363 research outputs found

    The Magdalene's Friend : The Control of Prostitutes in Glasgow, 1840-1890

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    This thesis is a contribution to three areas of sociological interest: the history of sexuality, the history of prostitution and, the more general area of the moral regulation of the working class in the nineteenth century. In order to accomplish this, the following research questions are raised. First, the system of moral policing and control introduced in Glasgow in the 1870's raises interesting questions concerning the difference between systems of police repression as an alternative to the state regulation of prostitution. The thesis attempts to evaluate the impact of the 'Glasgow System' which was developed as an alternative to state regulation in the 1870's. The Glasgow System was composed of the Glasgow Lock hospital, the Glasgow Magdalene Institution and the Glasgow Police Act (1866). The second issue addressed in this thesis concerns the internal management of the Glasgow Magdalene Institution. Nicole Rafter has identified 3 techniques for social control used in female penitentiaries in the nineteenth century: 1) physical incarceration of women who violated middle class standards of sexual behaviour, 2) resocialization, 3) the provision of stipends and rewards to women who successfully completed the two year stay in the Institution. The manner in which these techniques were used to control the sexual and vocational behaviour of the women who entered the Glasgow Magdalene Institution between 1960 and 1889 are examined. The final issue examined is the public discourse of the 'prostitution problem' in Scotland in the nineteenth century. Contributions to the discourse came from four main interest groups: the medical profession, philanthropists, local state representatives, and socialists, By the 1840's the socialists were marginalized. It is argued that through its control over key repressive and ideological apparatuses, such as the Glasgow police and Magdalene Institution the ideas of the dominant bourgeois discourse were reproduced in the institutional practices of these institutions

    Screening and classifying small-molecule inhibitors of amyloid formation using ion mobility spectrometry-mass spectrometry

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    The search for therapeutic agents that bind specifically to precursor protein conformations and inhibit amyloid assembly is an important challenge. Identifying such inhibitors is difficult because many protein precursors of aggregation are partially folded or intrinsically disordered, which rules out structure-based design. Furthermore, inhibitors can act by a variety of mechanisms, including specific or nonspecific binding, as well as colloidal inhibition. Here we report a high-throughput method based on ion mobility spectrometry–mass spectrometry (IMS–MS) that is capable of rapidly detecting small molecules that bind to amyloid precursors, identifying the interacting protein species and defining the mode of inhibition. Using this method we have classified a variety of small molecules that are potential inhibitors of human ​islet amyloid polypeptide (​hIAPP) aggregation or ​amyloid-beta 1-40 aggregation as specific, nonspecific, colloidal or non-interacting. We also demonstrate the ability of IMS–MS to screen for inhibitory small molecules in a 96-well plate format and use this to discover a new inhibitor of ​hIAPP amyloid assembly

    Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents

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    Reproductive disorders that are common/increasing in prevalence in human males may arise because of deficient androgen production/action during a fetal ‘masculinization programming window’. We identify a potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC size and intratesticular testosterone (ITT) increased ∼3-fold between e15.5-e21.5 which associated with a progressive decrease in the percentage of LC expressing COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces masculinization disorders, dose-dependently prevented the age-related decrease in LC COUP-TFII expression and the normal increases in LC size and ITT. We show that nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but does not affect an SF-1 dependent LC gene (3β-HSD) without overlapping sites. We also show that once COUP-TFII expression in LC has switched off, it is re-induced by DBP exposure, coincident with suppression of ITT. Furthermore, other treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and decreases ITT, as in rats. These findings suggest that lifting of repression by COUP-TFII may be an important mechanism that promotes increased testosterone production by fetal LC to drive masculinization. As we also show an age-related decline in expression of COUP-TFII in human fetal LC, this mechanism may also be functional in humans, and its susceptibility to disruption by environmental chemicals, stress and pregnancy hormones could explain the origin of some human male reproductive disorders

    Antibody-mediated protection against MERS-CoV in the murine model

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    Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV
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