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Le traitement des douleurs sévères repose dans la plupart des cas sur l’utilisation d’analgésiques opiacés. Cependant après administration répétée d’analgésique morphinique, on observe une tolérance aux agents morphiniques. Au niveau moléculaire, l’hypothèse physiopathologique met en avant la participation de systèmes ‘’dits anti-opiacés’’, comme le système du neuropeptide FF (NPFF). Dans un premier temps, une méthode de synthèse a été développée pour introduire divers α-aminoacides sur les chlorures d’α-hétéroaryle correspondants. Cette méthode originale, faisant appel aux conditions et catalyseurs décrits par Buchwald, a conduit à la découverte de ligands puissants de ces récepteurs. D’autre part, notre travail s’est basé sur la conception, la synthèse et l’étude des relations structure-activité d’autres familles de ligands pour les récepteurs du NPFF. Plusieurs séries de molécules ont été étudiées, parmi elles deux grandes familles : les aminoguanidines hydrazones et les quinolin-2-yl guanidines. Cette étude nous a permis d’identifier plusieurs ligands actifs in vitro (nanomolaire) et in vivo sur les récepteurs du NPFF. Ainsi nous disposons actuellement de ligands sélectifs vis-à-vis des deux récepteurs du NPFF. Une difficulté de synthèse des aryl/hétéroaryl guanidines a été rencontrée, en particulier avec les anilines appauvries en électrons. Pour cela nous avons développé une méthode de guanidinylation directe des halogénures d’aryle/hétéroaryle catalysée par le cuivre. Cette méthode de synthèse de dérivés de guanidines N-monosubstituées s’est montré très efficace, généralisable à quasiment tous les systèmes aromatiques et hétéroaromatiques. Enfin, quelques observations inattendues au cours de la réalisation de la réaction de Buchwald ont été décrites. / The treatment of severe pain involves in most cases the use of opioid analgesics such as morphine or fentanyl. However, after repeated administration of narcotic analgesics, a tolerance to opioid agents is observed. This result needs to gradually increase the dose of drug to obtain the desired analgesic effect. At the molecular level, the pathophysiological hypothesis emphasizes the participation of so-called ''anti-opioid'' systems, like the neuropeptide FF (NPFF) system. Initially, a synthetic method was developed to introduce various α-amino acids on various α-heteroaryl chlorides. This original method, using the conditions and catalysts described by Buchwald, led to potent NPFF receptor ligands. Then, our work was based on the design, synthesis and study of structure-activity relationships of other ligands for NPFF receptors. Several series of molecules have been studied. Among them two large families were selected: aminoguanidine hydrazones and quinolin-2-yl guanidines. This study allowed us to identify several potent ligands in vitro (nanomolar Ki) and active in vivo. So we have now selective ligands towards the two NPFF receptors. A loss of reactivity during the synthesis of aryl / heteroaryl guanidines was observed, in particular with electron deficient anilines. For these compounds we developed a new method of direct guanidinylation of aryl and heteroaryl halides catalyzed by copper. This method of synthesis of N-monosubstituted guanidines is very effective, generalizable to almost all aromatic and heteroaromatic systems. Finally, some unexpected observations during the completion of Buchwald reaction were described.

Orientador: Prof. Dr. Wendel Andrade Alves / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2015. / Com o desenvolvimento da nanociencia e nanotecnologia tem sido possivel construir e manipular diferentes materiais na escala nanometrica para as mais diversas aplicacoes como: em medicina, em cosmeticos, dispositivos eletronicos, sensores, biossensores, entre outras. Neste trabalho, apresentamos um estudo baseado na auto-organizacao de micro/nanoestruturas de peptideo (MNTs-FF), via fase solidavapor, sobre um eletrodo de ouro modificado com 4-mercaptopiridina (Au/MCP), visando aplicacao para deteccao de ureia. Estudamos a influencia do solvente no processo de nanoestruturacao do peptideo e observamos que o arranjo estrutural na qual a MNTs se cristaliza interfere fortemente na estabilidade do eletrodo, sendo a estrutura ortorrombica P22121, obtida em vapor de anilina, mais estavel do que a hexagonal P61, em vapor de agua. Essa diferenca estrutural e a chave para o bom desempenho do sensor, porque fornece uma interface contendo sitios de nitrogenio e oxigenio capaz de estabelecer ligacoes com a piridina do substrato (Au) e com os ions amonio e ureia, via interacoes cations ¿Î e ou ligacoes de hidrogenio, apresentando valor de sensibilidade e limite de deteccao para ureia de aproximadamente 81,3 ¿ÊA cm.2 mmol.1 L e 0,06 mmol L-1, respectivamente. A funcionalizacao das MNTs-FF com polianilina e pireno permitiu o ancoramento covalente da enzima urease a superficie do eletrodo Au/MCP/MNTs-FF, com sensibilidade e limite de deteccao frente a deteccao de ureia de 30.0 ¿ÊA cm-2 mmol L-1 e 0.17 mmol L-1 para o eletrodo contendo PANI/Urs, e 4.57 ¿ÊA cm-2 mmol L-1 e 0.15 mmol L-1 para o eletrodo pireno/Urs respecticamente. As MNTs-FF sintetizadas na presenca de nanotubos de carbono (NTc) nao apresentaram alteracao morfologica, porem, estudos de espectroscopia de impedancia eletroquimica (EIE) apontaram uma diminuicao na resistencia a transferencia de carga para o tres sistemas estudados: Au/MCP/MNTs-FF, Au/MCP/NTc/MNTs-FF, Au/MCP/NTc/MNTs-FF/Urs, Rtc 35,0, 0,80, 0,14 k¿¶, respectivamente, apresentando sensibilidade e limite de deteccao frente a deteccao de ureia de 1,5 ¿ÊA cm-2 mmol L-1 e 0,1 mmol L-1 respectivamente. / The development of nanoscience and nanotechnology open up possibilities for the building and construction of distinct materials in the nanometric scale for many different application, such as: in medicine, cosmetics, electronic devices, (bio) sensors, among others. In this work, we presented the self-assembly of peptide micro/nanostructures based in diphenylalanine (MNTs-FF), via solid-vapor phase, on gold electrode modified with 4-mercaptopyridine (Au/MCP), for urea sensing. We studied the influence of the solvent on the peptide self-assembly process, and observed that the structural arrangement in which the MNTs-FF crystallizes strongly influences the electrode stability, the orthorhombic P22121 structure were obtained under aniline vapor, that is more stable than the hexagonal P61 obtained under water vapor interaction. This structural difference is the key to the good sensing performance, because it provides an appropriate interface, containing nitrogen and oxygen sites able to establish bonds with the pyridine, and the ammonium ion or urea molecule, via cation ð interactions and or hydrogen bonds, with the sensitivity and detection limit for the urea sensing of ~ 81.3 ìA cm-2 mmol L-1 and 0.06 mmol L-1, respectively. The functionalization of MNTs-FF with polyaniline and pyrene allowed the covalent anchoring of the enzyme urease the surface of the electrode Au/MCP/MNTs-FF, with sensibility and detection limit for urea sensing of 30.0 ìA cm- 2 mmol L-1 and 0.17 mmol L-1 for the PANI/Urs, and 4.57 ìA cm-2 mmol L-1 and 0.15 mmol L-1 for the pyrene/Urs electrode respectively. The MNTs-FF synthesized in the presence of carbon nanotubes (NTC) showed no morphological change, however, studies of electrochemical impedance spectroscopy (EIS) showed a decrease in charge transfer resistance for the three systems studied, Au/MCP/MNTs-FF, Au/MCP/NTc/MNTs-FF, Au/MCP/NTc/MNTs-FF/Urs, Rtc 35,0, 0,80, 0,14 kÙ, respectively, the sensibility and detection limit for urea detection of 1.5 ìA cm-2 mmol L-1 and 0.1 mmol L-1 respectively.

Nora Koubová, Dětský koutek na Filozofické fakultě UK v Praze 1 Abstract: Koubová, Nora. Crèche at the Faculty of Arts CU in Prague. Prague: Faculty of Arts Charles University, 2014. Number of pages 79. Dissertation. The translated dissertation "Crèche at the Faculty of Arts CU in Pragueˮ discusses the establishment of a "co-operative model of a crèche care centre", with regards to the currently popular topic about the co-ordination of professional life and personal life (work-life balance). In the first part, the dissertation discusses the theoretical level of considered issues, includes overview and basic interpretation of legal framework, describes pre-school children care system and considers pre-school children care at universities. Also, it considers the corporate social responsibility of businesses and contemporary conditions and practices in the Czech Republic. Furthermore, the second part of the dissertation, with regards to the existing example of the "co-operative model of a crèche" at the Faculty of Arts, Charles University in Prague, aims to provide a solution for the parents that oscillate between personal life and professional life, and not wanting to give up one on the detriment of the other. Moreover, the dissertation considers the useful suggestions and requirements of the facility's...

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Energy poverty and lack of access to electricity is a global problem which is recognised in the sustainable development goal 7. Today 1.2 billion people live without access to electricity and most of them are situated in Sub-Saharan Africa where biomass still constitutes the main source of energy. Rural areas are unproportionally affected by this throughout SSA since grid-extension has been slow and most rural dwellers are not connected to any form of electricity grid. Extending the grid to more isolated rural areas may however be economically and politically infeasible which is why off-grid solutions is an attractive solution to close the energy poverty gap. Off-grid solar energy has during recent years been increasingly promoted as viable solution to provide clean, affordable and accessible energy to rural households in SSA. While there is extensive research available on the economic feasibility and socioeconomic impacts of off-grid solar energy, there has been limited research with explicit focus on how livelihoods of rural households in SSA have been impacted from a sustainable livelihood perspective. This case study on Tanzania argues that the sustainable livelihoods perspective is crucial in getting a holistic understanding of how off-grid solar energy has impacted rural households in SSA. Through qualitative interviews with a number of households, businesses and social services in three rural villages located in the Tanga region, this study found that off-grid solar energy overall seemed to have a positive impact on the communities and the livelihoods of individual households. However, some concerns are also raised with the sustainability of off-grid solar energy. While it has great recognised potential and direct impact, some key challenges were identified as issue of energy security for the household and concerns of economic feasibility in the solar energy sector.

Dans un contexte de développement spectaculaire des nano-objets, il est nécessaire de développer des moyens de caractérisation électrique haute fréquence sous pointes adaptés aux petites échelles. En particulier, deux verrous instrumentaux doivent être levés. D’une part, la principale difficulté pour caractériser des nano-composants est qu’ils présentent en régime dynamique de fortes valeurs d’impédances comparativement à celles des systèmes de mesure hyperfréquence usuels. D’autre part, Il existe une discontinuité de taille entre les nano-objets et les systèmes de mesure conventionnels. Compte tenu du challenge scientifique et d’un état de l’art relativement limité, plusieurs voies ont été explorées de concert. En premier lieu, dans le cadre d’un projet européen regroupant les acteurs de la métrologie, et du laboratoire commun IEMN-STMicroelectronics®, la traçabilité des mesures hautes impédances de nano-dispositifs est établie. Par ailleurs, il s’agit de développement de nouvelles générations de sondes GSG (Ground-Signal-Ground) en technologie MEMS (Microelectromechanical systems), miniaturisées et adaptées à la taille des nano-dispositifs. Les sondes sont montées sur une plateforme de nano-positionnement robotisée et intégrée dans un microscope électronique à balayage. / In the frame of the spectacular development of nano-objects, innovative on-wafer electrical measurement methods must be addressed at the nanoscale. In particular, two main issues have been identified. On one hand, nano-devices exhibit very high dynamic impedance in contrast with conventional measuring microwave instruments. On the other hand, there is an inherent size discontinuity between nano-objects and conventional measurement systems. Given the scientific challenge and a relatively limited state of the art, several avenues of investigation have been explored. First, as part of a European project bringing together metrology laboratories, and the joint laboratory IEMN-STMicroelectronics®, the traceability of nano-devices high impedance measurements is established. In a second step, the development of an electrical on-wafer measuring platform for nano-devices is described. This includes the development of new generations of GSG (Ground-Signal-Ground) miniaturized probes in MEMS (Microelectromechanical systems) technology with reduced access pads. The probes are mounted on a robotic nano-positioning platform integrated in a scanning electron microscope.

<p>The purpose with this essay is to analyze how football clubs can use Internet in sense of creating stronger relations towards their supporters and build an excellent experience before and after a specific football game. We have used the Swedish football club Kalmar FF as a role model throughout the essay. The techniques of the modern world are escalating and the World Wide Web tends to be more important in the way of creating experiences and relations. The essay is based on a qualitative research method which is based on and contains four independent interviews. The persons have been chosen by us for their knowledge in the specific subject. The material from these interviews is the fundamental which this analyze is based upon, the analyze can be found in the fourth chapter of this essay. We have also made a study where all the Swedish football clubs from the highest division are included.</p>

The purpose with this essay is to analyze how football clubs can use Internet in sense of creating stronger relations towards their supporters and build an excellent experience before and after a specific football game. We have used the Swedish football club Kalmar FF as a role model throughout the essay. The techniques of the modern world are escalating and the World Wide Web tends to be more important in the way of creating experiences and relations. The essay is based on a qualitative research method which is based on and contains four independent interviews. The persons have been chosen by us for their knowledge in the specific subject. The material from these interviews is the fundamental which this analyze is based upon, the analyze can be found in the fourth chapter of this essay. We have also made a study where all the Swedish football clubs from the highest division are included.

Syftet med den här uppsatsen är att studera om den nya Arenan kan komma att vara en bidragande faktor till säsongsförlängning i Kalmar. Eftersom den nya Arenan inte ännu är färdigbyggd, vill vi undersöka beslutsfattares syn på projektet samt hur ett sådant projekt kan komma att påverka Kalmar som destination. För att kunna studera verkligheten, utan att styras av redan befintliga teorier, valde vi i vår studie att använda oss av en induktiv ansats. Den större delen av vår datainsamling grundas på kvalitativa intervjuer, vilka vi kompletterade med diverse rapporter och skrivelser på hemsidor. Vår slutsats i den här uppsatsen är att den nya Arenan kan bidra till säsongsförlängning om verksamheten maxas. För att detta ska vara möjligt bör samtliga beslutsfattare börja spela i samma lag, klara och tydliga mål med projektet måste sättas upp och fokus bör läggas på hur ett projekt av den här storleken kan gynna hela Kalmar som destination, inte enbart en av de inblandade aktörerna.