The structural properties of the very neutron deficient systems around N~Z~40 have been studied in two experiments performed at the GANIL and Legnaro laboratories. The fragmentation of a 60 MeV/u92 Mo beam on a natural nickel target at the GANIL Laboratory, France, produced exotic nuclei along the proton drip line in the mass 80 region. Isomeric decays have been observed for the first time in the N=Z+2 systems 74 36Kr, 80 39Y and 84 41Nb. The isomer in 74 Kr is interpreted as the hindered decay from an excited 0+ state, supporting the long-standing prediction of prolate/oblate shape coexistence in this nucleus. Transitions from states below an isomer in the N=Z nucleus 86 43Tc have also been tentatively identified, making this the heaviest N=Z system for which gamma-ray decays from excited states have been observed. Conclusive evidence for the existence of the Z=N+1 isotopes 77 39Y, 79 40Zr and 83 42Mo has also been obtained together with upper limits on the particle decay lifetimes of the odd-proton systems 81 41 Nb and 85 43Tc. The reported instability of the lighter odd-Z, Tz = -1/2 systems 69Br and 73Rb makes the observed existence for 77 39Y particularly interesting. A possible explanation for the relative particle stability of 77 39Y is given in terms of the shape polarising effect of the N=Z=38 prolate shell gap on the nuclear mean field and the increased centrifugal barrier associated with the occupation of a g9/2 proton orbital. The second experiment was performed to further investigate the oblate nature of the isomeric state in 74Kr. The reaction 40Ca(40Ca, alpha2p)74Kr was used at a beam energy of 135 MeV obtained from the Tandem XTU accelerator. The EUROBALL gamma-ray array was used in conjunction with the ISIS charged particle silicon ball to study the states above and below the isomer. The ISIS ball was used to highlight channel selection of non-yrast states by particle gating. No evidence for the 0+2 isomer in 74Kr was observed in this work.

La compréhension des mécanismes de défense mis en place lors de la résistance des plantes vis-à-vis d'agents pathogènes a pour objectif de proposer des alternatives à l'utilisation de produits phytosanitaires utilisés en agriculture. Dans une première partie, nous avons étudié les mécanismes moléculaires impliqués dans la résistance induite aux pathogènes par l'acide β-aminobutyrique (BABA) chez la vigne. En effet, cet acide aminé non protéique favorise un état physiologique particulier, appelé potentialisation, dans lequel la plante est capable de mobiliser plus rapidement et/ou plus intensément ses réactions de défense en réponse à un stress. Contrairement aux éliciteurs comme les oligogalacturonates (OG), nous avons montré que le BABA seul n’induisait pas les événements précoces de signalisation sur suspensions cellulaires de vigne, tels que les variations de la concentration en calcium cytosolique libre ([Ca2+]cyt), la production de monoxyde d’azote (NO), la production d’H2O2, la phosphorylation de MAPkinases, ni l’expression de gènes de défense. Seules la production d’H2O2 et l’expression plus intense du gène RbohD codant une NADPH oxydase sont potentialisées par le BABA dans les suspensions cellulaires élicitées par les OG. In planta, le BABA potentialise également une production d’H2O2 en réponse à l’infection par l’oomycète Plasmopara viticola. L’utilisation d’un inhibiteur de NADPH oxydase abolit complètement cette production d’H2O2 et bloque partiellement la résistance induite par le BABA. Nous montrons donc que la potentialisation de la production d’H2O2 dépendante d’une NADPH oxydase contribue à l’établissement de la résistance induite par le BABA chez la vigne. Une deuxième partie a permis d’appréhender les événements cellulaires impliqués dans la résistance des plantes en se focalisant sur le mutant pad2 (phytoalexin deficient) d’Arabidopsis thaliana. Ce mutant présente une sensibilité accrue à différents pathogènes et contient un taux de glutathion de l’ordre de 20 % par rapport à l’écotype sauvage. Nous avons tout d’abord montré que le faible taux de glutathion dépendait d’une quantité réduite de la première enzyme de sa biosynthèse, la glutamate-cystéine ligase. Le glutathion étant impliqué dans la mise en place des réactions de défense, nous avons tenté de définir le lien entre la déficience en glutathion et la sensibilité de pad2 aux pathogènes. Nous avons tout d’abord montré que pad2 possédait un état redox du glutathion plus oxydé que le sauvage. Une analyse transcriptomique à l’état basal a révélé que la plupart des gènes différentiellement exprimés étaient réprimés chez pad2. Parmi ces gènes, certains codent des protéines impliquées dans les flux d’ions qui pourraient déréguler la dépolarisation membranaire. Nous avons ainsi confirmé que la dépolarisation de la membrane plasmique est amoindrie chez pad2 en réponse aux OG. De plus, des événements en aval tels que la production d’H2O2 et la production de NO sont également plus faibles chez le mutant par rapport au sauvage. Cette absence de la production d’H2O2 a également été spécifiquement observée sur plantes pad2 infectées par l’oomycète Phytophthora brassicae. Il en résulte un développement accru du pathogène corrélé à une absence de réponse hypersensible, une mort cellulaire localisée normalement observée dans le cas du sauvage résistant. En réponse aux OG ou à l’infection par P. brassicae, les analyses transcriptomiques font ressortir un fort enrichissement de gènes relatifs à la dégradation des protéines chez pad2. De manière globale, nos résultats suggèrent que la déficience en glutathion chez pad2 pourrait profondément modifier le turn-over des protéines, perturbant ainsi la signalisation cellulaire et les réponses biologiques associées. / Alternative strategies are required to reduce pesticide input into the environment for effective and sustainable plant protection. One solution is the activation of plant basal resistance that relies on the application of resistance inducer molecules. In the first part of this study, we analyzed the mode of action of β-aminobutyric acid (BABA), a non-protein amino acid, in the grapevine induced resistance. BABA confers a physiological state, called priming, during which plants are able to mobilize better and/or more rapidly defense responses to biotic or abiotic stress. Unlike oligogalacturonides (OG), we showed that BABA did not induce early signaling events in grapevine cells such as variations of cytosolic free calcium concentration, H2O2 and nitric oxide production, MAPkinase phosphorylation, nor the expression of defense-related genes. Among them, only H2O2 production and the expression of RbohD gene, which encodes a NADPH oxidase, are primed by BABA in OG-treated cells. Moreover, BABA-treated plants display a stronger accumulation of H2O2 in response to the oomycete Plasmopara viticola. Application of an NADPH oxidase inhibitor completely abolishes this H2O2 production and leads to a reduction of BABA-induced resistance against P. viticola. These data suggest that the priming of an NADPH oxidase-dependent H2O2 production contributes to BABA-induced resistance in grapevine. The second part consisted to analyze molecular events involved in plant resistance by using the pad2 (phytoalexin deficient) mutant of Arabidopsis thaliana which is susceptible to a broad range of pathogens. We showed that the glutathione depletion depends on the low amount of glutamate-cysteine ligase protein, the first enzyme involved in its biosynthesis. We studied molecular events, which are involved in defense mechanisms, to understand the impact of the glutathione content on pad2 susceptibility. Our results show that the redox state of glutathione is more oxidized in pad2 than in wild type Col-0. Since cellular redox state change is known to regulate gene expression, a basal transcriptome analysis has been performed in pad2 and wild type plants. Interestingly, most of the identified genes in pad2 are down-regulated, some of them encoding proteins involved in ion fluxes. As expected, the plasma membrane depolarization and events downstream like H2O2 and NO production are impaired in pad2 in response to OG. During infection with Phytophthora brassicae, the lack of H2O2 production is concomitant with an absence of the hypersensitive response, a localize cell death observed in the resistant wild type. After OG treatment or P. brassicae infection, microarray analysis brings out genes related to protein machinery including degradation in pad2. Taken together, these data suggest that the depletion of glutathione has an impact on protein turn-over which disturbs cell signaling events and related biological responses.

Ce travail a consisté à optimiser la synthèse de phosphates de calcium (CaP) déposés sur tissus de fibres de carbone (TFC) par procédé de sono-électrodéposition afin d’obtenir des revêtements uniformes. Les paramètres électrochimiques clés optimisés sont le type et la durée de polarisation cathodique ainsi que la température de l’électrolyte. Pour un potentiel constant de -1 V à 70 °C, un régime d’électrolyse contrôlé de l’eau conduit à la formation d’un revêtement plaquettaire d’hydroxyapatite déficitaire en calcium (CDA) carbonatée. Les plaquettes sont composées de particules lamellaires (de quelques dizaines à centaines de nm) constituées de CDA carbonatée de structure ordonnée au coeur et de structure désordonnée car hydratée en surface des particules, organisation typique des apatites biomimétiques. Le matériau hybride a été dopé en strontium, engendrant la formation de revêtements où les ions Ca²+ sont substitués par des ions Sr²+ de manière contrôlée, conférant au biomatériau de nouvelles propriétés en vue d’une application en régénération osseuse. Ce travail a aussi démontré la possibilité d’adsorber de façon sélective des principes actifs ciblés (tétracycline, naproxène, aspirine) dans chaque constituant du matériau hybride. Les courbes de désorption ont mis en évidence deux modes de libération selon le principe actif.Une évaluation biologique des différentes matériaux hybrides a été réalisée. L’étude in vitro a porté sur la viabilité et la prolifération d’ostéoblastes humains en surface des biomatériaux hybrides, démontrant leur biocompatibilité. L’intérêt d’un dopage (Sr²+, aspirine et naproxène) sur l’activité des ostéoblastes a été démontré. Une expérience pilote in vivo a été menée, consistant à créer un défaut osseux dans des fémurs de rats et à étudier l’influence du type de biomatériaux TFC/CaP sur les évolutions quantitative et qualitative de la régénération osseuse. / Optimization of the synthesis of calcium phosphates (CaP) on carbon fiber cloths (TFC) was performed in using sono-electrodeposition process in order to obtain uniform coatings. The electrochemical potential applied and the electrolyte temperature during the synthesis were determined as being key parameters. For a constant potential of -1 V at 70 ° C, a controlled water electrolysis regime results in the deposit of plate-like calcium-deficient apatite (CDA). This plate-like particles (from a few tens to hundreds of nm in length) consist in an ordered structure of carbonated CDA in their core and in a disordered structure in the hydrated surface, a typical organization of biomimetic apatites. The hybrid material was doped with strontium, resulting in a carbonated CDA coating where the Ca²+ ions are controllably substituted by Sr²+ ions, leading to new properties for a bone regeneration application. This work has also shown the possibility of selectively adsorb targeted active molecules (tetracycline, naproxen, aspirin) in each component of the hybrid material. The desorption curves revealed two modes of release depending on the active molecule.A biological evaluation of the different hybrid materials was carried out. The in vitro study investigated the viability and proliferation of human osteoblasts at the surface of hybrid materials, demonstrating their biocompatibility. The interest of a doping (Sr²+, aspirin and naproxen) on osteoblast activity was demonstrated. An in vivo pilot experiment was conducted, through the creation of a bone defect in rat thighbones to study the influence of TFC/CaP biomaterials on the quantitative and qualitative evolutions of bone regeneration.

Glutamate carboxypeptidase II (GCPII) is a transmembrane glycoprotein, which consists of short intracellular and transmembrane domains, and a large extracellular domain possessing carboxypeptidase activity. In the human body, GCPII fulfils a neuromodulatory function in the brain and facilitates folate absorption in the small intestine. In addition to the brain and small intestine, high level of GCPII is also present in the prostate and kidney. However, GCPII function in these tissues has not been determined yet. To study the role of GCPII in detail, several research groups attempted to inactivate GCPII encoding gene Folh1 in mice. Surprisingly, the experiments led to rather conflicting results ranging from embryonic lethality to generation of viable GCPII-deficient mice without any obvious phenotype. This dissertation project aimed to dissect the discrepancy using alternative strategy for gene modification. For this purpose, we designed TALENs that specifically targeted exon 11 of Folh1 gene and manipulated mouse zygotes of C57BL/6NCrl genetic background. We analysed all genetically modified mice of F0 generation for presence of TALEN-mediated mutations and established 5 different GCPII-mutant mouse colonies from founder mice that altogether carried 2 frame-shift mutations and 3 small in-frame...

Le travail décrit dans ce mémoire concerne l'étude de la métallation régiosélective de deux bicycles fusionnés complexes : les furo[3,2-b]- et [2,3-c]pyridines. L'influence de la nature du système basique sur le cours de la réaction et sur la régiosélectivité de la lithiation a été étudiée avec différentes bases : n-BuLi, LTMP, LDA et [n-BuLi/LiDMAE]. D'un point de vue fondamental, cette étude nous a permis d'établir quelques règles pour la fonctionnalisation des hétérocycles complexes, ce qui nous a conduit à l'obtention efficace et rapide d'une vaste chimiothèque de furo[3,2-b]- et [2,3-c]pyridines polyfonctionnalisés et refonctionnalisables. Quelques composés préparés ont ainsi été mis en jeu dans des réactions de couplage catalysées par les métaux de transition (Pd, Ni). Les difficultés rencontrées au cours de ce travail nous ont permises de mettre en évidence une séquence de double fonctionnalisation des hétérocycles ?-déficients par une séquence "one-pot" combinant le piégeage d'un intermédiaire lithié par un électrophile et l'addition nucléophile d'une espèce réactive générée in-situ. Le développement de cette séquence nous a conduits à l'obtention directe de pyrazines, pyridines et furo[3,2-b]pyridines disubstituées / The work described in this PhD thesis concerns a regioselective metalation study of two fused heterocycles : the furo[3,2-b]- et [2,3-c]pyridines. The influence of the lithiated agent on the reaction course and on the selectivity of the lithiation has been studied with several bases : n-BuLi, LTMP, LDA and [n-BuLi/LiDMAE]. From a fundamental point of view, this study allowed us to establish some rules concerning the functionalisation of fused heterocycles, and then, a chemical library of polyfunctionalised furo[3,2-b]- and [2,3-c]pyridines has been designed. Some of the compounds obtained in this way were engaged in metallo-catalysed coupling reactions. The difficulties we met during this work allowed us to discover a double functionalisation sequence of ?-deficient heterocycles via a cascade process combining the trapping of lithiated intermediates and the nucleophilic addition of some in-situ released species. The development of this sequence afforded direct access to difunctionalised pyrazines, pyridines and furo[3,2-b]pyridines

The State Institution for Education of Feebleminded Girls was one of the two swedish educational institutions established under state management in the 1920s and came to be the starting point for further government operations for the mentally deficient. The purpose of this paper was to investigate the activities of the State Institution for Education of Feebleminded Girls, out of what needs the institution filled in Sweden’s care for the mentally deficient. The institution has tried to be understood from the view of eugenics and the perspective of children that was current during the 1900s first half.To fulfill the purpose of the study, the archives for the State Institution for Education of Feebleminded Girls was studied and analyzed with basis of previous research on Sweden’s care for the mentally deficient and the impact from eugenics and Sweden’s child perspective.The study shows that the State Institution for Education of Feebleminded Girls mostly existed to educate students and adapt them to the community, which the institution did by education, disciplinary interventions and sterilizations. It is found in the study that the institution didn’t have any regular care of individuals in any great extent, which is also consistent with what previous research have reported concerning Sweden’s care for the mentally deficient. The study further shows that the State Institution for Education of Feebleminded Girls was largely coloured by the perception of mentally deficient as a threat to society. It appears that the institution primarily focused upon the interests of society and therefore often reduced the individual's interests and autonomy.

In many fields of science, engineering, and economics large amounts of data are stored and there is a need to analyze these data in order to extract information for various purposes. Data mining is a general concept involving different tools for performing this kind of analysis. The development of mathematical models and efficient algorithms is of key importance. In this thesis we discuss algorithms for the reduced rank regression problem and algorithms for the computation of the best multilinear rank approximation of tensors. The first two papers deal with the reduced rank regression problem, which is encountered in the field of state-space subspace system identification. More specifically the problem is \[ \min_{\rank(X) = k} \det (B - X A)(B - X A)\tp, \] where $A$ and $B$ are given matrices and we want to find $X$ under a certain rank condition that minimizes the determinant. This problem is not properly stated since it involves implicit assumptions on $A$ and $B$ so that $(B - X A)(B - X A)\tp$ is never singular. This deficiency of the determinant criterion is fixed by generalizing the minimization criterion to rank reduction and volume minimization of the objective matrix. The volume of a matrix is defined as the product of its nonzero singular values. We give an algorithm that solves the generalized problem and identify properties of the input and output signals causing a singular objective matrix. Classification problems occur in many applications. The task is to determine the label or class of an unknown object. The third paper concerns with classification of handwritten digits in the context of tensors or multidimensional data arrays. Tensor and multilinear algebra is an area that attracts more and more attention because of the multidimensional structure of the collected data in various applications. Two classification algorithms are given based on the higher order singular value decomposition (HOSVD). The main algorithm makes a data reduction using HOSVD of 98--99 \% prior the construction of the class models. The models are computed as a set of orthonormal bases spanning the dominant subspaces for the different classes. An unknown digit is expressed as a linear combination of the basis vectors. The resulting algorithm achieves 5\% in classification error with fairly low amount of computations. The remaining two papers discuss computational methods for the best multilinear rank approximation problem \[ \min_{\cB} \| \cA - \cB\| \] where $\cA$ is a given tensor and we seek the best low multilinear rank approximation tensor $\cB$. This is a generalization of the best low rank matrix approximation problem. It is well known that for matrices the solution is given by truncating the singular values in the singular value decomposition (SVD) of the matrix. But for tensors in general the truncated HOSVD does not give an optimal approximation. For example, a third order tensor $\cB \in \RR^{I \x J \x K}$ with rank$(\cB) = (r_1,r_2,r_3)$ can be written as the product \[ \cB = \tml{X,Y,Z}{\cC}, \qquad b_{ijk}=\sum_{\lambda,\mu,\nu} x_{i\lambda} y_{j\mu} z_{k\nu} c_{\lambda\mu\nu}, \] where $\cC \in \RR^{r_1 \x r_2 \x r_3}$ and $X \in \RR^{I \times r_1}$, $Y \in \RR^{J \times r_2}$, and $Z \in \RR^{K \times r_3}$ are matrices of full column rank. Since it is no restriction to assume that $X$, $Y$, and $Z$ have orthonormal columns and due to these constraints, the approximation problem can be considered as a nonlinear optimization problem defined on a product of Grassmann manifolds. We introduce novel techniques for multilinear algebraic manipulations enabling means for theoretical analysis and algorithmic implementation. These techniques are used to solve the approximation problem using Newton and Quasi-Newton methods specifically adapted to operate on products of Grassmann manifolds. The presented algorithms are suited for small, large and sparse problems and, when applied on difficult problems, they clearly outperform alternating least squares methods, which are standard in the field.

Le travail décrit dans ce mémoire concerne l'étude de la métallation régiosélective d’un bicycle fusionné: la furo[3,2-B]pyridine. L'influence de la nature du système basique sur le cours de la réaction et sur la régiosélectivité de la lithiation a été étudiée avec différentes bases : n-BuLi, LiTMP, LiDA et [n-BuLi/LiDMAE]. D'un point de vue fondamental, cette étude nous a permis d'établir quelques règles pour la fonctionnalisation des furopyidines, ce qui nous a conduit à l'obtention efficace et rapide d'une vaste chimiothèque de furo[3,2-B]pyridines polyfonctionnalisées et refonctionnalisables. Quelques composés préparés ont ainsi été mis en jeu dans des réactions de couplage catalysées par les métaux de transition (Pd, Ni). Deux séquences originales de lithiations en « one-Pot » ont également été développées et permettent l’obtention de squelettes furopyridiniques hautement fonctionnalisés avec d’excellents rendements / The work described in this PhD thesis concerns the regioselective metalation study of a fused heterocycle : the furo[3,2-B]pyridine. The influence of the basic system on the reaction and on the regioselectivity of the lithiation has been studied with several bases : n-BuLi, LiTMP, LiDA and [n-BuLi/LiDMAE]. From a fundamental point of view, this study allowed us to establish some rules concerning the functionalization of furopyridines and to obtain a chemical library of various polyfunctionalized furo[3,2-B]pyridines, in good overall yields. Some of the compounds synthesized in this way, were engaged as substrate in metallo-Catalysed cross-Coupling reactions. Two efficient one-Pot multiple lithiations processes have been developed and lead to highly substitued furopyridinic scaffolds in excellent yields

I denna uppsats undersöks hur föräldraförmågan konstrueras i rättsfall och hur olika domstolsinstanser med fokus på Högsta förvaltningsdomstolen, argumenterar för bifall respektive avslag för vård enligt LVU 2§ vilket handlar om föräldraförmågan. Genom en kvalitativ dokumentstudie undersöks sju domstolsavgöranden från förvaltningsrätten, kammarrätten och Högsta förvaltningsdomstolen där fokus ligger på Högsta förvaltningsdomstolens beslut. En hermeneutisk analysmetod används för att analysera materialet samt att socialkonstruktionismen som teori genomsyrar hela uppsatsen. För att fördjupa analysen tar vi stöd av tidigare forskning och vetenskapliga artiklar. Den tidigare forskningen innehåller studier som förklarar termen föräldraskap och vad som ingår i detta men även forskning kring tvångsomhändertagande av barn enligt LVU. Uppsatsens ämne uppkom efter debatter och kritik kring socialtjänstens arbete våren 2022. Det har i dessa debatter hävdats att socialtjänsten omhändertar barn utan giltiga skäl. Resultatet i vår uppsats visar dock på raka motsatsen. Resultatet visar på att en bristande föräldraförmåga inte föranleder ett omhändertagande utan snarare att flera brister i kombinationen med varandra utgör grund för LVU. Uppsatsens resultat visar att en förälder kan klassas som en tillräckligt bra förälder trots bristande föräldraförmågor. Det uppsatsens resultat dock visar på, vilket samstämmer med tidigare forskningen är att ett det krävs en hel del brister i föräldraskapet och omfattande problematik för att skäl för ett LVU enligt 2§ ska föreligga.

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