VictorJuiz/thesis huggingface dataset:
Voltage-gated calcium channel kinetics implicated in the process of fast neurotransmitter release

Voltage-gated calcium channels have long been known to be the controllers of neurotransmitter release. This study highlights kinetic differences in N-type channel populations in dorsal root ganglion soma and ciliary ganglion terminals, then extends these differences to physiological implications of neurotransmission. Opposing models hold that release sites are gated either by calcium domains of single, closely associated channels or by overlapping domains from many remote channels. This study reports a linear relationship between transmitter release and the number of open calcium channels indicative of single domain release site activation at the ciliary ganglion terminal. While consistent with results from squid giant synapse, this finding is at odds with the suggested overlapping domains of rodent synapses. However, these reports were reconciled by developing a model of 'percent domain overlap' whereby the degree of overlap is dependent on external calcium concentration. This relationship predicts the involvement of local calcium channels in release site activation.
The aftermath of Canada's implementation of the Doha Declaration on the future of pharmaceutical innovation

Pharmaceutical product patents have recently become the focus of attention for health activists and governments worldwide, largely because of their direct effect on people's lives and survival; particularly the thousands of people suffering from HIV/AIDS. On 30 August 2003, pursuant to the adoption of the Doha Declaration on TRIPS Agreement and Public Health [on 14 November 2001], the WTO Council for TRIPs met to find a solution to the difficulty faced by countries with insufficient or no capacity to manufacture drugs. It was resolved, during this meeting, that developed countries could now issue compulsory licenses for purposes of exporting HIV/AIDS drugs to developing countries. Prior to this resolution, compulsorily licensed products were restricted only to the domestic market of the country issuing the license. Canada became the first developed country to take the bold step of pledging that they will amend their patent laws for purposes of providing drugs to developing countries. This paper analyses the possible implications of Canada's decision with respect to other developed countries, drug manufacturers, and the future of international patent protection generally.

Keywords: Drugs, Canada
Technological innovations, Law and legislation
Technological innovations, Canada
Modulation of inflammatory mediators during aging and amyloid-beta pathology

An elevation in the expression of inflammatory mediators has been reported in aging and Alzheimer's disease (AD). As chronic inflammation has been associated with toxicity, this thesis focused on strategies that could reduce the expression of inflammatory mediators in aging, and help understand the role(s) of these mediators in AD. A promising approach to reduce inflammation used the activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). In chapter 4, oral or intracerebroventricular administration of the PPAR-gamma agonist, ciglitazone, potentiated IL-1beta and TNF-alpha expression in aging Fischer 344 (F344) rat brains. These results may be a consequence of the paradigm used, as F344 rats represent an 'unchallenged' naturally occurring aging model. In chapter 5, the expression of inflammatory mediators in AD, a neurodegenerative disease characterized by the aggregation of the amyloid-beta peptide (Abeta), was assessed using acute and chronic models of Abeta exposure as tools to study disease onset and progression, respectively. A single intracerebral injection of Abeta (acute model) in rats resulted in an increase in the expression of pro-inflammatory mediators, but not in TGF-beta1. In contrast, aging TgCRND8 mice (chronic model) revealed low levels of pro-inflammatory mediators, but increased levels of TGF-beta1 when compared to age-matched non-Tg mice. These results suggest that the increase in TGF-beta1 expression may require cumulative neuronal toxicity in addition to Abeta exposure. Intervention studies in AD including NSAID administration or genetic modulation in mouse models of AD highlight a role for inflammatory mediators as modulators of Abeta pathology. In chapter 6, the role of TGF-beta1 was evaluated through the administration of TGF-beta1 neutralizing antibodies for a 30-day period in TgCRND8 mice, which proved effective in reducing total soluble Abeta levels. Conclusion. This thesis showed that age-associated inflammation may not be repressed by the use of PPAR-gamma agonists. In addition, my results indicate that the expression of inflammatory mediators is regulated as a function of the duration of Abeta exposure. Finally, my findings showed for the first time that neutralization of one specific cytokine, without the use of genetic modifications, can alter Abeta pathology in a mouse model of AD.
Gendering the classical tradition of Quran exegesis: Literary representations and textual authority in medieval Islam

This dissertation examines the traditions attributed to early Muslim women that are quoted in classical Quran commentaries, and studies their literary functions within such works. Traditions of this type are diverse in literary form, as well as in the exegetical topics that they are made to address. Several exegetical works conventionally dated the formative period (i.e. prior to 338 A.H./950 C.E.) contain significant numbers of traditions which are ascribed to women--particularly, to 'A'isha bt. Abi Bakr (d. 58/678). Moreover, three of the h[dotbelow]adith compilations which came to be regarded as most authoritative by Sunnis have chapters on quranic exegesis which contain substantial numbers of such traditions. Furthermore, traditions ascribed to early Muslim women appear in many medieval commentaries on the Quran. While the existence of such traditions is well known to scholars in Quran and Tafsir Studies, surprisingly little research has been done on them. Therefore, little is known about these traditions, either as a category, or about the literary functions they have in exegetical works. This dissertation places traditions of this type in their literary-historical context, and then systematically surveys them. Utilizing gender as an analytical category, the textual functions of select traditions within the textual genre of medieval Quran commentary are examined. Moreover, the exclusionary discourse propounded in classical tafsir works, which brands women in general as intellectually deficient and unfit to exercise authority is critically examined, particularly with respect to its implications for our understanding of the literary functions of traditions attributed to women for medieval exegetes. This study demonstrates that gender is integral to matters of central concern to medieval Quran interpreters: exegetical authority, social hierarchy, communal and sectarian identities, and even the boundaries of the canon. For them, what was primarily at stake was not so much "the status of women" per se, but the (re)construction and maintenance of the gendered social hierarchy upon which they believed that a believing and righteous society is of necessity founded. Their (re)construction and (re)negotiations of the contours of the exclusionary discourse is an exegetical construction of gender itself, and with it interpretive authority.
An integrated methodological approach for the study of the transplacental transfer of glyburide: From the subcellular to the clinical perspective

Gestational diabetes, left untreated, can result in severe fetal consequences. Glyburide, a drug used to treat gestational diabetes, has been shown, to be actively effluxed out of the placenta in the fetal to maternal direction. ABC-transporters such as P-glycoprotein (PGP), breast Cancer resistant protein (BCRP) and the multi drug resistance proteins (MRP 1, 2 and 3) are expressed in the human placenta and may be involved in the transport of drugs from the fetus to the mother. The objective of the present thesis is to (1) determine which placental ABC efflux transporter(s) are involved in the active transport of glyburide in the human placenta and (2) to establish an integrative approach to investigating the transplacental behaviour of drugs in pregnancy. At the cellular level, functional studies in ABC transporter over-expressing cell lines were performed in the presence and absence of specific inhibitors. Cellular uptake studies have shown that glyburide is likely transported by BCRP and MRP3. Subsequently, the transport of glyburide in the presence of MRP inhibitor indomethacin was investigated in the dually perfused human placenta model. At the organ level, there was no significant difference in the rate of transfer of glyburide in the presence or absence of the MRP inhibitor indomethacin. At the subcellular level, 3H-glyburide efflux was measured in the presence and absence of specific ABC transporter inhibitors in purified placental brush border membrane vesicles. Vesicular uptake studies in the human placenta indicate that glyburide is likely transported by placental BCRP and not MRP 1, 2, or 3. Glyburide's efflux from the human placenta, poise this drug as a potential model for the design of pregnancy specific drugs. Furthermore, in the advent of their creation, an ethical analysis of performing clinical trials in women undergoing pregnancy termination is considered as a potential population for the study of drugs designed particularly for pregnancy. The presented integrative approach can be easily adopted clinically and would not only generate the information necessary to eliminate the dearth of data that exist regarding drug use in pregnancy but ultimately improve the therapeutic treatment of pregnant women and their unborn fetus.
Studies of autocrine VEGF signalling in rhabdomyosarcoma

Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis and tumour growth, exerts signals through two receptor tyrosine kinases, VEGFR1 and VEGFR2. Many tumours cells also express VEGF receptors and are influenced by autocrine VEGF signalling. Expression of VEGFR1 is induced in cells with a PAX3-FKHR translocation, a hallmark of alveolar rhabdomyosarcoma (ARMS). Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma, and the third most common extracranial childhood solid tumour. In our experiments, RT-PCR demonstrated the expression of VEGF and VEGFRs by RMS. The addition of exogenous VEGF resulted in ERK-1/2 phosphorylation and cell proliferation, both of which were reduced with VEGFR1 blockade. Treatment with VEGFR1 inhibitor alone slowed RMS growth. All-trans retinoic acid decreased VEGF secretion and slowed growth, which was rescued with exogenous VEGF treatment. These data suggest that autocrine VEGF signalling occurs in RMS and its inhibition may be an effective strategy for rhabdomyosarcoma treatment.
Women's access to education at the universities of Papua New Guinea

Women's access to the universities of Papua New Guinea is a measure of their ability to surmount barriers in a highly competitive, selective system. Papua New Guinea is a developing country which has had only about one hundred years of sustained contact with the outside world. The provenance of western-style education for its children has both helped the development of the country and placed a strain on its resources as the goal of universal education has been aimed for but not achieved. In traditional times, girls filled roles quite different from those of boys. In the modern state, girls who wish to achieve western goals such as education and, as a consequence, stable waged employment have to be very persistent in their attempts to be part of the system from the moment at which they might enter Grade One. Current statistics suggest that 30% of all Papua New Guinean children never receive schooling, while, in relation to their proportion of the population, more boys than girls are enrolled in the education system. Boys are generally able to access higher grade levels and better occupational training than girls and men are present in the waged workforce in much greater numbers than women. The factors that affect girls' access to the education system from the stage at which they either become enrolled in Grade One (and hence may commence their drive toward university) or are excluded from the system entirely are described and set within the context of the societies in transition which make up the state of Papua New Guinea. The various points of selection which girls encounter as their increasingly smaller numbers progress through the system are analysed as are the outcomes which pertain as girls leave their schooling behind and take up their several roles in their families, communities and the economy. The fact that women are the mainstay of the subsistence economy is emphasised, partly because this developing country is currently undergoing a severe contraction in its modern sector and more people must return to subsistence living in order to survive. Girls appear to make better use of the education they get, since they help their families and communities after they finish their schooling, while boys are more likely to contribute to social unrest through joining ‘raskol’ gangs and/or participating in tribal warfare. The qualities of strength, perseverance in the face of many difficulties and resistance to their relegation into a secondary role all stand the women of Papua New Guinea in good stead as they help the societies in which they live to adjust to the modern age.
The many faces of Sir Thomas Browne

My study illuminates aspects of Sir Thomas Browne's character through an analysis of his historical context, the letters to his two sons, Tom and Edward, and through an examination of some of his posthumously published works. I consider in chapter 1 the socio-political background of Browne's life and his upbringing. Much information about the inner Browne can be gleaned from an examination of his family life, now better understood through recent research. I explore the critical legacy, beginning with Samuel Johnson and including a number of French critics, for their original insights. In chapters 2 and 3, I observe Browne in his own family. In chapter 2, I analyze Browne's letters to his younger son, Tom, while he was in France as a boy. These letters provide information about contemporary English and French history, with material on the history of epistolarity. The later ones to Tom were written while he was at sea with the Royal Navy and end a few months before his early death. In chapter 3, on Browne's letters to his older son Edward, I discuss material concerning contemporary medicine and the medical profession in London. This group of letters also reveals the father's vicarious ambitions expressed through Edward's career. Chapter 4 assesses the influence of contemporary ideas about melancholy and of Browne's own melancholic temperament on his art. An analysis of melancholy in his society, as well as of his own innately melancholic temperament, reveals much about him. Having outlined the distinction between Aristotelian and Galenic melancholy, I consider Burton's treatment of the subject in relation to Browne's own melancholy. In chapter 5, I examine work that belongs to the final years of Browne's life. Passages from a memorial tract written shortly before his death, from his commonplace books and from Christian Morals, unpublished until 1716, are analyzed. The importance of what was prepared for publication and of what he left as a kind of spiritual legacy to his son is described. Browne's consistency of vision, compounded of the tensions that shaped him, suggests a final judgment.
Teammate support for injured athletes: Assessment and intervention considerations

Teammates trained to provide effective support may be well-positioned to help athletes cope with the experience of injury. However, researchers have not developed a scale that measures teammate support specific to the task of rehabilitation from injury and have yet to implement a support intervention involving teammates. Therefore, the aims of the present investigation were two-fold. The first purpose was to develop and assess the psychometric properties of a Teammate Support Following Injury (TSFI) scale. Five experts in the area of psychology of injury and five intercollegiate athletes reviewed the TSFI to establish face validity. Modifications to the initial TSFI resulted in a 26-item scale reflecting five dimensions of rehabilitation-specific social support including instrumental, informational, emotional, motivational, and athletic identity support. Then, 112 (63 male and 49 female) intercollegiate and competitive athletes who had incurred an injury that prevented them from participating in sport/exercise activity for the period of at least one week were asked to complete the TSFI. They also completed measures of emotional response, athletic identity, and perceived support to assess the content validity of the TSFI, and a demographic questionnaire. A principle axis factor analysis with oblique rotation performed on the data resulted in three factors designated as athletic identity, instrumental/rehabilitation, and emotional support. The three subscales of the TSFI had excellent internal reliability and acceptable levels of concurrent validity with a structural support measure. The second purpose was to gain a better understanding of the responses to the TSFI and to assess participants' experiences of support and preferences for a support intervention involving teammates. Six participants who scored in the upper and lower quartiles on the TSFI participated in a personal interview. A directed content analysis revealed that injured athletes may not need practical support from teammates and do not expect teammates to provide information during their recovery. The results also indicated various social processes, contextual factors, potential mediating mechanisms, and outcomes of support important to structuring support interventions. These findings are discussed and recommendations are made for future support interventions that involve teammates.
Developing a risk-model of time to first-relapse for children and adolescents with primary psychotic disorders or mood disorders with psychotic features

Primary psychotic disorders and mood disorders with psychotic features are serious and persistent mental health disorders that are increasingly being diagnosed in children and adolescents. Current relapse rates range from 34% within 6 months to over 80% within five years in adult patients with psychotic disorders. To date, children and adolescents with these psychiatric conditions have been largely ignored and no investigation has exclusively addressed relapse. The aim of this dissertation was to explore and critically examine the relapse of children and adolescents following first-episode psychosis or mood disorders with psychotic features, for which they received treatment in an inpatient hospital psychiatric unit. This research was guided by a biopsychosocial theoretical framework encompassing an inclusive, holistic and integrative framework that recognizes the importance of biological, psychological, social, and treatment factors. Key words. relapse, hospitalization, readmission, psychosis, first-episode, schizophrenia, mood disorders, predictors, risk factors, children, adolescents. The study employed a retrospective follow-up longitudinal cohort research design. Participants were recruited from across six inpatient hospital psychiatric units where they were treated. This study examined the relapse rate and associated predictors in children and adolescents by constructing a Kaplan-Meier survival curve for time to first-relapse; conducting univariate survival analysis on risk variables associated with time to first-relapse; and the development of a statistical risk-model for prediction of time to first-relapse. Of the 87 participants (n=87), approximately sixty percent (57%) experienced a recurrence by the end of follow-up, half of them within 34 months. Participants were enrolled in the study for a minimum two-year period with a mean of 3.9 years and standard deviation of 1.3 years. A Cox Proportional Hazards Regression identified four key risk factors for relapse: medication adherence, gender, clinical treatment, and maintenance of social support prior to first admission. The results in this study lend importance to the need to target programs to younger populations, specifically those in the early critical phase of their disorder. Equally important is the provision of education and services that promote medication adherence, as well as the identification and monitoring of re-emergence of symptoms. The results of this study also support the development of programs and services for children and adolescents with psychotic disorders and mood disorders with psychotic features.
Managing marine life: Scientific and practical work at two British marine stations, 1884--1902

The rise of a large-scale trawl-fishing industry in Britain during the second half of the nineteenth century had impacts beyond the nation's economy and food supply. As this industry, and the fish upon which it was based, became indispensable, anxieties grew that the trawlers were overfishing Britain's coastal waters, damaging young fish and sending too-small fish to market. A succession of Royal Commissions and parliamentary inquiries were uniform in their calls for marine fisheries science: scientists, with their privileged access to nature, were thought better placed than either fishermen or Commissioners to find the answers that would guide how Britain's trawl fisheries were managed. British marine naturalists like E. Ray Lankester of the Marine Biological Association (MBA), eager to establish marine research laboratories along their own coastline, saw their opportunity. In 1884, a small marine research laboratory opened at St. Andrews, Scotland, organized and staffed by William Carmichael M'Intosh; four years later, a larger coastal laboratory opened at Plymouth, organized by the MBA and staffed year-round by a Director and a Naturalist, paid workers dedicated to studying economically important food fish species. These stations had been founded in large part on the basis of promises that the scientific work undertaken there would be of practical value to Britain's fisheries. This dissertation examines what keeping those promises looked like. J.T. Cunningham, the Plymouth Laboratory's first staff Naturalist, was the embodiment of the MBA's promises to government and industry, his work simultaneously scientific and practical in method and outcome. In his studies of the growth, development, and colouration of flatfish like plaice, sole, and flounders, Cunningham had to develop supply chains of specimens coming into the laboratory and inventories of specimens living in the laboratory's tanks. M'Intosh, too, traced the development and migrations of young flatfish while developing sophisticated biological arguments against the possibility of overfishing the sea. Both men, and both laboratories, denied the distinction between scientific and practical work on food fish; the fish themselves figured equally as organisms and as commodities, as objects of study, exchange, and consumption.