280 research outputs found

    Selling Loyalist and Republican memories:the prospects for Dark (Troubles) Tourism in Northern Ireland

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    The purpose of this article is to investigate the Northern Ireland tourism industry with a special focus on Dark (Troubles) Tourism. The method is two surveys one of Northern Ireland residents and one of potential tourists resident overseas, a focus group and interviews with tour-guides and a local MP. Findings suggest widespread support for Troubles Tourism from both residents and potential tourists and a supportive attitude from our interviewees. The two sides to the conflict are now working side-by-side in this new form of tourism, but it is important that each side tell only its ‘own’ story. from its own perspective, and does not speak for others. We conclude that, not over-commercialized, Troubles Tourism can educate people as well as being a source of fascination

    Excitability and optical pulse generation in semiconductor lasers driven by resonant tunneling diode photo-detectors

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    We demonstrate, experimentally and theoretically, excitable nanosecond optical pulses in optoelectronic integrated circuits operating at telecommunication wavelengths (1550 nm) comprising a nanoscale double barrier quantum well resonant tunneling diode (RTD) photo-detector driving a laser diode (LD). When perturbed either electrically or optically by an input signal above a certain threshold, the optoelectronic circuit generates short electrical and optical excitable pulses mimicking the spiking behavior of biological neurons. Interestingly, the asymmetric nonlinear characteristic of the RTD-LD allows for two different regimes where one obtain either single pulses or a burst of multiple pulses. The high-speed excitable response capabilities are promising for neurally inspired information applications in photonics. (C) 2013 Optical Society of AmericaFCT [PTDC/EEA-TEL/100755/2008]; FCT Portugal [SFRH/BPD/84466/2012]; Ramon y Cajal fellowship; project RANGER [TEC2012-38864-C03-01]; Direcci General de Recerca del Govern de les Illes Balears; EU FEDER funds; Ministry of Economics and Competitivity of Spain [FIS2010-22322-C02-01

    Some aspects of posterior resin restorations : an in vivo and in vitro study

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    Thesis (M.D.S.)--University of Adelaide, School of Dentistry, 198

    Neuropathology and molecular biology of iatrogenic Creutzfeldt-Jakob disease in UK human growth hormone recipients

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    Creutzfeldt-Jakob disease (CJD) is the commonest form of human prion disease and occurs in sporadic, genetic and acquired forms. The causative agents (prions) appear to be composed entirely of a modified host protein, the prion protein, which undergoes misfolding to a disease-associated isoform closely associated with infectivity that is resistant to conventional methods of decontamination. Prions can be transmitted from one individual to another by medical and surgical procedures, resulting in iatrogenic CJD (iCJD). The commonest cause of iCJD is the inoculation of cadaveric pituitary-derived human growth hormone (hGH) to treat growth hormone deficiency in children; this form of treatment was abandoned in 1985 after the first UK case of iCJD in a hGH recipient was identified. Seventy-eight cases of iCJD have since occurred in the UK cohort of 1849 hGH recipients, including a case in 2016. This thesis describes a comprehensive tissue-based and molecular genetic analysis of the largest series (35 cases) of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show that the polymorphism at codon 129 of the prion protein gene strongly influences the disease incubation period in hGH-iCJD (from 7.8-32.3 years in this series) and interacts with the infectious prion strain to govern the molecular and pathological characteristics of iCJD. The findings are consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is found in the second most common form of sporadic CJD. The investigation also found accumulation of the amyloid beta (Aβ) protein associated with Alzheimer’s disease (AD) in the brains and cerebral blood vessels in 18/35 hGH-iCJD patients and 5/12 control patients who had been treated with hGH, but died from causes other than iCJD. In contrast, Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD (1/15 cases) and variant CJD (2/33 cases). These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and seeded into the brains of around 50% of all hGH recipients, producing AD-like neuropathology and cerebral amyloid angiopathy (CAA). This provides further evidence of the prion-like properties of Aβ and gives insight into the potential for possible transmission of AD/CAA. It is uncertain whether any Aβ seeding within the brains of surviving patients in the UK hGH recipient cohort will ultimately result in clinical AD; however, the CAA in these patients may be complicated by intracerebral haemorrhage resulting from rupture of the blood vessels damaged by Aβ accumulation within their walls

    The molecular epidemiology of variant CJD

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    The emergence of the novel prion diseases bovine spongiform encephalopathy (BSE) and, subsequently, variant Creutzfeldt-Jakob disease (vCJD) in epidemic forms has attracted much scientific attention. The oral transmission of these disorders, the causative relationship of vCJD to BSE and the resistance of the transmissible agents in both disorders to conventional forms of decontamination has caused great public health concern. The size of the still emerging vCJD epidemic is thankfully much lower than some early published estimates. This paper reviews current knowledge of the factors that influence the development of vCJD: the properties of the infectious agent; the route of inoculation and individual susceptibility factors. The current epidemiological data are reviewed, along with relevant animal transmission studies. In terms of genetic susceptibility, the best characterised is the common single nucleotide polymorphism at codon 129 of prion protein gene. Current biomarkers and future areas of research will be discussed. These issues are important in informing precautionary measures and the ongoing monitoring of vCJD

    Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner.

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    Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD). The absence of a human cell culture model that replicates human prions has hampered prion disease research for decades. In this paper, we show that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype-dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. Furthermore, iPSC-derived astrocytes can replicate prions associated with the major sporadic CJD strains found in human patients. Lastly, we demonstrate the subpassage of prions from infected to naive astrocyte cultures, indicating the generation of prion infectivity in vitro. Our study addresses a long-standing gap in the repertoire of human prion disease research, providing a new in vitro system for accelerated mechanistic studies and drug discovery

    Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease

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    Prions can be detected in blood from patients with variant Creutzfeldt-Jakob disease with high sensitivity and specificity.</jats:p
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