Clinical and molecular analysis of human reproductive disorders in Brazilian patients

Several genes that influence the development and function of the hypothalamic-pituitary-gonadal-axis (HPG) have been identified. These genes encode an array of transcription factors, matrix proteins, hormones, receptors, and enzymes that are expressed at multiple levels of the HPG. We report the experience of a single Endocrinology Unit in the identification and characterization of naturally occurring mutations in families affected by HPG disorders, including forms of precocious puberty, hypogonadism and abnormal sexual development due to impaired gonadotropin function. Eight distinct genes implicated in HPG function were studied: KAL, SF1, DAX1, GnRH, GnRHR, FSHß, FSHR, and LHR. Most mutations identified in our cohort are described for the first time in literature. New mutations in SF1, DAX1 and GnRHR genes were identified in three Brazilian patients with hypogonadism. Eight boys with luteinizing hormone- (LH) independent precocious puberty due to testotoxicosis were studied, and all have their LH receptor (LHR) defects elucidated. Among the identified LHR molecular defects, three were new activating mutations. In addition, these mutations were frequently associated with new clinical and hormonal aspects, contributing significantly to the knowledge of the molecular basis of reproductive disorders. In conclusion, the naturally occurring genetic mutations described in the Brazilian families studied provide important insights into the regulation of the HPG.

Collective Memory Embodied in Poetry as Poison. The Mnemonic Role of Romantic Poets Discussed on the Basis of Adam Mickiewicz’ Konrad Wallenrod and Forefathers (Part III)

This thesis constitutes an interdisciplinary approach to the Polish Romanticism combining literature studies with memory studies, nationalism research and psychoanalysis. This phenomenon-based study attempts to answer the question, how the Polish national poet Adam Mickiewicz (1798–1855) – or more exactly the implied authors in his works – perceived the role of poetry in mnemonic terms and how it changes in course of time. Consequently, ‘memory in literature’ (Astrin Erll and Ansger Nünning) is discussed here. Two pieces of writing by Mickiewicz – Konrad Wallenrod [1828] and the third part of Forefathers [1832], where a bard respectively a poetic genius appears – are seen as meta-texts defining goals of poets in time of the political non-existence of a state. Poetry is supposed to keep memory of the glorious past alive, kindle the love for the motherland, support the collective identity of a group and initiate a liberation movement. Poets function as memory guards, leaders of the nation and prophets. Thus, literature is a medium of collective memory – it stores crucial contents, transmits them and acts as a cue. Nevertheless, shifting the focus from the community towards well-being of individuals, which is consistent with the postmodern thinking, the impact that poetry has on members of a given memory culture (Jan Assmann) can be described in ‘vampiric’ terms (Maria Janion). Poetry embodying collective memory may be compared to ‘poison’, ‘infecting’ people with a nationalistic way of thinking to their disadvantage as far as their personal lives are concerned.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

Conflicting Memory in Estonia: How Do Estonian Russian-speakers Understand the Events of 1939-40?

This thesis studies the collective memory of the Russian-speaking minority living in Estonia. The minority is exposed to two national narratives regarding the incorporation of Estonia into the Soviet Union in 1940. According to the Estonian narrative, Estonia was occupied and annexed by the Soviet Union while the Soviet-Russian narrative sees the actions to have been legal and voluntary. This thesis firstly examines thoughts the existence of these two opposing narratives evoke among the Russian-speaking minority and secondly it explores whether the views of the minority compare with the two official yet divergent narratives. The study focuses on the second and third generation minority members. The topic belongs to the field of memory studies. The objective is to understand the views the Russian minority have towards the controversial events of the years 1939-40. To accomplish the objectives set, a web-based survey using open-ended and multiple-choice questions was conducted. The open-ended questions addressed the main research questions while the multiple-choice questions contributed to forming a more comprehensive understanding of the subject in question. In order to interpret the data, qualitative content analysis has been applied. Based on the findings, the Russian-speaking minority respondents’ understanding of the events of 1939-40 could be described as fragmented, inconsistent and including viewpoints that resulted from the merger of different storylines. There is no single cohesive or coherent narrative of the past amongst the minority. In addition to that, their views do not generally comply with the narrative of the Russian Federation as often referred to in literature, even though the minority respondents do not want to see the Soviet involvement as critically as the Estonian narrative does. Many respondents conceive the events of 1939-40 as ambiguous revealing the ability to be tolerant and receptive in their views regarding the past.

Globalization of pharmaceutical R&D. Pharmaceutical R&D governance forms in People's Republic of China

Yrityksen selviytyminen ja menestyminen ovat riippuvaisia sen kyvystä innovoida, luoda tietoa ja hyödyntää tietämystä ja keksintöjä (Dunk ja Kilgore 2001). Yrityksen menestyminen erityisesti korkean teknologian alalla on siten suoraan riippuvainen sen T&T:stä, johon tehdyt investoinnit tuovat merkittäviä taloudellisia etuja yritykselle uusien tuotteiden, palveluiden ja prosessien muodossa (McEvily ja Chakravarthy 1999). Teknologinen etumatka ja sen tuotteistaminen innovatiivisiksi tarjoamiksi mahdollistaa monopolististen etujen saavuttamisen yrityksen kansainvälisessä kilpailussa (Lall 1977). Tämä kaltainen kilpailuetu voidaan saavuttaa yrityksen kyvyllä yhdistää maantieteellisesti hajautettu T&T:nsä tehokkaaksi verkostoksi (Porter 1986). Boehen (2008) mukaan T&T:n globalisoitumista voidaan johtaa eri hallintömuodoilla: T&T:n kansainvälistymisellä, T&T:n ulkomaille sijoittamisella ja T&T ulkomaille ulkoistamisella. T&T:n globalisoituminen on osa 2000-luvun taloudellista muutosta, ja sille on esitetty useita vaikuttavia tekijöitä, kuten kustannuserot, työvoimaresurssit, erityisosaamiskeskukset, paikallinen teknologia osaaminen ja kohdemarkkinoiden potentiaali (bardhan 2006; Norwood, ym. 2006; von Zedtwitz ja Gassmann 2002). Tutkimuksen on osoitettu eroavan tuotekehityksestä ja eri tekijöiden on osoitettu vaikuttavan niihin (von Zedtwitz ja Gassmann 2002; Leifer ja Triscari 1987). Samoin T&T on osoitettu olevan jatkumo perustavanlaatuisesta soveltavaan ja lääkekehityksen muodostavan vastaavan T&T jatkumon (Lall 1980; Iansiti 1993), jonka yksittäiset osat vaikuttavat sen hallintomuotoon. Tutkimus esittää eri tekijöitä voivan hyödyntää hallintomuodosta riippuen. Tätä tutkimusta varten tutkija haastatteli lääketeollisuuden johtajia Kiinassa vahvistaakseen tai hylätäkseen eri tekijöitä ja niiden suhdetta lääketeollisen T&T:n hallintomuotoihin. Markkinoiden todettiin olevan ensisijainen tekijä mutta myös kustannuserojen, insentiivien, työvoimaresurssien ja erityisosaamiskeskusten merkitys T&T:n globalisoitumiseen vaikuttavina tekijöinä vahvistettiin yhdessä perusvaatimusten ja riskitekijöiden kanssa. Tutkimuksessa vahvistetaan myös lääketeollisen T&T-jatkumon vaikutus ja esitetään viitekehys hallintomuodoille.

Globalization of pharmaceutical R&D Pharmaceutical R&D governance forms in People's Republic of China

Firm's survival and success, which are dependent on its ability to innovate, to create knowledge and to capitalize on inventions and know-how, is in essence directly linked to its R&D process (Dunk and Kilgore 2001). Especially in technology driven industries, such as the pharmaceuticals, there are significant positive returns to R&D investments through introduction of new or improved products and services (McEvily and Chakravarthy 1999). Technological lead and its transformation to innovative products as fruits of corporate R&D can be seen as monopolistic advantage that helps enterprises to compete in today’s market (Lall 1977). This competitive advantage can be derived from corporation's ability to integrate its activities across geographic locations (Porter 1986). According to Boehe (2008) globalization of R&D can executed with different governance forms: R&D internationalization, R&D offshoring or R&D offshore outsourcing. Globalization of R&D is intervened with the changes in global economy of the 21st century. Some studies argue for its influencing factors to be access to vast skilled labor pools and centers of excellence (Bardhan 2006). Other studies indicate the R&D cost differentials between countries to be the major expected benefit (Norwood et al. 2006). Von Zedtwitz and Gassmann (2002) presented benefits as divided to accessing markets and customers or to accessing local science and technology. This study proposes that based on governance form distinct factor derived benefits can be capitalized. To corroborate or refute factors and their relations on R&D globalization governance forms, an empirical study based on expert interviews of pharmaceutical directors was conducted in the People's Republic of China. The market was found to be the major influencing factor. Local requirements and adaptation were corroborated as factors connected with markets. Furthermore, influencing factors, such as labour, centers of excellence, cost, financial incentives were corroborated together with conditional and risk factors. Furthermore this research argues that the globalization of pharmaceutical R&D is dependent on the financial, scientific and operational requirements of the drug discovery stage. And thus establishes the influence of drug discovery's stages continuum on pharmaceutical R&D globalization. Finally, a R&D globalization governance form decision framework is proposed based on the frameworks presented in literature and author's corroborated empirical findings.

(Re)writing the other/self : autoethnography in the transcultural arena of representation

Abstract: In Imperial Eyes Mary Louise Pratt (1992: 7, emphasis original) defines autoethnography as "instances in which colonized subjects undertake to represent themselves in ways that engage with the colonizer's own terms ... in response to or in dialogue with . . . metropolitan representations." Although Pratt's conceptualization of autoethnography has much to offer post-colonial studies, it has received little attention in the field. In this thesis, I interrogate Pratt's notion of autoethnography as a theoretical tool for understanding the self-representations of subordinate peoples within transcultural terrains of signification. I argue that autoethnography is a concept that allows us to move beyond some theoretical dualisms, and to recognize the (necessary) coexistence of subordinate peoples' simultaneous accommodation of and resistance to dominant representations of themselves. I suggest that even when autoethnographic expressions seem to rely on or to reproduce dominant knowledges, their very existence as speech acts implicitly resists dominant discourses which objectify members of oppressed populations and re-create them as Native Informants. I use Pratt's concept to analyze two books by Islamic feminist sociologist Fatima Memissi. Memissi's Dreams ofTrespass and Scheherazade Goes West illustrate the simultaneity of accommodation and disruption evident in autoethnographic communication. Across the two books, Memissi shows herself renegotiating the discourses which discipline her (and her speech). She switches back and forth between the positions of reader and author, demonstrates the reciprocity of the disciplinary gaze (she looks back at her dominants, reading their own reading of her representation of her social group), and provides a model of autoethnographic dialogue.

The inadequate dominance of realism : an analysis of the U.S. war on terror /

There has been and will continue to be substantial debate over how the international system can best be characterized. The objective of this paper is to demonstrate that the international system can best be characterized by the essential features of realism, but the use of realist policy prescriptions are inadequate when applied independently to deal with the threat of terrorism as it exists today. In order to demonstrate this an examination of realism in the international system, U.S. foreign policy, and case analysis of Afghanistan and Iraq will be undertaken to demonstrate that although realist policy prescriptions do have a role in dealing with modem transnational security threats, these prescriptions on their own are inadequate when dealing with terrorism.

The new woman, femininity and modernity in Margery Allingham's detective novels of the 1930s /

This thesis examines Death of a Ghost (1934), Flowers for the Judge (1935), Dancers in Mourning (1937), and The Fashion in Shrouds (1938), a group of detective novels by Margery Allingham that are differentiated from her other work by their generic hybridity. The thesis argues that the hybrid nature of this group of Campion novels enabled a highly skilled and insightful writer such as Allingham to negotiate the contradictory notions about the place of women that characterized the 1930s, and that in dOing so, she revealed the potential of one of the most popular and accessible genres, the detective novel of manners, to engage its readers in a serious cultural dialogue. The thesis also suggests that there is a connection between Allingham's exploration of modernity and femininity within these four novels and her personal circumstances. This argument is predicated upon the assumption that during the interwar period in England several social and cultural attitudes converged to challenge long-held beliefs about gender roles and class structure; that the real impact of this convergence was felt during the 1930s by the generation that had come of age in the previous decade-Margery Allingham's generation; and that that generation's ambivalence and confusion were reflected in the popular fiction of the decade. These attitudes were those of twentieth-century modernity--contradiction, discontinuity, fragmentation, contingency-and in the context of this study they are incorporated in a literary hybrid. Allingham uses this combination of the classical detective story and the novel of manners to examine the notion of femininity by juxtaposing the narrative of a longstanding patriarchal and hierarchical culture, embodied in the image of the Angel in the House, with that of the relatively recent rights and freedoms represented by the New Woman of the late nineteenth-century. Pierre Bourdieu's theory of social difference forms the theoretical foundation of the thesis's argument that through these conflicting narratives, as well as through the lives of her female characters, Allingham questioned the Hsocial myth" of the time, a prevailing view that, since the First World War, attitudes toward the appropriate role and sphere of women had changed.

Monstrum : the vampire in the detective story /

My approach to the vampire detective highlights its connections to the private detective's story and reveals the monstrous investigators' debt to early feminist forms of detection -specifically in their reformation of the' other' and of traditional forms of power and authority. Seen in this light the movement of horror's imaginary 'other' into the rational world of detection can be seen as not an abrupt breach of detection's realist conventions, but an almost seamless transition into symbolic spaces that point to the detective's primary function -- to make sense of the senseless. It is in this light that I explore the monster that is a detective as a symbol that is also a sense-maker, and a quintessential postmodern figure. I argue that the distinctions between monsters and 'others', and between popular narratives and postmodern religion have faded, culminating in a character that can not only model 'otherness' as an exemplary condition, but also provide strategies for modeling the form of active postmodern subjectivity that postmodern theorist Jim Collins' (1989) conceives of as heretical activity.

Will the "fight" ever end? : a critical reading of the metaphors and discourses that construct HIV/AIDS in an African context

In this thesis, I critically examine the discourses that inform how we conceptualise HIV/AIDS in Sub-Saharan Africa as they are produced in a sample of Canadian news articles, two nonfiction texts - Stephanie Nolen's 28 Stories of AIDS in Africa and Jonathan Morgan and the Bambanani Women's Group's Long Life ... Positive HIV Stories - as well as two literary texts - John Le Carre's popular fiction novel The Constant Gardener and an anthology of stories and poems from Southern Africa titled Nobody Ever Said AIDS, compiled and edited by Nobantu Rasebotsa, Meg Samuelson and Kylie Thomas. Paying particular attention to the role of metaphor in discursive formation, I have found that military metaphors, usually used in conjunction with biomedical discourses, continue to dominate what is said about HIV/AIDS. However, the use of military metaphors to conceptualise HIV/AIDS contributes to stigma and limits the effectiveness of responses to the pandemic. I argue that accessing alternative metaphors and discourses, such as biopsychosocial discourse, can lead to a more layered - and more beneficial - conceptualisation of HIV/AIDS, encouraging a more active response to the pandemic.

Relationship between photoperiod, plasma concentration of ionic calcium and the histology of the prolactin-secreting cells of the rostral pars distalis of the pituitary gland, the corpuscles of stannius and the ultimobranchial gland in the goldfish, Carassius auratus L. /

The relationship between photoperiod, plasma concentration of ionic calcium and the histology of the prolactin-secreting cells of the rostral pars distalis of the pituitary gland, the Corpuscles of Stannius and the Ultimobranchial gland were investigated. Neither the plasma concentration of ionic calcium nor histologically apparent prolactin cell activity could be correlated with photoperiod. Some evidence of a photoperiodic effect on both the Corpuscles of Stannius and the Ultimobranchial gland was obtained. The expected reciprocal relationship between the activity of these glands was not obvious at the histological level . Quantitative and qualitative analysis at the light microscope level revealed, however, that the hormone prolactin-secreting eta cells of the rostral pars distalis and the hypocalcin-secreting cells of the Corpuscles of Stannius may be arranged in a lamellar pattern comprized of synchronous bands of cells in like-phase of a secretory cycle consisting of four stages - synthesis, storage, release and reorganization. Such synchronized cell cycles in these glands have not heretofore been described in literature. It is suggested that the maintenance of at least 255? of the cells in any one phase of the cycle ensures a supply of the required hormone at all times.

Gender and Genre in 21st Century Visions of Sherlock Holmes

Sherlock Holmes has been one of the most-adapted characters in literature since his first appearance in A Study in Scarlet in Beeton's Christmas Annual in 1887. Each new adaptation must offer innovations that bring freshness and contemporary appeal to time-worn stories and concepts or risk irrelevancy; analyzing these changes closely sheds light on shifts in societal constructs. Taking this as a starting point, this thesis examines Sherlock and Elementary from a perspective of feminism and queer theory via methods of discourse and genre analyses, with texts ranging from 1931 to the present as objects of comparison. The research illuminates constructions of masculinity as they have changed over time, particularly the movement from an orderly, stable, rational construction of hegemonic masculinity to one that is chaotic, often violent, and anti-heroic in at least some aspects while still being invested in the status quo.

Dramatizing whoredom : prostitution in the work of Tennessee Williams

Cette thèse explore le leitmotiv de la prostitution dans l’oeuvre de Tennessee Williams et soutient que la plupart des personnages de Williams sont engagés dans une forme de prostitution ou une autre. En effectuant une analyse formaliste des textes de Williams qui illustrent toute forme de prostitution, avec une attention particulière à quatre grandes pièces, A Streetcar Named Desire (1947), Cat on a Hot Tin Roof (1955), Suddenly Last Summer (1958) et Sweet Bird of Youth (1959), cette présente étude fait valoir que le dramaturge utilise un mode de fiction—le gothique—en lien avec une pratique transgressive—la prostitution—pour relier les classes sociales et troubler les catégories de prostitution. Ce faisant, Williams offre une vision plus représentative et nuancée de la prostitution. Théoriquement, cette thèse repose sur des oeuvres critiques portant sur le genre, la sexualité et l'histoire de Michel Foucault, David Savran, et Michael Paller afin de situer la dramaturgie de Williams dans le contexte historique et culturel des années 1940 et 1950. La première partie de cette thèse (chapitres un et deux) fournit de nombreuses informations autobiographiques et biographiques qui expliquent pourquoi la prostitution est devenue le thème de prédilection pour Williams. Cette section met l’accent sur sa préoccupation constante à l’égard de sa prostitution artistique (en prostituant son art pour le succès commercial) et sexuelle (en payant pour des prostitués). Cette partie présente également un inventaire détaillé des prostituté(e)s, que je divise en trois catégories: 1) la prostitution des enfants, 2) la prostitution masculine et 3) la prostitution féminine. La deuxième partie de cette étude, composée des chapitres trois et quatre, identifie les personnages de Williams qui s’engagent dans une forme de prostitution morale. Ce groupe comprend ceux qui tirent directement profit de la prostitution des autres ainsi que ceux qui se marient uniquement pour un gain financier ou une promotion sociale ou les deux. L’oeuvre de Williams résiste la représentation stéréotypée de la prostituée en littérature comme étant uniquement de sexe féminin ou provenant des classes sociales défavorisées ou les deux. La prostituée de Williams n’est ni une figure romantique ni une rebelle menaçant la société. Cette thèse conclut qu’en représentant des enfants prostitués, des femmes de rue, des prostitués de sexe masculin, des souteneurs, des proxénètes, des propriétaires de bordels, des leaders corrompus et des personnes qui se prostituent en concluant des mariages de convenance, Williams a effectivement et incontestablement dramatisé la prostitution sous toutes ses formes.

Évaluation de la fréquence des micronoyaux et du potentiel clastogène et/ou aneugène du benzo-a-pyrène suite à une exposition in vitro des lymphocytes humains

Le benzo-a-pyrène (BaP) est un cancérogène reconnu pour l'homme, contaminant présent dans notre environnement. Il cause des dommages à l'ADN que nous avons mesurés dans les lymphocytes exposés à de faibles concentrations de BaP, provenant de 20 jeunes volontaires non fumeurs et en santé. Suite à l’exposition, la fréquence des micronoyaux (MN) augmente significativement et décrit une courbe dose-réponse non linéaire, suggérant le déclenchement du processus de détoxification et la réparation de l’ADN. Des différences entre les individus et entre les sexes sont présentes dans la réponse génotoxique produite par le BaP. Le test des aberrations chromosomiques montre que le pourcentage de chromosomes cassés augmente significativement dans les cellules exposées au BaP. Combinés avec l'augmentation de la fréquence des MN, nos résultats confirment l'effet clastogène du BaP déjà rapporté dans la littérature. L’hybridation in situ en fluorescence (FISH) des MN avec une sonde pancentromérique est aussi utilisée pour établir leur mécanisme de formation. La FISH révèle que la majorité des MN formés après une exposition au BaP contient un centromère et plus, ce qui est significativement différent de la condition non exposée. Plus précisément, dans nos conditions expérimentales, les MN induits par le BaP contiennent surtout trois centromères et plus, indiquant également la présence d'un effet aneugène. L'effet clastogène du BaP est relié à son rôle d'initiateur dans la cancérogenèse, alors que l'effet aneugène le relierait à l'étape de progression. Ces résultats sont importants puisque l'exposition aux composés de la classe du BaP est de longue durée (cigarette, air pollué).