280 research outputs found
Selling Loyalist and Republican memories:the prospects for Dark (Troubles) Tourism in Northern Ireland
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
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
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
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
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.
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
Prions can be detected in blood from patients with variant Creutzfeldt-Jakob disease with high sensitivity and specificity.</jats:p
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