7,030 research outputs found
Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection.
No full textThe S-type lectin galectin-9 binds to the negative regulatory molecule Tim-3 on T cells and induces their apoptotic deletion or functional inactivation. We investigated whether galectin-9/Tim-3 interactions contribute to the deletion and exhaustion of the antiviral T cell response in chronic hepatitis B virus infection (CHB). We found Tim-3 to be expressed on a higher percentage of CD4 and CD8 T cells from patients with CHB than healthy controls (p<0.0001) and to be enriched on activated T cells and those infiltrating the HBV-infected liver. Direct ex vivo examination of virus-specific CD8 T cells binding HLA-A2/peptide multimers revealed that Tim-3 was more highly upregulated on HBV-specific CD8 T cells than CMV-specific CD8 T cells or the global CD8 T cell population in patients with CHB (p<0.001) or than on HBV-specific CD8 after resolution of infection. T cells expressing Tim-3 had an impaired ability to produce IFN-γ and TNF-α upon recognition of HBV-peptides and were susceptible to galectin-9-triggered cell death in vitro. Galectin-9 was detectable at increased concentrations in the sera of patients with active CHB-related liver inflammation (p = 0.02) and was strongly expressed by Kupffer cells within the liver sinusoidal network. Tim-3 blockade resulted in enhanced expansion of HBV-specific CD8 T cells able to produce cytokines and mediate cytotoxicity in vitro. Blocking PD-1 in combination with Tim-3 enhanced the number of patients from whom functional antiviral responses could be recovered and/or the strength of responses, indicating that these co-inhibitory molecules play a non-redundant role in driving T cell exhaustion in CHB. Patients taking antivirals able to potently suppress HBV viraemia continued to express Tim-3 on their T cells and respond to Tim-3 blockade. In summary, both Tim-3 and galectin-9 are increased in CHB and may contribute to the inhibition and deletion of T cells as they infiltrate the HBV-infected liver
Michael Jones, jazz trumpet
No full textThis Graduate recital features Michael Jones (jazz trumpet), with Ryan Bosick (bass), J. B. Faires (bass), Tyrone Garner II (drums), Tim Gillins (trombone), Travis Wesley Hoover (piano), Josh Marcus (alto sax), and the EIU Jazz Ensemble, directed by Sam Fagalay
Tim Donovan Interview, 2005
No full textIn this 2005 interview, Tim Donovan, Director of the Ohio Canal Corridor, discusses the history of this non-profit organization dedicated to preserving and restoring the Ohio canal and its towpath. Donovan, who grew up on the west side of Cleveland in the 1950s, and attended St. Ignatius High School and Cleveland State University, recounts early jobs he had in the Cleveland area, including working at Jones & Laughlin\u27s steel mills and serving as a Census Bureau surveyor. He was working at J&L during the famous 1969 Cuyahoga River fire. Donovan also worked as a videographer, and it was this occupation which led him to his life\u27s work of preserving the Ohio Canal. In the balance of this interview, he discusses the many efforts he and others made, first to preserve the Warehouse District in the 1980s, and then the Ohio Canal from the mid 1980s to the present (2005). He discusses in detail how the non-profit corporation was built; contributions from the private sector, including American Steel & Wire and Alcoa; and critical federal preservation legislation passed during the Clinton Administration
Tim Donovan Interview, 2005
No full textIn this 2005 interview, Tim Donovan, Director of the Ohio Canal Corridor, discusses the history of this non-profit organization dedicated to preserving and restoring the Ohio canal and its towpath. Donovan, who grew up on the west side of Cleveland in the 1950s, and attended St. Ignatius High School and Cleveland State University, recounts early jobs he had in the Cleveland area, including working at Jones & Laughlin\u27s steel mills and serving as a Census Bureau surveyor. He was working at J&L during the famous 1969 Cuyahoga River fire. Donovan also worked as a videographer, and it was this occupation which led him to his life\u27s work of preserving the Ohio Canal. In the balance of this interview, he discusses the many efforts he and others made, first to preserve the Warehouse District in the 1980s, and then the Ohio Canal from the mid 1980s to the present (2005). He discusses in detail how the non-profit corporation was built; contributions from the private sector, including American Steel & Wire and Alcoa; and critical federal preservation legislation passed during the Clinton Administration
by Glen Norcliffe, Una Brogan, Peter Cox, Boyang Gao, Tony Hadland, Sheila Hanlon, Tim Jones, Nicholas Oddy, and Luis Vivanco (eds)
No full textDekker H-J. Book Review: by Glen Norcliffe, Una Brogan, Peter Cox, Boyang Gao, Tony Hadland, Sheila Hanlon, Tim Jones, Nicholas Oddy, and Luis Vivanco (eds). The Journal of Transport History. 2023;44(2):330-332
When Thinking Leads to Doing: the Relationship Between Fantasy and Reality in Sexual Offending.
No full textThis chapter is taken from the following text: Jones, T. & Wilson, D. (2008). Thinking & Doing; Fantasy & Reality: An Analysis of Convicted Paedophiles. In Birch, P., Ireland, C., & Ireland, J. (Eds.) The Assessment, Treatment and Management of Violent and Sexual Offenders, London: Willa
Australian Health Research Alliance: national priorities in data-driven health care improvement
No full textAbstract not available.Helena J Teede, Alison Johnson, Jim Buttery, Cheryl A Jones, Douglas IR Boyle, Garry LR Jennings, Tim Sha
Evaluating Citebase, an open access Web-based citation-ranked search and impact discovery service
No full textCitebase is a new citation-ranked search and impact discovery service that measures citations of scholarly research papers which are openly accessible on the Web, i.e. papers that are assessable continuously online. Other services, such as ResearchIndex, have emerged in recent years to offer citation indexing of Web research papers. In the first detailed user evaluation of an open access Web citation indexing service, Citebase has been evaluated by nearly 200 users from different backgrounds. The paper details the procedures used in the evaluation, and analyses the results of this study, which took place between June and October 2002. It was found that within the scope of its primary components, the search interface and services available from its rich bibliographic records, Citebase can be used simply and reliably for the purpose intended, and that it compares favourably with other bibliographic services. It is shown tasks can be accomplished efficiently with Citebase regardless of the background of the user. More data need to be collected and the process refined before it is as reliable for measuring citation impact of indexed papers. Better explanations and guidance are required for first-time users. Coverage is seen as a limiting factor, even though Citebase indexes over 200,000 papers from arXiv. Non-physicists were frustrated at the lack of papers from other sciences. The principle of citation searching of open access archives has thus been demonstrated and need not be restricted to current users. Since the evaluation, Citebase has become a featured service of the ArXiv physics eprint archives
Linking Innovative Potential to SME Performance: An Assessment of Enterprises in Industrial South Wales
No full textThe attraction of inward investment from the UK and from overseas was the main focus of regional development policy in Wales for much of the 1970s and 1980s. Whilst Wales has been particularly successful in attracting foreign enterprise, the contribution of new investors to improving longer term regional economic prospects has been questioned at several levels. With concerns over inward investor stability, embeddedness, and contribution to local value added, increasing weight has been given to the encouragement, and development of innovative indigenous SMEs in the Welsh economy. General and sectoral initiatives to encourage SME development and innovation in Wales have also taken place against a background of historically low levels of new firm formation in the region, together with the presence of factors expected to hinder SME growth including low levels of capital availability. Ultimately, it is hoped that a strongly performing indigenously controlled and innovative SME sector will go some way to improving regional growth prospects, and hence play a role in reducing the GDP per capita gap between Wales and the UK. During the 1990s a series of research and consultancy studies in Wales have been undertaken seeking to audit SME activities, define needs and identify market failures in provision of information and services. These have formed the basis of revised policy and then for new resource directions emanating at the European, regional and local levels. Encouraging innovative activity has been at the forefront of the network of initiatives currently underway in Wales. New initiatives have often been instituted without a clear appreciation of the nature of innovation, and how innovative activities link to innovative outputs and then feed through to improved business performance. This paper examines the link between innovative activity, outcomes and the performance of SMEs in Wales. A range of European, UK and locally developed initiatives in Wales seek to encourage innovative activity in indigenous SMEs. However, it is the contention of this paper that these initiatives have often been instituted without a clear appreciation of how, if, and which innovative activities feed through to improved business performance. The paper offers a general method of assessing the innovative potential (the configuration of management practices, capabilities, internal and external linkages facilitating the generation of appropriation of ideas) of manufacturing SMEs. This then leads on to an examination of how far innovative potential is connected to operational and general business performance. The paper describes how the model was developed and used to assess the innovative potential of a sample of manufacturing SMEs in Industrial South Wales, and how far the innovative potential can be linked to improved operational and business performance. The introduction to the paper reviews current literature on innovation in SMEs, and demonstrates how far recent studies have succeeded in measuring, and then linking innovative inputs of SMEs to innovative outputs and firm performance. The second section builds upon the review to develop a working model of an innovative SME. Innovation is considered not only in terms of new product or process development but more generally as practice. The model reveals the innovative firm as one that identifies, interprets, and applies knowledge effectively, and as appropriate throughout the organisation. The model described represents a synthesis of previous research. Key factors in the model include strategy and the techniques and practices deployed to facilitate the development and appropriation of ideas for innovation. Broadly this focuses on SME commitment to innovation, and management practices supporting this commitment. The third section describes how the model was operationalised into an auditing tool, and then used to assess the innovative potential of a sample of manufacturing SMEs in Industrial South Wales. The fourth section summarises the results from the initial research programme, and in particular, considers whether the unique operating structures usually associated with SMEs hinder or facilitate the adoption of new structures for organisational learning. Moreover the section examines whether the existence of certain configurations of practices coincide with improved business performance and operational efficiencies. The conclusions consider these results in the context of the directions being adopted by current regional SME policy initiatives in Industrial South Wales.
25. A Christmas conundrum: What ailed Tiny Tim?
No full textTiny Tim Cratchit is the captivating soul of one of the English language’s most beloved stories, Charles Dickens’ A Christmas Carol. His mysterious crippling disorder is quite the medical enigma, being intermittent, unilateral and fatal if left untreated. His tiny stature can also be counted amongst his symptoms. However, the most startling aspect of his condition is its ability to be cured in 1840s London with Ebenezer Scrooge’s limitless funds.
While Tim is saved after Scrooge’s reformation, Dickens never mentions what disease afflicted the little youngster. Upon examining Dickens personal health and previous literary talent of describing diseases unknown to medical science at the time, the ailment is validated as an accurate depiction of a real malady.
Two major theories exist as to the nature of the disease. Tuberculosis and renal tubular acidosis are offered as explanations to the interesting symptoms Tim experienced. The debate hinges on the interpretation of the original manuscript that, ‘Tiny Tim did not die.’ While survival is possible from the more common tuberculosis in 1843, a full cure was available from renal tubular acidosis via the alkali tonics available at that time. The debate may rage on indefinitely.
Callahan C. Tiny Tim remembered. Am J Dis Child 1991; 145:1355-6.
Jones P. Dickens’ literary children. Aust Pediatr J 1972; 8:233-45.
Lewis D. What was wrong with Tiny Tim? Am J Dis Child 1992; 146:1403-1407.</jats:p
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