Etudes biologiques de nouveaux radiotraceurs pour l'imagerie moléculaire de la maladie d'Alzheimer

La maladie d'Alzheimer (MA) est une pathologie neurodégénérative s'exprimant par des troubles de la mémoire et un déclin cognitif évoluant progressivement vers un stade de démence incurable. Elle représente la cause principale de syndrome démentiel puisque l'on estime qu'elle est à l'origine de plus de 70% des cas de démences. Du fait de sa prévalence élevée après 60 ans, la MA représente un problème majeur de santé publique. La MA se caractérise par la présence de deux types de lésions cérébrales : les dégénérescences neurofibrillaires (DNF) et les plaques amyloïdes. Cependant, aucun consensus clair ne se dégage concernant les relations qui lient les deux types de lésions. Leur présence ne peut être mise en évidence que par un examen post-mortem. La MA est par définition une pathologie évolutive, cet examen ne permet donc pas de caractériser de manière adéquate les processus dynamiques qui sous-tendent cette pathologie. La mise au point de techniques d'imagerie non invasives permettant de réaliser un suivi longitudinal in vivo de ces lésions s'avère déterminante dans la compréhension de la physiopathologie de la MA. Les travaux effectués au cours de cette thèse ont pour objectif la mise au point de nouveaux radiotraceurs des lésions amyloïdes et neurofibrillaires pour l'imagerie nucléaire. Cette approche se distingue en trois parties. Dans un premier temps, nous avons validé un modèle animal de la MA: les souris transgéniques 3xTgAD. Dans un second temps, nous avons réalisé l'évaluation biologique de différents radiotraceurs connus sur ce modèle animal : le 99mTc-HMPAO, le 18F-FDG et le 125I-IMPY. Enfin, nous avons initié le développement de plusieurs nouveaux traceurs pour permettre le suivi de la MA in vivo : les para-sulfonato-calixarènes qui présentent une affinité intéressante pour les plaques amyloïdes, les composés COB qui inhibent la formation des agrégats de peptides amyloïdes in vitro ainsi qu'un peptide, A93, associé à un vecteur qui pourrait interagir avec les dégénérescences neurofibrillaires.Alzheimer's disease (AD) is a neurodegenerative pathology showing cognitive and memory disorders which progress toward an incurable demential state. AD represents the principle cause of the dementia syndrome and it is estimated that AD is involved in 70% of dementia cases. AD prevalence is high in the over 60 years old population. This elevated prevalence is associated with an increasing number of elderly people. AD is therefore a major public health concern. AD is characterized by two types of specific cerebral lesions: neurofibrillary tangles (NFT) and amyloid plaques. However, there is no consensus on the links between these two types of lesions. To date, their presence can only be evaluated by a post-mortem examination. AD being a progressive pathology, this examination cannot be used to fully characterize the dynamic processes involved in AD. In this context, the development of non invasive imaging techniques to monitor the lesions progression in vivo could be determinant in AD pathophysiology understanding. Our objective is to develop new tracers of amyloid and neurofibrillary lesions for nuclear imaging. The first part of this study was dedicated to the validatation of an AD animal model: Transgenic 3xTgAD mice. The second part of this thesis focuses on the appreciatiation of the biological comportement of several known radiotracers of AD on this animal model. In the third part of this work, we initiate the development of several new tracers of AD-specific lesions. The para-sulfonato- calixarenes and the COB compounds for amyloid plaques detection and a peptide named A93, associated to a vector for the study of neurofibrillary tangles.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

The pretext of foresight to debate on irrigation groundwater management: lessons from six cases studies in France

International audienceThe transcription of the 2000’s European Water Framework Directive in France has led to define maximum volumes that can be abstracted in water bodies. In many French contexts, it requires reducing more or less drastically current water consumption, especially in agriculture where farmers were granted permits by the water policy authority, regardless the real level of water availability. To do so, French water law imposes, where water bodies are structurally in water scarcity, to create irrigation associations charged to share available water between farmers. And the challenge is particularly high in the groundwater case, where farmers are not embedded in collective irrigation schemes. Sharing rules have then to be designed from the ground up.This communication presents and critics the way that innovative management instruments were explored in six cases’ studies representative of the diversity of agricultural products and hydrogeological situations. These instruments were debated during 18 foresight workshops held with institutional representatives (50) and farmers (87). Foresight workshops had the advantages to make credible institutional and resource changes, and to retrieve from current but side-debates. In five cases, researchers took the lead of these workshops, and in the last one it was directly carried by a stakeholder (an Agriculture Chamber), which allows to test the transferability of such a method in real context with a direct implementing goal.Lessons are drawn at several levels. Firstly, debating on contrasted scenarios is a robust way to facilitate discussions on something not implemented yet in France. Secondly, the context highly matters, in particular the perception of the reality of groundwater scarcitylevel. Thirdly, to debate on groundwater management tools has to be firstly embedded in a more general discussion, on the future of agriculture or at least on more broadly water challenges (like in terms of quantity and quality)

Arquitetura de um sistema de recomendação para apoio à colaboração

Nas organizações, as pessoas aprendem compartilhando conhecimento. Este tipo de tarefa (chamada colaboração) é importante para a aprendizagem organizacional. A colaboração pode ser apoiada através de ferramentas de tecnologia da informação como chats, newsgroups, fóruns e listas de discussão por e-mail. Porém, este tipo de apoio só permite a comunicação, não ajudando as pessoas no processo de aprendizagem. Para minimizar este problema, há sistemas de recomendação cuja meta é ajudar as pessoas a adquirir conhecimento. Os sistemas de recomendação agem sugerindo o que é novo ou útil. Este trabalho apresenta a arquitetura de um sistema de recomendação para apoiar a colaboração entre pessoas em uma organização. O artigo discute a funcionalidade do sistema proposto, apresentando seus principais componentes e interações. O sistema analisa mensagens textuais enviadas durante a sessão, identifica o contexto da discussão e sugere documentos, autoridades (as pessoas com competência em um assunto) e discussões passadas dentro do mesmo contexto.Eje: Ingeniería de softwareRed de Universidades con Carreras en Informática (RedUNCI

Arquitetura de um sistema de recomendação para apoio à colaboração

Nas organizações, as pessoas aprendem compartilhando conhecimento. Este tipo de tarefa (chamada colaboração) é importante para a aprendizagem organizacional. A colaboração pode ser apoiada através de ferramentas de tecnologia da informação como chats, newsgroups, fóruns e listas de discussão por e-mail. Porém, este tipo de apoio só permite a comunicação, não ajudando as pessoas no processo de aprendizagem. Para minimizar este problema, há sistemas de recomendação cuja meta é ajudar as pessoas a adquirir conhecimento. Os sistemas de recomendação agem sugerindo o que é novo ou útil. Este trabalho apresenta a arquitetura de um sistema de recomendação para apoiar a colaboração entre pessoas em uma organização. O artigo discute a funcionalidade do sistema proposto, apresentando seus principais componentes e interações. O sistema analisa mensagens textuais enviadas durante a sessão, identifica o contexto da discussão e sugere documentos, autoridades (as pessoas com competência em um assunto) e discussões passadas dentro do mesmo contexto.Eje: Ingeniería de softwareRed de Universidades con Carreras en Informática (RedUNCI

Empirical demonstration of CO2 detection using macroporous silicon photonic crystals as selective thermal emitters

This study describes the detection of CO2 using macroporous silicon photonic crystals as thermal emitters. It demonstrates that the reduction of structural nonhomogeneities leads to an improvement of the photonic crystals’ emission. Narrow emission bands (¿~120) located within the R-branch of carbon dioxide were achieved. Measurements were made using a deuterated triglycine sulfate photodetector and the photonic crystals, heated to 400°C, as selective emitters. A gas cell with a CO2 concentration between 0 ppm and 10,000 ppm was installed in the center. Results show high sensibility and selectivity that could be used in current nondispersive infrared devices for improving their features. These results open the door to narrowband emission in the mid-infrared for spectroscopic gas detection.Postprint (author's final draft

Optimització del suport nutricional parenteral en nounats mitjançant la implementació de solucions estàndard

La desnutrició dels nadons pot comportar greus conseqüències en la seva salut i desenvolupament. És per això que l'inici precoç de nutrició per via endovenosa (nutrició parenteral) és una emergència nutricional. La fàcil prescripció, la disponibilitat immediata i menor risc d'errors de preparació converteixen a la nutrició parenteral estandarditzada en la més eficient. Tanmateix, aquesta ha de ser estable i estèril perquè el suport nutricional sigui segur. Des del servei de Farmàcia de l'Hospital Santa Creu i Santa Pau - UAB han aconseguit dissenyar dues nutricions parenterals estandarditzades binàries estables i estèrils durant 31 dies en refrigeració.La desnutrición de los bebés puede conllevar graves consecuencias en su salud y desarrollo. Es por eso que el inicio precoz de nutrición por vía endovenosa (nutrición parenteral) constituye una emergencia nutricional. La fácil prescripción, la disponibilidad inmediata y el menor riesgo de errores de preparación convierten a la nutrición parenteral estandarizada en la más eficiente. Sin embargo, esta debe ser estable y estéril para que el soporte nutricional sea seguro. Desde el servicio de Farmacia del Hospital Santa Cruz y Santa Pau - UAB han conseguido preparar dos nutriciones parenterales estandarizadas binarias estables y estériles durante 31 días en refrigeración

Deuteron cross section evaluation for safety and radioprotection calculations of IFMIF/EVEDA accelerator prototype

under construction in Japan. Interaction of these deuterons with matter will generate high levels of neutrons and induced activation, whose predicted yields depend strongly on the models used to calculate the different cross sections. A benchmark test was performed to validate these data for deuteron energies up to 20 MeV and to define a reasonable methodology for calculating the cross sections needed for EVEDA. Calculations were performed using the nuclear models included in MCNPX and PHITS, and the dedicated nuclear model code TALYS. Although the results obtained using TALYS (global parameters) or Monte Carlo codes disagree with experimental values, a solution is proposed to compute cross sections that are a good fit to experimental data. A consistent computational procedure is also suggested to improve both transport simulations/prompt dose and activation/residual dose calculations required for EVEDA