1,182 research outputs found

    A histological study of the spinal cord and peripheral nervous system in scrapie disease of sheep

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    This work records the results of a study of the spinal cords, spinal sensory ganglia, sympathetic ganglia, Gasserian ganglia and neurones in the adrenal glands of sheep affected with scrapie disease.It was suggested that many minor changes in sympathetic ganglia may be of a non -specific nature and it was concluded that there was no significant morphological difference, including vacuolation of neurones, between the gelglia of clinically healthy sheep and those with scrapie disease

    Information architecture for effective Workload Control: an insight from a successful implementation

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    The implementation of Workload Control (WLC), a Production Planning and Control concept uniquely designed for Make-To-Order companies, has been a constant challenge. Scholars argued that WLC is largely developed through simulations of well-defined environments while much more complex circumstances (e.g. information availability) have emerged in field research. A recent trend of WLC research is to improve the practical applicability of the concept, where empirical evidence is essential. However, success in WLC implementation remains impeded. The availability of data has been a significant area that frustrates the implementation process. While there is a tendency to simplify data requirements in recent WLC theory development, it is important to understand and maintain the information that is essential for the concept to be effective. For the first time in the field, this paper details the information architecture for WLC. Key informational entities of relevance to the input/output control functions in WLC as well as performance measurement are discussed based on evidence from a successful implementation. The paper not only sheds light for practitioners on how to construct an information system that facilitates successful WLC implementation but also has implications for future development of WLC mechanisms coping with information uncertainties in practice

    Chromatin Profiles of Chromosomally Integrated Human Herpesvirus-6A

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    Human herpesvirus-6A (HHV-6A) and 6B (HHV-6B) are two closely related betaherpesviruses that are associated with various diseases including seizures and encephalitis. The HHV-6A/B genomes have been shown to be present in an integrated state in the telomeres of latently infected cells. In addition, integration of HHV-6A/B in germ cells has resulted in individuals harboring this inherited chromosomally integrated HHV-6A/B (iciHHV-6) in every cell of their body. Until now, the viral transcriptome and the epigenetic modifications that contribute to the silencing of the integrated virus genome remain elusive. In the current study, we used a patient-derived iciHHV-6A cell line to assess the global viral gene expression profile by RNA-seq, and the chromatin profiles by MNase-seq and ChIP-seq analyses. In addition, we investigated an in vitro generated cell line (293-HHV-6A) that expresses GFP upon the addition of agents commonly used to induce herpesvirus reactivation such as TPA. No viral gene expression including miRNAs was detected from the HHV-6A genomes, indicating that the integrated virus is transcriptionally silent. Intriguingly, upon stimulation of the 293-HHV-6A cell line with TPA, only foreign promoters in the virus genome were activated, while all HHV-6A promoters remained completely silenced. The transcriptional silencing of latent HHV-6A was further supported by MNase-seq results, which demonstrate that the latent viral genome resides in a highly condensed nucleosome-associated state. We further explored the enrichment profiles of histone modifications via ChIP-seq analysis. Our results indicated that the HHV-6 genome is modestly enriched with the repressive histone marks H3K9me3/H3K27me3 and does not possess the active histone modifications H3K27ac/H3K4me3. Overall, these results indicate that HHV-6 genomes reside in a condensed chromatin state, providing insight into the epigenetic mechanisms associated with the silencing of the integrated HHV-6A genome

    Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells

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    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 \u3bcg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 \ub1 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 \ub1 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 \u3bcg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 \u3bcg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL

    Transgressing the moral economy: Wheelerism and management of the nationalised coal industry in Scotland

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    This article illuminates the links between managerial style and political economy in post-1945 Britain, and explores the origins of the 1984–1985 miners' strike, by examining in longer historical context the abrasive attitudes and policies of Albert Wheeler, Scottish Area Director of the National Coal Board (NCB). Wheeler built on an earlier emphasis on production and economic criteria, and his micro-management reflected pre-existing centralising tendencies in the industries. But he was innovative in one crucial aspect, transgressing the moral economy of the Scottish coalfield, which emphasised the value of economic security and changes by joint industrial agreement

    The Wicked Machinery of Government: Malta and the Problems of Continuity under the New Model Administration

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    This is a study focused on the early years of British rule in Malta (1800-1813). It explores the application to the island of the “new model” of colonial government, one based on direct rule from London mediated by the continuation of existing laws and institutions. Systemic deficiencies are identified. These tended to undermine the effectiveness of direct British rule. This study also reveals, in the context of legal and constitutional continuity, unresolved tensions between modernity and tradition. The political stability of the island was damaged and the possibility of continued British possession was threatened

    The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

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    First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

    The need to promote behaviour change at the cultural level: one factor explaining the limited impact of the MEMA kwa Vijana adolescent sexual health intervention in rural Tanzania. A process evaluation

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    Background - Few of the many behavioral sexual health interventions in Africa have been rigorously evaluated. Where biological outcomes have been measured, improvements have rarely been found. One of the most rigorous trials was of the multi-component MEMA kwa Vijana adolescent sexual health programme, which showed improvements in knowledge and reported attitudes and behaviour, but none in biological outcomes. This paper attempts to explain these outcomes by reviewing the process evaluation findings, particularly in terms of contextual factors. Methods - A large-scale, primarily qualitative process evaluation based mainly on participant observation identified the principal contextual barriers and facilitators of behavioural change. Results - The contextual barriers involved four interrelated socio-structural factors: culture (i.e. shared practices and systems of belief), economic circumstances, social status, and gender. At an individual level they appeared to operate through the constructs of the theories underlying MEMA kwa Vijana - Social Cognitive Theory and the Theory of Reasoned Action – but the intervention was unable to substantially modify these individual-level constructs, apart from knowledge. Conclusion - The process evaluation suggests that one important reason for this failure is that the intervention did not operate sufficiently at a structural level, particularly in regard to culture. Recently most structural interventions have focused on gender or/and economics. Complementing these with a cultural approach could address the belief systems that justify and perpetuate gender and economic inequalities, as well as other barriers to behaviour change
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