte sur l'évaluation de ces methodes pour la production de faisceaux de protons de classe multi-mégawatts, y compris la participation à des collaborations d'études internationales de design. Une evaluation de la methode ADSR comme candidat potential pour resoudre le probleme des dechets nucleaires est finalement etablie. / High power proton accelerators allow providing, by spallation reaction, the neutron fluxes necessary in thesynthesis of fissile material, starting from Uranium 238 or Thorium 232. This is the basis of the concept ofsub-critical operation of a reactor, for energy production or nuclear waste transmutation, with the objective ofachieving cleaner, safer and more efficient process than today’s technologies allow.Designing, building and operating a proton accelerator in the 500-1000 MeV energy range, CW regime,MW power class still remains a challenge nowadays. There is a limited number of installations at presentachieving beam characteristics in that class, e.g., PSI in Villigen, 590 MeV CW beam from a cyclotron, SNS inOakland, 1 GeV pulsed beam from a linear accelerator, in addition to projects as the ESS in Europe, a 5 MWbeam from a linear accelerator.Furthermore, coupling an accelerator to a sub-critical nuclear reactor is a challenging proposition: some ofthe key issues/requirements are the design of a spallation target to withstand high power densities as well asensure the safety of the installation.These two domains are the grounds of the PhD work: the focus is on the high power ring methods inthe frame of the KURRI FFAG collaboration in Japan: upgrade of the installation towards high intensityis crucial to demonstrate the high beam power capability of FFAG. Thus, modeling of the beam dynamicsand benchmarking of different codes was undertaken to validate the simulation results. Experimental resultsrevealed some major losses that need to be understood and eventually overcome.By developing analytical models that account for the field defects, one identified major sources of imperfectionin the design of scaling FFAG that explain the important tune variations resulting in the crossing of severalbetatron resonances. A new formula is derived to compute the tunes and properties established that characterizethe effect of the field imperfections on the transverse beam dynamics. The results obtained allow to developa correction scheme to minimize the tune variations of the FFAG. This is the cornerstone of a new fixed tunenon-scaling FFAG that represents a potential candidate for high power applications.As part of the developments towards high power at the KURRI FFAG, beam dynamics studies have toaccount for space charge effects. In that framework, models have been installed in the tracking code ZGOUBIto account for the self-interaction of the particles in the accelerator. Application to the FFAG studies is shown.Finally, one focused on the ADSR concept as a candidate to solve the problem of nuclear waste. In orderto establish the accelerator requirements, one compared the performance of ADSR with other conventionalcritical reactors by means of the levelized cost of energy. A general comparison between the different acceleratortechnologies that can satisfy these requirements is finally presented.In summary, the main drawback of the ADSR technology is the high Levelized Cost Of Energy comparedto other advanced reactor concepts that do not employ an accelerator. Nowadays, this is a show-stopper forany industrial application aiming at producing energy (without dealing with the waste problem). Besides, thereactor is not intrinsically safer than critical reactor concepts, given the complexity of managing the targetinterface between the accelerator and the reactor core.

Au cours des dernières décennies, de nombreux outils ont été développés pour comprendre et gérer les cycles anthropiques des matériaux, avec différentes approches. Chacune considère les flux de matière dans la société de différentes manières et chacune possède ses bases de données respectives alimentant leurs utilisations. Il ne semble toutefois pas y avoir de bases communes pour la communication entre les activités de conception et les activités de bouclage, ainsi que leurs parties prenantes respectives, ce qui entrave les échanges d'informations nécessaires à une bonne gestion des produits mis au rebut (et de leurs matériaux). Cette thèse apporte ainsi deux contributions originales à la conception circulaire de produits: un outil pour l'intégration de la circularité des matériaux dans la conception de produits et un cadre pour caractériser les réseaux de bouclage de matériaux. L'outil est composé d'un indicateur multicritères de la valeur circulaire des matériaux utilisé dans la méthode de conception pour la circularité des matériaux (Design for Material Circularity method). Le cadre s'appuie sur une analyse documentaire approfondie, enrichie par des entretiens avec des experts de l'industrie, et sert de base à la collecte de données et à la capitalisation des connaissances sur les filières de bouclage. Les filières de recyclage en boucle ouverte de huit matériaux, appartenant aux trois principales catégories de matériaux, sont caractérisées grâce à ce cadre (acier, aluminium, cuivre, métaux précieux, métaux de spécialité, terres rares, plastiques et verre). Deux études de cas détaillent le déploiement de ces contributions. La première porte sur le choix optimal du matériau et du scénario de fin de vie pour une bouteille de 1,5 litre. La deuxième vise à identifier les points chauds (hotspots) de circularité des matériaux et les scénarios de fin de vie idéaux pour un bloc-batterie véhiculaire au lithium. / In the last decades, many tools have been developed to understand and manage the anthropogenic cycles of materials, with different approaches. Each handles the material flows in society in different ways and each possesses its respective databases that fuel their uses. Yet there seems to be no common ground of communication between design activities and cycling activities, as well as their respective stakeholders, which hinders the information exchanges required for a proper management of discarded products (and their materials). This thesis provides two original contributions to circular product design: a tool for the integration of material circularity in product design and a framework to characterize material cycling networks. The tool is composed of a multi-criteria indicator for circular material value that is used in the Design for Material Circularity method. The framework is based on an extensive literature review enhanced by industry experts’ interviews and provides a basis for data collection and knowledge capitalization on cycling activities. The open-loop recycling networks of eight materials, from the three main material classes, are characterized using this framework (steel, aluminium, copper, precious metals, specialty metals, rare earth elements, plastics and glass). Two case studies detail the deployment of these contributions. The first focuses on the optimal choice of material and end-of-life scenario for a 1,5-litre bottle container. The second is aimed at identifying material circularity hotspots and ideal end-of-life scenarios for a vehicular lithium-ion battery pack.

Nos últimos anos a discussão acerca da autonomia da política monetária esteve polarizada entre dois grupos de autores. Baseados numa concepção arqueológica da moeda (Cencini, 1997), alguns afirmam que os Bancos Centrais, diante da integração entre os mercados financeiros, teriam perdido a autonomia para praticar políticas monetárias em favor do crescimento econômico. Em contraste, outro grupo de autores sustenta que mesmo no atual contexto de “perfeita mobilidade do capital”, sob certas condições, a autoridade monetária conserva amplos graus de liberdade para definir o nível da taxa de juros doméstica, em qualquer contexto considerado. O objetivo principal do estudo é analisar teoricamente a questão da autonomia da política monetária nos termos em que a mesma vem sendo discutida na atualidade, e subseqüentemente, através de um modelo macroeconômico de simulação, examinar as conseqüências de uma política de juros alternativa àquela que o Banco Central do Brasil vem adotando. Constatou-se que em uma economia de mercado, em que muitos insumos produtivos são reproduzíveis, incluindo a força de trabalho e os bens de capital, emerge uma relação definida entre a dimensão do consumo produtivo da força de trabalho, visando a preservação das condições materiais da economia, e a magnitude dos meios de pagamento existentes: os meios de pagamento podem ser criados e destruídos no sistema bancário por causa do pagamento de salários aos trabalhadores, sob demanda das empresas. Sob essa ótica há certa dificuldade analítica para se conceber os meios de pagamento exogenamente determinados. Ao contrário, o caráter institucional, discricionário da taxa monetária de juros segue simples e logicamente. O mercado financeiro atua no sentido de restaurar a liquidez das empresas de negócios facilitando a liquidação de seus empréstimos passados junto aos bancos comerciais. Através da aplicação de um modelo macroeconômico de simulação dois cenários alternativos foram gerados para os próximos oito anos de política (2008-2015). No cenário de mudança uma política de redução progressiva da taxa de juros para o patamar de 3,66% ao ano resulta em uma taxa de inflação muito similar ao cenário de continuidade, caracterizado por uma taxa de juros de 15,39% ao ano. Porém, no primeiro caso ocorre um aumento substancial no crescimento da capacidade produtiva da economia com uma taxa cambial mais competitiva, que estaria situada, em média, em R$/US$ 2,51. Por outro lado, no cenário de continuidade a perda anual, em média, no acréscimo da capacidade produtiva da economia é de 7,44%, associada a uma taxa cambial não competitiva, que em média estaria situada em R$/US$ 2,35. A estabilidade de preços foi preservada em todos os cenários. / In recent years several authors have questioned the power of monetary authority to fix domestic money rate of interest at lower levels of their neighbors. The main reason would be the increasing financial integration of markets, and their “capital flows”. The “Flow Theory” (Branson, 1970) asserts that in a world where capital is perfectly mobile the power of Central Bank would be reduced at minimal levels, because of the exogenous character of money. So, active monetary policies to attain and maintain full employment would be not possible in that world, as a low and still positive interest rate. The aim of this study is to evaluate theoretical and empirically this claim for a market economy, considering the case of Brazilian economy. The main theoretical conclusion does not confirm that claim. On the contrary, in a market economy where several inputs are reproducible, including labor force and capital equipment, a definite relation comes about between the length of productive consumption, to guarantee material conditions of the economy, and means of payment: immaterial means of payment can be created and destroyed by banks because of wages, on demand of enterprises in money market. In this way there are some analytical difficulties to conceive money as a stock of wealth, as a material and exogenous object. Yet, the institutional and conventional character of money rate of interest, in any context, follows simple and direct because of the social and circular nature of production. The power of monetary authority is reinforced this way. By applying a macroeconomic simulation model designed to Brazilian economy to investigate the effect of an interest rate at an international level over the accumulation rate, inflation and exchange rate, alternative scenarios were obtained to the next eight years of policy (2008-2015). The main results suggest that if Central Bank would decide to fix the money rate of interest at 3,66% per year, the accumulation rate would be substantially greater and the exchange rate would stabilize around R$/US$ 2,51. But, if the monetary authority chooses to fix politically a higher rate, say 15,39% per year, the accumulation rate would be substantially lower and the exchange rate would be around R$/US$ 2,35 for the next eight years. The stable prices were maintained in all scenarios. There is no trade-off between growth and stability. So, the best choice of monetary authority would be a low but still positive money rate of interest to permit a greater production level and competitiveness at international arena.

abstract: The photosynthetic reaction center is a type of pigment-protein complex found widely in photosynthetic bacteria, algae and higher plants. Its function is to convert the energy of sunlight into a chemical form that can be used to support other life processes. The high efficiency and structural simplicity make the bacterial reaction center a paradigm for studying electron transfer in biomolecules. This thesis starts with a comparison of the primary electron transfer process in the reaction centers from the Rhodobacter shperoides bacterium and those from its thermophilic homolog, Chloroflexus aurantiacus. Different temperature dependences in the primary electron transfer were found in these two type of reaction centers. Analyses of the structural differences between these two proteins suggested that the excess surface charged amino acids as well as a larger solvent exposure area in the Chloroflexus aurantiacus reaction center could explain the different temperature depenence. The conclusion from this work is that the electrostatic interaction potentially has a major effect on the electron transfer. Inspired by these results, a single point mutant was designed for Rhodobacter shperoides reaction centers by placing an ionizable amino acid in the protein interior to perturb the dielectrics. The ionizable group in the mutation site largely deprotonated in the ground state judging from the cofactor absorption spectra as a function of pH. By contrast, a fast charge recombination assoicated with protein dielectric relaxation was observed in this mutant, suggesting the possibility that dynamic protonation/deprotonation may be taking place during the electron transfer. The fast protein dielectric relaxation occuring in this mutant complicates the electron transfer pathway and reduces the yield of electron transfer to QA. Considering the importance of the protein dielectric environment, efforts have been made in quantifying variations of the internal field during charge separation. An analysis protocol based on the Stark effect of reaction center cofactor spectra during charge separation has been developed to characterize the charge-separated radical field acting on probe chromophores. The field change, monitored by the dynamic Stark shift, correlates with, but is not identical to, the electron transfer kinetics. The dynamic Stark shift results have lead to a dynamic model for the time-dependent dielectric that is complementary to the static dielectric asymmetry observed in past steady state experiments. Taken together, the work in this thesis emphasizes the importance of protein electrostatics and its dielectric response to electron transfer. / Dissertation/Thesis / Ph.D. Physics 2012

This study aims to develop an understanding of how circular economy should be implemented to result in sustainable development and to analyze the potential of one particular implementation to result in sustainable development. “The sustainable development way of implementing circular economy” is presented by understanding circular economy with system thinking and considering the factors affecting the implementation of circular economy. Interviews and text-analysis are conducted to analyze the character and potential of ReTuna, a reused items mall in Eskilstuna, to result in sustainable development. Results show circular economy should be implemented as a way of reasoning that can result in a systemic transformation of the economic system to result in eco-centric sustainability. Implementations that do not explicitly derive from a an understanding of circular economy as a new way of reasoning are despite this valuable due to a system’s character of interconnectedness. ReTuna is implemented as a set of practices and an organizational structure but it also demonstrates an honorable effort to change people’s perception of the human-nature relationship. It is concluded that way of implementation has to reflect and be synchronized with the aspiration behind implementing circular economy. ReTuna has potential to result in sustainability but does not yet.

Inspired by the way nature cycles waste in an ecosystem, the circular economy was developed as an alternative to the linear take-make-dispose model and designed to decouple economic growth from resource use. After developing a framework for what it means to be a business pursuing circularity, this thesis examines six different companies to explore the tension between the strategies and business models in theory and what business are implementing in practice today. This exploration continues with an in-depth analysis of the circular success of IKEA, finding that the gains from the circular economy for a large corporation are found within their own operations. With the company’s scale, IKEA is able to act as a transfer hub of technology and best practices, ultimately allowing the company to make a global impact.

This study and design concept explores the need for a change of the behaviour and recycling knowledge in Nybro Municipality, situated in Eastern Sweden.  The main aim of this study is to provide support for discussion and act as an inspiration for the future development of projects with participatory citizenship. Additionally, to invigorate the need for a sustainable and circular waste management to reach sustainable development.  The theoretical framework set up for this study focus on sustainable development, citizens’ behaviour and knowledge of recycling. The explorative research stage of the project is performed through several methods, including interviews with current waste management companies and Nybro Municipality’s Sustainability Department. Furthermore, a survey of the citizens of Nybro municipality, to investigate the behaviour and knowledge about recycling. Correspondingly, relevant secondary research and compulsory review of the context, waste management and circular economy in Sweden, but also the behaviour within recycling of the system users - citizens, is being examined. The project focuses on sorting and analysing the data and findings by using methods of several different visual thinking tools.  The outcome of the project is a proposal of a design concept to facilitate the recycling of waste for the citizens as the users. Moreover, to emphasize the need and importance of recycling our everyday waste materials. This project is not a solution-based project, but more widely to provide a basis for discussion and inspire.  The goal is to find a way that encourages citizens to recycle waste from products purchased in their daily living. A social design workshop, focusing on circular waste management and recycling behaviour, together with the citizens living in Nybro municipality, will be proposed and co-designed with the municipality’s sustainability department of Nybro Municipality.

The canonical Wnt pathway is a vitally important signalling pathway that plays an important role in cell proliferation, differentiation and fate decisions in embryonic development and in the maintenance of adult tissues. The twelve Armadillo (ARM) repeat-containing protein beta-catenin acts as the signal transducer in this pathway and is continuously degraded in the cytosol by the beta-catenin destruction complex (BDC). Upon receiving the Wnt signal the BDC is inactivated, allowing beta-catenin to accumulate in the cytosol and be transported to the nucleus where it binds to the TCF/LEF family of transcription factors, inducing the expression of cell cycle promotor genes. In this Thesis I describe investigations into the roles of leucine-rich repeat kinase 2 (LRRK2) and the transcription factor TCF7L2 within this signalling pathway. LRRK2 is a large multi-domain protein with strong links to Parkinson’s disease and suggested to play a role in inactivating the BDC in response to the Wnt signal. A recent paper proposed that the previously uncharacterised regions of LRRK2 contain a series of tandem repeat sub-domains. I began an investigation into these sub-domains but I was unable to produce soluble protein constructs despite the use of a range of common techniques, and so I was forced to conclude this project early. The main body of this thesis focuses on the interaction between the intrinsically disordered TCF7L2 and the repeat protein beta-catenin, a very long interface of approximately 4800 Å2 that spans from the third to the eleventh ARM repeat of beta-catenin and residues 12 to 50 of TCF7L2, as determined by X-ray crystal structures. First, a fluorescence reporter system for the binding interaction was developed and used to determine the kinetic rate constants for the association and dissociation of the wild-type construct using stopped-flow fluorescence spectroscopy and time-dependent fluorescence spectroscopy. It was found that association of TCF7L2 and beta-catenin was rapid (7.3 ± 0.1 x107 M-1s-1) with only a single phase was observed, whereas dissociation was biphasic and slow (5.7 ± 0.4 x10-4 s-1, 15.2 ± 2.8 x10-4 s-1). Using either of these two dissociation rate constants the calculated Kd value obtained is much lower than the values previously reported in the literature (8 ± 1 / 20 ± 2 pM compared with 16 nM). This reporter system was then used to investigate the striking variability between three crystal structures previously obtained for the TCF7L2-beta-catenin complex, in which different regions of TCF7L2 show different elements of secondary structure. Mutational analysis revealed that the interface residues on TCF7L2 identified in these structures make little or no contribution to the overall binding affinity, pointing to a transient nature of these contact in solution and suggesting that the observed differences between the structures are due to differences in crystal packing. Further experiments into the effect of osmolarity on the binding equilibrium and kinetics supported this conclusion and suggest a change in the association/dissociation mechanism as a function of ionic strength. Lastly, further mutational analysis of TCF7L2 revealed two regions that contribute particularly strongly to the binding kinetics, suggesting that TCF7L2-beta-catenin assembly proceeds via a two-site avidity mechanism. Some of the most destabilising variants display two additional dissociation phases, indicating the presence of an alternative dissociation pathway that is inaccessible to the wild-type. In summary, the results presented here provide insights into the kinetics of molecular recognition of a long intrinsically disordered region with an extended repeat protein surface, a process shown to involve multiple routes with multiple steps in each.