Made available in DSpace on 2014-06-12T15:07:38Z (GMT). No. of bitstreams: 2 arquivo1496_1.pdf: 7385804 bytes, checksum: c1b6062baf4cd970f534211e0d594ff7 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2005 / Esta dissertação analisa os arranjos de poder, os conflitos e alianças entre os atores organizacionais envolvidos na revitalização do bairro histórico de Jaraguá, em Maceió capital de Alagoas. Seu propósito é discutir sobre a contribuição das inter-relações organizacionais para a promoção do desenvolvimento local. Confere-se à pesquisa um caráter interdisciplinar, no qual o espaço urbano é observado, simultaneamente, por teorias organizacionais e de desenvolvimento. Metodologicamente, optou-se por uma abordagem qualitativa de análise de dados, a partir da realização de 25 entrevistas, aliadas ao levantamento bibliográfico e documental. O estudo tem perspectiva longitudinal com cortes transversais, imprimindo a revitalização de Jaraguá em três momentos, respectivamente: a fase de planejamento da intervenção urbana, a etapa de concretização das obras de reestruturação e, por fim, o efetivo funcionamento dos novos usos almejados para o espaço. Em cada um desses momentos, são mapeados os atores organizacionais relevantes, seus objetivos e suas bases de poder com fins de desvelar a configuração das inter-relações organizacionais. Paralelamente, analisa-se a estratégia de desenvolvimento traçada para o bairro, comparando-a às variáveis orientadoras de duas vertentes da literatura de desenvolvimento local: a social e a competitiva. Os resultados, analisados sob uma abordagem assimétrica de poder, sugerem que as interrelações organizacionais são predominantemente conflituosas e os arranjos de poder nãocooperativos. A revitalização do bairro apresentou ampla sintonia com uma estratégia de desenvolvimento local empresarialista urbana (competitiva). Conclui-se que, em função da divergência dos objetivos operativos dos atores, as inter-relações organizacionais no processo de revitalização de Jaraguá, desde o planejamento até a implementação, não favorecem o desenvolvimento local sustentável

The purpose of this study is to investigate the possible differences in the way American and Swedish journalists writing in English use maximizers, i.e. intensifying adverbs. In order to fulfill the purpose, information about how maximizers are used in two different sub-corpora, namely SWENC (The Swedish-English Corpus) and TIME (Time Corpus of American English) is collected. The data in SWENC has been collected from various websites where the crucial criterion was that the authors of the articles must have Swedish as their first language. The data from TIME has been collected from Time Magazine’s online corpora which is freely available on the Internet. The results show that there are some differences in the way Swedes and Americans use maximizers. The number of tokens for each maximizer does not differ to a great extent between the two corpora. However, there are larger deviances in the use of collocations and semantic prosody. The conclusion drawn from this is that there are indeed some differences in how American and Swedish journalists writing in English use maximizers, although they are not very many.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) has been a successful cellular therapy for patients suffering from hematological malignancies for many decades; however, the beneficial effects of graft-versus-leukemia (GVL) are classically offset by graft-versus-host disease (GVHD). GVHD occurs when major and/or minor human leukocyte antigen (HLA) mismatches between donor and recipient cause rapid expansion and activation of donor effector T cells (Teffs) resulting in end organ damage to the recipient’s epithelial tissues. Given the lymphoproliferative nature of this disease, the standard treatment option is broad immunosuppression, which can result in primary disease relapse, steroid refractory GVHD, and/or opportunistic infection. A more targeted therapy that can selectively suppress GVH responses with maintained GVL responses would achieve the optimal goal of allo-HCT. Regulatory T cells (Tregs) both natural (nTregs) or induced (iTregs) could be potential cellular therapies for the treatment of GVHD, given their innate suppressive function. Initial clinical trials using nTregs have yielded positive results; however, nTreg cellular therapy has been cumbersome due to the necessity for large scale ex vivo expansion given their low yield within an apheresis product and non-specific suppression. Conversely, iTregs can be generated from naïve T cells thus decreasing ex vivo culture times and can be educated with specific antigen thus providing targeted suppression, but a consensus on their efficacy for GVHD therapy has not been reached. Therefore, we investigated the efficacy of antigen specific iTreg therapy for the prevention of GVHD while maintaining GVL responses. In Chapter 2, we evaluated the effectiveness of monoclonal HY-specific iTregs in GVHD attenuation. We chose HY as a target antigen because it is a naturally processed, ubiquitously expressed minor mismatch antigen carried by only male donors/recipients cited to increase GVHD prevalence when donor and recipient are sex-mismatched. Utilizing HY-transgenic mice in which all T cells recognize HY antigen exclusively, we generated HY specific iTregs which effectively attenuating GVHD in male, but not female recipients in three murine bone marrow transplantation (BMT) models (major mismatch, parent to F1, and miHAg mismatch). We found HY specific iTregs lost stability in female recipients but remained stable and suppressive in male recipients suggesting expression of HY antigen was required for their suppressive function and stability. GVL responses were not compromised with the addition of HY specific iTregs in recipient mice using a pre-established tumor model. Thus, HY-specific iTregs can be generated and suppress GVHD in an antigen-dependent manner while sparing the GVL effect. In Chapter 3, we extend our findings in Chapter 2, which provided proof of principle that antigen specific iTregs effectively control GVHD; however, this therapy has a limited translational potential. Therefore, we generated alloreactive CD4 and CD8 iTregs and evaluated GVHD attenuation and GVL preservation in either full or haplo-MHC mismatched BMT models. We found alloreactive CD4 iTregs significantly suppress lethal GVHD, but completely abrogated the GVL effect against aggressive tumors. Conversely, alloreactive CD8 iTregs moderately attenuated GVHD and possessed direct cytotoxicity against tumor cells. Therefore, to rescue the impaired GVL effect mediated by CD4 iTregs, we established a combinational therapy with CD8 iTregs. Indeed we found combination CD4 and CD8 iTreg therapy significantly suppressed GVHD while sparing GVL responses compared to either CD4 or CD8 singular therapy. Mechanistically, this was achieved by potent suppression of both CD4 and CD8 Teffs coupled with preserved cytolytic molecule expression by both CD8 iTregs and Teffs. Taken together, we propose antigen specific iTreg therapy can effectively attenuate GVHD while preserving GVL responses. We further uncovered unique characteristics of CD4 and CD8 iTregs that can be exploited to achieve the optimal cellular therapy following allo-HCT.

In an increasingly globalized workplace, the ability to communicate effectively across cultures is critical. We propose that the quality of communication experienced by individuals plays a significant role in the outcomes of intercultural interactions, such as cross-border negotiations. In four studies, we developed and validated a multidimensional conceptualization of Quality of Communication Experience (QCE) and examined its consequences in intracultural versus intercultural business negotiation. We proposed and found three dimensions of QCE, namely Clarity, Responsiveness, and Comfort. Findings from intercultural and same-cultural negotiations supported the hypotheses that QCE is lower in intercultural than intracultural negotiation; and that a higher degree of QCE leads to better negotiation outcomes. Moreover, we found evidence that the beneficial effects of higher QCE on negotiation outcomes are more pronounced in intercultural than intracultural negotiation. We propose an agenda for future research and identify implications for practice.

The Duke of Uncertainty - Aspects of Professional Skillis a dissertation whose title is a literary metaphor designedto draw attention to encounters with unforeseen problems anddilemmas at work. The first part of the dissertation presents the skill andtechnology tradition that has developed over the last twentyyears through explorative case studies. These have covered theskills of various occupational groups, such as processoperators in the paper-and-pulp and chemicals industries,managers and systems engineers working on real timeapplications in specialized knowledge intensive firms as wellas doctors and nurses. The theoretical perspective is the epistemology of skillfocusing on the phenomenon of tacit knowledge. This has itsroots in Wittgenstein's philosophy of language as developed bythe philosophers Allan Janik and Kjell S. Johannessen. The methodological framework develops indirect analogicalthinking which is a prerequisite for knowledge based onexperience, through exemplification. The empirical part of the work shows knowledge offamiliarity among members of an occupational group with lowformal training but extensive practical experience, namelyassistant nurses. A comparative analysis is undertaken inrelation to previous case studies in the field of skill andtechnology aimed at occupational groups with high formaleducational qualifications. A particular aspect to which attention is drawn is therhythm in work that unites occupational groups regardless ofeducational background. Occupational skill is treated as acapacity developed to find rhythm in action when confrontedwith situations that are hard to handle. The dissertationconsiders aspects that can be tried out in other occupationalarenas and paves the way for identifying phenomena in workinglife that hinder the development of rhythm in work. The dissertation contributes to the setting-up ofundergraduate-level training for groups of people who have notpreviously had access to higher education, and aims tointroduce new aspects into the development of analoguethinking. Key words: practical versus theoretical knowledge, skillof epistemology, tacit knowledge, comparative case study,literary metaphor, analogical thinking, indirect method,occupational training. / <p>NR 20140805</p>

The purpose of this study is to pose possibilities in addressing the problem of ethnical discrimination, its development into supersessionism and the perpetual discriminatory practices in the contemporary church by engaging Acts 6:1-7 from a rhetorical and deconstructive perspective. The episode in Acts 6:1-7, where the seven men have been selected to deal with the issue of the “daily distribution of food” presents a problem with regard to its interpretation. The problem resides in the fact that the text itself contains a certain number of inconsistencies. The most obvious is the contradiction between the task assigned to the seven and their actual function in the subsequent narrative. The account of the selection of the seven has attracted the attention of many scholars. However, although they have identified the contradictions and incoherencies, the methodologies applied by these scholars to uncover the original meaning, did not enable them to dismantle the hierarchical dichotomies underlying the text, and to question how ethnical discrimination can be prevented as well as how the leadership is differently constructed. The objective of this study is to expose these contradictions and to ask how we can deal with this exposure, and how we can think with a text such as Acts 6:1-7 in addressing the problem of ethnical discrimination, supersessionism and leadership, not only in the church but also in its wider political manifestations. The research methodology used in this study derives from deconstruction and rhetoric within the wider ambit of critical theory. Acts 6:1-7, when read from a conjunction of rhetorical and deconstruction perspectives, demonstrates that there is indeed a problem of ethnicity in Acts 6, reveals how the author of Acts privileges an engendered masculinity ethos, exposes the absence of taking the plight of widows into full consideration, shows that the roots of supersessionism can be found in Acts 6: 1-7, and also infuses the notion of leadership with an ethical overturning that requires rethinking the implications for leadership. The significance of the study lies in considering how a continuation of ethnical discrimination in contemporary denominational context can be resisted via my thinking with Acts 6:1-7. / New Testament / D. Th. (New Testament)

Mesenchymal stem cells and their regenerative and immunomodulatory potential Abstract Mesenchymal stem cells (MSCs) possess multidirectional regenerative ability, which, together with their immunomodulatory potential, makes them promising cell type for therapy of wide variety of diseases. Despite ongoing research, which proved MSCs application to be safe, reported effect of MSCs administration on patients is not convincingly beneficial yet. In our work we focused on elucidation of MSCs role in regeneration of vital organs, heart and liver, where a large damage is life threatening for patients and any improvement in therapy would save many lives. Similar situation is in Graft versus host disease (GVHD), where MSCs immunomodulatory properties could be beneficial. Role of MSCs in heart regeneration was examined in vitro. Primary adult swine cardiomyocytes (CMCs) were co-cultured with or without swine MSCs for 3 days and morphological and functional parameters (contractions, current, respiration) of CMCs were measured. MSCs showed supportive effect on CMCs survival, especially at day 3 of the experiment, where in co-culture was significantly higher number of viable CMCs with physiological morphology and maintained function. Effect of MSCs on liver regeneration was observed in swine model of chronic liver...

Current learner-centered trends, such as supplying students with content on demand (CoD), coupled with research findings that indicate distributed practice is superior to massed practice in terms of increased memory function and that the Personalized System of Instruction (PSI) is superior to traditional instruction in terms of academic achievement, content retention, and student satisfaction, prompted an investigation merging these two lines of research. Although PSI is more feasible today based on advances in technology and students prefer its self-paced component, they often procrastinate. In fact, this problem is resurfacing in distance education courses and is reflected in low completion rates as well as in the number of nonstarters. Numerous researchers have used deadline contingencies to reduce procrastination without adversely affecting student achievement and satisfaction, but few have considered the benefit of enhanced memory. It was hypothesized that, by providing students with CoD, a lesser form of self-pacing, and by using contingencies to regulate the pace of assignment submissions, procrastination would be reduced and content retention subsequently increased without detriment to immediate achievement and student satisfaction. To quantify differences in procrastination level, a comprehensive, sensitive, and reliable measure of procrastination, called the rate of relative digression from a target response (RDTR), was proposed. Undergraduate, preservice teachers in an instructional technology course were randomly assigned to one of three treatments. All groups were given the same deadlines. For one treatment, the deadlines were recommended (R) with one absolute deadline at the end of the treatment interval. For another they were conditional (C) with opportunities to earn bonus and penalty points for early and late work. For a third, they were all absolute (A) with no assignment accepted for credit after its due date. Although many problems experienced by students in A made findings for this group inconclusive, analysis of differences between students in R and C indicated that C was superior in reducing procrastination and enhancing memory function without detriment to immediate achievement, pacing preference, and course satisfaction. Although more research is needed to replicate, extend, and clarify findings, these results support using conditional deadlines for assignments when learners are supplied CoD.

Fathers play a major role in their son’s lives. From teaching them how to play football to having the birds and the bees talk with them. Statistics show that a son is greatly affected by whether his father is around or not. So that leaves the question of are girls just as affected as boys are by a father’s presence? For example, what did Mulan, the movie character, have in her life that some girls do not? A rare, yet healthy bond with her father could be the very factor that affected her attitude, values, and beliefs tremendously. The Social Learning Theory and nature versus nurture ideology are used to explain how this factor could be the very difference in her overall development. Briefly discussed is the Social Learning Theory, nature versus nurture ideology, Chinese culture, Mulan’s relationship with her father and how it correlates with Mulan’s overall development.

Die akute Graft-versus-Host-Krankheit (GvHD) ist eine der Hauptkomplikationen nach einer allogenen hämatopoetischen Stammzelltransplantation, die die Effizienz der Therapie und deren Einsatz limitiert. Aktuelle Präventionsstrategien und Therapien beinhalten systemisch wirkende Immunsuppressiva. Diese haben oft zahlreiche Nebenwirkungen und erhöhen die Rate von Tumorrezidiven und schweren Infektionen. Therapierefraktäre Verläufe der GvHD sind häufig und können mit einer schlechten Prognose vergesellschaftet sein. Neuartige Präventions- und Behandlungsansätze sind daher Gegenstand intensiver Forschung. Eine zentrale Rolle in der Pathogenese der akuten GvHD spielen CD4+ T Zellen. Alloreaktive T Zellen vermitteln eine proinflammatorische Immunantwort, produzieren entsprechende Zytokine und aktivieren weitere Effektorzellen. Diese Immunkaskade induziert eine systemische Entzündungsreaktion und führt zu Organ- und Gewebsschädigung. Der spezifischen Modulation dieser alloreaktiven CD4+ T Zellen hin zu einer Toleranzentwicklung gegenüber dem Empfängergewebe wird eine große Bedeutung in der Entwicklung innovativer GvHD-Präventionsstrategien beigemessen. Es konnte in murinen Modellen gezeigt werden, dass die ex vivo-Behandlung eines allogenen bzw. xenogenen Transplantats mit dem CD4-gerichteten nicht-depletierenden Antikörper MAX.16H5 zu einer verminderten GvH-Reaktion führte. Eine Beeinträchtigung des Graft-versus-Leukämie-Effekts war nicht nachweisbar. Toleranzinduktionen durch monoklonale Antikörper gegen Oberflächenrezeptoren von Immunzellen im Rahmen von Autoimmunerkrankungen und GvHD werden in zahlreichen Studien untersucht. Darüber hinaus ist bekannt, dass in der GvHD-Pathogenese bestimmte microRNAs, 17 bis 25 Nukleotide lange, nicht kodierende, einzelsträngige RNA-Moleküle, eine Schlüsselrolle spielen. Die molekularen Mechanismen, die der Toleranzentwicklung des MAX.16H5 Antikörpers zugrunde liegen, sind jedoch nicht abschließend geklärt. Daher war es Ziel der vorliegenden Doktorarbeit (i) ein in vitro Stimulationsmodell für weitergehende Untersuchungen am MAX.16H5 Antikörper zu etablieren und (ii) durch Quantifizierung der microRNA-Expression unter T Zellstimulierung zur Aufklärung von molekularen Mechanismen der Toleranzinduktion des Antikörpers beizutragen. Das etablierte in vitro Stimulationsmodell diente zur Analyse und Phänotypisierung von CD4+ T Zellen nach Antikörperinkubation und Stimulation. Es konnte gezeigt werden, dass eine MAX.16H5-Behandlung zu einer verminderten Aktivierung (CD25-Expression) von T Zellen nach 24 h und 72 h in Kokultur mit murinen Milzzellen bei einem 10:1 bzw. 8,2:1 Verhältnis (humane CD4+ T Zellen zu murinen Milzzellen) führte. Dieses Modell kann als Grundlage für weitere in vitro Studien dienen, um Prozesse der Toleranzinduktion durch monoklonale Antikörper zu untersuchen, und liefert einen wichtigen Beitrag für die präklinische Analyse des MAX.16H5 Antikörpers im Hinblick auf die Entwicklung funktioneller Tests. Weiterhin wurde in dieser Arbeit die Expression von microRNAs in CD4+ T Zellen nach Bindung des MAX.16H5 Antikörpers untersucht. Hierzu wurden humane CD4+ T Zellen mit dem MAX.16H5 Antikörper behandelt und (i) ohne Stimulation, (ii) mit murinen Milzzellen bzw. (iii) mit Phytohämagglutinin inkubiert. Das microRNA-Expressionsprofil wurde mit Next Generation Sequencing bestimmt. In dieser Screeninganalyse wurden zahlreiche microRNAs gefunden, die unter den verschiedenen Stimulationsbedingungen nach MAX.16H5-Inkubation differentiell exprimiert waren. Die Expression der miR-18a-3p und miR-598-3p wurde anschließend mit qPCR näher untersucht. Eine statistisch signifikante Regulation konnte für miR-598-3p nach 72 h Inkubation nachgewiesen werden. Es ist der bisher einzige Hinweis auf einen molekularen Effekt der MAX.16H5-Behandlung auf CD4+ T Zellen. Ob dieser Unterschied funktioneller Natur, im Sinne eines Toleranz-induzierenden Phänotyps ist, werden zukünftige Studien zeigen. Zudem wird aktuell die miR-598-3p als potenzieller Biomarker für den Nachweis einer erfolgreichen Inkubation mit MAX.16H5 untersucht, was für zukünftige klinische Studien von großer Wichtigkeit ist.:1. Einleitung 1 1.1 Literaturübersicht 1 1.1.1 Die hämatopoetische Stammzelltransplantation 1 1.1.2 Die allogene Stammzelltransplantation 2 1.1.3 Die Graft-versus-Host-Krankheit 5 1.1.4 Die Prävention und Behandlung der akuten GvHD 8 1.1.5 Neue Strategien zur GvHD-Behandlung und -Prävention 10 1.1.6 Der Graft-versus-Leukämie-Effekt 13 1.1.7 Der CD4-gerichtete MAX.16H5 Antikörper zur Prävention der GvHD 14 1.1.8 Die Toleranzinduktion durch monoklonale Antikörper 16 1.1.9 Die microRNA 19 1.1.10 Die Rolle von miRNAs in der GvHD 20 1.1.11 Die Rationale für die Untersuchung von miR-18a-3p 21 1.1.12 Die Rationale für die Untersuchung von miR-598-3p 22 2 Fragestellung und Experimentdesign 23 3 Material und Methoden 25 3.1 Materialien 25 3.1.1 Verwendete Zellen 25 3.1.2 Geräte 25 3.1.3 Chemikalien, Medien und Reagenzien 26 3.1.4 Verbrauchsmaterialien 27 3.1.5 Oligonukleotide 28 3.1.6 Antikörper 28 3.1.6.1 Antikörper für Durchflusszytometrie 28 3.1.6.2 Antikörper für Zellinkubation 29 3.2 Methoden 29 3.2.1 Schematische Darstellung der methodischen Arbeitsschritte 29 3.2.2 Zellkulturarbeiten 31 3.2.2.1 Auftauen von Zellen 31 3.2.2.2 Konservierung von Zellen 31 3.2.2.3 Bestimmung der Zellzahl von PBMCs und Splenozyten 32 3.2.3 Isolation humaner PBMCs aus Spenderblut 32 3.2.4 Isolation muriner Milzzellen 33 3.2.5 Isolation humaner CD4+ T Zellen und MACS-Separation humaner und muriner Zellen 33 3.2.6 Inkubation mit dem murinem MAX.16H5 IgG1 Antikörper 35 3.2.7 Inkubation humaner CD4+ T Zellen 35 3.2.8 Durchflusszytometrie 36 3.2.9 RNA-Isolation 37 3.2.10 RNA-Fällung 38 3.2.11 Next Generation Sequencing von miRNAs 38 3.2.12 Next Generation Sequencing – Analyseschema 41 3.2.13 Reverse Transkription und qPCR 41 3.2.13.1 Reverse Transkription 42 3.2.13.2 qPCR 43 3.2.14 Statistische Analyse, Tabellen und Abbildungen 44 4. Ergebnisse 46 4.1 Etablierung eines in vitro Stimulationsmodells zur Analyse humaner CD4+ T Zellen nach Antikörperinkubation 46 4.2 Next Generation Sequencing zur miRNA-Expressionsanalyse in CD4+ T Zellen nach MAX.16H5 IgG1-Inkubation 50 4.2.1 FACS-Analyse isolierter CD4+ T Zellen vor und nach Antikörperinkubation 50 4.2.2 Separation muriner Milzzellen von humanen CD4+ T Zellen 53 4.2.3 NGS-miRNA-Expressionsanalyse in stimulierten und unstimulierten CD4+ T Zellen nach 72 h Inkubation 55 4.2.3.1 MiRNA-Expression nach MAX.16H5 IgG1-Inkubation und PHA-Stimulation 57 4.2.3.2 MiRNA-Expression nach MAX.16H5 IgG1-Inkubation und Stimulation mit murinen Milzzellen 59 4.2.3.3 MiRNA-Expression nach MAX.16H5 IgG1-Inkubation und ohne Stimulation 61 4.2.4 Zusammenfassung der Ergebnisse der NGS-Analyse 63 4.3 FACS-Analyse von CD4+ T Zellen nach 24 h und 72 h Inkubation 64 4.3.1 FACS-Analyse von CD4+ T Zellen nach 24 h Inkubation 64 4.3.2 FACS-Analyse von CD4+ T Zellen nach 72 h Inkubation 67 4.4 Validierung der Kandidaten-miRNA mittels qPCR 72 4.4.1 Expression von miR-18a-3p und miR-598-3p nach MAX.16H5 IgG1-Inkubation in CD4+ T Zellen nach 72 h 72 4.4.1.1 FACS-Analyse isolierter CD4+ T Zellen vor und nach Antikörperinkubation 72 4.4.1.2 FACS-Analyse der CD4+ T Zellen nach 72 h Inkubation 74 4.4.1.3 Separation muriner Milzzellen von humanen CD4+ T Zellen 78 4.4.1.4 Expression von miR-18a-3p und miR-598-3p 80 5. Diskussion 85 5.1 Die Expression von miR-18a-3p und der miR-17–92 Cluster 86 5.2 Die Expression von miR-598-3p 88 5.3 Die Differentielle Expression weiterer miRNAs 90 5.3.1 miR-223 90 5.3.2 Let-7d 91 5.3.3 miR-21 91 5.3.4 miR-181c 91 5.3.5 miR-10a 92 5.3.6 miR-150 92 5.3.7 miR-199a 92 5.3.8 miR-155 93 5.4 Die miRNA-Expressionsanalyse mit Next Generation Sequencing 93 5.5 Die Etablierung eines in vitro Stimulationsmodells 96 5.6 Verminderte T Zell-Aktivierung durch MAX.16H5 IgG1 98 6 Zusammenfassung der Arbeit 101 7 Literaturverzeichnis 104 A Erklärung über die eigenständige Abfassung der Arbeit 129 B Erklärung über die Vorbehaltlichkeit der Verfahrenseröffnung zur Verleihung des Titels Dr. med. 130 C Darstellung des wissenschaftlichen Werdegangs 131 D Danksagung 133