Although a seemingly basic and simple behavior, micturition necessitates precise integration and coordination of multiple divisions of the nervous system: visceral sensory, somatic motor, sympathetic, parasympathetic, as well as voluntary control from higher brain/ brainstem centers. When coordination of this circuitry falters, the consequences can be devastating and include severely decreased quality of life and substantial economic burden. This dissertation project investigates the potential role(s) of inflammatory mediators in bladder sensory physiology with the long term goal of elucidating potential targets for intervention. The overall hypothesis is that inflammatory-induced changes in the urinary bladder or afferent projections ultimately lead to dysfunctional micturition symptoms. Using a rodent model of cyclophosphamide (CYP)-induced bladder inflammation, we examined the expression and function of the chemokine/ receptor pair, CXCL12/CXCR4, and the activated (phosphorylated) form of ubiquitous signaling molecule, AKT using a multidisciplinary approach that includes: immunohistochemistry, protein and transcript quantification techniques, and in vivo bladder physiology studies combined with pharmacological tools. Peripheral chemokine levels are elevated in patients with various chronic pelvic inflammatory/ pain syndromes including interstitial cystitis/bladder pain syndrome (IC/BPS) and are implicated in numerous inflammatory and mechanical pain models in rodents. However studies had not previously shown a direct functional role for chemokine signaling in micturition. We hypothesized that CXCL12 and CXCR4 would increase in the urinary bladder with CYP-induced bladder inflammation and that CXCR4 receptor blockade with AMD3100 would reduce CYP-induced bladder hyperreflexia. ELISA, immunohistochemical and qRT-PCR experiments demonstrate duration-dependent increases in CXCL12 and CXCR4 protein and transcript expression in specific tissue compartments of the urinary bladder, mainly the urothelium. In vivo studies provide evidence of a role for chemokine signaling in the mediation of micturition function. Intravesical infusion with AMD3100, a CXCR4 receptor antagonist, significantly reduced CYP-induced bladder hyperreflexia as evidenced by increased bladder capacity, intercontraction interval and decreased voiding frequency. AKT is a putative cellular survival signal, however, recent studies also implicate the signaling molecule in the induction and maintenance of pain processes, development of long term plasticity (e.g. LTP and central sensitization) and visceral inflammation. Functional studies addressing the contribution of pAKT in micturition have not been performed. We hypothesized that increasing pAKT levels would contribute to CYP-induced bladder hyperreflexia. Western blot and immunohistochemical studies demonstrated that phosphorylation of AKT increases in the whole urinary bladder with CYP-induced bladder inflammation in a tissue compartment- and time-dependent manner. Intravesical infusion with inhibitors of AKT phosphorylation, AKT Inhibitor IV and deguelin, significantly improved symptoms of CYP-induced bladder hyperreflexia suggesting a functional role for pAKT in bladder physiology. These studies demonstrate the functional capacity of inflammatory mediators and inflammatory associated signaling pathways in micturition reflex pathways. Chemokine signaling via the CXCR4 receptor and upstream activators of AKT may provide therapeutic targets with respect to inflammatory-induced bladder sensory physiology dysfunction.

Veränd. Magisterarbeit Universität Hamburg, 2007. / Originaltitel: Der "Völkische Beobachter" über die UdSSR im Jahre 1939, (Titel der Magisterarbeit). Originaltitel: Der "Völkische Beobachter" über die UdSSR im Jahre 1939.

Jena, Universiẗat, Diss., 2006.

No description available.

Múltiplas lesões orais que progridem em um curso irreversível lento mediante expansão de áreas afetadas, no sentido de um pior prognóstico, caracterizam a leucoplasia verrucosa proliferativa. A referida lesão apresenta perfil agressivo circunstanciando indeterminado número de recidivas e alto potencial de transformação neoplásica. A tal fato, se atribui a frequente incidência em carcinoma verrucoso bem como em carcinoma espinocelular de boca invasivo e potencialmente metastático, inserindo-se este em índices de maior prevalência quando comparado ao carcinoma verrucoso em pacientes com leucoplasia verrucosa proliferativa. Vincula-se ao contexto supracitado, o envolvimento de vias de sinalização celular ocasionando o desarranjo de um complexo sistema o qual abarca atividade de oncogenes, inibição de genes supressores de tumor e alteração de reguladores do sistema de reparo do DNA, encerrando-se, por sua vez, em diversos fatores favoráveis à carcinogênese, dentro os quais a regulação negativa de cascatas pró-apoptóticas e estímulo à proliferação celular desordenada. A este processo se pode relacionar o desconcerto da via PI3K/Akt/mTOR e de um membro do complexo de pré-replicação, o MCM3. Para tanto, a análise pormenorizada do perfil evolutivo da lesão por meio do rol de diagnósticos pregressos, bem como por meio do cruzamento de dados epidemiológicos, além da caracterização de neoplasias malignas provenientes da leucoplasia verrucosa proliferativa por meio da expressão dos biomarcadores pAkt, pmTOR e MCM3, vêm a explanar aspectos ainda pouco estudados desta intrigante entidade clinicopatológica. Neste sentido, o presente trabalho analisou o histórico diagnóstico de 28 pacientes com leucoplasia verrucosa proliferativa submetendo à análise imuno-histoquímica para as supracitadas proteínas, o montante de 34 amostras dos mesmos pacientes, integrando estas, 28 de leucoplasia verrucosa proliferativa, 4 de carcinoma verrucoso e 2 de carcinoma espinocelular. Dos resultados obtidos, foi possível depreender a prevalência de lesões em mucosa jugal, rebordo alveolar e língua confirmando ainda seu perfil evolutivo em face às múltiplas lesões com alto potencial recidivante e latente insurgir do carcinoma espinocelular, este podendo ainda ser embasado por expressiva marcação de pmTOR, pAkt e MCM3. / Multiple oral lesions that progress in a slow irreversible course by expansion of affected areas, in the sense of a worse prognosis, characterize proliferative verrucous leukoplakia. The said lesion presents an aggressive profile, with an indeterminate number of recurrences and a high potential for neoplastic transformation. To this fact, it is attributed to frequent incidence in verrucous carcinoma as well as invasive and potentially metastatic invasive mouth squamous cell carcinoma, inserting itself in indices of higher prevalence when compared to verrucous carcinoma in patients with proliferative verrucous leukoplakia. It is linked to the aforementioned context, the involvement of cell signaling pathways, causing the disruption of a complex system which encompasses oncogenes activity, inhibition of tumor suppressor genes and alteration of DNA repair system regulators, ending in several factors favorable to carcinogenesis, in which negative regulation of pro-apoptotic cascades and stimulation to disordered cell proliferation. To this process one may relate the dissatisfaction of the PI3K / Akt / mTOR pathway and a member of the pre-replication complex, MCM3. Thus, the detailed analysis of the evolutionary lesion profile through the role of previous diagnoses and the cross-referencing of epidemiological data, as well as the characterization of malignant neoplasms from proliferative verrucous leukoplakia by the expression of the biomarkers pAkt, pmTOR and MCM3, come to clarify aspects that have not yet been studied in this intriguing clinicopathological entity. Thus, the present study analyzed the historical diagnosis of 28 patients with proliferative verrucous leukoplakia submitting to immunohistochemical analysis for the aforementioned proteins, the amount of 34 samples from the same patients, comprising 28 of proliferative verrucous leukoplakia, 4 of verrucous carcinoma and 2 of squamous cell carcinoma. From the results obtained, it was possible to detect the prevalence of lesions in the buccal mucosa, alveolar ridge and tongue, and the confirmation of its evolutionary profile in the face of the multiple lesions with high recurrent and latent insurgent potential of squamous cell carcinoma, which may be supported by a significant mark of pmTOR, pAkt and MCM3.

Das vorliegende Handbuch bietet vertiefende Informationen zur Individualbeschwerde nach dem Fakultativprotokoll zum Internationalen Pakt über bürgerliche und politische Rechte. Das Handbuch richtet sich in erster Linie an Praktiker/innen, die in ihrer Arbeit mit Menschenrechtsverletzungen konfrontiert sind, insbesondere Rechtsanwälte und Rechtsanwältinnen sowie Menschenrechtsorganisationen. In umfassender, aber komprimierter Form gibt es zuverlässige Hilfestellung bei der Einlegung einer Beschwerde. Darüber hinaus ist das Handbuch auch für Mitarbeitende in Ministerien, Universitäten und sonstigen Einrichtungen geeignet, die sich mit der Materie vertraut machen wollen. (Autorenreferat)

Afrikaans : Vanaf 1924 tot 1926 het die Pakt-regering gepoog om die posisie van blanke werkers deur middel van wetgewing te verskans. Die wetgewing sou egter ten nadele van swart werkers strek. As gevolg van die regeringsbeleid van ‘beskaafde arbeid’ was dit vir swartes onmoontlik om soos blankes, op ‘’n minimum loon aan te dring en te staak ten einde hoër salarisse te beding. Voorts is sekere poste vir blankes alleen gereserveer en is swartes afgedank om vir blanke werkers plek te maak. Swart werkers, en by name die organisasies wat hulle vir die belange van die swart gemeenskap beywer het, het nie die 'beskaafde arbeidsbeleid' bloot passief aanvaar nie. Die Industrial and Commercial Workers' Union, die African National Congress, die Gesamentlike Rade en die Kommunistiese Party van Suid-Afrika het algar georganiseerde versetaksies teen die arbeidswetgewing geloods. Die Pakt-regering het bykans geen ag op swart verset geslaan nie. Waar die Pakt tydens sy bewindname in 1924 met optimisme begroet is, was die regering gevolglik in 1929 ongewild by die swart bevolking. English : Between 1924 and 1926 the Pact Government attempted to safeguard the position of white labourers. Its legislation was, however, detrimental to the position of black labourers. As a result of the policy of 'civilized labour' it became almost impossible for black labourers to insist on a minimum wage or to strike in order to obtain higher wages. Furthermore, certain categories of jobs were reserved for whites only and blacks were replaced by whites. Black labourers and, in particular, those organizations that worked for the benefit of the black community, did not merely accept the policy of 'civilised labour' in a passive way. The Industrial and Commercial Workers' Union, the African National Congress, the Joint Councils and the Communist Party of South Africa all launched organised resistance actions against the labour legislation. The Pact paid virtually no attention to black resistance. Whereas the Pact was welcomed with enthusiasm when it came to power in 1924, during the 1929 election it was extremely unpopular with the black people of South Africa. / Dissertation (MA)--University of Pretoria, 2009. / Historical and Heritage Studies / unrestricted

The diploma thesis focuses on the identification of the impact of the euro on the macroeconomic indicators of selected eurozone member states and states outside the eurozone. Part of this work is also the confirmation or refutation of the Rose. To define the impact of the euro on individual indicators, it was firstly necessary to study professional sources, both domestic and foreign, and secondly to analyse panel data. The panel regression with fixed effects was used in the thesis. This analysis also explains the reasons for the resulting effects of the euro on the indicators.

The thesis focuses on the British approach to EMU fiscal rules. Theoretical and conceptual framework is based on the theory of differentiated integration dealing with a various forms of closer cooperation among EU Member States. The research is built on the theoretical approach as described by Frank Schimmelfennig, Dirk Leuffen and Berthold Rittberger. Authors provide an analysis of conditions of differentiated integration within the EU. The aim of this thesis is to answer the question of why the United Kingdom decided not to participate in the fiscal compact and, consequently, did not allow further differentiated integration within the treaties (which led to an arrangement outside the EU legal framework) while accepting the initial fiscal rules agreed in the 1990s as well as other crisis reforms of EU fiscal governance. The first part describes Maastricht and SGP fiscal rules and analyses both the UK's position within EMU and the SGP provisions applied to the UK. The next chapter examines the British approach towards both the SGP revisions and the Euro Plus Pact. The third part analyses the new fiscal compact and explains why the UK decided to use the veto. In conclusion, the thesis provides an answer to the research question as set down in the introduction.

Master thesis is dealing with the topic of Collective security during the time following World war the first, during the time of League of Nations duration. Except the introduction and conclusion Thesis is divided into five sections. First section is dealing with the issue of Collective security. In order to conduct deeper analysis, term is divided into two parts - Security and Collectiveness. Concept of Security is analysed further when four different aspects are identified. Collectiveness is also examined in order to define its meaning. First part also includes distinction between Collective security and Collective self-defence. Despite their different meanings these two terms are often interchanged. Second part deals with the events preceding the creation of League of Nations. Especially the Paris peace conference. Since it laid down the foundations for the new International organization and its prime document, the Covenant. Second part is also dealing with the demands of the victorious powers on a concept of Collective security. Since the victors did not share single opinion on how to organise new international organisation, the Covenant of League of Nations and its legal mechanisms are result of a diplomatic compromise. Third part is dealing with the specific parts of the Covenant. The parts related to...