Psykisk hälsa/ohälsa är ett svårdefinierat begrepp som sätter fingret på ett av de största folkhälsoproblemen i vårt land, där depression är en av de vanligaste diagnoserna. Manualerna DSM-IV TR och ICD-10 används inom stora delar av sjukvården, världen över, i syfte att ge kunskap om lämpligast behandling till patienter med psykiska besvär. Denna studie syftar till att, genom en kvalitativ analys, undersöka vilka grunder som finns bakom de vanligast använda diagnosmanualerna och vilka kriterier som krävs för att uppfylla två vanligt förekommande diagnoser, PTSD och svår depression. Vidare syftar studier till att belysa eventuella likheter och olikheter mellan dessa diagnoser och vad det kan föra med sig. Såväl psykologisk forskning som klinisk praktik utgår idag mestadels från psykiatriska diagnoser, vilket kan ha såväl fördelar som nackdelar, men samtidigt diskuteras huruvida man istället ska lägga fokus på en annan mer underliggande nivå, nämligen processerna som sträcker sig över diagnosernas gränser. Fördelarna med ett transdiagnostiskt perspektiv är att det delvis kan ge en förklaring till den höga komorbiditet som finns i kliniska grupper och som skulle kunna iakttas även i de sjukdomsbilder som denna studie fokuserar på. Unified Protocol är en annan behandlingsmodell som tas upp i studien, vilken baseras på en betydande fenotypisk över-lappning mellan olika ångeststörningar hos patienter, där personer med subkliniska nivåer av symtom ändå kan ha en nedsatt funktionsnivå och ett subjektivt lidande, fastän de inte uppfyller alla de diagnostiska kriterierna för en specifik störning. Resultatet visar på möjligheten att se över diagnosgränser, för att öka chanserna för ett tillfrisknande hos patienten. Människans upplevelser av olika situationer den befinner sig i formas av personens egen uppfattning om sin förmåga, eller oförmåga, att påverka resultatet. Att uppleva sig ha mist kontroll över sitt eget liv kan i sig leda till såväl depression som suicidala tankar/-handlingar. Om symtomen för depression jämförs med kriterierna som står att finna under diagnosbilden “Posttraumatiskt stressyndrom” under kapitlet “ångestsyndrom”, kan många likheter konstateras. Slutsatsen blir att likheterna i symtombild skulle ge patienter med PTSD en behandlingsrekommendation som inte alls överensstämmer med de rekommenderade riktlinjer som är utformade för PTSD. Trots diagnosernas likheter rekommenderas olikartad behandling, och även olika förutsättningar för att fungera i kombination med förvärvsarbete påvisas. Vid så lika symtombilder, men ändå så skilda rekommenderade behandlingsplaner utifrån de olika diagnoserna, torde risken för en felaktig rehabiliteringsplan vara över-hängande. / Mental health/illness is complex to define and this highlight of the biggest public health problems in our country, in which depression is one of the most common diagnoses. The manuals DSM-IV TR and ICD-10 is used in much of health care, worldwide, in order to provide knowledge of appropriate treatment for patients with mental disorders. This study aims to, through a qualitative analysis, examine the grounds behind the most commonly used diagnostic manuals and the criteria required to meet two common diagnoses, PTSD and severe depression. Further studies aimed to highlight any similarities and differences between these diagnoses and what it can bring. Both psychological research and clinical practice today is based mostly from psychiatric diagnoses, which can have both advantages and disadvantages, but also discussed whether they should instead focus on another more underlying level, namely the processes that extend across the diagnostic boundaries. The advantages of a trans-diagnostic perspective are that it may partly explain the high co-morbidity found in clinical groups and that could be observed even in those syndromes which this study focuses on. Unified Protocol is a different treatment model that is entered in the study, which is based on a significant phenotypic overlap between anxiety disorders in patients, where individuals with subclinical levels of symptoms still can have a reduced level of functionality and a subjective suffering, although they do not meet all the diagnostic criteria for a specific disorder. The result shows at the opportunity to review the diagnostic boundaries, to increase the chances for a recovery of the patient. The human experiences of different situations it is in the form of personal self-perception of their ability, or inability, to influence the outcome. To experience they have lost control over his own life in itself can lead to both depression that suicidal thoughts / actions. If the symptoms of depression compared with criteria that are to be found during diagnostic image "Post-traumatic stress disorder" in the chapter "disorder" can be found many similarities. The discourse comes to that the similarities in symptoms would provide patients with PTSD, a treatment recommendation, which did not conform to the recommended guidelines that are designed for PTSD. Despite the diagnosis, the similarities are recommended disparate treatment, and also different conditions to work in conjunction with work shown. At this same symptom pictures, yet so different recommended treatment plans based on the different diagnoses, would risk a false rehabilitation plan to be imminent

A proporção de idosos portadores da síndrome da imunodeficiência adquirida (aids) tem aumentado de maneira importante nos últimos anos e, até a presente data, existem poucos estudos que abordam a infecção nessa população especial. As particularidades imunológicas decorrentes do fenômeno da imunossenescência podem acarretar mudanças significativas na evolução da infecção pelo HIV, bem como na resposta ao tratamento. O objetivo maior desta Tese foi avaliar o impacto da idade na recuperação funcional do sistema imune de pacientes com aids acima de 55 anos, quando tratados adequadamente com terapia anti-retroviral, caracterizando a resultante imunológica da idade avançada e da infecção pelo HIV. Para tanto, foram estudados quatro grupos experimentais: indivíduos jovens saudáveis ou com aids, e indivíduos acima de 55 anos saudáveis ou com aids. Todos os pacientes com aids estavam recebendo terapia anti-retroviral, em sucesso terapêutico. No primeiro artigo apresentado, avaliamos resposta linfoproliferativa e produção de citocinas in vitro e resposta humoral in vivo mediante desafio antigênico com toxóide tetânico (TT) em indivíduos previamente vacinados contra o tétano. Os resultados mostraram deficiências imunológicas significativas relacionadas à idade avançada no que diz respeito a produção de IgG anti-TT, resposta linfoproliferativa e produção de IFN-. Em contrapartida, a produção de IL-10 foi significativamente maior nos indivíduos acima de 55 anos, infectados ou não pelo HIV. No segundo artigo, foram caracterizadas as subpopulações de células T mediante estímulo policlonal ou específico com antígenos do envelope do HIV (Env). Em culturas não-estimuladas de PBMC do grupo com aids e idade avançada, observamos frequência reduzida de células T naive e de memória central, associada a aumento de células T efetoras. Quando estimuladas policlonalmente, essas culturas apresentaram deficiência na produção de IFN- e hiperprodução de IL-10, como na resposta ao TT. Mediante estímulo específico com Env, a citometria de fluxo revelou frequência elevada de células T CD4+FoxP3-CD152+ com forte marcação intracelular para IL-10, indicando predomínio do fenótipo Tr-1, e não das células Treg clássicas. Interessantemente, em ambos os artigos, a replicação viral in vitro foi significativamente menor nos pacientes com aids acima de 55 anos, condizendo com a excelente resposta virológica desses pacientes ao tratamento antirretroviral. A neutralização da IL-10 com anticorpo anti-IL-10 nas culturas ativadas pelos peptídeos Env aumentou de forma significativa a replicação viral no sobrenadante. Tanto na resposta ao TT quanto aos peptídeos Env, o bloqueio da IL-10 aumentou os níveis de citocinas pró-inflamatórias, mas não melhorou a produção de IFN- dos pacientes acima de 55 anos com aids. Coletivamente, os achados dessa Tese revelam distúrbios em vários segmentos da resposta imune, particularmente no compartimento Th1, de pacientes acima 55 anos com aids e adequadamente tratados, sugerindo que, para esses pacientes, a reconstituição imune pós-tratamento não ocorre com a mesma eficácia que no jovem. Apesar do aumento da produção de IL-10 provavelmente contribuir, ao menos em parte, para o controle virológico, pode comprometer a resposta tanto ao próprio HIV, quanto a outros desafios antigênicos, a exemplo do toxóide tetânico. Sugere-se, portanto, a necessidade de recomendações específicas de manejo clínico para esse grupo de pacientes / The proportion of aged persons living with the acquired immunodeficiency syndrome (aids) has importantly increased in recent years and, up to the present moment, there are few studies that address the infection in this particular population. The immunological nuances resulting from the immunosenescence phenomenon may promote significant alterations in the clinical course of HIV infection, as well as in treatment response. The major purpose of this Thesis was to evaluate the impact of age on the functional immune recovery in aids patients aged more than 55 years, when adequately treated with anti-retroviral therapy, characterizing the immunological result of advanced age and HIV infection. Thus, four experimental groups were enrolled: healthy or HIV-infected young adults, and healthy or HIV-infected adults over 55 years old. All the HIV-infected patients had diagnosis of aids and were under anti-retroviral treatment with therapeutic success. In the first presented article, we evaluated the lymphoproliferative response and cytokine production in vitro and humoral response in vivo, after antigenic challenge with tetanus toxoid (TT) in previously immunized individuals against tetanus. The results revealed significant age-related immunological impairments concerning anti-TT IgG production, lymphoproliferative response and production of IFN-. On the other hand, the production of IL-10 significantly higher in individuals aged more the 55 years, HIV-infected or not. In the second article, T cell subsets were characterized after polyclonal activation or specific stimulus with antigens derived from the HIV envelope (Env). In fresh unstimulated PBMC cultures obtained from the aged aids patients, there was a reduced frequency of naïve and central memory T cells, associated with increased frequency of effector T cells. When polyclonally stimulated, these cultures showed deficient production of IFN- and hyperproduction of IL-10, like in response to TT. In Env-stimulated cultures, flow cytometry revealed high frequency of T CD4+FoxP3-CD152+ T cells with strong intracellular staining for IL-10, indicating a dominant Tr-1 phenotype, and not the classical Treg cells. Interestingly, in both articles, the viral replication in vitro was significantly lower aids patients over 55 years old, which is in consonance with their excellent virological response to anti-retroviral treatment. IL-10 neutralization with anti-IL-10 antibody in Env-activated cultures enhanced the viral replication in culture supernantants. Both in TT and in Env-peptides-stimulated cultures, the IL-10 blockade enhanced the levels of pro-inflammatory cytokines, but it did not improve IFN- production from aged aids patients. Altogether, the results reported in this Thesis reveal disturbances in several segments of the immune response, particularly in the Th1 compartment, of anti-retroviral-treated aids patients older than 55 years, suggesting that, for these patients, immune reconstitution after treatment does not occur with the same efficacy as in young patients. And although the enhanced IL-10 production probably contributes, at least in part, to the virological control, it can compromise the immune response both to HIV and to other antigenic challenges, such as tetanus toxoid. It is suggested, therefore, the need for specific recommendations regarding the clinical management of these patients

Dans cette étude, le comportement aérodynamique du jet pariétal (Re = 8000) cisaillé latéralement par un courant de perturbation externe (ELS) de profil de vitesse uniforme (Ulf) a été étudié et analysé. Les expérimentations ont été réalisées par PIV et LDV sur une maquette aéraulique isotherme à échelle réduite d’un meuble frigorifique de vente. L’étude est centrée sur la région du jet située à proximité de la section de soufflage (x/e < 10) qui correspond à la zone dans laquelle se développent les instabilités et le processus de transition vers la turbulence. L’analyse des résultats obtenus avec et sans perturbation a mis en évidence que la perturbation entraîne une diminution significative du pouvoir d’entraînement du jet, une forte décroissance de la vitesse moyenne maximale, un faible épanouissement du jet et une augmentation globale des valeurs des moments d’ordre deux de toutes les composantes des contraintes de Reynolds. L’analyse par PIV résolue en temps (10 kHz) montre une topologie déformée et allongée des structures de Kelvin-Helmholtz (K-H) pour (Ulf = 0,5 ms-1) et détachée pour (Ulf = 1 ms-1). Les résultats de l’interaction mutuelle ente les couches interne et externe indiquent que le courant ELS brise partiellement le mécanisme de formation des dipôles de vortex qui deviennent irréguliers et moins prédictifs, ce qui conduit à l’allongement de la zone de transition et retarde donc l’apparition de la zone auto-similaire du jet. D’après la technique POD, l’ELS engendre une redistribution énergétique entre les modes. Le courant ELS affecte également les instabilités K-H en perturbant leur organisation bidimensionnelle, leur topologie, leur alignement et leur fréquence de passage mettant en évidence l’effet inhibiteur exercé sur le développement des structures primaires. Les corrélations spatiales Rvv reflètent la diminution des échelles de longueur dans le cas d’un jet perturbé. / In this study, the aerodynamic behavior of the plane wall jet (Re = 8000) sheared laterally by an external lateral stream (ELS) of a uniform velocity profile (Ulf) was studied and analyzed. The experiments were carried out by PIV and LDV on a reduced-scale isothermal aeraulic model of a refrigerated display cabinet. The study focuses on the near-field region of the jet (x / e <10) which corresponds to the zone of transition to turbulence and onset and development of instabilities. The results obtained with and without perturbation showed a significant decrease in the entrainment rate, a strong decrease in the maximum velocity decay rate, a lower jet expansion and an overall increase in the values of second order moments of the Reynolds stress components. The time-resolved PIV analysis (10 kHz) shows a distorted and elongated topology of the Kelvin-Helmholtz (K-H) structures for (Ulf = 0,5 ms-1) and a detached topology for (Ulf = 1 ms-1). The results of the mutual interaction between the inner and outer layers indicate that the ELS partially breaks the vortex dipole formation mechanism which becomes irregular and less predictive, leading to the elongation of the transitional region and a lag effect in the beginning of the self-similarity region. POD technique reveals the role of the ELS in redistributing energy between the modes. The ELS also affects the K-H instabilities by disrupting their two-dimensional organization, topology, alignment and shedding frequency, highlighting the inhibitory effect exerted on the development of primary structures. The spatial correlations Rvv reflect the decrease of the length scales in the case of a perturbed jet.

Ce travail de thèse s'intéresse à l'optimisation des performances de transmissions multimédias par une approche originale combinant des circuits radiofréquences, tel que l'am-plificateur de puissance et les distorsions du canal de transmission. Les signaux OFDM sont très sensibles aux non-linéarités de l'amplificateur à cause des fortes fluctuations du niveau du signal, caractérisées par le PAPR. Afin de réduire le PAPR, on propose tout d'abord d'améliorer la méthode TR en termes de rapidité de convergence et de réduction du PAPR, en comparant plusieurs algorithmes d'optimisation. On montre que l'algorithme du gradient con-jugué offre les meilleures performances tout en respectant les spécifications fréquentielles du standard IEEE 802.11a. Par la suite, la méthode TR est évaluée expérimentalement en pré-sence d'un amplificateur de puissance (SZP-2026Z) en utilisant un banc de mesures. On montre ainsi que la méthode TR permet une amélioration de la qualité de transmission. Cette amélioration peut être utilisée pour modifier le point de fonctionnement de l'amplificateur et per-mettre ainsi une réduction de 18 % de la puissance consommée. Les résultats expérimentaux ont conduit au choix d'un modèle réaliste d'amplificateur en considérant les effets mémoires. Ce dernier a été intégré dans une chaîne de simulation SISO comprenant également un modèle réaliste de canal de transmission. La chaîne décrite a permis d'évaluer les performances de la méthode TR dans des conditions de transmission réalistes. Enfin, on propose d'appliquer la méthode TR dans une chaîne MIMO-OFDM en boucle fermée dédiée à la transmission de contenus multimédias scalables dans un environnement réaliste, en utilisant le standard IEEE 802.11n. Cette étude présente une évaluation originale de l'impact de la méthode TR sur la qualité visuelle des images transmises, en prenant en compte le contenu multimédia, la non-linéarité de l'amplificateur et les distorsions apportées par le canal. / In this thesis, we are interested on the performances optimization of multimedia transmissions systems with an original contribution combining RF circuits' imperfections presented by the power amplifier (PA) nonlinearities and the transmission channel distortions. The studied system uses the OFDM technique which is the most widespread multicarrier modulation in recent radio communications systems. However, its major drawback is the high PAPR value, which degrades the transmission quality due to the PA nonlinearities. To reduce the PAPR, we first propose to improve the TR method in terms of convergence speed and PAPR reduction, by studying several optimization algorithms. We show that the conjugate gradient algorithm provides the best performance while respecting the frequency specifica-tions of the IEEE 802.11a standard. Thereafter, TR method has been evaluated experimentally in the presence of a commercial PA (SZP-2026Z) and using a measurement bench. It is shown that the TR method improves the quality of service (QoS), with 18% reduction in PA power consumption. The experimental study has resulted to choosing a realistic PA model consider-ing memory effects. This PA model has been integrated into a SISO simulation chain includ-ing also a realistic channel model. This chain is used to evaluate the TR method performances under realistic transmission conditions. Finally, we propose to apply the TR method in a closed-loop MIMO-OFDM chain dedicated to the transmission of scalable multimedia con-tent in a realistic context with the IEEE 802.1n standard. This study presents a new contribu-tion of the TR method evaluation to improve the visual quality of the JPWL transmitted imag-es, considering in the same time the multimedia content, the PA nonlinearity and the channel transmission distortions.

Les récepteurs couplés aux protéines G constituent la plus grande famille de protéines membranaires et interviennent dans de nombreux processus physiologiques. La compréhension de l’interaction ligand-récepteur d’un point de vue mécanistique mais également thérapeutique est cruciale. Appartenant à la famille des récepteurs couplés aux protéines G, les récepteurs de la vasopressine et de l’ocytocine ont été choisis comme modèle d’étude. Ces hormones jouent un rôle important dans la modulation de l’attachement et de l’affect chez les mammifères. Afin d’accélérer la découverte de ligands ocytocinergiques et d’explorer les mécanismes fondamentaux de leurs interactions, nous avons conçu les premiers ligands fluorescents non peptidiques des récepteurs de la vasopressine V1a et de l’ocytocine. Ces ligands ont été utilisés pour développer des tests de liaisons par TR-FRET et démontrer la dimérisation des récepteurs de la vasopressine V1a et V2 sur cellules. Des études autour de petites plates-formes dérivées d’aza-dicétopipérazine ont permis d’accéder à un nouvel antagoniste non peptidique du récepteur de l’ocytocine. L’optimisation de dérivés benzodiazépines ocytocinergiques par des études de relations structure-activité a permis d’identifier les meilleurs agonistes non peptidiques du récepteur de l’ocytocine à ce jour. Une étude in vivo chez la souris et chez le singe est amorcée pour apporter dans un futur, une solution thérapeutique aux problèmes d’interaction sociale en général et d’autisme en particulier. / G protein coupled receptors are the largest membrane protein family and play an important role in a large number ofphysiological processes. The comprehension of the ligand-receptor interaction from a mechanistic point of view but alsofor therapeutic use is crucial. Belonging to the G protein coupled receptors, the oxytocin and vasopressin receptors havebeen used as a model system. These two hormones play an important role in the modulation of attachment and affectin mammals. To accelerate the discovery of new ligands for oxytocin and vasopressin receptors and to explore thefundamental role of their interactions, we designed the first non-peptide fluorescent ligands for oxytocin and vasopressin V1a receptors. These ligands have been used to develop new binding tests based on TR-FRET technology and to prove the V1a and V2 receptor dimerisation. In parallel, we developed a new non-peptide oxytocin antagonist around an aza-diketopiperazine platform. . Optimization of benzodiazepine derivatives enables us to identify the best non peptideoxytocin agonists to date. In vivo studies in mice and monkeys are initiated to bring in the future a therapeuticsolution to social interaction problems in general and autism in particular

The aim of this diploma thesis is to create universal application able to visualize M2M data and allows remote management of smart sensors using TR-069 protocol. First part of this thesis contains comprehensive evaluation of TR-069 standard and OSGi platform. Next, extensive analysis of embedded databases with detailed description of SQLite platform is provided. Auto-configuration server genieacs and modus TR-069 client, two parts needed for the proper run of remote configuration, are described in more detail in following section. Practical part of this thesis contains description of all created OSGi bundles together with communication interfaces. Moreover, the description of designed database and developed user interface is given.

L'existence de différentes phases, polymorphes, sels, solvates et co-cristaux génère de nombreuses questions concernant la caractérisation des matériaux à l'état solide, en particulier pour l'industrie pharmaceutique. Les problématiques relatives à l'identification des phases et à la surveillance des processus de crist(allisation et de transitions de phase ne peuvent toutefois pas toujours être résolues à l'aide de techniques d'analyse conventionnelles. Dans ce travail, nous développons une approche analytique basée sur le phénomène d'optique non-linéaire de génération de seconde harmonique (GSH). La GSH est une technique sensible et précise pour détecter l'absence de centre d'inversion au sein d'une structure cristalline et pour suivre des modifications subtiles de symétrie. A travers plusieurs exemples, nous montrons comment les mesures de GSH résolues en température (TR-SHG) peuvent être utilisées pour étudier les diagrammes de phases et pour suivre les mécanismes et cinétiques des transitions de phase, y compris pour des transitions de type ordre-désordre. La combinaison de la TR-SHG avec les techniques classiques (XRPD, DSC et microscopie) permet ainsi de démontrer l'utilité et le potentiel de l'optique non-linéaire dans la caractérisation des propriétés physico-chimiques des matériaux. / The existence of different phases, including polymorphs, salts, solvates and co-crystals generates concerns in the characterization of solid-state materials, especially for the pharmaceutical industry. Issues related to the identification of phases and the monitoring of phase transitions and crystallisation processes cannot be always solved using conventionnal techniques. In this work, a complementary analytical approach based on the nonlinear optical phenomena of second harmonic generation (SHG) is developed. SHG is a sensitive and accurate technique to detect the absence of inversion center in the crystalline structure and to capture subtle symmetry changes. Herein, through several examples we show how Temperature-Resolved SHG (TR-SHG) measurements van be used to study phase diagrams and for tracking mechanisms and kinetics of phase transitions including order-disorder phase transitions. The combination of TR-SHG with classical techniques (XRPD, DSC and microscopy) reveals in this study the usefulness and the potentials of nonlinear optics in material characterization.

[Aus dem Text:] Spanende Bearbeitung nimmt nach wie vor eine zentrale Stellung ein. Dies gilt nicht nur für die Gegenwart. Die betreffenden Unternehmen prognostizieren mehrheitlich sogar für die spanenden und trennenden Verfahren einen Bedeutungszuwachs. Dieser geht einher mit der eindeutigen Tendenz zu weiter wachsenden Genauigkeitsforderungen an die Fertigungsprozesse der Metall-, Kunststoff- und Elektroindustrie. Die gegenwärtigen und künftigen ökologischen, sozialen und wirtschaftlichen Rahmenbedingungen und gesellschaftlichen Zielstellungen, wie - die Ressourcenschonung – und hier insbesondere die Verbesserung der Energieeffizienz in der Produktionstechnik, - die Befriedigung individualisierter Bedürfnisse – mit dem daraus für die Fertigung folgenden Bedarf an weiterer Flexibilisierung sowie - die immerwährende Forderung nach weiterer Steigerung der Produktivität, führen im Zusammenhang mit der spanenden Genauigkeitsfertigung zu einem sich verschärfenden Zielkonflikt im Dreiecksverhältnis von Energieeinsatz, Genauigkeit und Produktivität bei der spanenden Bearbeitung.

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This thesis examines the urban topography of Berlin’s working-class districts, as seen in the art, architecture and other images produced in the city between 1924 and 1930. During the 1920s, Berlin flourished as centre of modern culture. Yet this flourishing did not exist exclusively amongst the intellectual elites that occupied the city centre and affluent western suburbs. It also extended into the proletarian districts to the north and east of the city. Within these areas existed a complex urban landscape that was rich with cultural tradition and artistic expression. This thesis seeks to redress the bias towards the centre of Berlin and its recognised cultural currents, by exploring the art and architecture found in the city’s working-class districts. The thesis adopts Henri Lefebvre’s premise that each society creates its own space in which it lives, works, and sustains its cultural identity. On this basis, working-class culture and the spaces in which it was practiced, are treated with equal weight. The thesis begins by examining how the laissez-faire economics of the German Empire (1871–1914), combined with a massive influx of rural migrants into Berlin, creating a complex industrial landscape, whose working-class inhabitants retained many pastoral traditions. The thesis moves on to study the works of a number of artists active in Berlin between 1924 and 1930, using examples of their work to examine the unique nature of the working-class districts, and the culture and traditions that took place within them. The second half of the thesis explores the working-class districts from an explicitly political perspective. The extensive house building programme that took place across Berlin throughout the twenties is explored in all its varied and conflicting political perspectives. What emerges is a picture of a growing schism between Berlin’s Social Democratic government, and Communist supporters in the working-class districts. 1929 emerges as a critical year in which political contestations of space between the two parties and their supporters reached new levels of hostility, as working-class culture clashed against Social Democratic urban policy.