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Epithelial cells are the first line of defense against invading pathogens and external threats in the environment. Keratinocytes, often not perceived of as immune cells, release cytokines in response to infection or injury to signal danger to neighboring cells and recruit effector leukocytes to prevent further damage to the host. IL-1 and IL-36 cytokines are a group of closely related proteins that share similarities in structure and function and have been shown to play key roles in inflammatory responses of epithelial tissues. While IL-1, consisting of IL-1α and IL-1β, have been widely studied and recognized as pinnacle cytokines in a variety of inflammatory responses, relatively little is understood about IL-36 cytokines since their discovery more than 15 years ago, and how they differ from their better-known IL-1 relatives. IL-36 cytokines, consisting of IL-36α, IL-36β, and IL-36γ, signal through the same receptor, IL-36R, which is expressed most abundantly on epithelial cells. IL-36 proteins garnered attention when it was discovered that a missense mutation in the gene encoding the naturally occurring receptor antagonist, IL-36Ra, was associated with the deadly form of psoriasis, generalized pustular psoriasis (GPP). This disease is characterized by episodic flares of keratinocyte hyperproliferation leading to red scaly lesions all over the body, excessive neutrophil recruitment to the epidermis resulting in pustule formation, and severe fever. Our data presented here demonstrate that IL-36α, but not IL-36β or IL-36γ is critical for the psoriatic phenotype, including epidermal thickening and neutrophil recruitment, generated during a murine model of psoriasis induced by the drug Imiquimod. Furthermore, IL-36α was found to induce IL-1α expression and vice versa through a signaling feedback loop which perpetuated disease. These data provide insight into mechanisms whereby IL-36 signaling can lead to excessive inflammatory effects in patients with pre-existing regulation deficiencies, which can lead to acute flares of disease. Beyond their association with disease, IL-1 has been shown to contribute to anti-bacterial and anti-viral responses of the immune system by upregulating inflammatory signals and chemoattractants. Herpes Simplex Virus-1 (HSV-1) is a human pathogen that has developed several strategies to manipulate elements of the immune system to avoid detection by the host. One such mechanism is the prevention of activation and release of IL-1β from infected cells thereby blocking its pro-inflammatory responses. Our data show that keratinocytes infected with HSV-1 actively release IL-1α to alert danger to neighboring cells to circumvent this blockage of IL-1β signaling. This release of IL-1α initiates recruitment of leukocytes to early HSV-1 microinfection sites resulting in increased protection against disease, as evident by the increased mortality rate of mice deficient in the IL-1 receptor, IL-1R1. This study, for the first time in vivo, demonstrates the ability of IL-1α to act as an alarmin to initiate an immune response to combat infection. The role of IL-36 cytokines during viral infections has been less defined than that of IL-1. Several studies have shown the upregulation of IL-36 expression during viral infections in epithelial tissues, such as HSV-1 and Influenza, yet a direct link has not been established between these proteins and anti-viral responses. Our research presented within this thesis show that IL-36β, but not IL-36α nor IL-36γ, provides protection against the lethal outcome of cutaneous HSV-1 infection, as demonstrated by IL-36β knockout mice dying earlier and more often than wild type mice. Surprisingly, while previous reports have found IL-36 cytokines to be capable of activating the adaptive immune system, our results found no significant differences in development of HSV-1 specific antibodies or CD8+ T cell development between wild type and IL-36β knockout mice. Furthermore, we found no significant differences in viral copy numbers at infection sites between the two groups. Although our data show that IL-36β clearly plays a critical role in controlling the outcome of HSV-1 infection, further studies are necessary to define the mechanisms behind this protection. The final section of this thesis focuses on the endogenous nature of IL-36 cytokines, specifically IL-36γ, and their potential processing. IL-36 cytokines were originally believed to be synthesized as full-length fully active proteins; however, large concentrations of the recombinant proteins were required to elicit cellular responses in vitro. Since then, studies have shown that IL-36 cytokines gained up to 1000-fold increases in reactivity following processing at very specific N-terminal locations of each individual cytokine, however this processing has never been shown to occur in vivo. These studies were recently expanded when neutrophil proteases were found to be responsible for processing of these proteins in vitro. Data presented here show, for the first time, that IL-36γ may be endogenously processed by neutrophils in wounded murine skin in vivo, yet, the amino acid processing site appears to be different from that predicted. Although further studies are required to fully characterize the nature of this processing, these data provide valuable insight into the natural mechanisms involved in the potential activation of these cytokines. Taken together, the research presented within this thesis sheds light on the mechanisms whereby IL-1 and IL-36 cytokines enhance immunological defenses against potential threats, and yet, can contribute to disease if unregulated. Furthermore, these studies demonstrate the evolutionary advantage of producing multiple cytokines that appear to have redundant roles within the body, yet can provide multiple levels of protection to the host. This knowledge contributes to our overall understanding of these proteins and their contribution to immunological systems within the body. / Microbiology and Immunology

IL-36 gamma is a proinflamatory cytokine which belongs to the IL-1 family of cytokines. It is expressed in the skin and by epithelial cells (ECs) lining lung and gut tissue. We used human 3-D organotypic cells, that recapitulate either in vivo human vaginal or cervical tissue, to explore the possible role of IL-36 gamma in host defense against pathogens in the human female reproductive tract (FRT). EC were exposed to compounds derived from virus or bacterial sources and induction and regulation of IL-36 gamma and its receptor was determined. Polyinosinic-polycytidylic acid (poly I:C), flagellin, and synthetic lipoprotein (FSL-1) significantly induced expression of IL-36 gamma in a dose-dependent manner, and appeared to be TLR-dependent. Recombinant IL-36 gamma treatment resulted in self amplification of IL-36 gamma and its receptor (IL-36R) via increased gene expression, and promoted other inflammatory signaling pathways. This is the first report to demonstrate that the IL-36 receptor and IL-36 gamma are present in the human FRT EC and that they are differentially induced by microbial products at this site. We conclude that IL-36 gamma is a driver for epithelial and immune activation following microbial insult and, as such, may play a critical role in host defense in the FRT.

久米村是十四至十五世紀琉球地方向明國朝貢初期移住那霸的福建人－「閩人三十六姓」－所形成的聚落。久米村人對琉球王國外交、文化、思想、信仰有深遠的影響。本論文以時間為縱軸，以民族集團客觀特徵的姓名、語言、信仰、主觀認同意識為橫軸，探討閩人三十六姓自十四世紀末移住琉球那霸久米村之後至今600年之間，在琉球‧沖繩社會脈絡下改變的過程和因應機制，以及客觀文化特徵與主觀認同意識的相互關係。 論文除「緒論」、「結論」外，本論有六章，第一章「久米村人的形成」，寫久米村人的人來源、社會組織、現況，和久米村的地理位置。第二章「久米村人的職業」，重點在描述久米村人在封貢體系中擔任外交官重要角色的實態。第三章「久米村的姓名」，探討久米村人的命名制度及其因時代所起的變化。第四章「久米村人的語言」，析論久米村人閩南話、漢語官話、琉球語及日語之使用與變遷。第五章「久米村人的宗教信仰」，研析久米村人之祖先崇拜、天妃信仰，以及琉球民間信仰與日本民間信仰對久米村人信仰的影響。三、四、五章並分別就姓名、語言、信仰之客觀的文化特徵，探討其作為久米村人民族邊界的有效性。第六章「久米村人的認定與認同」，敘述琉球王國的身分認定制度，並析論此一制度對久米村人主觀認同的影響。 關鍵詞：沖繩 閩人三十六姓 認定 認同 / Kume Village was initially formed by 36 Fujian clans in the 14th Century when the Ryukyu Islands became one of the tributaries to the Ming Empire of China. Kume Villagers had a great influence on the Ryukyu Kingdom in diplomacy, culture, thought, and belief perspectives. The tenets of this dissertation focus on the development of the people of Kume Village; their careers, the evolution of their languages, their system of assigning names to individuals, and how they related first to China, then later to the Okinawa Kingdom, Japan, and how they were perceived by Okinawans throughout this time. The dissertation consists of six chapters. The first chapter, "The Kume Village", writes where Kume villagers come from originally, its past and present social organization, and the Kume Village geographical position. The second chapter, "The Kume Villagers’ Social Niche", mainly describes the important role Kume villagers play in the tribute system as diplomats. The third chapter, "The Naming of a Kume Villager", discusses the Kume Villagers naming system and its evolution. The fourth chapter "The Kume Villager’s Language” analyzes these 4 languages: Southern Fujian, Chinese Mandarin, Ryukyu Islands, and Japanese as they are imported and integrated by the Kume community. The fifth chapter, "The Kume Villagers Religious Beliefs", analyzes the Kume Villagers worship of ancestors, Tian Fei beliefs, as well as how the Ryukyu Islands folklores and the Japanese folklores influenced Kume Villagers. The third, fourth, and fifth chapters test the validity of name, language, and general belief mores as robust ethnic boundaries. The sixth chapter, "Caste-assignment and Social Identity", narrates the establishment of distinct castes and government relegation of the Kume Villagers into an elite class and analyzes how this policy influenced Kume Villagers. Applying time and several ethnic features as its frames of reference, this dissertation debates in detail the development of the culture of Kume Villagers parallel to and as the result of their interaction with Okinawa society in the last 600 years. Keywords：Okinawa, 36 Fujian clans, Chinese overseas, Identity

2005 implementerades de nya regleringar för hur företag som använder IFRS som regelverk ska hantera goodwillposten. Tidigare linjära avskrivningar förbjöds och ersattes av en årlig prövning av goodwillvärdet för att se ifall nedskrivningsbehov förelåg. Regelverket infördes för att öka jämförbarheten företag emellan och för att minska väsentligheten på den svårbehandlade och ofta resurskrävande posten. Dessa svårigheter öppnar upp för subjektivitet i behandlandet av goodwill som ger företagsledningar möjlighet att manipulera redovisningen för egen vinning. Utifrån tidigare forskning har en teoretisk referensram tagits fram och utifrån denna har frågeställning och hypoteser arbetats fram. Studien inriktar sig och fokuserar på faktorerna kapitalstruktur och företagsstorlek. Undersökningen genomfördes med hjälp av ett systematiskt slumpmässigt urval över Nasdaq OMX Stockholm, med ett totalt urval på 50 företag. Årsredovisningar studerades för att ta fram nyckeltal som sedan beräknades och sattes in i statistiska tester för att besvara ställda hypoteser. Resultatet visar att utifrån observationer av skillnader mellan bolag som skriver ned goodwill kontra inte, kan ställda hypoteser bekräftas då empirin står i relation med teorin. Detta kan dock inte bekräftas genom statistiska tester, där en för svag signifikans uppstår. Faktorer som kapitalstruktur och företagsstorlek indikerar därför utifrån observationer, att ligga till grund för hur nedskrivningar av goodwill genomförs. Detta för att exempelvis kunna påverka resultatet och på så sätt kunna ge fördelar för företaget. Studiens resultat visar på att det subjektiva utrymmet i goodwillhanteringen existerar, vilket medför att det kan finnas anledning att tro att goodwillposten i vissa företag kan vara övervärderad. / In 2005, the new regulations were implemented for how companies using IFRS as a regulatory framework should handle the corporate goodwill. Previous straight-lined depreciation was banned and replaced by an annual review of the goodwill value to see if there was any need for impairment. The rules were introduced to increase comparability between companies and to reduce the importance of the difficult and often resource demanding section. These difficulties open for subjectivity in the treatment of goodwill that allows management to manipulate the accounting for their own gain. Based on previous research, a theoretical framework has been developed and from this the framed questions and hypotheses have been worked out. The study focuses on the factors capital structure and company size. The survey was conducted using a systematic random selection of Nasdaq OMX Stockholm, with a total selection of 50 companies. Annual reports were studied to produce key performance indicators which later were calculated and included in statistical tests to answer the hypotheses. The result shows that based on observations of differences between companies that makes a goodwill impairment versus not, assumed hypotheses can be confirmed as the empiricism is in relation to the theories. However, this can’t be confirmed by statistical tests, which is too weak of significance level. Factors such as capital structure and company size indicate therefore, based on observations, the basis for the goodwill impairment. This, for example, to influence the result to give benefits to the company. The study shows that the subjective space in goodwill management exists, which means there may be reason to believe that companies goodwill may be overvalued.

As the age increases, the physical fitness of seniors decreases. This shows the fragility of their body. Managing everyday activities becomes increasingly more difficult for them. Result of this is reduced self-sufficiency of the seniors, which leads to reduced mobility and to the greater loss of muscle mass and higher dependence on professional care. Aging is accompanied by loss of muscle mass and muscle strength - sarcopenia. This is one of the main causes of geriatric fragility. Sarcopenia presents a serious health problem with both social and economic consequences. The term sarcopenia (from Greek words sarx - meaning flesh referring to muscle and penia - loss) was first used in 1989 by Irwin Rosenberg to describe the loss of muscle mass accompanying aging. Exactly defining the term sarcopenia has helped explain this gradual loss of muscle mass. Three objectives were set in the thesis. The first objective was to find out whether sarcopenia reduces the quality of life in the elderly. The second goal was to determine, which quality of life tests are suitable for testing sarcopenia and the last one was whether the SARC - F questionnaire predicts sarcopenia.Quantitative research was used for the empirical part of this work. Data collection was performed using a method of a questionnaire. These were standardized questionnaires aimed at assessing sarcopenia and quality of life. The research was carried out with a total of 77 respondents with sarcopenia and respondents without sarcopenia. The quantitative part of the research was statistically processed using the MS Excel computer program.

Made available in DSpace on 2016-08-10T10:54:52Z (GMT). No. of bitstreams: 1 LUCIANO FERREIRA FREITAS.pdf: 1085209 bytes, checksum: 8cb6cea15bb3c1928d3054d4967c8bf7 (MD5) Previous issue date: 2015-10-02 / This study aims to evaluate the quality of life as well as the relationship of this with the socioeconomic and demographic profile and the length of service of workers motorcycle taxi drivers in the city of Aparecida de Goiânia-GO. For this, we carried out an analytical study of the quantitative cross-sectional with a sample of 133 male motorcycle taxi drivers. To check the profile of these workers, a sociodemographic questionnaire and the socioeconomic questionnaire was applied, Criteria of Economic Classification Brazil (CCEB). To assess quality of life, the WHO Quality of Life (WHOQOL-BREF) questionnaire and the Short Form Health Survey (SF-36) were used. Regarding sociodemographic profiles, there was a predominance of workers, married (53.4%), with up to two children (78.9%), aged 18-40 years old (56.4%), primary school education(64 7%), between one and five years of professional practice (57.9%), and belonging to the C economic class (66.2%). Concerning quality of life, WHOQOL-Bref, it was found that the domain "environment" (52.09) and the domain "social relations" (68.23) were the ones with lowest score and the best scores obtained were in "physical" domain (74.89) and "psychological" (70.52). In the SF-36, the domain "pain" (49.59) is the most negative impact on the quality of life of these professionals and the domain "functional capacity" (81.17) was the one who got the best score. Comparing the demographic data and the length of service with the quality of life WHOQOL-Bref, significant differences in the field "environment" (p = 0.029), indicating that the group with the lowest function of time had worse quality of life that the group with greater seniority. In the SF-36, there was a significant difference in the fields "vitality" (p = 0.025) and "mental health" (p = 0.005) relative to the variable "marital status" in which the married participants had better quality of life in these areas. There was also a significant difference on "vitality" (p = 0.029) relative to the variable "age in years", indicating that the age group up to 40 years had worse quality of life compared to the older group. Compared to the variable "schooling" there was significant difference in the field "general health" (p = 0.047) in those with primary education had a poorer quality of life to those with high school. There was a significant difference in the field "vitality" (p = 0.020) compared to the variable "function of time" in which the group with the shortest time had worse quality of life compared to the older group. When comparing the WHOQOL-Bref with socioeconomic data for all economic classes, the highest score was the "physical" domain and the lowest was in the field "environment." In the analysis of the areas of the SF-36 compared to the socioeconomic data, significant differences were found in the domain "pain" (p = 0.005), indicating the participants in classes D and E with worse quality of life compared to the B and C classes. This study has highlighted the need to implement strategies for improving the quality of life of this class of workers. / Este trabalho tem por objetivo avaliar a qualidade de vida, bem como as relações dessa com o perfil socioeconômico e sociodemográfico e o tempo de serviço dos trabalhadores mototaxistas da cidade de Aparecida de Goiânia-GO. Para isso, foi realizado um estudo analítico do tipo transversal quantitativo com uma amostra de 133 mototaxistas do sexo masculino. Para verificar o perfil desses trabalhadores, foi aplicado um questionário sociodemográfico e o questionário socioeconômico, Critério de Classificação Econômica do Brasil (CCEB). Para avaliar a qualidade de vida desses mototaxistas, utilizaram-se dois instrumentos, o Whoqol-Bref e o SF-36. Quanto ao perfil sociodemográfico, verificou-se a predominância de trabalhadores, casados (53,4%), com até dois filhos (78,9%), faixa etária de 18 a 40 anos (56,4%), ensino fundamental (64,7%), entre um a cinco anos de exercício da profissão (57,9%), e pertencentes à classe econômica C (66,2%). Em relação à qualidade de vida, no Whoqol-Bref, o domínio meio ambiente (52,09) e relações sociais (68,23) foram os de menor escore e os melhores foram no domínio físico (74,89) e no psicológico (70,52). No SF-36, o domínio dor (49,59) é o que mais interfere negativamente na qualidade de vida desses profissionais e o domínio capacidade funcional (81,17) foi o que obteve o melhor escore. Na comparação entre os dados sociodemográficos e o tempo de serviço com a qualidade de vida do Whoqol-Bref, houve diferença significativa no domínio meio ambiente (p=0,029), indicando que o grupo com menor tempo de função teve pior qualidade de vida em relação ao grupo com maior tempo de serviço. No SF-36, houve uma diferença significativa nos domínios vitalidade (p=0,025) e saúde mental (p=0,005) em relação à variável estado civil , em que os participantes casados apresentaram melhor qualidade de vida nestes domínios. Houve uma diferença significativa também no domínio vitalidade (p=0,029) em relação à variável idade em anos , indicando que o grupo com idade até 40 anos teve pior qualidade de vida em relação ao grupo mais velho. Na comparação com a variável escolaridade , houve diferença significativa no domínio estado geral de saúde (p=0,047), em que aqueles com ensino fundamental apresentaram pior qualidade de vida aos que possuem ensino médio. Houve diferença significativa no domínio vitalidade (p=0,020) na comparação com a variável tempo de função , em que o grupo com menor tempo teve pior qualidade de vida em relação ao grupo mais antigo. Ao comparar o Whoqol-Bref com os dados socioeconômicos, para todas as classes econômicas, a maior pontuação foi no domínio físico e a menor foi no domínio meio ambiente . Na análise dos domínios do SF-36 em comparação com os dados socioeconômicos, houve diferença significativa no domínio dor (p=0,005) indicando os participantes das classes D e E com pior qualidade de vida em relação aos das classes B e C. Este estudo permitiu evidenciar a necessidade de implantar estratégias em prol da melhoria da qualidade de vida dessa classe de trabalhadores.