Dissertationen zum Thema „Pagents“

This dissertation explores the adaptation of traditionally objectified women's spaces, into an arena for leadership development, research which incorporates the development of culturally relevant mechanisms of leadership training within Indigenous societies. Cultural pageants offer a place for young women to become spokespersons on social justice issues, without the sexual objectification of entering beauty pageants. Such pageants also provide a glimpse of how cultural groups wish their national identity to be portrayed to the general public. Fifty years in the making, today's Native Nations cultural pageants have been decolonized to present images of young leaders, confident in their heritage, introducing themselves in their Native language, and committed to cultural continuity and sustainable Nations. This research examines a state-wide Alaska Native pageant, Miss World Eskimo Indian Olympics, from three perspectives: 1) The young women who develop culturally based leadership skills; 2) The community, who gains language and cultural, revitalization and maintenance role models; 3) And the general public, who gains a much needed positive representation of a contemporary Indigenous women. This study draws from interdisciplinary theories and research methodologies (including observation, in-depth interviews, questionnaires, surveys, and archival research) and follows the young women through to the contest at the national level, Miss Indian World, run annually in Albuquerque, through Gathering of Nations. The underlying hypothesis is that women use cultural pageants as a stepping stone to advance their cultural leadership. In doing so, they promote factors of community well-being affecting Indigenous communities, such as suicide prevention, substance abuse, and language and cultural revitalization.

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Universidade Estadual Paulista (UNESP)
O objetivo deste trabalho foi estudar através do exame Imunoistoquimico, a correlação entre alguns fatores Anatomopatológicos (tipo histológico e grau nuclear) e alguns fatores biológicos (receptores hormonais de estrógeno e de progesterona, proteína c-erbB-2 e proteína p53, no carcinoma de Paget da mama, doença rara e especial. No período entre Janeiro de 1980 a Dezembro de 1998 foram tratados no Instituto Brasileiro de Controle do Câncer, 6.303 casos de câncer de mama, deste total 98 casos foram diagnosticados como carcinoma de Paget, cuja incidência foi de 1,55%. Estudamos retrospectivamente 60 casos, sendo que 38 deles foram excluídos da análise, devido a limitação e escassez da amostra no material disponível, a idade das pacientes variou entre 26 e 84 anos, com média de 55,4 anos, as informações clínicas e terapêuticas foram obtidas dos prontuários das pacientes considerando, idade na época do diagnóstico, tamanho do tumor quando palpável, estadiamento clínico, e o tipo de cirurgia realizada. As amostras de tecido mamário foram recuperadas dos arquivos do Departamento de Anatomia Patológica do I.B.C.C. / MATTOSINHO. Após a revisão histológica, realizada por dois patologistas os casos foram classificados em quatro grupos: Grupo A- Doença de Paget (forma pura) n = 09 Grupo B- Doença de Paget + neoplasia ductal “in situ”, n = 12 Grupo C- Doença de Paget, neoplasia ductal invasora, n = 30 Grupo D- Doença de Paget + neoplasia ductal “in situ”+ neoplasia ductal invasora, n = 09. Entre as variáveis anatomopatológicas, o grupo C prevaleceu com 30 casos (50%). O grau nuclear (GN-II) predominou com 45 casos (75%). Em relação as variáveis biológicas o receptor de estrógeno negativo predominou com 41 casos (68,3%), seguido pelo receptor de progesterona negativo com 40 casos (66,7%), podemos dizer que...
The objective of this paper was to study the immunohistochemical efects of Paget’s disease, a rare and special carcinoma of the breast, by correlating anatomopathological (histological and nuclear grade) and biological (estrogen and progesterone hormonal receptors, c-erbB-2 protein and p53 protein) factors. Between January 1980 and December 1998, 6303 cases of breast cancer were treated at the Brazilian Institute of Cancer Control; 98 of these were diagnosed with Paget’s carcinoma, an incidence of 1.55%. We retrospectively studied 60 of these cases; 38 were excluded due to lack of available sample material. Patient age varied between 26 and 84 years (mean 55.4), clinical and therapeutic information were obtained from patient’s medical records considering age at time of diagnosis, tumor size when palpable, clinical stage, and type of surgery performed. Samples of breast tissue were retrieved the Anatomical Pathology Department, I.B.C.C. / MATTOSINHO. After histological review, by two different pathologists, they were classified into four groups: Group A- Paget’s disease (pure form) n = 09 Group B- Paget’s disease + “in situ” duct neoplasia n = 12 Group C- Paget’s disease, invasive duct neoplasia n = 30 Group D- Paget’s disease + “in situ” duct neoplasia + invasive duct neoplasia n = 09.Invasive duct neoplasia was the most prevalent anatomopathological variable (Group C, n = 30, 50%). Nuclear grade (GNII) was found in 45 cases (75%). In relation to the biological variables, the negative estrogen receptor was predominant with 41 cases (68.3%), followed by the negative progesterone receptor with 40 cases (66.7%); this correlation had good concordance by the Kappa test. The c-erbB-2 protein was positive in 53 cases (88.3%) and p53 was negative in 47 cases (78.3%). From these results, we concluded that there was no statistical... (Complete abstract click electronic address below)

Introducción y objetivos: La enfermedad ósea de Paget (EOP) puede cursar con hipoacusia. Con el objetivo de cuantificar, caracterizar, determinar los factores de riesgo de hipoacusia y analizar las posibles relaciones de la hipoacusia con los hallazgos tomográficos en un grupo de pacientes con EOP, se realiza el presente estudio. Métodos: Se realizó un estudio observacional, transversal del tipo casos y controles que incluyó una cohorte de 76 sujetos con diagnóstico de enfermedad ósea de Paget (EOP) en el grupo caso y un grupo control de 134 sujetos. Se analiza la información clínica, demográfica, audiométrica y radiológica, mediante una TC de hueso temporal, de los sujetos incluidos. Resultados: El análisis comparativo entre el grupo de sujetos con EOP y el grupo control determinó que el grupo caso presentaban un umbral medio auditivo mayor (39,51 dB) que en el grupo control (37,28 dB) (p=0,069) y que presentaba hipoacusia transmisiva con mayor frecuencia (22,76%) que el grupo control (12,05%) (p=0,0062). El análisis de los factores de riesgo de hipoacusia determinó que la afectación craneal en la gammagrafía ósea, la edad y la HTA entre otros, constituían factores de riesgo de mayor pérdida auditiva en EOP. El estudio tomográfico constató que los pacientes con EOP presentaban una menor densidad ósea en unidades Hounsfield (UH) en el peñasco del temporal respecto al grupo control. Así mismo se pudo observar que la densidad ósea en la cápsula ótica en pacientes con EOP se correlacionaba con el umbral auditivo tanto de vía aérea como de vía ósea (p<0,05) y que la presencia de un gap en la audiometría se correlacionaba con la afectación por hueso pagético del temporal. Conclusiones: - El 63,45% de los sujetos con enfermedad ósea de Paget (EOP) padecen hipoacusia, con un umbral auditivo medio de 39,51dB. - Los sujetos con enfermedad ósea de Paget (EOP) presentaron una pérdida auditiva más severa y con mayor frecuencia de tipo transmisivo que el grupo control. - Los sujetos con afectación de la calota craneal por EOP presentaron mayor pérdida auditiva que los sujetos sin afectación craneal. La afectación de la calota craneal por la EOP y la edad constituyeron factores de riesgo de hipoacusia. - En los sujetos con EOP el umbral auditivo tanto de vía aérea como ósea se relaciona con la disminución de densidad en la cápsula ótica.
Introduction and objectives: Paget’s disease of bone (PDB) may lead to hearing loss. The present study is conducted with the aim of measuring, characterizing, determining the risk factors for hearing loss and analyse the possible relation of hearing loss with tomography findings in a group of subjects with PDB. Methods: An observational, transversal, case-control study was conducted, a cohort of 76 subjects diagnosed of Paget’s disease of bone (PDB) in the case group and a control group of 134 subjects were included. Clinical, demographic, audiometric and tomographic data (by means of a CT scan study) were analysed. Results: The comparative analysis between the subjects in the PDB group and the control group found that the case group showed higher hearing thresholds (39,51dB) comparing with the control group (37,28 dB) (p=0,069) and presented a greater rate of conductive hearing loss (22,76%) than the control group (12,05%) (p=0,0062). The study of risk factors for hearing loss found that skull involvement in bone scintigraphy, age and high blood pressure were risk factors for higher hearing impairment in PDB. The CT scan data showed that subjects in the PDB group had lower temporal bone density (Hounsfield Units, HU) comparing with the control group. It was also found that the otic capsule bone density in the PDB group correlated with both the air and bone conduction hearing thresholds (p<0,05) and that the finding of an air-bone gap in the audiogram correlated with Paget’s disease temporal bone involvement. Conclusions: − The 63,45% of subjects with Paget’s disease of bone (PDB) suffer hearing loss with a hearing threshold of 39,51dB on average. − The subjects with PDB showed a deeper hearing loss and a higher proportion of conductive type than the control group. − The patients with PDB and skull involvement presented a more severe hearing loss compared with the subjects without skull involvement. Skull involvement and age were found to be risk factors for hearing loss. − In the PDB group both the air and bone conduction hearing thresholds correlated with the otic capsule bone density.

La malaltia òssia de Paget (MOP) es caracteritza per ser un trastorn crònic i focal del remodelat ossi que comporta a l’aparició de complicacions com deformitats òssies, artropatia i fractures. La MOP presenta una gran variabilitat en la seva distribució en funció de l’edat, gènere, ètnia i àrea geogràfica. Recents estudis han descrit canvis seculars pel que fa a la prevalença, incidència i gravetat al diagnòstic de la MOP, mostrant una disminució en les últimes dècades. La MOP es considera actualment una malaltia multifactorial amb participació de factors ambientals i genètics. El gen que ha mostrat major susceptibilitat és el Sequestosoma1 (SQSMT1), les mutacions descrites en ell no explicarien de manera completa la patogènia de la MOP. En l’actualitat, són escassos els estudis sobre variacions genètiques en els gens TNFRSF11B i TNFRSF11A associats a MOP clàssica així com l’existència d’interaccions genètiques entre els dos gens i el gen SQSMT1, que condueixi a un increment de risc de MOP i fins i tot que influeixen en el seu fenotip. Amb la finalitat d’investigar el patró de comportament clínic-epidemiològic com genètic de la MOP de la nostra població de baixa prevalença, ens plantegem els següents objectius. Els objectius es van centrar en avaluar canvis en l’evolució del percentatge de nous diagnòstics de la MOP durant el període 1970-2009 i descriure en aquests pacients diferències pel que fa a la severitat al diagnòstic. Així com analitzar la importància d’alteracions moleculars en el gen SQSTM1 i la presència de variacions al·lèliques en els gens TNFRSF11B i TNFRSF11A, tant en la susceptibilitat per al desenvolupament de la MOP com la influència en el seu fenotip. Pacients i Mètodes: Estudi descriptiu ambispectiu observacional de pacients procedents de l’Hospital de la Mar-Parc de Salut Mar (Barcelona), una àrea de baixa prevalença. Es van incloure 393 pacients, diagnosticats entre 1970 i 2009. L’estudi molecular es va dur a terme mitjançant el genotipatge de les 21 variants polimòrfiques per a l’estudi dels gens TNFRSF11B i TNFRSF11A, així com la seqüenciació de el gen SQSTM1 en una població de 200 pacients afectes de MOP i 200 controls hipernormales. Resultats: En l’estudi s’observa un descens progressiu del percentatge del nous diagnòstics de MOP en relació a la població de referència, entre 1994 i 2009, més marcat en el grup de ≥ de 65 anys. Així mateix, s’ha constatat que els pacients afectes de MOP presenten una disminució en l’activitat biològica de la malaltia, una menor extensió de la malaltia i una major edat de presentació al diagnòstic, en funció de l’any de naixement i any del diagnòstic. En contraposició, s’ha observat major severitat en el moment del diagnòstic en els pacients amb edats al diagnòstic de <45 anys i ≥75 anys. S’han identificat 5 factors independents de mal pronòstic al diagnòstic, que afavoriran pitjors desenllaços. Pel que podem concloure, que en el moment de diagnòstic de MOP, l’expressió de la malaltia és menys severa i esdevé de forma més tardana. Els resultats de l’estudi molecular destaquen l’associació significativa entre els SNPs rs3018362 i rs1805034 del gen TNFRSF11A i rs11573871 del gen TNFRSF11B amb l’increment de risc de desenvolupar MOP així com la influència en el seu fenotip. Així mateix es va observar que la presència de l’al·lel T en el polimorfisme rs6567274 del gen TNFRSF11A es va associar amb una disminució de risc de desenvolupar la MOP, així com a un fenotip més lleu. En l’estudi molecular del gen SQSTM1 es van identificar 6 variants genètiques “missense” de nova descripció, associades amb una major susceptibilitat de desenvolupament de la MOP.
La enfermedad ósea de Paget (EOP) se caracteriza por ser un trastorno crónico y focal del remodelado óseo que conlleva a la aparición de complicaciones como deformidades óseas, artropatía por vecindad y fracturas. La EOP presenta una gran variabilidad en su distribución en función de la edad, género, etnia y área geográfica. Recientes estudios han descrito cambios seculares en cuanto a la prevalencia, incidencia y gravedad al diagnóstico de la EOP, mostrando una disminución en las últimas décadas. La EOP se considera actualmente una enfermedad multifactorial con participación de factores ambientales y genéticos. El gen que ha mostrado mayor susceptibilidad es el Sequestosoma1(SQSMT1), las mutaciones descritas en él no explicarían de forma completa la patogenia de la EOP. En la actualidad, son escasos los estudios acerca de variaciones genéticas en los genes TNFRSF11B y TNFRSF11A asociados a EOP clásica así como la existencia de interacciones genéticas entre ambos genes y el gen SQSMT1, que conduzca a un incremento de riesgo de EOP e incluso que influya en el fenotipo. Con la finalidad de investigar el patrón de comportamiento clínico-epidemiológico como genético de la EOP de nuestra población de baja prevalencia, nos planteamos los siguientes objetivos. Los objetivos se centraron en evaluar cambios en la evolución del porcentaje de nuevos diagnósticos de EOP durante el periodo 1970-2009 y describir en dichos pacientes diferencias en cuanto a la severidad al diagnóstico. Así como así como analizar la importancia de alteraciones moleculares en el gen SQSTM1 y la presencia de variaciones alélicas en los genes TNFRSF11B y TNFRSF11A, tanto en la susceptibilidad para el desarrollo de la EOP como la influencia en su fenotipo. Pacientes y Métodos: Estudio descriptivo ambispectivo observacional de pacientes procedentes del Hospital del Mar-Parc de Salut Mar (Barcelona), un área de baja prevalencia. Se incluyeron 393 pacientes, diagnosticados entre 1970 y 2009. En base al estudio molecular se llevó a cabo el genotipado de las 21 variantes polimórfica para el estudio los genes TNFRSF11B y TNFRSF11A, así como la secuenciación del gen SQSTM1 en una población de 200 pacientes afectos de EOP y 200 controles hipernormales. Resultados: En el estudio se observa un descenso progresivo del porcentaje de nuevos diagnósticos de EOP en relación a la población de referencia, entre 1994 y 2009, más marcado en el grupo de ≥ de 65 años. Asimismo, se ha constatado que los pacientes afectos de EOP presentan una disminución en la actividad biológica de la enfermedad, una menor extensión de la enfermedad y una mayor edad de presentación al diagnóstico, en función del año de nacimiento y año del diagnóstico. En contraposición, se ha observado mayor severidad en el momento del diagnóstico en los pacientes con edades al diagnóstico de <45 años y ≥75 años. Se han identificado 5 factores independientes de mal pronóstico al diagnóstico, que van a favorecer peores desenlaces. Por lo que podemos concluir, que en el momento de diagnóstico de EOP, la expresión de la enfermedad es menos severa y acontece de forma más tardía. Los resultados del estudio molecular destacan la asociación significativa entre los SNPs rs3018362 y rs1805034 del gen TNFRSF11A y rs11573871 del gen TNFRSF11B con el incremento de riesgo a desarrollar EOP así como la influencia en su fenotipo. Asimismo se observó que la presencia del alelo T en el polimorfismo rs6567274 del gen TNFRSF11A se asoció con una disminución de riesgo a desarrollar la EOP, así como a un fenotipo más leve. En el estudio molecular del gen SQSTM1 se identificaron seis variantes genéticas "missense" de nueva descripción, asociadas todas ellas a una mayor susceptibilidad en el desarrollo de la EOP.
Paget’s Disease of Bone (PDB) is characterized by a chronic and focal disorder of bone remodeling that leads to the appearance of complications as bone deformities, osteoarthritis and fractures. The PDB presents a great variability in its distribution depending on the age, gender, ethnics and geographic area. Recent studies have described secular changes in the prevalence, incidence and severity at diagnosis of PDB, showing a decline in the last decades. PDB is currently considered a multifactorial disease involving environmental and genetic factors. The gene which has shown higher susceptibility is the Sequestosome-1 (SQSTM1), the mutations described in it would not be able to explain completely the PDB pathogenesis. Nowadays, there are few studies on genetic variations in the TNFRSF11B and TNFRSF11A genes associated with classic PDB, as well as the existence of genetic interactions between both genes and the SQSMT1 gene, leading to an increased risk of PDB or even influencing the phenotype. To investigate the pattern of clinical-epidemiological and genetic behavior of the PDB in our low prevalence population, we propose the following objectives. The objectives were focused on evaluating changes in the evolution of the percentage of new PDB diagnoses during the period 1970-2009 and to describing in those patients differences in terms of severity at diagnosis. As well as to analyze the importance of molecular alterations in the SQSTM1 gene and the presence of allelic variations in the TNFRSF11B and TNFRSF11A genes, both in the susceptibility for the development of PDB and its influence on the phenotype. Patients and Methods: Descriptive, ambispective observational study of patients from Hospital del Mar-Parc de Salut Mar (Barcelona), a low prevalence area. 393 patients, diagnosed between 1970 and 2009, were included. Based on the molecular study, the genotyping of the 21 polymorphic variants was carried out for the study of the TNFRSF11B and TNFRSF11A genes, as well as the sequencing of the SQSTM1 gene in a population of 200 PDB affected patients and 200 hypernormal controls. Results: The study observed a progressive decrease in the percentage of new PDB diagnoses in relation to the reference population, between 1994 and 2009, more marked in the group ≥65 years old group. Thereby, it has been confirmed that the PDB-affected patients show a decrease in the biological activity of the disease, a lower extension of the disease, and a higher age of presentation at diagnosis, depending on the year of birth and the year of diagnosis. In contrast, it has been observed higher severity at diagnosis in patients with ages at diagnosis <45 years and ≥75 years. Five independent factors of poor prognosis at diagnosis have been identified, which will favor worse outcomes. We can conclude, that at the time of diagnosis of PDB, the expression of the disease is less severe and occurs later. The results of the molecular study highlight the significant association between SNPs rs3018362 and rs1805034 of the TNFRSF11A gene and rs11573871 of the TNFRSF11B gene with the increased risk of developing PDB as well as the influence on its phenotype. Thereby, it was observed that the presence of the T allele in the polymorphism rs6567274 of the TNFRSF11A gene was associated with a decreased risk of developing PDB, as well as a milder phenotype. In the molecular study of the SQSTM1 gene, six newly described “missense” genetic variants were identified, all associated with greater susceptibility in the development of PDB.
Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina

Résumé : La maladie osseuse de Paget (MP) est un désordre squelettique caractérisé par une augmentation focale et désorganisée du remodelage osseux. Les ostéoclastes (OCs) de MP sont plus larges, actifs et nombreux, en plus d’être résistants à l’apoptose. Même si la cause précise de la MP demeure inconnue, des mutations du gène SQSTM1, codant pour la protéine p62, ont été décrites dans une proportion importante de patients avec MP. Parmi ces mutations, la substitution P392L est la plus fréquente, et la surexpression de p62P392L dans les OCs génère un phénotype pagétique partiel. La protéine p62 est impliquée dans de multiples processus, allant du contrôle de la signalisation NF-κB à l’autophagie. Dans les OCs humains, un complexe multiprotéique composé de p62 et des kinases PKCζ et PDK1 est formé en réponse à une stimulation par Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL), principale cytokine impliquée dans la formation et l'activation des OCs. Nous avons démontré que PKCζ est impliquée dans l’activation de NF-κB induite par RANKL dans les OCs, et dans son activation constitutive en présence de p62P392L. Nous avons également observé une augmentation de phosphorylation de Ser536 de p65 par PKCζ, qui est indépendante d’IκB et qui pourrait représenter une voie alternative d'activation de NF-κB en présence de la mutation de p62. Nous avons démontré que les niveaux de phosphorylation des régulateurs de survie ERK et Akt sont augmentés dans les OCs MP, et réduits suite à l'inhibition de PDK1. La phosphorylation des substrats de mTOR, 4EBP1 et la protéine régulatrice Raptor, a été évaluée, et une augmentation des deux a été observée dans les OCs pagétiques, et est régulée par l'inhibition de PDK1. Également, l'augmentation des niveaux de base de LC3II (associée aux structures autophagiques) observée dans les OCs pagétiques a été associée à un défaut de dégradation des autophagosomes, indépendante de la mutation p62P392L. Il existe aussi une réduction de sensibilité à l’induction de l'autophagie dépendante de PDK1. De plus, l’inhibition de PDK1 induit l’apoptose autant dans les OCs contrôles que pagétiques, et mène à une réduction significative de la résorption osseuse. La signalisation PDK1/Akt pourrait donc représenter un point de contrôle important dans l’activation des OCs pagétiques. Ces résultats démontrent l’importance de plusieurs kinases associées à p62 dans la sur-activation des OCs pagétiques, dont la signalisation converge vers une augmentation de leur survie et de leur fonction de résorption, et affecte également le processus autophagique.
Abstract : Paget’s disease of bone (PDB) is a skeletal disorder characterized by focal and disorganized increases in bone turnover. In PDB, osteoclasts are larger, more active, more numerous, and resistant to apoptotic stimuli. While no single root cause has been identified, mutations to the gene encoding the p62 protein, SQSTM1, have been described in a significant population of patients with PDB. Among these mutations, the P392L substitution is the most prevalent, and overexpression of p62P392L in osteoclasts generates at least a partial pagetic phenotype in vitro. Normally this protein mediates a number of cell functions, from control of NF-κB signaling to autophagy. In human osteoclasts, a multiprotein complex containing p62 and protein kinases PKCζ and PDK1 (the principal kinase of Akt), form in response to stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL), the principal osteoclastogenic-signaling cytokine. We found that PKCζ is involved in RANKL-induced activation of NF-κB, and that it contributed to a basal activation of NF-κB observed in p62P392L mutants. This may be regulated in part by a PKCζ dependent increase in p65 phosphorylation at Ser536 which we characterized, independent of IκB. This could represent one alternative pathway by which mutant p62 leads to increased NF-κB activation. We observed increased basal phosphorylation of survival regulators ERK and Akt in PDB that was reduced upon PDK1 inhibition. The activity of 4EBP1 and Raptor, associated with mTOR activity, were also altered in pagetic osteoclasts and regulated by PDK1 inhibition. We then identified autophagic defects common to pagetic osteoclasts; with higher basal levels of LC3II (associated with autophagic structures), regardless of p62 mutation, and reduced sensitivity to autophagy induction in PDB. These results suggest an accumulation of non-degradative autophagosomes. Inhibition of PDK1 not only induced apoptosis in PDB and controls, but significantly reduced resorption in PDB, and with regards to autophagy, PDK1 inhibition was more potent in PDB than in controls. Therefore PDK1/Akt signaling represents an important checkpoint to PDB osteoclast activation. In sum, these results demonstrate the importance of several p62-associated kinases in the over-activation of pagetic osteoclasts, through increased survival and altered signaling. As p62 mutations alone do not account for most cases of PDB, the characterization of these pathways may identify a common factor linking pagetic osteoclasts. Therefore these studies represent a novel approach to osteoclast apoptosis, activation, and autophagy associated with PDB.

Thesis (Ph.D.)--Tufts University, 2001.
Adviser: Barbara Freedman. Submitted to the Dept. of Drama. Includes bibliographical references (leaves 191-207). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

La maladie de Paget est une ostéopathie caractérisée par une augmentation multifocale du remodelage osseux, qui débute par un front de résorption osseuse, suivi d'une formation osseuse excessive, avec un remodelage anarchique et intense. Les ostéoclastes "OCs" impliqués dans la phase initiale sont les cellules responsables dans l'initiation du processus pagétique. Les OCs pagétiques sont caractérisés par une résistance à l'apoptose, et des anomalies du processus de l'autophagie "en particulier défaut d'induction"; afin de voir si ces deux caractéristiques étaient liées, nous avons émis l'hypothèse d’un rôle des complexes Bcl2-Beclin1. Beclin-1 est une protéine inductrice de l'autophagie qui peut lier les protéines anti-apoptotiques de la famille Bcl-2; Bcl-2 inhibe alors Beclin-1 "et donc l'induction de l'autophagie" en conservant ses fonctions anti-apoptotiques. Dans le but d'étudier l'impact de l'expression de Bcl2 sur l’autophagie dans les OCs humains, nous avons utilisé un modèle de différenciation in vitro à partir de monocytes dérivés de sang de cordon ombilical, cultivés en présence de RANKL et MCSF pendant 21 jours. Ces conditions permettent d'obtenir des cellules multinucléées au phénotype ostéoclastique. Pour augmenter l’expression de Bcl-2 dans les OCs et analyser son impact sur l’autophagie par interaction avec Beclin-1, les cultures ont été stimulées par TNFα ou RANKL dans le but d'induire une activation de NF-κB. L'expression de Beclin1 et Bcl2 a été confirmée par immunobuvardage dans les OCs. L’autophagie était induite dans les cultures réalisées en conditions stringentes "milieu pauvre en nutriments", sans variation de l'expression de Bcl2 ou Beclin 1 selon les conditions, et sans impact de TNFa ou RANKL. TNFa stimulait de manière significative l'activation de NF-kB dans les cellules HEK mais pas dans les OCs. Toutefois, et quelque soit les conditions, les immunoprécipitations ne permettaient pas de retrouver d'association entre Beclin1 et Bcl2. En revanche, le partenaire d'interaction classique de Beclin1, PI3K type III, était associé à Beclin1. En conclusion, notre travail n'a pas permis d'étudier la formation des complexes Beclin1/Bcl2 et les relations entre apoptose et autophagie, en partie du fait de la complexité du modèle "effets multiples de NF-kB et TNFa" ce qui n'exclut pas l'hypothèse initiale "à ré-évaluer par une méthodologie plus appropriée". En revanche les différentes techniques d'analyse sont maintenant au point pour la poursuite de l'étude.
Abstract : Paget's disease is an osteopathy characterized by a multifocal increase in bone remodeling, which begins with excessive bone resorption followed by increased bone formation. Osteoclasts "OCs" were incriminated in the initiation of the pagetic process. Pagetic OCs are characterized by a resistance to apoptosis, and abnormalities in the process of autophagy “in particular induction defect”. In order to define whether these two characteristics were linked, we hypothesized the role of Bcl2-Beclin1 complexes. Beclin-1 is an autophagy-inducing protein that can bind anti-apoptotic proteins of the Bcl-2 family; Bcl-2 then inhibits Beclin-1 "and thus the induction of autophagy" while retaining its anti-apoptotic functions. To study the impact of Bcl2 expression on autophagy in human OCs, we used an in vitro differentiation model that uses monocytes, which are derived from umbilical cord blood and grown in the presence of RANKL and MCSF for 21 days. These conditions make it possible to obtain multinucleated cells with an osteoclastic phenotype. To increase the expression of Bcl-2 in OCs and analyze its impact on autophagy due to its interaction with Beclin-1, cultures were stimulated with TNFα or RANKL in order to induce NF-κB activation. The expression of Beclin1 and Bcl2 was confirmed by immunoblotting of Ocs cell lysates. Autophagy was induced in cultures carried out under stringent conditions "nutriment-deprived mediun", but we did not observe any variation in the expression of Bcl2 or Beclin 1 according to the culture conditions or TNFα or RANKL stimulation. TNFα significantly stimulated the activation of NF-κB in HEK cells but not in OCs. However, whatever the conditions, results from immunoprecipitaion experiments did not reveal any association between Beclin1 and Bcl2. On the other hand, the classic interaction partner of Beclin1, PI3K type III, was associated with Beclin1. In conclusion, our work did not allow us to demonstrate the formation of Beclin1 / Bcl2 complexes and the relationship between apoptosis and autophagy, partly because of the complexity of the model "multiple effects of NF-κB and TNFα". Our initial hypothesis should thereby be re-evaluated using a more appropriate methodology. On the other hand, the different techniques are now ready for further study.

Thesis (Ed.D.)--Georgia Southern University, 2007.
"A dissertation submitted to the Graduate Faculty of Georgia Southern University in partial fulfillment of the requirements for the degree Doctor of Education." Curriculum Studies, under the direction of William M. Reynolds. ETD. Electronic version approved: December 2007. Includes bibliographical references (p. 208-228) and appendices.

University of Technology, Sydney.
The reenactment of the past itself has a history. This thesis analyses self-styled 'historical reenactors' in the West and traces the history of the broader phenomenon of historical reenactment in the Australian context from the late nineteenth century to the present. The historical section focuses on several events significant in Australian cultural memory that have been reenacted over time. Historical parades, pageants and reenactments dramatically narrate culturally specific historical sensibilities and demonstrate inter and cross cultural exchanges of historical consciousness. I contend such performances have had a significant position in the formation of popular history since the late nineteenth century and that there is a continuity of conventions in performing the past. I have addressed the position of reenactments as part of a constant interest in the status and power of history in, and for, popular culture. I have shown how a form of history that operated for the public was transformed into a form of history operated by the public in a struggle for authority over the form and content of history. Historical reenactments have been useful avenues for elites to create didactic spectacular history that have also offered the opportunity for marginalised groups to make social and political gains through their participation in the making of public history. Considering the significance of reenactments in the formation of a distinctly Australian public history, they have received little attention from historians. As ephemera, reenactments sit awkwardly in the explanatory frameworks regularly used by historians. Using methodologies from a range of academic disciplines such as performance studies, anthropology and cultural studies, this thesis documents and interrogates the specific form of historical reenactment. In the sections of this thesis that analyse contemporary historical reenactments, I use my own experience as an historical reenactor of more than ten years in an ethnographic approach that reflects on the pleasures, promises and problems 'dressing up as if from the past' offers. In this history I draw continuities between past reenactments and present practices that assist in understanding historical reenactment as a specific cultural form. This thesis contends that reenactments over time have been characterised by three main elements: a collapsing of past and present, an avenue for a 'connectedness' with the past through a sensual experience, and an essential relationship with I authenticity.'

Chapter 3 describes the results of mutation screening of a candidate gene, SQSTM1, from one of the linkage regions implicated in the pathogenesis of PDB in families of mainly British descent.  Seven mutations that segregated with the disease were identified and all clustered in the ubiquitin-associated (UBA) domain of the protein. In Chapter 4, an association study and haplotype analysis was conducted in PDB families using SNPs in SQSTM1.  This revealed that the most common SQSTM1 mutation was predominantly carried on one of two common haplotype backgrounds, suggesting that a strong founder effect exists in this population.  The P392L mutations occurred on the same haplotype background in sporadic cases as in the PDB families, indicating that many ‘sporadic’ PDB cases may have occult familial PDB. A syndrome of PDB associated with inclusion body myopathy and dementia has recently been shown to be caused by mutations that cluster in the CDC48 domain of the VCP gene.  In Chapter 5, the VCP gene was screened for mutations in familial PDB and an association study was conducted in patients with sporadic PDB.  No mutations in this gene were found in the PDB families.  Haplotype analysis of a region spanning this gene also failed to support the involvement of polymorphisms in this gene in determining risk of sporadic PDB. In Chapter 6, genome-wide linkage analysis was conducted in PDB families without SQSTM1 mutations.  This revealed significant evidence of linkage at a locus on chromosome 10p13 (PDB6).  All families involved in this analysis were found to have a high likelihood of linkage at this locus.

In Chapter 4, I investigated the roles of the RANK signalling partners RANK ligand (RANKL) and osteoprotegerin (OPG) in the pathogenesis of sporadic and familial PDB. One polymorphism in the RANK gene and five polymorphisms in the OPG gene were examined in sporadic PDB cases and in sex- and age-matched controls. No allele-disease or genotype-disease association was observed for the RANKL polymorphism, suggesting RANKL is not directly involved in susceptibility to sporadic PDB. Genotypes at two OPG polymorphisms did significantly predict disease status in individuals affected with sporadic PDB, suggesting a role for OPG in the pathogenesis of sporadic PDB. The five OPG polymorphisms were also examined in families affected with PDB. No evidence was found to either suggest or exclude the involvement of any of the OPG polymorphisms in familial PDB. In Chapter 5, I performed a genome-wide search for PDB susceptibility loci in families with inherited PDB. Three regions of potential linkage were identified at 2q36, 5q35 and 10p11. Fine mapping was performed for the candidate region on chromosome 5q35, and eight families with a high probability of linkage to 5q35 were identified. In seven of the families, a shared haplotype transmitted only with affected family members was present. The shared haplotype varied between families and no common allele existed in the seven families for any of the nine markers studied. However, one area of shared haplotype occurred in all seven families across three of the markers, supporting evidence for a susceptibility gene for PDB on 5q35 in these families and narrowing the candidate region. In summary, this study has further highlighted the importance of genetic heterogeneity in the pathogenesis of PDB, excluding the previously identified PDB2 susceptibility locus and identifying three novel regions potentially harbouring susceptibility loci in the families studied. This study has also further defined the role of members of the RANK signalling pathway in the pathogenesis of familial and sporadic PDB.

Paget's disease of the bone is a skeletal disorder of unknown cause. This disease is characterised by excessive and abnormal bone remodelling brought about by increased bone resorption followed by disorganised bone formation. Increased bone turnover results in a disorganised mosaic of woven and lamellar bone at affected skeletal sites. This produces bone that is expanded in size, less compact, more vascular, and more susceptible to deformity or fracture than normal bone. Symptoms of Paget's disease may include bone pain, bone deformity, excessive warmth over bone from hypervascularity, secondary arthritis, and a variety of neurologic complications caused in most instances by compression of the neural tissues adjacent to pagetic bone. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. The identification of the molecular basis of Paget's disease is fundamental for an understanding of the cause of the disease, for identifying subjects at risk at a preclinical stage, and for the development of more effective preventive and therapeutic strategies for the management of the condition. With this in mind, the aim of this project is to identify genetic loci, in a large pedigree, that may harbour genes responsible for Paget's disease of bone. A large Australian family with evidence of Paget's disease was recruited for these studies (Chapter 3). This pedigree has characterised over 250 individuals, with 49 informative individuals affected with Paget's disease of bone, 31 of whom are available for genotypic analysis. The pattern of disease in these individuals is polystotic, with sites of involvement including the spine, pelvis, skull and femur. Although the affected individuals have a severe early-onset form of the disease, the clinical features of the pedigree suggest that the affected family members have Paget's disease and not familial expansile osteolysis (a disease with some similarities to Paget's disease), as our patients have extensive skull and axial skeletal involvement. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Due to the large size of this family and multiple affected members, this pedigree is a unique resource for the detection of the susceptibility gene in Paget's disease. The first susceptibility loci for Paget's disease of bone have been mapped by other investigators to chromosome 6p21 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees. Linkage analysis of the Australian pedigree in these studies was performed with markers at PDB1: these data showed significant exclusion of linkage, with LOD scores < - 2 in this region (Chapter 4). Linkage analysis of microsatellite markers from the PDB2 region excluded linkage with this region also, with a 30 cM exclusion region (LOD score < -2.0) centred on D18S42 (Chapter 4). This locus on chromosome 18q21.1-q22 contains a serine protease (serpin) cluster with similarities to chromosome 6p21. Linkage analysis of this region also failed to provide evidence of linkage to this locus (Chapter 4). These data are consistent with genetic heterogeneity of Paget's disease of bone. A gene essential for osteoclast formation encoding receptor activator of nuclear factor-kB (RANK), TNFRSF11A, has been previously mapped to the PDB2 region. Mutations in the TNFRSF11A gene have been identified segregating in pedigrees with Familial Expansile Osteolysis and early onset familial Paget's disease, however, linkage studies and mutation screening have excluded the involvement of RANK in the majority of Paget's disease patients. For the Australian pedigree, mutation screening at the TNFRSF11A locus revealed no mutations segregating with affected individuals with Paget's disease (Chapter 4). Based on these findings, our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree; this gene should be identifiable using a microsatellite genome-wide scan followed by positional cloning. A genome-wide scan of the Australian pedigree was carried out, followed by fine mapping and multipoint analysis in regions of interest (Chapter 5). The peak 2-point LOD scores from the genome-wide scan were LOD = 2.75 at D7S507 and LOD = 1.76 at D18S70. Two additional regions were also considered for fine mapping: chromosome 19p11-q13.1 with a LOD of 1.58 and chromosome 5q35-qter with a LOD of 1.57. Multipoint and haplotype analysis of markers flanking D7S507 did not support linkage to this region (Chapter 5). Similarly, fine mapping of chromosome 19p11-q13.1 failed to support linkage to this region (Chapter 5). Linkage analysis with additional markers in the region on chromosome 5q35-qter revealed a peak multipoint LOD score of 6.77 (Chapter 5). A distinct haplotype was shown to segregate with all members of the family, except the offspring of III-5 and III-6. Haplotype analysis of markers flanking D18S70 demonstrated a haplotype segregating with Paget's disease in a large sub-pedigree (descendants of III-3 and III-4) (Chapter 5). This sub-pedigree had a significantly lower age at diagnosis than the rest of the pedigree (51.2 + 8.5 vs. 64.2 + 9.7 years, p = 0.0012). Linkage analysis of this sub-pedigree demonstrated a peak two-point LOD score of 4.23 at marker D18S1390 (q = 0.00), and a peak multipoint LOD score of 4.71, at marker D18S70. An implication of these data is that 18q23 harbours a novel modifier gene for reducing the age of onset of Paget's disease of bone. A number of candidate Paget's genes have previously been identified on chromosome 18q23, including the nuclear factor of activated T cells (NFATc1), membrane-associated guanylated kinase (MAGUK) and a zinc finger protein. Candidate gene sequencing of these genes in these studies has failed to identify mutations segregating with affected family members in the sub-pedigree linked to chromosome 18q23 (Chapter 6). More recently, a mutation in the gene encoding the ubiquitin-binding protein sequestosome 1 (SQSTM/p62) has been shown to segregate with affected members of Paget's disease families of French-Canadian origin. In this study, a single base pair deletion (1215delC) was identified as segregating with the majority of affected members in the pedigree (Chapter 6). This deletion introduces a stop codon at amino acid position 392 which potentially results in early termination of the protein and loss of the ubiquitin binding domain. The three affected members of the family that do not share the affected haplotype do not carry a mutation in the coding region of SQSTM/p62. Screening of affected members from 10 further Paget's disease families identified the previously reported P392L mutation in 2 (20%) families. No SQSTM1/p62 coding mutations have been found in the remaining 8 families or in 113 aged matched controls. In conclusion, this project has identified genetic loci and mutations that segregate with individuals affected with Paget's disease. Further investigation of the functional significance of the genetic changes at these loci is expected to lead to a better understanding of the molecular basis of this disease.

Mutations affecting the p62 signalling adapter protein are commonly found in patients with the skeletal disorder Paget‟s disease of bone (PDB). We have extended previous in vitro functional analyses of PDB-mutant p62 proteins (Cavey et al., 2006) to study the effects of several uncharacterised PDB-associated mutations on the ubiquitin-binding properties of p62. These include mutations which affect regions of p62 outside of the ubiquitin-binding UBA domain (A381V, D335E and a mutant equivalent to a predicted product of the G1205C splice-site mutation which lacks amino acids 351-388), as well as a double mutation involving the P392L and S399P changes on the same allele. In accordance with previous findings, both of the non-UBA domain mutations (A381V, ∆351-388) showed deleterious effects on ubiquitin-binding by p62 in pull-down assays, further emphasising the important role of non-UBA domain sequences in mediating ubiquitin-recognition, as well as in PDB aetiology. The D335E mutant retained its ubiquitin-binding function in vitro. The P392L/S399P double mutant showed a more severe effect on ubiquitin-binding than either of the single P392L or S399P missense mutations alone; as this double mutation is associated with a particularly severe phenotype, our findings are supportive of the proposal that disease severity in PDB with p62 mutations may be directly related to the effects of the mutations on the ubiquitin-binding function of the p62 protein. Since the in vitro pull-down assays are semi-quantitative at best, we sought to investigate if a more quantitative biophysical approach, two dimensional Heteronuclear Single Quantum Coherence (2D-HSQC) protein NMR, might be applied to investigate the effects of PDB-associated mutations on protein (ubiquitin-binding) function. Our results showed that protein NMR was not optimal to quantitatively assess the effects of the mutations on the interaction between p62 and ubiquitin in vitro. Using confocal microscopy, co-transfection of U20S cells showed that the selected PDB-associated p62 mutants (A381V, P392L, G425R) co-localised with ubiquitin with a cellular phenotype indistinguishable from wild type, as each PDB mutant formed cytoplasmic bodies with an area ranging from the detection limit of the microscope to 40μm2 or higher; in contrast the E396X truncating mutant did not form cytoplasmic bodies nor co-localise with ubiquitin. In addition to interacting with ubiquitin, p62 also interacts with the LC3 (an autophagic marker) through its LC3 interacting region (LIR) to mediate the formation of autophagosomes. By co-transfecting p62 constructs with LC3 We found that some of the p62-positive cytoplasmic bodies were autophagosomes, and that the D335E mutation of p62 (which lies within the LIR) did not appear to affect the formation of autophagosomes. The effects of the wild type and PDB-mutant p62 proteins on NF-κB signalling were assessed in HEK293 cells co-transfected with an NF-κB luciferase reporter construct. A381V mutant p62 produced a level of activation of NF-κB signalling greater than wildtype and similar to that of UBA domain mutants, indicating that non-UBA and UBA domain mutations may exert their effects through a common mechanism involving dysregulated NF-κB signalling. To further examine the function of p62 in the regulation of NF-κB signalling, we went on to determine possible effects of PDB-associated mutations on p62-CYLD (a DUB enzyme) interactions. Unexpectedly we found that CYLD expression appears to abrogate the formation of the p62 cytoplasmic bodies previously shown to be ubiquitin-positive. Finally, we went on to study the interaction of p62 (and its PDB mutants) with another important regulator of NF-κB signalling, IKKγ/NEMO. We concluded that wild type and PDB-mutant p62 proteins are capable of recruiting NEMO to cytoplasmic bodies which may represent autophagosomes, but do not appear to accelerate its degradation.

Paget's disease of the bone is a skeletal disorder of unknown cause. This disease is characterised by excessive and abnormal bone remodelling brought about by increased bone resorption followed by disorganised bone formation. Increased bone turnover results in a disorganised mosaic of woven and lamellar bone at affected skeletal sites. This produces bone that is expanded in size, less compact, more vascular, and more susceptible to deformity or fracture than normal bone. Symptoms of Paget's disease may include bone pain, bone deformity, excessive warmth over bone from hypervascularity, secondary arthritis, and a variety of neurologic complications caused in most instances by compression of the neural tissues adjacent to pagetic bone. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. The identification of the molecular basis of Paget's disease is fundamental for an understanding of the cause of the disease, for identifying subjects at risk at a preclinical stage, and for the development of more effective preventive and therapeutic strategies for the management of the condition. With this in mind, the aim of this project is to identify genetic loci, in a large pedigree, that may harbour genes responsible for Paget's disease of bone. A large Australian family with evidence of Paget's disease was recruited for these studies (Chapter 3). This pedigree has characterised over 250 individuals, with 49 informative individuals affected with Paget's disease of bone, 31 of whom are available for genotypic analysis. The pattern of disease in these individuals is polystotic, with sites of involvement including the spine, pelvis, skull and femur. Although the affected individuals have a severe early-onset form of the disease, the clinical features of the pedigree suggest that the affected family members have Paget's disease and not familial expansile osteolysis (a disease with some similarities to Paget's disease), as our patients have extensive skull and axial skeletal involvement. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Due to the large size of this family and multiple affected members, this pedigree is a unique resource for the detection of the susceptibility gene in Paget's disease. The first susceptibility loci for Paget's disease of bone have been mapped by other investigators to chromosome 6p21 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees. Linkage analysis of the Australian pedigree in these studies was performed with markers at PDB1: these data showed significant exclusion of linkage, with LOD scores < - 2 in this region (Chapter 4). Linkage analysis of microsatellite markers from the PDB2 region excluded linkage with this region also, with a 30 cM exclusion region (LOD score < -2.0) centred on D18S42 (Chapter 4). This locus on chromosome 18q21.1-q22 contains a serine protease (serpin) cluster with similarities to chromosome 6p21. Linkage analysis of this region also failed to provide evidence of linkage to this locus (Chapter 4). These data are consistent with genetic heterogeneity of Paget's disease of bone. A gene essential for osteoclast formation encoding receptor activator of nuclear factor-kB (RANK), TNFRSF11A, has been previously mapped to the PDB2 region. Mutations in the TNFRSF11A gene have been identified segregating in pedigrees with Familial Expansile Osteolysis and early onset familial Paget's disease, however, linkage studies and mutation screening have excluded the involvement of RANK in the majority of Paget's disease patients. For the Australian pedigree, mutation screening at the TNFRSF11A locus revealed no mutations segregating with affected individuals with Paget's disease (Chapter 4). Based on these findings, our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree; this gene should be identifiable using a microsatellite genome-wide scan followed by positional cloning. A genome-wide scan of the Australian pedigree was carried out, followed by fine mapping and multipoint analysis in regions of interest (Chapter 5). The peak 2-point LOD scores from the genome-wide scan were LOD = 2.75 at D7S507 and LOD = 1.76 at D18S70. Two additional regions were also considered for fine mapping: chromosome 19p11-q13.1 with a LOD of 1.58 and chromosome 5q35-qter with a LOD of 1.57. Multipoint and haplotype analysis of markers flanking D7S507 did not support linkage to this region (Chapter 5). Similarly, fine mapping of chromosome 19p11-q13.1 failed to support linkage to this region (Chapter 5). Linkage analysis with additional markers in the region on chromosome 5q35-qter revealed a peak multipoint LOD score of 6.77 (Chapter 5). A distinct haplotype was shown to segregate with all members of the family, except the offspring of III-5 and III-6. Haplotype analysis of markers flanking D18S70 demonstrated a haplotype segregating with Paget's disease in a large sub-pedigree (descendants of III-3 and III-4) (Chapter 5). This sub-pedigree had a significantly lower age at diagnosis than the rest of the pedigree (51.2 + 8.5 vs. 64.2 + 9.7 years, p = 0.0012). Linkage analysis of this sub-pedigree demonstrated a peak two-point LOD score of 4.23 at marker D18S1390 (q = 0.00), and a peak multipoint LOD score of 4.71, at marker D18S70. An implication of these data is that 18q23 harbours a novel modifier gene for reducing the age of onset of Paget's disease of bone. A number of candidate Paget's genes have previously been identified on chromosome 18q23, including the nuclear factor of activated T cells (NFATc1), membrane-associated guanylated kinase (MAGUK) and a zinc finger protein. Candidate gene sequencing of these genes in these studies has failed to identify mutations segregating with affected family members in the sub-pedigree linked to chromosome 18q23 (Chapter 6). More recently, a mutation in the gene encoding the ubiquitin-binding protein sequestosome 1 (SQSTM/p62) has been shown to segregate with affected members of Paget's disease families of French-Canadian origin. In this study, a single base pair deletion (1215delC) was identified as segregating with the majority of affected members in the pedigree (Chapter 6). This deletion introduces a stop codon at amino acid position 392 which potentially results in early termination of the protein and loss of the ubiquitin binding domain. The three affected members of the family that do not share the affected haplotype do not carry a mutation in the coding region of SQSTM/p62. Screening of affected members from 10 further Paget's disease families identified the previously reported P392L mutation in 2 (20%) families. No SQSTM1/p62 coding mutations have been found in the remaining 8 families or in 113 aged matched controls. In conclusion, this project has identified genetic loci and mutations that segregate with individuals affected with Paget's disease. Further investigation of the functional significance of the genetic changes at these loci is expected to lead to a better understanding of the molecular basis of this disease.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text

Fem låtar från Richard Pages skiva Peculiar Life har analyserats med syfte att ta reda på vad det är som ger dem dess sound. Analyserna har gjorts genom läsning av bookleten till skivan, informationssökning på internet, genom att titta på videodagbok från inspelning av skivan och genom att lyssna på låtarna. Analyserna har delats upp i kategorierna skriven information, video, utrustning och låtanalyser. Analyserna har visat att alla led i produktionen har stor betydelse för slutresultatet. Informationen som samlats in har använts till att återskapa soundet genom att komponera, arrangera, producera, spela in och mixa fem egna låtar baserat på analyserna. En undersökning gjordes med en grupp bestående av 66 gymnasieelever på estetiskt program med syfte att ta reda på om de egenkomponerade låtarna har samma sound som referensmaterialet. Ljudklipp från referenslåtarna och de egenkomponerade låtarna spelades upp tätt efter varandra varpå eleverna fick besvara en lyssnarenkät som tagits fram. De kategorier som betygsattes i enkäten var harmonier, arrangering och produktion. På enkäten fanns en förklaring av kategorierna. Resultatet från enkäten har sammanställts och analyserats och visar på ett delvis lyckat genomförande inom samtliga bedömningskategorier. Det första låtparet fick högt betyg, det andra låtparet fick medelbetyg och det tredje låtparet högt betyg.

Originally issued as a Ph. D. thesis from the University of Oxford, 1993.
Title from introductory page (SAHO website, viewed July 28, 2005). Includes bibliographical references. HTML version of the print thesis.

L'estudi es proposa una visió de la vida quotidiana dels veïns de les viles de Mataró, d'Argentona i d'Òrrius, des de mitjans del segle XIV a finals del segle XV, partint de tres aspectes fonamentals per explicar-ho: la senyoria i els drets dominicals, el poblament i la societat. El primer capítol comença amb una breu introducció a la demografia de les tres parròquies que ha permès veure com Mataró augmentava molt la seva població en contrast amb Argentona i Òrrius on decreix lleugerament. S’ennumeren totes les senyories que hi havia, constatant una gran fragmentació senyorial pel que fa a la senyoria territorial, no la jurisdiccional que estava en mans dels castells respectius. La servitud i els mals usos, ens servirà per endinsar-nos en els remences, que sembla que representaven poc menys de la meitat dels habitants del territori durant la segona meitat del segle XIV. La senyoria comportava una sèrie d'exaccions i impostos senyorials, d'entre les quals destaca el lluïsme, el delme o el lloçol. Els censos emfitèutics era un altre de les rendes que es pagaven, principalment en espècie, malgrat que a mesura que anava avançant el segle XIV i el XV molts es van convertir en diner. Es tracten els destrets senyorials, els principals dels quals eren els molins i les ferreries, però també les escrivanies, el forn, el mercat, especialment important i dinàmic a Mataró, la carnisseria, i la pesca. Al territori, la totalitat del quatre molins d’aigua documentats es trobaven a la conca de la Riera d’Argentona. A Mataró, amb poca aigua, es va optar per construir un molí de vent a mitjan segle XV. Tot aquest territori estava poblat, bàsicament, de masos, sobretot a Argentona i a Òrrius. En canvi, Mataró va anar evolucionant, amb un poblament dispers predominant fins ben entrada la segona meitat del segle XIV, per acabar amb una gran majoria de focs "urbans" a finals del segle XV. Després de mitjans del segle XIV detectem un augment molt significatiu de les vendes de masos en detriment de la construcció de masies de nova planta. Els masos rònecs és un dels aspectes que hem pogut documentar més bé, i que dóna testimoni del que va representar el fenomen per al territori. Molts masos restaren abandonats abans de mitjans segle XIV, per bé que el seu procés d'enrunament s'aniria allargant, depenent dels casos, fins ben entrat el segle XV. Molts pagesos els van incorporar al seu patrimoni mitjançant compra o establiment, evidentment en condicions molt avantatjoses per part dels senyors. Pel que fa als preus dels masos, molt variables, sembla que tenien com a factor més determinant les càrregues que satisfeien en detriment del seu estat físic. L'estudi també confirma que els masos sovint tenien terres sota domini de diferents senyories, alhora que aquestes terres estaven molt fragmentades pel territori, documentant-se masos d'Argentona que tenien terres fins a set quilòmetres de la masia. La darrera part del capítol la dediquem al poblament agrupat, força destacat a Mataró, amb un gran impuls a finals del segle XIV i durant gran part del segle XV, amb la plaça del mercat com a eix central, amb el pou i forns comunals, les carnisseries i les botigues porticades. El darrer capítol es centra bàsicament en la família, en dos aspectes: el matrimoni i la mort. Veurem les estratègies matrimonials, on els cònjuges sovint trobaven la parella en la població d’origen o en la comarca, què representava la llegítima, i sobretot, què valia un dot. Un dels aspectes que permet conèixer millor l'entorn religiós del testador són els llegats religiosos, amb la qual cosa podem endinsar-nos en les esglésies i capelles de cada parròquia i conèixer, entre d'altres, els seus altars. Els llegats familiars ens apropen al seu entorn familiar. Clourem amb el paper i la importància de l'hereu o la pubilla i amb la clàusula final: l'hereu universal.
The purpose of this thesis/research is to have a vision of the residents’ routine life in Mataró, Argentona and Òrrius, from mid XIV century till end of XV Century. This research is based in three fundamental facts to explain it: the manor, the population and the society. The demography has allowed us to see how Mataró was rapidly increasing its population against Argentona and Òrrius where it was declining. We have documented a high amount of territorial manors, being the jurisdictional manors in hands of their own castles. During the second half of XIV Century, the "remences" (servile people) represented half of the territory’s population. The manor implied some sort of rights and for the payment of taxes. The census where paid mainly in kind, although, while years were passing by, this will turn into money. Among the manors rights we emphasize the mills and iron mongeries, but also the scribes, stoves, markets and meat shops. All the territory was populated, mainly with farms. Mataró since the second half of XVI Century, have experimented an urban growth surrounding the market square where it was located the water well, the communal stoves, the meat shops and the arcade stores. Some of the facts we have been able to document properly are the abandoned farms, which started on the XIII Century. Many farmers have taken the farms to their heritage buying them either through establishment which were always under advantageous conditions for the sirs. The farms usually have lands under the dominion of various manors and were fragmented around the territory, sometimes without territorial continuity. The last chapter is mainly based on the family, in two important facts: marriage and death. We've studied the dowry and the territorial origins of the consorts and spouses. Thanks to the will/testament we know about the religious environment of the testators being able to going deeper among the churches and chapels of each parish and acknowledge the altars. The family legacy is taking us closer to the family core. This research ends explaining the role and the relevance of the male heirs and the 'pubillas' (the female version of the male heir, the eldest daughter) and with the last review: the universal heir.

An exploratory analysis of national beauty pageants for children was conducted through the administration of a questionnaire and through observation. The population surveyed was mothers with daughters sixteen years old or under. Questionnaires were distributed at six national pageants in five states with a total of 134 respondents. The questionnaire probed a variety of areas concerning the child's involvement, expenses incurred, beauty enhancements worn, and general demographic information concerning the contestant's family. Attitudinal statements concerning the role of women in society and the importance of beauty in society were investigated. A comparison was made between the attitudes of the pageant mother and a sample of mothers taken from the 1993 General Social Survey. The results suggested that pageant mothers were more supportive about the changing roles of women. In addition, mothers were given an attractiveness scale on which they rated themselves and their daughters. Data analysis on a variety of variables was carried out at univariate and bivariate levels.

La maladie osseuse de Paget (MP) est une maladie métabolique de l’os. Bien que les facteurs génétiques jouent un rôle important dans la pathogénie de la MP, les facteurs environnementaux tels que la résidence rurale et l’exposition au chauffage au bois ont été associés avec la MP. Afin d’étudier le rôle des polluants de l'air extérieur et intérieur sur la MP, nous avons administré un questionnaire chez 140 patients canadiens-français avec la MP et 113 témoins sains. Ce questionnaire portait sur la pollution de l'air extérieur, comme la résidence près d'une autoroute, d’une station de bus, de train ou d’un aéroport, d’une station d'essence, et sur les polluants de l'air intérieur en mettant l'accent sur les combustibles de chauffage (charbon, bois, huile) et l'exposition au tabac. Dans un sous-groupe de patients, la concentration urinaire de 17 métaux lourds et de 11 hydrocarbures aromatiques polycycliques a été mesurée par spectrométrie de masse. À la lumière de ce que nous savions dès le questionnaire et les dosages urinaires, nous avons identifié certains toxiques pouvant être des facteurs de risque pour la MP. Pour explorer les effets in vitro de ces toxiques sur les ostéoclastes dans la MP, nous avons réalisé une différentiation in vitro de monocytes du sang périphérique provenant de plus de 40 participants, patients, porteurs sains de mutation dans le gène SQSTM1, et des témoins sains, en ostéoclastes traités avec ou sans les toxiques identifiés. La morphologie des ostéoclastes, le pourcentage de résorption osseuse, les niveaux d'expression génique, et les niveaux de stress oxydatif cellulaire ont été analysés. Les résultats ont montré un effet inhibiteur du condensé de la fumée de cigarette et des métaux lourds sur la morphologie et la fonction des ostéoclastes. De plus, des taux élevés de stress oxydatif chez les ostéoclastes des patients ont été observés, et un profil hétérogène des effets de métaux lourds sur l'expression des gènes a été identifié.
Paget's disease of bone (PDB) is a metabolic bone disease. Although genetic factors play an important role in the pathogenesis of PDB, environmental factors such as rural residence and the exposure to wood heating was associated with PDB. In order to study the role of outdoor and indoor air pollutants on PDB, we performed a survey in 140 French-Canadian patients with PDB and 113 healthy controls. The survey covered the outdoor air pollution such as the residence near a highway, a bus station, a train or an airport or a gas station, and indoor air pollutants by focusing on heating fuels (carbon, wood, oil) and exposure to tobacco smoke. In a subgroup of patients, urinary concentration of 17 heavy metals and 11 polycyclic aromatic hydrocarbons was measured by mass spectrometry. In light of what we knew from the survey and urinary assays, we identified certain toxics that could be risk factors for PDB. To explore the in vitro effects of these toxics on osteoclasts in PDB, we conducted in vitro monocytes differentiation from peripheral blood of more than 40 participants, patients, healthy carriers of p.Pro392Leu mutation, and healthy controls, which osteoclasts were treated with or without the identified toxic. The morphology of osteoclasts, the percentage of bone resorption, gene expression level, and cellular oxidative stress levels were assayed. The results showed an inhibitory effect of cigarette smoke condensate and heavy metals on morphology and function of patients’ osteoclasts. Further, high levels of oxidative stress in patients’ osteoclasts were observed, and a heterogenic profile of heavy metals effect on gene expression was identified.

I stand in front of the remnants of a building. Braces and beams create a silhouette against the sky. The walls and roof are missing, but the windows remain, and the sheet metal doors. The structure frames the emptiness. This former building became a metaphor for man. Vulnerable in the face of a sudden turn of events, we lack protection against the world around us. Only our skeleton, muscles and naked skin hold us together. And just as eyes are said to reflect the soul, the leftover windows provide a hint of the former building’s life. The windows became the key to this building’s history. We are dependent on our buildings, just as the buildings are dependent upon us. In times of change, our social structures support us. Our life cycles are the course of events that allow us to move on, change, and be unique. Marks are left with the passage of time. Facades can be open, opened, forced, closed, covered, empty, or ready to be filled. Facades can be the time that passes. We are facades in transition, but stable in our foundations.Nothing is really alive until there is something missing, and the opportunity to place ourselves into a context arises. And in that aspect, the emptiness following the fall of the Twin Towers is therefore more telling than the buildings themselves.Everything we see in a building tells a story. In this essay, the story of Berlin’s House of Parliament is told. I reflect on how man mirrors his present in a building that is in a process of transition and how we are forced to confront ourselves with its history. I consider how a new dimension is created when something is opened, handing over the inside to reveal its past. How time can alter a symbol’s meaning. Today the dome on the House of Parliament represents democracy, as opposed to one hundred years ago, when it stood for power.Facades are in constant change.Does a facade need to be affected by transformation, deconstruction and destruction so that we can understand its whole, or are there other ways to penetrate its surface? Is the structure’s ability to evolve andadapt that which fascinates us and allows us to see its possibilities?Both man and building need “change” in order to illustrate their past and interpret their present. This is most apparent in the moment that the "facade cracks". In the vacuum that is created, it becomes obvious that the present is not forever. To exist in the present, is to be in a state of change.

International Telemetering Conference Proceedings / October 22-25, 2001 / Riviera Hotel and Convention Center, Las Vegas, Nevada
Visitors to web pages are, in most cases, restricted to viewing information the page designer has anticipated they will be interested in viewing. Many times this is adequate, but there are instances where the visitor wants the information they view to be based on selections they choose. The Air Force Research Laboratory (AFRL) Space Vehicles Directorate anticipates selected customers will have a need to view very large data sets that vary from the satellite payload to the satellite state of health1, and will require controlling what they view in an “ad hoc” manner. In response, AFRL is using Java Server Pages developed within the data center to bring interactive and dynamic web page content to these customers.

Jill Hemming Austin PERFORMING THE PAST: TWO PAGEANT TRADITIONS IN NAUVOO, ILLINOIS The founders of American historical pageantry were keenly interested in the social effect of pageant performance on audience and participants. Their vision for social transformation through performance endures into the present day with those who continue to promulgate the form. Examining two enduring pageant traditions in Nauvoo, Illinois affords a better understanding of how the formal features of outdoor historical pageant production and the social relations that underlie them are still potentially powerful for those who participate in their production and performance. This dissertation encourages serious study of pageants as a unique performance form particularly attuned to the tasks of building continuities and tradition, the reinforcement of group sentiment, and the propitiation of group myth. Nauvoo, Illinois is a historically contested site boasting two historical pageants dedicated to the portrayal of the Nauvoo story: The Grape Festival Pageant and The Nauvoo Pageant. Christened ?Nauvoo? by Mormon [LDS] refugees in the mid-19th century, the thriving city?s overwhelming social discord drove the Mormons west, and the town was resettled and reclaimed by new seekers and settlers. The legendary quality of Nauvoo continued to grow in the Mormon imagination, eventually leading to a reclamation process including heritage development. Competing claims on local history has led to a heightened historical consciousness among townsfolk and ongoing public presentation from multiple perspectives. The two pageants are cultural displays that influence this ongoing social process. Both derive from distinct traditions--the local drama squarely planted in American historical pageantry and the Mormon-sponsored pageant deriving from LDS social and religious culture. Historical pageants have some unique formal features that make them particularly interesting to folklorists. They depend heavily on sacred localities, tradition, legend, and large-group participation for their success. The story told gains power from familiarity and reinforcement of cherished group values. However, changing tastes and sensibilities have challenged the survival of pageants as a relevant cultural form into the present. Drawing on interviews, field observation, and historical research, the contemporary context of the town and its two performances is fleshed out in the voices of four individuals who have participated in the pageants.

Genetic factors play an important role in the pathogenesis of Paget’s Disease of Bone (PDB). The most important predisposing gene is SQSTM1 which is mutated in about 10% of patients, additionally common variants at seven other loci have also been shown to predispose to PDB as well as environmental factors which are also important in the pathogenesis of PDB. Little research has been conducted on the relationship between the genetic variants that predispose to PDB and disease severity. Similarly, only limited information exists on the role that gene-environment interactions play in the pathogenesis of PDB or its severity. The aim of the present thesis was to explore these issues in participants of the Paget’s Disease Randomised Trial of Intensive versus Symptomatic Management study (PRISM) and other study cohorts. In chapter 3, I investigate the relationship between SQSTM1 mutation status, disease severity and clinical outcome in 737 patients from the PRISM study. Mutations of SQSTM1 were detected in 80/737 (10.9%) patients. Mutation carriers had an earlier age at diagnosis; a greater number of affected bones and more commonly had required orthopaedic surgery and bisphosphonate therapy than those without mutations. Quality of life was significantly reduced in carriers and during the study; fractures were more common although most of these occurred in unaffected bone. This study demonstrates that SQSTM1 mutations are strongly associated with disease severity and complications of PDB. In chapter 4, I study associations between common genetic variants identified by genome wide association (GWAS), clinical severity and extent of PDB, alone and in combination with SQSTM1 mutations. This showed that these common variants were also associated with severity and extent of PDB in PRISM, but with weaker effects than SQSTM1 mutations. The findings were replicated in a multinational study involving 1940 subjects from centres in Italy, Spain and Australia. In all cohorts the GWAS risk alleles acted in an additive manner with SQSTM1 mutations to regulate disease severity and extent. By combining information from SQSTM1 status and the new risk alleles, however, we are able to develop a genetic risk score which delineated three distinct groups with markedly differing effects on disease extent and severity. In chapter 5, I study associations between PDB, severity and extent in relation to circulating levels of IgG antibodies against various viruses including Rubella, respiratory syncytial virus, distemper, varicella zoster virus, measles and mumps. We found little evidence of an interaction between viral antibody titres and SQSTM1 in predicting disease severity with the notable exception of mumps virus where subjects with the highest levels of antibodies that were SQSTM1 positive had in increased age at diagnosis than the other genotype / viral antibody groups. Overall the studies do provide no support for the notion that patients with PDB have an abnormal antibody response to paramyxovirus or have had previous infections with these viruses more frequently than controls. This of course does not exclude the possibility that PDB patients might have a clinically occult slow virus infection which is not accompanied by an abnormality in the immune response. . This raises the possibility that genetic testing may be of value in identifying individuals at risk of developing severe disease and those at risk of complications. I also demonstrate that PBD patients have abnormalities in circulating antibodies to various viruses suggesting that the disease may be associated with disturbance in the response of the immune system to infectious agents but further investigation is required. This, perhaps, could explain the changes in the severity and prevalence of PDB that have been observed over recent years in several countries.

This multi-media art project investigates the notion of Cook Islands humour, and subsequently place, through the context of the religious pageant Nuku. This pageant has been practiced annually in the Cook Islands for over one hundred and sixty years. While it is not a pageant based on humour, I suggest, through experience and research, that many of the characteristics of Cook Islands humour are revealed in Nuku. The aim of this project is not to recreate the narrative set out in the Nuku pageant but to use this event to explore ways to visually express the humour of the Cook Islands. After researching and experimenting in two dimensional mediums, my emphasis changed to experimenting with three dimensional mediums, incorporating materials that have connotative meanings in Cook Islands society.

The microstructural impact of diagenetic or post mortem alteration has been assessed in predominately human skeletal tissues. The method of assessment selected was microscopical analysis, mainly using backscattered electron imaging in a scanning electron microscope and, to a lesser extent, confocal reflection microscopy. The microstructural morphologies of post mortem alteration were investigated in archaeological material, both normal and pathological, from terrestrial and marine contexts. Further studies were undertaken on a case-by-case basis on skeletal material which offered some unique pathology, environmental context, spatial relationship, time variable, or mortuary practice. Additionally, the effect of diagenetic change on mitochondrial DNA (mtDNA) recovery and the potential location of DNA within the skeletal tissues were investigated. Two quantitative studies were undertaken to validate and measure the observed mineral density changes. The investigations showed that post mortem alteration or diagenetic change to skeletal material can be extensive, and can occur shortly after death. Diagenesis did not represent a post burial phenomenon as the term diagenesis suggests, but was found to have begun above ground in a range of exposural contexts. The implication of gut bacteria in the promotion of early bacterially-related microstructural change was strong, and it is proposed that body status at the point of, or soon after, death is important. Post mortem alteration to skeletal microstucture can provide environmental information, since terrestrial and marine contexts exhibited distinct morphologies. It may also provide localized environmental information within a stratigraphic matrix. Characterizing the post mortem microstructural and density changes to bone has helped to elucidate the preservational status of mtDNA in terms of its relative retrieval in archaeological specimens, and the potential location of mtDNA in bone. It is proposed that the shift in mineral density that was found in bacterially-remodelled specimens from terrestrial contexts, relative to the excellent preservation of marine specimens, may help to explain why marine vertebrates far outnumber terrestrial ones in the fossil record, since bacterially driven microstructural change is here considered to be a destructive form of fossilisation.

Orientador: Laurival Antonio De Luca
Resumo: O objetivo deste trabalho foi estudar através do exame Imunoistoquimico, a correlação entre alguns fatores Anatomopatológicos (tipo histológico e grau nuclear) e alguns fatores biológicos (receptores hormonais de estrógeno e de progesterona, proteína c-erbB-2 e proteína p53, no carcinoma de Paget da mama, doença rara e especial. No período entre Janeiro de 1980 a Dezembro de 1998 foram tratados no Instituto Brasileiro de Controle do Câncer, 6.303 casos de câncer de mama, deste total 98 casos foram diagnosticados como carcinoma de Paget, cuja incidência foi de 1,55%. Estudamos retrospectivamente 60 casos, sendo que 38 deles foram excluídos da análise, devido a limitação e escassez da amostra no material disponível, a idade das pacientes variou entre 26 e 84 anos, com média de 55,4 anos, as informações clínicas e terapêuticas foram obtidas dos prontuários das pacientes considerando, idade na época do diagnóstico, tamanho do tumor quando palpável, estadiamento clínico, e o tipo de cirurgia realizada. As amostras de tecido mamário foram recuperadas dos arquivos do Departamento de Anatomia Patológica do I.B.C.C. / MATTOSINHO. Após a revisão histológica, realizada por dois patologistas os casos foram classificados em quatro grupos: Grupo A- Doença de Paget (forma pura) n = 09 Grupo B- Doença de Paget + neoplasia ductal "in situ", n = 12 Grupo C- Doença de Paget, neoplasia ductal invasora, n = 30 Grupo D- Doença de Paget + neoplasia ductal "in situ"+ neoplasia ductal invasora, n = 09. Entre as variáveis anatomopatológicas, o grupo C prevaleceu com 30 casos (50%). O grau nuclear (GN-II) predominou com 45 casos (75%). Em relação as variáveis biológicas o receptor de estrógeno negativo predominou com 41 casos (68,3%), seguido pelo receptor de progesterona negativo com 40 casos (66,7%), podemos dizer que... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The objective of this paper was to study the immunohistochemical efects of Paget's disease, a rare and special carcinoma of the breast, by correlating anatomopathological (histological and nuclear grade) and biological (estrogen and progesterone hormonal receptors, c-erbB-2 protein and p53 protein) factors. Between January 1980 and December 1998, 6303 cases of breast cancer were treated at the Brazilian Institute of Cancer Control; 98 of these were diagnosed with Paget's carcinoma, an incidence of 1.55%. We retrospectively studied 60 of these cases; 38 were excluded due to lack of available sample material. Patient age varied between 26 and 84 years (mean 55.4), clinical and therapeutic information were obtained from patient's medical records considering age at time of diagnosis, tumor size when palpable, clinical stage, and type of surgery performed. Samples of breast tissue were retrieved the Anatomical Pathology Department, I.B.C.C. / MATTOSINHO. After histological review, by two different pathologists, they were classified into four groups: Group A- Paget's disease (pure form) n = 09 Group B- Paget's disease + "in situ" duct neoplasia n = 12 Group C- Paget's disease, invasive duct neoplasia n = 30 Group D- Paget's disease + "in situ" duct neoplasia + invasive duct neoplasia n = 09.Invasive duct neoplasia was the most prevalent anatomopathological variable (Group C, n = 30, 50%). Nuclear grade (GNII) was found in 45 cases (75%). In relation to the biological variables, the negative estrogen receptor was predominant with 41 cases (68.3%), followed by the negative progesterone receptor with 40 cases (66.7%); this correlation had good concordance by the Kappa test. The c-erbB-2 protein was positive in 53 cases (88.3%) and p53 was negative in 47 cases (78.3%). From these results, we concluded that there was no statistical... (Complete abstract click electronic address below)
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Pourquoi publier un article d'actualité sur son mur Facebook ? Que signifie ce geste par rapport à d'autres formes d'interaction? Et qu'est-ce qu'apporte cette pratique aux multiples prises de la réception des médias? Cette recherche s'intéresse à l'activité de partage d'information en ligne, c'est-à-dire aux interactions numériques qui recourent à une information. Si les artefacts du web semblent généraliser le partage comme expression, force est de constater que les médias ne peuvent observer qu'une faible activité autour de leurs contenus. Le partage d'information n'est que la partie émergée de l'iceberg des sociabilités et des pratiques médiatiques. Un focus est réalisé sur les pratiques juvéniles. Les adolescents rappellent la prédominance du cadre interactionnel sur Facebook et expliquent que le dispositif permet de nombreuses stratégies. Dans ce contexte, les actualités ne trouvent une place qu'à condition d'avoir un sens social. Partager une information revient à dire sa réception du contenu, c'est du moins comme cela que le geste est lu. Enfin, cette recherche utilise les traces Facebook d'un large échantillon d'enquêtés grâce à l'application Algopol. Les médias forment une référence limitée mais stable parmi les liens publiés par les internautes. Les individus partagent de préférence certaines sources de médias, reproduisant en ligne des références a priori acquises hors ligne. Les enquêtés qui citent le même type de contenus ont de plus des similitudes sociodémographiques. Le partage d'information en ligne se développe à partir des pratiques médiatiques dans l'interstice des relations, entre exploration personnelle et réception des informations
Why do people post news on Facebook? What does a post mean compared to other forms ofexpression? And how does this activity contribute to media appropriation? This research focuses on sharing news, meaning an online interaction which uses information. This activity seems to be the social solution to supporting a person's online exploration. “Who shares what with whom?” is the question asked in this research through multiple approaches, both qualitative and quantitative. The first part is an exploration of online artefacts, counts of what media was shared online, and a few interviews. These diverse points of view show that sharing news enhances public expression of information, but only for some users. Sharing news is a limited part of online media consumption and online interaction. The second part of the research looks in detail at teenagers’ practices on Facebook. For young people on Facebook, all expression has to be social and online artefacts are a way to tell somebody one's position on an issue or on a relationship. News may be there to open interactions. The last part of the research deals with a large dataset of individual Facebook data, available thanks to Algopol Application. Analysis of the diversity of publications shows that the news people share online takes into account their offline media preferences and social activities. Sharing news is an online way of expression based on informations’ reception

Pourquoi publier un article d'actualité sur son mur Facebook ? Que signifie ce geste par rapport à d'autres formes d'interaction? Et qu'est-ce qu'apporte cette pratique aux multiples prises de la réception des médias? Cette recherche s'intéresse à l'activité de partage d'information en ligne, c'est-à-dire aux interactions numériques qui recourent à une information. Si les artefacts du web semblent généraliser le partage comme expression, force est de constater que les médias ne peuvent observer qu'une faible activité autour de leurs contenus. Le partage d'information n'est que la partie émergée de l'iceberg des sociabilités et des pratiques médiatiques. Un focus est réalisé sur les pratiques juvéniles. Les adolescents rappellent la prédominance du cadre interactionnel sur Facebook et expliquent que le dispositif permet de nombreuses stratégies. Dans ce contexte, les actualités ne trouvent une place qu'à condition d'avoir un sens social. Partager une information revient à dire sa réception du contenu, c'est du moins comme cela que le geste est lu. Enfin, cette recherche utilise les traces Facebook d'un large échantillon d'enquêtés grâce à l'application Algopol. Les médias forment une référence limitée mais stable parmi les liens publiés par les internautes. Les individus partagent de préférence certaines sources de médias, reproduisant en ligne des références a priori acquises hors ligne. Les enquêtés qui citent le même type de contenus ont de plus des similitudes sociodémographiques. Le partage d'information en ligne se développe à partir des pratiques médiatiques dans l'interstice des relations, entre exploration personnelle et réception des informations
Why do people post news on Facebook? What does a post mean compared to other forms ofexpression? And how does this activity contribute to media appropriation? This research focuses on sharing news, meaning an online interaction which uses information. This activity seems to be the social solution to supporting a person's online exploration. “Who shares what with whom?” is the question asked in this research through multiple approaches, both qualitative and quantitative. The first part is an exploration of online artefacts, counts of what media was shared online, and a few interviews. These diverse points of view show that sharing news enhances public expression of information, but only for some users. Sharing news is a limited part of online media consumption and online interaction. The second part of the research looks in detail at teenagers’ practices on Facebook. For young people on Facebook, all expression has to be social and online artefacts are a way to tell somebody one's position on an issue or on a relationship. News may be there to open interactions. The last part of the research deals with a large dataset of individual Facebook data, available thanks to Algopol Application. Analysis of the diversity of publications shows that the news people share online takes into account their offline media preferences and social activities. Sharing news is an online way of expression based on informations’ reception

El final de les dictadures socialistes europees va iniciar transformacions econòmiques, polítiques, socials i ideològiques importants i va obrir una sèrie de debats entorn els models que havien de guiar els canvis. La restitució dels drets de propietat privada va ser una de les preocupacions prioritàries dels nous governs post-socialistes. Considerant-se com l’element central pel progrés econòmic, polític i social d’aquests països, havia de ser la base per a la construcció d’una economia de mercat. En la última dècada, l'antropologia ha generat una visió crítica d’aquestes promeses del post-socialisme a partir de diverses experiències i de la crítica teòrica als plantejaments unilineals neoliberals.La privatització tan anhelada pels defensors del model liberal i la recuperació dels drets de la propietat tan anhelada també per part la població pagesa perseguien motivacions diferents i incompatibles. Contràriament a les expectatives generades durant la transició, la devolució de les terres als seus antics propietaris ha anat acompanyada d’un ‘retorn’ a una economia de subsistència i desmonetaritzada, de la revitalització d’institucions socials, econòmiques i polítiques costumàries pròpies de l'època pre-socialista. Aquest 'retorn' s'ha produït en un context macro polític, econòmic i demogràfic completament nou, caracteritzat per fenòmens com l'emigració massiva, la inflació, les conseqüències de l'anomenada revolució verda i la globalització de l'agricultura. La tesi pretén oferir una millor comprensió d’aquesta realitat dominant a tants llocs de l'Europa post-socialista rural mitjançant l'estudi de cas d’una comunitat pagesa a Transilvània. D'una banda, la cultura econòmica pagesa va ser un inconvenient per a la necessitat que tenia l'Estat socialista de dominar la producció agrària per tal d'alimentar el creixement industrial. D'altra banda, l'economia pagesa tampoc ha encaixat amb la teoria liberalque ha guiat el post-socialisme, segons la qual la possibilitat d'adquirir i alienar la terra, combinada amb la seguretat en la propietat, ofereix els incentius necessaris per a treballar més eficientment i innovar (Hann, 2003:7). Partint de l'etnografia, la tesi defensa que l’estudi de l’eficiència econòmica i de les regulacions legals de la propietat ha d’emmarcar-se necessàriament en el context social i cultural local. En aquest cas, el context social i cultural es relaciona amb el model de convivència propi de la comunitat pagesa que es regeix per valors morals, mitjans de subsistència, dret costumari, formes de producció i de propietat. Tot plegat s'ha de contextualitzar en l'actual sistema globalitzat de producció i comercialització dels productes agraris.És per això que l’àmbit d’estudi de la tesi se situa concretament en la intersecció entre l’economia i les relacions socials (de parentiu, de veïnatge i comunitàries) en el marc dels canvis macroeconòmics i polítics. Es tracta en definitiva de veure quines han estat les discrepàncies i conflictes ideològics, econòmics, socials, o morals i en quina mesura aquestes discrepàncies fan inviables els projectes polítics i econòmics imposats pel socialisme o pel liberalisme a nivell local. La proposta defensa que la fidelitat etnogràfica pot proporcionar una interpretació de la situació actual que consideri els marcs polítics i econòmics que en les darreres dècades han configurat el seu context, però alhora que eviti que l'explicació vingui donada des dels paradigmes que han inspirat aquests marcs polítics i econòmics (el marxisme o el neoliberalisme).
The collapse of European socialism was the start for a broad range of economic, political, social and ideological changes. These changes led to a series of debates about the models that should guide the process. The restitution of private properties was one of the key issues for the new post-socialist governments, and necessary condition of political and social progress in the framework of a market economy. But two decades later, the economic situation of the countries of Eastern and Central Europe compels us to inquiry on the shortcomings of the neoliberal agenda. In the last decade, Anthropology has developed a critical view of the post-socialist promises based on ethnographical experiences and on the theoretical criticism of neoliberal approaches. Private property rights were wanted by both, liberals (or neoliberals) and peasants, but they pursued different and in most cases incompatible goals. What it happened during the transition was against the expectations previously generated: the devolution of lands to their former owners was accompanied by a 'return' to a subsistence and demonetarized economy and to the reestablishment of rather old customary institutions. This process has taken place in a new macro-political, economic and demographic context, defined by mass emigration, inflation, the consequences of the so-called green revolution, and the agricultural globalization. The aim of the thesis is to contribute to the understanding of the complex situation of therural areas in post-socialist Europe through a case study of a Transylvanian peasant community. On the one hand, the economic peasant culture was seen as an obstacle for the socialist state as far as it wanted to control the agrarian production for feeding the industrial growth. On the other hand, the peasant economy did not fit with the neoliberal schemes, which have been dominant in the post-socialist period. These schemes expect that the market alienation of land, combined with the legal security of ownership, would give to the farmer the incentives he needs in order to innovate, and to increase productivity (Hann, 2003:7). Following the ethnographic account, this thesis poses that the economic efficiency and the legal rules of property must be confronted to the socio-cultural local context. In our case, the local context means a peasant community defined by moral values, customary law, and customary forms of production and property handling. The economic activity in the community is constantly defined by the overlapping of two spheres of social exchange: kinship and neighborhood. In addition, the local culture needs to be contextualized in the current globalized agricultural system of production and trade. The thesis focuses on the ideological, economic, social and moral conflicts, in order to understand the tensions provoked for the economic and political projects imposed first by socialism and afterwards by liberalism.The reliability of the ethnographic account should provide us with a fine-tuned interpretation of the present situation. This can help us to avoid the oversimplifications of both orthodox Marxism and orthodox neoliberalism perspectives.

Paget’s Disease of Bone (PDB) is a common condition characterised by focally increased bone turnover, which is believed to be caused by an aberrant osteoclast. Genetic factors are important in the pathogenesis of PDB and mutations in the TNFRSF11B encoding osteoprotegerin (OPG) and Sequestosome 1 (SQSTM1 ) encoding SQSTM1 or p62 cause juvenile and classic PDB of late onset respectively. OPG and p62 play an important role in the RANK-NFκB signalling pathway, key for normal osteoclastogenesis. I have shown that the TNFRSF11B G1181C polymorphism causing a lysine to asparagine change in the 3^rd codon of the OPG signal peptide (SP-OPG) predisposes to PDB. Heterozygous cases for G1181C are prone to severe disease as opposed to homozygous cases (a positive heterosis effect). There is a difference in cellular localisation of respective SP-OPG variants and a degree of cellular accumulation of the SP-OPG variant containing lysine in the 3^rd codon, suggesting that the latter may be inefficiently secreted at times of high demand at a local level, which could lead to increased bone resorption. Studies of p62 revealed a novel interaction between p62 and P-IκB-α and between p62 and VCP. PDB-causing mutations of the p62 UBA domain interfered with the interaction between p62 and P-IκB-α, but not between p62 and VCP, shedding a new light on the mechanism underlying the pathogenesis of PDB. Accumulation of IκB-α in the presence of the PDB-causing mutations of p62 was present, suggesting that p62 may regulate IκB-α degradation. Implications of these findings are discussed. This work provides novel insights into the molecular mechanisms underlying PDB and the findings are expected to become the groundwork for further studies trying to unravel the complexity of the pathogenesis of Paget’s disease of bone.

Miss America Pageant contestants (MAPCs) have been negatively stereotyped socially for their perceived lack of intelligence and nonconformance to feminist gender stereotypes of women. Stereotypes could affect an individual's social psyche and establish stigma, which could prevent a group from achieving their full potential. Stereotypes could also result in women having mental health disorders, low self-esteem, a decrease in self-efficacy, body image dissatisfaction, and eating disorders. The problem this study addressed was that women who participate in the Miss America Organization (MAO) preliminary pageants risk social stigma for taking part in a seemingly nonfeminist activity. Intercultural communication research (ICR) was the theoretical framework utilized to understand the role of cultural stereotypes, prejudice in communication, and self-perception among MAPCs. The main research question examined how local preliminary MAPC's decide to participate in pageantry in relation to their beliefs about stereotypes of MAPCs. For this multiple case study, a sample of MAPCs (n =5) from a Southeastern state was recruited to participate in interviews and provided narrative data that was coded and analyzed for themes of stereotypes, self-esteem, and self-efficacy. The key findings from this study revealed that the participants believed that societal stereotypes of MAPCs still exist, but the stereotypes did not influence participants' self-esteem, self-efficacy, and their decisions to compete and represent their social platform. The results also revealed a need for societal education about MAO pageant system's mission. Positive social change can come from understanding the MAPC subculture to dispel societal stereotypes and through presenting MAPCs' goals as social change agents.